Biomedical subjects

S Hirsch

Publications and source records attributed to S Hirsch.

At least 37 records · Page 2Linked to original sources

PubMed1995

Effects of long-term vitamin E supplementation in alcoholic cirrhotics.

OBJECTIVE: Alcohol ingestion promotes lipoperoxidation and alters cellular antioxidant mechanisms. Alpha-tocopherol levels decrease in alcoholics as severity of liver damage increases. The aim of this protocol was to study the effects of a long-term oral 500 mg vitamin E daily supplementation in decompensated ambulatory alcoholic cirrhotics. PATIENTS AND METHODS: 67 subjects were included in this double blind trial; 33 patients received vitamin E and 34 patients received placebo tablets of identical appearance during 1 year. Each month, the patients were seen by a nurse practitioner who was in charge of detecting alcohol ingestion and checking adherence to treatment. Every 3 months, the patients underwent a medical examination, and blood samples were taken for clinical laboratory analysis and serum vitamin E measurement. RESULTS: Alpha-tocopherol levels were significantly lower in patients with more severe liver disease. This difference was not significant when vitamin E levels were corrected by cholesterol. Oral supplementation significantly increased serum vitamin E levels in the experimental group. Alcohol ingestion and hospitalization rates were similar in both groups. Life table analysis did not show significant differences in mortality between the two groups. DISCUSSION: Vitamin E supplementation with adequate doses of an alpha-tocopheryl acetate formulation during 1 year did not influence hepatic laboratory parameters, mortality or hospitalization rates of decompensated alcoholic cirrhotics, although serum levels of the vitamin significantly increased.

Adult↗

PubMed1995

Comparison of Mycoplasma arthritidis strains by enzyme-linked immunosorbent assay, immunoblotting, and DNA restriction analysis.

Twenty Mycoplasma arthritidis strains or isolates were compared by a combination of enzyme-linked immunosorbent assay by an antiserum adsorption technique, Western immunoblotting, and restriction analysis of chromosomal DNA. Antigenic markers that defined strains related to strains 158p10p9, PG6, and H606 were identified. In addition, restriction analysis allowed all 20 strains to be divided into six groups. Results of restriction analysis corresponded generally with antigenic similarities, although the former did not allow grouping with as fine a precision as the latter. However, intrastrain antigenic variability, which is common among many Mycoplasma species, including M. arthritidis, introduced a complicating factor into our attempts at antigenic analysis. While serologic and antigenic analyses remain useful, we recommend that they be used with caution and in combination with other techniques for identifying and characterizing new isolates and newly acquired strains. Combinations of these techniques have proven to be useful in our laboratory for quality control and for uncovering interesting relationships among strains subjected to animal passage and their less virulent antecedents and among strains originally classified as the same but obtained from different sources and maintained, sometimes for decades, in different laboratories.

Animals↗

PubMed1995

Assessment of the practicality and safety of thrombolysis with anistreplase given by general practitioners.

BACKGROUND: Recent guidelines recommend that patients with obvious acute myocardial infarction receive thrombolysis, unless contraindicated, within 60-90 minutes of summoning assistance. If this target is to be achieved, an increasing number of general practitioners are likely to be involved in the administration of thrombolytic agents. AIM: This study aimed to assess the practicality and safety of thrombolysis with anistreplase when given by general practitioners. METHOD: An observational study was conducted in 805 general practices throughout the United Kingdom. Between March 1991 and September 1992, a total of 3383 patients with a clinical diagnosis of myocardial infarction were recruited--888 by 344 general practitioners who wished to include anistreplase in their management of myocardial infarction ('user' group) and 2495 by 776 general practitioners who did not wish to use anistreplase but who were willing to provide information about their cases ('comparison' group). RESULTS: More than half the patients were seen within two hours of onset of symptoms. A high frequency of contra-indications to thrombolysis, diagnostic uncertainty, and other, mainly practical, reasons limited the number of occasions on which anistreplase was administered. Thus, only 310 patients were given anistreplase in the community. The general practitioners in the study used anistreplase safely. Their diagnostic accuracy was high (of the 310 patients given anistreplase 69% had a definite, possible or probably myocardial infarction, 4% a definite non-cardiac diagnosis), the number of patients given anistreplase in spite of a documented contraindication was small (seven patients), and the doctors appeared to be aware of potential bleeding problems associated with thrombolysis. In all cases, the complications of acute myocardial infarction appeared to be managed appropriately. CONCLUSION: General practitioners can use anistreplase both appropriately and safely in the early management of acute myocardial infarction. Recognized contraindications to thrombolysis and practicalities of diagnosis and drug administration may, however, limit the number of occasions on which anistreplase is used.

Adult↗

PubMed1995

Mitogen induction of nuclear factors that interact with a delayed responsive region of the transferrin receptor gene promoter.

Activation of the human transferrin receptor promoter by mitogenic stimulation of quiescent cells is a delayed event that reaches a maximum several hours after stimulation. Previous results have defined a region of the transferrin receptor gene promoter that is required for increased expression in mitogen-activated cells (W. K. Miskimins and D. B. Brown, Exp. Cell Res., 191: 328-331, 1990; Q. Ouyang et al., Mol. Cell. Biol., 13: 1796-1804, 1993). This region contains two elements (elements A and B) that appear to cooperate in the response to mitogenic stimulation. Serum stimulation of quiescent cells leads to the induction of nuclear factors that bind to both the A and B elements. Induction of these factors is also a delayed response to serum stimulation and reaches a maximum 6-9 h after stimulation. Element A, which is an unusual GC-rich sequence, forms several serum-inducible DNA-protein complexes, all of which depend on contacts within GC boxes. A major inducible complex of element A contains a factor that is supershifted by antibodies against the transcription factor Sp1. The B element appears to have overlapping binding sites for two types of factors. One of these sites binds factors that are competed off by an AP-1 consensus-binding site. The other B element site binds inducible factors that interact with GC boxes, identical to those observed for element A.

3T3 Cells↗

PubMed1995

[Major histocompatibility system as a risk factor for alcoholic liver disease].

Several associations between alleles of the major histocompatibility system and alcoholic liver disease have been described. However, these are weak and change from one population to another. The aim of this work was to search for a possible genetic risk factor for alcoholic liver disease among Chilean alcoholics. We studied blood groups, serum proteins and HLA antigens in 39 alcoholic cirrhotics, 104 asymptomatic alcoholics and 44 non alcoholic controls. Asymptomatic alcoholics were also subjected to a percutaneous liver biopsy that showed moderate to severe histological liver damage in 46 subjects (44%). No differences in the studied genetic markers, were found among the four groups. It is concluded that this study does not confirm previously reported associations between genetic markers and alcoholic liver disease.

Adult↗

PubMed1995

[Patients with chronic airflow limitation: effects of the inspiratory muscle training with threshold load valve, built with appropriate technology, associated to nutritional support].

AIM: To assess prospectively the effects of a controlled program of inspiratory muscle training program and nutritional support in patients with chronic obstructive lung disease (COPD). PATIENTS AND METHODS: Twenty-three patients with COPD were randomly assigned into four groups. Group I received a 1000 kcal/day nutritional supplement, given as a casein based enteral nutritional formula; group III was subjected to inspiratory muscle training, using an inexpensive pressure threshold load valve constructed according to the Appropriate Technology principles of the WHO, adjusted at 30% of Maximal Inspiratory Mouth Pressure and received also the nutritional supplement; group IV was trained but did not receive the nutritional supplement and group II was not trained nor supplemented. Patients were studied during three months and monthly, inspiratory muscle function, exercise capacity and anthropometry were measured. RESULTS: A significant improvement in exercise capacity, maximal inspiratory pressure and inspiratory muscle endurance was observed in the four groups throughout the study. Trained subjects had greater improvement in their inspiratory muscle endurance, compared to untrained subjects. Nutritional support had no effect in inspiratory muscle function or exercise capacity. No changes in anthropometric measures were observed. CONCLUSIONS: The pressure threshold load valve used in this study, improved inspiratory muscle endurance and nutritional support had no effect in patients with COPD.

Aged↗

PubMed1995

Ultraviolet light and serum induce similar delayed responses that lead to activation of a mitogen-responsive promoter.

The transferrin receptor promoter is responsive to growth factors and mitogens. This induction is a delayed response and does not occur until several hours after stimulation of quiescent cells by mitogens. The results described here show that the transferrin receptor promoter is also activated by treatment with ultraviolet (UV) light. Activation of the promoter by UV light is dose dependent and requires the same cis-acting elements that are activated in response to serum and other mitogens. As with serum stimulation, activation of the promoter by UV light is a delayed event and is not initiated until 6 h after treatment. This coincides with the induction of nuclear factors that bind with specificity to the required cis-acting elements. A major GC-box binding factor induced by UV light is also induced by serum and has been shown to be supershifted by antibodies to the Sp1 transcription factor.

3T3 Cells↗

PubMed1994

A receptor component of the chloroplast protein translocation machinery.

The chloroplast outer envelope protein OEP86 functions as a receptor in precursor protein translocation into chloroplasts. Sequence analysis suggests that the precursor of OEP86 is directed to the chloroplast outer envelope by a cleavable, negatively charged, and unusually long amino-terminal peptide. This presequence is unlike other potential targeting signals and suggests the existence of another membrane insertion pathway. Insertion of precursor OEP86 required the hydrolysis of adenosine triphosphate and the existence of surface exposed chloroplast membrane components, and it was not competed by another precursor protein destined for the internal plastid compartments.

Adenosine Triphosphate↗

PubMed1994

A linkage study of distal chromosome 5q and bipolar disorder.

There are well-established abnormalities of hypothalamic-pituitary-adrenal (HPA) axis and beta 2 adrenergic receptor function in affective disorders. The genes for the glucocorticoid receptor (GRL) and the beta 2 adrenergic receptor (ADRB2) have been cloned and mapped to distal chromosome 5q. In this study, we have examined polymorphisms of these two candidate genes and other nearby markers for linkage to bipolar disorder in Amish pedigree 110 and three large Icelandic pedigrees. These loci were tested for linkage in two-point and multipoint analyses using a model of autosomal dominant transmission with age-dependent reduced penetrance. Two-point analyses revealed a maximum LOD score of 1.14 at theta = 0.20 from GRL. Linkage could be excluded to ADRB2, as well as to three nearby anonymous markers, D5S207, D5S70, and D5S119. Analyses of another anonymous marker, D5S36, were inconclusive. Multipoint analyses excluded linkage to a 55 cM region including the interval between D5S207 and D5S36 and flanking regions, with the exception of a 7 cM interval between GRL and ADRB2. Despite the intriguing positive LOD score obtained with GRL, linkage to bipolar disorder could not be demonstrated in the region examined.

Adolescent↗

PubMed1994

Splanchnic and systemic hemodynamics in early abstinence and after ethanol administration in non-cirrhotic alcoholic patients.

Thirteen asymptomatic chronic alcoholic patients were studied to investigate the early stages of portal hypertension in alcoholic liver disease and the effects of withdrawal and ethanol on hepatic function and hemodynamic variables. None of the patients presented clinical signs of decompensated liver disease, and their liver biopsies showed normal liver or moderate alterations only. In basal conditions and after an intravenous ethanol infusion (1 g/kg body weight), hepatic venous pressure gradient and hepatic blood flow using indocyanine green were measured through hepatic vein catheterization. Hepatic sinusoidal vascular resistance and indocyanine green intrinsic clearance were also calculated. Portal blood flow measurements were obtained by Doppler ultrasound. No correlation was observed between hepatic venous pressure gradient and histologic features, (steatosis, necrosis, fibrosis, inflammation and hepatocyte surface area). In basal conditions, portal hypertension was not found in any case. After ethanol, portal pressure increased significantly (p < 0.001); in four cases it rose to or above 5 mmHg. Portal blood flow, hepatic blood flow and hepatic vascular resistance also increased significantly. Intrinsic indocyanine green clearance decreased slightly but significantly. No significant correlations were found between portal pressure, hepatic resistance and the histologic parameters. It was concluded that alcoholic patients, without clinical or laboratory evidence of liver failure and with minimal or moderate histologic alterations, have normal portal pressures. After an intravenous ethanol load, however, four out of 13 patients (31%) reached levels of 5 mmHg or more, irrespective of their liver histology.

Adult↗

PubMed1994

[Amitriptyline in therapy of chronic tension headache].

In a double-blind, placebo-controlled trial, the effect of 75 mg of a slow-release formulation of amitriptyline on the clinical severity of chronic tension-type headache and on headache-associated neurophysiological parameters (EMG activity, exteroceptive suppression of temporal muscle activity, contingent negative variation (CNV) and experimental pain sensitivity) was investigated. All of the patients treated had a history of headaches of many years standing, and numerous failed attempts at treatment. In the amitriptyline group, a significant reduction in daily headache duration was already found in the third week of treatment, while in the placebo group no significant changes in headache duration were to be seen. In week 6 the amitriptyline group had a significantly shorter daily duration of headache than the placebo group. Treatment did not result in any significant effects on EMG recording of pericranial muscle activity either during relaxation or contraction, on exteroceptive suppression of the temporal muscle and on CNV. The sensitivity to suprathreshold experimental pain, however, was significantly reduced. The data show a statistically relevant reduction of daily headache duration in chronic tension-type headache. However, they also show that amitriptyline can only partly alleviate chronic headaches but cannot cure them.

Adolescent↗

PubMed1994

Ventricular mass in hypertensive and normotensive obese subjects.

Two-dimensional echocardiography was performed in 29 normotensive obese subjects and 21 hypertensive obese subjects representative of the Chilean population. The left ventricular mass (LVM) did not correlate with height or body surface area (BSA) in these patients, but positively correlated with body mass index (BMI), tricipital skinfold thickness and blood pressure (BP). The LVM/BSA ratio was significantly higher in the hypertensive subjects and was correlated with BP only. Left ventricular hypertrophy (LVM/BSA > 120 or 150 g/m2 in women or men, respectively) was found in 28% of normotensive and 58% of hypertensive subjects (P = 0.036). No statistical differences were found in relative wall thickness (RWT) between both groups. Posterior wall thickness was independently associated with BP while interventricular septum thickness was positively associated with the waist/hip ratio. Systolic function, evaluated through fractional shortening and end systolic diameters, was negatively and independently associated with body fat area. Left ventricular hypertrophy is a prevalent condition in these obese subjects. Hypertension seems to exert an additive effect, mainly increasing posterior wall thickness. Fat accumulation was negatively related to systolic function in this sample, irrespective of blood pressure.

Adult↗

PubMed1993

A genetic linkage study of bipolar disorder and 13 markers on chromosome 11 including the D2 dopamine receptor.

Chromosome 11 is a region of great interest in the search for genes for bipolar disorder. Although an initial report of linkage to 11p15 was not replicated in numerous subsequent studies, the remainder of the chromosome contains a variety of interesting candidate genes and regions. These include the D2 dopamine receptor and the site of a chromosomal translocation that has been reported to be associated with bipolar disorder. As part of a systematic survey of the genome for markers linked to bipolar disorder, we have examined 13 markers on chromosome 11 in three large Icelandic families and Amish pedigree 110. No clear evidence of linkage was obtained. The highest lod score was found at D11S29 (lod = 1.63 at theta = 0.1), which is in the general region of the reported translocation breakpoints. However, this lod is not statistically significant, and its meaning is further mitigated by strongly negative lods in two nearby flanking markers. Linkage to the D2 dopamine receptor locus was strongly excluded (lod = -4.02 at theta = 0.0). In two-point analyses, linkage to bipolar disorder could be excluded to eight of the 13 markers. Multipoint analyses, similarly, failed to reveal any evidence of linkage.

Adolescent↗

PubMed1993

The effect of induced abortion on subsequent fertility.

OBJECTIVE: To investigate the effect of induced abortion on subsequent fertility. DESIGN: 1. Prospective cohort study of women who had an unplanned pregnancy at recruitment. 2. Retrospective study of women who had a planned pregnancy at recruitment. SETTING: Joint Royal College of General Practitioners/Royal College of Obstetricians and Gynaecologists study based in general practice in England, Scotland and Wales, between 1976 and 1987. SUBJECTS: 1. Prospective study: Four hundred and thirty-three women with a recruitment unplanned pregnancy ending in induced abortion (abortion group) and 1035 women with a recruitment unplanned pregnancy which ended naturally (nonabortion group). All subsequently had a planned pregnancy, or were known to be trying to conceive at some point during the follow-up. 2. Retrospective study: Nine thousand two hundred and ninety-nine women who presented at recruitment with a planned pregnancy. MAIN OUTCOME MEASURE: The women's estimated length of planning time, expressed as a fertility rate ratio. RESULTS: Induced abortion was not related to future fertility. In the prospective study, the fertility rate ratio (FRR) of the abortion group relative to the nonabortion group was 0.94 (95% CI 0.83 to 1.07, P = 0.37). This result was supported by the retrospective study, which again showed no important difference between the two groups. CONCLUSION: Induced abortion does not appear to have an important effect on future fertility.

Abortion, Induced↗

PubMed1993

Leucine and glucose turnover in chronic alcoholics during early abstinence and after an ethanol load.

We studied leucine turnover using a primed infusion of [1-14C]-L-leucine and glucose turnover using a primed infusion of [6-3H]-D-glucose in five alcoholic patients without liver damage and five age-matched controls. Infusions were maintained for 6 hr, and at the end of the 3rd hour, a 0.8 g/kg iv ethanol load was administered in 20 min. Leucine flux, nonoxidative disposal and oxidation rates, and glucose rate of appearance were calculated during the 3rd and 6th hours of infusion. Ethanol disappearance rate and the percentage completely metabolized to CO2 and H2O in 3 hr were also calculated. Compared with controls, alcoholics had significantly higher basal leucine flux (55.6 +/- 12 vs. 37.3 +/- 9.3 microM/m2/min) and nonoxidative disposal (48.7 +/- 8.7 vs. 31.1 +/- 7.5 microM/m2/min). No differences were observed in basal glucose appearance rates in alcoholics and controls (397.6 +/- 115.2 vs. 349.4 +/- 120.6 microM/m2/min). Compared with controls, alcoholics had a higher alcohol disappearance rate (2.72 +/- 0.59 vs. 1.84 +/- 0.43 mM/kg/min) and percentage of ethanol metabolized to CO2 and H2O in 3 hr (40.6 +/- 10.2 vs. 22.9 +/- 6.9%). After the ethanol load, both leucine turnover and glucose rate of appearance decreased significantly only in alcoholics. There was a positive correlation between the change in leucine flux and ethanol disappearance rate and percentage metabolized to CO2 and H2O in alcoholics.

Acetaldehyde↗

PubMed1993

Mechanisms of attachment of Mycoplasma arthritidis to host cells in vitro.

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.

Animals↗

PubMed1993

[Prediction of histological liver damage in asymptomatic alcoholic patients by means of clinical and laboratory data].

Looking for a noninvasive method to predict liver histologic alterations in alcoholic patients without clinical signs of liver failure, we studied 187 chronic alcoholics recently abstinent, divided in 2 series. In the model series (n = 94) several clinical variables and results of common laboratory tests were confronted to the findings of liver biopsies. These were classified in 3 groups: 1. Normal liver; 2. Moderate alterations; 3. Marked alterations, including alcoholic hepatitis and cirrhosis. Multivariate methods used were logistic regression analysis and a classification and regression tree (CART). Both methods entered gamma-glutamyltransferase (GGT), aspartate-aminotransferase (AST), weight and age as significant and independent variables. Univariate analysis with GGT and AST at different cutoffs were also performed. To predict the presence of any kind of damage (Groups 2 and 3), CART and AST > 30 IU showed the higher sensitivity, specificity and correct prediction, both in the model and validation series. For prediction of marked liver damage, a score based on logistic regression and GGT > 110 IU had the higher efficiencies. It is concluded that GGT and AST are good markers of alcoholic liver damage and that, using sample cutoffs, histologic diagnosis can be correctly predicted in 80% of recently abstinent asymptomatic alcoholics.

Adult↗

PubMed1992

Predicting psychiatric admission rates.

OBJECTIVE: To determine the numbers of actual and expected psychiatric admissions for the residents of the district health authorities of England and to develop a model to indicate which social, health status, and service provision factors best explain the variation of the actual from the expected psychiatric admissions; to use this model to predict psychiatric admission for district health authorities as an aid to resource allocation. DESIGN: The actual psychiatric admission for district health authority residents were extracted from data of the 1986 Mental Health Enquiry. Expected admissions were calculated using the age, sex, and marital status structure of each district health authority and the national psychiatric admission rates related to age, sex, and marital status. Standardised psychiatric admission ratios were calculated as the ratios of the numbers of actual to expected psychiatric admissions. A wide range of social, health status, and service provision data were used as the explanatory variables in regression analyses to determine which combination of factors best explained the variation between districts of standardised psychiatric admission ratios. SETTING: The 168,652 psychiatric admissions recorded for the 1986 Mental Health Enquiry, after exclusion of mental handicap and psychogeriatric admissions. RESULTS: The actual number of psychiatric admissions varied from 79% above to 54% below the expected number of admissions from age, sex, and marital status for the districts of England. The most powerful variables to explain this variation were the rate of notification of drug misusers, standardised mortality ratios, and levels of illegitimacy in each district. A complex model was developed which could be used to predict district psychiatric admissions as an aid to resource allocation. A simpler model was also developed (which was less powerful than the more complex model) based on the underprivileged area score. One advantage of this model was that it could be used at the level of electoral wards as well as district health authorities.

Adolescent↗