Biomedical subjects

S Hirsch

Publications and source records attributed to S Hirsch.

At least 37 records · Page 2Linked to original sources

PubMed2000

[The importance of folic acid in current medicine].

Lately, folic acid deficiency is gaining a predominant role in the pathogenesis of congenital malformations and cardiovascular diseases in adults. The planning of individual and population preventive strategies for these diseases must consider this deficiency. This paper reviews the anatomical, biochemical and molecular bases of neural tube defects and cardiovascular diseases in adults. In these two frequent diseases, folic acid supplementation has shown a clear cut protective effect.

Adult↗

PubMed2000

Patient determinants of mental health interventions in primary care.

BACKGROUND: A large proportion of a general practitioner's (GP's) caseload comprises patients with mental health problems. It is important to ensure that care is provided appropriately, on the basis of clinical need. It is therefore necessary to investigate the determinants of the use of mental health care in the primary care sector and, in particular, to identify any non-clinical characteristics of patients that affect the likelihood of their receiving appropriate care. AIM: To identify and compare the influence of non-clinical patient factors on GPs' acknowledgement of mental problems and on their provision of mental health care. METHOD: Cross sectional study of adults aged 16 to 65 years old (n = 802) attending one of eight practices (20 GPs in total) in inner west London. RESULTS: Multivariable analysis showed that the combination of factors that best predict GPs' acknowledgement of the presence of mental problems are general health questionnaire (GHQ) scores (odds ratio [OR] = 1.10 per unit increase in score, 95% confidence interval [CI] = 1.07 to 1.13), previous mental symptoms (OR = 7.5, 95% CI = 4.3 to 12.9), increasing age (OR = 1.03 per one-year increase, 95% CI = 1.01 to 1.04) and physical health status (OR = 0.98 per unit increase in short form-36 (SF-36) score, 95% CI = 0.96 to 1.00). Multivariable analysis showed that the combination of factors that best predict intervention (prescription for psychotropic medication; return visit to GP; referral to psychiatric inpatients/outpatients; referral to other [specified] health professionals, or social services) are previous symptoms (OR = 7.4, 95% CI = 3.8 to 14.4), white ethnic group (OR = 2.2, 95% CI 0.9 to 5.5); and not owning a property (OR = 2.1, 95% CI = 1.1 to 4.0). Life events influenced intervention only in the presence of low GHQ scores (OR = 8.1, 95% CI = 2.7 to 24.0). CONCLUSIONS: Mental problems are common in primary care and their acknowledgement is a necessary but not a sufficient condition for intervention. Our results show that GPs' decisions about mental health interventions can be influenced by non-clinical patient factors, regardless of patients' clinical needs. The results suggest that current practice may not always be equitable, and point to the need for better understanding of the basis of these potential inequalities and for focused training.

Adolescent↗

PubMed1999

Cholecystokinin CCK(B) receptor mRNA isoforms: expression in schizophrenic brains.

In the light of earlier findings of reduced cholecystokinin (CCK) peptide and CCK mRNA levels in the cerebral cortex, we have used in situ hybridization to examine possible regulation of mRNAs coding for two isoforms of the CCK(B) receptor in frontal cortex (Brodmann's area 10) of schizophrenic patients. The hybridizations revealed a 51% decrease of the full length CCK(B) receptor mRNA in the outer layers (II-III) of the frontal cortex. The corresponding alterations for the truncated isoform were a 65% reduction in the outer layers and a 62% reduction in the inner layers (IV-VI) of the frontal cortex. This strengthens the hypothesis that CCKergic transmission in this part of the brain is involved in the pathophysiology of schizophrenia.

Adult↗

PubMed1999

Immunocytochemical characterization of reactive optic nerve astrocytes and meningeal cells.

Regeneration in the adult central nervous system (CNS) is thought to be hampered by the lesion-induced activation of astrocytes and meningeal cells and the consecutive formation of a glial scar. The substrate properties of reactive astrocytes differ significantly from their neonatal counterparts, which promote axon growth, but in spite of intensive studies the underlying molecular changes are still not fully understood. We have used two cell culture systems to compare the expression of certain surface molecules on neonatal astrocytes, reactive astrocytes and meningeal cells in vitro. Both, neonatal and reactive adult astrocytes exhibited a very similar expression of growth promoting molecules (NCAM, L1, laminin, fibronectin, DSD-1 proteoglycan) and potential inhibitors (tenascinC, chondroitin sulfate, and NG2-proteoglycan), whereas we could not detect the inhibitory keratan sulfate on either astrocyte population. In contrast, meningeal cells expressed considerable levels of keratan sulfate, but only minimal amounts of NCAM. In addition, the much higher expression of extracellular fibronectin around meningeal cells implies an excess formation of extracellular matrix (ECM). In coculture experiments, embryonic retinal ganglion cell (RGC) axons clearly avoided meningeal cells and instead preferred even reactive adult astrocytes. Our results suggest that the expression of inhibitory keratan sulfate proteoglycans together with a lack of NCAM and an excess production of ECM may be responsible for the non-permissiveness of meningeal cells. Compared to reactive astrocytes, meningeal cells are even worse a substrate for growing axons. None of the molecules investigated, however, seems to account for the different substrate properties of neonatal and reactive adult astrocytes.

Animals↗

PubMed1999

Growth promoting and inhibitory effects of glial cells in the mammalian nervous system.

In the central nervous system (CNS) of mammals axonal regeneration is limited by two main factors: first, the low intrinsic regenerative potential of adult CNS neurons and second, inhibitory influences of the glial and extracellular environment. Myelin-associated inhibitors of neurite growth as well as some properties of so called "reactive astrocytes" contribute to the non-permissive of CNS tissue for axonal growth. In contrast, the peripheral nervous system (PNS) environment is supportive of regeneration because Schwann cells provide suitable substrates for regrowing axons. Purified PNS myelin, however, inhibits growth of PNS and CNS axons to a similar extent as does CNS myelin. The molecular basis of glial substrate properties has been studied intensively in the recent years and a large number of molecules have been recognized which might play a role in the regulation of axonal growth. Although the exact mechanisms are still not fully understood, accumulating data shed light on the complex interactions between neurons and glia that are required to establish, maintain, and regenerate axonal connections in the nervous system. In the following chapter we review the role of glial cells in the CNS and PNS during processes of de- and regeneration with respect to our own work.

Animals↗

PubMed1999

Lauroyldextran and crosslinked galactomannan as coating materials for site-specific drug delivery to the colon.

Lauroyldextran (LD) and crosslinked galactomannan (XGM) were investigated as microbiologically degradable film coating materials for site-specific drug delivery to the colon. LD was used with degrees of substitution between 0.12 and 0.40, and swelling in aqueous media between 195 and 50%, XGM-batches showed swelling between 309 and 520%. Theophylline tablets were coated in a Hüttlin Kugelcoater with coating quantities of 4-17 mg/cm2. Sprayable coating formulations were obtained with 4% aqueous dispersions of XGM or 4% dispersions of LD in a 1:1 mixture of 1-propanol and water with 10% glycerol (based on the polymer) as a plasticizer. Theophylline dissolution was monitored in a USP XXIII paddle dissolution apparatus with buffer pH 5.5. After 4 h, which is an average small intestine transit time, colon conditions were simulated by adding galactomannanase or dextranase, respectively. Results showed similar dissolution rates for all XGMs and high-swelling LDs during the first 4 h and a relatively quick disintegration after enzyme addition. Both parameters decreased with increasing coating quantities. Dissolution from low-swelling lauroyldextrans was very low but no disintegration was observed after enzyme addition. The disintegration rate was found to be proportional to the square root of the enzyme activity. All swollen materials exhibited low mechanical stability. XGM coatings, especially at higher coating quantities, showed small transient ruptures at the edges not caused by enzyme addition. This behaviour was explained by internal stress due to the high degree of swelling. In principle, materials of both types proved to be suitable as degradable coating materials. The ideal zero-dissolution before and quick disintegration after enzyme addition, however, was not realized with the present materials.

Biodegradation, Environmental↗

PubMed1999

Nutritional support in alcoholic cirrhotic patients improves host defenses.

BACKGROUND: Malnutrition is usual in patients with alcoholic liver disease and is associated with a poor outcome. Nutritional support decreases nutrition-associated complications. AIM: To demonstrate that nutritional support in ambulatory alcoholic cirrhotic patients improves host defenses. METHODS: Thirty-one male outpatients with alcoholic cirrhosis CHILD-PUGH B or C were included. Twenty-five subjects completed six months consuming daily a nutritional supplement (Ensure, 1000 Kcal and 35 g protein), in addition to their regular diet. At entrance and every three months, a clinical assessment, nutritional evaluation and indirect calorimetry were performed. Liver function tests and LPS-induced monocyte production of cytokines, salivary secretory IgA, lactulose/mannitol ratio and breath hydrogen tests were also measured in these intervals. Delayed cutaneous hypersensitivity and IgG and IgM antibody response to endotoxin were assessed at entrance and at the end of the study. RESULTS: Patients drank 85% of the provided supplement as an average. REE, total body fat and serum albumin increased, basal breath hydrogen decreased and cellular immunity improved significantly during the follow up period (p< or =0.03). All the other parameters remained unchanged throughout the study. Six patients (16.2%) died during the study, five due to upper gastrointestinal bleeding. CONCLUSION: Nutritional support in alcoholic cirrhotic patients improves nutritional status and cell mediated immunity.

Adipose Tissue↗

PubMed1999

Assessment of a simple scoring system applied to a screening questionnaire of asthma in children aged 5-15 yrs.

The aim of the present study was to validate a simple scoring system using a parent-completed screening questionnaire to identify children aged 5-15 yrs who may have asthma. A stratified random sample of 157 children of 1,808 whose parents had answered a postal respiratory questionnaire underwent detailed clinical evaluation. The results were reviewed by three independent paediatricians whose opinions were combined to reach, for each child, decisions regarding three standards: 1) "possible asthma" defined as >50% likelihood of having asthma; 2) "possible asthma" defined as meriting a clinical trial of asthma medication; and 3) "probable asthma" defined as >90% likelihood of having asthma. The combined decisions were compared to three sets of questionnaire scores, in order to determine the positive predictive value, sensitivity and specificity of each set in identifying children with probable/possible asthma. The three sets of chosen questionnaire scores all had positive predictive values of 79-96% for predicting possible asthma, using either the combined expert opinion ">50% likelihood of asthma" or that of "warrants a trial of treatment" as the definition. This suggests that a low proportion of false positives would be obtained were this scoring system to be used for a screening programme. The combined decision >90% chance of asthma could be used as a means of estimating prevalence of asthma in the survey. When used for this, the prevalence of asthma in the surveyed population was 18.8% (95% confidence interval 13.1-26.3). In conclusion, the present scoring system, based on a simple respiratory questionnaire, provides a valid method of identifying children likely to have asthma, and who, if unknown to the medical services, would benefit from clinical review.

Adolescent↗

PubMed1999

[Nutritional status and energy expenditure in elders of differing socioeconomic level].

BACKGROUND: Income and socioeconomic status can influence nutritional status of individuals. Since elders are a more vulnerable group to nutritional deficiencies, socioeconomic status could have a special relevance on nutrition of elderly people. AIM: To assess the influence of socioeconomic status on the nutritional status of elders. MATERIAL AND METHODS: Elders of both sexes of high socioeconomic level and age and sex matched elders of low socioeconomic status were studied. Anthropometry, body composition using double beam X ray absorptiometry, resting energy expenditure using an open circuit indirect calorimeter, routine biochemistry, blood levels of folic acid, vitamin B12 and homocysteine were measured in all subjects. RESULTS: Fourteen female elders of high socioeconomic level, 14 females of low level and 12 males of each level were studied. Mean age of females and males was 71.5 +/- 3.7 and 73.9 +/- 4.2 years old respectively. Males and females of high socioeconomic status were taller than their counterparts of low status. Females of high socioeconomic status had a lower body mass index than their pairs of low status (26.3 +/- 3.8 and 30.2 +/- 5.6 kg/m2 respectively p < 0.02). Men of high economic status had a higher fat mass than their pairs of low level (20.3 +/- 3.5 and 15.1 +/- 5.5 kg respectively, p < 0.005). No differences in resting energy expenditure in women of differing socioeconomic level were observed. Men of high level had a higher energy expenditure that their counterparts of low level (36.0 +/- 4.9 and 32.8 +/- 2.2 Kcal/kg lean body mass/day respectively, p < 0.02). Low level male elders had higher serum total cholesterol and triglycerides. Folic acid, vitamin B12 and homocysteine levels were within normal limits. Dietary intake showed deficiencies in calorie, protein and vitamin intake in all subjects. CONCLUSIONS: In this group of elders, low socioeconomic level did not produce a significant impact on nutritional status.

Absorptiometry, Photon↗

PubMed1999

[New pieces in the puzzle of atherogenesis].

The contribution of high serum levels of cholesterol to atherogenesis has been widely recognized, but the mechanisms are not completely clear. Numerous publications have emphasized that oxidized, but not native low-density lipoproteins, are the particles incorporated into the arterial wall. A group of receptors generically called "scavenger" (SR), actively bind these modified lipoproteins and incorporate them into monocytes-macrophages, in the arterial intima. SR are not down regulated by intracellular concentrations of cholesterol, thus accumulating huge amounts of lipids, transforming monocyte-macrophages into foam cells, predominant cell type of the fatty streak. The simultaneous cytokine production and migration of other cellular types progressively transform this initial lesion into the organized atherosclerotic plaque. In this setting SR, which are up-regulated by oxidized LDL, play a central promoting role. Its presence has been demonstrated in arterial plaques both in human and animal models, and its blockade protects animals from development or progression of atherosclerosis. In humans, elevated antibody titers to oxidized LDL in patients with coronary stenosis, and increased SR activity, in pro-atherogenic conditions such as haemodialysis, indicate that this model may operate as well, but the evidences are still not solid enough to definitively conclude that the oxidized-LDL-SR hypothesis is a finished puzzle.

Animals↗

PubMed1998

Lipid turnover in alcoholics before and after an ethanol load.

Alcohol ingestion decreases plasma free fatty acids (FFAs) and lipid oxidation. This study was conducted to determine palmitate turnover in alcoholics during a short abstinence period and after an ethanol load and in a group of nonalcoholic control subjects, looking for correlations between palmitate turnover, FFA, acetate, and acetoacetate/beta hydroxybutyrate ratio (AKBR). Palmitate C14 turnover was studied in five alcoholics during early abstinence and after a 0.8 g/kg ethanol load, and in five nonalcoholic normal controls. Plasma levels of FFA, acetate, acetoacetate, and beta hydroxybutyrate were measured before and during the ethanol load. A needle hepatic biopsy was performed in alcoholics. FFA levels, palmitate flux, oxidation, and nonoxidative disposal were similar in alcoholics compared with control subjects, decreasing significantly after the ethanol load in both groups. AKBR and ketone bodies were similar in both groups in the basal period. After the alcohol infusion, AKBR decreased significantly. Acetoacetate levels did not change, and beta hydroxybutyrate and total ketone bodies increased significantly in alcoholics and control subjects. A positive correlation was found between FFA levels and palmitate flux. Liver biopsies showed mild changes in the patients studied. The similar inhibition of lipid turnover, FFA release, and the drop in AKBR observed after an alcohol load in alcoholics and control subjects suggest that this effect is mediated by alcohol metabolism and not by metabolic alterations present in alcoholics.

3-Hydroxybutyric Acid↗

PubMed1998

Preliminary applicability tests of different methacrylic acid copolymers, type C NF, particularly relevant to spreading and film formation.

The intention of this study was to show under which conditions a film forming methacrylic acid copolymer coating excipient, corresponding to the requirements of pharmacopoeia, but obtained from different sources, can be substituted without severe problems. The mechanical properties of the film coats were investigated by dynamic-mechanical thermo-analysis (DMTA) experiments to determine with respect to the glass transition the storage modulus E', the loss modulus E'', and the loss factor tan delta. Further determinations concerned the surface tensions of the different coating dispersions. This attribute plays an important role in spreading, distribution and coalescence of the film forming preparations. Finally by a series of small experimental fluidized bed batches cores containing a model drug were coated with the different methacrylic acid copolymers. The resistance of these coated tablets in 0.1 N HC1 as well as their dissolution rates in artificial intestinal juice were tested. The coatings proved themselves so similar that in this case substitutions of products of different provenance are possible. The determinations of surface tension and the DMTA measurements seem to be useful and reliable preliminary applicability tests.

Caffeine↗

PubMed1998

[Serum homocysteine levels in healthy Chilean adults].

BACKGROUND: Hyperhomocysteinemia is a newly recognized cardiovascular risk factor that is present in 10 to 20% of European and North American individuals. AIM: To measure homocysteine levels in healthy adults in Chile. SUBJECTS AND METHODS: Serum homocysteine levels were measured in healthy adults using a fluorimetric HPLC method. Folic acid, vitamin. B12, serum lipids, creatinine and glucose were also assessed. All subjects answered a dietary habits questionnaire. RESULTS: One hundred twenty eight subjects (90 female) aged 22 to 78 years old were studied. Homocysteine levels were 9.7 +/- 6.0 and 7.0 +/- 3.1 mumol/l in men and women respectively (p < 0.001). Folic acid levels were 6.1 +/- 2.7 and 6.1 +/- 2.9 ng/ml in men and women, and 24% of individuals had values below 4 ng/ml. Vitamin B12 levels were 393 +/- 147 and 393 +/- 163 pg/ml in the same groups. There was a negative correlation between homocysteine and folic acid levels and a positive correlation between homocysteine and creatinine levels. CONCLUSIONS: Homocysteine levels in healthy Chilean individuals are similar to those reported abroad. Low folic acid levels were found in 24% of subjects.

Adult↗

PubMed1997

Cardiovascular sequelae of toxaemia of pregnancy.

OBJECTIVE: To determine whether the rate of cardiovascular disease is different among parous women with a general practitioner reported history of toxaemia of pregnancy than among those not reported to have experienced toxaemia, or among nulliparous women. DESIGN: Prospective cohort study. SETTING: 1400 general practitioners throughout the United Kingdom. SUBJECTS: Women who had never used oral contraceptives who were recruited to the Royal College of General Practitioners' oral contraception study (original cohort about 23000). MAIN OUTCOME MEASURES: Age, social class, and smoking standardised incidence rates for hypertensive disease, acute myocardial infarction, other acute ischaemic heart disease, other chronic ischaemic heart disease, angina pectoris, total ischaemic heart disease, total cerebrovascular disease, and total venous thromboembolic disease in the three groups. RESULTS: Compared with parous women with no history of toxaemia, those who had experienced toxaemia had a significantly increased risk of hypertensive disease (relative risk (RR) 2.35), acute myocardial infarction (RR 2.24), chronic ischaemic heart disease (RR 1.74), angina pectoris (RR 1.53), all ischaemic heart disease (RR 1.65), and venous thromboembolism (RR 1.62). The rates for all cerebrovascular disease and peripheral vascular disease were also increased but not significantly. Nulliparous women were more likely to develop hypertension or all cerebrovascular disease later in life than parous women without a history of toxaemia. CONCLUSIONS: A history of toxaemia of pregnancy increases the risk of several distinct cardiovascular conditions later in life. Although causality cannot be inferred (other characteristics of the women may account for both an increased risk of toxaemia and a risk of subsequent vascular disease), the findings merit further research because of their potential importance.

Angina Pectoris↗

PubMed1997

The prevalence and morbidity of chronic fatigue and chronic fatigue syndrome: a prospective primary care study.

OBJECTIVES: This study examined the prevalence and public health impact of chronic fatigue and chronic fatigue syndrome in primary care patients in England. METHODS: There were 2376 subjects, aged 18 through 45 years. Of 214 subjects who fulfilled criteria for chronic fatigue, 185 (86%) were interviewed in the case-control study. Measures included chronic fatigue, psychological morbidity, depression, anxiety, somatic symptoms, symptoms of chronic fatigue syndrome, functional impairment, and psychiatric disorder. RESULTS: The point prevalence of chronic fatigue was 11.3%, falling to 4.1% if comorbid psychological disorders were excluded. The point prevalence of chronic fatigue syndrome was 2.6%, falling to 0.5% if comorbid psychological disorders were excluded. Rates did not vary by social class. After adjustment for psychological disorder, being female was modestly associated with chronic fatigue. Functional impairment was profound and was associated with psychological disorder. CONCLUSIONS: Both chronic fatigue and chronic fatigue syndrome are common in primary care patients and represent a considerable public health burden. Selection bias may account for previous suggestions of a link with higher socioeconomic status.

Adolescent↗

PubMed1997

[Markers of hepatic fibrogenesis in alcoholic patients].

BACKGROUND: An elevation of serologic markers of hepatic fibrogenesis has been reported in liver diseases of different etiologies. Among these, the N-terminal type III procollagen (P-III-P) and the P1 proteolytic fragment of laminin (P1 laminin) increase in alcoholic liver damage, in proportion to the progression of this condition. AIM: To study serum levels of P-III-P and P1 laminin in asymptomatic alcoholics with and without liver damage and decompensated alcoholic cirrhotics, compared to normal controls. METHODS: Serum P-III-P and laminin levels were measured in asymptomatic alcoholics during detoxification treatment. Liver biopsies were obtained, in order to detect liver damage, which was graded with a numeric score, considering values over 6 as severe damage. Serum fibrogenesis markers were also measured in a group of decompensated alcoholic cirrhotics. RESULTS: P-III-P levels were significantly higher in cirrhotic patients compared to alcoholics with or without liver damage and to normal controls. Laminin was not different between groups. P-III-P did not correlate with histologic score in asymptomatic patients. CONCLUSIONS: In this study P-III-P and P1 laminin were not usefull discriminators of severe liver damage among asymptomatic alcoholics; their levels were found to rise significantly only when liver disease has become clinically evident.

Adult↗

PubMed1997

[Results after two years of an alcoholic rehabilitation program].

BACKGROUND: Alcoholism is a serious public health problem in Chile and the best treatment strategy for this problem is far from being clear. AIM: To assess the long term results of an alcoholism rehabilitation program. PATIENTS AND METHODS: One hundred eighty two alcoholics admitted for treatment of their alcoholism were followed during two years in a special clinic. The effects of length of alcoholism, withdrawal symptoms on admission and the presence of histological liver damage on long term outcome were assessed using life table analysis. RESULTS: During the two years period, 75% of patients were lost from control and 63% relapsed in their alcoholic ingestion. None of the above mentioned parameters had an effect on relapse or loss from follow up. CONCLUSIONS: There are high attrition and failure rates and the length of alcoholism, degree of initial withdrawal and liver damage do not influence the long term results of this program.

Adult↗

PubMed1997

[Intestinal permeability in alcoholic patients without liver damage].

BACKGROUND: Chronic alcoholism may increase intestinal permeability. However, there are few studies of intestinal permeability in chronic alcoholic subjects. AIM: To study intestinal permeability in chronic alcoholic patients without clinical evidences of liver damage, during early abstinence, and in normal subjects. METHODS: Thirty seven male subjects were studied, 18 controls and 19 alcoholics. All subjects underwent an anthropometric assessment and dietary history. Lactulose/mannitol test was performed during the third day of abstinence in alcoholics. After an 8 hour overnight fast, subjects drank 200 ml of a solution containing 5 g lactulose and 5 g mannitol. Subsequently, urine was collected during the following 5 hours, where both sugars were measured by gas chromatography. RESULTS: Median values of lactulose/mannitol ratio were similar in alcoholics and controls (0.011, range 0.005-0.071 vs 0.014, range 0.005-0.027 respectively). However, absolute urinary excretion of both lactulose and mannitol was lower in alcoholics. There was no relationship between nutritional status and urinary excretion of lactulose, mannitol or lactulose/mannitol ratio. CONCLUSION: In these alcoholic patients, no changes were observed in intestinal permeability.

Adult↗