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Biomedical subjects

S Bernard

Publications and source records attributed to S Bernard.

At least 37 records · Page 2Linked to original sources

Comparison of immune parameters of sheep with naturally high or low plasma concentrations of melatonin.

Studies in rodents and humans have suggested that the pineal gland and its secretory product melatonin play an important role in the modulation of the immune system. In this study, we tested the hypothesis of a difference in immune parameters between ewes with naturally high vs. low circulating melatonin. Thus, two comparable groups of 10 Ile-de-France sheep were selected from a large flock, for their naturally high and low plasma concentrations of melatonin. The mean plasma melatonin concentrations during daytime (09:00 hr) and nighttime (24:00 hr) were, respectively, 9 and 664 pg/mL (high group) and 5 and 169 pg/mL (low group; P<0.01). Animals from both groups were subjected to various in vitro and in vivo measurements of the characteristics of their immune system. The total number of white blood cells (lymphocytes, polymorphonuclears, and monocytes) and the assessment of the sub-populations of blood lymphocytes (T4, T8, T19, B, and monocytes) did not show any significant differences between the two groups, sampled during day or night. The level of blood leukocytes proliferation after in vitro culture with ConA, LPS, or CWF stimulation, before or after experimental immunization, did not reveal any differences. No significant differences were registered in the production of antibodies between the two groups of animals. The results of the present experiment suggest that in natural conditions a high level of circulating melatonin does not modify the activity of the immune system in sheep.

Animals↗

Asystolic cardiac arrest in Melbourne, Australia.

OBJECTIVE: To study the outcome of victims of out-of-hospital cardiac arrest presenting to the Metropolitan Ambulance Service in asystole, in Melbourne, Australia. METHODS: A retrospective case-note review of all patients presenting to the Metropolitan Ambulance Service in asystole for 1997 was performed. Metropolitan Ambulance Service case notes and hospital records were examined to determine the presenting rhythm and the patients' outcome. RESULTS: In a 12-month period, 778 patients met the entry criteria. Age mean was 67 years, 36% female, 64% male. Metropolitan Ambulance Service response time to scene time was a mean of 9.76 min. Resuscitation was commenced on 37% of patients. There was one survivor (0.12%). CONCLUSION: Adult victims of out-of-hospital cardiac arrest presenting as asystole should not receive treatment.

Aged↗

Autism: a novel form of mercury poisoning.

Autism is a syndrome characterized by impairments in social relatedness and communication, repetitive behaviors, abnormal movements, and sensory dysfunction. Recent epidemiological studies suggest that autism may affect 1 in 150 US children. Exposure to mercury can cause immune, sensory, neurological, motor, and behavioral dysfunctions similar to traits defining or associated with autism, and the similarities extend to neuroanatomy, neurotransmitters, and biochemistry. Thimerosal, a preservative added to many vaccines, has become a major source of mercury in children who, within their first two years, may have received a quantity of mercury that exceeds safety guidelines. A review of medical literature and US government data suggests that: (i) many cases of idiopathic autism are induced by early mercury exposure from thimerosal; (ii) this type of autism represents an unrecognized mercurial syndrome; and (iii) genetic and non-genetic factors establish a predisposition whereby thimerosal's adverse effects occur only in some children.

Autistic Disorder↗

Effect of conventional controlled-rate freezing and vitrification on morphology and metabolism of bovine blastocysts produced in vitro.

This study compares the effects of conventional controlled-rate freezing and vitrification on the morphology and metabolism of in vitro-produced bovine blastocysts. Day 7 expanded blastocysts cultured in synthetic oviduct fluid with 5% fetal calf serum were frozen in 1.36 M glycerol, 0.25 M sucrose or vitrified in 25% glycerol, 25% ethylene glycol. Cell alterations and in vitro development were evaluated immediately after thawing or after 72 h. The effect of cryopreservation on inner cell mass and trophectoderm (TE) cell number as well as glucose, pyruvate, and oxygen uptakes, and lactate release by blastocysts were evaluated. Immediately after thawing, blastocysts showed equivalent cell membrane permeabilization after both cryopreservation procedures, while alterations in nuclear staining were more frequent in vitrified embryos. After culture, similar survival and hatching rates were observed. Both procedures decreased cell number immediately after thawing and after 72 h. However, the number of TE cells was lower in frozen embryos than in vitrified ones. In relation to this, frozen blastocysts showed a decrease in glucose, pyruvate, and oxygen uptake, although those parameters were not altered in vitrified embryos. An increased glycolytic activity was also observed in frozen embryos, indicating a stress response to this procedure.

Animals↗

Physics of iron at Earth's core conditions

The bulk properties of iron at the pressure and temperature conditions of Earth's core were determined by a method that combines first-principles and classical molecular dynamic simulations. The theory indicates that (i) the iron melting temperature at inner-core boundary (ICB) pressure (330 gigapascals) is 5400 (+/-400) kelvin; (ii) liquid iron at ICB conditions is about 6% denser than Earth's outer core; and (iii) the shear modulus of solid iron close to its melting line is 140 gigapascals, consistent with the seismic value for the inner core. These results reconcile melting temperature estimates based on sound velocity shock wave data with those based on diamond anvil cell experiments.

Journal Article↗

Association between microsomal triglyceride transfer protein gene polymorphism and the biological features of liver steatosis in patients with type II diabetes.

AIMS/HYPOTHESIS: Non-alcoholic steatohepatitis is frequent in Type II (non-insulin-dependent) diabetes mellitus and can lead to fibrosis and cirrhosis. The interindividual variability in the occurrence of nonalcoholic steatohepatitis suggests, however, a genetic modulation. Microsomal triglyceride transfer protein (MTP) is necessary for the assembly and secretion of VLDL and when the protein is not functional, such as in abetalipoproteinaemia, a steatohepatitis occurs. We therefore assessed the association between a functional polymorphism in the promoter region of MTP gene (-493 G/T) and the biological features of steatohepatitis in Type II diabetic patients. METHODS: We studied 271 patients with Type II diabetes. Determination of -493 G/T polymorphism was made by PCR-RFLP. Increased liver enzymes were used as surrogates of liver steatosis and alanine aminotransferase concentration was the outcome variable for the multivariate analysis. Liver ultrasonography was available for a subgroup of patients with newly diagnosed diabetes. RESULTS: The proportion of patients with increased alanine aminotransferase was higher in GG than in GT and TT subgroups (23%, 11% and 6%, respectively, p = 0.01). Additionally, patients with high alanine aminotransferase concentrations were more likely to be young (p = 0.01), male (p = 0.001), obese (p = 0.04) and have low HDL-cholesterol (p = 0.01). In multivariate analysis, the MTP genotype was independently associated with alanine aminotransferase concentration (p = 0.0023) as well as sex and body mass index but not HDL-cholesterol. CONCLUSION/INTERPRETATION: The -493 G/T MTP gene polymorphism is associated with biological surrogates of steatohepatitis in patients with Type II diabetes. The G allele which is responsible for a decrease in MTP gene transcription is prone to increase the intrahepatic triglycerides content, conferring by this a genetic susceptibility for steatohepatitis.

Adult↗

Severe hypertriglyceridaemia in Type II diabetes: involvement of apoC-III Sst-I polymorphism, LPL mutations and apo E3 deficiency.

AIMS/HYPOTHESIS: Hypertriglyceridaemia is common in Type II (non-insulin-dependent) diabetes mellitus. Only subgroups of patient however have type V hyperlipidaemia. To investigate the coordination between genetic factors in the modulation of hypertriglyceridaemia in Type II diabetes, we studied three major modifier loci: apoC-III (both Sst-I and insulin-responsive element polymorphisms), apolipoprotein E genotypes and lipoprotein-lipase mutations. METHODS: We studied apoCIII gene polymorphisms, apolipoprotein E genotypes and lipoprotein-lipase gene mutations in 176 patients with Type II (non-insulin-dependent) diabetes mellitus, either normolipaemic (group N, n = 116), mildly hypertriglyceridaemic (group T, n = 28) or with a history of severe hypertriglyceridaemia (triglyceride > 15 g/l) (group H, n = 32). RESULTS: Mild hypertriglyceridaemia in Type II diabetes did not associate with any gene variants in this study. Severe hypertriglyceridaemia was, however, associated with the presence of the apoC-III S2 allele (50% of the patients in group H compared with 15.5 % in group N, p < 0.0001). Additionally this particular phenotype was associated with a low prevalence of the apo E3 allele (35.9% in group H vs 18.1 % in group N, p < 0.005) and a statistically significant over-representation of the E2E4 genotypes. Inactivating lipoprotein-lipase mutations were found in four patients (three heterozygotes, one homozygote), none was found in group N or T. Thus 68.7 % of group H patients (22/32) (vs 21.4 % in group T, p < 0.0005) were carriers of either S2 allele, lipoprotein-lipase mutants or E2E4 genotype with most lipoprotein-lipase mutants or E2E4 genotypes or both in the non-carriers for the S2 allele (6/7). CONCLUSION/INTERPRETATION: Our results strongly support the hypothesis that severe hyperlipaemia in Type II diabetes crucially depends on genetic factors which impair the clearance of triglyceride-rich lipoproteins.

Adult↗

Fluticasone propionate-induced regulation of the balance within macrophage subpopulations.

In asthma, treatment with inhaled corticosteroids reduces chronic peribronchial inflammation and restores the balance within macrophage subpopulations. This study investigates whether corticosteroids can regulate monocyte differentiation in vitro and thereby influence the balance of functionally distinct macrophages. Graded doses of fluticasone propionate (FP) were added to cultures of normal peripheral blood monocytes in the presence or absence of IL-4. Cells were harvested after 7 days' culture. Double immunofluorescence studies were performed on cytospins of differentiated macrophages using the MoAbs RFD1 and RFD7 to distinguish inductive and suppressive macrophages by their respective phenotypes. Macrophage function was determined by quantifying allostimulation in a mixed leucocyte reaction and by measuring tumour necrosis factor-alpha (TNF-alpha) production. FP reduced the number of mature cells with a D1+ antigen-presenting phenotype and up-regulated the development of cells with the D1/D7+ and D7+ phenotypes. Functionally, this was associated with reduced stimulation of T cell proliferation in a mixed leucocyte reaction (MLR). Fluticasone also reversed the increase in both D1+ expression and TNF-alpha production induced by IL-4. The effect of FP persisted for 24 h after removal of FP from the culture medium. These results suggest that FP treatment of asthmatics may have a direct beneficial effect by normalizing the macrophage subset imbalance that contributes to the chronic peribronchial inflammation present in this condition.

Adrenal Cortex Hormones↗

Factors affecting the risk of behaviour problems in children with severe intellectual disability.

In order to examine the importance of a range of potential risk factors for behaviour problems in children with severe intellectual disability, a sample was identified by the administration of a screening version of the Vineland Adaptive Behaviour Scales (VABS) to the parents of children aged 4-11 years attending six special needs schools in three adjacent inner London boroughs. Parents whose children had a VABS standard score of < or = 50 were interviewed using the Disability Assessment Schedule and both parents and teachers completed the Aberrant Behaviour Checklist. Most behaviour problems were more common in ambulant children, but problems less dependent on the ability to walk, such as sleeping difficulties, screaming and self-injury, were equally common in ambulant and non-ambulant children. Among ambulant children, there were few significant associations between the severity of the child's behaviour problems and the age or sex of the child, the presence or absence of epilepsy, and various indices of socio-economic disadvantage. Sleeping difficulties, overactivity, self-injury, destructive behaviour and autistic features, such as social withdrawal and stereotypies, were strongly associated with skills deficits, but aggression, temper tantrums and general disruptive behaviour were not. Limitations in daily living skills were better predictors of behaviour problems than were poor communication skills.

Child↗

Detection of QTLs for heading time and photoperiod response in wheat using a doubled-haploid population.

The genetic basis of heading time in wheat (Triticum aestivum L.) was investigated through the study of flowering under normal autumn sown field conditions as well as photoperiod responses under a controlled environment. Quantitative trait loci (QTLs) for these traits were mapped in a doubled-haploid (DH) population derived from a cross between the wheat cultivars 'Courtot' and 'Chinese Spring'. A molecular marker linkage map of this cross that was previously constructed based on 187 DH lines and 380 markers was used for QTL mapping. The genome was well covered (85%) except for chromosomes 1D and 4D, and a set of anchor loci regularly spaced over the genome (one marker each 15.5 cM) was chosen for marker regression analysis. The presence of a QTL was declared at a significance threshold of alpha = 0.005. The population was grown under field conditions in Clermont-Ferrand, France during two years (1994-1995), in Norwich, U.K. over one year (1998), and also under controlled environments in Norwich. For each trait, between 2 and 4 QTLs were identified with individual effects ranging between 6.3% and 44.4% of the total phenotypic variation. Two QTLs were detected that simultaneously affected heading time and photoperiod response. For heading time, these two QTLs were detected in more than one year. One QTL located on chromosome arm 2BS near the locus Xfbb121-2B, co-segregated with the gene Ppd-B1 known to be involved in photoperiod response. This chromosome region explained a large part of the variation (23.4-44.4% depending on the years or the traits). Another region located on chromosome arm 7BS between the loci Xfbb324-7B and Xfbb53-7B also had a strong effect (7.3-15.3%). This region may correspond to a QTL for earliness per se.

Chromosome Mapping↗

Distribution of diacylglycerols among plasma lipoproteins in control subjects and in patients with non-insulin-dependent diabetes.

BACKGROUND: Diacylglycerols (DAGs), which are well-known components of insect lipophorins, have been recently recognized as a major glyceride of human high-density lipoprotein (HDL). Moreover, DAGs are good substrates for hepatic lipase and for the phospholipid transfer protein (PLTP). The present work was undertaken to determine the lipoprotein concentrations of DAGs, in control subjects, in non-insulin-dependent diabetic (NIDD) patients and in patients with severe hypertriglyceridaemia. MATERIALS AND METHODS: Lipoproteins were isolated from 11 control subjects, 17 diabetic patients and three hypertriglyceridaemic patients, using a combination of ultracentrifugation and precipitation. After lipid extraction, DAGs were separated by thin-layer chromatography and quantified by a glyceride assay. RESULTS: DAGs were detectable in all lipoprotein fractions of the three groups of subjects. Total DAGs were correlated with total triglycerides (TGs) and even more strikingly with very low-density lipoprotein triglycerides. Although the majority of DAG was recovered in apo B-containing lipoproteins, the proportion of DAG with respect to TG was most elevated in HDL. CONCLUSION: These findings indicate that DAGs are probably formed from TG during lipolysis and that they can be transported to HDL through the action of PLTP. This raises the question whether DAG might act as an inhibitor of phospholipid transfer by competition for binding to PLTP.

Adult↗

Community perceptions of the effects of rural hospital closure on access to care.

The purpose of this case study was to ascertain the perceptions of health professionals who were located in six rural communities where hospital closure occurred, regarding the impact of closure on community residents. These health professionals were asked to respond to questions about effects of hospital closures on the availability of medical services such as emergency care, physician services, hospital services and nursing home care. To control for trends in medical services utilization that were unrelated to hospital closure, the study design included comparison areas where similar hospitals remained open. A standardized questionnaire was administered to three health professionals in each of the areas that experienced a hospital closure and also in the matched comparison areas. Interviews of the health professionals in closure areas provide evidence suggestive of some perceived negative effects of hospital closure on these communities. These negative effects include difficulty recruiting and retaining physicians, concern of residents about the loss of their local emergency room, and increased travel times to receive hospital services. The perceived effects of closure appeared to be mediated by the distance required for travel to the nearest hospital. Respondents perceived increased travel times to most significantly affect vulnerable populations, such as the elderly, the disabled and the economically disadvantaged. Respondents in the majority of comparison areas also reported access barriers for vulnerable populations. These barriers primarily center on problems of obtaining transportation and enduring the rigors of travel. Improvements in the availability of transportation to medical care may offer some stabilization to communities where hospitals closed; however, it also is the case that transportation improvements are needed to increase access to care in rural communities where hospitals remained open.

Attitude to Health↗

Gravity is an important but secondary determinant of regional pulmonary blood flow in upright primates.

Original studies leading to the gravitational model of pulmonary blood flow and contemporary studies showing gravity-independent perfusion differ in the recent use of laboratory animals instead of humans. We explored the distribution of pulmonary blood flow in baboons because their anatomy, serial distribution of vascular resistances, and hemodynamic responses to hypoxia are similar to those of humans. Four baboons were anesthetized with ketamine, intubated, and mechanically ventilated. Different colors of fluorescent microspheres were given intravenously while the animals were in the supine, prone, upright (repeated), and head-down (repeated) postures. The animals were killed, and their lungs were excised, dried, and diced into approximately 2-cm3 pieces with the spatial coordinates recorded for each piece. Regional blood flow was determined for each posture from the fluorescent signals of each piece. Perfusion heterogeneity was greatest in the upright posture and least when prone. Using multiple-stepwise regression, we estimate that 7, 5, and 25% of perfusion heterogeneity is due to gravity in the supine, prone, and upright postures, respectively. Although important, gravity is not the predominant determinant of pulmonary perfusion heterogeneity in upright primates. Because of anatomic similarities, the same may be true for humans.

Algorithms↗

Pulmonary and bronchial circulatory responses to segmental lung injury.

In regional lung injury, pulmonary blood flow decreases to the injured regions, and anastomotic bronchial blood flow and total bronchial blood flow increase. However, the pattern of redistribution of the two blood flows to the injured and noninjured areas is not known. In six anesthetized sheep, pulmonary and bronchial blood flows were measured with 15-microm fluorescent microspheres by using the reference flow method. Blood flows were measured in the control state and 1 h after instilling 1 ml/kg of 0. 1 N hydrochloric acid into a dependent segment of the left lung. The lungs were then removed, dried, and cubed into approximately 2-cm cubes while spatial coordinates were noted. Blood flow to each piece was calculated. Mean pulmonary blood flow to the noninjured pieces went from 730 +/- 246 to 574 +/- 347 ml/min (P = 0.22), whereas in the injured pieces the pulmonary blood flow decreased from 246 +/- 143 to 56 +/- 46 ml/min (P < 0.01). In contrast, bronchial blood flow to the injured pieces increased from 0.51 +/- 0.1 to 1.43 +/- 0. 85 ml/min (P = 0.005). We measured the change in flow as it related to the distance from the center of the injured area. Pulmonary blood flow decreased most at the center of the injury, whereas bronchial blood flow doubled at the center of injury and decreased with the distance away from the injury. The absolute increase in bronchial blood flow was substantially less than the decrease in pulmonary blood flow in the injured pieces. We also partitioned the observed variation in pulmonary and bronchial blood flow into that attributable to structure and that due to lung injury and found that 48% of the variation in pulmonary blood flow could be attributed to structure, whereas in the bronchial circulation 70% was attributable to structure. The reasons for these differences are not known and may reflect the intrinsic properties of the systemic and pulmonary circulations.

Algorithms↗

Aerobic and strength training in patients with chronic obstructive pulmonary disease.

The purpose of this study was to evaluate whether strength training is a useful addition to aerobic training in patients with chronic obstructive pulmonary disease (COPD). Forty-five patients with moderate to severe COPD were randomized to 12 wk of aerobic training alone (AERO) or combined with strength training (AERO + ST). The AERO regimen consisted of three weekly 30-min exercise sessions on a calibrated ergocycle, and the ST regimen included three series of eight to 10 repetitions of four weight lifting exercises. Measurements of peripheral muscle strength, thigh muscle cross-sectional area (MCSA) by computed tomographic scanning, maximal exercise capacity, 6-min walking distance (6MWD), and quality of life with the chronic respiratory questionnaire were obtained at baseline and after training. Thirty-six patients completed the program and constituted the study group. The strength of the quadriceps femoris increased significantly in both groups (p < 0.05), but the improvement was greater in the AERO + ST group (20 +/- 12% versus 8 +/- 10% [mean +/- SD] in the AERO group, p < 0.005). The thigh MCSA and strength of the pectoralis major muscle increased in the AERO + ST group by 8 +/- 13% and 15 +/- 9%, respectively (p < 0.001), but not in the AERO group (3 +/- 6% and 2 +/- 10%, respectively, p > 0.05). These changes were significantly different in the two study groups (p < 0.01). The increase in strength of the latissimus dorsi muscle after training was modest and of similar magnitude for both groups. The changes in peak exercise work rate, 6MWD, and quality of life were comparable in the two groups. In conclusion, the addition of strength training to aerobic training in patients with COPD is associated with significantly greater increases in muscle strength and mass, but does not provide additional improvement in exercise capacity or quality of life.

Aged↗

Decrease in carotid intima-media thickness after one year growth hormone (GH) treatment in adults with GH deficiency.

An increased carotid arterial intima-media thickness (IMT) has been reported in hypopituitary adults untreated for GH deficiency. In the present study, the effect of GH replacement on IMT and cardiovascular risk factors was prospectively investigated, in GH deficiency patients treated at a mean dose of 1 UI/day during 1 yr (n = 22) and 2 yr (n = 11). The IMT measurements were performed by the same experienced physician, and the coefficient of variation (calculated in two control groups) was below 6.5%. IMT at baseline was related to conventional risk factors. After 1 yr GH treatment, IMT decreased from 0.78 +/- 0.03 mm to 0.70 +/- 0.03 mm (P < 0.001). The decrement was observed in 21 of 22 patients. After 2 yr GH treatment, IMT had stabilized at 0.70 +/- 0.04 mm and remained significantly different from baseline values (P < 0.003). GH treatment resulted in a moderate decrease in waist circumference and body fat mass and an increase in VO2 max. Conventional cardiovascular risk factors were unmodified except for a transient 10% decrease in low-density lipoprotein cholesterol at 6 months. The contrast between the limited metabolic effect of treatment and the importance and precocity of the changes in IMT suggests that the decrease in IMT was not exclusively attributable to a reversal in the atherosclerotic process. A direct parietal effect of GH replacement on the arterial wall might also be involved. The consequences, in terms of cardiovascular risk, should be established by randomized prospective trials.

Adult↗