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Biomedical subjects

T Lehmann

Publications and source records attributed to T Lehmann.

At least 91 records · Page 5Linked to original sources

High-performance liquid chromatographic monitoring of intravenously administered diacetylmorphine and morphine and their metabolites in human plasma.

A rapid and selective reversed-phase high-performance liquid chromatographic assay with gradient elution and diode-array detection for diacetylmorphine, morphine, codeine, and their free and glucuronidated metabolites in plasma, was developed. After addition of ethylmorphine as internal standard the plasma samples were extracted using C18 ODS-2 solid-phase columns with a recovery better than 80%. The limit of quantitation using an injection volume of 2 microl was 25 ng/ml for each compound. The intra- and inter-day precision was better than 5%. The described method cannot only be used for pharmacokinetic studies but also for intoxication cases to monitor a wide range of opiates.

Chromatography, High Pressure Liquid↗

A comparison of similarity measures for digital subtraction radiography.

Subtraction is useful in detecting small changes in sequentially acquired radiographs. Even if the imaging geometry is constant, radiographs must be registered after their digitization. To compare different algorithms for image registration and to register digital X-rays themselves, various similarity measures have been proposed. This study compares eight mathematical similarity standards using 172 radiographs acquired in different, but exactly known projection. Whenever the computation time is a critical factor, e.g. registering images using methods similar to correlation techniques, the entropy of the subtraction image's histogram function (EHDI) is found to be the best similarity standard. If not, e.g. comparative assessing different image registration techniques, the cross covariance coefficient (CCC) is appropriate.

Humans↗

Energy expenditure and substrates oxidative patterns, after glucose, fat or mixed load in normal weight subjects.

OBJECTIVES: To evaluate energy balance after three isocaloric oral loads of different composition and to establish possible relationships between the substrates oxidative patterns and the modifications of insulin and free fatty acids (FFA) plasma profiles. DESIGN: Each subject received, in a randomized order, three oral loads of 2658 +/- 45 kJ (636 +/- 11 Kcal) either as glucose, lipids (cream) or a mixture (glucose+cream). SETTING: The experiments were performed at the University Hospital of Geneva. SUBJECTS: Ten normal body-weight volunteers. METHODS: Energy expenditure (EE) and substrates oxidation were measured by indirect calorimetry during 8 h following each load. Plasma glucose, insulin and FFA were also measured. RESULTS: EE was 1776 +/- 107, 1818 +/- 125 and 1785 +/- 117 KJ over 8 h after glucose, mixed and lipids load, respectively. Glucose oxidation was the highest after oral glucose as compared to mixed and lipids load, while the highest value of lipids oxidation was measured after fat load. A significant relationship linked fat oxidation to plasma FFA (r = 0.54, P < 0.002) as well as to insulin (r = -0.40, P < 0.002). CONCLUSIONS: (a) The energetic cost of glucose and fat intake is the same; (2) after each load, the main source of energy corresponds to the substrate administered; (3) both plasma insulin and FFA influence the substrate oxidative patterns observed after each load; (4) alimentary fat may contribute to fat oxidation by maintaining elevated plasma FFA levels.

Aged↗

Lipoprotein distribution and composition in obesity: their association with central adiposity.

OBJECTIVE: To examine the relationships between the distribution and composition of subfractions of very low density (VLDL), low density (LDL) and high density (HDL) lipoproteins and central fat deposition as measured by the waist-to-hip ratio (WHR). DESIGN: Participants (n = 62, 44 women and 18 men; body mass index (BMI) > or = 25.0) were recruited from those consecutively attending the outpatient obesity clinic at the University Hospital, Geneva. MEASUREMENTS: Lipoprotein subfractions were isolated from fasting blood samples by cumulative flotation or density gradient ultracentrifugation. Concentration and composition were analysed as a function of obesity indices. RESULTS: There were significant correlations between the WHR and the profiles of the three major lipoprotein subclasses. Central obesity was associated with larger VLDL, small, dense LDL and lower levels of HDL-2 independently of other indices of obesity and plasma triglycerides. Central obesity was also significantly and independently associated with compositional anomalies, specifically an increased free cholesterol content of VLDL and LDL. CONCLUSIONS: Central body fat was associated with modifications of an atherogenic nature to lipoprotein distribution and composition. The data are consistent with an impact of body fat distribution on cardiovascular disease (CVD) via the agency of modified lipoprotein metabolism independently of raised triglycerides.

Adolescent↗

Microgeographic structure of Anopheles gambiae in western Kenya based on mtDNA and microsatellite loci.

The population genetic structure of the Anopheles gambiae in western Kenya was studied using length variation at five microsatellite loci and sequence variation in a 648-nt mtDNA fragment. Mosquitoes were collected from houses in villages spanning up to 50 km distance. The following questions were answered. (i) Are mosquitoes in a house more related genetically to each other than mosquitoes between houses? (ii) What degree of genetic differentiation occurs on these geographical scales? (iii) How consistent are the results obtained with both types of genetic markers? At the house level, no differentiation was detected by FST and RST, and the band sharing index test revealed no significant associations of alleles across loci. Likewise, indices of kinship based on mtDNA haplotypes in houses were even lower than in the pooled sample. Therefore, the hypothesis that mosquitoes in a house are more related genetically was rejected. At increasing geographical scales, microsatellite allele distributions were similar among all population samples and no subdivision of the gene pool was detected by FST or RST. Likewise, estimates of haplotype divergence of mtDNA between populations were not higher than the within population estimates, and mtDNA-based FST values were not significantly different from zero. That sequence variation in mtDNA provided matching results with microsatellite loci (while high genetic variation was observed in all loci), suggested that this pattern represents the whole genome. The minimum area associated with a deme of A. gambiae in western Kenya is therefore larger than 50 km in diameter.

Alleles↗

Patterns of mitochondrial variation within and between African malaria vectors, Anopheles gambiae and An. arabiensis, suggest extensive gene flow.

Anopheles gambiae and An. arabiensis are mosquito species responsible for most malaria transmission in sub-Saharan Africa. They are also closely related sibling species that share chromosomal and molecular polymorphisms as a consequence of incomplete lineage sorting or introgressive hybridization. To help resolve these processes, this study examined the partitioning of mtDNA sequence variation within and between species across Africa, from both population genetic and phylogeographic perspectives. Based on partial gene sequences from the cytochrome b, ND1 and ND5 genes, haplotype diversity was high but sequences were very closely related. Within species, little or no population subdivision was detected, and there was no evidence for isolation by distance. Between species, there were no fixed nucleotide differences, a high proportion of shared polymorphisms, and eight haplotypes in common over distances as great as 6000 km. Only one of 16 shared polymorphisms led to an amino acid difference, and there was no compelling evidence for nonneutral variation. Parsimony networks constructed of haplotypes from both species revealed no correspondence of haplotype with either geography or taxonomy. This trend of low intraspecific genetic divergence is consistent with evidence from allozyme and microsatellite data and is interpreted in terms of both extensive gene flow and recent range expansion from relatively large, stable populations. We argue that retention of ancestral polymorphisms is a plausible but insufficient explanation for low interspecific genetic divergence, and that extensive hybridization is a contributing factor.

Animals↗

Excretion of cannabinoids in urine after ingestion of cannabis seed oil.

Gas chromatographic-mass spectrometric (GC-MS) quantitation of 25 cannabis sed oils determined delta 9-tetrahydrocannabinol (THC) concentrations from 3 to 1500 micrograms/g oil. In a pilot study, the morning urine of six volunteers who had ingested 11 or 22 g of the oil, which contained the highest THC content (1500 micrograms/g), was collected for six days. The urine samples were screened by immunoassay, and the content of 11-nor-9-carboxy-delta 9-THC (THCCOOH) was determined by GC-MS. Urine samples were found cannabis positive for up to six days with THCCOOH-equivalent concentrations up to 243 ng/mL. by the Abuscreen OnLine immunoassay and THCCOOH contents from 5 to 431 ng/mL by the GC-MS method. All subjects reported THC-specific psychotropic effects.

Cannabis↗

Disease-modifying antirheumatic drugs.

The case for early intervention with disease-modifying antirheumatic drugs is strengthened by published reports during the past year. These drugs include methotrexate, gold sulfasalazine, and antimalarial agents. The American College of Rheumatology issued guidelines for the management of rheumatoid arthritis and for monitoring the toxicity of antirheumatic drugs. Studies on the mechanisms of action of disease-modifying antirheumatic drugs focused on their effects on cytokines and their receptors. The toxic effects of disease-modifying antirheumatic drugs remained an important issue, especially the adverse pulmonary effects of methotrexate. An important trial demonstrated a beneficial effect of triple disease-modifying antirheumatic drug therapy (methotrexate, sulfasalazine, and hydroxychloroquine) over individual agents.

Antimalarials↗

[Nutritional recommendations for diabetic patients: adaptation of the recommendations defined by the Diabetes and Nutrition Study Group of EASD].

Nutritional recommendations for diabetics are nowadays more flexible and better adapted to the individual patient. They resemble those offered to the public at large. Caloric intake is determined by body size and weight as well as physical activity. Approximately 60% of the energy should be consumed in the form of carbohydrates and monounsaturated fatty acids. The proportion of fatty acids and carbohydrates is fixed according to the individual nutritional habits. The intake of saturated and polyunsaturated fatty acids should be restricted. Meals and carbohydrates should be distributed over the day as three main meals with two to three snacks in between. Recommendations should always be adapted to the practical possibilities of the individual and to his particular metabolic situation.

Diabetes Mellitus↗

[Diet and dyslipidemia].

In this article recommendations for dyslipidemias are illustrated by practical dietary recommendations for an individual patient with combined hyperlipidemia. Recommendations in hypercholesterolemia above all consist in the replacement of saturated by unsaturated forty acids thus reducing automatically cholesterol, too. In hypertriglyceridemias reduction of body weight should often be combined with quantitative control of alcohol and simple carbohydrates. A list of foods to be chosen or to be avoided is provided.

Dietary Fats↗

Epidural lipomatosis: case report and literature review.

We report a case of symptomatic epidural lipomatosis in a 36-year-old man following a heart lung transplant and 3.5 years of steroid medication. A review of the pertinent literature emphasises the importance of including this diagnosis in the differential diagnosis of patients receiving steroid medication or markedly obese patients with back pain or symptoms suggesting spinal cord or cauda equina compression.

Adult↗

Genetic differentiation of Anopheles gambiae populations from East and west Africa: comparison of microsatellite and allozyme loci.

Genetic variation of Anopheles gambiae was analysed to assess interpopulation divergence over a 6000 km distance using short tandem repeat (microsatellite) loci and allozyme loci. Differentiation of populations from Kenya and Senegal measured by allele length variation at five microsatellite loci was compared with estimates calculated from published data on six allozyme loci (Miles, 1978). The average Wright's FST of microsatellite loci (0.016) was lower than that of allozymes (0.036). Slatkin's RST values for microsatellite loci were generally higher than their FST values, but the average RST value was virtually identical (0.036) to the average allozyme FST. These low estimates of differentiation correspond to an effective migration index (Nm) larger than 3, suggesting that gene flow across the continent is only weakly restricted. Polymorphism of microsatellite loci was significantly higher than that of allozymes, probably because the former experience considerably higher mutation rates. That microsatellite loci did not measure greater interpopulation divergence than allozyme loci suggested constraints on microsatellite evolution. Alternatively, extensive mosquito dispersal, aided by human transportation during the last century, better explains the low differentiation and the similarity of estimates derived from both types of genetic markers.

Alleles↗

Relation between cerebral oxygen delivery and neuronal cell damage in fetal sheep near term.

Asphyxia is one of the major causes for fetal brain damage. Although the quality of life of the so affected children is mostly very limited, the pathogenesis of hypoxic fetal brain damage is poorly understood. Particularly, there is a lack of studies, in which cerebral oxygen delivery is directly correlated to the extent of neuronal cell damage in the same brain specimens. Therefore, we measured cerebral oxygen delivery before (- 1 h), during (+3 min & +27 min) and after (+10 min, +4 h, +72 h) 30 min of ischaemia in 5 chronically catheterized normoxemic fetal sheep at 129 +/- 1 days gestation (term is at 147 days) using the microsphere method. In contrast to previous studies (Williams et al. 1990), we arrested carotid arterial blood flow above the lingual artery for 30 min during surgery. Seventy-two hours later the fetal brains were fixed in vivo under barbiturate anaesthesia of both the fetus and the ewe. After cerebral blood flow analysis neuronal cell damage was assessed with light microscopy in 43 specimens of the fetal brain after cresyl violet/fuchsin staining using a scoring system. After arrest of carotid arterial blood flow cerebral blood flow was reduced by 80%. Neuronal cell damage was focussed on the cerebral cortex. Almost no damage could be detected in deeper parts of the brain. In the cerebrum there was threshold oxygen delivery of 3 ml O2/100 g tissue/min, below which neuronal damage occurred. However, there was no correlation between cerebral oxygen delivery and neuronal cell damage in specimens of the cerebrum, in which oxygen delivery was less than 3 ml O2/100 g tissue/min, suggesting selective vulnerability. Therefore, in addition to the reduction in cerebral oxygen delivery, other variables, e.g. neurotransmitter release, receptor pattern or oxygen radicals, may be involved in the development of brain damage.

Analysis of Variance↗

An evaluation of evolutionary constraints on microsatellite loci using null alleles.

A test to evaluate constraints on the evolution of single microsatellite loci is described. The test assumes that microsatellite alleles that share the same flanking sequence constitute a series of alleles with a common descent that is distinct from alleles with a mutation in the flanking sequence. Thus two or more different series of alleles at a given locus represent the outcomes of different evolutionary processes. The higher rate of mutations within the repeat region (10(-3) or 10(-4)) compared with that of insertion/deletion or point mutations in adjacent flanking regions (10(-9)) or with that of recombination between the repeat and the point mutation (10(-6) for sequences 100 bp long) provides the rationale for this assumption. Using a two-phase, stepwise mutation model we simulated the evolution of a number of independent series of alleles and constructed the distributions of two similarity indices between pairs of these allele series. Applying this approach to empirical data from locus AG2H46 of Anopheles gambiae resulted in a significant excess of similarity between the main and the null series, indicating that constraints affect allele distribution in this locus. Practical considerations of the test are discussed.

Alleles↗