Bioelectrical Impedance Vector Analysis (BIVA) in Slovak population: application in a clinical sample

The purpose of this study is to provide new data on body composition in the Slovak population, particularly impedance vector components according to sex and age, relevant for bioelectrical impedance vector analysis (BIVA) in a clinical sample. The reference sample consisted of 1543 apparently healthy individuals (1007 females and 536 males), aged from 18 to 92 years and of 60 patients with Parkinson’s disease (PD) (26 females and 34 males), aged from 40 to 81 years. Bioelectrical parameters of resistance (R) and reactance (Xc) were measured with a monofrequency analyser (BIA 101). BIVA was used to analyse tissue electric properties in control subjects and patients with PD. The mean vector position differed significantly between PD patients and healthy controls in males of age subgroups 60–69 years and 70–79 years, respectively. These results were conterminous with significant Hotelling’s T²-test; 60–69 y T²=7.8, P=0.024 and 70–79 y T²=7.6, P=0.026. In the RXc-score graph three patients had values outside the 95% ellipse. Altered tissue electric properties were present in 23.5% of males and 15.4% of females. Distribution of impedance vector components in different age categories of healthy Slovak subjects are relevant to comparative population studies and to clinical practice.     

Effect of C677T methylenetetrahydrofolate reductase gene polymorphism on plasma homocysteine levels in ethnic groups

The objective of this study was to examine plasma homocysteine levels and C677T methylenetetrahydrofolate reductase (MTHFR) gene polymorphism in two ethnic groups from Slovakia. The samples consisted of general Slovak-Romany population (68 men and 81 women) from Southwestern Slovakia and the Slovak-Caucasians (174 men and 177 women) who participated in the CINDI project. The homocysteine levels were examined by HPLC, the analysis of MTHFR genotypes was done by PCR. The Slovak-Romany men (12.0+/-5.6 (S.D.) micromol/l) and women (9.2+/-2.6 microol/l) have significantly lower plasma homocysteine levels (p<0.024 and p<0.00001) when compared to Caucasians (13.3+/-5.1 micromol/l in men and 11.3+/-4.3 micromol/l in women). The genetic equilibrium is assumed for the gene frequencies of the MTHFR polymorphism in both samples. The distribution of MTHFR genotypes did not differ between the two populations (TT 13 vs. 10.6 %; CT 46.6 vs. 41.7 %; CC 40.4 vs. 47.7 %, chí(2)2 = 2.315, df=2, ns). The effect of MTHFR genotypes on homocysteine levels was not confirmed in the Slovak-Romanies and TT homozygosity significantly increased plasma homocysteine levels only in Slovak-Caucasians (11.5+/-4.4 micromol/l, ns; vs. 14.8+/-4.8 micromol/l, p 0.002, respectively). To our knowledge, this is the first epidemiological study in the Romany population examining distribution of the MTHFR genotypes and their effect on homocysteine levels. Further studies are needed to establish the variety of cardiovascular risk factors among Romanies in order to evaluate the significance of particular factors.     

A Poroelasticity Theory Approach to Study the Mechanisms Leading to Elevated Interstitial Fluid Pressure in Solid Tumours

Although the mechanisms responsible for elevated interstitial fluid pressure (IFP) in tumours remain obscure, it seems clear that high IFP represents a barrier to drug delivery (since the resulting adverse pressure gradient implies a reduction in the driving force for transvascular exchange of both fluid and macromolecules). R. Jain and co-workers studied this problem, and although the conclusions drawn from their idealized mathematical models offered useful insights into the causes of elevated IFP, they by no means gave a definitive explanation for this phenomenon. In this paper, we use poroelasticity theory to also develop a macroscopic mathematical model to describe the time evolution of a solid tumour, but focus our attention on the mechanisms responsible for the rise of the IFP, from that for a healthy interstitium to that measured in malignant tumours. In particular, we discuss a number of possible time scales suggested by our mathematical model and propose a tumour-dependent time scale that leads to results in agreement with experimental observations. We apply our mathematical model to simulate the effect of “vascular normalization” (as proposed by Jain in Nat Med 7:987–989, 2001) on the IFP profile and discuss and contrast our conclusions with those of previous work in the literature.     

Codon usage and base composition inRickettsia prowazekii

Codon usage and base composition in sequences from the A + T-rich genome ofRickettsia prowazekii, a member of the alpha Proteobacteria, have been investigated. Synonymous codon usage patterns are roughly similar among genes, even though the data set includes genes expected to be expressed at very different levels, indicating that translational selection has been ineffective in this species. However, multivariate statistical analysis differentiates genes according to their G + C contents at the first two codon positions. To study this variation, we have compared the amino acid composition patterns of 21R. prowazekii proteins with that of a homologous set of proteins fromEscherichia coli. The analysis shows that individual genes have been affected by biased mutation rates to very different extents: genes encoding proteins highly conserved among other species being the least affected. Overall, protein coding and intergenic spacer regions have G + C content values of 32.5% and 21.4%, respectively. Extrapolation from these values suggests thatR. prowazekii has around 800 genes and that 60–70% of the genome may be coding. Correspondence to: S.G.E. Andersson     

Activation of phospholipase D in a rat mast (RBL 2H3) cell line. A possible unifying mechanism for IgE-dependent degranulation and arachidonic acid metabolite release.

RBL 2H3 cells (a model of mast cell function) were sensitized with anti-TNP IgE (0.5 micrograms/ml) and triggered to secrete both histamine and arachidonic acid (AA) metabolites by the addition of TNP-OVA (0 to 100 ng/ml). After a 3-min delay, the release of both groups of mediators proceeded in a parallel manner. In cells labeled with [14C]-AA, TNP-OVA produced a rapid increase in phosphatidic acid (PA), and subsequently, 1,2-diacylglycerol (DAG) and intracellular AA levels. Concurrently, there was a decrease in [14C]-AA labeled phosphatidylcholine. The release of labeled AA from phosphatidylcholine in response to TNP-OVA was paralleled by a liberation of free choline but no evidence of liberation of phosphorylcholine. When ethanol (0.05 to 2% v/v) was included in the culture medium, phosphatidylethanol was synthesized at the expense of PA and DAG, with a resulting inhibition of secretion. D,1 propranolol, an inhibitor of PA phosphohydrolase, inhibited the IgE-dependent production of [14C]-DAG, and [14C]-free fatty acid but not [14C]-PA. The IgE-dependent release of both histamine and AA metabolites was completely inhibited by pretreatment with propranolol. Taken together, the above results suggest that phospholipase D is activated upon cross-bridging of IgE receptors on the surface of RBL 2H3 cells and that this may be a pivotal step in the signal transduction cascade leading to the release of both presynthesized and de novo synthesized mediators.     

A TEST FOR EVALUATING PEDAL GANGRENOUS LESIONS—Observation of Elevation Reactive Hyperemia as a Gauge of Blood Supply

Estimating the development of collateral circulation in peripheral vascular diseases is simplified by the use of an easy test—which can be done in an office—in which reactive hyperemia is observed in an extremity as it is gradually lowered after a period of elevation.The lower limits of filling pressures necessary to allow spontaneous healing of necrotic lesions under the conditions described seem to be in the range 35 cm. above the heart. Similarly the lower limit for the successful performance of amputations at the level of the forefoot or toes seems to be about 45 cm.As a result of over a thousand observations in a period of over five years, it is believed that the test provides in a few minutes a visual and reproducible picture of the filling pressures in the distal portions of the extremity which is useful in the determination of prognosis and the selection of treatment of gangrenous lesions of the foot.     

Antenatal screening for cystic fibrosis: a trial of the couple model.

OBJECTIVE--To assess the delivery and acceptability of antenatal couple screening for cystic fibrosis. Carrier status was notified only when both members of a partnership had cystic fibrosis alleles and therefore a one in four risk of having an affected child. DESIGN--Mouthwash samples were tested when both partners participated. Results were returned only to positive couples. SETTING--Two large maternity hospitals in Edinburgh. SUBJECTS--Screening was offered to all couples who booked at one of the two hospitals. MAIN OUTCOME MEASURES--(a) The take up of screening, carriers and carrier couples identified, take up of prenatal diagnosis, and numbers of affected fetuses detected; (b) questionnaire measures of patient satisfaction and stress. RESULTS--Screening was offered to 8536 couples. 714 (8.4%) were regarded as ineligible, usually because of late booking or absence of a partner. 1900 (24.3%) of the remainder declined screening. Among the 5922 screened couples, four tested positive--that is, both partners were cystic fibrosis heterozygotes. All four elected to have prenatal diagnosis. There were three terminations of pregnancy because of an affected fetus, one couple having two successive pregnancies with affected fetuses. The participation rate was 76% for eligible couples (5922/7822) and 69% for all couples (5922/8536). Only 89 screened couples (1.5%) requested information on individual carrier status. No anxiety was detected among a cohort of the screened population, and 99% of questioned participants expressed satisfaction with the concept of couple screening. CONCLUSIONS--Antenatal couple screening is a satisfactory and acceptable way of screening for cystic fibrosis and has been adopted as routine in the two trial hospitals.     

Genetic studies in Medzev, a village in south-eastern Slovakia. 3. Morphogenetic traits.

Eleven anthropometric traits, five indices and eight anthroposcopic and behavioural traits have been studied in the population of Medzev, which is located in the region Spis in South-Eastern Slovakia. An attempt has been made to compare the results of the present study with other population groups in Slovakia, particularly with an ethnogenetically related population from North-Eastern Slovakia (Chmel'nica). Barring zygomatic breadth in males, biogonial breadth in females, biacromial breadth und jugomandibular index in both sexes, hair pigmentation, ear lobe attachment and arm folding, the remaining traits show no significant differences between the Medzev and Chmel'nica population. On the whole, these two populations are closer to each other than to any other Slovakian group.