Acetaldehyde, ethanol and acetone concentrations in blood of alcohol-treated mice receiving aldehyde dehydrogenase-loaded erythrocytes.

Blood levels of acetaldehyde (ACh), ethanol and acetone were investigated in mice treated with ethanol for 6 months and receiving compatible erythrocytes (RBCs) overloaded with aldehyde dehydrogenase (AlDH). Following an acute dose of ethanol, ACh levels were significantly lower in these animals than in alcohol-treated mice receiving AlDH-unloaded RBCs, and were similar to the ACh levels of normal mice. The peak ethanol concentration was higher in normal mice than in both groups of alcohol-treated animals, while acetone concentrations were not significantly different in the three groups of animals.     

Effects of cadmium exposure on the cardiovascular system and on calcium metabolism: results of a cross-sectional population study.

This paper summarizes the findings of the Cadmibel Study, a cross-sectional population study of the health effects of cadmium, but only with respect to the cardiovascular system and calcium metabolism. The study disproved the hypothesis that exposure to cadmium would lead to an increase in blood pressure and in the prevalence of hypertension and other cardiovascular diseases. On the other hand, there was a positive relationship between urinary cadmium (Cd-U) and both serum alkaline phosphatase activity and urinary excretion of calcium. The regression coefficients obtained after adjustment for significant co-variates indicated that, when Cd-U increased two-fold, serum alkaline phosphatase and urinary calcium rose by 4% and 0.25 mmol/24 h, respectively. These findings suggest that calcium metabolism is gradually affected as cadmium accumulates in the body. The morbidity associated with the latter phenomenon is still unknown, and requires further investigation, preferably in a longitudinal prospective population study, in which the incidence of morbid events would be monitored in relation to the cadmium body burden.     

Mitochondrial DNA variability detected in a single wheat regenerant involves a rare recombination event across a short repeat

The mitochondrial genome of the selfed progeny of a plant regenerated from long-term somatic tissue culture displays specific structural rearrangements characterized by the appearance of novel restriction fragments. A mitochondrial DNA library was constructed from this selfed progeny in the SalI site of cosmid pHC79 and the novel fragments were subsequently studied. They were shown to arise from reciprocal recombination events involving DNA sequences present in the parental plant. The regions of recombination were sequenced and the nucleotide sequences were aligned with those of the presumptive parental fragments. We characterized an imperfect short repeated DNA sequence, 242 bp long, within which a 7-bb DNA repeat could act as a region of recombination. The use of PCR technology allowed us to show that these fragments were present in both parental plants and tissue cultures as low-abundance sequence arrangements.     

A quality-adjusted survival meta-analysis of adjuvant chemotherapy for premenopausal breast cancer

The purpose of this paper is to develop and apply a meta-analysis methodology, that does not require patient-level data, for comparing treatments in terms of quality-of-life-adjusted survival. As a motivating example, we considered adjuvant chemotherapy for breast cancer. This therapy has been shown to offer an improvement in recurrence-free and overall survival, especially for youger women, but its acute toxic effects discourage some physicians from prescribing it. To determine whether the benefit of adjuvant chemotherapy treatment outweighs its costs in terms of toxic effects, we performed a meta-analysis of quality-adjusted survival based on data from 1229 patients, 49 years of age or younger, randomized in eight clinical trials that compared chemotherapy versus no adjuvant systemic therapy. We conducted the meta-analysis by performing a quality-adjusted survival analysis known as a Q-TWiST analysis on each trial. A Q-TWiST analysis allows one to make treatment comparisons that incorporate differences in quality of life associated with various health states. In this analysis, we define as health states the periods of time patients spend: (i) with subjective toxic effects of chemotherapy; (ii) without symptoms of recurrence and toxicity, and (iii) following disease recurrence. We assigned weights to each health state which reflect their relative value in terms of quality of life and allowed them to vary in a sensitivity analysis. We then combined the individual trial results in a meta-analysis, using a multivariate regression model, in such a way that we could easily perform an overall sensitivity analysis. Individual patient-level data are not required to perform this meta-analysis methodology if the individual Q-TWiST analysis results for each trial are available.     

Incorporation of [35S]sulfate into glomerular membranes of rats chronically exposed to cadmium and its relation with urinary glycosaminoglycans and proteinuria.

The aim of the present work was to assess the effects of long-term exposure to Cd on the sulfatation of glomerular membranes and their relation with proteinuria and urinary glycosaminoglycans (GAG). For this purpose the in vitro incorporation of [35S]sulfate was investigated in female Sprague-Dawley rats given 100 ppm of Cd in drinking water for 7 months. When compared with their controls, glomeruli from Cd-treated rats showed a 12.8% decrease in the incorporation of the label into glomerular membranes. This effect, which was not explained by differences in viability or in sulfate uptake by the glomeruli, suggests that sulfatation of glomerular membranes is impaired in Cd-treated rats. In support of this, in another independent experiment, a decrease, 17.4% on average, of the sulfate content of glomerular membranes was observed in long-term Cd-treated rats (100 ppm in drinking water for 4 months). This effect was significantly correlated with albuminuria and transferrinuria but not with beta 2-microglobinuria, suggesting that a loss of heparan sulfate of the glomerular capillary wall could be involved in the Cd-induced glomerular proteinuria. On the other hand an enhanced urinary excretion of GAG, negatively correlated with the sulfate content of glomerular membranes, was also observed in Cd-treated rats. Moreover GAG excretion was associated with tubular and glomerular proteinuria, which suggests that GAG might be a useful marker of Cd-induced nephrotoxicity.     

The pharmacokinetics of lignocaine in humans during a computer-controlled infusion.

Several types of chronic pain syndromes are effectively treated with sodium channel blockers such as lignocaine. Further investigation of this therapeutic modality would be facilitated by refinement of the parameters describing lignocaine distribution and elimination. This would allow precise lignocaine infusion by a computer-controlled infusion to attain and maintain stable target lignocaine concentrations. Arterial blood samples were obtained at frequent intervals during a computer-controlled infusion of lignocaine in 12 adult human volunteers. Plasma lignocaine concentrations of 1, 2, 3, 4 and 5 microg/ml were targeted for 15 min at each concentration. A three-compartment mammillary pharmacokinetic model best described the resulting concentration vs time profile. A population pharmacokinetic analysis was performed using three different techniques; the two-stage, pooled and mixed effects modelling. There was marked overshoot of the plasma concentration above the target prior to refinement of the pharmacokinetic parameters. The best parameters of a three-compartment mammillary model fit to the measured concentration using the pooled data approach were: V(1) = 7.44, V(2) =11.5 and V(3) = 97.71; Cl(1) = 0.585, Cl(2) = 2.23 and Cl(3) =1.64 l/min. Similarly calculated parameters using NONMEM were V(1) = 6.99, V(2) =12.2 and V(3) =1341; Cl(1) = 0.703, Cl(2) =1.24 and Cl(3) =1.49 l/min. The addition of age as a covariate of the pharmacokinetic parameters improved the model in both cases. Height, lean body mass and body surface area as covariates of the pharmacokinetic parameters did not improve the predicted value of the model. Prospective testing of the pharmacokinetic parameters will be required to define whether they function well. The refinement of pharmacokinetic parameters for the computer-controlled intravenous infusion of lignocaine will facilitate further research in pain therapy. Published lignocaine pharmacokinetic values have a relatively large central volume of distribution, and hence, when implemented as a computer-controlled infusion, result in dramatic overshoot shortly after targeting a higher plasma concentration. In light of the long-lasting pain relief provided by sodium channel blockade in neuropathic pain states, overshoot of plasma concentrations must be avoided if the concentration vs effect relationship is to be defined.     

Cortical Reorganization Allows for Motor Recovery after Crossed Cerebrocerebellar Atrophy

The authors report the case of a 33-year-old woman who exhibited, at the age of 17, a left-sided hemiplegia, which was followed by good motor recovery, though with a permanent deficit in fine finger movements. She had a widespread loss of neural tissue in the right hemisphere (crossed cerebrocerebellar atrophy), including (1) marked atrophy and thinning of the precentral and postcentral gyri; (2) widespread deep white matter destruction, including the corticospinal tract; and (3) crossed cerebellar atrophy. Except over the supplementary motor area (SMA), transcranial magnetic stimulation did not elicit motor evoked potentials in the affected hand. Nevertheless, during opening and closing of the affected hand, functional magnetic resonance imaging showed an activation of the lesioned primary sensorimotor cortex (SMC), as well as of the intact SMA and the parietal areas, but not of the ipsilateral motor areas. The authors speculate that recovery was achieved by a motor command generated in the SMC and the parietal cortex, passing through corticospinal axons originating in the SMA.     

Access to primary health care for Australian young people: service provider perspectives.

BACKGROUND: To adequately address the complex health needs of young people, their access to services, and the quality of services received, must be improved. AIMS: To explore the barriers to service provision for young people and to identify the training needs of primary healthcare service providers in New South Wales (NSW), Australia. DESIGN OF STUDY: A cross-sectional, qualitative study of the perspectives of a range of health service providers. SETTING: A range of primary healthcare organisations across NSW. METHODS: Samples of general practitioners (GPs), youth health workers, youth health coordinators, and community health centre staff were drawn from urban and rural clusters across NSW. Focus groups and interviews were used to identify barriers to service provision and the training needs of service providers. Data were tape recorded, transcribed, and analysed. RESULTS: Barriers to service provision among GPs and community health centre staff included inadequate time, flexibility, skills, and confidence in working with young people, and poor linkages with other relevant services. Training needs included better knowledge of and skills in adolescent health requirements, working with adolescents, and working with other services. Barriers to service provision for youth health workers and coordinators included lack of financial resources and infrastructure. There were few linkages between groups of service providers. CONCLUSION: Models of service provision that allow stronger linkages between service providers, sufficient time for consultation with young people, adequate training and support of health professionals, and flexibility of service provision, including outreach, should be explored and evaluated.     

Efficacy of anti-digoxin antibodies in a premature neonate

Through the case report of severe digitalis intoxication in a premature born after 27 weeks of gestation with a birthweight of 800 g, the authors show that anti-digoxin antibodies constitute a very efficacious therapeutic tool which, up to the present, has not been used in prematures.