PRV-1, erythroid colonies and platelet Mpl are unrelated to thrombosis in essential thrombocythaemia

Females with the monoclonal type of essential thrombocythaemia (ET), based on the X-chromosome inactivation pattern (XCIP), have previously been shown to present a higher incidence of thrombosis than polyclonal ones. We aimed to assess correlations between XCIP, thrombosis, and three epigenetic markers of ET, namely PRV-1 overexpression, endogenous erythroid colony (EEC) formation, and reduced platelet Mpl content. Fifty-three (60%) of 88 subjects studied had monoclonal myelopoiesis and presented a 32% incidence of major thrombosis compared with 6% of polyclonal subjects (P = 0.009). The frequency of abnormalities of PRV-1, EEC, or Mpl was similar in monoclonal and polyclonal subjects (respectively, 28%, 48%, 75%, and 37%, 27%, 63%), and none of them correlated with thrombosis. We conclude that the exploited epigenetic markers constitute independent phenotypic variations and are not clustered according to monoclonality of myelopoiesis in ET; none of them could serve as a surrogate marker of thrombotic risk in male subjects with ET.     

Enhanced growth and improved vascular function in offspring from successive pregnancies in endothelial nitric oxide synthase knockout mice

OBJECTIVE: Transgenic mice that lack endothelial nitric oxide synthase have offspring with growth deficiency and abnormal vascular reactivity in later life. Our objective was to evaluate the role of parity in the modulation of the fetal programming of growth and vascular responses in these transgenic mice. STUDY DESIGN: Oligoparous (0-2 previous pregnancies) and multiparous (5-9 previous pregnancies) nitric oxide synthase knockout (-/-KO) female mice were bred with nitric oxide synthase -/-KO and wild type (+/+WT) male mice to produce nitric oxide synthase -/-KO and maternally derived heterozygous (+/-Mat) litters. The pups were weighed weekly. Carotid arteries of the adult females from these litters were used for in vitro vascular reactivity studies. RESULTS: Nitric oxide synthase knockout and nitric oxide synthase maternal litters that were born to oligoparous mothers had significant growth lag compared with corresponding multiparous litters. Length-tension characteristics were not different between the groups. However, optimal diameter, which is a measure of vascular tensile properties and resistance, was decreased in oligoparous compared with multiparous female offspring. Acetylcholine-mediated vasorelaxation was abolished, and contraction by phenylephrine and Ca ++ was increased in oligoparous, but not multiparous, female offspring ( P < .05). CONCLUSION: These data support the role of abnormal uterine environment in the fetal programming of postnatal growth and vascular function in later life. Successive pregnancies may lead to maternal uterine adaptations that bypass the lack of a functional nitric oxide synthase, which leads to improvement in postnatal growth and vascular function in the offspring. Given the reported effect of parity on the risk of preeclampsia, similar mechanisms may be operative in human pregnancy.     

Determination of telomere length by flow-fluorescence in situ hybridization in Down's syndrome patients

A new method for measuring telomere length in a population of Down's syndrome patients aged 18-60 years old is presented. The method is based on flow cytometry and quantitative fluorescence in situ hybridization (flow-FISH) on whole cells. At least three methods for measuring the length of telomere repeats have been described: (i) Southern blot analysis, and quantitative FISH using either (ii) digital fluorescence microscopy (Q-FISH) or (iii) flow cytometry (flow-FISH). Both Southern blot analysis and Q-FISH have specific limitations and are time-consuming, whereas flow-FISH needed relatively few cells (1.5-2.5 x 106) and could be completed in 24-48 h. The method can be used to rapidly determine telomere length in subsets of nucleated blood cells from patients with age-related diseases such as Down's syndrome, Alzheimer's disease and Werner syndrome.     

Clinical presentation and treatment of Wilson's disease: a single-centre experience

Thirty patients with Wilson's disease (WD) were observed at a movement disorder clinic between 1970 and 2000. Disease onset was at the mean age (SD) of 14.5 (+/-5.9) years. Presentation with hepatic disease occurred in 12 of 30 patients and with neurologic disease in 15. Three patients were asymptomatic at the time of diagnosis. The mean (SD) delay to diagnosis was 5.9 (+/-5.7) years. Five patients diagnosed in an advanced stage of disease died before initiating treatment. Eighteen patients were followed and treated with D-penicillamine alone or in combination with zinc sulphate. Treatment improved most of neurological symptoms. Dystonic postures, behavioural disturbances and dysarthria were the most resistant neurological signs. 'Pseudo-sclerotic' neurologic involvement predicted a good outcome, whereas hepatic onset and 'classic' neurologic involvement were associated with a poorer prognosis. Two of the 18 treated patients died of hepatic failure due to voluntary discontinuation of therapy. Both D-penicillamine and zinc sulphate were well tolerated. No teratogenic effect of D-penicillamine was observed throughout 5 pregnancies. Our results suggest that D-penicillamine or a combination of D-penicillamine and zinc sulphate is a safe and effective long-term treatment in patients with WD.     

Cancer cachexia and tumor growth reduction in Walker 256 tumor-bearing rats supplemented with N-3 polyunsaturated fatty acids for one generation

In this study we investigated the effect of lifelong supplementation of the diet with coconut oil (CO, rich in saturated fatty acids) or fish oil (FO, rich in n-3 polyunsaturated fatty acids, PUFAs) on tumor growth, animal survival, and metabolic indicators of cachexia in adult rats. Female Wistar rats were supplemented with CO or FO prior to mating and then throughout pregnancy and gestation, and then the male offspring were supplemented from weaning until 90 days of age. Then they were inoculated subcutaneously with Walker 256 tumor cells. Tumor weight at 14 days in control rats (those fed standard chow) was approximately 20 g. These animals displayed cancer cachexia, which was characterized by loss of weight, hypoglycemia, hyperlacticidemia, hypertriacylglycerolemia, and depletion of glycogen stores. Supplementation of the diet with CO did not change these parameters, except that there was a smaller decrease in serum triacylglycerol concentration. Supplementation of the diet with FO significantly decreased tumor growth (by approximately 60%), increased survival (50% at 30 days postinoculation vs. 30% in the controls and 13.5% in the CO group), and prevented the fall in body weight. Furthermore, FO supplementation partly abolished the fall in serum glucose, totally prevented the elevation in serum lactate concentrations, partly prevented the hypertriacylgylcerolemia, and preserved tissue glycogen stores. Lifelong consumption of FO, rich in n-3 PUFAs, protects against tumor growth and cancer cachexia and improves survival.     

Techniques for administering inhalation anesthetic agents, professional exposure, and early neurobehavioral effects

BACKGROUND: Occupational exposure to high concentrations of anaesthetic gases can cause neurobehavioral effects in operating room personnel. The measures taken to reduce waste gas exposures, including the installation of active scavenging devices and airconditioning systems, are not effective, so that the NIOSH recommendations for maximum exposure are currently unattainable in practice. OBJECTIVES: The aim of the present study was to measure operating room pollution and neurobehavioral functions in a group of anaesthesiologists during open-system and low-flow anaesthesia. METHODS: Environmental concentrations of N2O and isoflurance were measured by an infrared gas analyzer (Brüel & Kjaer) in open system and in low flow anaesthesia. Under the same stress condition, but with different exposure levels to anaesthetic gases, psychomotor vigilance and response speed were evaluated four times with the Reaction Time Test at the beginning and at the end of the first weekday shift and at the beginning and at the end of the last weekday shift. Exclusion criteria were considered excessive alcohol and coffee intake and use of CNS medication. RESULTS: Concentrations of N2O and isoflurane in the operating room were 4.83 ppm and 0.4 ppm respectively, which are lower compared with open systems: 301 ppm and 11.1 ppm respectively. The mean of the Reaction Time was significantly higher (p < 0.01) during work with the open system compared to work in low flow at the end of the first weekday shift and at the end of the last weekday shift. CONCLUSIONS: Low-flow anaesthesia appears to be effective in reducing waste gas exposure: lower flows produced lower values and protect the integrity of neurobehavioral functions.