Palliation of cardiac malformations associated with right isomerism (asplenia syndrome) in infancy

Right isomerism is characterized by the combination of an obstructed pulmonary outflow tract and a total anomalous pulmonary venous connection (TAPVC), which is obstructed in nearly half of the patients. Fourteen patients less than 2 years of age with right isomerism have been seen in our unit. Thirteen of them underwent palliation consisting of a systemic-pulmonary shunt (10 patients) or a combination of shunt and TAPVC repair (3). There were 7 hospital deaths (54%). The presence of obstructed pulmonary venous drainage was the major risk factor in the surgical treatment of these complex cardiac anomalies (p less than .02). Guidelines for the palliative management of right isomerism are suggested.     

Adrenal function under long-term raloxifene administration.

The aim of the present study was to evaluate the effect of long-term (12 months) administration of raloxifene hydrochloride (60 mg/day) on the steroid production of the adrenal cortex and on the hypothalamic-pituitary-adrenal axis in postmenopausal women. We performed a basal evaluation, a corticotropin releasing factor (CRF) (100 microg i.v. bolus) test and a dexamethasone (DXM) (0.25 mg) suppression-adrenocorticotropic hormone (ACTH) (10 microg i.v. bolus) stimulation test in 11 postmenopausal women, before and after 3, 6 and 12 months of raloxifene treatment. Raloxifene administration significantly modified circulating levels of adrenal steroids, decreasing cortisol (-24%), dehydroepiandrosterone (DHEA) (-36%), and its sulfate (DHEAS) (-41%), and androstenedione (-29%), and increasing circulating allopregnanolone (+39%) levels. Progesterone and 17OH-progesterone levels remained unmodified, while estradiol and estrone levels showed a significant decrease (-51% for estradiol and -61% for estrone). We also observed an increase in circulating ACTH (+58%) and beta-endorphin (+120%). No modifications in the hormonal responses to CRF were observed during the treatment. DXM significantly suppressed circulating steroids at any time with a lower suppression of cortisol from the third month and a higher suppression of DHEA at 12 months. ACTH administration was associated with a significantly blunted cortisol response from the sixth month and a significantly increased response of allopregnanolone from the third month. The present data exclude a raloxifene effect on pituitary sensitivity to CRF and demonstrate a reduced adrenal sensitivity to ACTH, sustained by the opposite changes in basal cortisol and Delta5 androgens, which were reduced, and in ACTH and beta-endorphin, which were increased, as well by the reduced response of cortisol to the direct ACTH stimulus. The reduction of circulating cortisol levels and cortisol response to the ACTH challenge suggests that raloxifene protects against the neurotoxic effects of endogenous glucocorticoids. Furthermore, the progressive increase in basal allopregnanolone and its increased response to ACTH indicate that chronic raloxifene administration exerts direct effects on the pattern of adrenal enzymes, leading to specific changes in the circulating levels of this anxiolytic progesterone metabolite. The important reduction in the circulating levels of estradiol and estrone under long-term raloxifene administration may represent a further mechanism by which this molecule may exert a protective effect against breast and endometrial malignancies.     

Advances in processing of surface myoelectric signals: Part 1

During sustained voluntary or electrically elicted muscle contractions the surface myoelectric signal is nonstationary and it undergoes progressive changes reflecting the modifications of the motor unit action potentials and their propagation velocity. In particular, during sustained electrical stimulation, the evoked signals show progressive amplitude, time scaling and shape modification. The quantitative evaluation of these changes is important for non-invasive muscle characterisation and may be performed in either the time or frequency domain using parametric and nonparametric spectral analysis as well as alternative methodologies. The paper introduces the detection techniques, reviews and compares the methods of spectral estimation based on FFT and autoregressive models, and discusses their applications and limitations in extracting information from the surface myoelectric signal with particular regard to myoelectric manifestations of localised muscle fatigue during sustained contractions.     

Fat distribution in European women: a comparison of anthropometric measurements in relation to cardiovascular risk factors

In this study in 437 women born in 1948 selected from five European towns we show that several anthropometric measurements are consistently and significantly associated with a metabolic risk profile in premenopausal women of 38 years of age. Among the circumferences, breast and waist circumference were, after adjustment for body mass index positively correlated with diastolic blood pressure, serum total cholesterol, HDL-cholesterol (negative associations), serum triglycerides, and serum insulin. The optimal level for measuring waist circumference was determined as being midway between the lower rib margin and the superior anterior iliac crest. Circumference ratios generally did show less consistent and similar or lower correlations with diastolic blood pressure, serum cholesterol and serum insulin. Waist/thigh circumference ratio showed the strongest partial associations with HDL-cholesterol and serum triglycerides among all anthropometric variables studied. The authors conclude that, independently of the degree of fatness, indicators of truncal fat distribution (in the region of the breast as well as the abdomen) are related to an unfavourable risk profile in European premenopausal women. The study gives a rationale for selecting the most informative anthropometric measurements to be added to height and weight in epidemiological studies.     

Activity of natural killer cells and granulocytes in peripheral blood and separated cells]

The natural killing of K 562 cells by whole blood from normal subjects was comparable with that shown by separated mononuclear cells. In order to establish the conditions for a reliable natural killer assay by using very small numbers of effector cells in whole blood, the isotope uptake of target cells was increased by a modified labelling method, which permitted the use of fewer target cells in the assay. The natural cytotoxicity of whole blood was augmented by interferon to the same extent as observed with separated mononuclear cells. The chemiluminescence of granulocytes in whole blood comparable with that of separated granulocytes. Taken together, these methods are considerably less tedious than the conventional methods, technique is also economical, and the results may reflect in vivo cytolytic processes much better.     

HLA antigens in Hungarian patients with idiopathic haemochromatosis.

Thirteen unrelated patients with idiopathic haemochromatosis (eight men, five women) were studied. The diagnosis was based on clinical, biological, and histochemical findings. HLA typing was performed in all 13 and in all of their available first degree relatives (n = 31). HLA A3 was present in nine of 13 probands (69.2% compared with 18.8% in the group of 53 healthy blood donors and 22.4% in a selected Hungarian population (n = 1910). HLA B7 was present in five of 13 probands (38.4% compared with 11.3% and 14.6%). An A3B7 antigen association was found in five of 13 patients. The A3B7 haplotype was found in three, A2B12 and A2B38 haplotypes were found twice in 10 genotyped probands. Pedigree studies showed that there was one unaffected homozygote, 24 heterozygotes, and six non-carriers. Extended family and population studies are necessary to establish the prevalence of the gene in Hungary and an association with haplotypes other than A3B7.     

Tumor necrosis factor production in septic conditions following pancreatitis (preliminary report)]

Detectable TNF levels in sera 33% of patients with sepsis following pancreatitis have been found. No correlation was observed between serum TNF concentration and the severity of illness. However, monocytes and granulocytes of septic patients exerted higher TNF-mediated cytotoxicity than leukocytes of normal blood donors. The in vitro TNF-producing capacity was also higher in the patients in the study group, and it decreased only before fatal outcoming of sepsis. Our results suggest that determination of the TNF-producing capacity of leukocytes might be more informative than measurement of the serum TNF level in the evaluation of the severity or prognosis of sepsis.     

Mapping of α- and β-globin genes on Antarctic fish chromosomes by fluorescence in-situ hybridization

The pathways and mechanisms of genomic change that have led to the peculiar haemoglobinless phenotype of the white-blooded Antarctic icefishes (16 species in the family Channichthyidae) constitute an important model for understanding the rapid diversification of the Antarctic notothenioid fish flock. To provide complementary structural information on genomic change at globin-gene loci in Antarctic fish species, cytogenetic studies and in-situ chromosomal mapping have been undertaken. Using a DNA probe containing one α- and one β-globin gene from the embryonic/juvenile globin gene cluster of the red-blooded species Notothenia coriiceps, we mapped the cluster on the chromosomes of Antarctic teleosts by fluorescence in-situ hybridization. As anticipated on the basis of its molecular organization, the cluster was located on a single chromosome pair in all of the red-blooded fish species probed (N. coriiceps, N. angustata, Trematomus hansoni, T. pennellii). In contrast, the α/β-globin probe did not recognize complementary sequences on the chromosomes of the white-blooded species Chionodraco hamatus and Channichthys rhinoceratus. These results represent the first example of chromosomal mapping of embryonic/juvenile globin genes in teleostean fishes. Beyond its relevance to the evolutionary history of Antarctic notothenioids, this work contributes to our understanding of the evolution of the chromosomal loci of globin genes in fishes and other vertebrates. This revised version was published online in July 2006 with corrections to the Cover Date.     

Heterotopic transplantation of cryopreserved tracheae in a rat model.

INTRODUCTION: The successful use of cryopreserved tracheal allografts in canine models suggests their use in humans. The grade of genetic difference, the mechanism of revascularisation and the method of cryopreservation are not clearly defined. The purpose of our study was to investigate the rejection of tracheal transplants in a standardised heterotopic rat model using different forms of cryopreservation. METHODS: Tracheae from Brown Norway rats were implanted into the omentum from Brown Norway rats or Lewis rats. We transplanted fresh isografts or allografts and pretreated isografts or allografts. Cryopreservation was performed in a medium containing 10% dimethyl sulphoxide at -80 degrees C for 28 days (I) or -196 degrees C for 84 days (II) or without medium at -80 degrees C for 28 days (III). The transplants were excised after 7 and 21 days, respectively. RESULTS: Histological examinations revealed normal structure and function of isografts after 21 days. In the cryopreserved isograft, the epithelium had disappeared and the tracheal lumen was partially obstructed by a non-compact fibrous tissue. In the fresh allografts, the epithelium was replaced by aggressive fibrous tissue, infiltrating the membranous part of the trachea and occluding the tracheal lumen. The cartilage was vital without any sign of rejection. In the cryopreserved allografts, the tracheal lumen was obstructed by dense fibrous tissue with an inflammatory reaction. The cartilage of cryopreserved allografts (II) and (III) had lost the nuclei corresponding to non-vital tissue. Only in the cryopreserved allografts (I) did we find nodular regeneration at the edges of the cartilaginous bow. CONCLUSIONS: The heterotopic transplantation model allows the study of the mechanisms leading to tracheal obstruction. Cryopreservation was found to have no clear advantage in reducing transplant immunogenicity. Cryopreservation leads to significant damage to the cartilage, the intensity of which is dependent on the mode of cryopreservation.