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PubMed2000

Autoantibody responses and pathology regulated by B7-1 and B7-2 costimulation in MRL/lpr lupus.

The activation of T lymphocytes requires both Ag-mediated signaling through the TCR as well as costimulatory signals transmitted through B7-1 and/or B7-2 with CD28. The interference of B7-mediated costimulatory signals has been proposed as one immunotherapeutic intervention for the prevention autoimmune disease. This study has examined autoantibody responses and autoimmune pathology in a murine model of human systemic lupus erythematosus (SLE), the MRL-lpr/lpr mouse, genetically deficient in B7-1 or B7-2, or in mice treated with B7-1/B7-2 blocking Abs. In contrast to other studies of murine models of SLE, MRL-lpr/lpr mice treated with B7 blocking Abs exhibit strong anti-small nuclear ribonucleoprotein (snRNP) and anti-DNA autoantibody responses with some changes in isotype switching as compared with untreated animals. All MRL-lpr/lpr mice deficient in B7-1 or B7-2 produce anti-snRNP and anti-DNA titers with isotypes virtually identical with wild-type animals. However, the absence of B7-2 costimulation did interfere with the spontaneous activation and the accumulation of memory CD4+ or CD8+ T lymphocytes characteristic of wild-type MRL-lpr/lpr mice. IgG and C3 complement deposition was less pronounced in the kidneys of B7-2 deficient MRL-lpr/lpr mice, reflecting their lessor degree of glomerulonephritis. By comparison, B7-1-deficient MRL-lpr/lpr mice had more severe IgG and C3 deposits in glomeruli.

Animals↗

PubMed2003

Virtual endoscopy of the cerebral ventricles based on 3-D ultrasonography.

Virtual endoscopy enables preoperative surgical planning based on "surgeons' view" information in the individual patient. In neurosurgery, magnetic resonance (MR) images are mainly used for planning of virtual neuroendoscopy (VNE). We studied the feasibility of three-dimensional (3-D) ultrasonography as the imaging modality for VNE in pediatric patients with hydrocephalus. 3-D ultrasonography data sets were obtained through the open anterior fontanelle and analyzed using perspective volume rendering, with delineation of the ventricular system for anatomical details in relation to standard ultrasonography and intraoperative anatomy, during endoscopy in two infants with hydrocephalus. VNE clarified anatomical variants seen on standard ultrasonography images, anticipated ventricular dysmorphia seen during neuroendosopy and enabled a realistic impression of an endoscopic inspection into the ventricular system of the two infants studied. Based on 3-D ultrasonography, VE enables detailed information on ventricular anatomy in pediatric patients for planning of endoscopic interventions.

Cerebral Ventricles↗

PubMed1992

Ca2+ homeostasis and fast-type sarcoplasmic reticulum Ca(2+)-ATPase expression in L6 muscle cells. Role of thyroid hormone.

The effect of thyroid hormone (L-tri-iodothyronine; T3) on the cytosolic free Ca2+ concentration ([Ca2+]i) in L6 myotubes was studied at rest and during activation to explore the possible mediating role of [Ca2+]i in the T3-induced net synthesis of fast-type sarcoplasmic reticulum (SR) Ca(2+)-ATPase. The mean [Ca2+]i at rest was approx. 115 nM in myoblasts, control myotubes and T3-treated myotubes. Therefore it is unlikely that the T3-induced elevation of Ca(2+)-ATPase levels is mediated by [Ca2+]i changes. To investigate the influence of the 4-fold higher Ca(2+)-ATPase levels in T3-treated myotubes (compared with controls) on [Ca2+]i, interventions with caffeine (10 mM) and a high extracellular K+ concentration ([K+]o) (30 mM) were applied which initially mobilize Ca2+ predominantly from the SR. The results showed a lower (caffeine) or not significantly different (high [K+]o) increase in [Ca2+]i in T3-treated myotubes compared with controls. No rise in [Ca2+]i was found in myoblasts with caffeine or high [K+]o. The role of [Ca2+]i in the regulation of Ca(2+)-ATPase levels was investigated by varying [Ca2+]i through exposure of cells to different concentrations of extracellular Ca2+ (0.2-1.8 mM) and ionomycin (0.1-0.25 microM). At subnormal [Ca2+]i (55 nM) the T3-induced net synthesis of Ca(2+)-ATPase was virtually abolished, and at supranormal [Ca2+]i (195 nM) it was greatly depressed. Intermediate stimulation of net Ca(2+)-ATPase synthesis was found at [Ca2+]i of 95 and 165 nM, with an optimum at approx. 125 nM. Similar but less pronounced effects were found for the basal Ca(2+)-ATPase levels. In contracting primary rat myotubes, Ca(2+)-ATPase levels were significantly lower than in tetrodotoxin-arrested myotubes. The same results were obtained in the presence of T3. Since the mean [Ca2+]i in contracting cells is higher than in resting cells, these data agree with those obtained in the L6 cells with ionomycin. A major conclusion of this study is the existence of a [Ca2+]i optimum, near resting levels, for the expression of the fast-type Ca(2+)-ATPase in the L6 muscle cell line.

Animals↗

PubMed1978

Prenatal removal of frontal association cortex in the fetal rhesus monkey: anatomical and functional consequences in postnatal life.

Anatomical and behavioral consequences were examined following bilateral or unilateral resections of the presumptive dorsolateral prefrontal cortex in 4 rhesus monkey fetuses at E102 (102nd embryonic day), E104, E106 and E119, with subsequent replacement in utero and delivery at later stages of development. Unoperated monkeys of appropriate pre- and postnatal ages served as controls for certain features of morphogenesis and tectogenesis. Monkeys given comparable unilateral or bilateral lesions at selected postnatal ages were used as controls for the behavioral effects of prenatal resection as well as for neuropathological examination. The behavioral evaluation provided evidence for extraordinary preservation of function after frontal cortical resection in the prenatal period. During the entire course of its postnatal development, a monkey that sustained bilateral resection as a fetus at E106 performed surprisingly well and clearly with the competence of unoperated monkeys of identical or older ages on tasks selective for dorsolateral prefrontal cortical function; it did not exhibit deficits characteristic of animals that have comparable or even smaller resections as juveniles or adults. Following either unilateral or bilateral resection prior to E106, ectopic sulci and gyri appeared in intact regions of the frontal lobe of each hemisphere, as well as in locations at a considerable distance from the lesions, such as the temporal and occipital lobes. The cytoarchitectonic characteristics of the cortex in these anomalous gyri were typical of adjacent cortex in the regions in which they appeared. Examination of the parvocellular subdivision of the mediodorsal thalamic nucleus yielded the novel finding that this principal source of essential projections to the dorsolateral prefrontal cortex contained a virtually normal number of neurons in postnatal monkeys, following unilateral or bilateral lesions performed at or before E106, and exhibited only a partial loss of neurons after surgery at E119. The same cells regularly degenerate following comparable resections in the postnatal period. The survival of these neurons in prenatally operated monkeys is unprecedented, and can be explained by several hypotheses, including the possibility that their axons become rerouted to their structures in the absence of their normal targets. The present results thus demonstrate that ablation of a circumscript area of the frontal cortex in a non-human primate a full two months before birth may leave the functions later to be subserved by that area unaffected. Such early surgical intervention results in significant alteration in the gross morphological characteristics of the cortex, and apparently induces a functionally compensatory reorganization of thalamocortical connections. Similar principles may account for sparing of function following early damage to the human brain.

Animals↗

PubMed2005

3D elastic registration of vessel structures from IVUS data on biplane angiography.

RATIONALE AND OBJECTIVES: Planar angiograms and intravascular ultrasound (IVUS) imaging provide important insight for the evaluation of atherosclerotic diseases and blood flow abnormalities. The construction of realistic three-dimensional models is essential to efficiently follow the progression of arterial plaque. This requires an explicit localization of IVUS frames from angiograms. Because of the difficulties encountered when trying to track the position of an IVUS transducer, we propose an elastic registration approach that relies on a virtual catheter path. MATERIALS AND METHODS: Deformable surface models of the lumen and external wall are constructed from segmented IVUS contours. A crude registration is obtained using a three-dimensional vessel centerline, reconstructed from two calibrated angiograms. Robust optimization of the virtual catheter path, position, absolute orientation, and regulation of the external wall shape is performed until near-perfect alignment of the back-projected silhouettes on image edges is reached. RESULTS: Visual assessment of the reconstructed vessels showed a good superposition of virtual models on the angiograms. We measured a 0.4-mm residual error value. A preliminary study of convergence properties on 15 datasets showed that initial absolute orientation may affect the solution. However, for follow-ups, coherent solutions were found among datasets. CONCLUSION: The advantages of the virtual catheter path approach are demonstrated. Future work will look at ways to single out the true solution with a better use of the available information in both modalities and additional validation studies on improved datasets.

Algorithms↗

PubMed2000

New definition of remission in childhood acute lymphoblastic leukemia.

The extent of clearance of leukemic cells from the blood or bone marrow during the early phase of therapy is an independent prognostic factor in acute lymphoblastic leukemia (ALL). Several methods are available to measure the minimal residual disease (MRD) remaining after initial intensive chemotherapy. The most promising are flow cytometric detection of aberrant immunophenotypes and polymerase chain reaction analysis of clonal antigen-receptor gene rearrangements. When applied together, these techniques enable one to monitor MRD in virtually all cases of ALL. Patients who achieve an 'immunologic' or 'molecular' remission (ie leukemic involvement of <0.01% of nucleated bone marrow cells at the end of remission induction therapy) are predicted to have a better clinical outcome than patients whose remission is defined solely by morphologic criteria. In studies to date, patients with MRD at a level of 10(-2) or more at the end of induction have fared almost as poorly as those with > or =5% blast cells in the bone marrow (ie induction failures). Sequential monitoring of MRD can improve the clinical utility of risk assessment still further. Additional studies are needed to determine the critical levels of MRD at various times of treatment and whether therapeutic intervention based on MRD findings can improve clinical outcome.

Child↗

PubMed1999

Variability of electrophrenic diaphragm twitch stimulation over time in normal subjects.

Transcutaneous electrophrenic twitch stimulation is a potentially powerful way to assess diaphragm contractile function in response to interventions which may alter respiratory muscle strength and endurance. At present, the variability of the transdiaphragmatic twitch pressure (Pdi(T)) over a several hour period is not well described. The present study examines the reproducibility of Pdi(T) amplitude and the twitch occlusion technique of assessing maximum transdiaphragmatic pressure (Pdi(max)) in seven normal adults stimulated intermittently every hour for a total 4-h period. In one subject, data were obtained on two occasions separated by a 2-month interval. Among all subjects, the Pdi(T) amplitude expressed as a percentage of the Pdi(max) was highly reproducible over 4 h (coefficient of variation 5.3). Peak Pdi(T) was inversely related to graded voluntary Pdi (r = -0.0996) and the relationship was virtually identical over 4 h (r = - 0.999, P = 0.96). These data show that Pdi(T) at functional residual capacity and the twitch occlusion relationship are highly reproducible.

Adult↗

PubMed2005

Patent foramen ovale closure in patients with cryptogenic thrombo-embolic events using the Cardia PFO occluder.

AIMS: We report our experience with three generations of the Cardia patent foramen ovale (PFO) occluder in patients with cryptogenic thrombo-embolic events (TE). METHODS AND RESULTS: Between 1998 and 2004, interventional PFO closure was attempted in 403 patients. Prior to PFO closure, 605 TE occurred, translating into an annual incidence of 3.1%. PFO closure was successful in all patients. Peri-procedural complications occurred in eight patients (2.0%). At 6 months follow-up, residual shunt was present in 10.8% of patients. Transient thrombi developed on 10 devices (predominantly generation II) and asymptomatic wire fractures were detected in 14 cases (generation I and II). The annual incidence of recurrent TE was 2.0% (n=13). Atrial septal aneurysm and prior device-related thrombus formation were identified as predictors of recurrent TE. CONCLUSION: Owing to technical improvements and modified adjunctive pharmacotherapy, the rate of thrombus formation has declined and wire fractures are virtually absent in generation III devices. The overall rate of recurrent TE is reduced by transcatheter PFO closure with the Cardia PFO occluder, and seems comparable to recurrence rates reported for other devices used for this purpose.

Adolescent↗

PubMed1993

Characterization of protein kinase C isotype expression in adult rat heart. Protein kinase C-epsilon is a major isotype present, and it is activated by phorbol esters, epinephrine, and endothelin.

The pattern of protein kinase C (PKC) isotype expression in whole extracts of dispersed, freshly isolated adult rat ventricular myocytes and adult rat heart ventricle was examined by immunoblot analysis using antisera specific for PKC-alpha, -beta 1, -gamma, -delta, -epsilon, -zeta, or -eta isotypes. This analysis revealed significant levels of expression of the Ca(2+)-independent isotype PKC-epsilon, which was detected as band of 97-kd molecular mass. PKC-zeta was detected principally as a 66-kd band that probably represented a proteolytic product of the holoenzyme. PKC-eta was detected only in whole ventricle as a doublet at 75 and 81 kd and was therefore probably present in nonmyocytic cells. PKC-alpha, -beta 1, -gamma, and -delta could not be detected. Because of our inability to detect PKC-alpha, -beta 1, -gamma, and -delta in whole extracts, PKC isotypes were partially purified from whole heart by DEAE Sepharose chromatography. PKC-alpha, -beta 1, -gamma, and -delta could still not be detected in the appropriate fractions. All PKC isotypes were detectable in appropriate positive control extracts (brain or certain cultured cell lines). In unstimulated isolated cardiomyocytes, the majority (80-95%) of the PKC-epsilon immunoreactivity was present in the soluble fraction of the extract. On exposure of the cardiomyocytes to 1 microM phorbol 12-myristate 13-acetate (PMA), PKC-epsilon undergoes a rapid (< 30 seconds), sustained (at least 60 minutes), and virtually complete association with the Triton X-100-soluble membrane fraction. There was an associated loss of PKC-epsilon from the soluble fraction. The EC50 for PMA of the translocation event was 15-37 nM. Exposure of cardiomyocytes to 1 microM 4 beta-phorbol 12,13-didecanoate or 1 microM phorbol 12,13-dibutyrate also resulted in translocation of PKC-epsilon to the membrane fraction, whereas exposure to 1 microM 4 alpha-phorbol 12,13-didecanoate was without effect. PKC-epsilon also translocated on exposure of cardiomyocytes to 50 microM epinephrine or 100 nM endothelin-1. However, in both cases, the extent of translocation was significantly less than that after exposure to PMA. We conclude that interventions that lead to hypertrophy of cardiomyocytes (phorbol esters, epinephrine, and endothelin-1) activate PKC-epsilon.

Animals↗

PubMed2002

Towards an endoscopic intra-uterine treatment for congenital diaphragmatic hernia.

Congenital Diaphragmatic Hernia (CDH) is a simple defect in the diaphragm that however can lead to severe or lethal pulmonary hypoplasia. Fetuses with their liver herniating into the thorax and with a small lung volume as reflected by a lung-to-head ratio below < 1.0, have virtually no chance to survive despite most modern postnatal care. They are therefore theoretical candidates for in utero therapy. There is a large experimental basis supporting tracheal occlusion (TO) as a method to trigger lung growth, although the optimal time and duration of TO remains to be defined in humans. Animal studies have also shown that TO can be performed completely endoscopically, by means of in utero tracheoscopy and endoluminal balloon placement. TO was therefore applied by leading fetal surgery centers. Initial results with tracheal clipping via hysterotomy were discouraging, but more recently fetoscopic clipping was associated with a nearly 70% survival. The time has now come to achieve TO by means of percutaneous fetoscopic balloon plugging. This will make the intervention more acceptable in a European setting, where open fetal surgery never took off.

Animals↗

PubMed2000

Why not relief?

The field of pain management is currently a battleground on several fronts with controversies virtually at every aspect of the subject with lack of education and misconception at the center of the fight. It has been shown that number of patients suffering with psychosomatic chronic pain are 2% or less. Similarly, it was also shown that the risk of true addiction in chronic pain patients was approximately 0.3%. Accurate anatomical diagnosis can be provided in only 15% of the patients utilizing traditional medical technology. The question of, "Why not relief?" should be raised in our society on a daily basis. It is imperative to understand the true nature of pain by separating the myth of psychological pain from the reality of organic pain and manage it appropriately utilizing all available means, not only narcotics and interventional technology, but also behavioral therapy.

Journal Article↗

PubMed2006

Can virtual reality improve anatomy education? A randomised controlled study of a computer-generated three-dimensional anatomical ear model.

INTRODUCTION: The use of computer-generated 3-dimensional (3-D) anatomical models to teach anatomy has proliferated. However, there is little evidence that these models are educationally effective. The purpose of this study was to test the educational effectiveness of a computer-generated 3-D model of the middle and inner ear. METHODS: We reconstructed a fully interactive model of the middle and inner ear from a magnetic resonance imaging scan of a human cadaver ear. To test the model's educational usefulness, we conducted a randomised controlled study in which 28 medical students completed a Web-based tutorial on ear anatomy that included the interactive model, while a control group of 29 students took the tutorial without exposure to the model. At the end of the tutorials, both groups were asked a series of 15 quiz questions to evaluate their knowledge of 3-D relationships within the ear. RESULTS: The intervention group's mean score on the quiz was 83%, while that of the control group was 65%. This difference in means was highly significant (P < 0.001). DISCUSSION: Our findings stand in contrast to the handful of previous randomised controlled trials that evaluated the effects of computer-generated 3-D anatomical models on learning. The equivocal and negative results of these previous studies may be due to the limitations of these studies (such as small sample size) as well as the limitations of the models that were studied (such as a lack of full interactivity). Given our positive results, we believe that further research is warranted concerning the educational effectiveness of computer-generated anatomical models.

Anatomy↗

PubMed2003

Door to balloon and door to needle: temporal trends in delays to reperfusion.

BACKGROUND: Reperfusion practices have changed markedly over the last few years with the introduction of primary percutaneous coronary intervention. This technique has gained growing popularity in Israel, but little published data are available regarding the delays to primary PCI in real life in this country. OBJECTIVES: To examine temporal trends in time to reperfusion achieved in a large tertiary center over 6 years. RESULTS: Between 1997 and 2002, 1,031 patients were admitted to our hospital with ST elevation myocardial infarction. Of these, 62% underwent thrombolysis and 38% primary PCI. The proportion of patients referred for primary PCI increased steadily, from 14% in 1997 to 68% in 2002. Door to treatment time among patients referred for thrombolysis or primary PCI was 54 +/- 42 and 117 +/- 77 minutes, respectively (P < 0.00001). The door to needle time in patients given thrombolysis remained virtually unchanged during the study period at around 54 minutes. In contrast, the door to balloon time progressively and substantially decreased, from 175 +/- 164 minutes in 1997 to 96 +/- 52 minutes in 2002. CONCLUSIONS: There is a steady increase in the proportion of patients referred for primary PCI than for thrombolysis. The door to needle delay in patients given thrombolysis substantially exceeds the recommended time. The door to balloon time has declined considerably but still slightly exceeds the recommended time. Given the inherent delay between initiation of lysis and arterial recanalization, it appears from our experience that PCI does not substantially delay arterial reperfusion as compared to thrombolysis. Efforts should continue to minimize delays to reperfusion therapy.

Analysis of Variance↗

PubMed1990

[Hypertensive hypertrophy of the left ventricle: its regression in hypertensive patients with different profiles of plasma renin activity, treated with enalapril].

STUDY OBJECTIVE: To determine the action of enalapril maleate in cardiac mass and ventricular performance; to investigate virtual differences of anti-hypertensive action, and regression of left ventricular hypertrophy, between subgroups of patients with different profiles of plasma renin activity (PRA). DESIGN: Randomized, single-blind, placebo-controlled study, along 14 weeks, the last 12 under active treatment with enalapril maleate. SETTING: Outpatient clinics of an university department of Internal Medicine and Cardiology. PATIENTS: Sequential series of twenty patients with mild to moderate essential hypertension. Two patients were lost to follow-up. Eighteen patients completed the study. Seventeen out of them were studied for plasma renin activities, and echocardiographic measurements were performed in ten, during the 2 weeks placebo period, and by the end of active treatment. No patients were excluded because of side-effects. INTERVENTION: After a 2-weeks washout period, enalapril maleate has been given in a single daily dose of 20 mg, at bedtime. In 14 patients the dosage was elevated to 40 mg once daily and, in 5 out of these, 12.5 mg hydrochlorothiazide once a day has been added. MEASUREMENTS AND MAIN RESULTS: The mean of systolic/diastolic sitting blood pressures was reduced from 171.6/112 to 151.6/98.1 mmHg (p less than 0.001). The mean of systolic/diastolic standing blood pressures lowered from 167.8/113.7 to 148.6/99.6 mmHg (p less than 0.001). No significant differences were found between blood pressure reductions in 5 patients with elevated PRA, 5 patients with slightly elevated PRA, and 7 patients with normal or low PRA. The analysis of echocardiographic measurements revealed regression of left ventricular hypertrophy (LVH) and, in one patient who had no criteria of LVH, actually occurred reduction of the thickness of ventricular walls. No unfavourable influence over ventricular function indices, neither systolic nor diastolic, was found. End-systolic stress and inotropic activity remained unchanged. The tolerability of the study drug was very good. CONCLUSIONS: Enalapril maleate appears, in this study, an effective anti-hypertensive compound. Its therapeutic action seems independent of the plasma renin activity profile. The drug induced regression of left ventricular hypertrophy after a period of 12 weeks of treatment, and did not promote any unfavourable influence over ventricular functions indices. Inotropic activity and end-systolic stress were not modified. The tolerability was very good.

Cardiomegaly↗

PubMed1996

Genetic testing and early thyroidectomy for inherited medullary thyroid carcinoma.

The recent identification of mutations in the RET proto-oncogene that are associated with multiple endocrine neoplasia type 2 (MEN 2) syndromes has allowed therapeutic intervention in affected individuals on the basis of direct genetic testing. The principal endocrine neoplasm that occurs in patients with the MEN 2 syndromes is medullary thyroid carcinoma. This thyroid neoplasm is the only consistently malignant feature of the MEN 2 syndromes and it is the most common cause of death in affected patients. Kindred members at risk for one of the MEN 2 syndromes can be studied by direct DNA analysis to determine whether they have inherited a RET mutation. Those with a positive test can be treated by early thyroidectomy and cured when the disease is microscopic and localized to the thyroid gland. Total thyroidectomy is performed as early as 5 years of age and is associated with minimal morbidity and virtually no mortality. Residual or persistent medullary thyroid carcinoma following thyroidectomy can best be determined by detecting increased levels of calcitonin following the administration of intravenous calcium gluconate and pentagastrin.

Adolescent↗

PubMed1985

Current status of renal angiography.

It is apparent that while indications for renal angiography remain, they have significantly decreased and changed over the years, with angiography having largely been replaced by other imaging modalities. It is perhaps indicative of the current role of renal angiography that at the 1985 courses and meetings of both the Society of Cardiovascular Radiology and the Society of Uroradiology there was virtually no discussion of this modality except as applied to the study and therapy of renovascular hypertension. Angiography is no longer the only and frequently not the best method of establishing the need for renal tumor surgery; however, it may prove indispensable in planning that surgery. It is no longer felt to be productive to use angiography in the differential diagnosis of chronic renal disease and renal failure or in the investigation of renal transplant rejection other than that related to anastomotic problems, despite the fact that the angiographic findings in these conditions have been well described. Magnetic resonance imaging shows early promise in this area of diagnosis. When angiography is performed, it is more often than not as a preliminary to an interventional, catheter-mediated procedure, rather than for a purely diagnostic purpose. As the efficient utilization of medical resources becomes of greater concern, the selection of the procedure most likely to be definitive from among the many imaging possibilities available in the genitourinary tract becomes a major responsibility of the treating physician and the radiologist in consultation. Both must be willing to adopt new and more efficient techniques as they become established, retaining older modalities in those situations in which the latter maintain superiority, at all times avoiding needless multiplicity of examinations.

Adrenal Gland Diseases↗

PubMed1994

Effects of exercise training on absolute and relative measurements of regional adiposity.

The purpose of the present study was to determine whether absolute and relative measurements of regional adiposity differ in their responses to exercise intervention and which measures are most predictive of changes in plasma lipids, insulin sensitivity and adiposity. Thirteen middle-aged men (BMI 30.4 +/- 1.5 kg/m2, age 47.2 +/- 1.5 years, mean +/- s.e.) were examined before and after 14 weeks of endurance-oriented physical activity (3-4 days/week, 30-45 min/day). Significant (P < 0.05) decreases in the absolute measures of chest, waist and hip girths and sagittal diameter were evident. The waist-to-hip ratios (WHR) of umbilicus/maximal hip and minimal waist/maximal hip decreased significantly (P < 0.05). However, the WHRs of umbilicus/anterior superior iliac spine and umbilicus/greater trochanters did not change due to parallel decreases in waist and hip girths. Trunk and extremity skinfolds decreased significantly (P < 0.05); however, trunk/extremity skinfold ratios were virtually unaltered. The training programme significantly (P < 0.05) increased insulin sensitivity (60%) and HDL (8%), and reduced triglyceride (25%) and total cholesterol/HDL (8%). Changes in these variables were related to changes in sagittal diameter and waist girth. These data indicate different responses to physical activity between measurements of regional adiposity, and emphasize the need for considering absolute central girths such as waist circumference and sagittal diameter when assessing fat topography and cardiovascular risk.

Adipose Tissue↗

PubMed2006

[Hepatitis C and liver transplantation: fibrosis progression and treatment. Or how to improve management].

Hepatitis C virus-related end-stage liver disease, alone or in combination with alcohol, has become the leading indication for liver transplantation in most transplant programs accounting for approximately half of transplants performed in European centers. Hepatitis C virus infection recurs virtually in every post-transplant patient. The natural history of hepatitis C after liver transplantation is variable. Progression of chronic hepatitis C virus is more aggressive after liver transplantation with a cumulative probability of developing graft cirrhosis estimated to reach 30% at 5 years. Approximately 10% of the patients with recurrent disease will die or require re-transplantation within 5 years post-transplantation. Several factors, including those related to the virus, the host, the environment and the donor, are probably implicated in the outcome. The immune status represents the main significant variable in influencing disease severity in hepatitis C virus-infected patients; with higher HCV viral load and the significant association described between the degree of immunosuppression and disease severity. Interventions to prevent, improve, or halt the recurrence of hepatitis C virus infection have been evaluated by multiple small studies worldwide with similar overall rates of virological clearance of approximately 9-30%. Current consensus recommends combination therapy with pegylated interferon and ribavirin for those patients with histological recurrence of hepatitis C virus infection and fibrosis. Therapy is adjusted to tolerance and rescued with granulocyte colony-stimulating factor and erythropoietin for bone marrow suppression. In this article we present a comprehensive review of post-transplant hepatitis C virus infection; in particular fibrosis progression and the major challenges according to treatment.

Antiviral Agents↗