Biomedical subjects
M Levy
Publications and source records attributed to M Levy.
Expectation values in density-functional theory, and kinetic contribution to the exchange-correlation energy.
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In vivo 31P NMR studies of paraplegics' muscles activated by functional electrical stimulation.
The bioenergetics of paralyzed muscles of spastic paraplegic patients under functional electrical stimulation (FES) was studied in vivo using 31P NMR. The protocol included rest, 3 min of induced tetanic isometric contraction through surface electrodes and 40 min of recovery. The continuous stimulation, the force recording and the 31P NMR measurements were sampled simultaneously inside the whole body imager. Normal values were found for the phosphorous metabolite ratios at rest. During contraction, prominent changes were detected including: a) accumulation of inorganic phosphate (Pi) accompanied by an unusually strong signal in the phosphomonoester (PME) region, b) phosphocreatine (PCr) decline, and c) a decrease in the intracellular pH. In the following recovery period the physiological state of the muscle was monitored and quantitated by 31P NMR. No metabolic and mechanical irreversible damage was detected in the paraplegics' muscles activated by FES under our experimental conditions.
Risk of agranulocytosis and aplastic anemia in relation to history of infectious mononucleosis: a report from the international agranulocytosis and aplastic anemia study.
The general objective of this study was to evaluate the risks of agranulocytosis and aplastic anemia in relation to drug use. Other potential risk factors, including history of infectious mononucleosis, were also evaluated. In an international population-based case-control study, cases of agranulocytosis and aplastic anemia and controls, who were patients with selected diagnoses, were identified from the same hospitals. Information on drug use was obtained in a structured interview. Limited information on environmental exposures and on selected items of medical history, including infectious mononucleosis, was also recorded. The possible effects of these factors on the risk of the two blood dyscrasias were evaluated. Relative risks were estimated by stratified analysis and by multiple logistic regression. Among 319 cases of agranulocytosis, 12 patients (4%) gave a history of infectious mononucleosis at least 1 year previously; among 2180 controls the corresponding number was 11 (0.5%) (multivariate relative risk estimate, 6.2; 95% confidence interval, 2.3-17). A nonsignificant elevation in the relative risk was observed for aplastic anemia. The data suggest that infectious mononucleosis may confer a long-term increase in the risk of agranulocytosis. However, the association was an unexpected one, identified in the course of multiple comparisons, and it must be independently confirmed.
Is liver transplantation indicated for cholangiocarcinoma?
Liver transplantation for unresectable primary liver cancer has met with skepticism due to early aggressive recurrences occurring in early series from many centers. The primary tumors for which transplantation has been performed have been hepatocellular carcinoma and cholangiocarcinoma. In an attempt to improve these poor results, we instituted a protocol with adjuvant chemotherapy and radiotherapy after liver transplantation for cholangiocarcinoma. Between December 1984 and December 1992, 701 patients underwent 795 liver transplants. Seventeen patients had a diagnosis of cholangiocarcinoma and form the basis of this review. Three patients were excluded from the study, two because of early postoperative deaths, and one because of an unknown bony metastasis present at the time of transplant. Eleven patients have experienced a recurrence, and 7 of these died secondary to their recurrence. Three patients are alive with no evidence of disease 44 months, 31 months, and 28 months, respectively, after transplant. The 1-year survival rate in these patients is 53%, and the disease-free survival rate is 40%. Patients were able to tolerate the adjuvant chemotherapy and radiotherapy without apparent morbidity or mortality. Unfortunately, this protocol does not appear to provide significant benefit. Until a better adjuvant therapy protocol is developed, it is questionable whether unresectable cholangiocarcinoma should be considered an indication for liver transplantation.
Renal response to ANP in normal dogs during extreme inhibition of distal Na+ transport.
Atrial natriuretic peptide (ANP) is thought to exert its major effect within the cortical and inner medullary collecting ducts (CCD and IMCD) by inhibiting Na+ transport along conductive channels and electroneutral pathways. These transport routes are also thought to be inhibited by a combination of amiloride, thiazide and bradykinin. We tested the ability of normal dogs to respond to ANP when various combinations of these Na+ transport inhibitors were present. In 24 dogs ANP raised UNaV from 31 +/- 6 to 223 +/- 41 mu Eq/min (P < 0.05), a delta of 192 mu Eq/min. Bradykinin alone did not depress delta UNaV in response to an ANP infusion. In the presence of extreme natriuresis caused by amiloride and thiazide, the response to ANP was magnified, presumably due to augmented Na+ delivery to the CCD and IMCD. When distal delivery of Na+ to one kidney was controlled by aortic clamping in the presence of amiloride, thiazide and bradykinin. delta UNaV in response to ANP was depressed (48 vs. 168 mu Eq/min). We conclude that in the presence of extreme inhibition of Na+ transport within the collecting ducts, ANP can still cause a further natriuresis, probably in the absence of augmented distal Na+ delivery.
Defining the year 2000 fruit and vegetable goal.
Various nutrition guidelines recommend increased consumption of fruits and vegetables (F+V); a Year 2000 goal targets five or more daily servings of F+V. Decisions are needed regarding how to define F+V to facilitate measurement of goal achievement. Four alternative definitions (narrow and broad, each with and without legumes) were developed and applied to food frequencies from 133 children and 211 parents. Results varied by definition. Mean intake met the goal of five or more daily servings regardless of definition and exceeded it for both broad definitions by children and both broad definitions and the narrow definition with legumes for adults. Median intakes met the goal for all definitions except for children with the narrow definition without legumes, and exceeded it for children with both broad definitions and for adults with the broad definition with legumes. These differences by definition indicate that a clear definition of F+V is needed.
Relationship between family environment and children's hemodynamic responses to stress: a longitudinal evaluation.
Because interpersonal relationships may have an impact on the risk of developing cardiovascular disease, the authors examined the prospective relationship of family functioning upon hemodynamic stress responses in 87 6- to 8-year-old children. The parents completed the cohesion, conflict, expressiveness, and control subscales of the Family Environment Scale; 2 years later, the authors assessed the children's hemodynamic responses to postural change, forehead cold stimulation, and treadmill exercise. Maternal reports of greater cohesion and expressiveness were related to less increases in systolic pressure and systemic vascular resistance in response to the forehead cold. Mothers' reports of expressiveness were related to lower systolic pressure and cardiac index reactivity to postural change. Fathers' reports of greater control were associated with greater diastolic pressure and vascular resistance increases to forehead cold and to greater vascular resistance responses to exercise. Paternal reports of greater conflict were associated with greater systemic vascular resistance increases and with lower cardiac index increases to exercise. Results suggest family functioning may predict later hemodynamic reactivity to stress. The findings are discussed in terms of previous research on parent-child interaction patterns and children's cardiovascular health.
The need to promote CAI.
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Causes of late graft loss after liver transplantation.
The causes of graft loss in liver transplant recipients with a graft functioning for more than 1 year post-transplant were analyzed. Of 500 liver transplants in 434 patients, 362 grafts were functioning for more than 1 year. After 1 year, 42 grafts were later lost (11.6%). Thirty-three grafts were lost by death and 9 retransplants were done with 8 patients. Of the grafts lost by death, 12 had no evidence of dysfunction. The actuarial 2- and 5-year graft survival in liver transplantation recipients with functioning grafts for more than 1 year was 91 and 83%, respectively. The graft loss rate was 3.4 times higher during the 2nd year post-transplant than during 2-5 years post-transplant. The most common causes of graft loss were chronic rejection (26.2%), recurrent hepatitis (23.8%), arterial thrombosis/stenosis (11.9%) and recurrent malignancy (9.5%). No graft was lost from acute rejection. There was no difference in timing of the graft lost between the different causes. The pretransplant diagnosis of hepatitis B, chronic rejection, and malignancy was associated with the highest frequency of late graft lost. In conclusion, long-term graft survival is good after liver transplantation in patients with a functioning graft for more than 1 year. The main causes of graft loss were chronic rejection and recurrent hepatitis. Prevention and treatment for these conditions may further improve the results after liver transplantation.
Applications of coordinate-scaling procedures to the exchange-correlation energy.
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A musculotendon model of the fatigue profiles of paralyzed quadriceps muscle under FES.
In a previous work, we studied the mechanical and the metabolic profiles of fatigue of paralyzed quadriceps muscle under activation by FES. The metabolic state of the muscle during stimulation of paraplegic patients was monitored, simultaneously with the decaying force, by using 31P nuclear magnetic resonance spectroscopy. In the present work, a musculotendon model was developed to enable prediction of the force output during continuous electrical stimulation. The model consisted of five elements, including the tendon, the parallel elastic, contractile and damper muscle elements, as well as the muscle mass. The mechanism of the contractile element was based upon the length-tension and the velocity-tension curves, the activation trajectory, and the experimentally obtained relationship between force and intracellular pH. In the equations obtained, three sets of parameters were used: 1) general muscle parameters, associated with the length-tension curves of tendon, fascia, and muscle and the velocity-tension curve of the contractile element; 2) specific anthropometric parameters of the muscle; and 3) fatigue parameters which were obtained from our previously recorded experimental data. The model was formulated to allow prediction of the quadriceps muscle force under dynamic activation and at various levels of stimulation. The model solution was for isometric contraction in supermaximal stimulation, and it provided the force decaying profiles, which were compared to those obtained experimentally. The parameters yielding the best fit between the model and the experimental results were indicated. Particularly, two muscle nonspecific parameters, namely, the muscle stress parameter and the parameter representing the ratio between the muscle's slack length and its length in vivo at various knee angles, were determined using the model. The muscle stress parameter was found to be between 60 and 64 N/cm2, and the length ratio was 0.952, 0.935, 0.920, and 0.901 for the 0, 30, 60, and 90 degrees knee angle, respectively. Finally, a sensitivity analysis was conducted of the model to perturbations of these two estimated parameters, revealing that the model was sensitive to these parameters.
Viral markers in the treatment of hepatitis B and C.
Acute hepatitis B virus (HBV) infection is typically distinguished from chronic disease by a positive IgM anti-hepatitis B core antigen (anti-HBc) test. Patients with chronic hepatitis B remain hepatitis B surface antigen (HBsAg) positive, often with raised serum alanine aminotransferase (ALT) activities, for more than six months. The presence of hepatitis B e antigen (HBeAg) and HBV-DNA correlates with infectivity (although patients infected with the pre-core mutated virus may be HBeAg negative). Immunity after HBV infection is characterised by the presence of anti-HBs and anti-HBc antibodies. Patients who respond to interferon alfa treatment lose HBV-DNA and HBeAg from serum and their ALT values return to normal; some also lose HBsAg and acquire anti-HBs. Diagnosis of acute hepatitis C virus (HCV) infection remains largely dependent on history and exclusion, as anti-HCV antibodies may appear late or never at all, although HCV-RNA may be detectable on polymerase chain reaction (PCR) within days of infection. Second generation ELISAs detect a range of anti-HCV antibodies in chronic infections, and confirmatory RIBAs have reduced the incidence of false-positive results. Direct tests for HCV antigens in serum are not yet available, although PCR testing for HCV-RNA can be used to confirm viraemia. Patients who respond to interferon alfa treatment show continuous normalisation of serum ALT values, and some lose HCV-RNA. Relapse occurs in about half of all those who respond.
Urinary sodium excretion in chronic caval dogs after combined infusions of mannitol and ANP.
We studied the natriuretic effects of a combined mannitol and atrial natriuretic peptide (ANP) infusion in chronic caval dogs (TIVC) either responsive or unresponsive to an initial ANP infusion (75 ng.kg-1.min-1). The increment in urinary Na+ excretion (delta UNaV) to the initial ANP infusion in 11 TIVC responders was 127 and 1 mu eq/min in 7 nonresponders. A modest mannitol dose was then infused so as to augment distal Na+ delivery to the distal nephron but not flood the terminal inner medullary collecting duct (IMCD) with enormous quantities of salt and water. After mannitol, UNaV was 26 +/- 8 mu eq/min in TIVC responders and 24 +/- 4 mu eq/min in nonresponders. In these two groups of dogs, delta UNaV after manitol was 13 and 10 mu eq/min, respectively, from the previous experimental phase. During this stable mannitol-induced modest natriuresis, ANP was reinfused at initial dose levels. In TIVC responders, delta UNaV was 186 mu eq/min, a value greater than that obtained initially (P < 0.05), and delta UNaV in nonresponders was now 52 mu eq/min (P < 0.05). Because control and postmanitol UNaV was equivalent for each group, in the face of similar levels of glomerular filtration rate, blood pressure, and renal perfusion, it is difficult to conclude that only augmented delivery of Na+ to the IMCD converted TIVC nonresponders into responding dogs after mannitol and ANP. Other modulating factors may be involved.
Multiplex families in IgA nephropathy.
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Propylthiouracil hepatotoxicity. A review and case presentation.
Propylthiouracil (PTU) is widely used to treat patients with hyperthyroidism. In rare cases, this drug has been found to have severe toxic effects on the liver. The case of a 14-year-old girl treated with PTU for hyperthyroidism who developed jaundice, severe hepatocellular dysfunction, and hepatomegaly is reported. Her condition gradually deteriorated, and she developed paranoid ideation, profound lethargy, and peripheral edema. After three weeks of prednisone therapy, clinical and laboratory signs of improvement were observed. This patient was one of only five pediatric cases among the 16 reported cases of PTU liver toxicity reported to date. Her history and the fatal outcome in some reported cases demonstrate the high degree of sensitivity required to recognize this potential complication in patients treated with PTU, particularly since its immediate discontinuance and steroid-therapy intervention may lead to recovery.
Postnatal adrenoreceptor maturation in porcine intrapulmonary arteries.
The effect of postnatal age on norepinephrine-induced alpha 2-adrenoreceptor-mediated release of endothelium-derived relaxing factor in porcine intramuscular pulmonary arteries was studied. Rings of pulmonary artery from fetal, newborn, 3-d-, 10-d-, 9-wk-, and 15-wk-old pigs with and without endothelium were suspended for isometric force measurement in Krebs-Ringer bicarbonate solution (37 degrees C, 95% O2-5% CO2). In 15- and 10-wk-old pigs, norepinephrine increased tone in arteries with and without endothelium but produced relaxations at high concentrations only in arteries with endothelium. These relaxations were not inhibited by the alpha 1-antagonist prazosin but were completely abolished by the alpha 2-antagonist yohimbine and the inhibitor of nitric oxide release N-omega-nitro-L-arginine methyl ester. This confirms that the norepinephrine-induced relaxations were due to alpha 2-mediated release of endothelium-derived relaxing factor. Arteries from only 50% of the 10-d-old animals showed endothelium-dependent relaxations, and at 3 d of age and younger no relaxations were seen. In animals less than 10 d old, only some of the vessels contracted to norepinephrine and the contractile response was diminished compared with 15-wk-old animals, whereas the response to prostaglandin F2 alpha and histamine was similar in the neonatal group (newborn, 3 d old, and 10 d old). This group showed a dose-dependent relaxation to nitric oxide, with 10-d-old animals more sensitive to nitric oxide than newborn animals.(ABSTRACT TRUNCATED AT 250 WORDS)