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Biomedical subjects

M Levy

Publications and source records attributed to M Levy.

At least 19 recordsLinked to original sources

Heparin-coated bypass circuits in cardiopulmonary bypass: improved biocompatibility or not.

Heparin bonding to bypass circuits has been found to reduce bleeding complications. Here, this process is reviewed with special attention to markers of inflammation and clinical outcome. Indicators of inflammation (i.e. cytokine levels, elastase and complement components) are decreased when using heparin bonded circuits compared to conventional bypass circuits. The decrease in the levels of these response modifiers appears minimal. Clinical outcomes, other than bleeding complications, have not been studied to any great extent with this technology. These lower levels of the various biological response modifiers are not correlated with lower levels of complications or shorter hospital stays. We conclude based on this data that it is not clear if this decrease translates into a clinical benefit in routine operative cases that require cardiopulmonary bypass.

Anticoagulants

Colchicine in breast milk of patients with familial Mediterranean fever.

OBJECTIVE: To clarify whether colchicine is excreted in breast milk, and to compare its concentrations in the serum and breast milk of lactating women who have familial Mediterranean fever (FMF). METHODS: Using a specific radioimmunoassay, we determined colchicine concentrations in the serum and breast milk of 4 patients at various time points, following oral administration of the drug. The study evaluated 4 patients with FMF who had been taking colchicine on a long-term basis. RESULTS: Colchicine was found to be excreted in breast milk. Its levels ranged between 1.9 and 8.6 ng/ml, which were similar to those found in the serum (parallel concentration time curves). However, there appeared to be a considerable variation in colchicine milk concentration among the different patients, which might be related to individual breast milk composition and, possibly, to other nutritional or metabolic factors. CONCLUSION: The extensive peripheral tissue binding and relatively low concentration of colchicine in breast milk suggests that the amount ingested by the infant is small. Furthermore, based on our clinical experience, nursing appears to be safe for lactating women with FMF who continue to take colchicine.

Administration, Oral

Membranous nephropathy following perinatal transmission of hepatitis B virus infection--long-term follow-up study.

In children with hepatitis B-associated membranous glomerulonephritis, the time of onset of the infection and the duration of the carrier state before diagnosis of the renal disease are always unknown. Moreover, follow-up is usually short. We report the unique observation of a French girl who was infected with hepatitis B virus by her mother who had acute hepatitis during the immediate postpartum period; the girl developed proteinuria at 6 years of age. The onset of the infection in the perinatal period, the mild liver abnormalities, and the absence of nephrotic syndrome did not justify any treatment. Spontaneous seroconversion to anti-HBe antibody positive occurred at 12 years of age. Proteinuria gradually diminished and was absent at 18 years. However, HBs antigenemia persists.

Adult

Effect of age on sperm fertility potential: oocyte donation as a model.

OBJECTIVE: To determine the effect of age on sperm fecundability using oocyte donation as an in vivo model. SETTING: Oocyte donation and IVF programs at the Instituto Valenciano de Infertilidad. DESIGN: Retrospective study in which four groups of oocyte donation cycles were established according to age of the male providing the semen sample: group 1 (n = 31) < 30 years; group 2 (n = 195) 31 to 40 years; group 3 (n = 98) 41 to 50 years; group 4 (n = 21) > 51 years, the oldest being 64 years. All donated oocytes were obtained from patients < 35 years old. MAIN OUTCOME MEASUREMENTS: Male age, sperm characteristics (volume, concentration, motility, morphology), fertilization, embryo quality, pregnancy, implantation, and abortion rates among recipients. RESULTS: Similar sperm characteristics in fresh as well as after preparation for IVF were observed among males of different ages. Fertilization, embryo quality, pregnancy, and implantation were similar among the established groups. The mean age of the females included in each group significantly increased from group 1 to group 4. CONCLUSIONS: Age (up to 64 years) does not affect sperm characteristics or its ability to fertilize human eggs. Similarly, embryo development in vitro as well as implantation in recipient uteri are not affected by age of the male providing the semen sample.

Abortion, Spontaneous

Oocyte donation in women with recurrent pregnancy loss.

The prognosis of couples with recurrent miscarriage is controversial despite efforts made during this century to learn about the physiopathology and treatment of this troublesome condition. Here we present our experiences of employing oocyte donation in eight couples in whom the woman was a low responder to gonadotrophin stimulation and had a previous history of recurrent abortion with negative routine infertility work-up for repeated pregnancy loss. Patients were desensitized with gonadotrophin-releasing hormone analogues and supplemented with oestradiol valerate for a minimum of 15 days until oocytes were donated from in-vitro fertilization and fertile donors. Then, progesterone was added until day 100 of pregnancy. A total of 12 oocyte donation cycles were performed in these patients. Clinical pregnancy and delivery rates per cycle were 75.0 and 66.6% respectively. The delivery rate per patient was 85.7% in this series, and the miscarriage rate per cycle was 11.1%. The results of ovum donation compared favourably with low responders without a history of recurrent abortion undergoing this treatment during the study period. These results strongly suggest that the oocyte may be the origin of infertility in women with idiopathic recurrent miscarriages. In addition, the results question the role of maternal local and systemic factors in early recurrent pregnancy loss, as well as the paternal contribution to its aetiology.

Abortion, Habitual

Multiple segmental gradual distraction of facial skeleton: an experimental study.

The method of distraction osteogenesis was used to move several facial segments in different directions with formation of new bone. On 3 young adult sheep a Le Fort II osteotomy, combined with circumferential orbital osteotomies, was performed. The periosteum over the osteotomies was preserved. Titanium bone screws were placed as bone markers. The segments were fixed with pins and plates to a combined distraction apparatus in order to advance the segments in different directions. By a gradual distraction, the midface was advanced forward by 30 mm. The left orbit was moved laterally 20 mm and the right orbit was moved forward 20 mm. In both orbits there was a concomitant globe movement. New bone formation in the distracted area was obvious radiographically, clinically, and histologically. In conclusion, multiple segmental distraction is possible in the adult sheep face and may offer three-dimensional (3D), controlled correction of complex face deformities.

Animals

Myasthenia gravis and hepatitis C virus infection.

Chronic hepatitis C virus (HCV) infections are often associated with extrahepatic immunological manifestations, including various autoimmune disorders. The aims of this study were to determine the prevalence of HCV markers in patients with myasthenia gravis (MG) and to determine any relationship with HCV infection. Eighty-three patients with MG. 40 men aged 20-93 years and 43 women aged 13-87 years (mean age 54 years) were studied. The MG patients were positive for antibody to acetylcholine receptor in addition, their sera was analysed for antibody to HCV (HCVAb) and HCV RNA, HCVAb was detected in two of the 83 patients (2.4%). Four patients were repeatedly HCV RNA positive. They were infected by HCV genotype 1 (one patient), HCV genotype 2a (two patients) and an undetermined HCV genotype in one patient. They received plasmapheresis or intravenous immunoglobulin treatment. Among the four patients, one was infected after the onset of MG without receiving a blood transfusion or using intravenous drugs. The other three had chronic hepatitis C which was discovered at the same time as MG and only one patient had been exposed to blood products. The prevalence of HCV markers in patients with MG (4.8%) was higher than that reported for the general French population, about 1%. This prevalence is similar to that occurring in patients exposed to plasmapheresis or intravenous immunoglobulin. In conclusion, HCV appears to play little, if any, role in causing MG. The higher prevalence of infection among MG patients may be related to transmission in the course of therapy.

Adolescent

"On the spot' vaccination: does it work?

OBJECTIVE: To trial and evaluate a system of "on the spot' vaccination for children up to the age of 15 years in the Early Childhood Centres of the Central Sydney Area Health Service, at the Royal Alexandra Hospital for Children and in a number of general practices in the area. METHODOLOGY: A brief questionnaire was used to collect data from parents and health care professionals about the child's vaccination status and vaccines given "on the spot'. RESULTS: Over an 8 week period in August-September 1993, 5162 questionnaires were completed; 71% of children were up to date with their vaccination. If Haemophilus influenzae type b vaccine, which had been introduced only 2 months before commencement of the study, was excluded, 84% of the children were up to date. A total of 441 children were given 663 vaccinations "on the spot'. Very few children were too ill to be vaccinated (6%). However, only 30% of those who needed vaccination "on the spot' actually received it (441 of 1480), and only 41% (24 of 58) of a subset of those who were not vaccinated were known to have complied 1 month later. Children attending Early Childhood Centres were younger than children attending general practices or the hospital. CONCLUSIONS: A high proportion of children who attended for routine or acute health care had vaccinations overdue (30%). If this scheme could be continued and expanded it would have an important impact on vaccination coverage, and hence on the incidence of vaccine-preventable diseases.

Child

Drugs in the aetiology of agranulocytosis and aplastic anaemia.

Agranulocytosis and aplastic anaemia are rare but serious conditions known to be caused by numerous drugs. Most of what is known or suspected about the aetiology is based on case reports, with only a few formal epidemiological studies that provide quantitative estimates of risk. Updated results have been obtained from a combined analysis of data from 3 case-control studies that used similar methods: the International Agranulocytosis and Aplastic Anemia Study (IAAAS), conducted in Israel and Europe; a study conducted in the northeast US; and a study conducted in Thailand. Totals of 362 cases of agranulocytosis, 454 cases of aplastic anaemia and 6458 controls were included in the analyses. The IAAAS and Thai study were population-based, providing estimates of the incidence of the 2 dyscrasias. The overall annual incidence of agranulocytosis in the ambulatory population was 3.4/10(6) in the IAAAS and 0.8/10(6) in Thailand; by contrast the incidence of aplastic anaemia was 2.0/10(6) in the IAAAS and 4.1/10(6) in Thailand. A total of 21 compounds were significantly associated with an increased risk of agranulocytosis in the IAAAS and US studies. Excess risks ranged from 0.06 to 13 cases/10(6) users/wk; the most strongly associated drugs were procainamide, anti-thyroid drugs and sulphasalazine. An association with drugs that had previously been suspected was also seen in Thailand. The overall aetiologic fractions of agranulocytosis due to drug use were 62% in the IAAAS, 72% in the US and 70% in Thailand. Eleven drugs were significantly associated with an increased risk of aplastic anaemia, with excess risks ranging from 1.4 to 60 cases/10(6) users in a 5-month period. The most strongly associated drugs were penicillamine, gold and carbamazepine. Aetiologic fractions were 27% in the IAAAS, 17% in the US and 2% in Thailand, which paralleled the prevalence of use of associated drugs in the 3 populations. The present results confirm that agranulocytosis is largely a drug-induced disease, with similar proportions accounted for in 3 disparate geographic regions. By contrast, although many of the expected associations were observed for aplastic anaemia, most of the aetiology is not explained by drugs. For all associated drugs, the excess risks are sufficiently low that blood dyscrasias should not figure prominently in the balancing of risks and benefits.

Agranulocytosis

A model of fatigue and recovery in paraplegic's quadriceps muscle subjected to intermittent FES.

The objective of this paper was to propose a mathematical model for the fatigue and recovery phases of a paraplegic's quadriceps muscle subjected to intermittent functional electrical stimulation (FES). The model is based on in vivo, noninvasive, recording of fatigue related metabolic parameters recorded during stimulation and recovery. Records of the time variations of the muscle's phosphorus metabolites, particularly the phosphocreatine (PCr) and inorganic phosphorus (Pi), obtained from 31P magnetic resonance spectroscopy (MRS), were used to calculate the intracellular pH level in the muscle and this latter parameter was incorporated in a musculo-tendon model. The fatigue-recovery model allows the transition from the fatiguing phase to the recovery phase as soon as the stimulation terminates and vice versa. This model was incorporated into a Huxley type muscle model expressing the dynamics of the muscle. Two ordinary differential equations describing the musculo-tendon dynamics and the dynamics of the activation were solved simultaneously and records of the force trajectory during intermittent stimulations were obtained. Study cases ranging from 5 to 30 s for each of the stimulation and recovery alternating phases were stimulated. The force and the total impulse in the modeled quadriceps muscle were computed. It was found that the greatest impulse was produced in intermittent stimulation of 40-50 s duty cycle, with a 50 percent ratio between the stimulation and recovery intervals. An additional series of six runs, including two contractions, one of 3 min and one of 1 min, separated by rest periods of 3, 6, 9, 12, 15, and 30 min was performed. From the predicted force trajectories obtained, the maximal force values served for comparison with measured values made on one patient.

Electric Stimulation

Surface localization of Helicobacter pylori urease and a heat shock protein homolog requires bacterial autolysis.

Helicobacter pylori is a gram-negative bacterium which causes chronic gastritis and is associated with peptic ulcer disease, gastric carcinoma, and gastric lymphoma. The bacterium is characterized by potent urease activity, thought to be located on the outer membrane, which is essential for survival at low pH. The purpose of the present study was to investigate mechanisms whereby urease and HspB, a GroEL homolog, become surface associated in vitro. Urease, HspB, and catalase were located almost exclusively within the cytoplasm in fresh log-phase cultures assessed by cryo- immunoelectron microscopy. In contrast, significant amounts of surface-associated antigen were observed in older or subcultured preparations concomitantly with the appearance of significant amounts of extracellular antigen, amorphous debris, and membrane fragments. By use of a variety of biochemical methods, a significant fraction of urease and HspB was associated with the outer membrane in subcultured preparations of H. pylori. Taken together, these results strongly suggest that H. pylori cells undergo spontaneous autolysis during culture and that urease and HspB become surface associated only concomitant with bacterial autolysis. By comparing enzyme sensitivity to flurofamide (a potent, poorly diffusible urease inhibitor) in whole cells with that in deliberately lysed cells, we show that both extracellular and intracellular urease molecules are active enzymatically. Autolysis of H. pylori is an important phenomenon to recognize since it likely exerts significant effects on the behavior of H. pylori. Furthermore, the surface properties of H. pylori must be unique in promoting adsorption of cytoplasmic proteins.

Antigens, Bacterial

Young children's cardiovascular stress responses predict resting cardiovascular functioning 2 1/2 years later.

BACKGROUND: Since the pathogenesis of coronary heart disease (CHD) has its origins in childhood, researchers have increasingly evaluated CHD risk factors in youth. In this study we examined the hypothesized behavioral risk factor of cardiovascular responsivity as a predictor of very young children's resting cardiovascular functioning 2 1/2 years later. SUBJECTS AND METHODS: During an initial visit to the laboratory, 97 children (30 blacks and 67 whites, 45 boys and 52 girls) aged 6-7 years completed three laboratory stressor tests (forehead cold pressor, postural change, and treadmill exercise). A comprehensive cardiovascular assessment was conducted during the tests. Resting cardiovascular activity (baseline values) was also assessed. Follow-up resting cardiovascular parameters were measured in the laboratory 2 1/2 years later. RESULTS: Cardiovascular stress responses were predictive of cardiovascular follow-up resting levels 2 1/2 years later. Multiple regression was used to evaluate the independent predictive power of stress responses after controlling for traditional risk factors. Follow-up resting systolic blood pressure (SBP) was predicted by the SBP response to postural change and treadmill exercise. Follow-up resting diastolic blood pressure (DBP) was predicted by the DBP response during treadmill exercise, particularly for blacks. The follow-up resting heart rate was predicted by the heart rate response to the forehead cold pressor and treadmill exercise. CONCLUSION: These results show that in very young children, stress responses are predictive of resting cardiovascular functioning 2 1/2 years later. Further developmental and longitudinal investigations will determine whether such responses are predictive of later preclinical manifestations of cardiovascular disease. If so, incorporation of stress testing in a standardized risk identification protocol might aid the design and practice of cardiovascular preventive medicine.

Analysis of Variance

The effects on platelet aggregation and prostanoid biosynthesis of two parenteral analgesics: ketorolac tromethamine and dipyrone.

The pharmacokinetics and effects on platelet function of dipyrone (1.0 g; 2.5 g; i.v.) and ketorolac tromethamine (30 mg; i.m.) were studied in a three-way crossover study in twelve healthy subjects. The biosynthesis of thromboxane A2 in clotting whole blood ex vivo as well as collagen-induced platelet aggregation were determined before and up to 48 h after administration. Both prostanoid biosynthesis and platelet aggregation were inhibited by ketorolac tromethamine for a significantly longer period of time than by both doses of dipyrone. The changes in platelet functions correlated well with the serum concentrations of ketorolac or 4-methylaminoantipyrine and 4-aminoantipyrine. Using the sigmoidal Emax model the mean serum concentration (SD) of ketorolac, 4-methylaminoantipyrine and 4-aminoantipyrine inhibiting platelet TXB2 generation by 50% (EC50) in vitro was found to be 0.088 +/- 0.031, 1.2 +/- 0.3 and 10.2 +/- 3.4 micrograms ml-1, respectively. In conclusion the recovery of platelet function after dipyrone administration is faster as compared to ketorolac tromethamine. This is in line with clinical observations and may be an advantage when these drugs are given as postoperative analgesics at the doses tested.

Adult

Renal natriuretic effects of atrial natriuretic peptide in dogs with alloxan-induced acute pulmonary edema.

OBJECTIVE: To test the effect of atrial natriuretic peptide (ANF) in dogs with acute pulmonary edema in the absence of urinary sodium retention. ANF is normally a potent natriuretic agent, although this effect is attenuated in generalized edema or acute renal failure. DESIGN: Animal study. SUBJECTS: Twenty-nine dogs. INTERVENTION: Induction of acute pulmonary edema with intravenously administered alloxan and administration of ANF according to five protocols. OUTCOME MEASURES: Natriuretic effect of ANF before and after the induction of pulmonary edema during the protocols. RESULTS: In six control animals, induction of pulmonary edema was associated with diuresis (mean 0.38, standard error of the mean [SEM] 0.003 mL/min before alloxan administration v. mean 0.75, SEM 0.11 mL/min after); natriuresis (mean 60, SEM 8 mumol/min before v. mean 103, SEM 12 mumol/min after); and a decline in blood pressure (mean 114, SEM 7 mm Hg before v. mean 93, SEM 9 mm Hg after) and in the glomerular filtration rate (mean 52, SEM 3.3 mL/min before v. mean 36, SEM 3.7 mL/min after). When isoncotic dextran solution was infused in dogs with pulmonary edema, blood pressure was maintained but the glomerular filtration rate still declined by 42% and there was natriuresis. When the renal arteries were clamped for 5 minutes during the infusion of alloxan, diuresis and natriuresis were prevented, but the glomerular filtration rate still declined, although blood pressure was maintained. ANF administered intravenously during pulmonary edema induced a further significant natriuresis in all experimental protocols. Catalase, administered intravenously as a bolus just before the alloxan infusion, prevented pulmonary edema and the associated renal changes. CONCLUSIONS: Although alloxan appears to be directly nephrotoxic, renal damage caused by this compound does not impair the natriuretic effect of ANF in acute pulmonary edema.

Acute Disease