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Biomedical subjects

M Levy

Publications and source records attributed to M Levy.

At least 307 records · Page 17Linked to original sources

Tissue plasminogen activator for the treatment of thromboembolism in infants and children.

We report our experience with the use of tissue plasminogen activator to treat 12 infants and children with various thromboembolic states after conventional thrombolytic agents had failed. The dosage range was between 0.1 to 0.5 mg/kg per hour. Complete clot dissolution occurred in seven cases after 2 hours to 3 days of therapy. Partial clot dissolution and clinical improvement were noted in another four patients. Bleeding complications were noted in 6 of the 12 patients and included bruising, oozing from various venipuncture sites, and bleeding; these complications were controlled by clinically available means. In all cases with bleeding the dose rate was in the higher range (0.46 to 0.50 mg/kg per hour). In one patient, restlessness, agitation, and screaming were noted during administration of tissue plasminogen activator and when it was reinstituted. We conclude that tissue plasminogen activator is effective in inducing clot lysis in children. Because the effective dose appears to overlap with those causing bleeding, we recommend that a dose of 0.1 mg/kg per hour be started and increased gradually if clot dissolution does not occur, with close monitoring for bleeding.

Adolescent↗

Mode of action of the antimycotic agent G2 isolated from alfalfa roots.

The mode of action of the antimycotic alfalfa root saponin, medicagenic acid 3-O-beta-D-glucopyranoside (compound G2), which possesses a pronounced antifungal activity against medically important yeasts and dermatophytes, was studied in Saccharomyces cerevisiae. Compound G2 caused lethal leakage of ions out of the yeast cells. Exposure of S. cerevisiae to compound G2 resulted in a disappearance of the main sterol, ergosterol, from the cell membranes, suggesting that compound G2 was highly specific for ergosterol. Independently, chemical data indicated that compound G2 forms stable complexes with both ergosterol and cholesterol. Addition of cholesterol or ergosterol protected the cells of S. cerevisiae and several pathogenic yeasts from the inhibitory activity of compound G2 by producing a higher ratio of sterols (mainly ergosterol) to phospholipids in the membranes. The fact that an amphotericin B-resistant Candida tropicalis was susceptible to G2 suggested that its mode of action was different from that described for polyene antibiotics. This was also confirmed by the finding that 0.2 M KCl did not protect S. cerevisiae cells against ion leakage with G2, but did so with amphotericin B.

Antifungal Agents↗

Pregnancy outcome following first trimester exposure to chloroquine.

Although the use of chloroquine (C) and hydroxychloroquine (HC) in the treatment of malaria prophylaxis during pregnancy is probably safe, the use of much higher doses for treatment of systemic lupus erythematosus (SLE) and rheumatoid arthritis during pregnancy has been controversial. We analyzed the cases of 24 pregnant women with a total of 27 pregnancies who had taken these drugs during their first trimester of pregnancy. C and HC were given in 11 patients with SLE, three with rheumatoid arthritis, and four for malaria prophylaxis. Most of these women had already been on antimalarial drugs for 1 to 172 months prior to pregnancy (mean, 32.2 months). Of the 27 pregnancies, 14 resulted in normal full-term deliveries, six were aborted due to severe disease activity or social conditions, three were stillbirths, and four pregnancies resulted in spontaneous abortions. No congenital abnormalities were detected in the 14 live births at ages between 9 months and 19 years (mean, 5.3 years). All these children are physically and developmentally normal with no clinical evidence of eye or hearing defects. The seven pregnancies that were associated with fetal loss occurred particularly in patients who had active SLE, although stillbirth and spontaneous abortion occurred also in patients with rheumatoid arthritis and in two of the three patients who had been treated prophylactically for malaria. Although of the 215 reported pregnancies with C and HC exposure, including our study, only seven (3.3%) had congenital abnormalities, the risk associated with antimalarials may be cumulative and further studies are needed to elucidate the safety of this drug later in pregnancy.

Abnormalities, Drug-Induced↗

Hepatitis B vaccine in pregnancy: maternal and fetal safety.

Perinatal transmission of hepatitis B (HB) virus occurs if the mother has had acute HB infection during late pregnancy or in the first months postpartum, or if the mother is a chronic HB antigen carrier. Vertical transmission from chronic carriers exceeds 90% and accounts for up to 40% of the world chronic carriers in endemic areas. Hepatitis in pregnancy is not associated with increased abortion rate, stillbirth, or congenital malformation. However, prematurity seems to be increased if hepatitis is acquired in the last trimester. Sixty percent of pregnant women who acquire acute HB infections at or near delivery will transmit the HB virus to their offspring. Although infection is rarely symptomatic, 70 to 90% of the babies will remain chronically infected into adult life and be prone to cirrhosis and hepatocellular carcinoma. Because of such high risks and the safety and efficacy (seroconversion 90 to 100%) of HB vaccine in preventing HB infection, it is recommended that HB vaccine be given to pregnant women at high risk. However, its safety to the fetus is not well documented. Only one human study reports the safety and efficacy of Heptavax, but only when administered (to 72 pregnant women) in the last trimester of pregnancy when embryopathy cannot occur. We report pregnancy outcome in ten women, mostly health care personnel or patients traveling to endemic areas exposed to the vaccine during the first trimester of pregnancy. No congenital abnormalities were observed and all the infants are physically and developmentally normal for their ages at 2 to 12 months. Although small, this cohort suggests safe use of the vaccine in early pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Postaxial acrofacial dysostosis (Miller) syndrome: a new case.

We describe a new case of postaxial acrofacial dysostosis (Miller) syndrome. This syndrome consists of mandibulofacial dysostosis, similar to that seen in Treacher Collins syndrome, and postaxial limb deficiency. The mode of inheritance remains uncertain.

Abnormalities, Multiple↗

Determinants of atrial natriuretic factor secretion in dogs expanded with isotonic saline or colloid solutions.

Through increments in blood volume and atrial pressure are thought to be the primary stimuli for ANF secretion, plasma levels of this peptide do not always behave as a simple function of volume status. To outline the relationship between the latter and cardiac ANF release, we used five different volume-expansion protocols in anesthetized dogs. A stepwise expansion of plasma volume (PV) was achieved by two consecutive infusions: 0.9% saline followed or preceded by 4 or 25% bovine serum albumin (BSA), 4 or 25% dextran (Dx), or homologous plasma. Saline expansion led to a two- to four-fold increase in arterial plasma ANF level in all five protocols. Both 4 and 25% BSA caused no or very modest increase in plasma ANF, while all other colloid expanders caused the expected ANF release. In all protocols, plasma ANF closely correlated with central venous pressure (CVP). BSA expansion was the only protocol with no correlation between PV and ANF release. Changes in serum Ca2+ could not explain this finding. During BSA expansion, the lack of atrial response was related to the absence of increment (or even fall) in CVP despite the expanded PV. Similarly, urinary Na+ excretion was correlated both with CVP and ANF level but not with PV in BSA expansion. When the dogs were depleted of histamine before BSA infusion, the atrial secretory response was restored, suggesting that this colloid was associated with augmented capillary leakiness and vascular fluid efflux. These results show that the expansion of PV leads neither to ANF release nor to Na+ excretion if it is not accompanied by an expanded central blood volume with elevated atrial pressure.

Animals↗

Does adenosine modulate the natriuretic response to ANP in normal dogs?

To determine if the usual natriuretic response to ANP could be altered by raising intrarenal levels of adenosine, ANP was administered to normal anesthetized dogs at 100 ng.kg-1.min-1 i.v. before and after the administration of adenosine (3 micrograms.kg-1.min-1) into the left renal artery (n = 8). For each kidney, the group mean delta UNaV in response to ANP was unchanged by the presence of adenosine. However, following intrarenal infusion of adenosine, this unaltered average response for the infused kidney was achieved by either attenuation or exaggeration of the natriuresis to ANP in half the dogs, respectively. When intrarenal levels of extracellular adenosine were elevated by the i.v. infusion of dipyridamole in seven dogs, there was uniform exaggeration of an ANP-induced natriuresis by an average of 145 mu equiv./min. The provision of theophylline by itself (an adenosine antagonist) had no effect on UNaV but prevented the dipyridamole-induced exaggerated natriuresis to ANP. The infusion of adenosine deaminase into one renal artery reduced the natriuretic response to ANP. We conclude that elevated intrarenal levels of adenosine will exaggerate an ANP-induced natriuresis possibly by altering intracytosolic Ca2+.

Adenosine↗

Nonspecific bronchial reactivity in asthmatic children depends on severity but not on age.

Bronchial reactivity to inhaled methacholine was measured by the steady-state tidal breathing method in asthmatic children aged 1 to 17 yr. The children were divided into three clinical groups according to their minimal therapeutic requirements: mild asthma, children requiring infrequent treatment with inhaled beta-agonists (81 patients); moderate asthma, children requiring daily preventive treatment with either cromolyn sodium or slow-release theophylline (67 patients); and severe asthma, children requiring daily preventive treatment with oral or inhaled steroids (34 patients). They were also divided into three age groups: from 1 to 6 yr, tested by using bronchial provocation with tracheal auscultation (BPTA) to determine the methacholine concentration causing wheezing (PCW); and from 7 to 11 yr and 12 to 17 yr, using lung function testing to determine the concentration causing a 20% fall in FEV1 (PC20). For the whole group the mean level of bronchial reactivity to methacholine correlated inversely with the severity of bronchial asthma according to the minimal drug requirements (p less than 0.0001) and was similar over the whole age range (p less than 0.9965) for each severity grouping. In the older children the difference between moderate and severe asthma was not significant, but this may have been a result of the effect of corticosteroids in the severe group. We concluded that age has no significant effect on the methacholine response in asthmatic children over a wide age range.

Adolescent↗

Mycoplasma pneumoniae infections and Stevens-Johnson syndrome. Report of eight cases and review of the literature.

On the basis of a literature review and eight cases of our own, we analyzed 37 cases of Mycoplasma pneumoniae (MP) infection and Stevens-Johnson syndrome (SJS). Our clinical and laboratory findings do not differ from those reported in the literature for MP infection with no exanthem or for SJS of various etiologies. Eighty percent of the children presented with symptoms of upper respiratory tract infection (URTI) (cough, fever, sore throat, malaise, headache), with a mean of 10 days (range 1 to 30) before skin rash broke out. Skin manifestations occurred in 94.2% of the patients after 3 to 21 days (mean 10.3 days) of fever. The exanthem, composed predominantly of maculopapular and vesicular, was distributed chiefly on the trunk and extremities and lasted less than 14 days in 87.8% of the patients. Stomatitis was observed in 91.6% of the patients and conjunctivitis in 50%. No consistent pattern seems to emerge by which one could predict the existence of MP infection causing SJS. The complications of SJS associated with MP seem less frequent (2.7%) and much less severe than in cases where SJS arises from other reported causes. Because coincidence cannot be excluded from the assessments of the degree and rate of improvement for the few patients treated with corticosteroid, from the low frequency of complications, and from the mortality rate of zero in this series of patients, the use of corticosteroids for SJS associated with MP infection is questionable.

Adolescent↗

[Congenital long QT syndrome. Mid-term prognosis].

Twenty-five cases of the congenital, idiopathic long QT syndrome, occasionally diagnosed at birth and persisting after the 4th day of life, were analysed retrospectively to determine the medium-term prognosis and to identify risk factors. The age of the patients varied: 13 neonates including 10 of less than 5 days of age, and 12 children 1 to 12 years old. Eleven patients belonged to families with long QT syndromes. The recruitment also varied: syncope or near syncope (9 cases), bradycardias or tachyarrhythmias (9 cases) or by systematic familial enquiry (7 cases). The corrected QT interval (QTc) was greater than 0.44 s in all patients, and 17 patients had conduction (atrioventricular or intraventricular) defects and/or ventricular arrhythmias (tachycardia, torsades de pointe or fibrillation). All except two older children were prescribed betablocker therapy and in 6 cases of resistant arrhythmias a pacemaker was implanted. There were 6 deaths: 4 deaths occurred in neonates who had the longest QT intervals (greater than 0.65 s) complicated by conduction defects and tachyarrhythmias. The other 2 fatalities were in older children who both died during syncope. The 19 survivors were followed up for 3 months to 16 years: 4 children with the shortest QTc values (0.44 to 0.48 s) have completely recovered; 2 neonates treated for 9 months and then weaned off therapy without any complications and 2 older children who were not treated. The other 15 cases are all under treatment but do well and have had no syncopal episodes during follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗

Worldwide perspective of hepatitis B-associated glomerulonephritis in the 80s.

Chronic HBsAg carriers may develop glomerulonephritis (GN). Besides membranous GN (MGN), which seems a well established association, membranoproliferative GN (MPGN) or proliferative GN are also encountered in these patients. It is clear that the variations in the incidence of hepatitis B virus (HBV) GN may be real or related to a more or less vigorous search for HBV in the different nephrologic centers. However, the frequency of HBV GN in a country correlates with the underlying prevalence of HBV infection in the general population. Geographic patterns of HBV prevalence vary greatly from areas of low endemicity where less than 1% of adults are chronic carriers to areas of intermediate and high endemicity where between 2 and 15% of adults are chronic carriers. The most important factor affecting prevalence is age of HBV infection. The probability of becoming a chronic carrier is greater following infection during infancy and early childhood. The rarity of HBV GN in the U.S. and in western Europe probably reflects the rarity of HBV infection, especially in children. The frequency of HBV GN is high in Asian or Black children. It is possible to hope that, with the extensive immunization in countries of high endemicity, the frequency of HBV GN will diminish. In the U.S. and in Europe, patients with HBV GN frequently belong to high risk groups for HBV infection. In these countries, the increase in the percentage of HBV infection due to sexual transmission or linked with drug abuse may lead to an increase in the percentage of adult patients with HBV GN.

Africa↗

Captopril pharmacokinetics, blood pressure response and plasma renin activity in normotensive children with renal scarring.

We studied blood pressure response, plasma renin activity (PRA) and captopril pharmacokinetics in 8 children receiving orally 0.7 mg/kg of the drug. The drug increased PRA in all patients, in 5 to abnormally high levels. Peak captopril concentrations were achieved between half an hour and 2 h, and ranged between 100 and 547 ng/ml. Mean elimination half-time (T1/2) was 1.5 h, ranging between 0.98 and 2.3 h. There was a significant positive correlation between the area under the curve (AUC) and elimination T1/2 of the drug. There was a significant inverse correlation between AUC or elimination T1/2 and percent change in diastolic blood pressure; the 2 children who had no change in diastolic blood pressure had the largest AUC and the lowest apparent clearance of captopril. The kidney is the major site of captopril's pharmacological action. It is possible that longer retention of captopril in the plasma, evidence by larger AUC, may reflect less captopril available to modulate renin activity in the kidney.

Administration, Oral↗

[Ultrafast computed tomography and measurement of the left ventricular volume].

Ultrafast computed tomography is a method of acquiring cardiac tomographic images 8 mm thick of high resolution in a very short time (about 50 ms). It is particularly well adapted to evaluation of the anatomy and quantification of the volume of the left ventricle. Acquisition of the image is initiated by the R wave of the electrocardiogram. Short axis or long axis views of the heart may be recorded. There are usually 12 short axis tomographic cuts from the apex to the base and for each there are 13 acquisitions in the RR cycle at 58 ms intervals. The half circulation time must be determined beforehand as 50 cc of contrast medium have to be injected peripherally to visualise the cardiac chambers. The contrast medium enhances the endocardium and papillary muscle borders enabling semi-automatic contour tracings. End diastole and end systole are easily determined from the 13 acquisitions in the cardiac cycle, and the wall motion of the left ventricle can be analysed using a cineloop facility. Akinesia, dyskinesia and even wall thickness can be determined. After tracing the endocardial contour, the microprocessor calculates the surface of the enclosed area, and the volume of this simple cylinder can be derived by multiplication of the thickness of each slice. The total volume at each of the 13 instances is obtained by summation. End diastolic, end systolic volumes and ejection fraction can thereby be determined. Left ventricular mass may also be evaluated by tracing the epicardial border.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Volume↗

Childhood immunisation advisory service for general practitioners.

A study of 270 general practitioners associated with the University of Sydney, Division of Family Medicine, was conducted to examine the need for a childhood immunisation advisory service. Forty-three per cent of respondents had deferred immunisation or altered the schedule of immunisation of children attending them over the previous month. The majority stated that an immunisation advisory service would be beneficial. The preferred option was a telephone service operating from 9 am to 5 pm.

Clinical Protocols↗

Asthma care.

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Asthma↗

Colchicine: a state-of-the-art review.

Colchicine is an ancient drug that is attracting renewed interest because of its actions at a subcellular level. Specifically, it interferes with microtubule growth and therefore affects mitosis and other microtubule-dependent functions. Various mechanisms have been proposed to account for the action of colchicine in acute gouty arthritis, its interaction with cellular membrane and cyclic 3',5'-adenosine monophosphate, and its action in amyloidosis. Pharmacokinetic studies have been relatively limited and their results somewhat contradictory, with mean terminal elimination half-lives of 19 minutes to 9 hours being reported. Some of these differences may be attributed to assay difficulties. Colchicine can cause gastrointestinal side effects and should be used with care to protect patients from toxic doses. Colchicine-induced myopathy and neuropathy may be more frequent than previously recognized, and therefore patients receiving long-term therapy should be monitored carefully. Bone marrow depression has been reported, primarily in cases of acute colchicine intoxication, and intravenous administration of the drug has been associated with severe pancytopenia and death. Colchicine intoxication causes multiple organ failure. Because of its cytogenic effects and reported association with Down's syndrome, the agent should not be used by pregnant women.

Amyloidosis↗

[Unfavorable outcomes in disseminated lupus erythematosus in children. Cooperative study in the Paris region].

Pediatric cases of systemic lupus erythematosus with an unfavorable outcome (terminal renal failure requiring chronic hemodialysis, or death) assembled during a retrospective multicenter study of pediatric SLE in the Paris metropolitan area were analyzed. Seven patients (6 girls, 1 boy) were entered into a chronic hemodialysis program. Four had diffuse proliferative glomerulonephritis, the pattern of glomerular disease classically responsible for end-stage renal failure. The other three patients had membranous glomerulonephritis with active segmental lesions, a form of glomerulopathy whose severe prognosis deserves to be emphasized. Nine other patients (8 girls, 1 boy) died. In six patients, death occurred as a result of a flare with malignant hypertension and progressive renal failure (1 case), pancreatitis (1 case), encephalopathy (2 cases) or cardiomyopathy (2 cases). An infectious disease (tuberculosis, mumps) was apparently the cause of the two cases of encephalopathy. One girl died as a result of a hemorrhagic syndrome with a cerebral hematoma. Two other girls died at home. Overall, among 111 children with SLE 14% had an unfavorable outcome. Sex and age at onset seemed to have no bearing on prognosis. Patients with renal involvement were apparently more likely to have an unfavorable outcome. Lastly, although the influence of ethnic origin is unproven, children living in foreign countries of French overseas territories, but treated in France have an increased risk for unfavorable outcomes.

Adolescent↗