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Biomedical subjects

M Levy

Publications and source records attributed to M Levy.

At least 91 records · Page 5Linked to original sources

Retrospective analysis of the frequency and recognition of adverse drug reactions by means of automatically recorded laboratory signals.

AIMS: To estimate the frequency of adverse drug reactions (ADRs) identified through the use of automatic signals generated from laboratory data (ALS) in hospitalised patients. To determine the frequency of spontaneous recognition of these ADRs by the attending physicians and to assess the potential value of ALS for detection of ADRs. METHODS: Laboratory results of patients hospitalised in a nine bed medical ward were automatically recorded over a period of 17 months. Values exceeding defined boundaries were used as ALS. Charts of every third patient were analysed retrospectively with regard to adverse drug related reactions and causality was evaluated as well as whether the ADR had been recognised during the period of hospitalisation. RESULTS: The charts and ALS of 98 patients were analysed. In 18 cases a drug-related adverse reaction was probable. Awareness to the reaction by the treating physicians was evident in 6 out of these 18 ADRs. Approximately 80% of the ADRs were considered predictable. Three ADRs were regarded as serious. CONCLUSIONS: Adverse drug reactions are common and often preventable. Only one third of ADRs which could have been detected through ALS were recognised by the attending physicians. An increased doctor's awareness of the frequency of drug related abnormal laboratory results by means of ALS is likely to increase the recognition rate of ADRs and might help to prevent them.

Adult↗

Mantoux positivity among prison inmates--New South Wales, 1996.

OBJECTIVES: To determine the prevalence of Mantoux positivity in a prison population; identify risk factors associated with tuberculosis infection; and assess the risk of tuberculosis transmission in a correctional system. METHOD: Cross sectional random sample (between May and August 1996) of inmates stratified by sex, age and Aboriginality. Participants were 789 adult inmates (657 male and 132 female) from 27 New South Wales (NSW) correctional centres (24 male and 3 female). RESULTS: Of the 789 inmates (657 male and 132 female) included in the survey, 639 were given a Tuberculin skin test (Mantoux). Eighty-four (13%) were Mantoux positive. A higher proportion of male inmates were Mantoux positive compared with females (14% vs. 8%, p = 0.08). Significant independent predictors of Mantoux positivity were: being male, aged over 25 years, Aboriginal, born overseas and resident at a jail where there had been a recent tuberculosis outbreak. CONCLUSION: Screening of inmates in NSW prisons based on the principle of risk stratification is appropriate. IMPLICATIONS: While the risk of tuberculosis transmission in NSW jails is currently considered low, continued surveillance is recommended.

Adolescent↗

Theileria sp. Infections associated with bovine fatalities in the United States confirmed by small-subunit rRNA gene analyses of blood and tick samples.

Theileria sp.-specific small subunit (SSU) rRNA gene amplification confirmed the presence of the organism in cattle and in Amblyomma americanum and Dermacentor variabilis ticks collected from a cattle herd in Missouri. Blood from the index animal had type A and type D Theileria SSU rRNA genes. The type D gene was also found in blood from two cohort cattle and tick tissues. The type A SSU rRNA gene was previously reported from bovine Theileria isolates from Texas and North Carolina; the type D gene was reported from a Texas cow with theileriosis.

Animals↗

[Importance of dual isotope myocardial tomoscintigraphy in the detection of coronary disease in the graft among 96 heart transplant recipients].

With a survival rate of 70% at 3 years, cardiac transplantation is the best treatment for end-stage heart disease. However, progressive development of graft atherosclerosis is frequent. Diagnosis of transplant coronary disease remains difficult and non-invasive tests have proved relatively insensitive. Therefore, coronary angiography performed annually is still the gold-standard test for the detection of heart transplant vasculopathy. We analyzed the records of 96 patients (82 men and 14 women) who were transplanted from 1986 to 1996. Mean age was 53 +/- 2.7 and time elapsed from transplantation was mean 5.3 +/- 10 years. All patients had rest myocardial TI 201 perfusion SPECT, followed by MIBI gated SPECT after exercise. MIBI gated SPECT allows simultaneous evaluation of perfusion, regional LV function and global ejection fraction. Angiocoronarography, performed in all patients during the six months following radionuclide investigation, showed the presence of coronary heart vasculopathy in nine (9.3%). Seven of these patients had abnormal dual isotope imaging and 2 of them had normal perfusion but altered LV regional function. Sensitivity of dual isotope scintigraphy was 77% and specificity was 97.7%. Dual isotope scintigraphy is helpful to detect coronary vasculopathy in heart transplant recipients and may reduce indications of angiocoronarography.

Coronary Angiography↗

DOTS (Directly Observed Treatment Strategy) project in Mongolia, 1995.

OBJECTIVE: To establish a tuberculosis (TB) control programme consistent with recommendations made by the WHO and the International Union Against Tuberculosis and Lung Disease (IUATLD) in a country where, as in control programmes of the former USSR, TB management previously relied on active case-finding with radiology and long-term monitoring and treatment of patients. DESIGN AND METHODS: A pilot DOTS strategy (directly observed treatment, short course) project was implemented in Dornod Aimak, Eastern Mongolia During a 6-week period, individuals with chronic cough of > or =3 weeks were screened with sputum smear microscopy. Smear-positive patients received a supervised 6-month regimen (2SRHZ/4RH). Outcome was assessed with smear examination 2, 5, and 6 months after the initiation of treatment. RESULTS: Screening of 1241 symptomatic individuals identified 169 smear-positive TB cases (14%). Most of them (92%) were cured as demonstrated by documented sputum conversion. Five patients completed treatment, but were not available for follow-up smear examination, four patients died and four defaulted. CONCLUSION: The DOTS strategy was successfully introduced in a former socialist model country, paving the way to national DOTS implementation in Mongolia. It may serve as an example for countries with a health care tradition similar to that of the Commonwealth of Independent States.

Antitubercular Agents↗

The stability of the RNA bases: implications for the origin of life.

High-temperature origin-of-life theories require that the components of the first genetic material are stable. We therefore have measured the half-lives for the decomposition of the nucleobases. They have been found to be short on the geologic time scale. At 100 degreesC, the growth temperatures of the hyperthermophiles, the half-lives are too short to allow for the adequate accumulation of these compounds (t1/2 for A and G approximately 1 yr; U = 12 yr; C = 19 days). Therefore, unless the origin of life took place extremely rapidly (<100 yr), we conclude that a high-temperature origin of life may be possible, but it cannot involve adenine, uracil, guanine, or cytosine. The rates of hydrolysis at 100 degreesC also suggest that an ocean-boiling asteroid impact would reset the prebiotic clock, requiring prebiotic synthetic processes to begin again. At 0 degreesC, A, U, G, and T appear to be sufficiently stable (t1/2 >/= 10(6) yr) to be involved in a low-temperature origin of life. However, the lack of stability of cytosine at 0 degreesC (t1/2 = 17, 000 yr) raises the possibility that the GC base pair may not have been used in the first genetic material unless life arose quickly (<10(6) yr) after a sterilization event. A two-letter code or an alternative base pair may have been used instead.

Animals↗

Activation of a metabotropic glutamate receptor and protein kinase C reduce the extent of inactivation of the K+ channel Kv1.1/Kvbeta1.1 via dephosphorylation of Kv1.1.

Various brain K+ channels, which may normally exist as complexes of alpha (pore-forming) and beta (auxiliary) subunits, were subjected to regulation by metabotropic glutamate receptors. Kv1.1/Kvbeta1.1 is a voltage-dependent K+ channel composed of alpha and beta proteins that are widely expressed in the brain. Expression of this channel in Xenopus oocytes resulted in a current that had fast inactivating and noninactivating components. Previously we showed that basal and protein kinase A-induced phosphorylation of the alpha subunit at Ser-446 decreases the fraction of the noninactivating component. In this study we investigated the effect of protein kinase C (PKC) on the channel. We showed that a PKC-activating phorbol ester (phorbol 12-myristate 13-acetate (PMA)) increased the noninactivating fraction via activation of a PKC subtype that was inhibited by staurosporine and bisindolylmaleimide but not by calphostin C. However, it was not a PKC-induced phosphorylation but rather a dephosphorylation that mediated the effect. PMA reduced the basal phosphorylation of Ser-446 significantly in plasma membrane channels and failed to affect the inactivation of channels having an alpha subunit that was mutated at Ser-446. Also, the activation of coexpressed mGluR1a known to activate phospholipase C mimicked the effect of PMA on the inactivation via induction of dephosphorylation at Ser-446. Thus, this study identified a potential neuronal pathway initiated by activation of metabotropic glutamate receptor 1a coupled to a signaling cascade that possibly utilized PKC to induce dephosphorylation and thereby to decrease the extent of inactivation of a K+ channel.

Amino Acid Sequence↗

Cerebrospinal fluid and plasma concentrations of dipyrone metabolites after a single oral dose of dipyrone.

OBJECTIVE: Dipyrone is a veteran analgesic and antipyretic drug. After oral administration it is rapidly converted by hydrolysis to 4-methylaminoantipyrine (MAA), which is further metabolized to 4-formylaminoantipyrine (FAA), 4-aminoantipyrine (AA) and 4-acetylaminoantipyrine (AAA). It is still debated whether the site of dipyrone action is in the central nervous system or in the periphery. The purpose of this study was to assess whether dipyrone metabolites cross the blood-brain barrier (BBB) when administered systemically. METHODS: Twenty-eight patients undergoing diagnostic lumbar puncture (LP) were randomly assigned to receive two 0.5-g dipyrone tablets either 30 min, 1, 1.5, 2, 4, 6, 8 h or 12 h before the lumbar tap. A 5-ml blood sample was drawn concomitantly. RESULTS: All four metabolites were found in the cerebrospinal fluid (CSF). Their appearance in the CSF lagged but followed that found in the plasma. Mean CSF/plasma ratios were 0.40 (for samples taken between 0.5-2 h) and 0.83 (for samples taken between 4-12 h) for MAA, 0.62 for AA, 0.55 for FAA and 0.40 for AAA (for all samples). Significant correlation was found between plasma and CSF concentrations for MAA, AA, FAA and AAA. CONCLUSION: The concentration-time course of dipyrone metabolite CSF concentrations are in agreement with that of their plasma concentrations and the analgesic effect of dipyrone.

Administration, Oral↗

Cerebrospinal fluid prostaglandins after systemic dipyrone intake.

OBJECTIVE: The object of this study was to evaluate the time course of thromboxane B2 and prostaglandin E2 concentrations in cerebrospinal fluid after oral administration of dipyrone (INN, metamizole). METHODS: A single 1.0 gm oral dose of dipyrone was given to consenting patients undergoing elective diagnostic lumbar puncture 0.5, 1, 1.5, 2, 4, 6, 8, or 12 hours before the tap. RESULTS: For thromboxane B2 a time decrease in cerebrospinal fluid concentration was apparent. In contrast, for prostaglandin E2 cerebrospinal fluid levels no consistent trend was observed. CONCLUSIONS: A time-related decrease in cerebrospinal fluid thromboxane B2 level was noted in patients receiving dipyrone. Thirty minutes after dipyrone intake cerebrospinal fluid thromboxane B2 levels already tended to be lower than those seen in patients with neurologic diseases who were not receiving dipyrone. These results are consistent with the hypothesis that dipyrone acts in the central nervous system by inhibition of particular prostanoids.

Administration, Oral↗

Colchicine: 1998 update.

OBJECTIVE: To present an update of the use of colchicine in patients with familial Mediterranean fever (FMF) and other rheumatic and nonrheumatic diseases. DATA SOURCES: Published studies on colchicine retrieved from MEDLINE searches from 1987 to 1997 and reports presented at national and international meetings. STUDIES SELECTION AND EXTRACTION: All studies were reviewed by the authors. Reports addressing the topics of colchicine pharmacokinetics, biological effects, indications for use, and side effects were selected. DATA SYNTHESIS: Colchicine is an alkaloid that may interfere with microtubule formation, thereby affecting mitosis and other microtubule-dependent functions. It has a bioavailability of 25% to 50% when administered orally. Colchicine and its metabolites are excreted through the urinary and biliary tracts. It may be used while breast feeding; however, amniocentesis should be performed when used in pregnancy. The drug may be given to children with FMF. The efficacy of colchicine has been proved in FMF, gout, Behcet's disease, and cirrhosis. Its place in the treatment of scleroderma, sarcoidosis, and skin disorders remains to be determined. Gastrointestinal side effects occur early and are most common manifestations of colchicine toxicity. Severe colchicine toxicity results in multiple organ failure, convulsions, coma, and death. Potentially, effective treatment with Fab anti-colchicine antibodies unfortunately is unavailable; therefore, treatment is supportive. CONCLUSIONS: Colchicine is a relatively safe and effective medication for several disorders when used in appropriate dosage in patients with normal kidney and liver function.

Behcet Syndrome↗

Does the lack of the P-glycoprotein efflux pump in neutrophils explain the efficacy of colchicine in familial Mediterranean fever and other inflammatory diseases?

Colchicine is an alkaloid drug commonly used in familial Mediterranean fever (FMF), gout, Behcet's syndrome, psoriasis and Sweet's syndrome. The exact mechanism of its action in these diseases is not entirely known. However, it has been shown that colchicine may inhibit neutrophil chemotaxis, thereby decreasing the inflammatory process. Recently, it was shown that colchicine accumulates in neutrophils in higher concentrations than in lymphomonocytes. Studies dealing with the multiple drug resistance (MDR) issue disclosed that neutrophils lack the P-glycoprotein (P-gly) membranal pump (encoded by the MDR1 gene). We propose that the preferential accumulation of colchicine in neutrophils compared with lymphomonocytes is due to the absence of the P-gly efflux pump in the former. This may explain the effectiveness of colchicine in diseases where increased chemotaxis is evident. The hypothesis may also provide an explanation for FMF patients who do not respond to the drug.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Phenotype-genotype correlation in Jewish patients suffering from familial Mediterranean fever (FMF).

Familial Mediterranean Fever is one of the most frequent recessive disease in non-Ashkenazi Jews. The gene responsible for the disease (MEFV) has very recently been identified. The M694V ('MED') mutation was found in about 80% of the FMF Jewish (Iraqi and North African) chromosomes. To see if the presence of this mutation could be correlated with particular traits of the disease, we examined a number of clinical features in a panel of 109 Jewish FMF patients with 0, 1 or 2 MED mutations. We showed that homozygosity for this mutation was significantly associated with a more severe form of the disease. In homozygous patients, the disease started earlier (mean age 6.4 +/- 5 vs 13.6 +/- 8.9) and both arthritis and pleuritis were twice as frequent as in patients with one or no M694V mutation. Moreover, 3/3 patients with amyloidosis displayed two MED mutations. No association was found with fever, peritonitis, response to colchicine and erysipeloid eruption. The present result strongly suggests the potential prognostic value of the presence of this mutation.

Africa, Northern↗

Computerized survelliance of adverse drug reactions in hospital: pilot study.

AIMS: To develop and assess the use of computerized laboratory data as a detection support tool of adverse drug reactions (ADRs) in hospital. METHODS: This was a retrospective observational study of 153 sequential medical admissions during a 2-month period to the 34-bed medical ward at the Hadassah University Hospital, Jerusalem, Israel. Measurements made were 1) Retrospective chart review for recognized and unrecognized adverse drug reactions (ADRs) and 2) Analysis of computerizied laboratory data according to defined automatic laboratory signals (ALS) for adverse reactions. RESULTS: Forty ADRs have been detected in 38 out of the 153 hospital admissions (24.8%). Nine reactions were considered severe. Altogether 212 ALS were generated involving 86 admissions. In 25 (65.8%) of the ADR-positive admissions ADRs were detected through automatic signals generated from the laboratory data. ALS were detected in 56 out of the 115 (48.7%) ADR-negative admissions. Twenty-four (60%) of the ADRs were not recognized as such by the attending physicians. Two of these reactions were severe. ALS could have generated an alert for 19 (79.2%) of the unrecognized reactions. CONCLUSIONS: Application of automatic laboratory signals can increase the rate of recognition of the ADRs and thereby improve medical care. The sensitivity and specificity of the method might be increased by refinement and redefinition of the signals.

Adult↗