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Biomedical subjects

M Levy

Publications and source records attributed to M Levy.

At least 73 records · Page 4Linked to original sources

Detection of artificial changes in mole size by skin self-examination.

BACKGROUND: The efficacy of the skin self-examination (SSE) to detect artificial changes in the size of nevi has not been evaluated in a controlled setting. OBJECTIVE: Our purpose was to determine the sensitivity and specificity of the SSE in detecting artificial changes in mole size in patients at high risk for melanoma. METHODS: In a single-center, single-blinded cross-over study, patients who had been performing the SSE confidently for at least 1 year examined their backs after the diameter of an existing mole was increased artificially in random order by 0, 2, or 4 mm. RESULTS: The specificity of the SSE was 62% (95% confidence interval [CI], 53%-72%) (N = 103). The sensitivity of the 2 mm change was 58% (95% CI, 49%-68%) and that of the 4 mm change was 75% (95% CI, 66%-83%). SSE performance was not related to perceived risk, number of moles, gender, age, or frequency of self-examination. CONCLUSION: Even in our highly motivated and selected group of high-risk patients, 25% could not detect an obvious increase in the diameter of an existing nevus, whereas 38% incorrectly identified a change when none was made. The SSE is only a moderately effective tool for the detection of acute, large, changes in mole size. The usefulness of the SSE in detection of new lesions or changes in existing lesions is likely due to a combination of factors or due to factors other than size, such as color, border irregularity, and texture, among others.

Adult↗

The effect of gas loading on the RUS spectra of spheres

Resonant Ultrasound Spectroscopy (RUS) of a spherical sample in a pressurizing gas atmosphere was investigated experimentally and theoretically. Measurements were made on a fused silica sphere in He, Ar, and N2 gases up to pressures of 120 bar. The pressure-dependent shift in the resonant frequency, delta f, and the Q-factor were measured for the S00, S11, and T02 modes. A theoretical model based on acoustic radiation impedance was used to calculate delta f and the radiation-resistance component, Qr, of the Q-factor. Agreement between theory and experiment was good for Qr, but there were discrepancies for delta f. It was found that the theoretical delta f due to gas-loading effects associated with acoustic radiation was very small and consistent with the observed dependence on pressure and gas species for the T02 mode but not for the S00 and S11 modes. We conclude that the T02 mode is the most reliable of these modes to use in measuring third-order elastic constants by RUS.

Journal Article↗

Herpes simplex virus type 2 in prisoners, New South Wales, Australia.

Our objectives were to determine the prevalence of, and risk factors for, herpes simplex virus type 2 (HSV-2) antibodies in male and female prisoners. A cross-sectional random sample was used consisting of 789 prisoners (657 males and 132 females) from 27 correctional centres across New South Wales (NSW), stratified by sex, age and Aboriginality. Participants were questioned about demographics and behavioural risk factors and were screened for serum antibody to HSV-2. The overall prevalence of HSV-2 antibodies was higher in females (58%) than males (21%), and in Aborigines (34%) compared with non-Aborigines (24%). HSV-2 prevalence increased with the number of sexual partners. Few prisoners (1%) reported a previous diagnosis of genital herpes. Independent risk factors for the presence of HSV-2 antibodies were increasing age and Aboriginality for men, and higher reported number of lifetime sexual partners and the presence of hepatitis C antibodies for women. HSV-2 infection is common in prison inmates. There is a need to incorporate information about STDs, including HSV-2, into education programmes for inmates.

Adult↗

Incidence and costs of adverse drug reactions during hospitalisation: computerised monitoring versus stimulated spontaneous reporting.

OBJECTIVE: To implement a computer-based adverse drug reaction monitoring system and compare its results with those of stimulated spontaneous reporting, and to assess the excess lengths of stay and costs of patients with verified adverse drug reactions. DESIGN: A prospective cohort study was used to assess the efficacy of computer-based monitoring, and case-matching was used to assess excess length of stay and costs. SETTING: This was a study of all patients admitted to a medical ward of a university hospital in Germany between June and December 1997. PATIENTS AND PARTICIPANTS: 379 patients were included, most of whom had infectious, gastrointestinal or liver diseases, or sleep apnoea syndrome. Patients admitted because of adverse drug reactions were excluded. METHODS: All automatically generated laboratory signals and reports were evaluated by a team consisting of a clinical pharmacologist, a clinician and a pharmacist for their likelihood of being an adverse drug reaction. They were classified by severity and causality. For verified adverse drug reactions, control patients with similar primary diagnosis, age, gender and time of admission but without adverse drug reactions were matched to the cases in order to assess the excess length of hospitalisation caused by an adverse drug reaction. RESULTS: Adverse drug reactions were detected in 12% of patients by the computer-based monitoring system and stimulated spontaneous reporting together (46 adverse reactions in 45 patients) during 1718 treatment days. Computer-based monitoring identified adverse drug reactions in 34 cases, and stimulated spontaneous reporting in 17 cases. Only 5 adverse drug reactions were detected by both methods. The relative sensitivity of computer-based monitoring was 74% (relative specificity 75%), and that of stimulated spontaneous reporting was 37% (relative specificity 98%). All 3 serious adverse drug reactions were detected by computer-based monitoring, but only 2 out of the 3 were detected by stimulated spontaneous reporting. The percentage of automatically generated laboratory signals associated with an adverse drug reaction (positive predictive value) was 13%. The mean excess length of stay was 3.5 days per adverse drug reaction. 48% of adverse reactions were predictable and detected solely by computer-based monitoring. Therefore, the potential for savings on this ward from the introduction of computer-based monitoring can be calculated as EUR56 200/year ($US59 600/year) [ 1999 values]. CONCLUSION: Computer monitoring is an effective method for improving the detection of adverse drug reactions in inpatients. The excess length of stay and costs caused by adverse drug reactions are substantial and might be considerably reduced by earlier detection.

Adverse Drug Reaction Reporting Systems↗

[Comparison of segmental wall motion in electrocardiogram-gated myocardial scintigraphy and transthoracic echocardiography].

ECG-gated myocardial scintigraphy (Gspect) is a recent method of assessing myocardial perfusion, left ventricular ejection fraction and regional wall motion in a single investigation. It reduces the time required for the evaluation of coronary patients by radionucleide cardiology. Many reports have validated the measurement of the left ventricular ejection fraction compared with other methods. However, there are fewer series reporting the results of regional wall motion. The authors compared segmental wall motion by Gspect after injecting Thallium or Mibi and by transthoracic echocardiography in 47 patients or 423 myocardial segments. The concordance of score (normal, hypokinetic, akinetic, dyskinetic) was 75% (Kappa = 0.538). If analysis was limited to a normal-abnormal differentiation (binary analysis) it increased to 83%. When perfusion was taken into consideration, it was 81% (normal perfusion), 63% (mild hypoperfusion) and 70% (moderate and severe hypoperfusion). This concordance improved in binary analysis respectively to 85, 74 and 86% respectively. When the typs of segment was taken into consideration, concordance varied from 57 to 100%. The concordances were 74% for Thallium and 78% for Mibi scintigraphy, improving to 82% and 85% respectively in binary analysis. Thus, analysis of LV regional wall motion by Gspect is comparable to transthoracic echocardiography. This result, completed by measurement of LV ejection fraction and of myocardial perfusion, provides a method of evaluation of coronary patients in a single investigation.

Aged↗

N-acetylcysteine suppression of the proliferative index in the colon of patients with previous adenomatous colonic polyps.

This investigation is part of an effort to develop chemoprevention for carcinogenesis of the large bowel. The agent investigated is N-acetylcysteine (NAC). We used as a predictive biomarker, the proliferative index (PI), in a short-term human study. Patients with previous adenomatous colonic polyps are a cohort with increased risk for colon cancer and an increased PI of colonic crypts. They were randomly assigned to an experimental group given 800 mg/day of NAC for 12 weeks or a placebo group. Using proliferative cell nuclear antigen immunostaining, the PI of colonic crypts was measured prior to and after the treatments. The PI of the NAC group was decreased significantly (P < 0.02) while the placebo group showed no difference (P > 0.45). Since this decrease in PI may be an indicator of decreased risk of colon cancer, more extensive studies of the potential of NAC as a chemopreventive agent for colon cancer appear warranted.

Acetylcysteine↗

The prebiotic synthesis of modified purines and their potential role in the RNA world.

Modified purines are found in all organisms in the tRNA, rRNA, and even DNA, raising the possibility of an early role for these compounds in the evolution of life. These include N6-methyladenine, 1-methyladenine, N6,N6-dimethyladenine, 1-methylhypoxanthine, 1-methylguanine, and N2-methylguanine. We find that these bases as well as a number of nonbiological modified purines can be synthesized from adenine and guanine by the simple reaction of an amine or an amino group with adenine and guanine under the concentrated conditions of the drying-lagoon or drying-beach model of prebiotic synthesis with yields as high as 50%. These compounds are therefore as prebiotic as adenine and guanine and could have played an important role in the RNA world by providing additional functional groups in ribozymes, especially for the construction of hydrophobic binding pockets.

Adenine↗

Production of guanine from NH(4)CN polymerizations.

The synthesis of adenine from the polymerization of concentrated ammonium cyanide solutions is well known. We show here that guanine is also produced by this reaction but at yields ranging from 10 to 40 times less than that of adenine. This synthesis is effective at both +80 and -20 degrees C. Since high concentrations of NH(4)CN are obtainable only by freezing, this prebiotic synthesis would be applicable to frozen regions of the primitive Earth, the Jovian satellite Europa and other icy satellites, and the parent body of the Murchison meteorite.

Cyanides↗

Computerized surveillance of adverse drug reactions in hospital: implementation.

OBJECTIVE: To implement and measure the effects of automatic computerized laboratory signals (ALS) as a detection support tool of adverse drug reactions (ADRs) in hospital. METHODS: This was a prospective observational study of a total of 192 patients (199 sequential medical admissions) during a 2-month period in a 34-bed medical ward at the Hadassah University Hospital, Jerusalem, Israel. The study involved the routine (daily) distribution to staff physicians of lists of automatic signals generated from computerized laboratory data as potential indicators of ADRs. Patient charts were reviewed by the clinical pharmacology team for ADRs and to see whether these were recognized by the staff physicians. RESULTS: Seventy-one ADRs were detected in 64 of the 199 (32%) admissions. Twenty-seven per cent of the ADRs were serious, 9% of the admissions were due to ADRs. Two hundred and ninety-five ALS were generated involving 69% of the admissions. Sixty-one per cent of the ADRs were identified by ALS. ALS were present in 58% of the ADR negative admissions. Eighty-five per cent of the ADRs were recognized as such and 19% of the ALS-positive ADRs were not recognized by the staff physicians. CONCLUSIONS: The routine implementation of ALS doubled the number of ADRs recognized by the physicians while patients were hospitalized in the medical ward. The use of the system appeared valid, simple and potentially cost-effective.

Adverse Drug Reaction Reporting Systems↗

The effect of short-term dipyrone administration on cyclosporin pharmacokinetics.

BACKGROUND: A large number of drugs have been shown to affect the metabolism of cyclosporin A (CSA) and, since cyclosporin is characterized by a narrow therapeutic range, the consequences of such drug interactions may often be of clinical importance. OBJECTIVE: To evaluate the effect of short-term administration of dipyrone on steady state CSA pharmacokinetics. METHODS: Six kidney- and two heart-transplanted patients on chronic CSA therapy participated in this study, which consisted of two 4-day study periods separated by 3-week washout periods. The patients received, in addition to their usual drugs, dipyrone 500 mg or placebo t.i.d., as identical-looking tablets, and the order of administration was randomized. CSA concentrations were measured in whole blood by means of radio-immunoassay (CYCLO-Trac SP) daily during the study periods and periodically over 24 h on the fourth study day. RESULTS: CSA concentrations over time were reduced after dipyrone (ANOVA, P < 0.01), but statistical significance was noted only at 2, 4, 5 and 10 h after drug intake (P < 0.05). Peak CSA concentration was not altered by dipyrone, but the time required to reach maximal concentration was longer with dipyrone treatment than with the placebo (3.8 +/- 2.6 h vs 2.1 +/- 0.6 h, P < 0.05). No consistent changes were noted for CSA trough level, elimination half-life and area under the concentration-time curve from 0 h to 12 h. Separate analysis of the kidney transplanted patients yielded similar results. CONCLUSIONS: Short-term administration of dipyrone is associated with a mild decrease in CSA blood concentration, which is most prominent in the first few hours after drug intake. In practice, no dose adjustment of CSA seems to be indicated during a short course of dipyrone treatment.

Adult↗

Phenotypic-genotypic analysis of CYP2C19 in the Jewish Israeli population.

OBJECTIVES: Evaluation of CYP2C19 activity and the frequency of CYP2C19 alleles in the Jewish Israeli population. METHODS: One hundred forty Jewish Israeli subjects received 100 mg racemic mephenytoin and collected urine for 8 hours. Urinary concentrations of mephenytoin enantiomers and 4'-hydroxymephenytoin were determined by gas-liquid chromatography and HPLC, respectively. CYP2C19 activity was derived from urinary S/R-ratio and 8-hour urinary excretion of 4'-hydroxymephenytoin. Mutations were identified by polymerase chain reaction and enzyme digestion with SmaI (CYP2C19*2) and BamHI (CYP2C19*3). RESULTS: Deficient mephenytoin hydroxylation was found in 4 subjects (2.9%; 95% confidence interval [CI], 0.1% to 5.7%) who were homozygous for CYP2C19*2. CYP2C19*2 was the major deactivating allele accounting for 15% (95% CI, 11% to 19%) of CYP2C19 alleles, whereas CYP2C19*3 was identified in 2 subjects (1%; 95% CI, 0% to 2%). Among 136 extensive metabolizers, 99 were homozygous for CYP2C19*1 and 37 were compound heterozygous CYP2C19*1/CYP2C19*2 (35 subjects) or CYP2C19*1/CYP2C19*3 (2 subjects). Gene dose effect was noted so that the S/R-ratio was significantly greater and urinary excretion of 4'-hydroxymephenytoin was significantly lower in compound heterozygous than in homozygous extensive metabolizers (0.310+/-0.209 versus 0.225+/-0.176, P < .04 and 48.6%+/-19.2% versus 56.3%+/-16.0%, P < .03, respectively). Female extensive metabolizers had a significantly lower excretion of 4'-hydroxymephenytoin than male extensive metabolizers (49.5%+/-17.6% versus 58.4%+/-16.7%, respectively, P < .005). CONCLUSION: The frequency of poor metabolizers of CYP2C19 and CYP2C19*2 allele in the Jewish Israeli population resembles findings in non-Asian populations. Complete concordance was noted between phenotypic and genotypic findings. CYP2C19 genotyping may enable subclassification of extensive metabolizers into subjects with high and low activity.

Adult↗

Anti-glomerular basement membrane glomerulonephritis after extracorporeal shock wave lithotripsy.

Extracorporeal shock wave lithotripsy (ESWL) is a common noninvasive procedure for removal of upper urinary tract stones. We present a case of a man who developed anti-glomerular basement membrane (anti-GBM) disease after ESWL and review the two other cases described in the medical literature. In all cases, the affected individuals expressed the HLA DR2/HLA DR15 major histocompatibility antigen and developed a rapidly progressive anti-GBM-induced glomerulonephritis 3 to 7 months after ESWL. Anti-GBM disease may be a rare complication of ESWL in susceptible individuals and should be considered in patients who develop acute renal failure after lithotripsy.

Acute Kidney Injury↗

Treatment of autoimmune blistering diseases.

The treatment of autoimmune blistering diseases remains therapeutically challenging. Significant improvement in the management of autoimmune bullous diseases has occurred as a consequence of improvements in our ability to predict, monitor, and treat the deleterious effects associated with the drugs used to treat these conditions and the introduction of new agents with lower toxicity. Examples include improvements in monitoring and preventing osteoporosis in patients on long-term systemic corticosteroids, the detection of those at risk for azathioprine toxicity bowing to low thiopurine methyltransferase activity, and the addition of agents such as mycophenolate mofetil and IVIG to our therapeutic armamentarium. These advances offer the promise of improved disease control with fewer side-effects and long-term toxicity for our patients.

Anti-Inflammatory Agents↗

Complete removal of nonpalpable breast malignancies with a stereotactic percutaneous vacuum-assisted biopsy instrument.

BACKGROUND: Several devices have been developed for sampling nonpalpable mammographic breast lesions. Complete removal of malignancies with a stereotactic percutaneous directional vacuum-assisted biopsy instrument has been reported. STUDY DESIGN: We reviewed our experience with the percutaneous vacuum-assisted biopsy instrument to identify instances of complete excision of cancers: no residual carcinoma found at surgical excision for malignancies diagnosed by the percutaneous vacuum-assisted biopsy instrument. The radiologic and pathologic characteristics of malignancies completely removed by the percutaneous vacuum-assisted biopsy instrument were compared with those of malignancies with residual carcinoma found at surgical excision. RESULTS: Fifty-two malignancies were diagnosed by the percutaneous vacuum-assisted biopsy instrument: 16 infiltrating ductal carcinomas, 5 infiltrating lobular carcinomas, and 31 ductal carcinomas in situ. No residual carcinoma was found at surgical excision in 9 (17%) of the 52 malignancies. Patients with complete removal of the malignant lesion were younger than patients with incomplete removal (52 versus 58 years; p = 0.069). Completely removed malignancies were smaller on mammography (4 versus 17 mm; p = 0.213), and more specimens were removed (19 versus 15; p = 0.074). All nine completely removed malignancies presented with calcifications without a mass (p = 0.112), and all nine were ductal carcinoma in situ (p = 0.019). CONCLUSIONS: Complete removal of nonpalpable breast malignancies is possible with the stereotactic percutaneous directional vacuum-assisted biopsy device. Complete removal is more likely with removal of a large number of specimens from small areas of mammographic calcifications due to ductal carcinoma in situ.

Biopsy↗