Chromosomal aberrations and micronucleus frequency in nurses occupationally exposed to cytotoxic drugs

In this study, we evaluated the effect of low level occupationalexposure of nurses in a medical oncology unit in Cairo, Egypt,to anticancer drugs. Twenty nurses who constantly handled thesedrugs and 20 controls, matched according to age and sex, wereexamined. Metaphase chromosomes were studied. Percentages ofmetaphases with chromosomal aberrations were significantly higher(P < 0.001) in the exposed group (6.1 ± 2.7) versusthe controls (2.6 ± 1.6). The detected chromosomal aberrationswere in the form of chromatid gaps, chromatid breaks and acentricfragments. Micronucleated peripheral blood lymphocytes werealso analyzed in cytochalasin B treated binucleated lymphocytes.There was significant increase in cells with micronuclei (P< 0.001) in nurses (10.05 ± 4.71) in comparison tothe matched control (5.42 ± 2.22) (P < 0.001). Nursesexposed to the cytotoxic drugs for     

Studies of the autoxidation of phenols catalyzed by the cobalt(II) complex of disodium N,N′-bis(salicylidene)-ethylenediamine-5,5′ -disulfonate bound to colloidal anion exchange resin

To overcome mass transfer limitations which are usually encountered on immobilizing active catalysts, cationic latex particles were used as support for the cobalt(II) complex of disodium N,N′-bis(salicylidene)ethylenediamine-5,5′-disulfonate ( 1 ). The cationic latex 2 was prepared by emulsion copolymerization of chloromethylstyrene (m/p-isomer mixture 60/40) and divinylbenzene (m/p-isomer mixture) followed by treatment with trimethylamine. The latexbound catalyst from 1 and 2 was found to considerably increase the reaction rate of the autoxidation of 2,6-di-tert-butylphenol in water as compared with the conventional polymer-free system. Reaction products were identified as the oxidative coupling product 3,3′,5,5′-tetra-tert-butyldiphenoquinone (3,3′,5,5′-tetra-tert-butyl-4,4′-dioxo-1,1′-bicyclohexa-2,5-dienylidene) and 2,6-di-tert-butyl-1,4-benzoquinone. All reactions showed an induction period before the start of dioxygen consumption. The rate of autoxidation in the three-phase mixtures of water, latex particles, and phenol droplets was not affected significantly by the method of mixing. The reaction rate increased as the concentration of 1 increased. Increasing the partial pressure of dioxygen in the range between 0,25 and 1,0 atm (2,53. 10⁴ – 1,01. 10⁵ Pa) gave a small increase in rate. The colloidal latex catalyst from 1 and 2 showed some loss of activity after successive runs.     

Biochemical characterization of a novel extended-spectrum beta-lactamase from Pseudomonas aeruginosa 802

Pseudomonas aeruginosa 802 was isolated at Rabta hospital in Tunis and was resistant to extended-spectrum cephalosporins and aztreonam. It produced a pI 7.6 extended-spectrum beta-lactamase (ESBL). The ESBL, named LBT 802, was purified to homogeneity by filtration on Sephadex G-75 followed by CM-Sepharose chromatography and high-performance liquid chromatography (HPLC) on a TSK-gel SP-5PW column. The LBT 802 enzyme had a molecular mass of 30 kDa. It showed a broad-substrate profile by hydrolyzing benzylpenicillin, ampicillin, cephalothin, cephaloridine, cefotaxime, ceftriaxone, and cefpirome but not ceftazidime, cefoxitin, imipenem, or aztreonam. The highest hydrolytic efficiency (Vmax/Km) was obtained for ampicillin, cephalothin, cephaloridine, and benzylpenicillin. Among extended-spectrum cephalosporins the best substrate was ceftriaxone followed by cefotaxime and cefpirome. LBT 802 activity was inhibited by clavulanic acid, sulbactam, imipenem, cefoxitin, and aztreonam. It showed its lowest Ki values for clavulanic acid, imipenem and sulbactam.     

Combined effect of Controlling Nutritional Status and Acute Kidney Injury on severe COVID-19 short-term outcomes

Introduction/ObjectivesAcute kidney injury (AKI) and malnutrition are two complications commonly reported in severe forms of COVID-19, their combined effect on short-term mortality is, however, not yet investigated. The objective of this study is to determine both their individual and combined effects on short-term prognosis.Materials and methodsThis is a prospective, uni-centric study, including 247 severe COVID-19 patients, admitted between April 25th and June 20th, 2020, at the University Hospital of Blida. AKI was defined according to the KDIGO-2012 guidelines. Nutritional status was assessed using the Controlling Nutritional Status (CONUT) score. The association with in-hospital mortality was assessed using the Kaplan-Meier method and proportional Cox regression.ResultsAmong the 247 severely affected COVID-19 patients included in this study, 34.4% developed AKI, 30.4 and 1.2%, respectively, had moderate and severe CONUT scores, 17.7% worsened and progressed to a critical state and 26.7% did not survive. Both AKI and CONUT score were significantly associated with mortality in a dose-response manner (pLog-Rank < 0.0001). Their relative risks are respectively (HR = 3.25 CI 95% [1.99–5.3] and HR = 2.42 CI 95% [1.5–3.9], p < 0.0001). In multivariate analysis, the highest risk was observed for the AKI-CONUT-high combination (HR = 3.0, 95% CI [1.5–6.1], p = 0.002).ConclusionA possible synergistic interaction between AKI and CONUT score for COVID-19 short-term mortality has been highlighted. Monitoring of renal function associated with assessment of nutritional status should be performed routinely and systematically from the early stages of admission.     

Bromazepam in generalized anxiety

Bromazepam was compared with placebo and with chlorprothixene in a randomized, double-blind group-comparative multicenter trial in general practice. Two hundred and forty-five patients with generalized anxiety disorder (DSM-III 1980) were treated for 2 weeks with two daily doses of bromazepam, 3 mg or chlorprothixene, 15 mg or placebo. Median reductions in Hamilton Anxiety rating were 12 (bromazepam), 10.3 (chlorprothixene) and 7.3 (placebo). The study revealed significant superiority of bromazepam over placebo (median differences 3.3, 95% confidence limits: 0.3 and 6.1) but not over chlorprothixene (median difference 1.4, 95% confidence limits –0.8 and +3.5). Significantly higher rates of tiredness, sedation and hypersomnia were found on bromazepam and chlorprothixene compared to placebo. Tolerance was rated as at least good in 85.6% on bromazepam, in 86% on chlorprothixene and in 87.8% on placebo. Neither previous psychopharmacological treatment nor presence of psychosocial stress were of perceptible influence. Bromazepam and chlorprothixene are both superior to placebo in generalized anxiety states treated in general practice, but spontaneous improvements/placebo effects are substantial.General practice The following general practitioners are gratefully acknowledged for their excellent co-operation: K. Andreasen (Grenaa), T. Andreasen (Helsingoer), C. Bjerre-Christensen (Viby J), J. Brix (Aabenraa), N.B. Caning (Stokkemarke), N. Christensen (Odense), P. Dehn-Jensen (Lyngby), J. Eggert (Langebaek), H. Fuglsang-Damgaard (Havndal), I. Fraemohs (Allingaabro), J. Gylling (Nykoebing Sjaelland), E. Halkjaer-Soerensen (Roedding), B. Hansson (Frederiksvaerk), C. Hauge (Espergaerde), S. Hede (Aalborg), G. Jensen (Copenhagen S), T. Knudsen (Arden), P. Kofod (Vejle), K. Kraen (Varde), V. Lade (Hjoerring), S. Mehlsen (Auning), J. Meyer-Christensen (Hobro), R. Michael (Langebaek), J. Munch (Oersted), L. Moeller-Hansen (Alleroed), U. Moeller (Graasten), K. Nielsen (Malling), S. Kjaerem Nielsen (Copenhagen), P.V. Nielsen (Odense), J. Peulicke (Espergaerde), O. Ravn (Roedding), C.U. Rosenberg (Aarhus), J. Rude (Goerlev), S. Spangsberg (Holbaek), H. Soegaard (Oelgod), O. Tang (Hoersholm)     

Cyclosporin A drug interactions. Screening for inducers and inhibitors of cytochrome P-450 (cyclosporin A oxidase) in primary cultures of human hepatocytes and in liver microsomes

In previous papers we demonstrated that cyclosporin A (CsA) was specifically oxidized in rabbit and human liver by cytochrome P-450IIIA. We therefore anticipated that any drug that is an inducer or an inhibitor of this cytochrome should lead to interaction with CsA when given in association with it. In order to confirm this hypothesis, primary cultures of human hepatocytes and human liver microsomes were used to "reproduce" in vitro clinically significant interactions observed between CsA and drugs known either as specific inducers (i.e., rifampicin) or as specific inhibitors (i.e., erythromycin) of P-450IIIA. Our results were in close agreement with the clinical reports. Human hepatocytes maintained in primary cultures for 72 hr in the presence of 50 microM rifampicin exhibited increased levels of P-450IIIA, determined by Western blot using specific antibodies, and concomitant increase in CsA oxidase activity, determined by HPLC analysis of extra and intracellular media. Conversely, these cultures exhibited erythromycin concentration-dependent decreases in CsA oxidase activity when incubated in the presence of 5, 20, and 100 microM erythromycin. In addition, a Lineweaver-Burk analysis of the erythromycin-mediated inhibition of CsA oxidase activity in human liver microsomes revealed competitive inhibition (with Ki of 75 microM) as expected, this macrolide being a specific substrate of P-450IIIA. Using this experimental approach, 59 molecules representative of 17 different therapeutic classes were screened for inducers and inhibitors of CsA oxidase activity. Our results allowed us to elucidate the molecular mechanism of previously observed, but unexplained, drug interactions involving CsA, and to detect drugs that should interfere with CsA metabolism as inducers or inhibitors. Drugs detected as potential inducers of CsA oxidase included: rifampicin, sulfadimidine, phenobarbital, phenytoin, phenylbutazone, dexamethasone, sulfinpyrazone, and carbamazepine. Drugs detected as potential competitive inhibitors included: triacetyloleandomycin, erythromycin, josamycin, midecamycin, ketoconazole, miconazole, midazolam, nifedipin, diltiazem, verapamil, nicardipine, ergotamine, dihydroergotamine, glibenclamide, bromocriptine, ethynylestradiol, progesterone, cortisol, prednisone, prednisolone, and methylprednisolone. Finally, cefoperazone, cefotaxime, ceftazidime, isoniazide, doxycycline, spiramycin, sulfamethoxazole, norfloxacin, pefloxacin, vancocin, trimethoprim, amphotericin B, valproic acid, quinidine, cimetidine, ranitidine, omeprazole, diclofenac, aspirin, paracetamol, debrisoquine, guanoxan, captopril, furosemide, acetazolamide, sparteine, gliclazide, and imipramine were found not to interfere with the hepatic metabolism of CsA.     

Enteral nutrition in intensive care patients: a practical approach.

Severe protein-calorie malnutrition is a major problem in many intensive care (ICU) patients, due to the increased catabolic state often associated with acute severe illness and the frequent presence of prior chronic wasting conditions. Nutritional support is thus an important part of these patient's management. Over the years, enteral nutrition (EN) has gained considerable popularity, due to its favorable effects on the digestive tract and its lower cost and rate of complications compared to parenteral nutrition. However, clinicians caring for ICU patients are often faced with contradictory data and difficult decision-making when having to determine the optimal timing and modalities of EN administration, estimation of patient requirements and choice of formulas. The purpose of this paper is to provide practical guidelines on these various aspects of enteral nutritional support, based on presently available evidence.     

Energy expenditure in anorexia nervosa: can fat-free mass as measured by bioelectrical impedance predict energy expenditure in hospitalized patients?

Anorexia nervosa (AN) is associated with a reduced metabolically active fat-free mass (FFM) and basal metabolic rate (BMR). Excessive refeeding results in major fat deposition which is not well tolerated by patients. Prediction of BMR is, therefore, a clinical issue during refeeding, but measurement by indirect calorimetry is time-consuming and not widely available. The study aim was to determine if and when BMR could be estimated from prediction formulas based on FFM derived from bioelectrical impedance analysis (BIA) in AN patients during refeeding. Indirect calorimetry and BIA were prospectively measured bi-weekly in 9 AN patients (body mass index 13.7 +/- 0.5 kg/m2) for 10 weeks of refeeding. Initial BMR was 969 +/- 46.7 kcal/d and 27.7 +/- 1.4 kcal/kg FFM, and at week 10 increased to 1360 +/- 44.6 kcal/d and 35.8 +/- 0.8 kcal/kg FFM. While correlations improved with increasing weight, FFM and body mass index, prediction formulas are insufficient to permit prediction of BMR based on weight or FFM, even after 10 weeks of refeeding. To allow for optimal nutritional support, indirect calorimetry measurements may be useful in the early weeks of refeeding because of a large variability of basal metabolic rate between patients.     

Acute myocardial infarction with normal coronary arteries. In vivo demonstration of coronary thrombosis during the acute episode

Two cases with acute myocardial infarction are presented. Both had thrombotic occlusion of the infarct-related artery. Following successful thrombolysis with streptokinase, coronary angiography was normal. These cases prove that "myocardial infarction with normal coronaries" can be associated with coronary thrombosis in the acute stage.