Risk Factors in the Use of Benzodiazepines

Gené-Badia J, Blay-Pueyo C and Soler-Vila M. Risk factorsin the use of benzodiazepines. Family Practice 1988; 5: 283–288. A case-control study was carried out on 107 benzodiazepine usersand 214 controls not treated with anxiolytic-hypnotic agents,chosen randomly and matched two to one for each case by age,sex and family doctor. The users presented a higher degree ofpsychic disorder than the controls, with depression, interpersonalsensitivity, and the total number of symptoms being the elementsdistinguishing the two groups. We have found two factors thatput the population at large at risk for using benzodiazepines;the family doctor's diagnosis of a mental disorder in the clinicalhistory and the daily use of drugs other than benzodiazepinesexplained the risk independently. The presence of chronic disorders,especially cardiological and musculoskeletal disorders, alsoshowed a significant risk, but were only explained by theirclose association with one of the first two factors. It is postulatedthat general practitioners, who are the principal prescribersof drugs, are causing over-medication in the population.     

Do Electrode and Lead Design Differences for Permanent Cardiac Pacing Translate into Clinically Demonstrable Differences? (Comparison of Sintered Platinum and Activated Vitreous and Porous Carbon Electrodes)

A randomized prospective study was undertaken to compare the electrical performances of three permanent, endocardial, tined pacing leads with different electrode designs--sintered platinum, vitreous carbon, and porous carbon. Ninety-nine patients received one of the leads (S80 31; 423S 32; S100 36). Acute R wave amplitude and ST elevation of the native endocardial electrogram, voltage threshold, impedance, and current flow at four pulse durations (0.25-1.0 msec) were measured. Voltage thresholds were measured noninvasively at each of four pulse durations at 2 days and 1, 3, and 6 months after implantation. No significant differences were found in sensing properties, or current flow at threshold at 0.5 msec pulse duration. The 423S lead had a significantly higher impedance at threshold and both a higher impedance and lower current flow at 5 V. No significant differences in threshold voltages were found between the three leads at any pulse duration, at any of the assessed times after implantation. Six-month thresholds for the S80, 423S, and S100 leads were 1.18 +/- 0.35, 1.17 +/- 0.29, and 1.06 +/- 0.38 V respectively at 0.5 msec pulse duration. Differences between 'high performance' pacing leads need to be of a greater order of magnitude before they can be exploited to give any real clinical advantage to patients.     

Acoustic rhinometry compared with anterior rhinomanometry in the assessment of the response to nasal allergen challenge

Acoustic rhinometry was used to assess nasal airway patency objectively and was compared with the more established method of anterior rhinomanometry. Ten patients with allergic rhinitis underwent 15 nasal challenges with allergen to which they showed positive skin-prick tests. Responses were assessed by measuring the minimum nasal cross-sectional area (Amin.) using acoustic rhinometry and by measuring nasal airway resistance (NAR) using anterior rhinomanometry. The measurements of Amin. and NAR showed a significant negative correlation. Acoustic rhinometry appears to be superior to anterior rhinomanometry in quantifying the response to nasal allergen challenge and may be particularly useful in patients with initial nasal blockage.     

Polychlorinated Biphenyl Congeners in Adipose Tissue Lipid and Serum of Past and Present Transformer Repair Workers and a Comparison Group

Polychlorinated Biphenyl Congeners in Adipose Tissue Lipid andSerum of Past and Present Transformer Repair Workers and a ComparisonGroup. FAIT, A., GROSSMAN, E., SELF, S., JEFFRIES, J., PELLIZZARI,E. D., AND EMMETT, E. A. (1989). Fundam. Appl. Toxicol 12, 42-55. The concentrations of individual PCB's were determined inboth serum and adipose tissue lipid from 35 transformer repairworkers currently exposed to PCBs, mainly Aroclor 1260, 17 previoustransformer repair workers, and 56 comparison workers neveroccupationally exposed to PCBs. The analysis used fused-silicacapillary gas chromatography with electron capture detector(FSCGC/ECD) and FSCGC with negative ion chemical ionizationmass spectrometry to verify PCB congener levels. Eighty-ninePCB peaks were identified and confirmed. More congeners weredetected in adipose tissue. In serum approximately 50% of peakswere below the level of detection. Statistical techniques toaccount for left and interval censoring allowed comparison ofconcentration distributions even where data were incomplete.We found that unquantifiable levels were unlikely to contributesubstantially to the true values for total [PCBs] over and beyondthe contribution of the measured values. However, the totalserum [PCBs] determined by FSCGC/ECD greatly exceeded that fromstandard packed cell gas chromatography (PCGC/ECD). The underestimationwas less marked for adipose samples. In serum the total [PCBs]was highest in currently exposed workers and lowest in unexposedworkers, with past-exposed workers clearly intermediate. Inadipose tissue [PCBs] in the currently exposed group was muchhigher than in the other two groups, in whom the distributionof results was broadly similar. In all worker groups hexachlorinatedand heptachlorinated species predominated followed by octachlorinatedand pentachlorinated. The relative distribution of individualPCB congeners in the three groups was similar although the amountsvaried. The seven major peaks in serum and adipose tissue were2,3,5,6,3',4',5'/2,3,4,5,2',4',5' hepta-CB; 2,3,4,2',3',5' hexa-CB;2,4,6,3',4',5'/ 2,4,5,2',4',5'/2,3,4,5,2',5' hexa-CB; 2,3,4,5,2',3',4'hepta-CB; 2,3,4,5,2',3',5',6'/2,3,4,5,6,2',3',5', octa-CB; 2,4,5,3',4',/3,4,5,2',3'penta-CB; and 2,3,4,2',3',4'/2,3,5,6,2',4',5'/2,3,4,5,2',4',6'multi-CB. The distribution of PCB peaks in our populations differsfrom that in capacitor workers (exposed to less highly chlorinatedPCBs) and from Yu-Cheng patients suggesting differing toxicpotentials from PCBs in these three circumstances.     

GENETIC POLYMORPHISM OF LIVER ALCOHOL DEHYDROGENASE IN SPANTSH SUBJECTS: SIGNIFICANCE OF ALCOHOL CONSUMPTION AND LIVER DISEASE

Class I alcohol dehydrogenase (ADH) phenotypes have been studiedby starch gel electrophoresis and activity analysis in livertissue obtained at necropsy from 61 non-alcoholic subjects withnormal liver (controls), and in biopsies from 60 chronic alcoholicswith liver disease and from 24 subjects with non-alcoholic liverdisease. Twenty-three per cent of controls exhibited the ADH₂^2–1phenotype, which represents the highest frequency for atypicalADH found in a Caucasian population. Both alcoholic and non-alcoholicpatients with liver disease showed a lower frequency of theatypical phenotype (6.6% and 8.8%, respectively). No differencesin the ADH₂ locus were detected among groups of patients withdifferent severity of alcoholic and non-alcoholic liver disease.Theallele frequencies of the ADH₃ locus for the controls (ADH₃¹= 0.63, ADH₃² = 0.37) are common to those of other Caucasianpopulations. Similar ADH₃ allele frequencies were observed inpatients with alcoholic and non-alcoholic liver disease. Discrepanciesbetween the various phenotyping and genotyping studies now knownfor several populations suggest that local differences may existin the distribution of the ADH polymorphism in even geographicallyclose regions, and that the effect of ADH polymorphism on vulnerabilitytowards alcohol may not be identical in different populations.     

1-Aminobenzotriazole-Induced Destruction of Hepatic and Renal Cytochromes P450 in Male Sprague-Dawley Rats

1-Aminobenzotriazole (ABT) is a suicide substrate of both hepaticand pulmonary cytochromes P450. The present studies were designedto compare the effects of ABT on hepatic and renal metabolism.Hepatic and renal microsomes and cytosol were prepared frommale Sprague-Dawley rats following ABT pretreatment (0–100mg/kg ip) for various times. Administration of 100 mg ABT/kgproduced profound reductions in P450 content in both liver andkidney within 2 hr; loss of P450 in both tissues persisted forat least 48 hours. ABT-induced destruction of P450 was dose-dependent.Maximal destruction of about 80% of total hepatic P450 occurredat dosages of ABT equal to or greater than 10 mg/kg. Maximaldestruction of about 80% of total renal P450 occurred at dosagesof ABT equal to or greater than 50 mg/kg. In vitro, ABT rapidlyand efficiently destroyed P450 in both hepatic and renal microsomesprepared from naive male Sprague-Dawley rats. Incubation ofhepatic or renal microsomes in vitro with ABT produced detectabledestruction of P450 within 5 min. Maximal destruction of P450occurred within 10 min in both hepatic and renal microsomesduring in vitro incubation with ABT. ABT-induced destructionof P450 in vitro was concentration-dependent. For hepatic microsomes,maximal destruction of about 70% of P450 required concentrationsof ABT equal to or greater than 10 mM. For renal microsomes,maximal destruction of about 80% of P450 required concentrationsof ABT equal to or greater than 10 mM. In both liver and kidney,only P450 content and P450-dependent activities were significantlydecreased. Cytochrome b₅, NADPH cytochrome c reductase, glutathioneS-transferase, glucuronyl transferase, and reduced glutathionecontents were unaltered. These data suggest that ABT selectivelyand effectively destroys both hepatic and renal P450. ABT maybe a useful tool to probe the potential role of P450 in thebioactivation of certain compounds.     

A Histochemical Method for Sulfatase Activity in Hemic Cells and Organ Imprints

1. A new histochemical method is described for arylsulfatase activity (ASA)in hemic cells and organ imprints. Some common limitations in histochemicaltechnics have been tested and appear to be minimized in this method.

2. With the present method, a wide series of hemic cells may be identified,and their ASA separately graded from 0-4.

3. A study has been made of normal ASA values in all series of humanhematopoietic cells and of neutrophilic granulocyte ASA in common laboratory animals. Eosinophils, megakaryocytes, and neutrophils have the highestASA. Increases in ASA occur early during cell maturation in neutrophils andeosinophils.

4. Humans have a higher ASA than the laboratory animals tested. Withincertain species, there is some general correlation between neutrophilic granulocyte ASA and ASA of other organs. Under these conditions, leukocyte ASAis a potentially useful general screening method for ASA.

5. Some factors which enhance or inhibit leukocyte ASA have been tested.

Submitted on August 15, 1960 Accepted on November 5, 1960