Human selenium status and glutathione peroxidase activity in north-west England

Nutritional selenium deficiency disease, due to low soil selenium content, is well recognized in British livestock. The adequacy of the selenium status of 25 healthy human volunteers, 50 blood donors, 94 general medical patients and 106 allergy clinic patients was investigated in 1987/8 by measuring serum selenium concentration and platelet glutathione peroxidase activity. Mean serum selenium concentration for the entire study population was 92 micrograms/l. Significant linear correlations between serum selenium concentration and peroxidase activity indicate that a substantial proportion of both healthy volunteers and medical patients are of low selenium nutritional status. Twenty-five per cent of healthy volunteers and 50 per cent of medical patients had serum selenium values below those required for full expression of selenium-dependent enzyme activity. Deficiency of the antioxidant activities of selenium and selenium-dependent enzymes may be relevant to geographical differences in morbidity from a wide range of human disease states.     

Microbiological and pharmacokinetic studies of acyl demycinosyltylosin and related tylosin derivatives

A series of tylosins and acyl derivatives of 23-O-demycinosyltylosin (DMT) were initially tested for in vitro antibacterial activity and serum levels in squirrel monkeys (po) and mice (iv). Overall, the DMT compounds were more active in vitro than the tylosins. Two tetraacylated DMTs, Sch 37644 and Sch 38646, were selected from the initial studies for further evaluation and compared to erythromycin and A-56268 (6-O-methyl erythromycin). Sch 37644 and Sch 38646 were 2 to 8-fold less potent in vitro against Gram-positive bacteria than erythromycin and A-56268. In squirrel monkeys, Sch 37644 (AUC, 19.7 micrograms.hour ml) and A-56268 (21.6 micrograms.hour/ml) had similar serum levels following po administration of 20 mg/kg, while Sch 38646 (11.8 micrograms.hour/ml) and erythromycin (1.5 micrograms.hour/ml) had lower levels. In mice administered 200 mg/kg orally, Sch 37644 (AUC, 19.4 micrograms.hour/ml) and Sch 38646 (15.4 micrograms.hour/ml) had higher serum levels than erythromycin (5.7 micrograms.hour/ml). A-56268 was the most active po macrolide in mouse protection studies (PD50S) against Staphylococci and Streptococci, while Sch 37644 and Sch 38646 were similar to erythromycin.     

Preventive care for patients following myocardial infarction. The Wessex Research Network (WReN)

OBJECTIVE: We aimed to assess general practice care for patients following a myocardial infarction (MI). METHOD: A structured review was carried out of general practice records of patients identified from hospital administration data. A total of 266 survivors following MI were identified from the discharge data of 13 hospitals in Southern England and registered with 71 GPs belonging to the Wessex Research Network. Median time since hospital discharge was 2.1 years. The main outcome measures were the provision of appropriate preventive care, including cardiac rehabilitation, drug therapy, and lifestyle advice for modifiable risk factors. RESULTS: Basic care was provided to nearly all patients; 253 (95.1%, 95% Cl 91.8-97.4) had blood pressure documented after their MI, 216 of 234 patients eligible for aspirin (92.3%; 88.1-95.4) had been recommended treatment, and the provision of advice on smoking cessation was documented for 27 of 33 continuing smokers (81.8%; 64.5-93.0). However, only 73 of 236 patients eligible to attend a structured rehabilitation programme (30.9%; 25.0-36.8) were documented as having received rehabilitation. Of 89 patients with heart failure following MI, 33 (37.1%; 27.1-48.0) had no record of having been offered treatment with an ACE inhibitor. Total cholesterol measurement was documented for only 144 patients (54.1%; 48.1-60.1). We estimate that there is still the potential to prevent between 4 and 9 deaths in this group of 266 surviving patients in the next 2 years by further improving the quality of follow-up care. CONCLUSIONS: Preventive care in patients with proven ischaemic heart disease in general practice remains haphazard, even among doctors enthusiastic to participate in research and to audit their quality of care. As general practitioners we should ensure that we are providing high quality preventive care to patients with clinical disease before we focus on the even more demanding task of primary prevention.      

Albuterol Delivery by Metered-Dose Inhaler With a Pediatric Mechanical Ventilatory Circuit Model

Study Objective . To determine albuterol delivery by metered-dose inhaler (MDI) in an in vitro pediatric mechanical ventilatory circuit model. The influence of a spacing device, endotracheal tube (ETT) diameter and length, and air humidity was also investigated. Design . An albuterol MDI canister was connected to an AeroVent spacer or Airlife MDI adapter and ETT 4.0, 5.0, or 6.0 mm at commercially available and equal lengths. The ETT tip was attached to an in-line filter holder with a 1-μm type A/E glass fiber filter. Ventilator settings were fractional concentration of inspired oxygen 50%, tidal volume 250 ml, inspiratory:expiratory (I:E) ratio 1:3, rate 25 breaths/minute, temperature 35°C, and a decelerating flow pattern. Ten albuterol canisters were activated two times each (total 2000 μg) into dry (4.0-, 5.0-, and 6.0-mm ETT) and humidified air (4.0- and 6.0-mm ETT) and repeated in triplicate. Percentage MDI output was determined by weighing the filter before and after drug administration (balance sensitivity 10 μg). Significant differences (p≤0.05) among the groups with and without a spacer and in dry and humidified air were determined by ANOVA with Scheffe's multiple comparison test. Multiple regression was used to determine significant associations between ETT diameter and length and delivery. Main Results . With the AeroVent spacer in humidified air, delivery with the 4.0- and 6.0-mm ETT was approximately 2.3% and 5%, respectively. The spacer and dry air significantly improved delivery. Conclusions . In humidified air, the dose of albuterol by MDI with an AeroVent spacer should be doubled for children intubated with 6.0-mm ETT, and four puffs administered for every one puff desired for 4.0-mm ETT. The results of this investigation should prove useful in initial clinical trials of albuterol MDI in ventilator-dependent infants and children.     

Encrustation of intraprostatic stents--a comparative study.

Metallic stents have been used in the management of prostatic disease in patients unfit for surgery. A variety of stents have become available but the optimum design and metal of construction has not yet been defined. This study examined one of the potential complications of stent insertion by demonstrating that they are susceptible to encrustation. Using an in vitro model it compares the ability of the different materials used in their construction to resist this encrustation. Titanium appears less able to resist deposition than the other metals examined. The long-term complication of encrustation may inhibit the use of some of these stents.     

AIDS and tuberculosis

The diagnostic and therapeutic implications of human immunodeficiency virus (HIV) infection and tuberculosis in South Africa, where tuberculosis remains a major health problem, are reviewed. Mycobacterium tuberculosis is a high-grade pathogen and is able to establish infection early in immunodeficiency. With HIV infection showing significant entry into the heterosexual population in the RSA, an increasing number of cases with both infections can be expected to occur. The radiological appearance in combined infection is variable, ranging from a formal cavitatory picture to the more common finding of diffuse pulmonary infiltration. Intrathoracic adenopathy is a more specific sign of tuberculosis in HIV infection, since it is not associated with persistent generalised lymphadenopathy and pulmonary opportunistic infections, such as Pneumocystis carinii pneumonia. Intercurrent pneumonic infections and other pulmonary manifestations of HIV disease render the interpretation of new infiltrates on chest radiography problematical. Tuberculin skin testing remains useful in HIV infection and should be performed in all HIV-infected patients. The value of tuberculosis serology still remains questionable. Standard antituberculosis drug regimens are effective, but maintenance treatment must be continued for life and should include isoniazid and rifampicin. BCG vaccination is recommended routinely at birth in infants with HIV infection and for asymptomatic HIV-infected individuals who have not previously been immunised.     

Simultaneous assay of felbamate plus carbamazepine, phenytoin, and their metabolites by liquid chromatography with mobile phase optimization

Felbamate is an investigational antiepileptic drug (AED) in clinical trials. A high-performance liquid chromatographic method for the simultaneous analysis of felbamate, phenytoin (PHT), 5-(p-hydroxyphenyl)-5-phenylhydantoin, carbamazepine (CBZ), carbamazepine-10,11-epoxide, and carbamazepine-10,11-diol in serum was developed by a mobile phase optimization technique. Capacity factors for the compounds of interest and 12 other AEDs and metabolites were determined with mixtures of methanol, acetonitrile, or tetrahydrofuran and a 0.01 M ammonium phosphate buffer, pH 6.5, on a reversed-phase C8 column. An optimized mobile phase composition was determined that could separate the compounds of interest and three internal standards in less than 15 min. Serum was extracted with CH2Cl2/ethyl acetate (2:1) after addition of three internal standards. The method was validated for within-day and between-day precision and accuracy for the six compounds. Coefficients of variation were generally less than 10% at all concentrations and less than 5% in the typical therapeutic range for each compound. The lower limit of detection was estimated at 0.2 micrograms/ml for CBZ and its metabolites and 0.5 micrograms/ml for felbamate and PHT. For felbamate, the lowest point on the standard curve was 1.88 micrograms/ml with a between-day variability of 10.3%. The assay was used to determine the serum concentrations of PHT and CBZ and its metabolites in a subject before, during, and after felbamate therapy.     

Granulomatous Pneumocystis carinii pneumonia in a patient with the acquired immunodeficiency syndrome.

A patient with an unusual granulomatous response to infection with Pneumocystis carinii is described. The diagnosis was made by open lung biopsy after two negative bronchoalveolar lavages.