Unchanged acetylation of isoniazid by alcohol intake.

SETTING: In 10 healthy subjects, the influence of acute alcohol intake on the pharmacokinetics of isoniazid (INH) was studied. OBJECTIVE: To test the hypothesis that alcohol increases the conversion of INH by acetylation into its metabolite acetylisoniazid. DESIGN: In a crossover design, an oral dose of 300 mg INH was administered on 2 separate days, 14 days apart, with or without alcohol to a serum alcohol of about 21 mmol/l (1 g/l) maintained for 12 h. RESULTS: Neither the metabolism of INH nor that of acetylisoniazid was changed by acute alcohol intake. CONCLUSION: Acute alcohol intake has no impact on the conversion of INH to its metabolite acetylisoniazid, which is catalysed by the enzyme N-acetyltranferase. Accordingly, a metabolic effect of acute alcohol intake on INH metabolism probably contributes little to the therapeutic failure of anti-tuberculosis treatment among alcoholics.     

Imaging of thoracic aortic dissection

Acute thoracic aortic dissection has a high mortality if untreated, so the diagnosis must be rapidly made if mortality is to be lowered significantly. Multiple imaging techniques are often used. This retrospective study from 1988 to 1993 assesses the usefulness in diagnosis of chest X-rays, computed tomography (CT) scanning, aortography, magnetic resonance imaging (MRI), trans-thoracic (TTE) and trans-oesophageal (TOE) echocardiography. Forty-two patients with a final clinical diagnosis of dissection were studied. The diagnosis was confirmed in 16 (13 at surgery and three at autopsy). Three died with dissection given as the only cause for death. Chest X-ray abnormalities were seen in all 19 patients with surgery or death from dissection, with a widened mediastinum and/or dilated aorta being present in 17. In the group of 16 patients with surgery or autopsy proof, CT scans found dissections in 9 of 12 patients studied and correctly classified the type in only five. Aortography was performed in five, with accurate depiction of dissection and type in all. TTE found dissections in three of eight patients imaged by this method. MRI and TOE were performed each on two patients, with accurate depiction of dissection and type in each. Because of the relatively low sensitivity of CT scanning in defining aortic dissections Westmead Hospital is currently assessing the use of TOE as the prime imaging modality prior to surgical intervention.     

Interobserver variation in the evaluation of neurological signs: observer dependent factors.

Introduction - Interobserver variation among four observers in evaluation of eight selected neurological signs was investigated. Material & methods - Two hundred and two consecutive unselected inpatients were examined by two senior neurologists and two trainees, all without knowledge of the neurological case history. The signs examined were: anisocoria, jerky eye movements, facial palsy, elbow extension force, finger-nose test, Barré sign, knee jerk, and extensor plantar reflex. Observed agreement rates and kappa coefficients were calculated in order to compare the interobserver variability among neurologists and trainees, and to evaluate differences in the interobserver variability between signs. Results - Observed agreement rates varied from 0.80 to 0.95 for neurologists and from 0.65 to 0.98 for trainees. For neurologists kappa coefficients ranged from 0.40 to 0.67 and for trainees from 0.22 to 0.81. The neurologists had higher kappa values than the trainees in 5 signs, but this difference was only statistically significant for jerky eye movements. For the individual signs the observed agreement rates were between 0.50 and 0.93 for all four examiners combined, and overall kappa values varied from 0.32 to 0.71 with highest agreement for facial palsy and lowest for knee jerk. Conclusion - The magnitude of the interobserver and intersign variation indicates that the interpretation of the neurological signs tested, without knowledge of the case history, should be done with some caution.     

Patency of the internal mammary artery used as sequential graft.

In 28 patients with the left internal mammary artery (IMA) used as a sequential coronary artery graft, clinical and angiographic evaluation was made 19-47 months postoperatively. Patency was 96% in the proximal anastomoses and 93% in all the anastomoses. Angiography, however, showed optimal function in only 75% of the distal graft ends. These observations indicate that routine use of left IMA as a sequential graft should be restricted to experienced surgeons. Clinical and angiographic findings did not always correlate, emphasizing that evaluation of IMA-graft patency should include angiography.     

Socioeconomic position and variations in coping strategies in musculoskeletal pain: a cross-sectional study of 1,287 40- and 50-year-old men and women.

OBJECTIVE: To examine the association between socioeconomic position and coping strategies in musculoskeletal pain. DESIGN AND SUBJECTS: Cross-sectional study of a random sample of 40- and 50-year-old Danes, participation rate 69%, n=7,125. The study included 1,287 persons who reported functional limitations due to musculoskeletal pain. METHODS: Data was collected by postal questionnaires and scales were developed on problem-solving coping and avoidant coping, based on a range of preliminary studies. Multivariate logistic regression analyses was used to study the correlation with socioeconomic position, measured by occupational social class. RESULTS: Among women, there was no correlation between social class and avoidant coping, but a significant decrease in the use of problem-solving coping by decreasing social class, adjusted odds ratio (OR) = 2.64 (95% confidence interval (CI) 1.31-5.32) in social class V vs social classes I + II. Among men, there was no correlation between social class and problem-solving coping, but a significant increase in the use of avoidant coping with decreasing social class, adjusted OR = 3.31 (95% CI 1.75-6.25) in V vs I + II. CONCLUSION: It is important for clinicians who advise and support patients in their response to musculoskeletal pain to be aware of socioeconomic differences in coping strategies. Gender differences in the association between socioeconomic factors and coping should be further investigated.     

Excitatory amino acid regulation of intracellular Ca2+ in isolated catfish cone horizontal cells measured under voltage- and concentration-clamp conditions.

[Ca2+]i was measured using fura-2-loaded isolated catfish horizontal cells in the presence of L-glutamate and the glutamate analogs kainate (KA), quisqualate (QA), and NMDA. Caffeine was used to release Ca2+ from intracellular stores. Cell membrane potential was controlled with a voltage clamp to prevent activation of voltage-dependent Ca2+ channels in the presence of agonist. All excitatory amino acid agonists produced a rapid and sustained rise in [Ca2+]i with the order of potency being QA greater than Glu greater than KA greater than NMDA. The agonist-induced [Ca2+]i increase was blocked in reduced [Ca2+]o and by 6-cyano-7-nitroquinoxaline-2,3-dione and 2-amino-5-phosphonopentanoate, which are specific blockers for QA/KA and NMDA receptors, respectively. The metabotropic receptor agonist trans-1-amino-1,3-cyclopentanedicarboxylic acid (ACPD; 10-200 microM) had no effect on [Ca2+]i. Hill coefficients from curves fitted to concentration-response data suggested an amplification of the Ca2+ signal that was interpreted as calcium-induced calcium release (CICR) from intracellular Ca2+ stores. Caffeine (10 mM) produced a rapid transient rise in [Ca2+]i, confirming the existence of a Ca(2+)-sensitive store. Following caffeine-induced depletion of Ca2+ from intracellular stores, agonists were still able to produce increases in [Ca2+]i, confirming Ca2+ influx through the agonist-gated channel. The agonist-induced increase in [Ca2+]i was decreased following caffeine-induced depletion, confirming a process of CICR. These results are consistent with the hypothesis that excitatory amino acids can produce direct modulation of [Ca2+]i by influx through the agonist-gated channel and by CICR from intracellular stores.     

Increased suicide risk among Danish women with non-melanoma skin cancer, 1971-1999.

More suicides than expected (standardized mortality ratio=1.3; 95% confidence interval=1.1-1.6) compared to the population risk were found among Danish women with a diagnosis of non-melanoma skin cancer in the period 1971-1999 but not among men. The increased risk might be associated with a different personality type in this cancer group.     

Transurethral resection versus transurethral incision of the prostate. A prospective randomized study

In this ongoing study, patients with an estimated prostate size of no more than 20 gm are randomized to undergo either transurethral resection of the prostate (TURP) or transurethral incision (TUIP) at the 6 o'clock position. To date, 93 patients have been included, and 3 months postoperatively, 80 to 90 per cent of the patients in each group reported improvement. There was also a significant decrease in symptom scores and a significant increase in maximum urinary flow rate, with great variation within each group but without difference between the groups. In both groups, there appears to be some deterioration over time. Operating time, estimated blood loss, time to catheter removal postoperatively, and duration of postoperative hospital stay were all significantly in favor of TUIP. Loss of ejaculation was reported by 37 per cent of patients after TURP and by 13 per cent after TUIP (not statistically significant). There was no difference between the groups in the need for further surgery. Therefore, TUIP is recommended as an alternative to TURP in patients with small prostates.