The complex nature of the mechanism of toxicity of antibiotic dithiacyclohexadiene polyines (thiarubrines) from the asteraceae

Thiarubrine A, a dithiacyclohexadiene polyine from the roots of Chaenactis douglasii, and a related dithiacyclohexadiene from Rudbeckia hirta exhibit strong light-independent antibacterial and antifungal activity. This activity is enhanced by exposure to visible light. Visible light also converts the compounds to the corresponding thiophenes. These are antibiotic only when irradiated with UV-A. Dithiacyclohexadienes are the first polyines to exhibit such complex mechanisms of toxicity towards microorganisms.     

Prediction of steady state bioequivalence relationships using single dose data II-nonlinear kinetics

Two nonlinear pharmacokinetic models were simulated to investigate the relationship between single and multiple dose bioequivalency parameters for drugs such as phenytoin and propranolol which exhibit either saturable elimination kinetics or a capacity limited first pass effect. Mean Tmax, Cmax and area under the plasma-concentration time curve values from 0 to infinity (AUC 0-infinity) were compared after a single and multiple dose(s) of a test or reference drug. The aim was to determine if there were systematic changes in the limits of the single dose confidence interval at steady state that would limit the usefulness of confidence intervals following a single dose in accurately predicting bioavailability following multiple dosing. The 90 per cent confidence interval expressed as a percentage of the reference mean for Tmax, Cmax, and AUC 0-infinity showed model dependent changes from single to multiple dosing in response to the level of data error and changes in absorption. Changes in clearance also seemed to have a marked effect on the observed limits of the single and multiple dose confidence intervals especially for Cmax which showed a characteristic change in the intervals as a function of the clearance ratio. The model used to describe phenytoin had confidence intervals for Cmax and AUC 0-infinity from single to multiple dosing that were similar to that seen for the experimental data. However, the model predictions for Tmax confidence intervals following single and multiple dosing was at variance with the experimental data for formulations A and B.     

The incidence of Hill-Sachs lesions in initial anterior shoulder dislocations

We undertook a prospective study using arthroscopy to determine the intraarticular derangement caused by initial anterior shoulder dislocations. Of our 32 patients, 15 (47%) had a grade I, grade II, or grade III Hill-Sachs lesion. The patients were 29 men and 3 women whose ages ranged from 15 to 28 years (mean 22 years). All of the patients studied were United States military personnel or members of their families. None of the patients had had prior injuries of the affected shoulder, and all underwent arthroscopy within 72 h of injury. Few reports describe a Hill-Sachs lesion in a patient following a single anterior dislocation. Early reports of this lesion were based on indirect (radiographic) evidence. Our arthroscopic findings indicate that the incidence of this lesion after one anterior dislocation is higher than previously thought.     

Concurrent review of the duration of antimicrobial prophylaxis in surgery.

The administration of prophylactic antibiotics in surgery is appropriate for many patients. Data have shown extending the duration of prophylaxis beyond 48 hours does not lower the rate of postoperative-infection. The purpose of this project was to concurrently assess the duration of prophylactic antibiotic use. A total of 95 patients were monitored over 3 weeks. Eighty patients (84.2%) received antimicrobial therapy. In 23 of these patients (28.75%) the duration of antibiotic administration was longer than 2 days without clinical or microbiological evidence of infection. In 5 other patients only postoperative antibiotics were prescribed. The cost difference between the actual duration of antibiotic administration and 2 days of the same regimen was +1,364.58. Extrapolating for one year, it can be estimated that antibiotic costs could be reduced about +23,600. Pharmacists can focus on the duration of antibiotic prophylaxis as a cost containment measure.     

Uptake of iodine-123 MIBG by pheochromocytomas, paragangliomas, and neuroblastomas: a histopathological comparison

The percentage uptake of [123I]metaiodobenzylguanidine (MIBG) by tumors of the paraganglion system is compared with the number of neurosecretory granules (assessed by both light and electron microscopy) in the subsequently resected tumors in six patients. Iodine-123 MIBG was injected intravenously; the tumor uptake of [123I]MIBG varied between 0.001% and 0.14% of the injected dose per gram of tumor tissue at 22 hr. The number of neurosecretory granules in tissue sections was scored on a scale of I-III. A direct proportional correlation was found between the percentage uptake of [123I]MIBG by the tumor and the number of neurosecretory granules in the tissue sections but not with plasma or urinary catecholamines. This technique for imaging reflects the storage status of the tumor better than plasma and urinary catecholamine measurements.     

Abnormal nephrogram pattern as an adverse reaction to contrast material. Case report

Up to now two abnormal nephrographic patterns have been described as a result of arterial hypotension as an adverse response to urographic contrast material. We would like to describe a third pattern.     

Recurrence, progression and survival in bladder cancer. A retrospective analysis of 232 patients with greater than or equal to 5-year follow-up

A retrospective study of 232 bladder tumours with minimum follow-up 5 years is presented. The carcinoma was superficial in 66%, muscle-invasive in 31% and could not be staged in 3%. Primary treatment was mainly transurethral resection for superficial tumour, but was cystectomy or radiotherapy in 22 of 29 T1 G3. Of the superficial tumours, 71% recurred. Progression to higher T stage occurred in 15% of Ta and 29% of T1 tumours, and half of these patients died of bladder cancer. The corrected 5-year survival rates in grades 1, 2A, 2B and 3-4 were 96, 84, 64 and 43%, and in stages Ta, T1, T2 and T3 they were 94, 69, 40 and 31%. All patients with T4 tumour died within 4 years. Among the 45 patients with 40 Gy irradiation + cystectomy, the corrected 5-year survival rate was 83% in superficial and 64% in muscle-invasive tumours, and among the 38 with radical radiotherapy the rates in T1-3 were 46, 36 and 13%. Transurethral resection was successful in most Ta cases. Most T1 tumours were, like T2-4, of higher grade than Ta. Prognosis was worse in T1 than in Ta. After progression to muscle-invasive disease, even during close follow-up the outlook was poor, as poor as for patients with primary muscle-invasive disease.