Correlation of quinidine absorption with disintegration and dissolution rates

The dissolution profiles of four commercial quinidine sulfate tablets were determined using the USP rotating-basked dissolution apparatus. Substantial differences in dissolution half-times were noted and compared to previously reported disintegration times, absorption rate constants, and times of appearance of peak serum concentrations. Rank-order correlations were observed among all combinations of in vivo and in vitro parameters, indicating that the absorption rates of these tablets are controlled by both disintegration and dissolution.     

Instrumented measurements of laxity in patients who have a Gore-Tex anterior cruciate-ligament substitute

Twenty patients who had substitution of the anterior cruciate ligament with a Gore-Tex synthetic ligament were evaluated preoperatively and postoperatively with the University of California at Los Angeles instrumented clinical-testing apparatus, which records anterior-posterior force versus displacement-response curves of the tibia with respect to the femur at 20 degrees of flexion of the knee. The mean age of the patients was thirty-three years (range, nineteen to fifty-four years). The duration of follow-up ranged from twenty-four to forty-four months (mean, thirty-one months). The mean preoperative difference in anterior laxity between the injured knee and the normal knee (4.5 millimeters with neutral rotation of the foot) was unchanged two years after the operation; at that time, all patients had an anterior laxity of the injured knee of more than eight millimeters, and 90 per cent had a difference in anterior laxity of more than two millimeters between sides. The mean values for anterior stiffness at fifty and 100 newtons of anterior force were unchanged after the operation, remaining at 40 to 50 per cent of normal levels. At 200 newtons, or 20.4 kilograms (forty-five pounds) of anterior force, the mean stiffness of the involved knee was 11 to 17 per cent greater than that of the normal knee. Clinically, there were improvements in both subjective and objective knee-rating scores. All but four patients had a reduction of at least one grade in the pivot-shift score; in thirteen, the pivot-shift sign was eliminated.(ABSTRACT TRUNCATED AT 250 WORDS)     

Human Y chromosome azoospermia factors (AZF) mapped to different subregions in Yq11

In a large collaborative screening project, 370 men with idiopathic azoospermia or severe oligozoospermia were analysed for deletions of 76 DNA loci in Yq11. In 12 individuals, we observed de novo microdeletions involving several DNA loci, while an additional patient had an inherited deletion. They were mapped to three different subregions in Yq11. One subregion coincides to the AZF region defined recently in distal Yq11. The second and third subregion were mapped proximal to it, in proximal and middle Yq11, respectively. The different deletions observed were not overlapping but the extension of the deleted Y DNA in each subregion was similar in each patient analysed. In testis tissue sections, disruption of spermatogenesis was shown to be at the same phase when the microdeletion occurred in the same Yq11 subregion but at a different phase when the microdeletion occurred in a different Yq11 subregion. Therefore, we propose the presence of not one but three spermatogenesis loci in Yq11 and that each locus is active during a different phase of male germ cell development. As the most severe phenotype after deletion of each locus is azoospermia, we designated them as: AZFa, AZFb and AZFc. Their probable phase of function in human spermatogenesis and candidate genes involved will be discussed.      

Determinants of acquisition of MR imaging units in an era of prospective payment

A survey was undertaken to examine the impact of Medicare's Prospective Payment System (PPS) and other recent changes in the health care environment on providers' decisions regarding acquisition of high-cost technologic equipment. The survey group included 199 hospitals and freestanding imaging centers known to have acquired magnetic resonance (MR) imaging units, as well as a random sample of 400 hospitals whose acquisition decisions were unknown to the authors. Fifty-eight percent of the known adopters and 61% of the randomly selected hospitals responded to the survey. Nonadopters' decisions were dominated by economic considerations, including the high cost of MR imagers and concerns about Medicare's reimbursement policies. Competition and a desire to provide the highest quality of care are counterbalancing the retardant effects of PPS, however, and are stimulating widespread diffusion of MR imagers.     

Intrathoracic Hodgkin's disease. A case presentation with multiple pulmonary nodules in the absence of mediastinal or hilar node disease

Patients with Hodgkin's disease (HD) most commonly present with peripheral lymph node enlargement. The finding of pulmonary parenchymal involvement is usually associated with hilar and/or mediastinal adenopathy; such instances are felt to represent spread to the lung by contiguity. Noncontiguous spread to peripheral lung parenchyma in the absence of hilar or mediastinal node involvement has rarely been reported. This is the first documented case report in a 32-year-old woman with nodular sclerosing HD. The unusual clinical presentation in this patient was associated with the histologic detection of vascular invasion in the lymph node and open-lung biopsy specimens.     

A method demonstrating motor endplates for light and electron microscopy

The cytochemical localization of acetylcholinesterase activity at motor endplates is commonly employed prior to electron microscopic examination. Methods which involve the use of thiocholine esters often lead to a loss of resolution due to the spread to surrounding tissues of an extremely dense reaction product. A method is presented in which esterase positive sites are revealed by incubation with hexazotized pararosaniline and indoxyl acetate. The osmiophilic property of the reaction product which remains localized to the synaptic cleft allows speedy identification and detailed examination of the endplate at the ultrastructural level. An application of the procedure is also described.     

Development of the conducting airway epithelium in fetal Syrian golden hamsters during normal and diabetic pregancies

The conducting airway epithelium of fetal Syrian golden hamsters was studied from gestational day 12 to day 15, during normal and uncontrolled diabetic pregnancies. Diabetes was induced in the pregnant hamsters by injecting streptozotocin at 60 mg/kg body weight, subcutaneously, early on gestational day 10. Cells in S-phase were labelled immunochemically with bromodeoxyuridine (BrdU), and the day on which endocrine cells and ciliated cells first appeared was determined. In control fetuses, the BrdU-labelling indices (LI's) of different anatomical airway levels were significantly different from one gestational day to the next. For example, the LI of the lobar bronchus was significantly different on each gestational day (P.0001), and the same was true of the bronchioles. Moreover, the difference between LI's of the lobar bronchus and bronchioles-terminal buds was highly significant on day 12 (P <.0001), and on day 13 the differences between lobar bronchus and bronchioles, lobar bronchus and terminal buds, and bronchioles and terminal buds were also highly significant (P .0001). However, on gestational days 14 and 15, the LI's were reduced and were comparable at different airway levels. The BrdU-labelling indices were very consistent among fetuses of the same age, and the differences between the average LI's for pups of different litters was numerically very small. Hyperglycemia (mild, moderate, severe) did not alter LI's in the fetal airway epithelial cells. Furthermore, although glycogen was not depleted from the airway epithelium of the hyperglycemic fetuses as it was in the controls, the endocrine cells first appeared on gestational days 12, 13, and 14, respectively, in the trachea, lobar bronchus and bronchioles, followed 1 day later by the ciliated cells, in the fetuses of control and diabetic mothers. In our experimental model, induction of diabetes in the pregnant hamsters on gestational day 10 did not appear to alter development or diferentiation of the fetal conducting airway epithelium.     

Corrected QT interval prolongation after an overdose of escitalopram, morphine, oxycodone, zopiclone and benzodiazepines

Escitalopram is the recently marketed S-enantiomer of the widely used antidepressant citalopram. Data from intentional overexposure to this medication are limited. Twelve-lead electrocardiogram (ECG) effects from racemic citalopram have been described; however, the present report is the first, to the best of the authors' knowledge, that describes all the reported abnormalities in a single patient receiving escitalopram. A 52-year-old man with a history of depression treated with escitalopram 10 mg/day, extended-release morphine 30 mg/day and zopiclone 15 mg/day was found unconscious at his home. He was known to have attempted suicide three weeks previously. Partially emptied bottles of escitalopram, morphine, oxycodone, zopiclone, lorazepam and diazepam were found close to the patient. He was transferred to the emergency department, where airway management and other supportive care were initiated. The patient was transferred to the intensive care unit. The initial 12-lead ECG demonstrated junctional rhythm at 48 beats/min, a wide complex escape (145 ms) with right bundle branch morphology and a prolonged corrected QT interval at 650 ms. Cardiac monitoring was undertaken. No ventricular arrhythmias or torsade de pointes were detected. No specific treatment for shortening the QT was implemented. Another 12-lead ECG performed 48 h later demonstrated sinus tachycardia with a normal corrected QT, normal PR interval and normal QRS duration. The effects of the overdose of escitalopram on the ECG and its interactions with other drugs are reviewed.