Effects of arginine vasopressin (AVP) infusions on circulating concentrations of platelet AVP, factor VIII: C and von Willebrand factor

To study the possible role of arginine vasopressin (AVP) in the control of haemostasis AVP infusions at 3 doses (0.1, 0.2 and 0.3 mU/kg/min) were performed in 6 male volunteers. Both plasma and platelet AVP concentrations rose in a dose-related manner. At doses of 0.2 and 0.3 mU/kg/min there was an increase in the plasma concentrations of both plasma Factor VIII and von Willebrand factor. The data support the hypothesis that AVP, by interacting with platelets and stimulating factor VIII and von Willebrand factor release, plays a role in the control of haemostasis.     

Evaluation of ambulatory care training by graduates of internal medicine residencies

In 1984, 154 physicians who had completed residencies in internal medicine at 15 major teaching hospitals in 1982 evaluated their residency training in ambulatory care. A majority of the physicians would have liked more experience in practical areas related to career planning and office management, more input from subspecialties such as orthopedics and dermatology, greater knowledge about the management of psychosocial problems, and more information about exercise and nutrition. Although many physicians also wanted more time devoted to several other topics, less than 20 percent recommended spending less time on 26 of the 27 topics being evaluated. Since these recommendations are similar to those reported in evaluation studies published over the past 25 years, it appears that training programs in internal medicine have not been successful in restructuring their curricula to meet many of the needs of practicing physicians.     

Carotid cavernous fistulae: indications for urgent treatment

Angiographic and clinical data from 155 patients with carotid cavernous fistulae were retrospectively reviewed to determine angiographic features associated with increased risk of morbidity and mortality. These features included presence of a pseudoaneurysm, large varix of the cavernous sinus, venous drainage to cortical veins, and thrombosis of venous outflow pathways distant from the fistula. Clinical signs and symptoms that characterized a hazardous carotid cavernous fistula included increased intracranial pressure, rapidly progressive proptosis, diminished visual acuity, hemorrhage, and transient ischemic attacks. Cortical venous drainage from the carotid cavernous fistula is secondary to occlusion or absence of the normal venous outflow pathways and is associated with signs and symptoms of increased intracranial pressure and an increased risk of intraparenchymal hemorrhage. Angiographic demonstration of a cavernous sinus varix, with extension of the sinus into the subarachnoid space, is associated with an increased risk of fatal subarachnoid hemorrhage. Identification of these high-risk features provides a basis for making decisions about treatment.     

Surgical treatment of active prosthetic valve endocarditis. Results in 66 patients

The results of combined medical and surgical management of 66 patients with active prosthetic valve endocarditis (APVE) are analyzed. Between 1970 and 1985, 3510 patients were operative survivors of mitral, aortic or double mitral-aortic valve replacement. Cumulative follow-up was 15,640 patient-years (mean 4.4 years). The overall annual incidence of reoperation for APVE was 0.42 +/- 0.05% (0.34 +/- 0.08% for biological and 0.46 +/- 0.06% for mechanical prostheses, p = n.s.). Early APVE occurred in 21 patients and 45 patients had late APVE. Indications for surgery were heart failure in 92%, systemic emboli in 5% and persistent sepsis in 3% of patients. Overall operative mortality (less than 30 days) was 38% (25/66). (Early APVE 52% and late APVE 31%). Anatomical location, valve design and number of prostheses implanted did not correlate with a higher operative risk. Overall endocarditis-related mortality was 56% (37/66). Uni and multivariate stepwise logistic regression analysis identified: 1) date of surgery (p = 0.01), 2) renal failure (p = 0.03) and 3) early APVE (p = 0.03) as predictors of endocarditis-related death. Actuarial survival at 1, 5 and 10 postoperative years was 41 +/- 6%, 30 +/- 6% and 24 +/- 7% respectively. This study confirms the high lethality of APVE. However, with adequate and aggressive combined medical and surgical management, some patients can be saved.     

Zero-Order Release Formulation of Oxprenolol Hydrochloride with Swelling and Erosion Control

Zero-order release of oxprenolol hydrochloride was obtained by controlling the swelling and erosion of the matrix. This formulation involves only mixing of drug, hydroxypropylmethylcellulose (HPMC), and sodium carboxymethylcellulose (Na CMC) at the ratio of 1:0.4:1.6, respectively, and compressing the mixture directly into tablets. The in vitro release pattern from this optimized matrix tablet was reproducible. Accelerated stability studies revealed that the optimized formulation remains stable for an approximately 2-year shelf life. This sustained-release (SR) tablet was evaluated in dogs, and for comparison a conventional (CV) formulation was also given at the same dose level. Plasma oxprenolol levels were monitored by a sensitive and specific high-performance liquid chromatographic (HPLC) method. Significant differences in the pharmacokinetic parameters, i.e., lower C _max, higher values of t _max, MRT, AUC, and plasma concentration at 24 hr, and nearly constant plasma levels over 12 hr, indicated that the SR matrix tablet is superior to the CV rapid-releasing formulation. The in vitro release parameters and in vivo pharmacokinetics correlated well.