Hydroxyapatite-oil composites for delivering AZT in simulated body fluid.

Hydroxyapatite (HA) has been used to deliver therapeutic drugs both in vitro and in vivo at a constant rate showing zero order kinetics. This study was designed specifically to analyze the effects of wheat germ (WG) incorporation with HA on the rate of delivery of AZT from an insert system over a one month period in vitro. Insert systems which were saturated with wheat germ oil delivered AZT at a slower rate over the one month period than did half-saturated or unsaturated insert systems. All systems containing 50 mg of AZT in the outer shell delivered 80% of the 100 mg AZT dosage over the first eight days. The systems which had a 100 mg AZT insert surrounded by an oily HA shell lacking AZT delivered AZT in a linear manner over the course of one month. The amounts and rates of AZT release from composites was indirectly proportional to the amount of wheat germ oil used. The results of this study show that the lipids incorporated in the ceramic composites can be tailored to deliver a 100 mg AZT dosage for a period of one month in vitro.

Early intervention for alcohol use: family physicians' motivations and perceived barriers.

OBJECTIVE: To elucidate family physicians' motivations concerning early intervention for alcohol use and their perceived barriers to such intervention. DESIGN: Qualitative study with the use of focus groups and semistructured interviews. SETTING: Community-based, fee-for-service family-medicine practices in London, Ont. PARTICIPANTS: Twelve focus-group participants recruited through telephone contact by two family physicians on the project team. Participants were required to be physicians in family practice in London. Twelve interview participants recruited through a grand-rounds presentation at two local hospitals. Participants were required to be physicians in a community-based family practice in which primary care was not delivered by residents and to have agreed to participate in all phases (e.g., needs assessment, training and evaluation) of a training program on interventions to help patients reduce alcohol consumption or quit smoking. MAIN OUTCOME MEASURES: Motivations concerning early intervention for alcohol use and perceived barriers to such intervention, as identified by physicians. RESULTS: Physicians in the focus groups and those interviewed endorsed their role in helping patients to reduce alcohol consumption and cited several reasons for the importance of that role. There was strong support for viewing alcohol use as a lifestyle issue to be dealt with in the context of a holistic approach to patient care. Participants cited many barriers to fulfilling their role and were particularly concerned about the appropriateness of asking all adolescent and adult patients about alcohol use, even at visits intended to discuss other issues and concerns. Physicians gave several motivations for improving their work in reduction of alcohol consumption, including their current frustration with the lack of a systematic strategy or tangible materials to help them identify and manage patients. CONCLUSIONS: Interventions with patients who use alcohol should be framed in the context of a holistic approach to family medicine. Qualitative knowledge of the motivations and barriers affecting physicians can inform future research and educational strategies in this area.

16,16-Dimethyl prostaglandin E2 delays collagen formation in nutritional injury in rat liver.

Chronic nutritional injury was induced in rats by a high-fat, lipotrope-deficient diet. The hepatoprotective effect of 16,16-dimethyl prostaglandin E2 on the deposition of collagen and fat was assessed by histological evaluation and measurement of hydroxyproline. Dose-response studies established that optimal protection was achieved by the twice daily administration of 16,16-dimethyl prostaglandin E2 at 100 micrograms per kg (subcutaneous) or 250 micrograms per kg (oral). 16,16-Dimethyl prostaglandin E2 and a crystalline analog [(p-acetamidobenzamido)phenyl ester of 16,16-dimethyl prostaglandin E2 significantly delayed both the deposition of collagen and the increase in hepatic hydroxyproline content. There was an excellent correlation between the histological assessment of collagen and the biochemical measurement of hydroxyproline. These data provide a rationale for the evaluation of prostaglandins in the treatment of human liver disease.

Prostacyclin inhibits gastric emptying and small-intestinal transit in rats and dogs.

Prostacyclin (PGI2) antagonizes 16,16-dimethyl prostaglandin E2-induced diarrhea in rats, presumably by inhibiting the fluid accumulation of "enteropooling" in the small intestine. The effect of PGI2 on gastric emptying, small intestinal transit, and colonic transit was examined in rats and dogs to determine if interference with propulsion might also contribute to the antidiarrheal properties of this compound. Rats implanted with chronic duodenal cannulas were given subcutaneous PGI2 (0.1-1000 microgram/kg) followed 10 min later by intragastric 51Cr and a visually detectable duodenal transit marker. Forty-five minutes later, the animals were killed. Small-intestinal transit was expressed as the percentage of small intestinal length traveled by the visually detected marker. Gastric emptying was expressed as the percentage of the total 51Cr found in the small intestine. Subcutaneous PGI2 inhibited gastric emptying maximally at 10 micrograms/kg. Small-intestinal transit was significantly decreased at 50 micrograms/kg and almost completely suppressed at 1.0 mg/kg. Subcutaneous naloxone (0.5 mg/kg) given 10 min before and 20 min after subcutaneous PGI2 administration did not block PGI2's effects. Intravenous or oral PGI2 in doses as high as 0.2 or 10 mg/kg, respectively, had none of these effects. However, a high-dose intravenous bolus (1.0 mg/kg) or infusion (1.0 mg/kg X 45 min) both inhibited gastric emptying. Small intestinal transit was only decreased by PGI2 infusion, suggesting that this parameter was more sensitive to a sustained blood level than gastric emptying. Hourly injections of subcutaneous PGI2 (0.5 mg/kg) had no effect on rat colonic transit measured over a 3-h period after deposition of the transit marker through a colonic cannula in a manner similar to that described for small-intestinal transit above. Small-intestinal transit was also measured in dogs given a barium suspension through a chronic duodenal cannula. The animals simultaneously received subcutaneous PGI2 (10 micrograms/kg) and were given an additional treatment and an abdominal x-ray every 30 min thereafter. In vehicle-treated dogs, barium reached the cecal area in an average of 2.8 h after instillation. In PGI2-treated dogs, barium never reached the cecum in the 5-h examination period. Thus, PGI2 inhibits gastric emptying in rat and small-intestinal transit in rat and dog but has no effect on rat colonic transit. These properties could contribute to PGI2's antidiarrheal activity.

The use of cervical flaps from irradiated necks in immediate reconstruction.

The use of cervical flaps for immediate reconstruction after operation in twenty-one patients in whom the neck received 4,000 to 6,000 r six weeks prior to operation is reported. Successful repair was achieved in a majority of these patients. We conclude that such flaps can be safely used imost instances, assuming they are designed to achieve maximum blood supply or are in an area that received minimal radiation exposure. We recommend this approach only when the radiation given is part of a course of previously planned, integrated therapy combining radiation and operation and when the major portion of the flap has not been exposed to more than 4,000 r.

Lessening of adverse biochemical effects of shock in newborn puppies by general anesthesia.

A shock preparation has been developed which produces the expected anaerobic metabolism in neonatal beagle puppies less than 7 days old. Lactic acid production was found to be significantly higher in shocked puppies operated upon under local anesthesia than when the same procedures were performed in shocked puppies under general endotracheal anesthesia. These findings suggest that general anesthesia may be safer in the very sick human neonate.