Cyclodextrin formulation of dorzolamide and its distribution in the eye after topical administration.

Due to limited aqueous solubility of dorzolamide at physiologic pH, the pH of Trusopt eye drops (cont. 2% dorzolamide) has to be kept at about 5.65, and to increase the topical bioavailability of the drug from Trusopt the contact time of the drug with the eye surface is increased by increasing the viscosity of the eye drops to 100 cps. This low pH and high viscosity can lead to local irritation. In this study, dorzolamide hydrochloride was formulated as 2% and 4% low viscosity solutions (viscosity 3 to 5 cps) containing randomly methylated beta-cyclodextrin at pH 7.45. These formulations were evaluated in rabbits. The animals were sacrificed at various time points after topical administration of the drug and the dorzolamide concentration determined in the different parts of the eye. Trusopt was used as a reference standard. The topical availability of dorzolamide from the cyclodextrin-containing eye drops appeared to be comparable to that from Trusopt and the drug reached retina and optic nerve to give measurable concentrations for at least 8 h after administration of the eye drops.     

Histological changes over time around the site of sustained release naltrexone-poly(DL-lactide) implants in humans.

In order to assess the histological tissue changes over time around the site of implant, tissue biopsies were taken at 1 to 38 months post-implant from 54 (34 male) consenting human subjects who had received the Australian subcutaneous naltrexone-poly(DL-lactide) implant for heroin dependence. The implant consists of multiple tablets containing compressed naltrexone-poly[trans-3,6-dimethyl-1,4-dioxane-2,5-dione] (DL-lactide) loaded microspheres. Assessment of tissue samples by pathologists showed an early phase (up to 12 months post-implant) of inflammation, foreign body reaction, and fibrosis. This subsided gradually over the next 12 months until tissue returned to normal by 25+ months. Sufficient evidence was not available to conclude that the poly(DL-lactide) implant matrix was totally biodegradable within the study period. While implant material was not identified in most of the latter biopsies, its presence was noted in one biopsy at 26 months post-implant. Nevertheless the study results did demonstrate the implant's biocompatibility by the lack of inflammation, foreign body reaction, and fibrosis detected by 25+ months. It seems highly probable that surgical technique rather than the implant itself was associated with the additional finding of fat necrosis. Moderate fat necrosis was observed as a common feature of biopsies carried out during the first 6 months following implant. It subsided to mild levels over the next 18 months, and was notably absent by 25+ months. The results of the study indicated that the Australian naltrexone-poly(DL-lactide) implant is well tolerated and may have a role for use in the management of medical conditions such as heroin dependence.     

Contribution of autologous blood transfusion in cardiac surgery in the adult

The use of autologous blood transfusion in cardiac surgery is still controversial. This study was prospectively designed to evaluate the haemodynamic and haematological benefits of this method, with special attention to its impact on reducing bank blood requirements. Between November 1983 and October 1984, 160 patients underwent cardiac surgery with extracorporeal circulation and were randomly assigned to two groups: group I (81 patients) was the control group and group II (79 patients) received autologous transfusion following extracorporeal circulation. Blood was withdrawn immediately after the induction of anaesthesia via a jugular catheter and stored in CPD solution at room temperature. The volume of blood removed was replaced with gelatin solutions; after bypass, blood was returned to the patient. There was no difference in systolic, diastolic or mean blood pressures between the two groups. Right atrial pressure and heart rate were not statistically different in both groups. Myocardial perfusion and myocardial oxygen consumption remained unchanged in group II compared with group I. Complete haematological evaluation was carried out before and during bypass, and thereafter daily for the first twelve days of the postoperative period. There was no significative difference between the two groups in platelet counts, fibrinogen levels, prothrombin and partial thromboplastin times. During extracorporeal circulation, mean haematocrit was 22.9 +/- 0.4% in group II and 25.3 +/- 0.5% in group I (p less than 10(-3)). The mean haematocrit time course was similar in both groups during the postoperative period and returned to preoperative value at discharge.(ABSTRACT TRUNCATED AT 250 WORDS)     

Influence of pregnancy, lactation, litter size and diet energy density on the stomach and intestine of sows

In the first experiment, 52 sows, each having raised one litter, were randomly assigned to the five following groups: control (nongravid) for pregnancy (CP), 110 d pregnancy (P110), control (nongravid) for lactation (CL), 4-wk lactation with 8 (L8) and with 12 (L12) piglets. In a second experiment, 36 sows, each having raised three litters, were randomly assigned to the following groups: control group (nongravid) fed a low-energy-density, 1% tallow diet (CLED) and two lactating groups, one fed the low-energy-density diet (LLED) and one fed a high-energy-density, 10% tallow diet (LHED). At slaughter, the stomach, small and large intestine and cecum were excised, emptied and freed from fat. Lengths and pre- and post-defatting weights were measured. Portions of tissues were homogenized and analyzed for protein, pepsin, maltase, RNA and DNA. Pregnancy had no effect on the weights of the different components of the gastrointestinal tract. Liver and small intestine weights were larger in lactating sows than in the CL group. Sows nursing 12 piglets had heavier livers than those nursing 8. The fundic mucosa of the latter had higher total pepsin activity and total protein and RNA contents than that of L12 sows. LHED sows had heavier small intestine and lower total pepsin content of the fundic mucosa than LLED sows.     

Health risks among submarine personnel in the U.S. Navy, 1974-1979

This study evaluated health risks associated with U.S. Navy submarine duty by comparing hospitalization rates of submariners with surface ship personnel. The groups were compared using age-adjusted hospitalization rates for 16 major diagnostic categories and several specific diagnoses postulated to be submarine associated. Submarine personnel did not have significantly higher hospitalization rates for any diagnostic categories nor for any of the submarine-associated illnesses. Submariner relative risk of hospital admissions was greater for a few selected diagnoses but statistical significance was not attained. Submarine personnel had lower hospitalization rates for nearly all of the diagnostic categories examined. Reasons for these lower rates may be stringent screening of submariners, higher levels of education among submariners, difficulty of evacuation from a submarine, and the healthy-worker effect. The health status of U.S. Navy personnel does not seem to be adversely affected by submarine duty.     

Methods of ultrasonic angiography and spectrum analysis of the Doppler signal in the diagnosis of the degree of occlusive lesions of the brachiocephalic arteries

Results of an examination of 39 patients are described and critically assessed. An analysis of the resolving power of the method of ultrasonic angiography in pathological formations of major vessels of the neck is given.