Bioavailability and corneal anti-inflammatory effect of topical suprofen

The bioavailability in rabbit cornea and aqueous humor of an ophthalmic formulation of suprofen, a nonsteroidal anti-inflammatory drug, was evaluated following topical administration of a single dose to the eye. The drug penetrated rapidly into the uninflamed cornea with intact epithelium; highest levels occurred during the first 30 to 45 min after instillation and decreased thereafter. The bioavailability of suprofen in cornea and aqueous humor following administration of a 1.0% concentration was twice that produced by a 0.5% concentration of the drug. Topical application of multiple doses of suprofen failed to suppress polymorphonuclear leukocyte invasion of the cornea if treatment was started after the induction of inflammation. Suprofen therapy initiated prior to the induction of corneal inflammation and maintained into the post-inflammation period did produce a significant (P less than 0.01) decrease in the numbers of PMNs that invaded the inflamed cornea. There was no significant difference (P greater than 0.05) in the corneal anti-inflammatory effect achieved by the 0.5% and 1.0% concentrations of suprofen when administered according to this regimen.     

The Characterization of Oxotremorine-Induced Hypothermic Response in the Rat

Abstract: Oxotremorine is a muscarinic receptor agonist that induces a variety of physiological and behavioural effects including hypothermia in mice. These effects are antagonized dose-dependently by classical anticholinergic compounds such as atropine. Although the oxotremorine-induced hypothermic response has been demonstrated in mice, few studies of the effects of this muscarinic agonist have been made in the rat. The following studies were made in male Sprague Dawley rats: 1. an investigation of the dose-response relationship between oxotremorine and hypothermia; 2. an examination of the effect of housing on the oxotremorine-induced hypothermic response, and 3. an investigation of the acute administration of various doses of atropine sulphate on the hypothermia caused by oxotremorine. The results indicate that the dose-response relationship between oxotremorine and the antagonism of hypothermia is similar in rat as it is in mice. The results also showed that this effect did not occur in group-housed animals.     

Gut contents: A significant contaminant of Mytilus edulis whole body metal concentrations

Ingested matter can have a significant effect on whole body metal concentration measurements in Mytilus edulis. Depuration of mussels in clean seawater for 36 h prior to dissection eliminates most of these contaminating gut contents. Depuration followed by metal analyses is the most direct method of determining mussel tissue metal bioburdens. After being transplanted into a plume of primary treated sewage effluent in Salem Harbor, Massachusetts for 32 days, Al, Cr, and Fe concentrations in depurated mussels were significantly lower than those determined for either non-depurated mussels or for depurated mussels to which fecal concentrations of Al, Cr, and Fe were added back in. Although mathematical methods developed by both Ouellette (1978) and Boehm et al. (1988) could be applied to non-depurated mussels in order to correct for errors associated with gut metal contamination, these indirect methods were not as reliable as depuration prior to analysis.     

The applicability and utility of the MMPI-based offender classification system in a correctional mental health unit

This study investigated the applicability and utility of Megargee and Bohn's MMPI-based offender classification system in correctional mental health units (MHUs). Previous studies found that 11 MHU samples (n = 1723) had substantially more offenders classified in the more pathological MMPI types than did 21 samples (n = 5881) drawn from general male populations in US prisons. In this study of 63 severely disturbed felons, 43% belonged to the most pathological type (‘group How’). Comparing MHU patients with general offenders from the same IvfIvIPI types on staff ratings and case history variables, we found that the MHU patients were significantly poorer in adjustment. Within the MHU sample, there was no difference in case history variables or adjustment ratings between those in the most and least severe MMPI types. These findings differed from those of studies using less severely disturbed, more heterogeneous, MHU populations. It was concluded that, in settings in which the entire population is flagrantly disturbed, the MMPI-based system is more useful in screening potential admissions than it is in making meaningful distinctions among those already admitted.     

ALFENTANIL PLASMA CONCENTRATION v. EFFECT RELATIONSHIPS IN CARDIAC SURGICAL PATIENTS

Effects of alfentanil, preceded by lorazepam, on suppressionof haemodynamic and somatic responses to noxious stimuli wasstudied in patients undergoing CABG. Plasma concentration ofalfentanil, somatic and haemodynamic responses were measuredat loss of consciousness, tracheal intubation, sternotomy andduring multiple applications of electrocoagulation. Additionalalfentanil was administered i.v. to control unwanted responses.Study 1 (six patients): lorazepam 0.08 mg kg^–1 by mouth1–2 h before operation, alfentanil priming infusion (60µg kg^–1 min^–1 for 10 min) followed by maintenanceinfusion (4.5 µg kg^–1 min^–1). With mean plasmaalfentanil 1178 (SEM 54) ng ml^–1, two patients requiredsupplementary alfentanil to suppress somatic motor responses;one patient required nitroglycerin to control an increase inarterial pressure which was unresponsive to additional alfentanilfollowing sternotomy. Study 2 (13 patients): lorazepam 0.04mg kg^–1 by mouth as premedication; one of three maintenanceinfusion rates of alfentanil: 5.4 (n=4), 6.6 (n=5), or 7.8 (n=4)µg kg^–1 min^–1, each preceded by a proportionalpriming infusion. With plasma alfentanil 2181 (62)ng ml^–1,somatic motor responses requiring additional alfentanil occurredin nine patients; haemodynamic responses in four of seven patientstested could not be controlled by alfentanil. The highest plasmaconcentration of alfentanil to prevent response to a stimulusother than tracheal intubation was different between the twostudies (P<0.05). We conclude that alfentanil alone is insufficientto suppress haemodynamic and somatic motor responses to noxiousstimulation during CABG and that the role of premedication issignificant. *Department of Anesthesia, Bowman-Gray School of Medicine Winston-Salem,NC 27103, U.S.A. 2114 de Mayo Road, Del Mar, Ca. 92014, U.S.A.     

Primary Health Care through a community based smoking-cessation program

The International Conference on Primary Health Care, meeting in Alma-Ata, in the Soviet Union, September 12, 1978, expressed the need for urgent action by all governments, all health and development workers and the world community, to protect and promote the health of all people of the world. The world was caught by the phrase which emerged from this conference, Health For All by the Year 2000 and many have examined the articles of the Alma-Ata declaration and tried to implement them in their corner of the world. This paper describes a community-based smoking-cessation program which was implemented in the province of Nova Scotia, Canada, during the years 1980–1984. Primary to this project was the belief that people have the right and the duty to participate individually and collectively in planning and implementing their health care. This paper describes one community's effort in putting this belief into practice.Carol Smillie, B.N. BE.d. M.S.c. is an Assistant Professor at the School of Nursing, Dalhousie University, Halifax, Nova Scotia, Canada B3H 3J5, Katherine Coffin, BA, MEd is the Program Officer, Nova Scotia Office, Health Promotion Directorate Health and Welfare Canada, 5251 Duke Street, Halifax, Nova Scotia. Canada B3J 1P3. Kathryn Porter, B.A. (Gen)., is the Information and Education Coordinator, Nova Scotia Division Canadian Cancer Society. Brenda Ryan, B.A., M.B.A. is Program Evaluation Analysist, Nova Scotia Department of Health, 6088 Hollis Street, Halifax. Nova Scotia, Canada. This Project was funded by Health and Welfare Canada, Nova Scotia Department of Health, Nova Scotia Division Canadian Cancer Society, Requests for reprints should be addressed to: Professor Carol Smillie.     

Intestinal 5-Fluorouracil Absorption: Use of Ussing Chambers to Assess Transport and Metabolism

We have employed an in vitro system to study transport and metabolism of organic molecules by gastrointestinal tissues. Such a system would aid in the evaluation of the potential for oral delivery of organic molecules. Transport and metabolism of 5-fluorouracil (5-FU) were studied using rabbit intestinal preparations. Unidirectional fluxes and metabolism were measured in vitro in Ussing chambers under short-circuit conditions. Results from these studies reveal that in ileum, proximal, and distal colon, steady-state fluxes of 5-FU (10 µM added to both bathing solutions) are established after 30 min and remain constant for at least 110 min. Transport of 5-FU under sink conditions with 10 µM 5-FU present in the mucosal or serosal bathing solution alone demonstrated similar rates of transport as under nonsink conditions. The concentration dependence of 5-FU fluxes indicates that the mucosal (m)-to-serosal (s) flux is composed of both a saturable and a linear component over the range of 1–100 µM in the ileum, whereas the s-to-m flux in the ileum and both fluxes in the colon are linear functions of concentration. Over the concentration range employed and the time course of these studies, 5-FU had no effect on the electrical properties of the ileum or colon. In the ileum, the m-to-s but not the s-to-m flux of 5-FU was reduced by (1) serosal ouabain (0.1 mM); (2) reduction of the bathing solution Na concentration; and (3) addition of uracil, thy mine, thymidine, uridine, 2-deoxyuridine, or uridine-5-monophosphate. These results indicate that 5-FU absorption in the ileum occurs by a Na-dependent mechanism that is inhibited by uracil and structurally related compounds. In distal colon, no evidence for an active transport mechanism was obtained. High-performance liquid chromatography (HPLC) analysis reveals that both ileum and distal colon metabolize 5-FU to more polar compounds. Metabolism in ileum is quantitatively greater than in distal colon. Metabolites are found predominantly on the side to which transport has occurred, suggesting that metabolism occurs concomitantly with transport. Since the intestinal cells metabolize 5-FU to more polar compounds and active absorption is inhibited in a competitive manner by related compounds, these results may provide an explanation for the variable oral activity reported for 5-FU.