EFFICACY OF SUCRALFATE IN PREVENTING GASTROINTESTINAL SIDE EFFECTS OF NSAIDs

To find out the efficacy of sucralfate in preventing gastrointestinal side effects of non-steroidal anti-inflammatory drugs (NSAIDs) a prospective, randomised single blind study was conducted from 1989 to 1992. Patients with osteoarthritis, rheumatoid arthritis and other long standing painful conditions, who were expected to receive NSAIDs for over three months, were recruited into the study. All medicines were discontinued for a period of 10–15 days prior to initial endoscopic assessment. NSAID therapy was started and the patients were randomised to receive either placebo (group A) or sucralfate (group B) in addition. Patient were reassessed clinically every week and an endoscopic examination was repeated after 6–8 weeks of follow-up. A total of 176 patients were studied in group A (n=91) and group B (n=85). At the end of 8 weeks gastrointestinal symptoms were present in 30.6% and 26.4% patients of group A and B respectively. Endoscopic assessment showed superficial lesions in 36.5% and 18.7% while endoscopic ulcer in 2.4% and 1.1% patients of groups A and B respectively. Thus in patients receiving chronic NSAID therapy, simultaneous administration of sucralfate reduces the incidence of superficial gastric lesions but has no significant effect on symptoms or ulcer formation.KEY WORDS: Gastropathy, Sucralfate, Nonsteroidal anti-inflammatory drugs     

A review of bipolar disorder among adults

OBJECTIVE: This paper reviews the epidemiology, etiology, assessment, and management of bipolar disorder. Special attention is paid to factors that complicate treatment, including noncompliance, comorbid disorders, mixed mania, and rapid cycling. Advances in biopsychosocial treatments are briefly reviewed, including new health service models for providing care. METHODS: A MEDLINE search was done for the period from January 1988 through October 1997 using the key terms of bipolar disorder, diagnosis, and treatment. Papers selected for further review included those published in English in peer-reviewed journals. Preference was given to articles reporting randomized, controlled trials. RESULTS: Bipolar disorder is a major public health problem. The etiology of the disorder appears multifactorial. Diagnosis often occurs years after onset of the disorder. Comorbid conditions are common. Management includes a lifetime course of medication and attention to psychosocial issues for patients and their families. Standardized treatment guidelines for the management of acute mania have been developed. New potential treatments are being investigated. CONCLUSIONS: Assessment of bipolar disorder must include careful attention to comorbid disorders and predictors of compliance. Randomized trials are needed to further evaluate the efficacy of medication, psychosocial interventions, and other health service interventions, particularly as they relate to the management of acute bipolar depression, bipolar disorder co-occurring with other disorders, and maintenance prophylactic treatment.     

The treatment of periprosthetic fractures of the femur using cortical onlay allograft struts

Periprosthetic fractures of the femur are a complex problem to treat. Careful planning is essential before embarking on such a technically demanding procedure. There are many factors to be considered, including the premorbid condition of the patient and previous experience and training of the surgeon. Important factors relating directly to the fracture include the site, stability of the implant, and the state of the surrounding bone stock.     

Cocaine's effects on speech sound identification and reaction times in baboons

The effects of cocaine on speech sound discriminations was examined to determine whether cocaine's previously demonstrated effect in reducing speech sound discriminability was dependent upon either the type of stimuli employed (simple tones versus complex speech) or the procedure (stimulus detection versus stimulus discrimination). Because of demonstrated similarities in the way that baboons and humans discriminate speech, and in the way the CNS is thought to encode and process speech sounds in these two species, baboons were trained to perform a choice procedure to identify the occurrence of different synthetic vowel sounds (/a/, /æ/, //, /U/, and /љ/). Animals held down a lever and released the lever only when one of four target vowels sounded, and not when a fifth, standard vowel sounded. Acute IM administration of cocaine (0.0032–1.0 mg/kg) produced dose-dependent decreases in vowel discriminability that were mostly due to elevations in false alarms (i.e., releases to the standard vowel) following cocaine. Cocaine also shortened reaction times to the stimuli in two of three baboons, but to a much lesser extent than observed previously. These results suggest that cocaine may interfere with the ability of the CNS to process the acoustic cues in speech sounds, and that the effects of cocaine on reaction times may depend upon the complexity of the reaction time procedure employed.     

Progressive-ratio performance maintained by drug infusions: Comparison of cocaine,diethylpropion, chlorphentermine,and fenfluramine

Cocaine, diethylpropion, chlorphentermine, and fenfluramine were compared on a drug-maintained progressive-ratio procedure in baboons. Intravenous infusions of drug were contingent on completion of a fixed-ratio response requirement (fixed number of lever-press responses) with a 3-h time-out period following each infusion. Prior to testing each dose of drug, stable self-infusion performance was first established with 0.4 mg/kg cocaine when the fixed-ratio requirement was 160. Subsequently, a test dose of drug was substituted for the standard dose of cocaine. If the dose of drug maintained a criterion level of self-infusion performance (six or more infusions per day for 2 days), the ratio requirement was systematically increased every day until the breaking point at which the self-infusion performance fell below a criterion level (one or zero infusionsper day). Fenfluramine did not maintain criterion self-infusion performance at any dose tested (0.02–5.0 mg/kg). The dose ranges of the other drugs that maintained maximum breaking points were 1.0–5.6 mg/kg for chlorphentermine, 1.0–3.0 mg/kg for diethylpropion, and 0.1–0.4 mg/kg for cocaine. Within-animal comparison of the maximum breaking points indicated that cocaine maintained the highest breaking points, followed in order by diethylpropion, chlorphentermine, and fenfluramine. The rank ordering of these drugs with the breaking point measure corresponds well with both the results of other animal experiments on measurement of reinforcing efficacy of these drugs and with the clinical information about the human subjective effects and abuse of these drugs.     

The effects of Δ9-tetrahydrocannabinol alone and in combination with cannabidiol on fixed-interval performance in rhesus monkeys

It has been reported that cannabidiol (CBD) antagonizes the effects of ⁹-tetrahydrocannabinol (THC) on operant behavior in rats and pigeons. We have replicated this finding with rhesus monkeys. Four rhesus monkeys were trained to lever press on a fixedinterval 5-min schedule of food presentation with a 1-min limited hold and 1-min time out between successive intervals. The effects of 0.3 and 1.0 mg/kg THC alone were determined three times during the experiment; before the CBD-THC interaction, after the CBD-THC interaction and once with the CBD vehicle. A dose of 30 mg/kg CBD, which alone resulted in a 24% reduction in responding, completely antagonized the response rate reduction produced by 0.3 mg/kg THC. The effects of THC revealed a rate-dependent effect that did not conform to the log-linear rate-dependency plots described for most other drugs.This research was reported at the FASEB Meeting in Atlantic City, NJ in 1978 [Fed. Proc. 37: 739 (Abs.) 1978]     

Inhibition of ferrochelatase and accumulation of porphyrins in mouse hepatocyte cultures exposed to porphyrinogenic chemicals

The ability of 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC), 3,5-diethoxycarbonyl-4-ethyl-1,4-dihydro-2,6-dimethylpyridine (EDDC) and griseofulvin to induce porphyria in primary cultures of mouse hepatocytes has been examined. Exposure of cultured mouse hepatocytes to DDC, EDDC or griseofulvin resulted in a marked inhibition of ferrochelatase which was sustained over the 4-day exposure period. Maximal concentrations of DDC (25 M), EDDC (25 M) and griseofulvin (25 M) resulted in 14-fold, 30-fold and 9-fold increases, respectively, in total porphyrin in the culture medium. Analysis of the porphyrins accumulating indicated a predominance of protoporphyrin with all three xenobiotics. Addition of 5-aminolaevulinic acid (ALA) to mouse hepatocyte cultures (10–1000 M) resulted in much larger increases (up to 164-fold) in porphyrin accumulation in the medium and the porphyrin accumulating was predominantly uroporphyrin. These studies have demonstrated that primary cultures of mouse hepatocytes provide a valid mechanism-based in vitro model of the hepatic porphyrias produced by the dihydropyridines and griseofulvin in mice.     

Limited capacity for the removal of O6-methylguanine and its regeneration in a human lymphoma line

The Raji human lymphoma line is able to remove O⁶-methylguanine(O⁶MeG) lesions introduced by treatment of cells with N-methyl-N'-nitro-N-nitroso-guanidine(MNNG). The reaction has a rapid phase in which 40% of theO⁶MeG is removed in the first 10 min. The capacity of cellsfor rapid O⁶MeG removal is limited and is saturated at concentrationsof MNNG which do not saturate the systems removing 3-methyladenine.Pretreatment of cells with MNNG inhibits their ability to removeO⁶MeG produced by a subsequent dose given after 2 h. Treatmentwith N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) is effectivein diminishing cellular capacity for O⁶MeG removal, and cellsunable to remove O⁶MeG and sensitive to the cytotoxic effectsof MNNG are also more sensitive to ENNG than their removal competentcounterparts. Regeneration of the ability to remove O⁶MeG requiresincubation of cells for periods > 24 h. The O⁶MeG removalsystem is similar to that found in adapted Escherichia colialthough the capacity of the Raji lymphoma line is much lowerthan that of the induced bacteria per unit of DNA.