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Biomedical subjects

T J Cook

Publications and source records attributed to T J Cook.

10 recordsLinked to original sources

Topically administered norfloxacin compared with topically administered gentamicin for the treatment of external ocular bacterial infections. The Worldwide Norfloxacin Ophthalmic Study Group.

In this double-masked study, we randomly assigned 488 patients with clinical signs of acute bacterial conjunctivitis or blepharitis, or both, to treatment with either norfloxacin ophthalmic solution 0.3% (245) or gentamicin ophthalmic solution 0.3% (243) for one week. Of the patients with positive cultures, 71% (85 of 120) of the norfloxacin-treated patients and 65% (86 of 133) of the gentamicin-treated patients were clinically cured. An additional 25% (30 of 120) of norfloxacin-treated patients and 32% (43 of 133) of gentamicin-treated patients were clinically improved. On the basis of posttreatment cultures, 89% of all cultured bacteria were eradicated (146 of 179 organisms) or suppressed (14 of 179 organisms) after treatment with norfloxacin. The condition of five norfloxacin-treated patients did not clinically improve, compared with the condition of eight gentamicin-treated patients. Both antibiotics had similar efficacy against gram-positive and against gram-negative organisms. One norfloxacin-treated patient and two gentamicin-treated patients withdrew from the study because of local intolerance. Norfloxacin appears to be an effective and relatively safe agent for the treatment of bacterial infections of the eyelids or conjunctiva, or both. In this study, norfloxacin was clinically and microbiologically similar in activity to gentamicin.

Administration, Topical

A study of neuropathy in HIV infection.

A prospective study of possible aetiological factors for neuropathy associated with HIV infection was performed in 80 patients and 28 homosexual controls. At entry to the study twelve patients (15 per cent) had evidence of a generalized neuropathy not due to any other cause and a further three patients developed symptomatic neuropathy during a mean (SD) follow-up of 20 (7.5) months. All but two of these neuropathies were of the distal symmetrical sensory type. Electrophysiology was consistent with an axonal pathology and nerve biopsy confirmed this as the major pathological change. Warming threshold was the diagnostic test most frequently abnormal, sometimes in the absence of other electrophysiological abnormalities. No association was seen with opportunistic infection (cytomegalovirus, herpes simplex, Pneumocystis pneumonia, toxoplasmosis, Cryptococcus infection or tuberculosis). HIV proviral DNA could not be detected in paraffin sections of peripheral nerve in six patients with neuropathy. The presence of the neuropathy did not show significant correlation with depression of the number of CD4+ T cells in the blood, impaired T cell function tests, or IgG, IgM, or IgA levels. Immune complexes containing C1q, but not those containing IgG, IgM, IgA or C3c, were significantly more common among neuropathic patients (p = 0.01).

AIDS-Related Opportunistic Infections

Nocturnal therapy with famotidine for 1 year is effective in preventing relapse of gastric ulcer.

A multicentre, double-blind, randomized, placebo-controlled trial was undertaken to investigate the therapeutic efficacy of a nocturnal dose of famotidine 20 mg to reduce the 1 year relapse rate of recently healed gastric ulcers. Twenty investigators in eight countries randomized 202 patients with endoscopically confirmed healed gastric ulcers. Repeat endoscopies were performed at 6 and 12 months or for symptoms compatible with ulcer relapse. A per protocol analysis of cumulative life table relapse at 12 months showed that famotidine 20 mg was superior to placebo in reducing gastric ulcer relapse, 24 versus 50%, respectively (P less than 0.01). Both placebo and famotidine were well tolerated. Since nocturnal dosing with famotidine 20 mg is effective in preventing gastric ulcer relapse over a 1-year period and is well tolerated, it offers a therapeutic option for the long-term treatment of patients with gastric ulcer.

Adult

Effects of simvastatin and probucol in hypercholesterolemia (Simvastatin Multicenter Study Group II).

This 12-week, randomized, double-blind, multicenter study compared the efficacy, tolerability and safety of simvastatin (a potent HMG-CoA reductase inhibitor) and probucol. Two doses of simvastatin, 20 or 40 mg once daily, were compared to probucol, 500 mg twice daily. Both simvastatin doses were significantly more effective than probucol in improving the plasma lipid profile. Mean reduction in low density lipoprotein (LDL) cholesterol was 34% with 20-mg simvastatin and 40% with the 40-mg dosage, compared to a mean reduction of 8% with probucol. Simvastatin significantly decreased total cholesterol, triglycerides and apolipo-protein B, and increased high density lipoprotein (HDL) cholesterol and apolipoprotein A-I. Probucol caused some reduction in LDL cholesterol but significantly decreased HDL cholesterol. Both simvastatin and probucol were well tolerated and no serious drug-related events occurred. Simvastatin appears to be a well-tolerated and effective new agent used once-a-day as an adjunct to diet in the management of patients with hypercholesterolemia.

Adult

The safety and efficacy of topical norfloxacin compared with placebo in the treatment of acute, bacterial conjunctivitis. The Norfloxacin-Placebo Ocular Study Group.

Two hundred and eighty-four patients with acute conjunctivitis were enrolled in a double-masked study comparing norfloxacin ophthalmic solution with placebo. The proportion of patients who were clinically improved after 5 days treatment was 88.1% in the norfloxacin group and 71.6% in the placebo group (p less than 0.01). The proportion of patients who had all organisms eradicated, including the coagulase-negative staphylococci, after two to three days treatment was 52.7% for norfloxacin and 23.9% for placebo (p less than 0.01) and 64.7% and 26.3% (p less than 0.01) respectively when the coagulase-negative staphylococci were not included. Adverse experiences occurred in 4.2% of the patients receiving norfloxacin compared to 7.1% of the placebo patients. None of the adverse experiences was serious.

Acute Disease

Protection against fatal endotoxin shock in mice by antihistamines.

Protection against endotoxin shock by antihistamines and similar pharmacologic agents has been reported in the literature. The authors tested the validity of this form of treatment by animal experiments which were conducted in three phases. During the first phase, 10 mice each were treated intravenously with various doses of gram negative endotoxin to determine the dose of endotoxin which would kill 80% of the animals (LD80). This dose was determined to be 36 mg/kg bodyweight. During the second phase, 10 mice each were pretreated with various doses of either diphenhydramine (Benadryl) or of hydroxyzine HCI (Atarax) one hour prior to the administration of the LD80 of endotoxin. It appeared that high doses of diphenhydramine as well as of hydroxyzine were highly fatal to most animals by causing severe convulsions within 3 to 6 hours at doses of 40 or 50 mg/kg. Doses of less than 1 mg/kg appeared to have no protective effect, while doses of 2.5 and of 5 mg/kg, given one hour prior to the LD80 of endotoxin, had some protective value. In the case of diphenhydramine, 60% of the animals survived with 5 mg/kg pretreatment. Hydroxyzine hydrochloride protected 100% of the 10 animals so treated during the initial experiment and 90% during a subsequent experiment, if given 1 hour before the endotoxin. The third phase of this experiment was designed to determine the optimal time at which hydroxyzine needs to be given to protect against fatal endotoxin shock. Given 6 hours before endotoxin, hydroxyzine appeared to protect half of the animals, 1 hour prior to endotoxin, 5 mg/kg of hydroxyzine protected 90% of animals; if given simultaneously, it protected all animals. When hydroxyzine was given 1 hour after endotoxin there was a 70% survival and, if given 3 hours after endotoxin, a 40% survival.

Animals