Clinical significance of topical instillation technique in Japanese glaucoma patients.

The clinical significance of a proper eye drop application technique was evaluated in Japanese glaucoma patients. Patients diagnosed with primary open-angle glaucoma having intraocular pressure (IOP) greater than 21 mmHg were treated with eye drops at home. In some patients, however, the topical treatment was ineffective. They returned to the hospital to receive surgical treatment. On admission, 56% of these patients had IOP greater than 21 mmHg. Patient instillation technique was evaluated based on the proximity of the eyedropper tip to the eyes, application position, eyelid closure, treatment (removal) of excess fluid, and nasolacrimal occlusion. In addition, pharmacists interviewed patients to determine the level of understanding of glaucoma, knowledge of prescribed drugs, home application technique, and sensation after application. Multivariate analysis revealed that the key factors influencing the control of IOP to less than 21 mmHg with topical medication were: application of drops in the center of the eye and removal of excessive fluid, in addition to gender and age. Proper topical application at home was dependent on the patient's understanding of the disease, knowledge of prescribed drugs, patient education on the use of drugs, the competence of the instructor, and knowledge of correct application technique. This study indicates that easily comprehensible patient education on the use of eye drops, the nature of glaucoma and the proper use of prescribed drugs is vital to improving the clinical efficacy of topical ophthalmic medication of glaucoma in adult patients.

Plasma alpha-one acid glycoprotein and haloperidol concentrations in schizophrenic patients.

Thirty six schizophrenic patients were randomly assigned to placebo or haloperidol treatment for 6 weeks. Blood samples to measure plasma alpha-one acid glycoprotein (AAG), haloperidol and reduced haloperidol concentrations were obtained at baseline and weeks 2, 4, and 6. Blood samples were obtained 10-12 h after the evening dose and prior to the morning dose. Haloperidol and reduced haloperidol was assayed by HPLC with electrochemical detection. Plasma AAG levels were assayed by radial immunodiffusion. Patients were clinically assessed by the Brief Psychiatric Rating Scale (BPRS) and Abnormal Involuntary Movement Scale at baseline and weeks 2, 4, and 6. BPRS scores did not significantly decrease during placebo treatment, although a slight drop in plasma AAG levels was found. Haloperidol produced a significant decrease in BPRS scores and plasma AAG levels. Mean plasma haloperidol levels were 12.9 +/- 14.7 ng/ml at week 6. Significant correlations between decreasing BPRS scores and plasma AAG levels were not found with only a strong trend at week 2 (r = 0.445, p = 0.073). The role of AAG and psychotropic drug disposition in psychiatric patients requires further evaluation.

Comparison of the effects of hydrochlorothiazide and furosemide on lithium disposition.

OBJECTIVE: This study examined the interaction between lithium and diuretics, comparing both the pharmacokinetic and the pharmacodynamic variable of hydrochlorothiazide, furosemide, and placebo. METHOD: The study, which took place in an outpatient research clinic of a university hospital, used a double-blind, placebo-controlled crossover design. The subjects were normal, healthy male volunteers who responded to recruitment announcements. Thirteen subjects entered and completed the study. All subjects took lithium, 300 mg b.i.d., for 6 weeks. Hydrochlorothiazide, 25 mg b.i.d.; furosemide, 20 mg b.i.d.; and placebo were given during weeks 2, 4, and 6 in a random order of assignment. Serum lithium levels and indices of diuretic activity were measured during each week. RESULTS: The subjects' serum lithium levels after 5 days of taking hydrochlorothiazide were significantly higher than after 5 days of taking furosemide and placebo. At the doses studied, hydrochlorothiazide was also more potent than furosemide in increasing plasma renin activity, increasing sodium excretion, and decreasing lithium excretion. CONCLUSIONS: The observed differences between diuretics in effects on serum lithium may have been due to differences in the potency of the diuretics at the doses studied as well as in the site of action of the diuretic effect. The results must be interpreted cautiously, however, because the effects were small and of questionable clinical significance, and the study used healthy volunteers and low doses of lithium instead of psychiatric patients and the usual therapeutic levels of lithium.

Immunologic responses following serial skin testing.

Twenty volunteers underwent intradermal skin testing with tetanus toxoid (TT) and varicella-zoster (VZ) antigens weekly for 7 weeks. In addition to measurements of delayed hypersensitivity skin test responses, in vitro antigen specific lymphocyte stimulation and antibody levels were monitored. Data for TT exhibited more variability than VZ, demonstrating a marked boost in antibody titers after the first skin test and a shift in the kinetics of the skin test reaction to later maximum responses after the first 3 weeks. In contrast, serial skin testing with VZ was not associated with changes in cellular immune assays. Following the initial VZ skin test there was a slight rise in antibody levels for one-third of studied individuals. These observations suggest that VZ skin test antigen is ideal for monitoring immune function and that repeated testing should not significantly influence in vitro assays.

Review of naltrexone, a long-acting opiate antagonist.

The basis for using narcotic antagonists for the treatment of opiate addiction is discussed briefly, and the chemistry, pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage of naltrexone hydrochloride, an opiate antagonist drug, are reviewed. Naltrexone is rapidly and completely absorbed after oral administration but undergoes substantial first-pass extraction and metabolism by the liver. Naltrexone has a half-life of 3.9-10.3 hours and a slow terminal elimination-phase half-life of 96 hours. The major metabolite of naltrexone is 6-beta-naltrexol, which is present in plasma in greater concentrations than the parent drug. Problems in study design and patient adherence to treatment have made assessment of naltrexone's clinical efficacy difficult; however, studies have consistently demonstrated that patients who remained off opiates longer were those who took naltrexone longer. Factors associated with successful treatment outcomes include sustained therapy with naltrexone, participation in multidisciplinary programs of behavioral therapy and psychotherapy, and good family and social support systems. Gastrointestinal irritation and, in some studies, clinically insignificant increases in blood pressure, have been the most common adverse effects. Currently available data suggest that naltrexone is a very safe drug. The usual dosage of naltrexone hydrochloride is 50 mg orally once daily or 350 mg orally per week in three divided doses. Patients should be detoxified and opiate free for two to five days before initiation of naltrexone therapy. Naltrexone appears to be a useful adjunct to therapy in opiate addicts who are well motivated and who have strong psychological support systems.

Studies on the mode of action of a bacteriocin produced by Bacillus stearothermophilus.

Thermocin 10 was purified by elution from a carboxymethyl cellulose column. The eluted thermocin was homogeneous and yielded single bands with identical relative mobility when stained for protein or glycoprotein. Thermocin 10 inhibited RNA synthesis 3 min after its addition. Cell motility, oxygen uptake, ATP synthesis, and DNA synthesis were inhibited 10 min after the addition of thermocin 10. Total cell protein was reduced to one quarter of its normal content in cells treated with thermocin.