International journal of clinical pharmacology, therapy, and toxicology最新文献

The effect of H2 receptor antagonists on immediate cutaneous response to allergens remain controversial. In the present study, the effect of 7-day administration of omeprazole, cimetidine, famotidine and ranitidine on histamine induced wheal and flare reaction was evaluated. A single blind randomized parallel group study with within patient comparison of responses was planned in non-ulcer dyspepsia patients eligible to receive H2 antagonists or omeprazole. None of the drugs produced any changes in the area of the wheal in comparison to respective baseline values. The area of flare was decreased by all the drugs and the percentage decrease in this parameter caused by omeprazole, cimetidine, famotidine and ranitidine was 2.4, 12.3, 20.2 and 13.2, respectively. Only famotidine caused a significant decrease in flare area (p < 0.05).

Children with parents who have premature cardiovascular disease often have high serum cholesterol levels. In order to prevent the formation of atherosclerotic lesions in the coronary arteries, efforts are called for identifying, treating and monitoring individual children and adolescents who have high serum cholesterol levels. The screening of children should be performed in the context of their continuing health care and particularly, adolescents who smoke cigarettes, have high blood pressure, or consume excessive amounts of saturated fatty acids, total fat and cholesterol and who are overweight should be subjected to cholesterol testing. On the basis of the data presented in this article, it will be prudent to test high serum cholesterol in all young people whose parents have a total serum cholesterol exceeding 240 mg/dl. A total serum cholesterol level of equal to or greater than 200 mg/dl or an LDL cholesterol level of equal to or greater than 130 mg/dl when associated with family history or parental hypercholesterolemia warrants further evaluation. Children and adolescents with high LDL cholesterol levels that are equal to or greater than 130 mg/dl should be considered to be possible secondary causes of hypercholesterolemia and therefore continuous monitoring and clinical evaluation of this population may be necessary. Other factors such as familial hyperlipidemia, hypoalphalipoproteinemia, diabetes and high alcohol intake also need careful assessment.

Tumor necrosis factor-alpha (TNF alpha), a potential regulator of HIV-1 replication, is involved in the progression of AIDS and associated disorders such as muscle wasting, fever and gastrointestinal problems. HIV-seropositive patients were assigned to receive zidovudine (ZDV; 100 mg 4-5 times/d) alone (n = 14), pentoxifylline (PTX; 400 mg every 8 h), a drug known to block TNF alpha release (n = 7), or PTX and ZDV (n = 11) for 12 weeks in a prospective, open-label study. Weekly compliance checks and biweekly blood and 24-h urine samples were obtained for immunological assessments. Baseline TNF alpha levels were elevated in all study patients, independent of disease stage. There were no appreciable differences in immunologic variables (CD4 counts, total and unbound p24 antigen, TNF alpha, beta 2-microglobulin, and urinary neopterin levels) between groups. The mean HIV-1 viral load, as measured by a quantitative polymerase chain reaction technique, was 1.9-fold above baseline values after 12 weeks of ZDV and PTX compared with 8- to 9-fold greater levels in patients given either agent alone (p < 0.05). TNF alpha levels correlated with viral load (r = 0.67; p < 0.0001) in patients given the combined drug regimen. Virological evidence of lack of progression in AIDS patients suggests the beneficial use of ZDV and PTX in delaying progressive HIV-1 disease compared with each drug alone.

In a single-blind, in-patient, crossover study, the influence on the circadian blood pressure (BP) profile of the 9:00 a.m. versus the 9:00 p.m. acute administration of a single dose of benazepril 10 mg, a new angiotensin-converting-enzyme inhibitor, was assessed in 10 hypertensive patients by means of 24-hour intraarterial ambulatory BP monitoring. Mean 24-hour BP for the three treatments (placebo, benazepril a.m., benazepril p.m.) were 155/93, 131/83 and 138/86 mmHg, respectively. No significant differences between the two benazepril schedules were found in terms of either 24-hour or day-time and night-time mean BP values. However, hourly averages showed that benazepril a.m. had a more sustained antihypertensive effect than benazepril p.m., where a loss of efficacy was observed 19 hours after the administration. BP responses to static and dynamic exercise and to cold pressor test were unchanged after both benazepril schedules, as were BP peaks. These results demonstrate that acute benazepril administration markedly reduces systolic and diastolic BP. The morning administration is preferable because it more effectively covers the whole 24 hours than an evening dose.

As urinary tract infections in immunosuppressed renal transplant patients present a major therapeutic problem for clinicians in charge of renal units, the efficacy of the antibiotic ciprofloxacin in such cases was tested in this study. Twenty-six patients, 16 women and 10 men, aged 20 to 56 years, who developed urinary tract infection (UTI) from 6 months to 10 years after renal transplantation were included in the study. Of these patients, 20 (77%) showed cystitis and/or prostatitis and 6 (23%) clinical symptomatology of acute or recurrent pyelonephritis. Patients with obstructive uropathy were excluded. Urine culture was positive for E. coli in 16/26 patients (61.5%) and for proteus mirabilis, klebsiella, staphylococcus aureus in 10/26 (38.5%). All patients were given ciprofloxacin 250 mg x 2 daily for 10 days and the results of the treatment were compared to those of 60 nontransplant patients (controls) with UTI. Fourteen patients (54%) were completely cured and 10(38%) showed improvement, while the respective results in the controls were 68% (41/60) and 28%. Relapses occurred in two patients, one in each group. Serious side effects were not observed. It is concluded that ciprofloxacin is an effective and safe drug for the treatment of UTI in renal transplant patients.

Natural killer cell activity (NKCA) in patients with septic shock was statistically significantly lower than the value recorded for a group of drug-free, healthy volunteers [9.1 +/- 7.8 (n = 20) and 20.6 +/- 16.6 (n = 15), respectively; Student's test, p < 0.05]. As expected, preincubation of peripheral blood lymphocytes from samples taken from a group of controls with either alpha-interferon or interleukin -2 resulted in an enhancement of NKCA for each and everyone of the subjects studied; however, results from a similar protocol using patient samples showed a lack of consistency, both in the direction and magnitude, in the elicited changes in NK lytic function. Whereas samples from same patient responded with either an increase or a decrease in NKCA to preincubation with both immunostimulators, others responded with NKCA upmodulation to one and downmodulation to other of these test substances. A better knowledge of the mechanism(s) responsible for the depressed expression of NKCA in septic shock patients, and its altered response to alpha-interferon and interleukin-2, could generate new modalities in the diagnosis and therapy of this condition.

A large number of studies indicate that the process of atherosclerosis begins in childhood; and that this process is related to elevated levels of serum cholesterol which are often predictive of elevated serum cholesterol levels in adulthood. Despite substantial success in reducing coronary heart disease (CHD) mortality in the past two decades, CHD disease remains the leading cause of death worldwide. Preventing or slowing the atherosclerotic process in childhood and adolescence could mean years of healthy life for many people. The US Department of Health and Human Services has recently published a report on these findings [National Cholesterol Education Program: Report of the expert panel on blood cholesterol levels in children and adolescents 1991]. In this and following series of articles, a summary from these data is discussed. The articles have been arranged in the following sub groups: 1) Cholesterol levels in children and adolescents. 2) Nutrition recommendations for healthy children and adolescents for cholesterol control. 3) Cholesterol detection, diagnosis and evaluation in individuals, and 4) treatment for normalizing levels of cholesterol.

A single food item cannot possibly provide all of the essential nutrients in the amounts required. The best way to insure an adequate diet is to choose a wide variety of foods from all food groups that are available. Toddlers, children, adolescents and even the elderly persons require sufficient calories for growth and the maintenance of body functions. Excessive calories however, can lead to obesity and therefore, those should be avoided. Ingestion of unsaturated fatty acids and consumption of carbohydrates, minerals, proteins and fiber are essential for optimal growth and development. A balance needs to be maintained in order to have lower average serum cholesterol levels and blood pressure. It has been shown that the lactating mother's diet does not have effect on the total fat content or the cholesterol content of breast milk. Breast milk has been strongly recommended for infants, provided the mothers remain healthy and normal. Finally, manufacturers of food items should be encouraged to promote consistently the recommended eating patterns especially among children and adolescents.

The interactions of chlorpromazine, clomipramine, maprotiline and viloxazine hydrochlorides, and of clorazepate dipotassium salt and diazepam with polyvinyl chloride (PVC) and Stedim 6 infusion bags were studied. Stedim 6, is anew multilayer film whose inner layer is made of polyethylene. The drugs were in 5% dextrose and 0.9% sodium chloride isotonic solutions and the influence of these was also considered. The remaining concentrations of each drug were determined at regular time intervals in a 24-h period, by a spectrofluorometric method for chlorpromazine hydrochloride and by ultraviolet spectrophotometric methods for the other drugs. No binding was observed for viloxazine and maprotiline hydrochlorides whatever the infusion solution and the plastic container. A slight retention in PVC bags, but not in Stedim 6 ones, was noted for clomipramine hydrochloride and clorazepate dipotassium salt. This was more marked in the sodium chloride solution than in the dextrose one. Diazepam and chlorpromazine hydrochloride were bound both in PVC and Stedim 6 bags, but more in the former and more again in the sodium chloride solution than in the dextrose one. The results were explained in terms of the degree of crystallinity of the plastic material and the degree of lipophilicity of the drugs. Practical consequences are discussed.

The current status of clinical pharmacology (CP) in the countries of the former Eastern block is presented. The difficulties in obtaining an accurate comparative view are pointed out. CP is unevenly developed in Eastern European countries and the number of hours devoted to basic/clinical pharmacology differs considerably 100/nil to 240/50. The same is true for the orientation of clinical pharmacology, where present. It is mainly basic in only a few countries (Rumania, Turkey, some parts of the former Yugoslavia) and mainly clinical in Czecho-Slovakia, Croatia, Hungary, Poland, Greece. The number of CP units and CP specialists varies greatly as well (from none to more than 10 per country). The awareness that CP, in many countries is still young and the branch of (clinical) medicine is of great importance, not only for rational pharmacotherapy but also for other services as well, education and research is growing. In spite of the fact that the present status of CP in Eastern European countries is generally unsatisfactory, there are realistic chances that in the (near?) future, CP will develop to match the activities now present in the more developed countries.