A study was made of clinical effectiveness and mechanism of action of the inhibitor of the specific 3',5'-cAMP phosphodiesterase papaverine in a therapeutic complex of measures designed to treat RA patients involving an immunodepressive preparation free from any cytopenic effect prospidin as a basic mediator. It has been shown that the papaverine antiarthritic action is associated with its positive effects on the unspecific component of the immune-complex inflammation, viz. processes of lipid peroxidation, activity of the antioxidant system of defence as well as on the vascular tone and microcirculation. All this improves tissue metabolism, and in this way enhances efficiency of RA basic therapy.
Previous studies have indicated that sex differences may exist in the pharmacological management of acute myocardial infarction (AMI), with female patients being treated less aggressively.
To determine if previously reported sex differences in AMI medication use were also evident among all AMI patients treated at hospitals in an urban Canadian city.
All patients who had a primary discharge diagnosis of AMI from all three adult care hospitals in Calgary, Alberta, in the 1998/1999 fiscal year were identified from hospital administrative records (n=914). A standardized, detailed chart review was conducted. Information collected from the medical charts included sociodemographic and clinical characteristics, comorbid conditions, and cardiovascular medication use during hospitalization and at discharge.
Similar proportions of female and male patients were treated with thrombolytics, beta-blockers, angiotensin-converting enzyme inhibitors, nitrate, heparin, diuretics and digoxin. Among patients aged 75 years and over, a smaller proportion of female patients received acetylsalicylic acid in hospital than did male patients (87% versus 95%; P=0.026). Multivariable logistic regression analysis revealed that, after correction for age, use of other anticoagulants/antiplatelets and death within 24 h of admission, sex was no longer an independent predictor for receipt of acetylsalicylic acid in hospital. Medications prescribed at discharge were similar between male and female patients.
The results from this Canadian chart review study, derived from detailed clinical data, indicate that the pattern of pharmacological treatment of female and male AMI patients during hospitalization and at discharge was very similar. No sex differences were evident in the treatment of AMI among patients treated in an urban Canadian centre.
Water fluoridation has not been introduced in Norway, although 99% of the population receive water with suboptimal fluoride levels. Alternative methods of fluoride prophylaxis have gained wide acceptance in this country. While less than 1% of the children received fluoride tablet in 1971, sales data in 1976 indicated a daily supply of fluoride tablets to 50% of the 0-5-year-olds and to 20% of the 6-11-year-olds. Most schoolchildren have joined mass prophylactic programs with regular with regular applications of fluoride solutions. Furthermore, fluoride-containing dentifrices have become available and are increasingly used. The increased use of fluoride has been paralleled by a marked reduction in caries and restorative need. During the past 5 years, a reduction of about 45% in the number of fillings inserted in 6-17-year-old children has been noted. In some areas, a 70% reduction has been recorded. The ratio between expenses for prophylaxis and savings in cost of treatment is favorable. The Norwegian Adverse Drug Reaction Committe received 34 case reports of adverse effects ascribed to fluoride prophylaxis, from 1970 to 1977. None of the 25 follow-up studies performed, suggested fluoride to have been responsible for the reported symptoms. In Norway, the benefits of fluoride prophylaxis are becoming increasingly evident.
Most dialysis patients are on 5 - 10 medications. The costs of these medications vary widely, ranging from pennies per day for water soluble multivitamins, to several thousand dollars per year for erythropoietin-stimulating agents. In Canada, public funding for drug therapies is undertaken by each province, with wide variability in coverage and on restriction criteria for expensive new drugs. For native Canadians and Inuit, access to drugs is superior to that of other Canadians through a federal program. The Canadian system for drug evaluation, where strict evidence-based medicine (EBM) and comparative effectiveness research (CER) is applied, is instructive and may provide clues to the future from an international perspective. Given the unique challenges in nephrology, it is predicted that access to new drugs and other therapies will be restricted by these evaluation methods. Indeed, it seems desirable for nephrology organizations to respond to this new threat in a pragmatic and balanced way. Part of that response might be a call for exceptional status for dialysis, with adjusted criteria of EBM and CER that would be more suitable, and stimulate innovation and research in nephrology.
Acetyldinaline: a new oral cytostatic drug with impressive differential activity against leukemic cells and normal stem cells--preclinical studies in a relevant rat model for human acute myelocytic leukemia.
Acetyldinaline [CI-994; GOE 5549; PD 123 654; 4-acetylamino-N-(2'-aminophenyl)-benzamide] is the acetylated derivative form of the original compound Dinaline (GOE 1734; PD 104 208). The efficacy and toxicity of Acetyldinaline for remission-induction treatment of leukemia were evaluated and compared with those observed in previous studies of Dinaline in the Brown Norway acute myelocytic leukemia, as a preclinical model for human acute myelocytic leukemia. There were three treatment groups. Leukemic animals received either 1 or 2 courses of 5 daily p.o. administrations of Acetyldinaline with a "full dose" of 23.7 mg/kg once daily (first group), a twice daily "half dose" of 11.85 mg/kg with an interval of 8 h (second group), or a "half dose" of 11.85 mg/kg once daily (third group). The drug-free interval between the 2 courses was 2 or 9 days. With repeated daily p.o. administrations of 23.7 mg/kg either in a single daily dose or a split daily dose of 2 x 11.85 mg/kg for 1 course, at least an 8-log leukemic cell kill was achieved. In contrast, with these treatment schedules, less than a 1-log cell kill of normal pluripotent hemopoietic stem cells (CFU-S) in the femoral bone marrow was found. Split daily dose treatment was more effective resulting in 37.5% cures, while no cures were observed with the single daily treatment for one course. Treatment with single daily dose of 23.7 mg/kg or a split daily dose of 2 x 11.85 mg/kg for 2 courses, with either a 2- or 9-day interval in between, resulted in lethal toxicity in most of rats. This result was comparable with that previously observed after equimolar doses of Dinaline (20 mg/kg). The half-dose once daily treatment with Acetyldinaline (11.85 mg/kg) for 1 or 2 cycles resulted in about a 4.5 or > 8-log leukemic cell kill, respectively. Toxic side effects, i.e., damage to the gastro-intestinal tract and hemorrhages in the lungs, were more pronounced with full dose either in the single or the split daily dose regimen. No significant toxicity was observed at the half-dose treatment once daily. In conclusion, the impressive differential activity against leukemic cells and normal stem cells observed in this relevant rat model for human acute myelocytic leukemia warrants the introduction of this compound in clinical phase I/II studies.
Three hermetics are assessed: chemically hardened Delton, light-hardened Estiseal, and composite Evikrol. The study was carried out in 126 children aged 6 years. The decrease of the increment of dental caries depends on the retention of hermetics on the occlusion surface of the teeth, and the efficacy of caries prevention in permanent teeth is much higher if hermetic sealing of fissures and fossae is combined with local fluorine prophylaxis and oral hygiene. All types of hermetics can be used to prevent permanent teeth caries, but chemically hardened ones should be preferred.
Pulse therapy with methylprednisolone (Solu-Medrol, Upjohn), 1000 mg daily over three successive days, was administered to patients in two randomized groups of 14 patients in each (23 patients with systemic lupus erythematosus, 5 with rheumatoid arthritis). In one of the groups the drug was taken per os, the other received it intravenously. There was no significant difference between the two groups in terms of clinical effectiveness and incidence of side effects However, the time-related course of such indices as erythrocyte sedimentation rate, the level of leukocytes, of total protein, urea, the blood antioxidant potential, permeability of erythrocytic membranes and capillary and tissue barrier proteinuria as well as the content of immune complexes in the arterial and venous blood was more striking with per os intake. Of the 14 patients, 11 demonstrated short-continued asymptomatic 35% rise in the activity of alaninaminotransferase.
Schoolchildren of 30 to 34 schools of Novgorod were vaccinated over a three-year period with Russian live cold-adapted attenuated vaccine for children and whole-virus inactivated vaccines and placebo for comparative field study of the vaccines properties and efficacy. In control trials both bi- and trivalent live attenuated vaccines were well tolerated and areactogenic. A whole-virus inactivated trivalent vaccine induced mild and moderate fever and local reactions in 2-4% of the vaccinees. Special observations are necessary to establish the possibility of use and to determine a dose of this inactivated vaccine for immunization of children, especially those of 7-10 years of age. All the vaccines induced HI antibody production in 50-80% and antineuraminidase in 50-70% of seronegative children. The pattern of the results was similar to that in revaccinated children with preexisting antibody at a level of 1:20, but much lower in children with the initial titre above 1:20. After the 3rd year of vaccination the immune response of the vaccinees was similar, most of the results depending on the initial antibody titre and also on the change of vaccine strains. This raises a question of the expediency of annual influenza revaccination of the same person after 2 years of successful immunization and of the necessity of vaccine strains replacement after 2-3 years of use.
Overall fifty one patients with chronic cardiac insufficiency (ChCI) were studied for changes in parameters characterizing hemodynamics and lipid peroxidation (LPO) under treatment with kapoten and prazosin. Kapoten was found to be capable of exerting an antioxidant effect and working in ways beneficial for the pulmonary circulation, while prazosin is generally indicated to patients with ChCI presenting with increased end diastolic pressure in the left ventricle. Prazosin activates LPO, for which reason its pro-oxidant action needs to be drug-corrected. Because of marked pharmacologic effects of both drugs in dealing with refractory circulatory insufficiency it is advisable that further studies be made in order that we might be able to determine indications for kapoten and prazosin therapy in coronary patients as well as those with arterial hypertension, cardiomyopathies, valvular defects, ChCI with complications more accurately.