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991.
Uchida Takahiro Martin Stephen Foster Todd P. Wardley Richard C. Grimm Susan 《Pharmaceutical research》1994,11(7):1009-1015
Poly(lactide-co-glycolide) microspheres containing different loads of OVA (0.05, 0.1, 0.5 and 1.0% w/w) were manufactured by a w/o/w emulsion/solvent evaporation method. Low load efficiencies of less than 20% were observed. Normal size distributions with mean volume diameters ranging from 3.7 to 4.7 µm were obtained for different batches. The in vitro release of OVA from different loaded microspheres showed an expected burst release with all batches. The in vivo dose study (1, 10, 25, 50 µg of OVA) was performed by subcutaneous and oral inoculation in mice by single (0 week) or double (0 and 3 weeks) administration of PLGA 50/50 microspheres containing 0.1% OVA. Subcutaneous administration showed an immune response (serum Ig levels by ELISA) statistically (Fishers paired t-test; P < 0.05) above OVA saline negative controls at 3, 6 and 12 weeks after administration. Oral administration of microspheres produced statistically higher systemic immune responses at the higher doses. Single and double inoculation orally and subcutaneously produced similar serum antibody levels. The in vivo load study was performed by subcutaneous and oral administration to mice of 25 µg OVA contained in various loaded (0.05, 0.1, 0.5 and 1.0% w/w) microspheres. Serum immune responses at 3, 6, and 12 weeks after inoculation were statistically above OVA saline controls and were inversely proportional to the OVA load using either route. This observation suggested a relationship between the number of microspheres delivered and the in vivo serum response. Single subcutaneous administration of 0.05 or 0.1% OVA loaded PLGA 50/50 microspheres induced larger immune responses compared with complete Freunds adjuvant. 相似文献
992.
Rusthoven JJ 《International journal of antimicrobial agents》1994,3(4):223-243
Biological response modifiers (BRMs) are agents which can modify the immune response to cancer or invasion of the organism by infectious agents. An explosive appearance of new BRMs has resulted from the development of recombinant gene technology and the availability of monoclonal antibodies. Colony-stimulating factors first became available for the prevention of neutropenia but may also have a role in the treatment of infections. Interleukin-1 is being tested as a modular of hematopoiesis and may be useful as a helper factor for T- and B-cell function. Immunoglobulins are being used against viral and bacterial infections while interferons can prevent viral upper respiratory infections and suppress or irradicate some viral hepatitides. Other BRMs which show promise include chemical agents and traditional herbal medicines. 相似文献
993.
994.
995.
M. Karita H. Sato Y. Koretsune K. Imai H. Ozaki H. Yokohama M. Hori T. Kamada H. Takeda M. Inoue 《European journal of clinical pharmacology》1995,48(6):467-471
The effects of a combination regimen of metoprolol and 1-adrenoceptor agonist denopamine on resting and exercise heart rate have been studied in 10 normal volunteers. Maximal ramp upright bicycle exercise was performed three times at 1-week intervals. Two hours before each exercise test, 5 mg metoprolol plus 20 mg denopamine, 5 mg metoprolol plus a denopamine placebo, or two placebos were orally administered in a double-blind fashion.During exercise after placebo administration, heart rate increased in parallel with the exercise intensity. Compared to the placebo values, resting heart rate was significantly decreased by an average of 10 beats · min–1 by 5 mg metoprolol, whereas it was not altered by the combination regimen. During exercise, however, both the combination regimen and metoprolol alone showed a significant negative chronotropic effect, decreasing peak exercise heart rate by an average of 14 and 21 beats · min–1, respectively. Peak oxygen uptake was also significantly decreased by both regimens.We conclude that concomitant administration of 5 mg metoprolol and 20 mg denopamine exerts an effective -adrenoceptor blocking action during exercise but a minimal effect at rest in normal subjects. The combination regimen appears to have a favourable pharmacological profile for -adrenoceptor blocker therapy in patients with chronic heart failure. 相似文献
996.
Milan Slavik P. Y. Liu Eric H. Kraut Ronald B. Natale Lawrence E. Flaherty Vernon K. Sondak 《Investigational new drugs》1995,13(2):143-147
Merbarone, NSC 336628, is an investigational anticancer drug with activity against experimental animal tumors including melanoma. This paper presents results of a Phase II clinical study of merbarone in patients with biopsy proven stage IV malignant melanoma without prior chemotherapy and with no evidence of CNS involvement. Thirty-five patients with median age 58 (range 27–81), with performance status 0–2 were treated with merbarone 1000 mg/m2/day for five days by intravenous continuous infusion repeated every 3 weeks. All patients (21 males and 14 females) were evaluable for toxicity. Two patients were not evaluable for response having been removed from protocol treatment due to toxicity and received other treatment during the first course of chemotherapy. Among the evaluable patients there was one complete response in a supraclavicular lymph node lasting four months and one partial liver response lasting three months. The remaining thirty-one patients were non-reponders. Of these one had a stable disease lasting 21 months. The overall objective response rate was 6% (2/35) with a 95% confidence interval of 1%–19%. Twenty-six of the 35 patients have died. The estimated median survival of the entire group was 9 months with a 95% confidence interval of six to eleven months. Renal toxicity was dose-limiting and manifested as increasing serum creatinine (54% of patients), proteinuria (51%) and hematuria (9%). One patient experienced grade 4 creatinine increase, proteinuria and acute renal failure. Other toxicities included nausea (71%), vomiting (51%), malaise (23%), weakness (20%), alopecia (17%), diarrhea (17%), anorexia (14%), transaminase (SGOT, SGPT) increase (14%), constipation (14%), alkaline phosphatase or 5nucleotidase increase (9%), and fever (9%). Hematologictoxicity (granulocytopenia, leukopenia, and anemia) was generally mild and infrequent (29%, only one patient had grade 4 granulocytopenia). Overall 9 patients (26%) had at least one grade 3 toxicity. We conclude that merbarone at this dose and schedule has detectable but minimal activity in the treatment of metastatic malignant melanoma and given the significant renal toxicity this schedule does not merit further evaluation in this disease. 相似文献
997.
Data from analgesic clinical trials have characteristics such as ordered categorical longitudinal responses with repeated measures, delay of effect with respect to analgesic plasma concentration, and right-hand censoring of response due to remedication. In order to determine the concentration-effect relationship of such data, we propose convolving an empirical function for plasma concentration, in the form of broken lines which connect each pair of neighboring observations, with a monoexponential function, to generate effect site concentration Effect site concentration and time are used, simultaneously, as independent variables in the fit of the model for the logit of the probability of having a specific pain relief (PR) score at each time point pre-remedication, via maximum likelihood. Using corresponding effect site concentration, the probabilities of having specific PR scores post-remedication are predicted via the concentration-response relationship established. The overall (pre- and post-remedication) predictions and corresponding standard errors for the responses are then estimated. Inference of the PR scoring, using a posterior method, is proposed. An illustration using real data is used to demonstrate these methods. 相似文献
998.
Zellman GL Bell RM Archie C DuPlessis H Hoube J Miu A 《Maternal and child health journal》1999,3(1):29-38
Objectives: To examine physician responses to suspected prenatal substance exposure and the reasons underlying these responses. Methods: National mail survey of practicing obstetricians and pediatricians who see neonates. Response rate: 63%. Results: More than 70% of physicians reported having ever suspected prenatal substance exposure. Response rates did not vary by specialty. Twenty-seven percent reported that they had never suspected prenatal substance exposure. The most common lifetime pattern (60%) was some response whenever prenatal substance exposure was suspected; next most common was no suspicion (27%). Just over 10% had a discretionary response: acting in some cases of suspected prenatal substance exposure but ignoring others. Two percent consistently ignored their suspicions. Getting help for the patient and protecting the fetus were the most common reasons to act. Among those who had ignored their suspicions, lack of sufficient evidence of substance use was the most often cited reason. There were some important specialty differences in reasons for response and non-response and in specific responses likely to be taken. Obstetricians are far more likely to provide the patient with information and get a substance use history; pediatricians are more inclined to involve outsiders. Conclusions: Obstetricians and pediatricians seem quite willing to act on their suspicions of prenatal substance exposure, and generally respond by taking positive actions. Specialty differences are few and reflect practice differences. 相似文献
999.
Moutquin JM 《Maternal and child health journal》1999,3(2):93-97
Objectives: To assess the achievements and effectiveness of efforts to reduce preterm deliveries through the collaborative efforts of funding agencies, scientists, obstetricians, pediatricians, and health care providers in Canada. Methods: Chronological review of studies carried out in Canada within the past two decades using several methodological approaches, including randomized clinical trials, surveys of women and physicians, and prospective cohort studies. Results: Tertiary prevention by treatment of spontaneous preterm labor with beta-agonists was effective in delaying delivery by 48 hr compared with placebo. Ongoing studies tested the comparative efficacy of oxytocin antagonists to beta-adrenergic agents. Recently, nitric oxyde donors have been tested. Secondary prevention using various approaches showed that high-risk factors could not be modified by these interventions. Before applying primary prevention approaches, surveys disclosed the lack of knowledge among both physicians and pregnant women. Conclusion: A recent Canadian consensus meeting emphasized the potential for success by using multidisciplinary, community-based health promotion approaches to prevent preterm labor; enhancing basic research in predictive markers such as cervical change, infection/inflammation, and psychosocial stress; and increasing political involvement of health decision makers. 相似文献
1000.
OBJECTIVE: To assess the quality of care provided to diabetic patients by family physicians in a university health clinic, using measures of glycemic and cardiovascular risk control as well as documentation of and adherence to World Health Organization (WHO) guidelines for diabetes primary care. DESIGN: Chart review of the previous year's medical notes for all identified diabetics in the practice over 2.5 years. RESULTS: Two-hundred and four diabetic patients were identified, with an estimated prevalence of 4.1%. The majority was type II diabetics, on oral hypoglycemic agents. Glycosylated hemoglobin was documented in 39.7% of patients, fasting plasma glucose in 99%, cholesterol in 93.1%, triglycerides in 91.2% and blood pressure in 85.8%; optimal control of these indicators was noted in 28.4%, 17.8%, 34%, 29.6% and 55.4% respectively. Fifty percent of the diabetics were referred for retinal checks. Physicians documented the presence of nephropathy in 46.8% and neuropathy in 59.6%; however, they documented patient instruction on foot care, diet, exercise and diabetes self-care poorly. CONCLUSION: There is a need for interventions to improve management and documentation in diabetes care in order to achieve early detection and prevention of complications. Developing a protocol for the clinic based on standard guidelines, and the use of flow sheets may be helpful in improving these intermediate indicators of quality of care. 相似文献