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At least 757 records · Page 42Linked to original sources

Secondary prevention of ischemic stroke with low dose acetylsalicylic acid.

In order to evaluate the efficacy of low dose acetylsalicylic acid (ASA) for the secondary prevention of ischemic stroke, this cooperative multicenter clinical trial was conducted on a non-blind basis. Patients having a first transient ischemic attack (TIA), reversible ischemic neurological deficit (RIND) or completed ischemic stroke were eligible for this trial. A total of 590 patients including 47 cases of TIA, 23 cases of RIND and 520 cases of completed stroke entered this study. These patients were allocated by the time of admission to one of the following 5 trial regimens: (1) vasodilators having no known inhibitory effect on platelet function (control group), (2) dipyridamole (DP) 50 mg 3 times a day (DP group), (3) ASA 300 mg once a day (ASA 300 mg group), (4) ASA 300 mg once in combination with DP 50 mg 3 times a day (ASADP group), and (5) ASA 100 mg once a day (ASA1 group). No difference in effect between the control and DP groups was observed, nor between the ASA 300 mg and ASADP groups. Therefore, we combined the control and DP groups to make a non-ASA group, and joined the ASA 300 mg and ASADP groups to make an ASA3 group. The differences in the cumulative event-free rate appeared to be significant between the non-ASA group and the ASA3 group and also between the non-ASA group and the ASA1 group. But the frequency distribution of age, territory of stroke, diabetes mellitus, cardiac disease, hematological disease and hyperuricemia were significantly different among these 3 study groups. We thus included these covariates in the Cox's proportional hazard model to control their possible confounding effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Gram-positive bacteraemia in granulocytopenic cancer patients.

In the four EORTC International Antimicrobial Therapy Cooperative Group trials, the frequency of gram-positive isolates has increased significantly from 29% of single-organism bacteraemias in trial I (1973-1976) to 41% in trial IV (1983-1985). In trial IV febrile and neutropenic (less than 1000 polymorphonuclear lymphocytes per microliter) cancer patients were randomized prospectively to receive either azlocillin plus a long course (at least 9 days) of amikacin, or ceftazidime plus a short course (3 days) of amikacin, or ceftazidime plus a long course of amikacin. Without modification of the allocated antibiotics, the overall response rates for gram-positive bacteraemias were similar for all three regimens (19/37 [51%], 8/23 [35%] and 14/30 [47%]), respectively. However, in patients with prolonged and severe neutropenia, treatment with azlocillin plus amikacin was significantly more effective than with ceftazidime plus 3 days' amikacin (7/10 vs. 0/7). The overall response rate for these infections was significantly lower than that observed in trial I (46% vs. 74%), but this was not associated with increased mortality. The response to treatment was significantly influenced by the susceptibility of the infecting strain to the beta-lactam. Multivariate analysis revealed that increasing age, presence of a central venous catheter and resistance to beta-lactam adversely affected outcome. Future studies should be designed to improve the outcome of gram-positive bacteraemia in neutropenic patients with cancer.

Agranulocytosis↗

Nausea and vomiting after gynaecological laparoscopy: comparison of premedication with oral ondansetron, metoclopramide and placebo.

We have compared the incidence of postoperative nausea and vomiting up to 48 h after day-case gynaecological laparoscopy after oral premedication with ondansetron 4 mg, metoclopramide 10 mg or a placebo allocated randomly and assessed blindly. Emetic symptoms (nausea or vomiting) occurred in 26% of patients who received ondansetron, 42% of those who received metoclopramide and 50% of those given placebo.

Adolescent↗

A controlled trial of oral hyposensitization in pollen asthma and rhinitis in children.

This study describes the effect of an orally administered grass-pollen vaccine, taken pre-seasonally, on the clinical symptoms of fifty-four children with hay fever, asthma or both, during the 1982 grass-pollen season. Oral mixed grass-pollen vaccine and a matched placebo were randomly allocated to form two matched groups. Although small differences were observed in favour of the active group for both hay fever and asthma, no significant advantage was demonstrated over placebo in terms of symptom scores or additional medication required.

Administration, Oral↗

[The effect of activated nuclear factor-kappaB in pathogenesis of acute pancreatitis].

OBJECTIVE: To explore the effect of the activated NF-kappaB and the interaction between activated NF-kappaB and tumor necrosis factor (TNF)-alpha in the process of acute pancreatitis. METHODS: 64 Wistar rats were randomly divided into two groups of 32 rats: pancreatitis group (to be made pancreatitis models) and control group. 1.5, 3.0, 6.0, and 12.0 hours after the onset of experiment the amount of ascitic fluid was measured, blood was extracted from abdominal aorta, changes of pancreas was observed, pancreatic tissues were stained with HE, and flow cytometry (FCM) and enzyme linked immuno-sorbent assay (ELISA) were used to examine the content of TNF-alpha protein and activation of NF-kappaB (number of positive cells/50 micro l) in the pancreatic tissues. The contents of amylase and lipase in plasma were examined. The pathology of pancreatic tissue was graded. RESULTS: The levels of activated NF-kappaB and TNF-alpha protein in the pancreatic tissue were all significantly higher than those of the control group at any time point (all P < 0.05). The levels of activation of NF-kappaB of the pancreatitis group at any time point were significantly higher than those of the control group (all P < 0.01) and reached its maximum about 3.0 hours after the onset of experiment and then declined. The levels of plasma amylase and lipase were significantly higher in the pancreatic group than in the control group at any rime point. (all P < 0.01). In the pancreatic group severe edema and congestion were found at the 3.0 h time point and bleeding and necrosis were found at the 6.0-hour time point. CONCLUSION: Activated NF-kappaB as initial factor plays an important role in the pathogenesis of acute pancreatitis, activates a lot of inflammatory media, and induces cascading reaction of inflammation. TNF-alpha is a pivotal factor in pancreatitis pathogenesis, it cooperates with amylase and lipase to intensify the leisure in pancreatic tissue resulting bleeding and necrosis.

Acute Disease↗

Premedication with nasal s-ketamine and midazolam provides good conditions for induction of anesthesia in preschool children.

PURPOSE: To evaluate the efficacy and safety of intranasally administered s-ketamine and midazolam for premedication in pediatric patients. METHODS: Ninety children were randomly allocated to receive intranasally administered s-ketamine 1 mg.kg(-1) and midazolam 0.2 mg.kg(-1) (Group K1, n = 30), s-ketamine 2 mg.kg(-1) and midazolam 0.2 mg.kg(-1) (Group K2, n = 30), or midazolam 0.2 mg.kg(-1) (Group M, n = 30) as premedicants, using a double-blind study design. Sedation and anxiolysis were evaluated using a sedation and cooperation scale and recorded at several time points. RESULTS: Acceptable conditions (K1: 23; K2: 26, M: 19) for parental separation were not different between groups. Induction conditions were acceptable in 26 patients in K2 (P < 0.05 vs M) (K1: 23; M: 19). Compared to baseline values individual conditions significantly improved in groups K1 and K2 from 2.5 min after premedication until induction of anesthesia (P < 0.003), in group M conditions improved only five minutes after premedication (P < 0.05). Adverse effects observed in this series were within an acceptable range and similar for the three groups. CONCLUSION: Intranasal administration of s-ketamine and midazolam is an appropriate premedication in preschool children.

Adjuvants, Anesthesia↗

Intralesional cyclosporine in the treatment of psoriasis. A clinical, immunologic, and pharmacokinetic study.

In a double-blind, vehicle-controlled study, all of six psoriatic plaques treated with intralesional cyclosporine administered three times weekly for 4 weeks showed complete clearing or incomplete but significant clearing in comparison with vehicle-treated plaques (p less than 0.01). Epidermal thickness decreased from 0.42 +/- 0.07 to 0.27 +/- 0.08 mm at 4 weeks (p less than 0.03). Biopsy specimens obtained on day 5, before any clinical improvement, revealed a significant reduction of epidermal DR+CD1- antigen-presenting cells, epidermal and dermal monocytes, and keratinocyte intercellular adhesion molecule-1 expression. By day 5 the stratum corneum reverted to normal in the plaques receiving cyclosporine. Pain at the injection site was the major side effect. Steady-state blood cyclosporine levels ranged from 20 to 30 ng/ml during the first 12 hours after injection and became undetectable at 48 hours. These data suggest that cyclosporine improves the skin of patients with psoriasis by a local mechanism of action.

Adult↗

Long-term prophylaxis of urinary infections in women: comparative trial of trimethoprim, methenamine hippurate and topical povidone-iodine.

We randomized 64 patients with a history of recurrent urinary tract infections among 3 regimens of long-term (1 year) prophylactic treatment: 20 were given 100 mg. trimethoprim at night, 25 received 1,000 mg. methenamine hippurate every 12 hours and 19 were asked to cleanse the perineum (especially the periurethral area) twice daily with povidone-iodine solution. The progress of patients in terms of urinary symptoms and/or bacteriuria, changes in periurethral flora, side effects, and hematological and biochemical profiles was followed at regular intervals. All treatments were effective in reducing the incidence of symptomatic attacks when compared to the 12 months immediately before therapy and there was little to choose between the individual regimens on this account. However, trimethoprim was tolerated better than were the other 2 treatment regimens. In the group given trimethoprim most of the breakthrough infections (71.4 per cent) that occurred were caused by trimethoprim-resistant organisms (usually Escherichia coli), while in the other 2 groups the incidence of trimethoprim-resistant organisms causing infection was low (2.7 per cent). Treatment with trimethoprim reduced significantly the periurethral colonization of Escherichia coli.

Administration, Topical↗

Quantitation of drug levels and platelet receptor blockade caused by a thromboxane antagonist.

SQ 28,668 is a structural analog of thromboxane A2. It inhibits the effects of thromboxane in vitro. Fifty-six healthy male subjects were given either placebo or three equal daily doses of SQ 28,668 ranging from 25 to 1200 mg. Plasma drug concentrations increased in a dose-dependent manner. The shape of the plasma drug concentration-time curve was consistent with enterohepatic recirculation. The effects of SQ 28,668 on ex vivo platelet aggregation suggested that SQ 28,668 is a specific competitive antagonist of thromboxane A2 with a platelet receptor dissociation constant (estimated by Schild analysis) of about 19 nmol/L. Approximately 94% occupation of thromboxane receptors by SQ 28,668 was required to produce a small but measurable increase of the template bleeding time. Dose-ranging studies of antithrombotic drugs are difficult and expensive. For this reason, a method was developed that allows estimation of the dose of a thromboxane receptor antagonist that would be expected to be therapeutically equivalent to a given dose of aspirin.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Effects of pseudoephedrine and triprolidine, alone and in combination, on symptoms of the common cold.

A total of 466 healthy adults from four different regions of England entered a double-blind, randomised trial to test the effectiveness of an antihistamine (triprolidine) and a decongestant (pseudoephedrine), alone or in combination, in relieving symptoms of the common cold. During the study 199 subjects reported a total of 243 colds. Subjects recorded the severity of 12 symptoms during treatment and noted separately the severity of a further seven symptoms that represented unwanted effects of treatment or served as an index of suggestibility. They were then asked about their overall improvement in symptoms during treatment and whether they thought they had taken placebo. Sneezing, nasal obstruction, and overall response to treatment were significantly improved (p <0.01) with psuedoephedrine or pseudoephedrine and triprolidine compared with placebo.

Clinical Trials as Topic↗

Evaluating antiangiogenesis agents in the clinic: the Eastern Cooperative Oncology Group Portfolio of Clinical Trials.

Recent evidence indicates that treatment with a humanized monoclonal antibody (bevacizumab) directed at vascular endothelial growth factor improves response and survival in metastatic colorectal cancer when added to standard chemotherapy, validating angiogenesis as a therapeutic target. Investigators from the Eastern Cooperative Oncology Group (ECOG) have initiated a number of Phase III studies that will help further define the role of antiangiogenic agents for the treatment of breast, colon, lung, renal, and head and neck cancer, as well as melanoma and myeloma. The agents being evaluated target various biological functions involved in angiogenesis, including vascular endothelial growth factor (bevacizumab), endothelial cell proliferation (thalidomide, IFN-alpha), and matrix metalloproteinases (marimastat). These clinical trials include correlative laboratory studies aimed at elucidating how these agents may exert their clinical effects. The portfolio of Eastern Cooperative Oncology Group studies will serve to further define the role of this therapeutic strategy for patients with advanced cancer.

Antibodies, Monoclonal↗

Maintenance ranitidine treatment after haemorrhage from a duodenal ulcer. A 3-year study.

Forty patients with a recently healed duodenal ulcer (DU) that presented with haemorrhage were entered into a blind, randomized study of maintenance ranitidine therapy (150 mg at night) versus a placebo preparation, to determine whether prolonged ranitidine therapy could influence the natural history of the ulcer diathesis. Duodenal ulceration or duodenal cap erosions of Lanza grade 3 recurred in 24 of the 40 patients studied during the 2-year trial period but was associated with further bleeding in only 2 cases. Maintenance ranitidine therapy significantly reduced the incidence and symptoms of DU/erosion recurrence at all time intervals beyond 3 months, the maximum protective effect being observed after 12 to 15 months of treatment (incidence, p less than 0.001; symptoms, p less than 0.03). The DU/erosion recurrence rate without treatment after 2 years of successful maintenance ranitidine therapy was significantly less than for patients randomized to the placebo group at entry to the study (p less than 0.03). Two years of maintenance ranitidine therapy appear to be beneficial for patients who have a healed DU that presented with haemorrhage. This treatment, however, cannot be recommended without reservation until the implications of the associated high incidence of asymptomatic duodenal ulceration have been fully evaluated.

Adult↗

Primary care physician recommendations for colorectal cancer screening. Patient and practitioner factors.

BACKGROUND: Current guidelines for colorectal cancer screening do not specify the role of age or comorbidity in patient selection. Reported screening practices may thus be influenced by patient, as well as physician, characteristics. METHODS: A questionnaire was sent to primary care physicians in 10 states to determine recommendations for fecal occult blood testing (FOBT) and sigmoidoscopy in 4 pairs of clinical vignettes that varied by patient age (65 or 75 years) and comorbidity (none, mild, moderate, and terminal). RESULTS: Among the 884 respondents (50%), most physicians recommended FOBT in all vignettes except those with a terminal illness and fewer than half recommended sigmoidoscopy in any vignette. Physician recommendations were influenced by comorbidity, but one third still recommended FOBT for terminally ill patients and less than 50% recommended sigmoidoscopy for patients with no comorbidity. Differences in recommended screening between vignettes that differed only in patient age were small. Among all subgroups of physicians, at least 30% recommended FOBT in terminally ill patients and no more than 60% recommended sigmoidoscopy in healthy patients. CONCLUSIONS: Primary care physicians were much more likely to recommend screening with FOBT than sigmoidoscopy, regardless of patient and practitioner factors. Although physician recommendations were influenced by patient comorbidity and age, they frequently recommended FOBT in clinically inappropriate settings and failed to recommend sigmoidoscopy when appropriate. Broad-based interventions to improve appropriate screening practices may be needed.

Aged↗

Virtues of a worldwide congenital heart surgery database.

The rationale for a congenital heart surgery database lies in the organized manner in which information can be compiled to accomplish programmatic evaluation, monitor clinical outcomes, comply with governmental requirements, perform retrospective and prospective clinical studies, and participate in local, national, and global improvement strategies. The task of inaugurating an effective congenital heart surgery database has taken many years and involved concurrent development efforts at multiple sites. Two such efforts took place in North America with the Society of Thoracic Surgeons Congenital Heart Surgery Database, and in Europe with the European Congenital Heart Defects Database. These initial efforts provided the impetus for development of an international congenital heart surgery database that would allow scientific exchanges on an international scale and promote multi-institutional evaluation of congenital heart surgery. Sample outcome templates from the Society of Thoracic Surgeons and the European Association for Cardio-thoracic Surgery's accepted minimum database data set are reviewed for the specific diagnostic entry ventricular septal defect, to familiarize the reader with potential available data summaries and outcome analyses, including risk stratification, when data harvest is performed. In Europe, the agreed upon minimum data set are now collected as part of the Pediatric European Cardiac Surgical Registry, while in North America users of the CardioAccess database and users of the minimum data set downloaded from the Society of Thoracic Surgeons web site are being notified of plans for a 2002 data harvest incorporating the minimum database data set. It is likely that the extant voluntary, minimal data set congenital heart surgery database will be replaced by a mandated system required by states, provinces, and countries. Data collection schemes and data validation programs will become standardized, which will result in improved data quality and uniform congenital heart center participation. As participation with valid data approaches 100% of congenital heart centers, the power and importance of the database increases exponentially. Reliable information can be used to assess residency/fellowship programs, resource allocation, major therapeutic trends, manpower issues, and in the end, all initiatives that will require accurate information.

Databases, Factual↗

Importance of bleomycin in combination chemotherapy for good-prognosis testicular nonseminoma: a randomized study of the European Organization for Research and Treatment of Cancer Genitourinary Tract Cancer Cooperative Group.

PURPOSE: This prospective randomized trial was designed to compare the efficacy of etoposide plus cisplatin (EP) versus bleomycin, etoposide, and cisplatin (BEP) chemotherapy in patients with good-prognosis metastatic nonseminomatous testicular cancer. PATIENTS AND METHODS: Four hundred nineteen patients with good-prognosis nonseminomatous testicular cancer were randomized to receive four cycles of cisplatin 20 mg/m2 on days 1 to 5 plus etoposide 120 mg/m2 on days 1, 3, and 5 with or without bleomycin 30 mg weekly. RESULTS: Of 395 eligible patients, 169 of 195 patients allocated to EP (87%) and 189 of 200 patients allocated to BEP (95%) achieved a complete response with chemotherapy alone or after postchemotherapy surgery. These results are significantly different (P = .0075). After a median follow-up duration of 7.3 years, eight patients (4%) on each treatment arm relapsed. In view of the low number of unfavorable treatment outcomes (11%), no significant differences were detected in time to progression (P = .136) and survival (P = .262). Both the acute and late pulmonary toxicity and neurotoxicity were significantly greater in patients who received BEP, whereas Raynaud's phenomenon occurred exclusively in patients who received BEP (P < .001). Two patients treated with BEP died of bleomycin pulmonary toxicity. CONCLUSION: BEP is the most effective combination regimen in the treatment of disseminated nonseminomatous germ cell cancer. In this particular BEP regimen with etoposide at a dose of 360 mg/m2 per cycle, even in good-prognosis patients, bleomycin cannot be deleted without compromising treatment efficacy, but its use is associated with more toxicity (particularly pulmonary) and efforts to reduce this merit further exploration.

Adolescent↗