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Biomedical subjects

V Cairns

Publications and source records attributed to V Cairns.

At least 19 recordsLinked to original sources

Combination of ramipril and hydrochlorothiazide in the treatment of mild to moderate hypertension: Part 1--A double-blind, comparative, multicenter study in nonresponders to ramipril monotherapy.

In a parallel-group multicenter study, the efficacy and safety of combination therapy with ramipril 5 mg plus hydrochlorothiazide 25 mg were compared double-blind with those of 5 mg and 10 mg ramipril monotherapy in patients with mild to moderate hypertension who had not responded adequately to ramipril 5 mg alone. Patients were initially treated single-blind for 1 week with ramipril 2.5 mg and 3 weeks with ramipril 5 mg. Of 240 patients enrolled, 165 were subsequently classed as nonresponders (diastolic blood pressure > 90 mmHg) and were randomized to one of the three double-blind treatments for a further 4 weeks. In the double-blind phase, the mean reductions in supine systolic and diastolic blood pressures at end point were significantly greater in the 5 mg plus 25 mg combination group (11.6/10.6 mmHg) than in the groups receiving ramipril 5 mg (6.2/5.9 mmHg; both p < 0.01) and ramipril 10 mg (7.4/7.1 mmHg; both p < 0.05). The proportion of responders at end point was also higher for combination therapy (72%) than for monotherapy (48% for ramipril 5 mg and 62% for ramipril 10 mg). All three treatments were well tolerated. Analysis of laboratory values revealed no clinically important changes.

Adult

The analysis of a multiple-dose, combination-drug clinical trial using response surface methodology.

We consider the situation where a multiple-dose, combination-drug clinical trial is conducted to identify one or more combinations that satisfy regulatory requirements. Generally, these requirements involve a compound hypothesis with multiple comparisons. The min test has been shown to be an optimal alpha-level test for testing a single combination drug. Analysis procedures in a multiple-dose, combination-drug study have typically involved classical ANOVA models or multiple regression models in a response surface methodology (RSM) framework. An inferential procedure based on an ANOVA model uses a screening test to address multiple comparison issues and multiple min tests to explicitly identify combinations satisfying regulatory requirements. An exploratory procedure based on RSM modeling is used to build a segmented linear model and a stairstep linear model to describe dose-response relationships. The two procedures are mutually supportive of one another in providing a broader assurance in the identification of effective combinations.

Analysis of Variance

Five-drug antiemetic combination for cisplatin chemotherapy.

A combination of metoclopramide, dexamethasone, droperidol, lorazepam, and diphenhydramine was used in prophylaxis of high-dose (greater than or equal to 100 mg/m2) or moderate dose (greater than or equal to 50 mg/m2) cisplatin. Sixty minutes prior to starting cisplatin, 16 mg dexamethasone, 50 mg diphenhydramine, and 0.5 mg lorazepam were given orally (PO). Droperidol 1 mg was given intramuscularly (IM) 15 minutes prior to beginning cisplatin. Repetitive doses of intravenous (IV) metoclopramide, 2 mg/kg in 75 ml 5% dextrose in water over 15 minutes was given 30 minutes prior to, and at 1 1/2, 4 1/2, and 7 1/2 hours after beginning cisplatin chemotherapy. Only patients with nausea and/or vomiting received subsequent doses of 2 mg/kg metoclopramide IV every 3 hours as needed. Patients refractory to metoclopramide were given 1 mg droperidol IM and 50 mg of diphenhydramine PO every 6 hours. There were 19 men and 9 women with a median age of 58 (range 31-75) years. Complete protection from nausea and vomiting in all courses of treatment occurred in 17 (61%) patients. In 63% and 70% of the 57 evaluable courses, there was neither nausea nor vomiting, during the first 24 hours after cisplatin. When present, nausea was mild and the median number of vomiting episodes was 2 (range 1-3). This antiemetic regimen was well tolerated. Toxicities were mild and occurred in 3 patients (angioneurotic edema, transient episode of facial twitching, and heaviness of tongue, respectively). The 5-drug antiemetic combination can prevent cisplatin-induced nausea and vomiting in a majority of patients.

Adult

Antihypertensive efficacy, tolerance, and safety of ramipril in young vs. old patients: a retrospective study.

The efficacy, tolerance, and safety of ramipril, an angiotensin-converting enzyme inhibitor, were assessed in 502 patients from five multicenter, double-blind studies who had mild-to-moderate essential hypertension. Each study was designed with a 4-week placebo run-in phase followed by 6 weeks of treatment with ramipril or one of five other antihypertensive treatments. A total of 412 young patients (17-65 years of age) and 90 old patients (66-87 years) in these studies received single daily doses of 5 or 10 mg of ramipril. At the end point of treatment, mean reductions in supine systolic blood pressure (19.4 mm Hg in young patients, 17.8 mm Hg in old) were significantly different, whereas mean reductions in supine diastolic blood pressure (13.3 mm Hg in young patients, 12.5 mm Hg in old) showed no significant difference. The number of responders was similar in both age groups: 68.6% and 71.1% of young and old patients respectively. No clinically relevant trends were observed in biochemical and hematological variables. Ramipril was well tolerated by both young and old patients, and there was little evidence that it was less safe in the elderly.

Adolescent

Antihypertensive efficacy, tolerance, and safety of long-term treatment with ramipril in patients with mild-to-moderate essential hypertension.

A total of 555 hypertensive patients took part in a 2-year multicenter, open-label study to determine the efficacy, tolerance, and safety of long-term therapy with ramipril. In the beginning, all patients were to receive 5 mg of ramipril/day. The dosage was then adjusted in accordance with response to treatment and ranged from 1.25-20 mg of ramipril daily. Of these patients, 129 also received 25 mg of hydrochlorothiazide daily at some point during the trial. To evaluate whether tolerance to ramipril developed during long-term treatment, a subgroup of 202 patients was analyzed for efficacy maintenance. Prior to enrolling in the 2-year study, these patients had received ramipril monotherapy in a short-term, double-blind study and had been classified as responders, i.e., their diastolic blood pressure had been maintained at less than or equal to 90 mm Hg. At the end of 104 weeks of treatment, 45.9% of patients were on 2.5 mg of ramipril alone and 43.6% were on 5 mg of ramipril alone. Only four patients required the addition of 25 mg of hydrochlorothiazide. No clinically important changes occurred, and kidney function was well maintained. The most frequently reported adverse events excluding intercurrent illnesses were dizziness/vertigo (6%), asthenia (4%), nausea (3%), headache (2%), and abdominal pain, gastrointestinal disorder, rash, and increased cough (1% each). Ramipril was safe, effective, and well tolerated in the long-term treatment of patients with mild-to-moderate essential hypertension.

Adult

Efficacy and safety of ramipril in combination with hydrochlorothiazide: results of a long-term study.

Hypertensive patients from a double-blind study comparing 5 mg of ramipril, 10 mg of ramipril, and 5 mg of ramipril + 25 mg of hydrochlorothiazide (HCTZ) were enrolled in an open 1-year extension study with ramipril and concomitant HCTZ. The starting dose of ramipril was 5 mg/day. Patients were given 25 mg of HCTZ in addition only if their diastolic blood pressure (DBP) was higher than 90 mm Hg. During treatment, the investigator was permitted to adjust the dosage of ramipril and HCTZ according to BP response and tolerance. A total of 159 patients were included in the 1-year study (86 men, 73 women, mean age of 54 years). One hundred twenty-one of the 159 patients received the combination of ramipril + HCTZ at some point in the study, 83 of them for more than 50 weeks. Thirty-eight patients were treated with ramipril alone over the entire study. In patients treated with ramipril monotherapy throughout the study, the largest drop in blood pressure occurred before visit 1. In patients treated with ramipril + HCTZ for greater than or equal to 50 weeks, the mean blood pressure continued to fall up to around week 10, while the therapy was being adjusted. Subsequently, the mean blood pressures remained low and fairly stable in both treatment groups. Similar results were seen in patients treated with the combination for less than 50 weeks. Adverse events were reported in 11 of the 38 patients in the ramipril group, in 22 of 83 patients treated with the combination for more than 50 weeks, and in 9 of 38 patients treated with the combination for 50 weeks or less. The analysis of the laboratory values revealed no general deterioration. It can be concluded that ramipril alone and in combination with HCTZ is an effective and safe drug for the long-term treatment of essential hypertension.

Adult

Clinical trial of high-dose oral medroxyprogesterone acetate in the treatment of metastatic breast cancer and review of the literature.

Recent studies have suggested that there are benefits from the use of high-dose parenteral medroxyprogesterone acetate (MPA) in the treatment of metastatic breast cancer. The present study was designed to assess the efficacy and toxicity of high-dose oral MPA in women with clinical parameters suggesting potentially hormonally sensitive metastatic breast cancer. The first 28 patients received 800 mg/day, and 11 of them had received no previous hormone (NPH) therapy. The response rate (complete plus partial) was 63% for those receiving NPH and 12% for those receiving previous hormone (PH) therapy. Toxicity was significant at these doses, especially for women treated for more than 5 weeks. Toxic effects included excessive weight gain, Cushingoid facies, worsening of diabetes mellitus, and other stigmata suggestive of hypercorticism. Nineteen other patients were treated at 400 mg/day with a 60% response rate for 10 NPH patients and 44% for patients with PH treatment. Toxicity was less severe in these patients. The median time to treatment failure was 23 weeks, and to survival, 119 weeks for all treated patients. Moderately high (400 mg/d) and higher dose (800 mg/d) oral MPA are capable of inducing reasonable response rates in patients with NPH treatment. The toxicity of these regimens was significant--profound weight gain was dose limiting in some patients. While effective, high-dose oral MPA is unlikely to supplant tamoxifen as first-line therapy in metastatic breast cancer.

Administration, Oral

A double-blind study to compare the efficacy, tolerance and safety of two doses of the angiotensin converting enzyme inhibitor ramipril with placebo.

In a randomized, double-blind trial, 2 doses of ramipril (2.5 and 5 mg once daily) were compared with placebo in patients with mild to moderate essential hypertension. A 2-week placebo run-in phase was followed by 4 weeks of treatment. Eighty-six patients entered the study and 17 withdrew during the course of the study. Both doses of ramipril appeared to be more effective than placebo in reducing blood pressure, but significant differences between 2.5 mg of ramipril and placebo were not found in any statistical analyses. In the endpoint analyses (taking the last measurement from each patient), the patients receiving 5 mg of ramipril had significantly larger decreases in blood pressure than the patients receiving placebo (t tests: standing systolic, p less than 0.001; supine diastolic, p less than 0.05; standing diastolic, p less than 0.05) and also than the patients receiving 2.5 mg of ramipril (standing systolic, p less than 0.05). It appears from the results of this study that the minimum effective dosage of ramipril is 5 mg once daily. No clinically relevant side effects or clinically relevant changes in laboratory values were observed.

Adult

Oral contraceptive use and blood pressure in a German metropolitan population.

The relationship between blood pressure (BP) and oral contraceptive (OC) use in women has been examined with the data from the Munich Blood Pressure Study (MBS), a cross-sectional study with follow-up of a random sample of 3198 Munich citizens aged 30-69 (response rate 69.3%). Multiple linear and logistic regression analyses were run with BP as the dependent variable and age, OC use, obesity, alcohol consumption, and smoking habit as the independent variables. All second and third order interactions between the independent variables were tested during a backward stepping procedure. OC use appeared as a significant main effect in most of the analyses. The coefficient of the OC variable was about 3 in the linear regression analyses for both systolic BP and diastolic BP, indicating an increase of about 3 mmHg in the systolic and diastolic BP of the OC users. An analysis of the change in BP after one year in relation to change in OC user status has also been made. It was observed that women ceasing to use OC had a clear decrease in BP while those starting to use OC had on average an increase in BP.

Adult

[Office visits and physical well-being of hypertensive patients. Results of the Munich blood pressure study].

The relationship between the frequency of physician visits, self-reported health of hypertensives and the awarenes, treatment and control of hypertension has been investigated, using data from the Munich Blood Pressure Study I (1980/81), a study with 2216 participants of a random sample of the adult population of Munich (30-69 y.). As hypothesized, the chance of detecting and treating high blood pressure increased with the frequency of physician visits. However, frequent physician visits did not guarantee an effective treatment of hypertension. 33% of the treated hypertensives who visited their physicians more than ten times in the preceding year failed to show normotensive or borderline blood pressure values. Additionally it could be seen that the awareness, treatment and control of hypertension was closely related to the number of self-reported chronic diseases and self-reported physical well-being. A relationship between social variables and treatment status was only observed for men: among hypertensive men, the proportion who were treated increased with the number of years of education but decreased with the number of household members.

Adult

Effect of tryptophan on informosomal and polyribosome-associated messenger RNA in rat liver.

The possible role that informosomal mRNA may play in the stimulation of hepatic protein synthesis induced by the acute administration of tryptophan was investigated. L-tryptophan (30 mg/100 g body weight) tube-fed to rats induced an increase (20%) in the amount of polyribosome-associated poly(A+)mRNA in the liver within 1 hour. On the other hand, the amount of the informosomal poly(A+)- mRNA revealed no significant increase or decrease. The size of the increase in the polyribosome-associated poly(A+)mRNA pool was equal to the entire amount of informosomal poly(A+)mRNA present in the hepatic cells. Therefore it was concluded that the failure to detect a significant decrease in the size of the informosomal mRNA pool indicated that the increase in the polyribosome-associated poly(A+)mRNA must be due to a different mechanism, such as enhanced nuclear-to-cytoplasmic translocation of nuclear poly(A+)mRNA, which had been reported earlier. To determine whether any qualitative or quantitative changes occurred in the RNA sequences along with the increase in poly(A+)mRNA following tryptophan administration, DNA/RNA hybridization studies were conducted by using hepatic polyribosome-associated poly(A+)- mRNA from tryptophan-treated and control rats. Although qualitatively no new species of mRNA were detected in the mRNA from tryptophan-treated rats, kinetic analysis of the hybridization curves indicated that there was a shift or accumulation of hepatic poly(A+)mRNA belonging to the intermediate and possibly the high frequency classes of polyribosome-associated poly(A+)mRNA in the livers of the tryptophan-treated rats.

Animals

Changes in patterns of mental illness over different hospital admissions.

Different diagnostic groups were compared in order to find out how constant individual patterns of illness remained over different hospital admissions. First, each of the syndrome scales in the Inpatient Multidimensional Psychiatric Scale and the Clinical Self-Rating Scales was examined to see how stable the patients' scores remained over two different admissions. Low correlations between scores on the two admissions were seen in the scales for mania and depression, reflecting changes in the clinical symptom patterns of patients with affective disorders. Many other scales, however, were fairly stable and were more closely connected with the given diagnosis. Secondly, each patient's pattern of illness on the first admission was compared with his or her pattern on the second admission. It was observed that patients with diagnoses of schizophrenia or schizo-affective psychosis tended to have less stable patterns of illness.

Affective Disorders, Psychotic

Some problems concerning the reliability and structure of the scales in the inpatient multidimensional psychiatric scale (IMPS).

Two problems concerning the IMPS are revealed. First, the importance of an appropriate reliability measure is demonstrated in a sample of 124 inpatients. Widely divergent results are found using three different intraclass correlation coefficients. The one producing the highest results was used by Klett and McNair (1966) and by Behrends et al. (1971). However, the results from this measure only apply to certain types of investigation. A measure more applicable to most investigations in psychiatric research (the intraclass correlation coefficient of individual ratings with between-rater variance included) produced results that were clearly lower, although still acceptable, with an average correlation of 0.72 between the 12 scales. Secondly, the multiplication of item scores by 2 or 8 when forming the scale scores is shown to lead to unusual and undesirable scale distributions in a sample of 1932 inpatients. The resulting implications for assessing change scores on some of the IMPS scales are discussed.

Adolescent

Plotting n-dimensional psychiatric data in 2 dimensions using Andrews' method.

Andrews' method of plotting n-dimensional data in 2 dimensions allows one to summarize all the data on one patient using a single curve. Comparisons have been made between different diagnostic groups on the basis of the 12 scales from the In-patient Multidimensional Psychiatric Scale (IMPS) using data from a sample of 787 newly admitted in-patients. For each diagnostic group, a figure was produced containing the Andrews' curves from all the patients in the group. Those groups that were particularly homogeneous or heterogeneous were noted. The main features of the different groups could be discerned.

Affective Disorders, Psychotic

Factors contributing to the length of general practice consultations.

Ten general practitioners in a study of general practice consultations were shown to differ significantly in the time they spent in their consultations. Patient demographic characteristics contributed little to differences in consultation time. Consultations in which (a) there was a diagnosis of psychological disorder, (b) the practitioner and the patients focused attention on psychosocial matters, and (c) psychotropic drugs were prescribed, were found to be associated with increased length of consultation time.

Family Practice

Amygdalotomy.

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Adolescent