Verapamil vs quinine in recumbent nocturnal leg cramps in the elderly

In an open-labeled trial with eight elderly patients (aged 62 to 87 years) suffering from nocturnal leg cramps refractory to treatment with quinine sulfate, we ruled out other active disease processes and substituted verapamil hydrochloride therapy (120 mg at bedtime). Response to treatment was assessed by biweekly observations by the primary care physician and nightly by the research registered nurse for the entire duration of the trial, lasting eight weeks. Observations made and clinical conditions reported were indicative of improvement and disappearance of cramping when therapy was changed from quinine to verapamil. This noteworthy improvement in patients with recumbent nocturnal leg cramps is an important finding and merits further investigation.     

Posture, Place, and Mood Effects on Ambulatory Blood Pressure

Ambulatory blood pressure was studied as a function of posture, place, and mood in 131 subjects classified according to race, gender, and hypertensive status. The effect of posture was significant and explained a substantial proportion of within-subject variability. After controlling for posture, significant place and mood effects were observed when subjects were sitting but not when they were standing. Home vs. work differences in both systolic and diastolic blood pressure were significantly greater in Whites than in Blacks. Similar differences in systolic blood pressure were greater in mild hypertensive than in normotensive subjects. The results of this study underscore the need to control for effects of posture when interpreting ambulatory blood pressure readings.     

Predicting Home and Work Blood Pressure Measurements from Resting Baselines and Laboratory Reactivity in Black and White Americans

The relationship between blood pressure in the laboratory (both at rest and in response to laboratory tasks) and ambulatory blood pressure at home and at work was evaluated. One hundred nineteen normotensive and unmedicated mild-moderate hypertensive black and white females and males participated in laboratory blood pressure monitoring at rest and during four challenging tasks (structured interview, video game, bicycle exercise, and cold pressor test) as well as ambulatory blood pressure monitoring while at home and at work. Baseline blood pressure taken while subjects were at rest was the strongest predictor of ambulatory systolic blood pressure (r = .64) and diastolic blood pressure (r = .77) at work. Among reactivity tasks the strongest predictors of ambulatory blood pressure in the total population were the structured interview and the video game (both psychological tasks) followed by the cold pressor test. Racial comparisons, however, determined that the cold pressor test predicted diastolic blood pressure significantly better for blacks (r = .73) than for whites (r = .40), suggesting a possible difference in blood pressure regulation.     

Reduced capacity for the reactivation of glucocorticoids in rheumatoid arthritis synovial cells: possible role of the sympathetic nervous system?

OBJECTIVE: Cortisol, the biologically active glucocorticoid, is a major endogenous antiinflammatory factor in rheumatoid arthritis (RA). The aim of this study was to examine the local conversion of cortisol to biologically inactive cortisone and vice versa (the cortisol-cortisone shuttle) in RA and osteoarthritis (OA) patients. METHODS: Thin-layer chromatography and phosphorimaging were used to examine the cortisol-cortisone shuttle in mixed synovial cells. Double immunohistochemistry was used to assess the key enzymes 11beta-hydroxysteroid dehydrogenase 1 (11beta-HSD1) and 11beta-HSD2 and their possible cellular locations. RESULTS: Double immunohistochemistry demonstrated 11beta-HSD1/2+ macrophages in the sublining area. The ratio of 11beta-HSD2+ cells to 11beta-HSD1+ cells was significantly higher in RA than in OA patients. Cortisol was converted to inactive cortisone in mixed synovial cells from RA and OA patients, which was largely inhibited by carbenoxolone (11beta-HSD1 and 11beta-HSD2 inhibitor). Using metyrapone to inhibit the 11beta-HSD1 reducing reaction (cortisone --> cortisol), we demonstrated that the capacity for reactivation of cortisone to cortisol was significantly higher in OA than in RA patients. Although the capacity for the cortisone-cortisol shuttle was higher in synovial cells from less-inflamed OA tissue compared with inflamed RA tissue, it was obvious that synovial inflammation in RA, but not OA, was related positively to the reactivation of cortisone. This indicates that in RA, a cause other than typical inflammatory factors inhibits the reactivation of cortisone. Since isoproterenol and adenosine inhibited the cortisol-cortisone shuttle, the loss of sympathetic nerve fibers (loss of beta-adrenergic agonist and adenosine) may be the missing link that accounts for the increased cortisol-cortisone shuttle in RA. CONCLUSION: This study demonstrates a reduced capacity for local reactivation of cortisone in RA synovial cells. Since synthetic glucocorticoids also use this reactivation shuttle, the results also apply to therapeutic glucocorticoids. This defective reactivation of cortisone may be an important unrecognized pathophysiologic factor in RA.     

Pharmacokinetics of ranitidine in patients with renal failure

The pharmacokinetics of ranitidine were studied in ten patients with renal failure (creatinine clearance, 6-54 mL/min) after intravenous (IV) (50 mg) and oral doses (150 mg). After oral administration, peak plasma concentrations of 378-808 ng/mL were obtained in two to six hours. Plasma concentrations declined very slowly and concentrations greater than 100 ng/mL were obtained for 16 to 20 hours after the dose. The elimination half-life following oral administration was 8.5 +/- 2.8 hours (standard deviation [SD]), and the bioavailability of ranitidine was 43.3% +/- 10.5%. After IV administration, the elimination half-life, plasma clearance, renal clearance, and volume of distribution were 7.0 +/- 1.0 hours, 170 +/- 38 mL/min, 36.0 +/- 25.0 mL/min, and 1.3 +/- 0.4 L/kg, respectively. About 20% of the IV dose and 9% of the oral dose were recovered unchanged in urine. There was a significant correlation between the renal clearance of ranitidine and creatinine clearance (r = .74, P less than .05) after IV administration. The elimination half-life in patients with renal insufficiency is about three times greater than that reported in the literature for healthy subjects. Similarly, the plasma clearance in these patients is about 20% of that reported in healthy subjects. The results indicate that ranitidine elimination is appreciably reduced in renal failure and that an adjustment of dose in patients with renal failure is warranted. A dose of 75 mg bid may be adequate in maintaining the therapeutic plasma concentrations that are required for adequate H2-blocking activity.     

Studies of heart function using apex cardiography in pregnancy-induced hypertension before and following therapy with dihydralazine sulfate

The apex cardiogram and its 1st differential quotient were simultaneously registered with the phonocardiogram, the electrocardiogram and the curve of the carotid pulse in 10 female patients with pregnancy-induced hypertension before and after the therapy with dihydralazine sulphate. 10 healthy pregnant women of the same trimenon served as comparative group. Altogether 20 parameters were investigated which are regarded as acknowledged indices of the compliance, the contractility and the ability of relaxation. The changes which we found point to an increase of the preload in H-gestosis, which seems to be regressive after the therapy with dihydralazine sulphate. The parameters of contractility and relaxation, including the systolic time intervals, remained uninfluenced.     

Recombinant erythropoietin in autologous blood donation

As a result of the AIDS crisis, public and physician pressure have increased the utilization of autologous blood products. Attitudes about homologous blood transfusion, however, have changed dramatically in recent years. A large segment of the population undergoing elective surgery is elderly and therefore has a significant incidence of cardiovascular disease and a slow response of the erythropoietic system when acute anemia occurs. However, preoperative autologous blood donation programs require 2-5 weeks to complete; the average yield is only 2.2 units per patient. As a consequence, autologous predonation is underused and homologous transfusion cannot be completely avoided in all patients. For several years recombinant human erythropoietin (rHuEPO) has been available and has been successfully used in the treatment of patients with renal anemia. This study evaluated the effect of r-HuEPO on patients with preoperative autologous blood collection. METHODS. Ten patients of both sexes scheduled for hip arthroplasty underwent a preoperative autologous program. During a period of 23 days prior to surgery autologous blood donation was performed with 7.5 ml/kg withdrawal on four occasions, the last one 5 days prior to surgery. Five patients were randomly treated with subcutaneous injections of rHuEPO (Erypo, Cilag GmbH, Sulzbach; Distributor: Fresenius AG, Oberursel, FRG) 200 IU/kg seven times, starting 3 days after the first blood withdrawal. All patients (n = 10) received oral iron therapy with iron sulphate 304 mg/die (= 100 mg iron/die). Patients with hypertension or recent myocardial infarction were excluded from the study. The hemoglobin level before donation had to be at least 11.0 g/dl. On each study day, a complete blood count and platelets, differential, and reticulocyte count were determined by standard methods as were transferrin, ferritin, and total iron-binding capacity. Blood loss and blood consumption during and after the operation were registered. The indication for blood transfusion (autologous/homologous) was based on hemoglobin values, which were not acceptable below 8.5 g/dl. RESULTS. No side effects of rHuEPO treatment were observed. Blood loss ranged from 650 to 1100 ml intraoperatively and 400 to 950 ml postoperatively with no differences between the groups. Patients with rHuEPO had no autologous red cell concentrates (aRCC) during the operation; two of them had two units of aRCC on the 2nd postoperative day. Two of the patients in the control group had intraoperative blood transfusions (2 and 3 units aRCC, respectively); all patients in this group were transfused postoperatively: 12 of the 20 units collected were utilized. At the onset of the operation the mean hemoglobin value in patients with rHuEPO was 13.5 +/- 0.4 g/dl compared to 11.3 +/- 0.3 g/dl in the controls. Reticulocytes increased significantly during the investigation period. On the 2nd, 3rd, and 4th days of autologous blood collection and before the onset of surgery, the number of reticulocytes was significantly greater in rHuEPO patients than in the controls. Further laboratory variables such as transferrin, ferritin, and total iron-binding capacity did not change significantly during the investigation period; there were no significant differences between the two groups. DISCUSSION. The results of the present study show that rHuEPO leads to an increase in reticulocytes with maintenance of hemoglobin levels during the phlebotomy program. As a consequence, patients with anemia and particular contraindications to homologous blood derivatives (irregular antibodies, Jehovah's Witnesses) may be able to undergo major surgery successfully. The possibility of shortening the intervals between phlebotomies would seem to be of major advantage; our data also suggest that an aggressive autologous blood collection program would increase yields over present programs. In our institute a minimum hemoglobin level of 11.5 g/dl is accepted for autologous donation.(ABSTRACT TRUNCATED AT 400 WORDS)     

Dose-ranging study to delineate the additive antihypertensive effect of guanabenz and captopril

This open crossover study in eight hypertensive patients defined a possible additive effect of oral guanabenz and captopril and determined a safe and effective dose range. Each group of four patients received placebo followed by ascending doses (on alternate days) of either guanabenz (2, 4, 8 mg) or captopril (6.25, 12.5, 25 mg) as initial monotherapy and were subsequently crossed over to the alternate monotherapy. Guanabenz and captopril were given concomitantly in increasing doses--the highest dose for both groups being 8 mg guanabenz/25 mg captopril. When guanabenz and captopril were given concomitantly, blood pressure decreased, both from the values during placebo administration and from the lead-in values recorded before each dose. Mean supine systolic and diastolic blood pressures after combination therapy decreased significantly (P less than .05) in a dose-related manner at most evaluations. The authors conclude that guanabenz and captopril have an additive effect when administered in combination to patients with hypertension.