The antihypertensive efficacy of losartan and amlodipine assessed with office and ambulatory blood pressure monitoring. Canadian Cozaar Hyzaar Amlodipine Trial Study Group.

BACKGROUND: Losartan potassium is a recently marketed angiotensin II receptor antagonist. Previous studies have suggested that its full antihypertensive efficacy may be delayed for up to 12 weeks. The authors compared the antihypertensive efficacy and tolerability of losartan at 6 and 12 weeks with those of amlodipine besylate, a commonly used calcium antagonist. METHODS: This multicentre, randomized, double-blind clinical trial studied 302 patients with mild or moderate hypertension in 1995. Of the 302, 97 also underwent ambulatory blood pressure monitoring (ABPM). After a 4-week placebo run-in period, the patients were randomly assigned to group A, B or C for 12 weeks. Those in groups A and B began treatment with losartan at 50mg/d, and those in group C began with amlodipine at 5 mg/d. If the blood pressure remained uncontrolled after 6 weeks, subjects in group A had their losartan dose doubled (to 100 mg/d), those in group B were given hydrochlorothiazide (12.5 mg/d) in addition to the losartan, which remained at 50 mg/d, and patients in group C had their amlodipine dose doubled (to 10 mg/d). RESULTS: At 12 weeks all 3 regimens reduced office-recorded diastolic blood pressure (DBP) with the patient sitting. The mean reduction in group A was 8.7 mm Hg (95% confidence interval [CI] 7.3 to 10.1) (p < 0.001), in group B 12.5 mm Hg (95% CI 11.0 to 14.0) (p < 0.001) and in group C 12.9 mm Hg (95% CI 11.4 to 14.5) (p < 0.001). Losartan alone lowered sitting DBP to a lesser degree than the other 2 treatments (p < 0.01). In contrast, ABPM readings, whether 24-hour, daytime or nighttime, were not different among the regimens. Comparison of the results at 6 weeks yielded similar findings. Adverse effects were uncommon and were not different among the groups, with the exception of ankle edema, which was more frequent in group C. INTERPRETATION: Losartan alone reduces both office and ABPM readings. The observed changes in office-recorded sitting DBP suggest that losartan is less effective than amlodipine or the combination of losartan and hydrochlorothiazide, but ABPM did not confirm this difference. Perhaps changes in office readings measure different attributes of a drug than does ABPM.

Dialyzer re-use--a multiple crossover study with random allocation to order of treatment.

A multiple crossover research study was used to evaluate the effect of dialyzer re-use on fever, blood leaks, serum urea and creatinine values and symptoms. Each of 6 crossover periods consisted of 4 weeks on either single-use or re-use, 1 week washout, 4 weeks on the alternative treatment and 1 week washout. The re-use consisted of 6 uses of each dialyzer and the washout weeks consisted of 3 single-use sessions. Analysis of paired observations within rather than between patients showed no effects of time (i.e. among crossover periods 1 through 6) or number of re-uses (i.e. among uses 1 through 6). There was no significant difference for temperature change during dialysis, blood leak rate, or the serum urea and creatinine values before the first dialysis of each washout period. There were no differences for symptoms of pruritus, cramps, nausea, headache, chest pain, backache or fatigue. There were no clinical advantages or disadvantages associated with dialyzer re-use.

Measurement of quality of life in end-stage renal disease: the time trade-off approach.

The quality of life of patients with end-stage renal disease was estimated using the time trade-off technique. The sample included 103 transplant, 60 hospital hemodialysis, 57 home/self-care, and 52 continuous ambulatory peritoneal dialysis patients. Test-retest reliability was high: intra-class correlation coefficient 0.81 (p less than 0.001). The correlations of the time trade-off with the Spitzer Quality of Life index and a visual analogue scale completed by the nephrologists, nurses, friends/relatives, and the patient were positive and statistically significant, but still relatively low (r = 0.22-0.43; p less than 0.01). The time trade-off demonstrated evidence for discriminative construct validity by ordering treatment groups according to a priori prediction. The mean time trade-off values and standard deviations (where death is 0 and full health is 1) were 0.43 (0.26) for hospital hemodialysis 0.49 (0.23) for home/self-care hemodialysis, 0.56 (0.29) for continuous ambulatory peritoneal dialysis, and 0.84 (0.24) for transplant. Analysis of variance showed transplant to be different from all other groups (p less than 0.001) with age, sex, time with end-stage renal disease, and work status making no significant independent contribution. The partial correlation coefficients between time trade-off score and items in the physical, social, and emotional functioning sub-scales of the Rand questionnaire showed that physical functioning was far more important than social or emotional functioning. The time trade-off is reliable, demonstrates evidence for validity, and suggests that the quality of life for patients with end-stage renal disease is much poorer than that reported previously.

Rhesus alloimmunization following intensive plasma exchange.

A 17-year-old woman was admitted to the hospital for the treatment of rapidly progressive systemic lupus erythematosus. She failed to improve when treatment with cyclophosphamide and prednisone and, therefore, was treated with intensive plasma exchange. A total of 24 liters of plasma was exchanged during six separate procedures over an 8-day period. The patient, who was blood group B Rh negative (Cde/cde), was found to have an IgG anti-D antibody reacting at a titer of 16 by the indirect antiglobulin technique 6 weeks after the first plasma exchange procedure. The titer of this antibody subsequently rose to 512. This patient, who had neither been pregnant nor received any blood products other than the plasma used during the plasma exchange, was presumably immunized by Rh positive red cells or stroma present in the transfused plasma. It is estimated that the patient received approximately 10(10) Rh positive cells, or approximately one ml of packed red cells--a quantity sufficient to cause Rhesus alloimmunization.

A lyophilized human reference plasma for coagulation factors. Evidence for stability of factors I, II, V, and VII through XII.

Results are reported of a one-year study on the stability of a lyophilized normal human reference plasma, originally standardized for eight clotting factor activities against a freshly prepared pool of citrated, platelet-poor normal human plasma. The stability of any particular coagulant activity in this reagent was represented mathematically as a function of the observed clotting times obtained under specific assay conditions, where any observed change in the clotting times over the trial period was taken to reflect a change in the stability of the reference plasma. Taking into consideration estimates of variability contributed by different donors of factor-deficient substrata-plasma, different lots of substrate from the same donor, different technologists, and certain age-of-substrate lot trends, there was no statistically significant change in functional activity for Factors V and VII through XII in the reagent when it was stored unreconstituted below -25C. By less rigorous criteria, both clottable fibrinogen (Factor I) and the thrombin-forming potential of prothrombin (Factor II) also were stable during this same period. Based on these results, it was concluded that when suitably prepared, lyophilized human plasma can be used as a stable, secondary standard reference for the assay of coagulation factors.

Monthly plasmapheresis for systemic lupus erythematosus with diffuse proliferative glomerulonephritis: a pilot study.

Twelve patients with systemic lupus erythematosus and biopsy-proved diffuse proliferative glomerulonephritis were randomly allocated to a control group (to continue receiving conventional therapy only) or to a plasmapheresis group (to receive conventional therapy along with one 4-I plasma exchange a month). The six patients treated with plasmapheresis had better preservation of renal function, reduced disease activity, fewer admissions to hospital and less need for steroid and immunosuppressive therapy than the six control patients. The patients treated with plasmapheresis also showed evidence of reduced immunologic activity and had no side effects attributable to the plasma exchange. These results suggest that monthly plasma exchange should be assessed in a controlled randomized trial as a possible therapeutic adjunct in patients with systemic lupus erythematosus and diffuse proliferative glomerulonephritis.

Digital stimulator control system for introducing premature stimuli.

A control system to convert a general-purpose stimulator into one which will generate premature stimuli at variable but controlled intervals is described. The control system was developed to sense spontaneous cardiac depolarizations and inject premature stimuli at preset elapsed times after every 10th or every spontaneous depolarization. The delay may be set by an analog circuit or by digital thumb-wheel switches. The output of the stimulator also may be coupled to the input, permitting the use of the system as a standard asynchronous stimulator with digital control of the pulse interval. A block diagram is presented to permit duplication of the system using standard digital and analog integrated circuits.