Liposomal amphotericin B for empirical therapy in patients with persistent fever and neutropenia. National Institute of Allergy and Infectious Diseases Mycoses Study Group

BACKGROUND: In patients with persistent fever and neutropenia, amphotericin B is administered empirically for the early treatment and prevention of clinically occult invasive fungal infections. However, breakthrough fungal infections can develop despite treatment, and amphotericin B has substantial toxicity. METHODS: We conducted a randomized, double-blind, multicenter trial comparing liposomal amphotericin B with conventional amphotericin B as empirical antifungal therapy. RESULTS: The mean duration of therapy was 10.8 days for liposomal amphotericin B (343 patients) and 10.3 days for conventional amphotericin B (344 patients). The composite rates of successful treatment were similar (50 percent for liposomal amphotericin B and 49 percent for conventional amphotericin B) and were independent of the use of antifungal prophylaxis or colony-stimulating factors. The outcomes were similar with liposomal amphotericin B and conventional amphotericin B with respect to survival (93 percent and 90 percent, respectively), resolution of fever (58 percent and 58 percent), and discontinuation of the study drug because of toxic effects or lack of efficacy (14 percent and 19 percent). There were fewer proved breakthrough fungal infections among patients treated with liposomal amphotericin B (11 patients [3.2 percent]) than among those treated with conventional amphotericin B (27 patients [7.8 percent], P=0.009). With the liposomal preparation significantly fewer patients had infusion-related fever (17 percent vs. 44 percent), chills or rigors (18 percent vs. 54 percent), and other reactions, including hypotension, hypertension, and hypoxia. Nephrotoxic effects (defined by a serum creatinine level two times the upper limit of normal) were significantly less frequent among patients treated with liposomal amphotericin B (19 percent) than among those treated with conventional amphotericin B (34 percent, P<0.001). CONCLUSIONS: Liposomal amphotericin B is as effective as conventional amphotericin B for empirical antifungal therapy in patients with fever and neutropenia, and it is associated with fewer breakthrough fungal infections, less infusion-related toxicity, and less nephrotoxicity.     

Amelioration of polyuria by amiloride in patients receiving long-term lithium therapy

Vasopressin-resistant diabetes insipidus is a common side effect of the treatment of affective disorders with lithium. We studied the effect of amiloride on lithium-induced polyuria in nine such patients receiving maintenance lithium therapy who had a vasopressin-resistant defect in urinary concentrating ability. After a mean (+/- S.E.) of 24 +/- 6 days of amiloride administration, the urine volume fell (from 4.7 +/- 0.6 to 3.1 +/- 0.3 liters per 24 hours; P less than 0.005), and the urine osmolality increased (from 228 +/- 35 to 331 +/- 34 mOsm per kilogram of H2O; P less than 0.001). The decrease in urine output was sustained during six months of observation in the absence of any significant change in plasma levels of lithium, potassium, or bicarbonate; urinary excretion of sodium or lithium; or creatinine clearance. Amiloride administration was also associated with a significant increase in urine osmolality (from 575 +/- 54 to 699 +/- 48 mOsm per kilogram of H2O; P less than 0.005) measured after fluid deprivation and the injection of exogenous vasopressin. We conclude that amiloride mitigates lithium-induced polyuria, at least partly, by blunting the inhibitory effect of lithium on water transport in the renal collecting tubule. Thus, amiloride may provide a specific therapy for polyuria in lithium-treated patients while obviating the need for potassium supplementation in the treatment of this kind of polyuria.     

Ventricular dysrhythmias in middle-aged hypertensive men treated either with a diuretic agent or a beta-blocker

The purpose of this study was to identify the frequency of cardiac dysrhythmias in two similar groups of hypertensive middle-aged males (age 45-66). They had previously been randomized either to a diuretic treatment (n = 42), or a beta-blocking agent (n = 41). A 24-hour ambulatory Holter monitoring, and serum potassium, was obtained in all patients, serum magnesium was measured in 35 patients. The mean number of ventricular premature beats (VPBs) and the frequency of complex arrhythmias (19 vs. 5) was significantly higher in the diuretic group (p less than 0.01). The serum potassium was significantly lower (p less than 0.001) in the diuretic group, and there was a significant (p less than 0.005) inverse correlation between the number of VPBs and the serum potassium in all treated patients. The patients with complex arrhythmias were older (p less than 0.01) than the remainder of the patients. No correlation between serum magnesium and VPBs or complex arrhythmias was found. This study demonstrates increased frequency of VPBs in older hypertensive males, treated with diuretics, and that hypokalaemia predisposes to increased cardiac arrhythmias. We conclude that in older mildly hypertensive men hypokalaemia should be avoided.     

Clinical evaluation of a new lipid-based delivery system for intravenous administration of amphotericin B

In a retrospective study a new lipid-based delivery system for administration of amphotericin B was evaluated in 26 treatment courses in 22 patients. Amphotericin B was given by infusion diluted in either the lipid solution (1 mg/kg/d; 13 courses) or dextrose (0.92 mg/kg/d; 13 courses). No differences were noted in the serum pharmacokinetics. Fever or rigors were observed in 6 of 13 courses in the conventional amphotericin B group versus none in the lipid amphotericin B group (p=0.007). Four of 13 courses of treatment were discontinued due to adverse effects in the conventional amphotericin B group compared to none in the other group (p=0.048). In the lipid amphotericin B group the decrease in creatinine clearance was significantly lower on the fourth day of treatment (p=0.04) and significantly fewer patients had a decrease of more than 25 % in creatinine clearance on the sixth day (4/12 vs 9/11 p=0.02). These preliminary findings suggest that this lipid amphotericin B formulation is well tolerated with few nephrotoxic effects.     

Lipoproteins, post-heparin lipoprotein lipase and hepatic triglyceride lipase in patients with and without severe hyperlipemia caused by alcoholism

Because of the high incidence for development of a secondary hyperlipemia during chronic alcohol intake, this study was performed to look for a possible reason, why some patients produce severe hyperlipemia and other ones not. 15 male patients with chronic alcoholism (group I) who produce under influence of alcohol a secondary type-V hyperlipoproteinemia (type-V HLP) were compared with 15 male controls. Additionally, 8 male patients with chronic alcoholism (group II) who were normolipemic under alcohol abuse, and 7 male patients (group II) who had also produced type-V HLP under chronic alcohol abuse, but were teetotal since at least 6 months, were investigated. In comparison with controls, patients of group I showed significantly (p less than 0.01) increased plasma concentrations of very low-density lipoproteins (VLDL) and significantly decreased plasma concentrations of low-density lipoproteins (LDL), high-density lipoproteins2 (HDL2) and HDL3 (all p less than 0.01). Furthermore, the activities of postheparin lipoprotein lipase (LPL) and hepatic lipase (HTGL) were significantly decreased (both p less than 0.01). In patients of group III, the plasma concentrations of lipoproteins did not differ significantly from controls, but the activity of LPL was also significantly impaired (p less than 0.01), whereas the activity of HTGL was distinctly (p less than 0.01) increased. No significant difference between patients of group II and controls could be demonstrated. It is concluded that severe alcohol intake strongly impairs LPL in patients with chronic alcoholism. The pronounced increase of HTGL in patients of group III seems to protect these individuals from producing severe hyperlipemia under the influence of alcohol.     

A controlled trial of fluconazole or amphotericin B to prevent relapse of cryptococcal meningitis in patients with the acquired immunodeficiency syndrome. The NIAID AIDS Clinical Trials Group and Mycoses Study Group.

BACKGROUND. After primary treatment for cryptococcal meningitis, patients with the acquired immunodeficiency syndrome (AIDS) require some form of continued suppressive therapy to prevent relapse. METHODS. We conducted a multicenter, randomized trial that compared fluconazole (200 mg per day given orally) with amphotericin B (1 mg per kilogram of body weight per week given intravenously) in patients with AIDS who had completed primary therapy for cryptococcal meningitis with amphotericin B (greater than or equal to 15 mg per kilogram). To be eligible, patients had to have at least two negative cultures of cerebrospinal fluid immediately before randomization. The primary end point was relapse of cryptococcal disease as confirmed by biopsy or culture. RESULTS. Of 218 patients initially enrolled, 119 were assigned to fluconazole and 99 to amphotericin B. Twenty-three patients were found not to have met the entry criteria; six other patients assigned to amphotericin B did not receive it and were lost to follow-up. Of the remaining 189 patients, after a median follow-up of 286 days 14 of 78 receiving amphotericin B (18 percent) and 2 of 111 assigned to fluconazole (2 percent) had relapses of symptomatic cryptococcal disease (P less than 0.001 by Fisher's exact test). There was a difference of 19 percent in the estimated probability of remaining relapse-free at one year between the fluconazole group (97 percent) and the amphotericin B group (78 percent) (95 percent confidence interval, 7 percent to 31 percent; P less than 0.001). Serious drug-related toxicity was more frequent in the amphotericin B group (P = 0.02), as were bacterial infections (P = 0.004) and bacteremia (P = 0.002). CONCLUSIONS. Fluconazole taken by mouth is superior to weekly intravenous therapy with amphotericin B to prevent relapse in patients with AIDS-associated cryptococcal meningitis after primary treatment with amphotericin B.     

A comparison of amphotericin B alone and combined with flucytosine in the treatment of cryptoccal meningitis.

We compared amphotericin B therapy for cryptococcal meningitis with a newer regimen containing both amphotericin B and flucytosine. In 50 patients with 51 courses of therapy adherent to the protocol, 27 courses were with amphotericin B and 24 with the combination. Even though the combination regimen was given for only six weeks and amphotericin B for 10 weeks, the combination cured or improved more patients (16 vs 11), produced fewer failures or relapses (three vs. 11), more rapid sterilization of the cerebrospinal fluid (P less than 0.001) and less nephrotoxicity (P less than 0.05) than did amphotericin B alone. The number of deaths was the same (five) with each regimen. Adverse reactions to flucytosine occurred in 11 of 34 patients but were not life threatening. We conclude that combined flucytosine-amphoericin B therapy is the regimen of choice in cryptococcal meningitis.     

Role of hypervolemia and renin in the blood pressure control of patients with pyelonephritis renal scarring

Patients with pyelonephritic renal scarring are at risk of developing renal failure and hypertension. We studied glomerular filtration rate (GFR), renal plasma flow (RPF), filtration fraction (FF), systolic (SBP) and diastolic (DBP) blood pressure, fractional sodium, potassium and phosphate excretion, peripheral renin activity (PRA), plasma aldosterone (p-Aldo), urinary albumin excretion (U-Alb) and urinary beta 2-microglobulin excretion (beta 2-M) in hydropenia and during transition to 3% volume expansion with isotonic saline infusion in 22 female patients with renal scarring due to pyelonephritis and 9 healthy controls. The patients had significantly lower GFR, higher SBP and higher PRA in hydropenia, but there was no significant difference in RPF, FF, DBP or p-Aldo. After volume expansion, SBP, DBP, PRA and p-Aldo were significantly higher in patients than in controls. Transition to 3% volume expansion was associated with a similar increase in SBP in both patients and controls, whereas DBP increased significantly more in the patients (p less than 0.01). Volume expansion resulted in a significant suppression of PRA and p-Aldo in both patients and controls. The patients with renal scarring had the same capacity to excrete sodium and water during transition to volume expansion as the healthy controls. The renin-aldosterone system seems abnormally activated and is probably more important than hypervolemia in the development of hypertension in this group of patients.     

Increased blood pressure during potassium depletion in normotensive men

Epidemiologic studies suggest an inverse relation between potassium intake and the prevalence of hypertension. To investigate the effect of dietary potassium restriction on blood pressure, we used a randomized crossover design to study 10 healthy, normotensive men randomly assigned to isocaloric diets (each lasting nine days) providing either low (10 mmol per day) or normal (90 mmol per day) amounts of potassium, while sodium intake was maintained at the subjects' usual levels (120 to 200 mmol per day). With the low-potassium diet, plasma potassium levels declined from 3.8 to 3.2 mmol per liter (P less than 0.001), but plasma sodium and chloride levels were unchanged. The average daily excretion of urinary sodium (+/- SEM) on the low-potassium diet was significantly lower than that with the normal-potassium diet (10 +/- 10 vs. 144 +/- 10 mmol; P less than 0.001). The mean arterial pressure did not change significantly during normal potassium intake, but it increased over the nine days of the low-potassium diet from 90.9 +/- 2.2 to 95.0 +/- 2.2 mm Hg (P less than 0.05). Both mean arterial (P less than 0.01) and diastolic (P less than 0.005) pressures were significantly higher after the low-potassium diet than after the normal-potassium diet. Potassium depletion suppressed plasma aldosterone levels but had no effect on plasma renin activity or on arginine vasopressin or catecholamine levels. A saline infusion further increased the mean arterial pressure in the potassium-depleted subjects but had no effect in the control group (P less than 0.05). We conclude that short-term potassium depletion increases blood pressure in healthy, normotensive men and permits further increases in blood pressure after saline loading. We found no evidence that the hypertensive effect of potassium depletion resulted from changes in either renal hemodynamics or circulating levels of vasoactive hormones.     

Plasma ultrafiltrable magnesium in insulin dependent diabetics.

Plasma ultrafiltrable (MgUF) and total magnesium concentrations were measured in 60 insulin dependent diabetics and compared with values in an age matched control group. Although the diabetic patients had lower plasma albumin concentrations (p less than 0.05), both ultrafiltrable and total magnesium concentrations were significantly decreased by 6.8% and 7.6%, respectively, compared with those of the controls (p less than 0.001). In the diabetic group MgUF varied inversely with fasting plasma glucose (r = -0.269, p less than 0.05). In 14 patients with significant hypomagnesaemia, fasting plasma glucose concentration was higher (p less than 0.01) and the diabetes was of shorter duration (p less than 0.05) than in 46 patients with an MgUF in the control range. The fasting urinary magnesium creatinine ratio was greater in the diabetic patients (p less than 0.05). Patients with retinopathy did not have lower plasma magnesium values than those without retinopathy.     

Psychological predictors of survival in cancer patients undergoing radiation therapy

In a prospective study to identify psychological factors affecting survival in cancer patients receiving radiation therapy, 101 consecutive patients were evaluated for anxiety, depression, and perception of the seriousness of the condition. In 3 years, the survivors were compared to the nonsurvivors. The survivors had significantly higher mean trait anxiety (p less than 0.05) than the nonsurvivors. State anxiety and depression scores also tended to be higher in the survivors (p less than 0.01). Self-assessment of the seriousness of their disease did not differentiate the two groups. The nonsurvivors had significantly more pain (p less than 0.05). Within the nonsurvivor group, survival time was negatively correlated with state anxiety (p less than 0.01), trait anxiety (p less than 0.02), and depression (p less than 0.01). In the nonsurvivors, women rated their condition to be significantly more serious than men (p less than 0.01). Female nonsurvivors tended to rate their condition to be more serious than female survivors (p less than 0.1), while male nonsurvivors rated their condition to be significantly less serious than male survivors (p less than 0.01). Only among female nonsurvivors did the seriousness rating correlate significantly with anxiety (p less than 0.01). The sex differences confirm our previous finding that men may tend to cope with cancer with more massive denial than women. We hypothesize that patients with higher anxiety and depression in the nonsurvivor group had a massive defensive failure, while those who had high anxiety levels in the survivor group had been more realistic about their disease.(ABSTRACT TRUNCATED AT 250 WORDS)     

Decreased skeletal muscle potassium in obesity

The effect of body weight on total body potassium, skeletal muscle electrolytes and fat content was studied in seven lean and seven obese middle-aged men and seven lean and eight obese middle-aged women. Total body potassium and total body fat increased with body weight (p less than 0.01 and less than 0.05 for men, and p less than 0.05 and p less than 0.001 for women, respectively). So did muscle fat in men (p less than 0.01), while muscle tissue potassium was decreased in both obese men (p less than 0.001) and obese women (p less than 0.05). The skeletal muscle Na/K-ratio tended to be higher in obese men (p less than 0.1) but was not related to body weight in women. Skeletal muscle magnesium was higher (p less than 0.01) in obese men than in lean men. No differences between lean and obese women were found. Obese men had higher diastolic blood pressure (p less than 0.05) than lean men, while there was no difference between obese and lean women. Compared with lean subjects, obese subjects thus had lower relative skeletal muscle mass and men, especially, had more fat and less potassium in the skeletal muscle.     

HLA in primary open-angle glaucoma

Histocompatibility antigen typing was carried out in 50 Caucasian patients with primary open-angle glaucoma (POAG) and 50 Caucasian ocular-normotensive subjects. HLA-A 3 was present in 46%, B7 in 52%, B12 in 50%, and either B7 or B12 in 88% of p,tients with POAG. These prevalences in POAG patients were significantly greater than in ocular-normotensive subjects (p less than 0.01, p less than 0.0005, p less than 0.001, and p less than less than 0.0005, respectively). The prevalences of A 3-B 7, A 3-B 12 and either combination were also significantly greater in POAG patients than in the ocular normotensives (p less than 0.005, p less than 0.005, and p less than 0.0005, respectively). HLA-BW 35 was noted to be in deficit in Caucasian POAG patients (8%) as compared to Caucasian ocular normotensives (32%; p less than 0.01).     

Intraerythrocytic sodium and potassium concentrations during acute and chronic digitalization

To assess the cellular effects of digoxin, intraerythrocytic sodium and potassium concentrations were measured in 17 patients during the early phase of digitalization, in 45 patients on long-term therapy and in 64 non-digitalized control patients. Acute digitalization raised intraerythrocytic sodium from 11.6 +/- 0.4 to 16.7 +/- 1.0 mmol/l (mean +/- SEM) (p less than 0.01) and reduced intraerythrocytic potassium from 100.1 +/- 1.3 to 95.9 +/- 1.8 mmol/l (p less than 0.01). These changes were strongly correlated with the steady-state plasma digoxin concentration. During a few weeks of digoxin therapy, the intraerythrocytic cation composition normalized gradually. In patients on chronic treatment, neither intraerythrocytic sodium (11.3 +/- 0.3 mmol/l) nor potassium concentrations (100.0 +/- 0.6 mmol/l) differed significantly from the values of the control group (11.4 +/- 0.2 and 99.9 +/- 0.5 mmol/l, respectively). The changes in intraerythrocytic cation concentrations, induced by acute digitalization, seem to disappear during chronic administration of the drug.     

Blood coagulation and fibrinolysis in patients with Beh?et's disease

In patients with Beh?et's disease, venous thrombosis has often been described as a complication. The pathogenesis of this complication, however, has not been fully understood. In this work, various parameters of blood coagulation and fibrinolysis were studied in 20 patients with Beh?et's disease and 13 sex-matched healthy volunteers. Patients were classified into three subgroups according to the number of clinical signs involved; group I (no sign): 4 patients; group II (one or two signs): 11 patients; group III (more than three signs): 5 patients. Patients with Beh?et's disease, showed an activation of blood coagulation, such as the shortening of prothrombin time (p less than 0.001), decreases in concentrations and activities of plasma antithrombin III (AT-III) (p less than 0.01) and elevated levels of plasma thrombin-antithrombin-III complex (TAT) (p less than 0.01), compared to the control group. Plasma levels (p less than 0.01) and activities (p less than 0.01) of protein C (PC) and total protein S (PS) levels (p less than 0.05) were increased in the patients. Decreased levels of alpha 2-plasmin inhibitor (p less than 0.001) also indicated an activation of fibrinolysis in the patients. When analyzed among the subgroups, patients belong to group II and III showed higher levels of plasma FDP D-dimer (p less than 0.05) and lower levels of plasminogen (p less than 0.05), as compared with patients in group I or control group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Age-related decline of vasopressin mRNA in the bed nucleus of the stria terminalis.

To determine whether aging influences arginine vasopressin (AVP) biosynthesis in the extrahypothalamic neurons of the bed nucleus of the stria terminalis (BNST), we used in situ hybridization and quantitative autoradiography to compare AVP mRNA in 3-month-old, 14-month-old, and 24-month-old male Fischer 344 rats. As AVP synthesis in the BNST has previously been shown to be steroid-dependent, plasma testosterone (T) was measured by radioimmunoassay. The 24-month-old animals had significantly fewer AVP-labelled cells than either the 3-month-old (p less than 0.01) or 14-month-old (p less than 0.05) animals. The cells that were present in the 24-month animals were less intensely labelled than in the other groups, as indicated by a significantly reduced number of grains per cell (p less than 0.01). Plasma T was also significantly lower in 24-month-old animals when compared with 3-month (p less than 0.01) or 14-month (p less than 0.05) groups. The results indicate that there is a marked age-related decline in vasopressin biosynthetic activity in neurons of the BNST.     

Influence of age on the metastatic behavior of breast carcinoma

The effects of aging on the biologic behavior of malignant neoplasms are poorly understood. To examine the question of a possible age effect on the metastatic behavior of tumors, we reviewed the clinical histories, autopsy protocols, and histologic slides of 187 patients with metastatic breast carcinoma who were subjected to complete autopsy at The Johns Hopkins Hospital. Patients were categorized in four groups according to the age of onset of breast carcinoma: group I had 12 young patients (less than 40 years old); group II had 41 patients, 40 to 46 years old, considered to be premenopausal; group II had 89 patients, 47 to 60 years old, considered to be early postmenopausal; and group IV had 45 patients over 60 years old, considered to be late postmenopausal. Group II patients survived about 50% longer than group III or IV patients (p less than 0.05), and groups I, II, and III patients had significantly greater numbers of metastases than group IV patients (p less than 0.05). There was a progressive decline in the frequencies of metastases in several locations as a function of age, such that group I and II patients had significantly more frequent metastases to the central nervous system (p less than 0.05), endocrine organs (p less than 0.01), ovary (p less than 0.05), pancreas (p less than 0.01), and gastrointestinal tract (p less than 0.05) than patients in group III or IV. These differences in number and distribution of metastases were not explainable on the basis of survival, therapy, or initial stage of disease. The results suggest that the process of aging may influence the metastatic behavior of breast carcinoma; hormonal and metabolic factors may be implicated.     

Increased plasma vasopressin and serum uric acid in the low renin type of essential hypertension

In 22 50-year-old men with long-standing, untreated essential hypertension of the low renin type, venous plasma vasopressin concentrations were about three times those of 15 matched normotensive control subjects (p less than 0.005). These patients also had increased arterial concentrations of noradrenaline and adrenaline (p less than 0.05) but there was no direct association between these two catecholamines and vasopressin. On the other hand, adrenergic beta-receptor blockade with oxprenolol reduced both blood pressure and plasma vasopressin (p less than 0.01) while venous plasma dopamine concentrations significantly increased. In addition, the hypertensives had highly significantly increased serum uric acid (p less than 0.001) that correlated positively with venous vasopressin concentrations (p less than 0.05). According to these data, patients with the volume-sustained low renin type of essential hypertension have increased plasma vasopressin concentrations that probably are inversely related to dopaminergic nervous activity. The data also indicate that increased plasma vasopressin correlates with serum uric acid, most probably through increased tubular reabsorption of this acid.     

Blood pressure regulation, peripheral renin activity and aldosterone in patients with pyelonephritic renal scarring

Patients with renal scarring due to previous upper urinary tract infections (UTI) are at risk of developing hypertension and renal insufficiency. In this study glomerular filtration rate (GFR), systolic (SBP) and diastolic (DBP) blood pressure, peripheral renin activity (PRA), plasma (p-Aldo) and urine aldosterone (u-Aldo), the urinary excretion of sodium (UNa) and potassium (UK) and the fractional sodium (CNa/CIn) and potassium (CK/CIn) excretion were determined in 22 female patients with verified renal scarring and a history of febrile UTI and in nine age-matched healthy women with normal i.v. urograms. The patients had significantly lower GFR, higher SBP, higher PRA and higher CK/CIn than the healthy controls. A significant correlation between CNa/CIn and SBP (r = 0.51, P less than 0.05), DBP (r = 0.50, P less than 0.05) and PRA (r = -0.47, P less than 0.05) was found. The ratio of UK/UNa was significantly correlated to SBP (r = -0.43, P less than 0.05), DBP (r = -0.44, P less than 0.05), PRA (r = 0.65, P less than 0.01) and p-Aldo (r = 0.68, P less than 0.01). It is concluded that the renin-aldosterone system probably is involved in the pathogenesis of hypertension in patients with pyelonephritic renal scarring and that screening determinations of UNa and UK may prove useful for detection of individuals with increased PRA and p-Aldo.     

Amiloride prevents thiazide-induced intracellular potassium and magnesium losses

To study the effect of a combination of amiloride, 5 mg, and hydrochlorothiazide, 50 mg (Moduretic), on plasma and skeletal muscle electrolytes in patients on long-term diuretic therapy (greater than 1 year) for arterial hypertension and/or congestive heart failure, 58 patients were recruited. Fifty-five patients completed the study, 27 controls and 28 in the treatment group. The Moduretic group demonstrated a significant increase in skeletal muscle potassium and magnesium values and a significant decrease in systolic blood pressure after 6 months on therapy. There was no significant change in these parameters in the control group. It is concluded that this combination of amiloride and hydrochlorothiazide is capable of preserving the internal and external balance of potassium and magnesium on a long-term basis in the patient categories studied.