Blood pressure-lowering effects of nifedipine/candesartan combinations in high-risk individuals: subgroup analysis of the DISTINCT randomised trial.

The DISTINCT study (reDefining Intervention with Studies Testing Innovative Nifedipine GITS-Candesartan Therapy) investigated the efficacy and safety of nifedipine GITS/candesartan cilexetil combinations vs respective monotherapies and placebo in patients with hypertension. This descriptive sub-analysis examined blood pressure (BP)-lowering effects in high-risk participants, including those with renal impairment (estimated glomerular filtration rate<90 ml min-1, n=422), type 2 diabetes mellitus (n=202), hypercholesterolaemia (n=206) and cardiovascular (CV) risk factors (n=971), as well as the impact of gender, age and body mass index (BMI). Participants with grade I/II hypertension were randomised to treatment with nifedipine GITS (N) 20, 30, 60 mg and/or candesartan cilexetil (C) 4, 8, 16, 32 mg or placebo for 8 weeks. Mean systolic BP and diastolic BP reductions after treatment in high-risk participants were greater, overall, with N/C combinations vs respective monotherapies or placebo, with indicators of a dose-response effect. Highest rates of BP control (ESH/ESC 2013 guideline criteria) were also achieved with highest doses of N/C combinations in each high-risk subgroup. The benefits of combination therapy vs monotherapy were additionally observed in patient subgroups categorised by gender, age or BMI. All high-risk participants reported fewer vasodilatory adverse events in the pooled N/C combination therapy than the N monotherapy group. In conclusion, consistent with the DISTINCT main study outcomes, high-risk participants showed greater reductions in BP and higher control rates with N/C combinations compared with respective monotherapies and lesser vasodilatory side-effects compared with N monotherapy.

A Dose-Ranging Study of the DPP-IV Inhibitor PF-734200 Added to Metformin in Subjects With Type 2 Diabetes*.

The purpose of this phase 2, multicentre, randomized, double-blind, placebo-controlled, 12-week dose-ranging study was to assess the efficacy, safety, and tolerability of the dipeptidyl peptidase-IV (DPP-IV) inhibitor PF-734200 in adult subjects with type 2 diabetes who were on a stable dose of metformin. Men and women with inadequate glycaemic control with metformin as their sole diabetes medication were randomized to placebo or PF-734200 2 mg, 5 mg, 10 mg, or 20 mg every day. A population subset underwent mixed meal tolerance tests (MMTT) at baseline and week 12. A total of 301 subjects were treated. At week 12, PF-734200 doses of ≥5 mg produced a statistically significant reduction in haemoglobin A (1C) (HbA (1c)) compared with placebo. The mean (95% confidence interval) placebo-adjusted changes in HbA (1c) were -0.31% (-0.70 to 0.08), -0.74% (-1.12 to -0.36), -0.70% (-1.02 to -0.38), and -0.75% (-1.07 to -0.43) for the 2 mg, 5 mg, 10 mg, and 20 mg doses, respectively. PF-734200 20 mg significantly reduced glucose area under the curve following MMTT (-12.8% [-22.9 to -2.7]; p=0.003) compared with placebo. The reductions observed with other doses were not statistically significant. PF-734200 was safe and well tolerated at all doses tested when added to metformin. PF-734200 safely and effectively lowered HbA (1c) in subjects receiving metformin. The 20 mg dose provided the greatest improvements in post-prandial glucose.

Efficacy and safety of the dipeptidyl peptidase-4 inhibitor PF-734200 added to metformin in Type 2 diabetes.

AIMS: PF-734200 is a potent and selective oral dipeptidyl peptidase-4 (DPP-4) inhibitor. This study assessed the efficacy and safety of PF-734200 at dose rates of 20 and 30 mg/day in subjects with Type 2 diabetes mellitus inadequately controlled on metformin monotherapy. METHODS: This was a placebo-controlled, double-blind, randomized, multicentre, 12 week study. Subjects with Type 2 diabetes mellitus were eligible if screening glycosylated haemoglobin (HbA(1c) ) was 7-11% (53.0-96.7 mmol/mol) and they had been receiving metformin monotherapy for ≥2 months. Subjects receiving metformin and an insulin secretagogue or metformin and thiazolidinedione needed to have a screening HbA(1c) of 6.5-9.5% (47.5-80.3 mmol/mol), measured prior to discontinuing the insulin secretagogue or thiazolidinedione. The primary end-point of the study was a change from baseline to week 12 in HbA(1c) levels. RESULTS: Baseline characteristics for 289 subjects randomized to PF-734200 or placebo groups were similar (mean age 56.5 years, mean body mass index 32.2 kg/m(2) and mean HbA(1c) 8.2%, 66.1 mmol/mol). In the predefined per protocol data set, least-squares mean HbA(1c) at week 12 was reduced by 0.79 (8.6 mmol/mol 95% confidence interval -1.10 to -0.49, -12.0 to -5.4 mmol/mol) and 0.92% (10.1 mmol/mol; -1.23 to -0.61, -13.4 to -6.7 mmol/mol) in the 20 and 30 mg groups, respectively, compared with placebo. Differences from placebo were statistically significant (P<0.0001), but the differences between the 20 and 30 mg groups were not. The intent-to-treat analysis yielded similar findings. CONCLUSIONS: The HbA(1c) was significantly and meaningfully reduced by both doses of PF-734200, but 20 mg appears to be the more appropriate therapeutic dose for Type 2 diabetes mellitus, contingent upon confirmation by long-term controlled studies.

Effects of isradipine or enalapril on blood pressure in salt-sensitive hypertensives during low and high dietary salt intake. MIST II Trial Investigators.

This large multicenter study, tested the antihypertensive effects of isradipine, a dihydropyridine calcium channel blocker and enalapril, an angiotensin-converting enzyme inhibitor, in salt-sensitive hypertensive patients under low and high salt intake diets. After a 3-week (weeks -9 to -6) of ad lib salt diet, those patients who had a sitting diastolic blood pressure (SDBP) of > or =95 but < or =115 mm Hg qualified to enter a 3-week (weeks -6 to -3) placebo run-in low salt diet (50 to 80 mmol Na+/day). Then high salt (200 to 250 mmol Na+/day) was added to the placebo treatment for 3 weeks (weeks -3 to 0). Those patients who demonstrated an increase in SDBP > or =5 mm Hg from the low to high salt diet were considered salt sensitive and were randomized into a 4-week (weeks 0 to 4) double-blind treatment period of either isradipine 2.5 to 10 mg twice a day, enalapril 2.5 to 20 mg twice a day, or placebo. Then they entered a 3-week (weeks 4 to 7) placebo washout phase of low salt diet (50 to 80 mmol Na+/day). After week 7 and while the low salt diet was continued the patients were restarted on their double-blind treatment for 4 more weeks (weeks 7 to 11) and the study was completed. Of 1,916 patients screened, 464 were randomized into the double-blind treatment phase and 397 completed the study. Both isradipine and enalapril decreased the sitting systolic blood pressure (SSBP) and SDBP during the high salt diet, to a similar degree, whereas enalapril caused a greater reduction in SSBP and SDBP than isradipine during the low salt diet (11.3 +/- 1.2/7.7 +/- 0.7 mm Hg v 7.7 +/- 0.9/4.8 +/- 0.6 mm Hg, mean +/- SEM, respectively, P < .02). Within drugs, the effect of isradipine on blood pressure (BP) was higher during the high than the low salt diet (14.9 +/- 1.5 v 7.6 +/- 1.3 mm Hg for SSBP and 10.1 +/- 0.6 v 4.8 +/- 0.9 mm Hg for SDBP, P < .001), but enalapril exerted a similar effect during both diets. Because salt restriction lowered both SSBP and SDBP, the lowest BP achieved with both drugs were during the salt restriction phase.

An elective-titration study of the comparative effectiveness of two angiotensin II-receptor blockers, irbesartan and losartan. Irbesartan/Losartan Study Investigators.

This multicenter, randomized, double-masked, elective-titration study was designed to compare the effectiveness, safety, and tolerability of irbesartan and losartan, two angiotensin II subtype AT1-receptor blockers, in the treatment of patients with mild-to-moderate hypertension. After a 3-week, single-masked, placebo lead-in period, 432 patients with a mean seated diastolic blood pressure (SeDBP) of 95 to 115 mm Hg were randomly allocated to receive either irbesartan 150 mg once daily (n = 213) or losartan 50 mg once daily (n = 219). At week 4, if SeDBP at trough (i.e., 24 +/- 3 hours after the previous dose) was > or = 90 mm Hg, the daily dose was doubled (to irbesartan 300 mg or losartan 100 mg). At week 8, if trough SeDBP was > or = 90 mm Hg, hydrochlorothiazide 12.5 mg once daily was added to the regimen; consistent with the prescribing information for losartan, the dose of losartan was reduced to 50 mg once daily on the addition of hydrochlorothiazide. A total of 370 patients (178 irbesartan and 192 losartan) were evaluable for efficacy. The mean change in trough SeDBP at week 8, the primary efficacy end point, was significantly greater in patients receiving irbesartan monotherapy than in those receiving losartan monotherapy (-10.2 mm Hg vs -7.9 mm Hg, respectively). At week 12, reductions in trough SeDBP and seated systolic blood pressure were greater with irbesartan treatment than with losartan treatment (-13.8 mm Hg vs -10.8 mm Hg and -18.0 mm Hg vs -13.9 mm Hg, respectively), and a greater proportion of irbesartan patients responded to therapy (i.e., trough SeDBP < 90 mm Hg or reduction in trough SeDBP > or = 10 mm Hg) compared with losartan patients (78% vs 64%, respectively). Both regimens were well tolerated.

Influence of race and dietary salt on the antihypertensive efficacy of an angiotensin-converting enzyme inhibitor or a calcium channel antagonist in salt-sensitive hypertensives.

Dietary salt restriction is a recommended adjunct with antihypertensive therapy. There may be racial differences in blood pressure response to salt restriction while on antihypertensive therapy. We performed a multicenter, randomized, double-blind, placebo-controlled, parallel-group clinical trial (black, n=96; Hispanic, n=63; white, n=232). Participants were initially preselected for stage I to III hypertension and then further selected for salt sensitivity (> or = 5 mm Hg increase in diastolic blood pressure after 3 weeks of low salt [< or = 88 mmol/d Na+] and high salt [>190 mmol/d Na+] diet). We compared the antihypertensive effect of an angiotensin-converting enzyme inhibitor (enalapril 5 or 20 mg BID) or a calcium channel antagonist (isradipine 5 or 10 mg BID) during alternating periods of high and low salt intake. The main outcome measure was blood pressure change and absolute blood pressure level achieved with therapy. During the high salt diet (314.7+/-107.5 mmol/d urinary Na+) there was greater downward change in blood pressure with both enalapril and isradipine compared with the low salt diet (90.1+/-50.8 mmol/d Na+); however, the absolute blood pressure achieved in all races was consistently lower on a low salt diet for both agents. Black, white, and Hispanic isradipine-treated salt-sensitive hypertensives demonstrated a smaller difference between high and low salt diets (black, -3.6/-1.6 mmHg; white, -6.2/-3.9 mmHg; Hispanic, -8.1/-5.3 mm Hg) than did enalapril-treated patients (black, -9.0/-5.3 mm Hg; white, -11.8/-7.0 mm Hg; Hispanic, -11.1/-5.6 mm Hg). On the low salt diet, blacks, whites, and Hispanics had similar blood pressure control with enalapril and isradipine. On the high salt diet, blacks had better blood pressure control with isradipine than with enalapril, whereas there was no difference in the blood pressure control in whites and Hispanics treated with either drug. Dietary salt reduction helps reduce blood pressure in salt-sensitive hypertensive blacks, whites, and Hispanics treated with enalapril or isradipine. These data demonstrate that controlling for salt sensitivity diminishes race-related differences in antihypertensive activity.

There are no racial, age, sex, or weight differences in the effect of salt on blood pressure in salt-sensitive hypertensive patients.

BACKGROUND: This report is part of a larger, multicenter, placebo-controlled study designed to test the effects of low and high salt intake on the antihypertensive action of enalapril maleate or isradipine in salt-sensitive, hypertensive patients. OBJECTIVE: To present our findings with respect to the effects of race, age, sex, and weight on the blood pressure response to low and high salt intake in salt-sensitive hypertensive patients before randomization into the larger study. PATIENTS AND METHODS: After 3 week (weeks -9 to -6) of ad lib salt intake (100-200 mmol/d of sodium), 1916 patients whose sitting diastolic blood pressure was between 95 and 115 mm Hg entered a 3-week period (week -6 to -3) of low salt intake (50-80 mmol/d of sodium) and then a 3-week period (week -3 to 0) of high salt intake (200-250 mmol/d of sodium). Of the 1916 patients, 624 were identified as being sensitive to salt by demonstrating an increase in sitting diastolic blood pressure of equal to or more than 5 mm Hg from the low to high salt intake. Of these patients, 367 were white, 156 were black, 92 were Hispanic, 8 were Asian, and 1 was American Indian. Also, 315 were men and 309, women; 351 were 55 years or younger and 273 were older than 55 years; and 195 had a body mass index of 27 or less and 429 had a body mass index higher than 27. RESULTS: The sitting blood pressure decreased with salt restriction and increased with salt load in all groups of patients (P < .001). There were no statistically significant differences in the blood pressure changes to salt changes by race, age, sex, and weight. CONCLUSIONS: This large, multicenter study did not demonstrate any statistically significant effect of race, age, sex, and weight on blood pressure response to salt changes in salt-sensitive hypertensive patients.

Blood pressure control with diltiazem XR, a novel extended-release formulation of diltiazem HCl, in mature and elderly hypertensive patients.

The safety and efficacy of an extended-release form of diltiazem HCl (diltiazem XR) in patients 55 years or older with mild-to-moderate essential hypertension were examined in a multi-center, double-blind, randomized, placebo-controlled, parallel-group study involving 350 patients with supine diastolic blood pressure (DBP) between 95 mm Hg and 114 mm Hg. Patients were randomized to a once-daily dose of diltiazem XR (240 mg) or placebo; 261 patients received diltiazem XR and 89 received placebo. After 4 weeks, the dose was doubled (to 480 mg) in patients whose supine DBP was > 90 mm Hg, and treatment was continued for another 4 weeks. Diltiazem XR consistently reduced blood pressure (BP) in the study population. At end-point, the mean reduction in supine DBP was 8.65 mm Hg in the diltiazem XR group and 2.75 mm Hg in the placebo group (P < 0.0001). Subgroup analysis confirmed the efficacy of diltiazem XR in men, women, patients between the ages of 55 and 64 years, patients 65 years or older, and non-black patients. Other BP values (supine systolic, standing diastolic, and standing systolic) also were significantly reduced in patients treated with diltiazem XR. BP reduction (supine DBP < or = 90 mm Hg or by > or = 10 mm Hg) was achieved in 58% of patients receiving diltiazem XR compared with 27% of patients receiving placebo. Decreases in apical heart rate were minimal and similar in both groups. No significant differences were noted in adverse events in the diltiazem XR and placebo groups: 36.4% of patients in the diltiazem XR group and 37.1% in the placebo group had no adverse experiences, and 63.6% and 62.9%, respectively, had at least one adverse event. Physical examination findings and laboratory values were clinically unremarkable and comparable in the diltiazem XR and placebo groups. Diltiazem XR given once daily at doses of 240 mg and 480 mg was safe and effective in lowering blood pressure in mature and elderly patients with mild-to-moderate hypertension.

A clinical trial evaluating the 24-hour effects of bisoprolol/hydrochlorothiazide 5 mg/6.25 mg combination in patients with mild to moderate hypertension.

This study used 24-h ambulatory blood pressure (BP) monitoring to investigate the effectiveness of a novel low-dose combination of bisoprolol/hydrochlorothiazide in adult patients with mild to moderate essential hypertension. Thirty-six patients with stable mild to moderate hypertension (sitting diastolic BP 95-114 mmHg) after a placebo run-in phase received oral bisoprolol/hydrochlorothiazide 5 mg/6.25 mg once daily for 4 weeks in a single-blind regimen. At office visits, BP and pulse were measured with statistically significant reductions (p < 0.01) recorded after 2 and 4 weeks of treatment. Twenty-four-h ambulatory BP monitoring at the completion of therapy revealed significant reductions (p < 0.01) in both systolic and diastolic 24-h, daytime, and nighttime BP, compared with the end of the placebo treatment phase. Systolic and diastolic load were also reduced (p < 0.01). The combination was well tolerated, and overall quality-of-life questionnaire scores indicated an improvement after bisoprolol/hydrochlorothiazide therapy (p = 0.02). No clinically significant changes from baseline in laboratory parameters were observed; in particular, serum potassium was unchanged. This is the first study to demonstrate the 24-h effectiveness of the bisoprolol/hydrochlorothiazide 5 mg/6.25 mg combination, using 24-h ambulatory BP monitoring. In addition, antihypertensive therapy with low doses of bisoprolol/hydrochlorothiazide in combination may improve tolerability.

A comparison of the safety of therapeutically equivalent doses of isradipine and diltiazem for treatment of essential hypertension.

We compared the safety of a new dihydropyridine calcium entry blocker, isradipine, with an equipotent dose of diltiazem in 174 mild hypertensives (diastolic blood pressure [DBP] 95 to 105 mm Hg). After appropriate washout and placebo periods, patients were randomly assigned to receive either 1.25 mg isradipine twice daily (Group I) or 40 mg diltiazem thrice daily (Group D). If DBP remained above 90 mm Hg, doses were increased to a maximum of 5 mg isradipine twice daily or 120 mg diltiazem thrice daily. Active therapy was given for a total of 12 weeks. Only 18 patients (nine from each group) did not complete the protocol. The patients were well-matched at baseline with a mean BP of 149/100 mm Hg for those who were randomized to isradipine and completed the protocol and 153/99 mm Hg for the diltiazem group. The responses to each drug were excellent with 72% of the isradipine patients and 73% of the diltiazem group having DBP less than 90 mm Hg at the completion of the study. Of the 156 patients who completed the protocol, only 18 patients (ten in Group I and eight in Group D) failed to respond. Both drugs were well-tolerated. No adverse reactions were reported by 68 percent of the patients in Group I and 65% of those in Group D. The most common side effect was headache (9.0% in Group I and 7.8% in Group D) followed by fatigue (5.2% in Group I and 3.9% in Group D). Age and race did not predict response to either agent but men responded slightly better to diltiazem than women. We conclude that isradipine and diltiazem are equally well tolerated and can be used successfully as a monotherapy to treat hypertension in a wide variety of patients.

Placebo-controlled trial of once-a-day isradipine monotherapy in mild to moderately severe hypertension.

The efficacy and safety of once-daily dosing of isradipine, a new calcium antagonist vasodilator, was evaluated in a multicenter, placebo-controlled trial in hypertensive patients who had supine diastolic blood pressure (SDBP) 100-119 mm Hg. After a 3-week single-blind placebo washout patients randomly received either isradipine, 5 mg once daily, or a matching placebo; if SDBP remained greater than or equal to 95 mm Hg or less than or equal to 10 mm Hg below baseline at four weekly clinic visits, isradipine was increased at weekly intervals by 5 mg once daily up to 20 mg and maintained during weeks 5 and 6. At week 6 mean supine blood pressure 24 hours after dosing had declined from 163 +/- 20/105 +/- 5 (N = 78) to 146 +/- 17/92 +/- 7 mm Hg (N = 60) on isradipine, 14.5 mg once daily, and from 163 +/- 20/105 +/- 6 (N = 85) to 157 +/- 18/99 +/- 10 mm Hg (N = 64) on placebo (P less than .001 between groups). Standing blood pressure decreased from 159 +/- 20/104 +/- 8 to 144 +/- 18/93 +/- 11 mm Hg with isradipine and from 160 +/- 22/105 +/- 9 to 154 +/- 19/101 +/- 11 mm Hg with placebo (P less than .001 between groups) without signs or symptoms of postural hypotension. A SDBP less than or equal to 90 mm Hg or a greater than or equal to 10 mm Hg fall below baseline was achieved in 41 of 78 isradipine-treated (53%) and 18 of 85 placebo-treated subjects (21%).(ABSTRACT TRUNCATED AT 250 WORDS)

Concomitant administration of terazosin and atenolol for the treatment of essential hypertension.

The safety and efficacy of once-daily terazosin hydrochloride administered concomitantly with once-daily atenolol for the treatment of essential hypertension were evaluated in this double-blind, multiclinic, placebo-controlled study. After each patient received 50 mg of atenolol daily for eight weeks, patients with a supine diastolic blood pressure (DBP) of 95 to 110 mm Hg and whose supine DBP had decreased at least 5 mm Hg were randomized to receive either terazosin (plus atenolol) or placebo (plus atenolol) for ten weeks. Patients assigned to the terazosin hydrochloride treatment group received increasing dosages (1,2,5, and 10 mg daily) [corrected] of terazosin at two-week intervals until the maximum dose was reached or until the supine DBP was decreased to less than 90 mm Hg. Terazosin-treated patients (n = 43) had significant mean decreases from the baseline in supine BP (systolic/diastolic = -8.8/-8.5 mm Hg) and standing BP (-10.9/-9.5 mm Hg), whereas the decreases in BP in the placebo-treated patients (n = 49; supine, -2.3/-2.6 mm Hg; standing, -1.4/-1.3 mm Hg) were not significant. When terazosin and placebo were compared, the differences in BP were significant. Terazosin-treated patients had significantly greater decreases in mean percent change of total cholesterol (-4.8%) and low-density lipoprotein plus very-low-density lipoprotein cholesterol (-6.3%) levels, compared with the placebo-treated patients (+0.6% and +1.1%, respectively). Concomitant administration of terazosin and atenolol to patients with essential hypertension was found to be safe and efficacious.

Controlled multicenter study of the antihypertensive effects of lisinopril, hydrochlorothiazide, and lisinopril plus hydrochlorothiazide in the treatment of 394 patients with mild to moderate essential hypertension.

Lisinopril (LIS) is a lysine analog of enalaprilat, the active metabolite of enalapril, an angiotensin-converting enzyme inhibitor (ACEI). Unlike enalapril, the precursor of enalaprilat, LIS is not a prodrug but has equal ACEI efficacy and potency and a slightly longer duration of action after oral administration. Short-term (12 weeks) and long-term (24 weeks) blood pressure control has been studied with LIS, hydrochlorothiazide (HCTZ), and LIS + HCTZ when given once a day. Drug treatment had three phases: (i) 2-4 weeks of single-blind placebo washout; (ii) 12 weeks of double-blind comparison therapy with LIS 20, 40, and 80 mg vs. HCTZ 12.5, 25, and 50 mg, vs. LIS + HCTZ 20 + 12.5, 40 + 25, and 80 + 50 mg; (iii) 13-24 weeks single-blind LIS vs. LIS + HCTZ. Starting double-blind therapy at the lowest dose, all three groups doubled the dose at weeks 4 and 8 if BP was not controlled with sitting diastolic BP (SDBP) less than 90 mm Hg. At the end of 12 weeks of double-blind therapy, uncontrolled HCTZ-only and LIS-only treatment groups were advanced to combination LIS + HCTZ therapy but uncontrolled LIS + HCTZ patients were dropped. Mean BP reductions (systolic/diastolic, mm Hg) for all three groups after 12 weeks of double-blind comparison therapy were: (i) LIS (n = 162), -16.6/-12.5; (ii) HCTZ (n = 155), -10.4/-6.8; (iii) LIS + HCTZ (n = 74), -23.9/-18.2 with p less than 0.01 for all groups compared to baseline.(ABSTRACT TRUNCATED AT 250 WORDS)

Applications of the Redy sorbent system to hemodialysis and peritoneal dialysis.

The application of sorbent technology to the treatment of uremia has been limited by the inability to adsorb urea adequately. Conversion of urea to ammonium carbonate and adsorption by zirconium phosphate provides a practical means of removing urea. This combination, together with hydrated zirconium oxide and carbon, removes uremic waste products from dialysate. Over 1500 patients are undergoing maintenance hemodialysis with this system. The dialysate composition can be modified for the treatment of patients with acute renal failure. This sorbent system is now being used for the regeneration of peritoneal dialysate. Twenty patients have undergone a total of 90 dialyses, each of 4 to 24 hours duration. One home patient has been solely on this system for two months. The application of sorbent technology to peritoneal dialysis may be the most promising approach to a wearable dialysis system.

Development of a sorbent peritoneal dialysate regeneration system--a progress report.

A sorbent regenerative dialysate system for peritoneal dialysis has been developed (Pericycle). Clinical results and data demonstrate that the sorbent system provides a suitable dialysate. The sorbents effectively remove uraemic metabolites from the dialysate. Calcium and magnesium removed by the cartridge and glucose metabolised by the patient are replaced by the infusion system. The machine pumps regenerated dialysate into and spent dialysate out of the patients. A pressure sensor in the patient line prevents excessive inflow and outflow pressures by stopping the inflow or outflow pump respectively. The Pericycle provides a simple, safe, portable method for conducting peritoneal dialysis in the home or hospital.

Withdrawal of antihypertensive therapy. Hypertensive crisis in renovascular hypertension.

Hypertensive crises were reported in three patients with hypertension associated with underlying renovascular occlusive disease during reduction of antihypertensive therapy. In each case, rebound hypertension was observed during clonidine hydrochloride withdrawal. Therapy with propranolol hydrochloride and diuretics had also been discontinued in two of the three patients. This and other reports of rebound hypertension during clonidine withdrawal are contrasted with the absence of reports of this syndrome in the setting of cessation of beta-adrenergic blockade therapy. This suggests that the discontinuation of clonidine therapy was primarily responsible for the hypertensive crises herein described. It is further concluded that rebound hypertension may follow gradual as well as abrupt reduction of clonidine dosage, and that patients with renovascular hypertension may be at greatest risk.

Sorbent regeneration of peritoneal dialysate: an approach to ambulatory dialysis.

Sorbent regeneration of peritoneal dialysate has been shown to be feasible in experimental and preliminary clinical studies and provides a realistic basis for the optimization of dialysis therapy and the potential development of an ambulatory dialysis system. Peritoneal dialysis efficiency can be significantly enhanced by continuous dialysate flow techniques and the mass transfer of uremic solutes can be theoretically augmented by the increased dialysis time made possible by a wearable design. Further optimization of end stage renal failure therapy may be achieved by the combined use of various methods for blood purification.