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.

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.

Open assessment of the safety and efficacy of thioridazine in the treatment of patients with borderline personality disorder.

A 12-week open study was conducted to assess the possible efficacy and safety of low-dose thioridazine in 11 outpatients (8 women, 3 men) with borderline personality disorder (BPD) diagnosed according to DSM-III-R (American Psychiatric Association 1987) and the Diagnostic Interview for Borderline Patients (DIB; Gunderson et al. 1981) criteria. Mean thioridazine dose averaged 92 mg per day across the duration of this study. At endpoint, there was a significant reduction in Brief Psychiatric Rating Scale (BPRS; Overall & Gorham 1988) scores, and patients appeared to be less symptomatic on the impulse action patterns, affects, and psychosis subscales of the DIB (modified to assess change). Subjects completing the entire study (n = 6) also showed improvement in interpersonal relations. On self-report measures, significant improvement was noted on most Hopkins Symptom Checklist-90 (SCL-90; Derogatis et al. 1973) subscales, particularly in hostility and additional depressive features. Subjects completing the entire study showed significant improvement in paranoid ideation, interpersonal sensitivity, and anxiety. Three patients, however, developed sustained melancholic depressions that necessitated their discontinuation from the study and the initiation of anti-depressant treatment. These three individuals were more schizotypal, schizoid, and paranoid at baseline according to Personality Disorder Examination (PDE; Loranger et al. 1987) structured interviews. Weight gain was not a significant problem, but sedation and erectile dysfunction were. Overall, these findings suggest that thioridazine may exert prominent effects on patients with BPD and that double-blind, placebo-controlled studies are warranted.

The biological and clinical significance of HCG-containing cells in seminoma.

The morphological appearance, incidence and prognostic significance of human chorionic gonadotrophin (HCG)-containing cells in seminomas were examined in a retrospective series of 228 orchidectomy specimens, obtained between 1958 and 1972. Sections from each tumour were stained with haematoxylin and eosin (H & E) and immunocytochemically for HCG. In 33 (14.5%) of the tumours HCG-containing cells were observed, but in only 12 were these recognised in an initial study of the H & E stained sections. HCG staining was seen predominantly in syncytiotrophoblastic giant cells and rarely in "mulberry" cells and mononuclear seminoma cells. Of the patients whose tumours included HCG-containing cells 23% died of their disease within 2 years of orchidectomy, compared with only 8% of the patients whose tumours lacked this feature. It is concluded that immunocytochemical staining for HCG should form part of the routine histological assessment of seminomas, and that the presence of HCG-containing cells indicates a more aggressive disease.

Urothelium and the Specific Red Cell Adherence Test.

The Specific Red Cell Adherence Test (SRCAT) has been modified to produce clearer, more consistent, permanent preparations. Normal urothelium, inflammatory lesions, squamous metaplasia, papillomata, flat in situ and papillary tumours and invasive neoplasms of the bladder have been studied. Inflammatory and squamous changes did not corrupt the test results. The SRCAT was found to be a highly significant test for identifying those patients at risk from invasive bladder tumour. ABH antigens in carcinoma in situ appeared to be non-uniformly distributed throughout the bladder urothelium; it is suggested that all subsequent biopsies from these patients should be tested.

Sympathetic orchiopathia--an experimental and clinical study.

An experimental and a clinical study have been performed to elucidate the nature of contralateral testicular damage following unilateral testicular injury--sympathetic orchiopathia. In an experimental study significant impairment of sperm production was produced by contralateral testicular damage which did not seem to be immunologically mediated or to involve the breakdown of the "blood-testis" barrier. In 5 subfertile patients with oligozoospermia and unilateral testicular damage, removal of the damaged testicle did not result in an improvement in their semen analysis.

Renal accumulation of ammonia: the cause of post-ischaemic functional loss and the "blue line".

The "blue line", a dark discoloration at the corticomedullary junction, is a constant finding after a significant period of renal ischaemia. In this study, it has been shown to be caused by packing of all of the peritubular capillaries at the corticomedullary junction with red blood cells. Five rats and 10 dogs were alkalinised by replacing their drinking water with 2% sodium bicarbonate for 2 weeks pre-operatively, in order to inhibit the glutaminase enzyme system and thereby decrease ammonia accumulation during ischaemia. Five rats and 6 dogs were used as unprotected controls. All animals were subjected to 60 min warm ischaemia. Renal function was significantly protected in the alkalinised rats (P less than 0.002) and dogs (P less than 0.001), with the serum creatinine rising to a maximum of 0.21 +/- 0.03 mmol/l in the alkalinised rats and 0.18 +/- 0.04 mmol/l in the alkalinised dogs. There was no "blue line" in the alkalinised animals. It is suggested that the "blue line" plays a central role in post-ischaemic renal failure. Prevention of ammonia formation by alkalinisation protects against ischaemic renal damage and the formation of the "blue line".

An ultrastructural study on the effects of warm ischaemia on the inosine-protected kidney.

Unperfused, saline-perfused and inosine-perfused rat kidneys were subjected to various times of warm ischaemia with and without resumption of blood flow. Tissues were examined with a transmission electron microscope. Inosine has a protective effect on the epithelial cells of the proximal convoluted tubules, where microvilli are less damaged by ischaemia than those of the proximal convoluted tubular cells of the control animals. Three is also a much higher ratio of autophagic vacuoles to lysosomes present in cells of inosine-treated kidneys, reflecting their ability to sequester and digest organelles damaged during ischaemia and thus protect themselves from degradation products. A major effect of inosine seems to be the preservation of the organelles and rush border of the cells of the proximal tubule during warm ischaemia.