The effects of nisoldipine on the total ischaemic burden: the results of the ROCKET study

This study was designed to examine the effects of nisoldipine(relative to placebo), a new dihydropyridine calcium entry blockingagent, in the treatment of silent ischaemia in conventionaldoses. A total of 409 patients with proven coronary artery diseasewere screened and of this 64 had at least six episodes or atotal duration of 30 mm of ST segment depression (1 mm lastingat least 1 min) over 48 h. Fifty-two patients ultimately completeda randomized double-blind cross-over study comparing nisoldipine5 mg twice a day, nisoldipine 10 mg daily and placebo. There was a reduction in the ST segment integral and numberof episodes of ST segment depression when compared to placeboon treatment with nisoldipine 5 mg twice a day and nisoldipine10 mg daily. However, the confidence limits were wide and crossedthe no-treatment effect line. In addition, the nisoldipine dosesneither affected the circadian distribution of ischaemic episodesnor caused an alteration of the workload achieved either atpeak exercise or at 1 mm ST segment depression measured 24 hafter nidoldipine 10 mg or 12 h after nisoldipine 5 mg. We conclude that frequent silent ischaemia in patients withproven coronary artery disease is relatively uncommon, it accountsfor approximately 16% of patients with positive exercise. Inthese patients nisoldipine, given as 5mg twice a day and 10mg daily, showed no significant therapeutic effects, eitheron the frequency or severity of silent ischaemia. New formulationsof slow release nisoldipine are consequently being developedso that a fuller 24 h therapeutic profile may be obtained.     

A study of the cellular and humoral immune response in patients with myelofibrosis

There was evidence of impaired cellular immunity in 10 patients with myelofibrosis. In-vitro lymphocyte transformation with phytohaemagglutin, concanavalin A, and dinitrochlorobenzene skin reaction were diminished. Signs of impaired humoral activity were also found, the primary response to a-Helix pomatia haemocyanin being impaired, particularly in the immunoglobulin-A class. Moreover three patients had a benign paraproteinaemia. Immune-complexes (1C) could be demonstrated with various test systems. The indirect granulocyte phagocytosis test was positive in 50%, the Clq-binding in 70% and the polyethylene glycol precipitation test in 50%. In most patients complement levels were normal, although the patient with the most advanced disease had low C3A, C3 and C4 levels accompanied by high levels of IC. No correlation could be shown between impaired immune response or levels of IC when they were related to spleen diameter or degree of anaemia. Some relation however existed between disturbed immune response and IC when they were related to time elapsed since diagnosis. It is suggested that the impaired immune response is the result of primary bone marrow disease and that the presence of IC may reflect the extent of fibrosis.     

Once- versus twice-daily administration of controlled-release isosorbide-5-mononitrate 60 mg in the treatment of stable angina pectoris: A randomized, double-blind, cross-over study

Thirty-seven patients with chronic, stable angina pectoris wereincluded in a randomized, double-blind cross-over study to assessthe efficacy of once- and twice-daily dosage regimens of 60mg isosorbide-5-mononitrate, in a controlied release formulation(5-ISMN Durules^® Astra). After 2 weeks of treatment, duringa symptom-limited bicycle ergometer exercise test performed3 h after the dose, the time to 1 mm ST segment depression wasobserved to be longer by once-daily than by a twice-daily dosageregimen (614 ± 165 vs 561 ± 148 s, P<0·01).The time to the end of exercise was also significantly prolongedby once-daily dosage, as compared with placebo (693 ±158 and 645 ± 173 s, respectively; P<0·05),which was not observed with the twice-daily regimen. Both dosageregimens still had a significant effect on the prolongationof the time to onset of angina 9 h after the dose: 420 ±164 s by placebo, 492 ± 161 s by once-daily dosage; P<0·01and 466 ± 154 s by twice-daily dosage; P<0·05.Anginal attack rate and nitroglycerin consumption was significantlylower during the once-daily dosage period as compared with placebo;this difference was not evident during the twice-daily administrationof the drug. Controlled-release 5-ISMN 60 mg given once daily was effectivein angina pectoris patients for at least 9 h after the doseand showed no clinical signs of tolerance after 2 weeks of thetreatment. Attenuation of the clinical effect was observed withthe twice-daily (in 12 h intervals) dosage regimen, presumablycaused by constantly high 5-ISMN plasma concentration.     

Central haemodynamics in acute myocardial infarction in relation to mortality and peak enzyme activity

The relation of central haemodynamic changes to subsequent mortalityand peak enzyme activity was investigated in 190 patients withacute myocardial infarction. The mean delay time from onsetof symptoms to the haemodynamic study was 7.2 hours. Major exclusioncriteria were heart rate < 65beats min^–1, systolicblood pressure < 105 mmHg and lung rales to a distance of> 10 cm above the lung bases. Nine patients (4.7%) died within15 days and 16 patients (8.4%) within 90 days after the infarction.Compared to survivors, non-survivors were characterized by baselinedepression of cardiac index, stroke volume index and left ventricularstroke work index, while pulmonary capillary wedge pressureand peripheral resistance were increased. However, a wide overlapbetween survivors and non-survivors makes the predictive valuelow in the individual patient. Peak serum aspartate aminotransferase (S-ASAT) activity wasweakly related to baseline pulmonary capillary wedge pressure(r = 0.28; P< 0.001) and stroke volume index (r = –0.22;P7lt;0.01). The correlation to pulmonary capillary wedge pressurewas only found in anterior (r = 0.34) infarcts. Peak serum lactatedehydrogenase (LD¹) was not correlated with baseline haemodynamics.     

Endometrial cancer: accuracy of the finding of a well differentiated tumor at dilatation and curettage compared to the findings at subsequent hysterectomy

Abstract. Obermair A, Geramou M, Gücer F, Denison U, Graf AH, Kapshammer E, Medl M, Rosen A, Wierrani F, Neunteufel W, Frech I, Speiser P, Kainz C, Breitenecker G, Austrian Gynecologic Oncology Group. Endometrial cancer: accuracy of the finding of a well differentiated tumor at dilatation and curretage compared to the findings at subsequent hysterectomy.
The objective of this study was to examine the accuracy of the finding of a histologically well differentiated endometrial carcinoma at dilatation and curettage (D & C) prior to hysterectomy. A retrospective multicentric chart review of 137 endometrial cancer patients was conducted, including all patients in whom a well differentiated endometrial carcinoma had been diagnosed by D & C. Histopathologic grading as determined by D & C was compared with the grading established at the final histologic examination after hysterectomy. Seventy-eight percent of all cases in which a well differentiated tumor was diagnosed with D & C were confirmed as well differentiated endometrial carcinomas, whereas 20.4% had to be upgraded as moderately differentiated tumors after evaluation of the hysterectomy specimen. In one case in which a uterine adenocarcinoma was diagnosed by D & C, a well differentiated adenocarcinoma was found to be combined with a carcinosarcoma in the hysterectomy specimen. In order to avoid false findings of a well differentiated tumor, the histologic grade should be confirmed by intraoperative frozen section examination. This is especially important in cases in which surgical staging was not planned initially.