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Compliance with nonrecapping needle policies is poor. Accidental needlestick injuries account for up to 80% of reported occupational needle exposures, and 45% of needlestick injuries occur at recapping. To determine the degree of compliance with in-house nonrecapping and needle disposal policies, the authors undertook an unannounced survey of needles disposed in designated sharps disposal containers and, via a questionnaire, surveyed attitudes to policies. The results show between 46 and 77% of needles were being recapped with 9 to 20% of bloodstained needles recapped before disposal. Recapping devices were rarely used and two-handed recapping techniques predominated. Highest rates of recapping were seen in intensive care, intermediate care and medical care units. Common reasons for recapping include inability to dispose immediately of needles properly, and sharps containers being too far away. Awareness of the risks of recapping was widespread with over 90% of respondents having been instructed in proper needle disposal techniques. While few health care professionals disagreed with non-recapping and needle disposal policies, many--for various reasons--persist in hazardous needle disposal practices.

Animal experiments suggest an inhibitory effect of calcium entry blockers on arterial calcinosis and the formation of atherosclerotic plaques. Experiments with isolated tissues suggest various mechanisms for an antiatherosclerotic effect of calcium entry blockers. INTACT, the International Nifedipine Trial on Antiatherosclerotic Therapy, is the first study investigating, with a prospective, placebo-controlled, randomized, double-blind design, the influence of a calcium entry blocker (nifedipine 80 mg/day) on the progression of coronary atherosclerosis in patients with proven coronary artery disease. Study endpoints were changes of established coronary stenoses (diameter reduction greater than or equal to 20%), as well as the formation of new stenoses as documented by coronary angiography. Standardized coronary angiograms were taken before and after a treatment period of 3 years. The angiograms were quantitatively analyzed with the computer-assisted edge detection system CAAS. Of the 425 patients included in the study, 282 patients (134 on nifedipine and 148 on placebo) revealed no protocol violations. In the inclusion angiograms of these patients, 893 coronary stenoses were detected which were not significantly influenced in their development by nifedipine. However, 196 entirely new coronary lesions, 185 stenoses and 11 occlusions, were found in the follow-up angiograms. There were 78 lesions in 54 patients (40%) on nifedipine (0.58 new lesions/patient) and 118 lesions in 73 patients (49%; n.s.) on placebo (0.8 new lesions/patient; p = 0.031). In two other studies on the inhibiting effect of dihydropyridine calcium entry blockers on the progression of coronary artery disease in man defining angiographic endpoints, the drugs were also shown to reduce the number of newly formed significant coronary lesions. If further trials in man confirm a protective role of calcium entry blockers against the formation of atherosclerotic coronary lesions, a new strategy in the prevention of coronary artery disease has to be considered.

In a setting where potable water is contaminated with Legionella pneumophila serogroup 1, we performed two case control studies. The first case control study consisted of 17 cases of nosocomial Legionnaires' disease (LD) and 33 control (the patients who were admitted to the ward where the case was admitted immediately before and after the case) subjects. Cases had a higher mortality rate 65% vs 12% (P less than 0.004); were more likely to have received assisted ventilation (P less than 0.00001); to have nasogastric tubes (P less than 0.0004) and to be receiving corticosteroids or other immunosuppressive therapy (P less than 0.0001). Based on the results of this study, sterile water was used to flush nasogastric tubes and to dilute nasogastric feeds. Only 3 cases of nosocomial LD occurred during the next year compared with 12 the previous year (P less than 0.0001). Nine cases subsequently occurred and formed the basis for the second case-control study. Eighteen control subjects were those patients admitted to the same unit where the case developed LD, immediately before and after the case. The mortality rate for the cases was 89% vs 6% for controls (P less than 0.00003). The only other significant difference was that cases were more likely to be receiving corticosteroids or other immunosuppressive therapy 89% vs 39% (less than 0.01). We hypothesized that microaspiration of contaminated potable water by immunocompromised patients was a risk factor for nosocomial Legionnaires' disease. From 17 March 1989 onwards such patients were given only sterile potable water. Only two cases of nosocomial LD occurred from June 1989 to September 1990 and both occurred on units where the sterile water policy was not in effect. We conclude that aspiration of contaminated potable water is a possible route for acquisition of nosocomial LD in our hospital and that provision of sterile potable water to high risk patients (those who are receiving corticosteroids or other immunosuppressive drugs; organ transplant recipients or hospitalized in an intensive care unit) should be mandatory.

Angioplasty of single total, subacute, or chronic coronary occlusions was performed in 90 patients. It was successful in 54 occlusions (60%), in 77% of those less than 6 weeks old, and in 44% of those of greater than 6 weeks' duration (p less than 0.005). All procedures were uneventful. Control angiography was performed in 53 (98%) patients with successful angioplasty after an average interval of 97 +/- 53 days. Stenosis had recurred in 16 patients (30%). During a follow-up period of 36 +/- 13 months, three patients died, five patients underwent coronary bypass operation, and 10 had reangioplasty. Despite an additional late angiographic recurrence of stenosis in seven patients, 36 patients revealed angiographic long-term success. In the 46 nonoperated patients, angina pectoris and exercise stress tests were substantially improved. Thus angioplasty of subacute and chronic total coronary occlusions is an uneventful procedure, the success rate depending on the duration of the occlusions. Despite a high angiographic recurrence rate, the angiographic and clinical long-term results are favorable.

Urinary tract infections (UTIs) occur frequently in hospitalized patients and are associated with significant morbidity. The infection control department of the Victoria General Hospital in Halifax, Nova Scotia conducted prospective hospital-wide surveillance for one month to evaluate the incidence of UTIs. There were 40 UTIs: 62.5% in patients with indwelling catheters; 20% in patients undergoing intermittent catheterization; and 17.5% in uncatheterized patients, for an attack rate of 19.9 per 1000 patient discharges. Escherichia coli was the most common organism, isolated in 47.5% of the study population. Trimethoprim-sulphamethoxazole was used to treat 57.5% of the UTIs. The findings from this survey are consistent with those of other authors in comparable institutions.

The influence of morphologic parameters on the recurrence of stenosis after percutaneous transluminal coronary angioplasty of 49 stenoses in aortocoronary venous bypass grafts of 41 patients was investigated. Vessel dimensions were measured quantitatively. Angioplasty was successful in 46 stenoses (94%) of 38 patients (93%). In 35 patients (92% of successfully treated patients) with 42 stenoses, control angiography was performed after a mean interval of 189 +/- 186 days. In 9 patients (26%), 9 stenoses (21%) had recurred. The diameter of the grafted coronary artery distal to the anastomosis was significantly smaller in grafted arteries with than without recurrent stenoses (1.92 +/- 0.52 vs 2.45 +/- 0.50 mm; p less than 0.01). Recurrence also correlated with the ratio between graft diameter and coronary artery diameter greater than 1.35 (p less than 0.02) and with the stenosis length greater than 10 mm before angioplasty (p less than 0.01). Graft age, graft diameter and stenosis location in the graft had no significant influence on recurrence. Thus, the diameter of the grafted coronary artery and the length of the critical stenosis are parameters for recurrence after angioplasty of graft stenoses and should be considered in the selection of patients for this intervention.

In 41 consecutive patients with 49 stenoses of aorto-coronary venous bypass (ACVB) grafts percutaneous transluminal angioplasty (PTA) was attempted. PTA was successful, i.e., the percent area stenosis was reduced by greater than 20% to less than 70% (quantitative measurement with a precision magnifying lens from two orthogonal angiographic views) in 46 stenoses (94%) of 38 patients (93%). In 35 patients (92%) with 42 stenoses control coronary angiography was performed after a mean interval of 189 +/- 186 days. Recurrence, defined as an increase of percent area stenosis to greater than or equal to 70%, was found in nine stenoses (21%) of nine patients (26%). Recurrence correlated with a stenosis length greater than 10 mm before PTA (5/8 vs 4/32 stenoses: p less than 0.01). In recurrent stenoses, the average diameter of the grafted native coronary artery was significantly smaller than in recurrence-free stenoses (1.92 +/- 0.52 mm vs 2.45 +/- 0.50 mm; p less than 0.01). Clinical data were collected from all 38 patients with successful PTA after an average of 30 +/- 17 months following PTA. In this interval, 11 patients had undergone re-angioplasty and eight patients were re-operated; in addition, there were three cardiac deaths. In the 27 surviving patients without re-operation (71%), angina pectoris had improved from a mean of 3.0 +/- 0.7 before PTA to 1.8 +/- 1.0 (CCS-classification) (p less than 0.001). In 19 of the 27 patients (70%) the exercise stress test was negative, in contrast to only three patients (11%) before PTA. Thus, in the majority of patients PTA of ACVB-graft stenoses improves quality of life.(ABSTRACT TRUNCATED AT 250 WORDS)

Substance P-like and somatostatin-like immunoreactivities (SPLI and SLI) were determined in ventricular fluid of patients with chronic pain syndromes and in a comparison group with multiple sclerosis, essential tremor, epilepsy and postanoxic myoclonus. Concentrations of SPLI and SLI were non-significantly decreased by 40% and 33% in chronic pain patients as compared with control patients without pain. There were no differences apparent between subgroups of pain patients (deafferentation pain, neoplasia-induced pain, thalamic pain). High pressure liquid chromatography combined with radioimmunoassay showed marked heterogeneity of SPLI and SLI.

Radiographic procedures which require the intravascular administration of water-soluble radiocontrast media are performed with increasing frequency. Each examination carries risks that are related either to the technique itself or to the opaque medium chosen. The pathogenesis of radiocontrast media-related adverse effects cannot be explained by a unique theory. The major factors implicated are direct chemotoxic effects and the physicochemical properties of contrast media, the latter being the basis for development of new contrast agents. With nonionic opaque media cardiovascular adverse effects, heat sensation and local pain are observed less frequently. However, it remains unclear whether the incidence of organ dysfunction or anaphylactic reactions with nonionic contrast media currently used can be reduced. This review compares ionic and nonionic contrast media, and current thoughts on the pathophysiology and treatment of adverse reactions are presented.

In a series of 447 patients with single vessel angioplasty, 27 (6.0%) had acute thrombotic occlusion early after the procedure. They were treated with combined intracoronary (20 mg)/intravenous (50 mg) thrombolysis with recombinant tissue-type plasminogen activator (rt-PA) and repeat mild balloon inflations. Reopening of the vessel was achieved in 22 patients (81.5%). Follow-up coronary angiography 24 to 36 h later revealed reocclusion in 12 patients (54.5%). Thrombin levels measured as thrombin-antithrombin-III complex in patients with successful thrombolysis and persistent patency decreased from 8.5 +/- 11.4 micrograms/liter at baseline to 3.5 +/- 1.4 micrograms/liter 120 min after the start of thrombolysis; these levels increased from 9.4 +/- 15.0 micrograms/liter at baseline to 15.7 +/- 13.5 micrograms/liter 120 min after the start of thrombolysis in the patients with unsuccessful thrombolysis or early reocclusion (p less than 0.05). When a borderline value for thrombin-antithrombin-III complex level of 6 micrograms/liter was selected to separate the two groups of patients, patients with an unfavorable clinical course were identified 120 min after the start of thrombolysis by levels greater than 6 micrograms/liter (sensitivity 100%, specificity 92.8%). Thus, after abrupt thrombotic vessel closure during coronary angioplasty, the short-term results of thrombolysis seem to be governed by the release of thrombin. In two thirds of patients, however, the thrombin release cannot be suppressed by concomitant aspirin and heparin therapy. Even after successful reopening of the vessel these patients should therefore undergo immediate aortocoronary bypass grafting.

INTACT (International Nifedipine Trial on Antiatherosclerotic Therapy) is a prospective, placebo-controlled, randomized, double-blind, multicenter trial analyzing the influence of 80 mg nifedipine/day on the angiographic progression of early stage coronary atherosclerosis. Coronary angiograms were taken in identical projections before and after a treatment period of 3 years. Quantitative analysis of the angiograms was performed with the computer-assisted contour detection system CAAS. For definition purposes, the coronary artery system was subdivided into 25 different segments, including all anatomic variants. Measurement parameters of segments were mean and minimal diameter, and of stenoses minimal diameter, percentage diameter reduction (at least 20%), length, and plaque area. The variable extent of the changes of these parameters in the different projections analyzed per patient in the two study angiograms was considered by separate computation of the maximal, mean, and minimal changes over these projections; the comparison of the parameter changes between the two treatment groups was performed separately according to these three modes. For all parameters, this comparison was performed on the basis of the individual 25 segments, as well as after aggregation of individual segments to arteries (RCA, LAD, and LCX), to groups of large and small segments, and to the entire coronary artery system. Assessment of changes of the coronary (patho)morphology by quantitative analysis of coronary angiograms is associated with a number of methodical limitations, which may lead to a certain variability of the results. However, due to the double-blind feature of INTACT, this variability should be comparable in the two groups of this study, allowing for a conclusive comparison.

Experimental studies have demonstrated a 30-50% reduction in the development of atheromatous lesions of the aorta in rabbits fed a diet rich in cholesterol when they were treated with nifedipine. Based on these favorable results, we designed a multicenter, placebo (PL)-controlled, randomized, double-blind study, to test the effect of 80 mg nifedipine (NIF) per day versus placebo on the progression of mild coronary artery disease (CAD) (further development of existing stenoses, especially formation of new stenoses and occlusions) over a duration of 3 years. Progression of CAD was assessed by coronary angiograms performed at entrance and at completion of the study, using a computer-assisted analysis system (CAAS) to quantitate various stenosis parameters (percent degree of stenosis and minimal stenosis diameter). Of the 425 patients enrolled, 348 (82%) underwent a second angiogram; 66 of them, however, terminated treatment prematurely after an average of 359 (placebo) and 467 days (nifedipine). A total of 282 patients (148 on placebo, 134 on nifedipine) completed the trial with full-length treatment. There were no differences between the two groups in the progression of the existing stenoses. Patients on nifedipine, however, demonstrated significantly fewer new lesions (stenoses greater than 20% or occlusions) than those on placebo: In the 282 patients undergoing the full-length treatment, there were 73 patients on placebo (49%) with 118 new lesions (0.8/patient) and 54 patients on nifedipine (40%) with 78 new lesions (0.58/patient), a difference of -27% (p = 0.031 by Cochran's linear trend test). The difference was greatest in the left anterior descending branch, with 28 patients on placebo developing 33 new lesions (0.22/patient), versus 16 patients on nifedipine with 18 new lesions (0.13/patient) (-40%; p = 0.045); and in the left circumflex branch, where 34 patients on placebo exhibited 39 new lesions (0.26/patient) versus 23 patients on nifedipine with 22 new lesions (0.16/patient) (-38%, p = 0.033). No differences were observed in the right coronary artery, the vessel with the highest number of existing and new lesions [PL] versus 0.27 [NIF] new lesions/patient) (-7.6%, p = 0.381). Hence, INTACT confirmed the previous experimental studies and demonstrates a significant reduction in newly formed coronary lesions in patients on nifedipine when compared with those on placebo, especially in the presence of early coronary artery disease.

In quantitative analysis of repeated coronary angiograms, a variable vasomotor tone of the epicardial coronary arteries may influence the accuracy of the results. Therefore, we evaluated the extent and reproducibility of coronary artery dilation with nitrocompounds. In 32 patients with coronary artery disease, the vasodilatory response of angiographically normal coronary segments to different nitrocompounds was analyzed with the computer-assisted contour detection system CAAS. Twenty patients received 5 mg or 10 mg of isosorbide dinitrate sublingually. After 10 to 15 min, a maximal diameter increase was measured with an average of 16 +/- 11% (5 mg: P less than 0.01) and 28 +/- 13% (10 mg: P less than 0.001) from control. Another 12 patients received 0.025 mg per kg body weight of SIN-1, the active metabolite of molsidomine, as an intravenous infusion over 5 min. A comparable maximal dilation (29 +/- 5%; P less than 0.001) occurred after 10 to 15 min and could not be enhanced further with 0.8 mg nitroglycerin administered sublingually (28 +/- 7%; n.s.). One hour after square root of Sin-1, coronary dilation was still 24 +/- 8% (P less than 0.001 compared with control), and 0.8 mg of nitroglycerin sublingually reestablished the previous maximal dilation of 28 +/- 8%. We conclude that high doses of nitrocompounds induce a reproducible maximal coronary dilation that eliminates a substantial source of error in quantitative analysis of repeated coronary angiograms. At present, sublingual administrations of either 10 mg isosorbide dinitrate once or 0.8 mg nitroglycerin repeatedly seem to represent the easiest practicable modes to achieve maximal coronary vasodilation for an adequate period.

The aetiology, morphology and clinical significance of Brunn's nests in human bladder urothelium are poorly understood. In the present study, 9% of a population of 100 consenting patients undergoing diagnostic or review cystoscopies were histologically found to have Brunn's nests, although their presence was not detected endoscopically. Of the nine cases, four were diagnosed with cystitis cystica, two with bladder papillomata, one with transitional cell carcinoma and cystitis cystica, and two were considered to be macroscopically normal. Mucosal biopsies were removed from areas unaffected by macroscopic abnormalities. Brunn's nests consisted of rounded collections of cells, whose nuclei contained prominent nucleoli and occasional nuclear bodies. The cytoplasm frequently contained clusters of mitochondria, together with Golgi membranes and cisternae of granular endoplasmic reticulum while small membrane bound vesicles containing electron dense material were present in some cells. Presumptive lysosomes were rarely observed. Thus Brunn's nest cells generally resembled normal urothelial cells in both their nuclear and cytoplasmic fine structure. Brunn's nests were surrounded by a basal lamina and loose connective tissue containing fenestrated capillaries.

In order to determine the relationship among ventricular arrhythmias, left ventricular dysfunction and sudden cardiac death (SCD), 75 consecutive patients with myocardial infarction, 38 of whom resuscitated from SCD, were studied retrospectively by 48 hour Holter electrocardiographic monitoring (ECGD), cardiac catheterization and radionuclide angiography (ACRD). The patients were divided in 3 groups, related to SCD occurrence and to the interval between acute myocardial infarction (AMI) and SCD: Group I (37 patients-control group) no cardiac arrest occurred; Group II (26 patients) resuscitated less than or equal to 48 hours after AMI; Group III (12 patients) resuscitated 6-12 weeks after AMI. ECGDs were recorded with an average of 2 (ECGD 1), 16 (ECGD 2) and 36 months (ECGD 3) after AMI. In ECGD 1, there were no differences in the frequency and complexity of ventricular arrhythmias among the 3 groups, whereas in ECGD 2 and 3 the incidence of complex ventricular arrhythmias was significantly higher in Group III than in the other 2 groups (p less than 0.05). In Group III, the complexity and frequency of ventricular arrhythmias increased both in ECGD 2 and 3 compared to ECGD 1 (p less than 0.05). Furthermore, between patients of Group II and III higher grade arrhythmias and more frequent ventricular premature beats (VPB) were noted in sudden death patients than in survivors. There was no statistical difference in mean cardiac index, left ventricular end-diastolic pressure and ejection fraction among the groups. In the ACRD 1 performed an average of 8 months after AMI, a slight decrease of ejection fraction in Group III compared to the other groups was noted (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Vasomotion of angiographically normal and stenotic epicardial coronary arteries was analyzed up to 15 minutes after the onset of an intravenous infusion (4 minutes) of 0.5 mg (13 patients, group A) or 1 mg nisoldipine (13 patients, group B). After both doses the maximal increase of the mean diameters of normal coronary segments was achieved not before the 15th minute, averaging 11 +/- 6% in group A (p less than 0.001) and 18 +/- 9% in group B (p less than 0.001). Eleven of 15 and 8 of 9 coronary stenoses in groups A and B dilated to 5-80% and 15-70%, respectively. The nisoldipine concentration reached maximal levels at the end of the infusion (fourth minute) with an average of 8 +/- 4 ng/ml and 17 +/- 7 ng/ml in groups A and B, respectively. A significant correlation between nisoldipine plasma levels and dilation of normal coronary segments was obtained only with the individual maxima of these parameters and only in group A (p less than 0.01). The hysteresis of the coronary dilation in relation to the drug plasma levels may be due to the high receptor affinity of nisoldipine. In either group nisoldipine provoked a persistent increase in coronary sinus oxygen saturation (p less than 0.01) and a substantial and prolonged drop in systolic and diastolic aortic pressure (p less than 0.001). Both doses of nisoldipine induced a rise in heart rate (p less than 0.01) and a slight drop in the rate-pressure product (p less than 0.05).

Animal experiments demonstrated a significant suppressive effect of various calcium channel blockers on the formation of atherosclerotic lesions. Therefore, a prospective, placebo-controlled, randomized, double blind multicenter study was performed to investigate the inhibitory influence of the calcium channel blocker nifedipine (80 mg/day) on the progression of coronary artery disease in man. Study endpoints were changes of coronary morphology documented by coronary angiography with particular respect to the formation of new coronary stenoses. In 348 out of 425 patients included in the study, coronary angiograms were repeated after three years. The angiograms were standardized by induction of a maximal coronary vasodilation with high doses of nitrates and by using absolutely identical angiographic projections. Quantitative analysis of coronary cineangiograms was performed with the computer-assisted contour detection system CAAS. Parameters were mean and minimal diameter of all segments and minimal stenosis diameter, percent diameter stenosis, length and plaque area of all stenoses. Continuous intake of study medication was registered in 282 patients, 134 on nifedipine and 148 patients on placebo. In these patients, a total of 3808 coronary segments with 893 stenoses (greater than or equal to 20% diameter reduction in at least one angiographic projection) were compared on the baseline and follow-up cineangiograms. The changes in all angiographic parameters analyzed averaged over all patients by considering all angiographic projections analyzed, indicated significant progression of the disease (p less than 0.006). The average changes in all parameters were even about three times more profound, when in the individual patients only the respective projections indicating the maximal changes were considered for the calculation (p less than 0.001). However, with neither of these two analysis modes, the differences in progression between the treatment groups were statistically significant. In the follow-up angiograms, a total of 196 new coronary lesions (185 stenoses, 11 occlusions) were found at previously normal arterial sites. In patients on nifedipine, an average of only 0.58 new lesions per patient were detected versus 0.80 lesions per patient on placebo (-27%; p = 0.031). INTACT is the first prospective angiographic trial on the progression of coronary artery disease using computer-assisted quantitative coronary angiography in such a high number of patients. All parameters analyzed indicated significant progression of coronary artery sclerosis. Nifedipine had no influence on the progression of preexisting coronary stenoses, but inhibited significantly the formation of new angiographically recognizable lesions. Further prospective coronary angiographic trials with calcium channel blockers using a comparably exact method are needed to confirm the results of this study.

In quantitative coronary angiographic studies, unintentional changes of coronary vasomotor tone may have a significant influence on the coronary artery diameters, thereby increasing the variability in the measurements. To obtain objective data on these measurement variabilities, two protocols were designed to assess the influences of ionic and nonionic radiographic contrast media on the mean diameters of angiographically normal coronary arteries. The vessel sizes were determined with the CAAS using automated edge detection techniques. In 21 patients (study no. I), coronary angiograms were taken in identical angiographic projections before (control), and immediately following several (at average 7) subsequent diagnostic dye injections administered over a period of about 7 min. The ionic contrast agent diatrizoate 76% induced a coronary dilation of 19 +/- 7% (mean +/- s.d., p less than 0.001; n = 10); the nonionic agent iopromide 370 increased the coronary artery diameters by only 6 +/- 4% (p less than 0.01; n = 11). In another 11 patients (study no. II) coronary angiograms were obtained using the nonionic contrast medium iopamidol 300 at 5, 8, 10 and 11 min after the control acquisition; this protocol was repeated in the same patients with diatrizoate 76%. With iopamidol, coronary diameter changes were not significant at any time; with diatrizoate, however, coronary dilation was measured at 10 min (2 +/- 2%; p less than 0.01) and at 11 min (10 +/- 3%; p less than 0.001). In a third study it was tested, whether standardization of coronary vasomotor tone (e.g. in coronary angiographic follow-up studies) is possible by the induction of a reproducible maximum coronary dilation with nitrocompounds. In 12 patients, the mean diameters of angiographically normal coronary segments were analyzed before and at various times after i.v. administration (over 4 min) of 0.025 mg SIN-1/kg bodyweight. Coronary dilation was maximal at 10 or 15 min after the onset of the SIN-1-infusion (29 +/- 5%; p less than 0.001). 0.8 mg nitroglycerin given s.l. at 15 min did not further dilate the coronary arteries (28 +/- 7%). One hour after SIN-1, coronary dilation still amounted to an average of 24 +/- 8% (p less than 0.001) and became 'maximal' again, when 0.8 mg nitroglycerin was again administered sublingually (28 +/- 8%; p less than 0.001). In conclusion, short-term variability of coronary vasomotor tone induced by ionic radiographic contrast media can be eliminated by the use of nonionic contrast agents and observation of injection intervals of at least 2 min. In quantitative coronary angiographic follow-up studies, as well as during acute interventions (e.g., PTCA), identical baseline vasomotor tone can be achieved by induction of the maximal coronary dilation using nitrocompounds.

The vasodilatory effects of nitrocompounds and calcium antagonists on epicardial coronary arteries represent substantial antianginal mechanisms in the presence of coronary vasospasm or eccentric coronary stenoses. With high doses of nitrocompounds, angiographically normal coronary segments can be dilated by an average of approx. 30%, some coronary stenoses even by up to 100%, usually without severe reduction of blood pressure. With calcium antagonists, a similar extent of dilation of normal coronary arteries and eccentric stenoses can be obtained. Our own group demonstrated an average dilation of normal coronary arteries of about 20% after intravenous administration of dihydropyridine calcium antagonists; however, the average systolic blood pressure dropped below 100 mmHg after these compounds. Hence, although in isolated human coronary arteries high concentrations of calcium antagonists were shown to induce a considerably greater vasodilation than nitrocompounds, the early drop in blood pressure prohibits a higher dosage of calcium antagonists in vivo. In the presence of coronary artery disease, particularly when associated with coronary vasospasm, a combination of the two groups of compounds might be recommendable, since an addition of the effects of coronary vasomotor tone is likely. Furthermore, the antianginal effects of a reduction of preload and afterload are complementary.

Changes in coronary vasomotor tone of large epicardial coronary arteries today can be assessed quite accurately by exact measurements of coronary diameters applying computer assisted systems. The effect of various vasodilators (nitrates, calcium antagonists, EDRF-dependent compounds) was tested in this way. It appears that normal coronary artery segments reach a maximum of dilator reserve with an increase of luminal diameter of approximately 30-40%; different patterns of kinetics were, however, encountered. beta-Blocking agents, both non-selective (propranolol) and selective (atenolol), were found to lead to a gradual vasoconstriction, i.e., a decrease in diameter by approximately 20-25% over 20 min, an effect which is overcome by nitrates. New beta-blocking compounds with vasodilator properties, such as celiprolol, show no constriction. The vasoconstrictor effect of propranolol and atenolol may not only be due to the decrease of flow following the drop in myocardial oxygen consumption, but could also reflect an unopposed alpha-adrenergic tone. The clinical aspects of this observation are discussed.

A comprehensive study of human bladder urothelium was undertaken to define the normal histological and fine structural features of this tissue. Urothelial biopsies from consenting male and female patients undergoing diagnostic or review cystoscopies were analysed. In 31 patients there was an apparently normal urothelium lining the bladder, and in 3 patients the trigone appeared normal. Normal urothelium was not observed to contain lymphocytes, lymphoid follicles, mast cells, Brunn's nests or cysts. No mitoses were seen despite examining about 50,000 urothelial cells. Trigonal and bladder urothelium normally consisted of 3 and 3-6 cell layers, respectively, but they shared the same basic architecture of basal, intermediate and superficial (or surface) cell types. The urothelium possessed a regular, polarised architecture of increasing morphological complexity and differentiation from base to surface. Occasional, slender, cytoplasmic projections were observed to reach the basal lamina from the intermediate cell layer, but not from the surface cell layer. Human urothelium should therefore be considered a stratified, not a pseudostratified, epithelium. The nuclear shape in cross-section was indented in the basal layer, and rounded in the superficial layer. Correspondingly, chromatin configurations of urothelial nuclei were evenly and finely granular in the superficial layer and condensed in the basal layer, suggesting a greater degree of transcriptional activity in the former. Intermediate cell nuclei assumed intermediate degrees of shape and chromatin configuration. Prominent nucleoli were found in the nuclei of all cell layers. Both basal and intermediate cell nuclei and superficial cell nuclei contained characteristic nuclear bodies. Urothelial cells of all layers were connected by interdigitations of cytoplasmic processes and by desmosomes. Clusters of mitochondria were seen throughout the urothelium. Elaborate Golgi membranes and rough endoplasmic reticulum, although rare in the basal layer, were observed in the remainder of the urothelium. Large, prominent lysosomes were identified with the electron microscope and histochemically in the surface layer. The superficial aspect of the urothelium was lined, at least in some regions, by an asymmetric luminal membrane. Tight junctions linked adjacent urothelial surface cells. Such junctions were not observed anywhere else in the urothelium. Fine cytoplasmic filaments, probably of the intermediate type, were most conspicuous in the surface layer. Overall, normal human bladder urothelium is arranged in increasing complexity from base to surface.

36 patients with chronic stable or the variant form of angina pectoris were subdivided according to their coronary angiogram into 4 groups: Group A with a single highgrade stenosis in one coronary artery, Groups B, C and D with different patterns of occluded, but collateralized coronary arteries supplying noninfarcted myocardium. All patients underwent multiple exercise step tests before (K) and after randomly assigned crossover treatment with 20 mg nifedipine (N), 20 mg isosorbiddinitrate (I), the combination of both (I + N) and Placebo (P). Peak and mean ischemic ST-segment depression, the occurrence of angina pectoris and heart rate were evaluated. The mean ischemic ST-segment depression decreased significantly after N in group A by -28% (p less than 0.01), but was not significantly altered in the groups B, C and D (B: -12%, C: +7%, D: +2%). After I, mean ST-segment depression decreased significantly in all groups (A: -36%, p less than 0.001; B: -27%, p less than 0.001; C: -22%, p less than 0.01; D: -29%, p less than 0.05). The combination of I + N was not better than I alone. Peak ST-depression and angina pectoris paralleled the results of mean ST-depression. The resting heart rate increased significantly after N only in group A (+9%, p less than 0.01) and increased after I in the groups A, B and C (A: +11%, p less than 0.05; B: +12%, p less than 0.05; C: +12%, p less than 0.01). During exercise, heart rate was not significantly different in any group or after any type of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

A number of animal studies revealed an inhibition or retardation of the progression of atherosclerosis by calcium-antagonists. Encouraged by these studies, a multicenter trial on the progression of coronary artery disease (CAD) in man was initiated testing the antisclerotic effect of nifedipine against placebo in 426 patients with mild to moderate coronary disease over 3 years. All patients underwent coronary angiography before entering the trial and will be restudied after 3 years; changes of the coronary artery lumen size are quantitatively assessed by a computer-assisted system (CAAS). INTACT (International Trial on Antiatherosclerotic Coronary Therapy) is therefore the first randomized prospective study on the progression of CAD based on a quantitated anigraphic control of the coronary system. This report presents the design of this still-ongoing study as well as inclusion and exclusion criteria. The quantitative evaluation of the coronary angiograms and the mode of compliance test are described in detail. A number of baseline data as well as the preliminary results of the quantitative evaluation of the first coronary angiograms are presented. Beside the results on the effect of the calcium-antagonist nifedipine on the progression of CAD, INTACT might also supply information on the antiatherosclerotic potency of other drugs administered additionally (beta-blockers and nitrates) and of HDL-cholesterol.

Quantitative in vivo analysis of the vasomotility of epicardial coronary arteries is based on the measurement of changes of the vessel diameters. Vessel contours can be determined with the help of a precision caliper by the investigator or with computer-assisted geometrical analysis systems applying a contour detection algorithm; the variability of the results from repeated coronary diameter measurements in the identical film frame is comparably low with all systems (less than or equal to 0.12 mm standard deviation). When investigating the influence of an intervention on coronary vasomotility the variability of the measurements can only be kept low by careful standardization of the entire method. Repeated coronary angiograms are performed in identical angiographic projections (mono- or biplane) with standardization of the inspiratory status of the patient and of the rate of contrast material injection (automatic injection pump). For quantitative analysis all coronary segments with a diameter greater than 1 mm which are clearly outlined, free from overlaps, and mainly run parallel to the image plane, are selected by the investigator in preferably end-diastolic cineframes. Whereas with a caliper and with most of the semi-automatic edge detection systems the segment diameter can only be measured at particular sites defined by the investigator, few systems are able to analyze and average the diameter over the entire segment length. The variability of measurements of the minimal diameters of coronary stenoses in different cine frames is particularly high; therefore, only distinct changes of this parameter (e.g. with the CAAS-system greater than 0.24 mm) may be considered significant.(ABSTRACT TRUNCATED AT 250 WORDS)

In 396 of 423 (93.6%) patients with mild to moderate coronary artery disease participating in a coronary angiographic follow-up trial, diameters of the epicardial coronary arteries were measured with an automatic contour detection system (CAAS). The underlying INTACT study (International Nifedipine Trial on Antiatherosclerotic Therapy), a prospective, placebo-controlled, randomized, double-blind multicenter trial, investigates the influence of the calcium antagonist nifedipine (80 mg/day) on the progression of coronary atherosclerosis over a three-year interval. The study is based on coronary angiograms repeated in identical projections after premedication with 10 mg isosorbide dinitrate sublingually. For quantitative analysis the coronary artery system was, in consideration of all anatomical variations, subdivided into 25 segments. In the first angiograms of the 396 patients evaluated up to April 1, 1988, altogether 5,425 different coronary segments could be analyzed over their entire length in one or more angiographic projections--on the average 13.7 +/- 2.8 segments per patient. Analysis parameters were the mean diameters of the entire segments and of the individual subsegments (about 5 mm in length). The 10 major proximal segments could be evaluated in 76-94% of patients respectively in more than two different angiographic projections on the average; in 0-13% of patients the respective segments were occluded. In 1-4% of patients the evaluation of these segments was prevented by poor film quality and in 1-16% of patients prevented by anatomical abnormalities (e.g., segment too short or too small). 184 segments were found occluded (RCA 42%, LAD 30%, CX 28%) and 909 mostly low-grade to moderate stenoses (RCA 34%, CX 32%, LAD 30%, left main 4%) were analyzed with a special algorithm. The following obstruction parameters were derived: minimal diameter, percentage severity, length, and plaque area. The present data demonstrate that in an angiographical multicenter follow-up study such as INTACT a nearly complete quantitative morphometric analysis of the visualized coronary artery system can indeed be obtained in virtually all angiograms when a computer-assisted contour detection system is applied.

Three growth rate experiments involving several sampling points were performed to investigate the previous finding that very low concentrations of HgCl2 inhibit the growth of murine lymphoblasts in vitro. However, results presented here do not confirm this, there being no significant differences between the three independent growth rate experiments.

Normal unstimulated urothelium of adult mice appears to be essentially quiescent, as demonstrated by an 3HTdR-pulse labelling index of 0.11%. There is no evidence that this labelling index may be artificially low. Results from continuous labelling experiments, where 3HTdR was supplied in the drinking water of mice for varying periods, render it possible that the urothelium satisfies its small renewal requirements via a low growth fraction of cycling cells. The remainder may consist of quiescent cells, which may be capable of resuming cell cycle progression when required, and of post-mitotic cells, which are incapable of further proliferation. There are three possible levels of adult urothelial proliferation with cell cycle times of about a) one year (if the urothelium is homogeneous and the growth fraction unity), b) three weeks (if the growth fraction is about 5%), and c) 15 h (when the urothelial cells are rapidly regenerating).

It is the objective of the INTACT-study to test in man, whether a significant retardation of the progression of coronary artery disease is attainable with the Ca-antagonist nifedipine; this may be possible on the basis of numerous animal experiments. INTACT is a prospective, randomized, double blind, placebo controlled investigation in 423 patients with preferably early stages of coronary sclerosis in whom a progression of the disease seems likely. A proper coronary angiogram led to inclusion of the patients in the study (October 1983-June 1985). Over the following 3-years-period patients received either nifedipine 80 mg/day or placebo. The study is concluded by a control coronary angiogram with angiographic projections which are identical to those of the first coronary angiography. The extent of coronary sclerosis is objectivated by computer-assisted quantitative measurement of the entire coronary arterial system with the CAAS-system (Rotterdam). For definition purposes the coronary artery system subdivided into 25 segments. Parameters for progression assessment will be mean segment diameter, minimal obstruction diameter, percentage severity of obstruction, length of obstruction and plaque area. So far 4826 coronary segments have been analyzed from the first angiograms of 383 patients. Per patient an average of 12.6 different segments could be evaluated in at least one angiographic projection. The major coronary segments could be measured in 72-93% of the patients in one or more angiographic projections (at the average about 2 different projections). Five hundred and forty-six coronary obstructions were analyzed; 131 of these were total occlusions. Only 9% of the length of the vessel contours detected by the computer algorithm required manual correction by the operators, suggesting a high reliability of the system. It can be concluded that quantitative measurement of the complete coronary artery system can indeed be obtained in a large angiographical multicenter study such as INTACT.

Therapeutic embolization of blood vessels by means of hardly steerable devices (e.g., metal coils, gel foam) can result in displacement of the emboli in the circulation. The embolization of an ACVB-graft erroneously implanted to the anterior cardiac vein was performed, applying a catheter system with a detachable silicone rubber balloon.

In 48 patients undergoing diagnostic coronary angiography changes of mean diameters of angiographically "normal" coronary segments after intracoronary injections of diatrizoate 76% or iopromide 370 performed in different intervals, were analyzed with a computer-assisted contour detection system (CAAS). Four study protocols were applied, differing in respect to the type of contrast medium administered and/or to the timing of the reference- and control-angiograms in the course of diagnostic coronary angiography. Coronary angiograms in identical projections were performed before (= reference) and directly after (1. control = C1) diagnostic angiography of the left coronary artery by injection of either diatrizoate 76% (group 1, 10 patients) or iopromide 370 (group II, 11 patients). Additional coronary angiograms were performed 1, 3, 6, and 10 min after C1. During diagnostic angiography in either group about eight dye injections were performed in about seven min. With diatrizoate 76% a significant coronary dilation averaging 18.9 +/- 6.7% (p less than 0.001) was observed at C1, depending on the number of diagnostic dye injections performed per min (mean 1.2 +/- 0.3) and on the interval between the last diagnostic injection and C1 (mean 73 +/- 35 s). Coronary dilation persisted up to the sixth minute (6.2 +/- 4.6%, p less than 0.01). With iopromide 370 a small but significant coronary dilation was observed merely at C1 (5.8 +/- 4.3%, p less than 0.05). In two other studies coronary angiograms were performed in identical projections immediately following complete diagnostic coronary angiography (reference) and in addition after 3, 4, 5, 6, 10, and 20 min (group III, 18 patients) and after 10, 20, and 30 min, respectively (group IV, 9 patients) by administration of diatrizoate 76% as the only contrast medium. Short injection intervals (1 min) resulted in a mild coronary dilation (mean up to 2.4 +/- 4.1% compared to reference; p less than 0.05), longer intervals (3-10 min) resulted in a marked diameter reduction (averaging up to -9.7 +/- 9%; p less than 0.05), probably a consequence of the return of coronary vasomotor tone to baseline levels. These results suggest that in quantitative coronary angiographic studies (e.g., testing coronary vasomotility) non-ionic contrast media should preferably be applied, and adequate injection intervals (greater than 2 min) are mandatory. In intervention- and follow-up studies based on repeated coronary angiograms dye-induced changes of coronary vasomotor tone can be avoided by premedication with vasodilating drugs, e.g. nitrates, and/or calcium antagonists.

Developing murine urothelium undergoes pronounced proliferation until at least 10 days after birth. Thereafter, both mitotic and [3H]TdR-labelling indices fall sharply with age. The ratio of labelling to mitotic indices also alters dramatically during development, which is probably due to both endoreduplication and changes in the relative durations of the DNA synthesis and mitotic phases. This ratio reaches stability at 5 weeks of age. The adult labelling and mitotic indices were 0.11 and 0.019% respectively, indicating a very slow turnover.

The maximal extent of the dilation of epicardial coronary arteries attainable with nitro-compounds was investigated in 12 patients with coronary artery disease. Before and 5, 10, 15, 19, 60 and 64 min after onset of a 4-min-intravenous infusion of 0.025 mg SIN-1/kg bodyweight coronary angiograms were performed in identical projection; simultaneously, the mean pulmonary wedge pressure (PWP) was measured. At 15 and 60 min, 0.8 mg nitroglycerin (NTG) were additionally administered as sublingual spray. Mean diameters of angiographically normal coronary segments were analyzed with the computer-assisted contour detection system CAAS; they increased by an average maximum of 29 +/- 5% prior to NTG (p less than 0.001). PWP decreased from 9.2 +/- 3.1 mmHg to an average minimum of 4.3 +/- 1.6 mmHg (p less than 0.01) prior to NTG. Neither of these SIN-1-effects was significantly augmented by additional NTG: at 19 min coronary dilation amounted to 28 +/- 7% (p less than 0.001), PWP to 3.9 +/- 1.0 mmHg (p less than 0.01). At 60 min coronary dilation still amounted to 24 +/- 8% (p less than 0.001), PWP to 6.2 +/- 2.5 mmHg (p less than 0.05). By the second administration of NTG the maximal effects attained before could be reproduced: coronary dilation 28 +/- 8% (p less than 0.001), PWP 4.6 +/- 2.2 mmHg (p less than 0.01). Thus, the dilation reserve of epicardial coronary arteries for nitrocompounds is approximately 30% on average. These results suggest the possibility of a reproducible maximal activation of the enzyme guanylate cyclase which seems to be the mediator of the nitro-compound-induced vasodilation.

Unlabelled: The diameter changes of angiographically normal epicardial coronary arteries were studied in 25 patients in correlation to nifedipine plasma levels. In group 1 (15 patients) 20 mg of s.l. nifedipine were administered. Measurements of the coronary lumen size (automated contour detection system, accuracy 0.12 mm) and detection of plasma levels (gas-chromatography) were done before and 10, 20 and 30 min after drug administration. According to the slope of nifedipine plasma levels, patients were divided into group 1 A (n = 4) and 1 B (n = 11). Plasma levels in both groups were: at 10 min, 27.8 +/- 9.8 and 13.5 +/- 4.5 ng/ml resp.; P less than 0.05; at 20 min, 54.0 +/- 11.7 and 21.7 +/- 6.6 ng/ml resp.; P less than 0.001; at 30 min, 79.1 +/- 9.3 and 28 +/- 9.8 ng/ml resp.; P less than 0.001. The corresponding diameter changes in A and B were: 7.3 +/- 5.1%/.-5.6 +/- 9.0% resp.; P less than 0.01; 11.4 +/- 4.1% and -4.5 +/- 11.3% resp.; P less than 0.01; 14.5 +/- 5.9% and 0.5 +/- 13.6% resp.; P less than 0.05. In group 2 (10 patients) 1 mg nifedipine was administered intravenously within 4 min. Measurements were done at 1 min intervals during infusion as well as 7 and 15 min after beginning and compared to a placebo group (n = 10). Peak plasma levels amounted to 16.7 +/- 5.7 ng/ml after 7 min. The maximum coronary dilation was reached after 4 min (verum 5.0 +/- 6.8%; placebo 3.2 +/- 3.6%). Significant differences between both groups were observed after 7 min (verum 4.1 +/- 5.3%; placebo -3.1 +/- 5.8%, P less than 0.05) and 15 min (verum 1.2 +/- 3.2%; placebo -6.2 +/- 8.4%; P less than 0.05)., Conclusion: based on significantly different plasma levels following sublingual application of 20 mg nifedipine a classification of patients into "early-" and "late-coronary-responders" could be established. After intravenous infusion of 1 mg nifedipine peak plasma levels were much lower than after sublingual application of 20 mg and coronary diameters showed only a mild increase.

Data are presented on the postnatal growth of the mouse bladder. Both bladder size (measured as surface area) and bladder wet weight increase steadily with age, respectively reaching 2.5 times and 4 times their newborn values by the age of ten weeks. Despite this growth, which may be due principally to non-urothelial components of the bladder, the body weight rises 10-15 fold above the newborn levels. The ratio of bladder weight to the total body weight steadily declines from a peak value in newborn mice to a stable plateau reached at about five weeks of age. The results indicate that a fairly mature bladder exists at birth.

Today, therapeutic occlusion of blood vessels can be performed not only by surgical ligation, but also by various transluminal embolization techniques. The use of hardly steerable emboli (e.g. metal coils or gel foam) is, however, associated with the risk of embolic displacement into the circulation. The present case describes the embolization of an ACVB-graft erroneously implanted to a cardiac vein, by means of a catheter system with a detachable silicone-rubber balloon (Bard-Parker mini-balloon system).

32 patients in an early state of coronary sclerosis were investigated in connection with diagnostic angiography. 8 patients received 2 mg gallopamil (G) and for every 12 patients 0.1 mg/kg propranolol (P), respectively, 0.12 mg/kg Atenolol (A). All medications were injected intravenously over 4 min. The angiograms were repeated in identical projections before (control) as well as 5, 10, 15, and 20 min after G and 2, 4, 6...up to 20 min after P and A. All angiograms were analyzed using a quantitative computerized contour detection system. 10 min after infusion of G 34 measured coronary segments showed a significant (p less than 0.05) medium dilation of 21 +/- 4.3% and after a further 10 min an insignificant increase in coronary diameter was observed up to 25 +/- 4%. After infusion of P and A a distinct vasoconstriction could be seen. Especially P showed a decrease in diameter of almost 25% in small coronary segments (less than 2.0 mm diameter). The dilatative effect of G i.v. seems to be important in the therapy of acute ischemic situations, for instance, for unstable angina, acute myocardial infarction, or during PTCA. The acute coronary vasoconstriction after infusion of P and A should be considered when used in acute ischemic events.

Thirty-six patients with chronic stable angina pectoris or with stable and vasospastic components of angina pectoris were classified by coronary arteriographic findings into 4 groups. Patients in group A had a single stenotic coronary artery; patients in groups B, C and D had occluded arteries, but these arteries had been collateralized to varying degrees, and an epicardial coronary steal phenomenon was possible. All patients underwent multiple exercise tests before and after randomized, double-blind, crossover treatment with 20 mg of nifedipine, 20 mg of isosorbide dinitrate, a combination of both, and placebo. Maximal and mean ST-segment depression, occurrence of angina pectoris and heart rate were evaluated. After nifedipine treatment, mean ischemic ST-segment depression was reduced 21% in group A (p less than 0.05), but was not significantly altered in the other groups (group B, 2% decrease; group C, 10% increase; group D, 3% decrease). However, isosorbide dinitrate reduced ST-segment depression significantly in all groups (group A, 29%, p less than 0.001; group B, 18%, p less than 0.01; group C, 19%, p less than 0.05; group D, 33%, p less than 0.05). The combination with nifedipine did not further improve the effect of isosorbide dinitrate. Maximal ST-segment depression and angina pectoris paralleled the changes in mean ST depression during the different medications. Heart rate at rest was not significantly changed after nifedipine treatment in any group, but increased significantly after isosorbide dinitrate treatment in groups B and C (group B, 12%, p less than 0.01; group C, 9%, p less than 0.05); heart rate during exercise did not differ significantly in any group or after any form of medication from placebo.

In 10 patients with coronary artery disease coronary angiograms were performed in identical projections before and 5, 10 and 15 min after sublingual administration of two chewing capsules with 5 mg of isosorbide dinitrate (ISDN) each. Simultaneously, blood samples were taken for gas-chromatographical determination of nitrate plasma levels. The average ISDN plasma levels amounted to 138 +/- 73 ng/ml, 102 +/- 76 ng/ml and 62 +/- 34 ng/ml in the fifth, tenth and fifteenth min, resp. In the fifteenth min significant isosorbide mononitrate plasma levels (greater than 70 ng/ml) were found only in three patients. Mean diameters of angiographically normal coronary segments were measured with the automatic edge detection system CAAS; they increased by an average of 20 +/- 10%, 26 +/- 11%, and 27 +/- 13% (p less than 0.001) in the fifth, tenth and fifteenth min, resp. Due to hysteresis of the coronary dilation in relation to ISDN plasma levels no significant correlation was found between these parameters. The minimal diameters of seven of 10 coronary stenoses analyzed in seven patients reacted with a maximal increase of 23%-98%. Thus, ISDN chewing capsules may be preferable for rapid and prolonged relief of anginal attacks as well as for potent dilation of epicardial coronary arteries as desired during angiography.

The diameter changes of angiographically normal coronary arteries following vasodilator drugs were studied in 41 patients. In group 1 (22 patients) angiograms and plasma levels were obtained before as well as 10, 20 and 30 minutes after 20 mg nifedipine s.l. (15 patients) or placebo (7 patients). A cluster analysis allowed a classification of patients into group A (N = 4) and B (N = 11) according to the slope of plasma level increase. Plasma levels A versus B were 27.8 +/- 9.8/13.5 +/- 4.5 ng ml-1; P less than 0.05; 54.0 +/- 11.7/21.7 +/- 6.6 ng ml-1; P less than 0.001; 79.1 +/- 9.3/28 +/- 9.8 ng ml-1; P less than 0.001. Corresponding diameter changes A versus B were: 7.3 +/- 5.1%/-5.6 +/- 9.0%; P less than 0.01; 11.4 +/- 4.1%/-4.5 +/- 11.3%; P less than 0.01; 14.5 +/- 5.9%/0.5 +/- 13.6%; P less than 0.05. In group 2 (N = 19) angiograms were obtained before as well as 2, 4, 7 and 15 minutes after administration of 10 mg isosorbide dinitrate (N = 9) or placebo (N = 10). Coronary dilation ISDN versus placebo was: 2.4 +/- 3.6%/0.9 +/- 4.0%; NS; 10.6 +/- 5.1%/3.1 +/- 3.8%; P less than 0.001; 12.3 +/- 5.9%/-0.3 +/- 6.4%; P less than 0.005; 10.5 +/- 6.5%/-4.0 +/- 7.7%; P less than 0.005. These data indicate that the interindividual variations of changes in coronary lumen size are due to different slopes of plasma level increase, most likely due to different rates of drug absorption after sublingual administration of nifedipine.(ABSTRACT TRUNCATED AT 250 WORDS)

The present research has employed a novel, nonradioactive technique to quantitatively study normal urothelial proliferation in foetal, neonatal, juvenile and adult mouse bladder. Using whole mount histological preparations, the total number of urothelial nuclei per mouse bladder, and per given urothelial cell layer, have been assessed to provide data of the (unstimulated) kinetic behaviour of basal urothelial cells (the proliferative population), to analyse characteristics of the normal urothelial cell cycle. The urothelial cell cycle time increases from 30.6 h (foetal) to 40 weeks (adult), the duration of mitosis from 0.23 h (foetal) to 2.71 h (adult) and the duration of DNA synthesis from 2.52 h (neonatal) to 10.83 h (adult). These are average values for the urothelial cell cycle, which do not preclude the possible existence of proliferative units. The ratio of superficial nuclei to basal and intermediate nuclei, possibly indicative of a urothelial proliferative unit, declines to reach a plateau (1:40) in adult mice. These findings indicate that rapid urothelial proliferation during early murine development was likely to be a) biologically useful, since intrauterine foetal metabolic activity may require a functional bladder urothelium at an early stage, b) kinetically similar to acutely regenerating adult urothelial cells after cytotoxic insult. During murine life, the range of durations of mitosis and DNA synthesis is much less than the range of cell cycle times. Normal unstimulated urothelium of adult mice was confirmed to proliferate slowly.

Six patients with angiographically documented coronary artery disease underwent multiple exercise tests before and after randomized double-blind crossover treatment with 200 mg 5,6-dimethoxy-2-(3[(alpha-(3,4-dimethoxy)phenylethyl)methylamino] propyl)-phthalimidine-hydrochloride (AQ-A 39 cl, in the following briefly called AQ-A 39) intravenously. Changes in ST-segment depression, angina pectoris, heart rate and blood pressure were evaluated. After AQ-A 39, the sum of ST-segment depression was significantly reduced compared with control and placebo by 48% (2p less than 0.025) and 42% (2p less than 0.05) respectively, maximal ST-segment depression by 45% (2p less than 0.025) and 35% (2p less than 0.05), respectively; the duration of angina pectoris was reduced by 50% and 33%, respectively. AQ-A 39 reduced heart rate at rest and during exercise; blood pressure, however, was not significantly altered. In conclusion, AQ-A 39 is an antianginal drug, which acts most probably by cardiac mechanisms and not by reduction of afterload. Thus, further studies about AQ-A 39 or its derivatives seem to be useful.

The molecular size distribution of somatostatin-like immunoreactivity (SLI) in the cerebroventricular fluid of patients with Parkinson's disease, dystonic syndromes, multiple sclerosis, basal and midline tumors, epilepsy and pain syndromes was investigated by separation with a Sephadex G-50f column and subsequent radioimmunoassay of the eluate. Marked heterogeneity of SLI was observed in most of the pools investigated. The most conspicuous feature of the elution profiles was the preponderance of the peak coeluting with synthetic somatostatin-14, whereas the peaks comigrating with synthetic somatostatin-28 and attributable to precursor-like SLI represented only minor or trace amounts of total immunoreactivity. These findings are consistent with the greater biological activity of somatostatin-14 in the human central nervous system, whereas somatostatin-28 appears to represent the more active form in the pituitary and in the intestinal mucosa. Solely in the case of brain tumor patients, some differences could be seen, resulting in an approximately equal distribution of somatostatin-14 and somatostatin-28 in two pools of ventricular fluid and by the detection of a degradation product of somatostatin-14 in another one. These observations could be explained by a lowered barrier function as a consequence of increased intracranial pressure in case of brain tumors, which is well in accordance with a markedly elevated total protein content being a sign of a lowered barrier function.