Efficacy of isosorbide mononitrate in angina pectoris

The rapid development of tolerance has limited the applicability of oral and transdermal nitrates in the long-term management of patients with chronic stable angina pectoris. Recent well-controlled trials have demonstrated that asymmetrical, or eccentric, dosing of oral isosorbide mononitrate, in which 20-mg doses are taken at 8 A.M. and 3 P.M., provides at least 12 hours of antianginal coverage. There is no evidence for the development of tolerance with this schedule, which allows for a 17-hour nitrate withdrawal period. Likewise, the asymmetrical 20-mg twice daily regimen has not been associated with the zero-hour effect that has been reported with higher oral doses of isosorbide mononitrate and with intermittent nitroglycerin patch therapy. This approach also avoids the development of a clinical rebound phenomenon, as measured by increased episodes of angina and nitroglycerin consumption, compared with the pretreatment period, during the nitrate-free interval at night and the early hours of the morning.     

Effects of amlodipine and isosorbide dinitrate on exercise-induced and ambulatory ischemia in patients with chronic stable angina pectoris

This study was designed to compare once-daily administration of 5-10 mg amlodipine with two daily doses of 40 mg sustained-release isosorbide dinitrate in 59 patients with stable angina using a randomized, double-blind, crossover study design. Anginal episodes, nitroglycerin consumption, and possible adverse events were recorded in a diary. A maximal symptom-limited bicycle exercise test and 48-hour ambulatory ECG monitoring were performed at baseline and at the end of each 5-week period of therapy. Exercise time, time to angina, time to ST depression, and maximal ST depression were measured during exercise. During ambulatory monitoring, the number of ischemic episodes and the duration per hour of ST depression were assessed. Amlodipine significantly reduced anginal episodes (P < 0.001) when compared with isosorbide dinitrate. Furthermore, amlodipine prolonged time to ST depression (P < 0.001) and time to angina (P < 0.05) when compared with isosorbide dinitrate. The number and duration of ischemic episodes during ambulatory monitoring were significantly reduced with amlodipine when compared with baseline values (P < 0.05), whereas no differences were found between isosorbide dinitrate and baseline. Adverse events were reported more frequently with isosorbide dinitrate than with amlodipine (P < 0.02). Amlodipine appears to be more effective and tolerable than sustained-release isosorbide dinitrate as monotherapy for chronic stable angina.     

Effect of supplemental oral L-arginine on exercise capacity in patients with stable angina pectoris

To determine if microscopic urinalysis is needed in all pediatric emergency room patients screened for urinary tract infections (UTI), we compared the dipstick urinalysis and complete urinalysis (dipstick and microscopy) with urine cultures in 236 children, aged 3 weeks to 21 years. The ability to detect UTI by dipstick only and by complete urinalysis was the same, however microscopic evaluation added many false-positive results without detecting additional UTIs. Because the ability to detect UTI (sensitivity) is maintained, we now offer a dipstick only urinalysis to our emergency room for children 2 years of age or older, with a microscopic analysis performed automatically if dipstick results are positive. If no microscopic urinalysis is required, testing turn-around time is reduced by 12.3 min/test and the hospital charge is reduced from U.S. $32 to U.S. $12.     

Coronary stenosis progression differs in patients with stable angina pectoris with and without a previous history of unstable angina

OBJECTIVES: To compare the evolution of stenoses responsible for acute coronary events with those not associated with acute coronary syndromes. METHODS AND RESULTS: We prospectively studied angiographic stenosis progression in 190 stable angina patients, with single vessel disease, who were awaiting non-urgent coronary angioplasty. Sixty four patients had a previous history of unstable angina (Group 1) and 126 patients had no history of unstable angina (Group 2). Culprit stenoses were classified as "complex' or "smooth'. At restudy, 8 +/- 4 months after the first angiogram, 12 of 63 culprit stenoses in Group 1 had progressed and seven of 125 in Group 2 (19% vs 6%, P = 0.0044). Thirteen of 68 complex culprit stenoses had progressed, compared with only 6 of 120 smooth culprit stenoses (19% vs 5%, P = 0.003). Coronary events occurred in 12 Group 1 patients and nine Group 2 patients (P = 0.02). CONCLUSIONS: In patients with stable angina, stenoses associated with previous episodes of unstable angina are more likely to progress than stenoses not associated with previous unstable angina. Unstable coronary atherosclerotic plaques, even those that have been clinically stable for more than 3 months, may retain the potential for rapid progression to total occlusion.     

Selection of drug therapy in stable angina pectoris

Given a strong match between regions of two sequences, how far can the match be meaningfully extended if gaps are allowed in the resulting alignment? The aim is to avoid searching beyond the point that a useful extension of the alignment is likely to be found. Without loss of generality, we can restrict attention to the suffixes of the sequences that follow the strong match, which leads to the following formal problem. Given two sequences and a fixed X > 0, align initial portions of the sequences subject to the constraint that no section of the alignment scores below -X. Our results indicate that computing an optimal alignment under this constraint is very expensive. However, less rigorous conditions on the alignment can be guaranteed by quite efficient algorithms. One of these variants has been implemented in a new release of the Blast suite of database search programs.     

Acute heavy alcohol intake increases silent myocardial ischaemia in patients with stable angina pectoris

PURPOSE: The purpose was to determine tumor neovascularisation via colour-coded Doppler (duplex) sonography and the "power mode", both visually and quantitatively, by means of videodensitometry. MATERIAL AND METHODS: 6 VX2 tumours of 4 to 11 mm size were implanted in 4 rabbits at various sites. The colour-coded duplex sonography and the new sonographic power technique were tested before and after having injected a new contrast medium (SH U 616A). RESULTS: If no contrast medium was injected, tumour neovascularisation was identified in only 50% of the cases. Injection of contrast medium increased signal intensity three to fourfold with all examined tumors. Combined use of the sonographic method by the power technique with injection of contrast medium is outstandingly suitable for tumor vessel imaging even of small tumors, as these initial results seem to show. CONCLUSION: If these results are corroborated by further studies, contrast-medium supported sonographic technique may possibly become established as an alternative method to other imaging procedures.     

A comparative study of eccentric and concentric coronary stenosis vasomotion in patients with Prinzmental''s variant angina and patients with stable angina pectoris

HPV is the commonest sexually transmitted viral infection in the United Kingdom and as such poses a major public health problem. In addition to the potential physical morbidity associated with genital warts, abnormal cervical cytology, and anogenital dysplasia and neoplasia, the associated psychological morbidity should not be forgotten. Although our knowledge of viral function and disease pathogenesis has advanced appreciably in recent years, we are still some way from developing an in vitro method of viral propagation. Vaccination against HPV infection will hopefully be achieved within the next 10 years, but a prevention and treatment strategy which is appropriate for both developed and developing nations must be our major long term goal.     

Suppressed anti-aggregating and cGMP-elevating effects of sodium nitroprusside in platelets from patients with stable angina pectoris

Short bowel syndrome (SBS) in the newborn results in limited intestinal absorptive capacity, leading especially to fatty acid (FA) malabsorption. It is unknown whether adaptation occurs in time in FA absorption, and whether this adaptation is chain-length dependent. The aid of the present study was to prospectively evaluate FA absorption and excretion during SBS in the newborn. Twenty-one neonates who underwent small bowel resection (of variable length) for various reasons (necrotizing enterocolitis, intestinal atresia, meconium peritonitis, cloacal extrophy, etc) were studied. Eight neonates had SBS, defined as a small bowel remnant of less than 50% of the original small bowel length related to gestational age. The mean remaining small bowel length in the SBS group was 34% (24% to 42%). The non-SBS control group consisted of 13 neonates who had only minor small bowel resections. The mean remaining bowel length for the non-SBS group was 95% (70% to 100%). The results show that the total fractional excretion of FA (FE-FA) at 2 weeks and 1, 2, 3, and 4 months postsurgery was 51% +/- 37%, 33% +/- 24%, 51% +/- 65%, 53% +/- 27%, and 7% +/- 2% in patients with SBS, versus 12% +/- 8%, 24% +/- 10%, 9% +/- 3%, 8% +/- 3% and 17% +/- 14% in the non-SBS controls, respectively (P < .05 by ANOVA). There appeared to be an amelioration in time in FA absorption, especially in the SBS group, after 3 months. FE-FA was chain-length related, being considerably less for C10 and C12 than for C14 and longer amounts. An amelioration of absorption occurred in the SBS patients, especially with the longer-chain FA. On the basis of the study data, the authors conclude that in the initial adaptation phase shorter chain lengths are better absorbed than longer chain lengths; however, in the latter FA group, substantial adaptation occurs with time.     

Beneficial effects of atrial natriuretic peptide on exercise-induced myocardial ischemia in patients with stable effort angina pectoris

BACKGROUND: It has been shown that atrial natriuretic peptide (ANP), an endogenous vasodilator, dilates coronary arteries and decreases coronary vascular resistance. The purpose of this study was to determine whether an intravenous administration of ANP attenuated exercise-induced myocardial ischemia in 14 patients with stable effort angina pectoris. METHODS AND RESULTS: The first 12 patients (patients 1-12) who had exercise-induced ST segment depression underwent treadmill exercise testing and the last seven patients (patients 8-14) underwent the exercise 201Tl-single-photon emission computed tomography (SPECT) study while synthetic 28-amino acid alpha-human ANP (0.1 micrograms/kg per minute) or saline was intravenously infused in a double-blind, cross-over manner. The duration of exercise testing was the same during ANP and saline infusion, which was determined in preliminary exercise testings in each patient to cause a transient perfusion defect and/or ischemic ST segment depression. During saline infusion, all 12 patients developed exercise-induced ischemic ST segment depression, whereas no significant ST segment depression appeared during ANP infusion. Average ST segment depression during ANP infusion was significantly less (p < 0.01) than that during saline infusion (0.0 +/- 0.0 versus 0.2 +/- 0.1 mV, mean +/- SD). The averaged extent and severity scores assessed by 201Tl-SPECT were smaller (p < 0.05) during ANP infusion than during saline infusion (extent score: 0.22 +/- 0.20 versus 0.42 +/- 0.20; severity score: 18.77 +/- 23.45 versus 38.24 +/- 24.04, respectively). ANP decreased resting systolic blood pressure from 125 +/- 15 to 110 +/- 15 mm Hg (p < 0.01) but did not alter resting heart rate. At peak exercise, systolic blood pressure, heart rate, and the rate-pressure products did not differ during ANP and saline infusion. At peak exercise, plasma ANP increased from 98 +/- 45 to 4,383 +/- 2,782 pg/ml and cGMP increased from 3.6 +/- 1.7 to 34.5 +/- 16.1 pmol/ml during ANP infusion; values were significantly higher than those during saline infusion (from 96 +/- 42 to 133 +/- 66 pg/ml and from 3.4 +/- 1.8 to 4.6 +/- 1.8 pmol/ml, respectively). CONCLUSIONS: An intravenous administration of ANP attenuated exercise-induced myocardial ischemia in patients with stable effort angina pectoris. Although the mechanism by which ANP attenuated myocardial ischemia was not defined, increased myocardial perfusion to the ischemic region might be an important factor.     

Influence of combination therapy (isosorbide dinitrate and molsidomine) on the incidence of angina pectoris in patients with coronary heart disease

Angina pectoris in patients with severe 3-vessel-disease refractory to treatment is a challenge for the treating physician. We have therefore tested the treatment efficacy of isosorbide dinitrate combined with molidomine on the frequency of angina pectoris in patients with symptoms refractory to treatment. PATIENTS AND METHODS: 15 patients with severe coronary heart disease were included in the study. The protocol included a 2-weeks stabilisation phase, followed by a 4-weeks treatment phase with 100 mg isosorbide dinitrate in the morning as well as 8 mg slow-release molsidomine at 6 p.m. RESULTS: Initially all of the 15 patients reported about daily angina pectoris attacks. After 4 weeks of treatment 4 out of 15 patients became free of symptoms. From the other 11 patients 6 reported an improvement, 5 an unchanged frequency of attacks. DISCUSSION: Combination treatment with isosorbide dinitrate with molsidomine in a slow-release form (in the nitrate free interval) showed a distinct improvement in patients with angina pectoris refractory to treatment with reduction of complaints. The effect of the combination is possibly based on a prolonged vasodilatation of the stenosed vessels and a prolonged reduction of filling pressure (reduction of preload).     

Platelet aggregability in vivo is attenuated by verapamil but not by metoprolol in patients with stable angina pectoris

One of the most widely studied simple sequences in the mammalian genome is the (TG)n dinucleotide sequence. Because these microsatellites are highly polymorphic, we chose to study microsatellites from cosmids to provide genetic markers for the porcine genome. After screening a porcine cosmid library with a (CA)10 probe, 20 cosmids containing microsatellites were subcloned and 17 microsatellites identified by sequencing. Oligonucleotide primers flanking the repeat were designed for seven (TG)n microsatellites with n > 14. These seven microsatellites revealed polymorphism and were regionally assigned to chromosomes by fluorescent in situ hybridization of initial cosmids. These seven loci will be useful for both the construction of the genetic map and as landmark loci on the physical map of the porcine genome.     

Effects of mental and physical stress on platelet function in patients with stable angina pectoris and healthy controls

The effects of mental and physical stress on platelet function in patients with stable angina pectoris and healthy controls were investigated. Platelet function was studied at rest, and during mental stress (colour word test), or after exercise (bicycle ergometry), in 113 angina patients (21 on aspirin) and 50 matched controls. Platelet function was assessed by filtragometry ex vivo (reflecting platelet aggregability), by measuring platelet secretion (beta-thromboglobulin and platelet factor 4 levels in plasma), and by Born aggregometry in vitro. At rest, platelet function did not differ between patients and controls. Exercise increased platelet aggregability and secretion similarly in both groups. Aspirin did not attenuate the platelet activating effect of exercise despite inhibition at rest. Mental stress increased heart rate, blood pressure and plasma catecholamines, but platelet responses were highly variable. However, mental stress tended to shorten filtragometry readings in patients but not in controls (P < 0.05 between the groups); plasma beta-thromboglobulin showed a similar difference between patients and controls (P < 0.05 between the groups; aspirin-treated patients included). Physical exercise activates platelets in patients with stable angina pectoris and healthy controls. Aspirin is not an effective inhibitor of exercise-induced platelet aggregation. Platelet responses to mental stress are variable, but more pronounced in angina patients.     

Effects of short-term reduction in serum cholesterol with simvastatin in patients with stable angina pectoris and mild to moderate hypercholesterolemia

To evaluate the effects of short-term cholesterol-lowering treatment on myocardial effort ischemia, 22 patients with stable effort ischemia and mild to moderate hypercholesterolemia (low density lipoprotein [LDL] cholesterol 160 to 220 mg/dl) were randomly allocated at baseline (TO) in 2 groups. Group A included 12 patients treated with simvastatin 10 mg bid; group B included 10 patients treated with placebo. All patients underwent a treadmill electrocardiography (ECG) test; total cholesterol, HDL and LDL cholesterol, triglycerides, plasma, and blood viscosity were measured. All tests were repeated after 4 and 12 weeks. For 18 of the same patients (11 taking simvastatin, 7 receiving placebo), forearm strain-gouge plethysmography was performed at baseline and after 4 weeks, both at rest and during reactive hyperemia. At 4 and 12 weeks, group A showed a significant reduction in total cholesterol (p <0.05) and LDL (p <0.05), with unchanged HDL, triglycerides, blood, and plasma viscosity. Effort was unmodified, ST-segment depression at peak effort and ischemic threshold were significantly improved after 4 and 12 weeks (all p <0.05) with unchanged heart rate x systolic blood pressure product. A significant increase in the excess flow response to reactive hyperemia was detected in group A (p <0.03); group B showed no changes in hematochemical and ergometric parameters. These data suggest that cholesterol-lowering treatment is associated with an improvement in myocardial effort ischemia; this might be explained by a more pronounced increase of coronary blood flow and capacity of vasodilation in response to effort.     

Molsidomine and isosorbide dinitrate: a comparative trial of tolerance in long-term intake by IHD patients with stable angina of effort

Potential tolerance to isosorbide dinitrate (ID) and molsidomine (M) was studied in 18 ischemic heart disease (IHD) patients with stable angina of effort entered in a double blind cross-over trial. Each drug was administered for 3 weeks 4 times a day in individual effective dose. Single doses of ID and M were similar by effectiveness, but after 3 weeks of regular intake their efficacy fell, ID becoming less potent than M. For ID, tolerance after long-term intake manifested in 7 out of 18 patients, for M--in 5 out of 18. Complete tolerance was registered in 3 of 18 and 1 of 18 patients, respectively. Thus, tolerance is possible for the two drugs, but for M it is less pronounced.     

Short-term effects of captopril on exercise tolerance in patients with chronic stable angina pectoris and normal left ventricular function

A double-blind, placebo-controlled, crossover study was carried out to evaluate the short-term effects of captopril on exercise tolerance in 18 normotensive patients with chronic stable angina pectoris and normal left ventricular function. Captopril 25 mg (or placebo) was given twice, i.e. in the evening (10 p.m.) and the following morning (8 a.m.), prior to a maximal symptom-limited bicycle exercise test (11 a.m.). Captopril reduced the systolic and diastolic blood pressures at rest (p < 0.01) without causing any reflex tachycardia. The time to onset of S-T depression was prolonged (p < 0.05), and the maximal S-T depression was reduced (p < 0.02). No differences were found between captopril and placebo in total exercise duration or time to onset of angina. The effects of captopril on exercise-induced ischemia were demonstrated most clearly in patients who responded with a greater than 10 mm Hg fall in the resting systolic blood pressure. In conclusion, this study suggests that captopril has anti-ischemic properties, which may be of importance in the treatment of patients with chronic stable angina and normal left ventricular function. These beneficial effects probably relate to a reduction in afterload and myocardial wall stress and therefore a reduction in myocardial oxygen demand.     

Rheological and hydrodynamic properties of blood from patients with stable angina pectoris: correction with high molecular polyethylene oxide]

This paper presents a case with 11-year history of disseminated cerebral polycystosis in a 23-year-old female. Physical examination and CT, MRT, histological and biochemical data suggest that the disease is morphologically progressive; however, the spread on brain lesions showed no correlation with relatively mild clinical manifestations of the disease. Variants of nosological interpretation of histological data are discussed.     

Chlamydia pneumoniae infection in patients with myocardial infarct and angina pectoris

In a prospective open study we investigated Chlamydia pneumoniae infections in 36 consecutively admitted patients: 26 males, mean age 53.4 yr, range 36-70 yr, 10 females mean age 57.7 yr, range 47-70 yr, suffering myocardial infarction (24 acute, 2 previous) or angina pectoris (10). Antibody serum levels were measured by the immunefluorescent method and they were as follows: negative 5, low 12, medium/high 11, chronic infection 5, recent infection 3. The 3 cases considered as recent infections are described in detail.