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Biomedical subjects

S Silber

Publications and source records attributed to S Silber.

At least 19 recordsLinked to original sources
PubMed1992

Replacement of frozen embryos generated from epididymal spermatozoa: the first two pregnancies.

This report describes the first two pregnancies which occurred after cryopreservation, thawing and transfer of embryos generated using epididymal spermatozoa from men with congenital absence of the vas deferens. Of the 32 embryos that were thawed, 24 survived (75%) and were replaced in seven transfer cycles resulting in two (29%) pregnancies successfully delivered. The demonstration that excess embryos obtained with the use of epididymal spermatozoa can be safely frozen/thawed, and that their survival is not different from other embryos generated by in-vitro fertilization, represents a great advantage for the reproductive performance of men with congenital absence of the vas deferens undergoing microsurgical aspiration of epididymal spermatozoa.

Cryopreservation↗
PubMed1990

Accuracy of digital Holter monitoring of extent and duration of ischemic episodes compared to analog recording.

Analog amplitude-modulated Holter devices are in widespread use for arrhythmia detection, but their reliability remains questioned for ST-segment analysis. In contrast, recently developed digital Holter devices immediately digitize and analyze the electrocardiogram (ECG) on-line and may therefore be more reliable for ST-segment analysis. To test this hypothesis, the results of digital, on-line, 2-channel ST-segment analysis were directly compared to those of analog amplitude-modulated recordings in identical leads (CM5 and CM3), using a stripchart recorder meeting the American Heart Association specifications as the standard. Thirty-five patients (25 with coronary artery disease and 10 control subjects) underwent graded treadmill exercise testing. The reference ECG mean value for ST-segment depression in CM5 was -1.4 +/- 1.2 mm and in CM3 -0.5 +/- 1.2 mm. For digital analysis, the mean values and correlation coefficients for CM5 were -1.5 +/- 1.1 mm (r = 0.97) and for CM3 -0.8 +/- 1.3 mm (r = 0.93). For analog recording, the results for CM5 were -2.1 +/- 1.7 mm (r = 0.88) and for CM3 -1.3 +/- 1.9 mm (r = 0.85). The mean duration of ST-segment depression with the reference ECG was 7.1 +/- 4.1 minutes. Digital Holter showed a significantly better agreement (7.4 +/- 4.4 min, r = 0.97) than analog Holter (9.6 +/- 5.6 min, r = 0.84). Because analog amplitude-modulated Holter recordings overestimated the degree and duration of ischemic episode, digital, on-line and full disclosure devices should be preferred to assess myocardial ischemia.

Algorithms↗
PubMed1990

Nitrates: why and how should they be used today? Current status of the clinical usefulness of nitroglycerin, isosorbide dinitrate and isosorbide-5-mononitrate.

Nitrates are highly effective both in terminating acute attacks of angina pectoris and in the prophylaxis of symptomatic and asymptomatic myocardial ischemia. Preload reduction by venodilatation is the prevailing mechanism of nitrates in patients with chronic stable angina and is the unique feature distinguishing them from beta and calcium-channel blockers. Nitrates dilate coronary arteries not only in pre- and poststenotic vessels, but also in eccentric lesions. In patients with endothelial dysfunction, nitrates seem to be the physiological substitute for endothelium-derived relaxing factor. During the past decade, however, there has been substantial evidence of a clinically relevant loss of the anti-ischemic effects ("nitrate tolerance"). Many studies with oral dosing of isosorbide dinitrate or isosorbide-5-mononitrate at least three times daily have proven nitrate tolerance in patients with coronary artery disease and/or congestive heart failure. Complete loss of anti-ischemic effects after repetitive, continuous patch attachments has also been found. As we first showed in 1983, intermittent therapy with once-daily ingestion of high-dose sustained-release isosorbide dinitrate was successful in preventing the development of tolerance. Similarly, tolerance to isosorbide-5-mononitrate also does not develop when it is ingested once daily. It is now generally accepted that a daily low-nitrate interval is required to prevent tolerance development. Although the minimal patch-free interval required to prevent tolerance needs further investigation, a 12-h patch-free interval should prevent tolerance in most patients. The prolonged duration of action of once-daily high-dosage administration of sustained-release formulations, the improved patient compliance with a single daily administration, and the increased likelihood of maximal anti-ischemic effects are important reasons for recommending high single daily doses of isosorbide dinitrate or isosorbide-5-mononitrate.

Angina Pectoris↗
PubMed1990

Relations of the myocardial imaging agents 99mTc-MIBI and 201T1 to myocardial blood flow in a canine model of myocardial ischemic insult.

Myocardial imaging with thallium 201 has proven to be an important clinical procedure to assess the severity of the myocardial ischemic insult. Uptake of 201Tl is related to perfusion to and extraction by intact myocardium. Recently, a newer group of agents based on 99mTc alkyl isonitriles has been developed and appears promising for myocardial imaging. Although the distribution of this new agent has been shown to be related to myocardial perfusion, its dependence on myocardial integrity has not been established. This study compared the distribution of 99mTc-2-methoxy-isobutyl-isonitrile (99mTc-MIBI) with that of 201Tl in a clinically relevant canine model of ischemic insult. Fifteen adult dogs underwent 2 hours of occlusion by left anterior descending coronary artery ligation followed by reperfusion. In one group of dogs, 201Tl and 99mTc-MIBI were administered 5 minutes before 35 minutes of reflow (group 1, n = 5). In the other animals, the agents were given 5 minutes after onset of reflow, and dogs were killed after 10 (group 2, n = 5) and 35 minutes of reperfusion (group 3, n = 5). 99mTc-MIBI activity was significantly correlated with 201Tl activity (r = 0.91, 0.77, and 0.92, for groups 1, 2, and 3, respectively). Both 201Tl and 99mTc-MIBI activities were correlated similarly with blood flow in all models. In groups 1 and 2, 201Tl and 99mTc-MIBI activities correlated directly with microsphere-determined blood flow, whereas in group 3, they correlated inversely. The present study shows that in these models of myocardial ischemic insult, 99mTc-MIBI distribution is closely related to that of 201Tl.

Animals↗
PubMed1989

Low incidence of sperm antibodies in men with congenital absence of the vas deferens.

The incidence of antisperm antibodies in serum and seminal fluid of 27 azoospermic men with congenital absence of the vas deferens is evaluated. The presence of antisperm antibodies was assessed using the immunobead test, the agglutination test, and immobilization test. Five patients with vasovasostomy or vasoepididymostomy attempts were included in the study and tested for the presence of antisperm antibodies. Contrary to a previous report, a low incidence (11%) of antisperm antibodies has been found in patients with congenital absence of the vas. In agreement with previous studies, in five patients who had failed vasoepididymostomy or vasovasostomy, a high incidence (71%) of antisperm antibodies was found.

Autoantibodies↗
PubMed1989

[Combination of anti-angina drugs].

Within the last decade it became obvious that the treatment of angina pectoris alone is not sufficient. Modern goals include the optimization of anti-ischemic treatment ("silent myocardial ischemia") without compromising quality of life, as well as the reduction of fatal and non-fatal cardiac events. The failure of nitrates to continuously protect from myocardial ischemia ("nitrate tolerance") requires a modification of the current step-care recommendations for medical treatment. Numerous combinations of nitrates, betablockers and calcium channel blockers compensate for each other regarding their effects on heart rate, contractility, peripheral resistance and coronary blood flow. Recommendations for combination therapy decisively depend on the choice of the first-line drug. Only nitrates reduce myocardial preload by venodilation and substitute for EDRF-deficiency. After headaches disappear, nitrates do not affect quality of life and they are cheap. The nitrate-induced acceleration of heart rate should be compensated by the addition of beta-blockers or heart rate-decreasing calcium channel blockers. Therefore, the combination of nitrates with heart-rate-increasing calcium channel blockers, such as nifedipine, should be avoided. Many studies have proven the superiority of different double and triple therapies, as compared to their single components. A few reports, however, did not confirm this increase of anti-ischemic efficacy with combination therapy. The improvement of prognosis is proven for beta blockers without ISA in subgroups of patients with acute or post myocardial infarction and can be assumed for nitrates as well. With regard to prognosis, calcium channel blockers were inferior to nitrates and beta blockers. The combination of nitrates with a non-ISA betablocker should be preferred in post myocardial infarction patients with ventricular arrhythmias, whereas the combination of nitrates with a heart rate decreasing calcium channel blocker should be preferred in patients with COPD, severe peripheral arterial disease or severe diabetes. The combination of nitrates with a heart-rate-increasing calcium channel blocker should be considered in patients with sinus bradycardia, first degree AV-block, or proven coronary spasm. In patients with congestive heart failure, betablockers and calcium channel blockers should be avoided. To optimize medical treatment of ischemic heart disease, intermittent high dosage ISDN plus a beta blocker without ISA or ISDN plus a calcium channel blocker like verapamil are recommended. Frequently, however, the patient decides by himself, based on unacceptable side effects.

Adrenergic beta-Antagonists↗
PubMed1989

[Combination therapy with isosorbide dinitrate and verapamil in patients with coronary heart disease and hypertension: effect on blood pressure, ischemia and left ventricular function].

In the treatment of myocardial ischemia in hypertensive patients, nitrates as the basic compound have to be combined with another substance in order to achieve a maximum effect and a 24-h-protection. As these patients often show an impaired left ventricular function because of arterial hypertension or previous myocardial infarction, a further deterioration of the left ventricular ejection fraction (EF) has to be avoided. We therefore investigated in a pilot study. EF, blood pressure, and ST-segment depression under isosorbide dinitrate 120 mg s.r. alone, and in combination with verapamil 120 mg s.r. in 14 male patients with angiographically proven coronary artery disease and arterial hypertension. EF at rest ranged from 29% to 76%. Radionuclide ventriculography was performed at rest and simultaneously with the ECG during exercise before medication, 2 h after ISDN and 4 h after the additional intake of verapamil. The systolic blood pressure at rest fell from 159 +/- 14 to 132 +/- 10 (p less than 0.001) after 2 h and to 132 +/- 16 mmHg after 6 h (p less than 0.01). During exercise there was a decrease from 196 +/- 21 to 174 +/- 21 (p less than 0.01) and to 178 +/- 22 mmHg (p less than 0.001), respectively. The ST-segment depression was reduced from 2.2 +/- 1.1 to 0.8 +/- 0.6 (p less than 0.01) and to 0.9 +/- 0.5 mm (p less than 0.001). EF at rest improved from 53 +/- 14% to 57 +/- 14% after ISDN alone and to 58 +/- 15% after ISDN + verapamil (p less than 0.01), and during exercise from 57 +/- 20% to 62 +/- 19% (p less than 0.05) and to 61 +/- 17% (n.s.). Even in the subgroup of patients with impaired LV-EF (8 at rest and 7 pts during exercise) there was a significant improvement (p less than 0.05) as well after ISDN alone, as there was with combination therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

[Extent of therapeutic effect and duration of 1 capsule of 120 mg isosorbide dinitrate in a slow release form].

In this randomised, double-blind placebo-controlled crossover study we investigated the efficacy of 120 mg isosorbide dinitrate s.r. 12 h after application in comparison to 2 and 6 h in 18 patients with angiographically proven coronary artery disease, stable exercise-induced angina and reproducible ST-segment depression. Bicycle ergometry was performed before, 2, 6 and 12 h after medication and nitrate plasma levels were drawn before each exercise test. After 2 h, the exercise-induced ST-segment depression in comparison to placebo was reduced from 2.3 mm +/- 0.8 to 0.7 +/- 0.5, after 6 h to 1.0 mm +/- 0.8) and after 12 h to 1.9 mm +/- 0.8 (p less than 0.01). 82% of the patients suffering from angina on the control exercise test before medication were free of symptoms 2 and 6 h after ISDN 120 mg s. r., but showed angina again after 12 h. In comparison to the plasma levels 2 h after ingestion, the concentrations in plasma after 12 h were much lower for ISDN, equal for IS-2-MN, and more than double for IS-5-MN. Thus, 12 h after ingestion of 120 mg ISDN s.r. there is still a significant reduction of ST-segment depression. This 12-h benefit is 40% od the maximum effect.

Aged↗
PubMed1988

The insufficient nitrate response: patients' characterization and response to beta and calcium blockade.

Little information has been published regarding the nitrate-induced changes of left ventricular volumes at rest and during exercise in relation to the degree of the anti-ischaemic response. Therefore we assessed the electrocardiographically defined nitrate response to a single tablet of 80 mg isosorbide dinitrate s.r. and compared it to the changes in end-diastolic volumes at rest and during exercise, as determined by radionuclide ventriculography. Thirty-four of the 63 patients were classified as good nitrate responders, whereas 29 patients showed insufficient nitrate response with regard to the reduction of exercise-induced ST-segment depression. The baseline characteristics were quite comparable. At rest the ISDN-induced decrease of the end-diastolic count rate was significantly less (-17%) in patients with insufficient ST-segment response when compared to patients with good ST-segment response (-25%). During exercise, in patients with good ST-segment response, ISDN reduced the end-diastolic volume significantly (-19%), whereas in patients with insufficient ST-segment response the end-diastolic volume remained unchanged. In this special subset of patients with insufficient nitrate response we further evaluated the effects of additional beta or/and calcium blockade. The benefits from verapamil were equivalent to propranolol. However, a considerable part of the patients investigated needed the combination of verapamil and propranolol for an optimal anti-ischaemic drug treatment. Thus, our data support the concept that preload reduction plays a major role for the anti-ischaemic effects of ISDN in patients with exercise-dependent ischaemia. Since, a suboptimal therapeutic effect must be considered, objective control of the nitrate therapy (usually by exercise- and Holter-ECG) must be regarded as obligatory for each individual patient if optimal results are to be expected.

Adult↗
PubMed1987

Induction and circumvention of nitrate tolerance applying different dosage intervals.

There is increasing evidence that constant nitrate plasma levels, as induced by at least three-times-daily ingestions of isosorbide dinitrate in sustained-release form, lead to an attenuation or even complete loss of the anti-ischemic effects (nitrate tolerance). Therefore, the dependence of tolerance development on dosage intervals according to once-daily and twice-daily ingestions was assessed. Tablets of isosorbide dinitrate (80 mg) in sustained-release form were administered once-daily at 8 A.M. (dosage interval 24 hours) or twice-daily at 8 A.M. and 8 P.M. (dosage interval 12 hours), as well as at 8 A.M. and 2 P.M., respectively (maximal dosage interval 18 hours). A total of 34 patients with angiographically proven coronary artery disease, a history of stable, exercise-dependent angina pectoris, and a reproducible, exercise-induced ST-segment depression of at least 0.15 mV (1.5 mm), who initially showed a response to 80 mg of isosorbide dinitrate, were enrolled. The anti-ischemic effects of isosorbide dinitrate on exercise-induced ischemia were objectively determined by the measurement of exercise-induced ST-segment depression before as well as two, six, and 12 hours after the ingestion at the first and the 15th day of the studies. Since the dosage interval of 12 hours resulted in constant plasma levels, the initially beneficial anti-ischemic effects of isosorbide dinitrate were considerably attenuated after two weeks of treatment. In contrast, the once-daily regimen with its intermittent peaks and valleys of nitrate plasma levels showed identical anti-ischemic effects at the 15th day as compared with the first day. Ingestions at 8 A.M. and 2 P.M. also circumvented the development of nitrate tolerance, however, combined with an even more pronounced anti-ischemic effect after 12 hours as compared with the once-daily regimen. Thus, the circumvention of nitrate tolerance requires a daily "nitrate-poor" interval. The best compromise between a maximal possible anti-ischemic effect and the circumvention of tolerance development was found for the "eccentric" dosage regimen in which the tablets were ingested in the morning and early afternoon.

Angina Pectoris↗
PubMed1987

The haemodynamic and anti-ischaemic effects of a single tablet of 80 mg isosorbide dinitrate in slow-release formulation and a review of nitrate tolerance.

There is increasing evidence that relatively constant plasma nitrate concentrations induced by 3-times-daily administration of isosorbide dinitrate can lead to an attenuation or even complete loss of the drug's anti-ischaemic effects (nitrate tolerance). We therefore assessed the dependence of nitrate tolerance development from the haemodynamic and anti-ischaemic effects of a slow-release tablet formulation of isosorbide dinitrate 80 mg, administered according to different daily dosage regimens in patients with angina. It was found that a once-daily regimen, with its consequent peak and trough plasma nitrate concentrations, is capable of protecting against exercise-induced myocardial ischaemia for about 12 hours with the circumvention of nitrate tolerance.

Adult↗
PubMed1986

Equal anti-ischemic properties of isosorbide dinitrate plus verapamil and isosorbide dinitrate plus propranolol. A randomized, double-blind and crossover study.

Although nitrates are the basic treatment for patients with ischemic heart disease and numerous clinical studies have compared the anti-ischemic effects of different combinations with beta-blockers and/or calcium antagonists, no study is known on a controlled intraindividual comparison of the combination nitrate plus beta-blocker with the combination nitrate plus a heart rate-decreasing calcium-antagonist. Therefore we performed a randomized, double-blind and crossover study to compare the effects of 80 mg isosorbide dinitrate in slow-release form (ISDN, once-daily) plus 120 mg verapamil (t.i.d.) with those of 80 mg ISDN plus 80 mg propranolol (b.i.d.). After these two phases of 3 weeks' duration respectively, patients received the combination of all three drugs with the same dosages in a single-blind manner. In addition to the standard inclusion criteria, a pathological exercise-ECG even after ISDN was required as well as a left ventricular ejection fraction (EF) of greater than or equal to 35%. This protocol could be completed in 26 of the 30 enrolled patients. The combination ISDN plus verapamil proved to exert the same anti-ischemic effects as the combination ISDN plus propranolol. The triple therapy showed a further improvement of exercise induced ischemia without deterioration of the EF at rest or during exercise. Even though only this triple therapy led to an optimal anti-ischemic result in about one third of the patients, it should be initiated cautiously, since symptomatic bradycardia may occur.

Blood Pressure↗