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Biomedical subjects

S Silber

Publications and source records attributed to S Silber.

At least 91 records · Page 5Linked to original sources

Pregnancies after testicular sperm extraction and intracytoplasmic sperm injection in non-obstructive azoospermia.

In this study (May 1 until August 31, 1994) a total of 15 azoospermic patients suffering from testicular failure were treated with a combination of testicular sperm extraction (TESE) and intracytoplasmic sperm injection (ICSI). Spermatozoa were available for ICSI in 13 of the patients. Out of 182 metaphase II injected oocytes, two-pronuclear fertilization was observed in 87 (47.80%); 57 embryos (65.51%) were obtained for either transfer or cryopreservation. Three ongoing pregnancies out of 12 replacements (25%) were established, including one singleton, one twin and one triplet gestation. The ongoing implantation rate was 18% (six fetal hearts out of 32 embryos replaced).

Adult↗

Recent concepts in the management of infertility because of non-obstructive azoospermia.

Testicular biopsy has been widely used for the diagnosis of male infertility. Since the introduction of intracytoplasmic sperm injection (ICSI), spermatozoa recovered from a testicular biopsy specimen can be successfully used for establishing pregnancies. A few spermatozoa may be recovered from a wet preparation of a testicular biopsy, not only in obstructive azoospermic patients, but also in many patients with non-obstructive azoospermia. In 36 out of 38 non-obstructive azoospermic patients sperm cells were recovered from a testicular biopsy specimen. However in two patients, spermatozoa could not be found after further preparation of the biopsy specimens for ICSI. In the remaining 32 patients, a normal fertilization rate of 56.8% per successfully injected oocyte was obtained after ICSI of testicular spermatozoa. In 84% of patients, embryos were replaced with an overall pregnancy rate of 28.9% per testicular biopsy or 34.3% per embryo transfer. The results clearly indicate that at present an excisional testicular biopsy should be offered to all azoospermic patient, irrespective of concentration of follicle stimulating hormone, testicular size or medical history.

Biopsy↗

Ongoing pregnancies and birth after intracytoplasmic sperm injection with frozen-thawed epididymal spermatozoa.

In seven patients who did not become pregnant following microsurgical epididymal sperm aspiration (MESA) and intracytoplasmic sperm injection (ICSI), a subsequent ICSI was performed using previously cryopreserved super-numerary epididymal spermatozoa without re-operating on the husband. During the original MESA procedure a mean sperm concentration of 12.3 x 10(6)/ml was achieved. The supernumerary spermatozoa were cryopreserved for later use. After thawing frozen epididymal spermatozoa a mean concentration of 1.9 x 10(6) spermatozoa/ml was obtained in straws containing a total volume of sperm suspension of 250 microliters. From 68 intact oocytes injected with frozen-thawed epididymal spermatozoa, a two pronuclear fertilization rate of 45% and a cleavage rate of 82% were obtained. A total of 17 embryos were replaced in the seven patients, resulting in two ongoing singleton pregnancies and one twin delivery. Six embryos were cryopreserved. In conclusion, it would appear mandatory to cryopreserve supernumerary spermatozoa during a MESA in order to avoid subsequent further scrotal surgery.

Adult↗

Refinements in the methodology of injection for transvaginal gamete intra-fallopian transfer.

Eighty-seven volunteer patients with non-tubal infertility initially intending to undergo gamete intra-Fallopian tube transfer (GIFT) via a transabdominal route were re-scheduled for ultrasound-guided transvaginal GIFT which was performed using a Jansen-Anderson tubal transfer set. Emphasis was placed on (i) definite ultrasound confirmation of the transfer catheter within the Fallopian tube, (ii) low transfer volumes (50 microliters), (iii) high sperm transfer densities and (iv) slow injection of gametes. Transvaginal Fallopian tube catheterization was possible in 83 patients (95.4%). Twenty-three of 83 (27.7%) patients conceived (clinical pregnancy). The viable ongoing pregnancy rate was 20.5%. These results compare favourably to those previously reported for both transvaginal and transabdominal GIFT. This study suggested that the fluid dynamics of gamete injection following transvaginal Fallopian tube catheterization are different to those following transabdominal methods. Further study is necessary to define the optimal methodology for transvaginal GIFT and to enhance the ability of the procedure to produce pregnancy rates comparable to transabdominal GIFT.

Adult↗

Relative force of human epididymal sperm.

OBJECTIVE: To assess the relative escape force of human epididymal sperm using a laser generated optical trap and compare it with that of human ejaculated sperm. DESIGN: Evaluation of the relative force generated by epididymal and ejaculated sperm using an 800-nm laser-generated optical trap system (titanium-sapphire, model 899-01; Coherent Innova, Palo Alto, CA). SETTING: University-based facility at the Beckman Laser Institute and Medical Clinic and Center for Reproductive Health, University of California, Irvine. INTERVENTIONS: A total of 2,720 sperm from 28 samples were randomly analyzed. Fifteen were ejaculated samples (1,650 sperm) obtained from men with proven fertilization, and 13 were epididymal samples (1,070 sperm) aspirated microsurgically from patients with obstructive azoospermia. An optical trap equipped with the 100x Neofluar objective was used to analyze an average of 100 sperm per patient. MAIN OUTCOME MEASURES: Determination of mean relative escape force values in milliwatts for epididymal and ejaculated sperm samples. RESULTS: The mean relative escape force for epididymal sperm was 32.4 mW, significantly lower than ejaculated sperm, which was 85.1 mW. By correlating epididymal sperm relative force with fertilization in vitro at an arbitrary cutoff value of 30 mW, it was found that no fertilization occurred if a sample had < 13% of sperm at that value. CONCLUSIONS: [1] The average relative escape force of the epididymal sperm was found to be 60% weaker than that of ejaculated sperm. [2] It is demonstrated that the noncontact laser optical trap is a sensitive tool that can evaluate single sperm force as a new physiological parameter.

Ejaculation↗

Evidence for a novel adenylyl cyclase in human epididymal sperm.

Since cAMP is considered to play a major role in the acquisition of maturation and fertilizing capacity of mammalian sperm, we investigated the expression of cAMP-synthesizing adenylyl cyclase (AC) in sperm retrieved directly from the human epididymis. Particulate fractions were prepared from purified epididymal sperm samples and AC was monitored by the direct conversion of ATP into cAMP. We report that in great contrast to human ejaculated sperm and other mammalian sperm cells, the human epididymal sperm do not express a Mn(2+)-sensitive AC. However, a functional AC was readily detectable in these sperm cells in the presence of saturating concentrations of Ca2+ (50mM) and bicarbonate (HCO3-, 50mM), a combination that causes maximal activation in human ejaculated sperm. Using these conditions, human epididymal sperm AC showed similar capacity to generate cAMP compared to human ejaculated sperm AC. When assays were performed in the presence of Mg2+ and a saturating concentration of GMP-P(NH)P (50 microM), the hydrolysis-resistant GTP analog, and forskolin (100 microM), no activity was detected indicating that the epididymal sperm AC differs from that in somatic cells. These data demonstrate that human epididymal sperm contain an AC that is unique and different from the enzyme system described in somatic cells and other mammalian sperm cells, including human ejaculated sperm.

Adenylyl Cyclases↗

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↗

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↗

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↗

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↗

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↗

[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↗

[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↗

[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↗

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↗