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Biomedical subjects

A Shulman

Publications and source records attributed to A Shulman.

At least 19 recordsLinked to original sources

Leupeptin protects sensory hair cells from acoustic trauma.

Calpains, a family of calcium activated proteases, promote the breakdown of cellular proteins, kinases, phosphatases and transcription factors. Calpain inhibitors attenuate some neurodegenerative processes in certain cell types. Here we show that leupeptin, a potent calpain inhibitor, protects the sensory hair cells in the inner ear from acoustic overstimulation (48 h, 100 or 105 dB SPL, octave band noise at 4 kHz). Acoustic overstimulation caused a significant increase in calpain immunolabeling in the sensory epithelium suggesting a possible role in noise-induced cochlear degeneration. Infusion of leupeptin into the inner ear significantly reduced the amount of sensory cell loss from acoustic overstimulation. However, leupeptin did not protect against hair cell loss from the ototoxic drug, carboplatin.

Animals

Incidence and perinatal outcome of multiple pregnancies after intracytoplasmic sperm injection compared to standard in vitro fertilization.

PURPOSE: Our purpose was to assess the incidence of multiple pregnancies and their obstetric outcome after intracytoplasmic sperm injection. METHODS: The study group comprised women who delivered twins or triplets after intracytoplasmic sperm injection and standard in vitro fertilization. The incidence and main perinatal outcome of 140 multiple pregnancies resulting from intracytoplasmic sperm injection or standard in vitro fertilization treatment were analyzed. RESULTS: A total of 60 multiple pregnancies was obtained after intracytoplasmic sperm injection (3.4 +/- 1.1 embryos/cycle) and 80 after standard in vitro fertilization (3.3 +/- 2.0 embryos/cycle). The incidence of multiple pregnancy, i.e., 22.6 compared to 20.7%, respectively, was calculated. The obstetric outcome of 47 multiple pregnancies after intracytoplasmic sperm injection was 39 twin deliveries at between 27 and 37 weeks of gestation (mean, 36 +/- 3.3) and 8 successful triplet deliveries between 26 and 36 weeks of gestation (mean 32.6 +/- 2.4). The outcome after regular in vitro fertilization was similar. No major malformations were observed. CONCLUSIONS: The results of this study showed that the incidence of multiple pregnancies after intracytoplasmic sperm injection was similar to that after standard, conventional in vitro fertilization. The perinatal outcome did not differ between both groups.

Adult

The best donor.

Oocyte donation has become a common treatment modality for a large spectrum of infertility conditions. The purpose of this study was to assess the success rate of a shared egg donation programme, and to define the profile of a successful 'donor-recipient' couple in view of the limitations imposed by the shared programme. The results of all consecutive cycles of egg donation from 1st January 1995 to 31st December 1996 were analysed. A total of 383 donor cycles were matched with 946 recipient cycles; clinical pregnancy rates were 23. 5 and 16.7% respectively. With the exception of endometriosis, which significantly reduced the pregnancy rate in both groups, similar pregnancy rates were obtained in both groups for all the other infertility aetiologies of the donors. The donor's age had no impact on pregnancy rate of the recipient, but pregnancy rate was significantly decreased in donors >35 years. Recipients >50 years had significantly reduced pregnancy rates and those >45 years a significantly increased abortion rate. Recipients with severe male factor infertility, who had intracytoplasmic sperm injection treatment, showed pregnancy rates equivalent to those recipients who had regular in-vitro fertilization. We conclude that in a shared egg donation programme, the recipients' pregnancy rate and outcome are dependent only on the donors' infertility aetiologies and on recipients' ages.

Adolescent

In-vitro fertilization treatment for severe male factor: the fertilization potential of immotile spermatozoa obtained by testicular extraction.

A retrospective analysis in 50 couples of 53 cycles of intracytoplasmic sperm injection (ICSI) with immotile spermatozoa from testicular-retrieved spermatozoa was performed to evaluate whether total immotile spermatozoa achieved after testicular sperm extraction could fertilize ova and result in pregnancies. We assessed the efficacy of ICSI with totally immotile testicular spermatozoa extracted from the testes of azoospermic patients with severe spermatogenic failure (group 1) and compared these results with those from spermatozoa which were recovered after several hours of incubation and were motile (group 2) at the time of injection. In 19 cycles, only totally immotile spermatozoa were injected at the time of ICSI. For the remaining 34 cycles, at least one motile spermatozoon was found for injection. The oocyte fertilization rates were 51% for group 1 and 62% for group 2 (P < 0.02). Eighteen of 19 cycles in group 1 (90%) and all 34 (100%) cycles in group 2 had embryos for replacement. The mean number of embryos per cycle was 5.2 +/- 0.8 and 7.5 +/- 0.9 in groups 1 and 2 respectively; this and the embryo quality (cumulative embryo scoring = 40 +/- 8 for group 1 and 50 +/- 7 for group 2), and clinical pregnancy rates (15.8% per oocyte retrieval in group 1 and 23.5% in group 2) were not significantly different between groups. Fertilization, cleavage and pregnancy can be achieved with intracytoplasmic testicular sperm injection from patients with immotile spermatozoa, at levels comparable with those of ICSI using motile spermatozoa.

Adult

Tracheostomy for ventilator dependence in the elderly patient: a preliminary report.

With advances in medical technology and increasing numbers of elderly patients surviving acute intensive care unit admissions, otolaryngologic consultation regarding tracheostomy for ventilator-dependent patients is expected to continue increasing. However, established treatment guidelines and defined outcomes in terms of health status, quality of life, and medical costs are lacking in this emotionally delicate setting. A retrospective case review of the outcomes of 19 elderly patients who underwent tracheostomy for ventilator dependence revealed that 14 had died within 40 days of surgery. The high number of deaths--which were caused by multiple organ failure, sepsis, and/or cardiopulmonary arrest--so soon after tracheostomy demands the implementation of outcomes research. In this article, we introduce outcomes analysis as a means of assessing the utility of tracheostomy for ventilator dependence in the elderly and to advocate the establishment of a multidisciplinary palliative-care unit for this group of patients.

Aged

Outcome of in vitro fertilization and intracytoplasmic injection of epididymal and testicular sperm extracted from patients with obstructive and nonobstructive azoospermia.

OBJECTIVE: To evaluate IVF outcome after epididymal and testicular sperm retrieval in patients with obstructive or nonobstructive azoospermia. DESIGN: Retrospective clinical analysis. SETTING: Public university-affiliated IVF unit. PATIENT(S): One hundred twenty-three azoospermic patients (178 cycles). INTERVENTION(S): Sixty-three patients (103 cycles) with obstructive azoospermia (group 1) underwent either epididymal or testicular sperm retrieval, and 60 patients (75 cycles) with nonobstructive azoospermia (group 2) underwent testicular sperm retrieval combined with IVF treatment. Mature oocytes were fertilized using intracytoplasmic sperm injection. After sperm preparation, supernumerary spermatozoa were cryopreserved. MAIN OUTCOME MEASURE(S): Oocyte fertilization rate and clinical pregnancy rate (PR). RESULT(S): The oocyte fertilization rate was 48.4% (534/1,104) in group 1 and 41.5% (312/751) in group 2 (not significant [NS] difference). A total of 100 cycles (97.1%) and 62 cycles (82.7%) in the obstructive and nonobstructive groups, respectively, had embryos for replacement (NS difference). The clinical PRs per ET cycle were 24% (24/100) and 17.7% (11/62) in the two groups, respectively. Oocyte fertilization rates, when fresh (46.4%) or frozen-thawed (41.8%) spermatozoa were used, were not significantly different in the two groups. The PR when fresh sperm were used was 23.6% (30/127), versus 14.3% (5/35) when frozen sperm were used (NS difference). The PR for women aged < or = 35 years was similar to that for women >35 years of age (20.7% or 29/140 and 18.2% or 4/25, respectively). CONCLUSION(S): Epididymal and testicular sperm obtained in azoospermic patients can fertilize oocytes successfully and may lead to high fertilization rates and PRs. Freezing of these spermatozoa does not reduce the outcome of treatment significantly.

Adult

In vitro fertilization treatment for severe male factor: a comparative study of intracytoplasmic sperm injection with testicular sperm extraction and with spermatozoa from ejaculate.

PURPOSE: Our purpose was to evaluate whether the source of spermatozoa influences the results of intracytoplasmic sperm injection (ICSI) treatment in couples with severe male-factor infertility. METHODS: A retrospective analysis of 40 cases of ICSI with testicular-retrieved spermatozoa, matched with 40 cases of ICSI with ejaculated spermatozoa, was performed. We included only couples with normoovulatory females younger than 37 years who were matched according to the day of ovum pickup with the patients in the study group. RESULTS: Eighty cycles were analyzed: 40 cycles using testicular spermatozoa and 40 cycles using ejaculated spermatozoa. In 32 (80%) of the 40 ICSI transcutaneous needle aspiration cycles, we obtained enough spermatozoa to inject all the mature oocytes retrieved. In eight (20%) cases there were not enough spermatozoa to inject all the oocytes. Only 76 (54%) of 141 available oocytes were injected in these eight patients. The oocyte fertilization rates were 42% for the study group and 55.5% for the controls (P < 0.005). Thirty-six (90%) patients in the group with nonobstructive a zoospermia (NOA) and 37 (92.5%) patients in the oligoteratoasthenospermia (OTA) group had embryos for replacement. The mean cleavage rates per cycle (96% with testicular and 93% with ejaculated spermatozoa), the mean number of embryos per transfer (3.72 +/- 1.6 in the NOA group and 4.24 +/- 1.5 in the OTA group), the embryo quality (cumulative embryo scoring = 34.03 +/- 22.62 in the testicular sperm group and 36.08 +/- 19.28 in the ejaculated sperm group), and the clinical pregnancy rates (22.5% in the NOA patients and 20% in the ejaculate group) were not significantly different between groups. CONCLUSIONS: High fertilization, cleavage, and pregnancy rates can be achieved with intracytoplasmic testicular sperm injection from patients with NOA, reaching levels comparable with those of ICSI using ejaculated spermatozoa.

Adult

Sperm motility is a major determinant of pregnancy outcome following intrauterine insemination.

PURPOSE: Our purpose was to assess whether one or more sperm parameters have predictive value for the outcome of intrauterine insemination treatment. METHODS: Infertile couples whose normoovulatory and normomechanical female partners underwent superovulation and intrauterine insemination were investigated. The semen profile of the male partner was discounted. In 160 couples, 544 cycles were obtained, resulting in 59 ongoing pregnancies (10.84%/cycle, 36.87%/patient). RESULTS: The only parameter found to be significantly correlated with a positive outcome was the degree of sperm motility following preparation for intrauterine insemination. Close to half (47.5%) of the couples with a very good or an excellent degree of sperm motility conceived, whereas only 8.3% of those patients who had poor or fair sperm motility conceived. None of the semen characteristics, such as volume, count, percentage motility, or percentage normal morphology, were found to correlate with cycle outcome. Although there was a progressive increase in the pregnancy rate with an increase in the total number of motile sperm inseminated, it did not reach significance. Seventy percent of the pregnancies were achieved within a maximum of three treatment cycles. The spermatogram is not accurate enough as a prognostic factor for treatment outcome. CONCLUSIONS: The degree of sperm motility, after appropriate preparation for intrauterine insemination, is the only parameter to be correlated with treatment outcome. For couples with a normal female partner, we suggest a maximum of three treatment cycles of induction of ovulation and intrauterine insemination, whenever good progressive motile sperm is obtained after suitable preparation. For cases with poor sperm progression, we suggest appropriate couple counseling and that an alternative assisted reproduction procedure be taken into consideration.

Adult

The outcome of in-vitro fertilization treatment by egg donation and intracytoplasmatic sperm injection for severe male factor infertility: a preliminary report.

Due to a paucity of donated eggs, we have excluded, until recently, couples with severe male factor infertility from our egg donation programme, except for those who accepted insemination with donor spermatozoa. The purpose of this study was to assess the feasibility of a shared in-vitro fertilization (IVF)-embryo transfer treatment whenever the recipients have severe oligoasthenoteratozoospermia (OTA) and need intracytoplasmic sperm injection (ICSI) for egg fertilization. The results from 163 consecutive couples with ovarian failure who underwent 273 cycles of IVF with donated eggs and augmented with ICSI were analysed. The rate of diploid fertilization was 54.7%; in 92.3% of the cycles, at least one embryo was available for transfer. Forty-seven clinical pregnancies were achieved, representing 18.6% conceptions per transfer. The highest pregnancy rate was achieved in menopausal patients aged 40-45 years (26.2% per cycle) and the lowest in patients >45 years old (10.8% per cycle, P = 0.03). Overall, 28.8% of the couples achieved a clinical pregnancy. A total of 196 treatment cycles resulted in 46 clinical pregnancies (23.5%) among the donors. No statistical differences were found in pregnancy rate achieved by the donors when compared with the recipients. We conclude that ICSI with egg donation is a reliable treatment in patients with ovarian failure and severe OTA.

Adult

Difficult or repeated sequential embryo transfers do not adversely affect in-vitro fertilization pregnancy rates or outcome.

In order to assist the medical team in the decision-making process and in adequate counselling of patients when encountering technical difficulties at the time of embryo transfer, we investigated the effect of difficult embryo transfer, with or without the need for cervical dilatation or repeated sequential attempts because of retained embryos in the catheter system, on in-vitro fertilization (IVF) pregnancy rates and outcome. A total of 854 consecutive embryo transfer procedures were prospectively categorized as (i) easy (smooth, unforced), (ii) difficult (requiring uterine manipulation or increased force or cervical grasping and/or accompanied by trauma), (iii) requiring cervical dilatation, or (iv) multiple (two or three) sequential attempts because of embryos retained in the catheter system. Embryo transfer was easy in 734 cases (85.9%). It was difficult in 72 (8.4%), cervical dilatation was required in 21 (2.5%), and one or two repeated attempts were needed in 27 cases (3.2%). Pregnancy rates for the different categories of embryo transfer were 23.3, 23.6, 23.8 and 29.6% respectively. There were no significant differences in the percentage of the ongoing/delivered pregnancies for the different categories of embryo transfer (69, 64.6, 60 and 62.5% respectively). There were no significant differences in the distribution of embryo transfer types among the six infertility specialists who performed the procedures. To conclude, embryo transfers that are difficult to perform or that require cervical dilatation or repeated attempts do not adversely affect pregnancy rates and outcome following IVF. Cervical dilatation, if needed for patients with cervical stenosis, should be performed at the time of the embryo transfer and not earlier. Surgical transmyometrial embryo transfer or rescheduling patients for delayed embryo transfer could be avoided in most patients. This information is important for patient management and counselling in cases of embryo transfer that are not easy to perform.

Decision Making

Renal reabsorption of inorganic phosphorus in pregnancy in relation to the calciotropic hormones.

OBJECTIVE: To measure renal reabsorption of inorganic phosphorus and the calciotropic hormones in early and late pregnancy. DESIGN: Prospective, cross-sectional study. SETTING: Endocrine Institute at Assaf Harofeh and E. Wolfson Medical Centers; the Department of Obstetrics and Gynaecology, Sheba Medical Centre and Tel Aviv University. POPULATION: Three groups of healthy women were studied: pregnant women at the end of the first trimester (n = 20), pregnant women at the end of the third, trimester (n = 22), and nonpregnant controls (n = 27). METHODS AND MAIN OUTCOME MEASURES: The renal tubular maximal phosphorus reabsorption per decilitre of glomerular filtrate (TmP/GFR) was measured in all women. Circulating levels of intact parathyroid hormone, calcitriol (1,25-dihydroxy vitamin D3) and insulin-like growth factor I were assayed in part of the women (8-11 of each group). RESULTS: TmP/GFR was elevated in the first trimester group (mean 0.263 mmol/L) compared with controls (95% CI 0.07-0.46, P = 0.003). Third trimester values did not differ from controls. Serum calcitriol in the first trimester group was higher (mean difference 17.68 pg/mL) compared with controls (95% CI 3.89-31.47, P = 0.006) and was higher still (mean difference 20.75 pg/mL) in the third trimester group (95% CI 1.01-40.49, P = 0.042). Serum parathyroid hormone in the first trimester group was lower than in controls or the third trimester group: mean differences were 4.40 pg/mL (95% CI-1.40 to 10.15, P = 0.078) and 8.18 pg/mL (95% CI 0.51-15.85, P = 0.019) respectively. Parathyroid hormone levels correlated negatively to calcitriol levels in the combined control and first trimester groups (r = -0.54, P = 0.022) and negatively to TmP/GFR values in the combined three groups (r = -0.68, P = 0.042). First trimester levels of insulin-like growth factor I were lower than those in controls or in the third trimester: mean differences were 10.24 nmol/L (95% CI 2.05-18.43, P = 0.007) and 13.57 nmol/L (95% CI 4.23-22.91, P = 0.003), respectively. CONCLUSIONS: The dominant change in mineral metabolism in pregnancy is a rise in calcitriol which most probably is responsible for the relative suppression of parathyroid hormone and thereby for the rise in TmP/GFR in early pregnancy. All the above support the transfer of minerals to the fetus without compromising maternal bone. The significance of circulating insulin-like growth factor I remains unclear.

Adult

Calcium channel blocking drugs in the management of drug dependence, withdrawal and craving. A clinical pilot study with nifedipine and verapamil.

OBJECTIVE: To determine if the calcium channel blocking agents (CCBs), nifedipine and verapamil are safe and effective therapeutic adjuncts in the management of withdrawal and craving in patients with chronic dependence on opiates, ethanol, amphetamine, benzodiazepines and marijuana. METHOD: Oral rapid acting nifedipine or verapamil was administered for 2 weeks (together with oral methadone in decreasing daily doses and specific symptomatic treatment, if appropriate), to patients with chronic dependence on various drugs of addiction. Several objective and subjective parameters were quantified to provide information about the patient's basic condition and progressive response to treatment, both before and after each CCB treatment. Patients also completed a daily questionnaire concerning their withdrawal intensity and provided a daily urine analysis. RESULTS: Both nifedipine and verapamil appeared to be safe and effective therapeutic adjuncts in the management of withdrawal and craving in 24 patients who successfully completed the trial. Although comparable in therapeutic efficacy in the doses used, verapamil produced far fewer and milder side effects than nifedipine. None of the verapamil side effects resulted in suspension or termination of treatment and it was the preferred agent, especially in patients presenting with a low blood pressure. CONCLUSIONS: In this pilot study nifedipine and verapamil appeared to be effective for the in-patient management of withdrawal and craving in a broad spectrum of chronic drug addicts. Verapamil produced fewer disturbing side effects compared with nifedipine and it may prove a safe, non-addicting and rational treatment in the long term management of chronic dependence, withdrawal and craving. As such, it may be especially valuable in offering the motivated chronic addict help and hope for the long term management of this problem in a community setting. The present results warrant the establishment of a verapamil based, double-blind, drug-matched or placebo-controlled clinical trial to test the validity and significance of these preliminary findings.

Adult

The role of a human chorionic gonadotropin burst in in vitro fertilization.

FINDINGS: No oocytes were found during four ovum pickups (OPU), despite a satisfactory ovarian response to controlled ovarian hyperstimulation. After the first attempt failed in the fourth case, five eggs were retrieved, fertilized, and cleaved after cycle rescue with hCG. CONCLUSIONS: Whenever oocytes are not aspirated during OPU due to a lack of hCG administration, the cycle may be rescued if 10,000 IU of hCG is injected immediately and OPU planned for 33-36 hr later.

Adult

Induction of artificial endometrial cycles with s.c. oestrogen implants and injectable progesterone in in-vitro fertilization treatment with donated oocytes: a preliminary report.

Endometrial preparation for embryo implantation in oocyte recipients with retained ovarian function presents a special problem. In all, 10 women with preserved ovarian function received donated oocytes in an in-vitro fertilization programme. In the preparatory cycles with oral oestrogens, all failed to develop adequate secretory endometrium because of ill-timed early luteinization occurring during the proliferative phase of the cycle. Subsequently the patients were treated with s.c. 17-beta oestradiol implants and injectable progesterone. The implants successfully induced complete down-regulation of the hypothalamus, pituitary axis, and prevented luteinizing hormone (LH) surge. In these preparatory cycles, all the treated patients produced adequate secretory endometrium. Clinical trials of 27 oocyte donation cycles yielded one biochemical and eight clinical pregnancies.

Adult

The significance of an early (premature) rise of plasma progesterone in in vitro fertilization cycles induced by a "long protocol" of gonadotropin releasing hormone analogue and human menopausal gonadotropins.

OBJECTIVE: Our purpose was to assess and clarify the mechanism of whether an early progesterone rise in cycles with gonadotropin-releasing hormone agonist (GnRH-a) is associated with an impairment of IVF outcome. METHODS: Seven hundred eighty-six cycles were induced with GnRH-a and human menopausal gonodotropin (hMG) ("long protocol"). Plasma progesterone (PP) levels on the day of human chorionic gonadotropin (hCG) administration were divided into three groups: < 0.9 ng/ml (Group A), 1-2 ng/ml (Group B), and > 2 ng/ml (Group C). We also analyzed the pregnancies achieved in our egg donation protocol in relation to the PP levels of each donor on the day of hCG administration. RESULTS: Group A involved 525 cycles, Group B had 223, and Group C had 38. The overall pregnancy rate per egg transfer was 19.2%, with the highest for Group A (22.3%), declining for Groups B (14.3%) and C (7.9%) (A = B = C; P < 0.005). The embryo implantation rate was found to be negatively correlated with the PP levels on the day of hCG administration. In contrast, there was an opposite trend between PP levels and the chance of conception in 30 pregnancies achieved by egg donation. CONCLUSION: Since premature luteinization is very unlikely to occur under the conditions of this study, our findings suggest that an early PP rise has a negative impact on endometrial receptivity but not on egg and embryo quality.

Adult

Sonographic assessment of cervical changes during pregnancy and delivery: current concepts.

Correct detection of premature contractions and incompetent uterine cervix is still a challenging obstetrical problem since these factors remain a major cause of perinatal loss. Ultrasonography offers additional important data for the prediction of these pathologies which have common sonographic patterns; shortening of the cervical length, funneling of the membranes and dilatation of the endocervical canal. The first section of this review highlights sonography of normal cervical anatomy, while the second section focuses on recent advances in sonographic detection of premature contractions and incompetent cervix. It is believed that due to its accuracy and reproducibility, this noninvasive technique should become more integrated into this aspect of antenatal care.

Cervix Uteri