Biomedical subjects
Publications and source records attributed to N Laufer.
A 68-yr-old female developed an acute embolic cerebrovascular event during a coronary bypass graft angioplasty. The patient was treated with microcatheter-directed, intra-arterial thrombolysis. The technique and a review of the literature for thrombolysis in cerebrovascular ischemic events are included.
PURPOSE: Our purpose was to compare the success rate of transferring frozen-thawed embryos generated from either intracytoplasmic sperm injection (ICSI) or conventional in vitro fertilization (IVF). METHODS: A retrospective review of all frozen-thawed embryo transfer (ET) cycles between January 1995 and April 1997 was performed. There were 83 and 204 transfer cycles of frozen-thawed multicellular embryos generated from conventional IVF (group A) and ICSI (group B), respectively. The survival rate of frozen-thawed embryos and the outcome following ET in both groups were assessed. RESULTS: The groups did not differ in age (31.7 +/- 4.6 and 30.6 +/- 6.0; mean +/- SD) or number of embryos transferred (3.5 +/- 1.1 and 3.8 +/- 1.3 for groups A and B, respectively). An acceptable pregnancy rate per ET was achieved in both groups, but the rate was significantly higher (P = 0.04) for group A than group B, 32.5 and 20%, respectively. Group A included frozen embryos of a higher quality than those of group B, but the proportion of embryos surviving after thawing was significantly higher for group B than group A (92.5 and 85.6%, respectively; P = 0.0004). The abortion rate did not differ between the two groups: 22 and 26.8% for groups A and B, respectively. CONCLUSIONS: Although an overall high pregnancy rate was achieved following frozen-thawed ET, it was lower for cycles in which embryos had been generated from ICSI. This difference may be attributed to a lower prefreezing embryo quality in the ICSI group. Embryos originating from ICSI were not vulnerable to cryopreservation and, when implanted, resulted in a comparable abortion rate to thawed embryos of conventional IVF.
OBJECTIVE(S): To correlate fertilization and clinical pregnancy rates (PRs) in low responders with their E2 levels (<500, 500-800, >800-1,000 pg/mL), age (20-30, 31-40, >40 years), number of follicles, and number of oocytes retrieved. DESIGN: A retrospective study. SETTING: The IVF unit of an academic hospital. PATIENT(S): One hundred forty-three women who failed to attain E2 levels of 1,000 pg/mL on the day of hCG administration. INTERVENTION(S): Controlled ovarian hyperstimulation, blood E2 and progesterone measurements, ultrasonographic scanning of ovarian follicles, oocyte retrieval after hCG administration, and ET. MAIN OUTCOME MEASURE: Clinical PR. RESULT(S): Although E2 levels, fertilization rates, age, and number of oocytes did not differ significantly between the three age groups, the PR achieved in the youngest group was approximately three times as high (19.3%) as that achieved in the two older groups. CONCLUSION: Young low responders represent a unique subset in that their age protects them from the deleterious effects of poor ovarian response.
PURPOSE: Our purpose was to review the available literature concerning the pathogenesis of ovarian hyperstimulation syndrome and, in light of the most recent information, to attempt to provide further insight on this iatrogenic complication associated with the induction of ovulation. METHODS: Published studies related to this topic were identified through a computerized bibliographic search. CONCLUSIONS: The exact mechanism for the development of ovarian hyperstimulation syndrome is still obscure. It is well established that the syndrome is associated with the process of ovulation induced by either luteinizing hormone or human chorionic gonadotropin. Following ovulation, one or more substances produced by the ovary are liberated in excess, increasing capillary permeability, resulting in the clinical features of the syndrome. It may well be that the syndrome is not triggered by a single mechanism but by the production and secretion of several substances acting in concert. These may include prostaglandins, cytokines, the ovarian reninangiotensin system, vascular endothelial growth factor, and nitric oxide.
Transfer of frozen-thawed embryos is usually carried out in a natural cycle or in a programmed cycle in which the endometrium is exogenously stimulated following down-regulation of the hypophysis. To analyse the possibility that the programmed cycle for embryo transfer can still be hormonally manipulated without the use of gonadotrophin-releasing hormone agonist (GnRHa) we have conducted a prospective randomized study that compared the outcome of frozen-thawed embryo transfer cycles using micronized 17beta-oestradiol and micronized progesterone preparations with and without the concomitant use of GnRHa. One hundred and six patients were randomly divided into two groups. In group A (53 patients) 4 mg/day of micronized 17beta-oestradiol was initiated following down-regulation of hypophysis. In group B (53 patients) oestrogen stimulation started on day 1 of the cycle without prior pituitary down-regulation using a dose of 6 mg/day for 7 days. In both groups, micronized progesterone in a dose of 900 mg/day was administered vaginally after at least 12 days of oestrogen stimulation. Embryo transfer embryo transfer took place 48-72 h thereafter according to the cryopreserved embryonic stage. Overall, none of the patients had any follicular development and only one cycle in group B had to be cancelled because of premature progesterone secretion. The two groups did not differ in age (31+/-5.6 and 31+/-5.0 years), number of embryos transferred per patient (3.4+/-1.2 and 3.3+/-1.0), and day of progesterone initiation (15+/-2.2 and 15+/-1.9 for groups A and B respectively). The endometrial thickness on the day of progesterone initiation was comparable in both groups (11 +/-1.6 and 10+/-1.6 mm for groups A and B respectively). Similarly, the pregnancy rate per embryo transfer and implantation rate in group A (26.4% and 9.5%) were comparable to those of group B (21.1% and 9%). These results indicate that programmed cycles can be successfully applied by administering a high dose of micronized 17beta-oestradiol starting on day 1 of the cycle. Compared to GnRHa programmed cycles, this approach is simpler, more convenient for both the patient and medical staff, and results in a similar success rate at a lower cost.
Psychiatric morbidity is common in primary care, a large proportion being treated without specialist referral. A significant proportion may be undetected or inadequately treated. This article describes current models of mental health services (MHS) working at the interface between primary care and MHS with review of data regarding these models and discussion of the application of these models to the Israeli health system. The shifted out-patient model, primarily provided by psychiatrists independent of the Primary and Secondary Care Teams, would seem to increase access to psychiatric services, increase treated prevalence of the disorders and attract a similar population to hospital out-patient services. The psychiatric community liaison model aims to improve primary care practitioner detection and management skills, might reduce referrals to psychiatrists with similar patient outcome and enables treatment of patients unwilling to see a mental health professional (MHP). The attached MHP Model would allow access to a greater range of psychosocial interventions provided by a primary care team member. The community mental health team, currently a model not in practise in Israel, provides a single point of referral for multidisciplinary care but has shown varying patterns of integration and responsiveness to primary care. Other interfaces of collaboration such as Balint groups and education are also discussed.
The objective of this study was to examine the effect of interleukin-1 beta (IL-1) on progesterone (P) biosynthesis and the potential intermediary involvement of prostaglandin (PG) E and nitric oxide (NO) in P accumulation in PMSG/hCG-primed rat corpora luteal (CL) cell cultures. Exposure of primed CL cells to IL-1 (10 ng/ml) for 48 h resulted in a 65-86% reduction (P < 0.01) in P accumulation concurrent with a 2-3.4-fold increase in PGE content, a 70% increase in PGF2 alpha content and a 1.9-3.3-fold increase in nitrite generation. These effects were abolished by the IL-1 receptor antagonist, suggesting specific IL-1 receptor-mediated effects. Indomethacin, a cyclooxygenase inhibitor, abolished PGE and PGF2 alpha production and attenuated the basal (but not IL-1-stimulated) accumulation of P. N(G)-Nitro-L-arginine (NNLA), a competitive inhibitor of nitrite synthesis, slightly reduced basal P accumulation but had no effect on IL-1-induced suppression of P accumulation. NNLA reduced basal PGE accumulation and IL-1-stimulated PGE accumulation (55 and 61%, respectively). Transforming growth factor beta 1 (TGF-beta 1; 10 ng/ml) significantly attenuated the IL-1-stimulated PGE and NO production (61 and 42%, respectively), but did not affect the ability of IL-1 to suppress P accumulation. Thus, NO, PGF2 alpha and PGE are not obligatory intermediaries of IL-1-mediated suppression of P accumulation in rat CL, but are involved in basal P biosynthesis and NO seems to have a regulatory role in the biosynthesis of PGE. The present observations suggest a pleiotropic response of PMSG/hCG-primed CL cells to IL-1, characterized by an independent suppression of P accumulation and a concomitant increase in NO, PGF2 alpha and PGE generation. Since IL-1 attenuates P accumulation, these findings may imply a direct autocrine/paracrine function for IL-1 in the maintenance or the demise of rat CL.
Reaction time and idiosyncrasy of word associations were examined in 30 schizophrenic patients, 2 h after administering a single dose of chlorpromazine, perphenazine or placebo. These patients were in the acute phase of their illness following 72 h cessation of oral neuroleptic treatment administered for 1-2 weeks. There was a statistically significant reduction in reaction times after administering perphenazine as compared to the placebo. Chlorpromazine showed some reduction in reaction times that was not statistically significant. Further study is needed to examine the relationship between such changes and other parameters, such as the patients' symptomatology and their social competence. Since many schizophrenic patients exhibit low or partial compliance, including patterns of intermittent taking of medication with a few days cessation, studies using such a model of a single dose of neuroleptic following several days withdrawal, may have clinical relevance. Another finding was a correlation between reaction time and the number of uncommon word associations produced. This correlation was beyond drug effect. Further study is needed to find out if such a correlation characterizes schizophrenic patients only.
PURPOSE: Our purpose was to study the unusual and rare late manifestation of severe pelvic abscess, following oocyte pickup (OPU), for in vitro fertilization and embryo transfer (IVF-ET). PATIENTS: The patients were three infertile women with stage IV endometriosis and ovarian endometriomata, as the sole reason for their infertility. Medical and surgical modalities to treat endometriosis and infertility proved to be unsuccessful. INTERVENTIONS: All patients were prepared for IVF-ET employing a long GnRH-a and hMG protocol. Transvaginal OPU was performed under ultrasound guidance. Intravenous (i.v.) prophylactic antibiotic was routinely administered. RESULTS: All women underwent ET, and one conceived. Forty, 24, and 22 days after OPU, respectively, these patients presented with acute symptoms of severe pelvic inflammatory disease (PID) and were found to have pelvic abscess. Broad-spectrum i.v. antibiotics were employed in all cases, however, two patients did not respond and bilateral adnexectomy was eventually performed. CONCLUSIONS: Severe endometriosis with ovarian endometriomata seems to be a significant risk factor for pelvic abscess development, following transvaginal OPU for IVF-ET. Prophylactic IV cefazolin does not seem to prevent this complication. Late manifestation of pelvic abscess supports the notion that the presence of old blood in an endometrioma provides a culture medium for bacteria to grow slowly after transvaginal inoculation.
OBJECTIVE: To determine the reproducibility of hysterosalpingogram (HSG) interpretation and clinical management recommendations among trained observers. DESIGN: Fifty HSG films were distributed to five fertility practitioners with a mean of 20 years clinical experience. Each observer evaluated components of uterine and tubal status and provided clinical recommendations for hysteroscopy and laparoscopy. SETTING: University hospital-affiliated reproductive endocrine practice. INTERVENTION(S): None MAIN OUTCOME MEASURE(s): The level of agreement among observers for each uterine and tubal category as determined by the kappa(kappa) statistic. Determinants of clinical recommendation for further diagnostic studies were assessed. RESULT(S): The level of agreement between observers as determined by kappa ranged from 0.645 in the hydrosalpinx category, indicating fair reliability, to 0.111 for pelvic adhesions, indicating poor reliability. The composite kappa for uterine status was 0.345 whereas the composite kappa for tubal status was 0.430. Agreement among observers concerning management showed marginal reproducibility with a kappa of 0.261. Overall, more than one abnormality of either the cavity or the fallopian tubes led to a diagnostic recommendation for further workup in > or = 90% of cases. CONCLUSION(S): In a group of five experienced clinicians, there was considerable variability in the interpretation as well as the clinical management of the HSG. Physicians caring for infertile couples should be aware of this discrepancy and should, if possible, review carefully both the original films as well as the report of the attending radiologist in formulating their diagnostic evaluation and management plan.
To examine the participation of the theca-interstitial (TI) compartment in cytokine modulation of ovarian function, the effects of interleukin-1beta (IL-1) on plasminogen activator (PA) activity and on prostaglandin E (PGE) and nitric oxide (NO) production were examined in cultures of pregnant mare serum gonadotrophin (PMSG)-primed rat TI cells. Exposure to IL-1 (10 ng/ml) resulted in a 25% reduction (P < 0.001) in PA activity, concurrent with a 4.6-fold increase in the ability of the corresponding conditioned media to inhibit exogenous urokinase activity. IL-1 also produced a 4.7-fold increase in PGE content and a 2.8-fold increase in NO generation. These effects of IL-1 were abolished by the IL-1 receptor antagonist, suggesting specific IL-1 receptor-mediated effects. Transforming growth factor (TGF)-beta1 (10 ng/ml) significantly attenuated the IL-1-stimulated PGE production and NO generation but did not affect the ability of IL-1 to suppress PA activity and stimulate urokinase inhibitor production. The NO synthase inhibitor N-nitro-L-arginine attenuated the IL-1-induced NO generation but had no effect on PA activity or PGE production. Thus, NO is not an obligatory mediator of IL-1 effects on plasminogen activation and PGE generation in rat ovary. The present observations attest to a pleiotropic response of PMSG-primed TI cells to IL-1, and suggest a paracrine/autocrine function for the TI compartment in ovulation and corpus luteum formation.
In vitro fertilization imposes an emotional and financial burden on infertile couples and has a relatively low success rate, but it offers their only means of conception. As uteroovarian perfusion varies during the menstrual cycle and may be related to uterine receptivity, we sought to identify hemodynamic parameters that would be of use in monitoring stimulated cycles and in making decisions about the timing of in vitro fertilization. Uteroovarian perfusion patterns in patients undergoing ovulation induction and embryo transfer were compared with normally cycling volunteers. Significant changes in ovarian perfusion were seen with suppression and stimulation. Despite manipulation, no difference in uterine perfusion was seen between the groups in the late luteal phase, the crucial time of implantation. We conclude that Doppler ultrasonography may be useful in monitoring artificial cycles and in predicting uterine receptivity.
Attempted suicide in adolescence is a major health problem and recent reports indicate a dramatic increase in the frequency of attempted and completed suicide among adolescents. The aim of this study was to evaluate the characteristics of adolescent admissions with attempted suicide in a large general hospital. The files of all children and adolescents admitted due to a suicide attempt between the years 1984 and 1994 were examined retrospectively, with regard to age, sex, method of attempt, season, year and length of hospitalization. Four hundred and four admissions with attempted suicide were recorded. The majority (83.7%) were females and drug overdose was the most common (92.8%) method used. Thirty patients (7.5%) repeated the attempt during the study period. No specific time of the year was associated with an increase in adolescent suicide attempt admissions. The most remarkable finding was that younger adolescents had a higher probability of performing a violent suicide attempt. Hypotheses for these trends are examined together with possible ramifications for treatment provision.
STUDY OBJECTIVES: To determine alfentanil levels with a specific radioimmunoassay in serum and ovarian follicular fluid. DESIGN: Observational study. SETTING: University hospital. PATIENTS: 14 ASA status I women undergoing oocyte retrieval for in vitro fertilization. INTERVENTIONS: General anesthesia was induced with alfentanil 15 micrograms/kg and midazolam 2 mg and maintained with alfentanil 0.5 mg, 60% nitrous oxide (N2O) in oxygen (O2) and midazolam up to a total of 4 mg. Oocyte retrieval was performed using a transvaginal ultrasound guided technique, 34 to 36 hours after human chorionic gonadotrophin administration. MEASUREMENTS AND MAIN RESULTS: Mean procedure time for oocyte retrieval was 18 +/- 2.4 (SEM) minutes. All patients were fully awake within 5 minutes and all patients except one were able to move from the operating table to the stretcher with minimal help. Mean total protein concentration in the follicular fluid was 3.8 +/- 0.4 mg%. Maximal serum alfentanil concentrations (Cmax) were attained 5 minutes after start of the procedure (tmax) and were 92 +/- 20 ng/ml. In contrast, alfentanil concentrations in the follicular fluid increased constantly throughout the procedure up to 8.9 +/- 0.8 ng/ml at 15 minutes. Clinical pregnancy rate was 3 of 14 patients. CONCLUSION: It is evident that during the oocyte retrieval procedure, the alfentanil concentrations in the follicular fluid are about ten-fold smaller than the serum alfentanil concentrations at the same time points. Similar pharmacokinetics have been shown when propofol was used as anesthetic. The low accumulation of alfentanil in the follicular fluid increases the attractiveness of alfentanil for anesthesia during oocyte retrieval for in vitro fertilization.
OBJECTIVE: An Rh-negative woman with preexisting anti-D antibodies may affect some or all subsequent fetuses, depending on the genotype of her Rh-positive partner. Currently, a reliable technique for an absolute determination of RhD genotype is not available. This study was initiated to develop an accurate method for RhD genotyping in men. STUDY DESIGN: RhD genotype was determined by deoxyribonucleic acid amplification of a D-specific sequence in single sperm cell samples. Micromanipulation techniques were used for sampling of single sperm cells, which were further amplified by multiplex nested polymerase chain reaction at the RhD locus. A RhD sequence amplification product was expected in all of the successfully amplified samples from Rh-positive homozygotes, in some of the samples from heterozygotes, and in none of the samples form Rh-negative subjects. RESULTS: RhD genotype was accurately determined in 10 of 10 donors. A total of 132 single sperm cells were analyzed (8 to 17 samples per donor), of which 96 were successfully amplified as assessed by an internal control. As expected, the specific region of the RhD gene was amplified in all, some, and none of the signal-positive sperm samples from Rh-positive homozygotes, heterozygotes, and Rh-negative subjects, respectively, allowing accurate determination of the genotype. CONCLUSION: An accurate diagnosis of the RhD genotype can be attained from single sperm cell analysis by means of polymerase chain reaction and may have major clinical applications in the management of Rh isoimmunization.
OBJECTIVE: To gain insight into the physiology of human endometrial development after artificial preparation with estrogen (E) and P, before oocyte donation. DESIGN: Review and analysis of relevant studies published in the last decade, identified through the literature and Medline searches. RESULTS: Oocyte donation represents a unique in vivo experimental model in the human that permits the study of endometrial development under controlled variable conditions. Early studies have shown that adequate endometrial preparation can be achieved by sequential E and P only. The successful implementation of the simplified approach to oocyte donation demonstrated that satisfactory endometrial receptivity is not dependent on incremental administration of E and P and similarly can be achieved by fixed dosages of these steroids. Moreover, numerous clinical oocyte donation studies have shown that both physiologic and supraphysiologic levels of E and P have resulted in good endometrial development and pregnancy rates, underlining the relative insensitivity of the endometrium to extreme hormonal conditions. In addition, it has been clarified that the endometrium is tolerant of some manipulations during the follicular phase. Contrary to morphological studies that demonstrated preservation of endometrial preparation after luteal E depletion, preliminary evidence suggests that the functional capacity of the endometrium could be affected adversely. CONCLUSION: In contrast to early oocyte donation studies, which indicated a correlation between morphologic integrity and functional capacity of the endometrium, some evidence presented in this review demonstrates that adequate endometrial morphology does not always imply normal endometrial receptivity.
A genetic assay by single blastomere analysis was developed for rhesus (RhD) blood group typing of early cleavage stage embryos. The method, which is based on the simultaneous amplification of an RhD-specific sequence and an internal control in single cells, was applied for the selective transfer of RhD-negative embryos in a family of an RhD sensitized woman and a heterozygote partner. The RhD status of two out of three biopsied embryos was determined. According to their amplified products, both were typed as RhD-negative and transferred to the uterus. Pregnancy was not achieved.
Nitric oxide (NO) has been suggested to be involved in ovarian physiology. Our aim was to study follicular nitrite and nitrate (NO3/NO2) levels in women undergoing in-vitro fertilization (IVF), and to examine their relationship to follicular size, oestradiol concentrations, and ovarian artery and intra-ovarian blood flow as measured by Doppler ultrasound. A total of 15 patients from the IVF programme of Hadassah University Hospital, Mt Scopus, Israel, participated in the study. Detailed transvaginal ultrasonographic examination was performed before ovum collection, and ovarian artery and intra-ovarian blood flow were measured. While aspirating the follicles, the content of two to four of the follicles in each ovary was collected individually, the volume of follicular fluid measured, and NO3/NO2 concentrations were determined. A statistically significant positive correlation was found between follicular fluid NO3/NO2 concentrations and follicular volume (r = 0.76), as well as between NO3/NO2 concentrations and oestradiol concentrations (r = 0.63). A statistically significant negative correlation was found between follicular fluid NO3/NO2 concentrations and ovarian flow parameters as well as between NO3/NO2 concentrations in follicles containing 4-5 ml and ovarian artery pulsatility index.