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Biomedical subjects

I Ben-Shlomo

Publications and source records attributed to I Ben-Shlomo.

At least 55 records · Page 3Linked to original sources

CA-125 is elevated in viable pregnancies destined to be miscarried: a prospective longitudinal study.

OBJECTIVE: To assess the predictive value of E2, hCG, CA-125, and morphometric parameters in early pregnancies with demonstrable fetal heartbeat, complicated by bleeding. DESIGN: Prospective longitudinal follow-up. SETTING: The emergency service of the Department of Obstetrics and Gynecology, "Rebecca Sieff" Hospital, Safed, Israel. PATIENTS: Twenty-five consecutive patients with vaginal bleeding during weeks 7 to 12 of pregnancy who had demonstrable fetal heartbeat. Ten women with normal pregnancies, serving as controls. MAIN OUTCOME MEASURE: The serum levels and the morphometric parameters were related to the outcome of pregnancy as revealed by future hospitalization, delivery, or telephone questioning. RESULTS: In the five patients who eventually aborted, the values of CA-125 were > 125 U/mL, whereas none of the successful pregnancies had a value > 93 U/mL. The mean values were 133 +/- 4.85 versus 36.95 +/- 23.1 U/mL for miscarriages and successful pregnancies, respectively. In normal pregnancies the respective value was 32.3 +/- 4.3 U/mL. Although mean E2 levels were lower in the serum of women who eventually aborted, there was a significant overlap of values with the successful pregnancies. All the other parameters measured had no correlation to the outcome of these pregnancies. CONCLUSION: CA-125 may serve as an accurate predictor of the outcome in early pregnancies with demonstrable fetal heartbeat, which are complicated by bleeding.

Abortion, Spontaneous↗

Cumulative pregnancy rate following in-vitro fertilization: the significance of age and infertility aetiology.

During the years 1984-1992, 951 couples completed 2252 in-vitro fertilization (IVF) treatment cycles at the In-Vitro Fertilization Unit of The Chaim Sheba Medical Centre. This study was conducted to evaluate the success of IVF using the cumulative pregnancy rate (CPR), with special emphasis on the optimal number of treatment cycles, the age of the patients and female infertility factors. It was found that the CPR showed a constant rise during the six initial IVF treatments (56% CPR), and plateaued in the subsequent three cycles (63% CPR). Various female infertility factors did not influence this rate. Women > or = 40 years of age have a significantly lower CPR. Thus, it was concluded that the CPR in IVF declined after the sixth initial treatment cycle, and in women > or = 40 years of age. The infertility factor did not significantly influence CPR.

Adult↗

Effect of bupivacaine-induced spinal block on the hypnotic requirement of propofol.

The hypnotic dose-response of propofol was compared with its combination with either bupivacaine-induced spinal block or intramuscular bupivacaine 12.5 mg in 105 men, divided into three groups of 35, undergoing lower abdominal, pelvic or lower limb surgery. Dose-response curves were determined for each group using bootstrap analysis. Bupivacaine-induced spinal block at the level of T8-T9 was found to reduce the ED50 of propofol by 39%. While this enhancement of hypnotic effect by spinal block is mostly attributable to reduced afferent input, differences in its potency between drugs suggest a role for additional factors.

Adult↗

A novel nonhepatic hydroxycholesterol 7 alpha-hydroxylase that is markedly stimulated by interleukin-1 beta. Characterization in the immature rat ovary.

During studies on the regulation of rat ovarian steroidogenic enzymes by interleukin-1 beta (IL-1 beta), we observed substantial metabolism of 25-hydroxycholesterol to two unusual polar products. This unexpected effect was observed both in isolated granulosa cells and in whole ovarian dispersates and was also induced by tumor necrosis factor alpha, but not by insulin-like growth factor I or follicle-stimulating hormone. The effect was dependent on time and the dose of IL-1 beta and was blocked by and IL-1 receptor antagonist. The formation of the polar metabolites was inhibited by ketoconazole and trilostane, but not by aminoglutethimide. Subsequent purification of these novel metabolites and analysis by gas chromatography/ mass spectrometry, NMR, and high performance liquid chromatography revealed them to be related 7 alpha-hydroxylated hydroxycholesterols (cholest-4-ene-7 alpha,25-diol-3-one and cholest-5-ene-3 beta,7 alpha,25-triol). IL-1 beta-stimulated ovarian 7 alpha-hydroxylase activity (3-10 pmol/min/mg of cellular protein) was nearly 4-fold that of control levels using 25-hydroxycholesterol as substrate. Activities at or below control levels were observed when IL-1 beta-treated cell sonicates were boiled or assayed in the presence of NADH (rather than NADPH), indicating that involvement of a nonenzymatic process was unlikely. IL-1 beta-stimulated 7 alpha-hydroxylase activity was inhibited to basal levels by a 10-fold excess of unlabeled 25- or 27-hydroxycholesterol, but not by cholesterol, pregnenolone, progesterone, testosterone, or dehydroepiandrosterone, suggesting that ovarian 7 alpha-hydroxylase is specific for hydroxycholesterols. Furthermore, when IL-1 beta-treated ovarian cultures were incubated with radiolabeled cholesterol or testosterone, no 7 alpha-hydroxylated products were observed. We were also unable to detect any mRNA transcripts for liver cholesterol 7 alpha-hydroxylase in IL-1 beta-stimulated ovarian cultures. This study describes an ovarian hydroxycholesterol 7 alpha-hydroxylase that differs from liver cholesterol 7 alpha-hydroxylase and from other nonhepatic progestin/ androgen 7 alpha-hydroxylases. The novel finding of the regulation of a 7 alpha-hydroxylase by IL-1 beta (and tumor necrosis factor alpha) suggests a unique role for cytokines in the regulation of cholesterol metabolism in the ovary and possibly other tissues.

Animals↗

The ovarian action of interleukin-1 is receptor mediated: reversal by a naturally occurring interleukin-1 receptor antagonist.

OBJECTIVE: To address indirectly the possibility that the ovarian action(s) of interleukin (IL)-1 are receptor mediated and to re-examine the recently reported proposition that the naturally occurring IL-1 receptor antagonist (IL-1ra) may in fact act in the capacity of mixed IL-1 receptor agonist/antagonist. DESIGN: In vitro treatment of isolated granulosa cell (GC) and whole ovarian dispersates of rat origin. RESULTS: Treatment of GC from immature rats with increasing concentrations of IL-1ra (10 to 5,000 ng/mL) proved without effect on either the basal or FSH (100 ng/mL)-supported accumulation of P. Likewise, cellular viability (as assessed by conversion of 3-[4,5-dimethylthiazol-2-yl]-2-5 diphenyltetrazolium bromide to spectrophotometrically detectable formazan) remained unaltered. However, the concomitant addition of increasing concentrations of IL-1ra (10 to 5,000 ng/mL) yielded dose-dependent reversal of the 10 ng/mL IL-1 beta-mediated inhibition of the FSH-supported accumulation of P. Similarly, the ability of IL-1 beta to exert a dose-dependent (0 to 30 ng/mL) anti-gonadotropic effect was attenuated progressively given the concurrent presence of increasing concentrations (1,000 and 5,000 ng/mL) of IL-1ra. Although treatment of whole ovarian dispersates with 10 ng/mL IL-1 beta resulted in a 5.4-fold increase in the accumulation of prostaglandin (PG)E2, this effect too was all but eliminated after the concomitant addition of 5 micrograms/mL IL-1ra. CONCLUSIONS: These observations support the nontoxic nature of IL-1ra, confirm its lack of agonistic activity, validate its utility as an experimental probe, and suggest that neither the basal nor the FSH-stimulated accumulation of P are subject to regulation by endogenously produced GC-derived IL-1-like activity. Moreover, these observations suggest that the ability of IL-1 beta to inhibit the gonadotropin-supported accumulation of P and to increase PGE2 accumulation is receptor-mediated.

Animals↗

A reappraisal of the feedback effects of oestradiol upon luteinizing hormone surge.

The objective of this study was to assess the temporal relationships of serum oestradiol and luteinizing hormone (LH) with regard to the feedback mechanism leading to the LH surge. Daily measurements of oestradiol, LH and follicle stimulating hormone were made in 65 women with ovarian failure undergoing an evaluation of endometrial response to oral cycle stimulation. Patients received incremental oral oestradiol valerate for varying durations at the in-vitro fertilization unit of the Sheba Medical Center, Tel Hashomer, Israel. The treatment protocol involved the administration of daily oestradiol valerate, starting with 1 mg/day, followed by a daily increment of 1 mg for a total of 4, 6 and 8 days. After the last day, a daily maintenance dose of 2 mg was continued. Serum oestradiol concentrations correlated with the dose of oral oestradiol valerate. Peak oestradiol concentrations (mean +/- SEM) were 572 +/- 60, 721 +/- 42 and 797 +/- 53 pg/ml for 4, 6 and 8 days of oestradiol valerate administration respectively. Serum LH, after an initial suppression, peaked 2 days after maximal oestradiol valerate dose and 1 day after peak serum oestradiol. The magnitude of the LH peak was proportional to the duration of incremental oestradiol valerate treatment. In conclusion, the LH surge is temporally related to the cessation of serum oestradiol increase. Consequently, the occurrence of this surge can be explained by a simple negative feedback inhibition of pituitary LH release rather than by a dual negative/positive mechanism.

Adult↗

Fertility, miscarriage and pregnancy after vertical banded gastroplasty operation for morbid obesity.

Vertical banded gastroplasty (VBG) is today the most widely performed bariatric operation. The procedures used previously for the same purpose resulted in metabolic derangements and other pathologies during pregnancy. In a retrospective study we compared the reproductive performance of nine women prior to VBG and after it. Of eighteen pregnancies prior to the operation, seven ended with miscarriage, while only one of fourteen pregnancies conceived after the operation was aborted. The rate of spontaneous conception was greatly increased after the operation and there were fewer complications in the course of the pregnancies. From the obstetrician and gynecologist's point of view VBG seems to be a good treatment for morbid obesity.

Abortion, Spontaneous↗

Twin pregnancies complicated by the death of one fetus.

The death of one fetus in a twin pregnancy can affect both the mother and the cotwin. Thirty women with twin pregnancies in whom the death of one fetus was diagnosed during the second half of pregnancy and a matched group of 30 women with uncomplicated twin pregnancies were investigated. The mean gestational age at delivery for the study and control groups was 32.0 +/- 5.0 (mean +/- SD) weeks and 32.8 +/- 3.9, respectively. Twelve pregnancies (40%) were monochorionic. In 15 (50%) the diagnosis was made during active labor. The cesarean delivery rate was higher in the study group than in the control group (18 vs. 11, chi 2 = 5.43, P < .02). The mean neonatal weight was similar in both groups (1,586 +/- 725 g vs. 1,543 +/- 691 g). The subgroup of neonates (n = 15) whose cotwins were diagnosed as dead during labor had higher birth weight as compared to the neonates (n = 15) in whom the diagnosis was made prior to delivery and were managed expectantly (1,829 +/- 859 vs. 1,346 +/- 474 g, P < .01). The week of delivery was similar in both subgroups. Neonatal mortality was 30% and 26.6%, while neonatal morbidity was 26.6% and 21.7%, respectively (NS). All the cases of neonatal mortality were in the subgroup of twins in which the diagnosis of in utero death was made before 32 weeks' gestation. The death of one fetus from a twin pregnancy did not significantly jeopardize maternal health, and the neonatal outcome in the remaining twins was primarily a function of gestational age.(ABSTRACT TRUNCATED AT 250 WORDS)

Birth Weight↗

Chemotaxis and chemokinesis of human spermatozoa to follicular factors.

Human spermatozoa accumulate in vitro in diluted follicular fluids obtained from follicles from which the eggs have been fertilized. Using capillary assays under a variety of experimental conditions (ascending or descending gradients of follicular fluid, or no gradient at all) and microscopic assays in which individual spermatozoa could be followed, we found that the sperm accumulation in follicular fluid was the result of both sperm chemotaxis and chemokinesis and eventually hyperactivation-like motility. We determined the optimal conditions for sperm accumulation, which involved sperm preincubation (possibly to induce sperm capacitation) and proper dilution of follicular fluid. In all the assays, the net accumulation was low, probably reflecting the chemotactic responsiveness of only a small fraction of the sperm population at any given time. We partially fractionated follicular fluid in a Centricon microconcentrator (Amicon, Danvers, MA) and by acetone precipitation, and found that at least one of the chemotactic factors is a small (< 10-kDa) molecule that is probably nonhydrophobic. This is the first time that sperm chemotaxis and chemokinesis in response to a follicular factor(s) in mammals has been established and has been distinguished from other processes that might cause sperm accumulation. The physiological significance of these findings is discussed.

Capillary Action↗

Interleukin-1 beta stimulates nitrite production in the rat ovary: evidence for heterologous cell-cell interaction and for insulin-mediated regulation of the inducible isoform of nitric oxide synthase.

Recent studies suggest that endogenously generated nitric oxide (NO) may mediate the effects of cytokines in a variety of tissues. In an effort to determine whether NO generation mediates any of the intraovarian actions of interleukin-1 beta (IL-1 beta), we have looked for and characterized the accumulation of nitrite by IL-1 beta-treated, cultured whole ovarian dispersates. Application of IL-1 beta significantly enhanced basal nitrite release in a dose-, cell density- and time-dependent manner, the latter characterized by a lag time of about 20 h, suggestive of induction of NO synthase (NOS). Cellular NOS activity was also elevated by IL-1 beta. Sustained nitrite accumulation required continuous application of IL-1 beta. The maximally stimulating dose of IL-1 beta (50 ng/ml) produced a 10-fold increase in nitrite accumulation by 96 h of culture, an effect reduced 23% when cells were cultured in substrate (i.e., arginine)-free media. IL-1 beta-stimulated nitrite accumulation was reduced to control levels by the simultaneous application of an IL-1 beta receptor antagonist, thereby suggesting a specific receptor-mediated effect. Both the control and IL-1 beta-stimulated levels of nitrite accumulation were attenuated in a dose-dependent manner by inhibitors that favor the inducible form of NOS. In contrast, selective inhibitors of the constitutive form of NOS were significantly less potent. No inhibition was noted after application of an inactive stereoisomeric analogue. IL-1 beta-induced nitrite accumulation was shown to require cell-cell interaction between granulosa and theca-interstitial cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Oxidoreductases↗

Rat ovarian granulosa cell as a site of endothelin reception and action: attenuation of gonadotropin-stimulated steroidogenesis via perturbation of the A-kinase signaling pathway.

Endothelins (ETs) are a family of vasoactive peptides that may be involved in granulosa cell (GC) luteinization or follicular maturation. However, the precise role of ET in ovarian physiology remains unknown. We have investigated whether the rat GC is a site of ET reception and have characterized the antigonadotropic effect of ET in cultured GC from immature rats. Two major ET binding species (52 and 30 kDa) were observed after cross-linking of GC membranes with radiolabeled ET-1, although the smaller protein may represent a degradative product. Unlabeled ET-1, ET-2, or ET-3 were equipotent in displacing radiolabeled ET-1 from these putative ET receptors, with EC50s of 0.3-0.7 x 10(-9) M. Similarly, ET-1, ET-2, and ET-3 were equipotent (EC50s of about 10(-10) to 10(-9) M) in inhibiting the FSH-supported accumulation of progesterone. ET-1 (10(-7) M) also inhibited (> 90%) FSH-supported estrogen accumulation. Maximum progesterone inhibition (> 90%) by ET-1 (10(-7) M) was achieved throughout the range of FSH does and cell densities tested and by 48 h or 72 h of culture. ET-1 was not cytotoxic in the dose range tested. Forskolin-stimulated progesterone accumulation was similarly inhibited by ET-1, suggesting that ET-1 inhibits cAMP-mediated (e.g., FSH or forskolin-stimulated) progesterone accumulation. ET-1 inhibited (74%) the FSH-stimulated accumulation of cAMP, suggesting that it acts at sites related to cAMP generation or degradation. In addition, ET-1 inhibited 8-bromo-cAMP-generated progesterone accumulation (60%), suggesting that it also acts at sites distal to cAMP generation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The morphogenic/cytotoxic and prostaglandin-stimulating activities of interleukin-1 beta in the rat ovary are nitric oxide independent.

Nitric oxide (NO) has been implicated as a mediator of physiologic and pathologic cellular injury. Since the cytokine interleukin-1 beta (IL-1 beta) induces nitric oxide synthase (NOS) activity as well as effects morphogenic/cytotoxic changes and increased prostaglandin (PGE2) levels in cultured whole ovarian dispersates, we set out to determine whether these actions are interrelated. Treatment with IL-1 beta resulted in a marked increase in media nitrite and nitrate accumulation, morphological alterations, and increased release of lactate dehydrogenase (LDH) into media. Addition of IL-1 receptor antagonist (RA) eliminated these IL-1 beta effects. In contrast, specific inhibitors of NOS failed to reverse IL-1 beta-induced morphogenic changes or LDH release in spite of complete reduction of media nitrite to control levels. Similarly, treatment with transforming growth factor beta 1, inhibited IL-1 beta-induced nitrite accumulation, but had no effect on the morphologic or cytotoxic endpoints. Moreover, the addition of sodium nitroprusside, an NO generator, resulted in progressive increments in media nitrite content without a corresponding increase in the IL-1 beta-associated morphogenic changes or media LDH content. Furthermore, IL-1-induced PGE2 accumulation remained unaffected by specific NOS inhibition. These observations support the view that NO does not mediate the morphogenic/cytotoxic or inflammatory-like (e.g., PGE2 inducing) properties of IL-1 beta in cultured whole ovarian dispersates. Although the precise role of NO in ovarian physiology remains unknown, it is possible that NO participates in the periovulatory modulation of ovarian blood flow by virtue of its potent vasodilatory activity.

Amino Acid Oxidoreductases↗

Complete failure of fertilization in couples with unexplained infertility: implications for subsequent in vitro fertilization cycles.

OBJECTIVE: To determine whether complete failure of fertilization of oocytes in couples with unexplained infertility persists during subsequent in vitro fertilization (IVF) cycles. DESIGN: A retrospective study of 120 cycles of IVF in 44 couples with unexplained infertility and complete failure of fertilization during their first IVF trial. SETTING: In vitro fertilization unit of the Sheba Medical Center. PATIENTS: Forty-four couples undergoing IVF for unexplained infertility. MAIN OUTCOME MEASURE(S): Fertilization rate of retrieved oocytes and pregnancy rate. RESULTS: Of the initial 44 couples, 37 underwent additional IVF cycles and 30 (81.1%) achieved fertilization. Seven patients conceived during the study period as a result of IVF and two conceived spontaneously. CONCLUSIONS: Complete failure of fertilization does not necessarily persist during subsequent IVF cycles. Therefore, at least two more IVF cycles should be attempted before reverting to other therapeutic options. However, although fertilization can be achieved in most couples, the mean oocyte fertilization rate during subsequent cycles in this group is low. This suggests an underlying undiagnosed pathology of oocyte/sperm interaction in some of these patients.

Female↗

Propofol and fentanyl act additively for induction of anaesthesia.

The induction dose-response of propofol was compared with the dose-response of its combination with fentanyl and with that of fentanyl alone in three groups of 60 women undergoing minor gynaecological surgery. Dose-response curves were determined for each group using bootstrap and isobolographic analyses. Propofol was found to act additively with fentanyl for induction of anaesthesia. Twenty-three percent of the ED50 of fentanyl was required in combination with 75% of the ED50 for propofol to achieve the ED50 of the combination. This indicates that, for induction of anaesthesia, propofol and fentanyl are not synergistic.

Adult↗

The effects of exercise induced tachycardia on the maternal electrocardiogram.

OBJECTIVE: To determine whether pregnancy has an effect on the maternal electrocardiographic response to stress. DESIGN: Eight maternal ECG parameters were screened before, during and after exercise induced tachycardia at 29 and 37 weeks gestation and at 6 weeks post partum for each participant. SETTING: General Hospital in Safed, Israel. SUBJECTS: Fifteen healthy, pregnant women aged 22 to 34 years with singleton pregnancies volunteered from the peripheral antenatal clinics. INTERVENTION: Exercise stress tests were performed on a Quinton 3000 treadmill stress test system according to a Modified Bruce Protocol, producing a heart rate of 85% of age predicted maximum. MAIN OUTCOME MEASURES: The ST-segment, T-wave, QRS complex, axis, rhythm, disorders of impulse conduction, the P-Q and Q-T intervals were screened before, during and after the exercise test. RESULTS: The study results suggest an increase in the ST-segment changes induced by stress at 37 weeks of pregnancy compared to 29 weeks (ST-depression in 6 women out of 15 versus 2, P = 0.125, McNemar's Test for Correlated Proportions-Exact Test, two tailed; 95% CI, 0.042-0.492, 0.01 < P < 0.05) and to the post partum test (ST-depression in 6 women out of 15 versus 1, P = 0.125; 0.029-0.637, 0.01 < P < 0.05). No significant alteration of the other ECG parameters. No significant correlation between blood haemoglobin level, serum levels of sodium, potassium, calcium, glucose and 17 beta-oestradiol with the appearance of the ECG change. CONCLUSIONS: The increase in the exercise induced ST-segment abnormalities at 37 weeks of pregnancy may be another physiological effect of late pregnancy which has not been demonstrated previously.

Adult↗