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Biomedical subjects

S Kol

Publications and source records attributed to S Kol.

At least 55 records · Page 3Linked to original sources

The incidence and possible relevance of Y-linked microdeletions in babies born after intracytoplasmic sperm injection and their infertile fathers.

Microdeletions linked to deletion intervals 5 and 6 of the Y chromosome have been associated with male factor infertility. Members from at least two gene families lie in the region containing azoospermia factor (AZF), namely YRRM and DAZ. With the advent of intracytoplasmic sperm injection (ICSI), it is possible for men with severe male factor infertility to produce a child. The genetic consequences of such a procedure have been questioned. This report describes the first study of a population (32 couples) of infertile fathers and their sons born after ICSI. The objectives were firstly to determine the incidence and map location of Y chromosome microdeletions and to compare the frequencies with other population studies involving severe male factor infertility, and secondly to formulate a working hypothesis concerning developmental aetiology of Y chromosome microdeletions. The incidence of microdeletions in the ICSI population was shown to be 9.4% (within the range 9-18% reported for populations of severe male factor infertility patients). Microdeletions in two out of three affected father/son pairs mapped in the region between AZFb and AZFc and the third involved a large microdeletion in AZFb and AZFc. Of three affected father/son pairs, microdeletions were detected in the blood of one infertile propositus father and three babies. Assuming that the gonomes of the ICSI-derived babies are direct reflections of those of their fathers germ lines, it is possible that two of three infertile fathers were mosaic for intact Y and microdeleted Y chromosomes. In such cases, the developmental aetiology of the microdeletion may be due to a de-novo microdeletion arising as a post-zygotic mitotic error in the infertile propositus father, thus producing a mosaic individual who may or may not transmit the deletion to his ICSI-derived sons depending on the extent of primordial germ cell mosaicism. In one of three affected fathers, the microdeletion detected in his blood was also detected in his ICSI-derived son. In this case the de-novo event giving rise to the microdeletion may have occurred due to a post- (or pre-) meiotic error in the germ line of this father's normally fertile father (i.e. the ICSI-derived baby's grandfather).

Adult↗

Undocumented embryos: do not trash them, FISH them.

Pronuclei formation is routinely assessed 16-20 h after oocyte insemination in in-vitro fertilization (IVF). Occasionally, the pronuclei disappear before this time, rendering them as 'undocumented'. Since the number of pronuclei detected is used to distinguish normal from abnormal embryos in the context of ploidy, the diploidy of undocumented embryos is questionable, and therefore they are routinely discarded. The introduction of fluorescent in-situ hybridization (FISH) technology allows the assessment of ploidy status in undocumented embryos that continue to cleave to form blostomeres. In this study, we used FISH to analyse the chromosomal status of 23 undocumented embryos obtained from 10 patients. Biopsied blastomeres were fixed and probed for five chromosomes (X, Y, 13, 18, 21). Diploidy was confirmed in 13 (57%) embryos while the remaining 10 embryos displayed various chromosomal anomalies. Six of the diploid embryos were transferred subsequently to the patients. One ongoing pregnancy was achieved following transfer of an undocumented, analysed embryo, which was already cleaved when assessed 20 h after insemination. We suggest that accelerated dismantling of the pronuclear membrane and subsequent cleavage do not necessarily indicate abnormal chromosomal content and may result in normal pregnancy. In a patient with a small number of embryos, FISH may be used to ascertain diploidy of undocumented embryos, thereby increasing the number of available embryos for transfer.

Blastomeres↗

Comparison of gonadotrophin-releasing hormone analogues and human chorionic gonadotrophin for the induction of ovulation and prevention of ovarian hyperstimulation syndrome: a case-control study.

Gonadotrophin-releasing hormone analogue (GnRHa) has been suggested as an alternative to human chorionic gonadotrophin (HCG) for triggering ovulation, while preventing ovarian hyperstimulation syndrome (OHSS). Since a prospective, controlled study would be unethical at this point, we used a retrospective, case-self control approach to compare GnRHa with HCG in that context. A group of 16 in-vitro fertilization (IVF) patients who had severe OHSS in previous cycles, in which HCG was given to trigger ovulation, were studied in subsequent cycles in which GnRHa was used. Each GnRHa cycle (case) was compared to a previous HCG cycle that resulted in OHSS (self control). None of these subsequent cycles resulted in severe OHSS. The use of GnRHa did not affect the number of oocytes retrieved or their quality. Serum oestradiol concentrations on the day of ovulation triggering were significantly (P < 0.01) higher in the GnRHa cycles compared to HCG cycles. Exogenous progesterone and oestradiol were effective in maintaining relatively constant serum oestradiol and progesterone serum concentrations during the luteal phase. Pregnancy rate per cycle was similar in the two groups. In conclusion, the use of GnRHa to induce ovulation in IVF patients, who are at high risk for developing OHSS, effectively eliminates this risk without affecting other parameters of the stimulation cycle.

Case-Control Studies↗

Thyroid function in early normal pregnancy: transient suppression of thyroid-stimulating hormone and stimulation of triiodothyronine.

In order to determine the effect of gestation on thyroid function in healthy subjects, we have prospectively evaluated thyroid function in pregnant individuals undergoing termination of pregnancy, and repeated the tests 2-3 months later. Venous blood was tested for human chorionic gonadotropin (hCG), thyroid-stimulating hormone (TSH), free thyroxine (FT4) and total triiodothyronine (TT3). Early pregnancy thyroid function tests showed a significant decrease (p < 0.001) in TSH and a significant increase (p < 0.001) in TT3 as compared to the nonpregnant state; FT4, however, did not change significantly. In 8 (11.2%) pregnant subjects, TT3 levels were above the normal range for nonpregnant controls. Elevated thyroid function in early pregnancy is transient, and does not usually warrant antithyroid treatment. Thus, any conclusion regarding thyroid function in early pregnancy should be based on pregnant controls rather than general population controls.

Abortion, Induced↗

Gas embolism in obstetrics and gynecology. A review.

OBJECTIVE: To review gas embolism in the field of obstetrics and gynecology, with an emphasis on the pathophysiology, clinical presentation and treatment options. STUDY DESIGN: A review of the world literature on gas embolism. CONCLUSION: Gas embolism is an unusual complication and has increased in frequency since the introduction of new invasive procedures. Since the clinical presentation of gas embolism has many faces, it is important to identify it as early as possible: timely treatment may be life saving, while a delay may have serious consequences.

Embolism, Air↗

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↗

Interpretation of nonstress tests by an artificial neural network.

OBJECTIVE: Our purpose was to evaluate an artificial neural network in the interpretation of nonstress tests. STUDY DESIGN: A nonlinear artificial neural network trained by backpropagation was taught to interpret records of nonstress tests by two learning sets. The first set contained nonstress tests that were similarly interpreted by three human experts; the second set contained a subset of nonstress tests that led to interobserver disagreement. Both "raw" fetal heart rate and uterine contraction data and 17 quantified variables obtained by automated computer analysis were introduced to the input layer. After training, the network was tested by presenting it with input patterns to which it had not been exposed. The performance of the system was examined in relation to the human expert. RESULTS: After training the neural network with the first set, a sensitivity of 88.9% and a false-positive rate of 4.3% were obtained at testing. When the learning and test set contained records that led to interobserver disagreement, a sensitivity of 86.7% and a false-positive rate of 19.7% were obtained. Sixty percent of fetal heart rate records interpreted as abnormal by the neural network were interpreted likewise by the human experts. CONCLUSIONS: The results obtained are encouraging in that the neural network could discriminate between normal and abnormal nonstress tests. Further evaluation of this new technique is mandatory to evaluate its efficacy and reliability in interpreting fetal heart rate records.

Algorithms↗

Intraovarian factors regulating ovarian function.

Ovarian folliculogenesis is a dynamic process marked by exponential expansion and differentiation of the granulosa cells, oocyte maturation, ovulation and corpus luteum formation. Although the central roles of gonadotropins and gonadal steroids in this explosive agenda are well accepted, the variable fate of follicles afforded comparable stimulation within the same ovary suggests the existence of an additional intraovarian system comprised of regulating species that 'fine-tune' the blood-borne hormones.

Estrogens↗

Spinal cord decompression sickness in sport diving.

OBJECTIVE: To summarize 16 years' experience in the diagnosis and treatment of spinal cord decompression sickness in Israel. DESIGN: The survey data were collected firsthand by physicians trained in underwater diving medicine. SETTING: The Israeli Naval Medical Institute, Israel's national hyperbaric referral center. PATIENTS: Sixty-eight sport divers diagnosed as having spinal cord decompression sickness. INTERVENTIONS: Hydration and 100% oxygen breathing until the patient reached the hyperbaric chamber. All patients received recompression therapy on US Navy treatment tables using oxygen, except for six who were treated by Comex Treatment Table CX-30, which uses helium in addition to oxygen. MAIN OUTCOME MEASURES: Neurological examination after the completion of recompression therapy. RESULTS: Forty-one percent of the dives were performed within the decompression limits of the US Navy standard decompression tables. Risk factors were fatigue, circumstances suggesting dehydration, and extreme physical effort. The most common presenting symptoms were paresthesias, weakness of the legs, lower back pain, or abdominal pain. Full recovery was achieved in 79% of the patients. Spinal symptoms appeared immediately on surfacing in six of the eight patients who continued to have multiple neurological sequelae. CONCLUSIONS: United States Navy air decompression tables appear not to be completely safe for sport divers. Even mild spinal symptoms identified on surfacing should be treated vigorously. High-pressure oxygen-helium therapy seems to be a promising alternative in cases of severe spinal cord decompression sickness.

Adult↗

Hyperbaric oxygenation for arterial air embolism during cardiopulmonary bypass.

The incidence of systemic air embolism during cardiopulmonary bypass is estimated to be 0.1%. However, the vast majority of instances are unreported and quietly ignored. The result may be disability or death. The control of air embolism obviously lies in prevention. The definite and specific treatment of this complication is hyperbaric oxygen. We report 6 patients referred to our institute because of air embolism during cardiopulmonary bypass. Of the 4 patients in whom hyperbaric oxygen therapy was delayed for 17 to 20 hours, 2 showed partial neurological improvement, as opposed to the success of hyperbaric oxygen therapy in the 2 patients in whom the delay was minimal. We conclude that as soon as the proposed open heart operation has been completed and there is an indication that air embolism has occurred, the patient should be treated with hyperbaric oxygen as quickly as possible, even before neurologic manifestations of cerebral ischemia appear.

Aged↗

The natural history of multiple pregnancies after assisted reproduction: is spontaneous fetal demise a clinically significant phenomenon?

OBJECTIVE: To determine the rate of spontaneous fetal demise after heartbeats are demonstrated in multiple pregnancies conceived after IVF-ET. DESIGN: Retrospective case series. SETTING: University-based IVF-ET program. PATIENTS: Eighty-one patients in whom initial transvaginal ultrasound (US) study, performed at 5 to 6 weeks of gestation, identified more than one gestational sac. Total number of sacs was 191. INTERVENTION: Patients were followed by serial US examinations. MAIN OUTCOME MEASURE: Outcome of pregnancies. RESULTS: Twenty-four empty gestational sacs were identified in 21 patients, of whom 15 delivered, 2 miscarried, and 4 are currently ongoing beyond first trimester. Of the 167 initially viable embryos, 9 (5%) underwent spontaneous fetal demise. In 5 of these 9 pregnancies, initial US identified significant interfetal size variation. CONCLUSIONS: The rate of spontaneous fetal demise for a specific embryo in multiple gestation, after fetal heartbeats have been identified in early pregnancy, is 5%. This rate is similar to that seen in spontaneous conceptions. The chance of future fetal demise increases if first trimester interfetal size variation is significant.

Abortion, Spontaneous↗

Use of gonadotropin-releasing hormone agonist to cause ovulation and prevent the ovarian hyperstimulation syndrome.

The physiologic basis and clinical applications of the use of GnRHa, rather than hCG, to induce the final stage of oocyte maturation and ovulation in gonadotropin-treated cycles were reviewed. A single mid-cycle dose of GnRHa is able to trigger a preovulatory LH/FSH surge, leading to oocyte maturation and pregnancy in women undergoing ovarian stimulation for IVF/ET or induction of ovulation in vivo. The limited information currently available suggests there are similar pregnancy rates in patients treated with either GnRHa or hCG. The potential clinical advantages of GnRHa over hCG in gonadotropin-treated cycles include 1) the ability to titrate the amplitude and duration of the LH surge, 2) better control of luteal steroid hormone levels, 3) a higher implantation rate, 4) a lower rate of multiple pregnancy, and 5) a reduced risk of OHS. To date, the GnRHa regimen has been effective in preventing OHS in patients at high risk for having this complication.

Estradiol↗

Oxy-helium treatment of severe spinal decompression sickness after air diving.

Spinal cord injury in DCS after air diving is relatively frequent and often has late sequelae. U.S. Navy oxygen tables are sometimes not satisfactory. The advantage of using helium in these cases is based theoretically on its physical properties and has been demonstrated in animal models. We have introduced the Comex-30 (CX-30) oxy-helium table as an integral part of our treatment protocol for severe spinal DCS. We summarize here our clinical experience with seven cases. A case was considered severe if clinical assessment suggested progressive neurologic injury to the spinal cord or roots. Except for one case, the initial treatment was CX-30 followed by HBO sessions as indicated. Of the seven patients treated, five made a full recovery and the remaining two were left with mild neurologic sequelae.

Adult↗

Pulmonary barotrauma after a free dive--a possible mechanism.

Pulmonary barotrauma during scuba diving is a life-threatening event. In a skin diver, who does not use compressed air, this complication is rare and its pathophysiology is not readily understood. We present a young, healthy skin diver who suffered pneumomediastinum and subcutaneous emphysema after a sequence of free dives to 5 m, and suggest a possible mechanism.

Adult↗