Bilateral retinal detachment in preeclamptic women with thrombophilia.
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Biomedical subjects
Publications and source records attributed to J B Lessing.
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A unique cast model of the placenta in a rare case of feto-feto-fetal triplet transfusion syndrome (FFFTTS) allowed the demonstration of why the transfusion syndrome developed in one fetus and not in the other two in that single placenta. The vasculature anatomy of a monochorionic triamniotic triplet placenta with FFFTTS of three healthy infants (one donor, two recipients) born in the 35th week of gestation was cast by means of dental casting materials. After the cast hardened, the tissue was corroded, revealing the cast blood vessels. The diameters and lengths of the chorionic blood and intraplacental vessels of the cast placenta were measured with a digital caliper. The cast revealed two artery-artery (A-A) anastomoses on the chorionic plate between the two recipients and the donor. Seven artery-vein (A-V) deep anastomoses connected only the arteries of the donor and the veins of the two recipients. The blood vessel connections among the fetuses allowed the evaluation of a pathologic case with its own control in a single placenta. From the vascular appearance, we speculate that the A-A anastomoses between the two fetuses protected them from developing blood transfusions, but that the A-V anastomoses contributed to their development.
Fertility preservation is of major importance for women with cancer in whom ovarian function may be disturbed by the use of potentially sterilizing chemotherapeutic drugs and/or pelvic irradiation. Cryopreservation of ovarian cortical tissue is one of the potential options for preserving fertility among these women. Cryopreserved thawed human ovarian tissue can be autografted either orthotopically or heterotopically, but may also be transplanted first into an animal host with subsequent maturation and collection of oocytes. The objective of this study was to investigate the prevalence of ovarian follicular apoptosis in fresh and frozen/ thawed human ovarian tissue as a measure of follicular viability. The study group included 6 women with cancer who underwent ovarian tissue cryopreservation (OTCP). Ovarian tissue samples (n = 2) were obtained from each woman with one sample undergoing evaluation for apoptosis immediately following removal (control, group A) and the other evaluated for apoptosis following freezing/thawing (group B). Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling (TUNEL) and 4'6' diamido-2-phenylindole hydrochloride (DAPI) staining methods were used to investigate follicular apoptosis. Morphological changes in the same samples were evaluated in hematoxylin and eosin (H&E)-stained sections. In each slide, only primordial and primary follicles were evaluated for abnormal morphology and apoptosis. Abnormal morphology was demonstrated in 23.8+/-8.7% of group A follicles compared to 48.3+/-11.2% of group B follicles (p < 0.05). Apoptosis was demonstrated in 25.4+/-8.4% of group A follicles compared to 60.9+/-6.0% of group B follicles (p < 0.05). We have shown that the ovarian follicles in group B demonstrated a higher incidence of apoptosis compared to those of group A. Therefore, the data suggest that follicular apoptosis might be a consequence of the freezing and thawing procedure. This may be used as a method for evaluating and comparing the outcome of different freezing/thawing protocols.
The adjusted incidence of cervical carcinoma among Israeli Jewish women is approximately 5 out of 100 000. This retrospective study sought to determine the clinical implications of finding atypical glandular cells of undetermined significance (AGUS) in cervical cytologic specimens in this population. Cervical cytologic examinations during January 2001-June 2003 diagnosed as AGUS were identified by a computerised database. Medical records were reviewed to determine the presence or absence of associated significant pathologic conditions of the cervix and identified 45 out of 11 800 patients (0.38%) with AGUS. AGUS was the only cytologic diagnosis in 14 patients, while 31 patients had both AGUS and an additional atypical squamous cell of undetermined significance (ASCUS). All subjects underwent colposcopy, endocervical curettage, and cervical biopsy. A clinically significant diagnosis (cervical intraepithelial neoplasia (CIN) II, CIN III, or carcinoma) was made in 24 patients (53.3%), including cancer in three (6.7%): one had microinvasive adenocarcinoma and two had microinvasive squamous cell carcinoma. Squamous carcinoma coexisting with a clinically significant lesion carried a risk of 61.3%, compared with a risk of 35.7% for AGUS alone (P=0.20). Detection of AGUS during cervical cytologic screening, especially with a coexisting ASCUS, indicates the existence of serious pathologic processes; management by cervical colposcopy, endocervical curettage, and cervical biopsy is recommended.
BACKGROUND: Many theories regarding the pathophysiology leading to ovarian hyperstimulation syndrome (OHSS) have been proposed and tested. Increased erythrocyte aggregation is associated with capillary slow flow and tissue hypoxaemia. We performed this study in order to assess the degree of erythrocyte aggregation in the peripheral blood of individuals with OHSS and undergoing controlled ovarian stimulation (COH). METHODS: Twenty women with severe OHSS, 20 women undergoing COH under IVF protocol, and 20 healthy matched controls were recruited for this prospective study. Blood samples were drawn for determination of erythrocyte aggregation as well as haematological indices. The percentage of slide covered by the cells ('erythrocyte percentage': EP) was determined using a simple slide test and image analysis. Lower EP values correspond to higher degrees of aggregation. RESULTS: The respective measures of EP were 59.2 +/- 3.0, 42.0 +/- 3.0 and 35.0 +/- 2.4% micro m for the controls, women with COH and OHSS (P < 0.01 between controls and the two stimulation groups). CONCLUSIONS: The degree of erythrocyte aggregation is enhanced in the peripheral venous blood of patients with both COH and OHSS. This finding, known to cause capillary leak, may contribute to the pathophysiology of the OHSS.
BACKGROUND: The LC Polscope facilitates visualization of the meiotic spindle in human oocyte. This study aimed to investigate meiotic spindle assembly in correlation to time elapsed after HCG administration, and to determine whether spindle imaging may serve to indicate the likelihood of fertilization and embryo cleavage. METHODS: Metaphase II (MII) oocytes from 103 couples who were being treated for male infertility were imaged with the Polscope prior to sperm injection. Spindle imaging was correlated to time elapsed from HCG administration, fertilization rate and embryo cleavage. The main outcome measures were spindle visualization, fertilization and embryo cleavage on day 3. RESULTS: A total of 770 MII oocytes were imaged. A spindle was imaged in a significantly higher number of oocytes from >or=38 h after HCG administration compared with those in the <38 h group (78.1-81.5% versus 61.6%; P < 0.001). The fertilization rate in oocytes with a visible spindle was statistically higher compared with oocytes in which spindle could not be detected (70.4% versus 62.2%; P = 0.035). We found no relationship between spindle imaging and embryo cleavage on day 3. CONCLUSIONS: Spindle imaging, in addition to first polar body appearance, is an accurate indicator for oocyte maturity. We suggest that spindle imaging be performed prior to sperm injection.
Hyperemesis gravidarum is a severe form of nausea and vomiting during the first trimester of pregnancy. Our objective was to assess the feasibility of nasojejunal feeding in our patients. Eleven pregnant women aged 23-46 years with hyperemesis gravidarum, persisting in spite of an in-hospital treatment of 2-15 days by intravenous fluids and antiemetic drugs and accompanied by weight loss, consented to have a nasojejunal feeding tube inserted endoscopically. Mean in-hospital weight loss prior to tube insertion was 2.2+/-1.1 kg (range 0.9-5.1 kg). A clear reduction in the extent of vomiting was already apparent within the first 48 h after tube insertion, but vomiting ceased completely after a mean of 5+/-4 days (range 1-13 days). Weight gain was recorded in six patients who stayed on tube feeding for more than 4 days. Patients were encouraged to start drinking and eating along tube feeding after 3-4 days. Ceasing vomiting and a concomitant sufficient oral intake of at least 1000 kcal/day resulted in the decision to remove the tube after 4-21 days. In three cases, however, the tube was expelled by recurrent vomiting after 1-4 days, or was blocked as in one case. The tube was not reintroduced and patients did not resume vomiting. There were no complications associated with this feeding approach in this population. Only one patient was readmitted. None of the rest resumed vomiting after tube withdrawal.The above suggests that nasojejunal enteral feeding can be an effective option in hyperemesis gravidarum persisting despite intravenous fluids and antiemetic drugs.
PROBLEM: The presence of interleukin-18 (IL-18) in serum and pre-ovulatory follicular fluid (FF) and its possible correlation to in-vitro fertilization/embryo transfer (IVF/ET) outcome and ovarian hyperstimulation syndrome (OHSS) development. METHOD OF STUDY: A prospective study was carried out. Assays for serum and pooled pre-ovulatory FF levels of IL-18 were performed on 30 patients who underwent oocyte retrieval for IVF/ET. RESULTS: Mean serum and FF levels of IL-18 were 370.4 +/- 224 and 228.9 +/- 208 pg/mL, respectively (r = 0.77, P < 0.0001). Levels of FF IL-18 were comparable between the two ovaries (right = 221 +/- 166.8 pg/mL, left = 237 +/- 171.9 pg/mL; r = 0.7550, P = 0.49). A positive correlation was found between IL-18 FF levels and number of retrieved oocytes (r = 0.45; P = 0.019). In three patients (10%) who developed OHSS, the mean serum level of IL-18 at day of ovum pickup was significantly higher compared with patients without OHSS (620 +/- 196 pg/mL versus 345 +/- 251 pg/mL, respectively, P = 0.04). CONCLUSIONS: Both pre-ovulatory FF and serum levels of IL-18 correlate with the number of retrieved oocytes. The serum IL-18 level at day of ovum pickup may predict consequent development of OHSS. Further investigations are warranted to determine the role of IL-18 in the folliculogenesis and OHSS pathogenesis.
Polycystic ovarian syndrome is seen in 5% of fertile aged women. However, there is no satisfactory PCOS model in experimental animals. To induce polycystic ovary phenotype in immature female rats, Wistar rats 21 days of age were injected daily with testosterone propionate 1 mg/100 g body weight dissolved in propylene glycol or propylene glycol for up to 35 days. Seven days of injection with testosterone (T) resulted in the appearance of large cystic follicles and a dramatic accumulation of multi-layer preantral follicles. At 42 days of age puberty in control animals was evident by the appearance of corpora lutea. In contrast in T treated animals no corpora lutea formation was seen even at the age of 56 days. Progesterone in the control animals was elevated at the age of 42 days in contrast with the T treated animals in which progesterone remained low (20% of control). While during 14 days of T injection most of the follicles did not have progressive apoptosis, at 21-35 days of injection (42-56 days of age) the vast majority of follicles became apoptotic. Progressive degeneration of oocytes was evident in T treated animals reaching 70-85% of total oocytes at 21-35 days of T injection compared to 30-40% in control animals. Western blot analysis of ovarian homogenates revealed gradual decrease in Bcl-2 content, evident at 28 and 35 days of T injection compared to control animals. Interestingly, the fasting glucose/insulin ratio was dramatically reduced in T treated animals following 14 days of testosterone treatment compared to controls. Our data suggest that T injection to immature female rats can induce polycystic ovaries, block ovulation and attenuate progesterone production. Moreover, normal/low glucose and high insulin blood levels in the testosterone treated rats raises the possibility that elevated androgens can lead to insulin resistance in this experimental PCOS model.
This study aimed to evaluate the clinical and economic implications of integrating human papilloma virus (HPV) load testing into the follow-up and management protocol of women postconisation for high-grade cervical intraepithelial neoplasia (CIN2-3). We evaluated 130 suitable women: 63 were screened biannually by Pap smears ('conventional approach') and 67 also had HPV-load testing ('HPV approach'). More stringent criteria for undergoing colposcopy or reconisation were observed by the former group compared to the latter. Both approaches were analysed for cost effectiveness. There were 33 out of 67 (49.2%) colposcopic referrals and 24 out of 67 (35.8%) reconisation/hysterectomies with the 'conventional approach' compared to 9 out of 63 (14.2%) and 7 out of 63 (11.1%) with the 'HPV approach'. Cervical intraepithelial neoplasia 2-3 residual disease was detected in 7 out of 67 (10.5%) and 7 out of 63 (11.1%) women. The 'conventional approach' had more negative colposcopic biopsies and more negative reconisation/hysterectomy histologies than the 'HPV approach'. The respective cost per detection of one case of residual disease was US$3573 and US$3485. The 'HPV approach' required fewer colposcopic and reconisation procedures to detect one case of residual CIN2-3. Its higher positive predictive value than that of cytology provided a significant decrease in false positive rates and a reduction of US$88 per detected case.
OBJECTIVES: To conduct a prospective evaluation of the incidence and neonatal outcome of fetuses with persistent right umbilical vein. This condition had traditionally been considered to be extremely rare and to be associated with a very poor neonatal prognosis, but later evidence has raised some doubts about the veracity of these contentions. METHODS: Between August 1995 and November 1998, 8950 low-risk patients were prospectively evaluated at two medical centers. The sonographic diagnosis of a persistent right umbilical vein was made in a transverse section of the fetal abdomen when the portal vein was curved toward the stomach, and the fetal gall bladder was located medially to the umbilical vein. RESULTS: Persistent right umbilical vein was detected in 17 fetuses during the study. Four of them had additional malformations, of which three had been detected antenatally. CONCLUSIONS: We established that the incidence of persistent right umbilical vein in a low-risk population is 1 : 526. We believe that the sonographic finding of this anomaly is an indication for conducting targeted fetal sonography and echocardiography. When the persistent right umbilical vein is connected to the portal system and other anomalies are ruled out, the prognosis can generally be expected to be favorable.
OBJECTIVES: To assess the contribution of additional examiners to: the average discrepancy between estimated and actual fetal weights; the correlation between estimated and actual fetal weights; the reduction in major (> 10%) discrepancies between estimated and actual fetal weights. DESIGN: Three experienced sonographers independently measured fetal biparietal diameter, head circumference, abdominal circumference and femur length in 39 fetuses at term. The estimated fetal weights were calculated for each examiner. Fetal biometric measurements were analyzed to obtain the source of differences in estimations among the examiners. Discrepancy, correlation and number of major (> 10%) discrepancies between the estimated and actual fetal weights were calculated for each examiner, and the contribution of additional examiners was analyzed. RESULTS: The differences in measurements of the biparietal diameter and femur length were lower than those of the head and abdominal circumferences. For each of the three examiners, the average discrepancy between the estimated and actual fetal weights was 6.1%, 5.9% and 6.3%. When the estimation was based on two examiners, the discrepancy decreased to 4.8-5.6%. The contribution of a third examiner was nil. Major (> 10%) discrepancies between estimated fetal weight and actual birth weight were found in seven, eight and nine estimations of the examiners. Estimation by two examiners decreased the number of major discrepancies, and estimation by all three examiners further decreased by approximately 50% the number of major discrepancies between the estimated and actual fetal weights. CONCLUSION: Measurements by multiple examiners changes only slightly the average number of discrepancies between estimated and actual fetal weights. However, the reduction in major (> 10%) discrepancies is statistically and clinically significant.
OBJECTIVE: To investigate placental apoptosis in discordant dichorial twins. METHODS: Placental samples were obtained from 7 third-trimester suitable twins. Discordancy was defined as a >25 per cent difference in newborn birth weight. Light microscopy using hematoxylin and eosin (H&E)-stained paraffin slides and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labelling (TUNEL) methods were used to confirm the incidence of apoptosis. Investigators were blinded to pregnancy outcome. RESULTS: Both methods revealed that the incidence of apoptosis in the placentas of the smaller fetuses was significantly higher than in placentas of the larger fetuses. The incidence of TUNEL-positive cells in the former was 1.4+/-0.26 per cent: this was significantly higher than the incidence of apoptosis in the placental specimens of the latter (0.9+/-0.07 per cent, P< 0.02 Wilcoxon rank test). The same results were obtained with H&E: the incidence of apoptosis detected in placentas from the former was 1.07+/-0.1 per cent compared to 0.72+/-0.08 per cent in those of the latter (P< 0.02 Wilcoxon rank test). CONCLUSIONS: Despite similar environment conditions, placental apoptosis is increased in the smaller fetus and thus might play a role in discordancy between twins. Since increased placental apoptosis has also been found in singleton intrauterine growth restriction, this supports the hypothesis that the smaller twin is selectively growth restricted.
Human and rat granulosa cells express receptors to leptin which synergies with glucocorticoid hormones in stimulation of ovarian steroidogenesis. To examine whether leptin affects follicular development and maturation, we injected recombinant ovine leptin (300 ng-10 microg/animal) daily to immature 21 day-old female rats. Non-treated rats reached puberty at 44.5+/-1.6 (n=9) days. In contrast, in leptin treated animals, puberty was reached at 34.5+/-1.6 (n=9) days. Ovarian sections revealed hypertrophy of granulosa cells in leptin treated animals. Moreover, the number of ovulations was 2-fold higher in the treated animals compared to controls (3-4 ovulations versus 7-8 on the first three estrous cycles, P<0.001). Leptin dramatically reduced incidence of follicular apoptosis measured by TUNEL, and was already evident after 7 days of leptin injection (12% of apoptosis in leptin treated group compared to 52% in controls, P<0.001). Maximal protection against apoptosis was achieved at 1-3 microg leptin/animal. The levels of FSH, LH, progesterone and the steroidogenic factors ADX and STAR were elevated earlier in development in the leptin treated animals compared to control animals which is in line with the achievement of early puberty in the leptin treated animals compared to non treated ones. To reveal whether modulation of death and survival genes is involved in leptin attenuation of follicular apoptosis, we examined the expression of the survival gene Bcl-2 and the death gene Bax in Western blots of ovarian homogenates. There was a pronounced elevation in Bcl-2 expression during 7-14 days of leptin injections up to 16.3-fold (P<0.001) compared to Bcl-2 expression in controls. Bax expression was elevated only 3.4 fold (P<0.001), leading to an increase in the Bcl-2/Bax ratio of 4.7 fold (P<0.001). Expression of the tumor suppressor gene p 53 and the oncogene Mdm2 did not change significantly. Our data suggests that leptin may be involved in accelerating follicular maturation by attenuating follicular atresia and increasing the ratio of Bcl-2/Bax.
Obstetric complications, such as severe pre-eclampsia, fetal growth restriction, abruptio placentae, or stillbirth are associated with abnormally elevated second-trimester maternal serum alpha-fetoprotein (MSAFP) and beta subunit of human chorionic gonadotrophin (betahCG). This has been attributed to placental abnormalities. Women with thrombophilias have been shown to have abnormalities of the placenta resulting in adverse pregnancy outcome in these patients. The purpose of the present study was to evaluate whether women with pregnancy complications and inherited thrombophilias have abnormally elevated second-trimester MSAFP or betahCG. Sixty-two women with pregnancy complications were tested for inherited thrombophilias several months after delivery. The thrombophilia group included 29 women with pregnancy complications and an inherited thrombophilia and the control group included 33 other patients without thrombophilia. Patients in the thrombophilia group had a higher median MoM MSAFP compared to the controls (1.337 vs. 1.086, p=0.0516). The incidence of abnormally elevated MSAFP (>2.5 MoM) was also significantly higher in the thrombophilia group compared to controls (21% vs. 3%, p=0.04). Neither the median MoM betahCG nor the incidence of abnormally elevated betahCG were significantly different between the groups. We conclude that second trimester MSAFP, but not betahCG, is abnormally elevated in patients with thrombophilia and obstetric complications.
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OBJECTIVE: To compare placental pathology between women with and without thrombophilia who had severe preeclampsia, intrauterine growth retardation, severe abruptio placentae, or stillbirth. METHODS: After delivery, 68 women with singleton pregnancies with one of the above complications were evaluated for an inherited thrombophilia: factor V Leiden, methylenetetrahydrofolate reductase and prothrombin gene mutation, and deficiencies of protein S, protein C, and antithrombin III. Thirty-two women were thrombophilic (group A), and 36 women were not (group B). There was no difference in maternal age, parity, and type of pregnancy complication. A single pathologist examined each placenta. RESULTS: The gestational age at delivery, birth weight, and placental weight were significantly lower in group A. Three parameters showed significant differences between the groups: thrombophilic women had a higher number of villous infarcts (P <.01), more multiple infarcts (P <.05), and a higher incidence of placentas with fibrinoid necrosis of decidual vessels (P <.05). CONCLUSION: Placentas of women with severe complications and thrombophilia have an increased rate of vascular lesions.
OBJECTIVES: To assess the role of diagnostic urethrocystoscopy in the evaluation of women with idiopathic detrusor instability (DI) refractory to conventional pharmacologic management. METHODS: One hundred consecutive women (mean age 62.1 +/- 15.1 years) with idiopathic DI refractory to conventional pharmacologic management were prospectively enrolled. All patients underwent a meticulous evaluation, including a detailed history, urogynecologic questionnaire, micturition diary and pad test, urinalysis and culture, physical examination, and urodynamic studies. Refractory DI was defined as the lack of clinical improvement after at least 6 months of conventional drug therapy. These patients underwent additional evaluation with diagnostic urethrocystoscopy. RESULTS: All patients had a normal urinalysis and negative cytologic findings. Diagnostic urethrocystoscopy revealed isolated bladder tuberculosis in one and transitional cell carcinoma in another. Seven other patients had bladder diverticula (only one of which was also diagnosed by sonographic examination) and 22 had mild-to-moderate bladder trabeculations. CONCLUSIONS: The absence of other alarming signs (ie, recurrent urinary tract infection, hematuria, significant residual urinary volume, positive cytologic findings, or suspicious sonographic findings) cannot confirm the lack of significant lower urinary tract abnormalities among patients with refractory DI. Diagnostic urethrocystoscopy, a simple and safe office procedure, facilitates timely diagnosis and appropriate treatment for these patients.