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Biomedical subjects

Zeev Blumenfeld

Publications and source records attributed to Zeev Blumenfeld.

At least 19 recordsLinked to original sources
PubMed2006

Fertility status among women treated for aggressive non-Hodgkin's lymphoma.

In young women treated for intermediate-high-grade non-Hodgkin's lymphoma with CHOP (cyclophosphamide, adriamycin, oncovine and prednisone), there is insufficient data concerning gonadotoxicity or the need for fertility-preserving measures. The aim of the present study was to evaluate the fertility status in the first complete remission of women who were treated for aggressive non-Hodgkin's lymphoma. A cohort of 36 women with aggressive non-Hodgkin's lymphoma in first remission, who were treated in five university-affiliated hospitals in Israel, was evaluated. All women were aged younger than 40 years at diagnosis and received frontline protocols, including cyclophosphamide and adriamycin, mostly CHOP. Menstrual cycle characteristics, as well as pregnancies before the diagnosis, during treatment and in first complete remission, were evaluated. The patients' mean age at the diagnosis was 28 +/- 7 years (range 17 - 40 years). All patients were treated with chemotherapy, although 10 patients received additional radiotherapy. Follow-up time at first complete remission was 84 +/- 48 months. Before diagnosis, all patients had menstrual cycles, which were regular in 31 (86%). Three patients received gonadtropin-releasing hormone analogs, whereas nine received contraceptive pills together with cytotoxic treatment. During treatment, 18 patients (50%) had amenorrhea, six (17%) had irregular menstrual cycles, and 12 (33%) continued their regular cycles. All but two women resumed menses in the first complete remission, and these were regular in 22 (61%) patients. In 63% of patients, the menstrual cycle recovered within 3 months of the discontinuation of chemotherapy. Eighteen patients (50%) became pregnant during the first complete remission. There was no significant difference between those patients who received fertility-preserving measures versus the remainder concerning regular menstrual cycles recovery or pregnancies. The two patients who developed amenorrhea were 40 years old at the time of diagnosis. In conclusion, the rate of gonadal dysfunction is very low among young, CHOP treated, non-Hodgkin's lymphoma female patients. Fertility-preserving techniques are not needed for women aged younger than 40 years and should probably be reserved for those who are at high risk for gonadal toxicity.

Adolescent↗
PubMed2006

Evaluation of ProC Global assay in women with a history of venous thromboembolism on hormonal therapy.

The risk of thrombosis in women increases significantly during treatment with hormonal therapy (HT). The aim of this study was to evaluate ProC Global assay in women with a history of venous thromboembolism (VTE) while using HT. Protein C activation time normalized ratio (PCAT-NR) levels were significantly lower in 32 women with a history of VTE while using HT (0.72 +/- 0.1) compared with 56 healthy controls without HT, matched by age at blood sampling (0.99 +/- 0.2) and 40 healthy controls with HT, matched by age and HT at VTE event (0.94 +/- 0.2) (P < 0.001 for both). PCAT-NR lower than the cut-off level of 0.8 was found in 23/32 (72%) patients compared with 5/56 (9%) age-matched controls (OR = 26, 95%CI: 7-106, P < 0.001) and 9/40 (22.5%) of HT-matched controls (OR = 9, 95%CI: 2.7-30, P < 0.001). Any thrombophilic risk factor was found in 20/32 (62.5%) of patients compared with 12/56 (21.4%) of agematched controls (OR = 6, 95%CI: 2.1-10, P < 0.001) and 12/40 (30%) of HT-matched controls (OR = 4, 95%CI: 1.3-11.8, P = 0.006). Out of the variables that are risk factors of VTE as age, HT or thrombophilic risk factor, ProC Global assay was found in the multivariate analysis - logistic regression, as the parameter that was the most associated with patient group [Exp(B) = 15.8, 95% CI: 4.2-59.0, P < 0.001]. In conclusion, abnormal PCAT-NR is associated with VTE in women using HT. ProC Global assay may potentially serve as a diagnostic tool for evaluating the risk of VTE in women prior to administration of HT.

Adult↗
PubMed2005

Does maternal height affect triplets' birth weight?

BACKGROUND: In cases of triplet gestation where patients are reluctant to undergo multifetal pregnancy reduction, it would be helpful to identify predictive factors regarding poor or better outcomes. One such possible factor may be maternal height, which is possibly predictive of gestational age and neonatal birth weight. MATERIAL/METHODS: To examine such a possible association, we have retrospectively evaluated 102 triplet gestations. Maternal height and BMI were compared and correlated to neonatal weight, week of delivery, NICU hospitalization duration, and other parameters of pregnancy outcome. RESULTS: Mothers taller than 165 cm gave birth to significantly heavier neonates than shorter parturients delivered of triplets. Individual and mean total triplet neonatal weights were positively correlated to maternal height. There was no significant correlation between preconceptional maternal BMI and triplet neonatal weight and week of delivery, NICU hospitalization or any other parameter. CONCLUSIONS: The taller patient (>165 cm) may be at a significantly lower risk of very low birth weight neonates and very premature delivery as compared to the shorter patient (< 165 cm). Therefore, the factor of maternal height may be taken into consideration in multiple gestation pregnancy consultations. Smaller mothers should never receive more than two embryos in IVF programs to reduce the risk of triplets almost completely.

Birth Weight↗
PubMed2005

Fertility and ovarian function are preserved in women treated with an intensified regimen of cyclophosphamide, adriamycin, vincristine and prednisone (Mega-CHOP) for non-Hodgkin lymphoma.

BACKGROUND: Intensive chemotherapy is widely used to improve the outcome of aggressive non-Hodgkin lymphoma (NHL). Since these regimens may cause premature ovarian failure (POF), the ovarian function was studied in 13 consecutive women aged < or =40 years, treated with four cycles of intensified CHOP (cyclophosphamide 2000-3000 mg/m2 per cycle doxorubicin 50 mg/m2, vincristine 1.4 mg/m2 (maximum 2 mg) and prednisone 100 mg/day were given every 3 weeks). METHODS: Patients aged <60 years with aggressive NHL were eligible for participating in a non-randomized phase II study if they had stage I, II, B, bulky, or stages III, IV disease with the age-adjusted international prognostic index of low-intermediate to high-risk score. Seven patients were concomitantly treated with D-TRP6-GnRH analogue (Decapeptyl; Ferring, Germany) for minimizing gonadal toxicity. RESULTS: With a median follow-up of 70 months only one patient had POF, while 12 patients retained fertility and eight conceived spontaneously delivering 12 healthy babies. CONCLUSION: It appears that high-dose cyclophosphamide does not affect the ovarian function or fertility in patients exposed to this medication during four consecutive cycles of intensified CHOP.

Adult↗
PubMed2005

Modulation of systemic hemostatic parameters by enoxaparin during gestation in women with thrombophilia and pregnancy loss.

Recurrent pregnancy loss (PL) is associated with maternal thrombophilia and prophylaxis with low molecular weight heparin (LMWH) can improve pregnancy outcome in this setting. The aim of this study was to investigate the modulation of systemic hemostatic parameters by enoxaparin in women with recurrent PL and to evaluate plasmatic parameters that would potentially enable monitoring LMWH prophylaxis effect during pregnancy. Study group included 87 women with thrombophilia and PL treated with enoxaparin 40 mg daily vs. 40 mg twice daily. The control group comprised 40 women with normal pregnancies. Blood samples have been collected throughout the period starting at 5-10 weeks of gestation until 6-10 weeks postpartum. The determined plasmatic markers included: anti-Xa activity, total and free tissue factor pathway inhibitor (TFPI), D-dimer, prothrombin fragment 1+2 (PT1+2), activated protein C resistance (APC-SR) and free protein S. Successful pregnancy outcome was recorded in 70 (80.5%) women treated with enoxaparin, without correlation to enoxaparin dosage. Seventeen women (19.5%) had pregnancy loss at 16+/-7 (6-32) weeks of gestation. Anti-Xa levels at 10-15 weeks of gestation were higher (0.39+/-0.38 u/ml) in the successful pregnancy outcome group compared to the abortion group (0.22+/-0.2 u/ml). Prophylactic anti-Xa activity levels (0.28+/-0.13 u/ml) were documented from 15 weeks of gestation until delivery in the successful pregnancy outcome group. Significant increase in anti-Xa, total TFPI and free TFPI levels (P<0.001) was achieved after beginning of LMWH prophylaxis in successful pregnancy outcome group but not in the abortion group. D-dimer and PT1+2 levels appeared to be significantly increased while APC-SR and free protein S levels gradually decreased during pregnancy, with no difference between study groups. These results suggest that LMWH prophylaxis during pregnancy enables modulation of systemic hemostatic parameters via inhibition of factor Xa and increase in plasmatic total and free TFPI levels.

Abortion, Habitual↗
PubMed2004

Hormonal suppressive therapy for endometriosis may not improve patient health.

OBJECTIVE: To critically examine the possible association between hormonal treatment of endometriosis and ovarian cancer. RESULT(S): The malignant potential of endometriosis has been suggested by several clinical studies. Although controversial, ovarian carcinoma of the endometrioid and clear cell subtypes has been associated with endometriosis, particularly among subjects with a longstanding disease. Furthermore, a significantly higher frequency of endometriosis has been found in patients undergoing surgery for endometrioid, clear cell, and mixed subtypes of ovarian carcinoma, as compared with the other subtypes. Changes in the genomic material in endometriotic implants were observed by many investigators in chromosomes 1, 5, 6, 7, 16, and 22 by several methods (fluorescent in situ hybridization, comparative genomic hybridization, and others). Because hormonal ablative treatments may suppress the normal, eukaryotic cells more than the aneuploid cells bearing chromosomal aberrations, it may increase the rate of dyskaryotic cells in the endometriotic implants, possibly augmenting the risk of malignant transformation. A recent published association between Danazol and ovarian cancer suggests that such a theoretical risk may occur. CONCLUSION(S): The hormonal ablative treatment of endometriosis may increase the risk of malignant transformation in the endometriotic implants by causing a negative selection and increasing the rate of dyskaryosis and loss of heterozygosity.

Danazol↗
PubMed2003

Assessment of uterine placental circulation in thrombophilic women.

Thrombophilia is associated with several complications of pregnancy including first and second trimester fetal loss, intrauterine fetal death, intrauterine growth restriction, preeclampsia, and placental abruption. Few studies have documented thrombotic lesions observed on the pathologic examination of the placenta in women with severe pregnancy complications. Moreover, a significantly higher rate of factor V Leiden and prothrombin G20210A gene mutations have been found in placentas with thrombotic events compared with normal placentas. In addition, clinical studies have been performed, using Doppler ultrasonography, to assess the uterine placental circulation in women with thrombophilia. Doppler studies of the umbilical artery in cases of intrauterine growth retardation have shown a high systolic to diastolic ratio (S/D) ratio, suggesting an increase in the resistance of the placental small vessels. When these placental vessels were examined after delivery, significant differences were found in comparison with placental vessels of normal pregnancies. Most of the Doppler studies of the umbilical and uterine arteries in pregnancies with thrombophilia were performed in women with antiphospholipid antibodies. The other pathologic conditions associated with thrombophilia and complications of pregnancy were published only recently. These few studies have demonstrated abnormal umbilical and uterine arteries blood flow in complicated pregnancies. Finally, few Doppler studies also suggest improved uterine placental circulation when women with thrombophilia received thromboprophylaxis.

Blood Circulation↗
PubMed2003

Gynaecologic concerns for young women exposed to gonadotoxic chemotherapy.

PURPOSE OF REVIEW: Due to the improved long-term survival of adolescents and young women with systemic malignancies such as lymphomas and leukaemia undergoing gonadotoxic chemotherapy, preservation of future fertility has been the focus of recent ubiquitous interest. This review summarizes, in brief, the recent progress in the various attempts to prevent premature ovarian failure in these young women with unconsumed fertility potential. RECENT FINDINGS: The investigational endeavours of ovarian cryopreservation await the clinical experience of auto- or xenotransplantation, or in-vitro maturation of thawed primordial follicles, and in-vitro fertilization. Although promising, this procedure is not available yet. Moreover, the risk of possible reimplantation of malignant stem cells with the thawed cryopreserved ovary has been highlighted following experimental animal observations. The gonadotropin-releasing hormone agonist has been efficient in primates in a prospective study, and in young women in several nonrandomized series. The disruption of the acid sphingomyelinase gene, or sphingosine-1-phosphate, in rodents can prevent follicle destruction by ionizing radiation, possibly indicating in-vivo protection in cancer patients at risk of iatrogenic sterilization. SUMMARY: The recent enormous scientific advance lends hope that the future may hold answers to the questions regarding safety and efficiency of oocyte, follicle, or ovarian tissue cryopreservation, and the most efficient means of using the thawed tissue - auto-, hetero-, or xenotransplantation versus IVM on the one hand, and in-vivo pharmacological attempts to minimize follicle depletion by gonadotropin-releasing hormone agonist or other modalities on the other hand. Until then, a combination of all the clinically available modalities should be offered to these young women with unconsumed fertility potential who face gonadotoxic therapy.

Adolescent↗
PubMed2003

Clinical and biological characterization of macroprolactinemia with and without prolactin-IgG complexes.

OBJECTIVE: Macroprolactinemia, which can be detected by a polyethylene glycol (PEG) precipitation test, is a clinically and biologically heterogeneous condition. In this study, we analyzed whether the clinical presentation, the hormonal findings and the in vitro lactogenic activity differed between macroprolactinemic patients with and without circulating prolactin (PRL)-IgG complexes. DESIGN: Clinical data were reviewed and additional hormonal studies were performed in 50 hyperprolactinemic patients with macroprolactinemia. METHODS: Macroprolactinemia was identified by a PRL recovery after PEG precipitation of <50%, as measured by an automated commercial immunoassay system and circulating PRL-IgG complexes by an abnormal PRL binding to anti-IgG agarose. RESULTS: PRL-IgG complexes were found in 46 patients. The origin of hyperprolactinemia in these 46 patients was idiopathic in 33 patients, while a pituitary lesion or stalk magnetic resonance imaging or computed tomography scan was detected in 13 patients found compression. Galactorrhea was found in 11 of these 46 patients, while this condition was present in three of the four patients without circulating PRL-IgG complexes. The median free PRL concentration was significantly lower in patients with PRL-IgG complexes than in the group without complexes (243 vs 969 mIU/l; P<0.005), whereas median total PRL immunoreactivity and median PRL bioactivity in the Nb2 assay were not significantly different. In patients with circulating PRL-IgG complexes, Nb2 bioassay results correlated significantly with total PRL immunoreactivity (r=0.64; P<0.0001), but not with free PRL results (r=0.24; P<0.17). CONCLUSIONS: These results indicate that PRL-IgG complexes (i) account for most cases of macroprolactinemia--as identified by PEG precipitation--in hyperprolactinemic patients presenting with a variety of diagnoses, (ii) are not associated with a specific clinical presentation, (iii) can be found in patients with diverse pituitary pathologies, and (iv) possess an in vitro lactogenic activity in the Nb2 bioassay in relation to their immunoreactivity.

Adolescent↗
PubMed2002

Effect of sera from women with systemic lupus erythematosus or antiphospholipid syndrome and recurrent abortions on human placental explants in culture.

BACKGROUND: Systemic lupus erythematosus (SLE) with or without evidence of antiphospholipid antibodies (aPA) and antiphospholipid syndrome (APS) is associated with a high rate of spontaneous abortions. The placenta is thought to be the site of pathological damage in many of these abortions. To test this hypothesis, we studied the effects of sera obtained from women with SLE with or without treatment on human placental explants in culture. METHODS: We cultured 5.5- to 7.5-week-old human placental explants in a culture medium containing F-12 DMEM and 10% FCS or in 90% human serum obtained from nonpregnant women with SLE prior to or after treatment. Culture was carried out for 96 hr. At the end of the culture period, we studied the secretion of the placental hormones estrogen (E2), progesterone (PGN), and human chorionic gonadotropin (hCG). In addition, we studied the proliferation rate (using PCNA staining) and the rate of apoptosis (using ApoTag) of the trophoblastic cells. RESULTS: Placentae grew better in normal human serum than in a chemically defined medium of F-12 DMEM and 10% FCS. Enhanced growth and higher secretion rates for hCG and estradiol (E2) were manifested in placentae cultured in control sera with no change in PGN secretion. Secretion rates of hCG and PGN (but not of E2 in the treated group) by placental explants were similar to that of controls. However, the serum levels prior to culture were not measured. Further, explants in serum from untreated women with SLE produced a significant decrease in the proliferation rate of the trophoblastic cells and an increase of apoptosis. Treatment significantly reduced the apoptotic rate and increased cell proliferation, but the cell proliferation rate was still lower than that noted in controls. CONCLUSIONS: We conclude that sera from women with SLE may directly damage the developing placenta reducing proliferation and enhancing apoptosis. Successful treatment of the women reduces that damage.

Abortion, Habitual↗
PubMed2002

Thrombophilia is common in women with idiopathic pregnancy loss and is associated with late pregnancy wastage.

OBJECTIVE: To describe the characteristics of thrombophilia in women with idiopathic pregnancy loss. DESIGN: Prospective observational study. SETTING: Tertiary referral center in a teaching academic hospital. PATIENT(S): One hundred forty-five patients with repeated pregnancy loss and 145 matched controls. INTERVENTION(S): Prospective assessment of thrombophilia in patients and controls. MAIN OUTCOME MEASURE(S): Prevalence of activated protein C (APC) resistance, protein C, protein S, and antithrombin III deficiencies, antiphospholipid antibodies, factor V Leiden, factor II G20210A, and MTHFR C677T mutations. RESULT(S): At least one thrombophilic defect was found in 66% of study group patients compared with 28% in control group patients. Combined thrombophilic defects were documented in 21% of women with pregnancy loss compared with 5.5% of control patients. Late pregnancy wastage occurred more frequently in women with thrombophilia compared with women without thrombophilia (160/429 [37%] vs. 39/162 [24%], respectively). APC resistance was documented in 39% of women with pregnancy loss compared with 3% of the control patients. APC resistance without factor V Leiden mutation was documented in 18% of women with pregnancy loss compared with none of the controls. While factor V Leiden mutation was more common in women with pregnancy loss (25% vs. 7.6%), factor II G20210A and homozygosity for MTHFR C677T contributed to pregnancy loss only in the presence of other thrombophilia. CONCLUSION(S): Thrombophilia was found in the majority (66%) of women with idiopathic pregnancy loss. APC resistance with or without factor V Leiden mutation is the most common thrombophilic defect, and combined thrombophilia is a frequent finding in women with pregnancy loss. Thrombophilia is associated with increased frequency of late pregnancy wastage.

Abortion, Habitual↗