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Biomedical subjects

R Halperin

Publications and source records attributed to R Halperin.

At least 37 records · Page 2Linked to original sources

Clinical and molecular comparison between borderline serous ovarian tumors and advanced serous papillary ovarian carcinomas.

The aim of this study was to characterize the clinical and molecular markers of borderline serous ovarian tumors (BSOT), and to study their expression in the progression from benign lesions to advanced serous papillary ovarian carcinomas (SPOC). The clinical records of 20 patients with BSOT and 22 patients with SPOC were reviewed. Specimens from all these cases and from six benign ovarian serous cystadenomas were evaluated for expression of estrogen receptors (ER), progesterone receptors (PR), p53. HER-2/neu and Ki-67 by immunohistochemical techniques. The mean patient age and the age at menarche differed significantly between the compared groups of BSOT and SPOC (p=0.0006 and p=0.0014, respectively). No difference was observed comparing the other clinical parameters. The immunohistochemical analysis demonstrated a significant increase in the expression of ER (100% vs 72.7%), and a significant decrease in the immunoreactivity for p53 (0% vs 45.4%) and Ki-67 (2% vs 26.8%) in cases of BSOT compared with those of SPOC (p=0.007, p=0.0003 and p=0.012, respectively). No significant difference was demonstrated comparing the expression of PR and HER-2/neu. The immunostaining of benign ovarian serous cystadenoma specimens did not differ significantly from immunoreactivity observed in cases of BSOT. According to immunohistochemical analysis, BSOT had much more in common with benign serous tumors than with SPOC. The main difference between BSOT and SPOC was regarding the overexpression of p53 and Ki-67.

Adult↗

Expression of the p53 gene and apoptosis in gestational trophoblastic disease.

In order to understand the involvement of the p53 tumour suppressor gene in the pathogenesis of gestational trophoblastic disease (GTD), we investigated its genetic status, protein expression and its role in apoptosis in samples of complete and partial hydatidiform mole as compared with those of normal placenta. Direct sequencing of polymerase chain reaction (PCR) products of the coding and non-coding regions of the p53 gene demonstrated no mutations in any of the studied samples. Immunohistochemical studies revealed increased expression of the p53 protein predominantly in the nuclei of villous cytotrophoblasts. This over-expression of p53 was found in all samples of complete mole, in 50 per cent of partial mole samples and in about 30 per cent of normal placenta cases, although no significant difference in the staining intensity and pattern was observed. An in situ detection of DNA nicking (TUNEL) staining, demonstrating apoptosis, was also detected predominantly in villous cytotrophoblasts and in stromal areas. The per centage of apoptotic cells in all studied samples, determined by flow cytometry, demonstrated a significant increase in apoptotic cells in samples of complete and partial hydatidiform mole compared with those of normal placenta (P< 0.0003 and P< 0.004, respectively). In conclusion, the current study may provide a possible explanation to the pathogenesis of GTD, probably associated with extensive p53-dependent apoptosis to modulate excessive trophoblastic proliferation.

Apoptosis↗

Placental levels of human decidua- associated protein 200 in normal pregnancy and missed abortion.

Levels of human decidua-associated protein (hDP)200 were measured in homogenized placental tissue samples obtained from 26 induced and 24 missed abortions at 8-23 weeks of pregnancy. No significant difference in the level of placental hDP200 was observed comparing normal pregnancies and missed abortions. Moreover, no significant change in the level of placental hDP200 was demonstrated throughout normal pregnancies and those ending with missed abortions. Our results show that the level of hDP200 in placental tissue, measured by double-site ELISA, is probably incompatible with the normal continuation of pregnancy.

Abortion, Missed↗

Placental apoptosis in normal and abnormal pregnancies.

The aim of this study was to demonstrate apoptosis in the human placenta in normal and abnormal pregnancies. The percentage of apoptotic cells in placental samples was quantified by analyzing the cell cycle of nuclei stained with propidium iodide using a flow cytometer. No significant difference in the percentage of apoptotic cells was observed comparing the group of normal pregnancies (first and second trimesters) with those of missed abortions. There was also no difference in the incidence of apoptosis comparing placental samples obtained from chromosomally normal and abnormal pregnancies. Yet, there was a significant increase in the incidence of apoptosis in placental samples obtained from second and third trimesters as compared with those obtained from the first trimester (p<0.04 and p<0.01, respectively). There was also a significant increase in the incidence of placental apoptosis in the third as compared with the second trimester (p<0.03).

Abortion, Missed↗

The existence of insoluble-rheumatoid factor based immune complexes in menstrual fluid.

The aim of this study was to examine the existence of insoluble immune complexes, composed of monoclonal rheumatoid factor (human decidua-associated protein-hDP 200) in the precipitate of menstrual fluid. The identification of precipitable immune aggregates was based on immunofluorescent staining and ELISA. Both assays demonstrated the existence of rheumatoid factor, as well as immunoglobulins IgG, IgM, IgA and IgE. The quantification of immunoglobulins by ELISA demonstrated the predominance of IgG and rheumatoid factor. Furthermore, ELISA was performed to demonstrate the rheumatoid factor activity in the precipitate obtained from menstrual fluid. Thus, the rheumatoid factor, identified by monoclonal antibody DEC 21, was demonstrated to form precipitable immune complexes, which might provide a physiological mechanism to remove the unnecessary antibodies formed due to fetal allograft or intra-uterine infection.

Antigen-Antibody Complex↗

Setup reproducibility in radiation therapy for lung cancer: a comparison between T-bar and expanded foam immobilization devices.

PURPOSE: Physiologic and non-physiologic tumor motion complicates the use of tight margins in three-dimensional (3D) conformal radiotherapy. Setup reproducibility is an important non-physiologic cause of tumor motion. The objective of this study is to evaluate and compare patient setup reproducibility using the reusable T-bar and the disposable expanded foam immobilization device (EFID) in radiation therapy for lung cancer. METHODS AND MATERIALS: Two hundred forty-four portal films were taken from 16 prospectively accrued patients treated for lung cancer. Patients were treated with either a pair of anterior and posterior parallel opposing fields (POF), or a combination of POF and a three-field isocentric technique. Each patient was treated in a supine position using either the T-bar setup or EFID. Six patients were treated in both devices over their treatment courses. Field placement analysis was used to evaluate 3D setup reproducibility, by comparing positions of bony landmarks relative to the radiation field edges in digitized simulator and portal images. Anterior-posterior, lateral, and longitudinal displacements, as well as field rotations along coronal and sagittal planes were measured. Statistical analyses of variance were applied to the deviations among portal films of all patients and the subgroup treated with both immobilization methods. RESULTS: For the T-bar immobilization device, standard deviations of the setup reproducibility were 5.1, 3.7, and 5.1 mm in the anterior-posterior, lateral, and longitudinal dimensions, respectively. Rotations in the coronal plane and the sagittal plane were 0.9 degrees and 1.0 degrees, respectively. For the EFID, corresponding standard deviations of set up reproducibility were 3.6 mm, 5.3 mm, 5.4 mm, 0.7 degrees and 1.4 degrees, respectively. There was no statistically significant difference (p = 0.22) in the 3D setup reproducibility between T-bar and EFID. Subgroup analysis for the patients who were treated with both immobilization devices did not reveal a difference either. There was no consistent systematic error from simulator to treatment unit identified for either immobilization device. CONCLUSION: Although the optimal immobilization technique and patient positioning for thoracic radiotherapy have yet to be determined, this study indicates that T-bar is comparable with EFID in its setup reproducibility. In view of the inherent advantages of T-bar, it has become a standard immobilization device at our institution. The observed range of displacements in field positioning with either immobilization device implies that one cm (two standard deviations [SD] of setup error) will be a more appropriate margin to allow for setup variability in radiation therapy for lung cancer.

Equipment Design↗

The level of human decidua-associated protein (hDP) 200, identified as a monoclonal rheumatoid factor in the fallopian tube.

PROBLEM: The aim of this study was to examine whether ectopic pregnancy is associated with increased levels of human decidua-associated protein (hDP) 200, identified as a monoclonal rheumatoid factor, in the related fallopian tube as compared with normal tubes. METHOD OF STUDY: Tubal fluid samples were obtained prospectively from two groups of patients: group I, 20 patients admitted for total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH and BSO); group II, 14 women with ectopic pregnancy, undergoing unilateral salpingectomy by laparoscopy or laparotomy. hDP 200 was assayed using double-site enzyme-linked immunosorbent assay. RESULTS: Very low levels of hDP 200 were found in normal tubes, while tubes with ectopic pregnancy demonstrated significantly higher levels of tubal fluid hDP 200 (P < 0.00001). In addition, in women with ectopic pregnancy, the uterine fluid level of hDP 200 was significantly lower than the level of hDP 200 in the tube containing ectopic pregnancy (P < 0.0001). CONCLUSION: The increased level of hDP 200 (a monoclonal rheumatoid factor) in the tube containing ectopic pregnancy, as compared with uterine cavity and normal tubes, might be associated with the implantation site of the pregnancy.

Adult↗

Peritoneal fluid analysis in the differentiation of ovarian cancer and benign ovarian tumor.

PURPOSE: The aim of the study was to try to identify the biochemical markers in peritoneal fluid which might be useful in discrimination between ovarian cancer and benign ovarian tumor. METHODS: The study included 75 patients: 43 with invasive ovarian cancer, 6 with borderline ovarian cancer and 26 with benign ovarian tumor. The peritoneal fluid samples from all these patients were subjected to cytologic examination and to analysis of lactate dehydrogenase (LDH), total protein, albumin and cholesterol. In addition, peritoneal fluid to serum ratio of LDH and total protein, as well as serum CA-125 were assayed. The biochemical parameters were compared between cases of ovarian cancer and cases of benign ovarian tumor, as well as between the different histological types and stages of ovarian cancer. RESULTS: All the examined parameters demonstrated a significant difference comparing patients with ovarian cancer and those with benign ovarian tumor (p<0.001). Yet, the greatest diagnostic accuracy was achieved by measuring peritoneal fluid LDH (86%) and cholesterol (93%). Moreover, significant differences in the level of assayed parameters were found when comparing different histological types and stages of ovarian cancer. In order to further corroborate the diagnostic performance, we combined the parameters of LDH and cholesterol with cytology, thus increasing the diagnostic accuracy to 96%. CONCLUSION: The association of peritoneal fluid LDH and cholesterol may represent a primary tool for the discrimination of patients with ovarian cancer (even borderline) from those with benign ovarian tumor, particularly in the presence of negative cytology.

Adult↗

Measurement of intrauterine human decidua-associated protein 200 and diagnosis of ectopic pregnancy.

The aim of the current study was to examine whether the measurement of intrauterine human decidua-associated protein (hDP) 200 might be of clinical value in the diagnosis of ectopic pregnancy versus early missed abortion. Uterine fluid levels of hDP 200 were measured in two groups of patients: 20 women with ectopic pregnancy, diagnosed by laparoscopy, and 20 women diagnosed (after curettage) as having a missed abortion. No significant difference in hDP 200 levels was observed comparing patients with ectopic pregnancy (mean 114.0+/-58.2 mU/ml) and patients with early missed abortion (mean 222.0+/-116.0 mU/ml), although a trend towards lower levels of uterine fluid hDP 200 was noted in the group of patients presenting with tubal pregnancy. Thus, according to our data, intrauterine hDP 200 is not sufficiently discriminative to be of clinical value in the diagnosis of ectopic pregnancy.

Abortion, Missed↗

Intrauterine levels of human decidua-associated protein (hDP) 200 in normal pregnancy and missed abortion.

Levels of human decidua-associated protein (hDP) 200 were measured in amniotic fluid samples, obtained from 32 induced and 21 missed abortions at 9-20 weeks of pregnancy. A 3-fold decrease in the hDP 200 level was observed between 9 and 20 weeks of normal pregnancy. Moreover, no significant difference was observed comparing the level of hDP 200 and the pattern of its decrease in missed and induced abortions. Thus, according to our results, hDP 200, being a monoclonal rheumatoid factor, is probably not required for the continuation of normal pregnancy.

Abortion, Missed↗

Prediction of the survival of patients with advanced ovarian cancer according to a risk model based on a scoring system.

PURPOSE OF INVESTIGATION: The aim of the study was to devise a scoring system based on significantly prognostic parameters which might predict the survival time for each individual patient. METHODS: The study group included 40 patients with stage III or IV invasive ovarian cancer, operated on between 1987 and 1994. Different preoperative and intraoperative parameters were examined and their impact on survival was assessed using the Kaplan-Meier method. Survival rates were compared by the log rank test. The parameters, which have been found to be significant prognostic factors, were incorporated into the final risk model, based on a scoring system. The scores were given according to the cut-off point of each prognostic parameter. A correlation coefficient was calculated from the survival curve, representing the combined scores of individual patients versus their survival. RESULTS: From all studied parameters, only gravidity, the stage of ovarian cancer and the preoperative levels of LDH and CA-125 were demonstrated to have a significant impact on survival. On the basis of these four parameters a scoring system was devised. The scores were given considering the cut-off level of each parameter: gravidity < or = 2 versus > 2; stage of the cancer - IIIA, IIIB and stage IIIC versus stage IV; LDH level < or = 240 versus > 240 U/L; CA-125 < or = 100 versus > 100 U/ml. The average of the combined scores representing the four parameters was the final risk factor, which was plotted against the survival of each individual patient. A correlation coefficient of -0.99 was found. CONCLUSIONS: Our data suggest that the survival of each individual patient with advanced ovarian cancer could be predicted quite accurately considering our risk model based on a scoring system which incorporates four preoperative and intraoperative parameters. This scoring system needs to be validated by larger prospective trials.

Adult↗

Well-differentiated versus less-differentiated endometrial carcinoma.

The aim of this study was to compare well-differentiated (grade 1) and less-differentiated (grades 2 and 3) endometrial carcinoma, concerning clinical risk factors, presenting symptoms and operative findings. Seventy-one surgically staged endometrial carcinoma cases were reviewed and retrospectively divided according to tumor differentiation into two groups: grade 1 cases (Group I; n=40) and grade 2 and 3 cases (Group II; n=31). No difference was found between the two groups when comparing patient age, gravidity and parity, history of hypertension, diabetes or other malignancies, duration of menopause, number of patients receiving hormonal replacement therapy and histological type of tumor. There was also no difference in presenting symptoms or in duration of uterine bleeding up to the diagnosis of endometrial carcinoma. On the other hand, patients with well-differentiated tumors, as compared to patients with less-differentiated endometrial carcinoma, were significantly more obese (p<0.02), had a smaller uterus (p<0.01) and presented with less advanced stage disease (p<0.0005). The fact that the age of the patients, as well as the duration of uterine bleeding before diagnosis, was similar in both groups may indicate that more advanced cases, as in group II, represent originally a more aggressive tumor rather than progression from a well-differentiated disease. This hypothesis needs further research.

Aged↗

Peritoneal fluid lactate dehydrogenase in ovarian cancer.

In attempt to identify patients with ovarian carcinoma and differentiate them from patients with benign ovarian tumor or other gynecological malignancies, peritoneal fluid and serum lactate dehydrogenase (LDH) levels were measured in 51 patients: 15 with ovarian carcinoma, 15 with endometrial carcinoma, 4 with cervical carcinoma, and 17 with benign ovarian tumor. Peritoneal fluid and serum LDH levels in ovarian cancer patients were significantly higher than those in patients with benign ovarian tumor (P < 0.001) or other gynecological malignancies (P < 0.001 and P < 0.03, respectively). Yet, peritoneal fluid LDH demonstrated higher diagnostic sensitivity (87%) and greater diagnostic accuracy (90%) than serum LDH (60 and 77%, respectively) or serum CA-125 (73 and 83%, respectively). Comparing the histological types of ovarian cancer, serous cystadenocarcinoma presented higher peritoneal fluid LDH levels than endometrioid or mucinous cystadenocarcinoma. No difference in peritoneal fluid LDH was observed comparing different stages of ovarian cancer. The results suggest that peritoneal fluid LDH may be an efficient biochemical marker in diagnosis of ovarian cancer.

Adolescent↗

Human decidua-associated protein (hDP) 200 identified as a monoclonal rheumatoid factor is not an acute phase reactant.

PROBLEM: The role of human decidua associated protein (hDP) 200, identified as a monoclonal rheumatoid factor, has not been determined yet. This study examines if this protein, being an immunoglobulin, participates in the inflammatory processes involving the uterus. METHOD: Uterine fluid samples were obtained prospectively from two groups of women: the study group, containing 26 women with laparoscopically verified pelvic inflammatory disease (PID), and the control group, containing 34 regularly cycling, fertile women, referred to the Family Planning Clinic. Uterine fluid sampling was performed once in each patient, and the concentration of uterine fluid hDP 200 was determined by double site ELISA, by using the monoclonal antibody DEC 21. RESULTS: A statistically significant decrease in uterine fluid hDP 200 concentration was observed in women with pelvic inflammatory disease as compared to regularly cyclin fertile women (P < 0.00004). The hDP 200 levels in women with PID ranged from 10 to 1,000 mU/ml, with no difference in hDP 200 concentration among intra-uterine device (IUD) users as compared to non-users. CONCLUSION: This study supports the concept that hDP 200, identified as monoclonal rheumatoid factor existing locally in the uterus, is not an acute phase reactant but is probably involved in the reproduction process.

Abdominal Abscess↗

Low levels of human decidua-associated protein 200 in uterine fluid reflect pathological conditions of the endometrium.

Uterine fluid levels of human decidua-associated protein (hDP) 200 were measured in regularly cycling fertile women, postmenopausal women with normal endometrium and in women with endometrial hyperplasia or endometrial carcinoma. A statistically significant decrease in hDP 200 levels (p < 0.0001) was observed in postmenopausal women and in women with endometrial hyperplasia or carcinoma as compared with regularly cycling women possessing a normal endometrium. Furthermore, a significant increase in the uterine fluid hDP 200 level (p < 0.0008) was observed in women with endometrial hyperplasia following treatment with medroxyprogesterone acetate. These findings suggest that uterine fluid hDP 200 may be a useful marker for screening endometrial pathology as a result of hormonal imbalance or as a result of malignant histological differentiation, and it may also be used to monitor the response of the endometrium to progestogen treatment.

Adult↗

Identification of a rat protein similar to the human decidua-associated protein (hDP) 200.

The possibility of using the rat as an experimental model for the further research of human decidua-associated protein (hDP) 200 was examined. A rat protein similar to the hDP 200 was identified and immunoaffinity purified, using a monoclonal antibody recognizing hDP 200. The protein was named rat decidua-associated protein (rDP) 200. The abundance of rDP 200 in endometrial tissue extracts and in uterine washings was measured throughout the oestrous cycle and on consecutive days, starting the day after the rats mated until the day after the blastocyst implantation. The results indicate that the highest concentration of rDP 200 in uterine washings may be related to oestrogen control and probably to the implantation process. Further studies are needed to confirm these findings.

Animals↗

Localized and diffuse ovarian cancer: is it the same entity?

In order to confront the question whether localized and diffuse ovarian cancers are the extremes of the same disease or two different entities, we compared anamnestic, intraoperative and laboratory findings, as well as the outcome. Sixty-four patients with invasive epithelial ovarian cancer were treated in our department between 1984-1991. After excluding patients with incomplete data, 59 women were finally included in the analysis. The patients were divided retrospectively into two groups according to the extent of the disease observed during the primary surgery. Disease confined to the ovaries was defined as localized form, and any other extraovarian involvement was defined as diffuse form. Twenty patients had localized (Group I), and 39 had diffuse disease (Group II). Comparing the two groups, no difference was observed concerning patient age, the age of menarche and menopause, gravity and parity, the percentage of smoking and hypertensive women, and the histologic type of the ovarian tumor. On the other hand, significant differences were obtained concerning the positive family history of cancer in localized versus diffused disease (10% versus 41%) (p < 0.04), the size of the tumor involving the ovaries (16.2 +/- 5.4 cm versus 7.0 +/- 3.1 cm) (p < 0.0001), the unilateral as opposed to bilateral disease (p < 0.0001), the volume of ascitic fluid (p < 0.002) and the histologic grade (p < 0.02). Laboratory parameters, including CA-125, serum albumin, total protein and lactate dehydrogenase differed significantly comparing the localized and diffused disease (p < 0.04, p < 0.0001, p < 0.003, p < 0.05, respectively). The median survival rate was significantly higher (p < 0.001) in patients with localized versus diffused disease. Our results support the concept that localized and diffused forms of ovarian cancer are probably two different entities.

Adult↗