Alex Rabinovich

Effects of THC on driving performance, physiological state and subjective feelings relative to alcohol

BACKGROUND The effects of marijuana or THC on driving has been tested in several studies, but usually not in conjunction with physiological and subjective responses and not in comparison to alcohol effects on all three types of measures. OBJECTIVE To assess the effects of two dosages of THC relative to alcohol on driving performance, physiological strain, and subjective feelings. METHOD We tested the subjective feelings and driving abilities after placebo, smoking two dosages of THC (13 mg and 17 mg), drinking (0.05% BAC) and 24 h after smoking the high dose THC cigarette, while monitoring physiological activity of the drugs by heart rate. Fourteen healthy students, all recreational marijuana users, participated in the study. RESULTS Both levels of THC cigarettes significantly affected the subjects in a dose-dependent manner. The moderate dose of alcohol and the low THC dose were equally detrimental to some of the driving abilities, with some differences between the two drugs. THC primarily caused elevation in physical effort and physical discomfort during the drive while alcohol tended to affect sleepiness level. After THC administration, subjects drove significantly slower than in the control condition, while after alcohol ingestion, subjects drove significantly faster than in the control condition. No THC effects were observed after 24 h on any of the measures.

Abnormal uterine bleeding as a presenting sign of metastases to the uterine corpus, cervix and vagina in a breast cancer patient on tamoxifen therapy.

Metastases to the female genital tract from extragenital cancers are uncommon. The ovaries are most often affected with the breast and gastrointestinal tract being the most common sites of the primary malignancy. Metastases to the uterus from extragenital cancers are significantly rarer than metastases to the ovaries and in the majority of cases the ovaries are also involved. A case of metastases restricted to the uterine corpus, cervix and vagina from breast carcinoma, without involvement of the ovaries, is described. The patient who had been on tamoxifen therapy presented with postmenopausal bleeding. The diagnosis of uterine metastases was established during endometrial ablation and confirmed by total abdominal hysterectomy and bilateral salpingo-oophorectomy. This case illustrates that abnormal uterine bleeding in a breast cancer patient, regardless of whether she is receiving or not receiving tamoxifen, should always alert the physician to consider the possibility of uterine metastases from breast carcinoma.

Peritoneal tuberculosis--an uncommon disease that may deceive the gynecologist.

OBJECTIVES To document women with peritoneal tuberculosis mimicking ovarian malignancy and to review pertinent literature. STUDY DESIGN The records of women with peritoneal tuberculosis who were managed at the Soroka Medical Center, Beer-Sheva, Israel between January 2000 and December 2001 were reviewed. RESULTS Four patients with peritoneal tuberculosis mimicking ovarian malignancy were encountered. Two presented with the classical symptomatology of advanced-stage ovarian carcinoma including ascites, abdominopelvic masses and elevated serum CA-125, and two presented with lower abdominal pain and adnexal mass. Laparoscopy in one patient and laparotomy in three patients revealed peritoneal tuberculosis and no malignancy. Of the three patients who had laparotomy, two underwent unnecessary extended surgery including total hysterectomy, bilateral salpingo-oophorectomy, omentectomy and bilateral pelvic lymphadenectomy, and one had conservative surgery including unilateral salpingo-oophorectomy. All patients were postoperatively treated with quadruple anti-tuberculosis chemotherapy. CONCLUSIONS Medical awareness of peritoneal tuberculosis is still lacking and many women with this disease are initially thought to have ovarian malignancy and undergo unnecessary extended surgery. Laparoscopy including biopsies seems to be a sufficient and safe method to provide diagnosis of peritoneal tuberculosis. If laparoscopy is not feasible, laparotomy should be performed. If no malignancy is detected and the diagnosis of peritoneal tuberculosis is confirmed, unnecessary extended surgery is avoided and anti-tuberculosis treatment is started.

Basal cell carcinoma of the vulva

Vulvar basal cell carcinoma (BCC) accounts for 7% of all vulvar cancers at two hospitals in the south of Israel. The purpose of this study was to investigate the clinical findings, treatment and outcome of patients with vulvar BCC treated at these institutions.

Placental site trophoblastic tumor: report of four cases and review of literature

Placental site trophoblastic tumor (PSTT) is a rare variant of gestational trophoblastic disease that originates from the implantation site intermediate trophoblast. We report four patients with PSTT and review pertinent literature. Three patients presented with disease confined to the uterus and one patient with disease extension beyond the uterus. Antecedent pregnancy was full-term pregnancy in three patients and termination of a 21-week pregnancy in one patient. Interval from the antecedent pregnancy was <1 year in three patients and 13 years in one patient. Primary treatment was simple hysterectomy in three patients and radical hysterectomy in one patient. Overall, three patients received chemotherapy; one had EP/EMA as adjuvant chemotherapy, one had EMA/CO for rising levels of serum β-hCG and one had BEP then VIP for recurrent disease. The three patients with disease confined to the uterus have remained after treatment alive and with no evidence of disease, whereas the one patient with disease extension beyond the uterus died of disease despite surgery and aggressive chemotherapy. It is concluded that disease extension beyond the uterus is the most important adverse prognostic factor. Other adverse prognostic factors are interval from antecedent pregnancy >2 years, age >40 years, and mitotic count >5 mitotic figures/10 high-power fields. Because of the relative insensitivity to chemotherapy, hysterectomy is the mainstay of treatment. EP/EMA seems to be the most effective first-line chemotherapy available to date for metastatic and relapsing PSTT

Three primary malignancies related to BRCA mutation successively occurring in a BRCA1 185delAG mutation carrier

The 185delAG and 5382insC mutations in the BRCA1 gene and the 6174delT mutation in the BRCA2 gene (the Ashkenazi mutations) have been found to be significantly more common among Jews of eastern European ancestry (1 in 40, 2.5%) in comparison to the general population (1 in 800 to 1 in 300, 0.12-0.33%). Carriers of these mutations, especially the BRCA1 185delAG mutation, have a significantly increased lifetime risk of breast and ovarian carcinoma and other carcinomas as compared to non-carriers. A case of three primary malignancies related to the BRCA1 185delAG mutation successively occurring in a carrier of this mutation, is described. The patient successively developed breast carcinoma, ovarian micropapillary serous carcinoma and peritoneal papillary serous carcinoma. Immunohistochemical staining results have indicated that these tumors are three separate primary malignancies. This case illustrates that ovarian serous borderline tumors (including micropapillary serous carcinoma) and peritoneal papillary serous carcinomas should be considered, like breast and ovarian carcinomas, tumors expressed in BRCA mutation carriers.

Squamous cell carcinoma of the vulva in the south of Israel: a study of 50 cases.

Background and Objectives: Vulvar carcinoma accounts for 4.9% of all female genital tract malignancies in the south of Israel. The most common histologic type is squamous cell carcinoma (82%). The purpose of this study was to investigate the clinical findings, treatment, and outcome of patients with vulvar squamous cell carcinoma in the south of Israel.

Expression of IL-10 in human normal and cancerous ovarian tissues and cells

IL-10 is an 18-kd polypeptide that has been shown to be secreted by multiple cell types, including T and B cells, monocytes and some human tumors. However, which cell population is responsible for the elevated IL-10 levels in the serum and ascites of ovarian cancer patients, whether ovarian carcinoma cells produce IL-10, and how IL-10 influences the development and progression of ovarian carcinoma are issues that remain unclear. The aim of our study was to examine IL-10 production and secretion by ovarian carcinoma tissues and cells, and to determine its possible role in the cell and tumor micro-environment. The mean IL-10 protein levels expressed in normal ovarian tissue homogenates were significantly higher compared to cancerous ovarian tissue (p = 0.002). Yet, the IL-10 mRNA expression was significantly higher in cancerous ovarian tissues as compared to normal tissues (p = 0.021). The IL-10 receptor mRNA expression levels of the cancerous ovarian tissue homogenates were slightly, but not significantly, higher than the normal tissues. IL-10 immunostaining revealed that in both normal and cancerous ovarian tissues, IL-10 expression could be detected mainly in epithelial cells. In normal ovarian tissues, similar levels of IL-10R were demonstrated in epithelial and stromal cells. However, in cancerous ovarian tissues, epithelial cells expressed higher levels of IL-10R than the stroma. Primary normal and cancerous ovarian cell cultures and SKOV-3 cells secreted similar amounts of IL-10 after 24 hours of incubation. Our results suggest that epithelial cells are the main source of IL-10 in the ovary. Nevertheless, the target cells for IL-10 are different in normal and cancerous ovarian cells. Thus, IL-10 and its receptor could be involved in the pathogenesis of ovarian carcinoma.

Native human autoantibodies targeting GIPC1 identify differential expression in malignant tumors of the breast and ovary

BackgroundWe have been studying the native humoral immune response to cancer and have isolated a library of fully human autoantibodies to a variety of malignancies. We previously described the isolation and characterization of two fully human monoclonal antibodies, 27.F7 and 27.B1, from breast cancer patients that target the protein known as GIPC1, an accessory PDZ-domain binding protein involved in regulation of G-protein signaling. Human monoclonal antibodies, 27.F7 and 27.B1, to GIPC1 demonstrate specific binding to malignant breast cancer tissue with no reactivity with normal breast tissue.MethodsThe current study employs cELISA, flow cytometry, Western blot analysis as well as immunocytochemistry, and immunohistochemistry. Data is analyzed statistically with the Fisher one-tail and two-tail tests for two independent samples.ResultsBy screening several other cancer cell lines with 27.F7 and 27.B1 we found consistently strong staining of other human cancer cell lines including SKOV-3 (an ovarian cancer cell line). To further clarify the association of GIPC1 with breast and ovarian cancer we carefully studied 27.F7 and 27.B1 using immunocytochemical and immunohistochemical techniques. An immunohistochemical study of normal ovarian tissue, benign, borderline and malignant ovarian serous tumors, and different types of breast cancer revealed high expression of GIPC1 protein in neoplastic cells. Interestingly, antibodies 27.F7 and 27.B1 demonstrate differential staining of borderline ovarian tumors. Examination of different types of breast cancer demonstrates that the level of GIPC1 expression depends on tumor invasiveness and displays a higher expression than in benign tumors.ConclusionThe present pilot study demonstrates that the GIPC1 protein is overexpressed in ovarian and breast cancer, which may provide an important diagnostic and prognostic marker and will constitute the basis for further study of the role that this protein plays in malignant diseases. In addition, this study suggests that human monoclonal antibodies 27.F7 and 27.B1 should be further evaluated as potential diagnostic tools.

Uterine sarcoma in the south of Israel: Study of 36 cases

Uterine sarcomas are rare, characterized by rapid clinical progression and poor prognosis, and their management has been a challenge. The purpose of this study was to investigate the clinical and histologic findings, treatment, and outcome of patients with uterine sarcoma in the south of Israel.