Biomedical subjects

U Beller

Publications and source records attributed to U Beller.

At least 73 records · Page 4Linked to original sources

PubMed1995

Primary lymphoma of the ovary. A case report and critical review of the literature.

Primary lymphoma of the ovary is an extremely rare cause of ovarian mass. Few cases have been recorded in English literature, and controversy still exists as to the existence of such an entity. We present a case whose diagnosis can be supported by rigorous diagnostic criteria--a long follow-up after surgery with only one course of adjunctive polychemotherapy. This case, together with a review of the literature, will enrich our knowledge on the issue and on the treatment of these patients.

Female↗

PubMed1994

Taxol: initial Israeli experience with a novel anticancer agent.

Taxol is a novel taxane derivative obtained from the bark of the Pacific yew, Taxus brevifolia, which has demonstrated substantial antitumor activity in early clinical trials. Intensive research efforts were necessary to overcome both supply problems and hypersensitivity reactions to the drug and thus assure its widespread use. Taxol is active in a variety of neoplasias, including advanced breast and ovarian tumors resistant to drugs such as doxorubicin and cisplatin, respectively. We report here the initial experience with taxol in these two disease entities in Israel, at three institutions within the framework of large multinational trials. These studies compared a) the use of two dose levels of taxol, and b) short, 3-h administration vs. a longer 24-h infusion of the drug. A total of 107 Israeli patients, 38 with ovarian cancer and 69 with breast cancer, were given 706 courses of taxol. Our results show that the administration of taxol at doses ranging between 135 and 175 mg/m2 is indeed feasible and that 3-h infusions are as well tolerated as longer administration. The main hematological toxicity was leukopenia, which was promptly reversible and was more pronounced both at the higher dose level and with the more prolonged infusion. Of the nonhematological side effects, the most prominent were alopecia, mild nausea and vomiting, limb paresthesias, fatigue and myalgia. Allergic reactions following routine premedication were mild and infrequent, never necessitating discontinuation of the drug. Clinically significant cardiac events did not occur. Taxol is an important addition to the anticancer chemotherapy armamentarium.

Adult↗

PubMed1994

Intrapartum bimanual tocolytic-assisted reversal of face presentation: preliminary report.

OBJECTIVE: To design and conduct a mode of vaginal delivery for mentoposterior-presenting fetuses when cesarean delivery is not possible. METHODS: Eleven orthodox Jewish parturients who refused cesarean delivery had intrapartum bimanual conversion of mentoposterior to occipitoanterior presentation, concomitant with ritodrine infusion in ten. RESULTS: Excluding the first case, in which ritodrine was not administered, the maneuver was successful and vaginal delivery was achieved. CONCLUSION: This maneuver, performed with intravenous ritodrine tocolysis, might be an alternative mode of delivery in the presence of mentoposterior presentation when cesarean delivery is not possible. More experience is needed with this technique before it is performed routinely.

Adult↗

PubMed1993

Maternal serum creatine kinase: a possible predictor of tubal pregnancy.

Tubal pregnancy remains a clinical challenge in spite of improvements in diagnostic tests and procedures. In a prospective study we evaluated the role of the serum creatine kinase as a possible marker for tubal pregnancy. Three groups of 17 patients each were included in the study: group A, documented tubal pregnancy; group B, spontaneous abortion; and group C, normal pregnancy. Serum was tested for creatine kinase in all of the patients. Creatine kinase level was > 45 IU/L in all patients with tubal pregnancy, significantly higher than the level in patients in either of the two other groups (p < 0.0001). We conclude that a high serum creatine kinase level can be an important diagnostic test in the evaluation of a suspected tubal pregnancy.

Abortion, Spontaneous↗

PubMed1993

Immunohistochemistry of phosphotyrosine residues: identification of distinct intracellular patterns in epithelial and steroidogenic tissues.

Tyrosine kinases are thought to play a major role in the control of cell growth and differentiation. Most of the work on the phosphorylated product was performed, however, on isolated proteins or cultured cell lines. To assess the overall involvement of tyrosine phosphorylation in vivo, a monoclonal antibody (MAb) against phosphotyrosine was applied to conventional histological sections of various tissues. With the immunoperoxidase staining method, two unique patterns of intracellular distribution of phosphotyrosine were identified among a large variety of normal tissues. (a) In many of the epithelia examined, a peripheral staining was observed, either at the apical aspect alone or at the entire contact region between neighboring cells. This pattern of staining seems to coincide with the distribution of a subset of cytoskeletal elements and requires pre-treatment with proteinase K. (b) In most steroidogenic tissues examined, vesicular cytoplasmic staining was evident, which seems to represent steroid-containing granules. In this case, proteolytic pretreatment is not essential and can be harmful. An extensive survey of human ovarian carcinoma biopsies failed to reveal any consistent staining pattern. These findings might indicate the involvement of tyrosine phosphorylation in basic cellular activities such as the assembly of the specialized cytoskeletal components.

Adrenal Glands↗

PubMed1993

Prophylactic effect of the open vaginal vault method in reducing febrile morbidity in abdominal hysterectomy.

In a randomized study, we evaluated the efficacy of the "open vaginal vault" method of abdominal hysterectomy, when cefonicid is administrated preoperatively, in reducing postoperative febrile morbidity. The vaginal vault was left open in 72 patients and closed in 65 patients in control groups. No significant difference in postoperative febrile morbidity was noticed in the two groups.

Cefonicid↗

PubMed1993

Serous papillary adenocarcinoma of the endometrium. A unique entity with a grave prognosis. Case report and review of the literature.

A case of Papillary Serous Adenocarcinoma of the endometrium is described. This unique variant of endometrial carcinoma was described initially only 10 years ago. The tumor has distinct pathological characteristics and a very grave prognosis. The importance of identifying this unique tumor type is related to appropriate treatment as well as to correct statistical analysis of endometrial carcinoma.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1992

Fetal hydrocephalus associated with maternal neurofibromatosis.

Neurofibromatosis (NF), an autosomal dominant inherited disorder affecting multiple organ systems, is rare among pregnant women. NF in pregnancy has been reported to be complicated by maternal hypertension, fetal intrauterine growth retardation and fetal wastage. A case of pregnancy associated with neurofibromatosis, complicated by pregnancy aggravated chronic hypertension, asymmetric intrauterine growth retardation and fetal hydrocephalus is described. Possible interrelations between those pathologies are discussed.

Female↗

PubMed1992

Onset of spontaneous labor and changes in E2 and progesterone levels--possible interrelation.

Unlike the findings in animal studies, in which a decline in progesterone levels is clearly associated with the onset of labor, investigation of progesterone levels among human parturients has resulted in controversy. This study was designed to address the issue and evaluate labor-onset related changes of estradiol-progesterone (E2-P) concentration in fetal scalp serum, umbilical vein serum and in the peripheral maternal serum. Seven women in spontaneous labor, were compared to 7 women in whom labor was induced. Our results reveal a significant decrease in the maternal serum P concentration when spontaneous labor is taking place (120.6 +/- 24.5 mg/ml verus 177.3 +/- 61.4 mg/ml, p < 0.05). Significant change in the ratio of the fetal scalp to the maternal serum E2/P ratio in women at spontaneous labor versus induced labor is also shown. We could not demonstrate any changes in the E2 levels in relation to labor. We conclude that the onset of labor in human pregnancy is most probably preceded by local changes in the levels of P and ratio of P to E2. These changes may play an important regulatory role in onset of labor.

Adult↗

PubMed1991

Phase I and pharmacologic evaluation of intraperitoneal 5-fluoro-2'-deoxyuridine.

Intraperitoneal (i.p.) 5-fluoro-2'-deoxyuridine (Floxuridine, FUdR, FdUrd) was evaluated in a phase I study at a starting level of 500 mg given on 1 day in 2 I 1.5% dialysate. Escalations within patients were allowed every other cycle. A total of 23 patients (age, 32-78 years) received 108 treatment courses. Local tolerance at all dose levels was excellent, with no cases of drug-related peritonitis being observed. Nausea and vomiting increased in severity in relation to dose and was universal at greater than 3,000 mg x 3 days. One patient each developed grade 1 mucositis as well as diarrhea at a dose of 3,000 mg x 3 days and leukopenia and thrombocytopenia at 5,000 mg x 3 days. Peritoneal fluid (PF) and plasma (PL) FdUrd profiles were monitored by an HPLC method in 13 subjects, with 7 being studied serially at 2-4 increment doses for up to 6 h. Profiles that exhibited apparent linear pharmacokinetics gave PF drug levels 2-4 logs higher than the PL counterparts, with the latter essentially declining in parallel to the former, indicating that the disposition of FdUrd from the peritoneal compartment is rate-determining. The mean terminal half-life for PF FdUrd was found to be 115 min and mean peritoneal clearance was 25 ml/min. The vast differences in drug levels and AUC found between the PF and the PL profiles suggests a high systemic clearance of FdUrd, which was confirmed in two patients receiving 2 g FdUrd by short i.v. infusion. A disproportionate increase in the plasma FdUrd levels and the corresponding AUC values was found with increasing dose, suggesting a disproportionate increase in the systemic partitioning of FdUrd when doses were escalated within a patient. Substantial levels of peritoneal 5-fluorouracil (FUra) were also detected in most of the subjects. Thus, FdUrd was found to have several desirable properties for i.p. administration: (1) a 2- to 4-log pharmacologic advantage. (2) the absence of local toxicities, and (3) a favorable antitumor spectrum and some evidence of antitumor effects in this phase I and pharmacology study. A 3,000-mg dose given in 2 1 1.5% dialysate for 3 consecutive days exhibited antitumor activity and produced no systemic toxicity except nausea and vomiting, which was controlled by antiemetics. This dose schedule is therefore recommended for phase II trials directed against small-volume disease in the peritoneal cavity, such as may be found in some stages of ovarian and gastrointestinal cancers.(ABSTRACT TRUNCATED AT 400 WORDS)

Ascitic Fluid↗

PubMed1991

Consolidation with intraperitoneal cisplatin in first-line therapy of advanced ovarian cancer.

Seventy-five patients with advanced epithelial ovarian cancer were treated with a combined modality regimen of systemic, induction chemotherapy followed by intraperitoneal therapy (IPT). All patients underwent initial surgery for staging and/or cytoreduction followed by cisplatin 20 mg/m2 intravenously (IV) for 5 days and cyclophosphamide 600 mg/m2 on day 4 every 3 to 4 weeks for two to four cycles. Patients were then evaluated for IPT and, if eligible, had an intraperitoneal (IP) catheter placed. IPT consisted of cisplatin 60 mg/m2 in 2 L on day 1 and IV cyclophosphamide 600 mg/m2 on day 2 every 3 weeks for three to six cycles. Patients who demonstrated a clinical complete response (CCR) were then referred for second-look laparotomy (SLL). Of 71 patients who completed the induction phase, 53 (75%) were eligible for IPT, and 49 patients entered the therapy phase. Toxicity of the combined modality approach was acceptable and did not differ from our previous experience using the same drugs systemically. Thirty-two of the 49 patients who completed IPT achieved a CCR, which was confirmed by SLL in 20 patients. Twenty recurrences were documented in the 32 CCR patients, 13 occurred in patients after SLL. Projected median survival of all patients is 38 months. Median survival correlated with amount of residual disease following initial surgery (23 months for bulky v 45 months for minimal residual; P less than .001) and with performance status ([PS]; 24 months for PS 2, 3 v greater than 46 months for PS O; P less than .001). Patients who presented with bulky tumors were less likely to reach the consolidation IPT phase. Incorporation of IP cisplatin into the first-line regimen for treatment of ovarian cancer does not appear to have major impact on the survival of all treated patients when compared with our historical control series. Combined IV and IPT cisplatin and cyclophosphamide is feasible with acceptable toxicity. Its impact on response and survival may be limited to only "good-prognosis" patients.

Adult↗

PubMed1990

Maintenance on extracellular matrix and expression of heparanase activity by human ovarian carcinoma cells from biopsy specimens.

A routine procedure has been developed for the isolation and maintenance in culture of human ovarian carcinoma cells derived from biopsy specimens. Cell attachment, plating efficiency and initial outgrowth were greatly improved by seeding the cells on a basement-membrane-like extracellular matrix (ECM) deposited by cultured corneal endothelial cells. These effects were most significant in serum-free conditions which markedly reduced the rate of cell attachment and growth on regular tissue culture plastic. In 60-80% of the cases and regardless of the patient's age, cells cultured on ECM in the absence of serum divided actively and formed a tightly packed epithelial cell monolayer. Fibroblast overgrowth and cell detachment often occurred on ECM in the presence of serum. Incubation of the human ovarian carcinoma cells with sulfate-labelled ECM, resulted in the release of heparan sulfate degradation fragments, 4- to 7-fold smaller than intact heparan sulfate side chains. This degradation was brought about by endoglycosidase (heparanase) activity expressed to a higher extent by cells that were first maintained in primary cultures as compared with cell aggregates taken directly from the biopsy specimen. In most cases, cells derived from metastatic tumors expressed a higher heparanase activity than cells from the primary ovarian tumor. This result corroborates previous studies, performed with cell lines, on the possible involvement of heparanase in tumor cell invasion and metastasis.

Autoradiography↗

PubMed1990

The prognostic significance of nuclear DNA content in malignant epithelial tumors of the ovary.

Recent studies have indicated that the nuclear DNA content of certain malignant neoplasms can be used as an adjunct in predicting their biologic behavior. The DNA content of 99 ovarian carcinomas was determined by flow cytometric analysis of nuclei obtained from paraffin-embedded tissue. Of the 99 tumors, 51 were diploid and 48 showed one or more aneuploid peaks. The 5-year survival for patients with diploid tumors (50%) was significantly higher than for patients with aneuploid tumors (22%) (P less than 0.01). Other factors which significantly affected survival were clinical stage (P less than 0.001), tumor pattern grade (P less than 0.01), DNA index (P less than 0.01), the presence of ascites (P less than 0.001), peritoneal carcinomatosis (P less than 0.0001), and residual tumor at second-look laparotomy (P less than 0.05). Diameter of the primary ovarian tumor, diameter of the largest peritoneal implant before debulking, and the percent S-phase had no significant correlation with survival. Of 16 patients with aneuploid tumors who underwent second-look laparotomy, nine (56%) had residual tumor, compared to six of 22 of patients with diploid tumors (27%). Of seven patients with aneuploid tumors and a negative second-look laparotomy, four (57%) died from recurrent tumor. By comparison, of 16 patients with diploid tumors and a negative second-look laparotomy, only four (25%) died from recurrent tumor. The determination of DNA ploidy in ovarian carcinomas may be used as an adjunct in predicting tumor behavior, response to chemotherapy, and late recurrence of disease.

Adult↗

PubMed1990

Phase II study of esorubicin (4'deoxydoxorubicin) in anthracycline naive patients with ovarian cancer.

Sixteen patients with metastatic ovarian cancer who had not previously been treated with anthracyclines were treated with 4'deoxydoxorubicin at a dose of 30 mg/m2 intravenously every 3 weeks. There were no clinical responses in this group of patients. Toxicities were infrequent with neutropenia and thrombocytopenia being dose limiting. Nausea and vomiting occurred in only 4 patients. We conclude that 4'deoxydoxorubicin is an inactive drug in this patient population and does not warrant further investigation in this disease.

Adult↗

PubMed1990

A cohort analysis of cervical cancer in Israeli Jewish women.

The incidence of squamous cell cervical cancer was studied in Jewish Israeli women between 1961 and 1981. The 1052 cases and the 27,832,272 women-years of observation were divided according to continent-of-origin, year-of-birth, and immigration-wave cohorts. Age-adjusted odds ratios were calculated for each cohort and compared. The incidence of cervical cancer was shown to have changed according to cohort year of birth, most significantly in women born in Europe and America. The highest risk in this group was seen in women born in 1891-1895 and 1941-1945 and the lowest in women born between 1926 and 1935. A high risk was also observed in all cohorts of North African women. There was a sharp rise in risk for women of all origins born after 1940. Immigration to Israel at a younger age was correlated with reduced risk for cervical cancer. It has been shown that epidemics of sexually transmitted diseases (STDs) are followed in time by epidemics of cervical cancer. Since there was an epidemic of STDs in Israel between 1967 and 1970, our results also suggest that there is a rise in the risk for cervical cancer in women who were sexually active during the epidemic of STDs. Because of the low rates for cervical cancer traditionally observed in Israeli women, routine screening was not done in Israel in the past. Should the relative risk for cervical cancer in women exposed during the 1967-1970 epidemic continue to be high, screening may prove worthwhile.

Adult↗

PubMed1990

Prognostic factors for malignant mixed müllerian tumors of the uterus.

This study examined factors affecting the survival of 28 consecutive patients with malignant mixed Mullerian tumors diagnosed at New York University Medical Center from 1971 through 1985. The cumulative 5-year survival for all patients was 38%. Patients with pedunculated tumors (18/25) had a significantly improved 5-year survival of 53% compared with patients having a tumor with a broad-based attachment (7/25), all of whom died within 1 year (p less than 0.01). Eleven patients whose tumors demonstrated vascular invasion had a worse prognosis compared with 14 patients without demonstrable vascular invasion (18% versus 53% 5-year survival; p less than 0.05). Interestingly, patients with pedunculated tumors persisted in having an improved survival even after correcting for vascular invasion, compared with patients having broad-based tumor attachment. Small tumor size (less than or equal to 7 cm) also proved to be a significant and independent prognostic indicator for improved survival. Advanced stage, heterologous sarcomatous elements, and deep myometrial invasion (greater than one-third invasion) tended to be associated with decreased survival, but not with statistical significance. Patient age and grade of the carcinoma element did not appear to affect survival.

Aged↗

PubMed1990

Intraperitoneal carboplatin: favorable results in women with minimal residual ovarian cancer after cisplatin therapy.

From August 1985 to November 1989 we conducted a trial of intraperitoneal (IP) carboplatin including a dose-escalation design in 25 women with advanced gynecologic malignancies. All had extensive prior therapy with cisplatin (median cumulative dose, 525 mg/m2). Carboplatin was administered IP in 2 L of 1.5% dextrose with a 4-hour dwell time every 4 weeks for six cycles at a starting dose of 200 mg/m2. Patients with reduced creatinine clearance (30 to 60 cc/min) were escalated more slowly than those with high (greater than 60 cc/min) clearance. Thrombocytopenia was dose-limiting and often more severe in patients with compromised renal function; there was no local drug toxicity. The median time of follow-up is 25 months. Complete responses (CRs) were documented in six of 23 assessable patients (26%) by repeat laparotomy, and an additional 11 patients (48%) had no disease evident by noninvasive restaging. Five of the CRs and six of the patients with no clinically evident disease have relapsed from 3 to 40 months after therapy. Six patients (26%) are alive and free of disease 8 to 47 (median, 20) months after therapy. IP carboplatin is effective against relapsed ovarian cancer, even after prior cisplatin therapy.

Adenocarcinoma↗

PubMed1989

Phase II study of carboplatin in recurrent ovarian cancer: severe hematologic toxicity in previously treated patients.

Carboplatin (CBDCA) is a second-generation cisplatin analog that has shown activity in early clinical trials. Its spectrum of toxicity is quantitatively and qualitatively different from that of the parent compound. Between November 1984 and September 1986 we conducted a phase II trial of CBDCA in 46 women with epithelial ovarian cancer. All patients had undergone at least one prior chemotherapy regimen; 41 (89%) had previously received cisplatin (mean cumulative dose, 540 mg/m2). The CBDCA dose was based on renal function and was injected i.v. once every 4 weeks. Patients were stratified on the basis of baseline creatinine clearance: those with a baseline creatinine clearance of greater than or equal to 60 ml/min received 400 mg/m2 CBDCA; those with a creatinine clearance between 30 and 60 ml/min received an initial dose calculated according to a previously published formula that corrected for renal insufficiency and projected nadir platelet counts of 75,000/mm3. Of 41 evaluable patients, 6 (15%) had an objective response [2 complete responses (CRs); 4 partial responses (PRs)]; 5 of the 6 responders had previously responded to cisplatin treatment. No responses were observed in 12 patients who had not responded to prior cisplatin therapy. Significant hematologic toxicity was seen. Of 18 patients with a creatinine clearance of greater than or equal to 60 ml/min (dose, 400 mg/m2), 6 had nadir platelet counts of less than 25,000/mm3, 4 with symptomatic bleeding. Of the 21 evaluable patients for whom the dose-modification formula was applied, 10 had nadir platelet counts of less than 75,000/mm3; 5 had counts of less than 50,000/mm3. CBDCA has activity even in patients who have previously undergone extensive cisplatin therapy; however, its toxicity is variable and thrombocytopenia is dose-limiting. We did not confirm the ability of the above-mentioned formula to calculate the CBDCA dose and accurately predict the nadir platelet count for all patients. Other factors, such as prior radiotherapy, may also be important in the dosing of CBDCA in pretreated patients.

Acute Disease↗