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Biomedical subjects

I Bernstein

Publications and source records attributed to I Bernstein.

At least 19 recordsLinked to original sources
PubMed2001

The clinical features of ovarian cancer in hereditary nonpolyposis colorectal cancer.

OBJECTIVE: Hereditary nonpolyposis colorectal cancer (HNPCC) is a hereditary cancer susceptibility disorder associated with a very high risk for carcinoma of the colon and an elevated risk for certain extracolonic cancers including ovarian cancer. Our aim in this study was to describe the clinicopathologic features of ovarian cancer in HNPCC family members. METHODS: . Members of the International Collaborative Group on HNPCC collected retrospective data on 80 ovarian cancer patients who were members of HNPCC families, including 31 known mutation carriers, 35 presumptive carriers (by colorectal/endometrial cancer status), and 14 at-risk family members. RESULTS: Mean age at diagnosis of ovarian cancer was 42.7. Nonepithelial tumors made up only 6.4% of the cancers, and borderline tumors comprised just 4.1% of the epithelial cancers. Among frankly malignant epithelial cases, most cancers were well or moderately differentiated, and 85% were FIGO stage I or II at diagnosis. Synchronous endometrial cancer was reported in 21.5% of cases. CONCLUSIONS: Ovarian cancer in HNPCC differs from ovarian cancer in the general population in several clinically important respects. It occurs at a markedly earlier age. It is more likely to be epithelial. If it is a frankly invasive epithelial cancer, it is more likely to be well or moderately differentiated. HNPCC patients with ovarian cancer are more likely to have a synchronous endometrial cancer than other ovarian cancer patients and are more likely to be diagnosed at an early stage.

Adult↗
PubMed1999

Regional hemodynamic adaptation during the menstrual cycle.

OBJECTIVE: To determine whether regional differences exist in uterine and systemic hemodynamic responses to the menstrual cycle, whether the hormonal environment correlates with the changes, and whether uterine artery hemodynamic adaptation depends on the side of ovulation. METHODS: Twenty nulliparas had transvaginal Doppler ultrasonographic assessment of the uterine and upper-extremity radial arteries at three time points in each of two menstrual cycles. Doppler indices (peak systolic velocity, end-diastolic velocity, time-averaged maximum velocity, resistance index [RI], and blood flow) were measured in the radial and uterine arteries. Women were examined in the menstrual (cycle day 2-3), follicular (cycle day 9-10), and luteal phases (cycle day LH surge plus 9-10). At each time, serum estradiol (E2) and progesterone were measured by radioimmunoassay. Statistical analyses were repeated-measures analysis of variance and the Fisher least significant difference procedure. RESULTS: Thirty-four nonconception ovulatory cycles were evaluated. Blood flow in each uterine artery increased significantly from a mean (+/- standard deviation) of 22.4 +/- 7.3 mL/minute in the follicular phase to 30.7 +/- 13.7 mL/minute in the luteal phase, which coincided with a reduction in the RI. The changes were independent of the side of ovulation. The radial artery did not parallel these changes (follicular blood flow of 27.2 +/- 13.9 mL/minute; luteal blood flow of 24.7 +/- 10.5 mL/minute). We did not identify any significant correlation between these changes and serum E2 or progesterone concentrations. CONCLUSION: We identified differences in the hemodynamic responses of the uterine artery compared with the radial artery during the menstrual cycle. We believe the difference indicates distinct regional control of vascular response during the menstrual cycle.

Adaptation, Physiological↗
PubMed1998

Prenatal diagnosis of the fetal Rhc genotype from peripheral maternal blood.

OBJECTIVE: To determine the fetal Rhc genotype by using the polymerase chain reaction (PCR) amplification procedure and maternal blood at the different steps of the fetal cell enrichment process. METHODS: Maternal peripheral venous blood samples were obtained from 11 pregnant women homozygous for the C antigen before amniocentesis. Three were not alloimmunized and eight were alloimmunized. The fathers were known to be heterozygous or homozygous for the c antigen by serologic testing. The mononuclear cell layer was isolated from maternal blood and flow sorted using monoclonal antibodies to CD36 or CD71 and glycophorin A. This was followed by PCR of the blood, mononuclear cells, and the sorted cells with allele-specific primers to RhCc genes. Gel electrophoresis was performed to predict fetal Rhc genotype. The fetal RhCc genotype was confirmed by serologic and DNA testing. RESULTS: All infants were positive for the Rhc gene. The positive fetal Rhc genotype was determined correctly in three of the 11 maternal blood samples without enrichment, in six of the nine mononuclear cell samples, and in seven of the eight sorted cell samples. The fetal genotype from one sorted sample was predicted to be homozygous C. One infant was determined by serology on cord blood to be negative for the c antigen, but repeated infant DNA amplification was consistent with the c genotype. CONCLUSION: Noninvasive fetal Rhc genotyping can be determined by PCR amplification of the rare fetal cells in maternal blood. These data reaffirm that enrichment of maternal blood for fetal cells is necessary to improve the sensitivity of the test.

Blood Grouping and Crossmatching↗
PubMed1997

Reduced frequency of extracolonic cancers in hereditary nonpolyposis colorectal cancer families with monoallelic hMLH1 expression.

Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant disease caused by mutations in one of at least four different DNA mismatch repair genes, hMLH1, hMSH2, hPMS1, and hPMS2. Phenotypically, HNPCC is characterized by the early onset of colorectal cancers and various extracolonic cancers. Depending on the presence or absence of extracolonic tumors, HNPCG-has been divided into two syndromes (Lynch syndrome I and Lynch syndrome II), but, so far, no correlation to distinct genotypes has been demonstrated. In this study, we present a frequent hMLH1 intron 14 founder mutation that is associated with a highly reduced frequency of extracolonic tumors. The mutation disrupts the splice donor site and silences the mutated allele. Tumors exhibited microsatellite instability, and loss of the wild-type hMLH1 allele was prevalent. We propose that the mutation results in a milder phenotype, because the mutated hMLH1 protein is prevented from exerting a dominant negative effect on the concerted action of the mismatch repair system.

Adaptor Proteins, Signal Transducing↗
PubMed1997

Hereditary non-polyposis colorectal cancer: clinical features and survival. Results from the Danish HNPCC register.

BACKGROUND: Hereditary non-polyposis colorectal cancer (HNPCC) is a dominantly inherited syndrome characterized by the development of colorectal cancer (CRC) and other carcinomas. Our aim was to evaluate tumour parameters and survival in HNPCC. METHODS: One hundred and eight Danish HNPCC patients were compared with 870 patients with sporadic colorectal cancer. RESULTS: The median age at CRC diagnosis was 41 years in the HNPCC group. HNPCC patients had significantly more carcinomas located to the right colon (68% against 49% in controls), more synchromous tumours (7% versus 1%), more metachronous CRC after 10 years (29% versus 5%), more localized carcinomas (62% versus 39%), and significantly higher crude cumulative 5-year survival (56% versus 30%). CONCLUSIONS: CRC in HNPCC behaves differently compared to sporadic cases concerning age of onset, frequency of multiple lesions, and location. The metastatic tendency is less than in sporadic CRC and the survival is better.

Adult↗
PubMed1997

Radioimmunotherapy strategies for non-Hodgkin's lymphomas.

Radioimmunotherapy offers an exciting new therapeutic modality for patients with relapsed non-Hodgkin's lymphoma; however, considerable debate exists regarding the optimal dose and administration schedule for radioimmunoconjugates. Myelosuppression has been the dose-limiting toxicity of most clinical trials employing radiolabeled antibodies, and this complication has generated both high-dose and low-dose treatment strategies. 'Low-dose' strategies are nonmyeloablative and rely upon repetitive infusions to effectively eradicate tumor masses. Trials incorporating low-dose radioimmunotherapy have documented high response rates, though the durability of these responses remains unclear. The most encouraging nonmyeloablative studies have documented objective responses in 70%-80% of patients, complete responses in 30%-50% of patients, minimal toxicity, and a median response duration of 12 months. In contrast, high-dose trials performed in conjunction with autologous hematopoietic stem cell transplantation have demonstrated objective responses in 95% of patients, complete responses in 85% of patients, with a progression-free survival of 62% and an overall survival of 93% with a median follow-up of two years. Toxicities are considerably higher than those reported with nonmyeloablative regimens, but are modest compared to conventional marrow transplant conditioning regimens incorporating total body irradiation (TBI). Ongoing trials integrating high-dose radioimmuotherapy with high-dose chemotherapy in an autologous transplantation setting are testing the hypothesis that targeted radiotherapy plus chemotherapy will provide increased efficacy and diminished toxicity as compared to nonspecific external beam TBI-containing regimens.

Antibodies, Monoclonal↗
PubMed1996

Assessment of lower urinary tract symptoms in women by a self-administered questionnaire: test-retest reliability.

A self-administered questionnaire assessing female lower urinary tract symptoms and their impact on quality of life is described and validated, on 56 females in six participating departments. The patients answered two identical questionnaires on separate occasions before treatment. Test-retest reliability of the questionnaire, correlation between the symptoms and their troublesomeness, and the reproducibility of this correlation were assessed. The percentage of mistakes in answers to each of the questions varied from 1.8% to 49.1%, mainly owing to missing answers in the item groups: appliances, sexual function and social activities. Test-retest showed a repeat frequency of 50.0%-91.0% for symptoms and 44.6%-82.1% for trouble. A highly significant positive correlation was found between symptoms and trouble, which was most pronounced for questions concerning pain and incontinence. This correlation was consistent within time. The primary validation of this questionnaire is good. Its relevance as a basis for medical priority and clinical decision making remains to be investigated.

Adolescent↗
PubMed1995

Ophthalmoscopy for congenital hypertrophy of the retinal pigment epithelium (CHRPE) in patients with sporadic colorectal carcinoma.

In order to investigate the frequency of congenital hypertrophy of the retinal pigment epithelium (CHRPE) in sporadic colorectal cancer, ophthalmoscopy was carried out in 34 patients with colorectal carcinoma without known familial disposition. CHRPE is one of the most frequent extracolonic manifestations in familial adenomatous polyposis. None of the patients showed any sign of CHRPE. It is concluded that although genetic factors are presumably of importance in the development of sporadic colorectal cancer, CHRPE cannot be used as a marker for future risk of colorectal carcinoma except in polyposis families.

Adult↗
PubMed1994

Retention of B-cell-specific monoclonal antibodies by human lymphoma cells.

The rates of endocytosis, intracellular degradation, and cell-surface shedding of 125I-labeled monoclonal antibodies (MoAbs) HD-37 (anti-CD19), B1 (anti-CD20), MB-1 (anti-CD37), BC8 (anti-CD45), and DA4-4 (anti-mu) by B-lymphoma cells were compared by cellular radioimmunoassay, ultrastructural autoradiography, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and thin layer chromatography using biopsy specimens from 12 patients with non-Hodgkin's lymphomas. 125I-BC8 was stably retained on the surface of lymphoma cells without appreciable internalization or shedding, whereas 125I-DA4-4 underwent rapid endocytosis and degradation. 125I-B1 was not internalized or degraded by tumor cells, but rapidly dissociated from the cell surface in intact form. Moderate rates of endocytosis, intracellular metabolism, and cell-surface shedding were shown by 125I-HD37 and 125I-MB-1. The 3 patients with diffuse, small cleaved-cell lymphomas internalized and degraded antibodies more slowly than did patients with other histologic subtypes. These kinetic differences may be important in the selection of MoAbs for immunotoxin and radioimmunoconjugate therapy of B-cell malignancies.

Antibodies, Monoclonal↗
PubMed1994

Post therapy imaging in high dose I-131 radioimmunotherapy patients.

The biodistribution of a trace-labeled I-131 antibody is used to predict the biodistribution of a high dose I-131 antibody for therapy. Internal radiation dose estimates derived from the trace-labeled antibody have been used to determine the I-131 doses in a phase I escalating dose therapy trial for hematologic malignancy. To confirm the hypothesis that the distribution of a trace- and high-dose labeled antibodies are similar, both trace (7-11 mCi, 259-407 MBq) and high-dose (100-800 mCi, 3700-29600 MBq) I-131 radiolabeled antibody infusion were imaged in 12 patients who were treated for leukemia or lymphoma. With specialized imaging techniques using lead attenuation sheets, clearance data from organs were obtained from serial gamma camera images. Biological clearance half times of I-131 from both trace and therapy level doses were in agreement. An exception was a patient who developed human antimouse antibody before therapy, and subsequently had rapid clearance of the therapy dose. The method was feasible, yielded reproducible results, and provided critical data for relating therapy toxicity to radiation absorbed dose estimates.

Biophysical Phenomena↗
PubMed1994

Treatment of newly diagnosed children and adolescents with acute myeloid leukemia: a Childrens Cancer Group study.

PURPOSE: The objectives of this study were to determine if the addition of etoposide, thioguanine, and dexamethasone to daunorubicin and cytarabine (five-drug regimen) during induction would improve remission induction rates and survival of children with acute myeloid leukemia (AML) when compared with the standard regimen of cytarabine and daunorubicin (7 + 3) and whether allogeneic bone marrow transplantation (BMT) or intensive chemotherapy consolidation with or without maintenance would give a superior outcome. PATIENTS AND METHODS: A total of 591 assessable children with AML entered Childrens Cancer Group (CCG) trial 213 between January 1986 and February 1989. The status of patients as of September 1, 1992 forms the basis of this report. The results were compared with previous AML studies. RESULTS: The projected survival rate of all patients at 5 years is 39% (event-free survival [EFS] rate, 31%), which is superior to that of the prior CCG study (P = .01). The induction rate was 79% for 7 + 3 and 76% for the five-drug regimen (not significant). Comparisons of BMT to chemotherapy favored BMT, but these differences do not always reach statistical significance (eg, 5-year disease-free survival [DFS] rate, 46% v 38% [P = .06] with donor available and 54% v 37% [P = .002] if treated according to protocol intent). No benefit for maintenance therapy was found and, in some comparisons, it was inferior to discontinuation of therapy (5-year survival rate, 46% v 68%, P < .01). CONCLUSION: The 5-year EFS rate of patients with AML is 31% and has improved. The five-drug induction regimen is no better than standard induction, BMT appears superior to chemotherapy, and maintenance therapy was not beneficial.

Adolescent↗
PubMed1991

Sexual activity and contraceptive use among low-income urban black adolescent females.

A modified form of Nathanson and Becker's (1983) Health Belief Model Questionnaire and other measures designed to assess cognitive processing were administered to low-income black adolescent female clients of an inner-city comprehensive health care clinic. The purpose of the study was to explore determinants of sexual activity and contraceptive use. Subjects were classified as not sexually active (n = 50), sexually active/noncontracepting (n = 20), or sexually active/contracepting (n = 72). Not sexually active subjects tended to be younger, more career motivated, to have a father at home, to be more influenced by family values, and to have more conservative attitudes regarding adolescent sexuality than did sexually active subjects. Sexually active/noncontracepting subjects tended to report fewer benefits and more barriers to the use of contraception. Level of cognitive processing did not differ among the three groups, but was at a lower-than-expected level for age. Finally, inconsistent contraceptive use was common to both sexually active groups.

Adolescent↗