Search PubMed⌕ Search

Biomedical subjects

B Levin

Publications and source records attributed to B Levin.

At least 55 records · Page 3Linked to original sources
PubMed2000

Average-risk screening: is public policy compatible with individual needs?

The issue of the appropriateness of population-based screening for colorectal cancer has been much debated in the literature. The purpose of screening is to find early-stage disease among average-risk members of the population so that timely treatment may be implemented and mortality reduced. The goal of public policies regarding screening should be to facilitate this result. The adequacy of current public policy for reduction of colorectal cancer mortality is the main focus of this article.

Colorectal Neoplasms↗
PubMed1999

Using missing data techniques to explore the lack of survival effect: illustration with the CABG patch trial.

The Multicenter Automatic Defibrillator Implantation Trial (MADIT) showed a conclusive 54 per cent reduction in mortality in patients with inducible sustained monomorphic ventricular tachycardia (VT) and impaired left ventricular function who received an implantable defibrillator compared with those who did not. The Coronary Artery Bypass Graft (CABG) Patch Trial, which studied a patient population with a similar extent of left ventricular dysfunction and overall cardiovascular risk, demonstrated no mortality benefit from placement of an implantable defibrillator. All patients in the MADIT trial were 'VT inducible', while this criterion was neither required nor evaluated for entry into the CABG Patch Trial. A statistical approach to estimating with good accuracy the fraction of CABG Patch patients who were inducible at the time of their randomization from the prevalence of VT inducibility in the surviving CABG Patch Trial control population during follow-up is presented. This more generally applicable approach estimates the mixing percentage using missing data techniques. We present the mathematical and physiological basis of the assumptions underpinning the mixture model and its estimation procedure. The mixture model forms the basis for the electrophysiological substudy to the CABG Patch Trial, which directly tests the hypothesis that the difference in the frequency of inducible VT between the MADIT and CABG Patch patients populations is sufficient to account for the difference in effect on mortality.

Algorithms↗
PubMed1999

Polymorphism of glutathione S-transferase loci GSTM1 and GSTT1 and susceptibility to colorectal cancer in Egypt.

Egypt has an unusually high proportion of early-onset colorectal cancer under age 40 years. Environmental exposures and low DNA repair capacity are among the risk factors. Because GSTM1 and GSTT1 gene deficiencies may act as risk modifiers for colorectal cancer risk, we investigated the relationship between genetic polymorphism in these genes and colorectal cancer risk in Egyptians. Sixty-six patients and 55 controls were included. Genotyping for GSTM1 and GSTT1 was conducted using PCR techniques and the results were related to epidemiologic and clinical information. No overall association was observed between GSTM1 or GSTT1 null genotypes and colorectal cancer risk. However, the data suggest a possible role for GSTM1 genotype in influencing tumor site. Furthermore, GSTM1 and GSTT1 genotypes, in conjunction with gender and place of residence, may play a role in modifying disease risk. Further studies on a larger population in Egypt are needed to generalize the results of this study.

Adult↗
PubMed1999

Cell-specific targeting of a thymidine kinase/ganciclovir gene therapy system using a recombinant Sindbis virus vector.

Transfer of the herpes simplex virus type I thymidine kinase (HSV-TK) gene into tumor cells using virus-based vectors in conjunction with ganciclovir (GCV) exposure provides a potential gene therapy strategy for the treatment of cancer. The possibility of using a novel targetable Sindbis virus expression vector containing the HSV-TK gene was examined. Baby hamster kidney (BHK) cells and several human tumor cells infected with a Sindbis virus containing the HSV-TK gene showed strong expression of HSV-TK protein. Cells transduced with the HSV-TK gene exhibited increased TK activity, ranging from 3- to 20-fold over an average baseline level. The human HeLa-CD4+ cells infected with recombinant Sindbis virus containing the HSV-TK gene were sensitive to low concentrations of GCV (0.1-1 microg/ml) and the 50% growth inhibitory concentration (IC50) was 0.6 microg/ml. We also demonstrated applications of cell type-specific Sindbis virus-mediated antigen-antibody targeting of the HSV-TK/GCV system in vitro. Sindbis virus containing the HSV-TK gene packaged in a helper virus displaying the IgG-binding domain of protein A on its envelope could infect various tumor cell lines in the presence of specific antibodies that recognize antigens on their surfaces. HSV-TK-transduced tumor cell lines exhibited sensitivity to GCV. Our data suggest the potential for targeted gene therapy of the HSV-TK/GCV system using a cell type-specific recombinant Sindbis virus vector-antibody system.

Animals↗
PubMed1999

Pregnancy rates after hysteroscopic polypectomy and myomectomy in infertile women.

OBJECTIVE: To compare reproductive benefits of hysteroscopic myomectomy and polypectomy for infertility to outcomes in infertile couples with normal hysteroscopic findings. METHODS: Women with diagnoses of infertility who had hysteroscopic evaluations by a single surgeon between 1975 and 1996 were sent a routine follow-up questionnaire regarding their reproductive histories. All 92 subjects who were located responded to the questionnaire, and 78 met inclusion criteria: age under 45 years, at least 12 months of infertility, and at least 18 months of follow-up with attempts to conceive, including in vitro fertilization in women with bilateral tubal occlusion. RESULTS: Of the 78 subjects, 36 had myomectomies, 23 had polypectomies, and 19 had normal cavities. Among the three groups, there were no significant differences in age, type of infertility, length of infertility, or follow-up after the procedure. Polypectomy subjects had significantly higher pregnancy and live birth rates than women with normal cavities. Women who had myomectomies larger than 2 cm had significantly higher pregnancy and live birth rates, achieving statistical significance at a myoma size of 3 cm or greater for live births. Spontaneous abortion rates among first pregnancies after myomectomy, polypectomy, or normal study were similar: 31.5%, 27.7%, and 37.5%, respectively. CONCLUSION: Both hysteroscopic polypectomy and hysteroscopic myomectomy appeared to enhance fertility compared with infertile women with normal cavities. Despite concern that hysteroscopic resection of a large myoma might ablate a large surface area of the endometrial cavity, the reproductive benefit appears greater than the risk.

Adult↗
PubMed1999

Cancer mortality in Menofeia, Egypt: comparison with US mortality rates.

OBJECTIVES: In developing countries where cancer registries are unavailable, mortality statistics from death certification may be a practical source of cancer statistics. We aimed at describing the cancer mortality in Egypt and comparing it to that in the US. METHODS: We used the mandatory and routinely available mortality records of Menofeia province in the Nile Delta region of Egypt, which is typical of the rest of Egypt. We determined cancer mortality rates, and compared them with the Surveillance, Epidemiology, and End Results (SEER) mortality rates of the US. RESULTS: Bladder and liver cancers were the two most common causes of cancer mortality in Menofeia, Egypt. When adjusted for age the Egyptian rates were much higher than the US rates (9.5/100,000 and 8.4/100,000 for bladder and liver cancer, respectively, compared with 2.3/100,000 and 2.5/100,000 for the same cancers from SEER data). We also observed that age-specific rates for early-onset colorectal cancer under age 40 and premenopausal breast cancer were higher in Egypt than in the US. CONCLUSION: This study confirms our earlier observations about the higher proportion of early-onset colorectal cancer in Egypt, and opens the door for future studies to investigate familial clustering of cancer in Egypt.

Adolescent↗
PubMed1999

Targeted gene transfer system using a streptavidin-transforming growth factor-alpha chimeric protein.

The previously reported streptavidin-TGFalpha chimeric protein-based delivery system (Ohno and Meruelo, DNA Cell Biol. 15:401-406, 1996) could efficiently transfer protein molecules into A431 cells via the epidermal growth factor (EGF) receptor. We have modified this delivery system for the transfer of DNA. For this purpose, we have linked the chimeric protein ST-TGFalpha to DNA through biotinylated polylysine molecules. We show with this system, in the presence of the endosome-destabilizing reagent chloroquine, an average of 50-fold increase in reporter gene expression in comparison with polylysine DNA complexes alone. This gene expression is specific for EGF receptor-expressing cells and is blocked by EGF-binding molecules. These results suggest that the ST-TGFalpha biotinylated polylysine system could be used to deliver DNA to targeted cells.

Animals↗
PubMed1999

Helical computerized tomography arteriography for evaluation of live renal donors undergoing laparoscopic nephrectomy.

PURPOSE: Traditionally, live renal donors are evaluated with excretory urography and renal arteriography. Helical computerized tomography (CT) arteriography offers a less invasive alternative for demonstrating necessary anatomical information before laparoscopic allograft harvest. We evaluate the accuracy of helical CT arteriography in depicting renal vascular anatomy with an emphasis on the detection of arterial and venous anomalies. MATERIALS AND METHODS: Imaging studies were done on 175 patients according to a standard CT arteriography protocol with early arterial phase scanning (14 to 20-second delay), and 1 mm. axial and 3-dimensional maximum intensity projection reconstructions. Renal vascular anatomy was mapped with attention to aberrant arterial and venous anatomy. Intraoperative findings were correlated at laparoscopic donor nephrectomy. RESULTS: There was overall agreement between CT arteriography and laparoscopic findings in 163 cases (93%). Supernumerary renal arteries were identified in 40 cases (23%). Sensitivity, specificity and accuracy of CT arteriography for arterial anatomy were 91, 98 and 96%, respectively. Cases with less than 2 mm. accessory arteries or early branching single vessels simulating dual arteries were misdiagnosed. Venous anomalies occurred in 11 patients (6.3%). Sensitivity, specificity and accuracy of CT arteriography for venous anatomy were 65, 100, and 97%, respectively. Misdiagnoses included early venous bifurcations and supernumerary tributary veins, which were poorly opacified. CONCLUSIONS: Helical CT is highly accurate and specific for the demonstration of renal arterial anatomy. Poor opacification resulted in a lower sensitivity for venous anatomy. Overall, helical CT provides essential anatomical information, and is an alternative to standard urography and arteriography.

Adult↗
PubMed1999

Higher cerebral function and hemispheric blood flow during awake carotid artery balloon test occlusions.

OBJECTIVES: Measures capable of detecting early alterations of brain function during acute cerebral ischaemia have not been adequately defined. Internal carotid artery (ICA) test occlusions provide a well controlled environment to investigate the effects of reversible acute hemispheric hypoperfusion on brain function. A continuous time estimation task was developed that reliably demonstrated alterations in higher cerebral function before development of any deficits in elementary neurological function during ICA balloon catheter test occlusions. In the present study, we hypothesised that alterations in our behavioural task would correlate significantly with absolute level of ipsilateral CBF. METHODS: Twenty five patients underwent awake ICA test occlusions during which sustained attention and ipsilateral CBF were measured simultaneously using our time estimation task and the intracarotid 133Xe washout method. Alteration in sustained attention was correlated with CBF after occlusion using Fisher's exact test. RESULTS: Deterioration in sustained attention was significantly associated with ipsilateral CBF below 30 ml/g/min (Fisher's exact test, p=0.047). Changes in individual patients' performance on the behavioural task correlated in real time with changes occurring either at the point of occlusion or at a specific threshold of induced hypotension. Sensitivity for our behavioural test in predicting CBF was 75%; specificity 70%. CONCLUSIONS: Monitoring sustained attention during carotid balloon test occlusions seems to be a sensitive means to detect decreases in CBF as measured by 133Xe washout. Correlation between higher cerebral function and CBF can allow more detailed investigations of physiological relations between cerebral haemodynamics and brain function in human conditions of cerebral ischaemia.

Adult↗
PubMed1999

Gallbladder carcinoma.

Carcinoma of the gallbladder has an unusual geographic and demographic distribution being more common in Israel, Bolivia, Chile and in Southwestern native Americans in the United States. Chronic cholecystitis, choledochal cysts and significantly high body mass index are associated risk factors. Over 90% of gallbladder carcinomas are adenocarcinomas. Advanced local and regional disease usually is present at the time of diagnosis. P53 protein overexpression and p53 mutation may be related to increasing grade of cytologic atypia and to invasiveness. K-ras gene mutation occurs in both dysplasia and carcinomas. Ultrasonography, CT, MRI are diagnostic measures that can provide accurate staging information. Overall, the curative resection rates for gallbladder carcinoma range from 10% to 30%. During laparoscopic cholecystectomy, gallbladder cancer may be inadvertently discovered necessitating a more extensive resection. For those with unresectable disease, palliative surgical, endoscopic or radiologic bypass procedures can improve quality of life. Other approaches to the management of advanced tumors include combined radiation and chemotherapy and systemic chemotherapy.

Gallbladder Neoplasms↗
PubMed1999

An overview of preventive strategies for pancreatic cancer.

Cancer chemoprevention is defined as the use of specific chemical compounds to prevent, inhibit or reverse carcinogenesis. Chemopreventive intervention can occur throughout carcinogenesis. Many specific food components (e.g. calcium, selenium, folic acid) may also be suitable for chemopreventive use. Chemopreventive drugs are usually administered chronically and are expected to have low toxicity. A variety of mechanisms explain the actions of chemopreventive compounds including modification of carcinogen activation and cellular uptake, inhibition of aberrant signal transduction, induction of apoptosis and inhibition of angiogenesis. As our understanding of carcinogenesis has developed, more specific pharmacologic targets are being selected, e.g. retinoid receptors or cyclo-oxygenases. Definitive, large-scale placebo-controlled randomized trials are necessary to determine the clinical efficacy of chemopreventive compounds. Recent examples include the striking effectiveness of tamoxifen in reducing the risk of breast cancer in women at high risk. Conversely, beta carotene increased the risk of lung cancer in those who continued to smoke and/or who were exposed to asbestos. The future development of predictive risk models that take into account gene-environment interactions will be of considerable value in deciding on specific chemopreventive interventions in those at increased risk by virtue of life style or occupational exposures.

Diet↗