"Multiple primary carcinomas of the large intestine"--50 years later.
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Biomedical subjects
Publications and source records attributed to B Levin.
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We have investigated the familial aggregation of colorectal cancer and hereditary nonpolyposis colorectal cancer (HNPCC) in Egypt because of the high incidence of colorectal cancer in Egyptian children and young adults and the prevalence of consanguinity there. In a pilot study, we conducted detailed interviews with 111 Egyptian colorectal cancer patients and 111 healthy Egyptian controls about their family histories of colorectal cancer, and other cancers, consanguinity, age at diagnosis, symptoms and recurrence. Eight patients (7.2%) had one or more first- or second-degree relatives under age 40 with colorectal cancer, suggestive of HNPCC by the Amsterdam criteria. One of these families had a typical history of HNPCC, with 4 relatives having colorectal cancer in 3 generations; 3 of these relatives were younger than age 45 at colon cancer diagnosis, and other relatives had extracolonic tumors. Another 14 patients (12.6%) had a first- or second-degree relative with a family history of other neoplasms such as endometrial, urinary and hepatobiliary cancers that could also be related to HNPCC. Four patients with early-onset colon cancer and a family history of other HNPCC-related cancers reported that their parents were first-degree cousins.
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Objective: To assess the reproductive benefits of hysteroscopic myomectomy and polypectomy for infertility when compared to infertile couples with a normal cavity at hysteroscopy.Material and Methods: All patients with a diagnosis of infertility who underwent hysteroscopic evaluation by a single surgeon between 1975 and 1996 were sent a questionnaire as routine follow-up regarding their reproductive history. All 100 subjects who were located responded to the questionnaire, and 78 subjects met the inclusion criteria; age <45 years, 12 months of infertility, and 18 months of follow-up with attempts to conceive including in vitro fertilization in patients with bilateral tubal occlusion.Results: Of the 78 subjects, 36 had undergone a myomectomy, 23 a polypectomy, and 19 had a normal cavity. Among the three groups there was no significant difference in their ages, types of infertility, length of infertility, or follow-up after the procedure. Using the Cox proportional hazard model, and adjusting for age, polypectomy patients had a significantly higher pregnancy rate (RR 3.89, P <.01) and a higher live birth rate (RR 2.42, P =.06) than patients with a normal cavity. Patients who had undergone a myomectomy also had a higher pregnancy rate (RR 2.02, P =.11) and live birth rate, but this did not achieve statistical significance. Pregnancy following a hysteroscopic myomectomy was associated with a larger fibroid resection (3.15 cm vs 2.5 cm P =.05). The spontaneous abortion rate following the myomectomy, polypectomy, or a normal study was equivalent, 28.1%, 23.1%, and 29.2%, respectively.Conclusions: Both hysteroscopic polypectomy and hysteroscopic myomectomy appear to enhance fertility when compared to infertile patients with a normal cavity. Despite concern that hysteroscopic resection of a large myoma may ablate a large surface area of the endometrial cavity, patients with larger myomas were more likely to conceive following resection.
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In this study, we developed a cell-specific mRNA transfection system using streptavidin-protein A (ST-PA) fusion protein and monoclonal antibodies (mAbs). We previously reported that ST-PA fusion protein and mAb complexes can transfer certain biotinylated proteins into specific cell types. At this time, we combined an in vitro transcribed biotinylated and self-replicating Sindbis virus genomic RNA with ST-PA fusion protein and mAbs. In the presence of cationic liposomes, to prevent RNA degradation, this complex is able to transfect a reporter gene to specific cancer cells in a mAb does-dependent manner. Even in the absence of cationic liposomes, biotinylated mRNA, ST-PA fusion, and mAb complexes can transfer some types of cancer cell suspension cultures. This cell-specific transfection system is a novel method of introducing various mRNAs into cells that results in high levels of transient protein expression.
The CABG Patch Trial is testing the hypothesis that prophylactic use of implantable cardiac defibrillators (ICDs) will improve survival in high-risk coronary heart disease patients undergoing CABG surgery. The original design called for 800 patients to be randomized to ICD prophylaxis or to no therapy and followed for 2 to 6.5 years (average, 40 months) to a common termination date. Since the ICD pulse generators used in this trial lasted about 42 months, the original design required ICD replacement in many patients. At its first two meetings in 1993, the Data and Safety Monitoring Board (DSMB) formalized a plan to adjust sample size in October 1994 if the control group mortality rate was lower than expected. In June 1994, an unanticipated and unique event--a subpoena from the Office of the Inspector General (OIG)--made it impossible to replace about half of the ICD generators and threatened to shorten follow-up substantially. If follow-up had been stopped on the date originally planned, but without replacing ICDs, the average follow-up would have fallen from 40 months to about 33 months. Also, in October 1994, the control group mortality rate was found to be somewhat lower than expected. Together, the abbreviated follow-up and lower control group mortality threatened to reduce power substantially. The DSMB reviewed several options for restoring power. Because mortality rates in the first month after CABG surgery were about seven times as high as thereafter and because ICD therapy did not reduce surgical mortality (death during the first 30 days), extending the follow-up benefits power more than does increasing the sample size. However, the limit on extending follow-up was 42 months (the expected battery life of the ICD). Data from the ICD-treated group was not reviewed or considered in making the decision. After reviewing many options for restoring power, the DSMB recommended that the sample size be increased from 800 to 900 patients and that almost all patients be followed for 42 months. This recommendation extended follow-up for 2 years beyond the original termination date planned for the trial and dictated that patients close out after 42 months rather than on a common termination date.
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Molecular genetic approaches for colorectal cancer screening using stool samples have the potential to be very specific, sensitive and cost effective. K-ras oncogene mutation, observed in about 50% of the colorectal tumours, serves as an ideal target for such an approach. Several studies have shown that K-ras gene mutations present in the tumours can be detected from the stool of patients with colorectal cancer. The challenge for clinical application, however, is to develop a simple method for robust PCR amplification and a reliable assay for K-ras gene mutation detection in the stool samples.
OBJECTIVES: This study investigated whether, in a general obstetric population, exercise in pregnancy affects the timeliness of delivery. The hypothesis was that maternal exercise would not raise the risk of preterm birth. METHODS: A community cohort of 557 prenatal patients was followed up until the time of delivery. Data were collected on exercise in each trimester: none, low-moderate (< 1000 kcal [4184 kJ]/wk in energy expenditure), or heavy (> or = 1000 kcal/wk). Timely delivery was adopted as an outcome criterion. Thus, in the analysis, a term birth was treated as optimal and survival techniques were used to estimate risks for both preterm and postdates delivery. RESULTS: No association was found between low-moderate exercise and gestational length. Heavier exercise appeared to reduce, rather than raise, the risk of preterm birth. The adjusted relative risk among conditioned heavy exercisers was 0.11 (95% confidence interval = 0.02, 0.81). After term, conditioned heavy exercisers delivered faster than nonexercisers. CONCLUSIONS: The most important finding was the lack of evidence that vigorous maternal exercise is a risk factor for preterm delivery. A promising finding was that conditioned heavy exercisers have timely deliveries.
An Egyptian hospital-based pilot case-control study was conducted to investigate the relationship between the expression level of mismatch repair (MMR) genes and the risk of colorectal cancer. The relative expression of five known MMR genes, i.e., hMSH2, hMLH1, hPMS1, hPMS2, and GTBP/hMSH6, was measured by a multiplex reverse transcriptase (RT)-polymerase chain reaction (PCR) in peripheral blood lymphocytes from 31 colorectal cancer patients and 47 age- and-sex matched controls. The expression of hMSH2, GTBP/hMSH6, hPMS1 and hPMS2 tended to be lower in patients than controls, but only the difference in hPMS2 expression was statistically significant (p<0. 01). Although 50% of the cases had chemotherapy or radiotherapy within the last six months before the blood was drawn, their gene expression was not statistically different from those who had not undergone such therapies. After adjustment for age and sex, the odds ratios (OR) calculated from a logistical regression model, using the median levels of gene expression of controls as cut-off values, indicated that increased risk was associated with reduced expressions of both hPMS1 (OR = 3.97, 95% confidence interval (CI) = 1.04 to 7.65) and hPMS2 (OR = 2.86, 95% CI = 1.05 to 7.76). Although the results of this study were inconclusive because of the small sample size and use of prevalent cases, it is biologically plausible that patients with colorectal cancers may have a lower expression of MMR genes than healthy controls because malfunction of these genes has been shown in hereditary nonpolyposis colon cancer. The involvement of low hPMS2 expression in colon cancer risk seems to be unique in the Egyptian population. Further studies with newly diagnosed patients before they begin therapy will provide more convincing data about the role of MMR gene expression in the etiology of colorectal cancers in Egypt.
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Steroid psychosis, including associated cognitive changes, is infrequent with short-term low-dose GC treatment, especially if only major objectively discernible effects are assessed. With long-term or high-dose treatment, however, or if milder subjectively discernible symptoms are also assessed, the incidence may be quite high. In lupus cerebritis, the differentiation between cognitive difficulties secondary to the underlying illness, which might warrant more aggressive GC treatment, versus those secondary to GC treatment itself, which might warrant dosage reduction, may be problematic, but certain guidelines have been proposed. Although GCs are widely prescribed and represent a clinically important class of medication, their deleterious effects may also be considerable. Glucocorticoids have prominent effects on central nervous system biochemistry and electrophysiology, and recent reports suggest they make certain hippocampal neurons more vulnerable to a variety of metabolic insults. Indeed, the clinical literature reviewed here is consistent with a disruption of hippocampus-dependent memory function (perhaps in conjunction with other areas of dysfunction), although in most cases the disruption is relatively mild and, in the vast majority, if not all cases, is reversible. From a clinical prospective, it is important to discuss potential neuropsychiatric side effects with patients before prescribing GC treatment. A greater understanding of the risk factors for experiencing SP and of its underlying mechanisms will lead to more informed clinical decision making and to a greater understanding of the role exogenous, and perhaps endogenous, GCs play in human cognition and behavior.
BACKGROUND: Colorectal cancer is the second leading cause of cancer deaths in the United States. Fecal occult blood testing has become a standard screening test for large-bowel cancers in the average asymptomatic population. Performance characteristics of the test and physician and participant compliance are the 2 major elements that impact the success of screening and early detection. OBJECTIVES: To evaluate the nonhydrated Hemoccult, rehydrated Hemoccult, and Hemoccult SENSA tests (SmithKline Diagnostics Inc, Palo Alto, Calif) and to assess participant and physician compliance. METHODS: A mass community-based screening study in an urban setting. Kits were distributed by a local pharmacy and at community sites. Diagnostic tests were completed through physicians' offices and clinics. Participants were asymptomatic and aged 50 years or older. Those who tested positive were advised to follow up with a physician. RESULTS: An overall positivity rate of 16% was reported for the 8293 kits that were processed. Rehydrated Hemoccult had a positivity rate of 15%; Hemoccult SENSA, 7%; and nonhydrated Hemoccult, 5%. The positive predictive value of nonhydrated Hemoccult was 14%; rehydrated Hemoccult, 7%; and Hemoccult SENSA, 11%. Of those who tested positive, 59% had a colonoscopy or flexible sigmoidoscopy and double-contrast barium enema examination on follow-up. Recommended follow-up was more frequent for those who consulted a gastroenterologist. CONCLUSIONS: Rehydrated Hemoccult yielded a higher positivity rate and lower positive predictive value than either Hemoccult SENSA or nonhydrated Hemoccult. Hemoccult SENSA approached the positive predictive value of nonhydrated Hemoccult. Adequacy of follow-up of patients testing positive for fecal occult blood needs improvement.
Although colorectal cancer is not a common cancer in Egypt, the age distribution of the disease shows that a high proportion occurs in children and adults under 40 years of age. We reviewed the records of 1,608 colorectal cancer patients treated in 4 cancer hospitals in Egypt during a period of 3 to 10 years. The hospitals in which about 85% of all colorectal cancer cases in Egypt were seen included Egypt's 2 major cancer centers, The National Cancer Institute (NCI) in Cairo and Tanta Cancer Center (TCC) in the mid-Nile Delta region, and 2 major university hospitals, Assiut University in South Egypt and Ain Shams University in Cairo. Our review showed that patients younger than 40 years represented 35.6% of all patients in the 4 cancer hospitals, and that these rates were similar among the hospitals and for the years reviewed. The male-to-female ratio increased from 1.0 to 1.7 for the age groups ranging from 0-9 and 30-39 years, and increased from 1.0 to 1.5 for the age groups ranging from 40-49 to over 60 years. More than half of all the patients had rectal tumors, and about 90% of the cancers were adenocarcinomas; 30.6% of patients younger than 40 years, compared with 13.8% of older patients, had mucin-producing tumors. This study confirmed the occurrence of a high colorectal cancer rate in young Egyptians, and it opens the door to future epidemiologic studies to identify causes and risk factors of this disease pattern in Egypt.
Sindbis virus can infect a broad range of insect and vertebrate cell types due to the widespread distribution of the cellular receptor for the virus. The development of Sindbis virus vectors that target specific cell types could have important implications for the design of gene therapy strategies. To achieve this goal we have designed and constructed Sindbis virus particles displaying the IgG-binding domain of protein A. The protein A-envelope chimeric Sindbis virus vector has minimal infectivities against baby hamster kidney and human cell lines. When used in conjunction with monoclonal antibodies that react with cell-surface antigens, however, the protein A-envelope chimeric virus was able to infect human cell lines with high efficiency. Infection rates were 90% or higher for human lymphoblastoid cells. A variety of cells could be targeted by changing the monoclonal antibody without generating a new recombinant virus.
BACKGROUND & AIMS: Despite the high prevalence of the hyperplastic polyp, little is known about its etiology. The aim of this study was to assess the relationship between diet and other lifestyle factors and the presence of colorectal hyperplastic polyps. METHODS: Information on diet and other known or suspected risk factors for colorectal cancer or adenoma was collected among 81 subjects with hyperplastic polyps and 480 controls. RESULTS: The multivariate-adjusted odds ratio (OR) for hyperplastic polyps for individuals in the upper vs. the lower quartile was 0.30 (95% confidence interval [CI], 0.10-0.88) for dietary fiber, 0.32 (95% CI, 0.11-0.96) for dietary calcium, 0.90 (95% CI, 0.27-2.95) for total fat, and 2.02 (95% CI, 1.05-3.91) for alcohol consumption. Compared with individuals in the lower category, those in the upper category of body mass index had a higher risk for hyperplastic polyps (OR, 4.50; 95% CI, 1.84-10.97). Cigarette smoking was associated with a higher risk (OR, 1.97; 95% CI, 1.02-3.81 for > 20 pack-years vs. never), whereas an inverse association was seen for use of aspirin and other nonsteroidal anti-inflammatory drugs (OR, 0.29; 95% CI, 0.12-0.67 for once per day or more vs. never). CONCLUSIONS: Hyperplastic polyps share common lifestyle risk factors with colorectal adenomas and carcinomas.