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Biomedical subjects

E Russek-Cohen

Publications and source records attributed to E Russek-Cohen.

At least 37 records · Page 2Linked to original sources

Evaluating treatments when a gender by treatment interaction may exist.

We propose a two-stage procedure for investigating whether males and females respond differently to treatment. The size of the first stage is based on the assumption of homogeneity of treatment effects across genders. Using stage I, we test for a gender by treatment interaction. If non-significant, we compute an overall average treatment effect and terminate the study. If we find an apparent interaction at the end of the first stage, we consider each gender separately. Because we now need to estimate treatment effects separately for each gender, we may have a need to collect additional information in a second stage. We consider the performance of our procedure for a normally distributed endpoint as well as for a survival model.

Colonic Neoplasms↗

Selecting the best dose when a monotonic dose-response relation exists.

We propose a method for selecting the best treatment when a monotonic dose-response relationship exists. Because of side effects associated with higher doses, the highest dose may not be the optimum, particularly when a lower dose gives a similar response. Rather than assume a particular functional relationship of dose to response, we use isotonic regression techniques. We consider the case of three treatment levels, which is applicable to many clinical trials. The lowest treatment level may represent a placebo or no treatment control. While we focus primarily on Bernoulli response variables, we also discuss a model for normally distributed data. We suggest a two-stage procedure that we have investigated via simulation.

Clinical Trials, Phase II as Topic↗

Supplement use, other dietary and demographic variables, and serum vitamin C in NHANES II.

OBJECTIVE: Our objective was to evaluate the effect of regular use of nutritional supplements on serum vitamin C levels in a multivariable regression model, taking into account other dietary and demographic variables which may affect nutritional status. METHODS: We analyzed NHANES II data for subjects age 3 to 74. Analysis was limited to regular supplement users and nonusers, excluding irregular users. Multivariable regression analysis was performed with SUDAAN, incorporating sample weights and accounting for the complex survey design. RESULTS: Regular supplement users had substantially higher serum vitamin C levels than nonusers (p < 0.001). The magnitude of the effect of supplement use on serum vitamin C was 0.23-0.33 mg/dL in children and teens, and 0.36-0.46 mg/dL in adults. In adults who smoked, bottom quartile vitamin C levels were 0.3 mg/dL in men and 0.4 mg/dL in women who did not use supplements, compared to 0.9 and 1.1 mg/dL in regular supplement users. There was a significant interaction of smoking and supplement use in men (p < 0.001). CONCLUSION: Regular supplement use has a strong impact on serum vitamin C levels, independent of other dietary and demographic characteristics of supplement users which may favor improved nutritional status.

Adolescent↗

Methionine uptake and cytopathogenicity of viable but nonculturable Shigella dysenteriae type 1.

A pathogenic strain of Shigella dysenteriae type 1 was selected for study to elucidate the physiology and potential pathogenicity of organisms in the viable but nonculturable (VBNC) state in the environment. Studies in our laboratory have shown that S. dysenteriae type 1 survives in laboratory microcosms in the VBNC state for long periods of time, i.e., more than 6 months. VBNC cells of S. dysenteriae type 1 were found to retain cytopathogenicity for cultured HeLa cells. To determine whether VBNC S. dysenteriae type 1 expressed protein after loss of culturability, 35S-labelled methionine was added to suspensions of VBNC cells. Total cellular proteins were extracted and examined by autoradiography. Results indicate that VBNC S. dysenteriae type 1 is capable of both active uptake of methionine and incorporation of methionine into protein. Amino acid uptake and protein synthesis substantiate the viability of cells of S. dysenteriae type 1 in the VBNC state, i.e., although the cells are unable to be cultured on laboratory media by standard bacteriological methods, the cells remain metabolically active. Furthermore, VBNC cells of S. dysenteriae type 1 may pose a potential public health hazard that has not yet been recognized.

Biological Transport, Active↗

Qualitative interactions in multifactor studies.

In clinical trials qualitative interaction or crossover interaction is said to occur when one treatment is superior for some sets of patients and the alternative treatment is superior for other subsets. Here we propose a definition of no qualitative interaction with respect to a single continuous covariate which implies that one treatment is superior to the other treatment over a prespecified range of the covariate. Further, in studies involving patients cross-classified by two or more prognostic factors, we define a marginal qualitative interaction with respect to a treatment factor and a prognostic factor by averaging in some sense over the remaining prognostic factors. In some situations, the methodology of Gail and Simon (1985, Biometrics 41, 361-372) is shown to be appropriate. Their procedure assumes independent estimates of treatment effect for each subset of patients and this may not be appropriate for the generalizations we propose. Therefore, we generalize the procedure of Gail and Simon to the case of two correlated estimates of treatment effect, providing a table of critical values. Results for one-sided tests for the case of J correlated estimates are also obtained. We also present an example illustrating our procedure.

Clinical Trials as Topic↗

Statistical model to determine the relationship of response and survival in patients with advanced ovarian cancer treated with chemotherapy.

BACKGROUND: A statistically appropriate analysis of the association between survival and response measures in patients with ovarian cancer could help to define the role of response rate in planning, monitoring, and interpreting the results of clinical trials. PURPOSE: This study was designed to investigate the relationship between antitumor response determined by clinical or pathological means and survival in patients with advanced ovarian cancer with no previous treatment. We focused on avoiding the limitations of the usual approach of comparing durations of survival for patients responding to therapy with those for nonresponders. METHODS: A new meta-analytic statistical model we developed was used to analyze data from 26 randomized clinical trials published between 1975 and 1989. Our model incorporates intra-study and inter-study sources of variability in the estimates of response and survival. The study also addresses the methodological problems of evaluating response as a surrogate end point and the relevance of this association to clinical decision making and the design of clinical trials. RESULTS: For 13 studies in which response was pathologically assessed, an improvement in surgically documented complete response rate was associated with an increase in median survival. A similar but apparently smaller effect was found for the association between objective clinical response and median survival in the 25 studies reporting these data. CONCLUSIONS: These results suggest that therapeutic measures must produce large improvements in clinical response rates to achieve meaningful effects on median survival. Improvement in surgically documented complete response rate appears to be more strongly associated with increased median survival and, hence, might be used for interim monitoring in clinical trials, but the role of second-look procedures in clinical management is controversial.

Antineoplastic Combined Chemotherapy Protocols↗

Distribution of viruses in the Chesapeake Bay.

High virus counts were found in water samples collected from the Chesapeake Bay. Viruses were enumerated by ultracentrifugation of water samples onto grids which were visualized by transmission electron microscopy. Virus counts in September 1990, April 1991, June 1991, August 1991, and October 1991 ranged between 2.6 x 10(6) and 1.4 x 10(8) viruses ml-1 with a mean of 2.5 x 10(7) viruses ml-1. Virus counts were usually at least three times higher than direct bacterial counts in corresponding samples. Virus counts in August and October were significantly higher than at the other sampling times, whereas bacterial counts were significantly lower at that time, yielding mean virus-to-bacterium ratios of 12.6 and 25.6, respectively. From analysis of morphology of the virus particles, it is concluded that a large proportion of the viruses are bacteriophages. The high virus counts obtained in this study suggest that viruses may be an important factor affecting bacterial populations in the Chesapeake Bay, with implications for gene transfer in natural aquatic bacterial populations and release of genetically engineered microorganisms to estuarine and coastal environments.

Bacteria↗

Detection of Vibrio cholerae O1 in the aquatic environment by fluorescent-monoclonal antibody and culture methods.

Vibrio cholerae O1 in plankton samples collected from ponds and rivers between February 1987 and January 1990 in Matlab, Bangladesh, was detected by the fluorescent-monoclonal antibody (FA) technique. Samples were collected at sites which were monitored fortnightly (fixed sites) as well as at sites that were part of a case-control study. FA results were compared with those obtained by conventional culture methods (CM). A total of 876 samples were collected; V. cholerae O1 was detected in 563 samples (64.27%) by the FA method and in 3 samples (0.34%) by CM. Of the fixed-site plankton samples, 439 (63.62%) were positive by FA and none were positive by CM. Of the 93 case sites sampled on the day after the occurrence of a case of cholera, 73 (78.49%) were positive for V. cholerae O1 by FA and 3 (3.2%) were positive by CM. In comparison, of the 93 first-day sample collections at control sites at the time a case of cholera occurred, only 51 (54.83%) were positive by FA and none were positive by CM. From the data, it is concluded that V. cholerae O1 is present throughout the year in the ponds and rivers of Bangladesh that were examined in this study and that V. cholerae can be detected by FA but not always by CM. The FA procedure was found to be very useful in detecting V. cholerae in plankton, with which it was associated and often occurred in large numbers in the nonculturable stage. Thus, studies investigating the significance of the role of environmental factors in the epidemiology of cholera can be performed effectively by using FA. Such studies are in progress.

Animals↗

Lower vertebral bone density in male long distance runners.

Bone density in 13 male long distance runners (28.7 +/- 1.2 yr, 67.6 +/- 2.0 kg) and 11 male nonrunners (26.8 +/- 1.3 yr, 71.0 +/- 2.2 kg) was compared. Bone was measured at the lumbar spine and mid-tibia using dual photon absorptiometry and at the mid-radius using single photon absorptiometry. Runners (mean weekly training 92.2 +/- 6.3 km) had significantly lower (P less than 0.05) vertebral bone mineral density (1.12 +/- 0.03 g.cm-2) than nonrunners (1.24 +/- 0.04 g.cm-2). Tibial and radial bone mineral density did not differ between the groups. Daily calcium intake for runners (1,373 +/- 486 mg) and nonrunners (1,267 +/- 236 mg) exceeded the RDA. The results of this study suggest that long distance running may lead to decreased vertebral bone mineral density. The hormonal changes that occur with endurance training may contribute to this decrease.

Adult↗

Serologic incidence of Cryptosporidium in Delmarva broiler flocks.

Banked serum samples collected from an industry-wide serologic survey of eighteen Delmarva broiler flocks conducted in 1985 were evaluated for the presence of Cryptosporidium- specific antibodies in an indirect enzyme-linked immunosorbent assay (ELISA). Evaluation of sera collected at 49-days posthatch showed that 38% of the broiler flocks were serologically positive, whereas 50% of samples obtained from flocks at 63-days during an extended growout were positive. From a performance standpoint, the top nine flocks in the study were essentially negative at the 49-day sampling. In order to more firmly establish the serologic prevalence of Cryptosporidium in Delmarva broiler flocks, a second serologic survey was conducted early in 1987. In this study, an estimated 22% of the 454 broiler flocks sampled at approximately 49 days of age were positive for Cryptosporidium. The negative Cryptosporidium serology in the top 25% of these flocks was associated with better performance, but positive Cryptosporidium serology was not clearly correlated with poor performance. Remarkable differences between Cryptosporidium serologic exposure rates of the growout companies were observed, with some companies having exposure rates as high as 40%, and others rates of less than 3%.

Animals↗

Bovine placental prostaglandin synthesis in vitro as it relates to placental separation.

Bovine placentomes were collected during late gestation, prepartum and immediately postpartum. Postpartum tissues were collected prior to fetal membrane separation. Maternal and fetal placentomal components each were examined for their ability to synthesize prostaglandins (PG's) from arachidonic acid (AA) and metabolize PGF2 alpha and PGE2 in vitro. Maternal placental PG synthesis was lower (P less than .05) than that for fetal placental tissue and was primarily PGF's. Fetal placental PG synthesis increased (P less than .05) prepartum and was primarily PGE's. Fetal placental PGE production predominated (P less than .05) postpartum if the fetal membranes were retained, while PGF production predominated (P less than .05) if the membranes were released. Maternal and fetal placental tissues were unable to convert PGE2 to PGF2 alpha (P greater than .05). Postpartum fetal placental tissue was able to convert PGF2 alpha to PGE2 (P less than .05) if the fetal membranes were retained but not if the membranes were released (P greater than .05). These results indicate that fetal placental synthesis of PGF's may be related to placental membrane separation. The shift in fetal placental PG production from PGE's to PGF's may be due to a cessation of the ability of released fetal tissue to convert PGF2 alpha to PGE2.

Animals↗

Simultaneous measures of rates of ruminal digestion and passage of feeds for prediction of ruminal nitrogen and dry matter digestion in lactating dairy cows.

Three ruminal-cannulated Holstein cows in early lactation were fed three diets, each containing different energy and protein supplements in two consecutive 3 X 3 Latin squares. Each supplement contained a combination of three different feedstuffs (ground corn, soybean meal and wheat mids; corn gluten feed, rolled oats and distiller's dried grains; ground barley, brewer's grains and cottonseed meal). Diets consisted of 30% corn silage, 10% alfalfa hay, 10% alfalfa haylage, 17.7% ground corn plus minerals and vitamins, with the remainder as supplemental feedstuffs individually marked for measurement of ruminal turnover and in situ digestion rates. An extra period at the end of each Latin square was used to measure ruminal turnover and in situ digestion of individual forages. Diet had no effect on dry matter intake or milk yield. Mean fractional turnover (per hour) rate, measured by labeling feedstuffs with cerium, samarium or lanthanum was .044, .048, .049, .043, .047, .046, .050, .047, .049, .037, .046 and .045 for corn, soybean meal, wheat mids, corn gluten feed, oats, distiller's dried grains with solubles, barley, brewer's dried grains, cottonseed meal, alfalfa hay, corn silage and alfalfa haylage (P greater than .1), respectively. In situ-predicted ruminal degradation of N weighted for rate of passage was 61.4, 67.0, 81.5, 74.8, 86.3, 71.0, 75.7, 52.1, 54.2, 60.8, 71.7 and 70.9% for respective feedstuffs (P less than .05). In comparison with mean literature values for in vivo-measured N degradability, mean literature value = 1.172 (in situ predicted) -9.73 (P less than .05, R2 = .51). Results are interpreted to indicate a tendency for overestimating ruminal N degradability by in situ methods in feedstuffs of low degradability, while underestimating degradability in more highly degraded feedstuffs. Estimates were 11 to 17 percentage units lower than literature values for alfalfa hay and haylage and 17 units lower than literature values for distiller's dried grains.

Animal Feed↗

Coincident plasmids and antimicrobial resistance in marine bacteria isolated from polluted and unpolluted Atlantic Ocean samples.

Sewage effluent and outfall confluence samples were collected at the Barceloneta Regional Treatment Plant in Barceloneta, Puerto Rico; outfall confluence samples at Ocean City, Md., were also collected. Samples from uncontaminated open ocean areas served as clean-water controls. Bacteria were enriched in marine broth 2216 amended with 1 microgram of one of a set of chemicals selected for study per ml: nitrobenzene, dibutyl phthalate, m-cresol, o-cresol, 4-nitroaniline, bis(tributyltin) oxide, and quinone. MICs of the chemicals were determined individually for all isolates. Bacterial isolates were evaluated for resistance to nine different antibiotics and for the presence of plasmid DNA. Treated sewage was found to contain large numbers of bacteria simultaneously possessing antibiotic resistance, chemical resistance, and multiple bands of plasmid DNA. Bacteria resistant to penicillin, erythromycin, nalidixic acid, ampicillin, m-cresol, quinone, and bis(tributyltin) oxide were detected in nearly all samples, but only sewage outfall confluence samples yielded bacterial isolates that were resistant to streptomycin. Bacteria resistant to a combination of antibiotics, including kanamycin, chloramphenicol, gentamicin, and tetracycline, were isolated only from sewage effluent samples. It is concluded that bacterial isolates derived from toxic chemical wastes more frequently contain plasmid DNA and demonstrate antimicrobial resistance than do bacterial isolates from domestic sewage-impacted waters or from uncontaminated open ocean sites.

Anti-Bacterial Agents↗

Presumptive diagnosis of subclinical infections utilizing computer-assisted analysis of sequential enzyme-linked immunosorbent assays against multiple antigens.

One-hundred-seventy-two serum samples, collected sequentially from four flocks of egg- and meat-type chickens, were evaluated for antibodies to multiple infectious agents by enzyme-linked immunosorbent assay (MELISA). The MELISA system used provided simultaneous measurement of antibody titers against avian infectious bronchitis (IB), infectious bursal disease (BD), Newcastle disease, avian encephalomyelitis and reovirus infections, and Mycoplasma gallisepticum. The use of computer-generated graphic print outs of relative MELISA titers provided immediate visulization of over 740 data points and convenient detection of any temporal changes in median titer class (MTC). The temporally changing MTC, or flock profiles obtained, indicated that negligible or waning IB immunity may be a common occurrence in previously vaccinated commercial chickens. These profiles further suggested that, despite no IB revaccination, these same flocks experienced episodes of reexposure to IB which otherwise may have been difficult to detect by conventional clinical or diagnostic laboratory protocols. MELISA profiles and sequential histologic examinations of bursas of Fabricius also provided evidence of a possible BD vaccination problem in young chickens that also experienced excessive losses from coccidiosis, ulcerative enteritis, and Marek's disease. Short sampling intervals were found to foster the detection and definition of fluctuations in MTC which otherwise may have been missed.

Animals↗

Cellular changes in the peripartum bovine fetal placenta related to placental separation.

Binucleate giant cells (BNC) decline in number and viability peripartum if the placenta is subsequently released normally. This suggests an involvement of BNC destruction in fetal membrane separation in the cow. Dexamethasone induction of parturition may result in fetal membrane retention through a stabilization of the BNC (possibly the BNC plasma membranes). Prostaglandin F2a treatment in vitro induced a loss of BNC when these were obtained from cows which subsequently retained the fetal membranes for a longer than normal interval. Overall, our results indicate an involvement of BNC loss and breakdown in placental separation and a possible involvement of prostaglandins and glucocorticoids in modulating this process.

Animals↗

Correlation of water activity and other environmental conditions with repeated detection of Salmonella contamination on poultry farms.

Three flocks on 13 different broiler farms were monitored for Salmonella over three consecutive growout periods using the drag swab (DS) technique. One house was consistently negative for Salmonella contamination (7.7%); four houses were consistently positive (30.8%); and eight houses (61.5%) alternated between either a DS Salmonella-negative or -positive status. Simultaneously, numerous environmental parameters of the litter surface were measured, including water activity (Aw), ammonia, temperature, pH, moisture content (MC), ash content, and volatile solids. Analysis of these data as a corollary to either Salmonella-negative or -positive DS results revealed significant correlation coefficients for some of the parameters, especially Aw. The results suggest that there should be further exploration of remedial intervention based on control of some of the physical features of litter (e.g., controlling litter Aw and possibly MC and pH levels) in poultry houses.

Agriculture↗

Monitoring poultry farms for Salmonella by drag-swab sampling and antigen-capture immunoassay.

Drag-swab (DS) sampling, at the rate of four DS gauze pads per flock (house); modified culture procedures (novobiocin-supplemented plating media and delayed secondary selective enrichment); and Salmonella antigen-capture (SAC) technology were combined in screening one layer flock and 38 market-age broiler flocks. The results showed that low (negative) SAC sample-to-positive control (S/P) ratios were related to the negative culture recovery of Salmonella. Similarly, high (positive) S/P ratios were related to and indicative of positive culture recoveries. Extensive sampling and testing of 18 of the 39 flocks disclosed A) that five flocks with negative culture recoveries from feathers and freshly voided feces had essentially no positive DS-SAC values, and B) that 13 flocks with positive culture recoveries from feathers and/or fresh feces all had positive DS-SAC values.

Animals↗