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J D Lewis

Publications and source records attributed to J D Lewis.

At least 37 records · Page 2Linked to original sources
PubMed2001

An open-label trial of the PPAR-gamma ligand rosiglitazone for active ulcerative colitis.

OBJECTIVES: Previous research has demonstrated that ligands for the gamma subtype of peroxisome proliferator-activated receptors (PPARs) reduce inflammation in two different murine models of colitis. This study was designed to examine the potential efficacy of rosiglitazone, a ligand for the gamma subtype of PPARs, as a therapy for active ulcerative colitis. METHODS: Fifteen patients with mild to moderately active ulcerative colitis despite therapy with 5-aminosalicylic acid compounds were enrolled in an open-label study of rosiglitazone (4 mg b.i.d. p.o.) for 12 wk. Thirteen of 15 patients were receiving concomitant therapy with corticosteroids and/or immunomodulator medications. Disease activity was measured with the Disease Activity Index. RESULTS: After 12 wk of therapy, four patients (27%) had achieved clinical remission, of whom three (20%) also had an endoscopic remission. Four additional patients (27%) had a clinical response without achieving remission. Two patients were hospitalized with worsened disease activity, and one patient was withdrawn for nephrotic syndrome. CONCLUSIONS: These data suggest that ligands for the gamma subtype of PPARs may represent a novel therapy for ulcerative colitis. A double blind, placebo-controlled, randomized trial is warranted.

Adult↗
PubMed2001

Interaction of eukaryotic translation initiation factor 4G with the nuclear cap-binding complex provides a link between nuclear and cytoplasmic functions of the m(7) guanosine cap.

In eukaryotes the majority of mRNAs have an m(7)G cap that is added cotranscriptionally and that plays an important role in many aspects of mRNA metabolism. The nuclear cap-binding complex (CBC; consisting of CBP20 and CBP80) mediates the stimulatory functions of the cap in pre-mRNA splicing, 3' end formation, and U snRNA export. As little is known about how nuclear CBC mediates the effects of the cap in higher eukaryotes, we have characterized proteins that interact with CBC in HeLa cell nuclear extracts as potential mediators of its function. Using cross-linking and coimmunoprecipitation, we show that eukaryotic translation initiation factor 4G (eIF4G), in addition to its function in the cytoplasm, is a nuclear CBC-interacting protein. We demonstrate that eIF4G interacts with CBC in vitro and that, in addition to its cytoplasmic localization, there is a significant nuclear pool of eIF4G in mammalian cells in vivo. Immunoprecipitation experiments suggest that, in contrast to the cytoplasmic pool, much of the nuclear eIF4G is not associated with eIF4E (translation cap binding protein of eIF4F) but is associated with CBC. While eIF4G stably associates with spliceosomes in vitro and shows close association with spliceosomal snRNPs and splicing factors in vivo, depletion studies show that it does not participate directly in the splicing reaction. Taken together the data indicate that nuclear eIF4G may be recruited to pre-mRNAs via its interaction with CBC and accompanies the mRNA to the cytoplasm, facilitating the switching of CBC for eIF4F. This may provide a mechanism to couple nuclear and cytoplasmic functions of the mRNA cap structure.

3T3 Cells↗
PubMed2001

Sex vs. gender.

Explore the source record for details and available documents.

Female↗
PubMed2000

Like attracts like: getting RNA processing together in the nucleus.

Structures visible within the eukaryotic nucleus have fascinated generations of biologists. Recent data show that these structures form in response to gene expression and are highly dynamic in living cells. RNA processing and assembly require many factors but the nucleus apparently lacks any active transport system to deliver these to the RNAs. Instead, processing factors move by diffusion but are concentrated by transient association with functionally related components. At sites of high activity this gives rise to visible structures, with components in dynamic equilibrium with the surrounding nucleoplasm. Processing factors are recruited from this pool by cooperative binding to RNA substrates.

Animals↗
PubMed2000

Fatal hyperammonemia after orthotopic lung transplantation.

BACKGROUND: A case of fatal hyperammonemia complicating orthotopic lung transplantation was previously reported. OBJECTIVE: To describe the incidence, clinical features, and treatment of hyperammonemia associated with orthotopic lung transplantation. DESIGN: Retrospective cohort analysis. SETTING: Academic medical center and lung transplantation center in Philadelphia, Pennsylvania. PATIENTS: 145 sequential adult patients who underwent orthotopic lung transplantation. MEASUREMENTS: Plasma ammonium levels. RESULTS: Six of the 145 patients who had had orthotopic lung transplantation developed hyperammonemia, all within the first 26 days after transplantation. The 30-day post-transplantation mortality rate was 67% for patients with hyperammonemia compared with 17% for those without hyperammonemia (P = 0.01). Development of major gastrointestinal complications (P = 0.03), use of total parenteral nutrition (P < 0.001), and lung transplantation for primary pulmonary hypertension (P = 0.045) were associated with hyperammonemia. CONCLUSIONS: Hyperammonemia is a potentially fatal event occurring after orthotopic lung transplantation. It is associated with high nitrogen load, concurrent medical stressors, primary pulmonary hypertension, and hepatic glutamine synthetase deficiency.

Adult↗
PubMed2000

Flexible sigmoidoscopy training and its impact on colorectal cancer screening by primary care physicians.

BACKGROUND: Colorectal cancer is an ideal disease for prevention with screening programs. Efforts to increase compliance with screening recommendations have included training primary care physicians to perform flexible sigmoidoscopy. OBJECTIVE: To assess the impact of flexible sigmoidoscopy training on compliance with current screening recommendations. METHODS: We performed a cross-sectional study of 232 patients cared for by physicians in a primary care network. MAIN OUTCOME MEASURES: Rates of screening for colorectal cancer and rates of undergoing flexible sigmoidoscopy were compared across patient groups according to the physician's training and whether the physician performs flexible sigmoidoscopy in his or her practice. RESULTS: Among 217 patients included in the analysis, 122 (56%) were cared for by physicians who were trained in flexible sigmoidoscopy, of whom 79 (36%) were cared for by physicians who perform flexible sigmoidoscopy in their practice. Patients cared for by physicians trained in flexible sigmoidoscopy were not significantly more likely to receive any colorectal cancer screening than were patients cared for by physicians not trained in flexible sigmoidoscopy (odds ratio, 1.16; 95% confidence interval, 0.67-2.01). However, patients cared for by physicians who perform flexible sigmoidoscopy in their practice were more likely to have undergone any colorectal cancer screening (odds ratio, 1.73; 95% confidence interval, 1.02-2.95) and flexible sigmoidoscopy (odds ratio, 2.69; 95% confidence interval, 1.14-6.36). CONCLUSION: Performance of flexible sigmoidoscopy by primary care physicians has the potential to increase the rate of colorectal cancer screening with flexible sigmoidoscopy.

Aged↗
PubMed2000

Characterization and evolutionary relevance of the sperm nuclear basic proteins from stickleback fish.

We have characterized the sperm nuclear basic proteins (SNBPs) of the sticklebacks in the suborder Gasterosteoidei. The complete amino acid sequence of the protamines from Aulorhynchus flavidus, Pungitius pungitius, Gasterosteus aculeatus, (anadromous) and G. wheatlandi, as well as the sequences of the protamines of several species pairs of freshwater G. aculeatus, have been determined. Analysis of the primary structure of these proteins has shown that: a) despite the relatively low amino acid complexity and small molecular mass of these basic proteins, they are very good molecular markers at the generic level. The bootstrap parsimony analysis using their sequences provides a phylogenetic relationship for the old anadromous species of Gasterosteoidei which is identical to that obtained from morphological and behavioral analysis; b) the comparison of the sequences also suggests that protamines from the suborder Gasterosteoidei have most likely evolved from a common gene in the early Acanthopterygii by an extension of the carboxy terminal portion of the molecule; c) protamines are not good markers for recent postglacial freshwater isolates of G. aculeatus. However, in the unique case of Enos Lake (British Columbia), we have been able to detect an additional minor protamine component in the benthic forms of G. aculeatus that is not present in the limnetic forms. Thus, this new protamine must have appeared during the past 12,000 years concomitantly with the speciation of benthics and limnetics in this lake.

Amino Acid Sequence↗
PubMed2000

Azathioprine for maintenance of remission in Crohn's disease: benefits outweigh the risk of lymphoma.

BACKGROUND & AIMS: Azathioprine is a commonly used and effective treatment for maintenance of remission for patients with steroid-dependent Crohn's disease (CD). However, azathioprine therapy is associated with an increased risk of non-Hodgkin's lymphoma. The objective of this analysis was to determine the impact of azathioprine therapy on survival and quality-adjusted life expectancy after accounting for both the benefits of therapy and potential increased risk of lymphoma. METHODS: A decision analysis using a Markov model depicting the natural history of alternative management strategies for maintenance of remission in patients with CD was performed. RESULTS: In the base-case analysis, treatment of CD patients with a steroid-induced remission with azathioprine resulted in an average increase in life expectancy of 0.04 years and 0.05 quality-adjusted years. The incremental gain in life expectancy decreased with increasing patient age and increasing risk of lymphoma. CONCLUSIONS: Therapy with azathioprine to preserve remission in patients with CD results in increased quality-adjusted life expectancy. This increase was greatest in young patients who have the lowest baseline risk of non-Hodgkin's lymphoma and who have the greatest life expectancy in the absence of a CD-related death.

Adolescent↗
PubMed2000

Endoscopic management of postoperative biliary complications in orthotopic liver transplantation.

BACKGROUND: Surgery, percutaneous cholangiography, and endoscopic retrograde cholangiopancreatography (ERCP) have been used in the management of biliary complications after orthotopic liver transplantation with varied results. We assessed the role of ERCP in the diagnosis, treatment, and outcome of post-orthotopic liver transplantation biliary complications. METHODS: We retrospectively reviewed the records of 260 patients who underwent orthotopic liver transplantation. We examined the number of patients referred for ERCP and the indication, diagnosis, therapeutic intervention, success, and complication rate of ERCP post orthotopic liver transplantation. We compared the survival and retransplantation rates of the patients who underwent ERCP with a control group of post-orthotopic liver transplantation patients not undergoing ERCP. RESULTS: Of the 260 patients undergoing orthotopic liver transplantation, 64 (24.6%) underwent 137 ERCPs. Two categories of indications for ERCP were identified: bile leak (n = 31) and obstruction (n = 39). ERCP identified the site of the bile leak in 27 of 31 cases (87.1%) and the leak was treated by endoscopic means in 26 of 31 (83.9%). Treatment success differed significantly based on location of the leak (T tube, 95.2% vs. anastomosis, 42.9%; p = 0. 009). ERCP identified the site of obstruction in 37 of 39 cases (94. 9%) and obstruction was relieved by endoscopic means in 25 of 35 cases (71.4%). ERCP was significantly less successful in the treatment of biliary casts (25.0%, p = 0.048). There was no difference in survival or retransplantation between patients who did and did not undergo ERCP. CONCLUSION: ERCP should be the primary method for diagnosis and treatment of post-orthotopic liver transplantation biliary complications. Endoscopic therapy is safe and effective for the majority of post-orthotopic liver transplantation complications and temporizes management for those complications that may require surgery.

Adolescent↗
PubMed2000

EUS in preoperative staging of pancreatic cancer.

BACKGROUND: Endoscopic ultrasound (EUS) is believed to be highly accurate in the local (T) and nodal (N) staging of pancreatic cancer. However, there are scant data concerning the predictive value of EUS for resectability of pancreatic adenocarcinoma. This study was performed to determine the accuracy of TNM staging by EUS in patients with pancreatic adenocarcinoma and to evaluate the role of preoperative TNM staging by EUS for determining resectability in patients with pancreatic adenocarcinoma. METHODS: This is a retrospective review of a cohort of 89 patients evaluated preoperatively with EUS for pancreatic adenocarcinoma between January 1995 and December 1997. Preoperative TNM classification by EUS was compared with surgical and histopathologic TNM staging. Resectability rates were determined and compared with the preoperative TNM staging by EUS. RESULTS: The overall accuracy of EUS for T and N staging was found to be 69% and 54%, respectively. The overall proportion of tumors that were deemed resectable by EUS and were actually found to be resectable during surgical exploration was 46%. The proportion of tumors staged as T4 N1, T4 N0, T3 N1 and T3 N0 by EUS that were found to be resectable during surgical exploration was 45%, 37%, 44% and 62%, respectively. CONCLUSIONS: In a tertiary referral patient population, EUS is not as accurate as previously reported in the T and N staging of pancreatic cancer. EUS is also not predictive of resectability in stage T3 or T4 pancreatic cancer.

Adenocarcinoma↗
PubMed2000

Characterization of gastrointestinal bleeding in severely ill hospitalized patients.

OBJECTIVE: To characterize the source of bleeding and the prognosis in critically ill patients with upper gastrointestinal hemorrhage that developed while in the hospital. SETTING: Intensive care units of a large academic tertiary-care center. DESIGN: Retrospective cohort study. SUBJECTS: Patients undergoing endoscopy in intensive care units for gastrointestinal bleeding that developed while in the hospital. MEASUREMENTS AND MAIN RESULTS: Medical records were available for 142 patients. Of these, 66 met the criteria for in-hospital bleeding. Peptic ulcer disease, present in 56% of patients, was the most common bleeding source identified. Of patients with peptic ulcer disease, nine of 37 (24%) had stigmata of recent hemorrhage. Ten patients (15%) received endoscopic hemostasis interventions (eight receiving therapy for bleeding ulcers, two receiving therapy for esophageal varices). The in-hospital mortality rate was 42%. The cause of death was sepsis and/or multiple system organ failure in 21 patients (75%); the gastrointestinal bleeding may have contributed to the onset of sepsis in one of these patients. No patients died directly of gastrointestinal bleeding. CONCLUSIONS: Critically ill patients who bleed while in the hospital have similar sources of bleeding and rates of endoscopically directed therapy as patients admitted to hospital with bleeding. The mortality rate is very high in patients with bleeding that develops in the hospital, and this is usually a result of systemic disease. These data may help clinicians and patients to estimate the potential benefit of urgent endoscopy in critically ill patients.

Adolescent↗
PubMed2000

Role of endoscopic ultrasound and magnetic resonance imaging in the preoperative staging of pancreatic adenocarcinoma.

OBJECTIVE: Endoscopic ultrasound (EUS) and magnetic resonance imaging (MRI) have both been assessed individually as staging modalities for pancreatic cancer. The aim of our study was to assess whether tumor staging by both EUS and MRI in the same cohort of patients could predict resectability and unresectability in patients with pancreatic cancer. METHODS: A review of 63 patients evaluated preoperatively with both EUS and MRI for pancreatic adenocarcinoma between January 1995 and December 1998 was done. Patients were staged as resectable or unresectable by predefined criteria. Preoperative staging by both modalities was compared to surgical outcome and the sensitivity and predictive values of each modality for determining resectability and unresectability was determined. RESULTS: EUS did not allow for complete T- and N-staging in 10 patients; therefore, for EUS, the final analysis was done on 63 of 73 patients (86%). EUS correctly staged 22 of 36 patients with resectable tumors. The sensitivity of EUS for resectability was 61%, with a positive predictive value of 69%. All 73 patients had complete MRI examinations; therefore, the final analysis was done on all 73 patients. MRI correctly staged 30 of 41 patients with resectable tumors. The sensitivity of MRI for predicting resectability was 73% with a positive predictive value of 77%. MRI and EUS both predicted resectability in 18 patients, of whom 16 (89%) were found to be resectable on surgical exploration. MRI and EUS both predicted unresectability in 17 (27%) patients, of whom 4 (24%) were found to be resectable on surgical exploration. When both MRI and EUS agreed on resectability, the positive predictive value for resectability was 89%. When both MRI and EUS agreed on unresectability, the positive predictive value for unresectability was 76%. CONCLUSIONS: Neither MRI nor EUS alone were highly sensitive or predictive of resectability. However, when both tests agreed on resectability, nearly all patients were found to be resectable on surgical exploration.

Adenocarcinoma↗
PubMed1999

Barriers to office-based screening sigmoidoscopy: does reimbursement cover costs?

Screening with flexible sigmoidoscopy may reduce mortality rates from colorectal cancer. Primary care physicians are able to provide this screening procedure, but many have been reluctant to do so, partly because of the impression that reimbursement rates are inadequate to cover physician costs. This study examines the cost of performing flexible sigmoidoscopy in a primary care practice and compares this cost with the new Medicare reimbursement rate for flexible sigmoidoscopy. Fixed and variable costs associated with the performance of office-based flexible sigmoidoscopy were derived from the published literature. The principal assumption in the analyses is that the time required to perform flexible sigmoidoscopy represents an opportunity cost because the physician could use that time to see additional patients during routine office hours. Sensitivity analyses were done across a range of estimates for the cost variables. When Medicare reimbursement rates were used, the physician's total cost for flexible sigmoidoscopy without biopsy was $86.86, which is similar to the Medicare reimbursement rate for screening flexible sigmoidoscopy (code 45330, $87.84). The calculations were most sensitive to estimates of equipment cost, procedure time, number of procedures performed per year, additional malpractice coverage, and revenue generated per hour of outpatient care. The estimated cost per procedure in a screening program that includes the ability to perform biopsy is $152.93, which exceeds Medicare reimbursement rates across the range of all variables included in the sensitivity analyses. Thus, low reimbursement may limit the adoption of screening flexible sigmoidoscopy with or without biopsy in primary care practices.

Biopsy↗
PubMed1999

The histidine-rich protamine from ostrich and tinamou sperm. A link between reptile and bird protamines.

We have characterized for the first time the proteins of two different species of palaeognathous birds, Struthio camelus australis (ostrich) and Nothoprocta perdicaria sanborni (Chilean tinamou). Similar to what had been previously reported in neognaths, the electrophoretic mobility, amino acid composition, and primary structure of the main protamine (P-II) component of these two species of birds are similar. However, in contrast to neognathous birds, the protamines from paleognaths display a higher electrophoretic mobility and a significantly different amino acid composition and protein sequence. The sperm and the main protamine component P-II from the ostrich reveal structural and compositional characteristics intermediate between neognathous birds and reptiles. The marked differences between the protamines and sperm structure of neognaths and paleognaths provide support to a phylogenetic relationship between neornithine birds in which these two groups represent two separate phylogenetic lines. Furthermore, these results shed some additional light on the controversial origin of birds. They provide further molecular support to the fossil record that suggests that reptiles and birds are closely related.

Alligators and Crocodiles↗