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Biomedical subjects

J D Lewis

Publications and source records attributed to J D Lewis.

At least 19 recordsLinked to original sources
PubMed2006

Childhood onset arthritis is associated with an increased risk of fracture: a population based study using the General Practice Research Database.

BACKGROUND: Childhood onset arthritis is associated with low bone mass and strength. OBJECTIVE: To determine whether childhood onset arthritis is associated with greater fracture risk. METHODS: In a retrospective cohort study all subjects with onset of arthritis between 1 and 19 years of age in the United Kingdom General Practice Research Database were identified. As controls, all sex and age matched subjects from a practice that included a subject with arthritis were included. Incidence rate ratios (IRRs) for first fracture were generated using Mantel-Haenszel methods and Poisson regression. RESULTS: 1939 subjects with arthritis (51% female) and 207 072 controls (53% female) were identified. The median age at arthritis diagnosis was 10.9 years. A total of 129 (6.7%) first fractures were noted in subjects with arthritis compared with 6910 (3.3%) in controls over a median follow up of 3.90 and 3.95 years in the subjects with arthritis and controls, respectively. The IRR (95% confidence interval) for first fracture among subjects with arthritis, compared with controls, according to the age at the start of follow up were 1.49 (0.91 to 2.31) for age <10 years, 3.13 (2.21 to 4.33) at 10-15 years, 1.75 (1.18 to 2.51) at 15-20 years, 1.40 (0.91 to 2.08) at 20-45 years, and 3.97 (2.23 to 6.59) at >45 years. CONCLUSIONS: Childhood onset arthritis is associated with a clinically significant increased risk of fracture in children, adolescents and, possibly, adults. Studies are urgently needed to characterise the determinants of structural bone abnormalities in childhood arthritis and devise prevention and treatment strategies.

Adolescent↗
PubMed2005

Increased risk of lymphoma among inflammatory bowel disease patients treated with azathioprine and 6-mercaptopurine.

BACKGROUND: Inflammatory bowel disease (IBD) is commonly treated with immunomodulators such as azathioprine and 6-mercaptopurine (6-MP). Studies examining lymphoma risk in IBD patients treated with these medications have been underpowered and have yielded conflicting conclusions. AIMS: The purpose of this meta-analysis was to provide a more precise estimate of the relative risk of lymphoma among IBD patients treated with azathioprine or 6-MP. METHODS: Studies were included if they were English language, full article, cohort studies specifically designed to evaluate cancer as an adverse outcome of treatment with azathioprine or 6-MP. Pooled standardised incidence ratios were calculated to estimate the relative risk of lymphoma associated with therapy. Heterogeneity was assessed using Poisson regression. Sensitivity analyses examined the influence of individual studies on risk estimate and heterogeneity statistics. RESULTS: Six studies were identified that met our inclusion criteria. When the data were combined across all studies, the pooled relative risk was 4.18 (95% confidence interval 2.07-7.51; 11 observed cases, 2.63 expected). Sensitivity analysis showed that exclusion of any one study had a relatively small effect on the pooled relative risk estimate (range 3.49-5.21) but excluding either the study with the highest or lowest estimated relative risk eliminated the statistically significant heterogeneity. CONCLUSIONS: Our data suggest an approximate fourfold increased risk of lymphoma in IBD patients treated with azathioprine/6-MP. The increased risk of lymphoma could be a result of the medications, the severity of the underlying disease, or a combination of the two.

Azathioprine↗
PubMed2001

Plant growth in elevated CO2 alters mitochondrial number and chloroplast fine structure.

With increasing interest in the effects of elevated atmospheric CO(2) on plant growth and the global carbon balance, there is a need for greater understanding of how plants respond to variations in atmospheric partial pressure of CO(2). Our research shows that elevated CO(2) produces significant fine structural changes in major cellular organelles that appear to be an important component of the metabolic responses of plants to this global change. Nine species (representing seven plant families) in several experimental facilities with different CO(2)-dosing technologies were examined. Growth in elevated CO(2) increased numbers of mitochondria per unit cell area by 1.3-2.4 times the number in control plants grown in lower CO(2) and produced a statistically significant increase in the amount of chloroplast stroma (nonappressed) thylakoid membranes compared with those in lower CO(2) treatments. There was no observable change in size of the mitochondria. However, in contrast to the CO(2) effect on mitochondrial number, elevated CO(2) promoted a decrease in the rate of mass-based dark respiration. These changes may reflect a major shift in plant metabolism and energy balance that may help to explain enhanced plant productivity in response to elevated atmospheric CO(2) concentrations.

Carbon Dioxide↗
PubMed2001

Effects of elevated atmospheric CO2 concentration on leaf dark respiration of Xanthium strumarium in light and in darkness.

Leaf dark respiration (R) is an important component of plant carbon balance, but the effects of rising atmospheric CO(2) on leaf R during illumination are largely unknown. We studied the effects of elevated CO(2) on leaf R in light (R(L)) and in darkness (R(D)) in Xanthium strumarium at different developmental stages. Leaf R(L) was estimated by using the Kok method, whereas leaf R(D) was measured as the rate of CO(2) efflux at zero light. Leaf R(L) and R(D) were significantly higher at elevated than at ambient CO(2) throughout the growing period. Elevated CO(2) increased the ratio of leaf R(L) to net photosynthesis at saturated light (A(max)) when plants were young and also after flowering, but the ratio of leaf R(D) to A(max) was unaffected by CO(2) levels. Leaf R(N) was significantly higher at the beginning but significantly lower at the end of the growing period in elevated CO(2)-grown plants. The ratio of leaf R(L) to R(D) was used to estimate the effect of light on leaf R during the day. We found that light inhibited leaf R at both CO(2) concentrations but to a lesser degree for elevated (17-24%) than for ambient (29-35%) CO(2)-grown plants, presumably because elevated CO(2)-grown plants had a higher demand for energy and carbon skeletons than ambient CO(2)-grown plants in light. Our results suggest that using the CO(2) efflux rate, determined by shading leaves during the day, as a measure for leaf R is likely to underestimate carbon loss from elevated CO(2)-grown plants.

Asteraceae↗
PubMed2001

Endoscopy for hematochezia in patients under 50 years of age.

The optimal strategy for evaluating rectal bleeding in young persons is unknown. This study examines the prevalence of adenomatous neoplasms identified at endoscopy for rectal bleeding. Retrospective cross-sectional analysis was made of patients under 50 years of age undergoing elective outpatient colonoscopy or flexible sigmoidoscopy for hematochezia. In all, 570 patients (309 F/261 M) met our inclusion criteria. The prevalence of neoplasms was 3.8% (95% CI 1.2-8.5%) among persons under 30, 2.8% (95% CI 0.9-6.3%) among persons age 30-39, and 10.9% (95% CI 7.4-15.4%) among persons age 40-49. The prevalence of neoplasms was higher in persons over age 40 (relative risk 3.43, 95% CI 1.70-6.94). Six of seven advanced neoplasms were identified in persons over age 40 (relative risk 7.4, 95% CI 0.89-60.7). In conclusion, the prevalence of colonic neoplasms in patients 40-50 years old with hematochezia is substantial. Among those persons younger than 40 years, the prevalence of colonic neoplasms is significantly lower.

Adolescent↗
PubMed2001

Inflammatory bowel disease is not associated with an increased risk of lymphoma.

BACKGROUND & AIMS: Previous studies of the risk of lymphoma in inflammatory bowel disease patients have provided conflicting results. This study examines the risk of Hodgkin's and non-Hodgkin's lymphoma among patients with inflammatory bowel disease. METHODS: The authors performed a retrospective cohort study using the General Practice Research Database. Inflammatory bowel disease patients were matched to randomly selected controls on age, sex, and primary care practice. Lymphoma rates were also compared with published age- and sex-specific rates. RESULTS: The study included 6605 patients with Crohn's disease, 10,391 with ulcerative colitis, and 60,506 controls followed for an average of 3.7, 3.9, and 4.4 years, respectively. The incidence of lymphoma was not increased in patients with inflammatory bowel disease (relative risk = 1.20; 95% CI, 0.67-2.06). In subgroup analyses, an increased risk was not observed among patients with Crohn's disease (relative risk = 1.39; 95% CI, 0.50-3.40) or ulcerative colitis (relative risk = 1.11; 95% CI, 0.51-2.19). Compared with inflammatory bowel disease patients not treated with azathioprine or 6-MP, the relative risk of lymphoma among the 1465 inflammatory bowel disease patients treated with these medications (average, 106 mg/day for 2.0 years) was 1.27 (95% CI 0.03-8.20). CONCLUSIONS: Patients with inflammatory bowel disease do not have an increased risk of lymphoma as compared with the general population. Although we cannot completely rule out a modest increased risk of lymphoma with azathioprine or 6-MP therapy, an increased risk was not observed in this cohort.

Adult↗
PubMed2001

Accuracy of EUS in the evaluation of Barrett's esophagus and high-grade dysplasia or intramucosal carcinoma.

BACKGROUND: Nonoperative therapy with intent to cure may be considered for patients with Barrett's esophagus and high-grade dysplasia or intramucosal carcinoma. However, a more advanced stage of disease must be precluded before such treatment. The potential of EUS for this purpose was evaluated. METHODS: EUS was performed in patients with Barrett's esophagus and high-grade dysplasia or intramucosal carcinoma based on endoscopy, endoscopic biopsies, and CT before esophagectomy. EUS findings were compared with surgical/pathologic evaluation. RESULTS: EUS suggested submucosal invasion in 6 patients and lymph node involvement in 5 patients. By surgical/pathologic evaluation, 5 of 22 patients (23%) had unsuspected submucosal invasion and 1 had lymph node involvement. EUS detected all 5 instances of submucosal invasion and the single instance of lymph node involvement. EUS was falsely positive for submucosal invasion in 1 patient and for lymph node involvement in 4 patients. Sensitivity, specificity, and negative predictive values of preoperative EUS for submucosal invasion were 100%, 94%, and 100%, and for lymph node involvement were 100%, 81%, and 100%, respectively. A nodule or stricture noted by endoscopy was associated with an increased likelihood of submucosal invasion. CONCLUSIONS: In patients with Barrett's esophagus and high-grade dysplasia or intramucosal carcinoma, EUS detected otherwise unsuspected submucosal invasion and lymph node involvement. Patients should be evaluated with EUS when nonoperative therapy is contemplated.

Adenocarcinoma↗
PubMed2001

A randomized, double-blind, placebo-controlled trial of single-dose intravenous secretin as treatment for children with autism.

OBJECTIVE: To determine whether a single injection of intravenous secretin results in measurable improvements in socialization and/or communication skills in children with autism. STUDY DESIGN: Sixty subjects with autism were randomly selected and assigned to either treatment or placebo group. Subjects in the treatment group received 2.0 clinical units of secretin per kilogram of body weight as a single intravenous dose. Subjects in the placebo group received normal saline solution. Neurodevelopmental and behavioral assessments were performed for all subjects before injection and at 3 and 6 weeks after injection. RESULTS: Assessment of language skills and parents' behavioral assessments revealed no significant differences between the treatment and placebo groups. Raters' assessments of severity of autistic symptoms did not differ for the 2 groups at 6 weeks after injection. A marginally statistically significant improvement in autistic behaviors was seen in the treatment group at 3 weeks after injection (P =.051). CONCLUSIONS: A single dose of intravenous secretin does not appear to have significant effects on either parents' perception of autistic behaviors or language skills at 6 weeks after injection. Transient, marginally significant improvements in autistic behaviors may occur in some children.

Autistic Disorder↗
PubMed2001

Origin of H1 linker histones.

In which taxa did H1 linker histones appear in the course of evolution? Detailed comparative analysis of the histone H1 and histone H1-related sequences available to date suggests that the origin of histone H1 can be traced to bacteria. The data also reveal that the sequence corresponding to the 'winged helix' motif of the globular structural domain, a domain characteristic of all metazoan histone H1 molecules, is evolutionarily conserved and appears separately in several divergent lines of protists. Some protists, however, appear to have only a lysine-rich basic protein, which has compositional similarity to some of the histone H1-like proteins from eubacteria and to the carboxy-terminal domain of the H1 linker histones from animals and plants. No lysine-rich basic proteins have been described in archaebacteria. The data presented in this review provide the surprising conclusion that whereas DNA-condensing H1-related histones may have arisen early in evolution in eubacteria, the appearance of the sequence motif corresponding to the globular domain of metazoan H1s occurred much later in the protists, after and independently of the appearance of the chromosomal core histones in archaebacteria.

Amino Acid Sequence↗
PubMed2001

Endosonography is superior to angiography in the preoperative assessment of vascular involvement among patients with pancreatic carcinoma.

Surgical exploration in patients with pancreatic carcinoma without adequate preoperative attempts to determine resectability results in resection in only a minority of patients. Besides distant metastases, involvement of the major vessels is the most important parameter for determining resectability in patients with pancreatic adenocarcinoma. Angiography has been an integral part of pancreatic cancer staging. Lately, endoscopic ultrasound (EUS) has emerged as a more accurate tool in the diagnosis and staging of pancreatic cancer. We hypothesize that EUS is more accurate than selective venous angiography (SVA) for assessing resectability of pancreatic adenocarcinoma based on preoperative evaluation of vascular involvement. Twenty-one patients who met the inclusion criteria were prospectively evaluated with both EUS and SVA before undergoing surgical exploration for attempted curative resection. Vascular involvement was determined by EUS and SVA using previously described criteria. The sensitivity, specificity, and overall accuracy of EUS and SVA in assessing vascular involvement were compared, using surgical exploration as the gold standard. Endoscopic ultrasound had a higher sensitivity than SVA for detecting vascular involvement (86% vs. 21%, respectively; p = 0.0018). The specificity and accuracy of EUS for detecting vascular involvement was 71% and 81%, respectively. In contrast, the specificity and accuracy of SVA for detecting vascular involvement was 71% and 38%, respectively. Endoscopic ultrasound is significantly more sensitive than angiography for detecting vascu lar involvement in patients with pancreatic adenocarcinoma and, thus, may improve patient selection for attempted curative resection.

Adult↗
PubMed2001

Inflammatory bowel disease associated with immune thrombocytopenic purpura in children.

OBJECTIVE: Previous reports suggest an association between inflammatory bowel disease (IBD) and immune thrombocytopenic purpura (ITP) in adults. To date, only five children with both diseases have been described. The aim of the study was to describe the characteristics of children with IBD and ITP. METHODS: Cases were obtained from the pediatric gastroenterology community by means of the pediatric gastroenterology internet bulletin board in June 1999. Eight cases were submitted from seven medical centers. Medical records were reviewed by two pediatric gastroenterologists and a pediatric hematologist. RESULTS: The age range of the patients was 2.1 to 16.5 years, with a mean age of 9.6 +/- 5.2 years. Four children had ulcerative colitis, three had Crohn disease, and one had indeterminate colitis. All had colonic involvement of IBD. Of eight patients, three had IBD first, three had ITP first, and two had both simultaneously. At ITP diagnosis, platelet count was less than 10,000/mL in five children, 17,000/mL in one child, and 50,000 to 60,000/mL in two children. Of the three children diagnosed with ITP first, two initially had rectal bleeding at the time of ITP diagnosis. Bone marrow evaluations, performed in six of eight children, were consistent with ITP. Six of the eight children had chronic ITP, including three children who were 5 years of age or younger. Therapy for ITP included steroids (n = 6), intravenous immunoglobulin (n = 6), Rh o (D) intravenous immunoglobulin (n = 2), and splenectomy (n = 1). CONCLUSIONS: The authors describe the largest pediatric case series of children with IBD and ITP. More than 50% of the children had the chronic form of ITP. Most patients responded to conventional therapy for ITP and IBD.

Adolescent↗
PubMed2001

Long term survival after pancreatic resection for pancreatic adenocarcinoma.

OBJECTIVE: The aim of this study was to determine the long term survival of patients with pancreatic adenocarcinoma who underwent surgical resection and to assess the association of clinical, pathological, and treatment features with survival. METHODS: Between January, 1990, and December, 1998, 125 patients underwent a pancreaticoduodenal or partial pancreatic resection for pancreatic ductal adenocarcinoma at our institution. The records of these patients were reviewed for demographics, tumor characteristics including size, histological grade, margin status, lymph node status, surgical TNM staging, and postoperative adjuvant therapy. The primary outcome variable analyzed was survival. RESULTS: A total of 116 patients had complete follow-up and were included in the final analysis. The median survival after surgery was 16 months. The 1-, 3-, 5-, and 7-yr survival rates for all 116 patients were 60%, 23%, 19%, and 11%, respectively. The 1-, 3-, 5-, and 7-yr survival rates for patients who received adjuvant therapy were 69%, 28%, 23%, and 18% compared with 20% and 0% in patients who did not receive adjuvant therapy (p < 0.0001). The 1-, 3-, 5-, and 7-yr survival rates for patients with negative lymph nodes were 73%, 38%, 26%, and 22% compared with survival rates of 52%, 14%, 14%, and 9% in patients with positive lymph nodes (p = 0.01). In multivariate analyses, adjuvant therapy was the only feature found to be strongly associated with survival (hazards ratio = 0.26, 95% CI = 0.15-0.44). CONCLUSIONS: The overall 5- and 7-yr survival rates of 19% and 11% in our study further validate that surgical resection in patients with pancreatic adenocarcinoma can result in long term survival, particularly when performed in association with adjuvant chemoradiation.

Adenocarcinoma↗
PubMed2001

Can EUS alone differentiate between malignant and benign cystic lesions of the pancreas?

OBJECTIVE: The aim of this study was to evaluate the ability of endoscopic ultrasound (EUS) alone to predict and differentiate malignant from benign cystic lesions of the pancreas. METHODS: From January, 1995, to August, 1999, 98 cases of pancreatic cystic lesions were evaluated by EUS; all of these were originally imaged by cross-sectional modalities that were not diagnostic. Among these, surgical/pathological correlation was available in 48 patients. The original endosonographic images were reviewed by two endosonographers who were blinded to each other's interpretation and to the surgical and pathological interpretation. The EUS images were assessed for the presence or absence of the following characteristics: 1) wall, 2) solid component, 3) septae, 4) lymphadenopathy, and 5) number of cysts. These characteristics were then correlated with the surgical and pathological findings and were assessed to determine if any were predictors of the lesion being benign or malignant. RESULTS: For reviewer A, the presence of a solid component by EUS was the only statistically significant predictor of malignancy (odds ratio = 4.73, 95% CI = 1.13-19.68, p = 0.03). However, 61% of patients with benign lesions were also interpreted by EUS to have a solid component. For reviewer B, none of the features were found to be significant predictors of a malignant lesion. When the results of both reviewers were combined, the presence of a solid component was not found to be a statistically significant predictor of malignancy (odds ratio = 1.046, 95% CI = 0.99-1.09, p = 0.07). CONCLUSION: Endosonographic features cannot reliably differentiate between benign and malignant cystic lesions of the pancreas after a nondiagnostic cross-sectional modality.

Adult↗