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Biomedical subjects

A Bitton

Publications and source records attributed to A Bitton.

At least 19 recordsLinked to original sources
PubMed2005

Severe hypoglycaemia post-gastric bypass requiring partial pancreatectomy: evidence for inappropriate insulin secretion and pancreatic islet hyperplasia.

AIMS/HYPOTHESIS: Postprandial hypoglycaemia following gastric bypass for obesity is considered a late manifestation of the dumping syndrome and can usually be managed with dietary modification. We investigated three patients with severe postprandial hypoglycaemia and hyperinsulinaemia unresponsive to diet, octreotide and diazoxide with the aim of elucidating the pathological mechanisms involved. METHODS: Glucose, insulin, and C-peptide were measured in the fasting and postprandial state, and insulin secretion was assessed following selective intra-arterial calcium injection. Pancreas histopathology was assessed in all three patients. RESULTS: All three patients had evidence of severe postprandial hyperinsulinaemia and hypoglycaemia. In one patient, reversal of gastric bypass was ineffective in reversing hypoglycaemia. All three patients ultimately required partial pancreatectomy for control of neuroglycopenia; pancreas pathology of all patients revealed diffuse islet hyperplasia and expansion of beta cell mass. CONCLUSIONS/INTERPRETATION: These findings suggest that gastric bypass-induced weight loss may unmask an underlying beta cell defect or contribute to pathological islet hyperplasia, perhaps via glucagon-like peptide 1-mediated pathways.

Adult↗
PubMed2005

Tobacco industry influence on the definition of tobacco related disorders by the American Psychiatric Association.

OBJECTIVE: The Diagnostic and statistical manual of mental disorders, third edition (DSM-III), published by the American Psychiatric Association (APA) in 1980, included the first official definitions by the APA of tobacco dependence and tobacco withdrawal. Tobacco industry efforts to influence the DSM-III were investigated. METHOD: Searches of previously secret tobacco industry documents, primarily the University of California San Francisco Legacy Tobacco Documents Library and British American Tobacco collections. Additional information was collected through discussions with editors of DSM-III, and library and general internet searches. RESULTS: The tobacco companies regarded the inclusion of tobacco dependence as a diagnosis in DSM-III as an adverse event. It worked to influence the content of the DSM-III and its impact following publication. These efforts included public statements and private lobbying of DSM-III editors and high ranking APA officers by prominent US psychiatrists with undisclosed ties to the tobacco industry. Following publication of DSM-III, tobacco companies contracted with two US professors of psychiatry to organise a conference and publish a monograph detailing controversies surrounding DSM-III. CONCLUSIONS: The tobacco industry and its allies lobbied to narrow the definition of tobacco dependence in serial revisions of DSM-III. Following publication of DSM-III, the industry took steps to try to mitigate its impact. These actions mirror industry tactics to influence medical research and policy in various contexts worldwide. Such tactics slow the spread of a professional and public understanding of smoking and health that otherwise would reduce smoking, smoking induced disease, and tobacco company profits.

Conflict of Interest↗
PubMed2003

The mechanisms of prednisone inhibition of inflammation in Crohn's disease involve changes in intestinal permeability, mucosal TNFalpha production and nuclear factor kappa B expression.

BACKGROUND: The clinical course of Crohn's disease after the induction of remission with medical therapy is characterized by unpredictable relapse. AIM: To evaluate three surrogate markers, intestinal permeability, mucosal TNFalpha and nuclear factor (NF)-kappaB/IkappaBalpha expression, in order to determine the relationship of these parameters to clinical relapse. METHODS: Thirty patients with active Crohn's disease were treated with a 10 week course of prednisone using a tapering dosing regimen. Intestinal permeability (lactulose/mannitol [L/M ratio]) was determined at baseline and at the end of prednisone tapering. TNFalpha production and the levels of expression of NF-kappaB/IkappaBalpha were measured in colonic mucosal biopsies obtained after the induction of remission. RESULTS: Twenty-two patients (73%) achieved remission and 50% of patients experienced a clinical relapse during the ensuing 12 months. Treatment with prednisone resulted in a significant decrease in the L/M ratio. Of the patients that relapsed, 75% had a raised L/M ratio at the time of remission compared with 20% of patients with a normal L/M ratio (P < 0.008; hazard ratio = 6.094; CI 1.55, 17.43). Mucosal TNFalpha production was greater in relapsers compared with those who remained in remission. The levels of NF-kappaB in relapsers were significantly greater and levels of cytosolic IkappaBalpha were significantly lower compared with those measured in patients who remained in remission. CONCLUSIONS: These findings underscore the importance of incorporating biological parameters of inflammation in determining the clinical course of Crohn's disease.

Adult↗
PubMed2003

Rectal tissue, plasma and urine concentrations of mesalazine after single and multiple administrations of 500 mg suppositories to healthy volunteers and ulcerative proctitis patients.

OBJECTIVE: Patients with ulcerative proctitis may have rectal mucosal properties different from healthy volunteers. This project compared the pharmacokinetics of rectally administered mesalazine in these two populations. METHODS: In two separate studies, nine patients with ulcerative proctitis and 16 healthy volunteers received a single 500 mg mesalazine suppository and then 500 mg every 8 h for 5 days. Blood samples were collected for 12 h in healthy volunteers and 30 h in patients, and urine for 24 h in healthy volunteers and 30 h in patients. Rectal biopsies were performed 8 h after the last dose. RESULTS: After a single dose to patients, mean mesalazine half-life (s.d.) was 5.0 (3.6) h. At steady-state, means (s.d.) were 89.1 (78.9) ng/mL for C(min), 361.1 (240.8) ng/mL for C(max), and 7.1 (7.3) h for half-life. Mean (range) rectal mesalazine concentrations were 167 (1.4-541.6) ng/mg tissue. After a single dose in healthy volunteers, mean (s.d.) half-life was 4.0 (4.7) h. At steady-state, means (s.d.) were 22.4 (61.6) ng/mL for C(min), 359.4 (166.3) ng/mL for C(max), and 0.9 (0.5) h for half-life. CONCLUSION: Mesalazine is released in the rectum of patients, with a bioavailability of about 40%. Tissue distribution is also appreciable. Both parameters appear higher than in healthy volunteers.

Adult↗
PubMed2001

Genetic variation in the 5q31 cytokine gene cluster confers susceptibility to Crohn disease.

Linkage disequilibrium (LD) mapping provides a powerful method for fine-structure localization of rare disease genes, but has not yet been widely applied to common disease. We sought to design a systematic approach for LD mapping and apply it to the localization of a gene (IBD5) conferring susceptibility to Crohn disease. The key issues are: (i) to detect a significant LD signal (ii) to rigorously bound the critical region and (iii) to identify the causal genetic variant within this region. We previously mapped the IBD5 locus to a large region spanning 18 cM of chromosome 5q31 (P<10(-4)). Using dense genetic maps of microsatellite markers and single-nucleotide polymorphisms (SNPs) across the entire region, we found strong evidence of LD. We bound the region to a common haplotype spanning 250 kb that shows strong association with the disease (P< 2 x 10(-7)) and contains the cytokine gene cluster. This finding provides overwhelming evidence that a specific common haplotype of the cytokine region in 5q31 confers susceptibility to Crohn disease. However, genetic evidence alone is not sufficient to identify the causal mutation within this region, as strong LD across the region results in multiple SNPs having equivalent genetic evidence-each consistent with the expected properties of the IBD5 locus. These results have important implications for Crohn disease in particular and LD mapping in general.

Chromosome Mapping↗
PubMed2001

Clinical, biological, and histologic parameters as predictors of relapse in ulcerative colitis.

BACKGROUND & AIMS: Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel disease. We aimed to assess whether clinical, biological, and histologic parameters in quiescent UC predict time to clinical relapse. METHODS: Seventy-four patients with clinically and endoscopically determined inactive UC were followed up for 1 year or for a shorter period if they had a relapse. Serum erythrocyte sedimentation rate; C-reactive protein, interleukin (IL)-1beta, IL-6, and IL-15 values; anti-neutrophil cytoplasmic antibody titers; and rectal biopsy specimens were obtained at baseline, at 6 and 12 months, and/or at relapse. Multivariate survival analysis was performed to determine independent predictors of clinical relapse. RESULTS: Twenty-seven patients relapsed (19/42 women; 8/32 men). Multivariate Cox regression analysis retained younger age (P = 0.003; hazard ratio, 0.4 per decade), greater number of prior relapses in women (P < 0.001; hazard ratio, 1.6 per prior relapse), and basal plasmacytosis (P = 0.003; hazard ratio, 4.5) on rectal biopsy specimens as predictors of shorter time to clinical relapse. Kaplan-Meier survival curves showed the 20-30-year-old age group and women with more than 5 prior relapses to be groups with shorter times to relapse. CONCLUSIONS: Younger age, multiple previous relapses (for women), and basal plasmacytosis on rectal biopsy specimens were independent predictors of earlier relapse. These findings may help identify patients with inactive UC who will require optimal maintenance medical therapy.

Adult↗
PubMed2001

Psychological distress, social support, and disease activity in patients with inflammatory bowel disease.

OBJECTIVES: The objectives of this study were to compare the psychological status of patients in active and inactive disease states, to assess social support, and to identify correlates of psychological distress in patients with inflammatory bowel disease (IBD). METHODS: This cross-sectional study was conducted in 200 patients (mean age 36.7 yr [SD = 14.8], 119 [59.5%] female) with long-standing IBD who were seen in tertiary care. Psychosocial assessments included psychological distress (Symptom Checklist-90R), social support (Social Support Questionnaire-6), perceived stress (Perceived Stress Scale-10), and recent minor stressful events (Weekly Stress Inventory). Disease activity was assessed with the Harvey Bradshaw Index. RESULTS: Patients reported higher levels of satisfaction with social support and smaller network sizes compared with normative values. Using multiple linear regression, the independent correlates of psychological distress (p = 0.0001; adjusted R2 = 0.62) were as follows: active disease (p = 0.0234), less time since diagnosis (p = 0.0012), and greater number (p = 0.0001) and impact of stressful events (p = 0.0003). A statistically significant interaction term (p = 0.0171) revealed that the relationship between psychological distress and perceived stress changes depending on the level of satisfaction with social support. For patients with low levels of perceived stress, satisfaction with social support did not affect levels of psychological distress. However, for patients who experienced moderate to high levels of perceived stress, high satisfaction with social support decreased the level of psychological distress. CONCLUSIONS: These findings suggest that strategies aimed at improving social support can have a favorable impact on psychological distress and, ultimately, can improve health outcomes in patients with IBD.

Adult↗
PubMed2001

Medical management of ulcerative proctitis, proctosigmoiditis, and left-sided colitis.

Ulcerative colitis distal to the splenic flexure includes disease confined to the rectum (proctitis), rectosigmoid (proctosigmoiditis or distal colitis), or extending to the descending colon or splenic flexure (left-sided colitis). These subtypes represent up to 60% to 80% of newly presenting cases of ulcerative colitis. Although these conditions are defined by the extent of colon that is affected, they also share the characteristic of being amenable to topical therapy. In general, the course of disease is milder and symptoms are less severe than in patients with more extensive colonic involvement. Nonetheless, symptoms may significantly impair patients' health-related quality of life. Treatment options include the oral and/or rectal 5-aminosalicylate (5-ASA) preparations. Rectal therapy delivering higher concentrations of active medication (5-ASA or glucocorticoids) directly to the inflamed mucosa while minimizing systemic absorption provides a highly effective and safe treatment. Oral glucocorticoids are indicated in patients who are resistant to or intolerant of 5-ASA therapy. Immunomodulators have an important role in individuals with glucocorticoid dependent or glucocorticoid refractory disease. This article reviews the clinical diagnosis and current medical management of ulcerative proctitis, proctosigmoiditis, and left-sided ulcerative colitis, including patients resistant to conventional medical therapy.

Administration, Oral↗
PubMed2000

Genomewide search in Canadian families with inflammatory bowel disease reveals two novel susceptibility loci.

The chronic inflammatory bowel diseases (IBDs)-Crohn disease (CD) and ulcerative colitis (UC)-are idiopathic, inflammatory disorders of the gastrointestinal tract. These conditions have a peak incidence in early adulthood and a combined prevalence of approximately 100-200/100,000. Although the etiology of IBD is multifactorial, a significant genetic contribution to disease susceptibility is implied by epidemiological data revealing a sibling risk of approximately 35-fold for CD and approximately 15-fold for UC. To elucidate the genetic basis for these disorders, we undertook a genomewide scan in 158 Canadian sib-pair families and identified three regions of suggestive linkage (3p, 5q31-33, and 6p) and one region of significant linkage to 19p13 (LOD score 4.6). Higher-density mapping in the 5q31-q33 region revealed a locus of genomewide significance (LOD score 3.9) that contributes to CD susceptibility in families with early-onset disease. Both of these genomic regions contain numerous genes that are important to the immune and inflammatory systems and that provide good targets for future candidate-gene studies.

Age of Onset↗
PubMed2000

Regional differences in serotonergic input to canine parasternal intercostal motoneurons.

There is a mediolateral gradient in activation of the parasternal intercostal (PI) muscle during inspiration. In the present study, we tested the hypotheses that serotonergic [5-hydroxytryptamine (5-HT)] input from descending central drive and/or intrinsic size-related properties of PI motoneurons leads to the differential activation of PI muscles. In dogs, PI motoneurons innervating the medial and lateral regions of the PI muscles at the T(3)-T(5) interspaces were retrogradely labeled by intramuscular injection of cholera toxin B subunit. After a 10-day survival period, PI motoneurons and 5-HT terminals were visualized by using immunohistochemistry and confocal imaging. There were no differences in motoneuron morphology among motoneurons innervating the medial and lateral regions of the PI muscle. However, the number of 5-HT terminals and the 5-HT terminal density (normalized for surface area) were greater in motoneurons innervating the medial region of the PI muscle compared with the lateral region. These results suggest that differences in distribution of 5-HT input may contribute to regional differences in PI muscle activation during inspiration and that differences in PI motoneuron recruitment do not relate to size.

Animals↗
PubMed1999

Transurethral thermotherapy for benign prostatic hyperplasia significantly decreases infravesical obstruction: results in 134 patients after 1 year.

PURPOSE: We prospectively evaluated a decrease in outflow obstruction caused by benign prostatic hyperplasia (BPH) with second generation thermotherapy. MATERIALS AND METHODS: Transurethral microwave therapy was given with local anesthesia to 134 patients with urodynamically and cystoscopically documented obstruction by BPH and preserved detrusor function. Of 134 patients 67 (50%) had a general health score of 3 or greater. RESULTS: Urgency was the main complaint during thermotherapy. After a median followup of 24 months (minimum 12) 100 patients were evaluable at 6 and 12 months. Of the initial 134 patients 17 (13%) who required additional treatment (repeat thermotherapy, transurethral prostatic resection, permanent cystostomy), 7 who died during followup for treatment unrelated reasons and 10 who were lost to followup or refused evaluation were excluded from further analysis. Mean International Prostate Symptom Score decreased from 22.5 before to 3.6 at 6 months after treatment and remained stable at 12 months. Mean Quality of Life Index improved from 4.3 before to 1 at 12 months after treatment. Mean maximum flow increased from 7.3 ml. per second before to 14.5 at 6 months and 13.9 at 12 months after treatment. Mean post-void residual decreased from 199 to 34.8 and 37.2 ml. at 6 and 12 months, respectively. Urodynamic evaluation of 84 patients after 6 months revealed a decrease in mean detrusor opening pressure from 96.8 to 53 cm. water and mean detrusor pressure at maximum flow from 99.8 to 59.7 cm. water. Mean ultrasonographic prostate volume decreased from 57.6 to 42.4 cc and a cavity in the prostate was documented in 65 of the 84 cases (77%). All changes between the pretreatment and posttreatment values at 6 and 12 months, respectively, were statistically significant (paired t test p<0.00001). CONCLUSIONS: Targeted transurethral thermotherapy with second generation microwave equipment is minimally invasive, easy to apply and generally well tolerated with local anesthesia. Infravesical outlet obstruction and voiding pressures as assessed by pressure flow studies significantly decreased 6 months after treatment. Subjective voiding symptoms as well as post-void residual urine were significantly decreased, and urinary flow was improved 6 and 12 months after treatment of documented BPH.

Aged↗
PubMed1997

[Therapeutic options in advanced cancer of the prostate].

Drug therapy modalities in locally advanced and metastatic carcinoma of the prostate are primarily palliative. Therefore, the goal of systemic therapy is prevention or palliation of complications, such as pain, obstructive symptoms and bleeding. Thus far, there seems to be no survival benefit from hormonal treatment. The first step is always withdrawal of male sex hormones by means of orchiectomy or administration of LH-RH analogues, 70 to 80% of the patients respond favorably. Orchiectomy and LH-RH analogues are considered equal with regard to effectiveness and side effects, however, in the latter case an antiandrogen must be administered during the two weeks prior to start of treatment to prevent the flare-up phenomenon. Estrogens are rarely used anymore, because they can cause cardiovascular complications. In asymptomatic patients, the question remains to be answered if androgen withdrawal should be performed immediately at the time of diagnosis or delayed in case of possible symptoms. Antiandrogen agents block directly the androgen receptors in the prostatic cell. However, monotherapy with antiandrogens is not yet an established procedure. Instead, since 5% of circulating androgens are of adrenal origin, antiandrogens are combined with either orchiectomy or LH-RH analogues for total androgen suppression. The benefit of such a combined androgen suppression could not be proven conclusively and might be minimal at best. Novel modalities of hormonal therapy like intermittent androgen suppression are currently being investigated. In most cases, tumor progression after hormonal therapy is due to hormone-refractory cell lines. Cytotoxic chemotherapy is largely ineffective in treating prostatic cancer. Commonly used chemotherapeutic substances lead to temporary remission in 10 to 20% of the patients at most. External beam irradiation or Strontium-89 therapy are useful in palliation of painful bone metastases.

Antineoplastic Agents, Hormonal↗
PubMed1997

[First evaluation of a year of ambulatory surgery in urology].

Day surgery in urology is in full growth actually. The present report is based on our first 120 patients. Low post-operative complication rate, patients' satisfaction and economical savings are the main factors for the important increase in this type of surgery.

Ambulatory Surgical Procedures↗
PubMed1996

Mesalamine-induced lung toxicity.

Lung toxicity associated with 5-aminosalicylate (5-ASA) agents is a rare entity. We report the case of a 32-yr-old woman with ulcerative colitis who developed progressive shortness of breath while taking one of the 5-ASA drugs, oral mesalamine. Bilateral pulmonary infiltrates, peripheral eosinophilia, and histological findings consistent with acute pneumonitis characterized the lung injury. Although the differential diagnosis is broad, mesalamine-induced lung damage must be considered in patients who develop unexplained respiratory symptoms while taking this agent.

Adult↗