Drug-Induced Esophagitis

Drug-induced esophagitis is being recognized increasingly in the past few years. We have reviewed 175 cases with a view to classifying this disease based on pathology. Drug-induced esophageal injury tends to occur at the anatomical site of narrowing, with the middle third behind the left atrium predominating. The disease is classified broadly into two groups. The first group is transient and self-limiting, as exemplified by tetracycline- and emepronium-induced injury (57.3%). The second is the persistent esophagitis group, often with stricture with two distinct entities: 1) patients on nonsteroidal antiinflammatory agents whose injury is aggravated by gastroesophageal reflux (26.2%) (reflux aggravated), and 2) patients with potassium chloride and quinidine sulfate-induced injury (16.2%) (persisting drug injury). We report a case that highlights the pathophysiology (delayed transit, persisting potassium within the stricture) of this type of injury which is not reflux aggravated.     

Seroprevalence of Chlamydia pneumoniae infection in Taiwan

OBJECTIVES: To survey the seroprevalence of Chlamydia pneumoniae (C. pneumoniae) infection in healthy subjects in Taiwan. MATERIALS AND METHODS: We used microimmunofluorescence antibody assay to survey the prevalence of antibodies to C. pneumoniae in 620 serum samples from healthy subjects aged 6 months to 86 years in Taiwan. RESULTS: The mean prevalence (+/-SD) of IgG antibodies against C. pneumoniae at titer greater than or equal 1:16 was 55.8% (range 7.8-81.8%). The antibody prevalence was low in children under the age of 10 years (7.8%), and increased rapidly with age. Most individual acquired infection during the second and third decades of life with highest antibody prevalence reached up to 81.8% at fifth decade of life and remained high (70%) thereafter. CONCLUSIONS: Chlamydia pneumoniae infection is highly endemic in Taiwan. These data contribute to the understanding of asymptomatic infections with C. pneumoniae in general population and should serve as a basis for studies on the role of C. pneumoniae infections and their related diseases.     

Peripheral versus central effects of glucagon-like peptide-1 receptor agonists on satiety and body weight loss in Zucker obese rats

The present study explores the potential utility of peripheral versus central administration of glucagon-like peptide-1 (GLP-1) receptor agonists in the regulation of feeding behavior in Wistar and Zucker obese rats. Acute central (intracerebroventricular [i.c.v.]) and peripheral (subcutaneous [s.c.]) administration of both GLP-1 (7-36) amide and exendin-4 resulted in a reduction in food intake for at least 4 hours, exendin-4 being much more potent than GLP-1 (7-36) amide, especially after peripheral administration. Both Zucker obese rats (fa/fa) and their lean littermates (Fa/-) responded to acute central and peripheral administration of exendin-4. Moreover, in situ hybridization revealed specific labeling for the mRNA for GLP-1 receptors in several brain areas of both the obese and lean rats. The presence of this receptor was also detected by affinity cross-linking assays. Long-term s.c. administration of exendin-4 (1 single injection per day, 1 hour prior to the onset of the dark phase of the cycle) decreased daily food intake and practically blocked weight gain in obese rats. In contrast to previous studies, these findings show that peripheral (s.c.) administration of both GLP-1 receptor agonists also induces satiety and weight loss in rats, and suggest the potential usefulness of exendin-4 as a therapeutic tool for the treatment of diabetes and/or obesity.     

Glucocorticoid and mineralocorticoid cross-talk with progesterone receptor to induce focal adhesion and growth inhibition in breast cancer cells

Progesterone receptor (PR), glucocorticoid receptor, and mineralocorticoid receptor belong to a subfamily of nuclear receptor superfamily with similar sequence and structural characteristics. Many reports have documented glucocorticoid-like effects of progesterone in various tissues. This study addresses the issue of cross-talk between corticosteroids and PR using PR-transfected MDA-MB-231 cells ABC28 and vector-transfected control cells CTC15. At physiological concentrations, dexamethasone, cortisol, and aldosterone mimic the effects of progesterone by inducing significant growth inhibition, cell spreading, and focal adhesions in PR-positive ABC28 cells. These hormones also induce progesterone-like effects in increasing the expression of p21(CIP1/WAF1) protein and decreasing the level of phospho-p42/p44 mAPK. Two lines of evidence suggest that these effects are mediated by cross-talk with PR. First, these compounds do not exhibit the same progesterone-like effects in PR-negative CTC15 cells. Second, PR blocker ZK98299 abolishes their effect on cell spreading and focal adhesion in ABC28 cells. The cross-talk is corticosteroid specific because estradiol and thyroid hormone triiodothyronine have no effect on PR-transfected cells ABC28. It is also interesting to note that dexamethasone induces a small but detectable increase of focal adhesions and limited growth stimulation in vector-transfected cells CTC15. In contrast, progesterone exhibits no detectable effect on CTC15 cells. This study provides evidence that glucocorticoid and mineralocorticoid cross-talk with PR to produce progesterone-like effects in breast cancer cells. Glucocorticoid receptor and PR share some overlapping activity in mediating focal adhesion but not in regulating cell proliferation.     

Acute exacerbation of COPD requiring admission to the intensive care unit

OBJECTIVE: The aim of this study was to summarize experiences of patients admitted to the intensive care unit (ICU) for an acute exacerbation of COPD and to identify factors associated with a poor outcome. METHODOLOGY: An observational case series of 102 consecutive admissions to the ICU for acute exacerbation of COPD between January 1998 and December 2002 were studied. RESULTS: In total, 102 admissions to the ICU were reviewed. There were no ICU deaths but there were 18 hospital deaths (18%). A total of 28 patients were treated with non-invasive positive pressure ventilation (NIPPV), of whom four (14% failure rate) subsequently required intubation and mechanical ventilation (MV). Another 16 patients (16%) were successfully weaned from MV with NIPPV. Nine patients (9%), who had more than one episode of re-intubation after weaning (RAW), were from the mechanically ventilated group. Tracheostomy was performed for four patients (3.9%). The median duration of both NIPPV and MV was 1 day. The median length of stay in the ICU and hospital were 2 days (SD, 7.2) and 8 days (SD, 9.6), respectively. Univariate analysis identified serum total protein to be associated with hospital mortality (P = 0.004) CONCLUSION: For patients with acute exacerbations of COPD in the ICU, serum total protein, a surrogate marker for nutrition, was significantly associated with hospital mortality.     

Prediction of mortality in community-living frail elderly people with long-term care needs

OBJECTIVES: To develop and validate a prognostic index for mortality in community‐living, frail elderly people. DESIGN: Cohort study of Program of All‐Inclusive Care for the Elderly (PACE) participants enrolled between 1988 and 1996. SETTING: Eleven PACE sites, a community‐based long‐term care program that cares for frail, chronically ill elderly people who meet criteria for nursing home placement. PARTICIPANTS: Three thousand eight hundred ninety‐nine PACE enrollees. The index was developed in 2,232 participants and validated in 1,667. MEASUREMENTS: Time to death was predicted using risk factors obtained from a geriatric assessment performed by the PACE interdisciplinary team at the time of enrollment. Risk factors included demographic characteristics, comorbid conditions, and functional status. RESULTS: The development cohort had a mean age of 79 (68% female, 40% white). The validation cohort had a mean age of 79 (76% female, 65% white). In the development cohort, eight independent risk factors of mortality were identified and weighted, using Cox regression, to create a risk score: male sex, 2 points; age (75–79, 2 points; 80–84, 2 points; ≥85, 3 points); dependence in toileting, 1 point; dependence in dressing (partial dependence, 1 point; full dependence, 3 points); malignant neoplasm, 2 points; congestive heart failure, 3 points; chronic obstructive pulmonary disease, 1 point; and renal insufficiency, 3 points. In the development cohort, respective 1‐ and 3‐year mortality rates were 6% and 21% in the lowest‐risk group (0–3 points), 12% and 36% in the middle‐risk group (4–5 points), and 21% and 54% in the highest‐risk group (>5 points). In the validation cohort, respective 1‐ and 3‐year mortality rates were 7% and 18% in the lowest‐risk group, 11% and 36% in the middle‐risk group, and 22% and 55% in the highest‐risk group. The area under the receiver operating characteristic curve for the point score was 0.66 and 0.69 in the development and validation cohorts, respectively. CONCLUSION: A multidimensional prognostic index was developed and validated using age, sex, functional status, and comorbidities that effectively stratifies frail, community‐living elderly people into groups at varying risk of mortality.     

Abdominosacral resection for midrectal cancer.

Abdominosacral resection is the most reliable radical sphincter-saving operation for midrectal cancers which are too low for anterior resection. The posterior incision provides maximum exposure for wide resection of the tumor, a measured distal margin, and an accurate anastomosis. The procedure can be carried out consistently to the pelvic floor without disrupting the anal sphincters and their innervation. Sphincter function is consistently preserved. Mortality rate is no higher than for other radical rectal resections. Morbidity can be limited by the selective use of protective colostomy. The use of mechanical retractors and the end-to-end stapler facilitates the operation and should encourage its wider application. The transsacral approach allows mobilization of the rectum to the levators in every case, and resection is limited only by the distance of the tumor from the sphincter, and not by poor exposure due to obesity or a narrow pelvis. In the treatment of 926 consecutive patients with rectal cancer, sphincter-saving resection was possible in 79%. In our experience, abdominosacral resection extends the range of sphincter-saving resection beyond that which is possible by the abdominal approach alone, with no compromise in safety and no increased risk of local recurrence or death from cancer.