Functional gastrointestinal disorders among people with sleep disturbances: a population-based study

OBJECTIVE: To determine whether unexplained gastrointestinal (GI) symptoms are more common in people with self-reported sleep disturbance. PARTICIPANTS AND METHODS: From November 1988 to June 1994, valid self-report questionnaires were mailed to age- and sex-stratified random samples of Olmsted County, Minnesota, residents aged 20 to 95 years. RESULTS: Of 2269 study participants (74% response rate), 52% were women (mean age, 45.0 years). The overall age- and sex-adjusted prevalence of sleep disturbance per 100 population was 13.5% (95% confidence interval [CI], 11.7%-15.3%). Among study participants with sleep disturbance, the prevalence of irritable bowel syndrome (IBS) was 33.3% (95% CI, 26.0%-40.5%) and the prevalence of frequent dyspepsia (FD) was 21.3% (95% CI, 14.4%-28.2%). After adjusting for age, sex, and somatization score, IBS was significantly more common in those with sleep disturbance (odds ratio, 1.6; 95% CI, 1.1-2.2), but the univariate association with FD was no longer statistically significant (odds ratio, 1.3; 95% CI, 0.9-1.9). CONCLUSIONS: Both IBS and FD are prevalent in those with self-reported sleep disturbance. Sleep disturbance was independently associated with IBS but not FD in the general population.     

Itolizumab,a novel anti-CD6 monoclonal antibody: a safe and efficacious biologic agent for management of psoriasis

Introduction: Psoriasis, a chronic immune-mediated skin disorder is associated with significant physical, psychological, and quality of life impairments. Along with well-documented genetic and environmental factors, immunological factors also contribute to the pathogenesis of psoriasis. Among the immunological factors, CD6 – dependent T-cell proliferation to form Th1 and Th17 cells play a major role in the pathogenesis of psoriasis. Itolizumab is the first humanized IgG1 monoclonal antibody, which selectively targets CD6.

Areas covered: The current article presents the pharmacology of itolizumab and provides a review of the currently available data on the efficacy and safety of itolizumab for management of moderate to severe plaque psoriasis.

Expert opinion: The use of biologics to attenuate the immune-mediated pathological events in psoriasis is a relatively well-established clinical practice. However, the safety and efficacy of biologics continues to be an unsettled topic of ongoing research. While available data seems to suggest that itolizumab may be a safer option, additional studies with higher sample sizes and active comparators are needed before definitive conclusions can be drawn on the place of itolizumab in the management of psoriasis.     

Nuclear factor-kappaB is central to the expression of truncated neurokinin-1 receptor in breast cancer: implication for breast cancer cell quiescence within bone marrow stroma

Breast cancer is a leading cause of mortality among women in the United States. Tac1 and neurokinin-1 (NK1) are involved in autocrine stimulation of breast cancer cells (BCCs). The single NK1 gene produces full-length (NK1-FL) and truncated (NK1-Tr) forms. NK1-Tr mediates malignancy in breast cells. We now report a critical role for nuclear factor-kappaB (NF-kappaB) in the expression of NK1-Tr, but not NK1-FL, in human BCCs. By Western and Northern blot analyses, NK1-FL and NK1-Tr were coexpressed in BCCs but were undetectable in nontumorigenic cells. Loss of repressive activity within the 5' flanking region of the NK1 partly accounts for constitutive expression of NK1 in BCCs but could not account for the presence of NK1-Tr. Transient transfections with dominant-negative and wild-type IkappaB show that activation of NF-kappaB is required for the expression of NK1-Tr. Tac1 gene was linked to the generation of NK1-Tr because its overexpression in BCCs led to the production of multiple cytokines that can activate NF-kappaB to mediate NK1-Tr expression. Studies with Tac1 knockdown BCCs and Tac1-expressing nontumorigenic breast cells verified a role for NF-kappaB in the expression of NK1-Tr. The quiescent phenotype of BCCs on contact with bone marrow stroma was partly explained by decreased NF-kappaB activation and undetectable NK1-Tr. In summary, this study shows a role for NF-kappaB in the expression of NK1-Tr in BCCs, which seems to be reversed by bone marrow stromal cells.     

Gastric metastases from esophageal cancer

Gastric metastases from esophageal cancer are seldom diagnosed antemortem. Two patients who had endoscopically detected gastric metastases from esophageal cancer are reported. One patient had a metastasis developing 6 months after radiation therapy; the other developed metastasis after surgical resection of the primary tumor.     

Medication induced esophageal injury

Five patients of medication-induced esophageal injury are reported. A history of ingestion of medications preceding the onset of dysphagia was obtained in all patients. Endoscopy revealed localised mucosal ulceration with surrounding edematous mucosa at the level of the aortic arch in four, and in the retro-cardiac esophagus in one patient. The medications involved were sustained release potassium chloride, doxycycline, ibuprofen, and an unidentified antibiotic and antihypertensive (one each). Healing of the esophageal ulcers was confirmed in all the patients by endoscopy.