Publications

Inflammatory bowel disease (IBD) patients display elevated levels of intraluminal nitric oxide (NO). NO can react with other molecules to form toxic compounds, which has led to the idea that NO may be an important mediator of IBD. However, the cellular source of NO and how its production is regulated in the intestine are unclear. In this study we aimed to determine if intestinal myofibroblasts produce NO in response to the IBD-associated cytokines IL-1β, TNFα, and IFNγ. Intestinal myofibroblasts were isolated from mice and found to express inducible nitric oxide synthase (iNOS) mRNA, but not endothelial NOS or neuronal NOS. Individual treatment of myofibroblasts with IL-1β, TNFα, or IFNγ had no effect on NO production, but stimulation with combinations of these cytokines synergistically increased iNOS mRNA and protein expression. Treatment with TNFα or IFNγ increased cell surface expression of IFNγRI or TNFRII, respectively, suggesting that these cytokines act in concert to prime NO production by myofibroblasts. Impairment of NF-κB activity with a small molecule inhibitor was sufficient to prevent increased expression of IFNγRI or TNFRII, and inhibition of Akt, JAK/STAT, or NF-κB blocked nearly all NO production induced by combinatorial cytokine treatment. These data indicate that intestinal myofibroblasts require stimulation by multiple cytokines to produce NO and that these cytokines act through a novel pathway involving reciprocal cytokine receptor regulation and signaling by Akt, JAK/STAT, and NF-κB.

BACKGROUND

Diabetes complications account for significant worldwide morbidity and mortality. Improving glycemic control decreases microvascular complications, particularly among patients with the worst control. Current performance measures fail to prioritize such individuals. The categorization of glycemic control within a safety-net clinic population was compared using a common performance measure against one derived from a metric accounting for change in glycated hemoglobin (A1c) over time.

METHODS

Retrospective cohort analysis of all patients in a safety-net primary care clinic population quality registry with confirmed diabetes mellitus who had at least two A1c values between 2007 through 2011. Patients were stratified into five groups' on the basis of maximum and earliest A1c level (< 7%, 7% to < 8%, 8% to < 9%, 9% to < 10%, and > 10%). The change in Alc was assessed over time and compared with standard healthcare effectiveness data and information set (HEDIS) performance measures.

RESULTS

Some 1122 patients were included in the analysis, with mean A1c of 7.9%. There was a modest annual decrease in the average A1c, and > 19% of patients improved by 1% or more during each of the previous three years. For patients who had maximum A1c values > or = 10%, there was a significantly greater reduction in A1c (p < .01), which was not reflected in the standard performance measure.

CONCLUSIONS

It is feasible for safety-net clinics to analyze their patients with diabetes by level of disease control on the basis of change in A1c over time. Patients with the worst glycemic control tend to have the greatest improvement but are often overlooked by conventional performance measures. Improved performance measures should focus on longitudinal diabetes control and emphasize reducing risk of complications among patients at highest risk.

Twitter.com is a "micro-blogging" website. Although Twitter use is growing rapidly, little is known about health behavior discussions on this site, even though a majority of messages are publicly available. We retrieved publicly available Twitter messages during a 5-week period in early 2012, searching separately for the terms "Pap smear" and "mammogram." We used content analysis to code each 140-character message, generating a separate coding framework for each cancer screening term and calculating the frequencies of comments. Using the brief account description, we also coded the author as individual, organization, or news media outlet. There were 203 Pap smear and 271 mammogram messages coded, over three fourths of which were from individual accounts. Overall, 22 % of Pap smear messages and 25 % of mammogram messages discussed personal experiences, including attending appointments, negative sentiment about the procedure, and results. Other messages from both individuals and organizations (8 % Pap smear, 18 % mammogram) promoted screening. About one quarter of the messages expressed personal experiences with cancer screening. This demonstrates that Twitter can be a rich source of information and could be used to design new health-related interventions.

Repeated pulmonary exacerbation and progressive lung function decline characterize cystic fibrosis (CF) disease, and represents one of the leading causes of mortality in this patient population. Recent studies have shown, using culture-independent assays, that multiple microbial species can be detected in airway samples from CF patients. Moreover, specific groups of bacteria within these bacterial communities or microbiota, are highly associated with disease-associated factors such as antibiotic administration. This raises the possibility that, as in other human niches, pathogenic processes in the CF airways represent polymicrobial activities and that microbiome composition and perturbations to these communities define patient pulmonary health status. Airway samples are typically collected through the mouth, and are thus susceptible to contamination by upper airway secretions; hence, caution must be exercised in interpreting these data. Nonetheless, given the continuum of the upper and lower respiratory tract, understanding the contribution of these mixed-species assemblages to airway health is essential to improving CF patient care. This article aims to discuss recent advances in the field of CF airway microbiome research and interpret these findings in the context of CF pulmonary disease.

We evaluated an African American woman referred in 1986 at age 33 years because of renal potassium and calcium wasting and chronic hip pain. She presented normotensive, hypokalemic, hypocalcemic, normophosphatemic, and hypercalciuric. Marked hyperparathyroidism was evident. Urinary cyclic adenosine monophosphate (cAMP) excretion did not increase in response to parathyroid hormone (PTH) infusion, indicating renal resistance to PTH. X-rays and bone biopsy revealed severe osteitis fibrosa cystica, confirming skeletal responsiveness to PTH. Renal potassium wasting, suppressed plasma renin activity, and elevated plasma and urinary aldosterone levels accompanied her hypokalemia, suggesting primary hyperaldosteronism. Hypokalemia resolved with spironolactone and, when combined with dietary sodium restriction, urinary calcium excretion fell and hypocalcemia improved, in accord with the known positive association between sodium intake and calcium excretion. Calcitriol and oral calcium supplements did not suppress the chronic hyperparathyroidism nor did they reduce aldosterone levels. Over time, hyperparathyroid bone disease progressed with pathologic fractures and persistent pain. In 2004, PTH levels increased further in association with worsening chronic kidney disease. Eventually hypercalcemia and hypertension developed. Localizing studies in 2005 suggested a left inferior parathyroid tumor. After having consistently declined, the patient finally agreed to neck exploration in January 2009. Four hyperplastic parathyroid glands were removed, followed immediately by severe hypocalcemia, attributed to "hungry bone syndrome" and hypoparathyroidism, which required prolonged hospitalization, calcium infusions, and oral calcitriol. Although her bone pain resolved, hyperaldosteronism persisted.