Maturity-onset diabetes of the young with necrobiosis lipoidica and granuloma annulare.

We describe a 12-year-old white girl with granuloma annulare localized to both ankles since she was five, necrobiosis lipoidica in the left pretibial region since she was ten, and a recent history of weakness, migraine, and weight loss. After initial evaluation, high fasting blood glucose levels and high hemoglobin A1c were found. The family history for non-insulin-dependent diabetes was suggestive of maturity-onset diabetes of the young. Coexistence of necrobiosis lipoidica and granuloma annulare, together with a family history of non-insulin-dependent diabetes, the age of onset, and the absence of ketosis, are specific features making possible, a clinical diagnosis. Genetic confirmation may not be so easily accessible or necessary.

Role of the intestinal tight junction modulator zonulin in the pathogenesis of type I diabetes in BB diabetic-prone rats.

Increased intestinal permeability has been observed in numerous human autoimmune diseases, including type-1 diabetes (T1D) and its' animal model, the BB-wor diabetic prone rat. We have recently described zonulin, a protein that regulates intercellular tight junctions. The objective of this study was to establish whether zonulin-dependent increased intestinal permeability plays a role in the pathogenesis of T1D. In the BB diabetic-prone rat model of T1D, intestinal intraluminal zonulin levels were elevated 35-fold compared to control BB diabetic-resistant rats. Zonulin up-regulation was coincident with decreased small intestinal transepithelial electrical resistance, and was followed by the production of autoantibodies against pancreatic beta cells, which preceded the onset of clinically evident T1D by approximately 25 days. In those diabetic prone rats that did not progress to diabetes, both intraluminal zonulin and transepithelial electrical resistance were similar to those detected in diabetic-resistant animal controls. Blockade of the zonulin receptor reduced the cumulative incidence of T1D by 70%, despite the persistence of intraluminal zonulin up-regulation. Moreover, treatment responders did not seroconvert to islet cell antibodies. Combined together, these findings suggest that the zonulin-induced loss in small intestinal barrier function is involved in the pathogenesis of T1D in the BB diabetic-prone animal model.

Deep sedation with propofol by nonanesthesiologists: a prospective pediatric experience.

BACKGROUND: The need to perform procedural sedation for children has increased in recent years, and so has the experience of nonanesthesiologists in this field. The use of propofol increases the success of satisfactory deep sedation, but it can produce rapid and profound decreases in level of consciousness and cardiorespiratory function. Data are needed to assess the safety of this drug outside an anesthesiology setting. OBJECTIVE: To assess safety and efficacy of procedural sedation with propofol in a pediatric ward of a tertiary-care pediatric teaching hospital with trained personnel and monitoring facilities. METHODS: Patients admitted to the hospital who needed invasive procedures underwent procedural sedation by the pediatric sedation unit with intravenous propofol. A training protocol was developed to educate nurses and residents. RESULTS: We performed 1059 procedures. Sedation was achieved in all procedures, and all but 1 were successfully performed. No patient required intubation. Transient desaturation resolving spontaneously occurred in 134 (12.7%) of 1059 patients. Major desaturation requiring a short course of ventilation occurred in 4 (0.8%) of 483 patients undergoing upper endoscopies, in 1 (0.3%) of 287 patients undergoing painful procedures, and in none of the 289 patients undergoing colonoscopies. Laryngospasm occurred in 10 (2.1%) of 483 patients undergoing upper endoscopies. CONCLUSIONS: In this experience, the use of propofol with concurrent oxygen administration allowed sedations in children with no significant complications for colonoscopies and painful procedures. Complications in the group of upper endoscopies appear too high for recommending propofol in a sedation unit with residents in attendance. This protocol of procedural sedation by nonanesthesiologists allowed a significant increase in the number of procedures performed with sedation and saved anesthesiology resources.

Prevalence of celiac disease in at-risk and not-at-risk groups in the United States: a large multicenter study.

BACKGROUND: Celiac disease (CD) is an immune-mediated enteropathic condition triggered in genetically susceptible individuals by the ingestion of gluten. Although common in Europe, CD is thought to be rare in the United States, where there are no large epidemiologic studies of its prevalence. The aim of this study was to determine the prevalence of CD in at-risk and not-at-risk groups in the United States. METHODS: Serum antigliadin antibodies and anti-endomysial antibodies (EMA) were measured. In EMA-positive subjects, human tissue transglutaminase IgA antibodies and CD-associated human leukocyte antigen DQ2/DQ8 haplotypes were determined. Intestinal biopsy was recommended and performed whenever possible for all EMA-positive subjects. A total of 13 145 subjects were screened: 4508 first-degree and 1275 second-degree relatives of patients with biopsy-proven CD, 3236 symptomatic patients (with either gastrointestinal symptoms or a disorder associated with CD), and 4126 not-at-risk individuals. RESULTS: In at-risk groups, the prevalence of CD was 1:22 in first-degree relatives, 1:39 in second-degree relatives, and 1:56 in symptomatic patients. The overall prevalence of CD in not-at-risk groups was 1:133. All the EMA-positive subjects who underwent intestinal biopsy had lesions consistent with CD. CONCLUSIONS: Our results suggest that CD occurs frequently not only in patients with gastrointestinal symptoms, but also in first- and second-degree relatives and patients with numerous common disorders even in the absence of gastrointestinal symptoms. The prevalence of CD in symptomatic patients and not-at-risk subjects was similar to that reported in Europe. Celiac disease appears to be a more common but neglected disorder than has generally been recognized in the United States.