Reversal of parenteral nutrition-associated liver disease with a fish oil-based lipid emulsion (Omegaven) in an adult dependent on home parenteral nutrition.

Patients with intestinal failure and short bowel syndrome usually require chronic parenteral nutrition (PN). PN is associated with risks, including infections, vascular thrombosis, and liver disease. PN-associated liver disease (PNALD) can progress from steatosis to chronic hepatitis and ultimately to cirrhosis. The etiology of PNALD is not completely understood. Therapies for PNALD include carbohydrate or lipid calorie reduction, antibiotics, or the use of ursodeoxycholic acid. When these efforts fail, therapeutic options are limited and liver transplantation may be required. The transition from a soybean- to a fish oil-based lipid formulation, such as the ω-3 parenteral lipid formulation (Omegaven), has shown a dramatic reversal of PNALD within the pediatric population. This is the first report of a PN-dependent adult in the United States complicated by PNALD and hepatic failure who had improvement of liver disease with an ω-3 fish oil-based parenteral formulation.

Delayed radionucleotide gastric emptying studies predict morbidity in diabetics with symptoms of gastroparesis.

BACKGROUND & AIMS: The aim of this study was to evaluate the prognostic value of gastric emptying studies on the morbidity associated with diabetic gastroparesis. METHODS: This was a parallel cohort study of 3 groups. Group A (n = 94) contained diabetic patients (type 1 and type 2) with classic symptoms of gastroparesis (including early satiety, postprandial fullness, bloating, abdominal swelling, nausea, vomiting, and retching) and delay in radionucleotide gastric emptying study. Group B (n = 94) contained diabetic subjects with classic symptoms of gastroparesis but negative scintigraphy. Group C (n = 94) contained diabetic subjects without symptoms of gastroparesis. Data were gathered on the number of days hospitalized and hospitalizations, office visits, emergency department visits, death rate, glycosylated hemoglobin levels, medications, and past medical history. RESULTS: Group A had significantly more hospital days per 1000 patient days (25.5) than both group B (5.1; P < .01) and group C (2.3; P < .01). Group A also had significantly more hospitalizations, office visits, and emergency department visits than both group B and group C. Deaths and mean glycosylated hemoglobin levels did not differ between the groups. Patients in group A were more likely to have cardiovascular disease (19.2% vs 6.4%, A vs C; P < .05), hypertension (63% vs 43%, A vs C; P = .005), and retinopathy (33% vs 11.7%, A vs C; P < .001). CONCLUSIONS: A delayed radionucleotide gastric emptying study predicts negative health outcomes in diabetic patients with symptoms of gastroparesis. We identified a correlation between diabetic gastroparesis and cardiovascular disease, hypertension, and retinopathy that may indicate an underlying vascular etiology.

Celiac disease: diagnosis, autoimmune mechanisms and treatment.

Celiac disease is a systemic autoimmune disorder triggered by the ingestion of gluten found in wheat and related grains. Once considered rare, celiac disease is now thought to affect more than one in 100 individuals, and is commonly associated with other autoimmune disorders. It predisposes patients to an increased risk of malignancy if left untreated. Celiac disease is HLA restricted as only HLA-DQ2 and -DQ8 are able to bind deamidated gluten with sufficient affinity to trigger an immune response. Both cellular and humoral immune activation occur, leading to local tissue damage and antibody formation. These antibodies, primarily to tissue transglutaminase, are the basis for highly accurate serologic testing, although the gold standard for celiac disease diagnosis remains small intestinal biopsy. Currently, the only treatment for celiac disease is a life-long gluten-free diet, although multiple novel therapeutic modalities are being studied. Although most individuals with celiac disease respond completely to gluten withdrawal, 10-20% have persistent symptoms at some point during their course and less than 1% develop refractory celiac disease, an entity of substantial morbidity.

The effects of cocaine on the rate independent brain stimulation reward threshold in the mouse.

Interest in the development of mouse models of drug abuse liability has increased with the introduction of selective gene expression. In the rat, the ability of drugs to lower brain stimulation reward (BSR) thresholds often correlates with high abuse liability. Measurement of BSR thresholds using rate-independent methods decreases the influence of impaired motor performance on threshold determination that may confound studies of mutant mice. In the present experiment, the effects of cocaine on mouse BSR thresholds were assessed using a modification of the rate-independent psychophysical method of limits as current intensity was systematically varied in a series of descending and ascending discrete trials. Bipolar electrodes were implanted into the medial forebrain bundle of male C57Bl/6N mice and the effects of intraperitoneal saline and cocaine (5.0-30.0 mg/kg) on BSR thresholds were assessed using a within-subject crossover design. Threshold was defined as the intensity at which the mouse would respond in 50% of the trials. Threshold levels were significantly lowered below levels of control following cocaine administration with the maximum lowering following a 20.0-mg/kg dose. These findings indicate that cocaine increases the sensitivity of the mouse to BSR, and that BSR thresholds can be determined using rate-independent methods in this species.

Structure function analysis of interleukin 7: requirement for an aromatic ring at position 143 of helix D.

The residues located at the carboxyl terminus of helix D in interleukin-7 (IL-7) have previously been targeted as important for recruitment and binding to the gamma chain component of the IL-7 receptor (IL-7R). In this study, Trp 143 of helix D was mutated to His, Phe, Tyr and Pro and these mutants, along with a W143A mutant previously described, were studied to determine the effects on activation of DNA synthesis and binding affinity to IL-7R positive 2E8 cells. The W143F and W143Y mutants were similar to wild type IL-7 in their binding properties and retained 85% and 74% of their activating properties, respectively. In contrast, the W143H mutant possessed a lower binding affinity and a corresponding decrease in activation, the W143A mutant possessed an over 100-fold decreased binding affinity and some residual activation activity and the W143P mutant possessed a greatly decreased binding affinity and did not activate. These results strongly suggest an aromatic residue is required at position 143 for IL-7R binding and subsequent signal transduction.