Eosinophilic esophagitis in children and adults: a systematic review and consensus recommendations for diagnosis and treatment.

Small numbers of intraepithelial esophageal eosinophils (IEE) may be seen in 50% of patients with gastroesophageal reflux disease and occasionally in normal volunteers. High concentrations of IEE are rarely seen in either setting. During a two-year period we idetified 12 adult patients with very dense eosinophil infiltrates in esophageal biopsies (defined as >20 IEE/high-power field). Dysphagia was the presenting complaint in each, but no evidence of anatomical obstruction could be found. Endoscopic esophagitis was absent, but biopsy showed marked squamous hyperplasia and many IEE. Eleven patients had normal esophageal acid exposure on 24-hr pH monitoring. Esophageal manometry showed a nonspecific motility disturbance in 10 patients. For comparison, 90 patients with excess esophageal acid exposure on 24-hr pH monitoring were studied. Thirteen (14%) had motility disturbance, and 21 (23%) had dysphagia. Esophageal biopsies were devoid of IEE in 47 patients; none of the 43 with IEE had infiltrates as dense as those seen in the 12 study patients. The presence of high concentrations of IEE in esophageal biopsies from patients with dysphagia, normal endoscopy, and normal 24-hr esophageal pH monitoring represents a distinctive clinicopathologic syndrome not previously described.

Esophageal Eosinophilia with Dysphagia A Distinct Clinicopathologic Syndrome

https://www.gastrojournal.org/article/S0016-5085(03)01515-4/pdf

Natural history of primary eosinophilic esophagitis: a follow-up of 30 adult patients for up to 11.5 years

Increased intestinal permeability to macromolecules and endotoxemia in patients with chronic alcohol abuse in different stages of alcohol-induced liver disease

Cytokines play a central role in the modulation of the intestinal immune system. They are produced by lymphocytes (especially T cells of the Th1 and Th2 phenotypes), monocytes, intestinal macrophages, granulocytes, epithelial cells, endothelial cells, and fibroblasts. They have proinflammatory functions [interleukin-1 (IL-1), tumor necrosis factor (TNF), IL-6, IL-8, IL-12] or antiinflammatory functions [interleukin-1 receptor antagonist (IL-1ra), IL-4, IL-10, IL-11, transforming growth factor beta (TGF beta)]. Mucosal and systemic concentrations of many pro- and antiinflammatory cytokines are elevated in inflammatory bowel disease (IBD). An imbalance between proinflammatory and antiinflammatory cytokines was found for the IL-1/IL-1ra ratio in the inflamed mucosa of patients with Crohn's disease, ulcerative colitis, diverticulitis, and infectious colitis. Furthermore, the inhibition of proinflammatory cytokines and the supplementations with antiinflammatory cytokines reduced inflammation in animal models, such as the dextran sulfate colitis (DSS) model, the trinitrobenzene sulfonic acid (TNBS) model, or the genetically engineered model of IL-10 knockout mice. Based on these findings a rationale for cytokine treatment was defined. The first clinical trials using neutralizing monoclonal antibodies against TNF alpha (cA2) or the antiinflammatory cytokine IL-10 have shown promising results. However, many questions must be answered before cytokines can be considered standard therapy for IBD.

Cytokines in inflammatory bowel disease.

Cefotaxime (HR 756) is a new semisynthetic parenteral cephalosporin with exceptional activity against gram-negative organisms and considerable stability against their beta-lactamases. To study its pharmacokinetic properties, 0.5-, 1-, and 2-g doses were administered to each of six volunteers intravenously over 15 min, followed by a sustaining infusions of 0.5, 1, and 2 g/h, respectively, for 3 consecutive hours. The loading doses produced mean peak levels of 41, 93, and 160 mug/ml, and mean steady-state serum concentrations were 27, 64, and 138 mug/ml, respectively. The mean terminal half-life was 75 +/- 7 min. The total volume of distribution averaged 0.22 +/- 0.03 liters/kg of body weight. Total body and renal clearances were 232 +/- 30 and 145 +/- 24 ml/min per 1.73 m(2), respectively; 63 +/- 9% of the administered dose was excreted through the kidneys in 24 h. To determine the effect of cefotaxime on the renal tubules, urinary alanine aminopeptidase excretion was measured before, during, and after the infusions. It remained within the normal range in all instances; however, 48 +/- 14% of the total daily alanine aminopeptidase output was recovered during the infusion period. Side effects were dose related and included fatigue, loose stools, and night sweats. No significant changes in hematology, serum chemistry, or urinalysis were recorded.

Human Pharmacology of Cefotaxime (HR 756), a New Cephalosporin

Distinct hemodynamic and gastric effects of human CGRP I and II in man

https://www.gastrojournal.org/article/0016-5085(92)90847-R/pdf

Pancreatic and hepatic abscesses: a late complication in 10 patients with chronic pancreatitis.

Clavulanic acid, a product of Streptomyces clavuligerus with β-lactam structure, is a potent inhibitor of several β-lactamases. To study its pharmacokinetic and CSF penetration in patients without meningeal inflammation, a single oral dose of 250 mg of clavulanic acid was given to 21 patients. One patient was studied in a multiple dose schedule. Fifteen of these 21 patients had a diagnostic lumbar puncture and 3 neurosurgical patients had a continuous CSF drainage. Serum and urine concentrations of clavulanic acid were available from 22 patients. The mean peak serum concentration was 4·3 mg/l and individual peak serum concentrations ranged from 0·1-9·5 mg/i between 40 and 60 mm after ingestion of clavulanic acid. Urinary recovery between 300 and 400 mm ranged from 0·8-54·3% of the administered dose. The mean absorption half life was 0·26 h and the mean elimination half life was 0·9 h. Considerable degradation of clavulanic acid occurred in vitro at 37°C. In pooled human serum, phosphate buffer pH 7 and 5, an hourly loss of activity of about 10, 7 and 10% respectively, was observed

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Human pharmacokinetics and CSF penetration of clavulanic acid

Eosinophilic gastroenteritis is a rare disease characterized by gastrointestinal symptoms, peripheral eosinophilia and massive infiltration of segments of the gastrointestinal tract by eosinophils. A case of this disease in a 25-year-old patient with symptoms of slight dysphagia and isolated esophageal involvement is described. Improvement of the symptoms, but not of the histological abnormalities, was obtained by steroids combined with withdrawal of the food components probably responsible for the symptoms.

Münch R

Papers

Human Pharmacology of Cefotaxime (HR 756), a New Cephalosporin

Distinct hemodynamic and gastric effects of human CGRP I and II in man

Pancreatic and hepatic abscesses: a late complication in 10 patients with chronic pancreatitis.

Human pharmacokinetics and CSF penetration of clavulanic acid

[Eosinophilic esophagitis, a rare manifestation of eosinophilic gastroenteritis].