Neurotensin serum levels and skin gene expression are increased in atopic dermatitis.

BACKGROUND: Neurotensin (NT) participates in immune responses, but the mechanisms are not known. We have previously shown that NT augments the ability of corticotropin-releasing hormone (CRH) to increase mast-cell-dependent vascular permeability in rodents. We also showed that NT stimulates human mastcell release of vascular endothelial growth factor, and that CRH is increased in the serum of patients with atopic dermatitis (AD), an inflammatory skin condition involving mast cells. OBJECTIVES: To measure serum levels of NT, and lesional skin expression of NT and the main NT receptor (NTR-1) in AD, and to compare it with skin expression in chronic urticaria (CU) and urticaria pigmentosa (UP). METHODS: Serum NT was measured with a Milliplex microbead array. Skin NT and NTR-1 gene expression was determined with quantitative polymerase chain reaction. Immunohistochemistry was performed using a mouse monoclonal antibody for NT, and a rabbit polyclonal antibody for NTR-1. Mast cells were counterstained with Leder dye. RESULTS: Neurotensin is significantly elevated in the serum of patients with AD compared with healthy controls (P = 0.0001). NT gene expression is also significantly increased in lesional skin of patients with AD compared with controls (P = 0.0194). Moreover, immunohistochemistry of AD lesions shows NT > NTR-1 staining of perivascular cells, many of which are identified as mast cells after staining with Leder dye. There was no statistically significant difference in NT and NTR-1 lesional skin gene expression in patients with either CU or UP. CONCLUSIONS: These results suggest that interactions between NT and mast cells may occur and contribute to AD pathogenesis.

Cisapride and ranitidine in the treatment of gastro-oesophageal reflux disease--a comparative randomized double-blind trial.

Forty patients with gastro-oesophageal reflux disease and oesophagitis, documented by endoscopy (grades I to III by the Savary-Miller classification) were randomized to participate in a comparative double-blind trial to receive cisapride (10 mg q.d.s.) or ranitidine (150 mg b.d.) for an 8-week period. Upper gastrointestinal endoscopy was performed immediately before the entry to the trial and after the 8-week period at the completion of the trial. The evaluable cohort included 37 patients who completed the trial, 18 in the cisapride group and 19 in the ranitidine group. Three patients were withdrawn from the trial; one on ranitidine developed severe anaphylactic reaction, one on cisapride severe dizziness and one on cisapride did not wish to continue on the trial. The results of the trial, regarding symptomatic and endoscopic improvement were comparable in the two groups. Both drugs were effective in controlling symptoms, such as acid regurgitation, retrosternal pain, retrosternal burning, epigastric fullness and discomfort (pain, burning, sense of pressure) and resulted in endoscopic healing of oesophagitis. With few exceptions, symptoms remained in remission 1 month after treatment in the majority of patients. Globally, both drugs were tolerated comparably, and adverse effects other than those which resulted in the withdrawal from the trial were minimal in both groups. The results of this trial indicate that cisapride and ranitidine, although of different pharmacological action, are comparable in their therapeutic effect in symptomatic improvement and endoscopic healing in patients with mild to moderate gastro-oesophageal reflux disease.

The impact of early or late diagnosis on patient survival in gastric cancer in Greece.

The purpose of this study was to investigate the reasons for delayed diagnosis of gastric cancer in the Greek population and correlate survival with early or late diagnosis. We studied 100 patients with gastric cancer proven at endoscopy. Early diagnosis (less than 3 months from the onset of symptoms) was established in 28 patients (28%), while the diagnosis was late (greater than 3 months) in 72 patients (72%). The reasons for late diagnosis were: 1. delayed consultation on the part of the patient, 2. incorrect medical diagnosis at a) initial evaluation, b) radiological evaluation and, as a result, c) failure to refer for endoscopy and biopsy. Patient survival correlated well with tumor resectability, irrespective of early or late diagnosis. In patients with early diagnosis and resectable tumor survival was 9.9 +/- 4.8 months (mean +/- SD) whereas with non-resectable tumor 4.8 +/- 4.0 months (p less than 0.01). In patients with late diagnosis, survival in resectable tumor was 13.5 +/- 11.7 months compared with 8.5 +/- 6.9 months in non-resectable tumor. No correlation was noted between survival and anatomic location of tumor or degree of histologic differentiation. Early diagnosis of gastric cancer is associated with a higher degree of resectability and therefore of better survival.

A comparative clinical trial of duodenal ulcer healing with two regimens of cimetidine: 800 mg once nightly and 400 mg twice daily.

The efficacy and safety of two dosage regimens of cimetidine were compared in a single-blind study of 50 adults with endoscopically proven duodenal ulcers. Patients were randomly allocated to receive 800 mg cimetidine taken once nightly or 400 mg cimetidine taken twice daily for 4 weeks. Following 4 weeks' treatment patients again underwent endoscopy and, if healing was incomplete, they received a further 4 weeks' treatment. At 4 weeks, healing occurred in 21/25 (84%) patients on the once-daily regimen and in 15/25 (60%) patients treated twice daily (P less than 0.05). Cumulative healing rates after 8 weeks' treatment were 92% and 96%, respectively. Symptomatic improvement was obtained to the same degree with both regimens. No adverse effects were recorded and laboratory values remained normal during both treatments. The results indicate that cimetidine given as one dose each night was superior to the twice-daily regimen.