Primary intraosseous manifestation of Rosai-Dorfman disease: 2 cases and review of literature.

Rosai-Dorman disease (RDD) is a rare disorder of proliferative histiocytes with an unknown etiology. It is also known as sinus histiocytosis with massive lymphadenopathy. Most patients present with painless cervical lymphadenopathy due to accumulation of histiocytes in the lymph nodes, often in conjunction with fever, elevated leukocyte count and erythrocyte sedimentation rate. Isolated skeletal involvement is very rare.

Classifying the adverse mitogenic mode of action of insulin analogues using a novel mechanism-based genetically engineered human breast cancer cell panel.

Insulin analogues are widely used in clinical practice. Modifications on the insulin molecular structure can affect the affinity and activation towards two closely related receptor tyrosine kinases: the insulin receptor (INSR) and the insulin-like growth factor 1 receptor (IGF1R). A switch towards higher IGF1R affinity is likely to emphasize mitogenesis rather than glucose metabolism. Relevant well-validated experimental tools to address the insulin analogue activation of either INSR or IGF1R are missing. We have established a panel of human MCF-7 breast cancer cell lines either ectopically expressing the INSR (A or B isoform) in conjunction with a stable knockdown of the IGF1R or ectopically expressing the IGF1R in conjunction with a stable knockdown of the INSR. In these cell lines, we systematically evaluated the INSR and IGF1R receptor activation and downstream mitogenic signalling of all major clinical relevant insulin analogues in comparison with insulin and IGF1R. While most insulin analogues primarily activated the INSR, the mitogenic activation pattern of glargine was highly similar to IGF1 and insulin AspB10, known to bind IGF1R and induce carcinogenesis. Yet, in a long-term proliferation assay, the proliferative effect of glargine was not much different from regular insulin or other insulin analogues. This was caused by the rapid enzymatic conversion into its two metabolic active metabolites M1 and M2, with reduced mitogenic signalling through the IGF1R. In summary, based on our new cell models, we identified a similar mitogenic potency of insulin glargine and AspB10. However, rapid enzymatic conversion of glargine precludes a sustained activation of the IGF1R signalling pathway.

Randomised clinical trial: the effects of amitriptyline on drinking capacity and symptoms in patients with functional dyspepsia, a double-blind placebo-controlled study.

BACKGROUND: Functional dyspepsia is one of the most prevalent (15-40%) functional gastrointestinal disorders. Antidepressants such as amitriptyline are often used in these patients, but clinical studies are currently lacking. AIM: To evaluate the effect of 8 weeks of treatment with amitriptyline on drinking capacity, symptoms evoked by a standardised drink test (primary endpoint) and clinical symptoms (secondary endpoint). METHODS: Patients meeting the Rome III criteria for functional dyspepsia (FD) were invited to participate in a double blind, randomised, placebo-controlled trial and were treated with either amitriptyline (12.5-50 mg) or placebo during 8 weeks. All included patients underwent a nutrient drink test before and after treatment. Drinking capacity and evoked symptoms were recorded. In addition, dyspeptic symptoms were weekly assessed using PAGI SYM (patient assessment of upper gastrointestinal symptom severity index) questionnaire. RESULTS: Thirty-eight patients (amitriptyline n=18, placebo n=20; age 41±2year, 61% F) completed the study. The drinking capacity of liquid meal was not affected by either amitriptyline or placebo treatment. Postprandial symptoms were not significantly different between amitriptyline and placebo. During the entire treatment, total symptom score (0.47 points, P=0.02) and nausea (0.86 points, P=0.004) on PAGI SYM were significantly reduced by amitriptyline compared with placebo. CONCLUSIONS: Amitriptyline did not affect drinking capacity and postprandial symptoms evoked by the drink test in FD patients. However, total clinical symptom score and nausea were reduced during 8 weeks of treatment. Our data suggest that amitriptyline particularly improves nausea in functional dyspepsia, but larger clinical trials are needed to further confirm our findings.

Intrapartum uterine rupture and inflammatory bowel disease.

The incidence of uterine rupture in pregnant women ranges from 0% to 1.1% in large series. This case report describes a woman with a history of obstetric complications, uterine rupture, and active inflammatory bowel disease that was treated with high-dose prednisone.