Adaptive changes of human islets to an obesogenic environment in the mouse.

AIMS/HYPOTHESIS: In this study, we used an immunodeficient mouse model to explore, in vivo, the longitudinal adaptation of human islets to an obesogenic environment. METHODS: Non-diabetic Rag2 (-/-) mice (n = 61) were transplanted with human islets (400 islet equivalents [IEQ]) from six pancreases: four non-diabetic and two with overt metabolic dysfunction (older, high HbA(lc) or history of diabetes). Animals were fed for 12 weeks with a control or high-fat diet (HFD), and followed for weight, serum triacylglycerol, fasting blood glucose and human C-peptide. After the mice were killed, human grafts and the endogenous pancreas were analysed for endocrine volume, distribution of beta and alpha cells, and proliferation. RESULTS: Transplanted mice on an HFD gained significantly more weight (p < 0.001) and had higher fasting glycaemia (2-12 weeks; p = 0.0002) and consistently higher fasting human C-peptide levels (2-12 weeks; p = 0.04) compared with those on the control diet. Histology demonstrated doubling of human islet graft volume at 12 weeks in animals on the HFD and increased beta cell volume (p < 0.001), but no change in alpha cell volume. Human islet function (hyperbolic product HOMA2%BS) at 12 weeks was four times lower in HFD animals (p < 0.001 vs controls) because of insufficient beta cell adaptation to decreased (70%) sensitivity (HOMA%S). Human islets obtained from donors with metabolic dysfunction failed to adapt to the HFD. CONCLUSIONS/INTERPRETATION: This longitudinal study provides direct evidence that human islets adapt both endocrine and beta cell mass, function and gene expression to obesity in vivo. The present model will facilitate the identification of mechanisms by which human islets adapt to obesity in vivo and the cell type(s) responsible, and factors predisposing human beta cells to decompensation.

[Therapeutic problems posed by hemiballism of metastatic origin]. / Problèmes thérapeutiques posés par un hémiballisme d'origine métastatique.

A 40 year old woman undergoing treatment for cancer of the breast presented with metastatic hemiballism. Diagnosis was supported by the presence of bone and liver metastases and by CT-scan showing an enhanced rapidly growing lesion in the subthalamic region contralateral to hemiballism. Treatment by corticotherapy and neuroleptics was ineffective. Radiotherapy was unsuccessful. Metastatic hemiballism is a rare disease with no effective treatment.

[Chronic paroxysmal hemicrania sensitive to indomethacin]. / Hémicrânie paroxystique chronique sensible à l'indométacine.

Chronic paroxysmal hemicrania is a new entity described in 1974. It appears to be rare, since 34 cases only have been reported in foreign literature. It is characterized by severe unilateral pain occurring several times a day for months or years and is resistant to all treatments, except indomethacin. The first 3 cases observed in France are reported and data from the literature are reviewed.

[Delayed contralateral hemiplegia complicating ophthalmic herpes zoster]. / Hémiplégie controlatérale retardée compliquant le zona ophtalmique.

Contralateral hemiplegia may develop a few weeks after the onset of an ophthalmic herpes zoster. This complication, which is not part of the herpetic encephalopathy, generally coexists with lesions of arteritis demonstrable by arteriography, affecting in most cases the proximal segments of the middle and anterior cerebral arteries and resulting in infarcts. The pathophysiology of these lesions is uncertain, but the vessels appear to be invaded by contiguity.

Reducing the number of animals used for microsurgery training programs by using a task-trainer simulator.

To master the skills needed for microsurgery techniques, residents must enrol in a long and complex training program that includes manipulations on simulators, on ex vivo tissues and finally in vivo training. This final step consists of performing vascular anastomoses on murine models. We propose here a simulation program designed to decrease the number of rats used during the final in vivo training. Our study presents the materials used, the various exercises proposed and their evaluations. Two identical student groups were compared in the framework of the University Diploma of Microsurgery. Group A (seven students) followed a classic training program, all of whom achieved permeable vascular anastomoses. A total of 149 rats were needed for this group. Group B (seven students) first validated their manipulations on the task-trainer simulation program. A mean of 6 h was necessary to obtain this validation. All these students achieved the required permeable vascular anastomoses but only 77 rats were used for this group. This simulation program spared 72 rats, abiding by the Russell and Burch concept of a humane experimental technique, namely the 3R principles. This home-made, cost-efficient and easy-to-use task trainer included various exercises with increasing difficulty levels and a progressive scoring system. We believe that microsurgery training needs to include both simple and sophisticated tools in order to reduce the number of animals used to master these surgical skills.

Subcorneal pustular dermatosis associated with rheumatoid arthritis and raised IgA: simultaneous remission of skin and joint involvements with dapsone treatment.

A 44 year old white woman with rheumatoid arthritis for 19 years developed subcorneal pustular dermatosis. She had increased polyclonal IgA and IgA rheumatoid factor. After 4 months' treatment with dapsone 100 mg daily the patient had neither skin lesions nor active joint disease.