Ten-year improvement of insulin resistance and growth with recombinant human insulin-like growth factor 1 in a patient with insulin receptor mutations resulting in leprechaunism.

AIM: Leprechaunism, a rare genetic disease resulting from mutations in two alleles of the insulin receptor gene, is characterized by severe insulin resistance, retarded growth and, usually, premature death. The ability of treatment with recombinant human insulin-like growth factor 1 (rhIGF1) to improve metabolic and clinical parameters in the long-term is still controversial. METHODS: Mutations were looked for in the insulin receptor gene of a four-month-old female baby with leprechaunism. The patient's skin fibroblasts were analyzed for response to insulin and IGF1. At the clinical level, the very long-term effects of treatment with rhIGF1/rhIGFBP3 were evaluated by clinical and metabolic parameters. RESULTS: The patient's diagnosis was based on compound heterozygous mutations in two alleles of the insulin receptor gene, thus confirming leprechaunism. Cultured fibroblasts showed a decreased number of insulin receptors and were insulin-resistant. However, IGF1 was able to stimulate IGF1 receptor signalling, suggesting possible activation of a salvage pathway. Treatment with IGF1/IGFBP3 for 8.7 years, then IGF1 for 2 years, resulted in normalization of circulating levels of IGF1 and IGFBP3. Large daily variations in glycaemia and insulinaemia persisted, but mean glycaemia decreased. Regarding growth, the patient's BMI Z score normalized and length/height score improved. Our patient presented normal neurological development and academic achievement. The treatment was free of adverse effects. CONCLUSION: Our results provide evidence that rhIGF1 with and without rhIGFBP3 can prevent fatal outcomes, and improve growth and metabolic parameters, for more than 10 years in a patient with leprechaunism. Long-term rhIGF1 for severe insulin resistance syndrome should be considered.

Update on human rabies in a dog- and fox-rabies-free country.

UNLABELLED: Rabies is responsible for 50,000 deaths per year worldwide. Mainland France has been officially freed from rabies in non-flying animals since 2001. METHOD: We wanted to provide an update on the French situation, using published data, and describe possible options since official guidelines are lacking. RESULTS: Post-exposure prophylaxis (PEP) (early and careful cleaning and dressing of the wound, vaccination, and in case of high-risk exposure, injection of specific anti-rabies immunoglobulins) is known to be efficient except in rare cases. It is recommended after grade II contact (+specific immunoglobulins in immunodepressed patients), or grade III contact (vaccination+immunoglobulins). DISCUSSION: Mainland France being rabies-free, 3 options may be considered in case of bite by a dog or a cat that cannot be monitored in France: (a) consider the risk of rabies as null, so no PEP should be administrated, whatever the severity of bites; (b) consider there is a weak but lethal risk, so the international recommendations should be applied, using immunoglobulins in some cases; (c) consider that the risk is extremely low but cannot be excluded, and that the patient should be vaccinated to be protected, but without adding immunoglobulins (whether in case of grade II or III bites). CONCLUSION: There are no national guidelines for rabies in France, and so the physician managing the patient is the one who will decide to treat or not.

Effect of time to treatment and age on one year mortality in acute STEMI: difference between thrombolysis and primary percutaneous coronary intervention.

CONTEXT: Although thrombolysis (THL) and primary percutaneous coronary intervention (PPCI) are two validated options in reperfusion algorithms for ST-elevation myocardial infarction (STEMI), recent papers seems to show that PPCI could be the best therapeutic option irrespective of the time to treatment (TT) and of the cardiovascular risk profile of the patient. The impact of TT and age on reperfusion strategies requires elucidation. The aim of this study was to analyze the effect of time to treatment and age on the 1-year mortality of patients presenting with STEMI, for each reperfusion strategy. MATERIALS AND METHODS: The study population consisted in 794 patients directly admitted to the cardiological intensive care unit for STEMI < or =12 hours. The relationship between TT and 1-year mortality was studied using logistic regression models. The models were implemented on the overall population and on 3 different age groups: [<65 years]; [> or =65 and <75 years]; [> or =75 years] for patients undergoing THL (n=299) and for patients undergoing PPCI (n=495). There was no significant between-group difference in all-cause 1-year mortality for the patients [<65 years] and those [> or =65 and <75 years]. In contrast, the 1-year mortality was significantly higher in the patients [> or =75 years] undergoing THL (51.4 vs. 15.3%; p<0.001). The analysis of the curves of mortality suggests that 1- year mortality of patients with STEMI depend not only on reperfusion strategy but so on the time to treatment and on the age of the patients. CONCLUSION: In STEMI, on a 1-year mortality criteria, PPCI is not always upper than THL, particularly for patients<65 years treated within the first two hours after symptoms onset. TT and age affects the results of the reperfusion strategies and must be still incorporated in the reperfusion algorithms of STEMI.

[Exercise deep venous thrombosis: myth or reality? About three cases of pulmonary embolism in long-distance runners]. / Maladie thromboembolique veineuse d'effort: mythe ou réalité? A propos de trois cas d'embolies pulmonaires chez des coureurs de fond.

The most frequent manifestation of exercise deep vein thrombosis (DVT) is the one occurring in upper limbs, in some specific and stereotypic conditions, sometimes complicated by pulmonary embolisms. A few cases of lower limbs DVT are reported in athletes. Some pathophysiologic arguments (rheological modifications, parietal lesions and coagulation abnormalities) suggest a link between DVT and exertion, but the causality is sometimes difficult to establish. We report three cases of pulmonary embolism occurring after a prolonged effort of running in trained marathon athletes. To our knowledge, very few similar cases have ever been reported. The possible responsibility of such physical efforts is discussed, as well as other potential cofactors such as coagulation abnormalities and hormonal contraception.

[Splenic volvulus on a mobile spleen]. / Volvulus splénique sur rate mobile.

We report a case of splenic volvulus caused by a mobile spleen. Preoperative ultrasonography and CT-scan did not provide the diagnosis. Splenectomy was performed at laparotomy, the only possible treatment in this exceptional case.

Remarks about the prognosis in case of antenatal diagnosis of gastroschisis.

We report our experience of 15 cases of gastroschisis which occurred between 1981 and 1993. All but one were diagnosed antenatally by ultrasound between 16 and 32 weeks of pregnancy. We made a termination of the pregnancy in 3 cases, for multiple malformations in 2 cases and one case of very early premature rupture of the membranes (PROM). When checked (11 cases), the karyotype was normal. We made a cesarean section in 11 cases: the indication was a complication for 6 (fetal distress, PROM, polyhydramnios, large dilatation of the gut). We noted growth retardation in 7 newborns and prematurity in 5/12 (mean gestational age of 36.8 weeks). The preoperative study of the gut noted 5 cases with intestinal damage and one case of complete necrosis of the gut. The global prognosis is not as good as usual, with a perinatal mortality of 41.6% (5/12). We discuss this latter point and examine the literature.

[Diffuse esophageal leiomyomatosis. Apropos of 3 cases]. / La léiomyomatose oesophagienne diffuse. A propos de 3 observations.

Three cases of diffuse esophageal leiomyomatosis are discussed. Two of these are familial one, the mother being affected. These familial cases can occur in association with Alport's syndrome. The occurrence of a case of esophageal leiomyomatosis imply a familial survey and the search of a renal or ocular disease. The surgical treatment of this affection in sub total oesophagectomy with esophageal substitution (with the colon especially). The long term prognosis is unknown, with the risk of renal failure if Alport's syndrome is associated or of other leiomyomatous localisation.

[A duplication of the alimentary tract with unusual localization in the submaxillary region]. / Une duplication digestive de localisation inhabituelle dans la loge sous-maxillaire.

Duplication cysts developed from the intra-oral digestive tract are exceedingly rare lesions of which only 15 cases have previously been reported. We report an additional case in a neonate with a large cystic lesion in the right submandibular area. Clinico-pathologic findings are described and the literature is reviewed. Criteria for the diagnosis of digestive tract duplication are recalled. Differential diagnosis and etiopathogenic theories are discussed.

[Avulsion of the ureter due to external violence. Report of four cases (author's transl)]. / Ruptures traumatiques de l'uretère. A propos de quatre cas.

Four cases of traumatic ureteral damage are presented. The etiology of ureteral injuries is gunshot wounds for one case and motor vehicle accidents for three cases. Need for a high index of suspicion and diagnostic measures with IUP is stressed. Prompt operative management is recommended. Conservative surgery is emphasized.