Determinants of liver damage associated with intravenous methylprednisolone pulse therapy in Graves' ophthalmopathy.

BACKGROUND: Intravenous methylprednisolone pulses (IVMP) are more efficacious and better tolerated than oral prednisone in Graves' ophthalmopathy (GO) patients. However, acute and severe liver damage has been reported in sporadic cases during IVMP, resulting in fatal acute liver failure in four patients so far. The mechanism causing the liver damage is incompletely understood. DESIGN: We performed a prospective observational study in 13 patients with dysthyroid optic neuropathy (group A) and in 14 patients with moderately severe GO (group B) who were treated with high-dose (group A) or low-dose (group B) IVMP; cumulative steroid doses were 8.45 g in group A and 4.5 g in group B, and follow-up time was 24 weeks. MAIN OUTCOME: Slight increases in serum aminotransferases (in alanine aminotransferase [ALAT] more than in aspartate aminotransferase [ASAT]) were observed, in seven patients exceeding the upper normal limit of 40 U/L. These changes were more prominent in group A than in group B as was also evident from a decrease in ASAT/ALAT ratio in group A but not in group B. Changes in serum aminotransferases occurred especially in the first 6 weeks of IVMP, becoming smaller thereafter with the decrease in steroid dosage. Pretreatment liver steatosis or diabetes were not related to liver damage, but preexistent viral hepatitis was. CONCLUSION: IVMP in GO patients causes dose-dependent liver damage by a direct toxic effect of glucocorticoids on hepatocytes. Nevertheless, IVMP seems to be pretty safe if cumulative doses exceeding 8 g are avoided and liver function is checked before and at regular intervals during pulse therapy.     

Comparative study of 3 therapeutic methods for Pouteau Colles' fracture. Apropos of 97 cases

Results of three therapeutic modalities used for the treatment of a homogeneous series of patients with a Pouteau Colles fracture are analyzed. Orthopedic treatment provided deceiving results. Pinning was, on the contrary, very effective, intrafocal pinning with immediate mobilization of the wrist appearing perfectly effective. Few complications were reported in contrast to plastered immobilizations. Good results were obtained in 80% of cases and functional recovery was rapid, indicating that this method represents undoubted progress when compared with conventional therapies.     

Prospective multicenter clinical trial of Uretex Sup for surgical treatment of stress urinary incontinence

AIM: To evaluate in a prospective multicenter study the efficacy and safety of the suburethral support Uretex (Sofradim, Trevoux, France) delivered by a suprapubic approach in the treatment of female stress urinary incontinence. METHODS: Between March 2002 and March 2003, 57 patients were treated for stress urinary incontinence with Uretex. Preoperative evaluation included urodynamic examination and questionnaires (symptoms and quality of life, Contilife). Forty patients had pure stress urinary incontinence and 17 mixed urinary incontinence. No associated procedure was performed. The objective cure rate was evaluated by clinical examination and pad-test, and the subjective cure rate was assessed through questionnaires at 1, 3 and 12 months. RESULTS: The mean follow-up was 13 months (range 11-24 months). During follow up, chronic urinary retention requiring a tape section occurred in one patient, and in another patient a delay of vaginal healing was followed by a sling exposure and resection at 4 months. No infection or urethral erosion was reported. The objective cure rate was 96.2%, and the subjective cure rate was 79.2%; four patients reported low leakage on stress and nine patients complained of urge incontinence (four de novo and five persistent). CONCLUSION: The suprapubic Uretex Sup procedure is a safe and effective treatment for women with stress urinary incontinence.     

NOS1 polymorphism is associated with atopy but not exhaled nitric oxide levels in healthy children

Exhaled nitric oxide (FE_NO) is raised in atopy. The mechanism for this is unclear. The aim of this study was to investigate whether the number of AAT repeats in intron 20 of the NOS1 gene, recently associated with variations in FE_NO in adults with asthma and cystic fibrosis, was associated with the raised FE_NO in healthy atopic children. Eighty-seven healthy children (44 girls, 42 atopic, age range 6–18 years) underwent measurements of FE_NO, spirometry, airway responsiveness and skin prick testing. Genotyping was carried out to determine the number of AAT repeats. There was no association between the number of AAT repeats and FE_NO in either the whole sample of healthy children (n = 87) or in the subsample of healthy atopics (n = 42). However, a greater number of atopic children had two high repeat alleles compared with non-atopic children (33.3% vs. 13.6%, respectively, p = 0.03). This suggests that variations in the NOS1 gene may contribute to atopy without this relationship being reflected by FE_NO.     

Effect of acute tyrosine depletion in using a branched chain amino-acid mixture on dopamine neurotransmission in the rat brain.

Central dopamine function is reduced by decreasing the availability of the catecholamine precursor, tyrosine, using a tyrosine-free amino acid mixture containing multiple large neutral as well as branched chain amino-acids, which compete with tyrosine for uptake into the brain. Current mixtures are cumbersome to make and administer, and unpalatable to patients and volunteers. Here, we investigate whether individual or limited amino-acid combinations could reduce brain tyrosine levels and hence dopamine function. Measurements of regional brain tyrosine levels, catecholamine and indoleamine synthesis (L-DOPA and 5-HTP accumulation, respectively) were used to identify an effective paradigm to test in neurochemical, behavioral and fos immunocytochemical models. Administration of leucine or isoleucine, or a mixture of leucine, isoleucine, and valine reduced tyrosine and 5-HTP, but not L-DOPA accumulation. A mixture of leucine, valine, and isoleucine supplemented with tryptophan reduced brain tyrosine and L-DOPA, but not 5-HTP. In microdialysis experiments this amino-acid mixture reduced basal and amphetamine-evoked striatal dopamine release, as well as amphetamine-induced hyperactivity. This mixture also reduced amphetamine-induced fos expression in striatal areas. In conclusion, the present study identified a small combination of amino acids that reduces brain tyrosine and dopamine function in a manner similar to mixtures of multiple amino acids. This minimal mixture may have use as a dopamine reducing paradigm in patient and volunteer studies.     

白藜芦醇甙对内毒素刺激小鼠腹腔巨噬细胞产生TNFα和NAG的影响

收集小鼠腹腔巨噬细胞，调整细胞浓度为５×１０￣５／ｍｌ，加入２４孔培养板每孔１ｍｌ，内毒素刺激前后不同时间加入白藜芦醇甙培养，检测上清中肿瘤坏死因子，溶酶体酶（Ｎ－乙酰－β－Ｄ氨基葡萄糖苷酶ＮＡＧ）的变化，结果说明：白藜芦醇甙可减少上清中ＴＮＦ＿α和ＮＡＧ的量，通过此可减少内毒素刺激产生的由ＴＮＦ＿α和ＮＡＧ介导的组织损伤。     

Therapeutic diagram in advanced cancers of the esophagus

Only palliative treatment may be contemplated when advanced oesophageal cancers present with dysphagia. Operability depends on respiratory, hepatic and nutritional status. Resectability may be assessed on the information provided by bronchoscopy, thoracic CT scan and surgical exploration. Advanced resectable oesophageal cancers require oesophagectomy without thoracotomy and radiotherapy. We performed 93 oesophagectomies in 106 advanced oesophageal cancers with a mortality rate of less than 2%. Non resectable advanced oesophageal cancers require bypass procedures. We performed 13 in the 106 cases. Inoperable advanced oesophageal cancers require radiotherapy in the absence of a fistula, laser therapy or an endoprosthesis for dysphagia.