Multi-center study on the characteristics and treatment strategies of patients with Graves' orbitopathy: the first European Group on Graves' Orbitopathy experience

To improve management of patients with Graves' orbitopathy, a multi-center collaborative approach is necessary in order to have large enough sample sizes for meaningful randomized clinical trials. This is hampered by a lack of consensus on how to investigate the eye condition. The European Group on Graves' Orbitopathy aims to overcome this and has designed a preliminary case record form (CRF) to assess Graves' orbitopathy patients. This form was used in this first multi-center study. AIM: To investigate patient characteristics and treatment strategies in 152 new consecutively referred patients with thyroid eye disease seen in nine large European referral centers. METHODS: Newly referred patients with Graves' orbitopathy were included who were seen between September and December 2000. Demographic data and a complete ophthalmological assessment were recorded. RESULTS: One-hundred and fifty-two patients (77% females) were included. Diabetes was present in 9%, and glaucoma or cataract in 14% of patients. Forty percent were current smokers, 9% also had dermopathy, and only 33% reported a positive family history of thyroid disease. Mild eye disease was seen in 40%, moderately severe eye disease was seen in 33% and severe eye disease was seen in 28% of patients. Soft tissue involvement was the most frequent abnormality (seen in 75%), proptosis > or =21 mm was found in 63%, eye motility dysfunction in 49%, keratopathy in 16% and optic nerve involvement was found in 21% of patients. According to the clinical impression, 60% had active eye disease. Immunosuppressive treatment was planned more frequently in active patients (57/86; 66%) than in inactive patients (5/57, 9%; Chi-square 46.16; P<0.02). There were no important differences among the eight centers regarding the severity and the activity of their patients. CONCLUSIONS: In view of the large number of patients recruited in only 4 months, multi-center studies in the eight EUGOGO centers appear to be feasible.     

Carcinosarcoma of the ureter: A rare,pleomorphic, aggressive malignancy

AIM: To examine histological nature and clinical process of ureteral carcinosarcomas. METHODS: We report on a new case of carcinosarcoma of the ureter. The literature was reviewed and histological and clinical features were elucidated. RESULTS: Fourteen cases of ureteral carcinosarcomas have been reported. The nomenclature used for these tumors either in the pathology reports or in literature is confusing. In contrary to obscure tumor biology, prognosis was clearly bad as the majority of the patients died within 2 years after diagnosis. CONCLUSIONS: Terminology confusion is due to the rarity of this entity and lack of its biology knowledge. Patients present after the age of 60 with hematuria and obstruction. Nephroureterectomy is the only hope of cure but, due to tumor aggressiveness, recurrences occur almost always and prognosis is poor.     

Abnormal mitochondrial respiration in skeletal muscle in patients with peripheral arterial disease

OBJECTIVE: Discrete morphologic, enzymatic and functional changes in skeletal muscle mitochondria have been demonstrated in patients with peripheral arterial disease (PAD). We examined mitochondrial respiration in the gastrocnemius muscle of nine patients (10 legs) with advanced PAD and in nine control patients (nine legs) without evidence of PAD. METHODS: Mitochondrial respiratory rates were determined with a Clark electrode in an oxygraph cell containing saponin-skinned muscle bundles. Muscle samples were obtained from the anteromedial aspect of the gastrocnemius muscle, at a level 10 cm distal to the tibial tuberosity. Mitochondria respiratory rate, calculated as nanoatoms of oxygen consumed per minute per milligram of noncollagen protein, were measured at baseline (V(0)), after addition of substrates (malate and glutamate; (V(SUB)), after addition of adenosine diphosphate (ADP) (V(ADP)), and finally, after adenine nucleotide translocase inhibition with atractyloside (V(AT)). The acceptor control ratio, a sensitive indicator of overall mitochondrial function, was calculated as the ratio of the respiratory rate after the addition of ADP to the respiratory rate after adenine nucleotide translocase inhibition with atractyloside (V(ADP)/ V(AT)). RESULTS: Respiratory rate in muscle mitochondria from patients with PAD were not significantly different from control values at baseline (0.31 +/- 0.06 vs 0.55 +/- 0.12; P =.09), but V(sub) was significantly lower in patients with PAD compared with control subjects (0.43 +/- 0.07 vs 0.89 +/- 0.20; P <.05), as was V(ADP) (0.69 +/- 0.13 vs 1.24 +/- 0.20; P <.05). Respiratory rates after atractyloside inhibition in patients with PAD were no different from those in control patients (0.47 +/- 0.07 vs 0.45 +/- P =.08). Compared with control values, mitochondria from patients with PAD had a significantly lower acceptor control ratio (1.41 +/- 0.10 vs 2.90 +/- 0.20; P <.001). CONCLUSION: Mitochondrial respiratory activity is abnormal in lower extremity skeletal muscle in patients with PAD. When considered in concert with the ultrastructural and enzymatic abnormalities previously documented in mitochondria of chronically ischemic muscle, these data support the concept of defective mitochondrial function as a pathophysiologic component of PAD.     

Effects of single dose administration of ifosfamide on testes and semen characteristics in the rabbit

The effects on testes and semen characteristics were studied in the rabbit after a single dose administration of the chemotherapeutic agent ifosfamide. Sexually mature male rabbits received a single intravenous injection of either 0, 60, 90, 120, or 240mg/kg body weight ifosfamide. Two phases of experimentation were conducted, lasting 1 and 18 weeks, respectively, at the end of which half of the animals from each treatment group were euthanized. Reproductive organs weighing, as well as testicular qualitative and quantitative histological examinations were performed 1 and 18 weeks post-treatment, while semen quality and libido were evaluated on a weekly basis. A decrease in the paired testes weight (90, 120, and 240mg/kg groups) and the accessory sex glands weight (240mg/kg group) were noted 1 week post-treatment. Although no histopathologic lesions or significant changes in the quantitative histologic examination were observed, semen quality examination revealed transient oligospermia (60, 90, 120, and 240mg/kg groups), teratozoospermia (120 and 240mg/kg groups), and asthenozoospermia (240mg/kg group), which returned to normal by the 6th (60 and 90mg/kg groups), 7th (120mg/kg group), or 8th week after treatment (240mg/kg group). Libido remained normal. The results suggest that ifosfamide, at a single dose, causes transient and dose-dependent depression of spermatocytogenesis (240mg/kg), spermiogenesis (60, 90, and 120mg/kg), and sperm maturation in the epididymis (240mg/kg).     

Topographic mapping of retinal function with the SLO-mfERG under simultaneous control of fixation in Best's disease

PURPOSE: To introduce the scanning laser ophthalmoscope-evoked mfERG (SLO-mfERG) as a new method to measure focal retinal function. METHODS: Sixty-two healthy individuals and 12 patients with Best's disease were examined. mfERGs were recorded using a scanning laser ophthalmoscope as a stimulator and trigger device (He-Neon 632.8 nm) as well as a fundus-monitoring system (Infrared 730 nm). RESULTS: Amplitudes in the central concentric area were found to be significantly lower in patients with Best's disease than in healthy controls, while no significant differences were found for the more peripheral areas. CONCLUSION: SLO-mfERG is a reliable new technique for topographic mapping of retinal function under simultaneous control of fixation.