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OBJECTIVE: Glucocorticoid (GC) sensitivity is highly variable among individuals and has been associated with susceptibility to develop (auto-)inflammatory disorders. The purpose of the study was to assess GC sensitivity in Behçet's disease (BD) by studying the distribution of four GC receptor (GR) gene polymorphisms and by measuring in vitro cellular GC sensitivity. METHODS: Healthy controls and patients with BD in three independent cohorts were genotyped for four functional GR gene polymorphisms. To gain insight into functional differences in in vitro GC sensitivity, 19 patients with BD were studied using two bioassays and a whole-cell dexamethasone-binding assay. Finally, mRNA expression levels of GR splice variants (GR-α and GR-ß) were measured. RESULTS: Healthy controls and BD patients in the three separate cohorts had similar distributions of the four GR polymorphisms. The Bcll and 9ß minor alleles frequency differed significantly between Caucasians and Mideast and Turkish individuals. At the functional level, a decreased in vitro cellular GC sensitivity was observed. GR number in peripheral blood mononuclear cells was higher in BD compared with controls. The ratio of GR-α/GR-ß mRNA expression levels was significantly lower in BD. CONCLUSIONS: Polymorphisms in the GR gene are not associated with susceptibility to BD. However, in vitro cellular GC sensitivity is decreased in BD, possibly mediated by a relative higher expression of the dominant negative GR-ß splice variant. This decreased in vitro GC sensitivity might play an as yet unidentified role in the pathophysiology of BD.

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Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) is regarded with other molecules such as HLA, PTPN22 and CARD15 as genetic master switches of autoimmunity. Single nucleotide polymorphisms (SNPs) in the genes encoding these molecules have been associated with autoimmune conditions. We analysed the SNPs -318C/T and 49A/G in CTLA-4 in patients with Behcet's disease (BD), patients with intermediate uveitis and appropriate controls. Blood was collected from 236 patients with BD from the UK and the Middle East (ME), all fulfilling the International Study Group criteria for the diagnosis of BD, and 143 patients with idiopathic intermediate uveitis were recruited from the Medical Eye Unit at St Thomas' Hospital. Samples from healthy individuals from each geographical centre were used as controls. DNA was prepared by standard methods, and SNPs -318 and 49 in CTLA-4 were detected by a polymerase chain reaction-sequence specific primers (PCR-SSP) assay using primer mixes. The results showed that there was no association with either polymorphism in patients with BD from the UK or the ME. Similarly, there was no association in patients with intermediate uveitis. Moreover, there was no association with SNP in CTLA-4 and disease manifestations in BD or outcome in patients with intermediate uveitis. Both BD and intermediate uveitis have HLA associations, but there is no difference in distribution of CTLA-4 polymorphisms that are associated with other autoimmune diseases. The lack of association with polymorphisms in CTLA-4 and other master controlling genes of autoimmunity suggests that mechanisms that mediate such a description for BD and intermediate uveitis have still to be elucidated.

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OBJECTIVE: To reevaluate the effect of subthreshold repetitive transcranial magnetic stimulation (rTMS) on concurrent fine movement in PD. BACKGROUND: A previous study showed a beneficial effect of rTMS on the performance of six patients with PD on the Grooved Pegboard test. METHODS: The authors repeated this experiment in 11 patients with idiopathic PD who performed the test while the stimulating coil discharged continuously at 5 Hz, either over the contralateral motor cortex at just below the threshold for movement, or in the air near the head as a control. Patients were tested twice under both conditions. RESULTS: Although some patients performed faster with rTMS, others showed the opposite effect. There was no significant effect of rTMS in the group, nor did baseline performance or the order of conditions interact with the effect of rTMS. CONCLUSIONS: Based on this larger and more comprehensive study, simultaneous, 5-Hz subthreshold rTMS over the motor cortex does not have consistent or potentially therapeutic effects on movement in PD.

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A case of pseudoachalasia resulting from adenosquamous carcinoma arising from the mucous epithelium of a Barrett's esophagus is presented. This case represents an unusual combination of Barrett's esophagus giving rise to an esophageal carcinoma with squamous as well as glandular features, rather than the usual adenocarcinoma and pseudoachalasia.

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OBJECTIVE: To discuss a case of chondromyxoid fibroma presenting with low back pain. CLINICAL FEATURES: A 50-yr-old man had an 8-yr history of low back pain. This was diagnosed and treated as arising from the disc and caused by spinal stenosis. Magnetic resonance imaging findings supported the clinical findings. Years later, a plain radiograph of the pelvis revealed an incidental abnormality of the right ilium, and the patient was subsequently referred to a musculoskeletal tumor center for treatment. INTERVENTION AND OUTCOME: The lesion was surgically removed and the defect was reconstructed via bone allograft. CONCLUSION: Such tumors are a rare cause of back pain. Tumors of the pelvis can at times present as back pain. In cases of refractory back pain, an X-ray of the pelvis can be a useful screening investigation. Chondromyxoid fibromas are rare tumors best treated by excision if they are amenable or by curettage and bone grafting procedures.

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OBJECTIVE: To introduce an alternative method for conization of the cervix using a Teflon-coated hot knife and to evaluate thermal distortion, adequacy of excision, operating time, blood loss, and short- and long-term effects of this method. METHODS: Between 1987-1993, 88 patients underwent cervical conization using a Teflon-coated hot knife at temperatures ranging from 110-130C. Histopathologic slides were reviewed simultaneously by two pathologists, who assessed thermal distortion, adequacy of excision, and interpretability of the surgical margins. Clinical information was obtained prospectively, including operating time, blood loss, and depth and volume of the excised cone. In addition, data were accumulated retrospectively from 40 randomly selected patients who underwent cold-knife conization between 1985-1990. Short- and long-term data were assessed for healing and scarring and the adequacy of postoperative Papanicolaou smears in the hot-knife patients. RESULTS: Thermal injury was minimal, with 300 mu or less in 83 patients (92%) and 350-600 mu in four patients. One patient had thermal distortion of 1500 mu. All slides were interpreted adequately. Blood loss was mild to moderate in 84 of 88 patients (95%) in the hot-knife group and in 34 of 40 patients (85%) in the cold-knife group. No patient in the hot-knife group needed blood transfusion or hospitalization. Operating time was reduced by as much as 67% when the hot knife was used. Thirteen percent of the hot-knife patients developed stenosis of the external os. No patient in the hot-knife group developed recurrence within 2 years of surgery. CONCLUSION: Using a Teflon-coated hot knife for conization of the cervix produces adequate surgical margins and reduces blood loss and operating time over that with cold-knife conization. Long-term follow-up reveals no increase in cervical stenosis and demonstrates adequate cytologic smears in the hot-knife patients.

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