Expression of pendrin in benign and malignant human thyroid tissues

The Pendred syndrome gene (PDS) encodes a transmembrane protein, pendrin, which is expressed in follicular thyroid cells and participates in the apical iodide transport. Pendrin expression has been studied in various thyroid neoplasms by means of immunohistochemistry (IHC), Western blot and RT-quantitative real-time PCR. The expression was related to the functional activity of the thyroid tissue. Follicular cells of normal, nodular goitre and Graves' disease tissues express pendrin at the apical pole of the thyrocytes. In follicular adenomas, pendrin was detected in cell membranes and cytoplasm simultaneously in 10 out of 15 cases. Pendrin protein was detected in 73.3 and 76.7% of the follicular (FTC) and papillary (PTC) thyroid carcinomas, respectively, where pendrin was solely localised inside the cytoplasm. An extensive intracellular immunostaining of pendrin was observed in six out of 11 (54.5%) of positive FTCs and 19 out of 23 (82%) of PTCs. Focal reactivity was detected in one follicular- and three papillary carcinomas, whereas pendrin protein was absent in three of 15 FTC and four of 30 PTC; mRNA of pendrin was detected in 92.4% of thyroid tumours. The relative mRNA expression of pendrin was lower in cancers than in normal thyroid tissues (P<0.001). The pendrin protein level was found to parallel its mRNA expression, which was not, however, related to the tumour size and tumour stage. In conclusion, pendrin is expressed in the majority of differentiated thyroid tumours with high individual variability but its targeting to the apical cell membrane is affected.     

Two corticosteroid-free regimens-tacrolimus monotherapy after basiliximab administration and tacrolimus/mycophenolate mofetil-in comparison with a standard triple regimen in renal transplantation: results of the Atlas study

BACKGROUND: The side effects associated with corticosteroids have led to efforts to minimize their use in renal transplant patients. In this study we compared two corticosteroid-free tacrolimus-based regimens with a standard triple therapy. METHODS: This was a 6-month, phase III, open-label, parallel-group, multicenter study. The total analysis set comprised 451 patients, randomized (1:1:1) to receive tacrolimus (Tac) monotherapy following basiliximab (Bas) administration (n=153), Tac/mycophenolate mofetil (MMF) (n=151), or, Tac/MMF/corticosteroids triple therapy as a control (n=147). RESULTS: The study was completed by 91.2% (triple therapy), 94.7% (Tac/MMF), and 82.4% (Bas/Tac) of patients. Patient baseline characteristics were similar in all groups. The incidences of biopsy-proven acute rejection were 8.2% (triple therapy), 30.5% (Tac/MMF), and 26.1% (Bas/Tac), p<0.001 (multiple test for comparison with triple therapy); Bas/Tac vs. Tac/MMF, p=ns. The incidences of corticosteroid-resistant acute rejection were 2.0%, 4.0%, and 5.2%, p=ns. Graft survival (95.9%, 96.7%, and 94.7%, p=ns) and patient survival (100%, 99.3%, and 99.3%, p=ns) were similar in all groups. Median serum creatinine at month 6 was 123.0 micromol/L (triple therapy), 134.7 micromol/L (Tac/MMF) and 135.8 micromol/L (Bas/Tac). The overall safety profiles were similar; differences (p<0.05) were reported for anaemia (24.5% vs. 12.6% vs. 14.5%), diarrhoea (12.9% vs. 17.9% vs. 5.9%), and leukopenia (7.5% vs. 18.5% vs. 5.9%) for the triple therapy, Tac/MMF, and Bas/Tac group, respectively. The incidences of new-onset diabetes mellitus were 4.6%, 7.1%, and 1.4%, respectively. CONCLUSION: Corticosteroid-free immunosuppression was feasible with the Bas/Tac and the Tac/MMF regimens. Both corticosteroid-free regimens were equally effective in preventing acute rejection, with the Bas/Tac therapy offering some safety benefits.     

Surgical complications of simultaneous pancreas-kidney transplantation: a 16-year-experience at one center

Fifty-one simultaneous pancreas-kidney transplants (SPKT) were performed between 1988 and 2004 in patients of mean age 34 years and 23 years duration of diabetes treatment. All kidney and pancreas recipients were on maintenance hemodialysis therapy prior to SPKT. The pancreas with duodenal segment and the kidneys were harvested from cadaveric heart-beating donors. Cold ischemia time in UW solution varied from 4 to 14 hours (mean, 9 hours 35 minutes). Twenty patients had the duodenal segment sutured to the urinary bladder, and the remaining 31 grafts were drained to an isolated ileal loop. Quadruple immunosuppression was administered as well as an anticoagulant and antibiotic prophylaxis. Forty-nine patients (49/51, 96%) regained insulin independence in the immediate postoperative period; 44 (86%) displayed immediate graft function. The remaining patients experienced postoperative ATN, the longest duration was 18 days. Of 51 patients, 38 (14.5%) are alive (follow-up, 6 to 180 months), 26 (68.5%) have good pancreatic function, and 34 (89%), good kidney function. Nineteen (50%) patients regard their quality of life as improved compared to their pretransplant status, which is mainly attributed to being dialysis and insulin free. Of 19 patients, 14 (74%) reported measuring glycemia regularly due to fear of losing the pancreas graft. Of 19 persons, seven (37%) returned to work after transplantation. Four (8.3%) lost their kidney graft secondary to vascular complications (n = 2) or rejection (n = 2). Four pancreas grafts with bladder drainage required conversion to enteric drainage owing to persistent urinary infections or urinary fistulae. Fifteen (29%) patients lost their pancreatic grafts within 1 year of transplantation due to the following: vascular complications (n = 12), septic complications (n = 1), or rejection (n = 2). Thirteen patients died within 1 year after transplantation, 5 of septic complications, 5 of neuroinfection, 1 of pulmonary embolism, and 2 of myocardial infarction. In conclusion, SPKT is a successful treatment for diabetic nephropathy, burdened by the possibility of serious complications.     

Mean time and first-pass metabolism

Summary The theoretical principles are outlined for estimating the fraction of a drug undergoing first-pass metabolism using only the plasma levels found after a single oral dose. Data for 3 drugs are used to illustrate the method. It involves analysis of the parent drug and the metabolite formed during the first passage through the gut wall and liver and evaluation of their total mean times. The mean time characteristics of molsidomine, nortriptyline and propranolol are considered and they confirm the theoretically deduced dependency of the mean time of the parent drug and the metabolite. Whether the results are more precise than those obtained from comparison of areas after oral and intravenous administration is discussed. From the data presented it is clear that the mean time method depends on the scatter inherent in the data. In order to estimate the true first-pass effect, greater scatter requires an increased number of data pairs, i.e. subjects. If intravenous data are not available, however, the method described provides a rough but worthwhile estimate of the first pass effect.Dedicated to Professor Dr. H.J. Dengler, Bonn, on the ocassion of his 60th birthday     

"Burning mouth syndrome"--is not a symptom of gastro-oesophageal reflux disease

Burning mouth syndrome (BMS) is a predominantly oral condition characterized by the occurrence of a chronic burning that commonly involves the anterior tongue, painful sensation, dryness and taste alterations. The syndrome is reported more often in women, usually without any oral mucosal signs and laboratory abnormalities. Its etiopathogenesis remains poorly understood, and there is no consensus on diagnostic criteria and treatment strategies. Tongue burning is though to be also one of a non-oesophageal symptom of gastro-oesophageal reflux disease. As reported below, although this symptom may well be diagnostically misleading, careful diagnosis based on clinical signs may distinguish patients with BMS from those with reflux disease, and successful management of burning mouth is often enables.     

Giant cell reparative granuloma of the orbit associated with cherubism

PURPOSE: To report a case of cherubism with extensive, bilateral orbital involvement occurring in a 27-year-old woman who had the diagnosis established at the age of 4 years. DESIGN: Single interventional case report. INTERVENTION: Ophthalmologic examination and computed tomography were performed. The patient underwent multiple surgical excisions using a bicoronal and transorbital approach. The excised orbital tissues were studied histopathologically. RESULTS: Computed tomography showed bilateral inferior lateral masses involving the orbital floors and producing marked superior displacement of the orbital contents. The intrinsic expansile bone lesions involved the inferior and lateral orbital walls with apical compression of the optic nerves. Histopathologic examination of the masses revealed scattered giant cells in a fibroblastic stroma containing small vascular channels. The lesion was interpreted as giant cell reparative granuloma. CONCLUSIONS: Giant cell reparative granuloma is an uncommon bone lesion that might involve the orbit. Cherubism should be included in the differential diagnosis of lesions that show the histopathologic features of giant cell reparative granuloma.