Botulinum toxin and neuromotor rehabilitation: An integrated approach to idiopathic cervical dystonia.

Currently, the best treatment option for idiopathic cervical dystonia (ICD) is injection of botulinum toxin (BTX) into the affected muscles, whereas rehabilitative approaches have given disappointing results. We evaluated whether the association of an ad hoc rehabilitative program may improve the clinical efficacy of BTX treatment in a single-center, cross-over, controlled study. Forty patients with ICD were randomly assigned to two different treatment groups: (1) BTX type A (BTX-A) plus a specific program of physical therapy (BTX-PT) or (2) BTX-A alone (BTX-0). Patients in the BTX-PT group showed a longer duration of the clinical benefit (118.8 vs. 99.1 days) and needed a lower dose of BTX at reinjection (284.5 vs. 325.5 units). In addition, they showed more marked reductions in their disability in activities of daily living (-9.7 vs. -4.85 points) and subjective pain (-13.35 vs. 6.95 points) scores. Association of BTX-A therapy with a specific program of physical therapy may improve ICD treatment outcome.     

Diagnostic utility of S100A1 expression in renal cell neoplasms: an immunohistochemical and quantitative RT-PCR study.

S100A1 is a calcium-binding protein, which has been recently found in renal cell neoplasms. We evaluated the diagnostic utility of immunohistochemical detection of S100A1 in 164 renal cell neoplasms. Forty-one clear cell, 32 papillary, and 51 chromophobe renal cell carcinomas, and 40 oncocytomas, 164 samples of normal renal parenchyma adjacent to the tumors and 13 fetal kidneys were analyzed. The levels of S100A1 mRNA detected by quantitative RT-PCR analysis of frozen tissues from seven clear cell, five papillary, and six chromophobe renal cell carcinomas, four oncocytomas, and nine samples of normal renal tissues adjacent to neoplasms were compared with the immunohistochemical detection of protein expression. Clear cell and papillary renal cell carcinomas showed positive reactions for S100A1 in 30 out of 41 tumors (73%) and in 30 out of 32 (94%) tumors, respectively. Thirty-seven renal oncocytomas out of 40 (93%) were positive for S100A1, whereas 48 of 51 (94%) chromophobe renal cell carcinomas were negative. S100A1 protein was detected in all samples of unaffected and fetal kidneys. S100A1 mRNA was detected by RT-PCR in all normal kidneys and renal cell neoplasms, although at very different levels. Statistical analyses comparing the different expression of S100A1 in clear cell and chromophobe renal cell carcinomas observed by immunohistochemical and RT-PCR methods showed significant values (P<0.001), such as when comparing by both techniques the different levels of S100A1 expression in chromophobe renal cell carcinomas and oncocytomas (P<0.001). Our study shows that S100A1 protein is expressed in oncocytomas, clear cell and papillary renal cell carcinomas but not in chromophobe renal cell carcinomas. Its immunodetection is potentially useful for the differential diagnosis between chromophobe renal cell carcinoma and oncocytoma. Further, S100A1 protein expression is constantly detected in the normal parenchyma of the adult and fetal kidney.     

Gains of chromosomes 7, 17, 12, 16, and 20 and loss of Y occur early in the evolution of papillary renal cell neoplasia: a fluorescent in situ hybridization study.

It has been suggested that gains of chromosomes 7 and 17 and loss of Y occur in renal papillary adenoma and that progression to papillary renal cell carcinoma is marked by gains of additional chromosomes, most frequently 12, 16, and 20. Previous studies have included very few lesions of <5 mm in diameter, a requirement of the present definition of papillary adenoma. Ten papillary adenomas (ranging from 1 to 5 mm in diameter) from autopsy material and 10 surgically resected papillary renal cell carcinomas were studied with fluorescence in situ hybridization in paraffin sections using centromeric probes for chromosomes 7, 12, 16, 17, 20, and Y diluted 1:100 with tDenHyb1 buffer. The signals in 50 to 150 nuclei were counted in each tumor. Controls for all the probes were normal renal tissues from the same patients. Three or more signals per nucleus were frequently observed in papillary adenomas: chromosome 7 (range, 10 to 50%; > or = 30% in 9 of 10), 17 (range, 10 to 47%; > or = 30% in 7), 16 (range, 1 to 63%; > or = 10% in 5), 12 (range, 0 to 32%; > or =10% in 4), and 20 (range, 5 to 49%; > or = 10% in 5). Loss of the Y chromosome was observed in 80 to 90% of nuclei in 9 adenomas from males. Three or more signals were frequent in papillary renal cell carcinomas: chromosome 7 (range, 32 to 63%; > or =30% in 10 of 10), 17 (range, 28 to 61%; > or = 30% in 7), 16 (range, 0 to 45%; > or = 10% in 6), 12 (range, 1 to 37, > or = 10% in 5), 20 (range, 2 to 44%; > or = 10% in 4). No signal for Y was observed in 12 to 88% (> or = 81% in 6) of nuclei in 7 carcinomas from males. Statistical analysis showed no difference between adenomas and carcinomas. Gains of chromosomes 7, 17, 16, 12, and 20 and loss of the Y chromosome occur early in the evolution of papillary renal cell neoplasia in tumors that are only a few millimeters in diameter. Progressive gains of these chromosomes do not appear to correlate with the transition from adenoma to carcinoma.     

The brain as a target for adrenocortical steroids: cognitive implications.

It is well established that a reciprocal control exists between the brain and glucocorticoid hormones. The brain regulates adrenocortical function via hypothalamic corticotrophin releasing hormone-41 (CRH-41), glucocorticoids act at specific receptors in the hippocampus, thus promoting negative feedback mechanisms. Because the hippocampus is a major site for memory processes, a role for excessive/long-lasting plasma glucocorticoid levels has been suggested in conditions of mental impairment. Major depression, Cushing's disease, and dementia of the Alzheimer type are disorders which share hyperactivity of the hypothalamo-pituitary-adrenal axis, as well as symptoms of cognitive decline. Although the mechanisms leading to hypercortisolemia appear to be different in each case, the neuropsychological features of these three disorders accord with the hypothesis of glucocorticoid-associated brain damage. It therefore is important to find pharmacological strategies that will avert or reduce these potential consequences on brain function.     

Fluorescence in situ hybridization analysis of chromosome 12p in paraffin-embedded tissue is useful for establishing germ cell origin of metastatic tumors.

The over-representation of chromosome 12p sequences is crucial for the development of invasive testicular germ cell tumors. Testicular cancer patients may have metastatic tumors of diverse histologic types, including adenocarcinoma, undifferentiated carcinoma, sarcoma, or other malignancies that lack features of germ cell tumors. We sought to investigate the possible germ cell origin of such tumors using interphase fluorescence in situ hybridization. In all, 10 metastatic malignant somatic-type tumors from patients with histories of testicular cancer, as well as one malignant somatic-type tumor from a patient with primary mediastinal germ cell tumor were studied and included: adenocarcinoma (five cases), poorly differentiated carcinoma (one), sarcoma (four), and neuroendocrine carcinoma (one). The tumors were analyzed using fluorescence in situ hybridization using 12p spectrum green and 12 centromeric spectrum orange probes in paraffin sections. The patients ranged in age from 27 to 55 years (mean, 43). Colon and lung cancers from patients without germ cell tumors were used as controls. Adequate signals were observed in all tumors. Gain of chromosome 12p was seen in six tumors. None of the control tumors showed 12p amplification. Fluorescence in situ hybridization for 12p amplification in routinely processed surgical specimens is a useful adjuvant diagnostic tool in confirming the germ cell origin of metastatic tumors having the histologic appearance of somatic-type neoplasms.     

Integrating support vector machines and neural networks.

Support vector machines (SVMs) are a powerful technique developed in the last decade to effectively tackle classification and regression problems. In this paper we describe how support vector machines and artificial neural networks can be integrated in order to classify objects correctly. This technique has been successfully applied to the problem of determining the quality of tiles. Using an optical reader system, some features are automatically extracted, then a subset of the features is determined and the tiles are classified based on this subset.