Spinocerebellar ataxia types 2 and 3 segregating simultaneously in a single family.

Spinocerebellar ataxia (SCA) types 2 and 3 are autosomal-dominant neurodegenerative disorders caused by mutations in two different genes. We identified mutations for SCA2 and SCA3 segregating simultaneously in a single Brazilian family. The index patient had SCA2, whereas her two second-degree cousins had SCA3. Disease was more rapidly progressive in the SCA2 patient, who presented severe brainstem and pancerebellar atrophy, as opposed to the two SCA3 patients, who had only mild cerebellar vermian atrophy. In such situations, molecular confirmation of all patients may avoid misdiagnosis of SCA subtypes and eventual errors in predictive testing of unaffected family members.     

Expression of retinoblastoma protein in human growth hormone-secreting pituitary adenomas

The retinoblastoma gene (RB1) is a tumor-suppressor gene in chromosomal region 13q14.2. Its role in the pathogenesis of pituitary tumors has not been fully clarified. Some studies have shown that losses in this chromosomal region are related to aggressive tumor behavior, although the retinoblastoma protein (pRB) is still expressed. Conversely, lack of expression of pRB was observed in one fourth of GH-secreting pituitary adenomas (GH-tumors). In order to further study the expression of pRB in GH-tumors, we evaluated this protein in 49 tumors from patients with acromegaly (20 noninvasive, 25 invasive, and 4 with no information) and 8 normal pituitaries using immunohistochemistry (IHC). Nuclear staining for pRB ranged from 0 to 90% (median 40%) in the tumors and from 40 to 80% (median 58%) in normal pituitaries. In 10 tumors (20% of total) the adenomatous cells were negative (5 cases) or had very low labeling (5 cases) for pRB. Sixty three percent (31/49) of the tumors showed staining in 10–80% of the cells and in 16% (8/49) of the cases >80% of the adenomatous cells were positive for pRB. The expression of pRB was not different in invasive and noninvasive tumors. In conclusion, pRB is underexpressed in a subgroup of GH-tumors, and this may represent an early event in the pathogenesis of this tumor subtype.     

DNA damage in cytologically normal urothelial cells of patients with a history of urothelial cell carcinoma

In order to determine if patients with a history of previous urothelial cell carcinoma (UCC) but with current normal urinary cytology have DNA damage in urothelial cells, the single-cell gel electrophoresis (comet) assay was conducted with cells obtained by urinary bladder washings from 44 patients (28 with a history of previous UCC). Increased DNA damage was observed in cytologically "normal" urothelial cells of patients with a history of UCC when compared with referents with no similar history and after correcting the data for smoking status and age (P < 0.018). Increased DNA damage also correlated with the highest tumor grade, irrespective of time or course of the disease after clinical intervention (Kendall tau correlation, 0.37, P = 0.016). Moreover, aneuploidy, as assessed by DNA content ratio (DCR; 75th/25th percentile of total DNA fluorescence of 50 comets/patient) was unaltered by smoking status, but increased with UCC grade: 1.39 +/- 0.12 (median +/- 95% confidence interval; referents); 1.43 +/- 0.11 (Grade I UCC; P = 0.264, against referents); 1.49 +/- 0.16 (Grade II UCC; P = 0.057); 1.57 +/- 0.16 (Grade III UCC; P = 0.003). Micronucleated urothelial cells (MNC) were also scored on Giemsa-stained routine cytological smears and were found not to correlate with DNA damage or DCR. MNC frequencies were higher for patients with a history of UCC and/or smoking than referents with neither history, but there was no statistical difference between groups. Taken together, these results suggest that the normal-appearing urothelium of patients resected for UCC still harbor genetically unstable cells.     

Immune regulatory mechanisms influence early pathology in spinal cord injury and in spontaneous autoimmune encephalomyelitis

Injuries to the central nervous system (CNS) trigger an inflammatory reaction with potentially devastating consequences. In this report we compared the characteristics of the inflammatory response on spinal cord injury (SCI) caused by a stab wound between the T7 and T9 vertebrae and spontaneous experimental autoimmune encephalomyelitis (EAE). SCI and EAE were compared in two types of myelin basic protein Ac1-11-specific T-cell receptor transgenic mice: T/R+ mice harbor regulatory T cells, and T/R- mice lack regulatory T cells. Our results show that 8 days after SCI, T/R- mice developed a strong T-cell infiltrate in the spinal cord, with remarkable down-modulation of CD4 expression that was accompanied by a local increase in Mac-3+ and F4/80+ reactivity and diffuse local and distal astrogliosis. In contrast, T/R+ mice exhibited a modest increase in CD4+ cells localized to the site of injury, without CD4 down-modulation; focal astrogliosis was restricted to the site of the lesion, although Mac-3+ and F4/80+ cells were also present. Similarly to T/R- mice that underwent SCI, T cells displaying down-modulated CD4 expression were found in the CNS of older T/R- mice afflicted by spontaneous EAE. Overall, our results suggest that common mechanisms regulate T-cell accumulation in CNS lesions of different causes, such as mechanic lesion or autoimmune-mediated damage.     

Bloqueo del plano del músculo erector de la columna para analgesia de dolor lumbar crónico: serie de casos

BackgroundChronic low back pain (CLBP) is a frequent condition, poorly managed with conventional treatments. The ultrasound-guided erector spinae plane block has increasingly been used in the management of acute and chronic pain. We aimed to determine this technique's analgesic efficacy in patients with moderate to severe CLBP.MethodsTen consecutively selected patients: adults, regularly followed in our Pain Clinic with moderate/severe long-term CLBP refractory to pharmacological treatment, VAS > 4. Prospective data collection: before the intervention –demographical data, past medical history, current pain therapies, VAS pain level, Brief Pain Inventory– Short Form and Neuropathic Pain Questionnaire; 30 minutes after – VAS and satisfaction level; 24 and 72 hours, 7 days and 1 month after - complications and pain level.ResultsMajority of females (90%), mean age of 70.3 years-old. All had primary musculoskeletal CLBP. 90% experienced severe pain (VAS > = 7) in the last 24 hours. Half presented neuropathic characteristics. Patients were very satisfied with the technique (mean: 8.75) with immediate pain relief (VAS mean: 2.3). 24 and 72 hours, 7 days and 1 month after the treatment VAS means were 3.2, 3.1, 3.8 and 6.2. We report a 20.8 days duration mean. No short or long-term complications.Discussion and conclusionsUltrasound-guided erector spinae plane block has preliminary advantages in CLBP: easily performed with low complications risk, immediate discharge home with absence of motor block, 100% efficacy at short and medium-terms. Even though pain's relief was shorter than a month, it is a useful tool allowing patients’ well-being, physical rehabilitation and exercise during this period.     

Treatment of diarrheal dehydration.

A regimen for the treatment of diarrheal dehydration is presented. It was devised for use in conditions found in developing countries. Application to large number of patients has been successful. One of its characteristics is the infusion at the start of treatment of a larger amount of fluid than generally recommended. The advantages of magnesium supplementation and phosphate supplementation have been studied. Fecal electrolyte composition has been studied during recovery from diarrheal dehydration. Components of acid balance and generation have been measured with the "net acid" balance technique.     

Discrimination between normal and glaucomatous eyes with the Topographic Scanning System: a preliminary report.

BACKGROUND AND OBJECTIVE: To evaluate the ability of the Topographic Scanning System (TopSS; Laser Diagnostic Technologies, San Diego, CA) to differentiate individuals with glaucoma from normal subjects. PATIENTS AND METHODS: The subjects were divided into two groups: primary open-angle glaucoma and normal. All individuals underwent a complete ophthalmic evaluation, a 24-2 full threshold Humphrey visual field evaluation, and a TopSS examination. Cut-off points were selected, receiver operator characteristic (ROC) curves were created, and sensitivity and specificity were calculated for individual TopSS parameters and combinations of variables using multivariate analysis. RESULTS: One hundred twelve patients with glaucoma and 88 normal individuals were enrolled in the study. The best TopSS individual parameters were: average disc diameter (sensitivity: 64%, specificity: 89%, area under ROC curve: 0.824), total disc area (sensitivity: 85%, specificity: 66%, area under ROC curve: 0.802), and cup area (sensitivity: 69%, specificity: 85%, area under ROC curve: 0.797). The multivariate analysis resulted in an area under the ROC curve of 0.91 (sensitivity: 90%, specificity: 81%). CONCLUSIONS: This preliminary report suggests that the use of a multivariate discriminant formula may enhance the ability to differentiate individuals with glaucoma from normal subjects with the TopSS, with high sensitivity and specificity. Further studies investigating a random population are needed to test the validity of this formula.     

Sudomotor dysfunction is frequent and correlates with disability in Friedreich ataxia

Objectives

To evaluate autonomic symptoms and function in Friedreich’s Ataxia (FRDA).