The TOR1A polymorphism rs1182 and the risk of spread in primary blepharospasm

We studied the influence of the rs1182 polymorphism of the TOR1A gene on the risk of dystonia spread in two representative cohorts of patients presenting with primary blepharospasm (BSP), one from Italy and the other from the United States of America. The relationship between rs1182 polymorphism and spread was estimated by Kaplan‐Meier survival curves and Cox proportional hazard regression models adjusted by age and sex, age of BSP onset. In both series, patients carrying the T allele (G/T or T/T) in the rs1182 polymorphism were more likely to have dystonia spread as compared with the homozygous carriers of the common G allele. The comparable findings obtained in two independent cohorts support a genetic contribution to BSP spread. © 2009 Movement Disorder Society     

In-tandem insight from basic science combined with clinical research: CD38 as both marker and key component of the pathogenetic network underlying chronic lymphocytic leukemia

The absence of mutations in the IgV genes, together with the presence of ZAP-70 and CD38, are the most reliable negative prognostic markers for chronic lymphocytic leukemia (CLL) patients. Several lines of evidence indicate that CD38 may be not only a diagnostic marker but also a key element in the pathogenetic network in CLL. First, CD38 is a receptor that induces proliferation and increases survival of CLL cells. Second, CD38 signals start upon interaction with the CD31 ligand expressed by stromal and nurse-like cells. Third, CD38/CD31 contacts up-regulate CD100, a semaphorin involved in sustaining CLL growth. Fourth, evidence that nurselike cells express high levels of CD31 and plexin-B1, the high-affinity ligand for CD100, offers indirect confirmation for this model of receptor cross-talk. Elements of variation in the clinical course of CD38(+) CLL patients include (1) potential intersection with ZAP-70, a kinase involved in the CD38 signaling pathway in T and natural killer (NK) cells, and (2) the effects of genetic polymorphisms of the receptors involved, at least of CD38 and CD31. Consequently, CD38 together with ZAP-70 appear to be the key elements of a coreceptor pathway that may sustain the signals mediated by the B-cell receptor and potentially by chemokines and their receptors. This would result in acquisition of increased survival potential, providing clues to the poorer prognosis of CD38(+) patients.     

Total hip arthroplasty with shortening osteotomy in congenital major hip dislocation sequelae

We retrospectively evaluated the postoperative results of total hip arthroplasty (THA) in patients presenting with Crowe group IV dislocated hips. Overall, results were compared with regard to the type of osteotomy performed (Z or oblique) to define the correct indications for surgical technique and choice of prosthetic implant. Thirty-three subtrochanteric shortening and derotational osteotomies in primary THA were performed in 26 patients secondary to congenital hip dislocation. A Z osteotomy was performed in 14 cases and an oblique osteotomy in 19. The surgical approach was direct lateral, and surgery was aimed at restoring the anatomic hip center. Femoral and acetabular fixation was uncemented. The most used stem was the S-ROM (DePuy, Leeds, United Kingdom), and the couplings used were ceramic-ceramic (7 cases), ceramic-polyethylene (3 cases), metal-polyethylene (15 cases), and metal-metal (3 cases). Mean follow-up was 88±45 months. According to the Merle D'Aubigné score, the overall clinical results were good in 23 cases, satisfactory in 6, and fair in 4. Union of the osteotomy occurred in 97% of cases, and the mean time required for osteotomy union was 6±2 months without significant differences between Z and oblique osteotomies. At last follow-up, there was loosening of 1 cup and 1 stem, and revision was necessary. Twelve percent of patients experienced postoperative dislocation and 9% developed neuropraxia of the femoral nerve. The clinical and radiological results were similar in both groups, with a high rate of pain relief, an improvement in limb-length discrepancy, and reduced limping, leading to a smaller or no insole. Currently, the more complex Z osteotomy has been abandoned, because a modular stem prosthesis with metaphyseal sleeve allows the oblique osteotomy to be used with an easier and shorter surgical procedure.     

MRI role in morphological and functional assessment of the levator ani muscle: Use in patients affected by stress urinary incontinence (SUI) before and after pelvic floor rehabilitation

Objective

Pelvic floor dysfunctions affect a very high proportion of female population. Magnetic resonance imaging is the only technique able to provide a multiplanar overview of pelvic organs and muscles without the use of ionizing radiation. The aim of our prospective study is to objectively evaluate the effectiveness of perineal re-education applying MR technique.

Materials and methods

22 patients affected by stress urinary incontinence were enrolled in our prospective study. They underwent urogynaecological, urodynamic examinations, and a questionnaire about symptoms (ICIQ-UI) to investigate the degree of their interference with daily activities. Then they underwent a morphological and dynamic MR exam.

Results

The pre-perineal rehabilitation MR examinations showed an asymmetry of the levator ani muscle in 87% of patients; the remaining 13% showed a muscular bilateral volume reduction. In the group with unilateral defect, the muscle total volume had values between 15 and 21 cm³. Its overall volume was 34.2% smaller on the defective side (9.28 ± 0.26 cm³) compared to the normal side (12.64 ± 12.31 cm³, P < 0.001).In patients with a bilateral impairment, the muscle was replaced by fibro-fatty tissue, without a significant asymmetry between the two sides. The post-perineal rehabilitation MR tests showed three different degrees of response to therapy, with a “complete response” found in 67% of patients and no response in 13%.

Conclusions

MR is an useful tool in the management of patients affected by stress urinary incontinence with indication for perineal rehabilitation. Its objective data allow to distinguish different types of response to therapy and, consequently, different outcomes in terms of additional treatments.     

Propofol infusion syndrome: an overview of a perplexing disease.

Propofol (2, 6-diisopropylphenol) is a potent intravenous hypnotic agent that is widely used in adults and children for sedation and the induction and maintenance of anaesthesia. Propofol has gained popularity for its rapid onset and rapid recovery even after prolonged use, and for the neuroprotection conferred. However, a review of the literature reveals multiple instances in which prolonged propofol administration (>48 hours) at high doses (>4 mg/kg/h) may cause a rare, but frequently fatal complication known as propofol infusion syndrome (PRIS). PRIS is characterized by metabolic acidosis, rhabdomyolysis of both skeletal and cardiac muscle, arrhythmias (bradycardia, atrial fibrillation, ventricular and supraventricular tachycardia, bundle branch block and asystole), myocardial failure, renal failure, hepatomegaly and death. PRIS has been described as an 'all or none' syndrome with sudden onset and probable death. The literature does not provide evidence of degrees of symptoms, nor of mildness or severity of signs in the clinical course of the syndrome. Recently, a fatal case of PRIS at a low infusion rate (1.9-2.6 mg/kg/h) has been reported. Common laboratory and instrumental findings in PRIS are myoglobinuria, downsloping ST-segment elevation, an increase in plasma creatine kinase, troponin I, potassium, creatinine, azotaemia, malonylcarnitine and C5-acylcarnitine, whereas in the mitochondrial respiratory electron transport chain, the activity of complex IV and cytochrome oxidase ratio is reduced. Propofol should be used with caution for sedation in critically ill children and adults, as well as for long-term anesthesia in otherwise healthy patients, and doses exceeding 4-5 mg/kg/h for long periods (>48 h) should be avoided. If PRIS is suspected, propofol must be stopped immediately and cardiocirculatory stabilization and correction of metabolic acidosis initiated. So, PRIS must be kept in mind as a rare, but highly lethal, complication of propofol use, not necessarily confined to its prolonged use. Furthermore, the safe dosage of propofol may need re-evaluation, and new studies are needed.     

A reliability study of impairment and disability scales for myasthenia gravis patients

The authors developed two scales to be adopted for the evaluation of myasthenia gravis (MG) patients. The first scale (MG impairment scale) is based on objective patient evaluation and on patients' responses to standardized questions relating to the functioning of specific muscle groups. It consists of 13 items exploring strength and 10 items exploring fatigability. The second scale (MG disability scale) evaluates disability in those everyday activities that are often impaired in MG patients. Test-retest reliability of each item and of the global score (sum of single item scores) was assessed by the weighted K statistic and by the intraclass correlation coefficient. Reliability was invariably 'substantial', and for single items 'almost perfect' for the MG impairment scale, and invariably 'almost perfect' for the MG disability scale. The internal structure of the MG impairment scale was explored by means of the principal component analysis. This analysis resulted in three main (rotated) factors, which loaded respectively onto 'ocular', 'spinal' and 'bulbar' functions. For these factors, we report factor score coefficients that can be used to compute single patients' scores, which in turn may be used in further analyses, particularly for follow-up studies. We also report the results of an analysis of the correlations between the two scales. The MG impairment and the MG disability scales are proposed for application in both clinical and research settings.     

Interobserver agreement of the dermoscopic diagnosis of 129 small melanocytic skin lesions

AIM AND BACKGROUND: Dermoscopic diagnosis of pigmented skin lesions is based on the evaluation of dermoscopic criteria (classical pattern analysis) and on alternative diagnostic methods, such as the ABCD (A, asymmetry; B, border; C, color; D, differential structures) rule based on the total dermatoscopic score. The aim of the study was to investigate the interobserver agreement of standard dermoscopic criteria between two observers and the diagnostic validity of dermoscopic diagnosis by pattern analysis and by the ABCD rule. STUDY DESIGN: The study included a total of 129 small (< or = 5 mm) melanocytic skin lesions selected from all lesions observed in consecutive patients between April 1996 and September 1998. Before surgery, each lesion was photographed with a Dermaphot. Dermoscopic images were examined independently by two observers to evaluate the presence or absence of standard dermoscopic criteria and to establish the dermoscopic diagnosis by pattern analysis and by the ABCD rule. RESULTS: Interobserver agreement for dermoscopic criteria varied from moderately good to good, with the highest agreement for radial streaks (k = 0.96) and the lowest for pseudopods (k = 0.49). Interobserver agreement was moderately good in dermoscopic diagnosis by pattern analysis (k = 0.48) and by the total dermatoscopic score (k = 0.44). The sensitivity and specificity of dermoscopic diagnosis by pattern analysis were 40% and 99%, respectively, for both observers. As regards the total dermatoscopic score (a cutoff score of < or = 5.45 vs > 5.45), sensitivity ranged from 80% to 100% and specificity from 48% to 59%. CONCLUSIONS: The study showed that the pattern analyses as well as the ABCD rule give a poor discrimination between benign and malignant lesions and do not add relevant information for management decision in small melanocytic lesions. However, close follow-up examinations of small equivocal melanocytic lesions using digital equipment allow evaluation of their dermoscopic features during progression and whether their rather commonly found atypical dermoscopic features are lost during their natural course of growth.     

Intracellular accumulation and reduced sarcolemmal expression of dysferlin in limb--girdle muscular dystrophies

Dysferlin has recently been identified as a novel gene involved in limb-girdle muscular dystrophy type 2B (LGMD2B) and its allelic disease, Miyoshi myopathy. The predicted structure of dysferlin suggests that it is a transmembrane protein possibly involved in membrane fusion. Thus, unlike previously identified structural proteins in muscular dystrophy, dysferlin is likely involved in a novel pathogenic mechanism for this disease. In this study, we have analyzed the expression of dysferlin in skeletal muscle of patients with disruptions in the dystrophin-glycoprotein complex and patients with a clinical diagnosis of LGMD2B or Miyoshi myopathy. We show expression of dysferlin at the sarcolemma in normal muscle and reduced sarcolemmal expression along with accumulation of intracellular staining in dystrophic muscle. Electron microscopy in Miyoshi myopathy biopsies suggests that the cytoplasmic staining could be a result of the abundance of intracellular vesicles. Our results indicate that dysferlin expression is perturbed in LGMD and that both mutations in the dysferlin gene and disruption of the dystrophin-glycoprotein complex can lead to the accumulation of dysferlin within the cytoplasm.