In-bore MRI targeted biopsy. Lights and shadows.

Multiparametric Magnetic Resonance Imaging (MpMRI) and MRI-guided biopsy (MRGB) are the diagnostic gold standard in the management of men with suspicious prostate cancer (PCa). There are not enough studies, yet, that compare TRUS-MRGB, COG-TB and IB-MRGB. Despite IB-MRGB could be more accurate in detecting PCa in smaller lesions and a less operator dependent technique, there are still some concerns regarding high resource costs and the chance of missing lesions not visible at MRI or detected by systematic biopsy.

Etiology, presentation and management of urinary tract infections in multiple sclerosis patients: A review of the current literature.

Urinary tract infections (UTIs) present a formidable challenge in the care of individuals affected by multiple sclerosis (MS). Lower urinary tract dysfunction is a prevalent issue among MS patients, predisposing them to an elevated risk of UTIs. When left untreated, UTIs can further exacerbate the already compromised quality of life in individuals with MS. The diagnosis and management of UTIs in MS patients necessitate a careful clinical evaluation. The objective of this review is to delineate preventive strategies and current and developing therapeutic approaches for preventing and treating UTIs associated with urinary dysfunction, catheterization, and upper urinary tract infections in patients with MS. Effectively addressing UTIs and urinary tract dysfunction in individuals with multiple sclerosis calls for a comprehensive, interdisciplinary approach.

Methylation Analysis of Urinary Sample in Non-Muscle-Invasive Bladder Carcinoma: Frequency and Management of Invalid Result.

BACKGROUND: Numerous studies showed that methylation analysis represents a newly developed urinary marker based on DNA methylation changes in a panel of genomic biomarkers and it could represent a valid tool in terms of the diagnosis and prediction of high-grade urothelial carcinoma recurrences. One of the limits of the use of this new molecular method during a follow-up is represented by the number of invalid tests in routine practice. METHOD: A total of 782 patients with a diagnosis of non-muscle-invasive high-grade carcinoma (NMIBC) was studied. The Bladder EpiCheck test (BE) was performed together with cytology in all cases within 1 year after the end of treatment. In 402 patients, the urinary samples were voided urine (UV), while, in 380 cases, the samples were collected after bladder washing (IU). For all the patients with invalid BE results, a second BE test was performed following the instructions for use that indicated the test should be repeated with a new urinary sample in the case of an invalid result. RESULTS: Analyzing the two different groups (UV and IU), we found the invalid BE results seemed to be not related to urinary samples (p = 0.13 Fisher's exact test), suggesting that the collection method was not relevant in order to reduce the number of invalid tests. CONCLUSIONS: In the follow-up for NMIBC, for patients for whom a BE test is planned, a combined approach of cytology and a methylation test is recommended in order to repeat the BE test with an invalid result only in those cases with a cytological diagnosis of atypical urothelial cells (AUC) suspicious for high-grade urothelial carcinoma (SHGUC) and high-grade urothelial carcinoma (HGUC).

Changing paradigm of sacral neuromodulation and external anal sphincter repair for faecal incontinence in specialist centres.

AIM: The aim of this study was to determine whether the paradigm of surgical intervention for faecal incontinence (FI) has changed between 2000 and 2013. METHOD: This was a multi-centre retrospective study of patients who had undergone either sacral neuromodulation (SNM) or delayed sphincter repair or sphincteroplasty (SR) as a primary surgical intervention for FI in five centres in Europe and one in the United States. The flow of patients according to the intervention, sustainability of the treatment at a minimum follow-up of 5 years, complications and requirement for further interventions were recorded. RESULTS: A total of 461 patients (median age 56 years, range 24-90 years, 41 men) had either SNM or SR as an index operation during the study period [SNM 284 (61.6%), SR 177 (38.4%)]. Among SNM patients, there were 169 revisional operations (change of battery and/or lead, re-siting or removal). At the time of last follow-up 203 patients (71.4%) continued to use SNM. Among SR patients, 30 (16.9%) had complications, most notably wound infection (22, 12.4%). During follow-up 32 patients (18.1%) crossed over to SNM. Comparing two 4-year periods (2000-2003 and 2007-2010), the proportion of patients operated on who had a circumferential sphincter defect of less than 90° was 48 (68%) and 45 (46%), respectively (P = 0.03), while those who had SNM as the primary intervention increased from 29% to 89% (P < 0.05). CONCLUSION: The paradigm of surgical intervention for FI has changed with increasing use of SNM.

ECG-gated CT angiography of the thoracic aorta: the importance of evaluating the coronary arteries.

AIM: To evaluate the feasibility of coronary artery disease (CAD) evaluation using electrocardiogram-gated computed tomography CT of the thoracic aorta. MATERIALS AND METHODS: A total of 477 patients, who underwent CT angiography of the thoracic aorta, were included retrospectively. Dose-length products (DLP) were recorded. Two blinded readers graded image quality of the coronary arteries on a three-point scale. Coronary artery stenosis has only been reported if considered significant, i.e., ≥50%. The type of plaque responsible for the stenosis was considered. The normal distribution of the data was assessed using Shapiro-Wilk and Anderson-Darling tests. Results were expressed as means and standard deviations and percentages. Inter-reader agreements were analysed by calculating the intraclass correlation coefficient, and by using Cohen kappa statistics. RESULTS: The mean DLP was 566±90.4 mGy∙cm, corresponding to an effective dose of 9.6±1.5 mSv. Five point three percent of asymptomatic patients were positive for CAD with stenosis ≥50%. All patients with coronary stenosis presented with a soft plaque. Two anomalous coronary origins were found. The inter-reader agreement was excellent in defining both the quality of the examination and the degree of coronary stenosis (k=0.85). CONCLUSION: The opportunity to prove the presence of CAD in asymptomatic patients during a ECG-gated CT of the thoracic aorta can have an extremely important clinical impact, promoting the best therapeutic pathway for the patient. Therefore, coronary arteries should always be analysed carefully and reported in ECG-gated CT angiography of the thoracic aorta.

A simple bowel habit score for colorectal patients.

PURPOSE: The assessment of bowel habit is important in the management of patients with colorectal disease. There is not an ideal and practical bowel habit scoring system. The current scores have been designed only for a subclass of patients having a particular disorder. Furthemore, they are complex and time consuming. We propose a simple score to quickly assess the bowel function in all patients with proctological disorders. METHODS: We developed a bowel habit scoring system including three parameters: bowel frequency, stool consistency, and urgency. A three-point scale was applied. Three main categories of bowel habit were derived: slow (3-4 points), normal (5-6 points), and quick (7-9 points). We applied this score to all patients undergoing colorectal visit in outpatient office between January 2014 and December 2015. RESULTS: Eight hundred and ninety patients were included. In 819 patients (92 %), the score was completed. The mean time to assess the score was 28 s (range 12-80 s). The mean age was 49.2 years (range 14-93). The males were 435 (53.1 %). Two hundred and forty patients (29.3 %) had "slow", 521(63.6 %) had "normal", and 58 (7.1 %) had "quick" habit. Patients with constipation or fissure had higher incidence of slow habit compared with all other patients (60.5 vs 25.2 %, P < 0.05; 42.8 vs 17.2 %, P < 0.05). Patients with incontinence or inflammatory bowel disease had higher incidence of quick bowel habit compared with all other patients (72.7 vs 5.7 %, P < 0.05; 28.5 vs 5.6%, P < 0.05). CONCLUSIONS: This bowel habit score is easy and quick to apply with high rate of feasibility. It could be useful to manage patients with colorectal disorders.

Engineered cardiac micromodules for the in vitro fabrication of 3D endogenous macro-tissues.

The in vitro fabrication of an endogenous cardiac muscle would have a high impact for both in vitro studies concerning cardiac tissue physiology and pathology, as well as in vivo application to potentially repair infarcted myocardium. To reach this aim, we engineered a new class of cardiac tissue precursor (CTP), specifically conceived in order to promote the synthesis and the assembly of a cardiac extracellular matrix (ECM). The CTPs were obtained by culturing a mixed cardiac cell population, composed of myocyte and non-myocyte cells, into porous gelatin microspheres in a dynamic bioreactor. By engineering the culture conditions, the CTP developed both beating properties and an endogenous immature cardiac ECM. By following a bottom-up approach, a macrotissue was fabricated by molding and packing the engineered tissue precursor in a maturation chamber. During the macrotissue formation, the tissue precursors acted as cardiac tissue depots by promoting the formation of an endogenous and interconnected cardiac network embedding the cells and the microbeads. The myocytes cell fraction pulled on ECM network and induced its compaction against the internal posts represented by the initial porous microbeads. This reciprocal interplay induced ECM consolidation without the use of external biophysical stimuli by leading to the formation of a beating and endogenous macrotissue. We have thus engineered a new class of cardiac micromodules and show its potential for the fabrication of endogenous cardiac tissue models useful for in vitro studies that involve the cardiac tissue remodeling.

Ultrasound and thyroiditis in patient candidates for thyroidectomy.

AIM: Thyroiditis is often associated with nodules based on the Bethesda classification system, and the presence of thyroiditis can make thyroid surgery difficult using both conventional techniques and minimally invasive videoassisted approaches (MIVAT). METHODS: We analyzed 326 patients who underwent total thyroidectomy in 2012. We collected all data in dedicated database. The patients were divided in 4 groups: group 1 no affected by thyroiditis, group 2 affected by thyroiditis, group 3 only histological diagnosis of thyroiditis, group 4all patients affected by thyroiditis. RESULTS: Group 1 included 201 cases, group 2 included 64 patients, group 3 included 61 patients. No statistically significant difference between group 2 and 3 about Ultrasound (US) examination. Statistically significant difference in incidence of "THYR 3-4" between group 1 and group 4. No differences in MIVAT vs. Conventional group. CONCLUSION: US examination of the thyroid is essential for the diagnostic study of the gland also in the selection of a surgical approach. Thyroiditis is a relative contraindication to MIVAT but the experience of the endocrine surgeon is the most important factor to reduce intra and postoperative complications together a correct collaboration in multidisciplinart endocrinological team.

Treatment with atorvastatin is associated with a better prognosis in chronic heart failure with systolic dysfunction: results from The Daunia Heart Failure Registry.

BACKGROUND: Few works have evaluated the effect of statins on left ventricular dysfunction in patients with chronic heart failure (CHF), by using tissue Doppler imaging (TDI). We therefore aimed to investigate whether atorvastatin treatment may influence prognosis and myocardial performance evaluated by TDI in subjects with CHF. METHODS: Five hundred thirty-two consecutive CHF outpatients enrolled in a local registry, the Daunia Heart Failure Registry, were prospectively analysed. 195 patients with CHF and left ventricular ejection fraction (LVEF) ≤40 %, either in treatment with atorvastatin (N: 114) or without statins (N: 81), underwent TDI examination. Adverse events were evaluated during follow-up. RESULTS: The atorvastatin group showed a lower incidence of adverse events (cardiac death: 0 % vs 7 %, p < 0.01), and better TDI performance (E/E' 15 ± 5.7 vs 18 ± 8.3, p < 001) than controls. Ischaemic CHF patients in treatment with atorvastatin also showed a lower incidence of adverse events (death: 10 % vs 26 %, p < 0.05; sustained ventricular arrhythmias: 5 % vs 19 %, p < 0.05, cardiac death: 0 vs 8 %, p < 0.05) and better TDI performance (E/E' ratio: 15.00 ± 5.68 vs 19.72 ± 9.14, p < 0.01; St: 353.70 ± 48.96 vs 303.33 ± 68.52 msec, p < 0.01) than controls. The association between atorvastatin and lower rates of cardiac death remained statistically significant even after correction in a multivariable analysis (RR 0.83, 95 % CI 0.71-0.96, p < 0.05 in CHF with LVEF ≤40 %; RR 0.77, 95 % CI 0.62-0.95, p < 0.05 in ischaemic CHF with LVEF ≤40 %). CONCLUSIONS: Treatment with atorvastatin in outpatients with systolic CHF is associated with fewer cardiac deaths, and a better left ventricular performance, as assessed by TDI.

Cardiopulmonary exercise test predicts sustained ventricular arrhythmias in chronic heart failure.

BACKGROUND: The cardiopulmonary exercise test (CPX) is an affordable tool for risk prediction in patients with chronic heart failure (CHF). We aimed to determine the role of CPX parameters in predicting the risk of incidence of sustained ventricular arrhythmias (SVA) in CHF. METHODS: Sixty-one consecutive patients with CHF enrolled in the Daunia Heart Failure Registry underwent CPX and were followed for 327 ± 247 days. Clinical follow-up was performed every month and anticipated in case of re-hospitalisation for cardiac disease. Incidence of SVA was evaluated by direct clinical examination (ECG, ambulatory ECG). RESULTS: Patients with episodes of SVA (N 14) showed lower values of pVO2 and PetCO2, and higher values of VE/VCO2, VE/VCO2 slope, and VE%. After correction for age, gender, diabetes, ischaemic heart disease and left ventricular ejection fraction, peak VO2 (hazard ratio (HR) 0.68, 95 % confidence interval (CI) 0.51-0.91, p < 0.05), VE% (HR 1.38, 95 % CI 1.04-1.84, p < 0.05), VE/VCO2 (HR 1.38, 95 % CI 1.04-1.82, p < 0.05), VE/VCO2 slope (HR 1.77, 95 % CI 1.31-2.39, p < 0.01), PetCO2 (HR 0.66, 95 % CI 0.50-0.88, p < 0.01) were found as predictors of SVA. At Kaplan-Meier analysis, lower event-free rates were found in subjects with peak VO2 values below median (log rank p < 0.05), values of VE/VCO2 above mean (p < 0.05), higher VE/VCO2 slope tertiles (p <0.05), and values of PetCO2 below median (p < 0.05). CONCLUSIONS: CPX provides prognostic independent information for risk of SVA in subjects with CHF.

Thermochemotherapy for non-muscle-invasive bladder cancer: is there a chance to avoid early cystectomy?.

OBJECTIVES: Non-muscle-invasive bladder cancer is characterized by a high recurrence rate after primary transurethral resection. In case of bacillus Calmette-Guérin-refractory neoplasms, cystectomy is the gold standard. In this study the effects of thermochemotherapy with mitomycin C were evaluated in high-risk bladder cancer nonresponders to previous therapy. PATIENTS AND METHODS: Between January 2006 and December 2009, 30 patients were enrolled with recurrent stage carcinoma in situ, Ta and T1, grade G1 to G3 non-muscle-invasive bladder cancer refractory to chemotherapy or immunotherapy and so becoming suitable for radical cystectomy. All patients underwent endovesical thermochemotherapy: 16 patients underwent a prophylactic scheme and 14 patients underwent an ablative scheme. RESULTS: All the patients completed the study. The mean follow-up for all the patients enrolled was 14 months. Thirteen of 30 patients (43.30%) were disease free and 17 patients (56.70%) had recurrence. In the prophylactic group, 7 of 16 patients (43.75%) were disease free and 9 patients (46.25%) had tumor recurrence; no progression was observed. In the ablative group, 3 patients (17, 64%) had progression to muscle-invasive disease. Side effects were generally mild. CONCLUSIONS: Thermochemotherapy could be considered an additional tool in patients refractory to intravesical therapies before considering early cystectomy.

Value of current chemotherapy and surgery in advanced and metastatic bladder cancer.

The aim of the present paper was to review findings from the most relevant studies and to evaluate the value of current chemotherapy and surgery in advanced unresectable and metastatic bladder cancer. Studies were identified by searching the MEDLINE® and PubMed® databases up to 2011 using both medical subject heading (Mesh) and a free text strategy with the name of the known individual chemotherapeutic drug and the following key words: 'muscle-invasive bladder cancer', 'chemotherapeutics agents', and 'surgery in advanced bladder cancer'. At the end of our literature research we selected 141 articles complying with the aim of the review. The results showed that it has been many years since the MVAC (methotrexate, vinblastine, adriamycin, cisplatin) regimen was first developed. The use of cisplatin-based combination chemotherapy is associated with significant toxicity and produces long-term survival in only approximately 15-20% of patients. Gemcitabine + cisplatin represents the gold standard in the treatment of metastatic bladder cancer. In conclusion, the optimal approach in the management of advanced urothelial cancer continues to evolve. Further progress relies on the expansion of research into tumor biology and an understanding of the underlying molecular 'fingerprints' that can be used to enhance diagnostic and therapeutic strategies. Cisplatin-based therapy has had the best track record thus far.

[Androgen-deprivation therapy in prostate cancer: clinical evidence and future perspectives]. / La deprivazione androgenica nel carcinoma prostatico: evidenze cliniche e prospettive future.

Androgens are involved in the development and progression of prostate cancer even if the mechanism is not well-recognized. For this reason androgen-deprivation therapy remains a milestone for the treatment of patients with advanced and metastatic disease and, in the last years, in conjunction with radiotherapy and surgery in locally advanced tumors. Alternative options, such as intermittent deprivation suppression, seem to be promising in terms of clinical benefits and toxicity profile. However, current therapies present side effects, such as testosterone surge with consequent clinical flare-up, metabolic syndrome and hormone-resistance, which develops after a variable number of years. Novel therapies such as LH-RH antagonists and prolonged depot LH-RH analogues have been developed in order to avoid clinical flare-up and testosterone microsurges. Novel androgen synthesis inhibitors, such as abiraterone acetate and MDV3100, have been recently discovered and tested as promising hormonal second-line agents in patients with castration-resistant prostate cancer. Finally, long-term side effects from androgen deprivation, such as osteoporosis, sarcopenic obesity and cardiovascular morbidity should be carefully monitored and properly treated.

[Prostatitis syndromes and sporting activities]. / Sindromi prostatiche e sport.

INTRODUCTION: Prostatitis-like syndromes are high prevalent health problems and frequently considered by patients and physicians as strictly correlated to sports causing perineal compression. These syndromes and their relationships with sporting activities have been discussed in this report. METHODS: We reviewed peer-reviewed scientific articles published by May 2009 and searched according to the following term selection: prostatitis, pudendal nerve, sport, cycling. RESULTS: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a major healthcare burden heavily affecting patients' Quality of Life. No clear evidence of any direct etiologic relationship has been found in literature between prostatitis, either bacterial or non-bacterial, and sports activities. On the other hand, some types of sport causing perineal compression, such as cycling, can exacerbate symptoms of acute and chronic prostatitis; a temporary sport discontinuation is justified in these patients. CP/CPPS may be often caused by pudendal nerve entrapment (PNE). Prostatitis-like urogenital neuropathic pain together with voiding and sexual dysfunctions are the hallmark of PNE. A common feature is that flexion activities of the hip, such as climbing, squatting, cycling provoke or worsen urogenital pain or pelvic pain. Many of the patients with PNE are cyclists, played American football, lifted weights, or wrestled as teenagers and young adults. PNE represents the most common bicycling associated urogenital problems. CONCLUSIONS: Overall, studies show that no causal relationship has been demonstrated between prostatitis and sporting activities. Conversely, urologists should be aware that sports involving vigorous hip flexion activities or prolonged perineal compression are a potential and not an infrequent cause of uroandrological symptoms caused by pudendal nerve entrapment.

[Doping and urologic tumors]. / Doping e neoplasie urologiche.

Several substances such as growth hormone (GH), erythropoietin (Epo), and anabolic steroids (AS) are improperly utilized to increase the performance of athletes. Evaluating the potential cancer risk associated with doping agents is difficult since these drugs are often used at very high doses and in combination with other licit or illicit drugs. The GH, via its mediator, the insulin-like growth factor 1 (IGF-1), is involved in the development and progression of cancer. Animal studies suggested that high levels of GH/IGF-1 increase progression of androgen-independent prostate cancer. Clinical data regarding prostate cancer are mostly based on epidemiological studies or indirect data such as IGF-1 high levels in patients with prostate cancer. Even if experimental studies showed a correlation between Epo and cancer, no clinical data are currently available on cancer development related to Epo as a doping agent. Androgens are involved in prostate carcinogenesis modulating genes that regulate cell proliferation, apoptosis and angiogenesis. Most information on AS is anecdotal (case reports on prostate, kidney and testicular cancers). Prospective epidemiologic studies failed to support the hypothesis that circulating androgens are positively associated with prostate cancer risk. Currently, clinical and epidemiological studies supporting association between doping and urological neoplasias are not available. Nowadays, exposure to doping agents starts more prematurely with a consequent longer exposition period; drugs are often used at very high doses and in combination with other licit or illicit drugs. Due to all these elements it is impossible to predict all the side effects, including cancer; more detailed studies are therefore necessary.

Methodology of superficial bladder cancer trials: objective evaluation of treatment - the need for standardization.

The formulation of proper evaluation criteria after superficial bladder cancer therapy poses several methodological problems that are often peculiar to the disease. The Achilles' heel of many trials is possibly found in the criteria used in the evaluation of the trial's outcome. As a consequence, total agreement regarding the criteria for response and the evaluation of response is needed. The adoption of standard response criteria should be given high priority. Uniform criteria of response should be chosen because they meet standards of reliability and statistical validity. Thus, the criteria must be reproducible and correlate with some measures of patient benefit such as quantity and quality of survival. A proposal for standardization in superficial bladder cancer clinical trials is presented based upon the current knowledge of methodology used for conducting clinical trials and upon the experience coming from clinical research groups.

[Contrast media in urogenital radiology].

BACKGROUND. Contrast media are widely used in urogenital radiology. The ideal contrast agent should be totally inert, causing no interactions with organism, and with a rapid and complete excretion. Adverse reactions could occur after using any type of contrast media. Contrast enhanced procedures are performed with increasing frequency and the patients population is progressively older and with multiple co-morbid conditions, thus contrast media toxicity is becoming a serious problem. Contrast media-induced nephropathy (CIN) is considered an important cause of hospital-acquired renal failure. The administration of gadolinium-based contrast agents has been recently associated with the development of a serious adverse reaction, potentially lethal in patients with renal insufficiency, named nephrogenic systemic fibrosis (NSF). METHODS. Literature review on contrast media in urogenital radiology, CIN, NSF. CONCLUSIONS. Since 1996, the Contrast Media Safety Committee of the European Society of Urogenital Radiology (ESUR) has released its guidelines regarding safety about the use of contrast media. CIN, and the emerging NSF, are topics of increasing interest for urologists, radiologists, nephrologists, dermatologists and all the clinicians. Contrast media have progressively become safer in the last years. Even if rare, some adverse reactions still occurr up to now. CIN and its prevention remain an issue under debate. In the past, whenever a patient required a contrast-enhanced imaging study, the trend was to select magnetic resonance imaging with gadolinium-based contrast agents in order to avoid the well-known CIN of iodinated-based contrast agents. The awareness of NFS is changing the contrast-enhanced imaging in patients with renal failure. At present we have to investigate NSF etiopathogenesis, in order to prevent and eventually to cure it. The understanding of the risk factors for both CIN and NSF is an emerging need, the adoption of all preventive measures to reduce the risks remain a mandatory issue.

In vitro effect of amikacin on rat and human detrusor muscle contraction.

INTRODUCTION: Normal and abnormal bladder contractions are principally mediated by acetylcholine released from postganglionic parasympathetic nerves. Since amikacin was reported to affect neurotransmission by a prejunctional mechanism, we investigated the effect of amikacin on isolated detrusor smooth muscle contraction to further evaluate its potential relaxant properties. MATERIALS AND METHODS: Detrusor smooth muscle obtained from 15 rats and 8 patients undergoing surgery were studied through measurement of isometric muscular contraction induced with electrical field stimulation (EFS) (10-60 Hz), carbachol (10(-7) to 10(-3)M) and nicotine (10(-7) to 10(-3)M) in the presence or absence of 1 mM amikacin in a low-Ca medium. RESULTS: Amikacin (1 mM) significantly reduced EFS-induced contraction of isolated rat and human detrusor muscle by 33 +/- 6.57% (p < 0.005) and 40 +/- 1.14% (p < 0.001), respectively. Contraction was restored after addition of calcium chloride (1 mM). The effect of amikacin was comparable to that of magnesium ions. Rat and human detrusor contractile response to nicotine was inhibited by 70 +/- 8.27% (p < 0.001) and 64 +/- 14.09% (p < 0.01) after the addition of amikacin (1 mM), while no significant effect was observed on carbachol-induced stimulation. CONCLUSION: Amikacin significantly inhibited detrusor contraction evoked by prejunctional stimulation in vitro, suggesting a depressant effect on autonomic neurotransmission in urinary bladder.

Candidate-gene testing for orphan limb-girdle muscular dystrophies.

The term limb-girdle muscular dystrophies (LGMD) identify about two dozens of distinct genetic disorders. Additional genes must play a role, since there are LGMD families excluded from any known locus. The aim of our work is to test a number of candidate genes in unclassified LGMD patient and control DNA samples. We selected the following 11 candidate genes: myozenin 1, 2 and 3, gamma-filamin, kinectin-1, enolase-3 beta, ZASP, TRIM 11 and TRIM 17, OZZ and zeta-sarcoglycan. These candidates were chosen for a combination of different reasons: chromosomal position, sequence homology, interaction properties or muscular dystrophy phenotypes in animal models. The exon and flanking intron sequences were subjected to molecular testing by comparative mutation scanning by HT-DHPLC of LGMD patients versus control. We identified a large number of variations in any of the genes in both patients and controls. Correlations with disease or possible modifying effects on the LGMD phenotype remain to be investigated.