Search

Objective A multicentre observational study was aimed to assess the prevalence of late-onset Pompe disease (LOPD) in a large high-risk population, using the dried blood spot (DBS) as a main screening tool. Design/methods 17 Italian neuromuscular centres were involved in the late-onset Pompe early diagnosis (LOPED) study. Inclusion criteria were: (1) age ≥5 years, (2) persistent hyperCKaemia and (3) muscle weakness at upper and/or lower limbs (limb-girdle muscle weakness, LGMW). Acid α-glucosidase (GAA) activity was measured separately on DBS by fluorometric as well as tandem mass spectrometry methods. A DBS retest was performed in patients resulted positive at first assay. For the final diagnosis, GAA deficiency was confirmed by a biochemical assay in skeletal muscle, whereas genotype was assessed by GAA molecular analysis. Results In a 14-month period, we studied 1051 cases: 30 positive samples (2.9%) were detected by first DBS screening, whereas, after retesting, 21 samples were still positive. Biochemical and molecular genetic studies finally confirmed LOPD diagnosis in 17 cases (1.6%). The median time from the onset of symptoms/signs to diagnosis was 5 years. Among those patients, 35% showed presymptomatic hyperCKaemia and 59% showed hyperCKaemia+LGMW, whereas 6% manifested with LGMW. Conclusions LOPED study suggests that GAA activity should be accurately screened by DBS in all patients referring for isolated hyperCKaemia and/or LGMW. A timely diagnosis was performed in five patients with presymptomatic hyperCKaemia, but two had already manifested with relevant changes on muscle morphology and MRI. Consequently, enzyme replacement therapy was started in 14/17 patients, including the 2 patients still clinically presymptomatic but with a laboratory evidence of disease progression.

Aims. To assess in a sample of people with mental disorders: 1) fear of crime and perceived insecurity; 2) the association between fear of crime and insecurity; 3) the incidence of crimes. Methods. Twenty-four Italian mental health centres have been invited to participate in the study from the network of the Early Career Psychiatrists' Committee of the Italian Psychiatric Association. In each participating centre, the first 20 patients consecutively accessing the mental health centre between February and April 2011 have been recruited. All patients have been assessed using validated assessment tools. Results. The final sample consists of 426 patients. They are mostly female (70.1%), with a mean age of 45 years (±13.5), and with a good level of education. Fifty-two percent of patients have a diagnosis of mood disorders, and 37.8% on anxiety spectrum disorders. About half of the sample declares that the most prominent feeling toward life is uncertainty. Almost all patients report to have at least one big fear, with the most frequently report being: 1) loss or death of a loved one (41.2%); 2) financial constraint (28.4%); 3) physical or mental health problems (26.5%). Discussion and conclusions. Our results show the presence of a common sense of uncertainty among patients, probably as a result of the historical moment we are facing. It is reasonable that this attitude toward life can have a detrimental impact on patients' psychological and physical wellbeing, contributing to high levels of distress. Further studies are needed in order to clarify the possible relationship between fears, uncertainty and mental disorders

Buccal mucosal grafts are widely used in the treatment of primary hypospadias and urethral stenosis owing to their elasticity, optimal attachment, possibility of generous harvesting and easy preparation. The aim of this study was to check whether buccal mucosal flaps are also valuable in redo surgery for hypospadias complicated by large breaks in the urethra and with scarce residual genital tissue.Fourteen patients aged between 3 and 11 years old (mean age 6.6) were selected and operated between December 1993 and June 1999. The patients presented extensive fistulous tracts, roughly ellipsoidal in shape and with a maximum diameter of between 7 and 42 mm (mean length 18 mm). The original technique was: Duplay (7 patients); Onlay buccal graft (1 patient); Snodgrass (1 patient); Tubulised preputial flap (2 patients); Onlay preputial graft (2 patients); Tubulised vesical mucosal flap (1 patient). The mucosal flap, taken from the lower lip, was used to cover the gap as an onlay patch and recovered with residual genital skin with the interposition, where possible, of a de-epithelised flap.An optimal cosmetic and functional result was achieved in 10/14 cases with flowmetry25 percentile according to Toguri nomograms. Three patients presented fistulas: one punctiform fistula resolved spontaneously. The other two cases resolved after corrective surgery. One patient showed meatal regression with slight stenosis that was resolved with MAGPI.These results appear to be encouraging. Buccal mucosal graft may represent a valid alternative also in the treatment of secondary hypospadia with large breaks in the urethra. No complication was reported in the harvesting area, even if this was carried out at a second stage in the labial area.

The objective of this study was to describe a large Italian cohort of patients with late-onset glycogen storage disease type 2 (GSDII) at various stages of disease progression and to evaluate the clinical effectiveness of alglucosidase alpha enzyme replacement therapy (ERT). Previous studies showed in late-onset patients ERT efficacy against placebo and variable response in uncontrolled studies. Seventy-four juvenile or adult GSDII patients were treated with ERT in a multicenter open label, non-randomized study, from 12 months up to 54 months. Recombinant human alpha glucosidase (rh-GAA) was injected by intravenous route at 20 mg/kg every second week. Patients were divided into three groups according to ERT duration: Group A received treatment for 12–23 months (n = 16), Group B for 24–35 months (n = 14), and Group C for more than 36 months (n = 44). Clinical assessment included a 6-min walk test (6MWT), forced vital capacity (FVC), the Walton and Gardner-Medwin score, the number of hours of ventilation, body mass index, echocardiography and blood creatine kinase (CK). Included in our cohort were 33 males and 41 females (M:F = 0.8:1), with a mean age at first symptoms of 28.3 years (range 2–55 years) and a mean age of 43 years at study entry (range 7–72 years). Seven wheelchair bound patients, as well as 27 patients requiring ventilation support, were included. After treatment we could observe an increase in distance walked on the 6MWT in the large majority of patients (48/58; 83%), with an overall mean increase of 63 m (from 320 ± 161 to 383 ± 178 m). After treatment in the majority of patients FVC was improved or unchanged (45/69; 65%). In ventilated patients we observed an improvement in average number of hours off the ventilator (from 15.6 to 12.1 h). Six patients stopped mechanical ventilation and two others started it. The effect of therapy was not related to ERT duration. Nine of 64 patients (13%) that underwent to echocardiography showed a variable degree of cardiac hypertrophy (left ventriculum or septum), and a positive effect was observed after 36 months of ERT in one adult case. Discontinuation of treatment occurred in four patients: one drop-off case, one patient died for a sepsis after 34 months of treatment and two patients stopped ERT for worsening of general clinical condition. Mild adverse effects were observed in four cases (5%). This study represents the largest cohort of late-onset GSDII patients treated with ERT, and confirm a positive effect of treatment. These results, obtained in a large case series on therapy, indicate a favourable effect of ERT therapy, even in more advanced stage of the disease.

Introduction: The clinical course of late-onset Pompe disease is heterogeneous, and new clinical outcome measures are needed to evaluate enzyme replacement therapy (ERT). Methods: We correlated the 6-Minute Walk Test (6MWT), Walton and Gardner-Medwin (WGM) score, and GSGC (Gait, Stairs, Gower, Chair) scores in 40 patients. Results: At baseline, the GSGC score correlated with both WGM (P < 0.001, n = 33) and 6MWT (P < 0.001, n = 26). After 1 year of ERT, we observed a significant change in gait, stairs and chair performance on the GSGC scale. The 6MWT significantly increased from 319 to 371 meters in 32 patients, and the WGM score was reduced. Conclusions: GSGC is a group of functional tests that requires only a few minutes to perform, therefore, this score might be a good indicator to be used in future studies. Muscle Nerve 45: 831–834, 2012

We report two large kindreds with Parkinson's disease (PD) apparently inherited in autosomal dominant fashion. Forty-one persons in four generations have been affected; we have examined 7 of them. The two kindreds originated in a single small town in southern Italy and therefore are probably related. The illness was typical for PD except for early onset at a mean age of 46.5 years and a rapid course that averaged 9.7 years from onset to death. Clinical appearance and response to levodopa were typical for PD. Only one instance of definite nonpenetrance is known. Autopsy of 2 patients in one kindred showed the pathological changes typical of PD with Lewy bodies. Disease duration among affected persons who spent most of their lives in Italy was longer than for their affected US relatives, suggesting that exogenous agents may influence the course of this genetic illness. We conclude that what is probably a single gene without an additional environmental insult can cause the pathological changes typical of PD. Our findings therefore enhance the likelihood of a significant genetic component in the cause of sporadic PD. By identifying a toxic gene product, future molecular genetic studies in our kindred(s) may provide insight into the pathogenesis of sporadic PD.

This report describes an experimental condition in which clonidine administration does not modify paradoxical sleep (PS) directly, but is followed by a secondary rebound. After oral consumption of minute doses of clonidine (CLN), 12 subjects showed no direct effect of CLN, but showed a significant increase of PS production in the following placebo night. Four other subjects experienced a decrease of PS under CLN and no rebound the next night. In addition, these four subjects had mechanisms of slow wave sleep production significantly weaker than the first 12 subjects.

The Authors submitted 53 randomly selected patients affected by systemic lupus erythematosus (SLE) to neurologic evaluation to investigate the prevalence of neurologic manifestations, establish relationships to clinical and epidemiological findings and antinuclear antibodies and/or lupus anticoagulant (LAC), as well as to assess the usefulness of electroencephalogram (EEG), saccadic eye movements (SEM) analysis, brain computerized tomography (CT). Twenty-two patients (41.5%) had nervous system involvement on anamnestic and/or clinical examination: there were seizures in 5 patients, headache in 3, involuntary movements in 3, psychosis in 2 and cerebrovascular disorders in 9. The patients were subdivided into 2 groups, with neuro-SLE and without neuro-SLE, according to clinical and/or anamnestic evidence of nervous system involvement. There were no differences between the two groups of patients regarding disease duration, disease activity, presence of antinuclear antibodies and/or LAC. EEG and/or SEM and/or brain CT abnormalities were found in 38 cases, 18 of which had no clinical evidence of neuro-SLE. Instrumental evaluation can thus document subtle nervous dysfunction and offers the possibility of classification into: a) non-neuro-SLE; b) subclinical neuro-SLE; c) overt neuro-SLE.

Aims: This article aims to (1) explore the levels of perceived insecurity in a sample of patients with mood or anxiety disorders and (2) assess whether living in ‘big cities’ can influence the levels of patients’ perceived insecurity and social contacts compared to living in a non-urbanized context. Methods: A total of 24 Italian mental health centers (MHCs) have been invited to participate. Twenty patients consecutively accessing the MHC have been recruited. All patients have been assessed using validated assessment tools. Results: The sample consisted of 426 patients, mostly female, with a mean age of 45 years. Globally, 52.2% of patients had a diagnosis of mood disorders, and 37.8% had anxiety disorders. Half of the sample declared that the main feeling toward life is uncertainty; higher levels of pessimistic views toward life have been detected in patients living in urban areas. A positive association between negative attitudes toward life and higher levels of depressive and anxiety symptoms, poor social functioning and higher levels of perceived psychological distress has been found. Conclusion: Our findings confirm the presence of a common sense of perceived uncertainty among our sample. Such attitude toward life can have a detrimental impact on patients’ psychological and physical well-being, contributing to high levels of distress.

Neuroacanthocytosis (NA) syndromes are a group of genetically defined diseases characterized by the association of red blood cell acanthocytosis, progressive degeneration of the basal ganglia and neuromuscular features with characteristic persistent hyperCKemia. The main NA syndromes include autosomal recessive chorea-acanthocytosis (ChAc) and X-linked McLeod syndrome (MLS). A series of Italian patients selected through a multicenter study for these specific neurological phenotypes underwent DNA sequencing of the VPS13A and XK genes to search for causative mutations. Where it has been possible, muscle biopsies were obtained and thoroughly investigated with histochemical assays. A total of nine patients from five different families were diagnosed with ChAC and had mostly biallelic changes in the VPS13A gene (three nonsense, two frameshift, three splicing), while three patients from a single X-linked family were diagnosed with McLeod syndrome and had a deletion in the XK gene. Despite a very low incidence (only one thousand cases of ChAc and a few hundred MLS cases reported worldwide), none of the 8 VPS13A variants identified in our patients is shared by two families, suggesting the high genetic variability of ChAc in the Italian population. In our series, in line with epidemiological data, McLeod syndrome occurs less frequently than ChAc, although it can be easily suspected because of its X-linked mode of inheritance. Finally, histochemical studies strongly suggest that muscle pathology is not simply secondary to the axonal neuropathy, frequently seen in these patients, but primary myopathic alterations can be detected in both NA syndromes.

Autosomal recessive Pompe disease is a lysosomal disorder caused by mutations of the acid-?-glucosidase (GAA) gene. Deficiency of GAA enzyme leads to glycogen accumulation and autophagy impairment in cardiac and skeletal muscles, but also in lymphocytes. Since an effective therapy is available, a rapid, sensitive, and specific test is crucial to early identify affected subjects. Number of lymphocytes containing PAS-positive vacuoles was evaluated on blood films from 72 consecutive adult patients with hyperckemia and/or muscle weakness, 13 genetically confirmed late-onset-Pompe-disease (LOPD) and 13 of their offspring. GAA activity, measured on dried blood spot (DBS) in all patients inversely correlated with number of PAS-positive lymphocytes. More than 4 PAS-positive lymphocytes were found in 11 out of the 72 patients (6 new diagnosis of LOPD, 3 different glycogen storage myopathies, 1 glucose-6-phosphate dehydrogenase deficiency, 1 caveolinopathy), in all 13 LOPD patients and in the 13 LOPD offspring. These latter resulted to have all a single GAA mutation but low GAA levels. Immunostaining with the autophagy markers LC3 and p62 confirmed the autophagic nature of lymphocytes vacuoles. ROC curve assessment of PAS-positive lymphocytes disclosed 100% of sensitivity and 94% of specificity in recognizing both compound heterozygous and heterozygous GAA carriers. The other myopathies with more than 4 PAS-positive lymphocytes appeared to be all related to impaired autophagy, which seems to be responsible of PAS-positive vacuolated lymphocytes formation. Quantification of PAS-positive lymphocytes in blood films is useful to identify autophagic vacuolar myopathies and should be routinely used as first level test for Pompe disease.

We recently described a complex multisystem syndrome in which mild-moderate myopia segregated as an independent trait. A plethora of genes has been related to sporadic and familial myopia. More recently, in Chinese patients severe myopia (MYP25, OMIM:617238) has been linked to mutations in P4HA2 gene. Seven family members complaining of reduced distance vision especially at dusk underwent complete ophthalmological examination. Whole-exome sequencing was performed to identify the gene responsible for myopia in the pedigree. Moderate myopia was diagnosed in the family which was associated to the novel missense variant c.1147A > G p.(Lys383Glu) in the prolyl 4-hydroxylase,alpha-polypeptide 2 (P4HA2) gene, which catalyzes the formation of 4-hydroxyproline residues in the collagen strands. In vitro studies demonstrated P4HA2 mRNA and protein reduced expression level as well as decreased collagen hydroxylation and deposition in mutated fibroblast primary cultures compared to healthy cell lines. This study suggests that P4HA2 mutations may lead to myopic axial elongation of eyeball as a consequence of quantitative and structural alterations of collagen. This is the first confirmatory study which associates a novel dominant missense variant in P4HA2 with myopia in Caucasian patients. Further studies in larger cohorts are advisable to fully clarify genotype-phenotype correlations. We recently described a complex multisystem syndrome in which mild-moderate myopia segregated as an independent trait. A plethora of genes has been related to sporadic and familial myopia. More recently, in Chinese patients severe myopia (MYP25, OMIM:617238) has been linked to mutations in P4HA2 gene. Seven family members complaining of reduced distance vision especially at dusk underwent complete ophthalmological examination. Whole-exome sequencing was performed to identify the gene responsible for myopia in the pedigree. Moderate myopia was diagnosed in the family which was associated to the novel missense variant c.1147A > G p.(Lys383Glu) in the prolyl 4-hydroxylase,alpha-polypeptide 2 (P4HA2) gene, which catalyzes the formation of 4-hydroxyproline residues in the collagen strands. In vitro studies demonstrated P4HA2 mRNA and protein reduced expression level as well as decreased collagen hydroxylation and deposition in mutated fibroblast primary cultures compared to healthy cell lines. This study suggests that P4HA2 mutations may lead to myopic axial elongation of eyeball as a consequence of quantitative and structural alterations of collagen. This is the first confirmatory study which associates a novel dominant missense variant in P4HA2 with myopia in Caucasian patients. Further studies in larger cohorts are advisable to fully clarify genotype-phenotype correlations.

The superior sagittal sinus (SSS) of the mammalian brain is a pain-sensitive intracranial vessel thought to play a role in the pathogenesis of migraine headaches. Here, we aimed to investigate the presence and the potential co-localization of some neurotransmitters in the human SSS. Immunohistochemical and double-labeling immunofluorescence analyses were applied to paraformaldehyde-fixed, paraffin-embedded, coronal sections of the SSS. Protein extraction and Western blotting technique were performed on the same material to confirm the morphological data. Our results showed nerve fibers clustered mainly in large bundles tracking parallel to the longitudinal axis of the sinus, close in proximity to the vascular endothelium. Smaller fascicles of fibers encircled the vascular lumen in a spiral fashion, extending through the subendothelial connective tissue. Isolated nerve fibers were observed around the openings of bridging veins in the sinus or around small vessels extending into the perisinusal dura. The neurotransmitters calcitonin gene related peptide (CGRP), substance P (SP), neuronal nitric oxide synthase (nNOS), vasoactive intestinal polypeptide (VIP), tyrosine hydroxylase (TH), and neuropeptide Y (NPY) were found in parietal nerve structures, distributed all along the length of the SSS. Overall, CGRP- and TH-containing nerve fibers were the most abundant. Neurotransmitters co-localized in the same fibers in the following pairs: CGRP/SP, CGRP/NOS, CGRP/VIP, and TH/NPY. Western blotting analysis confirmed the presence of such neurosubstances in the SSS wall. Overall our data provide the first evidence of the presence and co-localization of critical neurotransmitters in the SSS of the human brain, thus contributing to a better understanding of the sinus functional role.

Background: Natalizumab is an effective therapy in relapsing–remitting multiple sclerosis (RRMS), as it reduces lymphocyte transmigration through the blood–brain barrier (BBB) and induces lymphocytosis. Objectives: To analyse natalizumab-induced lymphocytosis (NIL) as a biomarker of drug efficacy. Materials and methods: We enrolled 50 relapsing–remitting (RR) and progressive–relapsing (PR) natalizumab-treated patients who had received at least 16 infusions and had been tested for lymphocyte count 24 hours before each administration. Clinical, MRI and hematological data were collected. Patients were divided into responders and sub-optimal responders according to the experience of at least one clinical and/or instrumental relapse during the treatment. Results: In 15 (30%) patients, an instrumental/clinical (14) or only instrumental (one) relapse occurred. We found a statistically significant difference in the mean percentage of the lymphocytes between the two groups over the first ten administrations ( p=0.04). The comparison between the time-to-relapse in the groups with high and low levels of lymphocytes showed that the group with a low NIL had a greater risk of relapse ( p=0.03). Conclusions: We suggest that NIL could be a biomarker of therapeutic efficacy in patients with RRMS treated with natalizumab, and that the risk of relapse may be higher in patients with a lower-than-expected NIL.

Background and objectives Although minor erythrocyte antigens are not considered clinically significant in sporadic transfusions, they may be relevant for multi-transfusion patients. When serological assay is not conceivable, molecular genotyping allows predicting the red blood cell phenotype, extending the typing until minor blood groups. The aim of this study was to evaluate the utility of blood group genotyping and compare the molecular typing of erythrocyte antigens with the established serological methods. Materials and methods We selected 225 blood donors and 50 transfusion-dependent patients at the Division of Immunohematology of the Second University of Naples. Blood samples were analyzed with NEO Immucor automated system and genotyped for 38 red blood cell antigens and phenotypic variants with the kit HEA BeadChip™. The comparative study was conducted for RhCE and Kell antigens whose typing is available with both methods. Results We observed a good correlation between serological and molecular methods for donors that were concordant for 99.5% (224/225) and discordant for 0.5% (1/225). Patients resulted concordant only for 46.0% (23/50) and discordant for 54.0% (27/50); discrepancies were 46.0% (23/50) and 8.0% (4/50) for RhCE and Kell systems respectively. Through molecular genotyping we also identified polymorphisms in RhCE, Kell, Duffy, Colton, Lutheran and Scianna loci in donors and patients. Conclusions Blood group genotyping is particularly useful for poly-transfused patients. Molecular analysis confirms and extends serological test data and then allows us to obtain a better match. This molecular assay can be used in the future to prevent alloimmunization in transfusion-dependent patients.

Recent evidences have shown that several host genetic factors influence susceptibility or protection to hepatitis C virus (HCV) infection. There are controversial data regarding the associations of human leukocyte antigens (HLA) and the clearance or progression of HCV. The aim of this study was to investigate whether particular HLA molecules were associated with HCV infection in recipients awaiting kidney transplantation considered at high-risk to infection due to protracted hemodialysis treatment. To this purpose, 301 kidney recipients with HCV infection and 1103 uninfected recipients were examined for HLA class I and II molecules. In our case-control study, HLA-A * 26 is positively associated with HCV infection while HLA-A * 29, -B * 40 and -DRB1 * 01 are negatively associated with HCV infection. Multiple logistic regression analysis demonstrated that age (OR = 1.02; 95% CI = 1.01–1.04; p * 26, -A * 29, -B * 40 and -DRB1 * 01 [(OR = 1.54; 95% CI = 1.03–2.30; p = 0.03); (OR = 0.50; 95% CI = 0.26–0.99; p = 0.05); (OR = 0.42; 95% CI = 0.23-0, 7; p = 0.01); (OR = 0.62; 95% CI = 0.41-0, 94; p = 0.03); respectively] are independent predictors of HCV infection. Our results suggest that particular HLA molecules, as host genetic factors, may have a relationship with susceptibility or protection to HCV infection also in recipients awaiting kidney transplantation.

We investigated the efficacy of S-Adenosyl-L-Methionine (SAMe) augmentation in patients with treatment-resistant depressive disorder (TRD). Thirty-three outpatients with major depressive episode who failed to respond to at least 8 weeks of treatment with two adequate and stable doses of antidepressants were treated openly with fixed dose of SAMe (800 mg) for 8 weeks, added to existing medication. The primary outcome measure was the change from baseline in total score on Hamilton Rating Scale for Depression (HAM-D). The Clinical Global Impression of Improvement (CGI-I) was rated at the endpoint. Patients with a reduction of 50% or more on HAM-D total score and a CGI-I score of 1 or 2 at endpoint were considered responders; remission was defined as a HAM-D score ≤7. Secondary outcome measures included the Snaith-Hamilton Pleasure Scale (SHAPS) and the Sheehan Disability Scale (SDS). At 8 weeks, a significant decrease in HAM-D score was observed with response achieved by 60% of the patients and remission by 36%. Also a statistically significant reduction in SHAPS and SDS was observed. Our findings indicate that SAMe augmentation may be effective and well tolerated in stage II TRD. However, limitations of the present study must be considered and further placebo-controlled trials are needed.

To assess in a sample of people with mental disorders: 1) fear of crime and perceived insecurity; 2) the association between fear of crime and insecurity; 3) the incidence of crimes. Twenty-four Italian mental health centres have been invited to participate in the study from the network of the Early Career Psychiatrists' Committee of the Italian Psychiatric Association. In each participating centre, the first 20 patients consecutively accessing the mental health centre between February and April 2011 have been recruited. All patients have been assessed using validated assessment tools. The final sample consists of 426 patients. They are mostly female (70.1%), with a mean age of 45 years (± 13.5), and with a good level of education. Fifty-two percent of patients have a diagnosis of mood disorders, and 37.8% on anxiety spectrum disorders. About half of the sample declares that the most prominent feeling toward life is uncertainty. Almost all patients report to have at least one big fear, with the most frequently report being: 1) loss or death of a loved one (41.2%); 2) financial constraint (28.4%); 3) physical or mental health problems (26.5%). Our results show the presence of a common sense of uncertainty among patients, probably as a result of the historical moment we are facing. It is reasonable that this attitude toward life can have a detrimental impact on patients' psychological and physical wellbeing, contributing to high levels of distress. Further studies are needed in order to clarify the possible relationship between fears, uncertainty and mental disorders.

To assess the presence of viral ribonucleic acid (RNA) in nerve tissues of 15 patients with hepatitis C virus (HCV) infection and peripheral neuropathy with (11) or without (4) mixed cryoglobulinemia, nested reverse transcription-polymerase chain reaction (RT-PCR) was performed. Amplification of HCV-RNA was successful in 7 patients with and 3 without mixed cryoglobulinemia. This study demonstrates that the nested RT-PCR technique is a sensitive method to detect viral RNA in nerve tissue, and offers further evidence that in patients with HCV infection peripheral neuropathy can occur in the absence of mixed cryoglobulinemia.

Objective To evaluate the efficacy of MAGPI's procedure in children who had a meatal regression after hypospadias repair. Patients and methods Twenty-one children affected by post-hypospadias repair meatal regression underwent a modified MAGPI repair between January 1992 and January 1999: the patients, aged between 3 and 12 years (mean 5.9), had previously undergone hypospadias repair according to the techniques of Duplay (11 patients), Mathieu (2 patients), Snodgrass (5 patients) or the onlay buccal mucosa graft (3 patients). The outcome of the procedure was evaluated in terms of urinary stream and cosmetic appearance. Results The results were good in 18 patients, fair in 2, unchanged in 1. Conclusions MAGPI's repair has proven to be very effective as a secondary procedure in meatal regression after hypospadias correction, with minimal morbidity and a highly successful outcome in terms of satisfactory functionality and cosmetic appearance, and the recovery of gaps as large as 9 mm.

Fecal incontinence, with or without persistent constipation is often underestimated in children affected by spina bifida. Medullar lesions to the L-S metameres result in a slowing of rectal and/or rectal-sigmoid motility, loss of anal or rectal sensation, deranged external anal sphincter function, altered motility of the anal levator muscles, and loss of motor coordination of the internal sphincter. We conducted an electromyographic and electromanometric evaluation of the anorectal tract in a group of children affected by myelomeningocele (MMC) in an attempt to evaluate the degree of functional damage and to provide appropriate treatment.Anorectal manometry was conducted in 83 children affected by MMC (2-16 yrs, mean age: 8.4 yrs); surface electromyography was also performed in 37 of these children. We thus evaluated overall sphincter pressure, the inhibitory anal reflex, the rectal sphincteric reflex and rectal motility during stimulation and at rest. Recording perfusion catheters (0.1 ml/sec) were placed at rectal and anal level; rectal stimulation was conducted with an endorectal balloon.In all patients there was a reduction in overall sphincter pressure (15-25 mmHg; n.v. 45+/-25 mmHg) and the functional length of the anal canal (1-1.8 cm) compared with age matched controls. The inhibitory anal reflex was normal in all patients, although its amplitude, duration and sensitivity were not constant. Similar findings were obtained for the rectal-sphincteric reflex. The rectal sigmoid motility results were difficult to interpret: sudden, fast and high pressure waves of peristaltic progression were followed by prolonged pauses. No correlation was found between urodynamic and anorectal manometric data. Treatment consisted in daily emptying of the rectum so as to avoid fecal retention. Fifteen patients, who presented prolapse and sphincteric hypotonia (/=10 mmHg), underwent cerclage by 2/0 prolene, with sustained good RESULTS.While evaluation parameters of the neuropathic bladder are well standardised, data on the neuropathic rectum are contradictory. Moreover, the results of functional examination are not always an aid to treatment strategy. Therefore, further studies are required to establish an appropriate diagnostic-therapeutic protocol.

To determine objectively, using uroflowmetry, the functional results of the tubularized-incised plate urethroplasty to repair midshaft-proximal hypospadias.Twenty-one patients (mean age 4 years, mean follow-up 1.8 years) were selected from those undergoing surgery between January 1996 and January 1998 at our institution. All patients had midshaft-proximal hypospadias and were treated using the Snodgrass technique. Patients were included if they were able to void volitionally and had no fistula. The flow pattern, maximum (Qmax) and mean flow rate (Qave) were measured; the results were expressed as percentiles and compared with published values from normal children. The Qmax and Qave were considered normal if25th percentile, as equivocally obstructed when in the 5-25th percentile and obstructed if5th percentile.Fourteen patients were considered normal, four as equivocally obstructed and three as obstructed. Of the second group, one patient had a urethral diverticulum at the native meatus (confirmed by voiding cysto-urethrography) and the remaining three patients had meatal stenosis that responded to dilatation, with normal flow in two and improvement in the other. Of the obstructed group, one patient responded to dilatation and two underwent meatoplasty.The tubularized-incised plate repair provides satisfactory functional results for midshaft-proximal hypospadias; uroflowmetry is an important noninvasive tool to evaluate this technique. A long-term follow-up is needed to confirm these results.

Objective: To conduct the genotype-phenotype correlation in a family in which several individuals share clinical and electrophysiologic features of paramyotonia congenita (PC). Background: PC, hyperkalemic periodic paralysis (HyperPP), and potassium-aggravated myotonias form the group of hereditary sodium channelopathies. Each of these disorders is associated with different point mutations in SCN4A , the gene encoding the α-subunit of the adult human skeletal muscle sodium channel. However, in HyperPP families, evidence of a causative gene different from SCN4A has been found. Methods: We conducted direct clinical examination, electrophysiologic (EMG/electroneurographic) and cardiologic studies, as well as laboratory screening in several affected and nonaffected members of the family. We performed the genotype-phenotype correlation by microsatellite linkage and cDNA-mutation analyses of the SCN4A gene. Results: Affected members in this family showed clinical and electrophysiologic features typical of PC. The disease phenotype segregated with the chromosomal region that includes the SCN4A gene. Analysis of the entire cDNA sequence of the SCN4A gene in the index case disclosed a G3826A transition, which results in the Val1276Ile substitution. However, PCR–single-stranded confirmation polymorphism and direct sequencing analysis of the segment coding for Val-1276 on genomic DNA confirmed the G3826A transition in the index case but was negative in 11 affected members of the family; however, neither mutations nor aberrant splicings causative of the PC phenotype in this family were found on SCN4A . Conclusion: The existence of a second gene different from SCN4A that can give rise to a clinical PC phenotype can be speculated upon.

Many authors have shown the role of uroflowmetry in the follow-up of patients operated on for hypospadias. This technique has also been used to assess the validity of the operative technique.Sixty patients have been selected among those operated on for hypospadias from January 1990 till January 1996 at the Pediatric Surgery Department of the Second University of Naples, Italy. These patients underwent uroflowmetry with a rotating disk sensor at clinic. Postoperative time at uroflowmetry ranged between 6 months and 6 years. Flow pattern, maximum flow rate (Q max) and mean flow rate (Q ave) were measured. Results are expressed as percentiles and compared with those obtained from Toguri. Q max and Q ave greater than 25 degrees percentile were considered normal; Q max and Q ave between 25 degrees and 5 degrees percentile were considered query obstructed; Q max and Q ave below the 5 degrees percentile were considered obstructed.Forty-two patients (70%) presented values above the 25 degrees centile, 8 patients (13.4%) presented an obstructed-like flow and 10 children (16.6%) showed a query obstructed flow. Three patients from the latter group presented within three months an obstructed-like flow.Uroflowmetry is an important tool in the follow-up of patients operated on for hypospadias that are at risk for stenosis and then requiring a further treatment, either dilatation or surgery.