The prevalence of faecal incontinence in myotonic dystrophy type 1.

Faecal incontinence is recognised as a feature of myotonic dystrophy along with other symptoms of bowel dysfunction, but its prevalence is poorly defined. We have surveyed 152 unselected myotonic dystrophy patients. We identified issues with bowel control in 104 (68% of the study population). Forty-eight (32%) reported faecal incontinence in the 4 weeks prior to completion of the questionnaire. Fifty-six patients (37%) reported having to change their lifestyle because of incontinence issues at some point in the prior 4 weeks. This study shows a high frequency of life-changing symptoms in a large unselected, cohort of patients with myotonic dystrophy type 1, and highlights lower gastrointestinal symptoms as an important issue for further research.

Imaging features and diagnosis of tuberculosis of the breast.

AIM: To outline the pathophysiology, clinical presentation, imaging features, and relevant investigations of the different subtypes of breast tuberculosis (TB). MATERIALS AND METHODS: A review was undertaken of all cases (33 in total) of breast TB presenting to Barts Health NHS Trust within a 10-year period, including patient demographics, imaging features, and route of diagnosis. RESULTS: Thirty-three cases of proven granulomatous TB of the breast were identified (11 mastitis obliterans, 10 nodular caseous form, five sclerosing form, four disseminated disease, and three abnormal axillary lymph nodes). No cases of miliary breast TB were identified. Fine-needle aspiration cytology aided diagnosis in six patients (<20% of cases); however, the majority of patients required further investigation; namely core biopsy. Over a third of patients (12/33) had multiple clinic attendances prior to diagnosis. Mean delay in diagnosis was 3.7 months (median 0 months, IQR= 3). CONCLUSION: Breast TB is a rare challenging diagnosis with a wide range of imaging features. Core biopsy is essential for definitive diagnosis. A multidisciplinary approach involving surgeons, radiologists, TB consultants, and microbiologists is required, coupled with a high index of clinical suspicion in order to aid timely diagnosis, and initiate prompt treatment to reduce complications.

Modafinil for excessive daytime sleepiness in myotonic dystrophy type 1--the patients' perspective.

Excessive daytime sleepiness (EDS), of very similar pattern to that seen in narcolepsy syndrome, is extremely common in myotonic dystrophy type 1 (DM1). In a significant minority it has a profound disabling effect on employment, social functioning and activities of daily living. Limited published studies have shown inconsistent results from use of the psychostimulant drug modafinil. A recent European Medicines Agency (EMA) review concluded that on current evidence regarding safety and efficacy, modafinil's use should be restricted to the treatment of narcolepsy. In other conditions (although DM1 was not specifically considered) it was concluded that there was insufficient evidence of benefit to outweigh potentially serious side-effects, including severe skin reactions and cardiac arrhythmia. Clinicians with extensive experience in the management of DM1 have found modafinil to be extremely effective in appropriately selected patients with a very low incidence of serious side-effects. Given the recent EMA review, patients have expressed concern about the potential restriction of the use of modafinil in DM1. This brief review is an audit of the experience of a large group of patients and their clinicians concerning EDS and DM1 and concludes that despite the limited literature there is strong evidence to support the use of modafinil in carefully selected patients.

SEPN1-related myopathies: clinical course in a large cohort of patients.

OBJECTIVE: To assess the clinical course and genotype-phenotype correlations in patients with selenoprotein-related myopathy (SEPN1-RM) due to selenoprotein N1 gene (SEPN1) mutations for a retrospective cross-sectional study. METHODS: Forty-one patients aged 1-60 years were included. Clinical data including scoliosis, respiratory function, and growth measurements were collected by case note review. RESULTS: Mean age at onset was 2.7 years, ranging from birth to the second decade of life. All but 2 remained independently ambulant: one lost ambulation at age 5 years and another in his late 50s. The mean age of starting nocturnal noninvasive ventilation (NIV) was 13.9 years. One child required full-time NIV at the age of 1 year while in 2 cases NIV was started at 33 years. Two patients died from respiratory failure at the age of 10 and 22 years, respectively. The mean age at scoliosis onset was 10 years, in most cases preceded by rigidity of the spine. Fourteen patients had successful spinal surgery (mean age 13.9 years). Twenty-one were underweight; however, overt feeding difficulties were not a feature. CONCLUSIONS: This study describes the largest population affected by SEPN1-RM reported so far. Our findings show that the spectrum of severity is wider than previously reported. Respiratory insufficiency generally develops by 14 years but may occur as early as in infancy or not until the fourth decade. Motor abilities remain essentially static over time even in patients with early presentation. Most adult patients remain ambulant and fully employed.

[The anthropology of women in the Orthodox Jewish community of Antwerpen: identity, emancipation and integration]. / De antropologie van vrouwen in de Joods-Orthodoxe gemeenschap van Antwerpen: eigenheid, emancipatie en integratie.

This contribution contains a synthesis of the results of two socio-cultural anthropological research projects among Orthodox Jewry concerning the 'identity', 'emancipation' and 'integration' of women. First the meaning of female religiosity from the perspective of strictly Orthodox, including Chassidic, women is discussed. Whereas in the public and institutional religious sphere men are the paradigmatic "Orthodox Jews", due to the sacralisatie of daily life, religious roles for women are not less extensive or any less important but are predominantly situated in the private and domestic sphere. It is argued that from an anthropological and gender critical perspective, women's religious gender identity therefore cannot be straightforwardly interpreted as either "oppressed" nor "emancipator". The second study concerns Jewish Orthodox women (ranging from strictly to modern Orthodox) in Antwerp who transgress religious gender norms by studying or working in the surrounding secular society. Their life stories show very different trajectories of encounters with the "outside world" that are sometimes enriching yet sometimes also experienced in terms of intercultural conflicts. It is concluded that maintaining cultural identity, next to emancipation and integration from within the Orthodox Jewish community is not impossible, but that this requires minimal mutual dialogue and understanding.

The misuse of the faecal occult blood test under the lower gastrointestinal two week wait rule.

AIM: To find the proportion of patients with a faecal occult blood (FOB) performed as part of the referral for the lower gastrointestinal two week wait (2WW) referral system, and whether this correlates with the cancer status. METHOD: All patients referred to the colorectal cancer service using the 2WW referral criteria, between August 2005 and August 2007, were identified using the hospital's cancer audit database. Faecal occult bloods and cancer status were recorded for each patient. RESULTS: Two thousand one hundred and fifty-nine patients (1177 female: 903 male; median age 58; age range 18-98) were referred by general practitioners. The FOBT was only performed on three samples in all cases. In total, 172 of 2159 patients (7.9%) had an FOB performed prior to their referral, with 55 of 172 patients (31.9%) as part of the referral for 2WW. Sixteen of 172 patients (9.3%) had an FOB performed in the presence of overt rectal bleeding. In only 2 of 172 patients (1.1%) the FOB correlated with a colorectal cancer. Unnecessary testing for FOB costs has cost pound4072.96 in total. DISCUSSION: A significant number of faecal occult bloods are being performed and the detection rate, even in this symptomatic group of patients, is very low. It is evident that the test is being performed in the community on three samples and not six. This, combined with the high false positive rate, leads to patients not only undergoing unnecessary psycho-social consequences but could potentially lead to significant risks from unnecessary invasive investigation as well as the added financial burden of test itself.

The molecular basis of the folate-sensitive fragile site FRA11A at 11q13.

We report on the molecular basis of the rare, folate-sensitive fragile site FRA11A in chromosome band 11q13 in a family with cytogenetic expression. Five individuals express the fragile site and one was mentally retarded. Expansion of a polymorphic CGG-repeat located at the 5' end of the C11orf80 gene causes FRA11A. The CGG-repeat elongation coincides with hypermethylation of the adjacent CpG island and subsequent transcriptional silencing of the C11orf80 gene. This gene has no homology with known genes. A relationship between cytogenetic expression of the fragile site and the mental handicap seems unlikely, as FRA11A was found in a mentally retarded patient as well as in phenotypically normal carriers from the same family. However, incomplete penetrance cannot be entirely excluded.

Minicore myopathy with ophthalmoplegia caused by mutations in the ryanodine receptor type 1 gene.

BACKGROUND: Minicore myopathy (multi-minicore disease [MmD]) is a congenital myopathy characterized by multifocal areas with loss of oxidative activity on muscle biopsy. MmD is clinically heterogeneous and distinct phenotypes have been associated with recessive mutations in either the selenoprotein N (SEPN1) or the skeletal muscle ryanodine receptor (RYR1) gene, also implicated in central core disease and malignant hyperthermia. External ophthalmoplegia is an additional finding in a subset of patients with MmD. OBJECTIVE: To clinically and genetically examine families with MmD and external ophthalmoplegia. METHODS: The authors investigated 11 affected individuals from 5 unrelated families. Clinical, histopathologic, and imaging studies were performed and RYR1 haplotyping and mutational analysis were carried out. RESULTS: All patients had multiple cores involving the entire fiber diameter on longitudinal sections. Weakness and wasting in the shoulder girdle, scoliosis, moderate respiratory impairment, and feeding difficulties were prominent. In contrast to SEPN1-related myopathies, soleus was more severely affected than gastrocnemius on muscle MRI. Haplotyping suggested linkage to the RYR1 locus in informative families and mutational screening revealed four novel RYR1 mutations in three unrelated families; in addition, functional haploinsufficiency was found in one allele of two recessive cases. CONCLUSION: These findings expand the phenotypic spectrum associated with mutations in the skeletal muscle ryanodine receptor (RYR1) gene. Recessive mutations of domains commonly affected in malignant hyperthermia appear to be particularly prevalent in multi-minicore disease with external ophthalmoplegia and might suggest a different pathomechanism from that involved in central core disease.

Localisation of merosin-positive congenital muscular dystrophy to chromosome 4p16.3.

The congenital muscular dystrophies (CMD) are a heterogeneous group of autosomal recessive disorders, which present within the first 6 months of life with hypotonia, muscle weakness and contractures, associated with dystrophic changes on skeletal muscle biopsy. We have previously reported a large consanguineous family segregating merosin-positive congenital muscular dystrophy, in which involvement of known CMD loci was excluded. A genome-wide linkage search of the family conducted using microsatellite markers spaced at 10-Mb intervals failed to identify a disease locus. A second scan using a high-density SNP array, however, permitted a novel CMD locus on 4p16.3 to be identified (multipoint LOD score 3.4). Four additional consanguineous CMD families with a similar phenotype were evaluated for linkage to a 4.14-Mb interval on 4p16.3; however, none showed any evidence of linkage to the region. Our findings further illustrate the utility of highly informative SNP arrays compared with standard panels of microsatellite markers for the mapping of recessive disease loci.

Congenital muscular dystrophy with short stature, proximal contractures and distal laxity.

We report 5 cases (2 familial and 3 sporadic) who share a diagnosis of congenital muscular dystrophy (CMD) in association with short stature, proximal contractures, rigidity of the spine and distal joint laxity as well as early respiratory failure and mild to moderate mental retardation. The expression of collagen VI was confirmed to be normal on muscle biopsies of all 5 patients and in the informative family linkage to any of the three COL6 A loci was excluded. These findings extend the phenotypes within the CMD classification.

Congenital form of spinal muscular atrophy predominantly affecting the lower limbs: a clinical and muscle MRI study.

We describe clinical and muscle magnetic resonance imaging (MRI) findings in 11 cases (three familial and eight sporadic) with the form of spinal muscular atrophy characterised by predominant involvement of the lower limbs with weakness of the proximal and distal muscles and marked atrophy of the distal leg and foot muscles. All patients presented at birth with talipes, which were in extension in seven of the 11. Arm muscle and function were preserved and lower limbs appeared to be disproportionately shorter compared to trunk and upper limbs. Functional abilities were markedly affected and only one of the 11 is able to walk independently for long distances, while six require support of crutches and two use callipers for walking. One child lost ambulation following a fall. The course of the disease is relatively stable and the progression of disability appeared to be related mostly to increased contractures rather than to loss of muscle strength. Respiratory and cardiac function were well preserved. A neurogenic disorder was suggested by electromyography and/or muscle biopsy in all patients, while motor nerve conduction was consistently normal. Muscle MRI of the thighs revealed diffuse atrophic appearance with relative hypertrophy of the adductor longus and of the semitendinosus. Genetic studies excluded the involvement of the survival motor neuron gene but none of these families was sufficiently informative to study linkage to the locus on chromosome 12q23-q24 previously found to be involved in patients with similar phenotype. In our experience this form of spinal muscular atrophy affecting predominantly the lower limbs is a relatively common form and should be considered in the differential diagnosis of infants with talipes and weakness in the lower limbs. The identical clinical and imaging features of the sporadic and familial cases suggest that these cases are likely to be affected by the same condition.

The Southwest of Scotland Structural Chromosomal Abnormalities Database: an assessment of its contribution to genetic counselling in affected families.

AIM: To assess the effect of establishing a genetic database on the provision of genetic counselling to individuals and families with structural chromosomal abnormalities. METHOD: For the four year period 1997-2000, we compared all cytogenetics laboratory records with entries on the database to determine its completeness. We assessed the extent to which families had been followed up, compared these findings with a previous four year period (1977-1980) and sought to discover why some families were not followed up. RESULTS: Of 215 probands identified during 1997-2000, 19 (9%) were not recorded on the register. Approximately one third of families were followed up completely, one third were partially followed up and one third had had no follow-up, for a variety of reasons. In this last group, there was evidence that some had received inadequate or incorrect genetic advice. There was no evidence that the database improved follow-up in families with structural chromosome abnormalities. Over 20 years, there has been a downward trend in the proportion of cases referred to the genetic clinic. CONCLUSIONS: Our register can be used to monitor trends in clinical practice but has had no direct effect on the service provided to patients and their families.

Muscle fibrillin deficiency in Marfan's syndrome myopathy.

OBJECTIVE: To report a family with Marfan's syndrome in whom a myopathy was associated with respiratory failure; muscle biopsies from affected individuals were examined to determine whether there were abnormalities in fibrillin. METHODS: 21 family members underwent detailed clinical examination, including neurological and pulmonary assessment. Muscle biopsies in the most severely affected cases were immunostained using monoclonal antibodies to specific fibrillin components. Genomic DNA from all 21 members was analysed for mutations in the fibrillin gene, FBN1, on 15q21. RESULTS: 13 individuals had a C4621T base change in exon 37 of the FBN1 gene, which in four cases segregated with muscle weakness or evidence of respiratory muscle dysfunction or both. Their muscle biopsies revealed an abnormality in fibrillin immunoreactivity. CONCLUSIONS: Abnormalities in fibrillin can be detected in muscle biopsies from patients with Marfan's syndrome who have myopathy. This pedigree, with a point mutation in FBN1, also draws attention to the potential for respiratory failure associated with myopathy.

Non-progressive mental retardation and peripheral neuropathy in a mother and her son.

The association of facial dysmorphism, moderate mental retardation and peripheral neuropathy was observed in a mother and her son. The son also has pyramidal tract involvement in the lower limbs. Although exactly the same association has not been described previously, it seems probable that it results from variable expression of a dominant gene defect.

Some peoples' psychological experiences of attending a sexual health clinic and having a sexually transmitted infection.

This study considers aspects of the experiences of a group of people attending a sexual health clinic and receiving the diagnosis of a sexually transmitted infection (STI). The study was conducted in the form of action research using a qualitative approach. Participants consisted of eight attenders at a sexual health clinic who had been diagnosed with a sexually transmitted infection. Counselling skills and techniques were used throughout semi-structured interviews to explore participants' feelings about these issues. Thematic analysis was used to generate themes of importance to the participants. Some people who had been to a sexual health clinic and received a diagnosis of a sexually transmitted infection were found to experience feelings of anxiety, stigma and isolation. This study is of value to all those working in the field of sexual health with an interest in understanding the issues that are important to the client group.

Water sorption and solubility of resin-based materials following inadequate polymerization by a visible-light curing system.

The water sorption and solubility of three hybrid and one microfine composite are reported. The values obtained are dependent on composite type and resin system. Incomplete polymerization of the two materials resulted in increased solubility and sorption due to incomplete conversion of the monomer. The marked increased in both parameters will have clinical significance on the durability of the material.

Variations in tooth surface temperature in the oral cavity during fluid intake.

Measurements were made of the extremes in temperature which occur at different sites in the oral cavity during fluid intake. The results indicate that temperatures noted at the tooth surface, within the mouth, during fluid intake were less than the temperatures of the fluid imbibed. Variations in temperature were noted in different areas of the mouth. This may be associated with the position of the tongue during swallowing and the effect of the tissues of the oral cavity as heat absorbers. The range of temperatures noted at the tooth surface and the duration of the temperature changes were at variance with those utilized in many thermocycling studies. It is suggested that closer alignment with the clinical situation is desirable.