Pneumoperitoneum complicating mechanical ventilation in congenital myotonic dystrophy

We have studied the train-of-four (TOF) response mechanomyographically during onset of neuromuscular block produced by subclinical doses of suxamethonium in order to follow the augmentation of the first twitch of the TOF (T1) and TOF fade compared with control TOF responses before the drug was given. In the groups given suxamethonium 0.05, 0.1, 0.2 and 0.3 mg kg-1, the increments in T1 after administration of the drug were observed before twitch depression occurred; these were mean 22.3 (SEM 8.1)%, 19.2 (3.3)%, 10.8 (2.0)% and 4.2 (2.2)%, respectively. This effect was more marked with the lower doses (P < 0.05). The degree of TOF fade was moderate during onset of neuromuscular block and depended on the dose of drug. The results of this study suggest that low doses of suxamethonium produced transient increase in muscle tension and twitch depression with significant TOF fade. We conclude that suxamethonium was associated with presynaptic effects as a consequence of brief stimulation of acetylcholine release followed by progressive diminution at the neuromuscular junction.     

Steinert''s congenital myotonic dystrophy. Genetic aspects

The study of the air contamination was carried out in six fruit farms located in the region of Grójec and Warka. The measurements were carried out during the application of "Fastac 10EC" insecticide (alphamethrin) in fruit growing at work sites of tractor drivers operating the sprayers. The mean concentrations of alphamethrin at individual work sites were low and ranged between 0.001 and 0.0039 mg/m3 of the air. Due to the lack of maximum allowable concentration (MAC), the inhalation toxicity of alphamethrin of 320 mg/m3 (4-h), toxicity class of alphamethrin (III) and MAC of natural pyrethrum were considered. In this context the determined concentrations seem to be safe.     

Contrasts in clinical presentation and genetic transmission of myotonic dystrophy

Myotonic dystrophy, the most common inherited neuromuscular disease, is an autosomal dominant muscular dystrophy characterized by myotonia and distal muscle weakness. It is caused by an increase in the number of cytosine-thymine-guanine (CTG) nucleotide repeats present on the long arm of chromosome 19. Two patients were evaluated, one with classic adult-onset myotonic dystrophy and the other with congenital myotonic dystrophy. Contrasts in the clinical features and genetic transmission of this disease and clinical management are reviewed.     

A study of the cognitive and psychological profile in 16 children with congenital or juvenile myotonic dystrophy

Cost-effectiveness analysis for cervical cancer screening in Japan was performed to estimate the cost per life-year saved by the screening; cost-effectiveness ratio (CER). The analysis was made using a simulation model to estimate long-term cost and effectiveness of the screening programs. CER of cervical cancer screening was estimated to be US$ 40,604 which was 2.4 times more expensive than that for gastric cancer screening but was about the same as that for colorectal cancer screening. It was within the range of cost-effectiveness of other cancer screening programs financed under the Health and Medical Services Law for the Aged in Japan. We performed sensitivity analysis on the following seven estimates, the screening charge, the sensitivity and the specificity of the screening test, the frequency of carcinoma in situ (CIS) among cases detected in the screening program, the initial cost and the terminal cost for patients with invasive cancer, and the incidence rate of cervical cancer. The sensitivity analysis demonstrated that the screening charge was the most influential factor on CER. CER was fairly stable under various assumptions on the accuracy of the screening test, the frequency of carcinoma in situ (CIS), the treatment cost for patient, and the incidence of cervical cancer. CER was less sensitive to the changes in incidence, even to as low as a 50% decrease of the current figure. Then if the incidence rate becomes 85% of the current figure in 2015, CER would be US$ 48,176 and it was suggested that the cervical cancer screening would remain reasonably cost-effective until the year 2015.     

Electron microscopic study of extraocular muscles in myotonic dystrophy

A study was made of the effect of morphine on electrical activity within single ganglia of Auerbach's plexus of guinea pig longitudinal muscle-myenteric plexus as monitored by means of external electrodes. Morphine produces a concentration dependent block of single spike activity. This effect is competitively antagonized by naloxone. The ED50 for morphine effect is about 7 X 10(-7) M. Naloxone and dextrorphan have no effect on electrical activity. Acetylcholine in the concentration range of 10(-7)--10(-5) M augments electrical activity of ganglia. Morphine has little if any effect on the enhanced stimulation produced by acetylcholine thus indicating that the drug does not act directly upon the ganglion. Our results suggest that a specific opiate receptor is present on the preganglionic nerve terminals and that morphine and other opiates block ganglionic transmission by inhibiting the release of preganglionic acetylcholine.     

Expanding complexity in myotonic dystrophy

Myotonic dystrophy (DM) is a highly variable multisystemic disease belonging to the rather special class of trinucleotide expansion disorders. DM results from dynamic expansion of a perfect (CTG)n repeat situated in a gene-dense region on chromosome 19q. Based on findings in patient materials or cellular and animal models, many mechanisms for the causes and consequences of repeat expansion have been proposed; however, none of them has enjoyed prolonged support. There is now circumstantial evidence that long (CTG)n repeats may affect the expression of any of at least three genes, myotonic dystrophy protein kinase (DMPK), DMR-N9 (gene 59), and a DM-associated homeodomain protein (DMAHP). Furthermore, the new findings suggest that DM is not a simple gene-dosage or gain-or-loss-of-function disorder but that entirely new pathological pathways at the DNA, RNA, or protein level may play a role in its manifestation.     

Segregation distortion in myotonic dystrophy

Myotonic dystrophy (DM) is an autosomal dominant disease which, in the typical pedigree, shows a three generation anticipation cascade. This results in infertility and congenital myotonic dystrophy (CDM) with the disappearance of DM in that pedigree. The concept of segregation distortion, where there is preferential transmission of the larger allele at the DM locus, has been put forward to explain partially the maintenance of DM in the population. In a survey of DM in Northern Ireland, 59 pedigrees were ascertained. Sibships where the status of all the members had been identified were examined to determine the transmission of the DM expansion from affected parents to their offspring. Where the transmitting parent was male, 58.3% of the offspring were affected, and in the case of a female transmitting parent, 68.7% were affected. Studies on meiotic drive in DM have shown increased transmission of the larger allele at the DM locus in non-DM heterozygotes for CTGn. This study provides further evidence that the DM expansion tends to be transmitted preferentially.     

Extraocular muscle surgery in myotonic dystrophy

A 44-year-old woman with severe variant angina refractory to maximal medical therapy and at risk of sudden death was successfully treated by a NIR stent implantation on a moderate lesion of LAD. Six months later she was asymptomatic, without in-stent restenosis. This procedure represents an alternative treatment for patients with refractory vasospastic angina.     

Mechanisms of diarrhoea in myotonic dystrophy

BACKGROUND: Gastrointestinal (GI) symptoms are common in myotonic dystrophy (MD). Diarrhoea is one of the more disabling of these GI complaints. The mechanisms behind diarrhoea in MD have not previously been investigated systematically. OBJECTIVE: To elucidate the mechanisms behind diarrhoea in MD. METHODS: Twenty patients with MD and suffering from diarrhoea were investigated in order to detect malabsorption (blood tests and faecal fat excretion) and bile acid malabsorption ([75Se]selenahomocholic acid-taurine (SeHCAT) retention) and to study intestinal morphology (duodenal and rectal biopsies). RESULTS: Two patients had deficiency of folic acid and four showed reduced levels of pancreatic isoamylase, but none of them had steatorrhoea. Two out of eight patients had abnormal bile acid breath tests with normal SeHCAT, indicating small bowel bacterial overgrowth and 12 displayed reduced SeHCAT retention. Duodenal biopsies were normal in eight patients and five out of nine rectal biopsies displayed slight inflammation. CONCLUSIONS: A possible mechanism of diarrhoea in MD could be identified in most of the patients. Bile acid malabsorption seems to be a frequent cause and can be treated successfully.     

Sevoflurane anesthesia for myotonic dystrophy

We successfully anesthetized a 14-year-old boy with myotonic dystrophy for orthopedic surgery using sevoflurane. Sevoflurane enabled anesthetic induction and tracheal intubation without intravenous anesthetics and muscle relaxants. Sevoflurane also provided stable anesthetic maintenance without intravenous anesthetics. The patient showed rapid anesthetic recovery and adequate spontaneous breathing. We conclude that sevoflurane is a useful anesthetic for patients with myotonic dystrophy.     

Immunohistochemical study of intracytoplasmic inclusion bodies of the thalamus in myotonic dystrophy

Intracytoplasmic inclusion bodies of the thalamus in eight patients with myotonic dystrophy (MyD) were studied immunohistochemically. The intracytoplasmic inclusion bodies of the thalamus (thalamic inclusions, TIs) were strongly immunostained with anti-ubiquitin antibody (Ab) and some of them were mildly stained with anti-microtubule associated protein 1 (MAP 1) and anti-MAP 2 antibodies. However, TIs did not react with any of the following: anti-neurofilament protein Ab, anti-tau Ab, anti-paired helical filament Ab, anti-tubulin Abs (alpha and beta), anti-neuron-specific enolase Ab, anti-glial fibrillary acidic protein Ab, anti-synaptophysin Ab, anti-myelin basic protein Ab, anti-actin Ab and anti-phosphorylated epitope of neurofilaments Ab. Thus, our study demonstrates the unique immunohistochemistry of TIs in MyD which differentiates them from other intracytoplasmic inclusions in various neurodegenerative disorders.     

Brain disease and molecular analysis in myotonic dystrophy

Abnormal amplification of a CTG repeat on chromosome 19 is the molecular basis of myotonic dystrophy (DM). Expansion of the repeat has been correlated with severity of several clinical features of the disease. We performed extensive cognitive testing, cerebral magnetic resonance imaging (MRI) and a molecular analysis in 28 cases of DM to determine the relationship between the molecular defect and brain disease. Performance in two or more cognitive tests was pathological in 10 cases. Fourteen patients had subcortical white matter lesions on MRI, 14 had cerebral atrophy. Amplification of the CTG repeat showed a strong correlation with cognitive test deficits when exceeding a length of over 1000 trinucleotides. MRI lesions were associated with impaired psychometric performance, but MRI and molecular findings were only weakly related. Disease duration influenced the appearance and amount of white matter lesions on MRI. Quantification of CTG repeat size may allow an early estimate on the probability of brain involvement in DM; cognitive dysfunction is associated with white matter lesions and cerebral atrophy later on in the course.     

Are muscle fibers denervated in myotonic dystrophy?

An underlying neurogenic abnormality has recently been postulated in the muscular dystrophies. To test this hypothesis, we applied a widely accepted criterion of denervation-ie, and increase in extrajunctional acetyicholine (ACh) receptor sites--to muscles biopsy specimens from nine patients with myotonic dystrophy and three with amyotrophic lateral scierosis (ALS). The ACh receptor sites were determined by means of iodine 125-labeled alpha-bungarotoxin binding, measured by scintillation counting and autoradiography. None of the myotonic dystrophy muscles showed increased extrajunctiona ACh receptor sites, even in the smallest fibers. By contrast, muscle biopsy specimens from patients with ALS showed notably increased extrajunctional ACh receptor sites, especially in the small fibers. Our findings do not support the hypothesis of a neurogenic defect in myotonic dystrophy.     

Severe capsulorhexis contracture after cataract surgery in myotonic dystrophy

A 42-year-old woman with myotonic dystrophy developed bilateral severe capsulorhexis contracture after uneventful phacoemulsification cataract surgery with implantation of 1-piece poly(methyl methacrylate) intraocular lenses (IOLs). The anterior capsular opening in her right eye constricted to a diameter of 0.7 mm, reducing visual acuity to counting fingers. Complete closure of the capsulorhexis with IOL encapsulation developed in her left eye, reducing visual acuity to hand movements. Surgical anterior capsulectomies restored visual acuity to 6/9 in both eyes. Myotonic dystrophy may predispose to the development of severe capsulorhexis contracture after cataract surgery.     

Insulin resistance and clinical evolution in infantile myotonic dystrophy

1. Extensor digitorum longus muscles of C57 BL/10 and mdx mice were overloaded by removing the synergist tibialis anterior muscle of 9-12-day-old animals. The effect of this operation on the weight, contractile properties and force of the extensor digitorum longus muscle was examined at two different ages, i.e. at 2-3 months (young group) and at 5-8 months (old group). The changes with age in both the control and overloaded muscles of normal and mdx mice are also described. The values obtained from the overloaded muscles were always compared with those for the control, unoperated extensor digitorum longus. 2. In the normal strain of mice the weight of the overloaded extensor digitorum longus muscle in the younger group was increased and it remained higher in the older animals. In the mdx mice the overloaded extensor digitorum longus muscles weighed more in the younger animals but not in the older group of mice. 3. The twitch and tetanic tensions of the overloaded muscles were slightly, but not significantly, increased in the younger group of mdx mice, whereas in the older animals there was a significant decrease in both twitch and tetanic tensions. 4. Thus the overloaded muscles from mdx mice progressively deteriorated with age. In both strains of mice the overloaded muscles become less fatigable with time.     

Molecular genetics and merosin abnormality in Fukuyama-type congenital muscular dystrophy (FCMD)

Fukuyama-type congenital muscular dystrophy (FCMD), the second most common form of muscular dystrophy in Japan, is an autosomal recessive severe muscular dystrophy associated with brain anomalies. After our initial mapping of FCMD to chromosome 9q31-33, we revealed that the gene lies within a region of < 100 kb containing D9S2107(9q31) by linkage-disequilibrium mapping. A-3 kb insertion was found in most FCMD chromosomes with the founder haplotype. On the other hand, a significant reduction in immunostaining of an extracellular matrix, laminin alpha 2 (merosin) has been noted in the FCMD muscle. Others reported basal lamina abnormalities in the FCMD muscle and brain in electron microscopic examination. We here describe recent advances in molecular genetics of FCMD and abnormalities of the basement membranes.     

Clinical manifestations of myotonic dystrophy: epidemiologic survey

BACKGROUND: The presence of a local aggregation of cases of myotonic dystrophy (MD) allows the evaluation of clinical symptoms of the disease in a sample in which the influence of a possible genetic heterogeneity is decreased. METHODS: The degree of global neuromuscular handicap and the incidence and severity of four of the most characteristic symptoms (cataracts, myotonia, muscular weakness and neuropsycologic disturbances) were studied in 183 patients with MD (146 typical adult forms, 19 neonatal, and 18 partial syndromes) in relation with the age of onset of the symptomatology or length of disease. RESULTS: Only 8.3% of the patients (excluding the neonatal forms) were severely handicapped, and the degree of neuromuscular handicap depended fundamentally on the age of onset of the disease. Cataracts and myotonia were present in 87 and 89% of the patients, respectively. Almost all the patients above the age of 40 presented cataracts. No clinical or subclinical evidence of neuromuscular involvement was present in 11% of the patients with MD. These patients principally corresponded to the group in whom the disease initiated over the age of 50. CONCLUSIONS: The age of onset of the symptomatology appears to be the determining factor to establish both the global prognosis of neuromuscular incapacity of patients with myotonic dystrophy and the explanation of the chronology of the appearance of the most characteristic symptoms of the disease. The presence of carriers without neuromuscular symptomatology is of note, this fact reinforcing the need to incorporate DNA examination in the evaluation of asymptomatic relatives or with exclusive ocular symptomatology.