[Survey for assessing how Duchenne muscular dystrophy is explained to children with the disorder].

OBJECTIVE: There are many difficulties in disclosing Duchenne muscular dystrophy (DMD) to children with the disorder. The purpose of this study was to assess the explanation of DMD given to affected children by child neurologist. METHODS: The questionnaire was mailed to board-certified child neurologists of the Japanese Society of Child Neurology. The questionnaire consisted of questions on how physicians explained the condition to children with DMD (their patterns of explanation) and their attitude towards the children while explaining the disease. RESULTS: We received 311 replies. The contents of physicians' explanations were categorized and correspondence analysis revealed medical support" (explanation about the symptoms, prognosis, medical responses) and "humanistic support" (telling purpose in life, patient group introduction). Parents' understanding of the disease, acceptance, and trust relationships were considered important factors for disease explanation by the physicians. Physicians agreed with the need of clinical psychologist and other psychological professionals when they tell their diagnosis, and agreed with telling the diagnosis to a DMD child reached a certain age. CONCLUSIONS: It was revealed that physicians' explanation were largely categorized into two groups, and the important factors for disease explanation and physicians' attitudes towards disclosure of the diagnosis. This information will help in explaining the disease to children with DMD.

[A longitudinal cause-of-death analysis of patients with Duchenne muscular dystrophy].

Mechanical ventilation (MV) and cardiac protective therapy have improved the prognosis and quality of life of patients with Duchenne muscular dystrophy (DMD). To understand how these therapies have changed prognosis, we performed a cause-of-death analysis in DMD patients. Mean age at death before initiation of MV (January 1977-July 1984) was 18.9±4.1 years. After the introduction of MV, from August 1984 to December 1993 (1(st) term), it was 20.0±4.5 years, from January 1994 to December 2003 (2(nd) term), it was 25.2±4.6 years, and from January 2004 to December 2010 (3(rd) term), it was 31.1±5.4 years. Almost half of all deaths before MV were due to respiratory failure (RF). Because MV was performed by a tracheostomy in the initial stage, some patients were reluctant to use it, and as a result, RF accounted for 43% of deaths in the 1(st) term. Over time, patients started to accept non-invasive ventilation and home mechanical ventilation, which became available in the 1990s. Consequently, no DMD patients have died from RF since 2000. Respiratory physiotherapy and risk management became important tools, because many patients undergo decades of respiratory managements at home. Cardiac treatments for patients with DMD consisted mainly of diuretics and digitalis in the 1(st) term, angiotensin-converting enzyme inhibitors (ACEI) in the 2(nd) term, and a combination of ACEIs and beta blockers in the 3(rd) term. Compared to the 2(nd) term, the ratios of severe cardiac dysfunction (fractional shortening <10%, left ventricle diastolic dimension >75mm, plasma brain natriuretic peptide >1,000pg/ml) were reduced in the 3(rd) term. In the 3(rd) term, 14% of patients died from renal failure nevertheless their cardiac indices remained mildly abnormal or normal. We should pay enough attention for cardio-renal association.

A cross-sectional study for glucose intolerance of myotonic dystrophy.

We made a cross-sectional study to analyze glucose intolerance of myotonic dystrophy type 1 (DM1) with several examination including oral glucose tolerance test (OGTT), insulin tolerance test (ITT) and adiponectin. Ninety-five DM1 patients participated in this study. Health examination data from general people were used as controls. In DM1, homeostasis model assessment-insulin resistance (HOMA-IR) was higher than control even in the lowest fasting blood sugar (FBS) stage (<80 mg/dl) and insulin sensitivity assessed by ITT was low regardless of their FBS. Insulinogenic index of DM1 was positively correlated to HOMA-IR. Insulinogenic index and sum of IRI in OGTT were markedly elevated in the lowest FBS stage and declined along with elevation of FBS. Consequently, as many as 13.3% of DM1 patients with 90-110 mg/dl of FBS exhibited DM pattern, while only 1.9% in control. Adiponectin was higher in DM1 than control. Although age correlated with adiponectin in both control and DM1, its impact was stronger in DM1. DM1 predisposes insulin resistance and compensatory hyperinsulinemia exist even in patients with low FBS. We should pay attention to glucose intolerance of DM1 patients earlier than that of the general population. It seemed that 90 mg/dl of FBS is an important index as an indication of careful managements.

[Prolonged apnea/hypopnea during water swallowing in patients with amyotrophic lateral sclerosis].

PURPOSE: Swallowing difficulty is increased along with progression of respiratory disturbance in patients with Amyotrophic Lateral Scalerosis (ALS). To analyze the respiratory patterns during swallowing is important for the management of this disease. In this study, we evaluated apnea/hypopnea during water swallowing and the respiratory cycle at rest and after water swallowing. METHOD: We evaluated respiratory patterns in swallowing in 10 ALS patients (66.0 +/- 7.1 years old), in 10 Myotonic dystrophy (MD) patients (46.5 +/- 12.2 years old), and in 10 healthy volunteers as control subjects (61.7 +/- 10.0 years old). The ALS and MD patients had consulted the Department of Neurology of Toneyama National Hospital or Tokushima National Hospital between April 2002 and July 2006. Respiratory patterns were evaluated by simultaneous recording of cervical swallowing sound in water swallow. A hypersensitive microphone measured cervical sound. A thermister was used for pneumography. The means of four continuous respiratory cycles at rest and after swallow of 3 ml water were used for analysis. Respiration with amplitude of 1/2 or smaller than that of the pneumography at rest was defined as hypopnea, and the apnea/hypopnea duration was evaluated as the respiratory suppression time. STATISTICAL ANALYSIS: All analyses were performed using SPSS 11.0J (SPSS Inc., Chicago, IL). RESULTS: In the ALS group, the respiratory cycle was 3.15 +/- 0.76 sec (2.31-4.39 sec) at rest, while after swallowing, it was 2.78 +/- 0.83 sec (1.77-4.80 sec) (p = 0.1). In the MD group, the respiratory cycle was 2.56 +/- 0.46 sec (1.91-3.67 sec) at rest, while after swallowing, it was 2.94 +/- 0.60 sec (2.03-4.29 sec). In the control group, it was 3.46 +/- 0.57 sec (3.18-4.34 sec) at rest and 3.24 +/- 0.50 sec (2.64-4.04 sec) after swallowing. The apnea/hypopnea duration during water swallow was 14.33 +/- 8.89 sec (2.50-30.68 sec) in the ALS group, 3.66 +/- 1.58 sec (1.78-6.42 sec) in the MD group, and 3.64 +/- 1.00 sec (2.34-5.56 sec) in the control group. The apnea/hypopnea duration in the ALS group was significantly longer than that in MD and control groups (p = 0.005, p = 0.004 by the t-test). The ALS patients with severe respiratory failure or with aspiration in videofuoroscopy showed extended apnea/hypopnea duration. CONCLUSION: Prolonged apnea/hypopnea was observed during water swallowing in ALS patients. We speculate that this prolongation is caused by severe swallowing disturbance and respiratory failure, which increases the risk of aspiration. The respiration of ALS patients should be closely monitored during eating.

Cardiac troponin I for accurate evaluation of cardiac status in myopathic patients.

BACKGROUND: Brain natriuretic peptide (BNP) and left ventricular ejection fraction (LVEF) are standard indexes for cardiac function. However, they can not reveal myocardial damage directly and they often remain normal even in advanced cardiomyopathy in immobilized patients. Myocardial markers such as MB type of creatine kinase (CK-MB), heart-type fatty acid binding protein (H-FABP) and cardiac troponins are expected to evaluate active myocardial degeneration. However, their availabilities in these patients have not been examined yet. METHODS: Participants were 129 patients with dystrophinopathies; 100 Duchenne muscular dystrophy (DMD), 25 Becker muscular dystrophy (BMD) and 4 DMD/BMD carriers. Various serological cardiac indexes, including CK-MB, H-FABP, cardiac troponin I (cTnI), BNP and LVEF were measured and statistical analysis was done. RESULTS: CK-MB and H-FABP was highly associated with creatine kinase (CK). On the contrary, cTnI, BNP and LVEF were independent from CK. In DMD, relatively high cTnI values were observed in patients with motor ability of rowing wheelchair and in their second decade. BNP and LVEF was strongly correlated. However, cTnI was independent from LVEF and only weak correlation could be detected between cTnI and BNP. CONCLUSION: cTnI had been proven to be expressed in myocardium exclusively. Our results also certified that cTnI can assess cardiac degeneration independently from skeletal muscle degeneration and is practical index even in myopathic patients. Our findings also suggested that cardiac degeneration was preceded to functional impairment in many cases. It indicated that cTnI enable us to detect early stage of cardiac degeneration and initiate intervention at proper stage.

[Videofluorographic assessment of swallowing function in patients with Duchenne muscular dystrophy].

OBJECTIVE: To identify the characteristics of swallowing function in patients with Duchenne muscular dystrophy (DMD). METHODS: Swallowing function was evaluated using videofluorography (VF) in a cross-sectional observational study of 102 DMD patients (mean age 21.5 years) who had dysphagia or in whom dysphagia was suspected based on clinical signs. Reduced tongue movement, impaired bolus transport to the pharynx, decreased pharyngeal contraction, bolus delivery into the airway, and bolus residue at the epiglottic vallecula and at the piriform recess were qualitatively evaluated for test swallows of jelly and juice. During VF, the length of time of both the oral and pharyngeal phases of swallowing was measured in 59 patients. RESULTS: Patients started to show oral phase abnormalities in their mid-teens and pharyngeal phase abnormalities such as pharyngeal residue around age 20. Oral phase abnormalities was higher with juice than with jelly. Total oral/pharyngeal transit duration was longer with age, and total duration of hyoid maximum elevation was shorter with age. CONCLUSION: The weak positive correlation of total oral/pharyngeal transit duration and age was presumably due to gradual onset of functional abnormalities associated with deteriorated swallowing muscles starting in the teenage years. Reduced tongue movement and impaired bolus transport to the pharynx was more common in teenage DMD patients because they have limited tongue movements associated with structural abnormalities such as macroglossia and open bite. VF showed that the swallowing difficulties were more severe during the oral phase than in the pharyngeal phase in the teenage patients. The pharyngeal phase disorders such as pharyngeal residue and decreased pharyngeal contraction were seen more often in the patients in their 20s, presumably due to deterioration of swallowing muscles that becomes more apparent in the older age group.

Tracheo-arterial fistula in tracheostomy patients with Duchenne muscular dystrophy.

A tracheo-arterial fistula is a serious and life threatening potential complication of a tracheostomy. Since 1984, we experienced nine fatal cases of tracheo-arterial fistula among 60 Duchenne muscular dystrophy (DMD) patients who underwent a tracheostomy. Representative cases included a patient with lordosis (Case 8), in whom the fistula was located in the brachiocephalic artery close to the trachea, and another with severe scoliosis (Case 9), which caused the aorta to compress the trachea. Such anatomical changes can be the cause of a fistula between the trachea and brachiocephalic artery. The anatomical locations between the trachea and brachiocephalic artery are modified by thoracic deformities in DMD patients, and should be confirmed using computed tomography (CT) prior to a tracheostomy procedure. Further, during such a procedure, the tracheal stoma must be placed in a location clearly away from the arteries, and should be followed by regular post-operative examinations using CT and careful management to avoid a tracheo-arterial fistula.

[Anti-beta 1 adrenoreceptor antibody is frequently elevated in patients with muscular dystrophy].

Various autoantibodies had been detected in patients with dilated cardiomyopathy (DCM). Among them, anti-beta 1 adrenoreceptor antibody (ARAb) had been proven to act as agonist on beta 1 adrenoreceptor and cause DCM. Cardiomyopathy is also serious problem in progressive muscular dystrophy (PMD). Because cardiac dysfunction is quite variable even in siblings sharing identical mutations, it is highly possible that there are some modifier factors. Thus, we measured ARAb in 93 patients with PMD and 11 patients with DCM to clarify immune function for cardiac impairment of PMD. The titer was abnormally elevated in 30.1% of PMD, 72.7% of DCM and 75.0% (9/12) of PMD patients with symptomatic cardiac failure. ARAb was weakly correlated to fractional shortening, brain natriuretic peptide, noradrenalin and severity of premature ventricular contractions (Lown grade). During the study period, four patients developed cardiac failure and ARAb was increased in all these patients. In DMD, although the patients receiving both beta blocker and angiotensin converting enzyme inhibitor showed worst cardiac function, the titers were rather low compared to patients with angiotensin converting enzyme inhibitor alone. Four of five patients initiating beta blocker showed decrease of ARAb. Autoantibodies for myocardium actually exist in PMD in certain ratio as is the case with DCM. It is highly possible that immune system plays some role in cardiac impairment even in PMD. We should pay enough attention to immune system to elucidate the mechanism of cardiac dysfunction and refine strategy of cardiac treatments.

Coagulation system activated in Duchenne muscular dystrophy patients with cardiac dysfunction.

We investigated basic abnormalities of coagulation and fibrinolysis in Duchenne muscular dystrophy (DMD) patients with cardiac dysfunction. Forty seven patients with DMD, aged 13-37 years old, were enrolled. Based on left ventricular ejection fraction (LVEF) results determined by echocardiography, patients were divided into 3 groups: LVEF less than 30% (markedly depressed group), LVEF between 30 and 50% (slightly depressed), and LVEF greater than 50% (normal). We measured serum levels of total fibrin and fibrinogen degradation products (FDP), as well as plasma fibrinogen, thrombin-antithrombin complex (TAT), prothrombin fragment (F1+2), and D-dimer. The levels of TAT and F1+2 in the markedly depressed group were significantly elevated compared with the other groups, whereas FDP, fibrinogen, and D-dimer levels did not differ among the groups. We concluded that activated coagulation is associated with cardiac dysfunction in patients with DMD.

[How we have treated and cared patients with Duchenne muscular dystrophy and severe congestive heart failure].

Patients with Duchenne muscular dystrophy (DMD) and severe congestive heart failure (CHF) frequently feel mental anguish due to severe mental and physical restriction. Since therapy is not efficacious enough, their quality of life is often disturbed during the terminal stage. We retrospectively evaluated the treatment and care for 11 cases of DMD with severe CHF in our hospital. All cases had unrest and anxiety, which were successfully treated with benzodiazepines and haloperidol. In many cases, patients' families craved for patients' comfort without mental and physical pain. Nine cases resulted in death and 2 cases survived. We also sent a questionnaire to doctors of muscular dystrophy wards of 27 Japanese national hospital, inquiring about therapy protocol, monitoring system, intravenous nutrition, limitation of feeding/recreation/visitors, management of pain/anxiety/sedation, and cardiopulmonary resuscitation (CPR). Sixty-eight doctors answered the questionnaire. Forty-seven doctors (69%) had the experience to treat DMD patients with severe CHF. The majority of them monitored electrocardiography, SpO2 and blood pressure. About a half adopted intravenous nutrition. If recovery was expected, limitation of feeding/recreation/visitors was based mainly on discussion with the patients and their families. If recovery was impossible, the limitation was decided according to their wishes. Nonsteroidal anti-inflammatory drugs were properly used for pain, and minor and major tranquilizers for sedation. Morphine was also used. Only one doctor adopted positive CPR, while the others answered "do not CPR" or "do CPR according to the wish of patients' families". The burden to patients and their families during treatment is unavoidable but should be reduced as much as possible. Medical staffs should ask themselves about the problems to support the families as well as patients repetitively.

How Physicians Support Mothers of Children with Duchenne Muscular Dystrophy.

Communicating about Duchenne muscular dystrophy and its prognosis can be difficult for affected children and their family. We focused on how physicians provide support to the mothers of children with Duchenne muscular dystrophy who have difficulty communicating about the condition with their child. The eligible participants were certified child neurologists of the Japanese Society of Child Neurology. Participants responded to questionnaires consisting of free descriptions of a vignette of a child with Duchenne muscular dystrophy and a mother. We analyzed 263 responses of the participants. We found 4 themes on advising mothers, involving encouraging communication, family autonomy, supporting family, and considering the child's concerns. These results provide a better understanding of the communication between physicians and family members who need help sharing information with a child with Duchenne muscular dystrophy. These findings will assist clinical practitioners in supporting families and the affected children throughout the course of their illness.

[A case of Satoyoshi syndrome complicating marginal gingivitis of the mandible and dislocation of the temporomandibular joint].

Satoyoshi syndrome is a very rare disorder, characterized by progressive painful intermittent muscle spasms beginning in adolescence. Universal alopecia, diarrhea, amenorrhea and bony deformities are also cardinal features of this syndrome. Skeletal abnormalities, such as joint deformity, epiphysial destruction and retarded growth, are observed in approximately half of patients. However, no bony changes have previously been reported in the region of the head. We present here a male patient with Satoyoshi syndrome. Muscle cramps began in the lower extremities when he was 13 years old, and gradually spread. At the age of 17 years, masticatory muscle cramps made it difficult to eat and speak fluently, and were considered a cause of malacia in this patient. Finally, recurrent severe cramps in the masseter muscles caused marginal gingivitis of the mandible, necessitated extraction of the teeth and caused dislocation of the temporomandibular joint. After treatment with dantrolen sodium at doses up to 150 mg/day, painful spasm decreased significantly. Since masticatory muscles can cause significant stress to the teeth and the temporomandibular joint, sufficient attention should be paid to the oral region to avoid complications in patients with Satoyoshi syndrome.

[A case of Duchenne muscular dystrophy showing coagulation cascade activation induced by muscle destruction due to convulsion].

A male patient with advanced Duchenne muscular dystrophy (DMD) had tonic-clonic convulsion. He showed transient elevations of serum creatine kinase (CK) and plasma D-dimer. Serum CK, ordinarily 122-386 IU/l, was elevated to 9,262 IU/l, while plasma D-dimer, below 66 ng/ml in normal subjects, was at 543 ng/ml, and these levels were significantly correlated. Serum fibrin and fibrinogen degradation products levels were within a normal range. In the present case, acute muscle destruction due to tonic-clonic convulsion was considered to transiently activate a coagulation cascade. Plasma D-dimer elevation is the result of fibrin thrombus and can induce thrombosis, such as a pulmonary embolism. Thrombosis is a serious life-threatening complication of DMD, though the mechanism remains unclear. There were no thrombotic complications in the present patient, however, acute muscle destruction enhances the coagulation and fibrinolysis status in patients with advanced DMD and may be a candidate cause of thrombosis.

[Process of swallowing disturbance in amyotrophic lateral sclerosis--evaluation of videofluorography and respiratory function].

We investigated the process of swallowing disturbance in the patients with amyotrophic lateral sclerosis (ALS). Swallowing function of 11 patients with ALS (67.5 +/- 7.5 y.o.) was evaluated by videofluorography (VF) and swallowing part of ALS functional rating scale (FRSsw) more than 2 times during the course. Percent of forced vital capacity (%FVC) was also measured. VF measures were oral leakage, poor bolus formation, retention in oral cavity, abnormal transport to pharynx as oral stage and delayed swallowing reflex, laryngeal penetration, aspiration, nasal regurgitation, retention in valleculae and pyriform, and abnormal opening of pharyngo-esophageal segment as pharyngeal stage. FRSsw were defined as 4: normal eating habits, 3: early eating problems--occasional choking 2: dietary consistency changes, 1: needs supplemental tube feeding and 0:NPO (exclusively parental or enteral feeding). According to VF findings in the course of oral stage and pharyngeal stage, in some patients, the disturbance of oral stage preceded that of pharyngeal stage, while in the other patients, the disturbance of pharyngeal stage disturbance preceded that of oral stage, and in another patients were mixed course. There was poor relationship between the FRSsw and VF measure. Even in the patients of FRSsw 4 & 3. penetration/aspiration were found. %FVC was 70.0 +/- 17.3% in patients with FRSsw 4 & 3, 43.1 +/- 17.6% in patients with FRSsw 2 and 40.4 +/- 16.2% in patients with FRS 1 & 0. In the individual course, FRSsw decreased in parallel with %FVC. We conclude that there are various course of swallowing disturbance on VF findings, the oral stage disturbance proceed, the pharyngeal stage disturbance proceed or mixed. Swallowing function deteriorate in parallel with respiratory function in ALS patients. We have to take measures against the dysphagia even in early stage.

[A case of Duchenne muscular dystrophy complicated by thrombotic thrombocytopenic purpura].

We experienced a patient with Duchenne muscular dystrophy (DMD) complicated by thrombotic thrombocytopenic purpura (TTP). This patient exhibited abrupt high fever, renal dysfunction and thrombocytopenia from February 2, 2002. Hemolysis was also indicated by indirect dominant hyperbilirubinemia, although hemoglobin was only slightly decreased. No central nervous system signs and symptoms were detected. TTP was suggested by these findings and confirmed by decreased activity (21%) of von Willebrand factor cleaving protease activity. Plasma exchange was performed for 4 days from February 5, and enabled recovery. Thrombosis, such as cerebral and lung infarction, has occasionally been seen in DMD. Recently, several findings associating muscle degeneration with hypercoagulation have been reported, for example, a strong correlation between serum CK level and FDP. In seven cases of DMD with pulmonary infarction, transient elevation of serum CK was detected prior to LDH elevation. However, there have been no reports of TTP in DMD patients. Since serum CK was not elevated during our patient's clinical course, it is unlikely that muscle degeneration played a role in TTP in this patient. It should be noted that endothelial abnormalities have been reported in DMD, since endothelial injury is considered a fundamental factor in TTP.

[A clinical trial of creatine monohydrate in muscular dystrophy patients].

To investigate the effects of creatine monohydrate on muscle performance and cognitive functions in muscular dystrophy patients, we made an open trial. Twenty-nine individuals, including 14 myotonic dystrophy (DM), seven facioscapurohumeral muscular dystrophy (FSHD), two limb-girdle muscular dystrophy and six healthy volunteers, were enrolled in this study and 27 participants completed it. All participants took creatine 20g/day for an initial week and 5g/day for successive eight weeks. Somatotonic measurements, global subjective assessment, muscle performance, cardiopulmonary function, cognitive function, laboratory studies and magnetic resonance spectroscopy (MRS) were evaluated at both pre and post examination. Subjective improvements were reported from twelve individuals. Contrary adverse effects were also complained from ten individuals, although all these problems were not serious. Quantitative muscle power was slightly but significantly increased in the patients and the number of the patients who failed to complete cycle ergometer test was decreased. Phosphocreatine concentrations of left calf muscle were not different between pre and post trial examination. No obvious changes were detected in cardiopulmonary assessment, cognitive function and laboratory date. Creatine has certain expectance for muscular dystrophy patients in motor performance. The effect may be achieved not only by increase of energy buffer, because clinical improvements were observed in our study nevertheless no increase was detected in phosphocreatine concentration. The usage of creatine should be managed under medical monitoring since ideal protocol has not yet been established and adverse effects can not be ignored.

[Erythrocyte from Duchenne muscular dystrophy is fragile].

Intermittent indirect hyperbilirubinemia was occasionally observed in Duchenne muscular dystrophy (DMD) patients. We suspected that hyperbilirubinemia might be caused by hemolysis of fragile erythrocytes due to damaged endothelium, which was reported in DMD. To examine the fragility of erythrocytes, we performed osmotic resistance test in 25 DMD, 12 myotonic dystrophy (DM), 12 amyotrophic lateral sclerosis (ALS) and 24 healthy volunteers (male 15, female 9). Minimum resistance (beginning point of hemolysis) of DMD (0.447 +/- 0.016%) was higher than that of age matched male controls (0.425 +/- 0.018%: p = 0.0008) and that of DM (0.440 +/- 0.015%) was also higher than that of total controls (0.423 +/- 0.016%, p = 0.0077). The number of poikilocytes was increased in DMD (35.45 +/- 41.17 per a high magnitude field), however no obvious correlation was detected between the ratio of poikilocytes and resistances. Total bilirubin showed correlation (p = 0.029) to minimum resistance. These findings suggested that erythrocyte membrane is fragile in DMD. Involvement of endothelial damage could not be proven, because all investigated patients showed normal tissue plasminogen activator inhibitor-1. Although the mechanism of fragile erythrocytes in DMD is still unknown, we should pay attention to interpret bilirubin in DMD, because hemolysis due to erythrocyte fragility may influence the value.

[An ambiguous pedigree of facioscapulohumeral muscular dystrophy which showed double EcoRI/BlnI resistant short fragments].

We report a facioscapulohumeral muscular dystrophy (FSHD) pedigree having double short (25 kb and 33 kb) BlnI resistant (4 q-like) fragments. Two of three male siblings developed shoulder-girdle weakness and minimum facial involvement from their adolescence. Although the rest (third) brother had non-progressive hemi-palsy in face and upper-extremity and strabismus caused by birth trauma, he had no clinical symptoms of FSHD. Mother presented mild shoulder weakness after cholecystectomy at the age of 50 years, but with no facial involvement and normal serum creatine kinase (CK) level (45 IU/L). On the contrary, father had high CK level (450 IU/L) despite no neurological abnormalities. After EcoRI/BlnI double digestion, two short fragments were detected in the two affected siblings. Then, all family members were examined to determine pathognomonic fragment. Consequently, mother (25 kb and 90 kb) and the third non-affected brother (25 kb and 51 kb) had two 4 q-like fragments, however, three 4 q-like fragments were detected in father (33 kb, 51 kb and 130 kb), proband (25 kb, 33 kb and 130 kb) and affected brother (25 kb, 33 kb and 51 kb). These findings revealed that the 4 q-like 33 kb fragment actually located on 10q26 through inter-chromosomal exchange. Thus the 25 kb fragment inherited from mother was determined as co-segregating with the disease. To ensure genetic diagnosis for FSHD, investigation of family members is surely required.

[A case of thymoma-associated myasthenia gravis with antibodies against interferon-alpha--a clinico-immunological follow up of the symptoms and its titer].

A 73-year-old woman developed myasthenia gravis (MG) with thymoma. She had a very high level of serum antibodies against interferon-alfa (IFN-alpha). We observed the changes to her clinical symptoms and titer of the antibody during therapeutic course. Although she underwent thymectomy, intravenous methylprednisolone therapy, and oral tacrolimus administration, MG symptoms of the patient were not significantly improved and the antibody titer remained at a high level. IFN-alpha is a potent immunomodulating cytokine that regulates MHC class II expression on antigen presenting cells and activities of NK cells, B cells, and helper/suppressor T cells. This case suggests that IFN-alpha related immunological perturbation participates in the pathogenesis of thymoma-associated myasthenia gravis.

[Soluble adhesion molecules in muscular dystrophy].

To determine whether soluble adhesion molecules are affected in muscular dystrophy, we measured serum levels of creatine kinase (CK), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1 (sICAM-1), soluble (s) E-selectin, and fibrin and fibrinogen degradation products (FDP) in 25 patients with Duchenne muscular dystrophy (DMD), 7 with Becker muscular dystrophy, 7 with Fukuyama type congenital muscular dystrophy, 6 with myotonic dystrophy (MyD), and 5 with spinal muscular atrophy (SMA) type 2, and also serum sVCAM-1, sICAM-1, and sE-selectin in 9 healthy controls. The levels of sVCAM-1 in the patients with DMD were 367.0-852.0 ng/ml (552.8 +/- 23.1) and significantly elevated than those in the patients with MyD, SMA type 2, and controls. The levels of sICAM-1 and sE-selectin in the patients with muscular dystrophy were 0.2-376.0 ng/ml and 17.9-119.0 ng/ml, respectively. They were also elevated than those in the patients with SMA type 2 and controls, but not significantly. The levels of sVCAM-1 and sE-selectin in the patients with DMD significantly correlated with age. There was no correlation between the levels of soluble adhesion molecules and those of CK or FDP in any groups. These changes of soluble adhesion molecules may reflect the process of muscle destruction and endothelial cell activation in muscular dystrophy.