Effect of Nasal Obstruction on Continuous Positive Airway Pressure Treatment: Computational Fluid Dynamics Analyses.

OBJECTIVE: Nasal obstruction is a common problem in continuous positive airway pressure (CPAP) therapy for obstructive sleep apnea and limits treatment compliance. The purpose of this study is to model the effects of nasal obstruction on airflow parameters under CPAP using computational fluid dynamics (CFD), and to clarify quantitatively the relation between airflow velocity and pressure loss coefficient in subjects with and without nasal obstruction. METHODS: We conducted an observational cross-sectional study of 16 Japanese adult subjects, of whom 9 had nasal obstruction and 7 did not (control group). Three-dimensional reconstructed models of the nasal cavity and nasopharynx with a CPAP mask fitted to the nostrils were created from each subject's CT scans. The digital models were meshed with tetrahedral cells and stereolithography formats were created. CPAP airflow simulations were conducted using CFD software. Airflow streamlines and velocity contours in the nasal cavities and nasopharynx were compared between groups. Simulation models were confirmed to agree with actual measurements of nasal flow rate and with pressure and flow rate in the CPAP machine. RESULTS: Under 10 cmH2O CPAP, average maximum airflow velocity during inspiration was 17.6 ± 5.6 m/s in the nasal obstruction group but only 11.8 ± 1.4 m/s in the control group. The average pressure drop in the nasopharynx relative to inlet static pressure was 2.44 ± 1.41 cmH2O in the nasal obstruction group but only 1.17 ± 0.29 cmH2O in the control group. The nasal obstruction and control groups were clearly separated by a velocity threshold of 13.5 m/s, and pressure loss coefficient threshold of approximately 10.0. In contrast, there was no significant difference in expiratory pressure in the nasopharynx between the groups. CONCLUSION: This is the first CFD analysis of the effect of nasal obstruction on CPAP treatment. A strong correlation between the inspiratory pressure loss coefficient and maximum airflow velocity was found.

Clinical features and a mutation with late onset of limb girdle muscular dystrophy 2B.

OBJECTIVE AND METHODS: Dysferlin encoded by DYSF deficiency leads to two main phenotypes, limb girdle muscular dystrophy (LGMD) 2B and Miyoshi myopathy. To reveal in detail the mutational and clinical features of LGMD2B in Japan, we observed 40 Japanese patients in 36 families with LGMD2B in whom dysferlin mutations were confirmed. RESULTS AND CONCLUSIONS: Three mutations (c.1566C>G, c.2997G>T and c.4497delT) were relatively more prevalent. The c.2997G>T mutation was associated with late onset, proximal dominant forms of dysferlinopathy, a high probability that muscle weakness started in an upper limb and lower serum creatine kinase (CK) levels. The clinical features of LGMD2B are as follows: (1) onset in the late teens or early adulthood, except patients homozygous for the c.2997G>T mutation; (2) lower limb weakness at onset; (3) distal change of lower limbs on muscle CT at an early stage; (4) impairment of lumbar erector spinal muscles on muscle CT at an early stage; (5) predominant involvement of proximal upper limbs; (6) preservation of function of the hands at late stage; (7) preservation of strength in neck muscles at late stage; (8) lack of facial weakness or dysphagia; (9) avoidance of scoliosis; (10) hyper-Ckaemia; (11) preservation of cardiac function; and (12) a tendency for respiratory function to decline with disease duration. It is important that the late onset phenotype is found with prevalent mutations.

[Two cases of Duchenne muscular dystrophy complicated with dilated cardiomyopathy and cerebral infarction].

We report two cases of Duchenne muscular dystrophy (DMD) complicated with dilated cardiomyopathy (DCM), who were affected with cerebral infarction. Case 1 suddenly developed dysarthria and right facial weakness at age 21. Cranial CT study disclosed a low density area in the left basal ganglia and internal capsule. Case 2 had a history of transient ischemic attack (TIA) at age 21. Five months after the TIA, he developed right hemiplegia and dysarthria, and a low density area in the corona radiate in left cerebral hemisphere was observed in cranial CT. These two cases showed the radiographic cardiomegaly with cardio thoracic ratio (CTR) of 72.8% and 66.6%, the decreased echocardiographic left ventricular ejection fraction below 20%, and the elevated titer of thrombin-anti-thrombin III complex (TAT) and D-dimer. The autopsy of Case 2 at age 26 disclosed the remarkable degeneration and fibrosis of myocardium and old ischemic lesion in the left cerebral frontal cortex. Despite the negative finding of the emboli in the left heart, cardiogenic cerebral infarction secondary to DCM was strongly suspected in both cases.

[Effect of intermittent positive pressure ventilation on life-span and causes of death in Duchenne muscular dystrophy].

We have been introducing the intermittent positive pressure ventilation (IPPV) therapy in Duchenne muscular dystrophy (DMD) since 1990. Then, the changes of life-span and causes of mortality by IPPV were investigated in this study. The subjects were 157 patients of long-term followed up DMD in our hospital. The Kaplan-Meier's survival curve of 73 IPPV treated patients showed a median survival time of 31.0 years of age, whereas that of 20.4 years in 84 patients not treated by IPPV. The actual mean age of death in 29 IPPV treated patients was 25.68 +/- 5.18 years-old (M +/- SD), which was significantly higher than that in 74 patients with not-IPPV treated of 19.76 +/- 3.47. The IPPV treatment changed the major causes of death; 59.5% to 3.5% for respiratory failure, 12.2% to 37.9% for cardiac failure, and 0% to 10.3% for repiratory trouble. There were certain number of patients who died of repiratory infection, respiratory tract disorder, digestive organ disorders and sudden death. Thus, IPPV therapy is significantly effective for prolongation of life-span in DMD, and it seems to be necessary to establish the treatment strategy for cardiac failure and other potentially fatal complications.

[A patient with limb girdle muscular dystrophy type 2B (LGMD2B) manifesting cardiomyopathy].

A 57-year-old woman first noticed difficulty in walking at the age of 34 years, and since then muscle wasting and weakness in the lower limbs and proximal portion of the upper limbs had progressed slowly. Serum CK was elevated. Immunohistochemical study of the biceps brachii muscle showed deficiency of dysferlin in sarcolemma, and the dysferlin gene analysis disclosed 3370 G-->T missense mutation. These findings led us to diagnose her as LGMD2B. Moreover echocardiogram revealed ventricular enlargement and diffuse hypokinesia suggesting secondary cardiomyopathy atributable to muscular dystrophy. Careful cardiac monitoring should be carried out in dysferlinopathy patients.