Bradycardia Is a Specific Phenotype of Catecholaminergic Polymorphic Ventricular Tachycardia Induced by RYR2 Mutations.

Objective Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a lethal inherited disease characterized by ventricular arrhythmias induced by physical exercise or emotional stress. The major cause of CPVT is mutations in RYR2, which encodes the cardiac ryanodine receptor channel. Recent advances in sequencing technology have yielded incidental findings of RYR2 variants in other cardiac diseases. Analyzing the characteristics of RYR2 variants related to CPVT will be useful for differentiation from those related to other cardiac diseases. We examined the phenotypic characteristics of patients with RYR2 variants. Methods Seventy-nine probands carrying RYR2 variants whose diagnoses were either CPVT (n=68) or long QT syndrome (LQTS; n=11) were enrolled. We compared the characteristics of the electrocardiogram (ECG) and the location of the RYR2 mutations-N-terminal (NT), central region (CR) or C-terminal (CT)-between the two patient groups. Results Using the ECGs available from 53 probands before ß-blocker therapies, we analyzed the heart rates (HRs). CPVT probands showed bradycardia more frequently (25/44; 57%) than LQTS probands (1/9; 11%; p=0.024). In CPVT patients, 20 mutations were located in NT, 25 in CR and 23 in CT. In LQTS patients, 5 mutations were located in NT, 2 in CR and 4 in CT. There were no significant differences in the locations of the RYR2 mutations between the phenotypes. Conclusion Bradycardia was highly correlated with the phenotype of CPVT. When a clinically-diagnosed LQTS patient with bradycardia carries an RYR2 mutation, we should be careful to avoid making a misdiagnosis, as the patient may actually have CPVT.

Prevalence of protein-energy wasting (PEW) and evaluation of diagnostic criteria in Japanese maintenance hemodialysis patients.

BACKGROUND AND OBJECTIVES: The International Society of Renal Nutrition and Metabolism (ISRNM) has recently recommended the use of the term "protein-energy wasting" (PEW). PEW is a state of malnutrition with decreased body stores of protein and energy fuel in hemodialysis patients and is known as a risk factor for morbidity and mortality. We examined the prevalence of PEW and the characteristics of PEW patients in a hemodialysis center in Japan. METHODS AND STUDY DESIGN: Fifty-nine outpatients undergoing maintenance hemodialysis at Iga City General Hospital were evaluated. We observed their biochemical data, body composition, dietary intake, and the number of steps prospectively. PEW was defined according to ISRNM criteria. RESULTS: Nine patients (15% of total) were diagnosed as having PEW. Among indicators of PEW criteria, the relevance ratios of "reduced muscle mass" and "unintentional low dietary energy intake" were significantly higher in PEW than in non-PEW. The number of steps was lower, and serum levels of glucose and C-reactive protein were higher in PEW. CONCLUSION: About 15% of Japanese hemodialysis patients are estimated to have PEW. Our results suggested that major contributing factors to PEW were reduced muscle mass, unintentional low dietary energy intake, lower amount of exercise, insulin resistance, and chronic inflammation.

Clinical analysis of longstanding subacute myelo-optico-neuropathy: sequelae of clioquinol at 32 years after its ban.

One thousand and thirty-one longstanding patients with subacute myelo-optico-neuropathy (SMON; 275 males, 756 females; mean age +/- S.D., 72.9 +/- 9.6 years; age at onset 37.6 +/- 9.8 years; duration of illness 35.3 +/- 4.0 years) were examined in 2002, 32 years after banning of clioquinol. At onset, 66.7% of patients were unable to walk, and 4.7% complete blindness. At present time, about 41% of patients were still difficult to walk independently, including 15.8% of completely loss of locomotion. One point six percent of patients were in complete blindness and 5.8% had severe visual impairment. The majority (95.6 - 97.7%) of patients exhibited sensory disturbances including superficial and vibratory sensations and dysesthesia. Dysautonomia was observed as leg hypothermia in 79.8%, urinary incontinence in 60.7%, and bowel disturbance in 95.3%. As complication, high incidence was revealed with cataract (56.2%), hypertension (40.2%), vertebral disease (35.5%), and limb articular disease (31.5%). These results indicate the serious sequelae of clioquinol intoxication, SMON.