Role of HCN4 channel in preventing ventricular arrhythmia.

Bradycardia is a trigger of ventricular arrhythmias in patients with arrhythmia including Brugada syndrome and long QT syndrome. The HCN4 channel controls the heart rate, and its mutations predispose to inherited sick sinus syndrome and long QT syndrome associated with bradycardia. We found a 4 base-insertion at the splice donor site of the HCN4 gene in a patient with idiopathic ventricular tachycardia, which was supposed to generate a truncated channel. To investigate the role of the HCN4 channel in ventricular arrhythmia, we introduced a ventricular action potential of I(f) channel produced by HCN4 in a computer simulation model and found that the I(f) channel generated a leaky outward current during the plateau phase of ventricular action potential. Currents through the I(f) channel were suggested to contribute to the shortening of the action potential duration and the prevention of early after-depolarization in bradycardia. These observations suggested that the HCN4 channel played a preventive role in triggering bradycardia-induced ventricular arrhythmias.

Severe abdominal pain associated with allergic reaction to nafamostat mesilate in a chronic hemodialysis patient.

A 33-year-old woman was referred from an outside dialysis clinic to our hospital because of severe abdominal pain during hemodialysis. She had been on chronic hemodialysis for the past 11 years due to chronic glomerulonephritis. Nafamostat mesilate was used as an anticoagulant for hemodialysis, because it was during her menstrual period with hypermenorrhea. On admission, she had no abdominal pain or gynecological abnormalities. On the second day, she had similar abdominal pain during hemodialysis with nafamostat mesilate in our dialysis unit. The abdominal pain disappeared within 60 minutes after discontinuing the hemodialysis. We re-started dialysis using heparin instead of nafamostat mesilate and she had no symptoms. The titer of total immunoglobulin E was high. The drug lymphocyte stimulation test was positive for nafamostat mesilate and antigen specific immunoglobulin E to nafamostat mesilate was highly positive in her blood. Although an allergic reaction to nafamostat mesilate is a rare complication, it should be one of the differential diagnoses of abdominal pain occurring during hemodialysis.

Increase in pulse pressure relates to diabetes mellitus and low HDL cholesterol, but not to hyperlipidemia in hypertensive patients aged 50 years or older.

Higher pulse pressure is associated with higher cardiovascular risk. We investigated the relationship between pulse pressure and known metabolic risk factors in hypertensive patients who had not experienced stroke or myocardial infarction. In a multicenter cross-sectional survey made in 1995, we registered 939 hypertensive patients aged > or = 50 years. Of these, 734 had never experienced stroke or myocardial infarction. We divided these 734 patients into two groups based on the value of their pulse pressures: 396 patients with a pulse pressure > or = 60 mmHg, and 338 patients with a pulse pressure<60 mmHg. The average pulse pressure value was 72 +/- 12 mmHg in the former group, and 49 +/- 8 mmHg in the latter group. The former group exhibited advanced age, a higher women-to-men ratio, lower high-density lipoprotein (HDL) cholesterol, and higher systolic and lower diastolic blood pressure. Diabetes mellitus (DM) and left ventricular hypertrophy were more frequently noticed in the former group than in the latter group. The prevalence of hyperlipidemia, however, was similar in the two groups. The association of pulse pressure with DM and low HDL cholesterol was statistically significant by multiple logistic analysis adjusted for age, sex, and other known cardiovascular risk factors. In conclusion, pulse pressure increases with advancing age. DM made a substantially larger contribution to the increase in pulse pressure than hyperlipidemia.

End-stage renal disease associated with familial Mediterranean fever.

A 39-year-old man had been suffering from periodic fever since childhood. He was started on hemodialysis due to secondary amyloidosis on December 2000. The patient was believed to have Familial Mediterranean fever (FMF) because of recurrent fever with peritonitis, arthritis and inflammatory changes and secondary amyloidosis in his kidneys, heart and colon. No other family member had recurrent fever. IL-6, TNF, and dopamine beta-hydroxylase were not increased in the febril phase. The patient was homozygous for the M6941 mutation. We report the first Japanese case of FMF associated with amyloidosis and confirmed by a gene mutation.

A patient with adult-onset type II citrullinemia on long-term hemodialysis: reversal of clinical symptoms and brain MRI findings.

A 40-year-old woman was referred for several episodes of coma lasting from 2 hours to 2 days. She had been on maintenance hemodialysis for polycystic kidney disease for 9 months. Laboratory findings showed high serum levels of ammonia and citrulline, and a diagnosis of adult-onset type II citrullinemia was made. Multiple areas of focal brain edema were shown by magnetic resonance imaging. The clinical manifestations of coma and abnormal behavior were resolved with intensified dialysis (ie, four 5-hour sessions per week with glycerol and continuous ambulatory peritoneal dialysis). No abnormal shadow was present on follow-up magnetic resonance imaging. Such intensified dialysis therapy may be effective for adult-onset type II citrullinemia and may be applicable even in patients who do not have end-stage renal disease if liver transplant is not an option.

[A case of hemodynamic brain infarction with postprandial hypotension].

A 76-year-old man with left internal carotid artery occlusion developed a progressing right hemiparesis. Brain MRI presented reinfarctions in the left anterior border zone and terminal zone in the left deep white matter. Ambulatory blood pressure monitoring showed a decrease in systolic blood pressure by more than 20 mmHg one hour after starting meals, which is considered as postprandial hypotension. The recurrent stroke occurred probably by a hemodynamic mechanism with the presence of internal carotid artery occlusion and postprandial hypotension. Administration of voglibose, an alpha-glucosidase inhibitor, improved postprandial hypotension. In patients with severe carotid or intracranial artery disease, the postprandial hypotension should be carefully monitored for prevention of hemodynamic brain ischemia.