Yasuhisa Wakabayashi

Specific immunoadsorption therapy using a tryptophan column in patients with refractory heart failure due to dilated cardiomyopathy.

Background: Certain cardiac‐specific autoantibodies found in patients with dilated cardiomyopathy (DCM) play a role in mediating myocardial damage and fatal ventricular arrhythmias resulting in sudden cardiac death. Immunoadsorption therapy (IA) is one of the therapeutic tools to remove such autoantibodies. Clinical studies from Germany have shown that nonspecific IA using columns loaded by sheep antihuman IgG or protein A improved hemodynamic data and affected favorably cardiac function and survival in patients with heart failure (HF) due to DCM. The goal of this study is to determine if IA therapy using the high‐profile tryptophan column, which has high affinity for IgG3 subclass, affects favorably cardiac function in patients with severe HF who are refractory to conventional therapy. Methods and Results: IA therapy was conducted in 16 patients with DCM (age 53 ± 4, male 8, New York Heart Association functional class III/IV, mean ejection fraction 18 ± 2%). Study subjects had autoantibodies directed against either β1‐adrenergic or M2‐muscarinic receptors. Plasma brain natriuretic peptide levels were significantly decreased after IA (P = 0.016). Plasma inflammatory cytokines including interleukin‐6 and tumor necrosis factor‐α did not change after each session of IA. Six‐minute walk distance was significantly increased after IA (P = 0.01). Left ventricular ejection fraction increased by 3% 3 months after IA (P = 0.039). Conclusions: Our initial experience demonstrated safety and short‐term efficacy of IA using a new IgG3‐specific tryptophan column for patients with advanced HF due to DCM. Long‐term follow‐up is needed to confirm the effects on cardiac function and morbidity/mortality in such patients. J. Clin. Apheresis, 2011.

Decreased VLDL apoprotein CII/apoprotein CIII ratio may be seen in both normotriglyceridemic and hypertriglyceridemic patients on chronic hemodialysis treatment☆

Pathogenetic factors that may be related to uremic hypertriglyceridemia were studied in 27 patients who had been undergoing chronic hemodialysis treatment for over two years. They were divided into two groups consisting of 14 hypertriglyceridemic (HTG) patients with fasting serum triglycerides (TG) of 170 mg/dL or higher, aged 45 +/- 11 yr (mean +/- SD) and 13 normotriglyceridemics (NTG) with serum TG less than 170 mg/dL aged 42 +/- 9 yr. Serum lipid, lipoprotein [low density lipoprotein (LDL) and very low density lipoprotein (VLDL)] and apoprotein (Apo) levels, as well as ultracentrifugally obtained VLDL apo subfractions and serum carnitine were compared between the two groups, which enabled us to rule out various factors inherent to uremic state and present in both groups. The HTG group of patients, who showed (by definition) significantly elevated TG (300 +/- 167 mg/dL v 123 +/- 30 mg/dL in NTG) and VLDL levels, concomitantly showed significantly increased serum total cholesterol (P less than .001) and LDL (P less than .001), and significantly decreased apo AI/apo B, or an index of risk of atherogenesis (P less than .05). Serum apo CII (7.3 +/- 3.3 mg/dL v 3.6 +/- 1.0 mg/dL in NTG), apo E (4.8 +/- 2.8 mg/dL v 2.9 +/- 1.3 mg/dL) and VLDL/serum apo CII (38 +/- 18 v 22 +/- 12), ie, the amount of VLDL covered by a unit of apo CII, were elevated in the HTG compared with the NTG group of patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Shunt nephritis: histological dynamics following removal of the shunt. Case report and review of the literature.

Diffuse crescentic glomerulonephritis was observed in a 40-year-old male patient who had a ventriculoatrial shunt implanted after a traffic accident 10 years previously. Immediately after treatment with immunosuppressants and plasma pheresis, signs of meningitis and septicemia developed. The responsible organism isolated was Staphylococcus albus. After the shunt was removed, clinical signs and renal function improved, associated with normalization of hypocomplementemia and disappearance of cryoglobulin and circulating immune complexes. Repeat renal biopsy performed 5 months after the removal of the shunt revealed mild mesangial proliferative and sclerotic glomerulonephritis with fibrous crescents. No apparent deposits observed in the initial biopsy were found on ultrastructural and immunofluorescent examinations. The reported cases with serial renal biopsies before and after the removal of the shunt were reviewed.

Activated Charcoal Interrupts Enteroenteric Circulation of Phenobarbital

The possibility of activated charcoal interrupting the enteroenteric circulation of phenobarbital was conducted in rabbits prepared by colectomy biliary drainage to block enterohepatic circulation. Fifty minutes after the administration of phenobarbital IV over ten minutes, activated charcoal (N = 7) or non-adsorbent gel (N = 8) were placed into the intestine at a dose of 4 g/kg. Blood was taken hourly for 5 h from the femoral artery and portal vein for the determination of phenobarbital concentration by the homogeneous enzyme immunoassay. The arterio-portal differences of phenobarbital concentrations were significantly greater in the animals treated with the charcoal at 2, 3 and 4 h after the treatment. There were significantly shorter plasma half lives of phenobarbital in the animals given charcoal (3.8 +/- 0.3 h vs 6.9 +/- 0.9 h, p < .02). This study provided evidence of significant enteroenteric circulation of phenobarbital which can be interrupted by the activated charcoal and removed by the mechanism of intestinal dialysis.

Immunoadsorption therapy for dilated cardiomyopathy using tryptophan column—A prospective, multicenter, randomized, within‐patient and parallel‐group comparative study to evaluate efficacy and safety

Over the past few decades, several cardiac autoantibodies have been reported in sera from patients with dilated cardiomyopathy (DCM). Immunoadsorption (IA) therapy is one of the therapeutic tools to remove such autoantibodies. The objective of this study was to investigate functional effects of IA therapy using a tryptophan column in severe DCM patients. Of 49 patients enrolled, 44 were randomized from 10 sites in Japan. IA therapy was conducted in 40 patients with DCM (refractory to standard therapy for heart failure, New York Heart Association [NYHA] class III/IV, left ventricular ejection fraction [LVEF] <30%). Mean echocardiographic LVEF was significantly improved (23.8 ± 1.3% to 25.9 ± 1.3%, P = 0.0015). However, mean radionuclide LVEF over 3 months of IA therapy was not significantly improved (20.8 ± 1.1% to 21.9 ± 1%, P = 0.0605). The cardiothoracic ratio was also significantly decreased (P = 0.0010). NYHA functional class (P < 0.0001), subjective symptoms assessed by a quality of life questionnaire (P = 0.0022), maximum oxygen consumption (P = 0.0074), and 6‐minute walk distance (P = 0.0050) were improved after IA therapy. Subgroup analysis revealed improvement of echocardiographic LVEF in patients with higher baseline autoantibody scores but not in those with lower scores. IA therapy improved subjective symptoms and exercise capacity in patients with refractory heart failure resulting from DCM. Favorable effect on cardiac function was noted in patients with higher autoantibody scores. J. Clin. Apheresis 31:535–544, 2016.