Katsunobu Yoshioka

Radiosurgery for nonfunctioning pituitary adenomas.

OBJECTIVE:We evaluated the effectiveness of gamma knife radiosurgery in the treatment of nonfunctioning pituitary adenomas. METHODS:Between January 1994 and December 1999, we treated 34 patients with nonfunctioning pituitary adenomas. Thirty-one of these patients were followed for more than 30 months. Their mean age was 52.9 years. All patients underwent resection before radiosurgery. In four patients, treatment was performed with staged radiosurgery. The treatment volume was 0.7 to 36.2 cm3 (median, 2.5 cm3). The treatment dose ranged from 8 to 20 Gy (median, 14.0 Gy) to the tumor margin. In 15 patients (48.4%), the tumor either compressed or was attached to the optic apparatus. The maximum dose to the optic apparatus was from 2 to 11 Gy (median, 8 Gy). RESULTS:Patients were followed for 30 to 108 months (median, 59.8 mo). The tumor size decreased in 18 patients (58.1%), remained unchanged in 9 patients (29.0%), and increased in four patients (12.9%). The 5-year actual tumor growth control rate was 93%. Among patients with tumor growth, two cases were secondary to cyst formation. Two patients (6.5%) required adrenal and thyroid hormonal replacement during the follow-up period after radiosurgery because of radiation-induced endocrinopathy. None of the patients sustained new cranial nerve deficits, which included optic neuropathy. CONCLUSION:In this series, radiosurgery had a high tumor growth control rate during the long-term follow-up period. Furthermore, we observed a low morbidity rate, with endocrinopathies and optic neuropathies. This low rate included even patients in whom the tumor compressed or was attached to the optic apparatus. We emphasize the necessity of long-term follow-up to evaluate late complications.

Sodium Sensitivity of Blood Pressure Appearing Before Hypertension and Related to Histological Damage in Immunoglobulin A Nephropathy

Abstract—Patients with renal parenchymal disease exhibit sodium-sensitive hypertension. We examined patients with immunoglobulin A (IgA) nephropathy to determine whether this sensitivity appears before hypertension begins and whether this sensitivity is related to histological damage. Thirty-eight patients with IgA nephropathy followed a diet with an ordinary sodium level for 1 week and a sodium-restricted diet for 1 week, in random order, and were divided into 3 groups by their systemic blood pressure on the diet with an ordinary sodium level (optimal, <120/<80 mm Hg, n=15; normal to high-normal, 120 to 139/80 to 89 mm Hg, n=18; hypertensive, ≥140/≥90 mm Hg, n=5). The sodium sensitivity index was calculated as the reciprocal of the slope of the pressure-natriuresis curve drawn by linkage of 2 datum points obtained during the different diets. The scores for glomerulosclerosis and tubulointerstitial damage were evaluated semiquantitatively. The sensitivity index, glomerulosclerosis score, and score for tubulointerstitial damage were higher in patients with normal to high-normal blood pressure or hypertension than in patients with optimal pressure. The sensitivity index was significantly correlated with glomerulosclerosis (P =0.001) and tubulointerstitial damage (P =0.002). In patients with normal to high-normal pressure, sodium restriction lowered blood pressure to the optimal range and decreased proteinuria. In patients with IgA nephropathy, sodium sensitivity of blood pressure related to renal histological damage appears before hypertension.

Relationship of renal histological damage to glomerular hypertension in patients with immunoglobulin A nephropathy

OBJECTIVE Studies of experimental animals show glomerular hypertension to be important in the progression of glomerular disease. We evaluated this connection clinically by examining the relationship between glomerular hemodynamics and histological changes in patients with immunoglobulin (Ig)A nephropathy. METHODS The subjects were 23 patients with IgA nephropathy. All patients underwent renal biopsies. Glomerular hemodynamics, in terms of glomerular capillary hydraulic pressure (PGC) and the whole-kidney ultrafiltration coefficient, were calculated from the renal clearance, plasma total protein concentration, and pressure-natriuresis relationship. The severity of glomerulosclerosis, tubulointerstitial damage and mesangial matrix expansion was evaluated semiquantitatively. RESULTS PGC ranged from 33-69 mm Hg, and the mean arterial pressure (MAP) from 79-112 mm Hg. Their correlation was not significant (r= 0.29, P= 0.18). PGC was significantly correlated with the glomerulosclerosis score, and also with the score for tubulointerstitial damage (r= 0.65, P < 0.001 and rs = 0.59, P = 0.007, respectively), but not with the score for mesangial matrix expansion (r= 0.08, P= 0.72). MAP was significantly correlated only with the score for tubulointerstitial damage (rs = 0.63, P = 0.004). In multiple linear regression analysis of the histological changes and hemodynamics, the glomerulosclerosis score and the score for tubulointerstitial damage were correlated with PGC, but not with MAP. CONCLUSION These clinical results support the speculation that glomerular hypertension is involved in the glomerulosclerosis and tubulointerstitial damage that occurs in IgA nephropathy.

Reversible posterior leukoencephalopathy syndrome : a possible manifestation of Wegener's granulomatosis-mediated endothelial injury

We present the case of a 15-year-old girl who had Wegener’s granulomatosis with severe intestinal involvement. During the clinical course, she developed generalized seizures and was diagnosed with reversible posterior leukoencephalopathy syndrome (RPLS). Plasma exchange combined with steroid pulse therapy was initiated and showed marked improvement. This is one of the few cases of RPLS without severe hypertension or renal failure, suggesting that RPLS is likely to be a manifestation of Wegener’s granulomatosis-mediated endothelial injury.

Clinical efficacy of insulin-like growth factor-1 in a patient with autoantibodies to insulin receptors: a case report.

The type B insulin-resistance syndrome is characterized by the presence of anti-insulin receptor antibodies that cause severe insulin resistance. Treatments including steroids, cyclophosphamide, plasmapheresis, or insulin-like growth factor-1 (IGF-1) are chosen according to severity of insulin resistance. We describe a patient with type B insulin resistance syndrome who was treated successfully with human recombinant (hr) IGF-1, although this treatment provoked a severe allergic reaction. An elderly man with impaired glucose tolerance and unpredictable hypoglycemic episodes which were gradually worsening increased in hemoglobin (Hb)A1c concentration from 6.5 to 13.4%. His fasting and postprandial hyperglycemia were associated with severe hyperinsulinemia. The patient was diagnosed with type B insulin-resistance syndrome by the presence of anti-insulin receptor antibodies. Double-filtration plasmapheresis, plasma exchange, and immunosuppressive therapy with cyclophosphamide and cyclosporin all failed to suppress anti-insulin receptor antibodies more than transiently. When we attempted the treatment by daily administration of hrIGF-1, fasting and postprandial plasma glucose concentrations became normal and HbA1c levels decreased to 7.1% over 2 months, until on one occasion administration resulted in anaphylaxis. After the patient became stable, desensitization therapy was performed successfully, and hrIGF-1 could be administered again with the plasma glucose returning. We concluded that IGF-1 therapy was an effective treatment choice for type B insulin-resistance syndrome in cases whose plasma exchange and immunosuppressive therapy have failed.

Tubulointerstitial nephritis and uveitis (TINU) syndrome caused by the Chinese herb ''Goreisan''

A 58-year-old man was admitted to our hospital complaining of fever and arthralgia. His clinical course and marked ciliary hyperemia led us to suspect tubulointestinal nephritis and uveitis (TINU) syndrome, which was confirmed ophthalmologically and by renal biopsy. Results of a drug-induced lymphocyte-stimulating test were positive for the Chinese herb “Goreisan.” This is the first case in which the use of “Goreisan” was causally related to TINU syndrome.

Glomerular Charge and Size Selectivity Assessed by Changes in Salt Intake in Type 2 Diabetic Patients

OBJECTIVE To evaluate glomerular charge selectivity in patients with type 2 diabetes, we studied changes in fractional clearance of proteins with different sizes and charges when patients were placed on two diets with different salt contents. RESEARCH DESIGN AND METHODS Nineteen patients with type 2 diabetes and normoalbuminuria (<20 μg/min, n = 8), microalbuminuria (20–100 μg/min, n = 7), or advanced albuminuria (>100 ug/min, n = 4) were placed on a low-salt diet (85 mEq of sodium daily) or a high-salt diet (255 mEq of sodium daily) for 1 week, and then on the other diet, in random order. Fractional clearances of albumin and immunoglobulin G (IgG) were calculated on the last 3 days of each diet. RESULTS In patients with normoalbuminuria, the high-salt diet increased the fractional clearance of IgG, which is electrically neutral, but the fractional clearance of albumin, which is anionic, was unaltered, suggesting that the pore charge of the glomerular barrier was unaffected. However, in patients with microalbuminuria, the high-salt diet increased the fractional clearances of IgG and albumin equally, indicating some neutralization of the pore charge. Fractional clearance of IgG in these first two groups was similar when salt intake was low, so pore size was the same in these groups. In patients with advanced albuminuria, fractional clearance of IgG was higher than in the other groups, indicating that size selectivity had worsened. CONCLUSIONS In type 2 diabetic patients, charge selectivity is lost before size selectivity as diabetic nephropathy progresses.

Glycemic response during exercise after administration of insulin lispro compared with that after administration of regular human insulin.

To examine the glycemic response during exercise after administration of short-acting insulin lispro, we compared changes in plasma glucose concentrations during exercise performed by patients with diabetes after the administration of either insulin lispro or regular human insulin. Seven patients with diabetes (two with type 1 and five with type 2) participated in this study. Each of the insulin-depleted subjects received the same number of units of either insulin lispro or regular human insulin, delivered subcutaneously to the abdomen. The next day, each subject received a similar injection of the solution not previously administered. After each injection, the subjects were fed a standard meal of approximately 9 kcal/kg body weight. One hour after eating the test meal, the subjects performed 30 min of cycle ergometer exercise at 50% maximal oxygen uptake. Plasma glucose, insulin, glucagon, growth hormone (GH), and catecholamine concentrations were then measured at specific intervals. Insulin concentrations were higher and peaked earlier after administration of insulin lispro than after administration of regular human insulin. The length of time, needed to reach minimum plasma glucose concentration after exercise was begun, was significantly shorter after administration of insulin lispro, and the percentage of plasma glucose decrease induced by exercise relative to the peak concentration was significantly greater. No differences were found in the concentration changes of counterregulatory hormones between the insulin lispro data and the regular human insulin data. Compared with regular human insulin, insulin lispro induces a more rapid and greater decrease in plasma glucose concentration during exercise because of its faster absorption.

Usefulness of a semi-quantitative procalcitonin test and the A-DROP Japanese prognostic scale for predicting mortality among adults hospitalized with community-acquired pneumonia.

Background and objective:  The solid‐phase immunoassay, semi‐quantitative procalcitonin (PCT) test (B R A H M S PCT‐Q) can be used to rapidly categorize PCT levels into four grades. However, the usefulness of this kit for determining the prognosis of adult patients with community‐acquired pneumonia (CAP) is unclear.

Post-transplant diabetes with anti-glutamic acid decarboxylase antibody during tacrolimus therapy.

A 54-year-old man undergoing hemodialysis because of end-stage renal failure was transplanted with a cadaver kidney in November 1997. He had no history of diabetes. Tacrolimus was used as the primary immunosuppressant. Three weeks after transplantation, he developed insulin-requiring diabetes mellitus. Anti-glutamic acid decarboxylase antibody was not detected on the third post-operative day, but appeared 4 weeks after transplantation. The recipient had DNA haplotypes that indicated susceptibility to Type 1 diabetes in Japanese subjects. Immunosuppressive therapy was changed from tacrolimus to cyclosporin. Thereafter, titer of anti-glutamic acid decarboxylase antibody disappeared and the patients insulin requirement was notably reduced. The mechanism underlying the development of diabetes in this case appears to be, in part, direct beta-cell toxicity due to tacrolimus therapy, resulting in secondary beta-cell autoimmunity. This case suggests that tacrolimus therapy after transplantation should be used with caution in patients with genetic susceptibility to Type 1 diabetes.