Evaluation of diabetic neuropathy using the tone-entropy analysis, a noninvasive method to estimate the autonomic nervous function.

It is clinically important to diagnose diabetic neuropathy at the early stage. In this study, the toneentropy analysis of electrocardiogram was applied to diabetic patients to evaluate its usability in the screening of diabetic neuropathy. Consecutive 102 diabetic patients were invited to the study. Electrocardiogram was obtained and analyzed for the tone and the entropy using an original software developed previously. Nerve conduction velocity (NCV) was examined on the median, the posterior tibial and the sural nerves. Patients were divided into quartile subpopulations according to the NCVs in the analysis. Both the tone and the entropy significantly correlated with NCVs, while coefficient of variation in R-R intervals did not show a significant correlation. The correlation was most significant between the entropy and the NCV on the sural nerve. When a multivariate analysis (ordinary regression) was applied to examine independent effects of the factors influencing the NCV on the sural nerve, the entropy was the most potent independent factor (beta = 1.14 +/- 0.32, P = 0.0004) along with sex (beta = 0.43 +/- 0.19, P = 0.02) and BMI (beta = 0.11 +/- 0.05, P = 0.04). The tone-entropy analysis on electrocardiogram may be a promising non-invasive screening method for diabetic neuropathy.

Primary pulmonary squamous cell carcinoma associated with elevated IL-6, leukocytosis, hypercalcemia, phagocytosis, reactive lymphadenopathy and glomerular mesangial cell proliferation via the production of PTH-rP and G-CSF.

We report an autopsied case of a 74-year-old man with primary pulmonary squamous cell carcinoma (SCC) associated with leukocytosis, hypercalcemia, phagocytosis in the bone marrow, reactive lymphadenopathy and mesangial cell proliferation in the glomerulus. Laboratory examination revealed increased serum levels of parathyroid hormone-related peptide (PTH-rP), granulocyte colony stimulating factor (G-CSF), interleukin-6 (IL-6) and soluble interleukin 2 receptor (s-IL2R). An autopsy showed moderately differentiated SCC at the left lower lobe of the lung, of which tumor cells distinctly showed cytoplasmic immunoreactivity to anti-G-CSF and anti-PTH-rP antibodies. Thus, pulmonary SCC seemed to produce both G-CSF and PTH-rP, causing leukocytosis, hypercalcemia, and IL-6 production from the bone. IL-6 also might have stimulated the proliferation of SCC and glomerular mesangial cells, and induced phagocytosis, reactive lymphadenopathy and hepatosplenomegaly by interacting with the mononuclear phagocytic system.

MPO-ANCA-positive IgA nephropathy successfully treated with tonsillectomy.

A 20-year-old Japanese woman was admitted to a hospital because of gross hematuria. She was diagnosed with IgA nephropathy with a poor prognosis, based on the formation of many crescents in the glomerulus and monocyte infiltration in the interstitium in a renal biopsy specimen in February 2003. Myeloperoxidase (MPO)-antineutrophil cytoplasmic antibody (ANCA) was not identified at that time. After treatment with high-dose steroid pulse therapy and heparin/warfarin, her urinary protein improved, to 0.5 g/day. However, 1 year after the steroid pulse therapy, urinary protein was increased to 1.2 g/day, associated with repeated episodes of tonsillitis. A second renal biopsy was performed, and showed an improving tendency, compared to the findings of the previous one, although some crescent formation and adhesions of Bowman's capsule remained. Interestingly, MPO-ANCA was positive in the serological examination done at this time. One month and a half after the second renal biopsy, she had a tonsillectomy, followed by a regimen of 5 mg oral prednisolone daily, in order to prevent the progression of IgA nephropathy. After the tonsillectomy, her urinary protein level was markedly improved, at 0.14 g/day. Her creatinine clearance was ameliorated, at 102 ml/min, and in addition, MPO-ANCA had disappeared. This case suggests that an inflammation such as tonsillitis may be associated not only with the activity of IgA nephropathy but also with the production of MPO-ANCA.

Increased resting metabolic rate in patients with type 2 diabetes mellitus accompanied by advanced diabetic nephropathy.

Thirty-three patients with type 2 diabetes mellitus (16 men, 17 women) were divided into 3 groups based on urinary excretion of albumin (U-Alb)--group A: U-Alb < 30 mg/d; group B: 30 mg/d < or = U-Alb < or = 300 mg/d; and group C: 300 mg/d < U-Alb. Serum creatinine levels were lower than 2.0 mg/dL in all the subjects. There was no difference in age, sex, therapy, body weight, body mass index (BMI), lean body mass (LBM), or hemoglobin A(1c) (HbA(1c)) levels among the 3 groups. Resting metabolic rate (RMR) (kJ/h/m(2)) and adjusted RMR for lean body mass (kJ/h/m(2)) were significantly increased in group C compared with groups A and B. Hb concentrations, serum albumin levels, and creatinine clearance were much lower in group C than in groups A and B (P < .001). There were no difference in serum urea nitrogen, total cholesterol, cholinesterase and free thyroxine, or plasma insulin-like growth factor I (IGF-I) levels among the 3 groups. Linear regression analysis revealed an inverse correlation between RMR and serum albumin levels, correlation between RMR and U-Alb, and inverse correlation between RMR and Hb concentrations, respectively, in these patients. In conclusion, RMR in diabetic patients correlated directly with U-Alb and inversely with serum albumin and Hb concentration. These findings suggest that RMR is related with urinary albumin loss and anemia in patients with type 2 diabetes mellitus accompanied by diabetic nephropathy.

Relationship between visceral fat accumulation and anti-lipolytic action of insulin in patients with type 2 diabetes mellitus.

Insulin resistance is closely related to developing type 2 diabetes mellitus. Visceral fat accumulation is associated with insulin resistance, which affects the free fatty acid (FFA) metabolism. We investigated the interactions among visceral fat accumulation, FFA metabolism and insulin resistance in 20 patients with type 2 diabetes mellitus, including 11 obese and 9 non-obese subjects. Body fat distribution was estimated by measuring the areas of both subcutaneous and visceral fat mass on abdominal computed tomography at the umbilical level. Glucose infusion rate (GIR) and plasma FFA responses to insulin were determined as an index of insulin resistance and anti-lipolytic action, respectively, in a euglycemic hyperinsulinemic clamp study. There was an inverse correlation between GIR and insulin-induced decrease in plasma FFA in all diabetic patients (r = -0.652, P < 0.01). Visceral fat mass area was well correlated with GIR (r = -0.583, P < 0.01) and insulin-induced decrease in plasma FFA (r = 0.724, P < 0.001), whereas subcutaneous fat mass area was not correlated either with GIR or plasma FFA decrease. These findings suggest that visceral fat accumulation results in increasing the resistance against the anti-lipolytic action of insulin, and that FFA metabolism is closely related with glucose utilization in patients with type 2 diabetes mellitus.

[A case of large-cell lung cancer successfully treated with docetaxel in combination with carboplatin and radiotherapy].

A 64-year-old male was referred to our hospital in September, 2000 for further examination of an abnormal chest shadow discovered in a regular health check-up. Chest X-P and CT revealed a large tumor in the left upper lobe, in association with hilar lymphadenopathy and costal invasion. Serum CEA was increased, and lung biopsy revealed a large-cell carcinoma. We performed chemoradiotherapy before surgery. Radiation (total 48 Gy) and 3 courses of chemotherapy with docetaxel (60 mg/m2) in combination with carboplatin (AUC = 6,600 mg) resulted in a remarkable reduction in the size of the mass, to less than 50%, and normalized serum CEA. Left upper lobectomy, lymphadenectomy and costectomy were performed. However, no tumor cells were detectable in the ablative specimen pathologically. These findings suggest the efficacy of chemoradiotherapy including docetaxel with carboplatin in patients with large-cell lung cancer.

Regulation of human growth hormone secretion and its disorders.

Growth hormone (GH) secretion from anterior pituitary is regulated by the hypothalamus and the mediators of GH actions. Major regulatory factors include GH releasing hormone (GHRH), somatostatin (SRIF), GH releasing peptide (ghrerin) and insulin-like growth factor (IGF-I). The principal physiological regulation mechanisms of GH secretion are neural endogenous rhythm, sleep, stress, exercise, and nutritional and metabolic signals. GH deficiency results from various hereditary or acquired causes, which may be isolated or combined with other pituitary hormone deficiencies. GH deficiency can be treated with recombinant human GH, which results in accelerating growth in children and normalization of intermediary metabolism in adults. GH hypersecretion mostly results from a pituitary tumor and causes acromegaly or gigantism. Hypersecretion of GH can be treated by transshenoidal surgery. Medical treatment with octreotide and analogs is also effective to reduce GH secretion in combination with or without the surgery.

A case of autoimmune hypophysitis associated with Graves' disease.

In a 76-year-old woman with hyperthyroidism, hyperprolactinemia and thickening of the pituitary stalk on magnetic resonance imaging (MRI) was presented. Thyroid stimulating antibody (TSAb) was positive and anti-pituitary antibodies against 49 and 68 kD human anterior pituitary membrane antigens were detected immunologically. Secretion of pituitary hormones was almost normal except for suppressed TSH and hyperprolactinemia. As autoimmune etiologies were likely involved in the disorders, autoimmune hypophysitis associated with Graves' disease was arrived at as the plausible diagnosis.