Type B insulin resistance syndrome with systemic lupus erythematosus.

Type B insulin resistance syndrome is a rare disease. Auto-antibodies to the insulin receptor frequently appear in the case of systemic lupus erythematosus (SLE). We report herein a case of a 56-year-old man who had presented discoid skin lesions since 1990. He was admitted to the hospital because of unconsciousness and severe hypoglycemia in 2006, and was diagnosed as having Type B insulin resistance syndrome with the presence of insulin receptor antibody. He had frequently repeated hypoglycemic and hyperglycemic episodes in spite of treatment with prednisolone (5 - 10 mg/day), and mild proteinuria of 1.5 g/day was observed. His laboratory findings on admission revealed pancytopenia and positive titer for antinuclear antibody (ANA). From these findings and his past history of skin lesions, we diagnosed him as SLE. We performed renal biopsy and his histological diagnosis was lupus nephritis Class 5 with the findings of podocytic shedding. Prednisolone dosage was increased from 10 to 60 mg/day. Thereafter, his glucose metabolism improved and proteinuria disappeared. The dose of prednisolone was tapered to 30 mg/day without recurrence of hypoglycemia and proteinuria. Early treatment with prednisolone might ameliorate proteinuria and insulin resistance. We experienced a rare case of Type B insulin resistance syndrome with increased activity of SLE, complicated with lupus nephritis. It appears that Type B insulin resistance syndrome should be suspected in differential diagnosis of hypoglycemia in SLE patients.

Association of endothelial nitric oxide synthase Glu298Asp polymorphism with end-stage renal disease.

BACKGROUND: Impairment of nitric oxide generation caused by gene polymorphism is considered as a major factor in the deterioration of progressive renal disease, including diabetic nephropathy and hypertension. The aim of the present study was to examine the Glu298Asp polymorphism of endothelial nitric oxide synthase (eNOS) in patients with end-stage renal disease (ESRD). METHODS: The Glu298Asp polymorphism in exon 7 was determined in 100 ESRD patients who were maintained on hemodialysis at Dr. Soetomo Hospital, Surabaya, Indonesia, and in a control group of 100 unrelated healthy individuals. In the patient group, 39 patients had Type 2 diabetes mellitus (DM), 44 hypertension (HT) and 17 miscellaneous conditions. The mean length of time from onset of ESRD to the start of this study was 24.37 +/- 32.37 months (Mean +/- SD). RESULTS: The positivity of Glu298Asp in the ESRD group was significantly higher than that in the control group (p < 0.0001). The odds ratio for this group was 4.57 (95% confidence interval 2.52 - 8.31). The positivity of 298Asp in Type 2 DM ESRD with subgroup was significantly higher than that in healthy controls (p < 0.0001). The positivity of 298Asp in the subgroup of patients with HT-derived ESRD was also significantly higher (males p < 0.036, females p < 0.005) than that in healthy control group. Homozygotes with glutamate to aspartate substitution at nucleotide position 7702 showed a single band at 457 bp. CONCLUSION: It appears that Glu298Asp may be a predisposing factor in DM-derived and HT-derived ESRD.

Improvement of peritoneal calcification after parathyroidectomy in a peritoneal dialysis patient.

Peritoneal calcification is one of the complications of peritoneal dialysis (PD). It can become serious, leading to severe abdominal pain and even death. Possible mediators of peritoneal calcification in PD patients are assumed to include acetate buffer, overdosage of vitamin D, repeated peritonitis, hypertonic dialysate, calciphylaxis and secondary hyperparathyroidism (SHPT). However, the mechanism and treatment of peritoneal calcification are controversial. Few reports have appeared on improvement of peritoneal calcification after parathyroidectomy (PTX) for SHPT of long duration. We report herein the case of a 48-year-old man on dialysis for 17 years including PD for 14 years. In 1989, he was admitted to hospital because of end-stage renal disease (ESRD), and started treatment with PD. Abdominal computed tomography (CT) first showed peritoneal calcification in August 2002. Peritoneal calcification did not improve despite conventional treatment including discontinuation of PD, control of calcium phosphate product to less than 55 mg2/dl2, removal of the peritoneal catheter and empirical prednisolone (PSL) usage. The intact parathyroid hormone (i-PTH) level was increased over 1,000 pg/ml and extra-osseous calcification occurred. Total PTX was performed in November 2004. Postoperatively, the i-PTH level decreased immediately and calcium phosphate product was maintained in the reference range. Abdominal CT after PTX showed improvement of peritoneal calcification in September 2005. It appeared that PTX could be used to treat patients with persistent peritoneal calcification not responding to conventional treatment. It was postulated that SHPT might play a crucial role in accelerating peritoneal calcification in PD patients.

M-cadherin, a candidate gene for type 2 diabetes and related phenotypes in a KK/Ta mouse model.

The KK/Ta strain serves as a suitable polygenic mouse model for type 2 diabetes associated with fasting hyperglycaemia, glucose intolerance, hyperinsulinaemia, mild obesity and dyslipidaemia. Recently, we reported the susceptibility loci contributing to type 2 diabetes and related phenotypes in KK/Ta mice. In the present study, to identify susceptibility genes for type 2 diabetes and related disorders, GeneChip Expression Analysis was employed to survey the gene expression profile in the liver of KK/Ta and BALB/c mice. M-cadherin, a calciumdependent intercellular adhesion molecule, showed increased expression in the liver of KK/Ta mice, and sequence analysis revealed three missense mutations. The relationship between these polymorphisms and various phenotypes in 208 KK/Ta x (BALB/c x KK/Ta) F1 backcross mice was analysed. Statistical analysis revealed that M-cadherin exhibits linkage to levels of triglyceride and insulin in sera, glucose tolerance and body weight. Although it has been postulated that M-cadherin may be important for the regulation of morphogenesis of skeletal muscle cells, these results suggest that M-cadherin may influence hypertriglyceridaemia, glucose intolerance, hyperinsulinaemia and obesity in KK/Ta mice.

Clinical application of evoked spinal cord potentials elicited by direct stimulation of the cord during temporary occlusion of the thoracic aorta.

Evoked spinal cord potentials elicited by direct stimulation of the cord were used to monitor spinal cord ischemia in 68 patients undergoing temporary occlusion of the thoracic aorta (29 thoracic nondissecting aortic aneurysms, 9 nondissecting thoracoabdominal aneurysms, and 30 dissecting aneurysms). "Immediate" postoperative paraplegia developed in three patients and "immediate" paraparesis developed in one, whereas "delayed" paraplegia developed in two others. During aortic crossclamping, four response patterns of the spinal cord potentials were obtained: (1) no change (n = 53), (2) change with return (n = 10), (3) change with inconsistent return (n = 2), and (4) change without return (n = 3). Neurologic complications occurred in 2%, 0%, 100% of these groups, respectively. Delayed paraplegia developed on the second postoperative day in only one patient with a false-negative result, and the potentials correlated well with this patient's clinical neurologic recovery. The aortic crossclamp time was significantly longer in the patients with "change with inconsistent return" and "change without return" than in the other two groups (p < 0.01). Femoral artery pressure and the cardiopulmonary bypass flow rate were also significantly lower in these groups than in the other two groups (p < 0.02 and p < 0.01, respectively). We conclude that intraoperative monitoring of direct spinal cord responses is useful for the early detection of spinal cord ischemia for assessing the efficacy of surgical countermeasures.

Surgical treatment of aortic dissection: application of Ivalon sponge to the dissected lumen.

With canine disease models for aortic dissection, we performed comparative evaluations of several surgical procedures for the management of this dissection. From these experimental procedures, we developed a new operative technique, the Ivalon sponge occlusion method, designed to promote thrombus formation and to mesh (organize) effectively with the tissue ingrowth of the peripheral dilated, dissected aortic lumen. The details of the technique are described. It has been used successfully in 12 patients with DeBakey type I and type III aortic dissection. Based on our experimental and clinical evaluations, although the results are preliminary, we believe this operative technique is a simple, effective approach for the management of extended aortic dissection.

An (CA)n dinucleotide repeat polymorphism of the interleukin-6 (IL-6) gene is associated with metacarpal bone mineral density in hemodialysis patients.

Genetic factors may play an important role in the pathogenesis of reduced bone mineral density (BMD). IL-6 is a multifunctional cytokine and a candidate gene for regulation of bone mineral density (BMD). The relationship between a microsatellite polymorphism of the IL-6 gene and metacarpal BMD in Japanese hemodialysis patients was examined. We selected 165 patients (96 males and 69 females) with a mean age of 62.0 +/- 13.7 years (mean +/- standard deviation (SD) in this study. They were dialyzed for an average of 75.8 +/- 60.8 months (mean +/- SD). The microsatellite polymorphism in the IL-6 gene was examined. According to the number of cytosine-adenine repeats, varying from 13 to 18, 6 alleles could be distinguished. Patients were categorized based on the presence or absence of the allele with 126 bp (i.e. 14 CA repeats) (allele A, all others allele O). The frequencies of IL-6 gene genotypes in hemodialysis patients were 16.4% for OO, 52.1% for AO and 31.5% for AA. The BMD score adjusted for age and body weight (Z score) in the AA genotype group (-0.93 +/- 1.17) was significantly lower than that in the OO (-0.09 +/- 1.42, mean +/- SD, p < 0.005) or AO group (-0.48 +/- 1.15, mean +/- SD, p < 0.01). Serum intact PTH in the OO genotype group (79.3 +/- 84.6) was lower than that in the AA (120.8 +/- 113.6, mean +/- SD, p 0.10) or AO group (132.1 +/- 106.5, mean +/- SD, p < 0.05). These results suggest that polymorphism of the IL-6 gene may be a useful marker for reduced BMD.

Association of the DD genotype and development of Japanese type 2 diabetic nephropathy.

We determined the insertion/deletion (I/D) polymorphism of the angiotensin-coverting enzyme (ACE) gene in a multicenter trial of ethnically homogeneous Japanese type 2 diabetes mellitus (DM) patients. All patients (n = 748) were divided into 5 groups as follows: group I (normoalbuminuric patients), group II (microalbuminuric patients), group III (overt albuminuric patients with serum creatinine (s-Cr) levels of less than 1.2 mg/dl), group IV (overt albuminuric patients with s-Cr levels of more than 1.3 mg/dl but excluding hemodialysis patients), and group V (hemodialysis patients). We selected patients with a diabetic duration of more than 15 years in the mild stage (groups I and II), but placed no limits on those in the advanced and end-stages (groups III, IV and V). The frequency of the DD genotype was slightly higher in the advanced and end stages. The frequency of the DD genotype in the mild stage differed from that in the end stage (II/ID/DD 47.8%/41.0%/11.2% vs. 37.0 %/43.3%/19.7% p = 0.07, II + ID/DD 88.8%/11.2% vs. 80.3%/19.7%, p < 0.05). D allele frequency in the mild stage also differed from that in the end stage (I/D 68.3%/31.7% vs. 58.7%/41.3%, p < 0.02). The presence of the DD genotype increased the risk of end-stage renal disease (ESRD) more than that of the other genotypes (odds ratio ID/II = 1.37, 95% CI 0.82-2.27; DD/II = 2.27, 95% CI 1.12-4.61). It appears that the DD genotype is associated with progression of Japanese type 2 diabetic nephropathy.

X-ray study of deformation density and spontaneous polarization in ferroelectric NaNO2

The deformation electron density of ferroelectric sodium nitrite has been determined from X-ray diffraction data at 30 K, using Hirshfeld deformation functions. Owing to the strong correlation between odd terms of the deformation coefficients, constraints were imposed in the refinement. The net charges for Na, N and O atoms were estimated to be 0.27, 0.20 and -0.24 e, respectively. The calculated spontaneous polarization using these net charges and atomic dipole terms, 7.8 microC cm(-2), is much closer to the recently measured value, 12 microC cm-2, as compared with the value calculated from the formal point charges (74 microC cm(-2)).

Modern trends in the management of aortic aneurysms. Review of 450 cases experienced.

Treatment of various aortic aneurysms in 450 cases experienced during the past 25 years was analysed. One hundred and five patients were treated with survival rate of 80.2% in the thoracic aortic aneurysm group, 65 patients with survival rate of 76.9% in the dissected aneurysm of the aorta group, 175 patients with survival rate of 93.1% in the nonruptured abdominal aortic aneurysm group and 37 patients with survival rate of 75.7% in the ruptured abdominal aortic aneurysm group. From 1981 to the present time, considerable improvement of the operative results has been achieved with refinement of cardiovascular adjunctive techniques and operative procedures with careful management of the patients. Survival rates are now reached to 88.7% in the thoracic aortic aneurysm, 81.0% in the dissected aneurysm, 100% in the nonruptured abdominal aortic aneurysm and 81.2% in the ruptured abdominal aortic aneurysm. From the careful analyses of the results, prompt diagnosis, distinct treatment policy, strict operative indication and better surgical procedure are considered to have contributed to these excellent operative results.

[A case of extra-anatomic bypass for ruptured thoracoabdominal aortic aneurysm with tuberculosis].

Now aneurysmectomy and graft replacement is the most popular surgical method of aortic aneurysm, but there are many opinions about surgical methods and assist circulation for emergency operation of ruptured aortic aneurysm. We experienced the case of ruptured thoracoabdominal aortic aneurysm with tuberculosis, and rescued the patient by extra-anatomic bypass (EAB). A 60-year-old woman, who had been treated with tuberculosis for about 40 years, was operated on for cold abscess of her left psoas muscle by other orthopedic surgeons. At that time, massive bleeding happened, and she was transferred to us under diagnosis of ruptured thoracoabdominal aortic aneurysm. EAB, as emergency operation, was done because we considered it was dirty and dangerous to replace the prosthesis beside the abscess. The postoperative course was almost uneventful except the evidence of Gaffky's first stage. We considered EAB was an useful method for emergency cases and some infectious aortic aneurysms.

[Surgical management of congenitally corrected transposition of the great arteries].

From 1962 to 1990, we have experienced 12 patients with congenitally corrected transposition of the great arteries (CTGA). Associated cardiac defects were present in all cases, most frequently ventricular septal defect (100%), and pulmonary stenosis (67%), Palliative procedures were done in 5, corrective operations in 6. One patient underwent corrective procedure 27 years after palliation. The hospital mortality rate was 8% (1/12), and 1 late death (8%) was seen in this series. In most cases, we approached the defect through the mitral valve, and the deLeval method was very useful in placing stitches along the trabecular septum. AV conduction disturbance could be avoided in 5 of 6 patients who underwent the closure of ventricular septal defect. Pulmonary stenosis was relieved by valvotomy and/or infundibulectomy, or implantation of an extracardiac conduit according to their anatomy. Cardiac function of systemic ventricle (morphologic right ventricle) were well preserved in the case undergoing intracardiac repair and also in the palliative cases. Careful observation is needed in these cases.

[Replacement of omniscience mitral valve in suboptimal opening].

This 57-year-old female of MS had been treated by MVR with a 25 mm Omniscience valve on October 26, 1983. She was doing well until November 1984 when she developed general malaise and dyspnea. She was hospitalized again on June 3, 1985. Studies including echocardiogram and cardiac catheterization revealed mitral stenosis. The echocardiogram showed rapid blood stream toward the interventricular septum. The maximum opening angle of the disc was measured 30 degrees on the cine film. The cardiac catheterization showed increased PA and PA wedge pressures. The Omniscience valve was replaced with a 25 mm SJM valve on July 19, 1985. The postoperative course was uneventful. The postoperative echocardiogram and cardiac catheterization showed significant improvements in flow pattern and intracardiac pressure. She is doing well as an instructor of Japanese dancing after discharge from the hospital.

[A case of leukemic lymphoma complicated by M-proteinemia: effectiveness of long-term daily administration of oral low-dose etoposide in continuing remission].

A 51-year-old man was admitted with systemic lymph node adenopathy. Hematological examination on admission revealed leukocytosis, and 35% of leukocytes were classified as pathologically abnormal. Moreover, increases in serum IgM (kappa type) and plasma viscosity were recognized. Following biopsy of the lymph node, a diagnosis of non-Hodgkin's lymphoma (diffuse, mixed type) was made. After the implementation of combination chemotherapy, the results of hematological and physical examinations improved. As the nadir receded, serum IgM increased once more, and nine courses of chemotherapy were necessary. In order to promote steady progress toward discharge, etoposide therapy was instituted. Subsequent low-dose etoposide therapy at 50 mg/day rarely resulted in an increase in serum IgM, subjective or objective adverse effects, except for mild lekopenia. After discharge the patient was placed on intermittent etoposide therapy and remained in a state of remission for approximately 11 months. Fortunately, his rehabilitation was successful, and he returned temporarily to his former position. The 2nd remission has continued for approximately seven months. Consequently, long-term low-dose etoposide therapy is speculated to be a significantly useful therapeutic technique for intractable malignant lymphoma.

Minor gene effect of leptin receptor variant on the body weight in KK/Ta mice.

OBJECTIVE: Leptin is an adipocyte-derived hormone involved in body weight regulation that acts through the leptin receptor. Previous studies exploring potential association between the leptin receptor (Lepr) variant and obesity have reported conflicting results. The objectives of the present study are to evaluate (1) whether the Lepr variant contributes to type 2 diabetes and its related disorders such as obesity and (2) whether the gene interaction between Lepr and Zn-alpha(2) glycoprotein1 (Azgp1) genes is recognized using genetically homogeneous type 2 diabetic KK/Ta mice. METHODS: The levels of leptin (Lep) and Lepr mRNA in adipose tissues and brain were measured by relative quantitative RT-PCR. The levels of leptin protein in sera were measured by enzyme-linked immunosorbent assay. Genotyping of backcross mice was performed using a mismatch primer. RESULTS: Leptin protein and its mRNA levels were increased in KK/Ta mice. Lepr mRNA levels of KK/Ta mice did not differ from those of BALB/c mice. Sequence analysis revealed that the coding region of Lep in KK/Ta mice was identical to that in BALB/c mice. Six nucleotide polymorphisms were observed in the coding region of Lepr. In KK/Ta x (BALB/c x KK/Ta) F1 backcross mice, the Lepr variant of KK/Ta mice failed to alter any of the variables of obesity except for body weight at 20 weeks of age. However, it enhanced the effect of Azgp1 on body weight. CONCLUSION: It is concluded that the Lepr variant contributes to obesity to some degree in KK/Ta mice.