Relation between soluble interleukin 2 receptor and clinical findings in patients with systemic lupus erythematosus.

The concentration of soluble interleukin 2 receptor (IL-2R) was determined in the serum of 54 patients with systemic lupus erythematosus (SLE) by an enzyme linked immunosorbent assay (ELISA) using two monoclonal antibodies with the IL-2R. Concentrations of soluble IL-2R in the serum of the patients with SLE (study group) were significantly higher than in 20 normal subjects (control group). The relation between concentrations of soluble IL-2R and clinical findings was investigated. The concentration of soluble IL-2R showed no particular relation with the clinical manifestations and did not correlate with the level of anti-DNA antibody or CH50. Significant correlation between the concentration of soluble IL-2R and disease activity did exist, however. Furthermore, the concentration of soluble IL-2R in some cases changed simultaneously with the disease activity. Thus the concentration of soluble IL-2R may serve as a new clinical indicator of disease activity in patients with SLE.     

Effect of interferon treatment on serum 2',5'-oligoadenylate synthetase levels in hepatitis C-infected patients

Interferon (IFN) is widely used for patients with hepatitis C. Less than half of treated patients respond to IFN therapy, however, and increased resistance to IFN is particularly observed in genotype 1b patients. Recently, genotype 1b patients with the wild type sequence in the NS5A gene were shown to be resistant to therapy, suggesting that the NS5A protein may be involved to IFN resistance. Thus, we investigated the serum 2',5'-oligoadenylate synthetase (2',5'-OAS) levels before and during IFN treatment. In addition, other biochemical markers and NS5A mutations were also examined in 30 HCV genotype 1b-positive patients. Before IFN treatment, 2',5'-OAS activity in sera was significantly lower in wild type patients than in mutant type patients. All patients were subsequently enrolled in IFN therapy, and 2',5'-OAS activity was elevated both in wild and mutant type patients, irrespective of the number of mutations in NS5A. Logistic regression analysis revealed that clearance of serum HCV RNA was independently related to the pretreatment viral load and NS5A mutations, but not to serum 2',5'-OAS activity. We concluded that the NS5A protein, that is associated with the outcome of IFN therapy, affects the kinetics of IFN-induced molecules, such as 2', 5'-OAS. 2',5'-OAS activity does not, however, seem to be related to long-term virological response to IFN therapy.     

Overlap syndrome of autoimmune hepatitis and primary biliary cirrhosis triggered by fluvastatin

Although statins are generally well-tolerated drugs, recent cases of autoimmune hepatitis (AIH) associated with their use have been reported. A 59-year-old Japanese man reported with liver damage, which appeared one month after beginning treatment with fluvastatin and continued after discontinuation of the drug. Although drug-induced liver injury was possible, positive autoantibody tests (antinuclear antibodies >1/1280, anti-mitochondrial M2 antibodies 21 index value) also suggested autoimmune liver disease. Liver biopsy findings were consistent with an overlap of autoimmune hepatitis and primary biliary cirrhosis. Treatment with prednisone and ursodeoxycholic acid led to a good response. In this patient, manifestation of AIH and primary biliary cirrhosis overlap syndrome was possibly triggered by statin use. Autoimmune liver disease should be considered as a possible diagnosis in patients with evidence of prolonged liver damage after discontinuation of statins.     

Hypoproteinemia in the second trimester among patients with preeclampsia prior to the onset of clinical symptoms

Objective: To find a risk factor for “uncomplicated” preeclampsia (PE) comparing blood biochemical parameters between women with uncomplicated PE and healthy pregnant women in each trimester of pregnancy. Methods: A retrospective study was performed on 83 cases of uncomplicated PE, selected from 434 patients with PE, disregarding subjects with other complications relevant to hypertension during pregnancy. The study was limited to women with PE occurring in the third trimester, and records of blood biochemical parameters were evaluated. Controls were recruited from 108 healthy volunteers with normal singleton pregnancies. Results: A significant decrease in total protein was observed in the uncomplicated PE group in the second trimester prior to the onset of clinical symptoms. Conclusion: Hypoproteinemia during pregnancy may be a risk factor for this pathophysiology, and the maintenance of sufficient protein in early pregnancy could contribute to prophylaxis for women with uncomplicated PE.     

Quantitative insulin sensitivity check index is a useful indicator of insulin resistance in Japanese metabolically obese, normal-weight subjects with normal glucose tolerance

To clarify whether quantitative insulin sensitivity check index (QUICKI) is useful as an indicator of insulin resistance in Japanese metabolically obese, normal-weight (MONW, body mass index (BMI) <25 and visceral fat area (VFA) > or = 100 cm2 by abdominal computed tomography scanning) subjects with normal glucose tolerance (NGT). Insulin resistance was measured by QUICKI and euglycemic hyperinsulinemic clamp study (clamp IR) in 27 MONW and 27 normal subjects (BMI <25 and visceral fat area <100 cm2). QUICKI (P<0.01) and clamp IR (p<0.01) were significantly decreased in MONW subjects compared with normal subjects. QUICKI was significantly associated with VFA [MONW subjects: r = -0.459, p<0.02; all (MONW and normal) subjects: r = -0.506, p<0.0001] and with the serum levels of triglycerides (MONW subjects: r = -0.386, p<0.05; all subjects: r = -0.505, p<0.001) in MONW and all subjects. There were significant correlations between clamp IR and VFA (MONW subjects: r = -0.562, p<0.01; all subjects: r = -0.575, p<0.0001), fasting serum levels of insulin (MONW subjects: r = -0.673, p<0.001; all subjects: r = -0.619, p<0.0001) or serum levels of triglycerides (MONW subjects: r = -0.485, p<0.02; all subjects: r = -0.565, p<0.0001) in MONW and all subjects. QUICKI was significantly correlated with clamp IR in MONW (r = 0.754, p<0.0001) and in all subjects (r = 0.568, p<0.0001). QUICKI may be an useful method for assessing insulin resistance in Japanese MONW subjects with NGT.     

Correlation of urine type I collagen-cross-linked N telopeptide levels with bone scintigraphic results in prostate cancer patients

The diagnostic potential of a new bone resorption marker, type I collagen-cross-linked N telopeptide (NTx), for bone metastasis of prostate cancer was evaluated. Ninty-one prostate cancer patients underwent bone scintigraphy, and urine NTx/creatinine (NTx/Cr) was measured. Urine NTx/Cr levels were compared with bone scintigraphic results. Urine NTx/Cr levels in the bone metastasis-positive group (n = 47) were 92.9 +/- 105.1 nmol/L of bone collagen, which is equivalent to per millimole of urinary creatinine (nmol/L BCE/mmol/L Cr), significantly higher than the level of the bone metastasis-negative group (n = 44) (59.0 +/- 41.6 nmol/L BCE/mmol/L Cr). When patients were classified by the extent of disease grade (EOD grade) nomenclature, the urine NTx/Cr level of the EOD (4+) group was 209.5 +/- 186.5 nmol/L BCE/mmol/L Cr. This level was significantly higher than those of the EOD (-) group (59.0 +/- 41.6 nmol/L BCE/mmol/L Cr), EOD (1+) group (59.0 +/- 47.8 nmol/L BCE/mmol/L Cr), and EOD (2+) group (81.1 +/- 41.3 nmol/L BCE/mmol/L Cr). However, no significant difference was observed between the EOD (-) and EOD (1+) groups. The mean change in urine NTx/Cr level 3 to 17 months after the first bone scintigraphy and urine NTx/Cr examination in the bone metastasis-progression group (n = 8) was 11.0 +/- 31.2 nmol/L BCE/mmol/L Cr, significantly higher than that in the bone metastasis-regression group (n = 15) (-26.8 +/- 40.7 nmol/L BCE/mmol/L Cr). In conclusion, urine NTx /Cr can be measured noninvasively and reflects the state of bone metastasis. However, the sensitivity of urine NTx/Cr is not as high as that of bone scintigraphy. Therefore, it may provide an auxiliary diagnostic index for bone scintigraphy.