A genome-wide association study of coping behaviors suggests FBXO45 is associated with emotional expression.

Individuals use coping behaviors to deal with unpleasant daily events. Such behaviors can moderate or mediate the pathway between psychosocial stress and health-related outcomes. However, few studies have examined the associations between coping behaviors and genetic variants. We conducted a genome-wide association study (GWAS) on coping behaviors in 14088 participants aged 35 to 69 years as part of the Japan Multi-Institutional Collaborative Cohort Study. Five coping behaviors (emotional expression, emotional support seeking, positive reappraisal, problem solving and disengagement) were measured and analyzed. A GWAS analysis was performed using a mixed linear model adjusted for study area, age and sex. Variants with suggestive significance in the discovery phase (N = 6403) were further examined in the replication phase (N = 7685). We then combined variant-level association evidence into gene-level evidence using a gene-based analysis. The results showed a significant genetic contribution to emotional expression and disengagement, with an estimation that the 19.5% and 6.6% variance in the liability-scale was explained by common variants. In the discovery phase, 12 variants met suggestive significance (P < 1 × 10-6 ) for association with the coping behaviors and perceived stress. However, none of these associations were confirmed in the replication stage. In gene-based analysis, FBXO45, a gene with regulatory roles in synapse maturation, was significantly associated with emotional expression after multiple corrections (P < 3.1 × 10-6 ). In conclusion, our results showed the existence of up to 20% genetic contribution to coping behaviors. Moreover, our gene-based analysis using GWAS data suggests that genetic variations in FBXO45 are associated with emotional expression.

Evaluation of the safety and efficacy of Glycyrrhiza uralensis root extracts produced using artificial hydroponic and artificial hydroponic-field hybrid cultivation systems.

Glycyrrhiza uralensis roots used in this study were produced using novel cultivation systems, including artificial hydroponics and artificial hydroponic-field hybrid cultivation. The equivalency between G. uralensis root extracts produced by hydroponics and/or hybrid cultivation and a commercial Glycyrrhiza crude drug were evaluated for both safety and efficacy, and there were no significant differences in terms of mutagenicity on the Ames tests. The levels of cadmium and mercury in both hydroponic roots and crude drugs were less than the limit of quantitation. Arsenic levels were lower in all hydroponic roots than in the crude drug, whereas mean lead levels in the crude drug were not significantly different from those in the hydroponically cultivated G. uralensis roots. Both hydroponic and hybrid-cultivated root extracts showed antiallergic activities against contact hypersensitivity that were similar to those of the crude drug extracts. These study results suggest that hydroponic and hybrid-cultivated roots are equivalent in safety and efficacy to those of commercial crude drugs. Further studies are necessary before the roots are applicable as replacements for the currently available commercial crude drugs produced from wild plant resources.

Effects of IL6 C-634G polymorphism on tooth loss and their interaction with smoking habits.

OBJECTIVE: To examine the association between an IL6 (Interleukin-6) polymorphism (C-634G or rs1800796) and tooth loss, and an interaction between the polymorphism and smoking habits for the loss. MATERIAL AND METHODS: Our subjects were 4917 check-up examinees ages 35-69. They reported tooth loss and lifestyle in a questionnaire. We regressed the number of teeth on the IL6 genotype, gender, age, smoking, drinking, diabetes, hypertension, physical activity, energy intake, education, and brushing. We further estimated multivariate-adjusted odds ratios (ORs) for having <20 teeth. RESULTS: Participants with a GG genotype tended to have less teeth than those with CC; ß = -0.798 (95% confidence interval [CI] = -1.501--0.096). Subjects with a GG genotype were more likely to have <20 teeth than those with CC; OR was 1.56 (95% CI = 1.08-2.25). Association between current smoking and tooth loss was stronger among those with GG than among those with CC. In a multiple regression analysis, a significant interaction was found between GG genotype and current smoking in the prediction of tooth loss (P = 0.018). CONCLUSION: The IL6 C-634G polymorphism was significantly associated with tooth loss. Our results suggest greater effects of smoking on tooth loss in GG genotype individuals.

Protein degradation by the ubiquitin-proteasome pathway and organ fibrosis.

Abnormal and exaggerated deposition of extracellular matrix proteins is the common feature of fibrotic diseases. The resulting fibrosis disrupts the normal architecture of the affected organs and finally leads to their dysfunction and failure. At present, there are no effective therapies for fibrotic diseases. Protein degradation via the ubiquitin-proteasome system is the major pathway for non-lysosomal proteolysis and controls many critical cellular functions including cell-cycle progression, deoxyribonucleic acid repair, growth and differentiation. Therefore, aberration of the system leads to dysregulation of cellular homeostasis and development of many diseases such as cancers, degenerative diseases and fibrotic diseases. Although the ubiquitin-proteasome system has mainly been investigated in the field of cancers so far and several anti-cancer drugs that modulate the activity of the system have been used clinically, the recent findings regarding the system and fibrosis can provide a rational basis for the discovery of novel therapy for fibrotic diseases. In this article, we discuss (i) the basic mechanism of the ubiquitin-proteasome system and (ii) the recent findings regarding the association between the system and pathological organ fibrosis. These examples indicate that the ubiquitin-proteasome system plays diverse roles in the progression of fibrotic diseases, and further studies of the system are expected to reveal new strategies for overcoming pathological fibrosis.

Factors that contribute to faecal cyclooxygenase-2 mRNA expression in subjects with colorectal cancer.

BACKGROUND: We previously reported that a faecal cyclooxygenase-2 (COX-2) mRNA assay was useful for identifying colorectal cancer (CRC). This study sought to investigate the factors that contribute to faecal COX-2 mRNA expression in subjects with CRC. METHODS: The study cohort comprised 78 patients with CRC and 36 control subjects. The expressions of COX-2, beta-2-microglobulin (B2M), carcinoembryonic antigen (CEA), E-cadherin (E-cad), and CD45 mRNA in faeces and COX-2 mRNA expression in tissue were determined by quantitative real-time RT-PCR. RESULTS: The level of faecal expression of COX-2 mRNA in CRC was significantly higher than that in controls. A significant correlation was found between faecal COX-2 mRNA expression and faecal B2M, CEA, E-cad, or CD45 mRNAs, markers of exfoliated total cells, colonocytes, and leukocytes, respectively. A significant correlation was found between the expression of COX-2 mRNA in faeces and tumour surface area, COX-2 mRNA expression in primary tumour. There was no difference in faecal COX-2 mRNA expression between proximal CRC and distal CRC. CONCLUSION: COX-2 mRNA expression in faeces seems to originate from tumour lesion and to be affected by factors such as the number of exfoliated cells, exfoliation of inflammatory cells, COX-2 mRNA expression in tumour, and tumour size.

Associations of plasma IL-8 levels with Helicobacter pylori seropositivity, gastric atrophy, and IL-8 T-251A genotypes.

There are few data on circulatory pro-inflammatory cytokine levels and cytokine gene polymorphisms in H. pylori-positive patients. A cross-sectional study was conducted to examine the effects of H. pylori infection, gastric atrophy, and the IL-8 T-251A polymorphism on plasma IL-8 levels in 98 Japanese adults. Seventy-one subjects were positive for H. pylori infection. The geometric mean of plasma IL-8 concentration was significantly higher in subjects with H. pylori infection than in those without (P=0.001). The development of atrophy was negatively associated with IL-8 levels in the H. pylori-positive subjects, although not significantly. Plasma IL-8 levels in the T/T genotype were associated with H. pylori infection and atrophy status (P=0.016). Our findings suggested that circulating IL-8 levels were associated with H. pylori infection. The effect of H. pylori infection on plasma IL-8 levels was not clearly modified by the IL-8 T-251A polymorphism.

[13C]-pantoprazole breath test to predict CYP2C19 phenotype and efficacy of a proton pump inhibitor, lansoprazole.

BACKGROUND: (13)CO(2) is produced on metabolism of (13)C-labelled-pantoprazole ([(13)C]-pantoprazole) by CYP2C19. AIM: To investigate whether the [(13)C]-pantoprazole breath test can predict CYP2C19 status and efficacy of proton pump inhibitors (PPIs) in Japanese. METHODS: We classified 110 healthy volunteers as rapid metabolizers (RM), intermediate metabolizers (IM) or poor metabolizers (PM) of CYP2C19 by genotyping. Breath samples were collected at 10-min intervals for 60 min after dosing with 100 mg [(13)C]-pantoprazole. Changes in the carbon isotope ratios ((13)CO(2)/(12)CO(2)) in carbon dioxide in breath samples were measured and expressed as a delta-over-baseline (DOB) ratio ( per thousand). Of the 110 subjects, twenty-two randomly selected subjects underwent intragastric pH monitoring on day 7 of dosing with 30 mg of lansoprazole. RESULTS: The DOB values of RMs were the highest and those of PMs the lowest of the three groups. Statistically significant differences were observed in the area-under-the-curve (AUC)(20-60 min) of DOB among the three groups. The mean 24-h intragastric pHs attained by lansoprazole 30 mg for 7 days were inversely correlated with the AUC(20-60 min) of DOB. CONCLUSIONS: [(13)C]-pantoprazole breath test can easily estimate the individual activity of CYP2C19 and predict the efficacy of a PPI (i.e. lansoprazole). This test would be useful for individualized medicine with a PPI.

Human Sgo1 downregulation leads to chromosomal instability in colorectal cancer.

BACKGROUND AND AIMS: Chromosomal instability (CIN) is recognised as a hallmark of cancer and is caused by a spindle assembly checkpoint disorder or chromosome mis-segregation during mitosis. Although the recent identification of human shugoshin (hSgo1), an important player in proper chromosome segregation, has suggested the involvement of hSgo1 in colorectal tumourigenesis, little is known about how it is involved. The aim of this study was to obtain information about the status of hSgo1 in human colorectal cancer. METHOD AND RESULTS: Among the 46 colorectal cancer cases, hSgo1 mRNA expression was decreased in the tumour tissue in comparison with the corresponding normal tissue (p = 0.032). Human Sgo1-downregulated tumours (tumour to normal mucosa ratio<0.5) had preferential location on the left side large bowel rather than on the right side (p = 0.012), and a higher variation of centromere numbers revealed by fluorescence in situ hybridisation (FISH). To assess the effects of hSgo1 downregulation, hSgo1 knockdown was performed by transfecting the diploid HCT116 cell line with a short hairpin RNA expression vector. hSgo1 knockdown cells proliferated slowly because of both G(2)/M arrest and apoptosis (p<0.001), and markers of CIN in the form of aneuploidy (p<0.001) and micronuclei (p<0.005) were later observed in hSgo1 knockdown cells. Increased centrosome amplification (p<0.05), the presence of binucleated cells and mitotic catastrophes were also noted in hSgo1 knockdown cells. CONCLUSIONS: These findings suggest that hSgo1-downregulated colorectal cancers have a clinicopathological character of CIN, and hSgo1 downregulation leads to CIN in colorectal cancer cells.

Effect of MDR1 C3435T polymorphism on cure rates of Helicobacter pylori infection by triple therapy with lansoprazole, amoxicillin and clarithromycin in relation to CYP 2C19 genotypes and 23S rRNA genotypes of H. pylori.

BACKGROUND: Polymorphism in MDR1 is associated with variation in the plasma level of a proton pump inhibitor. AIM: To investigate whether MDR1 polymorphism is associated with eradication rates of Helicobacter pylori by a triple therapy with lansoprazole, amoxicillin and clarithromycin in relation to CYP2C19 genotype status and bacterial susceptibility to clarithromycin. METHODS: A total of 313 patients infected with H. pylori completed the treatment with lansoprazole 30 mg b.d., clarithromycin 200 mg b.d. and amoxicillin 750 mg b.d. for 1 week. MDR1 C3435T polymorphism and CYP2C19 genotypes of patients and sensitivity of H. pylori to clarithromycin were determined. RESULTS: Logistic regression analysis revealed that the MDR1 polymorphism as well as CYP2C19 genotypes of patients and clarithromycin-resistance of H. pylori were significantly associated with successful eradication. Eradication rates for H. pylori were 82% (83/101: 95% CI = 73-89), 81% (112/139: CI = 73-87), and 67% (44/73: CI = 48-72) in patients with the MDR1 3435 C/C, C/T and T/T genotype, respectively (P = 0.001). CONCLUSIONS: Polymorphism of MDR1 is one of the determinants of successful eradication of H. pylori by the triple therapy with lansoprazole, amoxicillin and clarithromycin, together with CYP2C19 genotype and bacterial susceptibility to clarithromycin.

Pharmacogenomics-based tailored versus standard therapeutic regimen for eradication of H. pylori.

Helicobacter pylori eradication rates by triple therapy with a proton pump inhibitor, amoxicillin, and clarithromycin at standard doses depend on bacterial susceptibility to clarithromycin and patient CYP2C19 genotypes. We examined the usefulness of a personalized therapy for H. pylori infection based on these factors as determined by genetic testing. First, optimal lansoprazole dosing schedules that would achieve sufficient acid inhibition to allow H. pylori eradication therapy in each of different CYP2C19 genotype groups were determined by a 24-h intragastric pH monitoring. Next, 300 H. pylori-positive patients were randomly assigned to the standard regimen group (lansoprazole 30 mg twice daily (b.i.d.)), clarithromycin 400 mg b.i.d., and amoxicillin 750 mg b.i.d. for 1 week) or the tailored regimen group based on CYP2C19 status and bacterial susceptibility to clarithromycin assessed by genetic testing. Patients with failure of eradication underwent the second-line regimen. The per-patient cost required for successful eradication was calculated for each of the groups. In the first-line therapy, the intention-to-treat eradication rate in the tailored regimen group was 96.0% (95% CI=91.5-98.2%, 144/150), significantly higher than that in the standard regimen group (70.0%: 95% CI=62.2-77.2%, 105/150) (P<0.001). Final costs per successful eradication in the tailored and standard regimen groups were $669 and $657, respectively. In conclusion, the pharmacogenomics-based tailored treatment for H. pylori infection allowed a higher eradication rate by the initial treatment without an increase of the final per-patient cost for successful eradication. However, the precise cost-effectiveness of this strategy remains to be determined.

Ubiquitin-dependent degradation of SnoN and Ski is increased in renal fibrosis induced by obstructive injury.

Transforming growth factor-beta (TGF-beta) plays a critical role in the progression of renal fibrosis. The activity of TGF-beta is tightly controlled by various mechanisms, among which antagonizing Smad-mediated gene transcription by co-repressors represents one of the important components. We investigated the expression, degradation, and ubiquitination of Smad transcriptional co-repressors SnoN (ski-related novel gene N) and Ski (Sloan-Kettering Institute proto-oncogene) in renal fibrogenesis. We also studied the involvement of Smad-ubiquitination regulatory factor 2 (Smurf2) in ubiquitination of SnoN protein. The kidneys of mice with unilateral ureteral obstruction (UUO) and those of sham-operated mice were used. Renal lesions and the expression of TGF-beta1, type I collagen, SnoN, Ski, and Smurf2 were examined by immunohistochemistry, Western blot, and/or real-time reverse transcriptase-polymerase chain reaction. Degradation and ubiquitination of SnoN/Ski proteins were also investigated. The obstructed kidneys of UUO mice showed progressive tubulointerstitial fibrosis, high expression levels of TGF-beta1, type I collagen, SnoN and Ski mRNAs, and low levels of SnoN and Ski proteins. Both degradation and ubiquitination of SnoN/Ski proteins were markedly increased in the obstructed kidneys, in which Smurf2 expression was increased. Smurf2 immunodepletion in extracts of obstructed kidneys resulted in reduced ubiquitination of SnoN. Our results suggest that the reduction of SnoN/Ski proteins resulting from increased ubiquitin-dependent degradation is involved in the progression of tubulointerstitial fibrosis.

Poor metabolizer genotype status of CYP2C19 is a risk factor for developing gastric cancer in Japanese patients with Helicobacter pylori infection.

BACKGROUND: Cytochrome P450 2C19 (CYP2C19) polymorphism has been associated with the development of lung, liver or oesophageal cancer by detoxification of carcinogen(s) or activation of procarcinogen(s). AIM: To clarify the association between CYP2C19 polymorphisms and gastric cancer development in Japanese. Methods : We determined CYP2C19 genotypes (CYP2C19*1, *2 and *3) in 111 Helicobacter pylori-positive patients with gastric cancer and 315 H. pylori-positive controls without gastric cancer consisting of patients with gastritis only or peptic ulcer. Frequencies of CYP2C19 genotypes and serum pepsinogen I and II levels, a biomarker of gastric atrophy, in the gastric cancers and controls were compared. RESULTS: Frequencies of homozygous extensive metabolizers, heterozygous extensive metabolizers and poor metabolizers were 31.5%, 42.3% and 26.2% in the gastric cancers and 38.1%, 47.0% and 14.9% in the controls, respectively (P = 0.046). Poor metabolizers were associated with an increased risk for developing gastric cancer with the age- and sex-adjusted odds ratio (OR) of 1.975 [95% confidence interval (CI): 1.068-3.649], especially for diffuse type (OR: 3.385, CI: 1.187-9.648). There is no significant association between CYP2C19 genotypes and serum pepsinogen I level or pepsinogen I/II ratios, although serum pepsinogen I level in gastric cancers were significantly decreased. CONCLUSIONS: In H. pylori-positive Japanese, poor metabolizers of CYP2C19 appear to be at an increased risk for developing gastric cancer, especially diffuse type, and may require an intensive follow-up for scrutinizing possible gastric cancer development.

Effect of concomitant dosing of famotidine with lansoprazole on gastric acid secretion in relation to CYP2C19 genotype status.

BACKGROUND: Famotidine increases Helicobacter pylori-eradication rates by a triple lansoprazole/amoxicillin/clarithromycin therapy in patients with the rapid extensive metabolizer genotype of CYP2C19. AIM: To determine the effect of famotidine on the gastric acid inhibition by lansoprazole in relation to CYP2C19 genotypes. METHODS: Twenty healthy volunteers with different CYP2C19 genotypes--consisting of six rapid extensive metabolizers, nine intermediate metabolizers and five poor metabolizers--underwent three 7-day courses with placebo, lansoprazole 30 mg twice daily, and lansoprazole 30 mg twice plus famotidine 20 mg twice daily. Lansoprazole was dosed after breakfast and dinner. Famotidine was dosed after lunch and at bedtime. Intragastric pH monitoring was performed for 24 h on day 7 of each course. RESULTS: With placebo, no difference was observed in intragastric pH profiles among the three CYP2C19 genotype groups. With lansoprazole 30 mg twice daily, the median of 24-h intragastric pH in poor metabolizers (6.1) was significantly higher than those of rapid extensive metabolizers (4.5) and intermediate metabolizers (5.0), respectively (P = 0.0176 and 0.0388), whereas with lansoprazole 30 mg twice and famotidine 20 mg twice daily, the medians were 5.4, 5.7, and 6.1, respectively (not significant). CONCLUSION: Acid inhibition by lansoprazole was influenced by CYP2C19 genotype status. This influence was offset by the concomitant use of famotidine.

High ratio of 1,25-dihydroxyvitamin D3 to parathyroid hormone in serum of tuberculous patients with end-stage renal disease.

AIM: Diagnosis of tuberculosis is sometimes difficult because of the low specificity of diagnostic procedures especially in patients on end-stage renal disease (ESRD). As abnormal vitamin D metabolism has been reported in tuberculosis, the aim of the present study was to determine whether serum concentration of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) may be a useful diagnostic indicator of tuberculosis in patients with ESRD. PATIENTS AND METHODS: Serum concentrations of 1,25-(OH)2D3, parathyroid hormone (PTH), and calcium were compared in 6 patients with ESRD and active tuberculosis (ESRD-TB group) and 110 patients with ESRD and no tuberculosis (ESRD group). These parameters were compared before and after treatment for tuberculosis in patients of ESRD-TB group. RESULTS: Hypercalcemia was observed in all 6 patients in the ESRD-TB group. Both higher serum concentration of 1,25-(OH)2D3 and lower serum concentration of PTH were observed in the ESRD-TB group relative to the ESRD group, suggesting enhanced extrarenal production of 1,25-(OH)2D3 and suppressed secretion of PTH by hypercalcemia in the ESRD-TB group. However, these parameters could not be used to distinguish the ESRD-TB group from the ESRD group. The ratio of 1,25-(OH)2D3 to PTH in serum was above 0.9 in the ESRD-TB group and below 0.9 in the ESRD group. Antituberculous treatment reduced this ratio to the range observed in the ESRD group. CONCLUSION: High ratio of 1,25-(OH)2D3 to PTH in serum is noted in active tuberculous patients with ESRD because of enhanced extrarenal production of 1,25-(OH)2D3.

Association between blood indoxyl sulfate and carbonyl stress marker in hemodialysis patients.

BACKGROUND: Indoxyl sulfate (IS) is a protein-bound solute, which is progressively retained in blood according to the decline of renal function. However, clinical relevance of excess IS in hemodialysis (HD) patients remains unknown. PATIENTS AND METHODS: We measured serum IS and clinical parameters including pentosidine, carboxymethyllysine (CML) and homocysteine levels in 55 HD patients (age: 67 +/- 2 years, time on HD: 67 +/- 11 months, male/female = 30/25), and examined the relationship between IS and these data. RESULTS: Serum IS was markedly increased in HD patients (80.49 +/- 6.17 microg/ml) compared to normal range (< 1.9 microg/ml). IS was significantly and positively correlated with time on HD (p < 0.01), blood urea nitrogen (p < 0.01), beta2-microglobulin (p < 0.03), and protein catabolic rate (PCR) (p < 0.01). The patients with increased IS needed a higher erythropoietin dosage. Blood IS was positively correlated with pentosidine (r = 0.505, p < 0.01) and CML (r = 0.275, p < 0.05). In contrast, blood IS was not associated with nutritional and inflammatory parameters. A stepwise multiple regression analysis revealed that time on HD, PCR and pentosidine were significant determinants of IS. CONCLUSIONS: Serum IS was related to time on HD and dietary protein intake. Accumulated IS may be associated with enhanced carbonyl stress in chronic HD patients.

A case of anaphylactoid shock induced by the BS polysulfone hemodialyzer but not by the F8-HPS polysulfone hemodialyzer.

A 57-year-old woman was admitted because of severe bradycardia and hypotension caused by an anti-arrhythmic agent and beta-blocker. For 19 months before admission, she had been undergoing hemodialysis with an F8-HPS polysulfone membrane hemodialyzer without any complications. In 2 dialysis sessions after admission, when a BS polysulfone membrane was used, she experienced anaphylactoid shock with severe hypotension leading to syncope, dyspnea and vomiting, just after the start of hemodialysis. After the anaphylactoid shock, her dialyzer membrane was changed to a cellulose triacetate membrane and she did not suffer from such attacks. This case indicates that severe anaphylactoid shock may be caused by a biocompatible dialyzer membrane and that the reactions of patients to each polysulfone membrane may differ among polysulfone membranes made by different manufacturers.

Measurement of des-gamma-carboxy prothrombin levels in hemodialysis patients positive for anti-hepatitis virus C antibody.

BACKGROUND: The prevalence of anti-hepatitis virus C (HCV) antibody is much higher in hemodialysis (HD) patients than in the normal population. Recently, blood des-gamma-carboxy prothrombin (PIVKA-II) has been demonstrated as a sensitive marker for the early detection of hepatocellular carcinoma (HCC). In this study, we measured blood PIVKA-II in HD patients positive for anti-HCV antibody or hepatitis B virus surface (HBs) antigen to examine if HD therapy may affect the measurement of PIVKA-II. PATIENTS AND METHODS: Ninety-four stable HD patients who had anti-HCV antibodies (n = 86) or HBs antigen (n = 8) without any evidence of HCC were enrolled in the study (age: 60 +/- 11 years, duration of HD: 17 +/- 10 years, male/female = 63/31). Five patients had liver cirrhosis and another 5 patients received warfarin treatment. We simultaneously measured serum PIVKA-II and alpha-fetoprotein (AFP), and compared the association between these markers and HCV RNA titer and laboratory parameters. RESULTS: Serum PIVKA-II became positive (> or = 40 mAU/ml) in only 5.6% (5/89) of patients without warfarin administration, ranging from 47 to 71 mAU/ml. Seventy out of 89 patients (78.7%) were below 20 mAU/ml. Serum PIVKA-II did not correlate with biochemical parameters including HCV RNA, while serum AFP was significantly correlated with serum AST (r = 0.21, p < 0.05), gamma-GTP (r = 0.21, p < 0.01) and platelet counts (r = -0.29, p < 0.01), respectively. In contrast, 5 patients receiving warfarin had an extremely high PIVKA-II value ranging from 1,930 to 19,900 mAU/ml. PIVKA-II was significantly and inversely correlated with the thrombotest value (r = -0.72, p = 0.01). CONCLUSION: The positivity of blood PIVKA-II in HD patients with hepatitis viremia was identical to that in patients without renal failure. Warfarin treatment dramatically increased serum PIVKA-II more than 1,000 mAU/ml. These findings suggested that HD treatment itself did not affect the measurement of PIVKA-II, but vitamin K deficiency can readily influence the PIVKA-II level in dialysis patients.

Focal segmental glomerulosclerosis in a case of panhypopituitarism: a possible role of growth hormone treatment.

Panhypopituitarism manifests various symptoms including growth failure, hypothyroidism, adrenal insufficiency and hypogonadism. Dwarfism is an important problem in children with this condition, and long-term treatment with recombinant human growth hormone (GH) is usually required. We report a 24-year-old man with panhypopituitarism complicated by focal segmental glomerulosclerosis (FSGS). The patient had been treated with GH for hypopituitary dwarfism from 3 years of age. Proteinuria was initially noticed at 15 years of age and persisted despite cessation of GH supplementation at 18 years of age. A renal biopsy specimen showed glomerular hypertrophy and limited glomerulosclerosis, compatible with FSGS. To our knowledge, this is the first reported case of panhypopituitarism complicated by FSGS. Our case suggests that GH treatment for dwarfism may induce irreversible glomerular disease.

Ultrasound changes of the carpal tunnel in patients receiving long-term hemodialysis: a cross-sectional and longitudinal study.

BACKGROUND: Carpal tunnel syndrome (CTS) is one of the major problems of long-term hemodialysis (HD), but sometimes difficult to distinguish from uremic or diabetic neuropathy by clinical symptoms. PATIENTS AND METHODS: To evaluate the diagnosis of CTS more precisely, we examined the ultrasonographic alterations of the carpal tunnel and tendons of 90 wrists from 45 patients undergoing HD for more than 5 years. We measured the thickness of the palmar radiocarpal ligament (PRL), corresponding to the posterior wall of the carpal tunnel (CT), and the width of the CT, and compared those values with sensory (SCV), motor conduction velocity (MCV) of the median nerve and clinical symptoms. In addition, we longitudinally measured CT and PRL in the same patients for 5 years, and compared ultrasonographic changes and clinical parameters. RESULTS: A linear positive relationship was found between HD duration and PRL thickness (r = 0.43, p < 0.01) or CT width (r = 0.53, p < 0.01). CT diameter was negatively correlated with MCV (r = -0.30, p < 0.01) and SCV (r = -0.33, p < 0.04). PRL thickness was also inversely correlated with MCV (r = -0.44, p < 0.01) and SCV (r = -0.46, p < 0.01) of the median nerve, respectively. The wrists with clinical CTS and/or previous CTS surgery had significantly greater CT and PRL values compared to patients without CTS (CT: 6.1 0.2vs. 8.0+/-0.3 mm,p<0.01;PRL: 1.9+/-0.1 vs. 3.6 +/- 0.2 mm, p < 0.01). There was a significant increase in CT width from 6.2 +/- 0.2 to 7.1 +/- 0.2 mm (p < 0.01) and PRL thickness from 2.4 +/- 0.2 to 2.8 +/- 0.2 mm (p <0.01) during the 5-year observation, respectively. PRL thickness was constantly increased at the rate of 0.4 mm during the study. However, no significant association was found between the 5-year increases in CT and PRL distance and age, gender, the prevalence of diabetes, or laboratory parameters such as blood beta2-microglobulin, pentosidine and Kt/V(urea). CONCLUSION: Our data suggest that echographic evaluation of the wrist tissue thickness was useful to assess the progression of CTS. Serial measurements of the wrist by echography may be helpful to clarify the advance of subclinical CTS in patients receiving long-term HD.