CASE REPORT: Pure Red Cell Aplasia Associated with Parvovirus B19 Infection in a Patient with Ulcerative Colitis

Anemia is a common problem that results from various causes in patients with ulcerative colitis (UC), but there is little information on the association of UC with pure red cell aplasia (PRCA). We describe the first case of parvovirus-induced PRCA in UC. A 28-year-old woman with chronic UC was admitted to the hospital for treatment of active pancolitis. Three courses of pulse therapy with methylprednisolone provided complete remission. However, the patient developed reticulocytopenia and a subsequent fall in hemoglobin to 6.2 g/dl. Bone marrow examination revealed selective aplasia of red cell precursors and giant pronoromoblasts. Enzyme immunoassay identified specific immunoglobulin M antibody against parvovirus B19 in the serum. Based on these findings, the diagnosis of PRCA caused by the virus was made. The patient was treated with a 3-day course of intravenous immunoglobulin (5 g/day), resulting in brisk reticulocytosis, folowed by normalization of hemoglobin level. In conclusion, Chronic or acute blood loss in UC associated with enhanced red cell turnover might be a risk factor for PRCA when affected patients contract parvovirus B19 infection.     

Thiazolidinedione derivatives ameliorate albuminuria in streptozotocin-induced diabetic spontaneous hypertensive rat

Recent reports have shown that thiazolidinediones have preventive effects on urinary albumin excretion in diabetes. However, the mechanism leading to these effects has not yet been elucidated. We studied here the effects of thiazolidinediones on albuminuria and hemodynamic and morphological changes in the kidneys of streptozotocin (STZ)-induced diabetic spontaneous hypertensive rats (SHRs). Diabetes was induced in SHRs by intravenous injection of STZ (50 mg/kg). The diabetic SHRs were divided into the following 3 groups: (1) STZ-SHRs given normal chow (STZ), (2) STZ-SHRs given chow mixed with 0.1% troglitazone (STZ + tro), and (3) STZ-SHRs given chow mixed with 0.001% pioglitazone (STZ + pio). Three groups of nondiabetic SHRs were also investigated: (4) SHR, (5) tro, and (6) pio. We evaluated the urinary albumin excretion rate (AER) every 4 weeks. After 12 weeks of treatment, the animals were killed and renal morphological examinations were performed. Thiazolidinediones did not affect blood pressure or blood glucose levels. Urinary AER were markedly increased in STZ-SHRs. After 12 weeks of treatment with thiazolidinediones, the urinary AER was significantly decreased while creatinine (Cr) clearance was left unchanged. Histologically, the loss of anionic sites of glomerular basement membranes (GBM) evaluated with polyetyleneimine was suppressed significantly in the diabetic SHRs treated with thiazolidinediones. In conclusion, administration of thiazolidinediones in diabetic SHRs decreased the urinary AER and suppressed the loss of anionic sites of GBM without affecting blood pressure, blood glucose levels, or Cr clearance. These results clarify the novel therapeutic action of thiazolidinediones on diabetic nephropathy.     

Antiarrhythmic effect of bisoprolol, a highly selective beta1-blocker, in patients with paroxysmal atrial fibrillation

In the treatment of arrhythmia, beta-blockers are mainly used to regulate the heart rate. However, beta-blockers are also known as drugs with an antiarrhythmic effect due to the suppression of sympathetic activity. We evaluated the antiarrhythmic effects of a highly selective beta(1)-blocker, bisoprolol, in patients with diurnal paroxysmal atrial fibrillation (P-AF). A total of 136 patients with symptomatic diurnal P-AF were enrolled. Patients were divided into a diurnal-specific P-AF group and a diurnal & nocturnal P-AF group, as well as into a bisoprolol single use group and a combined use group with an antiarrhythmic drug. The effects of bisoprolol were evaluated in 3 categories: subjective symptom improvement, quality of life (QOL) improvement, and elimination of P-AF episode in Holter electrocardiograms (ECGs). For patients with effective treatment, a long-term effect up to 24 months was evaluated. Five patients (3.7%) discontinued bisoprolol due to side effects. Following administration of bisoprolol, 109 patients (80%) experienced subjective symptom improvement, 103 patients (76%) experienced QOL improvement, and elimination of P-AF episodes in ECGs was observed in 84 patients (62%). The elimination rate of P-AF episodes in ECGs was higher in the diurnal P-AF group than in the diurnal & nocturnal P-AF group (P=0.042). There was no significant difference between the bisoprolol single use group and the combined use group. A long-term suppressive effect by bisoprolol was observed in 70 of 83 patients (84%). The results demonstrate that bisoprolol has an antiarrhythmic effect against sympathetic diurnal P-AF, improving subjective symptoms and QOL and eliminating P-AF episodes in ECGs.     

Aspirin-Intolerant Asthma (AIA) Assessment Using the Urinary Biomarkers, Leukotriene E(4) (LTE(4)) and Prostaglandin D(2) (PGD(2)) Metabolites

The clinical syndrome of aspirin-intolerant asthma (AIA) is characterized by aspirin/nonsteroidal anti-inflammatory drug intolerance, bronchial asthma, and chronic rhinosinusitis with nasal polyposis. AIA reactions are evidently triggered by pharmacological effect of cyclooxygenase-1 inhibitors. Urine sampling is a non-invasive research tool for time-course measurements in clinical investigations. The urinary stable metabolite concentration of arachidonic acid products provides a time-integrated estimate of the production of the parent compounds in vivo. AIA patients exhibits significantly higher urinary concentrations of leukotriene E(4) (LTE(4)) and 1,15-dioxo-9α-hydroxy-2,3,4,5-tetranorprostan-1,20-dioic acid (tetranor-PGDM), a newly identified metabolite of PGD(2), at baseline. This finding suggests the possibility that increased mast cell activation is involved in the pathophysiology of AIA even in a clinically stable condition. In addition, lower urinary concentrations of primary prostaglandin E(2) and 15-epimer of lipoxin A(4) at baseline in the AIA patients suggest that the impaired anti-inflammatory elements may also contribute to the severe clinical outcome of AIA. During the AIA reaction, the urinary concentrations of LTE(4) and PGD(2) metabolites, including tetranor-PGDM significantly and correlatively increase. It is considered that mast cell activation probably is a pathophysiologic hallmark of AIA. However, despite the fact that cyclooxygenease-1 is the dominant in vivo PGD(2) biosynthetic pathway, the precise mechanism underlying the PGD(2) overproduction resulting from the pharmacological effect of cyclooxygenease-1 inhibitors in AIA remains unknown. A comprehensive analysis of the urinary concentration of inflammatory mediators may afford a new research target in elucidating the pathophysiology of AIA.     

Soluble type II transforming growth factor-beta receptor attenuates expression of metastasis-associated genes and suppresses pancreatic cancer cell metastasis

Pancreatic ductal adenocarcinoma (PDAC) is a deadly malignancy that frequently metastasizes and that overexpresses transforming growth factor-beta s (TGF-beta s). To determine whether TGF-beta s can act to enhance the metastatic potential of PDAC, PANC-1 human pancreatic cancer cells were transfected with an expression construct encoding a soluble type II TGF-beta receptor (sT beta RII) that blocks cellular responsiveness to TGF-beta 1. When injected s.c. in athymic mice, PANC-1 clones expressing sT beta RII exhibited decreased tumor growth in comparison with sham-transfected cells and attenuated expression of plasminogen activator inhibitor 1 (PAI-1), a gene associated with tumor growth. When tested in an orthotopic mouse model, these clones formed small intrapancreatic tumors that exhibited a suppressed metastatic capacity and decreased expression of plasminogen activator inhibitor 1 and the metastasis-associated urokinase plasminogen activator. These results indicate that TGF-beta s act in vivo to enhance the expression of genes that promote the growth and metastasis of pancreatic cancer cells and suggest that sT beta RII may ultimately have a therapeutic benefit in PDAC.     

Treatment for Churg-Strauss syndrome: induction of remission and efficacy of intravenous immunoglobulin therapy.

Churg-Strauss syndrome (CSS) is characterized by the presence of asthma, eosinophilia, and small-vessel vasculitis with granuloma. It is a distinct entity, as determined from all classifications of systemic vasculitis. The poor prognostic factors in CSS are renal insufficiency, cardiomyopathy, severe gastrointestinal (GI) tract, and central nervous systems (CNS) involvement. The initial management of CSS should include a high dose of a corticosteroid: prednisone at 1 mg/kg/day or its equivalent for methylprednisolone with tapering over 6 months. In patients with severe or rapidly progressing CSS, the administration of methylprednisolone pulse at 1 g/body/day for 3 days is recommended. When corticosteroid therapy does not induce remission, or when patients have poor prognostic factors, immunosuppressive cytotoxic therapy is indicated. However, some patients with severe CSS often show resistance to conventional treatment. We think that IVIG therapy is a hopeful candidate for second-line treatment for CSS patients, particularly in the case of neuropathy and/or cardiomyopathy, which are resistant to conventional therapy. However, there is not much evidence supporting the effectiveness of IVIG in CSS, and the mechanisms underlying the action of IVIG remain unclear. Now we are performing clinical trials of IVIG therapy for CSS patients who are resistant to conventional treatment, through a nationwide double-blinded placebo-controlled study in Japan.     

Ambulatory blood pressure, blood pressure variability and the prevalence of carotid artery alteration: the Ohasama study

OBJECTIVES: To investigate the association between ambulatory blood pressure (BP) variables (level, short-term variability, circadian variation and morning pressor surge) and carotid artery alteration in a general population. METHODS: We measured ambulatory BP every 30 min in 775 participants (mean age 66.2 +/- 6.2 years, 68.8% women) from the Japanese general population. Short-term BP variability during the daytime and night-time were estimated as within-subject standard deviation of daytime and night-time BP, respectively. Circadian BP variation was calculated as the percentage decline in nocturnal BP. Morning pressor surge was defined as morning BP minus pre-waking BP. The extent of carotid artery alteration was evaluated as the average of common carotid intima-media thickness (IMT) and the presence of focal carotid plaque. RESULTS: Daytime and night-time BP values were more closely associated with carotid artery alteration than casual BP. With mutual adjustment for daytime and night-time BP, the latter (P < 0.0001) was more closely associated with IMT, which represents diffuse arterial thickening and arteriosclerosis, than daytime BP (P = 0.2). Night-time systolic BP variability was positively associated with carotid plaque (focal atherosclerotic lesions) independently of possible confounding factors, including night-time systolic BP (P = 0.01). A diminished nocturnal decline in systolic BP was associated with a greater IMT after adjustment for confounding factors (P = 0.03). A morning pressor surge was not associated with carotid artery alteration. CONCLUSION: Ambulatory BP levels and BP variability were closely associated with carotid artery alteration, suggesting that these parameters are independent risk factors or predictors of carotid artery alteration.     

Autonomic cardiovascular responses to heme oxygenase inhibition in conscious rats

Carbon monoxide (CO) is produced in the course of heme degradation from biliverdin by heme oxygenase (HO) in various tissues, including the central nervous system. Recent studies suggest the inhibition of HO activity increases arterial pressure mediated by the autonomic nervous system. The present study was designed to investigate the autonomic regulation of cardiovascular responses to inhibition of endogenous CO production by the HO inhibitor Zinc deuteroporphyrin 2, 4-bis glycol (ZnDPBG) by using direct sympathetic nerve recordings in conscious, chronically instrumented rats. ZnDPBG induced increases in mean arterial pressure (MAP) (P<0.05) and renal sympathetic nerve activity (RSNA) (P<0.05) but no significant change in heart rate (P>0.05) in intact rats. In atropine-treated rats, ZnDPBG also induced increases in MAP (P<0.05) and RSNA (P<0.05) but no change in heart rate (P>0.05). In sinoaortic denervated rats, ZnDPBG induced increases in MAP (P<0.05), heart rate (P<0.05), and RSNA (P<0.05). ZnDPBG shifted the baroreflex curve for RSNA upward and to the right, which was characterized by increases in the maximum and minimum response and midpoint pressure without altering the maximum gain. These results indicate that inhibition of HO activity within the central nervous system causes sympathoexcitation, resulting in an increase in arterial pressure. We conclude that the CO/HO system plays an important role in cardiovascular regulation by modulating sympathetic tone.     

Salmon growth hormone receptor: molecular cloning, ligand specificity, and response to fasting

To better understand the role of growth hormone in regulating fish growth, the cDNA of growth hormone receptor (GHR) was cloned from the liver of masu salmon (Oncorhynchus masou) and characterized. The masu salmon GHR (msGHR) sequence revealed common features of a GHR, including a (Y/F)GEFS motif in the extracellular domain, a single transmembrane region, and Box 1 and Box 2 in the intracellular domain. However, the amino acid sequence identity was low (49%) compared to GHRs of other vertebrates including seven teleosts, and the putative msGHR protein lacked one pair of cysteine residues in the extracellular domain. To verify the identity of the msGHR, the recombinant protein of the extracellular domain was expressed with a histidine tag protein (His-msGHR-ECD), refolded and purified for analysis of its ligand specificity. In competition experiments, the specific binding between His-msGHR-ECD and radioiodine-labeled salmon GH was displaced completely by only salmon GH, and not by salmon prolactin or somatolactin. A real-time RT-PCR assay was used to measure salmon GHR mRNA in the liver of fed and fasted coho salmon (Oncorhynchus kisutch). The levels of hepatic GHR mRNA were lower in fasted fish compared to fed fish after 3 weeks, suggesting that GHR gene expression is reduced following a long-term fast. These results confirm the identity of the salmon GHR based on ligand specificity and response to fasting.     

The subjective incremental cost of informed consent and documentation in hospital care: a multicentre questionnaire survey in Japan

Objective  To reveal the amount of time and financial cost required to obtain informed consent and to preserve documentation.
Methods  The questionnaire was delivered to all staff in six acute care public hospitals in Japan. We examined health care staff perceptions of the time they spent obtaining informed consent and documenting information. All data were collected in 2006 and estimates in the past week in 2006 were compared to estimates of time spent in a week in 1999. We also calculated the economic costs of incremental amounts of time spent in these procedures.
Results  In 2006, health care staff took about 3.89 hours [95% Confidence Interval (CI) 3.71–4.07] per week to obtain informed consent and 6.64 hours (95% CI 6.40–6.88) per week to write documentation on average. Between 1999 and 2006, the average amount of time for conducting informed consent was increased to 0.67 ( P  < 0.001) hours per person-week, and the average amount of time for documentation was increased to 0.70 ( P  < 0.001) hours per person-week. The annual economic cost of activities for informed consent and documentation in a 100-bed hospital increased from 117 755 to 449 402 US dollars.
Conclusions  We found a considerable increase in time spent on informed consent and documentation, and associated cost over a 7-year time period. Although greater attention to the informed consent process should be paid to ensure the notions of patient autonomy and self-determination, the increased resources devoted to these practices must be considered in light of current cost containment policies.