Clonal evolution and lack of cytogenetic response are adverse prognostic factors for hematologic relapse of chronic phase CML patients treated with imatinib mesylate

We followed 141 patients treated with imatinib mesylate (> 300 mg) for chronicphase chronic myelogenous leukemia (CML) following failure of treatment with interferon. During 12 months from the start of imatinib mesylate treatment, 96.5% achieved a complete hematologic response, 47.0% achieved a major cytogenetic response, and 32.4% achieved a complete cytogenetic response. The proportion of patients with hematologic relapse was 10.9% at 12 months and 14.6% at 18 months. In a univariate Cox regression analysis, the only pretreatment characteristics that correlated with an increased risk of hematologic relapse were hemoglobin level less than 120 g/L (12 g/dL) (P =.02), increased bands in the peripheral blood (P =.01), and clonal evolution (P <.0001). In a multivariate analysis, an elevated platelet count (P =.03) and clonal evolution (P <.0001) were the only significant factors for hematologic relapse. During treatment, the absence of a major cytogenetic response within the first 6 months also significantly correlated with relapse (P =.03). Notably, patients failing to achieve a major cytogenetic response by 6 months had a significantly higher rate of hematologic relapse (27%) compared with those who achieved a major cytogenetic response by 6 months (3%), and patients with clonal evolution had a significantly higher risk of hematologic relapse (50%) than those without clonal evolution (9%).     

Management of patients with stercoral perforation of the sigmoid colon： Report of five cases

To our knowledge,stercoral perforation of the colonis rarely seen with fewer than 90 cases reported inthe literature till date.We explored the principles ofmanagement to prevent impending mortality in fivepatients with this condition.Five patients,two malesand three females,whose median age was 64 years,had sustained stercoral perforation of the sigmoid colon.Chronic constipation was the common symptom amongthese patients.Three patients underwent a Hartmann'sprocedure and another two were treated with segmentalcolectomy with anastomosis and diverting colostomy.There was one surgical mortality and the other patientshad an uneventful hospital stay.Timely intervention toprevent and/or treat any associated sepsis along withextensive peritoneal lavage and surgical intervention toremove diseased colonic tissue at the primary stercoralulceration site coupled with aggressive therapy for peri-tonitis are key treatment modalities in salvaging patientspresenting with stercoral perforation of the colon.     

Transfusion audit of fresh-frozen plasma in southern Taiwan

BACKGROUND AND OBJECTIVES: The demand for transfusions has increased rapidly in southern Taiwan. Between 1993 and 2003, requests for fresh-frozen plasma (FFP) in particular rose dramatically at Kaohsiung Medical University Hospital (KMUH). Transfusion orders were not tightly regulated, and inappropriate use of blood products was common. MATERIALS AND METHODS: We carried out a prospective analysis of transfusion requests from October 2003 to January 2004 at KMUH, and then repeated the audit for another 3-month period after the clinical faculty had undergone five sessions of education on transfusion guidelines. Later, our consultant haematologist applied computerized guidelines to periodic audits. RESULTS: A 5.2% decrease in inappropriate FFP usage followed the educational programme and a further 30% reduction took place after the application of computerized transfusion guidelines. With the guidelines and periodic audits, FFP transfusions decreased by 74.6% and inappropriate requests from 65.2% to 30%. CONCLUSIONS: Hospital policy, computerized transfusion guidelines and periodic audits greatly reduced inappropriate FFP transfusions. An educational campaign had a more limited effect.     

Type 2 diabetes and hepatocellular carcinoma: A cohort study in high prevalence area of hepatitis virus infection

This study aimed to elucidate the relationship of type 2 diabetes, other known risk factors, and primary hepatocellular carcinoma (HCC) in countries with a high prevalence of hepatitis infection. We followed a prospective cohort of 54,979 subjects who participated in the Keelung Community-Based Integrated Screening program between 1999 and 2002. A total of 5,732 subjects with type 2 diabetes cases were identified at enrollment on the basis of fasting blood glucose level, and a total of 138 confirmed HCC cases were identified either through two-stage liver cancer screening or linkage with the National Cancer Registry. The independent effect of type 2 diabetes on the incidence of HCC and the interaction between type 2 diabetes and hepatitis infection or lipids profile were assessed using the Cox proportional hazards regression model. After controlling for age, sex, hepatitis B virus (HBV), hepatitis C virus (HCV), smoking, and alcohol consumption, the association between type 2 diabetes and incidence of HCC (excluding 33 prevalent cases identified at enrollment) was modified by HCV status and cholesterol level. The associations were only statistically significant (adjusted hazard ratio [HR] = 2.08 [1.03-4.18]) for being HCV negative and for having hypercholesterolemia (adjusted HR = 2.81 [1.20-6.55]). These statistically significant findings remained even excluding cases of diabetes newly diagnosed at enrollment. In conclusion, in an area with a high prevalence of hepatitis virus infection, type 2 diabetes increases the risk of developing HCC in those who are HCV negative or have a high level of total cholesterol.     

Cerebrovascular disease associated with sickle cell pulmonary hypertension

In patients with sickle cell disease, anemia is a recognized risk factor for stroke, death, and the development of pulmonary hypertension. We have proposed that hemolytic anemia results in endothelial dysfunction and vascular instability and can ultimately lead to a proliferative vasculopathy leading to pulmonary hypertension. Consistent with this mechanism of disease, we now report a case series of six patients with obliterative central nervous system vasculopathy who also have pulmonary hypertension and high hemolytic rate. These patients, identified in the course of a prospective screening study for pulmonary hypertension, presented with neurological symptoms prompting neuroimaging studies. Compared to 164 other patients of similar age in the screened population, those with newly diagnosed or clinically active cerebrovascular disease have significantly lower hemoglobin levels and higher levels of lactate dehydrogenase. A review of the literature suggests that many clinical, epidemiological, and physiological features of the arteriopathy of pulmonary hypertension closely overlap with those of stroke in sickle cell disease, both known to involve proliferative vascular intimal and smooth muscle hypertrophy and thrombosis. These cases suggest that cerebrovascular disease and pulmonary hypertension in sickle cell disease share common mechanisms, in particular, reduced nitric oxide bioactivity associated with particularly high-grade hemolysis. Clinicians should suspect occult cerebrovascular disease in sickle cell patients with pulmonary hypertension.     

Improved survival of persons with human immunodeficiency virus type 1 infection in the era of highly active antiretroviral therapy in Taiwan

We assessed the survival of 1,044 HIV-infected persons enrolled in three periods: period 1, 1994 to 1997 (before the introduction of highly active antiretroviral therapy [HAART]); period 2, 1997 to 2000 (early-HAART); and period 3, 2000 to 2004 (late-HAART). As of 30 June 2005, 259 (24.8%) persons had died after a median observation duration of 985 days (range, 2 - 4,025 days). The mortality rate declined from 33.75 per 100 person-years in the pre-HAART era to 6.51 per 100 person-years in the late-HAART era (P < 0.0001). The adjusted hazard ratios for death in persons with a baseline CD4 count of <200 cells/mul in periods 2 and 3 were 0.605 (P = 0.007) and 0.371 (P < 0.0001), respectively, when compared with persons enrolled in period 1; the adjusted hazard ratio for death was 0.611 for persons enrolled in period 3 when compared to period 2 (P = 0.01). Our study suggested that the survival of persons in the late stage of HIV infection in Taiwan continued to improve in the late HAART era.     

Imaging the Impact of Nox4 in Cycling Hypoxia-mediated U87 Glioblastoma Invasion and Infiltration

Purpose

We determined the impact of the cycling hypoxia tumor microenvironment on tumor cell invasion and infiltration in U87 human glioblastoma cells and investigated the underlying mechanisms using molecular bio-techniques and imaging.

Procedures

The invasive phenotype of U87 cells and xenografts exposed to experimentally imposed cycling hypoxic stress in vitro and in vivo was determined by the matrigel invasion assay in vitro and dual optical reporter gene imaging in vivo. RNAi-knockdown technology was utilized to study the role of the NADPH oxidase subunit 4 (Nox4) on cycling hypoxia-mediated tumor invasion.

Results

Cycling hypoxic stress significantly promoted tumor invasion in vitro and in vivo. However, Nox4 knockdown inhibited this effect. Nox4-generated reactive oxygen species (ROS) are required for cycling hypoxia-induced invasive potential in U87 cells through the activation of NF-??B- and ERK-mediated stimulation of MMP-9.

Conclusions

Cycling hypoxia-induced ROS via Nox4 should be considered for therapeutic targeting of tumor cell invasion and infiltration in glioblastoma.     

Comparison of single daily dose of methimazole and propylthiouracil in the treatment of Graves' hyperthyroidism

OBJECTIVE: The present study was to compare the efficacy of a single daily dose of methimazole (MMI) and propylthiouracil (PTU) in the treatment of Graves' hyperthyroidism. BACKGROUND: Antithyroid drugs, MMI and PTU, are widely used in the treatment of hyperthyroidism. Previous studies in the treatment of hyperthyroidism with a single daily dose of antithyroid drugs have demonstrated a more favourable result with MMI. However, the efficacy of a single daily dose of PTU was inconsistent. In this study, we examined the therapeutic efficacy of single daily doses of MMI and PTU on the change of thyroid hormones and thyrotropin receptor antibodies (TRAb) levels. METHODS: Thirty patients with newly diagnosed Graves' hyperthyroidism were randomly divided into two groups, each receiving a single dose of either 15 mg MMI or 150 mg PTU daily for 12 weeks. The therapeutic efficacy was determined by serum total triiodothyronine (TT3), total thyroxine (TT4), thyrotropin (TSH), free thyroxine (FT4), and TRAb levels at baseline and at the end of 4, 8 and 12 weeks during the study period. RESULTS: There was no significant difference in baseline thyroid function parameters. Serum TT3, TT4 and FT4 levels in the MMI-treated group were significantly lower than those of the PTU-treated group after 4 weeks and through the end of the study. MMI also has superior effect on reducing serum TRAb levels than PTU after 8 weeks and at the end of the study. CONCLUSION: During the 12-week treatment of Graves' hyperthyroidism, a single daily dose of 15 mg MMI was much more effective in the induction of euthyroidism than a single daily dose of 150 mg PTU. In the doses used in this study, MMI is preferable to PTU when a once-daily regimen of antithyroid drug is considered for the treatment of Graves' hyperthyroidism.     

Poor responders to intravenous omeprazole in patients with peptic ulcer bleeding

BACKGROUND/AIMS: Although proton pump inhibitors are highly effective in raising intragastric pH, there still remains a small group of patients who resist acid suppression. A high dose of omeprazole has been shown to reduce rebleeding rate in patients with bleeding peptic ulcers after endoscopic therapy. The primary objective of this study was to assess the incidence of peptic ulcer bleeding patients who were resistant to intravenous omeprazole. The secondary objective was to evaluate the relationship between intragastric pH and rebleeding rate in studied patients after successful endoscopic therapy. METHODOLOGY: Between Oct. 1996 and Aug. 1999, 88 bleeding peptic ulcer patients who had obtained initial hemostasis with endoscopic therapy were enrolled in this study. In these patients, 40 mg of omeprazole was given as intravenous bolus followed by 40 mg intravenously every 6 h for 3 days. Thereafter, omeprazole was given 20 mg orally once daily for 2 months. The intragastric pH was recorded for 24 hours after the first dose of omeprazole. The occurrence of rebleeding was observed for 14 days. RESULTS: The mean intragastric pH value of these 88 patients was 6.07, (95% CI: 5.91-6.23). Four patients (5%) were found to have omeprazole resistance (pH < 4.0, 50% of the time). By the 3rd days after entering the study, more patients with a mean pH < 6 rebled (5/25 vs. 3/63, p<0.05). CONCLUSIONS: About five percent of patients with peptic ulcer bleeding respond poorly to intravenous omeprazole. Rebleeding rate is higher in patients with a mean intragastric pH of less than 6.     

Musculoskeletal ultrasound imaging training,use, and knowledge among rheumatologists in China

Clinical Rheumatology - Musculoskeletal ultrasound (MSUS) has been extensively studied by rheumatologists in Europe and the Americas, but less is known about MSUS use in Asia. Our hypothesis is...