Comparative analysis of clinical outcomes after allogeneic bone marrow transplantation versus peripheral blood stem cell transplantation from a related donor in Japanese patients

A reduced incidence of graft versus host disease (GvHD) has been documented among Japanese allogeneic bone marrow transplantation (BMT) patients, as the Japanese are genetically more homogeneous than western populations. To clarify whether this ethnic difference affects the results of allogeneic peripheral blood stem cell transplantation (PBSCT), we conducted a nationwide survey to compare clinical outcomes of allogeneic PBSCT (n = 214) and BMT (n = 295) from a human leucocyte antigen-identical-related donor in Japanese patients. The cumulative incidence of grades II-IV acute GvHD was 37.4% for PBSCT and 32.0% for BMT. The cumulative incidence of extensive chronic GvHD at 1 year was significantly higher after PBSCT than BMT (42% vs. 27%; P < 0.01). The organ involvement patterns of GvHD were different between the two groups. By multivariate analyses, the incidence of chronic GvHD was significantly increased in PBSCT, whereas the stem cell source did not affect the incidence of acute GvHD, transplant-related mortality, relapse or survival. We concluded that Japanese PBSCT patients have an increased risk of chronic GvHD compared with BMT patients, but the incidence of acute GvHD was still lower than in western populations. Thus, the choice of haematopoietic stem cell source should be considered based on data for individual ethnic populations.     

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.     

Trends in Asthma Mortality in Japan

Asthma mortality has been increasing in many developed countries in recent years, so we have described the epidemiological features of asthma in Japan. Data on all certified asthma deaths from 1950 to 1997 were obtained from The National Vital Statistics, published annually by the Ministry of Health and Welfare. Trends in crude and age-adjusted asthma mortality rates, as well as age-specific mortality rates, were analyzed. Age and birth cohort effects on mortality rates were also examined using multiplicative models. Between 1950 and 1980, crude asthma mortality rates steadily decreased in both sexes and began to level off thereafter. Age-adjusted mortality rates have also decreased since 1950, and showed a persistent downward trend in both sexes even in recent years. Asthma mortality rates were higher in males than in females during the entire study period. When analysis was restricted to those aged 5 to 34 years, an upward trend since 1980 was observed. The multiplicative model showed a rapidly decreasing cohort effect on mortality among those born after 1860. However, the slope increased in the cohorts born after 1950 in both sexes. The age effect increased linearly with advancing age after 50 years in both sexes. Overall asthma mortality rates have been decreasing during the past five decades in Japan, but the mortality rate has increased among the 5-34-year-old age group since 1980. The high fatality rate stemming from the overuse of beta 2-agonists may account for the mortality increase.     

Increased macrophage colony-stimulating factor levels in patients with Graves’ disease

Previous studies have found markedly elevated serum concentrations of proinflammatory cytokines in patients with Graves’ disease (GD). We investigated the role of macrophage colony-stimulating factor (M-CSF) in GD. We assayed concentrations of M-CSF in sera from 32 patients with GD (25 untreated; 7 receiving thiamazole therapy). We also studied 32 age-matched healthy subjects as controls. Relationships between serum M-CSF and both thyroid state and serum lipids were examined. Moreover, to examine the effect of thyroid hormone alone on serum M-CSF, T3 was administered orally to normal subjects. Serum concentrations of M-CSF in GD patients who were hyperthyroid were significantly increased compared with GD patients who were euthyroid (P < 0.05) and control subjects (P < 0.0001). Serum M-CSF concentrations correlated closely with T3 levels in patients (r = 0.51, P < 0.005). Serial measurement of five individual patients revealed that serum concentrations of M-CSF were significantly decreased (P < 0.05), reaching normal control values upon attainment of euthyroidism. Furthermore, oral T3 administered to 15 volunteers for 7 days produced significant increases in serum levels of M-CSF (P < 0.05). The close correlation between serum M-CSF and serum thyroid hormone levels suggests that high circulating levels of thyroid hormones may directly or indirectly potentiate the production of M-CSF in patients with GD.     

Clinicopathology of pancreaticobiliary maljunction: relationship between alterations in background biliary epithelium and neoplastic development

Background/Purpose

Between 1988 and 2003, 38 patients underwent biliary resection for pancreaticobiliary maljunction (PBM). We reviewed the histopathologic findings for the surgically resected specimens to compare the clinical and pathologic features and assess the relationship between changes in the background biliary epithelium and the development of neoplasms.

Methods

Papillary hyperplasia (PHP) seen in the biliary epithelium of patients with PBM, was classified into grades 0–III in the gallbladder and grades 0–II in the extrahepatic bile duct, according to the extent, and was assessed for links with tumors in the same specimens.

Results

The incidence of gallbladder carcinoma was 13/21 in grades I–II, versus 0/16 in grade III, while the incidence of bile duct carcinoma was 4/20 in grade I versus 0/5 in grade II. Furthermore, these incidences for patients below age 50 years and age 50 or older were 1/18 versus 12/20, and 0/14 versus 6/17, respectively.

Conclusions

PHP of the biliary epithelium in PBM patients is an important precursor lesion, especially for gallbladder cancer, and the risk becomes greater with age, regardless of the type of pancreatobiliary junction (PBJ) and its location in the biliary tract.     

Different hypersensitivities against homologous proteins of MGL_1304 in patients with atopic dermatitis

Background

Atopic dermatitis (AD) is exacerbated by sweating, and the skin of most patients with AD are resided by Malassezia (M.) fungi. Recently, MGL_1304 produced by Malassezia globosa was identified as the major histamine releasing antigen in human sweat.

Pain in patients with fibromyalgia syndrome

Chronic diffuse pain and hyperalgesia are two cardinal features of pain in fibromyalgia syndrome (FMS). Advancement in understanding the pathophysiology and treatment efficacy often depends on pain that is defined and measured. Pain is a subjective phenomenon that we can measure only by indirect methods. In this article, we provide methodological guidelines for pain assessment and review recent developments in understanding pain mechanisms and evaluating treatments in FMS. Finally, we demonstrate the heterogeneity of the FMS population and suggest the need for matching treatments to patient characteristics in order to improve clinical outcomes.     

Eigenspace Template Matching for Detection of Lacunar Infarcts on MR Images

Detection of lacunar infarcts is important because their presence indicates an increased risk of severe cerebral infarction. However, accurate identification is often hindered by the difficulty in distinguishing between lacunar infarcts and enlarged Virchow-Robin spaces. Therefore, we developed a computer-aided detection (CAD) scheme for the detection of lacunar infarcts. Although our previous CAD method indicated a sensitivity of 96.8 % with 0.71 false positives (FPs) per slice, further reduction of FPs remained an issue for the clinical application. Thus, the purpose of this study is to improve our CAD scheme by using template matching in the eigenspace. Conventional template matching is useful for the reduction of FPs, but it has the following two pitfalls: (1) It needs to maintain a large number of templates to improve the detection performance, and (2) calculation of the cross-correlation coefficient with these templates is time consuming. To solve these problems, we used template matching in the lower dimension space made by a principal component analysis. Our database comprised 1,143 T₁- and T₂-weighted images obtained from 132 patients. The proposed method was evaluated by using twofold cross-validation. By using this method, 34.1 % of FPs was eliminated compared with our previous method. The final performance indicated that the sensitivity of the detection of lacunar infarcts was 96.8 % with 0.47 FPs per slice. Therefore, the modified CAD scheme could improve FP rate without a significant reduction in the true positive rate.