Prediction of operative mortality based on impairment of host defense systems in patients with esophageal cancer

To determine whether operative risk based on impaired defense systems can be predicted, we examined 21 markers in 32 patients with esophageal cancer seen between 1983 and 1985 and related them to postoperative deaths. A discriminant analysis proved useful in determining whether the patient would be at risk of operative mortality, based on impaired defense systems. This model, the host defense index (HDI), was then used clinically to evaluate findings in 64 patients seen between 1986 and 1991. During this period, a change in policy for performing transthoracic esophagectomy on and perioperative care for patients with impaired defense systems was associated with a decrease in operative mortality. Thus, the HDI is beneficial to predict the risk of operative mortality based on impaired defense systems in patients with esophageal cancer. © 1993 Wiley-Liss, Inc.     

Impact of ecological factors on concern and awareness about disability: A statistical analysis

The barriers that people with disabilities face around the world are not only inherent in the limitations resulting from the disability itself, but, more importantly, these barriers rest with the societal technologies of exclusion. A multiple regression analysis was conducted to examine the statistical relationship between the national level of development, the level of democratization, and the level of education of a country's population on one hand, and expressed concern for people with disabilities on another hand. The results reveal that a greater worry for the well-being of people with disabilities is correlated with a high level of country development, a decreased value of political stability and absence of violence, a decreased level of government effectiveness, and a greater level of law enforcement. There is a direct correlation between concern for people with disabilities and people's awareness about disabilities. Surprisingly, the level of education has no impact on the compassion toward people with disabilities. A comparison case for in depth illustration is discussed.     

Contact allergy to aliphatic polyisocyanates based on hexamethylene-1,6-diisocyanate (HDI)

Background. Aliphatic polyisocyanates based on hexamethylene 1,6‐diisocyanate (HDI) are components of lacquers, coatings, and spray paints. They are mainly composed of HDI trimers, but also contain larger oligomers, and minute amounts of HDI monomers (<1%). HDI trimers occur as biuret, isocyanurate and asymmetrical types. Objectives. We report on 4 patients with allergic contact dermatitis/contact allergy resulting from HDI‐based polyisocyanates in polyurethane paints. Methods. The patients were examined at the Finnish Institute of Occupational Health in 2000–2009. The first two patients were diagnosed by testing with their own polyurethane hardeners and ingredients of the hardeners. In 2002, HDI isocyanurate (HDI‐IC) trimer was added to our isocyanate series, and the last two patients were screened with the series. Results. Patient no. 1 was exposed and sensitized to HDI biuret trimer, patient no. 2 to HDI‐IC trimer, and patient no. 4 to HDI asymmetrical trimer. Patient no. 3 was positive with HDI‐IC trimer. He had been handling several paint hardeners containing HDI‐based polyisocyanates, but the subtypes of the trimers remained unidentified. All 4 patients were negative with HDI monomer. Conclusions. HDI trimers are novel contact allergens in workers who handle polyurethane paints. The allergic reactions cannot be explained by sensitization to HDI monomer.     

慢性丙型肝炎铁沉积的组织病理学与血清铁指标的相关性研究

目的探讨慢性丙型肝炎铁沉积的组织病理学与血清铁蛋白的相关性。方法对92例慢性丙型肝炎患者行肝穿刺活检,以组织病理学方法探测铁(histologically detectabliron,HDI)含量并以免疫组织化学法检测铁蛋白(immunohistoche-micall detectable ferri-tin,IDF)含量;同时监测患者血清铁、血清铁蛋白指标。结果血清铁与慢性丙肝的炎症分级(P=0．006)以及血清铁蛋白(P=0．005)和组织铁蛋白(P=0．039)与慢性丙肝的纤维化程度具有相关性。结论在慢性丙型肝炎中,血清铁水平反映了近期内肝细胞炎症、坏死的程度;血清铁蛋白和组织铁蛋白水平显示了肝脏纤维化的进展程度。     

Suberoylanilide hydroxamic acid is effective in preclinical studies of medulloblastoma

Purpose Suberoylanilide hydroxamic acid (SAHA) has been studied in adult solid and hematologic malignancies. However, little information has been reported on the effects of SAHA on central nervous system (CNS) tumors including medulloblastoma, the most common malignant brain tumor in children. We investigated SAHA in preclinical medulloblastoma models to determine its anti-cancer efficacy as well as its ability to␣affect intracranial lesions when administered systemically.Experimental design and results Tissue culture studies were performed treating primary human fibroblasts, established medulloblastoma cell lines, and primary human medulloblastoma tumors with SAHA. At 10 μM concentration, SAHA had little effect on normal fibroblasts but caused >90% apoptosis in cultured medulloblastoma cells. Primary medulloblastomas from patients were sensitive to SAHA compared to vehicle alone in ex vivo studies. In athymic mice with medulloblastoma xenograft tumors, oral SAHA resulted in apoptosis of tumor tissue and significantly slowed tumor growth. In the ND2:Smo transgenic mouse medulloblastoma model, SAHA treatment caused significant apoptosis in these cerebellar tumors.Conclusions SAHA effectively induces cell death in established medulloblastoma cell lines, human patient primary tumor cultures, medulloblastoma xenografts and intracranial spontaneous medulloblastomas. Fibroblasts in culture and mice treated with SAHA did not reveal prohibitive toxicity profiles. These findings support the advancement of SAHA to pediatric clinical trials.     

Lack of mutagenic activity of 1,6-hexamethylene diisocyanate.

1,6-Hexamethylene diisocyanate (HDI) is an aliphatic diisocyanate used in the manufacture of higher molecular weight biuret and trimer polyisocyanate resins. These resins are commonly used in polyurethane paints, resulting in potential occupational, and to a lesser extent consumer exposures. Because some isocyanates have been reported to be mutagenic, HDI was tested in the bacterial reverse mutation assay (Ames test), CHO/HGPRT gene mutation assay, and in the mouse micronucleus test, using vapor-phase exposures. Although indicators of toxicity were observed in each test, HDI did not induce mutagenic or clastogenic effects in any of the three assays.     

Isocyanate vapor-induced antigenicity of human albumin

BACKGROUND: The bioreactivity of isocyanate, a leading cause of occupational asthma, has led to uncertainty regarding the chemical's antigenicity and mechanisms that elicit immunopathology. OBJECTIVE: To understand better the biologically relevant antigenic forms of hexamethylene diisocyanate (HDI), commonly used in the auto body industry. METHODS: Human albumin was exposed to HDI vapors through a novel approach designed to model the air-liquid interface of the human airway. Vapor HDI-exposed albumin was characterized by electrophoresis, chemical substitution analysis, mass spectrometry, and serology studies on auto body shop workers (N=203) and HDI asthmatics (N=11). RESULTS: HDI vapors caused significant changes in the shape and/or charge of human albumin, which differed from albumin exposed to liquid phase HDI, with lower isocyanate substitution ratios and distinct electrophoretic mobility. Specific sites of vapor HDI conjugation to albumin were identified at His(247) and Lys(414). Vapor HDI-exposed albumin was specifically recognized by the humoral arm of the human immune system, with a strong dependence on albumin as the carrier. Vapor HDI-exposed albumin-specific IgG titers were significantly associated with HDI exposure (P=.001), and specific IgE was detectable in 55% (6/11) of isocyanate asthmatics versus 1.5% (3/203) of exposed healthy workers. Parallel studies using HDI-exposed albumin conjugates produced by previously published methods showed less significant associations of HDI-specific IgG and IgE with exposure and disease, respectively. CONCLUSION: HDI-albumin conjugates produced by novel vapor phase exposure methods may be more physiologically relevant than those produced by previously published methods and of greater utility in characterizing the immune responses associated with HDI exposure and asthma.     

The guinea pig model of diisocyanate sensitization: II. Physiologic studies

The qualitative and quantitative properties of diisocyanate-specific IgE antisera derived from an IgE-susceptible strain of guinea pigs were investigated by passive sensitization of immunologically virgin recipient animals. These animals received infusions of antisera 48 hr before intravenous challenge with specific ligands conjugated to an unrelated carrier protein, human transferrin. The pulmonary response was sublethal and could be measured by physiologic methods. Various measurements were obtained in anesthetized guinea pigs placed in a whole-body pressure plethysmograph. Tidal volume (V_t), dynamic compliance (C_{L dyn}), and pulmonary conductance (G_L) were calculated from simultaneous recordings of transpulmonary pressure. V_t, and flow. Frequency at 1 and 2 min after intravenous challenge were also measured. Mean respiratory frequency was significantly increased in experimental animals 1 min after challenge with homologous hapten-protein conjugates, while maximum changes of V_t, c_{L dyn}, and G_L occurred 2 min after intravenous challenges. A preponderant number of physiologic abnormalities occurred in animals challenged with homologous hapten-protein conjugates. The mean percent change of V_t and C_{L dyn} from baseline levels was significantly decreased after intravenous challenges with homologous ligands in animals passively sensitized with both hexamethylene diisocyanate—(HDI) and toluene diisocyanate-specific antisera. However, decrease of mean G_L after challenge with homologous hapten-protein conjugates was significant only in animals passively sensitized with HDI-specific antisera. When the number of positive postchallenge pulmonary function responses was compared with the mean geometric titers of IgE antisera, it was observed that moderate or severe physiologic responses were associated with infusions of IgE antisera having titers of 160 or greater. These experiments suggest that antibody concentration may be a critical determinant in distinguishing between clinical, subclinical and nonreactive states induced by diisocyanate sensitization.     

Incidence and Mortality of Bladder Cancer and their Relationship with Development in Asia

Background: Over the past decade, bladder cancer was associated with a significant increase. Given theimportance of the impact of socioeconomic status on the distribution of cancer incidence and mortality, and theneed to information on these parameters for prevention planning, the aim of this study was to evaluate datafor bladder cancer and their relationship with human development index (HDI) and its components in Asia in2012. Materials and Methods: The study was conducted based on data from the world data of cancer and theWorld Bank (including the HDI and its components). The incidence and mortality rates were drawn for Asiancountries. To analyze data, correlation tests between incidence and death rates, and HDI and its components wereemployed with a significance level of 0.05 using SPSS software. Results: A total incidence of 696,231 cases (68.7%in males and 31.3% in females, sex ratio of 2.19:1) and 524,465 deaths (67.0% in men and 32.9% in women, sexratio was 2.03:1) were recorded in Asian countries in 2012. Correlation between HDI and standardized incidencerate was 0.241 overall (p=0.106), 0.236 in men (p=0.114) and -0.250 in women (p=0.094). Also between HDI andstandardized mortality rate 0.025 (p=0.871) in men 0.118 (p=0.903) and in women 0.014 (p=0.927). Conclusions:Bladder cancer incidence is higher in developed countries, but the rate is declining, and in less developed anddeveloping countries it is growing. There was no statistically significant correlation between the standardizedincidence rate of bladder cancer and the HDI and its dimensions in Asia, except for the level of education.