The changing scene of allogeneic stem cell transplantation for chronic myeloid leukemia—a report from the German Registry covering the period from 1998 to 2004

Due to the recent changes in the indication to allogeneic stem cell transplantation (SCT) in chronic myeloid leukemia (CML), we retrospectively analyzed 1,716 patients with different CML stages who received an allograft from related (n?=?767) or unrelated donors (n?=?938) within the German Registry of Stem Cell Transplantation (DRST) from 1998 to 2004. Myeloablative conditioning was performed in 724/871 cases (83%), dose-reduced conditioning in 147/871 (17%). Annual transplantations were decreasing from 357 to 98 (28%) in the period of study, but the proportion of advanced cases was increasing from 32% (112/346) to 53% (50/94) of all SCTs. Stage of disease, intervals from diagnosis, and patients’ age were independent prognostic parameters, while peripheral stem cells and unrelated transplantation seemed equal to bone marrow/related transplantation. This study demonstrates that allo-SCT still has an important role in advanced CML, which emphasizes the need for optimized transplantation strategies for these high-risk patients.     

Hormonal imbalance in two types of endometrial cancer and genetic polymorphism of steroidogenic enzymes

OBJECTIVES: Modern data on endometrial cancer (EC) incidence demonstrate that it is one of the most prevalent gynecologic malignancies. It is possible that some allelic polymorphisms of the genes involved in steroidogenesis or steroid metabolism differently contribute into susceptibility to described types of this disease, namely to type I (which is considered to be hormone dependent) and type II. METHODS: Distribution of allelic polymorphisms of CYP17 (17alpha-hydroxylase/17,20-lyase), CYP19 (aromatase), catechol-O-methyltransferase (COMT) and CYP1B1 (primarily, estrogen 4-hydroxylase) genes was compared totally in 156 endometrial cancer patients, approximately two-third of who belonged (on the basis of case history and some characteristics of host and tumor) to type I of the disease, and one-third to type II. Blood leukocytes were used as source of normal DNA for PCR-genotyping. RESULTS: No differences were found in distribution of CYP17 and CYP1B1 genotypes between patients belonging to type I or II of the disease. On the other side, in case of CYP19, the ratio of incidence of A6A6 genotype to the frequency of A1A6 and A3A6 genotypes was higher in type II patients (1.0) than in type I patients (0.3). Besides, incidence of high activity (HH) COMT genotype was higher among patients with type I of disease than in patients with type II of it (33.3% versus 14.7%, OR=2.9, z=1.96, p=0.05) revealing tendency to the lower inactivation of catecholestrogens in the latter group. CONCLUSION: It may be suggested that more aggressive clinically and frequently receptor-negative type II of endometrial cancer is associated with indirect signs of mainly intratumoral hyperproduction of estrogens (excess of CYP19 A6A6 genotype) without their sufficient inactivation into methoxyderivatives that warrants further study.     

Association between two mu-opioid receptor gene (OPRM1) haplotype blocks and drug or alcohol dependence

We examined 13 single nucleotide polymorphisms (SNPs) spanning the coding region of the mu-opioid receptor gene (OPRM1), among 382 European Americans (EAs) affected with substance dependence [alcohol dependence (AD) and/or drug dependence (DD)] and 338 EA healthy controls. These SNPs delineated two haplotype blocks. Genotype distributions for all SNPs were in Hardy-Weinberg equilibrium (HWE) in controls, but in cases, four SNPs in Block I and three SNPs in Block II showed deviation from HWE. Significant differences were found between cases and controls in allele and/or genotype frequencies for six SNPs in Block I and two SNPs in Block II. Association of SNP4 in Block I with DD (allele: P=0.004), SNP5 in Block I with AD and DD (allele: P< or =0.005 for both) and two SNPs in Block II with AD (SNP11 genotype: P=0.002; SNP12 genotype: P=0.001) were significant after correction for multiple testing. Frequency distributions of haplotypes (constructed by five tag SNPs) differed significantly for cases and controls (P<0.001 for both AD and DD). Logistic regression analyses confirmed the association between OPRM1 variants and substance dependence, when sex and age of subjects and alleles, genotypes, haplotypes or diplotypes of five tag SNPs were considered. Population structure analyses excluded population stratification artifact. Additional supporting evidence for association between OPRM1 and AD was obtained in a smaller Russian sample (247 cases and 100 controls). These findings suggest that OPRM1 intronic variants play a role in susceptibility to AD and DD in populations of European ancestry.     

Extravascular lung water determined with single transpulmonary thermodilution correlates with the severity of sepsis-induced acute lung injury

OBJECTIVE: To find out if the extravascular lung water index (EVLWI) and the derived permeability indexes determined by the single transpulmonary thermodilution technique are associated with markers of acute lung injury in human septic shock. DESIGN: Prospective, observational study. SETTING: Mixed intensive care unit of a 900-bed university hospital. PATIENTS: Thirty-eight consecutive adult patients with septic shock and acute lung injury. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The variables were assessed over a 72-hr period and included hemodynamics, EVLWI, and pulmonary vascular permeability indexes determined with the single indicator transpulmonary thermodilution technique, lung compliance, oxygenation ratio (Pao2/Fio2), lung injury score, cell counts, and the plasma concentration of endothelin-1. At day 1, EVLWI was elevated (>or=7 mL/kg) in 28 (74%) patients and correlated with lung compliance (r=-.48, p=.002), Pao2/Fio2 (r=-.50, p=.001), lung injury score (r=.46, p=.004), roentgenogram quadrants (r=.39, p=.02), and platelet count (r=-.43, p=.007). At day 3, EVLWI correlated with compliance (r=-.51, p=.002), Pao2/Fio2 (r=-.49, p = .006), and lung injury score (r=.53, p=.003). At day 3, EVLWI and pulmonary vascular permeability indexes were higher in nonsurvivors (p<.05). The plasma concentration of endothelin-1 (mean+/-sd) was significantly higher in patients with elevated EVLWI (>or=7 mL/kg) (3.85+/-1.40 vs. 2.07+/-0.38 pg/mL, respectively). Twenty-two (59%) patients died before day 28. CONCLUSIONS: In human septic shock, EVLWI demonstrated moderate correlation with markers of acute lung injury, such as lung compliance, oxygenation ratio, roentgenogram quadrants, and lung injury score. In nonsurvivors, EVLWI and permeability indexes were significantly increased at day 3. Thus, EVLWI might be of value as an indicator of prognosis and severity of sepsis-induced acute lung injury.     

Coping patterns as a valid presentation of the diversity of coping responses in schizophrenia patients

This study aimed to identify coping patterns used by schizophrenia inpatients in comparison with those used by healthy individuals, and to explore their association with selected clinical and psychosocial variables. The Coping Inventory for Stressful Situations (CISS) was used to assess coping strategies among 237 inpatients who met DSM-IV criteria for schizophrenia and 175 healthy individuals. Severity of psychopathology and distress, insight into illness, feelings of self-efficacy and self-esteem (self-construct variables), social support, and quality of life were also examined. Factor analysis, analysis of covariance and correlations were used to examine the relationships between the parameters of interest. Using dimensional measures, we found that emotion-oriented coping style and emotional distress were significantly higher in the schizophrenia group, whereas the task-oriented coping style, self-efficacy, perceived social support and satisfaction with quality of life were lower compared with controls. When eight CISS coping patterns were defined, the results revealed that patients used emotion coping patterns 5.5 times more frequently, and task and task-avoidance coping patterns significantly less often than healthy subjects. Coping patterns have different associations with current levels of dysphoric mood and emotional distress, self-construct variables, and satisfaction with quality of life. Thus, the identified coping patterns may be an additional useful presentation of the diversity of coping strategies used by schizophrenia patients. Coping patterns may be considered an important source of knowledge for patients who struggle with the illness and for mental health professionals who work with schizophrenia patients.     

Randomized study of different anti-stigma media

OBJECTIVE: We designed our study to assess if computer-assisted anti-stigma interventions can be effective in reducing the level of psychiatric stigma in a sample of special education university students. METHODS: We enrolled 193 graduate students. They had two study visits with an interval of 6 months. The participants were randomly distributed into three study groups: 76 students read anti-stigma printed materials (reading group, RG), and 69 studied an anti-stigma computer program (program group, PG), and 48 students were in a control group (CG) and received no intervention. We used the Bogardus scale of social distance (BSSD), the community attitudes toward the mentally ill (CAMI) questionnaire, and the psychiatric knowledge survey (PKS) as the main outcome measures. RESULTS: After the intervention BSSD, CAMI and PKS scores significantly improved both in RG and PG. After 6 months in RG two out of three CAMI subscales and PKS scores were not different from the baseline. In PG all stigma and knowledge changes remained significant. CONCLUSIONS: This study demonstrated that computers can be an effective mean in changing attitudes of students toward psychiatric patients. PRACTICE IMPLICATIONS: A computer-mediated intervention has the potential for educating graduate students about mental disease and for reducing psychiatric stigma.