Impact of disparity of minor histocompatibility antigens HA-1, CD31, and CD49b in hematopoietic stem cell transplantation of patients with chronic myeloid leukemia with sibling and unrelated donors

Despite human leukocyte antigen (HLA) identity between donor and recipient, several patients develop acute graft-versus-host disease (aGVHD) after hematopoetic stem cell transplantation (HSCT) because of minor histocompatibility antigen (mHag) incompatibilities. The impact of multiple mHag disparities on the clinical outcome after HSCT still remains to be determined. We studied the genomic polymorphisms of HA-1, CD31, and CD49b and correlated mHag distribution with the occurrence of aGVHD after HSCT from HLA-matched sibling and unrelated donors. All 163 patients examined in our single-center study underwent HSCT for chronic myeloid leukemia in the first chronic phase. HA-1 and CD31 disparities are associated with increased aGVHD incidence in a subgroup of patients who test HLA-B44 supertype positive in univariate analysis. However, in a multivariate analysis, only increased patient age was confirmed as an independent aGVHD risk factor. Our findings indicate that the impact of mHag disparity on aGVHD development in HSCT from HLA-matched sibling and unrelated donors seems to be subordinated to classic aGVHD risk factors.     

Validation of the Korean version of the Bayer activities of daily living scale

The Bayer-activities of daily living (B-ADL) is a brief and internationally applicable ADL instrument which has been validated in three European countries. The B-ADL has been developed to provide a tool for the assessment of functional deficits in performance of every day tasks as they are observed in mild to moderate stages of dementia. The B-ADL has been constructed for use in clinical trials as well as in clinical practice. From an international perspective the major application is the evaluation of treatment effects in clinical studies and the current study was to validate the Korean version of the B-ADL. The B-ADL was administered to a total of 129 subjects with varying degrees of cognitive decline. A substantial cross-sectional correlation between B-ADL and MMSE scores was found. The internal consistency of B-ADL was above 0.98. A factor analysis revealed that a one factor solution accounted for most of the total variance. The B-ADL global score significantly increased as the severity of dementia, assessed by global deterioration scale increased from stage 1 to 5. Test-retest reliabilities of B-ADL global score and each item were very high. All of these results were very similar to those from three European countries except for the proportion of 'non-applicability' in some ADL items. These findings provide evidence that the Korean version of B-ADL can be useful not only for clinical purposes but also for international multicentre studies.     

Inhaled iloprost in patients with chronic thromboembolic pulmonary hypertension: effects before and after pulmonary thromboendarterectomy

BACKGROUND: In primary pulmonary hypertension, aerosolized prostanoids selectively reduce pulmonary vascular resistance and improve right ventricular function. In this study, hemodynamic effects of inhaled iloprost, a stable prostacyclin analogue, were evaluated in patients with chronic thromboembolic pulmonary hypertension (CTEPH) before and early after pulmonary thromboendarterctomy (PTE). METHODS: Ten patients (mean age 49 years old [32 to 70 years old], New York Heart Association functional class III and IV) received a dose of 33 micro g aerosolized iloprost immediately before surgery (T1), after intensive care unit admission (T2), and 12-hours postoperatively (T3). Effects on pulmonary and systemic hemodynamics and gas exchange were recorded and compared with preinhalation baseline values. RESULTS: Preoperatively, inhaled iloprost did not significantly change mean pulmonary artery pressure (mPAP), cardiac index (CI), or pulmonary vascular resistance (PVR). Postoperatively, inhaled iloprost induced a significant reduction of mPAP and PVR and a significant increase of CI at T2 and T3. Preinhalation versus postinhalation PVR was as follows: at T1, 847 versus 729 dynes. s. cm(-5), p = 0.45; at T2, 502 versus 316 dynes. s. cm(-5), p = 0.008; and at T3, 299 versus 227 dynes. s. cm(-5), p = 0.004. CONCLUSIONS: In patients with CTEPH, inhalation of iloprost elicits no significant pulmonary vasodilation before surgery, and may have detrimental effects on systemic hemodynamics. Postoperatively, it significantly reduces mPAP and PVR, and enhances CI. Following PTE, inhalation of iloprost is useful to improve early postoperative hemodynamics.     

The Common 677C>T Gene Polymorphism of Methylenetetrahydrofolate Reductase Gene is not Associated with Breast Cancer Risk

Methylenetetrahydrofolate reductase (MTHFR) is involved in folate metabolism and plays a role in DNA biosynthesis, methylation, and repair in actively dividing cells. A common 677C>T polymorphism in the gene for MTHFR, leading to a thermolabile enzyme with decreased activity, has been associated with reduced plasma folate levels and elevated homocysteine levels and could be a risk factor for breast cancer. In the present case-control study, MTHFR genotype was determined in 500 women with clinically verified breast cancer and 500 female age-matched healthy control subjects. The homozygous TT genotype was found in 13.0% patients and 13.1% controls (P = n.s.). The odds ratio of TT homozygotes for breast cancer was 0.99 (95% confidence interval 0.68–1.43). The MTHFR genotype was furthermore not associated with tumor size, histological grading, estrogen or progesterone receptor status and age at diagnosis. In a subgroup of 116 premenopausal patients, no increased frequency of the homozygous 677T genotype was found (13.8%). Therefore, we conclude that the MTHFR 677C>T polymorphism is not associated with individual susceptibility to breast cancer.     

Acute pseudo-obstruction of the small intestine following high-dose chemotherapy and stem cell support

BACKGROUND: Acute intestinal pseudo-obstruction is a potentially life-threatening disease which is characterized by massive dilation of the colon or small intestine without mechanical obstruction and may develop after surgery or severe illness. PATIENTS AND METHODS: We report 2 cases in which acute small intestinal pseudo-obstruction occurred after high-dose chemotherapy and autologous stem cell support. In 1 patient explorative abdominal laparoscopy was performed to rule out mechanical ileus. However, after having initiated treatment with acetylcholinesterase inhibitors a prompt small intestinal decompression was observed in both patients. CONCLUSIONS: Acetylcholinesterase inhibitors should be considered as an early conservative intervention in the treatment of acute intestinal pseudo-obstruction to avoid surgery of patients undergoing high-dose chemotherapy with autologous stem cell support.     

Registering event-related auditory potentials (P300) in patients with cochlear implants

Event-related auditory evoked potentials can contribute to the evaluation of discrimination abilities of cochlear implant users. Auditory P300 potentials to a frequency contrast were obtained in six post-lingually deaf adults using a cochlear implant and in a control group of normal hearing subjects. The aim of this study was to investigate how these potentials were determined by the stimulation pattern of the cochlear implant. To visualise these stimulation patterns colour-coded plots (stimulograms) were calculated based on the stimulus and the fitting file of the individual subject as inputs. These stimulograms were used to evaluate the influence of various stimulation parameters on the stimulation contrast used in an oddball paradigm. The influence of discrimination difficulty on the P300 response is demonstrated.     

A common 936 C/T gene polymorphism of vascular endothelial growth factor is associated with decreased breast cancer risk

A common 936 C/T polymorphism in the gene for the vascular endothelial growth factor (VEGF) has been associated with VEGF plasma levels. In our case-control study, we investigated the role of this polymorphism for breast cancer risk. VEGF genotype was determined in 500 women with breast cancer and 500 sex- and age-matched healthy control subjects. Carriers of a 936T-allele were more frequent among controls (29.4%) than among patients (17.6%; p = 0.000014). The odds ratio for carriers of a 936T-allele for breast cancer was 0.51 (95% confidence interval 0.38-0.70). Additionally, VEGF plasma levels were determined in 21 nonsmoking post-menopausal controls; carriers of a 936T allele had significantly lower levels (median 23 pg/ml; range 6-50 pg/ml) than noncarriers (37; 21-387; p = 0.034). We conclude that carriers of a VEGF 936T-allele are at decreased risk for breast cancer, this, however, requiring further confirmation in a larger study.     

Angiogenesis: molecular mechanisms and functional interactions--2nd Kloster Seeon Meeting of the German Priority Research Grant "Angiogenesis"

The German Priority Research Program "Angiogenesis" (www.angiogenese.de) hosts a biannual meeting in the Kloster Seeon in Southern Germany. The 2nd Kloster Seeon Meeting "Angiogenesis: Molecular Mechanisms and Functional Interactions" was held in September 2002. It included sessions on hypoxia, the biology of endothelial precursor cells, angiogenic growth factors including VEGFs, the angiopoietins, ephrins, and FGFs, mechanisms of vascular sprouting and cell-cell contacts during angiogenesis, angiogenic signaling, lymphangiogenesis, angiogenesis during tumor invasion and metastasis, and on novel angiomanipulatory therapies. This report summarizes the key findings reported during the platform presentations of the meeting.     

Combined treatment of metastatic osteosarcoma of the spine

We report on a 28-year-old male with a single metastasis of an osteosarcoma in the twelfth thoracic vertebra occurring 9 years after initial diagnosis of the primary tumour in the left distal femur and neoadjuvant treatment according to a modified T-10 protocol. After pre-operative second-line combination chemotherapy with doxorubicin, carboplatin and etoposide leading to regression of the primarily inoperable metastasis wide resection of the tumour employing total spondylectomy was done. The duration of response had been 65 months since the end of subsequent postoperative chemotherapy with the same regimen. Copyright Copyright 1999 S. Karger AG, Basel     

Prognostic relevance of three histological grading methods in breast cancer.

Histological grading is an important parameter for the risk assessment in patients with breast cancer. However, up to now differing grading methods are used which have not been compared with respect to their prognostic significance. In the present study the prognostic significance of three different methods of histological grading (Elston, Contesso, Helpap) was determined in a sample of 292 patients. Furthermore, results obtained in needle biopsies were compared with those obtained in surgical resection specimens in 31 cases. The mitotic counts and the Contesso method were performed on two microscopes with different field areas (0.238 mm2 and 0.345 mm2). Univariate and multivariate analysis revealed that all three histological grading methods had a high prognostic value concerning overall survival (OS) and disease-free survival (DFS). Using univariate and multivariate analysis the Elston method performed best to determine OS and DFS (p<0.0001 and p<0.001). The field area of the microscope had a minor influence on the mitotic count and on the results of the Contesso method. The histological grading was reliable in needle biopsies: the best agreement to grading obtained in the definitive surgical specimen was achieved with the Elston method (kappa statistic 0.727). As a conclusion, we could show that determination of the histological grade is an important prognostic factor in breast cancer with the Elston method giving the best results. Also, we could demonstrate that histological grading in needle biopsies is reliable enough to allow a preoperative risk estimation.