Trypanosoma Theileri (?) in Deutsch-Ostafrika

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Regional heterogeneity of myocardial perfusion in healthy human myocardium: assessment with magnetic resonance perfusion imaging.

The knowledge of myocardial perfusion in healthy volunteers is fundamental for evaluation of patients with ischemic heart disease. The study was conducted to determine range, regional variability, and transmural gradient of myocardial perfusion in normal volunteers with Magnetic Resonance Perfusion Imaging (MRPI). Perfusion was assessed in 17 healthy volunteers (age: 20-47 yr, 11 males) at rest and adenosine-induced hyperemia using a 1.5 T MR scanner. Perfusion was quantified (mL/g/min) for the transmural myocardium and separately for the endo- and epimyocardium in the anterior, lateral, posterior, and septal left ventricular wall using the Fermi model for constrained deconvolution. Regional variabilities for resting, hyperemic perfusion, and perfusion reserve were 22 +/- 8%, 21 +/- 10%, and 35 +/- 18%. Mean resting, hyperemic perfusion, and perfusion reserve were 1.1 +/- 0.4 mL/g/min, 4.2 +/- 1.1 mL/g/min, and 4.1 +/- 1.4. Perfusion in the septum was higher at rest (1.3 +/- 0.3 mL/g/min vs. 1.0 +/- 0.3 mL/g/min, p < 0.05) and lower during hyperemia (3.6 +/- 0.8 mL/g/min vs. 4.5 +/- 1.1 mL/g/min, p < 0.03), resulting in a reduced perfusion reserve (PR) (3.2 +/- 0.9 vs. 4.5 +/- 1.4, p < 0.01) in the septum vs. the combined anterior, lateral, and posterior segments. Resting (0.9 +/- 0.3 mL/g/min vs. 1.4 +/- 0.5 mL/g/min, p < 0.01), but not hyperemic perfusion, was lower in the epi- vs. endomyocardium, resulting in a higher epimyocardial PR (4.8 +/- 1.8 vs. 3.5 +/- 1.4, p < 0.01) in all regions but the septum, where endo- and epimyocardial perfusion and perfusion reserve were not different. A considerable regional variability of myocardial perfusion was confirmed with MRPI. The exceptional anatomical position of the septum is reflected by the lack of a perfusion gradient, which was demonstrated in all other regions but the septum.     

The ulnar digital artery perforator flap: A new flap for little finger reconstruction - A preliminary report

An ulnar digital artery perforator flap was used for little finger reconstruction. The flap has a reliable blood supply, being perfused by a constant sizeable perforator. This paper describes a study of a cadaveric dissection with methylene blue dye that was conducted to prove the rationality and reliability of the blood supply. The position of the perforator is confirmed intraoperatively by an exploratory incision before committing to the distal incision. The flap used to cover the flexor aspect of the little finger in three cases yielded positive results. To our knowledge, a digital artery perforator flap of this nature is unprecedented. We propose to call this flap the B.J. Flap after our institute.     

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Clinicopathological analysis of ATRX,DAXX and NOTCH receptor expression in angiosarcomas

Aims

Multiple genetic alterations, including alternative lengthening of telomeres (ALT) and NOTCH mutations, have been described in angiosarcoma. Loss of α‐thalassaemia/mental retardation syndrome X‐linked (ATRX) and death domain‐associated protein 6 (DAXX) expression is frequently associated with the ALT phenotype. Additionally, inhibition of NOTCH signalling induces the development of malignant vascular tumours in mice, indicating a tumour suppressive role of the NOTCH pathway in the pathogenesis of angiosarcoma. The aim of this study was to evaluate the immunohistochemical expression of ATRX, DAXX and NOTCH receptors (NOTCH1 and NOTCH2) in a large cohort of angiosarcomas, and study their clinicopathological and prognostic significance.

Methods and results

One hundred and forty cases of angiosarcoma were stained for ATRX, DAXX, NOTCH1 and NOTCH2. ATRX loss (<10% labelling) was seen in seven of 118 (6%) cases, and was more frequent in deep soft tissue tumours than in other body sites (P = 0.004). Angiosarcomas with ATRX loss were associated with worse event‐free survival than angiosarcomas with retained ATRX expression (P = 0.003). DAXX was retained in all specimens examined. Decreased NOTCH1 expression (≤1+ intensity) was seen in 29 of 123 (24%) cases, and was associated with a cutaneous site of origin (P = 0.013) and advanced disease (P = 0.026). NOTCH2 expression was decreased in 16 of 103 (16%) cases, was associated with visceral tumours (P = 0.001), and correlated with worse disease‐specific survival (P = 0.033).

Conclusions

ATRX, NOTCH1 and NOTCH2 expression varies in angiosarcomas and shows significant correlations with site of origin and poor clinical outcome, thus highlighting the biological heterogeneity within this tumour type.     

Anti-thymocyte globulin overcomes the negative impact of HLA mismatching in transplantation from unrelated donors

OBJECTIVE: About one third of patients requiring allogeneic hematopoetic stem cell transplantation (HSCT) would not find a matched sibling or alternative donor. Allogeneic HSCT from matched unrelated and mismatched donors carries an increased risk of graft-vs-host disease (GVHD) and transplant-related mortality (TRM). MATERIALS AND METHODS: We used anti-thymocyte globulin (ATG-Fresenius) at a median dose of 90 mg/kg body weight as part of a total body irradiation or busulfan-based conditioning regimen for prevention of serious GVHD. All patients received cyclosporine A and short-course methotrexate. We compared outcomes of 65 recipients of human leukocyte antigen (HLA)-mismatched unrelated grafts and 194 recipients of HLA-matched unrelated grafts. Mismatches involved one or two loci. Both groups were comparable in age, graft source, diagnosis, stage of disease, and conditioning regimen, and differed only in dose of ATG administered. RESULTS: For matched and mismatched transplants, respectively, there was no significant difference in graft failure (0.5% vs 3%; p = 0.16), in the cumulative incidence of grade II to IV acute GVHD (45% vs 35%; p = 0.14) and no difference in overall chronic GVHD (42% vs 40%; p = 0.68). Estimated overall survival (OS) and disease-free survival (DFS) at 5 years were 55% vs 50% (p = 0.99) and 47% vs 47% (p = 1.0), respectively. The cumulative incidence of relapse and TRM at 5 years were 24% vs 25% (p = 0.63), and 29% vs 27% (p = 0.59), respectively. CONCLUSION: Inclusion of ATG-Fresenius in the conditioning regimen permits HSCT from mismatched unrelated donors without excess TRM and GVHD, resulting in identical OS and DFS of recipients of HLA-matched and HLA-mismatched grafts.     

A cluster randomized controlled trial of visual, cytology and human papillomavirus screening for cancer of the cervix in rural India

The impact of screening by visual inspection with acetic acid (VIA), cytology or HPV testing on cervical cancer incidence and mortality is investigated in a cluster randomized controlled trial in India. We report findings after the screening phase, when 52 clusters, with a total of 142,701 women aged 30-59 years in Osmanabad District, India, were randomized into 4 arms for a single round of screening by trained midwives with either VIA, cytology or HPV testing as well as a control group. All laboratory tests were done locally. Test-positive women underwent investigations (colposcopy/biopsy) and treatment in the base hospital. Data on participation, test positivity, positive predictive value and detection rates of cervical neoplasia were analyzed using cluster design methodology. Of the eligible women, 72-74% were screened. Test positivity rates were 14.0% for VIA, 7.0% for cytology and 10.3% for HPV. The detection rate of high-grade lesions was similar in all intervention arms (0.7% for VIA, 1.0% for cytology and 0.9% for HPV testing) (p = 0.06, Mann-Whitney test). While the detection rate for VIA dropped to 0.5% with declining test positivity during the course of the study, it remained constant for cytology and HPV testing. Over 85% of women with high-grade lesions received treatment. Our results show that a high level of participation and good-quality cytology can be achieved in low-resource settings. VIA is a useful alternative but requires careful monitoring. Detection rates obtained by HPV testing were similar to cytology, despite higher investments.     

Peripheral T cells of patients with B cell non-Hodgkin's lymphoma show a shift in their memory status

BACKGROUND: Tumor-infiltrating T cells have a positive influence on the clinical course of B cell non-Hodgkin's lymphoma (NHL). T cells in the peripheral blood of patients with B cell NHL, however, have so far rarely been examined. METHODS: Using flow cytometry we examined lymphocyte subpopulations and numbers of na?ve/memory T cell subtypes among peripheral T cells of patients with B cell NHL (N=22), patients with metastasized solid tumors (N=27), and healthy controls (N=20). In addition, we analyzed the intracellular content of effector molecules granzyme B and perforin and expression of the T cell receptor zeta chain. RESULTS: We observed increased percentages of potentially highly cytotoxic CD8+CD56+ T cells in the peripheral blood of patients with NHL. Both, patients with NHL and patients with solid tumors showed a much higher expression of the chemokine receptors CCR4 and CCR5 on their T cells than healthy controls, suggesting a polarization of their T cells following stimulation with antigen and/or cytokines in vivo. Furthermore, patients with B cell NHL and patients with solid tumors had far lower percentages of na?ve CD45RA+CCR7+ T cells than healthy controls and, in the case of CD4+ T cells, patients with solid tumors. In contrast, patients with B cell NHL showed markedly increased levels of memory effector CD45RA-CCR7- CD4(+) T cells when compared to healthy controls and patients with metastasized solid tumors. Patients with NHL also showed elevated levels granzyme B within CD8(+) T cells, indicating that the increase in memory effector cells was of functional relevance. CONCLUSIONS: These findings indicate a marked shift in the composition of peripheral T cells of patients with B cell NHL from na?ve to memory effector-type cells.