Atypical cause of forearm skin ulceration in a leukaemic child: mucormycosis. A case report

Primary cutaneous mucormycosis is an uncommon, deep and aggressive fungal infection occurring mainly in immunosuppressed or diabetic patients. Rapid diagnosis and therapy are necessary to prevent a fatal outcome. An eight-year-old leukaemic child presented with a dark necrotic ulcer on the volar-ulnar aspect of the left forehand. The lesion had developed over seven days, beginning as a vasculo-haemorrhagic erythematous plaque. There was no known history of trauma to the area, but skin necrosis from external compression caused by an intravenous line could not be completely ruled out. The lesion rapidly progressed to a 5 x 8 cm painful necrotic ulcer with an erythematous border. Treatment with ichthyol dressing and intra-venous antibiotherapy failed to improve the condition. Wide debridement was performed and specimens were sent for microbiology and pathology examinations. Microscopic examination demonstrated broad, irregularly walled, non-septate fungal hyphae that were consistent with Mucor. Amphotericin B was administrated intravenously (1 mg/kg/day) and hydrogel and hydrophile adhesive polyurethane foam dressings were applied. After 12 days, the soft tissue defect was covered with a split-thickness skin graft, harvested from the lateral aspect of the thigh. Diagnosis of this infection is based on complete histopathological and microbiological studies. Awareness, and a high index of suspicion are required because of the potential fulminant and fatal course.     

Age-related differences in vasoconstrictor responses to isoprostanes in piglet pulmonary and mesenteric vascular smooth muscle

Isoprostanes are prostaglandin (PG)-like compounds produced nonenzymatically by free radical-catalyzed peroxidation of arachidonic acid. Isoprostanes evoke potent vascular effects but their actions in the neonatal vasculature are poorly known. We aimed to study the effects of 8-iso-PGE(1), 8-iso-PGE(2), 8-iso-PGF(1alpha), 8-iso-PGF(1beta), 8-iso-PGF(2alpha), and 8-iso-PGF(2beta) in pulmonary arteries (PA), pulmonary veins (PV), and mesenteric arteries (MA) from newborn and 2-wk-old piglets. Isoprostanes produced concentration-dependent contractions of PA, PV, and MA (magnitudes up to 1.5- to 2-fold greater than the responses to 62.5 mM KCl) but they were markedly less potent vasoconstrictors than the thromboxane A(2) (TXA(2)) mimetic U46619. Neonatal PA were more sensitive to 8-iso-PGF(1alpha), 8-iso-PGF(1beta), and 8-iso-PGF(2beta) than 2-wk-old PA. Neonatal PV were more sensitive to 8-iso-PGE(2) and 8-iso-PGF(1alpha), and neonatal MA were more sensitive to 8-iso-PGE(2), 8-iso-PGF(1alpha), 8-iso-PGF(1beta), 8-iso-PGF(2alpha), and 8-iso-PGF(2beta) than the corresponding 2-wk-old vessels. The sensitivity to U46619 decreased with postnatal age in MA but did not change in PA and PV. The contractile responses to all the isoprostanes and to U46619 were reverted by the TXA(2) receptor (TP) antagonist SQ 29,548. Moreover, isoprostane-evoked contractions in 2-wk-old PA were reduced by inhibitors of tyrosine kinase (genistein) and Rho kinase (Y 27632 and hydroxyfasudil) but not by inhibitors of protein kinase C (chelerythrine), mitogen-activated protein kinase kinase (PD 98059) or p38-kinase (SB 203580). In conclusion, isoprostanes produced compound-, tissue-, and age-dependent constriction of neonatal porcine pulmonary and mesenteric vascular smooth muscle. Isoprostane-evoked PA vasoconstriction involved TP receptors and activation of tyrosine kinases and Rho kinases.     

Comparison of health-seeking behaviour between poor and better-off people after health sector reform in Cambodia

This study compared health-seeking behaviour between poor and better-off people after health sector reform in Cambodia. The survey was conducted in the Prek Dach Health Centre coverage area, which is located in South-east Cambodia. The study population consisted of 257 housewives of reproductive age, selected at random. Data were collected through household surveys with a structured questionnaire. Data collected included socio-demographic information on the housewives, as well as episodes of illness of family members within 30 days prior to the survey. Two indicators, the floor area of living space and a rating scale on asset ownership, were used to identify poor and very poor people. When a family member became ill, subjects most often used home remedies as a first step, followed by self-medication. Subsequently, people used self-medication or the private health sector. Very poor people used the health centre more often than better-off people as a first step. For the second step, use of the health centre was also high among the poor compared with better-off people, although the difference was not statistically significant. Keeping the treatment fees low and abolishing informal fees maintained the affordability of health-centre services for the poor. However, this benefit diminished quickly with distance from the health centre. The significant difference between poor and better-off people disappeared for villages situated more than 2 km from the health centre. Thus, the health centre in the studied area was shown to be effective in providing primary health care to the economically disadvantaged, but only within a limited geographic area.     

Regional variation and time trends in mortality from ischaemic heart disease: East and West Germany 10 years after reunification

STUDY OBJECTIVE: Within Europe, a pronounced geographical gradient of mortality from ischaemic heart disease has been observed with the highest burden in the north east and the lowest in the south west. The study objective was to compare mortality from ischaemic heart disease between former East and West Germany since reunification. DESIGN: Analyses of age standardised mortality rates from ischaemic heart disease (ICD-9 410-414, ICD-10 I20-I25) between 1990-1991 and 2000. SETTING: Former East and West Germany. MAIN RESULTS: After a peak in the early 1990s, mortality from ischaemic heart disease has substantially declined in both parts of Germany (from 222 to 169 per 100 000 in the East and from 150 to 116 per 100 000 in the West). The regional difference, however, remained rather constant: the rate ratio between the pooled mortality in the East compared with the West was 1.51 (95% CI 1.46 to 1.56) in 1991 and 1.45 (95% CI 1.39 to 1.50) in 2000. These rate ratios were higher in women (1.63 in 1991 and 1.52 in 2000) compared with men (1.45 and 1.44, respectively). CONCLUSIONS: Within Germany, there has been a pronounced east-west gradient of mortality from ischaemic heart disease since reunification. Further insight into possible underlying reasons may lead to improved preventive strategies.     

Somatic loss of maternal chromosome 11 causes parent-of-origin-dependent inheritance in SDHD-linked paraganglioma and phaeochromocytoma families

Germline mutations in succinate dehydrogenase subunits B, C and D (SDHB, SDHC and SDHD), genes encoding subunits of mitochondrial complex II, cause hereditary paragangliomas and phaeochromocytomas. In SDHB (1p36)- and SDHC (1q21)-linked families, disease inheritance is autosomal dominant. In SDHD (11q23)-linked families, the disease phenotype is expressed only upon paternal transmission of the mutation, consistent with maternal imprinting. However, SDHD shows biallelic expression in brain, kidney and lymphoid tissues (Baysal et al., 2000). Moreover, consistent loss of the wild-type (wt) maternal allele in SDHD-linked tumours suggests expression of the maternal SDHD allele in normal paraganglia. Here we demonstrate exclusive loss of the entire maternal chromosome 11 in SDHD-linked paragangliomas and phaeochromocytomas, suggesting that combined loss of the wt SDHD allele and maternal 11p region is essential for tumorigenesis. We hypothesize that this is driven by selective loss of one or more imprinted genes in the 11p15 region. In paternally, but not in maternally derived SDHD mutation carriers, this can be achieved by a single event, that is, non-disjunctional loss of the maternal chromosome 11. Thus, the exclusive paternal transmission of the disease can be explained by a somatic genetic mechanism targeting both the SDHD gene on 11q23 and a paternally imprinted gene on 11p15.5, rather than imprinting of SDHD.     

Allogeneic dendritic cells fused with tumor cells: preclinical results and outcome of a clinical phase I/II trial in patients with metastatic renal cell carcinoma

Therapeutic vaccination with dendritic cells (DC) can lead to tumor regression in animal models and has shown promising results in the first clinical trials of metastatic renal cell carcinoma and malignant melanoma. In vitro data and results of a clinical phase I/II trial using DC tumor fusions in patients with progressive metastatic renal cell carcinoma are presented here. In addition to toxicity and feasibility, complex immune monitoring was a point of interest. DC precursor cells were obtained from the peripheral blood mononuclear cells (PBMCs) of healthy donors and were fused with either allogeneic (8 patients) or autologous (4 patients) renal tumor cells. In total, 12 patients with progressive metastatic renal cell carcinoma were treated with an average of 2.8 x 10(7) tumor cells fused with 1.8 x 10(7) DC each administered on days 0, 28, and 56 intradermally. Fusion efficacy for the tumor cells used was 14.3% +/- 7.8%. Cell viability was 59.8% +/- 6.8% after fusion and irradiation. We observed no adverse effects and no difference in clinical outcome between the allogeneic and the autologous treatment. Eight patients remained in a progressive disease state and four patients in a stable disease state. T-cell immunity was carefully monitored before, during, and after treatment. Delayed-type hypersensitivity (DTH) reaction using tumor cells was positive after treatment in 7 of 12 patients, 2 of whom were found to have stable disease. An increase in the reactivity against recall antigens was seen in most patients. Interestingly, cytotoxicity of peripheral blood lymphocytes (PBLs) against renal cell carcinoma cells increased during treatment as well as the percentage of interferon-gamma-secreting cells. This effect was significantly enhanced within the group that had stable disease. The lack of adverse effects together with positive immunologic signs justifies further investigation of this novel therapeutic approach. Further studies are necessary to test for clinical effectiveness in patients with tumors, especially those with less advanced disease.