Risk factor for invasive zygomycosis in patients with hematologic malignancies

Zygomycosis (mucormycosis) is a relatively uncommon infection in immunocompromised patients most often diagnosed in patients with haematological malignancies and neutropenia. Postmortem series demonstrate a high mortality rate up to 80%. Pulmonary involvement mimicking the more frequently diagnosed invasive aspergillosis is the typical clinical presentation. Other risk factors for the development of zygomycosis that have been described in other patient populations include diabetic ketoacidosis, iron overload, use of deferoxamine and steroids. If these factors are also associated with zygomycosis in patients with haematological malignancies has not been described. In a retrospective case-control study including 13 patients with zygomycosis and 13 control patients with the same underlying diseases, without zygomycosis we determined the frequency of various risk factors. Patients with zygomycosis experienced a longer period of neutropenia (17 vs. 13 days) and lymphopenia (23 vs. 20 days). A relapse of their underlying disease was diagnosed more frequently in patients with zygomycosis (7/13 vs. 3/13) as were a diagnosis of diabetes mellitus (6/13 vs. 3/13) and a cardiovascular disease (6/13 vs. 1/13). The previous use of steroids was more frequent in patients with zygomycosis (8/13 vs. 4/13) as was a systemic antifungal prophylaxis with itraconazole (9/13 vs. 4/13). Knowledge of these risk factors may be of benefit in diagnosing and monitoring zygomycosis in patients with haematological malignancies.     

Occurrence of chromosome 9 and p53 alterations in multifocal dysplasia and carcinoma in situ of human urinary bladder

To define the genetic changes of flat urothelial lesions, carcinoma in situ (CIS) and moderate dysplasias (DII) were investigated for alterations in the two chromosomal regions most frequently involved in bladder cancer. Overall, 33 CIS and 16 DII from 21 patients were used to microdissect urothelium. Dual color fluorescence in situ hybridization (FISH) using gene locus probes of 9q22 (FACC), 9p21 (CDK), 17p13 (p53), and related centromeric probes was applied on interphase nuclei. In parallel, preamplified DNA of these samples was used for loss of heterozygosity (LOH) analyses with eight microsatellite markers on chromosomes 9p, 9q and 17p, and for sequencing of exons 5-9 of p53. Data indicated nearly identical deletion frequencies for chromosomes 9 and 17 for CIS (chromosome 9, 86%; p53, 84%). DII showed a lower deletion rate in comparison with CIS (chromosome 9, 75%; p53, 53%). A very high correlation between the results of FISH and LOH analyses was found. p53 mutations were detected in 12 of 15 patients (CIS, 72%; DII, 67%). In three of 16 patients with multifocal tumors, oligoclonal lesions were identified by LOH analyses, a finding further supported by sequencing of p53, by which two different p53 deletions were detected in two cases. In conclusion, data from microdissected flat urothelial lesions indicate that chromosome 9 deletions cannot be regarded as indicators of papillary growth, because they are found frequently in both types of flat lesions of the urothelium: those associated with papillary tumors and those that are not. The similar distribution and lower amount of genetic changes in DII render DII a possible precursor lesion of CIS.     

Deteriorating ischaemic stroke. cytokines,soluble cytokine receptors,ferritin, systemic blood pressure,body temperature,blood glucose,diabetes, stroke severity,and CT infarction-volume as predictors of deteriorating ischaemic stroke

The immune reactivity implicated in the pathogenesis of Guillain-Barré syndrome (GBS) and related diseases, which occur following infection with specific strains of Campylobacter jejuni bearing sialylated lipopolysaccharide structures that cross-react with specific gangliosides, is consistent with provocation of inflammation via molecular mimicry. In this review, we have focused upon microbial characteristics and structures, the fine structure of the essential carbohydrate determinants, and the application of our proposed criteria, modified from those of Koch for causation of infectious and of Witebsky for autoimmune diseases, to the circumstance of infectious induction of autoimmune disorder.     

Socioeconomic situation and health outcomes of single parents

Objective  

Individualization and pluralization of lifestyles have led to a continually growing number of one-parent families (lone parents) in the Federal Republic of Germany. In 2003, there were approximately 2.4 million lone parents with children living in Germany. Over 80% of lone parents are women. The objective of this review is to summarize the scientific evidence concerning health outcomes and socioeconomic conditions of lone parents.     

Impact of cadaveric renal donor morbidity on long-term graft function

The significance of donor age, cause of death, and morbidity for the outcome of renal cadaveric transplantation was evaluated in 534 cases from 1994 through 2001. Half of the kidneys (49.4%) were from donors without identified risk, the others were age 50-64 or > or =65 years, had died of cerebrovascular lesion (CVL), or had known cardiovascular disease, or hypertension. Only death from CVL influenced cumulative graft survival (P=0.04), the actual survival at 6 months being 87% vs 95% with other donors (P=0.004). Clearance of 51Cr EDTA (glomerular filtration rate, GFR) after 1 year was a more sensitive marker of graft quality and was significantly reduced with each tested risk factor. For instance, the median GFR (range) in the three donor age groups was 52 (9-125), 37 (13-83), and 29 (15-60) ml/min, respectively (P<0.0001). Combinations of risk factors significantly increased their impact on GFR. However, the overall results with such suboptimal donors should rather encourage a widening of the donor acceptance criteria.     

Short stature in a girl with partial monosomy of the pseudoautosomal region distal to DXYS15: further evidence for the assignment of the critical region for a pseudoautosomal growth gene(s)

This report describes a 12 year 10 month old girl with short stature and a non-mosaic 46,X,Xp+ karyotype. Her height remained below −2 SD of the mean, and her predicted adult height (143 cm) was below her target height (155·5 cm) and target range (147·5 cm−163·5 cm). Cytogenetic and molecular studies showed that the Xp+ chromosome was formed by an inverted duplication of the Xp21.3−Xp22.33 segment and was missing about 700 kb of DNA from the pseudoautosomal region distal to DXYS15. The results provide further support for the previously proposed hypothesis that the region between DXYS20 and DXYS15 is the critical region for a pseudoautosomal growth gene(s).     

Prenatal exposure to medroxyprogesterone acetate (MPA) in girls

(1) Studies on the long-term effects of progesterone administration during gestation have suggested that it has a mild influence on postnatal female behavior causing even greater femininity than expected in normal controls. (2) However, it has been difficult to distinguish the effects of the prenatal hormone from those of the maternal disease state (toxemia). (3) In a new study, girls (n= 15) with prenatal exogenous hormonal exposure due to maternal intake of medroxyprogesterone acetate (MPA) were compared with a closely matched control group. (4) The results suggested that MPA was not associated with genital abnormalities in genetic females. (5) Behavior effects of prenatal MPA appeared to be subtle and included a lower incidence of being labeled a tomboy during childhood and a more constant preference for feminine clothing styles. (6) We conclude that prenatal MPA may have an enhancing effect on female sexually dimorphic behavior.     

Studies on the increased absorption of ouabain,phenolsulphonphthalein and pralidoxime caused by sodium lauryl sulphate from single loop preparations in the rat

Summary In concentrations above the critical micelle concentration (effective range about 2 mM to about 22 mM) sodium lauryl sulphate caused graded increases in the absorption of ouabain, phenolsulphonphthalein and pralidoxime from jejunal loops in anaesthetized rats. The surfactant-caused increases in the absorption of phenolsulphonphthalein and pralidoxime were significantly reduced if the sodium chloride of the medium was replaced by mannitol, respectively sucrose, or by sodium phosphate, and also if ouabain was added to the medium. The extent in absorption in the absence of surfactant was not altered. The surfactant-caused increase in the absorption of ouabain was not reduced by the mentioned sodium chloride exchanges in the medium. It is suggested that the increased absorption caused by sodium lauryl sulphate must be ascribed to a direct effect on the intestinal membrane. The results indicate some kind of Na-dependence for the increase in absorption observed for phenolsulphonphthalein and pralidoxime. Additional studies are in progress to further elucidate the observations mentioned.     

Stepwise occurrence of a complex unbalanced translocation in neuroblastoma leading to insertion of a telomere sequence and late chromosome 17q gain

In neuroblastoma, the most frequent genetic alterations are unbalanced translocations involving chromosome 17. To gain insights into these rearrangements, we have characterized a previously identified der(1)t(1;17) of the CLB-Bar cell line. The 17q breakpoint was mapped by FISH. Subsequently, a rearranged fragment was identified by Southern analysis, cloned in a lambda vector and sequenced. The chromosome rearrangement is more complex than expected due to the presence of an interstitial 4p telomeric sequence between chromosome 1p and 17q. Three different genes, which may play a role in neuroblastoma development, are disrupted by the translocation breakpoints. Indeed, the 3'UTR of the PIP5K2B gene on chromosome 17q is directly fused to the (TTAGGG)n repeat of the chromosome 4p telomere, and the (1;4) fusion disrupts the MACF1 (microtubule-actin crosslinking factor 1) and POLN genes, respectively. Interestingly, the (1;4) fusion was present at diagnosis and at relapse, whereas the (4;17) fusion was detected at relapse only, leading to a secondary 17q gain confirmed by array CGH therefore indicating that 17q gain may not be a primary event in neuroblastoma. Finally, screening of a panel of neuroblastoma cell lines identified interstitial telomeric sequences in three other cases, suggesting that this may be a recurrent mechanism leading to unbalanced translocations in neuroblastoma.