Reasons for treating secondary AML as de novo AML

In a Danish bi‐regional registry‐based study, we conducted an analysis of the incidence and clinical importance of secondary acute myeloid leukaemia (AML). In a total of 630 cases of AML, we found 157 (25%) cases of secondary AML. The secondary leukaemia arose from MDS (myelodysplastic syndrome) in 77 cases (49%), CMPD (chronic myeloproliferative disorder) in 43 cases (27%) and was therapy‐related AML (t‐AML) in 37 cases (24%). Median age at diagnosis of AML was 69 yr in secondary cases when compared to 66 yr in de novo cases (P = 0.006). In univariate analyses, secondary AML was associated with an inferior complete remission (CR) rate (P = 0.008) and poorer overall survival (OS, P = 0.003) whereas in complete remitters, disease‐free survival (DFS) of secondary cases was equal to that of de novo cases. Interestingly, in all further analyses of CR‐rates, OS and DFS, when correcting for the influence of age, cytogenetic abnormalities, performance status and leucocyte count (WBC), presence of secondary AML completely lost prognostic significance. We conclude that the presence of secondary AML does not per se convey an unfavourable prognosis and that patients with secondary AML should be offered the chance of benefiting from treatment according to current frontline AML protocols.     

Lack of evidence for persistent nasal colonization with community-acquired methicillin-resistant Staphylococcus aureus in a central European cohort

One hundred and three patients who had previously tested positive for community-acquired methicillin-resistant Staphylococcus aureus (cMRSA) were followed up for a mean time of 32.6 months. Eighty patients had a history of skin or soft tissue infection, and the remainder were mostly asymptomatic carriers. Of 103 patients, only two reported ongoing symptoms with abscess formation. Of 81 nasal swabs available, 30.9% were positive for S. aureus but only four yielded Panton–Valentine leukocidin-positive methicillin-resistant S. aureus. In summary, we were unable to find persistent health issues or nasal colonization with cMRSA in a cohort of previously cMRSA-infected/colonized patients.     

SIV/Macaque Model of HIV Infection in Cocaine Users: Minimal Effects of Cocaine on Behavior, Virus Replication, and CNS Inflammation

Studies of the effects of drugs of abuse on HIV immune status, disease progression, and neuroAIDS have produced conflicting data and have not definitively shown whether this combination promotes cognitive impairment or disease progression. Using a consistent SIV?Cmacaque model, we investigated the effects of cocaine on behavior, virologic parameters, and CNS inflammation. Macaques received either vehicle or chronic administration of behaviorally active doses of cocaine (1.7 or 3.2?mg/kg/day). Chronic cocaine administration reduced CD8+ T cell counts during acute and late stage infection but had no effect on CD4+ T cell counts. Low-dose cocaine-treated animals had lower CSF vRNA levels late in infection, but cocaine did not alter plasma viral load or vRNA or protein in brain. There were no differences in CSF CCL-2 or interleukin (IL)-6 levels or severity of encephalitis in cocaine-treated as compared to vehicle-treated macaques. There were no differences in brain inflammation or neurodegeneration markers, as determined by interferon (IFN)-??, MxA, CCL2, IL-6, TNF??, IFN??, and indolamine 2,3-deoxygenase mRNA levels. APP levels also were not altered. The executive function of inhibitory control was not impaired in cocaine-treated or control animals following SIV infection. However, animals receiving 3.2?mg/kg/day cocaine performed more slowly in a bimanual motor test. Thus, chronic administration of cocaine produced only minor changes in behavior, encephalitis severity, CNS inflammation/neurodegeneration, and virus replication in SIV-infected pigtailed macaques, suggesting that cocaine would have only modest effects on the progression of neuroAIDS in HIV-infected individuals.     

Wound management for 287 patients with chronic leg ulcers demands 12 full-time nurses Leg ulcer epidemiology and care in a well-defined population in southern Sweden

Objective. To investigate quality of life, measured by the SF-36 scales, in a population-based sample of women who have survived cancer at any site and, specifically, breast cancer. Design. A representative cohort of women was observed over 24 years with regard to cancer prevalence, incidence, and quality of life. Setting. Gothenburg, Sweden. Subjects. A total of 1462 women aged 38–60 years at baseline. Main outcome measures. Differences in quality of life between cancer survivors and cancer-free controls measured by the SF-36 Short Form Health Survey, with adjustment for age and additionally for social status, and history of major disease (diabetes, stroke, and myocardial infarction) at follow-up in 1992–93. Results. In women who had survived cancer, a lower feeling of general health was the only score found to be significantly associated with having had cancer. Similar analysis was conducted separately for breast cancer cases. Survivors of breast cancer reported lower vitality and when controlled for major disease also lower general health compared with women who had not had cancer. All other results were independent when adjusted for social status, and also for history of major disease. Conclusions. Women who have survived cancer report lowered general health, and breast cancer cases lowered vitality, but considering the non-significant results for the other scores and summary scales it can be concluded that the well-being of women who have survived a cancer on the whole did not differ profoundly from that of other women.     

Redistributive effects of the Swedish social insurance system

BACKGROUND: Four principles are used to distribute payments via the Swedish social-insurance system in cases of temporary or permanent illness and death. This paper studies the redistributive effects on income of these four principles. METHODS: The analysis is based on aggregate social-insurance data from the 25 municipalities that comprise Stockholm County in Sweden. For nine different types of social-insurance payments based on the four principles, the degree of income redistribution is measured according to concentration indexes and differences between Gini coefficients with social-insurance payments excluded and included. RESULTS: The concentration indexes for payments from the nine social-insurance schemes in total is -0.0469. The Gini coefficient falls from 0.0437 excluding insurance payments (i.e. for income only from gainful work, IGW) to 0.0379 when including insurance payments with income from gainful work (IGW + TP). That is, the Gini coefficient is 15% lower when insurance payments are included. Decomposition by payment shows that the largest redistribution effect on income inequality is made by disability pension. CONCLUSION: Municipalities with low average income are favoured by the Swedish social-insurance system. Payment principles can be ranked according to their redistributive capacity: mix of compensating-lost-income and flat-rate, compensating-lost-income, means-testing, flat-rate, and need-based respectively. The nine social-insurance schemes contribute very differently to income redistribution. Disability pension and sickness allowance contribute most to income redistribution and reducing income inequality.     

Pharmacological characterization of the novel nociceptin/orphanin FQ receptor ligand,ZP120: in vitro and in vivo studies in mice

1 This study reports on the pharmacological characterization of ZP120, a novel ligand of the nociceptin/orphanin FQ (N/OFQ) peptide receptor, NOP. ZP120 is a structure inducing probes modified NOP ligand: Zealand Pharma proprietary SIP technology was used to increase the enzymatic stability and half-life of peptide. 2 In vitro, ZP120 mimicked the inhibitory effects of N/OFQ in the electrically stimulated mouse vas deferens, showing however higher potency (pEC(50) 8.88 vs 7.74), lower maximal effects (E(max) 69+/-5% vs 91+/-2%), and slower onset of action. Like N/OFQ, the effects of ZP120 were not modified by 1 micro M naloxone, but they were antagonized by the NOP receptor selective antagonist J-113397 (pA(2) 7.80 vs ZP120, 7.81 vs N/OFQ). 3 In vivo, ZP120 mimicked the effects of N/OFQ, producing pronociceptive effects in the tail withdrawal assay and decreased locomotor activity after i.c.v., but not after i.v. administration in mice. ZP120 elicited similar maximal effects as N/OFQ, but it was about 10 fold more potent and its effects lasted longer. 4 In conclusion, the novel NOP receptor ligand ZP120 is a highly potent and selective partial agonist of the NOP receptor with prolonged effects in vivo.     

Colchicine induces apoptosis in organotypic hippocampal slice cultures

The microtubule-disrupting agent colchicine is known to be particular toxic for certain types of neurons, including the granule cells of the dentate gyrus. In this study we investigated whether colchicine could induce such neuron-specific degeneration in developing (1 week in vitro) and mature (3 weeks in vitro) organotypic hippocampal slice cultures and whether the induced cell death was apoptotic and/or necrotic. When applied to 1-week-old cultures for 48 h, colchicine induced primarily apoptotic, but also a minor degree of necrotic cell death in the dentate granule cells, as investigated by cellular uptake of the fluorescent dye propidium iodide (PI), immunostaining for active caspase 3 and c-Jun/AP-1 (N) and fragmentation of nuclei as seen in Hoechst 33342 staining. All four markers appeared after 12 h of colchicine exposure. Two of them, active caspase 3 and c-Jun/AP-1 (N) displayed a similar time course and reached a maximum after 24 h of exposure, 24 h ahead of both PI uptake and Hoechst 33342 staining, which together displayed similar time profiles and a close correlation. In 3-week-old cultures, colchicine did not induce apoptotic or necrotic cell death. Attempts to interfere with the colchicine-induced apoptosis in 1-week-old cultures showed that colchicine-induced PI uptake and formation of apoptotic nuclei were temporarily prevented by coapplication of the protein synthesis inhibitor cycloheximide. Application of the pancaspase inhibitor z-VAD-fmk almost completely abolished the formation of active caspase 3 protein and apoptotic nuclei induced by colchicine, but the formation of necrotic nuclei increased correspondingly and the PI uptake was unaffected. We conclude that colchicine induces caspase 3-dependent apoptotic cell death of dentate granule cells in hippocampal brain slice cultures, but the apoptotic cell death is highly dependent on the developmental stage of the cultures.