The cause of death in bacterial meningitis.

BACKGROUND: Death from bacterial meningitis is rarely attributed to the actual event causing death. The present study therefore categorized and characterized the cause and time of death due to bacterial meningitis. METHODS: In a cohort of patients > 15 years of age with community acquired bacterial meningitis the medical records were reviewed, and a clinical cause of death categorized into six main categories: 1) CNS complications, 2) Systemic complications, 3) Combination of systemic and CNS complications, 4) Sudden death, 5) Withdrawal of care, or 6) Unknown. RESULTS: We identified 358 patients of which 84 (23%) died in-hospital. Causes of death were ascribed to CNS complications in 43%, Systemic complications in 39%, Combined CNS and systemic complications in 4%, Sudden death in 7% and withdrawal of care in 5%. Brain herniation, circulatory failure, intractable seizures and other brain injury were the most common specific causes of death within 14 days from admission (55%). CONCLUSION: Fatal complications due to the primary infection - meningitis - is most common within 14 days of admission. The diversity of complications causing death in meningitis suggest that determining the clinical cause of death is essential to the evaluation of novel treatment strategies.

Magnetic ordering in TmGa.

We have determined the magnetic structure of the intermetallic compound TmGa by high-resolution neutron powder diffraction and (169)Tm Mössbauer spectroscopy. This compound crystallizes in the orthorhombic (Cmcm) CrB-type structure and its magnetic structure is characterized by magnetic order of the Tm sublattice along the a-axis. The initial magnetic ordering occurs at 15(1) K and yields an incommensurate antiferromagnetic structure described by the propagation vector k1 = [0 0.275(2) 0]. At 12 K the dominant ferromagnetic ordering of the Tm sublattice along the a-axis develops in what appears to be a first-order transition. At 3 K the magnetic structure of TmGa is predominantly ferromagnetic but a weakened incommensurate component remains. The ferromagnetic Tm moment reaches 6.7(2) µB at 3 K and the amplitude of the remaining incommensurate component is 2.7(4) µB. The (169)Tm hyperfine magnetic field at 5 K is 631(1) T.

Low-dose growth hormone for 40 weeks induces HIV-1-specific T cell responses in patients on effective combination anti-retroviral therapy.

Recombinant human growth hormone (rhGH) administered to combination anti-retroviral therapy (cART)-treated human immunodeficiency virus-1 (HIV-1)-infected individuals has been found to reverse thymic involution, increase total and naive CD4 T cell counts and reduce the expression of activation and apoptosis markers. To date, such studies have used high, pharmacological doses of rhGH. In this substudy, samples from treated HIV-1(+) subjects, randomized to receive either a physiological dose (0·7 mg) of rhGH (n = 21) or placebo (n = 15) daily for 40 weeks, were assessed. Peptide-based enzyme-linked immunospot (ELISPOT) assays were used to enumerate HIV-1-specific interferon (IFN)-γ-producing T cells at baseline and week 40. Individuals who received rhGH demonstrated increased responses to HIV-1 Gag overlapping 20mer and Gag 9mer peptide pools at week 40 compared to baseline, whereas subjects who received placebo showed no functional changes. Subjects with the most robust responses in the ELISPOT assays had improved thymic function following rhGH administration, as determined using CD4(+) T cell receptor rearrangement excision circle (TREC ) and thymic density data from the original study. T cells from these robust responders were characterized further phenotypically, and showed decreased expression of activation and apoptosis markers at week 40 compared to baseline. Furthermore, CD4 and CD8 T cell populations were found to be shifted towards an effector and central memory phenotype, respectively. Here we report that administration of low-dose rhGH over 40 weeks with effective cART resulted in greater improvement of T lymphocyte function than observed with cART alone, and provide further evidence that such an approach could also reduce levels of immune activation.

Neutron study of the magnetism in NiCl2·4SC(NH2)2.

We study the strongly anisotropic quasi-one-dimensional S = 1 quantum magnet NiCl2·4SC(NH2)2 using elastic and inelastic neutron scattering. We demonstrate that a magnetic field splits the excited doublet state and drives the lower doublet state to zero energy at a critical field Hc1. For Hc1 < H < Hc2, where Hc2 indicates the transition to a fully magnetized state, three-dimensional magnetic order is established with the AF moment perpendicular to the magnetic field. We mapped the temperature/magnetic field phase diagram, and we find that the total ordered magnetic moment reaches m(tot) = 2.1 µB at the field µ(0)H = 6 T and is thus close to the saturation value of the fully ordered moment. We study the magnetic spin dynamics in the fully magnetized state for H > Hc2, and we demonstrate the presence of an AF interaction between Ni(2+) on the two interpenetrating sublattices. In the antiferromagnetically ordered phase, the spin-waves that develop from the lower-energy doublet are split into two modes. This is most likely the result of the presence of the AF interaction between the interpenetrating lattices.

Aurora kinases in childhood acute leukemia: the promise of aurora B as therapeutic target.

We investigated the effects of targeting the mitotic regulators aurora kinase A and B in pediatric acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). Aurora protein expression levels in pediatric ALL and AML patient samples were determined by western blot and reverse phase protein array. Both kinases were overexpressed in ALL and AML patients (P<0.0002), especially in E2A-PBX1-translocated ALL cases (P<0.002), compared with normal bone-marrow mononuclear cells. Aurora kinase expression was silenced in leukemic cell lines using short hairpin RNAs and locked nucleic acid-based mRNA antagonists. Aurora B knockdown resulted in proliferation arrest and apoptosis, whereas aurora A knockdown caused no or only minor growth delay. Most tested cell lines were highly sensitive to the AURKB-selective inhibitor barasertib-hydroxyquinazoline-pyrazol-anilide (AZD1152-HQPA) in the nanomolar range, as tested with an MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay. But most importantly, primary ALL cells with a high aurora B protein expression, especially E2A-PBX1-positive cases, were sensitive as well. In adult AML early clinical trials, clear responses are observed with barasertib. Here we show that inhibition of aurora B, more than aurora A, has an antiproliferative and pro-apoptotic effect on acute leukemia cells, indicating that particularly targeting aurora B may offer a new strategy to treat pediatric ALL and AML.

Long-term high-physiological-dose growth hormone reduces intra-abdominal fat in HIV-infected patients with a neutral effect on glucose metabolism.

OBJECTIVES: The aim of the study was to investigate the effect of long-term high-physiological-dose recombinant human growth hormone (rhGH) therapy on fat distribution and glucose metabolism in HIV-infected patients. METHODS: Forty-six HIV-infected Caucasian men on highly active antiretroviral therapy (HAART), with an age range of 21-60 years and no significant comorbidity, were included in this randomized, placebo-controlled, double-blind, single-centre trial. Twenty-eight subjects were randomized to 0.7 mg/day rhGH, and 18 subjects to placebo, administered as daily subcutaneous injections between 1 and 3 pm for 40 weeks. Endpoints included changes in visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), limb fat mass, percentage of limb fat, plasma lipids, insulin resistance and glucose tolerance. RESULTS: VAT and trunk fat mass decreased significantly in the GH group compared with the placebo group [-19 cm(2) (-11%) vs. 12 cm(2) (6%), P=0.03, and -548 g (-9%) vs. 353 g (6%), P<0.01, respectively]. The beneficial fat redistribution in the GH group occurred without concomitant changes in subcutaneous fat at the abdomen or extremities. rhGH therapy was well tolerated. Insulin resistance, glucose tolerance, and total plasma cholesterol and triglycerides did not significantly change during intervention. CONCLUSIONS: Daily 0.7 mg rhGH treatment for 40 weeks reduced abdominal visceral fat and trunk fat mass in HIV-infected patients. This treatment appeared to be safe with respect to glucose tolerance and insulin sensitivity.

The prevalence of metabolic syndrome in Danish patients with HIV infection: the effect of antiretroviral therapy.

OBJECTIVES: The prevalence of metabolic syndrome (MS) in HIV-infected patients on highly active antiretroviral therapy (HAART) is a subject of debate. We investigated the prevalence of MS in a cohort of Danish HIV-infected patients and estimated the effect of the various classes of antiretroviral therapies on the prevalence of MS and its components. METHODS: A cross-sectional study was performed in which data were obtained from fasting blood tests, anthropometry, an interview questionnaire and whole-body dual-energy X-ray absorptiometry (DEXA) scans. MS was defined using the National Cholesterol Education Programme (NCEP) Adult Treatment Panel (ATP) III diagnostic criteria. RESULTS: Five hundred and sixty-six patients were included in the study, of whom 27% were diagnosed with MS. In univariate analysis, the duration of treatment with different drug classes was associated with the prevalence of MS. In multivariate analysis, no association was demonstrated between therapeutic duration or modality and the occurrence of MS. Current nonthymidine reverse transcriptase inhibitor (NRTI) and protease inhibitor (PI) therapies were both associated with increased plasma triglycerides (TG) [odds ratio (OR) 3.42, 95% confidence interval (CI) 1.73-6.74; and OR 1.96, 95% CI 1.19-3.22, respectively]. CONCLUSIONS: MS is prevalent in HIV-infected Danes. However, treatment with specific drug classes does not seem to confer an elevated risk for MS, other than the risk conferred by known acute effects on triglycerides.

Bose-Einstein condensation of S = 1 nickel spin degrees of freedom in NiCl2-4SC(NH2)2.

It has recently been suggested that the organic compound NiCl2-4SC(NH2)2 (DTN) undergoes field-induced Bose-Einstein condensation (BEC) of the Ni spin degrees of freedom. The Ni S = 1 spins exhibit three-dimensional XY antiferromagnetism above a critical field H(c1) approximately 2 T. The spin fluid can be described as a gas of hard-core bosons where the field-induced antiferromagnetic transition corresponds to Bose-Einstein condensation. We have determined the spin Hamiltonian of DTN using inelastic neutron diffraction measurements, and we have studied the high-field phase diagram by means of specific heat and magnetocaloric effect measurements. Our results show that the field-temperature phase boundary approaches a power-law H - H(c1) proportional variant T(alpha)(c) near the quantum critical point, with an exponent that is consistent with the 3D BEC universal value of alpha = 1.5.

Ultrasonography may be misleading in the diagnosis of ruptured and dislocated ulnar collateral ligaments of the thumb.

To find out if a non-invasive technique (ultrasonography) was able to identify a dislocated ligament of a metacarpophalangeal joint of the thumb with instability of the ulnar collateral ligament, 14 consecutive patients with clinical rupture of the ulnar collateral ligament were examined with ultrasonography before the ligament was explored. At exploration all ligaments were ruptured, and only five out of the 14 were dislocated. Ultrasonography recognised only two of the dislocated ligaments, and in half of the 14 patients the ultrasound scan gave incorrect information about the position of the ligament. We conclude that ultrasonography is not adequate for identifying dislocated ulnar collateral ligaments of the metacarpophalangeal joint of the thumb, and exploration is indicated in those with clinical instability in which palpation either suggests a dislocated ligament or is inconclusive.

Efficacy and safety of prolonged thromboprophylaxis with a low molecular weight heparin (dalteparin) after total hip arthroplasty--the Danish Prolonged Prophylaxis (DaPP) Study.

The aim of this study was to compare the efficacy and safety of prolonged (35 days) thromboprophylaxis with a standard length (7 days) regimen of a low molecular weight heparin in patients undergoing total hip arthroplasty. The study was multicentre, randomised, double-blind, and prospective with two groups. Following seven days on a standard length regimen of dalteparin (5000 antifactor Xa units subcutaneously once daily starting 12 h before surgery), patients were randomized to continue the prophylaxis with either subcutaneous injections of dalteparin or placebo injections for a further 28 days. Efficacy was evaluated at the end of the study (day 35) in all patients with bilateral ascending phlebography to detect deep vein thrombosis. Bleeding complications and other adverse events were registered throughout the study period. Three hundred consecutive patients agreed to participate before the operation: 281 were finally randomised and 215 completed the study; two patients died before randomisation; 17 developed deep vein thrombosis; none developed pulmonary embolism; and five of 113 patients (4.4%, 95% CI 1-10%) developed deep vein thrombosis in the dalteparin group, compared with 12 of 102 (11.8%; 95% CI 6-20%) in the placebo group (p=0.039). Deep vein thrombosis in the proximal veins was diagnosed in one patient (0.9%; 95% CI 0-5%) in the dalteparin group, and in five (5.0%; 95% CI 2-11%) in the placebo group (p=0.076). Major bleeding was observed in one patient in the placebo group; minor bleeding complications and adverse events were equally distributed between the groups. We concluded that prolonged (35 days) thrombo prophylaxis with dalteparin is more effective than a standard length (7 days) regimen without increased risk of bleeding complications or other adverse events.

Ring chromosome 22 and neurofibromatosis.

Variable constitutional mosaicism, mos45,XY,-22/46,XY,-22,+mar/46,XY,-22,+r(22)/47,XY,-22,+r(22)+mar/ 47, XY,-22,+r(22)*2, was found in PHA-stimulated peripheral blood, in a lymphoblastoid cell line and in cultured skin fibroblasts from a mentally retarded patient with neurofibromatosis. Both the ring chromosome and the small extra marker chromosome stained positively by in situ hybridization with a chromosome 14/22-specific alphoid repeat probe. DNA dosage analysis showed constitutional loss of one copy of the arylsulfatase A gene (ARSA), consistent with its terminal location on 22q. There was no evidence of constitutional loss of D22S1 or D22S28 which flank the neurofibromatosis type 2 (NF2) locus. Analysis of two DNA samples from a skin neurofibroma indicated retainment of two copies of D22S1, whereas the results were ambiguous with respect to tumor-specific loss of one copy of D22S28. It is suggested that the development of neurofibromatosis of unclear type in two r(22) carriers might be associated with somatic mutation of the NF2 locus due to instability of the ring chromosome(s), and in analogy, that somatic mutation of either NF1 or NF2 may account for some cases of neurofibromatosis which do not meet the criteria of either NF1 or NF2. The occurrence of seminoma in the proband may be fortuitous, but could also be due to the presence of a seminoma-associated locus on chromosome 22.

[Medial stress syndrome in military conscripts]. / Det mediale tibiale stress-syndrom hos vaernepligtige.

Thirty-two Danish recruits had signs and symptoms compatible with shin splints. 65% of the cases noticed symptoms during the first four weeks of conscription. 78% were free from symptoms after 30 days exemption from physical exercise. The patients were examined together with a group without shin splints. The passive subtalar joint mobility was identical in the two groups. When examining the subtalar joint position in the standing position, increased eversion was found in the group with shin splints.

Revaccination of adults against diphtheria. II: Combined diphtheria and tetanus revaccination with different doses of diphtheria toxoid 20 years after primary vaccination.

Immunity following diphtheria vaccination in childhood is temporary, and recent outbreaks of diphtheria in adult populations evoked interest in the effect of and side-reactions to revaccination of adults. 237 military recruits were randomly allocated to revaccination with 6 Lf tetanus toxoid or 6 Lf tetanus toxoid combined with 2 Lf or 5 Lf diphtheria toxoid. Side-reactions were recorded one week later, and antitoxin response was assessed after 4 weeks. Protective serum diphtheria antitoxin levels were attained by all subjects receiving diphtheria toxoid containing vaccines. Antibody response was related to dose, indicating a safer long-term protection by revaccination with 5 Lf diphtheria toxoid. All vaccinees, except one without documentation for primary vaccination, attained high tetanus antitoxin levels. Interference phenomena between toxoids were insignificant. Mild local reactions were reported by 22% of the vaccinees. More pronounced local reactions were experienced by 5% and systemic reactions by 3%, independent of vaccine. No serious reactions were observed. Reactions were significantly related to tetanus antitoxin response only. It was concluded that combined revaccination of adults, primary vaccinated around 20 years previously, may be performed without immune assessments.