Immune-globulin prophylaxis of respiratory syncytial virus infection in patients undergoing stem-cell transplantation

Thirty-two patients undergoing allogeneic hematopoietic stem-cell transplantation were given respiratory syncytial virus (RSV) immune globulin (RSVIG) at the time of transplantation and again 3 weeks later. Antibody titers to RSV, human parainfluenza virus 3, measles, and influenza H1N1, H3N2, and B were measured prior to administration of RSVIG and 6 more times over the course of the subsequent 6 weeks. Baseline antiviral titers and increases in antibody after administration of RSVIG were extremely variable for all the viruses. In 18 patients in whom the baseline titers of antibody titers to RSV-F protein were 1:640-1:2048, there was a 7.7-fold initial increase in these titers after the first dose of RSVIG, compared with a 2.1-fold increase in 14 patients with baseline titers of 1:4096-1:20,840; increases in titers of antibody against the other viruses after the first dose of RSVIG reflected similar variability. The subset of patients with the lowest titers appear to receive the greatest benefit from administration of RSVIG.     

Hearing loss and cognitive decline in the general population: a prospective cohort study

Journal of Neurology - Previous studies identifying hearing loss as a promising modifiable risk factor for cognitive decline mostly adjusted for baseline age solely. As such a faster cognitive...     

Cross-reactivity patterns of T cells specific for iodinated contrast media

BACKGROUND: Approximately 3% of patients exposed to iodinated contrast media develop delayed hypersensitivity reactions. OBJECTIVE: We wanted to better understand the molecular basis of contrast media cross-reactivity. METHODS: Cross-reactivity was assessed by skin testing and measurement of T-cell activation (CD69 upregulation) and proliferation ((3)H-thymidine uptake, 5,6-carboxyfluorescein diacetate succinimidyl ester staining) of PBMCs, T-cell lines, and T-cell clones of 2 patients with delayed hypersensitivity reactions to iohexol and iomeprol, respectively. Thirteen different contrast media and potassium iodide were compared. RESULTS: Skin testing and analyses of PBMCs, T-cell lines, and clones showed broad cross-reactivity in both patients. Broad as well as more restricted cross-reactivity patterns were found in iohexol-specific and iomeprol-specific CD4(+) T-cell clones, whereas 1 iomeprol-specific CD8(+) T-cell clone showed no cross-reactivity at all. The reactivity to equimolar concentrations of iohexol and its dimer iodixanol was very similar, suggesting that the dimer was not more stimulatory than its monomer. Consistently low reactivity to iobitridol was found in both patients, but never to iodide. A frequency analysis of contrast medium-specific peripheral T cells gave values between 0.6 % (iomeprol) and 0.05 % (iobitridol). CONCLUSION: Clinically observed cross-reactivity between different contrast media is a result of the presence of contrast media-specific T cells, some of which show a broad cross-reactivity pattern. Iodide ions, known to be present at low concentration in contrast media solutions, do not seem to be the causative moiety. CLINICAL IMPLICATIONS: Detailed in vitro analysis might help identify noncross-reactive contrast media.     

Burkholderia pseudomallei Isolates in 2 Pet Iguanas,California, USA

Burkholderia pseudomallei, the causative agent of melioidosis, was isolated from abscesses of 2 pet green iguanas in California, USA. The international trade in iguanas may contribute to importation of this pathogen into countries where it is not endemic and put persons exposed to these animals at risk for infection.Key words: Burkholderia pseudomallei, iguana, zoonoses, abscess, melioidosis, bacteriaBurkholderia pseudomallei, a gram-negative bacterium, is the causative agent of melioidosis. Melioidosis is endemic in countries in Southeast Asia and in northern Australia, and has been sporadically reported from Central and South America (1). In the United States, most case-patients have traveled to disease-endemic areas (2).B. pseudomallei infection occurs through direct cutaneous inoculation with soil or water containing B. pseudomallei and through ingestion or inhalation of aerosolized bacteria. In humans, the incubation period is typically 1–21 days, but some patients demonstrate clinical signs years after exposure (1). Acute melioidosis can manifest as a severe pneumonia and septicemia, with death rates >40% in countries where access to medical care is limited. In chronic melioidosis, abscesses occur in various organs, including the lungs, liver, spleen, and cutaneous sites (1,3). In animals, abscesses and acute illness are common (4).B. pseudomallei is classified by US federal agencies as a tier 1 select agent. Tier 1 agents are believed to pose the greatest threat for deliberate misuse and potential harm to public health. Multiple regulations restrict access to these agents and reduce the risk of their release from secure settings (5). Infection is generally diagnosed by culture. Commercially available bacterial identification systems may provide initial identification; however, B. pseudomallei may be misidentified by some systems (6). Other identification tests are available, including PCR and antigen detection; these are not commonly used outside disease-endemic regions (3,7,8).     

Spanish Menopause Society position statement: Use of denosumab in postmenopausal women

Denosumab is a new drug developed for the treatment of osteoporosis. Moreover, increasing evidences link denosumab with benefits in cancer, an area of interest for those in charge of the postmenopausal health. Denosumab has shown efficacy in the control of bone loss associated with hypogonadic states created by chemotherapy in breast and other cancers. Moreover, some studies reveal efficacy in reducing the progression of metastases. A panel of experts from the Spanish Menopause Society has met to develop usage recommendations based on the best available evidence.     

A case of autonomic failure in post-craniectomy syndrome of the trephined

Clinical Autonomic Research -     

Hypoxic downregulation of cellular proliferation and loss of phenotype stability in human osteoblasts is mediated by HIF-1α

Both, skeletal development and fracture healing depend on an orchestrated sequence of cellular growth and differentiation processes. Regional changes in tissue oxygen tension were proposed as key regulators of osteoblast proliferation and phenotype. Hypoxia results in the stabilization of hypoxia-inducible factor-1α (HIF-1α), thus influencing expression of a multitude of genes required for cellular adaptation. In the present study we dissected the effects of HIF-1α on cellular proliferation and gene expression of primary human osteoblasts. Primary human osteoblasts were studied by transfecting siRNA and plasmids coding for human HIF-1α. Gene expression was analyzed by western blot and quantitative PCR. Functional assays were performed to study HIF-1α function, i.e. proliferation and cell cycle analysis. As previously reported exposure to hypoxia led to a stabilization of HIF-1α on protein level and resulted in reduced rates of proliferation and osteocalcin expression. Furthermore, the expression of the proproliferative gene survivin was significantly reduced (p < 0.01). Knock down of HIF-1α attenuated hypoxic downregulation of proliferation (p < 0.05), and osteocalcin (p < 0.05) as well as survivin (p < 0.05) expression significantly. Importantly, the isolated overexpression of HIF-1α impaired proliferative activity and led to significantly reduced rates of expression of osteocalcin (p < 0.05) and survivin (p < 0.01). The present study shows that HIF-1α might reduce proliferation and survivin expression in primary human osteoblasts independently from cellular hypoxia. Furthermore, HIF-1α promoted the loss of the characteristic osteoblastic marker, osteocalcin in vitro. These findings underline the important role of HIF-1α in bone physiology and pathophysiology. Modulating HIF-1α function in hypoxic environments could be of value for future therapeutic approaches.     

Multiple functional domains of the heparin molecule.

Affinity-fractionated porcine heparin was randomly scissioned by chemical techniques to give hexasaccharides, octasaccharides, decasaccharides, and mucopolysaccharide fragments of approximately 14 residues and approximately 16 residues that were able to complex with the protease inhibitor. Direct measurements of the kinetic behavior of the hexasaccharides, octasaccharides, and decasaccharides showed that these fractions greatly enhanced the rate of Factor Xa inactivation by antithrombin. Indeed, these species exhibited specific molar activities that ranged from 6.9% (hexaccharide) to 60.9% (decasaccharide) of that of the heparin fragment of approximately 16 residues. However, these oligosaccharides exhibited essentially no ability to accelerate thrombin-antithrombin interactions. The avidity of the hexasaccharides, octasaccharides, and decasaccharides for the protease inhibitor increased as a function of size with the respective dissociation constants ranging from 5.5 X 10(-6) M to 2.9 X 10(-7) M. These data suggest that the region of the heparin molecule needed for catalyzing Factor Xa-antithrombin interaction is intimately related to the antithrombin binding domain. The smallest complex carbohydrate fragment that accelerated the inactivation of thrombin by antithrombin had approximately 14 residues. This fraction had an avidity for the protease inhibitor of 2.8 X 10(-7) M and specific molar activities of 140 units per mumol (thrombin neutralization) and 460 units per mumol (factor Xa inactivation). The largest heparin fragment examined contained approximately 16 residues. This fraction had an avidity for antithrombin of 2.4 X 10(-7) M and specific molar activities of 500 units per mumol (thrombin neutralization) and 560 units per mumol (Factor Xa inactivation). Detailed kinetic analyses showed that these two species are able to directly activate antithrombin to the same extent with respect to thrombin inhibition. However, the larger mucopolysaccharide fragment is also capable of approximating free enzyme with protease inhibitor.     

Automated assay of ceruloplasmin by kinetic analysis of o-dianisidine oxidation.

Automated procedures for the kinetic assay of serum ceruloplasmin activity using a bichromatic and a centrifugal analyzer are described. The method is based on the oxidase activity of ceruloplasmin at pH 5.0 with o-dianisidine as substrate. Enzyme activity is reported in I.U./l, based on the molar absorption coefficient of o-dianisidine consumed. The substrate is stable and is not subject to non-enzymatic oxidation. Comparison with a manual reference end-point assay using the same substrate indicates good correlation of the bichromatic and centrifugal methods. The analytical precision is comparable to the manual assay for both methods.