Humoral immune response and delayed type hypersensitivity to influenza vaccine in patients with diabetes mellitus

The antibody response and delayed type hypersensitivity reaction to commercially available trivalent influenza vaccine in 159 patients with diabetes mellitus was compared with response and reaction in 28 healthy volunteers. A correction for prevaccination titres was made. No differences were found between diabetic patients and control subjects with respect to antibody response to the three vaccine strains as measured by the difference between geometric mean titres of post- and prevaccination sera. In Type 1 (insulin-dependent) diabetic patients the incidence of non-responders to two vaccine components was significantly increased (p less than 0.05). The delayed type hypersensitivity reaction to influenza antigen was significantly decreased in patients with high concentrations of glycosylated haemoglobin (p less than 0.01). These findings suggest a role for impaired immune response in the increased influenza morbidity and mortality in patients with diabetes mellitus. Implications for therapy and vaccination strategy are discussed

Revised estimates of influenza-associated excess mortality, United States, 1995 through 2005

<p>Abstract</p> <p>Background</p> <p>Excess mortality due to seasonal influenza is thought to be substantial. However, influenza may often not be recognized as cause of death. Imputation methods are therefore required to assess the public health impact of influenza. The purpose of this study was to obtain estimates of monthly excess mortality due to influenza that are based on an epidemiologically meaningful model.</p> <p>Methods and Results</p> <p>U.S. monthly all-cause mortality, 1995 through 2005, was hierarchically modeled as Poisson variable with a mean that linearly depends both on seasonal covariates and on influenza-certified mortality. It also allowed for overdispersion to account for extra variation that is not captured by the Poisson error. The coefficient associated with influenza-certified mortality was interpreted as ratio of total influenza mortality to influenza-certified mortality. Separate models were fitted for four age categories (<18, 18–49, 50–64, 65+). Bayesian parameter estimation was performed using Markov Chain Monte Carlo methods. For the eleven year study period, a total of 260,814 (95% CI: 201,011–290,556) deaths was attributed to influenza, corresponding to an annual average of 23,710, or 0.91% of all deaths.</p> <p>Conclusion</p> <p>Annual estimates for influenza mortality were highly variable from year to year, but they were systematically lower than previously published estimates. The excellent fit of our model with the data suggest validity of our estimates.</p

Awareness of vaccination status and its predictors among working people in Switzerland

BACKGROUND: Adult vaccination status may be difficult to obtain, often requiring providers to rely on individual patient recall. To determine vaccination status awareness and the sociodemographic predictors of awareness for tetanus, hepatitis A and B, tick born encephalitis (TBE) and influenza vaccination. METHODS: Multivariate analyses were used to evaluate a questionnaire survey of 10 321 employees (4070 women and 6251 men aged 15–72 years) of two companies in Switzerland. RESULTS: Among 10 321 respondents, 75.5% reported knowing their tetanus vaccination status, 64.1% hepatitis A, 61.1% hepatitis B, 64.3% TBE and 71.9% influenza. Between 1 in 4 and 1 in 3 employees were not aware of their vaccination status. Differences in awareness for the five vaccinations considered correlated with gender and language. These differences persisted in multivariate analyses. CONCLUSION: Women employees, German-speaking employees and employees who paid more attention to their diet were more often aware of their vaccination status. A more reliable and readily accessible data source for vaccination status is needed in order to capitalize on opportunities to update vaccinations among Swiss employees

Oral Administration of GW788388, an Inhibitor of Transforming Growth Factor Beta Signaling, Prevents Heart Fibrosis in Chagas Disease

Cardiac damage and dysfunction are prominent features in patients with chronic Chagas disease, which is caused by infection with the protozoan parasite Trypanosoma cruzi (T. cruzi) and affects 10–12 million individuals in South and Central America. Our group previously reported that transforming growth factor beta (TGFß) is implicated in several regulatory aspects of T. cruzi invasion and growth and in host tissue fibrosis. In the present work, we evaluated the therapeutic action of an oral inhibitor of TGFß signaling (GW788388) administered during the acute phase of experimental Chagas disease. GW788388 treatment significantly reduced mortality and decreased parasitemia. Electrocardiography showed that GW788388 treatment was effective in protecting the cardiac conduction system, preserving gap junction plaque distribution and avoiding the development of cardiac fibrosis. Inhibition of TGFß signaling in vivo appears to potently decrease T. cruzi infection and to prevent heart damage in a preclinical mouse model. This suggests that this class of molecules may represent a new therapeutic tool for acute and chronic Chagas disease that warrants further pre-clinical exploration. Administration of TGFß inhibitors during chronic infection in mouse models should be further evaluated, and future clinical trials should be envisaged

Diversity of Prophage DNA Regions of Streptococcus agalactiae Clonal Lineages from Adults and Neonates with Invasive Infectious Disease

The phylogenetic position and prophage DNA content of the genomes of 142 S. agalactiae (group-B streptococcus, GBS) isolates responsible for bacteremia and meningitis in adults and neonates were studied and compared. The distribution of the invasive isolates between the various serotypes, sequence types (STs) and clonal complexes (CCs) differed significantly between adult and neonatal isolates. Use of the neighbor-net algorithm with the PHI test revealed evidence for recombination in the population studied (PHI, P = 2.01×10−6), and the recombination-mutation ratio (R/M) was 6∶7. Nevertheless, the estimated R/M ratio differed between CCs. Analysis of the prophage DNA regions of the genomes of the isolates assigned 90% of the isolates to five major prophage DNA groups: A to E. The mean number of prophage DNA fragments amplified per isolate varied from 2.6 for the isolates of prophage DNA group E to 4.0 for the isolates of prophage DNA group C. The isolates from adults and neonates with invasive diseases were distributed differently between the various prophage DNA groups (P<0.00001). Group C prophage DNA fragments were found in 52% of adult invasive isolates, whereas 74% of neonatal invasive isolates had prophage DNA fragments of groups A and B. Differences in prophage DNA content were also found between serotypes, STs and CCs (P<0.00001). All the ST-1 and CC1 isolates, mostly of serotype V, belonged to the prophage DNA group C, whereas 84% of the ST-17 and CC17 isolates, all of serotype III, belonged to prophage DNA groups A and B. These data indicate that the transduction mechanisms, i.e., gene transfer from one bacterium to another by a bacteriophage, underlying genetic recombination in S. agalactiae species, are specific to each intraspecies lineage and population of strains responsible for invasive diseases in adults and neonates

Vaccination with hemagglutinin or neuraminidase DNA protects BALB/c mice against influenza virus infection in presence of maternal antibody

<p>Abstract</p> <p>Background</p> <p>Maternal antibody is the major form of protection against disease in early life; however, its presence interferes with active immunization of offspring. In order to overcome the immunosuppression caused by maternal antibody, several immune strategies were explored in this paper using mouse model and influenza vaccines.</p> <p>Results</p> <p>The results showed that: i) when the offspring were immunized with the same vaccine as their mothers, whether inactivated or DNA vaccine, the presence of maternal antibody inhibited offspring immune response and the offspring could not be protected from a lethal influenza virus infection; ii) when the offspring, born to mothers immunized with inactivated vaccine, were immunized with NA DNA vaccine, the interference of maternal antibody were overcome and the offspring could survive a lethal virus challenge; iii) when the offspring were immunized with different DNA vaccine from that for their mothers, the interference of maternal antibody were also overcome. In addition, high-dose inactivated vaccine in maternal immunization caused partial inhibition in offspring when the offspring were immunized with HA DNA vaccine, while lower dose caused no significant immunosuppression.</p> <p>Conclusion</p> <p>To avoid the interference of maternal antibody in influenza vaccination of offspring, mothers and their offspring shall not be immunized with the same vaccine. If mothers are immunized with inactivated vaccine, NA DNA vaccine for the offspring shall be effective; and if mothers are immunized with HA (NA) DNA, NA (HA) DNA for the offspring shall be effective.</p

Neuropsychological patterns following lesions of the anterior insula in a series of forty neurosurgical patients

In the present study we investigated the effects of lesions affecting mainly the anterior insula in a series of 22 patients with lesions in the left hemisphere (LH), and 18 patients with lesions involving the right hemisphere (RH). The site of the lesion was established by performing an overlap of the probabilistic cytoarchitectonic maps of the posterior insula. Here we report the patients\u2019 neuropsychological profile and an analysis of their pre-surgical symptoms. We found that pre-operatory symptoms significantly differed in patients depending on whether the lesion affected the right or left insula and a strict parallelism between the patterns emerged in the pre-surgery symptoms analysis, and the patients\u2019 cognitive profile. In particular, we found that LH patients showed cognitive deficits. By contrast, the RH patients, with the exception of one case showing an impaired performance at the visuo-spatial planning test were within the normal range in performing all the tests. In addition, a sub-group of patients underwent to the post-surgery follow-up examination

In vitro antimicrobial activity of natural toxins and animal venoms tested against Burkholderia pseudomallei

BACKGROUND: Burkholderia pseudomallei are the causative agent of melioidosis. Increasing resistance of the disease to antibiotics is a severe problem in treatment regime and has led to intensification of the search for new drugs. Antimicrobial peptides are the most ubiquitous in nature as part of the innate immune system and host defense mechanism. METHODS: Here, we investigated a group of venoms (snakes, scorpions and honey bee venoms) for antimicrobial properties against two strains of Gram-negative bacteria Burkholderia pseudomallei by using disc-diffusion assay for in vitro susceptibility testing. The antibacterial activities of the venoms were compared with that of the isolated L-amino acid oxidase (LAAO) and phospholipase A(2 )(PLA(2)s) enzymes. MICs were determined using broth dilution method. Bacterial growth was assessed by measurement of optical density at the lowest dilutions (MIC 0.25 mg/ml). The cell viability was measured using tetrazolium salts (XTT) based cytotoxic assay. RESULTS: The studied venoms showed high antimicrobial activity. The venoms of C. adamanteus, Daboia russelli russelli, A. halys, P. australis, B. candidus and P. guttata were equally as effective as Chloramphenicol and Ceftazidime (30 μg/disc). Among those tested, phospholipase A(2 )enzymes (crotoxin B and daboiatoxin) showed the most potent antibacterial activity against Gram-negative (TES) bacteria. Naturally occurring venom peptides and phospholipase A(2 )proved to possess highly potent antimicrobial activity against Burkholderia pseudomallei. The XTT-assay results showed that the cell survival decreased with increasing concentrations (0.05–10 mg/mL) of Crotalus adamanteus venom, with no effect on the cell viability evident at 0.5 mg/mL. CONCLUSION: This antibacterial profile of snake venoms reported herein will be useful in the search for potential antibacterial agents against drug resistant microorganisms like B. pseudomallei

The cranial nerves

With the exception of the olfactory and optic nerves, all cranial nerves enter or leave the brain stem. Three of the cranial nerves are purely sensory (I, II and VIII), five are motor (III, IV, VI, XI and XII) and the remaining nerves (V, VII, IX and X) are mixed. The olfactory nerve will be discussed in Chap. 14, the optic nerve in Chap. 8 and the cochlear nerve in Chap. 7. The nuclei of the cranial nerves are arranged in an orderly, more or less columnar fashion in the brain stem: motor nuclei, somatomotor, branchiomotor and visceromotor (parasympathetic), derived from the basal plate, are located medially, whereas sensory nuclei, somatosensory, viscerosensory and vestibulocochlear, derived from the alar plate, are found lateral to the sulcus limitans. The cranial nerves innervate structures in the head and neck as well as visceral organs in the thorax and abdomen. The cranial nerves control eye movements, mastication, vocalization, facial expression, respiration, heart rate and digestion. One or several of the cranial nerves are often involved in lesions of the brain stem, of which the location can usually be determined if the topographical anatomy of the cranial nerves and their nuclei is known. Several examples are shown in Clinical cases. Following a few notes on the development of the brain stem and congenital cranial dysinnervation disorders (Sect. 6.2), the following structures will be discussed: (1) ocular motor nerves and the effects of lesions of individual ocular motor nerves (Sect. 6.3); (2) eye movements and some disorders affecting them (Sect. 6.4); (3) the trigeminal nerve and changes in the blink reflex (Sect. 6.5); (4) the facial nerve and peripheral facial nerve paralysis (Sect. 6.6); (5) the gustatory system (Sect. 6.7); (6) the vestibulocochlear nerve, vestibular control and some peripheral and central vestibular syndromes (Sect. 6.8); and (7) the last four cranial nerves and some disorders affecting them (Sects. 6.9 and 6.10). The English terms of the Terminologia Neuroanatomica are used throughout.</p