Necrotizing myositis and septic shock caused by Haemophilus influenzae type f in a previously healthy man diagnosed with an IgG3 and a mannose-binding lectin deficiency

An increased incidence of infections by Haemophilus influenzae type f (Hif) has recently been suggested, but such infections have mainly been regarded as opportunistic. We present here a dramatic case of Hif necrotizing myositis and septic shock. A subsequently diagnosed IgG3 and mannose-binding lectin deficiency possibly contributed to the severe outcome.     

High levels of education are associated with an increased risk of latent autoimmune diabetes in adults: results from the Nord-Trøndelag health study

OBJECTIVE

To investigate whether the risk for autoimmune diabetes in adults differs between socioeconomic groups and to compare such risk with that for type 2 diabetes.

RESEARCH DESIGN AND METHODS

The inhabitants of the Norwegian county of Nord-Trøndelag were investigated by questionnaires and clinical examinations on three occasions during 1984–2008. We used information from a subset consisting of 56,296 subjects (participating in at least two surveys), including 122 incident cases of autoimmune diabetes in adults (aged ≥35 and anti-GAD positive) and 1,555 cases of type 2 diabetes (aged ≥35 and anti-GAD negative). Hazard ratios (HRs) of diabetes associated with self-reported education and occupation were estimated by Cox proportional hazards models.

RESULTS

High levels of education (university versus primary school) were associated with an increased risk of autoimmune diabetes (HR 1.98 [95% CI 1.21–3.26]), after adjustment for BMI, lifestyle factors, and family history of diabetes. Case subjects with high levels of education had lower levels of C-peptide, tended to have higher levels of anti-GAD, and were more often treated with insulin. Conversely, these subjects had a reduced risk of type 2 diabetes (HR 0.69 [95% CI 0.57–0.82]), a risk that was partly explained by lower BMI and more physical activity (adjusted HR 0.89 [95% CI 0.74–1.06]).

CONCLUSIONS

High levels of education are associated with an increased risk of autoimmune diabetes in adults, a finding that may be mediated by effects on autoimmune activity. Because the association is not explained by traditional risk factors, other, currently unidentified, environmental factors are likely to be involved.There is some evidence indicating that socioeconomic conditions during early life can affect the incidence of autoimmune diabetes. Lower rates of childhood diabetes have been reported in more materially deprived areas, and children in families with a high socioeconomic position seem more prone to develop type 1 diabetes (1–3). It has been hypothesized that these associations result from differences in environmental factors, such as feeding patterns, hygiene standards, and lack of infections in early life, conditions that may affect the immune system and trigger an autoimmune reaction (4,5). Whether socioeconomic factors associate with autoimmune diabetes that develops at adult age is, however, not known. Contrasting with data on childhood type 1 diabetes, the risk of developing type 2 diabetes is more pronounced in lower socioeconomic groups (6–8). This association can be explained, at least in part, by traditional risk factors such as overweight and physical inactivity (9).Autoimmune diabetes in adults comprises latent autoimmune diabetes in adults (LADA) as well as “classical” type 1 diabetes. Autoimmunity is indicated by the presence of antibodies against β-cell–associated antigens, such as GAD (10). LADA is by far the most common form of adult-onset autoimmune diabetes and is estimated to account for 2–12% of all diabetes cases (11). As indicated by the name, onset of LADA is slower than type 1 diabetes, and insulin treatment is typically not required at the time of diagnoses. Even though it is characterized by autoimmunity, LADA patients also display features of type 2 diabetes with risk associations to being overweight and physical inactivity (12).The aim of this study was to investigate whether the risk of developing autoimmune diabetes in adults differs between socioeconomic groups and to compare such risk with that for type 2 diabetes. Furthermore, we aimed to analyze whether evidence could be found for a role of autoimmunity and whether associations found could be explained by traditional risk factors for type 2 diabetes, such as family history of diabetes, being overweight, physical inactivity, or smoking.     

Comparison of plasmid vaccine immunization schedules using intradermal in vivo electroporation

In vivo electroporation (EP) has proven to significantly increase plasmid transfection efficiency and to augment immune responses after immunization with plasmids. In this study, we attempted to establish an immunization protocol using intradermal (i.d.) EP. BALB/c mice were immunized with a plasmid encoding HIV-1 p37Gag, either i.d. with the Derma Vax EP device, intramuscularly (i.m.) without EP, or with combinations of both. A novel FluoroSpot assay was used to evaluate the vaccine-specific cellular immune responses. The study showed that i.d. EP immunizations induced stronger immune responses than i.m. immunizations using a larger amount of DNA and that repeated i.d. EP immunizations induced stronger immune responses than i.m. priming followed by i.d. EP boosting. Two and three i.d. EP immunizations induced immune responses of similar magnitude, and a short interval between immunizations was superior to a longer interval in terms of the magnitude of cellular immune responses. The FluoroSpot assay allowed for the quantification of vaccine-specific cells secreting either gamma interferon (IFN-γ), interleukin-2 (IL-2), or both, and the sensitivity of the assay was confirmed with IFN-γ and IL-2 enzyme-linked immunosorbent spot (ELISpot) assays. The data obtained in this study can aid in the design of vaccine protocols using i.d. EP, and the results emphasize the advantages of the FluoroSpot assay over traditional ELISpot assay and intracellular staining for the detection and quantification of bifunctional vaccine-specific immune responses.     

Postural balance in low back pain patients: Intra-session reliability of center of pressure on a portable force platform and of the one leg stand test

Low back pain (LBP) patients have poorer postural control compared to healthy controls, and the importance of assessing and addressing balance is a matter of debate. In the clinic, balance is often tested by means of the one leg stand test (OLST) while research often employs center of pressure (CoP) on a force platform. Portable force platforms might be of clinical relevance, but their reliability for LBP patients in a clinical setting has not been demonstrated. As LBP patients are more dependent on vision compared to healthy controls, the ratio of tests performed with eyes open and eyes closed (Romberg Ratio) might be of clinical interest. This study aimed to assess postural balance in LBP patients by analyzing intra-session reliability of CoP parameters on a portable force platform, the Romberg Ratio, and the OLST. Furthermore, we aimed to determine whether CoP parameters and OLST measure identical aspects of postural stability. We examined 49 LBP patients and found acceptable reliability of the CoP parameters’ trace length and velocity, whereas reliability regarding C90 area, the Romberg Ratio, and the OLST was poor. Correlations between the CoP parameters and OLST were insignificant. Reliability of trace length and velocity is acceptable and can be used as parameters when assessing CoP in LBP patients.     

Factor IXa as a target for pharmacologic inhibition in acute coronary syndrome

Anticoagulant therapy, combined with platelet-directed inhibitors, represents a standard-of-care in the management of patients with acute coronary syndrome, particularly those who require percutaneous coronary interventions. While a vast clinical experience, coupled with large clinical trials have collectively provided guidance, an optimal anticoagulant drug and applied strategy, defined as one that reduces thrombotic and hemorrhagic events consistently, with minimal off-target effects and active control of systemic anticoagulation according to patient and clinical-setting specific need, remains at large. An advancing knowledge of coagulation, hemostasis, and thrombosis suggests that factor IXa, a protease that governs thrombin generation in common thrombotic disorders may represent a prime target for pharmacologic inhibition.     

Social responsiveness scale-aided analysis of the clinical impact of copy number variations in autism

Recent array-based studies have detected a wealth of copy number variations (CNVs) in patients with autism spectrum disorders (ASD). Since CNVs also occur in healthy individuals, their contributions to the patient's phenotype remain largely unclear. In a cohort of children with symptoms of ASD, diagnosis of the index patient using ADOS-G and ADI-R was performed, and the Social Responsiveness Scale (SRS) was administered to the index patients, both parents, and all available siblings. CNVs were identified using SNP arrays and confirmed by FISH or array CGH. To evaluate the clinical significance of CNVs, we analyzed three families with multiple affected children (multiplex) and six families with a single affected child (simplex) in which at least one child carried a CNV with a brain-transcribed gene. CNVs containing genes that participate in pathways previously implicated in ASD, such as the phosphoinositol signaling pathway (PIK3CA, GIRDIN), contactin-based networks of cell communication (CNTN6), and microcephalin (MCPH1) were found not to co-segregate with ASD phenotypes. In one family, a loss of CNTN5 co-segregated with disease. This indicates that most CNVs may by themselves not be sufficient to cause ASD, but still may contribute to the phenotype by additive or epistatic interactions with inherited (transmitted) mutations or non-genetic factors. Our study extends the scope of genome-wide CNV profiling beyond de novo CNVs in sporadic patients and may aid in uncovering missing heritability in genome-wide screening studies of complex psychiatric disorders.