Response Strategies against Meningitis Epidemics after Elimination of Serogroup A Meningococci,Niger

To inform epidemic response strategies for the African meningitis belt after a meningococcal serogroup A conjugate vaccine was introduced in 2010, we compared the effectiveness and efficiency of meningitis surveillance and vaccine response strategies at district and health area levels using various thresholds of weekly incidence rates. We analyzed reports of suspected cases from 3 regions in Niger during 2002–2012 (154,392 health area weeks), simulating elimination of serogroup A meningitis by excluding health area years with identification of such cases. Effectiveness was highest for health area surveillance and district vaccination (58–366 cases; thresholds 7–20 cases/100,000 doses), whereas efficiency was optimized with health area vaccination (5.6–7.7 cases/100,000 doses). District-level intervention prevented <6 cases (0.2 cases/100,000 doses). Reducing the delay between epidemic signal and vaccine protection by 2 weeks doubled efficiency. Subdistrict surveillance and response might be most appropriate for meningitis epidemic response after elimination of serogroup A meningitis.     

DPOAE level mapping for detecting noise-induced cochlear damage from short-duration music exposures

Distortion product otoacoustic emission (DPOAE) level mapping provides a comprehensive picture of cochlear responses over a range of DP frequencies and f₂/f₁ ratios. We hypothesized that individuals exposed to high-level sound would show changes detectable by DPOAE mapping, but not apparent on a standard DP-gram. Thirteen normal hearing subjects were studied before and after attending music concerts. Pure-tone audiometry (500-8,000 Hz), DP-grams (0.3-10 kHz) at 1.22 ratio, and DPOAE level maps were collected prior to, as soon as possible after, and the day after the concerts. All maps covered the range of 2,000-6,000 Hz in DP frequency and from 1.3 to -1.3 in ratio using equi-level primary tone stimuli. Changes in the pure-tone audiogram were significant (P ≤ 0.01) immediately after the concert at 1,000 Hz, 4,000 Hz, and 6,000 Hz. The DP-gram showed significant differences only at f₂ = 4,066 (P = 0.01) and f₂ = 4,348 (P = 0.04). The postconcert changes were readily apparent both visually and statistically (P ≤ 0.01) on the mean DP level maps, and remained statistically significantly different from baseline the day after noise exposure although no significant changes from baseline were seen on the DP-gram or audiogram the day after exposure. Although both the DP-gram and audiogram showed recovery by the next day, the average DPOAE level maps remained significantly different from baseline. The mapping data showed changes in the cochlea that were not detected from the DP-gram obtained at a single ratio. DPOAE level mapping provides comprehensive information on subtle cochlear responses, which may offer advantages for studying and tracking noise-induced hearing loss (NIHL).     

IgG4 serology of loiasis in three villages in an endemic area of south-eastern Gabon

Human filariasis due to Loa loa differs from other filariasis in that the majority of infected subjects are without circulating microfilariae (occult loiasis). In search for alternative diagnostic methods, which do not depend on circulating microfilariae or the (rather infrequent) eye-passage of adult worms, it was shown earlier that IgG4 antibodies directed against Loa loa adult worm antigen are apparently a good marker of occult loiasis and specific with regard to the sympatrically occurring Mansonella perstans . In this study we evaluated an IgG4 antibody-based ELISA using crude extract of Loa loa microfilariae (which is easier to obtain than adult worm) to estimate the prevalence of loiasis in 3 villages in South-East Gabon. Of 222 examined individuals (80 children < 16 years, 142 adults) 44 (20%) carried Loa loa microfilariae and 170 (77%) M. perstans . Using the mean OD-value + 1 standard deviation of 9 sera from patients solely infected with M. perstans (from the Gambia, where Loa loa is not endemic) as a cut-off, 35 of the 44 microfilaraemic Loa loa patients and 2 of the 9 Gambian controls were positive. This shows that our method had a sensitivity of 80% and a specificity of 78%. Among the remaining 178 subjects who had no microfilariae of Loa loa , as many as 97 (55%) had significant levels of specific IgG4 antibodies against Loa loa , suggesting that they carried occult loiasis. The mean IgG4 level in these putatively occult loiasis patients was slightly but significantly lower than in microfilaraemic subjects ( P < 0.03). In conclusion, despite the limited sensitivity and specificity of our method, IgG4- ELISA at present is a very useful tool in estimating the real prevalence of loiasis in epidemiological surveys and at the individual level can confirm the diagnosis of L. loa amicrofilaraemic subjects with clinical signs suggesting loiasis.     

A Prospective Study of Relationships between Benign Gastric Ulcer, Candida, and Medical Treatment

Results of a multicenter prospective study on the relationships between benign gastric ulcer, Candida, and medical treatment is reported. In a group of 66 patients, mycetes were seen in six cases (9.1 %). Candida-contaminated ulcers were diagnosed solely by histological examination, with periodic acid-Schiff staining being more effective than hematoxylin and eosin staining. All contaminated ulcers were healed by treatment either with cimetidine alone, or combined cimetidine-carbenoxolone, without antimycotics. No cases of Candida-contaminated ulcers were seen after 6 wk of treatment. The finding of contamination was more common in older patients. Under the conditions of our study, Candida-contamination of benign gastric ulcers does not affect the rate of healing, does not need specific treatment, and has no particular endoscopic features. Cimetidine or carbenoxolone treatment was not associated with persistence of the fungus.     

Polymorphism of HLA-DMA and DMB alleles in patients with systemic lupus erythematosus

OBJECTIVE: To evaluate the contribution of HLA-DM alleles to susceptibility to systemic lupus erythematosus (SLE) in a Caucasian population. METHODS: HLA-DMA and DMB alleles were studied in 73 patients with SLE, 147 randomly selected controls, and 86 HLA-DRB1 genotype matched controls by oligotyping of polymerase chain reaction amplified genomic DNA with sequence-specific oligonucleotide probes. RESULTS: There was a significant presence of HLA-DMA*0103, DMA*0104, and DMB*0102 in the SLE patients compared with the randomly selected controls. After stratification of patients and matched controls according to DRB1 genotypes, only HLA-DMA*0104 was increased in SLE patients negative for the SLE susceptibility HLA-DR alleles. For the patients and controls positive for HLA-DR allele-susceptibility for SLE, HLA-DMA*0103, DMA*0104, DMB*0102, and DMB*0103 alleles tended to be more frequent, but without reaching statistical significance. No correlation was found between HLA-DM phenotype frequencies and any clinical or biological manifestations of SLE. CONCLUSION: This is the first study evaluating the influence of HLA-DM in a Caucasian SLE population. Our results suggest that HLA-DMA*0104 may represent a novel allele of susceptibility to SLE.     

Translocation t(5;12)(q31-q33;p12-p13): a non-random translocation associated with a myeloid disorder with eosinophilia

SUMMARY. To investigate the clinical significance of determination of plasma tissue factor (TF) antigen, we have developed a highly sensitive enzyme-linked immunosorbent assay (ELISA) for plasma TF, using two different monoclonal antibodies against TF apoprotein, 6B4 (catching antibody) and 5G9 (detecting antibody), and tetramethyl benzidine/H₂O₂ as substrates. Titration curves of recombinant human TF in buffer containing Triton X-100 were linear within the range from 50 to 2000pg/ml. The total assay time was 3h. Ultracentrifugation and immunoblot analysis indicated that human plasma and urine contained 50 000 g sedimentable and non-sedimentable forms of TF, both of which were detected by our ELISA method.
Plasma and urine concentrations of TF in healthy subjects and patients with various diseases were measured by the ELISA method. In healthy subjects, plasma and urinary TF levels were found to be 149± 72pg/ml (n = 30) and 175±60pg TF/urine creatinine mg (n = 95). respectively. TF was increased in plasma of patients with disseminated intravascular coagulation (DIC), thrombotic thrombocytopenic purpura, vasculitis associated with collagen diseases, diabetic microangiopathy and chronic renal failure receiving haemodialysis, but not in the plasma of endotoxaemic patients without DIC. The plasma TF/serum creatinine ratio did not show a positive correlation. Measurement of TF antigen in plasma may be useful for evaluating the endothelial damage and cell destruction in TF-containing tissues.     

N1pc reversal following repeated eccentric visual stimulation

Early event‐related potential (ERP) hemispheric asymmetries recorded at occipitoparietal sites are usually observed following the sudden onset of a lateral peripheral stimulus. This is usually reflected in an onset‐locked larger N1 over the posterior contralateral hemisphere relative to the ipsilateral hemisphere, an early ERP asymmetry labeled N1pc. When the peripheral sudden onset is followed by a central stimulus, or by a bilaterally balanced visual array of stimuli, these events evoke a reversed N1pc, that is, a larger N1 over the hemisphere ipsilateral to the peripheral sudden onset. This N1pc reversal has been taken as evidence for a remapping of the visual space from an absolute, retinally based frame of reference to a relative, attentionally based frame of reference that codes the spatial positions of objects relative to the peripheral sudden onset, rather than relative to the fovea. Here, we pit the reference frame‐remapping account against an alternative account based on reduced neural reactivity following the peripheral sudden onset. In three experiments, we varied the spatial location of an object relative to a preceding sudden onset, and tested the opposite predictions generated by the frame‐remapping and the reduced neural reactivity accounts. Taken together, the results from the present experiments were consistent with the reduced neural reactivity account and inconsistent with the frame‐remapping account.     

Trouble psychotique partagé ou trouble délirant induit ? Étude d’un cas clinique

Can a delusional idea be contagious? This question may seem paradoxical when we know that the very definition of delirium correspond to “an erroneous belief (…) maintained despite the very generally shared opinion” (DSM4) and so implies that peers do not share the beliefs expressed by the subject. However, cases of collective delirium have been described for many years, and have been the subject of numerous scientific publications since the 19th century. Among them, an entity emerged : “folie à deux”, in which a primary active subject could induce his delusions to a secondary subject, more vulnerable, said induced and passive. In 1877, Lasègue and Falret first introduced the term “folie à deux” and proposed the diagnostic criteria. They describe nine essential criteria among which, three would be the sine qua non conditions that can allow the outbreak of a delirium shared by two. They are the presence of an active element of superior intelligence, the existence of a common life between the two individuals, sufficiently long and intimate and a “closed and isolated” environment. These criteria were subsequently supplemented to arrive at the current definitions of induced delusional disorder (ICD10) and shared psychotic disorder (DSM4). This rare disorder has been the subject of numerous publications. However, these publications were often divided over both its epidemiology, its diagnostic criteria, and the specific treatment to be offered. The two recent definitions resulting from current classifications can also illustrate this dichotomy on certain criteria, beyond the very semantics which here oppose the terms “induced delusional” and “shared psychosis”. Moreover, this disorder has the particularity to question its real existence as it is currently challenged in the new classifications of the DSM V and ICD 11. We can therefore see that if the subject fascinates, it divides. What is it really? Can a delirium really be transmitted? Can a psychosis really be shared? And if so, is one of the two definitions more suitable to describe this disorder? What future can we imagine for this pathology? During the hospitalization of a patient for a “délire à deux”, concerning two persons from two different families sharing a delirium of filiation, we observed the current issues around this disorder and we asked ourselves which treatment to administer to these patients. The hospitalization took place over two stages: the first stage to understand the disorder, the second one to treat it. À family interview was conducted in the presence of the dyad of patients, to explore the interactional elements together, and establish the diagnosis. A preliminary step essential to therapeutic work on the question of loyalty and differentiation. This clinical case recalls the value of an integrated approach based on the systemic epistemology, both for the diagnostic phase than during therapeutic support. The objective of this work is to study, through an atypical clinical case and a review of recent literature, the different diagnostic, therapeutic and evolutionary perspectives of this particular pathology.     

Analysis of LMNB1 Duplications in Autosomal Dominant Leukodystrophy Provides Insights into Duplication Mechanisms and Allele‐Specific Expression

Autosomal dominant leukodystrophy (ADLD) is an adult onset demyelinating disorder that is caused by duplications of the lamin B1 (LMNB1) gene. However, as only a few cases have been analyzed in detail, the mechanisms underlying LMNB1 duplications are unclear. We report the detailed molecular analysis of the largest collection of ADLD families studied, to date. We have identified the minimal duplicated region necessary for the disease, defined all the duplication junctions at the nucleotide level and identified the first inverted LMNB1 duplication. We have demonstrated that the duplications are not recurrent; patients with identical duplications share the same haplotype, likely inherited from a common founder and that the duplications originated from intrachromosomal events. The duplication junction sequences indicated that nonhomologous end joining or replication‐based mechanisms such fork stalling and template switching or microhomology‐mediated break induced repair are likely to be involved. LMNB1 expression was increased in patients’ fibroblasts both at mRNA and protein levels and the three LMNB1 alleles in ADLD patients show equal expression, suggesting that regulatory regions are maintained within the rearranged segment. These results have allowed us to elucidate duplication mechanisms and provide insights into allele‐specific LMNB1 expression levels.     

Transthyretin Antisense Oligonucleotides Lower Circulating RBP4 Levels and Improve Insulin Sensitivity in Obese Mice

Circulating transthyretin (TTR) is a critical determinant of plasma retinol-binding protein 4 (RBP4) levels. Elevated RBP4 levels cause insulin resistance, and the lowering of RBP4 levels improves glucose homeostasis. Since lowering TTR levels increases renal clearance of RBP4, we determined whether decreasing TTR levels with antisense oligonucleotides (ASOs) improves glucose metabolism and insulin sensitivity in obesity. TTR-ASO treatment of mice with genetic or diet-induced obesity resulted in an 80–95% decrease in circulating levels of TTR and RBP4. Treatment with TTR-ASOs, but not control ASOs, decreased insulin levels by 30–60% and improved insulin sensitivity in ob/ob mice and high-fat diet–fed mice as early as after 2 weeks of treatment. The reduced insulin levels were sustained for up to 9 weeks of treatment and were associated with reduced adipose tissue inflammation. Body weight was not changed. TTR-ASO treatment decreased LDL cholesterol in high-fat diet–fed mice. The glucose infusion rate during a hyperinsulinemic-euglycemic clamp was increased by 50% in high-fat diet–fed mice treated with TTR-ASOs, demonstrating improved insulin sensitivity. This was also demonstrated by 20% greater inhibition of hepatic glucose production, a 45–60% increase of glucose uptake into skeletal and cardiac muscle, and a twofold increase in insulin signaling in muscle. These data show that decreasing circulating TTR levels or altering TTR-RBP4 binding could be a potential therapeutic approach for the treatment of type 2 diabetes.