A test of the assumptions of the transtheoretical model in a post-traumatic stress disorder population

Prior reports suggest an ambivalence regarding treatment in individuals with Post-Traumatic Stress Disorder (PTSD). A model that accommodates such ambivalence is the Transtheoretical Model of Behavior Change (TTM, also known as the Stages-of-Change Model). Fifty veterans presenting for treatment completed self-report measures (94% response rate) that assessed disorder variables and constructs relating to the TTM. While the relationships between the components of each specific construct were found to be consistent with the findings of other studies and a number of predicted relationships between variables were confirmed, many results were inconsistent with the TTM. Notwithstanding questions about the suitability of the self-report measures, the unique characteristics of the veteran sample and the small sample size, the results suggest that the assumptions of the TTM were not met in veterans with PTSD. Copyright © 2005 John Wiley & Sons, Ltd.     

Intermittent preventive sulfadoxine-pyrimethamine treatment of primigravidae reduces levels of plasma immunoglobulin G, which protects against pregnancy-associated Plasmodium falciparum malaria

Pregnancy-associated malaria (PAM) is an important cause of maternal and neonatal suffering. It is caused by Plasmodium falciparum capable of inhabiting the placenta through expression of particular variant surface antigens (VSA) with affinity for proteoglycans such as chondroitin sulfate A. Protective immunity to PAM develops following exposure to parasites inhabiting the placenta, and primigravidae are therefore particularly susceptible to PAM. The adverse consequences of PAM in primigravidae are preventable by intermittent preventive treatment (IPTp), where women are given antimalarials at specified intervals during pregnancy, but this may interfere with acquisition of protective PAM immunity. We found that Kenyan primigravidae receiving sulfadoxine-pyrimethamine IPTp had significantly lower levels of immunoglobulin G (IgG) with specificity for the type of parasite-encoded VSA-called VSA(PAM)-that specifically mediate protection against PAM than did women receiving a placebo. VSA(PAM)-specific IgG levels depended on the number of IPTp doses received and were sufficiently low to be of clinical concern among multidose recipients. Our data suggest that IPTp should be extended to women of all parities, in line with current World Health Organization recommendations.     

Hearing impairment as an early sign of alpha‐mannosidosis in children with a mild phenotype: Report of seven new cases

Alpha‐mannosidosis (AM) is a very rare (prevalence: 1/500000 births) autosomal recessive lysosomal storage disorder. It is characterized by multi‐systemic involvement associated with progressive intellectual disability, hearing loss, skeletal anomalies, and coarse facial features. The spectrum is wide, from very severe and lethal to a milder phenotype that usually progresses slowly. AM is caused by a deficiency of lysosomal alpha‐mannosidase. A diagnosis can be established by measuring the activity of lysosomal alpha‐mannosidase in leucocytes and screening for abnormal urinary excretion of mannose‐rich oligosaccharides. Genetic confirmation is obtained with the identification of MAN2B1 mutations. Enzyme replacement therapy (LAMZEDE^R) was approved for use in Europe in August 2018. Here, we describe seven individuals from four families, diagnosed at 3–23 years of age, and who were referred to a clinical geneticist for etiologic exploration of syndromic hearing loss, associated with moderate learning disabilities. Exome sequencing had been used to establish the molecular diagnosis in five cases, including a two‐sibling pair. In the remaining two patients, the diagnosis was obtained with screening of urinary oligosaccharides excretion and the association of deafness and hypotonia. These observations emphasize that the clinical diagnosis of AM can be challenging, and that it is likely an underdiagnosed rare cause of syndromic hearing loss. Exome sequencing can contribute significantly to the early diagnosis of these nonspecific mild phenotypes, with advantages for treatment and management.     

Preservation of the pattern of tyrosine phosphorylation in human neutrophil lysates. II. A sequential lysis protocol for the analysis of tyrosine phosphorylation-dependent signalling

In stimulated neutrophils, the majority of tyrosine phosphorylated proteins are concentrated in Triton X-100 or NP-40 insoluble fractions. Most immunobiochemical studies, whose objective is to study the functional relevance of tyrosine phosphorylation are, however, performed using the supernatants of cells lysed in non-ionic detergent-containing buffers (RIPA lysis buffers). This observation prompted us to develop an alternative lysis protocol. We established a procedure involving the sequential lysis of neutrophils in buffers of increasing tonicities that not only preserved and solubilized tyrosine phosphorylated proteins but also retained their enzymatic activities. The sequential lysis of neutrophils in hypotonic, isotonic and hypertonic buffers containing non-ionic detergents resulted in the solubilisation of a significant fraction of tyrosine phosphorylated proteins. Furthermore, we observed that in monosodium urate crystals-stimulated neutrophils, Lyn activity was enhanced in the soluble fraction recovered from the hypertonic fraction, but not from that of the first hypotonic lysis. The distribution of tyrosine phosphorylated proteins between the NP-40 soluble and insoluble fractions was both substrate- and agonist-dependent. In neutrophils stimulated with fMet-Leu-Phe, MSU crystals or by CD32 ligation, the tyrosine phosphorylated proteins were mostly insoluble. On the other hand, in GM-CSF-treated cells, the phosphoproteins were more equally distributed between the two fractions. The results of this study provide a new experimental procedure for the investigation of tyrosine phosphorylation pathways in activated human neutrophils which may also be applicable to other cell types.     

Autocrine IL-10 impairs dendritic cell (DC)-derived immune responses to mycobacterial infection by suppressing DC trafficking to draining lymph nodes and local IL-12 production

The production of IL-12 by dendritic cells (DC) early in an immune response is considered critical for the polarization of CD4(+) T lymphocyte response towards a Th1 pattern, a key process in the clearance of intracellular pathogens. Infection of bone marrow-derived DC with Mycobacterium bovis Bacillus Calmette Guérin (BCG) induced a concurrent and dose-dependent releaseof IL-10 and IL-12. Here we examined whether the production of IL-10 by DC affected their IL-12 response to mycobacterial infection and the generation of protective immune responses in vivo. Compared to wild-type (WT) DC, DC deficient for IL-10 synthesis (IL-10(-/-)) showed increased IL-12 production in response to BCG infection and CD40 stimuli in vitro. Moreover, when transferred into mice, infected IL-10(-/-) DC were more efficient than WT DC at inducing IFN-gamma production to mycobacterial antigens in the draining lymph nodes (DLN).This effect was associated with increased trafficking of IL-10(-/-) DC to the DLN and enhanced IL-12 production by DC within the DLN. These data show that autocrine IL-10 exerts a dual inhibitory effect on the induction of primary immune responses by DC: first, by down-regulating the migration of infected DC to the DLN and second, by modulating the IL-12 production by DC in the DLN.     

Accessibility, clinical effectiveness, and practice costs of providing a telephone option for routine asthma reviews: phase IV controlled implementation study.

BACKGROUND: Attendance for routine asthma reviews is poor. A recent randomised controlled trial found that telephone consultations can cost-effectively and safely enhance asthma review rates; however, concerns have been expressed about the generalisability and implementation of the trial's findings. AIM: To evaluate the effectiveness of a telephone option as part of a routine structured asthma review service. DESIGN OF STUDY: Phase IV controlled before-and-after implementation study. SETTING: A large UK general practice. METHOD: Using existing administrative groups, all patients with active asthma (n = 1809) received one of three asthma review services: structured recall with a telephone-option for reviews versus structured recall with face-to-face-only reviews, or usual-care (to assess secular trends). Main outcome measures were: proportion of patients with active asthma reviewed within the previous 15 months (Quality and Outcomes Framework target), mode of review, enablement, morbidity, and costs to the practice. RESULTS: A routine asthma review was provided for 397/598 (66.4%) patients in the telephone-option group compared with 352/654 (53.8%) in the face-to-face-only review group: risk difference 12.6% (95% confidence interval [CI] = 7.2 to 17.9, P<0.001). The usual-care group achieved a review rate of 282/557 (50.6%). Morbidity was equivalent in the three groups; however, enablement (P = 0.03) and confidence (P = 0.007) in asthma management were greater in the telephone-option versus face-to-face-only group. The cost per review achieved by providing the telephone-option service was lower than the face-to-face-only service (10.03 pounds versus 12.74 pounds, mean difference 2.71 pounds; 95% CI = 1.92 to 3.50, P<0.001); usual-care costs were 11.85 pounds per review achieved. CONCLUSION: Routinely offering telephone reviews cost-effectively increased asthma review rates, enhancing patient enablement and confidence with management, with no detriment to asthma morbidity. Practices should consider a telephone option for their asthma review service.