Disseminated talc granulomatosis. An unusual finding in a patient with acquired immunodeficiency syndrome and fatal cytomegalovirus infection

The association of disseminated magnesium silicate talc granulomatosis and acquired immunodeficiency syndrome is reported in a male homosexual who used intravenous drugs and who died of overwhelming cytomegalovirus (CMV) infection. Autopsy findings included widespread deposition of talc crystals in the lungs, liver, lymph nodes, bone marrow, and spleen. Typical CMV inclusions were seen in the lungs, kidneys, adrenal glands, gastrointestinal tract, and right eye. There was no evidence of malignancy. Analysis of peripheral blood neutrophil function revealed impaired chemotaxis and chemokinesis, but opsonophagocytosis had remained normal. The CMV infection in the small bowel was extensive and resulted in severe destruction of the muscularis propria and neural plexi, leading to marked dilatation and persistent diarrhea. The terminal course was marked by intractable hypotension, pneumonitis, and malnutrition, which could be attributed respectively to CMV involvement of the adrenal glands, lungs, and small bowel. The etiology and possible role of systemic talc granulomatosis in the development of immunosuppressive illness is reported herein.     

Stimulation of β-adrenoceptors inhibits store-operated channel currents via a cAMP-dependent protein kinase mechanism in rabbit portal vein myocytes

Previously we have described the properties of store-operated channel currents (SOCs) in freshly dispersed rabbit portal vein smooth muscle cells. In addition to Ca²⁺ store depletion these SOCs could also be activated by α-adrenoceptor stimulation and diacylglycerol (DAG) via a protein kinase C (PKC)-dependent mechanism. In the present study we have investigated the effect of β-adrenoceptor stimulation on SOCs in rabbit portal vein myocytes. With whole-cell recording the selective β-adrenoceptor agonist isoprenaline reduced the current evoked by cyclopiazonic acid (CPA, sarcoplasmic/endoplasmic reticulum ATPase inhibitor) by over 85%. With cell-attached patch recording, bath application of isoprenaline produced a pronounced inhibition of SOC activity evoked by either CPA or the acetoxymethyl ester form of BAPTA (BAPTA-AM). SOC activity evoked by CPA, the DAG analogue, 1-oleoyl-acetyl- sn -glycerol (OAG) or the phorbol ester, phorbol-12,13-dibutyrate (PDBu) was also markedly inhibited by the adenylate cyclase activator, forskolin, and the cell-permeable non-hydrolysable analogue of cyclic adenosine monophosphate (cAMP), 8-Br-cAMP. With inside-out patches, bath application of PDBu evoked channel currents with similar properties to SOCs which were inhibited by over 90% by a catalytic subunit of protein kinase A (PKA) and by 8-Br-cAMP. Moreover bath application of PKA inhibitors, H-89, KT5720 and an inhibitory peptide to quiescent cell-attached or inside-out patches, activated channel currents with similar properties to SOCs. These data suggest that in rabbit portal vein myocytes, stimulation of β-adrenoceptors inhibits SOC activity via a cAMP-dependent protein kinase signal transduction cascade. In addition it is concluded that constitutive PKA activity has a profound inhibitory effect on SOC activity in this vascular preparation.     

Distribution of mutations in the PEX gene in families with X-linked hypophosphataemic rickets (HYP)

Mutations in the PEX gene at Xp22.1 (phosphate-regulating gene with homologies to endopeptidases, on the X-chromosome), are responsible for X-linked hypophosphataemic rickets (HYP). Homology of PEX to the M13 family of Zn2+ metallopeptidases which include neprilysin (NEP) as prototype, has raised important questions regarding PEX function at the molecular level. The aim of this study was to analyse 99 HYP families for PEX gene mutations, and to correlate predicted changes in the protein structure with Zn2+ metallopeptidase gene function. Primers flanking 22 characterised exons were used to amplify DNA by PCR, and SSCP was then used to screen for mutations. Deletions, insertions, nonsense mutations, stop codons and splice mutations occurred in 83% of families screened for in all 22 exons, and 51% of a separate set of families screened in 17 PEX gene exons. Missense mutations in four regions of the gene were informative regarding function, with one mutation in the Zn2+-binding site predicted to alter substrate enzyme interaction and catalysis. Computer analysis of the remaining mutations predicted changes in secondary structure, N-glycosylation, protein phosphorylation and catalytic site molecular structure. The wide range of mutations that align with regions required for protease activity in NEP suggests that PEX also functions as a protease, and may act by processing factor(s) involved in bone mineral metabolism.      

Detecting antibodies with similar reactivity patterns in the HLDA8 blind panel of flow cytometry data

The blind panel collected for the 8th Human Leucocyte Differentiation Antigens Workshop (HLDA8; ) included 49 antibodies of known CD specificities and 76 antibodies of unknown specificity. We have identified groups of antibodies showing similar patterns of reactivity that need to be investigated by biochemical methods to evaluate whether the antibodies within these groups are reacting with the same molecule. Our approach to data analysis was based on the work of Salganik et al. (in press) [Salganik, M.P., Milford E.L., Hardie D.L., Shaw, S., Wand, M.P., in press. Classifying antibodies using flow cytometry data: class prediction and class discovery. Biometrical Journal].     

Limiting factors for cytopathological diagnosis of high-grade squamous intraepithelial lesions: a cytohistological correlation between findings in cervical smears and loop electrical excision procedure.

The present study sought possible factors leading to the cytological diagnosis of atypical squamous cells of uncertain significance (ASCUS) in cases of high-grade squamous intraepithelial lesions (HSIL). Based on retrospective histopathological analysis of loop electrical excision procedure (LEEP) products that diagnosed HSIL, two study groups were randomly selected. The first was consisted of cases with two consecutive Papanicolaou (Pap) smears with the diagnosis of ASCUS. The second (control) group was represented by cases diagnosed as HSIL by cytology. From the Pap smears diagnosed as ASCUS, the sampling limitations was different from control group (P < 0.05). The median size of the largest lesion in each case with ASCUS was 2.66 mm (+/- 1.71 mm). In the control group, the median size of the largest lesion was 5.15 mm (+/-2.58 mm) (P < 0.05). The size of the lesion and sample limitations led patients with cervical intraepithelial neoplasms to be diagnosed as ASCUS for two consecutive times, after a 6-mo period.     

Fra(2) (q13) and inv(9) (p11q12) in autism: causal relationship?

Twenty individuals with autism or related disorders underwent chromosome analysis and physical examinations with documentation of minor anomalies. Chromosome anomalies were identified in 3: 2 had the heritable folate sensitive fra(2) (q13) site and 1 had an inv(9) (p11q12). No heritable chromosome variants or anomalies were seen in 20 age and sex-matched control individuals. When patients with the fra(2) were excluded from analyses, there was no difference in the frequency of chromosome breaks and/or gaps between the study group and control group. The results of this study suggest that heritable folate sensitive fragile sites and other chromosome variants may be more commonly seen in individuals with autism or related disorders in childhood than in the general population.     

Temporal trends in correlates of HIV testing uptake in South Africa: evaluation and population-level impacts of socio-economic factors and information sources

Aim

The primary objective of this study was to investigate temporal changes in HIV testing rates and quantify the degree to which these trends can be attributed to certain socio-economic characteristics, as well as exposure to information sources.

Subjects and methods

Data from a nationally representative sample of 30,020 sexually active black Africans who participated in the first, second, third and fourth South African National HIV, Behaviour and Health Surveys conducted in 2002, 2005, 2008 and 2012, respectively. Multivariable logistic regression models and population-attributable risks were calculated for the socio-economic characteristics and the information sources.

Results

The socio-economic characteristics of the survey participants remained stable over time, while HIV testing rates increased substantially from 20% in 2002 to 70% in 2012. However, there was little improvement in condom use rates. Combined impact of education, employment and geographical locations were associated with increased levels of HIV testing rates. Most of the survey participants (> 80%) were exposed to several mass-media and interpersonal information sources. The combined impact of mass-media tools on HIV testing rates ranged between 48 and 60%, while 40–50% of the HIV tests were collectively attributed to the interpersonal information sources.

Conclusion

We observed significant temporal changes in population-level impacts of several key socio-economic characteristics and information sources on HIV testing rates. Widespread nationwide HIV awareness efforts led to significant increases in access to testing facilities and substantial increases in HIV testing rates over time. However, this increase was not mirrored in condom use behaviour.

     

Diagnosis of pulmonary embolism: Ventilation perfusion scintigraphy versus helical computed tomography pulmonary angiography

The present study compared the accuracy of ventilation perfusion scintigraphy (VQS) and CT pulmonary angiography (CTPA) for the diagnosis of pulmonary embolism. This was a prospective observational study of 112 patients with suspected pulmonary embolism (PE) who could be studied with both investigations within 24 h. Results were compared to final diagnosis at completion of 6-month follow up, using receiver operating characteristic (ROC) analysis. Pulmonary embolism was diagnosed in 27 referred patients (24%). The sensitivity and specificity of VQS and CTPA were similar to that reported from the literature. A normal VQ scan had the highest negative predictive value (100%), while a high-probability VQ scan had the highest positive predictive value (92%). There was no overall difference (area under the ROC curve (AUC)) between VQS (AUC (95% CI) = 0.82 (0.75,0.89)) and CTPA (AUC = 0.88 (0.81,0.94)) for the diagnosis of PE. Among patients with abnormal chest X-rays, CTPA (AUC 0.90 (0.83,0.97)) appeared somewhat better than VQS (AUC 0.78 (0.68,0.88)) but this difference did not reach statistical significance. In this instance, CTPA is at least as accurate as VQS and may provide an opportunity to make alternative diagnoses.     

Spatial clustering of “measured” and “unmeasured” risk factors for HIV infections in hyper-endemic communities in KwaZulu-Natal,South Africa: results from geoadditive models

Sub-Saharan Africa contains more than 60% of all HIV infections worldwide. HIV prevalence was currently estimated to be at least 15% in KwaZulu-Natal and the epidemic is described as hyper-endemic. Knowledge of spatial clustering of risk factors which are linked to new HIV infections is important for prioritizing areas to change the trajectory of the epidemic. Geoadditive models were used to investigate spatial characteristics of the risk factors from two clinical trial units (Umkomaas and Botha's Hill) in the province of KwaZulu-Natal, South Africa. Study population was a cohort of women who screened and enrolled in an HIV prevention biomedical intervention trial. The results suggest high HIV incidence rates (5.8 and 8 per 100 person-year). Considerable spatial variations in behavioural factors within a relatively small geographical region, low level of education, early age at sexual debut, higher number of sexual partners, not being married/cohabitating with a sexual partner and sexual activity in exchange for money, gift and drugs were all determined to be clustered in certain regions; they were accounted for 25% (Umkomaas) and 65% (Botha's Hill) of the excess new HIV infections in two clinical trial units. Results from our study highlighted existence of significant spatial heterogeneity in “measured” and “unmeasured” risk factors in a relatively small region. As the HIV funding has been declining, identifying, targeting and reaching the most-at-risk individuals will likely play a significant role in developing the most efficient and cost-effective prevention programmes and subsequently will change the trajectory of the epidemic.     

Seeing It Helps: Movement-related Back Pain Is Reduced by Visualization of the Back During Movement

OBJECTIVES:: The aim of this study was to determine whether visualization of the back influenced parameters of movement-related pain in people with chronic nonspecific low back pain. METHODS:: We used a randomized cross-over experiment in which 25 participants performed repeated lumbar spine movements under 2 conditions. In the visual feedback condition, patients were able to visualize their back as it moved by the use of mirrors. In the control condition, the mirror was covered so no visualization of the back was possible. RESULTS:: The average postmovement pain intensity after participants had moved with visual feedback was less (35.5±22.8 mm) than when they moved without visual feedback (44.7±26.0 mm). This difference was statistically significant (mean difference=9.3, 95% confidence interval: 2.8-15.7 F(1,22)=8.82, P=0.007). The average time to ease after participants had moved with visual feedback was shorter (44.5 s±53.8) than when they moved without visual feedback (94.4 s±80.7). This difference was also statistically significantly (mean difference=49.9, 95% confidence interval: 19.3-80.6, F(1,22)=8.82, P=0.003). DISCUSSION:: Patients with chronic nonspecific low back pain reported less increase in pain and faster resolution of pain when moving in an environment that enabled them to visualize their back. This is consistent with emerging research on the use of mirror visual feedback in other long-standing pain problems and suggests that similar lines of inquiry may be worth pursuing in the chronic nonspecific low back pain population.