Prelamin A mediates inflammation in dilated and HIV associated cardiomyopathies

Cardiomyopathies are complex heart muscle diseases that can be inherited or acquired. Dilated cardiomyopathy can result from mutations in LMNA, encoding the nuclear intermediate filament proteins lamin A/C. Some LMNA mutations lead to accumulation of the lamin A precursor, prelamin A, which is disease causing in a number of tissues yet its impact upon the heart is unknown. Here we discovered myocardial prelamin A accumulation occurred in a case of dilated cardiomyopathy and show that a novel mouse model of cardiac specific prelamin A accumulation exhibited a phenotype consistent with ‘inflammatory cardiomyopathy’ which we observed to be similar to HIV associated cardiomyopathy, an acquired disease state. Numerous HIV protease therapies are known to inhibit ZMPSTE24, the enzyme responsible for prelamin A processing, and we confirmed that accumulation of prelamin A occurred in HIV+ patient cardiac biopsies. These findings: (1) confirm a unifying pathological role for prelamin A common to genetic and acquired cardiomyopathies; (2) have implications for the management of HIV patients with cardiac disease suggesting protease inhibitors should be replaced with alternative therapies i.e. non-nucleoside reverse transcriptase inhibitors; and (3) suggest that targeting inflammation may be a useful treatment strategy for certain forms of inherited cardiomyopathy

Chronic Cough and Eosinophilic Esophagitis: An Uncommon Association

An increasing number of children, usually with gastrointestinal symptoms, is diagnosed with eosinophilic esophagitis (EE), and a particular subset of these patients complains of airway manifestations. We present the case of a 2-year-old child with chronic dry cough in whom EE was found after a first diagnosis of gastroesophageal reflux disease (GERD) due to pathological 24-hour esophageal pH monitoring. Traditional allergologic tests were negative, while patch tests were diagnostic for cow's milk allergy. We discuss the intriguing relationship between GERD and EE and the use of patch test for the allergologic screening of patients

Polydrug Use among IDUs in Tijuana, Mexico: Correlates of Methamphetamine Use and Route of Administration by Gender

Tijuana is situated on the Mexico–USA border adjacent to San Diego, CA, on a major drug trafficking route. Increased methamphetamine trafficking in recent years has created a local consumption market. We examined factors associated with methamphetamine use and routes of administration by gender among injection drug users (IDUs). From 2006–2007, IDUs ≥18 years old in Tijuana were recruited using respondent-driven sampling, interviewed, and tested for HIV, syphilis, and TB. Logistic regression was used to assess associations with methamphetamine use (past 6 months), stratified by gender. Among 1,056 participants, methamphetamine use was more commonly reported among females compared to males (80% vs. 68%, p < 0.01), particularly, methamphetamine smoking (57% vs. 34%; p < 0.01). Among females (N = 158), being aged >35 years (AOR, 0.2; 95% CI, 0.1–0.6) was associated with methamphetamine use. Among males (N = 898), being aged >35 years (AOR, 0.5; 95% CI, 0.3–0.6), homeless (AOR, 1.4 (0.9–2.2)), and ever reporting sex with another male (MSM; AOR, 1.9; 95% CI, 1.4–2.7) were associated with methamphetamine use. Among males, a history of MSM was associated with injection, while sex trade and >2 casual sex partners were associated with multiple routes of administration. HIV was higher among both males and females reporting injection as the only route of methamphetamine administration. Methamphetamine use is highly prevalent among IDUs in Tijuana, especially among females. Routes of administration differed by gender and subgroup which has important implications for tailoring harm reduction interventions and drug abuse treatment

Hyper-IgG4 disease: report and characterisation of a new disease

BACKGROUND: We highlight a chronic inflammatory disease we call 'hyper-IgG4 disease', which has many synonyms depending on the organ involved, the country of origin and the year of the report. It is characterized histologically by a lymphoplasmacytic inflammation with IgG4-positive cells and exuberant fibrosis, which leaves dense fibrosis on resolution. A typical example is idiopathic retroperitoneal fibrosis, but the initial report in 2001 was of sclerosing pancreatitis. METHODS: We report an index case with fever and severe systemic disease. We have also reviewed the histology of 11 further patients with idiopathic retroperitoneal fibrosis for evidence of IgG4-expressing plasma cells, and examined a wide range of other inflammatory conditions and fibrotic diseases as organ-specific controls. We have reviewed the published literature for disease associations with idiopathic, systemic fibrosing conditions and the synonyms: pseudotumour, myofibroblastic tumour, plasma cell granuloma, systemic fibrosis, xanthofibrogranulomatosis, and multifocal fibrosclerosis. RESULTS: Histology from all 12 patients showed, to varying degrees, fibrosis, intense inflammatory cell infiltration with lymphocytes, plasma cells, scattered neutrophils, and sometimes eosinophilic aggregates, with venulitis and obliterative arteritis. The majority of lymphocytes were T cells that expressed CD8 and CD4, with scattered B-cell-rich small lymphoid follicles. In all cases, there was a significant increase in IgG4-positive plasma cells compared with controls. In two cases, biopsies before and after steroid treatment were available, and only scattered plasma cells were seen after treatment, none of them expressing IgG4. Review of the literature shows that although pathology commonly appears confined to one organ, patients can have systemic symptoms and fever. In the active period, there is an acute phase response with a high serum concentration of IgG, and during this phase, there is a rapid clinical response to glucocorticoid steroid treatment. CONCLUSION: We believe that hyper-IgG4 disease is an important condition to recognise, as the diagnosis can be readily verified and the outcome with treatment is very good

Global distributions of acetone in the upper troposphere from MIPAS spectra

This study reports the first global measurements of acetone (C&lt;sub&gt;3&lt;/sub&gt;H&lt;sub&gt;6&lt;/sub&gt;O) in the upper troposphere (UT). Profiles were obtained between 9 km and 15 km from measurements made by the Michelson Interferometer for Passive Atmospheric Sounding (MIPAS) onboard Envisat in August 2003. Errors per profile are lower than 40 % between 180 hPa and 350 hPa. We report strong hemispheric differences in the acetone volume mixing ratios (VMRs), with average concentrations highest in the Northern Hemisphere (NH) mid-latitude UT, between 1000 pptv and 1600 pptv with maxima up to 2300 pptv. Our results show a strong enhancement of acetone relative to CO, particularly over Europe (7 pptv ppbv&lt;sup&gt;−1&lt;/sup&gt;), confirming aircraft studies. Ten-day backward trajectories from these high European values show strong contributions from air flows over North America (56 %) and 25 % from Southernmost Asia. Enhanced acetone is also observed over Greenland, Siberia and biomass burning regions of Africa. Zonal distributions show that acetone VMRs decrease rapidly with increasing altitude (decreasing pressure), particularly in the NH. Poleward of 45° S, acetone VMRs remain fairly consistent with average VMRs between 400 pptv and 500 pptv. In 5-day averages at 9 km, NH VMRs poleward of 45° N are consistently higher than Southern Hemisphere observations poleward of 45° S, by between 750 pptv and 1100 pptv. The results show a clear influence of mid-latitude and transport processes on the acetone summertime distribution

A comparison of the rostrocaudal open mouth and rostro 10 degrees ventro-caudodorsal oblique radiographic views for imaging fluid in the feline tympanic bulla

Fluid within the tympanic bulla is an indication of middle ear disease. Radiography has a relatively low accuracy for the detection of soft tissue opacification in the tympanic bulla, and the most useful radiographic projection, the rostrocaudal open mouth (RCd (open mouth)), is technically difficult to perform in dogs and cats. An alternative projection for the feline tympanic bulla, the rostro 10° ventro-caudodorsal oblique (R10°V-CdDO), was compared to the RCd (open mouth) in 41 feline cadaver heads with the tympanic bullae randomly filled with KY jelly. Computed tomography was used as the gold standard. Each tympanic bulla was recorded as being positive or negative for soft tissue opacification. Although there was no significant difference between the accuracy of the two views, the R10°V-CdDO was subjectively more accurate and easier to perform, and in a live patient may be performed without the need for general anesthesia. The R10°V-CdDO projection is a good alternative to the RCd (open mouth) projection for detecting otitis media in the cat