1,237 research outputs found
My approach to interstitial lung disease using clinical, radiological and histopathological patterns
The complex world of interstitial lung disease presents nearly insurmountable challenges to the general surgical pathologist faced with a lung biopsy in this setting. The pathology is often inflammatory and always requires clinical and radiological context for a relevant and clinically useful histopathological diagnosis. A pattern-based histopathological approach to interstitial lung disease provides a âmapâ for the general pathologist to navigate this area successfully, especially so when used with aid of the clinical and radiological patterns of presentation
Recommended from our members
NMHCs and halocarbons in Asian continental outflow during the Transport and Chemical Evolution over the Pacific (TRACE-P) Field Campaign: Comparison with PEM-West B
We present an overview of the spatial distributions of nonmethane hydrocarbons (NMHCs) and halocarbons observed over the western north Pacific as part of the NASA GTE Transport and Chemical Evolution over the Pacific (TRACEâP) airborne field campaign (FebruaryâApril 2001). The TRACEâP data are compared with earlier measurements from the Pacific Rim during the Pacific Exploratory MissionâWest B (PEMâWest B), which took place in FebruaryâMarch 1994, and with emission inventory data for 2000. Despite the limited spatial and temporal data coverage inherent to airborne sampling, mean levels of the longerâlived NMHCs (including ethane, ethyne, and benzene) were remarkably similar to our results during the PEMâWest B campaign. By comparison, mixing ratios of the fire extinguisher Halonâ1211 (CF2ClBr) increased by about 50% in the period between 1994 and 2001. Southern China (south of 35°N), and particularly the Shanghai region, appears to have been a substantial source of Halonâ1211 during TRACEâP. Our previous analysis of the PEMâWest B data employed methyl chloroform (CH3CCl3) as a useful industrial tracer. However, regulations have reduced its emissions to the extent that its mixing ratio during TRACEâP was only oneâthird of that measured in 1994. Methyl chloroform mixing ratio âhot spots,â indicating regions downwind of continuing emissions, included outflow from the vicinity of Shanghai, China, but particularly high emission ratios relative to CO were observed close to Japan and Korea. Tetrachloroethene (C2Cl4) levels have also decreased significantly, especially north of 25°N, but this gas still remains a useful indicator of northern industrial emissions. Methyl bromide (CH3Br) levels were systematically 1â2 pptv lower from 1994 to 2001, in accord with recent reports. However, air masses that had been advected over Japan and/or South Korean port cities typically exhibited elevated levels of CH3Br. As a consequence, emissions of CH3Br from Japan and Korea calculated employing CH3Br/CO ratios and scaled to CO emission inventory estimates, were almost as large as for all of south China (south of 35°N). Total east Asian emissions of CH3Br and CH3Cl were estimated to be roughly 4.7 Gg/yr and 167 Gg/yr, respectively, in 2001
Associations between adherence, depressive symptoms and health-related quality of life in young adults with cystic fibrosis
BACKGROUND: Cystic fibrosis (CF) is a life shortening disease, however prognosis has improved and the adult population is growing. Most adults with cystic fibrosis live independent lives and balance the demands of work and family life with a significant treatment burden. The aim of this study was to examine the relationships among treatment adherence, symptoms of depression and health-related quality of life (HRQoL) in a population of young adults with CF. METHODS: We administered three standardized questionnaires to 67 patients with CF aged 18â30 years; Morisky Medication Adherence Scale, Major Depression Inventory, and Cystic Fibrosis Questionnaire-Revised. RESULTS: There was a response rate of 77 % and a majority of the young adults (84 %) were employed or in an education program. Most participants (74 %) reported low adherence to medications. One third (32.8 %) of the participants reported symptoms of depression. HRQoL scores were especially low on Vitality and Treatment Burden, and symptoms of depression were associated with low HRQoL scores (p < 0.01) with medium to large deficits across on all HRQoL domains (Cohenâs d 0.60â1.72) except for the domain treatment burden. High depression symptom scores were associated with low adherence (r = â0.412, p < 0.001). CONCLUSIONS: Despite improved physical health, many patients with CF report poor adherence, as well as impaired mental wellbeing and HRQoL. Thus, more attention to mental health issues is needed
In Vitro HIV-1 Evolution in Response to Triple Reverse Transcriptase Inhibitors & In Silico Phenotypic Analysis
Background Effectiveness of ART regimens strongly depends upon complex
interactions between the selective pressure of drugs and the evolution of
mutations that allow or restrict drug resistance. Methods Four clinical
isolates from NRTI-exposed, NNRTI-naive subjects were passaged in increasing
concentrations of NVP in combination with 1 ”M 3 TC and 2 ”M ADV to assess
selective pressures of multi-drug treatment. A novel parameter inference
procedure, based on a stochastic viral growth model, was used to estimate
phenotypic resistance and fitness from in vitro combination passage
experiments. Results Newly developed mathematical methods estimated key
phenotypic parameters of mutations arising through selective pressure exerted
by 3 TC and NVP. Concentrations of 1 ”M 3 TC maintained the M184V mutation,
which was associated with intrinsic fitness deficits. Increasing NVP
concentrations selected major NNRTI resistance mutations. The evolutionary
pathway of NVP resistance was highly dependent on the viral genetic
background, epistasis as well as stochasticity. Parameter estimation indicated
that the previously unrecognized mutation L228Q was associated with NVP
resistance in some isolates. Conclusion Serial passage of viruses in the
presence of multiple drugs may resemble the selection of mutations observed
among treated individuals and populations in vivo and indicate evolutionary
preferences and restrictions. Phenotypic resistance estimated here âin silicoâ
from in vitro passage experiments agreed well with previous knowledge,
suggesting that the unique combination of âwet-â and âdry-labâ experimentation
may improve our understanding of HIV-1 resistance evolution in the future
Three cases of amoebic liver abscess causing inferior vena cava obstruction, with a review of the literature
Amoebic liver abscess is a common disease, especially in endemic areas, but it is a rare cause of inferior vena cava (IVC) obstruction, with only a few cases appearing in the literature. We report three cases of amoebic liver abscess complicated with obstruction of the IVC and which responded to conservative treatment or radiological intervention
Antiviral Resistance and Correlates of Virologic Failure in the first Cohort of HIV-Infected Children Gaining Access to Structured Antiretroviral Therapy in Lima, Peru: A Cross-Sectional Analysis
Background: The impact of extended use of ART in developing countries has been enormous. A thorough
understanding of all factors contributing to the success of antiretroviral therapy is required. The current study aims to
investigate the value of cross-sectional drug resistance monitoring using DNA and RNA oligonucleotide ligation assays
(OLA) in treatment cohorts in low-resource settings. The study was conducted in the first cohort of children gaining
access to structured ART in Peru.
Methods: Between 2002â5, 46 eligible children started the standard regimen of AZT, 3TC and NFV Patients had a
median age of 5.6 years (range: 0.7-14y), a median viral load of 1.7·105 RNA/ml (range: 2.1·103 â 1.2·106), and a median
CD4-count of 232 cells/ÎŒL (range: 1â1591). Of these, 20 patients were classified as CDC clinical category C and 31/46 as
CDC immune category 3. At the time of cross-sectional analysis in 2005, adherence questionnaires were administered.
DNA OLAs and RNA OLAs were performed from frozen PBMC and plasma, RNA genotyping from dried blood spots.
Results: During the first year of ART, 44% of children experienced virologic failure, with an additional 9% failing by the
end of the second year. Virologic failure was significantly associated with the number of resistance mutations detected by
DNA-OLA (p < 0.001) during cross-sectional analysis, but also with low immunologic CDC-scores at baseline (p < 0.001).
Children who had been exposed to unsupervised short-term antiretrovirals before starting structured ART showed
significantly higher numbers of resistance mutations by DNA-OLA (p = 0.01). Detection of M184V (3TC resistance) by
RNA-OLA and DNA-OLA demonstrated a sensitivity of 0.93 and 0.86 and specificity of 0.67 and 0.7, respectively, for the
identification of virologic failure. The RT mutations N88D and L90M (NFV resistance) detected by DNA-OLA correlated
with virologic failure, whereas mutations at RT position 215 (AZT resistance) were not associated with virologic failure.
Conclusions: Advanced immunosuppression at baseline and previous exposures to unsupervised brief cycles of ART
significantly impaired treatment outcomes at a time when structured ART was finally introduced in his cohort. Brief
maternal exposures to with AZT +/â NVP for the prevention of mother-to-child transmission did not affect treatment
outcomes in this group of children. DNA-OLA from frozen PBMC provided a highly specific tool to detect archived drug
resistance. RNA consensus genotyping from dried blood spots and RNA-OLA fromplasma consistently detected drug
resistance mutations, but merely in association with virologic failur
Expression of HSP47 in Usual Interstitial Pneumonia and Nonspecific Interstitial Pneumonia
BACKGROUND: Heat shock protein (HSP) 47, a collagen-specific molecular chaperone, is involved in the processing and/or secretion of procollagens, and its expression is increased in various fibrotic diseases. The aim of this study was to determine whether quantitative immunohistochemical evaluation of the expression levels of HSP47, type I procollagen and α-smooth muscle actin (SMA) allows the differentiation of idiopathic usual interstitial pneumonia (UIP) from UIP associated with collagen vascular disease (CVD) and idiopathic nonspecific interstitial pneumonia (NSIP). METHODS: We reviewed surgical lung biopsy specimens of 19 patients with idiopathic UIP, 7 with CVD-associated UIP and 16 with idiopathic NSIP and assigned a score for the expression of HSP47, type I procollagen and α-SMA in type II pneumocytes and/or lung fibroblasts (score 0 = no; 1 = weak; 2 = moderate; 3 = strong staining). RESULTS: The expression level of HSP47 in type II pneumocytes of idiopathic UIP was significantly higher than in CVD-associated UIP and idiopathic NSIP. The expression of HSP47 in fibroblasts was significantly higher in idiopathic UIP and idiopathic NSIP than in CVD-associated UIP. The expression of type I procollagen in type II pneumocytes was significantly higher in idiopathic UIP than in idiopathic NSIP. The expression of type I procollagen in fibroblasts was not different in the three groups, while the expression of α-SMA in fibroblasts was significantly higher in idiopathic UIP than in idiopathic NSIP. CONCLUSION: Our results suggest the existence of different fibrotic pathways among these groups involved in the expression of HSP47 and type I procollagen
Erythropoietin/erythropoietin receptor system is involved in angiogenesis in human neuroblastoma
Ribatti D, Poliani P L, Longo V, Mangieri D, Nico B & Vacca A (2007) Histopathology50, 636â641 Erythropoietin/erythropoietin receptor system is involved in angiogenesis in human neuroblastom
How far will we need to go to reach HIV-infected people in rural South Africa?
Background: The South African Government has outlined detailed plans for antiretroviral (ART) rollout in KwaZulu-Natal Province, but has not created a plan to address treatment accessibility in rural areas in KwaZulu-Natal. Here, we calculate the distance that People Living With HIV/AIDS (PLWHA) in rural areas in KwaZulu-Natal would have to travel to receive ART. Specifically, we address the health policy question 'How far will we need to go to reach PLWHA in rural KwaZulu-Natal?'. Methods: We developed a model to quantify treatment accessibility in rural areas; the model incorporates heterogeneity in spatial location of HCFs and patient population. We defined treatment accessibility in terms of the number of PLWHA that have access to an HCF. We modeled the treatment-accessibility region (i.e. catchment area) around an HCF by using a two-dimensional function, and assumed that treatment accessibility decreases as distance from an HCF increases. Specifically, we used a distance-discounting measure of ART accessibility based upon a modified form of a two-dimensional gravity-type model. We calculated the effect on treatment accessibility of: (1) distance from an HCF, and (2) the number of HCFs. Results: In rural areas in KwaZulu-Natal even substantially increasing the size of a small catchment area (e.g. from 1 km to 20 km) around an HCF would have a negligible impact (~2%) on increasing treatment accessibility. The percentage of PLWHA who can receive ART in rural areas in this province could be as low as ~16%. Even if individuals were willing (and able) to travel 50 km to receive ART, only ~50% of those in need would be able to access treatment. Surprisingly, we show that increasing the number of available HCFs for ART distribution ~ threefold does not lead to a threefold increase in treatment accessibility in rural KwaZulu-Natal. Conclusion: Our results show that many PLWHA in rural KwaZulu-Natal are unlikely to have access to ART, and that the impact of an additional 37 HCFs on treatment accessibility in rural areas would be less substantial than might be expected. There is a great length to go before we will be able to reach many PLWHA in rural areas in South Africa, and specifically in KwaZulu-Natal.David P Wilson and Sally Blowe
- âŠ