tbuckley/cabot-search huggingface dataset:
The effect of sulphur dioxide exposure on indices of heart rate variability in normal and asthmatic adults
Authors: W.S. Tunnicliffe, M.F. Hilton, R.M. Harrison, J.G. Ayres
Journal: European Respiratory Journal (2001)

Sulphur dioxide (SO 2 ) is an important air pollutant and causes bronchoconstriction in normal and asthmatic adults. This paper has explored the autonomic consequences of SO 2 exposure using the spectral analysis of heart rate variability. Electrocardiogram recordings were made in 12 normal and 12 asthmatic adults undergoing pollutant exposures. Exposures were of a 1 h duration, double blind, in random order, ≥2 weeks apart and included air and 200 parts per billion SO 2 . Spectral analysis of R-R intervals was performed. SO 2 exposure was associated with an increase in total power (TP) and high (HF) and low frequency (LF) power in the normal subjects, and a reduction in these indices in the subjects with asthma. The difference in TP with SO 2 exposure compared to air was +1730 ms 2 in the normal group and −1021 ms 2 asthmatic group (p&lt;0.003). For HF the respective values were +964 ms 2 and −539 ms 2 (p=0.02) and for LF, +43 7 ms 2 and −57 2 ms 2 (p=0.01). No change in lung function or symptoms was observed in either group. This suggests that SO 2 exposure at concentrations which are frequently encountered during air pollution episodes can influence the autonomic nervous system. This may be important in understanding the mechanisms involved in SO 2 induced bronchoconstriction, and of the cardiovascular effects of air pollution.
DISAPPOINTING RESULTS WITH BILATERAL PREFRONTAL LOBOTOMY IN CHRONIC SCHIZOPHRENIA
Authors: GERT HEILBRUNN, PAUL HLETKO
Journal: American Journal of Psychiatry (1943)

Bilateral prefrontal lobotomy was performed on 10 chronically disturbed schizophrenics and one mentally deficient patient. Insignificant amelioration of symptoms was noted in two and no improvement in all the other patients. One patient became decidedly worse and developed convulsive seizures two months following the operation. On the basis of our experience, therefore, frontal leucotomy is not recommended as a therapeutic procedure in chronic schizophrenia.
Evaluation of cardiac functional abnormalities in systemic sclerosis by dobutamine stress echocardiography: a myocardial echostress scleroderma pattern
Authors: A Vacca, R Montisci, A Cauli, P Garau, P Colonna, M Ruscazio, G Passiu, L Meloni, S Iliceto, A Mathieu
Journal: Annals of the Rheumatic Diseases (2006)

In this study, we investigate the possibility of detecting, by dobutamine stress echocardiography (DSE), the presence of early or subclinical myocardial functional changes in patients with systemic sclerosis (SSc) without symptoms of ischaemic cardiac involvement.
Initial dose intensity has limited impact on the outcome of ABVD chemotherapy for advanced Hodgkin lymphoma (HL): data from UKLG LY09 (ISRCTN97144519)
Authors: W.S. Owadally, M.R. Sydes, J.A. Radford, B.W. Hancock, M.H. Cullen, S.P. Stenning, P.W.M. Johnson
Journal: Annals of Oncology (2009)
The Late Phase of Preconditioning
Authors: Roberto Bolli
Journal: Circulation Research (2000)

Abstract —Unlike the early phase of preconditioning (PC), which lasts 2 to 3 hours and protects against infarction but not against stunning, the late phase of PC lasts 3 to 4 days and protects against both infarction and stunning, suggesting that it may have greater clinical relevance. It is now clear that late PC is a polygenic phenomenon that requires the simultaneous activation of multiple stress-responsive genes. Chemical signals released by a sublethal ischemic stress (such as NO, reactive oxygen species, and adenosine) trigger a complex cascade of signaling events that includes the activation of protein kinase C, Src protein tyrosine kinases, and nuclear factor κB and culminates in increased synthesis of inducible NO synthase, cyclooxygenase-2, aldose reductase, Mn superoxide dismutase, and probably other cardioprotective proteins. An analogous sequence of events can be triggered by a variety of stimuli, such as heat stress, exercise, and cytokines. Thus, late PC appears to be a universal response of the heart to stress in general. Importantly, the cardioprotective effects of late PC can be reproduced pharmacologically with clinically relevant agents (eg, NO donors, adenosine receptor agonists, endotoxin derivatives, or opioid receptor agonists), suggesting that this phenomenon might be exploited for therapeutic purposes. The purpose of this review is to summarize current information regarding the pathophysiology and mechanism of late PC.
Management of Patients with Chronic Renal Insufficiency in the Northeastern United States
Authors: ANNAMARIA T. KAUSZ, SAMINA S. KHAN, REKHA ABICHANDANI, WAQAR H. KAZMI, GREGORIO T. OBRADOR, ROBIN RUTHAZER, BRIAN J. G. PEREIRA
Journal: Journal of the American Society of Nephrology (2001)

Abstract. Comorbid conditions that develop during chronic renal insufficiency (CRI) contribute to the high morbidity and mortality among patients with end-stage renal disease (ESRD). Thus, appropriate management during CRI may lead to improved ESRD outcomes. A retrospective cohort study was performed to describe the management of patients with CRI. A total of 602 patients with CRI (creatinine ≥1.5 mg/dl for women and ≥2.0 mg/dl for men) were seen between October 1994 and September 1998 at five nephrology outpatient clinics in the Boston area. The mean (SD) age of the patients was 63 (15.5) yr, and 53% were male. At the first nephrology visit, mean (SD) serum creatinine was 3.2 (1.6) mg/dl, and mean (SD) predicted GFR was 22.3 (8.9) ml/min per 1.73 m 2 . Laboratory tests for iron levels were performed in only 18% of patients, serum parathyroid hormone levels were obtained in only 15%, lipid studies were obtained in fewer than half, and among patients with diabetes, only 28% had a glycosylated hemoglobin level measured. A hematocrit &lt;30% was present in 38%, and abnormal calcium-phosphorus metabolism was noted in 55%. Only 59% of patients who had hematocrit &lt;30% received recombinant human erythropoietin. Among patients who received recombinant human erythropoietin, only 47% received iron. Angiotensin-converting enzyme inhibitor use was recorded for only 65% of patients with diabetes (49% of patients overall). Among patients who were known to have progressed to ESRD, only 41% had permanent access placed before initiation of dialysis. There seems to be room for improvement in the management of patients with CRI, which could result in a slower rate of progression of CRI and reduced severity of comorbid conditions.
Long-Term Predictors of Insulin Resistance
Authors: Ulf Risérus, Johan Ärnlöv, Lars Berglund
Journal: Diabetes Care (2007)

OBJECTIVE—Predictors of insulin resistance have hitherto only been examined in cross-sectional studies without information on lifestyle factors. Few researchers have measured insulin sensitivity directly and compared different metabolic and lifestyle predictors in a large population. RESEARCH DESIGN AND METHODS—Our aim was to investigate independent long-term predictors of insulin sensitivity in a large population-based sample (the Uppsala Longitudinal Study of Adult Men cohort) of 50-year-old men who underwent a euglycemic clamp 20 years later (n = 770). Subjects with diabetes and treatment of cardiovascular disease at baseline were excluded. In linear regression models, metabolic (BMI, triglycerides, HDL cholesterol, glucose, and blood pressure) and lifestyle factors (physical activity, smoking, saturated fat biomarkers, and socioeconomic status) were independent variables at baseline (age 50 years) and insulin sensitivity–dependent variables at follow-up (age 70 years). A subsample of only normal-weight men from the initial population was also examined (n = 440). RESULTS—BMI was the strongest predictor of insulin sensitivity even after addition of metabolic factors. One SD (±2.8) increase in BMI corresponded to a mean 19% decrease in insulin sensitivity. After addition of lifestyle factors, all factors except triglycerides and smoking were significant predictors. BMI remained the strongest predictor (β = −0.67 [95% CI −0.83 to −0.51], P &amp;lt; 0.0001) followed by physical activity, HDL cholesterol, saturated fat, and socioeconomic status (all P &amp;lt; 0.05). BMI remained the strongest predictor in normal-weight subjects also (P &amp;lt; 0.001). In addition, after adjustment for baseline insulin concentrations, BMI remained the strongest predictor (P &amp;lt; 0.001). CONCLUSIONS—Multiple factors, including novel factors such as saturated fat and socioeconomic status, independently predict insulin sensitivity after 20 years. BMI is, however, the single strongest predictor, even in normal-weight subjects.
Establishment and characterization of paclitaxel-resistant prostate cancer cell lines
Authors: Atsushi Mizokami, Tadashi Takeda, Koji Izumi, Kazutaka Narimoto, Yukyo Li, Evan T. Keller, Jian Zhang, Mikio Namiki
Journal: Cancer Research (2006)

1253  Despite an initial response to androgen deprivation therapy, prostate cancer (PCa) eventually progresses from an androgen-dependent to an androgen-independent phenotype. After PCa recurs, we often treat with chemotherapy using paclitaxel or docetaxel. These anticancer drugs are effective to 60% of recurred PCa. However, PCa becomes resistant to chemotherapy again and the patients die after several months. In order to know the mechanism of paclitaxel-resistance of PCa, we established paclitaxel-resistant DU145 and PC-3 cell lines (DU145-TxR and PC-3-TxR) by a gradual increase of paclitaxel concentration. DU145-TxR and PC-3-TxR cells were 34-fold and 43-fold more resistant than parent cells, respectively. Furthermore, these cells showed cross resistance in estramustine, docetaxel, vinblastin, and doxorubicin but did not show resistance in CDDP and VP-16. In order to know the mechanism of paclitaxel-resistance, we examined the expression level of MDR-1, MRP1-7, apoptosis-related genes (Bcl-2, Bax, Fas, caspase-8) in DU145-TxR and PC-3-TxR cells. Only MDR-1 mRNA was up-regulated in DU145-TxR and PC-3-TxR compared to parent cells. To confirm if MDR-1 contributes to paclitaxel-resistance in PCa, we transfected MDR-1 siRNA into DU145-TxR and PC-3-TxR to decrease MDR-1 expression and investigated paclitaxel sensitivity of these cells. Transfection of MDR-1 siRNA recovered from paclitaxel-resistance in DU145-TxR but not in PC-3-TxR, suggesting that MDR-1 plays an important role in paclitaxel-resistance but other factors may be involved in this phenomenon in some PCa cells.
Bone loss in patients with active early rheumatoid arthritis: infliximab and methotrexate compared with methotrexate treatment alone. Explorative analysis from a 12-month randomised, double-blind, placebo-controlled study
Authors: G Haugeberg, P G Conaghan, M Quinn, P Emery
Journal: Annals of the Rheumatic Diseases (2009)

<h3>Objective:</h3> To examine the effect of infliximab plus methotrexate (MTX) compared with placebo plus MTX on bone loss in patients with early rheumatoid arthritis (RA) in a double-blind randomised study design. Further, to explore the associations between bone loss and markers of RA disease. <h3>Methods:</h3> All 20 patients with RA (10 patients in each treatment group) had active, early RA. Bone mineral density (BMD) was assessed at the hand, lumbar spine (L2–4) and hip by dual energy <i>x</i>-ray absorptiometry at baseline and 12 months' follow-up. Clinical data were collected at regular visits. <h3>Results:</h3> BMD loss was significantly reduced in the infliximab group compared with the placebo group at the femoral neck (−0.35% vs −3.43%, p = 0.01) and total hip (−0.23% vs −2.62%, p = 0.03) but not at the hand (−2.09% vs −2.82%, p = 0.82) and spine (−0.75% vs −1.77%, p = 0.71). Measures of disease process and joint damage were found to be independently associated with bone loss. <h3>Conclusions:</h3> This study provides strong evidence of a causal link between inflammation and bone loss in RA. The anti-inflammatory effect of infliximab was potent enough to arrest inflammatory bone loss at the hip but not at the spine and hand.
Waist circumference correlates with liver fibrosis in children with non-alcoholic steatohepatitis
Authors: M Manco, G Bedogni, M Marcellini, R Devito, P Ciampalini, M R Sartorelli, D Comparcola, F Piemonte, V Nobili
Journal: Gut (2008)

Waist circumference is widely accepted as a risk factor for cardiovascular disease and metabolic syndrome. Non-alcoholic fatty liver disease (NAFLD) is a feature of the metabolic syndrome. A contribution of metabolic syndrome, and especially of waist circumference, to liver fibrosis in children with NAFLD is strongly suspected.Cross-sectional study.Department of Hepatogastroenterology and Nutrition, Paediatric Hospital "Bambino Gesù", Rome, Italy.197 consecutive Caucasian children with NAFLD (136 males and 61 females) aged 3-19 years.Multivariable logistic regression models were used to examine the contribution of gender, age, body mass index (BMI) and metabolic syndrome components (waist circumference, high-density lipoprotein (HDL)-cholesterol, triglycerides, blood pressure and glucose) to the odds of liver fibrosis as detected by liver biopsy.92% of the children had BMI > or = 85(th) percentile and 84% had a waist > or = 90(th) percentile for gender and age. Ten per cent of the children had metabolic syndrome and 67% had liver fibrosis, mostly of low degree. At multivariable analysis, waist was the only metabolic syndrome component to be associated with liver fibrosis. This was seen both when the components of the metabolic syndrome were coded as dichotomous (odds ratio (OR) = 2.40; 95% confidence interval (CI), 1.04 to 5.54) and continuous (OR = 2.07; 95% CI, 1.43 to 2.98 for a 5 cm increase). In the latter case, age was also associated with the outcome (OR = 0.70; 95% CI, 0.55 to 0.89 for a 1 year increase).Abdominal rather than generalised obesity contributes to liver fibrosis in children with NAFLD. Waist is also the only component of the metabolic syndrome to be associated with fibrosis in these children. Therefore, the presence of abdominal obesity is an additional criterion for the selection of children and adolescents who should undergo extensive investigation, including liver biopsy.
Overexpression of transforming growth factor-beta 1 mRNA is associated with up-regulation of glomerular tenascin and laminin gene expression in nonobese diabetic mice.
Authors: C W Yang, M Hattori, H Vlassara, C J He, M A Carome, E Yamato, S Elliot, G E Striker, L J Striker
Journal: Journal of the American Society of Nephrology (1995)

Nonobese diabetic (NOD) mice spontaneously develop immune-mediated insulin-dependent diabetes mellitus and nephropathy, providing an opportunity to study the early molecular events in a model of diabetic glomerulosclerosis. The expression of several genes coding for growth factors and extracellular matrix was examined in microdissected glomeruli, by the use of reverse transcription-competitive polymerase chain reaction, in diabetic NOD mice (mean duration of diabetes, 28.5 +/- 7 days) and age-matched nondiabetic NOD mice with normal glucose tolerance. The levels of mRNA coding for transforming growth factor-beta 1, tenascin, and laminin B1 increased 1.9-, 2.0-, and 1.7-fold, respectively, whereas platelet-derived growth factor (PDGF)-B, alpha 1(IV) collagen, 72-kd collagenase, alpha-smooth muscle actin, and beta-actin mRNA remained stable in the diabetic mice. The kidney advanced glycosylation end-products levels increased 2.1-fold in the diabetic mice, and the diabetic glomeruli showed an accumulation of tenascin and laminin but not of type IV collagen by immunofluorescence microscopy. There was no increase in cell number per glomerulus after the onset of diabetes, a finding consistent with stable PDGF-B and alpha-smooth muscle actin mRNA levels. These findings provide evidence that increased glomerular transforming growth factor-beta 1, but not PDGF-B, mRNA is associated with the up-regulation of tenascin and laminin expression after advanced glycosylation endproduct accumulation, early after the onset of diabetes.
HYDROGEN ION CONCENTRATION IN EXUDATES OF PNEUMOCOCCUS INFECTION
Authors: William H. Kelley, E. N. Scadron, B. M. Shinners
Journal: The Journal of Experimental Medicine (1938)

The hydrogen ion concentration in the lesions of experimental pneumococcus infection has been estimated directly by pH determinations on exudates from living animals. For indirect evidence of an increase in hydrogen ion concentration within the lesions, the difference in sugar content between exudate and blood from animals with pneumococcus infection has been measured. With sanguinous exudate from the consolidated lungs of dogs with experimental pneumococcus pneumonia, the findings were not always consistent, but usually there was either direct or indirect evidence of increased hydrogen ion concentration. The physicochemical changes in exudate from animals treated with artificial pneumothorax showed no important differences from those in other specimens. In concurrence with Lord's (1, 2) observation of increased acidity in pneumonia exudate obtained at autopsy, sugar concentrations, which are low in the blood, were markedly reduced in exudates from animals which had died of the infection. Serous exudates from dermal pneumococcus infection in rabbits uniformly showed definite acidity by both direct and indirect methods of estimation. The hydrogen ion concentrations in exudate from dermal pneumococcus infection in rabbits varied between pH 6.87 and 6.66 but were not always proportional to the difference in sugar concentrations between the exudate and blood. While these hydrogen ion concentrations are similar to those attained in the pneumonic exudate from dogs, they are of lesser magnitude than those which Takahashi (3) has described in the pus of secondary empyema due to the pneumococcus.
P125 Heroin Smoking is Associated with Early Onset COPD with Predominant Emphysema
Authors: PP Walker, E Thwaite, S Amin, J Curtis, PM Calverley
Journal: Thorax (2013)

<h3></h3> An association between opiate smoking and acute severe asthma is recognised but a relationship with COPD is not clearly established and limited to case reports. Anecdotally there is limited knowledge about the pulmonary effects of heroin smoking amongst drug users, drug service workers and healthcare professionals. To examine this relationship we studied a convenience sample of 41 heroin smokers who presented to our service with respiratory symptoms and were diagnosed with COPD. All completed spirometry and underwent a CT scan while 20 had alpha-1-antitrypsin level measured and 9 had DLco measured. Visual emphysema extent was recorded by two thoracic radiologists with a third adjudicating where there was a more than 1 point difference in grading. Emphysema was assessed in both lungs at 3 levels (cranial, middle and caudal) with grade 1 representing 1–5% emphysema, 2 = 6–25% emphysema, 3 = 26–50%, 4 = 51–75% and 5 &gt;75% emphysema. Mean age at presentation was 40.7 (SD 5.4) years with all subjects aged 50 years or younger and 18/41 (44%) were younger than 40 years. Mean pack years cigarette smoking was 27 (19) and subjects had smoked heroin for 14.8 (6.6) years. Mean pre-bronchodilator FEV1 was 0.99 (0.52) L; 29.9 (17.6)%predicted and FEV1/FVC was 0.36 (0.13). Nine subjects had moderate (GOLD stage II), 7 severe (GOLD stage III) and 25 had very severe (GOLD stage IV) COPD. DLco was 41 (23)%predicted in the 9 subjects and alpha-1-antitrypsin level was normal in the 20 subjects who had it measured. Twenty nine CT scans were high resolution and suitable for detailed analysis. 28/29 (97%) subjects had at least grade 1 upper lobe emphysema and mean upper lobe emphysema extent (average of the 2 upper lobe scores) was 3.0 (1.4) with 15/29 (52%) subjects having grade 3 emphysema or worse. Overall emphysema extent (average of all 6 scores) was 2.5 (1.1). Moderate bronchiectasis was seen on only 3 scans and no subject had severe bronchiectasis. The other 12 CT scans could not be precisely graded but all had been reported as showing emphysema (2 mild, 2 moderate, 1 moderate to severe and 7 severe). Heroin smoking is associated with very early onset severe COPD with predominant emphysema. This is an important public health message needing dissemination to heroin smokers, drug service workers and healthcare professionals.
Overexpression of Apollon, an Antiapoptotic Protein, Is Associated with Poor Prognosis in Childhood <i>De novo</i> Acute Myeloid Leukemia
Authors: Ki Woong Sung, Jaewon Choi, Yu Kyeong Hwang, Sang Jin Lee, Hee-Jin Kim, Soo Hyun Lee, Keon Hee Yoo, Hye Lim Jung, Hong Hoe Koo
Journal: Clinical Cancer Research (2007)

The genes that encode inhibitor of apoptosis proteins are frequently overexpressed in human cancers and can be associated with resistance to therapy. The overexpression of Apollon, a member of inhibitor of apoptosis proteins, is intuitively expected to be associated with unfavorable clinical features in malignant diseases; however, there have been no clinical studies reporting the prognostic relevance of Apollon expression in human malignancies. This study was done to investigate the clinical relevance of the expression of Apollon in childhood de novo acute myeloid leukemia.In 55 pediatric patients with de novo acute myeloid leukemia, the level of Apollon expression was determined by using quantitative reverse transcriptase-PCR and was analyzed with respect to the patients' clinical features and treatment outcomes.Apollon expression was found to be higher in patients with a leukocyte number of >or=10,000/microL, patients with extramedullary disease, and patients with the French-American-British classification subtype M7. In addition, Apollon overexpression (>or=median expression) was associated with an unfavorable day 7 response to induction chemotherapy and also associated with a poorer 3-year relapse-free survival rate (48.3 +/- 11.2% versus 78.7 +/- 8.5%, P = 0.040).This is the first study demonstrating the prognostic implication of the Apollon expression in human cancers, indicating that Apollon overexpression may be used as a poor prognostic marker in childhood acute myeloid leukemia through validation by further studies.
Evolution of hereditary non-polyposis colorectal cancer.
Authors: J R Jass, S M Stewart
Journal: Gut (1992)

The prevalence of colorectal adenoma in 23 affected patients with hereditary non-polyposis colorectal cancer (HNPCC) was compared with that in an age matched forensic autopsy population. The mean ages at diagnosis of colorectal cancer in men (13) and women (10) were 39 and 37 years respectively. In HNPCC patients who presented below the age of 50 years, at least one adenoma was found in 3 of 10 (30%) men and in 4 of 9 (44%) women. In the age matched autopsy specimens of large bowel, a solitary adenoma was found in 2/42 (5%) men (p = 0.015) and 1/21 (5%) women (p = 0.0075). Of the 11 adenomas from HNPCC patients, nine were greater than 1 cm and six showed a pure villous architecture. Contiguous adenocarcinoma was observed with six adenomas. Adenomas do not occur in large numbers in HNPCC, but develop at a young age, attain a large size, often show a villous configuration, and are more prone to malignant conversion than sporadic adenomas.