tbuckley/cabot-search huggingface dataset:
Snoring and hypertension: a 10 year follow-up
Authors: E Lindberg, C Janson, T Gislason, K Svardsudd, J Hetta, G Boman
Journal: European Respiratory Journal (1998)

In many cross-sectional studies an association has been found between snoring and hypertension. However, differing results have been obtained when confounding factors have been taken into account. To establish whether snoring is a risk factor for developing hypertension, a population-based, prospective survey was performed. In 1984 and 1994, 2,668 males, aged 30-69 yrs at baseline, answered questionnaires concerning sleep disturbances and somatic disease. Of the habitual snorers in 1984, 12.5% reported that they had developed hypertension during the period, compared with 7.4% of the remaining subjects (p&lt;0.001). In a multiple logistic regression model persistent snoring, i.e., reported habitual snoring in both 1984 and 1994, was found to be an independent predictor for the development of hypertension among males aged 30-49 yrs (odds ratio 2.6, 95% confidence interval 1.5-4.5) after adjustments for age, body mass index (BMI), weight gain, smoking, alcohol dependence, and physical inactivity. Among the subjects aged 50-69 yrs in 1984, no association between snoring and development of hypertension was found. Although based only on reported data, the results indicate that persistent snoring is an independent risk factor for the development of hypertension among males aged &lt;50 yrs. Prospective surveys, including whole-night sleep recordings, are needed to establish whether this is due to a higher prevalence of obstructive sleep apnoea syndrome among snorers or whether nonapnoeic snorers with increased upper airway resistance also have an increased risk of developing hypertension.
Successful use of bortezomib in a patient with systemic lupus erythematosus and multiple myeloma
Authors: K. Frohlich, J. U. Holle, P. M. Aries, W. L. Gross, F. Moosig
Journal: Annals of the Rheumatic Diseases (2010)

<h3>Abstract</h3> Since Braak’s hypothesis stating that sporadic Parkinson’s disease follows a specific progression of the pathology from the peripheral to the central nervous system and can be monitored by detecting accumulation of the alpha-Synuclein protein. There is growing interest in understanding how the gut (commensal) microbiome can regulate alpha-Synuclein accumulation which can lead to PD. We studied a transgenic rat model overexpressing the human alpha-Synuclein and found that the protein overexpression resulted in gut alpha-Synuclein expression and aggregation in the gut neurons with advancing age. A progressive gut microbial composition alteration characterized by the reduction of Firmicutes to Bacteroidetes ratio could be detected in the young transgenic rat model and interestingly this ratio was then increased with aging. This observation was accompanied in older animals by intestinal inflammation, increase gut permeability and a robust alteration in metabolites production characterized by the increase of succinate level in the feces and serum. Manipulation of the gut bacteria by short-term antibiotics treatment revealed a complete loss of short-chain fatty acids (SCFAs) and reduction in succinate levels. Although antibiotics treatment did not change alpha-synuclein expression in the enteric nervous system of the colon, it can reduce alpha-synuclein expression in the olfactory bulb of the transgenic rats. In summary, synchronous with ageing, our data emphasize that the gut microbiome dysbiosis leads to a specific alteration of gut metabolites which are reflected in the serum and can be modulated by the environment.
Liver structure and function following small bowel resection
Authors: M. C. Gupta, G. Neale, R. H. Dowling
Journal: Gut (1973)

The observation that patients with extensive small bowel resection have impaired hepatocellular function with reduced BSP clearance and fatty change in biopsies from the liver led to a systematic study of liver structure and function following proximal and distal small bowel resection in the rat. While anaesthesia and surgery impaired BSP clearance per se, small bowel resection further reduced BSP clearance with impairment of both uptake and excretion phases of BSP excretion. The increased BSP retention was more marked after distal than after proximal small bowel resection, but in both experimental groups the abnormalities of BSP excretion spontaneously returned to normal three to four weeks after surgery. Circulating liver enzymes were normal but serum alkaline phosphatase was significantly depressed, particularly after distal resection. Isoenzyme studies showed that the depression of serum AP was due to a reduced intestinal isoenzyme. While serum levels remained consistently depressed up to eight weeks after proximal resection, in parallel with mucosal regeneration, serum AP returned to normal two to four weeks after ileectomy. While these minor changes in hepatic structure and function would normally be of little clinical importance, the additional insult of hepatic dysfunction may well be important in malnourished patients after extensive small bowel resection.
Left Axis Deviation in Tricuspid Atresia and Single Ventricle
Authors: CATHERINE A. NEILL, A. J. BRINK
Journal: Circulation (1955)

The electrocardiograms from 28 unselected autopsied cases of tricuspid atresia, and eight autopsied cases of single ventricle were analysed: only those cases of single ventricle which showed left axis deviation were included. Electrocardiographic evidence of left ventricular preponderance in the precordial and unipolar limb leads was found in 27 of the 28 cases of tricuspid atresia, and three of the eight of single ventricle: In only two cases of single ventricle was the electrocardiogram identical with that seen in tricuspid atresia, and in one of them tricuspid stenosis was present. Right auricular hypertrophy as evidenced by high peaked P waves, together with presystolic hepatic pulsations occurred in tricuspid atresia in those instances in which, at autopsy, the interauricular communication was found to be small.
B-cell depletion inhibits arthritis in a collagen-induced arthritis (CIA) model, but does not adversely affect humoral responses in a respiratory syncytial virus (RSV) vaccination model
Authors: Kyri Dunussi-Joannopoulos, Gerald E. Hancock, Arthur Kunz, Martin Hegen, Xiaochuan X. Zhou, Barbara J. Sheppard, Jennifer Lamothe, Evelyn Li, Hak-Ling Ma, Philip R. Hamann, Nitin K. Damle, Mary Collins
Journal: Blood (2005)
Serum Uric Acid Levels and Incident Chronic Kidney Disease in Patients With Type 2 Diabetes and Preserved Kidney Function
Authors: Giacomo Zoppini, Giovanni Targher, Michel Chonchol, Vittorio Ortalda, Cataldo Abaterusso, Isabella Pichiri, Carlo Negri, Enzo Bonora
Journal: Diabetes Care (2011)

Recent studies have suggested an association between hyperuricemia and adverse renal outcomes in nondiabetic populations. Data on the relationship between hyperuricemia and the risk of incident chronic kidney disease (CKD) in type 2 diabetic patients with normal or near-normal kidney function are lacking. We determined whether baseline serum uric acid levels predict the subsequent development of CKD in patients with type 2 diabetes.We followed 1,449 type 2 diabetic patients with normal kidney function and without overt proteinuria for 5 years for the occurrence of incident CKD (defined as overt proteinuria or estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m(2)).During a 5-year follow-up period, 194 (13.4%) patients developed incident CKD. The cumulative incidence of CKD was significantly greater in patients with hyperuricemia than in those without hyperuricemia (29.5 vs. 11.4%, P < 0.001). In univariate logistic regression analysis, the presence of hyperuricemia roughly doubled the risk of developing CKD (odds ratio [OR] 2.55 [95% CI 1.71-3.85], P < 0.001). After adjusting for age, sex, BMI, smoking status, diabetes duration, systolic blood pressure, antihypertensive treatment, insulin therapy, HbA(1c), eGFR, and albuminuria, hyperuricemia was associated with an increased risk of incident CKD (adjusted OR 2.10 [1.16-3.76], P < 0.01). In continuous analyses, a 1-SD increment in the serum uric acid level was significantly associated with a 21% increased risk of CKD.In type 2 diabetic individuals with preserved kidney function, hyperuricemia seems to be an independent risk factor for the development of incident CKD.
The Spread of Alcohol Consumption Behavior in a Large Social Network
Authors: J. Niels Rosenquist
Journal: Annals of Internal Medicine (2010)

Background: Alcohol consumption has important health-related consequences and numerous biological and social determinants. Objective: To explore quantitatively whether alcohol consumption behavior spreads from person to person in a large social network of friends, coworkers, siblings, spouses, and neighbors, followed for 32 years. Design: Longitudinal network cohort study. Setting: The Framingham Heart Study. Participants: 12 067 persons assessed at several time points between 1971 and 2003. Measurements: Self-reported alcohol consumption (number of drinks per week on average over the past year and number of days drinking within the past week) and social network ties, measured at each time point. Results: Clusters of drinkers and abstainers were present in the network at all time points, and the clusters extended to 3 degrees of separation. These clusters were not only due to selective formation of social ties among drinkers but also seem to reflect interpersonal influence. Changes in the alcohol consumption behavior of a person's social network had a statistically significant effect on that person's subsequent alcohol consumption behavior. The behaviors of immediate neighbors and coworkers were not significantly associated with a person's drinking behavior, but the behavior of relatives and friends was. Limitations: A nonclinical measure of alcohol consumption was used. Also, it is unclear whether the effects on long-term health are positive or negative, because alcohol has been shown to be both harmful and protective. Finally, not all network ties were observed. Conclusion: Network phenomena seem to influence alcohol consumption behavior. This has implications for clinical and public health interventions and further supports group-level interventions to reduce problematic drinking. Primary Funding Source: National Institutes of Health and the Robert Wood Johnson Foundation. The Framingham Heart Study is supported by the National Heart, Lung, and Blood Institute.
Type of PKD1 Mutation Influences Renal Outcome in ADPKD
Authors: Emilie Cornec-Le Gall, Marie-Pierre Audrézet, Jian-Min Chen, Maryvonne Hourmant, Marie-Pascale Morin, Régine Perrichot, Christophe Charasse, Bassem Whebe, Eric Renaudineau, Philippe Jousset, Marie-Paule Guillodo, Anne Grall-Jezequel, Philippe Saliou, Claude Férec, Yannick Le Meur
Journal: Journal of the American Society of Nephrology (2013)

Autosomal dominant polycystic kidney disease (ADPKD) is heterogeneous with regard to genic and allelic heterogeneity, as well as phenotypic variability. The genotype-phenotype relationship in ADPKD is not completely understood. Here, we studied 741 patients with ADPKD from 519 pedigrees in the Genkyst cohort and confirmed that renal survival associated with PKD2 mutations was approximately 20 years longer than that associated with PKD1 mutations. The median age at onset of ESRD was 58 years for PKD1 carriers and 79 years for PKD2 carriers. Regarding the allelic effect on phenotype, in contrast to previous studies, we found that the type of PKD1 mutation, but not its position, correlated strongly with renal survival. The median age at onset of ESRD was 55 years for carriers of a truncating mutation and 67 years for carriers of a nontruncating mutation. This observation allows the integration of genic and allelic effects into a single scheme, which may have prognostic value.
Pharmacogenetic Assessment of Toxicity and Outcome in Patients With Metastatic Colorectal Cancer Treated With LV5FU2, FOLFOX, and FOLFIRI: FFCD 2000-05
Authors: Valérie Boige, Jean Mendiboure, Jean-Pierre Pignon, Marie-Anne Loriot, Marine Castaing, Michel Barrois, David Malka, David-Alexandre Trégouët, Olivier Bouché, Delphine Le Corre, Isabelle Miran, Claire Mulot, Michel Ducreux, Philippe Beaune, Pierre Laurent-Puig
Journal: Journal of Clinical Oncology (2010)

The aim was to investigate whether germline polymorphisms within candidate genes known or suspected to be involved in fluorouracil (FU), oxaliplatin, and irinotecan pathways were associated with toxicity and clinical outcome in patients with metastatic colorectal cancer (mCRC).Blood samples from 349 patients included in the Fédération Francophone de Cancérologie Digestive 2000-05 randomized trial, which compared FU plus leucovorin (LV5FU2) followed by FU, leucovorin, and oxaliplatin (FOLFOX) followed by FU, leucovorin, and irinotecan (FOLFIRI; sequential arm) with FOLFOX followed by FOLFIRI (combination arm) in terms of progression-free survival (PFS) and overall survival, were collected. Twenty polymorphisms within the DPD, TS, MTHFR, ERCC1, ERCC2, GSTP1, GSTM1, GSTT1, and UGT1A1 genes were genotyped.The ERCC2-K751QC allele was independently associated with an increased risk of FOLFOX-induced grade 3 or 4 hematologic toxicity (P = .01). In the sequential arm, TS-5'UTR3RG and GSTT1 alleles were independently associated with response to LV5FU2 (P = .009) and FOLFOX (P = .01), respectively. The effect of oxaliplatin on tumor response increased with the number of MTHFR-1298C alleles (test for trend, P = .008). The PFS benefit from first-line FOLFOX was restricted to patients with 2R/2R (hazard ratio [HR] = 0.39; 95% CI, 0.23 to 0.68) or 2R/3R (HR = 0.59; 95% CI, 0.42 to 0.82) TS-5'UTR genotypes, respectively. Conversely, patients with the TS-5'UTR 3R/3R genotype did not seem to benefit from the adjunction of oxaliplatin (HR = 0.96; 95% CI, 0.66 to 1.40; trend between the three HRs, P = .006).A pharmacogenetic approach may be a useful strategy for personalizing and optimizing chemotherapy in mCRC patients and deserves confirmation in additional prospective studies.
Heme Oxygenase-1 Attenuates Glucose-Mediated Cell Growth Arrest and Apoptosis in Human Microvessel Endothelial Cells
Authors: Nader G. Abraham, Taketoshi Kushida, Jack McClung, Melvin Weiss, Shuo Quan, Rocky Lafaro, Zbigniew Darzynkiewicz, Michael Wolin
Journal: Circulation Research (2003)

Heme oxygenase-1 (HO-1) is a stress protein that has been suggested to participate in defense mechanisms against agents that may induce oxidative injury, such as heme and inflammatory molecules. Incubation of endothelial cells in a high-glucose (33 mmol/L) medium for 7 days resulted in a decrease of HO activity by 34% and a decrease in HO-1 and HO-2 proteins compared with cells exposed to low glucose (5 mmol/L) (P<0.05) or cells exposed to mannitol (33 mmol/L). Overexpression of HO-1 was coupled with an increase in HO activity and carbon monoxide synthesis, decreased cellular heme, and acceleration in all phases of the cell cycle (P<0.001). The rate of cell cycle or cell birth rate was increased by 29% (P<0.05) in cells overexpressing HO-1 but decreased by 23% (P<0.05) in cells underexpressing HO-1 compared with control cells. Exposure to high glucose significantly decreased cell-cycle progression in control cells and in cells underexpressing HO-1 but did not decrease cell-cycle progression in cells overexpressing HO-1. High glucose induced p21 and p27 in control cells but not in cells overexpressing HO-1. The addition of tin-mesoporphyrin (SnMP), an inhibitor of HO activity, reversed the HO-1-mediated decrease of p21 and p27 in cells overexpressing HO-1. These findings identify a novel effect of HO-1 on endothelial cell growth and indicate that heme metabolism and HO-1 expression regulate signaling systems in cells exposed to high glucose, which controls cell-cycle progression.
Case-control study of risk of dehydrating diarrhoea in infants in vulnerable period after full weaning
Authors: S. C. Fuchs, C. G. Victora, J. Martines
Journal: BMJ (1996)

<h3>Abstract</h3> <b>Objectives</b>: To investigate risk factors for dehydrating diarrhoea in infants, with special interest in the weaning period. <b>Design</b>: Case-control study. <b>Setting</b>: Metropolitan area of Porto Alegre, Brazil. <b>Subjects</b>: Cases were 192 children aged 0-23 months hospitalised with acute diarrhoea and moderate to severe dehydration. Controls were 192 children matched for age and neighbourhood who did not have diarrhoea in the previous week. <b>Main outcome measures</b>: Associations between dehydrating diarrhoea and child9s age, type of milk consumed, time since breast feeding stopped, and breast feeding status. <b>Results</b>: In infants aged &lt;12 months the risk of dehydrating diarrhoea was significantly higher in the first 9 months of life (P&lt;0.001), and in those aged 12-23 months the risk was again greater in younger children (12-17 months) (P = 0.03). The type of milk consumed before start of diarrhoea episode was strongly associated with dehydration independent of socioeconomic, environmental, maternal reproductive, demographic, and health services factors. Compared with infants exclusively breast fed, bottle fed infants were at higher risk (odds ratio (95% confidence interval) for cow9s milk 6.0 (1.8 to 19.8), for formula milk 6.9 (1.4 to 33.3)). Compared with those still breast feeding, children who stopped in the previous two months were more likely to develop dehydrating diarrhoea (odds ratio 8.4 (2.4 to 29.6)). This risk decreased with time since breast feeding stopped. <b>Conclusion</b>: These results confirm the protective effect of breast feeding and suggest there is a vulnerable period soon after breast feeding is stopped, which may be of relevance for developing preventive strategies. <h3>Key messages</h3> In this study infants who were exclusively breast fed were six times less likely to have dehydrating diarrhoea than bottle fed infants Partially breast fed infants were at intermediate levels of risk Children who were recently weaned showed a higher risk of dehydrating diarrhoea than those who had been weaned for six months or more Recently weaned children presenting with diarrhoea should receive closer attention from health workers
The impact of serum uric acid on cardiovascular outcomes in the LIFE study
Authors: Aud Høieggen, Michael H. Alderman, Sverre E. Kjeldsen, Stevo Julius, Richard B. Devereux, Ulf de Faire, Frej Fyhrquist, Hans Ibsen, Krister Kristianson, Ole Lederballe-Pedersen, Lars H. Lindholm, Markku S. Nieminen, Per Omvik, Suzanne Oparil, Hans Wedel, Cong Chen, Björn Dahlöf, None for the LIFE Study Group
Journal: Kidney International (2004)
Serological Testing Versus Other Strategies for Diagnosis of Active Tuberculosis in India: A Cost-Effectiveness Analysis
Authors: David W. Dowdy, Karen R. Steingart, Madhukar Pai
Journal: PLoS Medicine (2011)

Background Undiagnosed and misdiagnosed tuberculosis (TB) drives the epidemic in India. Serological (antibody detection) TB tests are not recommended by any agency, but widely used in many countries, including the Indian private sector. The cost and impact of using serology compared with other diagnostic techniques is unknown. Methods and Findings Taking a patient cohort conservatively equal to the annual number of serological tests done in India (1.5 million adults suspected of having active TB), we used decision analysis to estimate costs and effectiveness of sputum smear microscopy (US$3.62 for two smears), microscopy plus automated liquid culture (mycobacterium growth indicator tube [MGIT], US$20/test), and serological testing (anda-tb ELISA, US$20/test). Data on test accuracy and costs were obtained from published literature. We adopted the perspective of the Indian TB control sector and an analysis frame of 1 year. Our primary outcome was the incremental cost per disability-adjusted life year (DALY) averted. We performed one-way sensitivity analysis on all model parameters, with multiway sensitivity analysis on variables to which the model was most sensitive. If used instead of sputum microscopy, serology generated an estimated 14,000 more TB diagnoses, but also 121,000 more false-positive diagnoses, 102,000 fewer DALYs averted, and 32,000 more secondary TB cases than microscopy, at approximately four times the incremental cost (US$47.5 million versus US$11.9 million). When added to high-quality sputum smears, MGIT culture was estimated to avert 130,000 incremental DALYs at an incremental cost of US$213 per DALY averted. Serology was dominated by (i.e., more costly and less effective than) MGIT culture and remained less economically favorable than sputum smear or TB culture in one-way and multiway sensitivity analyses. Conclusions In India, sputum smear microscopy remains the most cost-effective diagnostic test available for active TB; efforts to increase access to quality-assured microscopy should take priority. In areas where high-quality microscopy exists and resources are sufficient, MGIT culture is more cost-effective than serology as an additional diagnostic test for TB. These data informed a recently published World Health Organization policy statement against serological tests. Please see later in the article for the Editors' Summary
Chemokines in Renal Injury
Authors: Arthur C. K. Chung, Hui Y. Lan
Journal: Journal of the American Society of Nephrology (2011)

The main function of chemokines is to guide inflammatory cells in their migration to sites of inflammation. During the last 2 decades, an expanding number of chemokines and their receptors have driven broad inquiry into how inflammatory cells are recruited in a variety of diseases. Although this review focuses on chemokines and their receptors in renal injury, proinflammatory IL-17, TGFβ, and TWEAK signaling pathways also play a critical role in their expression. Recent studies in transgenic mice as well as blockade of chemokine signaling by neutralizing ligands or receptor antagonists now allow direct interrogation of chemokine action. The emerging role of regulatory T cells and Th17 cells during renal injury also forges tight relationships between chemokines and T cell infiltration in the development of kidney disease. As chemokine receptor blockade inches toward clinical use, the field remains an attractive area with potential for unexpected opportunity in the future.
The changed image of botulinum toxin
Authors: V P. Misra
Journal: BMJ (2002)

Over the past decade botulinum toxin has had a makeover. Earlier it was known as one of the most potent biological neurotoxins—in botulism it blocks the release of acetylcholine at the neuromuscular junction and can cause fatal muscular paralysis. Today botulinum toxin is widely known as a pharmaceutical agent with multiple uses and has been propelled into the public eye after it was widely reported in the lay press as an antiwrinkle drug for facial cosmetic enhancement. This has established its new image as a glamour drug. Botulinum toxin is reported to be useful in more than 50 conditions, with indications spanning many specialties.1 But the toxin is licensed for only a few specific conditions, based on clear scientific evidence of its efficacy and safety. Some “off licence” indications are substantiated by some evidence, but its efficacy in several other conditions is based on anecdote …