tbuckley/cabot-search huggingface dataset:
Re: The Diesel Exhaust in Miners Study: A Nested Case–Control Study of Lung Cancer and Diesel Exhaust and a Cohort Mortality Study With Emphasis on Lung Cancer
Authors: Thomas W. Hesterberg, Christopher M. Long, Peter A. Valberg
Journal: JNCI Journal of the National Cancer Institute (2012)

When the Diesel Exhaust in Miners Study (DEMS) was initiated in the early 1990s, one key goal was to develop quantitative estimates of historical exposure to diesel exhaust (DE). It was recognized that the epidemiological results would only be as robust as the exposure assessment upon which they are based. Respirable elemental carbon (REC), a surrogate of diesel exhaust particulates, was selected as the primary exposure variable, yet in very recent years investigators turned to an alternative exposure assessment methodology that relied instead on carbon monoxide (CO) measurements. Assumptions were also made regarding engine horsepower and mine ventilation to “back
Lung Development and Susceptibility to Ventilator-induced Lung Injury
Authors: Alik Kornecki, Shinya Tsuchida, Hari Kumar Ondiveeran, Doreen Engelberts, Helena Frndova, A. Keith Tanswell, Martin Post, Colin McKerlie, Jaques Belik, Alison Fox-Robichaud, Brian P. Kavanagh
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Rationale: Ventilator-induced lung injury has been predominantly studied in adults. Objectives: To explore the effects of age and lung development on susceptibility to such injury. Methods: Ex vivo isolated nonperfused rat lungs (infant, juvenile, and adult) were mechanically ventilated where VT was based on milliliters per kilogram of body weight or as a percentage of the measured total lung capacity (TLC). In vivo anesthetized rats (infant, adult) were mechanically ventilated with pressure-limited VTs. Allocation to ventilation strategy was randomized. Measurements: Ex vivo injury was assessed by pressure–volume analysis, reduction in TLC, and histology, and in vivo injury by lung compliance, cytokine production, and wet- to dry-weight ratio. Main Results: Ex vivo ventilation (VT 30 ml · kg−1) resulted in a significant reduction (36.0 ± 10.1%, p < 0.05) in TLC in adult but not in infant lungs. Ex vivo ventilation (VT 50% TLC) resulted in a significant reduction in TLC in both adult (27.8 ± 2.8%) and infant (10.6 ± 7.0%) lungs, but more so in the adult lungs (p < 0.05); these changes were paralleled by histology and pressure–volume characteristics. After high stretch in vivo ventilation, adult but not infant rats developed lung injury (total lung compliance, wet/dry ratio, tumor necrosis factor α). Surface video microscopy demonstrated greater heterogeneity of alveolar distension in ex vivo adult versus infant lungs. Conclusion: These data provide ex vivo and in vivo evidence that comparable ventilator settings are significantly more injurious in the adult than infant rat lung, probably reflecting differences in intrinsic susceptibility or inflation pattern.
Efficacy of early neonatal supplementation with vitamin A to reduce mortality in infancy in Haryana, India (Neovita): a randomised, double-blind, placebo-controlled trial
Authors: Sarmila Mazumder, Sunita Taneja, Kiran Bhatia, Sachiyo Yoshida, Jasmine Kaur, Brinda Dube, G S Toteja, Rajiv Bahl, Olivier Fontaine, Jose Martines, Nita Bhandari
Journal: The Lancet (2014)
POSTURAL REACTIONS TO VESTIBULAR STIMULATION IN SCHIZOPHRENIC AND NORMAL SUBJECTS
Authors: ANDRAS ANGYAL, MAX A. SHERMAN
Journal: American Journal of Psychiatry (1942)

1. Postural reactions to caloric stimulation of the vestibular organ were measured in a group of 20 chronic schizophrenic patients and in a group of 20 normal persons. The blind-folded subjects were instructed to mark time in place, and the reaction was measured by the degree of rotation about the vertical axis of the body. 2. The test was first administered without vestibular stimulation in order to determine the amount and direction of the rotation, which is an expression of the dominance of one side of the body. Such "basal trends," which were present in all subjects, were taken into account when calculating the amount of vestibular reaction. 3. The mean total vestibular reaction measured in degrees of rotation was, in the patients, less than one-half that of the normal subjects. In spite of the great variability of the phenomenon studied, this difference is statistically highly significant. 4. The total duration of the reaction, as well as the degree of rotation per time unit was found to be significantly less in the patients than in the normal controls. That is, the reaction of the patients was more fleeting and less intense than that of the normal controls. 5. It is suggested that the difference found may be due either to the depressed activity of the nervous mechanisms involved or to a diminished muscle tonus of the schizophrenic patients.
PPAR γ insufficiency enhances osteogenesis through osteoblast formation from bone marrow progenitors
Authors: Toru Akune, Shinsuke Ohba, Satoru Kamekura, Masayuki Yamaguchi, Ung-il Chung, Naoto Kubota, Yasuo Terauchi, Yoshifumi Harada, Yoshiaki Azuma, Kozo Nakamura, Takashi Kadowaki, Hiroshi Kawaguchi
Journal: Journal of Clinical Investigation (2004)

Based on the fact that aging is associated with a reciprocal decrease of osteogenesis and an increase of adipogenesis in bone marrow and that osteoblasts and adipocytes share a common progenitor, this study investigated the role of PPARγ, a key regulator of adipocyte differentiation, in bone metabolism. Homozygous PPARγ-deficient ES cells failed to differentiate into adipocytes, but spontaneously differentiated into osteoblasts, and these were restored by reintroduction of the PPARγ gene. Heterozygous PPARγ-deficient mice exhibited high bone mass with increased osteoblastogenesis, but normal osteoblast and osteoclast functions, and this effect was not mediated by insulin or leptin. The osteogenic effect of PPARγ haploinsufficiency became prominent with aging but was not changed upon ovariectomy. The PPARγ haploinsufficiency was confirmed to enhance osteoblastogenesis in the bone marrow cell culture but did not affect the cultures of differentiated osteoblasts or osteoclast-lineage cells. This study demonstrates a PPARγ-dependent regulation of bone metabolism in vivo, in that PPARγ insufficiency increases bone mass by stimulating osteoblastogenesis from bone marrow progenitors.
Beneficial effect of arachidonic acid during hemorrhagic shock in the dog.
Authors: J T Flynn, A M Lefer
Journal: Circulation Research (1977)

Arachidonic acid (AA), precursor of the bisenoic prostaglandins was infused at a rate of 120 mug/kg per min into the vena cava of dogs subjected to hemorrhagic shock to assess the effects of stimulation of the prostaglandin (PG) synthetase system on the shock state. Hemorrhagic shock was induced by bleeding to a mean arterial blood pressure (MABP) of 40 mm Hg for 150 minutes followed by reinfusion of all remaining shed blood. In sham shock dogs receiving AA vehicle (0.1 M Na2C03), there were no significant changes in MABP, superior mesenteric artery flow (SMAF), renal artery flow (RAF), PGF2 or PGF2alpha concentrations, or in cathepsin D or myocardial depressant factor (MDF) activities during a 260-minute experimental period. During oligemia, untreated hemorrhagic shock dogs exhibited dramatic reductions in MABP, SMAF, and RAF which were transiently restored following reinfusion, but markedly decreased 100 minutes after reinfusion. Cathepsin D, MDF, PGE2, and PGF2alpha values increased significantly in these dogs. AA given during oligemia did not prevent changes in SMAF or RAF, but maintained MABP at near-normal values after reinfusion. AA also significantly protected against the plasma accumulation of both cathepsin D an MDF is hemorrhagic shock dogs. Circulating PGF2alpha and PGE2 values increased rapidly in AA-treated dogs and plateaued at 3.6 and 4.8 times control values, respectively, during oligemia. Hemorrhagic shock dogs receiving AA plus Na meclofenamate, a PG synthetase inhibitor, were not significantly different from shock dogs receiving vehicle except that the circulating PG concentrations did not increase. Thus, products of the PG synthetase system appear to prevent the plasma accumulation of lysosomal hydrolases nand of MDF, and may significantly preserve MABP after hemorrhagic shock in the dog.
Hyperextension injuries to the cervical cord in the elderly.
Authors: T. P. Enevoldson
Journal: BMJ (1989)

identifying them at present.The only measures now available to reduce the number of mothers sensitised are, firstly, to ensure that all mothers at risk receive anti-D immunoglobulin, and, secondly, that at least the mothers in their first pregnancy receive anti-D immunoglobulin antenatally.
THE ACTION OF RENIN ON RABBITS WITH RENAL HYPERTENSION
Authors: John Taggart, D. R. Drury
Journal: The Journal of Experimental Medicine (1940)

Our results lead us to believe that renin in the form in which it is extracted from the kidney cannot be the agent causing chronic renal hypertension. The reasons against accepting renin as the pressor substance responsible for the hypertension of renal ischemia may be summed up as follows:— 1. The high blood pressure levels of renal ischemia cannot be approximated by any constant injection of renin that will maintain a sustained increase in normal animals. 2. The ratio of size of response to size of dose becomes progressively less as the amount of the dose is increased. If the hypertension of renal ischemia were due to a large elaboration of renin in the body, a small dose injected would be expected to have much less effect than in a normal individual. This is not the case; the response of the hypertensive animal to a given dose of renin is the same. Also animals with increased blood pressure due to a constant infusion of renin respond differently qualitatively and quantitatively to renin than do animals hypertensive from renal ischemia. 3. Since renin exhibits the phenomenon of tachyphylaxis one cannot explain the sustained hypertension of renal ischemia as due to a substance toward which the body becomes refractory as more and more of it is given. If tolerance results from the presence in the renin preparation of an antagonistic contaminant which persists longer in the body than the pressor agent, renal hypertension is definitely not caused by renin. This follows from our observations that rabbits hypertensive from renal ischemia, and in which tolerance is produced, maintain the blood pressure they had before injection of any renin.
Cost effectiveness of computer tailored and non-tailored smoking cessation letters in general practice: randomised controlled
Authors: A S. Lennox
Journal: BMJ (2001)

To develop and evaluate, in a primary care setting, a computerised system for generating tailored letters about smoking cessation.Randomised controlled trial.Six general practices in Aberdeen, Scotland.2553 smokers aged 17 to 65.All participants received a questionnaire asking about their smoking. Participants subsequently received either a computer tailored or a non-tailored, standard letter on smoking cessation, or no letter.Prevalence of validated abstinence at six months; change in intention to stop smoking in the next six months.The validated cessation rate at six months was 3.5% (30/857) (95% confidence interval 2.3% to 4.7%) for the tailored letter group, 4.4% (37/846) (3.0% to 5.8%) for the non-tailored letter group, and 2.6% (22/850) (1.5% to 3.7%) for the control (no letter) group. After adjustment for significant covariates, the cessation rate was 66% greater (-4% to 186%; P=0.07) in the non-tailored letter group than that in the no letter group. Among participants who smoked <20 cigarettes per day, the cessation rate in the non-tailored letter group was 87% greater (0% to 246%; P=0.05) than that in the no letter group. Among heavy smokers who did not quit, a 76% higher rate of positive shift in "stage of change" (intention to quit within a particular period of time) was seen compared with those who received no letter (11% to 180%; P=0.02). The increase in cost for each additional quitter in the non-tailored letter group compared with the no letter group was pound 89.In a large general practice, a brief non-tailored letter effectively increased cessation rates among smokers. A tailored letter was not effective in increasing cessation rates but promoted shift in movement towards cessation ("stage of change") in heavy smokers. As a pragmatic tool to encourage cessation of smoking, a mass mailing of non-tailored letters from general practices is more cost effective than computer tailored letters or no letters.
Drugging Undruggable Molecular Cancer Targets
Authors: John S. Lazo, Elizabeth R. Sharlow
Journal: The Annual Review of Pharmacology and Toxicology (2015)

Cancer, more than any other human disease, now has a surfeit of potential molecular targets poised for therapeutic exploitation. Currently, a number of attractive and validated cancer targets remain outside of the reach of pharmacological regulation. Some have been described as undruggable, at least by traditional strategies. In this article, we outline the basis for the undruggable moniker, propose a reclassification of these targets as undrugged, and highlight three general classes of this imposing group as exemplars with some attendant strategies currently being explored to reclassify them. Expanding the spectrum of disease-relevant targets to pharmacological manipulation is central to reducing cancer morbidity and mortality.
Evaluation of the magnitude of gastro-oesophageal reflux in Barrett's oesophagus.
Authors: P Parrilla, A Ortiz, L F Martinez de Haro, J L Aguayo, P Ramirez
Journal: Gut (1990)

A manometric study to determine the role of gastro-oesophageal reflux in Barrett's oesophagus was performed on 20 patients with Barrett's oesophagus and 53 patients with reflux oesophagitis without Barrett's oesophagus (25 with mild oesophagitis and 28 with severe oesophagitis). For the same reason, the 20 patients with Barrett's oesophagus also underwent 24 hour continuous oesophageal pH monitoring, and the results obtained were compared with those of 20 oesophagitis patients without Barrett's oesophagus (10 with mild oesophagitis and 10 with severe oesophagitis). The manometric results show that the motor changes found in the Barrett's group are specific but similar to the motor dysfunction associated with reflux oesophagitis. Motor anomalies are probably related more to the inflammatory process in the oesophageal wall than to the metaplastic changes themselves. The pH monitoring results show that while reflux in the Barrett's oesophagus patients was greater overall than in the oesophagitis group without Barrett's oesophagus, the changes are similar when the results are compared with the severe oesophagitis group. In conclusion there are other factors besides gastro-oesophageal reflux involved in the pathogenesis of Barrett's oesophagus.
Medical education for the future
Authors: R. Hamilton
Journal: Journal of the Royal Society of Medicine (2005)

In the words of Dr Alan Greenspan, Chairman of the US Federal Reserve Board, ‘the obsolescence of human skills is greater than at any other time in history’. This will be as true of medicine in the 21st century as in his world of business. Indeed, the two seem set to forge ahead at unprecedented speed. The challenge facing medical education will be to keep pace with a phase of astonishing change.

In fifty years' time the medical students of today will be at or nearing retirement. I wonder how we shall look back on our undergraduate training and the way we were prepared for this radically changing world. Here are some of my guesses about the medical landscape of fifty years hence.
From disruption to consensus: the thousand mile journey
Authors: Adam Weir
Journal: British Journal of Sports Medicine (2013)

When EB White, the author of Charlotte's web, said “there is nothing more likely to start disagreement among people or countries than an agreement” he may not have had medical consensus statements in mind, but his words hold true. Keep this in mind when you read the British Hernia Society's 2014 position statement based on the Manchester Consensus Conference: ‘Treatment of the Sportsman's groin’.1 While it is easy to be critical we should give credit where it is due.

Aali Sheen and his coauthors are to be congratulated for their achievement of reaching an agreement in the field of groin injuries. It is a tremendous advance to bring together a coauthor group of surgeons from different countries, who have published different opinions as to aetiology, use differing terminology and advocate different surgical techniques. Their statement does not however signify that the mission to solve the groin's mysteries has been accomplished. As the title of this editorial suggests, we should see this agreement as the first step on a long journey.

Inguinal disruption (ID) was agreed on as being the preferred term to use when describing athletes with ‘groin pain predominantly in the groin area near the pubic tubercle’. The term was chosen as it was felt to most accurately reflect the underlying pathology. While I follow the reasoning behind the choice, the effect of adding yet another term into the groin literature to accompany sportsman's hernia, sportsman's groin, Gilmore's groin, etc should be considered. Without placing the injury …
Immunohistochemical Localization of Multispecific Renal Organic Anion Transporter 1 in Rat Kidney
Authors: AKIHIRO TOJO, TAKASHI SEKINE, NORIKO NAKAJIMA, MAKOTO HOSOYAMADA, YOSHIKATSU KANAI, KENJIRO KIMURA, HITOSHI ENDOU
Journal: Journal of the American Society of Nephrology (1999)

Abstract. Renal proximal convoluted tubules have an important role, i.e. , to excrete organic anions, including numerous drugs and endogenous substances. Recently, multispecific organic anion transporter 1 (OAT1) was isolated from rat kidney. In this study, the cellular and subcellular localization of OAT1 in rat kidney was investigated. Kidneys from normal rats were perfused and fixed with periodate-lysine-paraformaldehyde solution and were then processed for immunohistochemical analysis using the labeled streptavidin-biotin method, preembedding horseradish peroxidase method, and immunogold method. Light microscopic examination revealed immunostaining for OAT1 in the middle portion of the proximal tubule (S2 segment), but not in the initial portion of the proximal convoluted tubule, next to the glomerulus. Nephron segments other than the S2 segment and the renal vasculature were not stained with antibody to OAT1. Electron-microscopic observation using a preembedding method revealed that OAT1 was exclusively expressed in the basolateral membrane of S2 segments of proximal tubules. The immunogold method showed no labeling for OAT1 in the cytoplasmic vesicles, suggesting that OAT1 may not move together with organic anions into the cells. These results are consistent with previous physiologic data showing that organic anions, including para -aminohippurate, are taken up by the basolateral Na + -independent organic anion/dicarboxylate exchanger and excreted at S2 segments. In conclusion, OAT1 was localized to the basolateral membrane of S2 segments of proximal tubules in rat kidneys.
Motor pattern of the left colon before and after surgery for rectal cancer: possible implications in other disorders.
Authors: B N Catchpole
Journal: Gut (1988)

The motility of the descending colon was studied in nine patients before and after resection of the rectum for cancer. This operation parasympathectomises and generally also sympathectomises the remaining left colon. Motor activity was significantly reduced by sleep before and after surgery. There was also a reduction in awake motility after surgery which is attributed to extrinsic denervation. The reduced motility may explain the increased frequency of motions passed after surgery.
The Utility of Transbronchial Needle Aspiration in the Staging of Bronchogenic Carcinoma
Authors: EDWARD M. HARROW, WAJDY ABI-SALEH, JAMES BLUM, TIMOTHY HARKIN, STEFANO GASPARINI, DOREEN J. ADDRIZZO-HARRIS, ALEJANDRO C. ARROLIGA, GREGORY WIGHT, ATUL C. MEHTA
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

We conducted a prospective multi-institutional clinical study involving community hospitals and academic medical centers to more carefully define the value of computerized tomography (CT) of the chest with transbronchial needle aspiration (TBNA) in the staging of bronchogenic carcinoma (CA), and to assess the predictors of a positive aspirate. Of 360 individuals determined to have bronchogenic carcinoma, 50 of 81 (62%) with small cell carcinoma (SCC) and 135 of 279 (48%) with non-small cell carcinoma (NSCC) had positive aspirates (p = 0.034). TBNA precluded additional thoracic surgery in a total of 104 of 360 (29%) patients and was exclusively diagnostic of carcinoma in 65 of 360 (18%) cases. Right-sided tumors were more likely to have a positive mediastinal TBNA (p = 0.002 to 0.01) as were histologic (67 of 118 [57%]) rather than cytology aspirates (228 of 532 [41%]) (p < 0.001). Sensitivity was > 57% in lymph nodes (LN) ⩾ 10 mm, and among LN of equivalent size, right paratracheal and subcarinal sites were most likely to establish malignancy. Preoperative CT is a valuable adjunct in the staging of CA by TBNA. Increasing LN size, right-sided tumors, right paratracheal and subcarinal locations, use of a histology needle, and the presence of SCC are the best predictors of a positive aspirate. Harrow EM, Abi-Saleh W, Blum J, Harkin T, Gasparini S, Addrizzo-Harris DJ, Arroliga AC, Wight G, Mehta AC. The utility of transbronchial needle aspiration in the staging of bronchogenic carcinoma.
Weak Expression of Focal Adhesion Kinase (pp125FAK) in Patients with Cervical Cancer Is Associated with Poor Disease Outcome
Authors: Boris Gabriel, Axel zur Hausen, Elmar Stickeler, Carola Dietz, Gerald Gitsch, Dagmar-C. Fischer, Jiri Bouda, Clemens Tempfer, Annette Hasenburg
Journal: Clinical Cancer Research (2006)

Abstract Purpose: The pp125 focal adhesion kinase (FAK) plays a pivotal role in tumor cell signaling. FAK expression has been linked to tumor cell invasion and metastasis, but data on cervical cancer are inconclusive. Our goal was to investigate FAK expression in cervical cancer and to assess whether its expression correlates with prognosis. Experimental Design: FAK expression was examined using immunohistochemistry with sections from 162 resected cervical cancer specimens. Kaplan-Meier survival curves were used to determine the significance of FAK expression in the prognosis of cervical cancer patients. Results: Specific FAK expression was found in the tumor cells, whereas normal cervical epithelium showed barely any FAK expression. Of 162 invasive cervical cancer specimens, 55 (34%) revealed weak expression of FAK, whereas moderate and strong expression was found in 63 (39%) and 44 (27%) tumors, respectively. Patients with tumors expressing weak amounts of FAK were characterized by a significantly poorer overall survival compared with those with moderate and high intratumoral FAK expression (P = 0.002). Weak expression of FAK correlated with pelvic lymph node metastasis (P = 0.026) and recurrent disease (P = 0.013). Multivariate Cox regression analysis revealed decreased FAK expression and pelvic lymph node metastasis to be significant independent factors predictive of poor disease outcome (hazard ratio, 0.36; P = 0.005; hazard ratio, 2.38; P = 0.018, respectively). Conclusions: Weak expression of FAK in invasive cervical cancer is a strong independent predictor of poor patient outcome. Further studies are warranted to elucidate whether FAK expression analysis is a suitable tool identifying patients at high risk even at an early clinical stage.