tbuckley/cabot-search huggingface dataset:
Porphyria cutanea tarda and haemochromatosis: a family study.
Authors: D G Seymour, G H Elder, A Fryer, A Jacobs, G T Williams
Journal: Gut (1990)

A female patient aged 73 presented with a history of general malaise and hyperpigmentation. Iron studies in the patient and immediate family members indicated that the proband was homozygous for haemochromatosis, but subsequent investigations revealed that porphyria cutanea tarda was responsible for her signs and symptoms. Venesection of four units of blood brought her symptoms under control. The interplay between porphyria cutanea tarda and excess iron deposition is discussed as is the role of extending investigations to first and second degree relatives when either haemochromatosis or porphyria cutanea tarda is suspected.
Disability in rheumatoid arthritis in the era of biological treatments
Authors: Eswar Krishnan, Bharathi Lingala, Bonnie Bruce, James F Fries
Journal: Annals of the Rheumatic Diseases (2011)

Rheumatoid arthritis (RA) is a disabling disease. The authors studied the impact of new, expensive and occasionally toxic biological treatments on disability outcomes in real-world populations of patients with RA.The authors analysed Health Assessment Questionnaire Disability Index data on 4651 adult patients with RA collected prospectively from 1983 to 2006. They studied trends in disability using multilevel mixed-effects multivariable linear regression (mixed) models that adjusted for the effects of time trends in gender, ethnicity, age, smoking behaviour and disease duration.Overall, the patients were predominantly female (76%), were predominantly white (88%), had 13 years of education and have had RA for 13 years, on average. The time period from 1983 to 2006 saw major increases in the use of disease-modifying agents and biological agents, and a decrease in smoking. After adjustments, the disability rates declined at annual rates of 1.7% (1.5-1.8%) overall and 2.7% (2.4-3.1%) among men. The annual rate of disability declines in the biological era was greater than that in the preceding period, suggesting accelerated improvement. These declines were documented in all patient subgroups such as men, women, African-Americans, obese, older age groups and early disease (p<0.001), but not among the 1401 patients (where disability remained stable) who died on follow-up.Aggressive use of traditional disease-modifying agents and introduction of biological agents were associated with substantial gains in disability outcomes. Our finding supports the prevailing notion that 'tight inflammation control' is a desirable therapeutic strategy.
Brain Activation Measured With fMRI During a Mental Arithmetic Task in Schizophrenia and Major Depression
Authors: Kenneth Hugdahl, Bjørn Rishovd Rund, Anders Lund, Arve Asbjørnsen, Jens Egeland, Lars Ersland, Nils Inge Landrø, Atle Roness, Kirsten I. Stordal, Kjetil Sundet, Tormod Thomsen
Journal: American Journal of Psychiatry (2004)

The authors used functional magnetic resonance imaging (fMRI) to investigate brain activation in patients with schizophrenia and major depression while they performed two tasks-a vigilance task and a mental arithmetic task-that differed in cognitive complexity.In the vigilance task, the participants had to press a response button whenever a specific number was seen on a screen inside the MR scanner. In the mental arithmetic task, the participants had to add two consecutive numbers and press the response button whenever the sum was 10. fMRI was performed with a 1.5-T MR scanner. Twelve patients with recurrent nonpsychotic unipolar major depression, 12 patients with schizophrenia, and 12 healthy comparison subjects were included in the study.Performance data showed that the patients were impaired relative to the comparison subjects and showed no difference in performance between the patient groups. The patients with schizophrenia, but not those with major depression, had less activation in prefrontal brain regions, relative to the comparison participants. However, subtracting brain activation during the vigilance task from activation during the mental arithmetic task showed that the schizophrenia patients had activation in parietal areas.A double dissociation of parietal and frontal lobe activation was found for the schizophrenia patients and the depression patients. The greater parietal lobe activation in the patients with schizophrenia may reflect a compensatory strategy for the failure to recruit cognitive processes that involve frontal lobe areas when solving a mental arithmetic task.
Endocannabinoids Acting at Cannabinoid-1 Receptors Regulate Cardiovascular Function in Hypertension
Authors: Sándor Bátkai, Pál Pacher, Douglas Osei-Hyiaman, Svetlana Radaeva, Jie Liu, Judith Harvey-White, László Offertáler, Ken Mackie, M. Audrey Rudd, Richard D. Bukoski, George Kunos
Journal: Circulation (2004)

Endocannabinoids are novel lipid mediators with hypotensive and cardiodepressor activity. Here, we examined the possible role of the endocannabinergic system in cardiovascular regulation in hypertension.In spontaneously hypertensive rats (SHR), cannabinoid-1 receptor (CB1) antagonists increase blood pressure and left ventricular contractile performance. Conversely, preventing the degradation of the endocannabinoid anandamide by an inhibitor of fatty acid amidohydrolase reduces blood pressure, cardiac contractility, and vascular resistance to levels in normotensive rats, and these effects are prevented by CB1 antagonists. Similar changes are observed in 2 additional models of hypertension, whereas in normotensive control rats, the same parameters remain unaffected by any of these treatments. CB1 agonists lower blood pressure much more in SHR than in normotensive Wistar-Kyoto rats, and the expression of CB1 is increased in heart and aortic endothelium of SHR compared with Wistar-Kyoto rats.We conclude that endocannabinoids tonically suppress cardiac contractility in hypertension and that enhancing the CB1-mediated cardiodepressor and vasodilator effects of endogenous anandamide by blocking its hydrolysis can normalize blood pressure. Targeting the endocannabinoid system offers novel therapeutic strategies in the treatment of hypertension.
ATP-Sensitive K <sup>+</sup> Channels, Adenosine, and Nitric Oxide–Mediated Mechanisms Account for Coronary Vasodilation During Exercise
Authors: Yutaka Ishibashi, Dirk J. Duncker, Jianyi Zhang, Robert J. Bache
Journal: Circulation Research (1998)

Abstract —We previously reported that combined blockade of adenosine receptors and ATP-sensitive K+ channels (K + ATP channels) blunted but did not abolish the response of coronary blood flow to exercise. This study tested the hypothesis that the residual increase in coronary flow in response to exercise after adenosine receptor and K + ATP channel blockade is dependent on endogenous NO. Dogs were studied at rest and during a four-stage treadmill exercise protocol under control conditions, during K + ATP channel blockade with glibenclamide (50 μg · kg −1 · min −1 IC) in the presence of adenosine receptor blockade with 8-phenyltheophylline (8-PT, 5 mg/kg IV), and after the addition of the NO synthase inhibitor N G -nitro- l -arginine (LNNA, 1.5 mg/kg IC). During control conditions, coronary blood flow was 49±3 mL/min at rest and increased to 92±8 mL/min at peak exercise. LNNA alone or in combination with 8-PT did not alter resting coronary flow and did not impair the normal increase in flow during exercise, indicating that when K + ATP channels are intact, neither NO nor adenosine-dependent mechanisms are obligatory for maintaining coronary blood flow. Combined K + ATP channel and adenosine blockade decreased resting coronary flow to 27±3 mL/min ( P &lt;.05), but exercise still increased flow to 45±5 mL/min ( P &lt;.05). The subsequent addition of LNNA further decreased resting coronary flow to 20±2 mL/min and markedly blunted exercise-induced coronary vasodilation (coronary vascular conductance, 0.20±0.03 mL · min −1 · mm Hg −1 at rest versus 0.24±0.04 mL · min −1 · mm Hg −1 during the heaviest level of exercise; P =.22), so that coronary flow both at rest and during exercise was below the control resting level. The findings suggest that K + ATP channels are critical for maintaining coronary vasodilation at rest and during exercise but that when K + ATP channels are blocked, both adenosine and NO act to increase coronary blood flow during exercise. In the presence of combined K + ATP channel blockade and adenosine receptor blockade, NO was able to produce approximately one quarter of the coronary vasodilation that occurred in response to exercise when all vasodilator systems were intact.
Quantitative Assessment of Hepatic Function by Breath Analysis after Oral Administration of [^14C]aminopyrine
Authors: GERSHON W. HEPNER
Journal: Annals of Internal Medicine (1975)

The rate of hepatic metabolism of dimethylaminoantipyrine (aminopyrine), which occurs primarily through N-demethylation, was assessed by measurement of the specific activity of 14CO2 excreted in breath samples obtained 2 hours after oral administration of a trace dose of [14C]aminopyrine. The percentage of administered 14C excreted in 14CO2 in 2 hours was 7.0 ± 1.3 (SD)% in control patients, and significantly less (P < 0.01) in patients with portal cirrhosis (2.6 ± 1.2%), fatty liver (4.7 ± 1.1%), hepatitis (2.6 ± 1.4%), and hepatic malignancy (3.5 ± 1.8%). In 16 of 24 subjects with cholestasis not caused by malignant disease the mean 14CO2 excretion was normal. The 14CO2 excretion in patients with portal cirrhosis correlated highly with aminopyrine metabolic clearance rate (r = 0.92), serum albumin (r = 0.75), and retention of bromsulphalein (r = 0.73). Abnormal 14CO2 excretion returned to normal in patients with hepatitis, when the hepatitis resolved. The data suggest that the aminopyrine breath test is a safe, simple, qualitative and quantitative liver function test.
Biologic and oral disease-modifying antirheumatic drug monotherapy in rheumatoid arthritis
Authors: Paul Emery, Anthony Sebba, Tom W J Huizinga
Journal: Annals of the Rheumatic Diseases (2013)

Clinical evidence demonstrates coadministration of tumour necrosis factor inhibitor (TNFi) agents and methotrexate (MTX) is more efficacious than administration of TNFi agents alone in patients with rheumatoid arthritis, leading to the perception that coadministration of MTX with all biologic agents or oral disease-modifying antirheumatic drugs is necessary for maximum efficacy. Real-life registry data reveal approximately one-third of patients taking biologic agents use them as monotherapy. Additionally, an analysis of healthcare claims data showed that when MTX was prescribed in conjunction with a biologic agent, as many as 58% of patients did not collect the MTX prescription. Given this discrepancy between perception and real life, we conducted a review of the peer-reviewed literature and rheumatology medical congress abstracts to determine whether data support biologic monotherapy as a treatment option for patients with rheumatoid arthritis. Our analysis suggests only for tocilizumab is there evidence that the efficacy of biologic monotherapy is comparable with combination therapy with MTX.
Predicting pulmonary hypertension with standard computed tomography angiography
Authors: Onno Spruijt, Frances de Man, Rutger Lelij, Harm Jan Bogaard, Nico Westerhof, Anton Vonk-Noordegraaf
Journal: European Respiratory Journal (2013)

Rationale:  Since standard non-ECG gated computed tomography angiography (CTA) is a widely available and frequently used diagnostic test and is part of the normal clinical work-up of pulmonary hypertension (PH), predicting PH by CTA could be of clinical interest. Although research has shown the value of measurements of the pulmonary artery (PA) for predicting PH, less is known about the predictive value of ventricular measurements on CTA.   Objective:  To investigate whether the predictive value of CTA for PH can be increased when PA and ventricular measurements are combined.   Methods:  Retrospective study design. 59 PH patients (48 patients with pulmonary arterial hypertension and 11 patients with chronic trombo-embolic pulmonary hypertension) and 28 non-PH controls underwent right heart catheterization and CTA. Pulmonary artery/ascending aorta diameter ratio on the axial view (PA/AA AX ), right ventricle/left ventricle diameter ratio on the axial view (RV/LV AX ) and RV/LV diameter ratio on a manually reconstructed four chamber view (RV/LV 4CH ) were obtained as CT parameters for predicting PH.   Results:  Multivariate binary logistic regression analysis showed that only PA/AA AX  and RV/LV 4CH , were independent predictors of PH. The highest sensitivity in combination with the highest positive predictive value (PPV) was obtained when PA/AA AX  and RV/LV 4CH  were combined (Table 1).   Conclusion:  Predicting PH using the combination of the PA/AA AX  and RV/LV 4CH  is better than using PA/AA AX  alone.
The steady-state turnover of murine epidermal Langerhans cells
Authors: None Ghaznawie, None Papadimitriou, None Heenan
Journal: British Journal of Dermatology (1999)

We have investigated the steady-state turnover of murine epidermal Langerhans cells (LCs) using an X-irradiation model, 3H-thymidine autoradiography and cultured epidermal sheet explants, and by assessing the LC population in normal mice. The LC density after whole-body irradiation without any cutaneous shielding was not significantly different from that in skin shielded during whole-body irradiation (P > 0.05), indicating that the additional irradiation to the skin did not contribute to a decrease in LC density. In both instances, the LC number gradually decreased in a linear fashion. The results indicate that epidermal LCs continuously leave the epidermis and are continually replaced by circulating precursor cells from the bone marrow at a steady rate. Autoradiographic studies after a pulse injection of 3H-thymidine showed a labelling index of 0.013%, indicating that local mitosis is not an important contributor to the maintenance of the epidermal LC population. Although local X-irradiation resulted in temporary reduction of LC density, epidermal sheet explant culture obtained immediately after local X-irradiation showed no difference in LC density as compared with control unirradiated skin, indicating that the decrease in LC density was not due to significant LC destruction. From these data, we calculated that the half-life of murine LCs in the epidermis is approximately 9 days.
Prevalence and Prediction of Coronary Artery Disease in Patients With Liver Cirrhosis
Authors: Jihyun An, Ju Hyun Shim, Seon-Ok Kim, Danbi Lee, Kang Mo Kim, Young-Suk Lim, Han Chu Lee, Young-Hwa Chung, Yung Sang Lee
Journal: Circulation (2014)

There is conflict regarding the prevalence of coronary artery disease (CAD) in patients with liver cirrhosis. This study aimed to investigate the prevalence of silent CAD in comparison with the general population, and to identify the relevant risk factors in patients with liver cirrhosis.This retrospective study included 1045 prospectively registered consecutive patients with liver cirrhosis without any history of chest pain or CAD, who underwent computerized coronary angiography as a pretransplant workup. These were matched with 6283 controls with healthy livers, based on propensity scores according to established cardiovascular risk factors. Obstructive CAD was defined as ≥50% luminal narrowing in any artery. A matched analysis of 853 pairs showed that the proportion of subjects with obstructive CAD did not differ significantly between the cirrhotic and control groups (7.2% versus 7.9%, P=0.646), in agreement with the outcome of multivariate analysis for its predictors, with an adjusted odds ratio for liver cirrhosis of 1.06 (P=0.690). Nonobstructive CAD was more prevalent in the matched cirrhotic cases (30.6% versus 23.4%, P=0.001). In the pooled cirrhotic cohort, older age, male sex, hypertension, diabetes mellitus, and alcoholic cirrhosis were independently associated with obstructive CAD (adjusted odds ratios, 1.07, 2.74, 1.69, 2.37, and 2.17, respectively; P<0.05 for all), whereas liver function and coagulation parameters were not.Asymptomatic cirrhotic patients and nonhepatic subjects are similar in terms of the prevalence of occult obstructive CAD. Traditional cardiovascular risk factors are related to critical coronary stenosis in cirrhotic patients, and thus may be helpful indicators for more careful preoperative evaluation of coronary risk.
Timing of Low Tidal Volume Ventilation and Intensive Care Unit Mortality in Acute Respiratory Distress Syndrome. A Prospective Cohort Study
Authors: Dale M. Needham, Ting Yang, Victor D. Dinglas, Pedro A. Mendez-Tellez, Carl Shanholtz, Jonathan E. Sevransky, Roy G. Brower, Peter J. Pronovost, Elizabeth Colantuoni
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Reducing tidal volume decreases mortality in acute respiratory distress syndrome (ARDS). However, the effect of the timing of low tidal volume ventilation is not well understood.To evaluate the association of intensive care unit (ICU) mortality with initial tidal volume and with tidal volume change over time.Multivariable, time-varying Cox regression analysis of a multisite, prospective study of 482 patients with ARDS with 11,558 twice-daily tidal volume assessments (evaluated in milliliter per kilogram of predicted body weight [PBW]) and daily assessment of other mortality predictors.An increase of 1 ml/kg PBW in initial tidal volume was associated with a 23% increase in ICU mortality risk (adjusted hazard ratio, 1.23; 95% confidence interval [CI], 1.06-1.44; P = 0.008). Moreover, a 1 ml/kg PBW increase in subsequent tidal volumes compared with the initial tidal volume was associated with a 15% increase in mortality risk (adjusted hazard ratio, 1.15; 95% CI, 1.02-1.29; P = 0.019). Compared with a prototypical patient receiving 8 days with a tidal volume of 6 ml/kg PBW, the absolute increase in ICU mortality (95% CI) of receiving 10 and 8 ml/kg PBW, respectively, across all 8 days was 7.2% (3.0-13.0%) and 2.7% (1.2-4.6%). In scenarios with variation in tidal volume over the 8-day period, mortality was higher when a larger volume was used earlier.Higher tidal volumes shortly after ARDS onset were associated with a greater risk of ICU mortality compared with subsequent tidal volumes. Timely recognition of ARDS and adherence to low tidal volume ventilation is important for reducing mortality. Clinical trial registered with www.clinicaltrials.gov (NCT 00300248).
Helper and killer T cells do not express B cell immunoglobulin joining and constant region gene segments.
Authors: M Kronenberg, M M Davis, P W Early, L E Hood, J D Watson
Journal: The Journal of Experimental Medicine (1980)

We have analyzed four kinds of T cells for rearrangement and expression of immunoglobulin genes. These cells include: (a) whole thymus; (b) WEHI-22, a T-cell lymphoma; (c) HT-1, an major histocompatibility complex-restricted T helper line; and (d) CTLLi6, an H-2 alloreactive killer cell line. None of the B-cell joining and constant gene segments are rearranged in the T cells. The monoclonal cells do not express any C kappa, C lambda, Cmu or C alpha RNA species. Small amounts of C kappa, C alpha, and Cmu sequences are present in RNA prepared from the thymus, although the significance of this RNA for T-cell antigen receptor synthesis is uncertain. The data support the hypothesis that expression of B-cell joining and C gene segments is unnecessary for T-cell helper and T-cell killer activity.
EFFECT OF PURIFIED ENZYMES ON VIRUSES AND GRAM-NEGATIVE BACTERIA
Authors: Malcolm H. Merrill
Journal: The Journal of Experimental Medicine (1936)

Evidence is presented that some viruses behave like proteins in that they are inactivated by proteolytic enzymes, whereas others prove more or less resistant. Ten strains of living Gram-negative bacteria resisted the action of purified trypsin and chymotrypsin, while the killed organisms were rapidly digested. Gram-positive bacteria, on the other hand, were resistant whether living or dead. The findings are discussed.
Noninvasive ventilation (NIV) for acute hypercapnic respiratory failure (AHRF): Is the helmet an effective interface? A pilot RCT
Authors: Chiara Mega, Lara Pisani, Paolo Navalesi, Andrea Bellone, Raffaele Scala, Vanessa Repetto, Corrado Zenesini, Luca Fasano, Manuela Del Forno, Stefano Nava
Journal: European Respiratory Journal (2012)

To date the helmet is rarely used in AHRF, despite in hypoxic respiratory failure, it is employed as a “rotating” strategy when the facial mask is poorly tolerated.  In a multicenter RCT, we compared the clinical efficacy of a new helmet designed to specifically improve the performance in COPD vs a full face mask during an episode of AHRF.  17 COPDs with AHRF were randomly assigned to receive NIV either with full face mask (GroupA,n=9pH=7,26±0.07PaCO 2 =73.7±10.8mmHg,PaO 2 /FiO 2 =97.3±53.7) or the helmet (GroupB,n=8pH=7.24±0.05PaCO 2 =83.3±14.2mmHg,PaO 2 /FiO 2 =100.6±41).In the former group the ventilator settings were decided according to the usual practice (i.e. the maximal inspiratory pressure tolerated and CPAP=4cmH20),while in latter group according to published data(Crit Care Med 2009; 37:1921).  ABGs were evaluated at admission,1 and 6 hour and then everyday until discharge. Vital parameters, discomfort scale, dyspnea score and adverse events were recorded.  Baseline characteristics did not differ significantly between the two groups. 2 and 1 patients for groupA and B respectively required intubation. NIV improved gas exchange vs baseline (p  In conclusion in this pilot RCT we have shown that the helmet may be a valid alternative to the “classical” full face mask during an episode of AHRF, making the former interface possible alternative for “rotating” strategy.
Does Prostate-Specific Antigen Screening Influence the Results of Studies of Tomatoes, Lycopene, and Prostate Cancer Risk?
Authors: E. Giovannucci
Journal: JNCI Journal of the National Cancer Institute (2007)

In this issue of the Journal, Kavanaugh et al. ( 1 ) describe how the U. S. Food and Drug Administration (FDA) evaluated the scientific evidence for proposed qualified health claims for tomatoes and lycopene with respect to the risks of prostate cancer and other types of cancers. After the authors qualitatively reviewed the studies, they concluded that there was “a very low level of comfort that a relationship exists between the consumption of tomatoes and/or tomato sauce and prostate cancer risk.” This conclusion is disappointing given that some initial studies of tomato product intake or circulating lycopene levels suggested an association with a reduced risk of prostate cancer, providing some hope for prostate cancer prevention ( 2 – 6 ). However, a number of recent studies, including some ( 7 – 9 ) too recent to be included in the review by Kavanaugh et al. ( 1 ), have not supported this association or have been equivocal. Should we now conclude that tomatoes or lycopene are unlikely to have any role in prostate carcinogenesis? Before we do, we should consider a potentially complicating factor, which is that most of the recent studies have been conducted in populations in which most prostate cancers are identified through prostate-specific antigen (PSA) screening. In interpreting the evidence for a risk factor in relation to prostate cancer risk, two major considerations are how PSA screening influences the diagnosis and epidemiology of prostate cancer and when during prostate carcinogenesis that risk
Anti-cockroach and anti-mouse IgE are associated with early wheeze and atopy in an inner-city birth cohort
Authors: Kathleen M. Donohue, Umaima Al-alem, Matthew S. Perzanowski, Ginger L. Chew, Alina Johnson, Adnan Divjan, Elizabeth A. Kelvin, Lori A. Hoepner, Frederica P. Perera, Rachel L. Miller
Journal: Journal of Allergy and Clinical Immunology (2008)