tbuckley/cabot-search huggingface dataset:
Pine dust, atopy and lung function: a cross-sectional study in sawmill workers
Authors: J. Douwes
Journal: European Respiratory Journal (2006)

An increased risk of asthma symptoms has previously been shown in 772 pine sawmill workers. The aim of the current study was to assess the association between dust exposure, lung function and atopy. Subjects with (n = 59) and without (n = 167) asthma symptoms were randomly selected from the previous survey. Lung function and atopy were determined using spirometry and skin-prick tests, respectively. Inhalable dust levels were measured on the same day. The geometric mean dust concentration was 0.52 mg·m<sup>-3</sup>. Exposure to dry but not to green dust was associated with asthma symptoms. Green dust was associated with atopic sensitisation, particularly against outdoor allergens; no association was found for dry dust. Forced vital capacity, forced expiratory volume in one second and peak expiratory flow were significantly lower in workers exposed to high levels of green dust (-350 mL, -260 mL and -860 mL·s<sup>-1</sup>, respectively) and dry dust (-230 mL, -190 mL and -850 mL·s<sup>-1</sup>, respectively). These associations were observed both in subjects with and without asthma symptoms. No associations with cross-shift changes in lung function were found. Exposure to green pine sawdust may be a risk factor for atopy. Both green and dry dust were associated with obstructive as well as restrictive pulmonary effects.
Meta-analysis of the Relationship Between Dose and Benefit in Phase I Targeted Agent Trials
Authors: S. Gupta, S. Hunsberger, S. A. Boerner, L. Rubinstein, R. Royds, P. Ivy, P. LoRusso
Journal: JNCI Journal of the National Cancer Institute (2012)

To date, the primary objective of phase I trials has been to safely select the maximum tolerated dose (MTD) of a drug or drug combination for utilization in subsequent trials. Although conventional cytotoxic chemotherapy is generally more effective at the MTD than molecularly targeted agents (MTAs), recent single-institution data suggest that molecularly targeted agent may not require an MTD for efficacy. We analyzed patient outcome results in MTA phase I trials at multiple institutions throughout North America sponsored by the National Cancer Institute's Cancer Therapy Evaluation Program. We retrospectively collected and analyzed data on patients treated on monotherapy phase I trials investigating novel MTAs with a defined MTD from 2000 to 2009. Logistic regression analysis was used to test whether there was an increase in the probability of a response as dose increased. A Cox proportional hazards model was used to determine if overall survival increased with increasing dose. All statistical tests were two-sided. We analyzed 1908 patients treated on 55 eligible clinical trials. The probability of both overall response (complete response plus partial response) and overall survival increased with increasing dose (odds ratio for increased response = 1.56, P = .10; hazard ratio for death = 0.37, P = .008) when controlling for study as a covariate. Patients treated in the context of phase I trials with MTAs continue to derive reasonable clinical benefit. Contrary to other single institution data, our data suggest clinical benefit in terms of increasing response and overall survival with increasing dose.
Relation of V <sub>max</sub> to Different Models of Cardiac Muscle
Authors: WILLIAM W. PARMLEY, LEONARD CHUCK, EDMUND H. SONNENBLICK
Journal: Circulation Research (1972)

The present study was undertaken to reevaluate the effects of preload on maximum velocity of shortening at zero load, V max , relative to the length-tension curve. Force-velocity relations were measured from afterloaded isotonic contractions and were calculated from isometric contractions of isolated cat papillary muscles. Results were interpreted in the light of three alternative mechanical models of muscle. V max was obtained by mathematical extrapolation of each force-velocity relation to zero load using a hyperbolic least-squares analysis performed on an IBM 360 computer. With the application of all three muscle models to isotonic force-velocity relations, V max was relatively constant at low preloads but was reduced substantially as muscle length approached L max (the length at the peak of the active length-tension curve). In force-velocity relations from isometric contractions, similar results were obtained with the two-element and Voigt models of muscle. With the Maxwell model, V max remained more nearly constant near L max . Peak developed force (isometric contraction), maximum dP/dt, peak calculated velocity of the contractile element (V CE ), and V max were compared in terms of their dependence on preload and length over the entire length-tension curve (using the Maxwell model). Peak V CE and V max were similar and were less dependent on preload than maximum dP/dt or developed force.
Heterogeneity of Diabetes Outcomes Among Asians and Pacific Islanders in the U.S.
Authors: Alka M. Kanaya, Nancy Adler, Howard H. Moffet, Jennifer Liu, Dean Schillinger, Alyce Adams, Ameena T. Ahmed, Andrew J. Karter
Journal: Diabetes Care (2011)

OBJECTIVE Ethnic minorities with diabetes typically have lower rates of cardiovascular outcomes and higher rates of end-stage renal disease (ESRD) compared with whites. Diabetes outcomes among Asian and Pacific Islander subgroups have not been disaggregated. RESEARCH DESIGN AND METHODS We performed a prospective cohort study (1996–2006) of patients enrolled in the Kaiser Permanente Northern California Diabetes Registry. There were 64,211 diabetic patients, including whites (n = 40,286), blacks (n = 8,668), Latinos (n = 7,763), Filipinos (n = 3,572), Chinese (n = 1,823), Japanese (n = 951), Pacific Islanders (n = 593), and South Asians (n = 555), enrolled in the registry. We calculated incidence rates (means ± SD; 7.2 ± 3.3 years follow-up) and created Cox proportional hazards models adjusted for age, educational attainment, English proficiency, neighborhood deprivation, BMI, smoking, alcohol use, exercise, medication adherence, type and duration of diabetes, HbA1c, hypertension, estimated glomerular filtration rate, albuminuria, and LDL cholesterol. Incidence of myocardial infarction (MI), congestive heart failure, stroke, ESRD, and lower-extremity amputation (LEA) were age and sex adjusted. RESULTS Pacific Islander women had the highest incidence of MI, whereas other ethnicities had significantly lower rates of MI than whites. Most nonwhite groups had higher rates of ESRD than whites. Asians had ~60% lower incidence of LEA compared with whites, African Americans, or Pacific Islanders. Incidence rates in Chinese, Japanese, and Filipinos were similar for most complications. For the three macrovascular complications, Pacific Islanders and South Asians had rates similar to whites. CONCLUSIONS Incidence of complications varied dramatically among the Asian subgroups and highlights the value of a more nuanced ethnic stratification for public health surveillance and etiologic research.
Antihypertensive Effects of the Putative T-Type Calcium Channel Antagonist Mibefradil Are Mediated by the L-Type Calcium Channel Ca <sub>v</sub> 1.2
Authors: Sven Moosmang, Nicole Haider, Birgit Brüderl, Andrea Welling, Franz Hofmann
Journal: Circulation Research (2005)

The role of T-type Ca2+ channels for cardiovascular physiology, in particular blood pressure regulation, is controversial. Selective blockade of T-type Ca2+ channels in resistance arteries has been proposed to explain the effect of the antihypertensive drug mibefradil. In the present study, we used a third generation, time- and tissue-specific conditional knockout model of the L-type Ca2+ channel Cav1.2 (Cav1.2SMAKO mice) to genetically dissect the effects of mibefradil on T- and L-type Ca2+ channels. Myogenic tone and phenylephrine-induced contraction in hindlimb perfusion experiments were sensitive to mibefradil in control mice, whereas the drug showed no effect in Cav1.2-deficient animals. Mean arterial blood pressure in awake, freely moving control mice was reduced by 38+/-2.5 mm Hg at a dose of 1.25 mg/kg bodyweight mibefradil, but not changed in Cav1.2SMAKO mice. These results demonstrate that the effect of the putative T-type Ca2+ channel-selective blocker mibefradil on blood pressure and small vessel myogenic tone is mediated by the Cav1.2 L-type Ca2+ channel.
Assessing the Outcome of the Management of Diabetic Foot Ulcers Using Ulcer-Related and Person-Related Measures
Authors: William J. Jeffcoate, Susan Y. Chipchase, Paul Ince, Fran L. Game
Journal: Diabetes Care (2006)

The purpose of this study was to compare different outcome measures in the audit of management of diabetic foot ulcersData collected prospectively in a consecutive cohort of patients referred to a specialist multidisciplinary foot care clinic between 1 January 2000 and 31 December 2003 were analyzed. A single index ulcer was selected for each patient and classified according to both the Size (Area and Depth), Sepsis, Arteriopathy, and Denervation [S(AD)SAD] and University of Texas (UT) systems. Ulcer-related outcomes (healing, resolution by ipsilateral amputation or by death, and persisting unhealed) were determined at 6 and 12 months and compared with patient-related outcomes (survival, any amputation, and being free from any ulcer) at 12 months.In 449 patients (63.7% male, mean age 66.7 +/- 13.2 years), 352 (78.4%) ulcers were superficial [S(AD)SAD/UT grade 1] and 134 of these (38.1% of 352) were neither ischemic nor infected. A total of 183 (40.8% of 449) ulcers were clinically infected, and peripheral arterial disease was present in 216 patients (48.1%). Seventeen patients (3.8%) were lost to follow-up and were excluded from analysis. Of the ulcers, 247 (55.0% of 449) and 295 (65.7%) healed without amputation by 6 and 12 months, respectively. Median (range) time to healing was 78 (7-364) days. Of all index ulcers, 5.8 and 8.0% were resolved by amputation, and 6.2 and 10.9% by death by the same time points; 27.8 and 11.6% persisted unhealed. In contrast, patient-related outcomes revealed that of 449 patients only 202 (45.0%) were alive, without amputation, and ulcer free at 12 months. This group had had 272 (1-358) days without any ulcer. A total of 48 (10.7%) patients had undergone some form of amputation, and 75 (16.7%) had died.These data illustrate the extent to which ulcer-related outcomes may underestimate the true morbidity and mortality associated with diabetic foot disease. It is suggested that when attempts are made to compare the effectiveness of management in different centers, greater emphasis should be placed on patient-related outcome measures.
Key Role of Amino Acid Repeat Expansions in the Functional Diversification of Duplicated Transcription Factors
Authors: Núria Radó-Trilla, Krisztina Arató, Cinta Pegueroles, Alicia Raya, Susana de la Luna, M. Mar Albà
Journal: Molecular Biology and Evolution (2015)

The high regulatory complexity of vertebrates has been related to two rounds of whole genome duplication (2R-WGD) that occurred before the divergence of the major vertebrate groups. Following these events, many developmental transcription factors (TFs) were retained in multiple copies and subsequently specialized in diverse functions, whereas others reverted to their singleton state. TFs are known to be generally rich in amino acid repeats or low-complexity regions (LCRs), such as polyalanine or polyglutamine runs, which can evolve rapidly and potentially influence the transcriptional activity of the protein. Here we test the hypothesis that LCRs have played a major role in the diversification of TF gene duplicates. We find that nearly half of the TF gene families originated during the 2R-WGD contains LCRs. The number of gene duplicates with LCRs is 155 out of 550 analyzed (28%), about twice as many as the number of single copy genes with LCRs (15 out of 115, 13%). In addition, duplicated TFs preferentially accumulate certain LCR types, the most prominent of which are alanine repeats. We experimentally test the role of alanine-rich LCRs in two different TF gene families, PHOX2A/PHOX2B and LHX2/LHX9. In both cases, the presence of the alanine-rich LCR in one of the copies (PHOX2B and LHX2) significantly increases the capacity of the TF to activate transcription. Taken together, the results provide strong evidence that LCRs are important driving forces of evolutionary change in duplicated genes.
Pericardioscopy and aimed pericardial biopsy after complete drainage of pericardial fluid: improved visualization, sampling efficiency and safety
Authors: P.M. Seterović, A.D. Ristić, P. Petrović, R. Maksimović, B. Obrenović, M. Ostojić, S. Simounovic, A. Kus̀ić, M. Vraneš, P. Djukić, R. Mijanović
Journal: Journal of the American College of Cardiology (1998)
The effect of loading speed on the force frequency spectrum during eccentric &amp; concentric calf exercise
Authors: S Chaudhry, H R C Screen, R C Woledge, D Bader, D Morrissey
Journal: British Journal of Sports Medicine (2011)

Introduction Heavy load eccentric training (ET) has been shown to be more effective than concentric training (CT) in treating Achilles tendinopathy.1 2 It is unclear at what speed ET should be performed to treat the condition with greatest efficacy. Recent studies have indicated that high frequency tendon force fluctuations may underpin therapeutic mechanotransduction, but the effect of training speed on resulting tendon vibration remains unexplored. The aim of this study was to compare tendon vibration during ET and CT at three speeds commonly employed during conservative treatment. Methods 24 healthy volunteers (12 male and 12 female, age=27.8±1.9 years) performed ET and CT exercises for the Achilles tendon either at a fast (loading phase=1.5 s), medium (loading phase=3 s) or slow pace (loading phase=6 s). Tendon vibration was measured by analysing the power spectra of the ground reaction force vector using a fast Fourier transform with 1Hz windows, and compared using ANOVA. Results High frequency vibrations (8–13 Hz range) were greatest during fast and medium speed ET, with a mean of 15.8 N 2 /Hz (sd=8.8). This was significantly greater than all other combinations of conditions and speeds (p value range across these frequencies=0.03–0.001). No significant differences between any combinations of speed and loading condition were found in the 1–7 Hz low frequency range (p value range=0.11–0.98). Conclusion The observed high frequency Achilles tendon force fluctuations during fast and medium speed ET were mostly in the higher frequency range, reflecting where physiological tremor particularly occurs. This may reflect inefficient recruitment of large motor units at high speeds, creating oscillation frequencies that are known to stimulate mechanotransduction in tenocytes. These findings were made in normal subjects and pave the way for exploration in patients with tendinopathic disease.
A role of parathyroid hormone for the activation of cardiac fibroblasts in uremia.
Authors: K Amann, E Ritz, G Wiest, G Klaus, G Mall
Journal: Journal of the American Society of Nephrology (1994)

Intermyocardiocytic fibrosis, i.e., nonreparative interstitial fibrosis with collagen fiber deposition, is commonly found in uremic patients and animals. The volume density of interstitial tissue in the left papillary muscle of uremic animals was found to be increased (from 1.9 +/- 0.7 to 4.2 +/- 1.1%; P < 0.001). The nuclei of interstitial cells, but not of endothelial cells, were enlarged, pointing to an activating signal that specifically acts on interstitial cells. Because of the known action of parathyroid hormone (PTH) on the heart, a potential role of PTH in the genesis of fibrosis was explored by comparing subtotally nephrectomized (NX) parathyroidectomized (PTX) rats receiving by osmotic minipump either saline or rat 1,34 PTH (100 ng/kg per hour dissolved in NaCl). Animals were on a standard 0.95% Ca diet. After PTX, they were switched to a high-calcium (3%) diet. At the end of the 14-day experiments, NX-PTX-PTH animals and NX-PTX-solvent animals were comparable with respect to mean body weight (335 versus 338 g), serum creatinine (1.2 versus 1.2 mg/dL), and serum-Ca (2.66 versus 2.63 mmol/L). The volume densities of cardiac interstitium were 4.71 +/- 0.87 versus 1.49 +/- 0.49, and those of capillaries were 8.07 +/- 1.54 versus 7.94 +/- 2.62, respectively (P < 0.001 by analysis of variance). Thus, PTX abolished and PTH restored intermyocardiocytic changes of experimental uremia. These observations argue for a permissive role of PTH for fibroblast activation and the genesis of the cardiac fibrosis of uremia.
Nocturnal asthma and urinary adrenaline and noradrenaline excretion
Authors: C. A. Soutar, M. Carruthers, C. A. C. Pickering
Journal: Thorax (1977)

<b>Soutar, C. A., Carruthers, M., and Pickering, C. A. C. (1977).</b><i>Thorax</i>, <b>32</b>, 677-683. <b>Nocturnal asthma and urinary adrenaline and noradrenaline excretion.</b> Urinary adrenaline and noradrenaline excretion, heart rate, and peak expiratory flow rate have been measured every two hours for 24 hours in seven asthmatic patients suffering from nocturnal or early morning exacerbations of dyspnoea. The excretions of these catecholamines were normal or slightly raised, this being consistent with a normal response to asthma or the conditions of the test. The expected physiological fall in catecholamine excretion occurred at night. In every patient the peak expiratory flow rate fell to its lowest values during the period of lowest catecholamine excretion, and the mean two-hourly peak expiratory flow rate for all seven patients was significantly related to the sum of the mean adrenaline and noradrenaline excretion in each preceding two-hour period (p&lt;0·05). Individually, in three patients the relationship between peak expiratory flow rate and adrenaline and noradrenaline excretion during the evening and night was so close as to be consistent with the hypothesis that changes in sympathetic tone mediated the changes in asthma. In a further three patients the relationship was present but less clear, and in one the changes in peak flow rate and catecholamine excretion were dissociated. Studies of mean heart rate and sinus arrhythmia gap suggested that an increase in vagal tone at night might have mediated the early morning asthma in the patient in whom changes in catecholamine excretion were dissociated from change in peak flow rate. These findings would be consistent with the view that the physiological reduction in sympathetic tone at night mediates the nocturnal and early morning exacerbation of dyspnoea in some asthmatics, although other mechanisms such as alterations in vagal tone must be important in others. Confirmation of a causal relationship requires further study.
Survival and Development of Cardiovascular Disease by Modality of Treatment in Patients with End-Stage Renal Disease
Authors: FRANCESCO LOCATELLI, DANIELE MARCELLI, FERRUCCIO CONTE, MARCO D'AMICO, LUCIA DEL VECCHIO, AURELIO LIMIDO, FABIO MALBERTI, DONATELLA SPOTTI
Journal: Journal of the American Society of Nephrology (2001)

Patients undergoing dialysis are at high risk for cardiovascular disease (CVD). The aim of this study was to evaluate the influence of hemodialysis (HD) versus peritoneal dialysis (PD) on survival and the risk of developing de novo CVD. Of the 4191 patients with end-stage renal disease (ESRD) who started renal replacement treatment (RRT) in Lombardy between 1994 and 1997, 4064 (who were on dialysis 30 d after the start of RRT) were considered for survival analysis: 2772 were on HD (mean age 60.9 yr; 21.2% diabetic) and 1292 on PD (mean age 63.6 yr; 16% diabetic). The 3120 patients who were free of CVD at the start of RRT were included in the analysis of the risk of developing de novo CVD. HD and PD were compared by use of a Cox-regression proportional hazard model, stratified by diabetic status; the explanatory covariates were age and gender. The death rate was 13.3 per 100 patient-years (13.0 on HD and 13.9 on PD); 197 (6.3%) of the 3120 patients included in the CVD analysis developed de novo CVD (128 on HD and 69 on PD). After adjustment for age, gender, and established CVD and stratification by diabetic status, there was no significant between-treatment difference in 4-yr survival (relative risk [RR], 0.91; 95% confidence interval [CI], 0.79 to 1.06). The risk of de novo CVD did not differ significantly by treatment modality (RR, 1.06; 95% CI, 0.79 to 1.43). The risk of mortality and de novo CVD for new patients with ESRD assigned to HD or PD was similar in Lombardy in the period 1994 through 1997.
A phase II placebo-controlled study of tralokinumab in moderate-to-severe asthma
Authors: Edward Piper, Christopher Brightling, Robert Niven, Chad Oh, Raffaella Faggioni, Kwai Poon, Dewei She, Chris Kell, Richard D. May, Gregory P. Geba, Nestor A. Molfino
Journal: European Respiratory Journal (2012)

Pre-clinical data demonstrate a pivotal role for interleukin (IL)-13 in the development and maintenance of asthma. This study assessed the effects of tralokinumab, an investigational human IL-13-neutralising immunoglobulin G4 monoclonal antibody, in adults with moderate-to-severe uncontrolled asthma despite controller therapies. 194 subjects were randomised to receive tralokinumab (150, 300 or 600 mg) or placebo subcutaneously every 2 weeks. Primary end-point was change from baseline in mean Asthma Control Questionnaire score (ACQ-6; ACQ mean of six individual item scores) at week 13 comparing placebo and combined tralokinumab dose groups. Secondary end-points included pre-bronchodilator lung function, rescue β 2 -agonist use and safety. Numerical end-points are reported as mean± sd . At week 13, change from baseline in ACQ-6 was -0.76±1.04 for tralokinumab versus -0.61±0.90 for placebo (p=0.375). Increases from baseline in forced expiratory volume in 1 s (FEV 1 ) were 0.21±0.38 L versus 0.06±0.48 L (p=0.072), with a dose-response observed across the tralokinumab doses tested. β 2 -agonist use (puffs per day) was decreased for tralokinumab -0.68±1.45 versus placebo -0.10±1.49 (p=0.020). The increase in FEV 1 following tralokinumab treatment remained evident 12 weeks after the final dose. Safety profile was acceptable with no serious adverse events related to tralokinumab. No improvement in ACQ-6 was observed, although tralokinumab treatment was associated with improved lung function.
Management of Intractable Nausea and Vomiting in Patients at the End of Life
Authors: Gordon J. Wood, Joseph W. Shega, Beth Lynch, Jamie H. Von Roenn
Journal: JAMA (2007)

Nausea and vomiting, symptoms that occur commonly near the end of life, represent a substantial source of physical and psychological distress for patients and families. In the context of the case of Mr Q, a 50-year-old man with metastatic esophageal cancer admitted to the hospital with intractable nausea and vomiting, we review the evaluation and treatment of this symptom complex. A thorough history and physical examination are essential first steps in the management of these patients because they define the severity of the symptoms and clues to their underlying etiology. Once the most likely cause is determined, the clinician discerns the mechanism, specific transmitters, and receptors by which this etiology is triggering nausea and vomiting. Subsequent pharmacological management focuses on prescribing the appropriate antagonist to the implicated receptors. If symptoms are refractory despite adequate dosage and around-the-clock prophylactic administration, an empirical trial combining several therapies to block multiple emetic pathways should be attempted. Less traditional agents are also discussed, although evidence for their use is limited. Often, oral administration of medication is not feasible and alternate routes such as rectal suppositories, subcutaneous infusions, and orally dissolvable tablets should be considered. Using this step-wise approach, nausea and vomiting can be successfully managed in most patients at the end of life.