tbuckley/cabot-search huggingface dataset:
S9 Inhaled and systemic corticosteroid response in moderate-to-severe asthma assessed by extended exhaled nitric oxide and lung function
Authors: P. A. Williamson, P. M. Short, B. J. Lipworth
Journal: Thorax (2011)

<h3>Introduction and Objectives</h3> Alveolar nitric oxide (CANO) has been proposed as a potential biomarker of small airway inflammation in severe asthma. We wished to investigate the effects on CANO of the addition of coarse or fine particle inhaled corticosteroids to standard therapy in severe asthma. <h3>Methods</h3> Severe asthmatics taking =1600 μg/daybudesonide or equivalent performed a randomised open-label crossover study. Subjects with FEV<sub>1</sub>&lt;80%, gas trapping and elevated CANO (=2 ppb) entered a 6 week dose-ramp run-in of Fluticasone/Salmeterol (FPSM) 250/50 μg twice daily for 3 weeks, then 500/50 μg twice daily for 3 weeks. Patients then received additional HFA-BDP200 μg twice daily or FP 250 μg twice daily for 3 wks in a cross-over. Participants then received prednisolone (PRED) 25 mg/day for 1 week. Nitric oxide, lung function, mannitol challenge, systemic inflammatory markers and urinary cortisol were measured. <h3>Results</h3> 15 patients completed perprotocol: mean (SD) age, 51 (12) yr; FEV<sub>1</sub>, 58 (13)% predicted; residual volume, 193 (100)% predicted; mannitol PD10 177 (2.8) μg. There was no significant difference between FPSM and any add-on therapy for CANO. FPSM/BDP and FPSM/PRED suppressed JawNO and FENO compared to FPSM alone. There was no significant difference between treatments for pulmonary function or bronchial challenge. ECP, e-selectin and ICAM-1 were significantly suppressed by FPSM/PRED compared to FPSM and FPSM/FP but not FPSM/BDP. Plasma cortisol was significantly suppressed by FPSM/PRED only. <h3>Conclusion</h3> In severe asthma, alveolar nitric oxide is insensitive to changes in dose and delivery of inhaled corticosteroids and is not suppressed by systemic corticosteroids. Additional inhaled HFA-BDP caused reductions in FENO and JawNO without adrenal suppression. Oral prednisolone reduced FENO and JawNO with suppression of systemic inflammatory markers and urinary cortisol.
Proximal myopathy after prolonged total therapeutic starvation.
Authors: I N Scobie, W F Durward, A C MacCuish
Journal: BMJ (1980)

Addiction to Distalgesic (dextropropoxyphene)Distalgesic is a proprietary preparation containing dextropropoxyphene 32-5 mg and paracetamol 325 mg per tablet.It is widely prescribed for mild to moderately severe pain.Both components are effective analgesics by mouth.Dextropropoxyphene was introduced in 1957 as a substitute for codeine.Five other proprietary preparations containing dextropropoxyphene are now available in the United Kingdom.Dextropropoxyphene is similar in structure to methadone.It is a centrally acting drug without antipyretic or anti-inflammatory on 10 June
Alcohol as a Risk Factor for Type 2 Diabetes
Authors: Dolly O. Baliunas, Benjamin J. Taylor, Hyacinth Irving, Michael Roerecke, Jayadeep Patra, Satya Mohapatra, Jürgen Rehm
Journal: Diabetes Care (2009)

OBJECTIVE To clarify the dose-response relationship between alcohol consumption and type 2 diabetes. RESEARCH DESIGN AND METHODS A systematic computer-assisted and hand search was conducted to identify relevant articles with longitudinal design and quantitative measurement of alcohol consumption. Adjustment was made for the sick-quitter effect. We used fractional polynomials in a meta-regression to determine the dose-response relationships by sex and end point using lifetime abstainers as the reference group. RESULTS The search revealed 20 cohort studies that met our inclusion criteria. A U-shaped relationship was found for both sexes. Compared with lifetime abstainers, the relative risk (RR) for type 2 diabetes among men was most protective when consuming 22 g/day alcohol (RR 0.87 [95% CI 0.76–1.00]) and became deleterious at just over 60 g/day alcohol (1.01 [0.71–1.44]). Among women, consumption of 24 g/day alcohol was most protective (0.60 [0.52–0.69]) and became deleterious at about 50 g/day alcohol (1.02 [0.83–1.26]). CONCLUSIONS Our analysis confirms previous research findings that moderate alcohol consumption is protective for type 2 diabetes in men and women.
P109 Intravenous aminophylline in the treatment of severe asthma: do we need ECG monitoring?
Authors: J. G. G. B. Penge, J. Hull, K. Guha, A. Menzies-Gow
Journal: Thorax (2011)

<h3>Introduction</h3> Intravenous (IV) aminophylline has an established role in the management of acute severe asthma, with beneficial bronchodilatory, anti-inflammatory and immunomodulatory effects. However, concern is often raised regarding its potential to prolong the QT interval and precipitate cardiac arrhythmias, given its catecholamine enhancing effect.1 Despite this, the influence of IV aminophylline on electrocardiographic (ECG) parameters in patients with acute severe asthma is not fully known. We routinely perform 12-lead electrocardiography on all patients before and 24 h after commencing IV aminophylline. <h3>Objective</h3> To evaluate the effect of intravenous aminophylline on ECG parameters in patients with acute severe asthma. <h3>Method</h3> We assessed electrocardiographic parameters in 26 (21 female) consecutive patients, with a mean (SD) age of 48 (11) years, admitted with severe asthma. We measured serum electrolytes, aminophylline levels and ECG parameters at baseline and within 48 h of commencing IV aminophylline. ECGs were independently assessed by a cardiologist blinded to patient identity and ECG timings. <h3>Results</h3> No significant difference in mean QTc, PR or QRS interval was found following treatment (Abstract P109 table 1). Furthermore, there was no difference in number of atrial or ventricular ectopics, T-wave amplitude or frequency of arrhythmias. However, in four patients the QTc was prolonged above the upper limit of normal (447 ms to 519 ms, 450 ms to 516 ms, 516 ms to 568 ms and 471 ms to 548 ms). <h3>Conclusions</h3> These findings are largely reassuring with regard to the safety of IV aminophylline in severe asthma, in terms of its effects on standard electrocardiographic variables and the incidence of arrhythmias. There was, however, evidence of QTc prolongation in four subjects indicating a need for caution and ECG checks, especially with concomitant use of QT prolonging drugs.
Practice Research: General practitioners' awareness of colorectal cancer
Authors: S. Nichols
Journal: BMJ (1986)

A survey was carried out in Portsmouth to find out what general practitioners knew about colorectal cancer and what their views were on screening. A random sample of general practitioners was interviewed by questionnaire and the remainder asked to complete the questionnaire themselves. The overall response rate was 62%. There was a higher response rate from women doctors and from the group that was interviewed. For some questions there was a difference in the pattern of responses given by the interview group and the group who completed the questionnaire themselves. The level of knowledge of colorectal cancer varied according to which aspect was questioned. The general practitioners knew the symptoms well but were less aware of the vital statistics and risk factors. Most doctors were not in favour of screening by testing for faecal occult blood.
Comparison of the tumorigenic response of SENCAR and C57BL/6 mice to benzo(a)pyrene and the inter-experimental variability over a three-year period.
Authors: S Nesnow, H Bergman, T J Slaga
Journal: Environmental Health Perspectives (1986)

SENCAR and C57BL/6 mice were compared for their ability to produce tumors after benzo(a)pyrene [B(a)P] initiation and 12-O-tetradecanoylphorbol-13-acetate (TPA) promotion. SENCAR mice initiated with 101 micrograms/mouse B(a)P and promoted with TPA (2 micrograms/mouse, twice weekly) produced large numbers of papillomas, whereas C57BL/6 mice produced none after 26 weeks of promotion. Continued treatment of the B(a)P-initiated C57BL/6 mice with TPA up to 52 weeks did not induce any papillomas nor did higher doses of B(a)P. Application of increased doses of TPA (10 micrograms/mouse, twice weekly) to B(a)P-initiated C57BL/6 mice (404 micrograms/mouse) for 50 weeks produced few papillomas. Substantial papilloma formation in C57BL/6 mice was observed after weekly treatment with B(a)P (101 micrograms/mouse), with maximal production occurring at weeks 39 to 41 of treatment. In contrast, SENCAR mice treated according to the same protocol produced an equivalent response with maximal papilloma formation occurring 12 to 13 weeks earlier. Therefore, C57BL/6 mice exposed to B(a)P are capable of producing papillomas under certain experimental conditions. The inter-experimental variability of B(a)P-induced (50.5 micrograms/mouse) papilloma formation after 30 weeks of TPA promotion (2 micrograms/mouse, twice weekly) was examined in SENCAR mice over a 37-month period. Low statistical variation was observed in papilloma multiplicity, papilloma incidence, or papilloma latency. Male and female SENCAR mice produced equal values in the three parameters: 4.4 +/- 1.6 papillomas/mouse, 87% +/- 10% of the mice bearing papillomas, and 9.6 +/- 1.3 weeks (time at which 10% of the mice bore papillomas). The numbers of papillomas per mouse did not follow a Poisson distribution.(ABSTRACT TRUNCATED AT 250 WORDS)
Immunomodulatory drugs can inhibit the extracellular release of HMGB1 from cultured human monocytes
Authors: H. Schierbeck, H. Wahamaa, T. Ostberg, U. Andersson, H. Erlandsson Harris
Journal: Annals of the Rheumatic Diseases (2010)

BackgroundThe endogenous, nuclear protein High Mobility Group Box chromosomal protein 1(HMGB1) is secreted by activated macrophages/monocytes and, once extracellular, promotes infl ammation.Extracellular HMGB1 is present in the synovitis of patients with rheumatoid arthritis (RA) and blockade of HMGB1 by specifi c antibodies ameliorates experimental arthritis.In addition, intra-articular injections of recombinant HMGB1 induce arthritis in mice.The authors hypothesise that HMGB1 represents an endogenous mediator of arthritis as well as a target molecule for successful therapeutic intervention in RA.As no HMGB1-specifi c therapy exists for use in humans, the authors decided to investigate whether HMGB1 secretion is inhibited by antirheumatic and anti-infl ammatory drugs already in use in clinical practice.Methods Cultures of primary human monocytes were preincubated with cortisone, dexamethasone, gold sodium thiomalate, methotrexate, chloroquine, colchicine, pravastatin, interleukin 1 (IL1) receptor antagonist or soluble tumour necrosis factor (TNF) receptor for 1 h and then activated with lipopolysaccharide (LPS) + interferon γ (IFNγ).HMGB1 and TNF secretion were determined after 24 and 9 h of stimulation in enzyme-linked immunosorbent spot assays.Cell viability was recorded by Annexin V staining.The effects of the investigated drugs were evaluated by comparing the number of spots in wells treated with a given drug with the number of spots formed by non-exposed activated cells.Results Addition of dexamethasone or chloroquine significantly suppressed both HMGB1 secretion and TNF secretion.In contrast, gold sodium thiomalate signifi cantly suppressed HMGB1 secretion but did not affect TNF secretion.Cortisone, methotrexate, colchicine, pravastatin, soluble TNF receptor and IL1 receptor antagonist did not inhibit HMGB1 secretion.
Thyroid Hormone Use and Bone Mineral Density
Authors: Jesse C. Krakauer
Journal: JAMA (1994)

To the Editor.  —Dr Schneider and colleagues 1 provide important new data on the long-term effect of thyroid hormone use on bone. Use of  dose thyroid hormone was associated with significantly decreased bone mineral density (BMD) measured at multiple skeletal sites in the nearly 1000 women studied in a retirement community. Overall, for the 20% who were thyroid hormone users, multivariate-adjusted BMD was significantly lower at the midshaft radius, total hip, and lumbar spine sites, but the mean differences from nonusers were small in absolute number and amounted to 3.8%, 3.3%, and 3.2%, respectively (data from Schneider et al, 1 Table 2). Schneider et al present evidence that thyroid hormone use is itself associated with osteopenia and not just the occurrence of prior endogenous hyperthyroidism. Yet controversy remains regarding the risk of bone loss from prescription thyroid hormone excess whether intentional as suppressive therapy or inadvertent. Furthermore, from other
Traffic-Related Air Pollution and Acute Changes in Heart Rate Variability and Respiratory Function in Urban Cyclists
Authors: Scott Weichenthal, Ryan Kulka, Aimee Dubeau, Christina Martin, Daniel Wang, Robert Dales
Journal: Environmental Health Perspectives (2011)

Background: Few studies have examined the acute health effects of air pollution exposures experienced while cycling in traffic.Objectives: We conducted a crossover study to examine the relationship between traffic pollution and acute changes in heart rate variability. We also collected spirometry and exhaled nitric oxide measures.Methods: Forty-two healthy adults cycled for 1 hr on high- and low-traffic routes as well as indoors. Health measures were collected before cycling and 1–4 hr after the start of cycling. Ultrafine particles (UFPs; ≤ 0.1 μm in aerodynamic diameter), particulate matter ≤ 2.5 μm in aerodynamic diameter (PM2.5), black carbon, and volatile organic compounds were measured along each cycling route, and ambient nitrogen dioxide (NO2) and ozone (O3) levels were recorded from a fixed-site monitor. Mixed-effects models were used to estimate associations between air pollutants and changes in health outcome measures relative to precycling baseline values.Results: An interquartile range increase in UFP levels (18,200/cm3) was associated with a significant decrease in high-frequency power 4 hr after the start of cycling [β = –224 msec2; 95% confidence interval (CI), –386 to –63 msec2]. Ambient NO2 levels were inversely associated with the standard deviation of normal-to-normal (NN) intervals (β = –10 msec; 95% CI, –20 to –0.34 msec) and positively associated with the ratio of low-frequency to high-frequency power (β = 1.4; 95% CI, 0.35 to 2.5) 2 hr after the start of cycling. We also observed significant inverse associations between ambient O3 levels and the root mean square of successive differences in adjacent NN intervals 3 hr after the start of cycling.Conclusions: Short-term exposures to traffic pollution may contribute to altered autonomic modulation of the heart in the hours immediately after cycling.
Effect of quinidine on electrical and motor activity of canine small bowel.
Authors: J M Garrett, J F Schlegel, C F Code
Journal: Gut (1966)

EDITORIAL COMMENT This is a valuable contribution to knowledge of the way in which drugs may affect intestinal motility.A study on the effects of quinidine exemplifies the use of an elegant experimental technique in which the electrical activity in the wall of the gut, the intraluminal pressure, and the transit rate of intestinal contents are related.The results with quinidine are very interesting and further studies of this type should advance our understanding of gastrointestinal pharmacology.
Endoscopic Partial Resection of a Duodenal Duplication Cyst
Authors: S. Wada, T. Higashizawa, K. Tamada, T. Tomiyama, A. Ohashi, Y. Satoh, K. Sugano, H. Nagai
Journal: Endoscopy (2001)

A case of symptomatic duodenal duplication cyst is reported. The patient underwent endoscopic partial resection of the cystic wall using the O-ring ligation kit. After resection, the abdominal pain disappeared. Endoscopic partial resection is useful for diagnosis and treatment of duodenal duplication cyst.
Significance of Von Willebrand Factor in Septic and Nonseptic Patients with Acute Lung Injury
Authors: Lorraine B. Ware, Mark D. Eisner, B. Taylor Thompson, Polly E. Parsons, Michael A. Matthay
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

Systemic endothelial activation and injury are important causes of multiorgan system failure. We hypothesized that plasma levels of von Willebrand factor (VWF), a marker of endothelial activation and injury, would be associated with clinical outcomes in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). In 559 patients with ALI/ARDS enrolled in the National Heart, Lung, and Blood Institute ARDS Network trial of two VT strategies, plasma VWF levels were measured at randomization (mean 350 +/- 265% of normal control plasma) and Day 3 (344 +/- 207%). Baseline VWF levels were similar in patients with and without sepsis, and were significantly higher in nonsurvivors (435 +/- 333%) versus survivors (306 +/- 209%) even when controlling for severity of illness, sepsis, and ventilator strategy (increased odds ratio of death of 1.6 per SD size increase in VWF; 95% confidence interval, 1.4-2.1). Higher VWF levels were also significantly associated with fewer organ failure-free days. Ventilator strategy had no effect on VWF levels. In conclusion, the degree of endothelial activation and injury is strongly associated with outcomes in ALI/ARDS, regardless of the presence or absence of sepsis, and is not modulated by a protective ventilatory strategy. To improve outcomes further, new treatment strategies targeted at the endothelium should be investigated.
Functional diarrhoea: the acid test.
Authors: K W Heaton
Journal: BMJ (1985)

It is better for the patients if they are not singled out, sequestered, and so stigmatised.Similarly I doubt whether it is practical to have special nurses, some with psychiatric training, to look after them, or for specialist social workers to devote a substantial part oftheir time to such patients.On the other hand, the report gives sound advice on developing a network of medical, nursing, and social work services, including the primary health care team, to provide any necessary aftercare and follow up.This is where present arrangements are weakest.This sensible report takes account of the changing medical situation and advocates simple policies for seeing that patients are properly evaluated and treated.Purged of its overzealous organisational urgings, as it surely will be in practice, it deserves widespread support.I hope that it will come to be recognised that these patients need treatment not just to prevent later suicide but because they are presently distressed and suffering.
Surgical Treatment of Extracranial Arterial Occlusion
Authors: William S. Fields
Journal: JAMA (1971)

<h3>To the Editor.—</h3> Roth's evaluation of the paper concerning the results of surgical and nonsurgical treatment of carotid artery lesions is obviously carefully considered. As senior author of that publication, I must agree with him wholeheartedly in respect to his criticism. I would hasten, however, to point out two comments in the publication which he must have read but upon which he failed to remark. First, Patients subjected to surgery and surviving the risk of surgical mortality or completed stroke or both can not, therefore, be directly compared to patients never subjected to such risk. This is in part due to the so-called "harvesting effect" whereby those patients dying because of surgical challenge were, in fact, less able to withstand the special surgical stress than were the survivors. This effect may also relate to the spectrum of technical complications and uncertainities which are part of any surgical procedure. Since nonsurgically
Differential effects of BMI on diabetes risk among black and white Americans.
Authors: H E Resnick, P Valsania, J B Halter, X Lin
Journal: Diabetes Care (1998)

OBJECTIVE: To determine whether the associations of BMI and fat distribution with diabetes risk are modified by race. RESEARCH DESIGN AND METHODS: Data from the National Health and Nutrition Examination Survey, Epidemiologic Follow-up Study (1971-1992), were used to investigate potential interactions of BMI and fat distribution with race. Incident diabetes was defined by self-report of physician-diagnosed diabetes, hospital and nursing home discharge records, and death certificates. RESULTS: Among the 1,531 black and 9,852 white subjects who were nondiabetic at baseline, 1,139 (10.0%) developed diabetes during 20 years of follow-up. Although the cumulative risk of diabetes increased with baseline BMI in all four race-sex groups, the sex-specific odds ratios (ORs) for black:white subjects decreased with increasing BMI. In particular, for BMI of 22 kg/m2, the OR of diabetes for black:white individuals was 1.87 and 1.76 (P &amp;lt; 0.01) for men and women, respectively; for BMI of 32 kg/m2, the OR decreased to 0.99 and 1.20 (NS) for men and women, respectively. Skinfold ratio was also associated with increased diabetes risk in all race-sex groups, but did not modify the association between race and diabetes. CONCLUSIONS: These findings suggest that the effect of BMI on diabetes risk is different for black and white Americans, with a larger risk for blacks than whites at low BMI and an equivalent risk for both groups at high BMI. A lower degree of visceral adiposity among blacks at higher BMI or a greater impact of visceral adiposity among blacks at low BMI may help explain the interaction of race and BMI on diabetes risk.
Self poisoning by adolescents.
Authors: E. A. Procter
Journal: BMJ (1992)

Injuries sustained on "bouncy castles" SIR,-We wish to report the dangers of playing on "bouncy castles."A bouncy castle is an inflatable children's playground, consisting essentially of a rubber matress inflated with air.Three walls generally surround the castle, with the fourth side open to allow entry and exit, but some castles are open on all four sides.They are popular in fairgrounds and recreational halls.During last summer five children and one adult were treated at Northwick Park Hospital for injuries sustained while they were playing on bouncy castles.All injuries were to the arm or neck.Three supracondylar fractures of the humerus occurred.Two of these required open reduction and internal fixation with Kirschner wires.The third was managed with a collar and cuff support.A girl aged 6 sustained a fracture of the mid-shaft of the humerus, which was managed with a hanging cast support.The neck injuries occurred in a 52 year old man and a 12 year old boy.These were both soft tissue injuries caused by flexion and were managed conservatively.
Gun Carrying and Homicide Prevention
Authors: Lawrence W. Sherman
Journal: JAMA (2000)

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