tbuckley/cabot-search huggingface dataset:
Levels of Hematopoiesis Inhibitor <i>N</i> -Acetyl-Seryl-Aspartyl-Lysyl-Proline Partially Explain the Occurrence of Anemia in Heart Failure
Authors: Peter van der Meer, Erik Lipsic, B. Daan Westenbrink, Ruud M.A. van de Wal, Regien G. Schoemaker, Edo Vellenga, Dirk J. van Veldhuisen, Adriaan A. Voors, Wiek H. van Gilst
Journal: Circulation (2005)

Background— Anemia is common in patients with chronic heart failure (CHF) and is associated with a poor prognosis. However, only a minority of patients with CHF have impaired renal function or underlying hematinic deficiencies. It has been shown that inhibition of the renin-angiotensin system is associated with the development of anemia. The aim of the present study was to determine possible mechanisms linking anemia to renin-angiotensin system activity in CHF patients. Methods and Results— We initially evaluated 98 patients with advanced stable CHF who were treated with ACE inhibitors (left ventricular ejection fraction, 28±1%; age, 69±1 years; 80% male), 10 of whom had an unexplained anemia (normal hematinics and no renal failure). These 10 anemic patients were matched with 10 nonanemic patients in terms of age and left ventricular ejection fraction. Serum ACE activity was 73% lower in anemic CHF patients compared with nonanemic CHF patients ( P =0.018). Moreover, serum of these patients inhibited in vitro the proliferation of bone marrow–derived erythropoietic progenitor cells of healthy donors by 17% ( P =0.003). Levels of the hematopoiesis inhibitor N -acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP), which is almost exclusively degraded by ACE, were significantly higher in anemic CHF patients and were clearly correlated to erythroid progenitor cell proliferation ( r =−0.64, P =0.001). Conclusions— Serum ACE activity is markedly lower in anemic CHF patients, and serum of these patients inhibits hematopoiesis. The clear correlation between Ac-SDKP and proliferation of erythroid progenitor cells suggests an inhibitory role of Ac-SDKP on hematopoiesis in CHF patients, which may explain the observed anemia in patients treated with ACE inhibitors.
Relation between α , β , and γ Human Amiloride– Sensitive Epithelial Na<sup>+</sup> Channel mRNA Levels and Nasal Epithelial Potential Difference in Healthy Men
Authors: GAIL OTULAKOWSKI, SUSANNE FLUECKIGER-STAUB, LYNDA ELLIS, KUMAR RAMLALL, OLIVIER STAUB, DAVID SMITH, PETER DURIE, HUGH O'BRODOVICH
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

To analyze messenger RNA (mRNA) levels for the α , β , and γ subunits of the human amiloride–sensitive epithelial Na+ channel (hENaC) in respiratory epithelia, we developed a competitive quantitative reverse transcriptase–polymerase chain reaction (QRT–PCR) assay specific for each subunit, using two human respiratory epithelial-cell lines. We next determined the relation between hENaC mRNA levels and the biologic activity of the hENaC in the respiratory epithelium of eight normal men. The electrical potential difference (PD) between the epithelium of the inferior nasal turbinate and the subcutaneous space was measured, using control and amiloride (100 μ M) solutions. QRT–PCR measurement of hENaC-subunit mRNAs and epithelial-specific cytokeratin 18 mRNA allowed us to normalize hENaC expression to epithelial-cell RNA. Respective values for α , β , and γ hENaC mRNA levels in epithelium obtained at the site of maximal PD were 39 ± 4.0, 7.5 ± 0.92, and 1.8 ± 0.25 attomol/fmol cytokeratin mRNA, respectively. Respiratory epithelial PD exhibited a significant negative correlation with γ hENaC (r2 = 0.72, p < 0.01), tended to increase with increasing α hENaC, and was unaffected by β hENaC mRNA levels. Our results suggest that hENaC activity in vivo is influenced by expression of the gene for γ hENaC. The assay used in the study provides a useful tool for evaluating Na+-channel expression in clinically relevant patient populations.
Regional Variation in Cardiovascular Disease Risk Factors Among American Indians and Alaska Natives With Diabetes
Authors: Stephen J. Rith-Najarian, Dorothy M. Gohdes, Raymond Shields, Betty Skipper, Kelly R. Moore, Bernadine Tolbert, Terry Raymer, Kelly J. Acton
Journal: Diabetes Care (2002)

To compare by region risk factors for cardiovascular disease among American Indian populations with diabetes.Trained providers from 185 federal, urban, and tribally operated facilities reviewed the records from systematic random samples of the patients included in the local diabetes registries in the 1998 Indian Health Service (IHS) Diabetes Care and Outcomes Audit. Selected measures of cardiovascular risk were aggregated by region and adjusted to calculate regional rates for patients <45 years of age (n = 2,595) and those aged > or =45 years (n = 8,294).Among the younger group of patients with diabetes, the rates of elevated HbA(1c) (> or =9%) and tobacco use varied significantly among regions. High rates of obesity (78%) and elevated HbA(1c) (56%) were found in the Southwest. High rates of tobacco use (55%) but the lowest rates of elevated HbA(1c) (27%) were found in Alaska. Among patients aged > or =45 years, all measures including rates of proteinuria, cholesterol > or =200 mg/dl, and mean blood pressure > or =130/85 varied significantly among all regions. Tobacco use was highest in the Great Lakes (44%) and Great Plains (42%) regions and lowest in the Southwest (14%) and Colorado Plateau (8%) regions. Proteinuria was found most frequently in the Southwest (35%), Colorado Plateau (30%), and Pacific regions (35%). Older individuals with diabetes were more likely than younger individuals to have proteinuria and blood pressure > or =130/85.American Indians and Alaska Natives with diabetes carry a large burden of potentially modifiable cardiovascular risk factors, but there is significant regional variation.
Changes in blood supplies, regulations, and transfusion practice
Authors: J Adrian Copplestone
Journal: BMJ (2005)

Clinicians need to prepare for shortages now 

In the United Kingdom, we have come to take for granted the supply of blood for transfusion. Changes that might reduce the supply of blood are afoot and are going to affect all clinicians who use blood and blood products. We need to act now to decrease our dependence or we will be faced with deciding which patient is going to get the remaining bag of blood in the blood fridge—with all the clinical and ethical problems that will ensue. I outline why blood shortages may occur and describe some simple methods to avoid the use of donor blood.

A second possible case of variant Creutzfeldt-Jakob disease (vCJD) transmitted by transfusion has been reported,1 leading to further tightening of the exclusion of blood donors who may have had a transfusion since 1980. These restrictions have reduced the number of donors and total number of red cell donations. This comes on top of a general trend of falling numbers of donors.2 The Department of Health has recently circulated a plan for the management of shortages in case blood supplies run low.3 Hospitals will need …
Failure of Nissen fundoplication in chronic cough: Evidence for gaseous reflux
Authors: Dejene Shiferaw, Warren Jackson, Jennifer M. Burke, Jaymin B. Morjaria, Alyn H. Morice
Journal: European Respiratory Journal (2012)

Introduction:

Accurate diagnosis and management of airway reflux induced chronic cough is challenging. Nissen Fundoplication (NF) is a recognised treatment option for patients who fail medical treatment. Unfortunately some patients continue to be symptomatic even after NF.

Aim:

To assess pharyngeal gaseous pH in patients who failed to respond to NF

Methods:

Retrospective case review of 22 patients who remained symptomatic post NF at Castle Hill Hospital, UK. All subjects had pre-NF oesophageal manometery, 24 hours ambulatory PH monitoring and a post -NF airway pH measurement using Restech Dx-pH measurement system. Some of these patients had follow up 24 hour ambulatory PH monitoring.

Results:

Total of 22 patients (18 female) with a mean age of 45(range22-72) constituted the study population. All of these patients continued to have troublesome cough evidenced by a high Hull Cough Hypersensitivity Score with a mean score of 39(range 25-66), normal < 12.

15(68%) of these patients had an abnormal airway pH study with a mean upright Ryan score of 145(range17.72-573.46), normal < 9.41. All of the 7 patients who had 24 hour oesophageal pH monitoring had a normal DeMeester score with a mean of 3.47(range0.5-11.7), normal < 14.72.Out of the 7 with normal DeMeester 5 had an abnormal airway PH with a mean Ryan score of 175.28(range17.5-573.46).

Conclusion:

The data suggest that NF eliminated significant acid liquid reflux. A significant proportion of patients continued to have airway gaseous reflux as evidenced by a positive Ryan score. This implies that the aetiology of chronic cough lies in impaction of gaseous reflux in the pharynx and upper airways rather than the liquid reflux detected on conventional testing.
Bone-patellar tendon-bone autografts versus hamstring autografts for reconstruction of anterior cruciate ligament: meta-analysis
Authors: David J Biau, Caroline Tournoux, Sandrine Katsahian, Peter J Schranz, Rémy S Nizard
Journal: BMJ (2006)

<h3>Abstract</h3> <b>Objectives</b> To compare bone-patellar tendon-bone autografts with hamstring autografts for reconstruction of the anterior cruciate ligament. <b>Data sources</b> Medline, WebSPIRS, Science Citation Index, Current Contents databases, and Cochrane Central Register of Controlled Trials. <b>Review methods</b> All randomised controlled trials reporting one or more outcome related to stability (instrumented measurement of knee laxity, Lachman test, or pivot shift test) and morbidity (anterior knee pain, kneeling test, loss of extension, or graft failure). Study quality was assessed by using a 5 point scale. Random effect models were used to pool the data. Heterogeneity in the effect of treatment was tested on the basis of study quality, randomisation status, and number of tendon strands used. <b>Results</b> 24 trials of 18 cohorts (1512 patients) met the inclusion criteria. Study quality was poor for nine studies and fair for nine studies. The weighted mean difference of the instrumented measurement of knee laxity was 0.36 (95% confidence interval 0.01 to 0.71; P = 0.04). Relative risk of a positive Lachman test was 1.22 (1.01 to 1.47; P = 0.04), of anterior knee pain 0.57 (0.44 to 0.74; P &lt; 0.0001), of a positive kneeling test 0.26 (0.14 to 0.48; P &lt; 0.0001), and of loss of extension 0.52 (0.34 to 0.80; P = 0.003). Other results were not significant. <b>Conclusion</b> Morbidity was lower for hamstring autografts than for patellar tendon autografts. Evidence that patellar tendon autografts offer better stability was weak. The poor quality of the studies calls into question the robustness of the analyses.
The STRIDE Weight Loss and Lifestyle Intervention for Individuals Taking Antipsychotic Medications: A Randomized Trial
Authors: Carla A. Green, Bobbi Jo H. Yarborough, Michael C. Leo, Micah T. Yarborough, Scott P. Stumbo, Shannon L. Janoff, Nancy A. Perrin, Greg A. Nichols, Victor J. Stevens
Journal: American Journal of Psychiatry (2014)

Objectives: The STRIDE study assessed whether a lifestyle intervention, tailored for individuals with serious mental illnesses, reduced weight and diabetes risk. The authors hypothesized that the STRIDE intervention would be more effective than usual care in reducing weight and improving glucose metabolism. Method: The study design was a multisite, parallel two-arm randomized controlled trial in community settings and an integrated health plan. Participants who met inclusion criteria were ≥18 years old, were taking antipsychotic agents for ≥30 days, and had a body mass index ≥27. Exclusions were significant cognitive impairment, pregnancy/breastfeeding, recent psychiatric hospitalization, bariatric surgery, cancer, heart attack, or stroke. The intervention emphasized moderate caloric reduction, the DASH (Dietary Approaches to Stop Hypertension) diet, and physical activity. Blinded staff collected data at baseline, 6 months, and 12 months. Results: Participants (men, N=56; women, N=144; mean age=47.2 years [SD=10.6]) were randomly assigned to usual care (N=96) or a 6-month weekly group intervention plus six monthly maintenance sessions (N=104). A total of 181 participants (90.5%) completed 6-month assessments, and 170 (85%) completed 12-month assessments, without differential attrition. Participants attended 14.5 of 24 sessions over 6 months. Intent-to-treat analyses revealed that intervention participants lost 4.4 kg more than control participants from baseline to 6 months (95% CI=–6.96 kg to –1.78 kg) and 2.6 kg more than control participants from baseline to 12 months (95% CI=–5.14 kg to –0.07 kg). At 12 months, fasting glucose levels in the control group had increased from 106.0 mg/dL to 109.5 mg/dL and decreased in the intervention group from 106.3 mg/dL to 100.4 mg/dL. No serious adverse events were study-related; medical hospitalizations were reduced in the intervention group (6.7%) compared with the control group (18.8%). Conclusions: Individuals taking antipsychotic medications can lose weight and improve fasting glucose levels. Increasing reach of the intervention is an important future step.
Bisphosphonates for Treatment and Prevention of Bone Metastases
Authors: M. Dror Michaelson, Matthew R. Smith
Journal: Journal of Clinical Oncology (2005)

Bone metastases are a major cause of morbidity for men with prostate cancer. Complications of bone metastases include pain, fractures, and spinal cord compression. Although they appear osteoblastic by radiographic imaging, most bone metastases are characterized by excess osteoclast number and activity. In addition, pathologic osteoclast activation is associated with increased risk of skeletal complications. Zoledronic acid, a potent inhibitor of osteoclast activity, differentiation, and survival, decreases the risk of skeletal complications in men with androgen-independent prostate cancer and bone metastases. Other bisphosphonates, including pamidronate and clodronate, seem to be ineffective in this setting. The reduction in risk of skeletal complications with zoledronic acid must be weighed against potential adverse effects. Additional studies are needed to determine the optimal timing, schedule, and duration of treatment in men with bone metastases as well as the potential role of bisphosphonates in other settings including the prevention of bone metastases.
Exploring the unknown: assumptions about allelic architecture and strategies for susceptibility variant discovery
Authors: Mark I McCarthy
Journal: Genome Medicine (2009)

Identification of common-variant associations for many common disorders has been highly effective, but the loci detected so far typically explain only a small proportion of the genetic predisposition to disease. Extending explained genetic variance is one of the major near-term goals of human genetic research. Next-generation sequencing technologies offer great promise, but optimal strategies for their deployment remain uncertain, not least because we lack a clear view of the characteristics of the variants being sought. Here, I discuss what can and cannot be inferred about complex trait disease architecture from the information currently available and review the implications for future research strategies.
Superficial Thrombophlebitis Followed by Pulmonary Embolism
Authors: A Huang, K S Hindle
Journal: Journal of the Royal Society of Medicine (2001)

Dr Kesteven and Mr Robinson (April 2001 JRSM, pp. 186-187) suggest that anticoagulation may provide symptomatic relief for acute thrombophlebitis but there is no evidence to support this. Although Hirudoid cream and piroxicam gel appear to be ineffective as analgesics1, non-steroidal anti-inflammatory drugs may be beneficial2. More important is the prevention of extension by the thrombus into the deep veins and hence the risks of pulmonary embolism and post-thrombotic leg syndrome. Early ligation of the affected vein with removal of all phlebitic veins may prevent proximal extension, especially when the thrombus is near the saphenofemoral junction3. Furthermore, this is as effective as long-term anticoagulation in preventing deep venous thrombosis4 and may be considered in those who would otherwise find prolonged anticoagulation treatment and monitoring difficult.
Effect of inhaled frusemide and oral indomethacin on the airway response to hypertonic saline challenge in asthmatic subjects
Authors: L. T. Rodwell, S. D. Anderson, J. Spring, S. Mohamed, J. P. Seale
Journal: Thorax (1997)

BACKGROUND: Inhaled frusemide inhibits airway narrowing and causes a transient increase in forced expiratory volume in one second (FEV1) during hypertonic saline challenge. This inhibitory effect could be secondary to prostaglandin release during challenge. The involvement of prostaglandins in the inhibitory action of frusemide during challenge with 4.5% NaCl was investigated by premedicating with indomethacin, a prostaglandin synthetase inhibitor. METHODS: Fourteen asthmatic subjects (eight women) aged 26.6 (range 18-56) years participated in a double blind, placebo controlled, crossover study. The subjects attended five times and inhaled 4.5% NaCl for 0.5, 0.75, 1, 1.5, 2, 4, 8, 8, and 8 minutes, or part thereof, or until a provocative dose causing a 20% fall in FEV1 (PD20 FEV1) was recorded. Indomethacin (100 mg/day) or placebo were taken three days before all visits, except control day. The FEV1 was measured and frusemide (38.0 (6.4) mg, pH = 9) or vehicle (0.9% NaCl, pH = 9) were inhaled 10 minutes before the challenge. Bronchodilation was calculated as the percentage rise in FEV1 from the prechallenge FEV1 to the highest FEV1 recorded during the challenge. RESULTS: Frusemide caused a fold increase in PD20 FEV1 compared with the vehicle which was similar in the presence of both indomethacin and placebo (3.7 (95% CI 2.0 to 7.3) versus 3.3 (2.0 to 5.4)). Frusemide, but not vehicle, also caused a transient percentage rise in FEV1 during challenge with 4.5% NaCl which was not blocked by indomethacin (3.6% (1.2 to 6.0)) or placebo (3.1% (1.0 to 5.2)). CONCLUSIONS: Inhaled frusemide inhibited airway narrowing and caused a transient increase in FEV1 during challenge with 4.5% NaCl. These effects were not blocked by indomethacin, which suggests that the inhibitory action of frusemide is not secondary to prostaglandin release.
Plasma Chemokines in Early Wheezers Predict the Development of Allergic Asthma
Authors: Lieke L. Reubsaet, Jenny Meerding, Wilco de Jager, Isme M. de Kleer, Maarten O. Hoekstra, Berent J. Prakken, Femke van Wijk, Hubertus G. Arets
Journal: American Journal of Respiratory and Critical Care Medicine (2013)
Plasma concentrations of fluticasone propionate and budesonide following inhalation from dry powder inhalers by healthy and asthmatic subjects
Authors: T W Harrison
Journal: Thorax (2003)

<b>Background:</b> All currently available inhaled corticosteroids reach the systemic circulation and have the potential to produce adverse effects with long term use. This risk is often assessed by measuring the effect of different inhaled corticosteroids on the hypothalamic-pituitary-adrenal (HPA) axis in healthy subjects. Absorption of fluticasone propionate and its effects on the HPA axis are greater in healthy subjects than in subjects with moderately severe asthma, but we have failed to show any difference in morning budesonide plasma levels or systemic effects between healthy and asthmatic subjects following inhalation of budesonide. To provide more information on the absorption of fluticasone propionate and budesonide, we have compared the plasma levels of both drugs over 8 hours in healthy and asthmatic subjects. <b>Methods:</b> The area under the plasma concentration-time curves (AUC) and the maximum concentration (Cmax) of fluticasone propionate and budesonide after a single inhaled dose of each drug were compared in 12 healthy control subjects and 12 subjects with moderately severe asthma. <b>Results:</b> Peak plasma levels of budesonide occurred much earlier and were approximately 20-fold higher than those of fluticasone propionate in both healthy and asthmatic subjects. The AUC and Cmax for fluticasone propionate were lower by 307 (95% CI 62 to 522) pg/ml/h or 43% (p=0.02) and 52 (95% CI –11 to 115) pg/ml or 39% (p=0.1) in subjects with asthma compared with healthy control subjects. In contrast, the AUC and Cmax for budesonide were almost identical between the two groups (mean differences 826 (95% CI –1493 to 3143) pg/ml/h (p=0.5) and 157 (95% CI –1026 to 1339) pg/ml (p=0.8). <b>Conclusions:</b> Following inhalation, healthy subjects have higher plasma levels of fluticasone propionate than subjects with asthma whereas budesonide plasma levels are similar in the two groups of subjects. Comparing the systemic effects of budesonide and fluticasone propionate in healthy subjects is unlikely to be relevant to subjects with asthma.
Early Growth in Offspring of Diabetic Mothers
Authors: Leslie Touger, Helen C. Looker, Jonathan Krakoff, Robert S. Lindsay, Valerie Cook, William C. Knowler
Journal: Diabetes Care (2005)

OBJECTIVE—By age 5 years, offspring of diabetic mothers (ODMs) are heavier and have altered glucose metabolism compared with offspring of mothers without diabetes (non-DMs). This study evaluates the growth pattern of ODMs before the age of 5 years. RESEARCH DESIGN AND METHODS—Anthropometric measures (z scores) from birth, 1.5 years, and 7.7 years in Pima Indian children were compared by maternal diabetes status. RESULTS—After adjustment for earlier gestational age at delivery (37.8 vs. 39.3 weeks, P &amp;lt; 0.01), ODMs were heavier at birth (z score birth weight 0.49 vs. −0.04, P &amp;lt; 0.01) than non-DMs. At age 1.5 years, ODMs were shorter than the non-DMs (z score = −0.24 vs. 0.12, P &amp;lt; 0.01) but their weight and relative weight (RW; weight adjusted for age, sex, and length or height) were similar. From birth to 1.5 years, ODMs showed significant “catch down” of weight compared with non-DMs (change in weight z score from birth to 1.5 years of ODMs and non-DMs was −0.56 and 0.12, respectively, P &amp;lt; 0.01). By age 7.7 years, ODMs were heavier (weight z score 0.89 vs. −0.07, P &amp;lt; 0.01) but had similar height as non-DMs. Differences in glucose and insulin concentrations at age 7.7 years were dependent on RW. CONCLUSIONS—ODMs had a dramatically different growth pattern from that of non-DMs. Gestational age–adjusted birth weight was higher. During the first 1.5 postnatal years, the change in weight z score and attained height were reduced. Subsequently, height caught up to that of non-DMs, while weight gain greatly exceeded that of non-DMs.