tbuckley/cabot-search huggingface dataset:
Effect of glucose-insulin-potassium infusion on thallium myocardial clearance.
Authors: R A Wilson, R D Okada, H W Strauss, G M Pohost
Journal: Circulation (1983)

Factors influencing the rate of 201Tl clearance from the myocardium have not been clearly defined. This study determined the effect of an intravenous infusion of glucose-insulin-potassium (GIK) on the net 201Tl clearance rates from myocardium with and without initial 201Tl loading. Anesthetized open-chest dogs underwent 5 min of left anterior descending coronary artery occlusion and intravenous 201Tl was injected and the occlusion released 5 min later. Thirty minutes after 201Tl injection, 30 ml of either GIK (nine dogs) or saline (five dogs) was infused intravenously. The clearance rates of 201Tl from the anterior wall (without initial 201Tl loading) and from the posterior wall (with initial 201Tl loading) were monitored with miniaturized cadmium telluride detectors placed on the myocardium. Calculation of net myocardial clearance rates was performed by linear regression analysis from serial 1 min counts. Compared with saline infusion, GIK increased the net clearance of 201Tl from both myocardial regions with and without initial loading. The most marked change induced by GIK infusion was in the myocardial region without initial 201Tl loading; a net increase in 201Tl activity (72 +/- 42 cpm/30 min) was converted into a net loss (-594 +/- 228 cpm/30 min). There was no significant change in 201Tl clearance after the saline infusion. Heart rate, aortic and left atrial pressure, sonomicrometer-measured transmural myocardial wall thickness, microsphere-determined myocardial blood flow, and blood glucose and potassium concentrations did not change significantly during GIK or saline infusions. Thus, GIK infusion appears to increase net 201Tl clearance from myocardial zones with and without initial 201Tl loading.
Influence of a Functional Polymorphism Within the Promoter of the Serotonin Transporter Gene on the Effects of Total Sleep Deprivation in Bipolar Depression
Authors: Francesco Benedetti, Alessandro Serretti, Cristina Colombo, Euridice Campori, Barbara Barbini, Daniela di Bella, Enrico Smeraldi
Journal: American Journal of Psychiatry (1999)

OBJECTIVE: A functional polymorphism in the transcriptional control region upstream of the coding sequence of the 5-hydroxytryptamine transporter (5-HTT) has been reported. This polymorphism has been shown to influence the antidepressant response to fluvoxamine and paroxetine. The authors tested the hypothesis that the allelic variation of the 5-HTT-linked polymorphic region (5-HTTLPR) could influence the response of depressed patients to total sleep deprivation. METHOD: Sixty-eight drug-free inpatients with bipolar depression underwent a night of total sleep deprivation. 5-HTTLPR was genotyped in these patients. Changes in perceived mood were rated on a visual analogue scale and analyzed by using repeated measures analysis of covariance. RESULTS: Patients who were homozygotic for the long variant of 5-HTTLPR showed a significantly better mood amelioration after total sleep deprivation than those who were heterozygotic and homozygotic for the short variant. CONCLUSIONS: The influence of 5-HTTLPR on response to total sleep deprivation is similar to its observed influence on response to serotonergic drug treatments. This finding supports the hypothesis of a major role for serotonin in the mechanism of action of total sleep deprivation in depression.
Systemic inflammation, genetic susceptibility and lung function
Authors: J. Sunyer, R. Pistelli, E. Plana, M. Andreani, F. Baldari, M. Kolz, W. Koenig, J. Pekkanen, A. Peters, F. Forastiere
Journal: European Respiratory Journal (2008)

Local inflammation in airway diseases is well recognised, but less is known about the association between low-grade systemic inflammatory processes and lung function. The aim of the present study was to assess the association between inflammatory markers and lung function, taking into account polymorphisms in genes coding for inflammatory markers. In 134 post-myocardial infarction patients, six repeated measurements of C-reactive protein (CRP), interleukin (IL)-6 and fibrinogen in peripheral blood were assayed using high-sensitivity tests. Spirometry was conducted at baseline. Genotyping of single nucleotide polymorphisms was performed in genes coding for the inflammatory markers. CRP and IL-6 levels were negatively associated with forced expiratory volume in one second (FEV 1 ), forced vital capacity (FVC) and mean forced expiratory flow between 25 and 75% of FVC (FEF 25–75% ). In the CRP gene, both the polymorphism rs1205 and the haplotype 2 showed a protective association with FEV 1 and FEF 25–75% , and, to a lesser extent, with FVC. rs1205 and haplotype 2 were both negatively associated with CRP levels in peripheral blood. Analysis with instrumental variables also showed a protective effect between these CRP gene polymorphisms and lung function. Results are very suggestive that heritability of lung function is at least partly controlled by the CRP gene. Applying a Mendelian randomisation approach, the study supports a causal association between low-grade general inflammation and airway diseases.
Effects of anti-IgE in asthmatic subjects
Authors: A. J. Frew
Journal: Thorax (1998)

A humanized murine monoclonal antibody directed to the Fc epsilon R1- binding domain of human IgE (rhuMAb-E25) has been shown to inhibit the binding of IgE to mast cells without provoking mast cell activation. To examine the effects of neutralizing IgE on allergic airway responses, we assessed the effects of 9 wk of treatment with rhuMAb-E25 in a parallel group, randomized, double-blind, placebo-controlled study of 19 allergic asthmatic subjects. We found that treatment with rhuMAb-E25 reduced the serum IgE, increased the dose of allergen needed to provoke an early asthmatic response, reduced the mean maximal fall in FEV1 during the early response (30 +/- 10% at baseline to 18.8 +/- 8%, versus 33 +/- 8% at baseline to 34 +/- 4% after placebo; p = 0.01), and reduced the mean maximal fall in FEV1 during the late response (24 +/- 20% at baseline to 9 +/- 10% versus 20 +/- 17% at baseline to 18 +/- 17% after placebo; p = 0.047). We conclude that an anti-IgE monoclonal antibody, which inhibits binding of IgE to its receptor, suppresses the early- and late-phase responses to inhaled allergen in allergic asthmatic subjects. Targeting IgE with rhuMAb-E25 might be a useful treatment for allergic asthma.
Deletion of the Kinase Domain in Death-Associated Protein Kinase Attenuates Tubular Cell Apoptosis in Renal Ischemia-Reperfusion Injury
Authors: Masanori Kishino, Kazunori Yukawa, Katsuaki Hoshino, Akihiko Kimura, Nobuyuki Shirasawa, Haruhisa Otani, Tetsuji Tanaka, Kyoko Owada-Makabe, Yuji Tsubota, Masanobu Maeda, Masakazu Ichinose, Kiyoshi Takeda, Shizuo Akira, Masatoshi Mune
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. Death-associated protein kinase (DAPK) is a calcium/calmodulin-dependent serine/threonine kinase localized to renal tubular epithelial cells. To elucidate the contribution of DAPK activity to apoptosis in renal ischemia-reperfusion (IR) injury, wild-type (WT) mice and DAPK-mutant mice, which express a DAPK deletion mutant that lacks a portion of the kinase domain, were subjected to renal pedicle clamping and reperfusion. After IR, DAPK activity was elevated in WT kidneys but not in mutant kidneys (1785.7 ± 54.1 pmol/min/mg <i>versus</i> 160.7 ± 60.6 pmol/min/mg). Furthermore, there were more TUNEL-positive nuclei and activated caspase 3-positive cells in WT kidneys than in mutant kidneys after IR (24.0 ± 5.9 nuclei or 9.4 ± 0.6 cells per high-power field [HPF] <i>versus</i> 6.3 ± 2.2 nuclei or 4.4 ± 0.7 cells/HPF at 40 h after ischemia). In addition, the increase in p53-positive tubule cells after IR was greater in WT kidney than in mutant kidneys (9.9 ± 1.4 cells/HPF <i>versus</i> 0.8 ± 0.4 cells/HPF), which is consistent with the theory that DAPK activity stabilizes p53 protein. Finally, serum creatinine levels after IR were higher in WT mice than in mutant mice (2.54 ± 0.34 mg/dl <i>versus</i> 0.87 ± 0.24 mg/dl at 40 h after ischemia). Thus, these results indicate that deletion of the kinase domain from DAPK molecule can attenuate tubular cell apoptosis and renal dysfunction after IR injury.
Primary pulmonary nocardiosis: case report
Authors: P. B. Hamal
Journal: Thorax (1974)

<b>Hamal, P. B. (1974).</b><i>Thorax</i>, <b>29</b>, 382-386. <b>Primary pulmonary nocardiosis: a case report.</b> A case of fulminating pulmonary nocardiosis is reported. Diagnosis was made before death but too late for treatment to be effective. At necropsy extensive multiple pulmonary abscesses with involvement of the pleura, resulting in an empyema, were discovered. One cervical node showed a similar abscess. No brain lesions nor involvement of other organs was seen. Gram-positive organisms were seen in the lesions but acid-fastness could not be demonstrated.
The Interim Analysis of the Optima (observation of GPI-anchored protein-deficient [PNH-type]) Cells in Japanese Patients with Bone Marrow Failure Syndrome and in Those Suspected of Having PNH) Study
Authors: Hideyoshi Noji, Tsutomu Shichishima, Chiharu Sugimori, Naoshi Obara, Kohei Hosokawa, Shigeru Chiba, Yoshihiko Nakamura, Kiyoshi Ando, Satoru Hayashi, Yuji Yonemura, Tatsuya Kawaguchi, Haruhiko Ninomiya, Jun-ichi Nishimura, Yuzuru Kanakura, Shinji Nakao
Journal: Blood (2014)
CPAP, Weight Loss, or Both for Obstructive Sleep Apnea
Authors: Julio A. Chirinos, Indira Gurubhagavatula, Karen Teff, Daniel J. Rader, Thomas A. Wadden, Raymond Townsend, Gary D. Foster, Greg Maislin, Hassam Saif, Preston Broderick, Jesse Chittams, Alexandra L. Hanlon, Allan I. Pack
Journal: New England Journal of Medicine (2014)

Obesity and obstructive sleep apnea tend to coexist and are associated with inflammation, insulin resistance, dyslipidemia, and high blood pressure, but their causal relation to these abnormalities is unclear.We randomly assigned 181 patients with obesity, moderate-to-severe obstructive sleep apnea, and serum levels of C-reactive protein (CRP) greater than 1.0 mg per liter to receive treatment with continuous positive airway pressure (CPAP), a weight-loss intervention, or CPAP plus a weight-loss intervention for 24 weeks. We assessed the incremental effect of the combined interventions over each one alone on the CRP level (the primary end point), insulin sensitivity, lipid levels, and blood pressure.Among the 146 participants for whom there were follow-up data, those assigned to weight loss only and those assigned to the combined interventions had reductions in CRP levels, insulin resistance, and serum triglyceride levels. None of these changes were observed in the group receiving CPAP alone. Blood pressure was reduced in all three groups. No significant incremental effect on CRP levels was found for the combined interventions as compared with either weight loss or CPAP alone. Reductions in insulin resistance and serum triglyceride levels were greater in the combined-intervention group than in the group receiving CPAP only, but there were no significant differences in these values between the combined-intervention group and the weight-loss group. In per-protocol analyses, which included 90 participants who met prespecified criteria for adherence, the combined interventions resulted in a larger reduction in systolic blood pressure and mean arterial pressure than did either CPAP or weight loss alone.In adults with obesity and obstructive sleep apnea, CPAP combined with a weight-loss intervention did not reduce CRP levels more than either intervention alone. In secondary analyses, weight loss provided an incremental reduction in insulin resistance and serum triglyceride levels when combined with CPAP. In addition, adherence to a regimen of weight loss and CPAP may result in incremental reductions in blood pressure as compared with either intervention alone. (Funded by the National Heart, Lung, and Blood Institute; ClinicalTrials.gov number, NCT0371293 .).
JNK inhibition sensitises hepatocellular carcinoma cells but not normal hepatocytes to the TNF-related apoptosis-inducing ligand
Authors: S R Mucha, A Rizzani, A L Gerbes, P Camaj, W E Thasler, C J Bruns, S T Eichhorst, E Gallmeier, F T Kolligs, B Goke, E N De Toni
Journal: Gut (2008)

<h3>Background:</h3> cJun terminal kinase (JNK) is constitutively activated in most hepatocellular carcinomas (HCCs), yet its exact role in carcinogenesis remains controversial. While tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is known as a major mediator of acquired immune tumour surveillance, and is currently being tested in clinical trials as a novel cancer therapy, the resistance of many tumours to TRAIL and concerns about its toxicity in vivo represent obstacles to its clinical application. In this study we investigated whether JNK activity in HCC could contribute to the resistance to apoptosis in these tumours. <h3>Methods:</h3> The effect of JNK/Jun inhibition on receptor-mediated apoptosis was analysed by pharmacological inhibition or RNA interference in cancer cells and non-tumour cells isolated from human liver or transgenic mice lacking a phosphorylation site for Jun. <h3>Results:</h3> JNK inhibition caused cell cycle arrest, enhanced caspase recruitment, and greatly sensitised HCC cells but not normal hepatocytes to TRAIL. TRAIL-induced activation of JNK could be effectively interrupted by administration of the JNK inhibitor SP600125. <h3>Conclusions:</h3> Expression and TRAIL-dependent feedback activation of JNK likely represent a mechanism by which cancer cells escape TRAIL-mediated tumour surveillance. JNK inhibition might represent a novel strategy for specifically sensitising HCC cells to TRAIL thus opening promising therapeutic perspectives for safe and effective use of TRAIL in cancer treatment.
Recombinant human DNase I in cystic fibrosis patients with severe pulmonary disease: a short-term, double-blind study followed by six months open-label treatment
Authors: PI Shah, A Bush, GJ Canny, AA Colin, HJ Fuchs, DM Geddes, CA Johnson, MC Light, SF Scott, DE Tullis, al. et
Journal: European Respiratory Journal (1995)

Chronic pulmonary infection is the major cause of morbidity and mortality in cystic fibrosis (CF). Recombinant human deoxyribonuclease (rhDNase) in vitro has been shown to dramatically reduce the viscoelasticity of the sputum from CF patients. Phase II and III clinical trials have shown the drug to be safe, and that patients with a forced vital capacity (FVC) of > 40% predicted show an improvement in pulmonary function when receiving rhDNase. The current study evaluates the safety and efficacy of rhDNase in the most severly ill CF patients (FVC < 40% predicted). A double-blind, randomized, placebo-controlled trial in which patients received either 2.5 mg rhDNase twice daily or placebo for a period of 14 days followed by a 6 month open extension period (OEP) is reported. Seventy patients were recruited for the double-blind study, and 64 entered the OEP of whom 38 completed. During the OEP, all patients received 2.5 mg rhDNase twice daily. In both the double-blind period and the OEP the drug appeared to be safe. During the double-blind study, forced expiratory volume in one second (FEV1) and FVC improved in both groups but there was no statistically significant difference between the groups. In the OEP, there was mean improvement in percentage predicted FEV1 and FVC, 9 and 18%, respectively, for all patients participating. In conclusion, DNase is safe when administered in conjunction with a rigorous regimen of chest physiotherapy to severely ill patients (FVC < 40% predicted) with CF. The double-blind, 14 day study showed no significant improvement in pulmonary function but some patients may have improved after longer administration of rhDNase.
Let's stop consenting patients
Authors: D. K. Sokol
Journal: BMJ (2014)

The term negatively affects how clinicians perceive consent



A patient who underwent an unsuccessful operation claimed that the surgeon did not obtain valid consent—that he booked her in for surgery without mentioning the less invasive alternatives. In another consent case, Birch v University College Hospital, the patient was informed of the risks of the catheter angiography that led to her stroke but not the comparative risks of magnetic resonance imaging.1 The clinicians were found negligent for failing to do so. I have elsewhere mentioned the usefulness of a consent acronym popular in some US hospitals: PARQ. It stands for “procedure” (what it entails), “alternatives” (including doing nothing), “risks” (of the procedure and the alternatives), and “questions” (invite the patient to ask questions).2 In these hospitals clinicians write “PARQ” in the notes to show that they have considered each element.

In the first case above the medical notes suggested that …
Relationship Between Coronary Microvascular Dysfunction and Cardiac Energetics Impairment in Type 1 Diabetes Mellitus
Authors: G. Nallur Shivu, T.T. Phan, K. Abozguia, I. Ahmed, A. Wagenmakers, A. Henning, P. Narendran, M. Stevens, M. Frenneaux
Journal: Circulation (2010)

Asymptomatic subjects with diabetes mellitus have an impaired cardiac energetics status that may play a significant role in the development of heart failure. In the present study, we assessed the role of microvascular dysfunction in the development of impaired cardiac energetics in subjects with type 1 diabetes mellitus.Twenty-five asymptomatic subjects with type 1 diabetes mellitus (mean age +/-1 SD 33+/-8 years) and 26 age-, sex-, and body mass index-matched healthy control subjects (32+/-8 years old) were recruited into the study. The type 1 diabetes mellitus subjects were divided into 2 age-matched groups (newly diagnosed [<5 years] and longer-duration [>10 years] diabetes) to assess the impact of microvascular disease. All subjects had an echocardiogram and an exercise ECG performed, followed by magnetic resonance spectroscopy and stress magnetic resonance imaging. Compared with healthy control subjects, the phosphocreatine/gamma-ATP ratio was reduced significantly both in subjects with longer-term (2.1+/-0.5 versus 1.5+/-0.4, P<0.000) and newly diagnosed (2.1+/-0.5 versus 1.6+/-0.2, P<0.000) diabetes. The phosphocreatine/gamma-ATP ratio was similar in newly diagnosed diabetes subjects and those with longer-term disease (1.6+/-0.2 versus 1.5+/-0.4, P=0.32). The mean myocardial perfusion reserve index in the longer-term type 1 diabetes mellitus subjects was significantly lower than in healthy control subjects (1.7+/-0.6 versus 2.3+/-0.4, P=0.005). On univariate analysis, there was no significant correlation of phosphocreatine/gamma-ATP ratio with myocardial perfusion reserve index (r=0.21, P=0.26).We demonstrate that young subjects with uncomplicated type 1 diabetes mellitus have impaired myocardial energetics irrespective of the duration of diabetes and that the impaired cardiac energetics status is independent of coronary microvascular function. We postulate that impairment of cardiac energetics in these subjects primarily results from metabolic dysfunction rather than microvascular impairment.
Relation between hospital orthopaedic specialisation and outcomes in patients aged 65 and older: retrospective analysis of US Medicare data
Authors: T. P Hagen, M. S Vaughan-Sarrazin, P. Cram
Journal: BMJ (2010)

To explore the relation between hospital orthopaedic specialisation and postoperative outcomes after total hip or knee replacement surgery.Retrospective analysis of US Medicare data, 2001-5.3818 US hospitals carrying out total joint replacement. Population 1 273 081 Medicare beneficiaries age 65 and older who underwent primary or revision hip or knee replacement.Hospitals were stratified into fifths on the basis of their degree of orthopaedic specialisation (lowest fifth, least specialised; highest fifth, most specialised). The primary outcome was defined as a composite representing the occurrence of one or more of pulmonary embolism, deep vein thrombosis, haemorrhage, infection, myocardial infarction, or death within 90 days of the index surgery.As hospital orthopaedic specialisation increased from the lowest fifth to highest fifth, the proportion of people admitted who were women or black, or who had diabetes or heart failure progressively decreased (P<0.001), whereas procedural volume increased. Compared with the most specialised hospitals (highest fifth), after adjustment for patient characteristics and hospital volume, the odds of adverse outcomes increased progressively with decreased hospital specialisation: lowest fifth (odds ratio 1.59, 95% confidence interval 1.53 to 1.65), second fifth (1.32, 1.28 to 1.36), third fifth (1.24, 1.21 to 1.28), and fourth fifth (1.10, 1.07 to 1.13).Increased hospital orthopaedic specialisation is associated with improved patient outcomes after adjusting for both patient characteristics and hospital procedural volume. These results should be interpreted with caution because the possibility that other unmeasured confounders related to socioeconomic status or different factors are responsible for the improved patient outcomes rather than hospital specialisation can not be excluded. The findings suggest that hospital specialisation may capture different components of hospital quality than the components captured by hospital volume.
Nephronophthisis-Associated Ciliopathies
Authors: Friedhelm Hildebrandt, Weibin Zhou
Journal: Journal of the American Society of Nephrology (2007)

Nephronophthisis (NPHP), an autosomal recessive cystic kidney disease, represents the most frequent genetic cause of end-stage kidney disease in the first three decades of life. Contrary to polycystic kidney disease, NPHP shows normal or diminished kidney size, cysts are concentrated at the corticomedullary junction, and tubulointerstitial fibrosis is dominant. NPHP can be associated with retinitis pigmentosa (Senior-Løken syndrome), liver fibrosis, and cerebellar vermis aplasia (Joubert syndrome) in approximately 10% of patients. Positional cloning of six novel genes (NPHP1 through 6) as mutated in NPHP and functional characterization of their encoded proteins have contributed to the concept of "ciliopathies." It has helped advance a new unifying theory of cystic kidney diseases. This theory states that the products of all genes that are mutated in cystic kidney diseases in humans, mice, or zebrafish are expressed in primary cilia or centrosomes of renal epithelial cells. Primary cilia are sensory organelles that connect mechanosensory, visual, osmotic, and other stimuli to mechanisms of cell-cycle control and epithelial cell polarity. The ciliary theory explains the multiple organ involvement in NPHP regarding retinitis pigmentosa, liver fibrosis, ataxia, situs inversus, and mental retardation. Mutations in NPHP genes cause defects in signaling mechanisms, including the noncanonical Wnt signaling pathway. The "ciliopathy" NPHP thereby is caused by defects in tissue differentiation and maintenance as a result of impaired processing of extracellular cues. Nephrocystins, the proteins that are encoded by NPHP genes, are highly conserved in evolution. Positional cloning of additional causative genes of NPHP will elucidate further signaling mechanisms that are involved, thereby establishing therapeutic approaches using animal models in mouse, zebrafish, and Caenorhabditis elegans.