tbuckley/cabot-search huggingface dataset:
Quantitative Computed Tomography Measures of Emphysema and Airway Wall Thickness Are Related to Respiratory Symptoms
Authors: Thomas B. Grydeland, Asger Dirksen, Harvey O. Coxson, Tomas M. L. Eagan, Einar Thorsen, Sreekumar G. Pillai, Sanjay Sharma, Geir Egil Eide, Amund Gulsvik, Per S. Bakke
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

There is limited knowledge about the relationship between respiratory symptoms and quantitative high-resolution computed tomography measures of emphysema and airway wall thickness.To describe the ability of these measures of emphysema and airway wall thickness to predict respiratory symptoms in subjects with and without chronic obstructive pulmonary disease (COPD).We included 463 subjects with chronic obstructive pulmonary disease (COPD) (65% men) and 488 subjects without COPD (53% men). All subjects were current or ex-smokers older than 40 years. They underwent spirometry and high-resolution computed tomography examination, and completed an American Thoracic Society questionnaire on respiratory symptoms.Median (25th percentile, 75th percentile) percent low-attenuation areas less than -950 Hounsfield units (%LAA) was 7.0 (2.2, 17.8) in subjects with COPD and 0.5 (0.2, 1.3) in subjects without COPD. Mean (SD) standardized airway wall thickness (AWT) at an internal perimeter of 10 mm (AWT-Pi10) was 4.94 (0.33) mm in subjects with COPD and 4.77 (0.29) in subjects without COPD. Both %LAA and AWT-Pi10 were independently and significantly related to the level of dyspnea among subjects with COPD, even after adjustments for percent predicted FEV(1). AWT-Pi10 was significantly related to cough and wheezing in subjects with COPD, and to wheezing in subjects without COPD. Odds ratios (95% confidence intervals) for increased dyspnea in subjects with COPD and in subjects without COPD were 1.9 (1.5-2.3) and 1.9 (0.6-6.6) per 10% increase in %LAA, and 1.07 (1.01-1.14) and 1.11 (0.99-1.24) per 0.1-mm increase in AWT-Pi10, respectively.Quantitative computed tomography assessment of the lung parenchyma and airways may be used to explain the presence of respiratory symptoms beyond the information offered by spirometry.
Double-blind study of erbium 169 injection (synoviorthesis) in rheumatoid digital joints.
Authors: C J Menkes, A L Go, P Verrier, M Aignan, F Delbarre
Journal: Annals of the Rheumatic Diseases (1977)

A double-blind study of erbium 169 injection into rheumatoid digital joints was carried out with saline as control. 201 joints in 36 patients were studied (137 metacarpophalalangeal, 64 proximal interphalangeal). Erbium 169 was injected into 121 joints and saline water into 80 joints. Local injection of corticosteroids was given to both groups. A definite improvement was observed in 55% to 58% of cases with erbium 169 (+prednisolone acetate) and in 26% to 28% of cases with saline (+prednisolone acetate). The difference was highly significant.
Leukopenia After Postmastectomy Irradiation
Authors: Richard Belgrad
Journal: JAMA (1976)

To the Editor.—  With reference to the article, Leukopenia After Postmastectomy Irradiation (235:747, 1976) by Lewis and Patterson, it has been previously noted by others that transient leukopenia is found in some women after irradiation of the internal mammary nodes for carcinoma of the breast. Drs Lewis and Patterson again confirm this phenomenon and raise provocative questions of concern to those of us responsible for deciding whether the patient requires radiation. The inference that radiation therapy results in an impaired immune response, a greater incidence of systemic metastasis, or in secondary cancers—or that it may compromise prophylactic chemotherapy—has not been demonstrated. To the contrary, postoperative radiation has improved the survival rate for some patients receiving mediastinal irradiation, ie, for bronchogenic carcinoma; and the combination of radiation therapy and chemotherapy has improved results with several tumors, eg, oat-cell carcinoma of the lung and advanced Hodgkin disease. Furthermore, postmastectomy irradiation can eradicate
Hepatitis C impairs survival following liver transplantation irrespective of concomitant hepatocellular carcinoma
Authors: Espen Melum, Styrbjörn Friman, Kristian Bjøro, Allan Rasmussen, Helena Isoniemi, Henrik Gjertsen, Lars Bäckman, Antti Oksanen, Michael Olausson, Frans F. Duraj, Bo-Göran Ericzon
Journal: Journal of Hepatology (2007)
Explaining the Decline in Coronary Heart Disease Mortality in England and Wales Between 1981 and 2000
Authors: Belgin Unal, Julia Alison Critchley, Simon Capewell
Journal: Circulation (2004)

Coronary heart disease mortality rates have been decreasing in the United Kingdom since the 1970s. Our study aimed to examine how much of the decrease in England and Wales between 1981 and 2000 could be attributed to medical and surgical treatments and how much to changes in cardiovascular risk factors.The IMPACT mortality model was used to combine and analyze data on uptake and effectiveness of cardiological treatments and risk factor trends in England and Wales. The main data sources were published trials and meta-analyses, official statistics, clinical audits, and national surveys. Between 1981 and 2000, coronary heart disease mortality rates in England and Wales decreased by 62% in men and 45% in women 25 to 84 years old. This resulted in 68 230 fewer deaths in 2000. Some 42% of this decrease was attributed to treatments in individuals (including 11% to secondary prevention, 13% to heart failure treatments, 8% to initial treatments of acute myocardial infarction, and 3% to hypertension treatments) and 58% to population risk factor reductions (principally smoking, 48%; blood pressure, 9.5%; and cholesterol, 9.5%). Adverse trends were seen for physical activity, obesity and diabetes.More than half the coronary heart disease mortality decrease in Britain between 1981 and 2000 was attributable to reductions in major risk factors, principally smoking. This emphasizes the importance of a comprehensive strategy that promotes primary prevention, particularly for tobacco and diet, and that maximizes population coverage of effective treatments, especially for secondary prevention and heart failure. These findings may be cautiously generalizable to the United States and other developed countries.
Abstract 5255: Kv1.3 Channels Play a Role in Coronary Metabolic Dilation
Authors: Vahagn Ohanyan, Ian N Bratz, William M Chilian
Journal: Circulation (2009)

The coupling between metabolism and flow in the heart is critical for normal cardiac function because the myocardium depends on a continuous supply of oxygenated blood for aerobic metabolism and energy production. Recently we proposed that one component of this coupling is mediated by mitochondrial production of H2O2, which produces dilation through redox-dependent activation of 4-aminopyridine (4-AP) sensitive ion channels. 4-AP is thought to preferentially block the Kv1 family of ion channels, but its antagonistic effects also extend to other families of Kv channels, e.g., Kv4. Our goal was to ascertain if a particular Kv1 channel, Kv1.3, that is known to be redox sensitive, serves as a metabolic sensor in the heart to engender coupling of metabolism to flow. To accomplish this goal we implemented a murine model (C57/B6, n =10) of coronary metabolic dilation (during anesthesia) in which cardiac work (CW: product of stroke volume × heart rate × mean arterial pressure) was altered by i.v. infusion of norepinephrine (NE). Coronary blood flow (contrast echocardiography, units of ml/min per g) was simultaneously measured during the changes in CW. Arterial pressure and heart rate were measured using a Millar transducer in the abdominal aorta, and stroke volume was measured via echocardiography. NE at 2.5 and 5 ug/kg/min increased CW over baseline by 130% and 221%, respectively. Under these conditions coronary flow increased from a baseline of 2.3±0.9 to 5.2±1.5 (NE2.5) and to 7.4±1.8 (NE5) (both P&lt;0.05 vs baseline [mean± SD]). To ascertain the role of Kv1.3 channels, we used the potent Kv1.3 channel antagonist correolide (C: 0.8 mg/kg, i.v.). Whereas correolide did not affect basal flow, the Kv1.3 antagonist blunted metabolic dilation during NE infusion: 4.3±0.9 (C+NE2.5) and 5.2±1.2 (C+NE5: P&lt;0.05 vs NE5). At the highest dose of NE the % increase in flow under control conditions (229%) was greatly attenuated by correolide (132%). Since cardiac myocytes are not reported to express Kv1.3 channels, we do not believe the results are related to an effect of correolide on cardiac myocytes. Rather, we conclude that Kv1.3 channels play a role in coupling coronary flow to cardiac work and that mice have the ability to more than double coronary flow under high levels of cardiac work.
Treatment of Pancreatic Cancer
Authors: Ronald A. Malt
Journal: JAMA (1983)

ADENOCARCINOMA of pancreatic ductal cells is almost always fatal. Despite many thousands of pancreatoduodenectomies during the last 40 years, fewer than 100 cured patients are known. The past 20 years have produced only about 50 five-year survivors among 1,250 patients treated for cure (4% rate), and many of those have later died of recurrent cancer. To the contrary, some patients counted as cures have only been explored, not resected. Thus, the traditional logic of oncological surgery—resecting local disease and the pathways of its local spread and nodal metastases—dictates ineffective treatment of pancreatic cancer because the disease is usually systemic by the time of diagnosis. Progress requires (1) identifying the causes of pancreatic cancer so as to minimize them, (2) detecting the cancer while it is localized, (3) devising effective nonsurgical therapy for residual local disease and suppression of metastases, and (4) ensuring valid assessments of surgical and nonsurgical treatments by
The "Pill" and deep-venous thrombosis.
Authors: R. J. Hetherington
Journal: BMJ (1967)

This letter was written in answer to a report questioning the reliability of the diagnosis of venous thrombosis in nonfatal cases.  The author agrees that there is an increased incidence of something (pseudothrombosis?).  He also points out that about 66% of deep-venous thromboses are not diagnosed during life.  He further stipulates that since platelet adhesiveness has been shown to be increased in venous thromboembolism and in oral contraceptive users it may in many users connote a liability to thrombosis when accompanied by other blood changes.
Netherton syndrome in two Japanese siblings with a novel mutation in the SPINK5 gene: immunohistochemical studies of LEKTI and other epidermal molecules
Authors: Y. Shimomura, N. Sato, N. Kariya, S. Takatsuka, M. Ito
Journal: British Journal of Dermatology (2005)

Background Netherton syndrome (NS) is a severe autosomal recessive disorder characterized by ichthyosiform erythroderma, bamboo hair and atopy. The disease is caused by mutations in the SPINK5 gene, which encodes a putative serine protease inhibitor, LEKTI (lymphoepithelial Kazal‐type‐related inhibitor). Previous studies have clearly shown a crucial role for LEKTI in skin barrier formation. Objectives To identify pathogenic mutations in two Japanese siblings with NS, and further to investigate the consequences of the mutations at the protein level. Methods To screen for mutations in the SPINK5 gene, all of its exons and splice junctions were amplified by polymerase chain reaction and directly sequenced. In addition, immunohistochemical staining of LEKTI, desmoglein (Dsg) 1 and elafin was performed with their specific antibodies. Results Mutation analysis resulted in the identification of compound heterozygous mutations, Q713X and R790X, in the SPINK5 gene of both patients. The former one is a novel mutation. Immunohistochemical studies in one patient demonstrated a complete absence of LEKTI and a strong expression of elafin in the patient's skin. Dsg1 was normally expressed in our patient. Conclusions In this report, we describe compound heterozygous mutations in the SPINK5 gene in two Japanese siblings with NS. The result of immunohistochemistry shows LEKTI deficiency and upregulation of elafin in the skin of one patient. Furthermore, our data indicate that degradation of Dsg1 does not always occur in NS.
Correction of Total Anomalous Pulmonary Venous Drainage in Infancy Utilizing Deep Hypothermia with Total Circulatory Arrest
Authors: DAVID H. DILLARD, HITOSHI MOHRI, EUGENE A. HESSEL, HOWARD N. ANDERSON, RONALD J. NELSON, EDWARD W. CRAWFORD, BEVERLY C. MORGAN, LOREN C. WINTERSCHEID, K. ALVIN MERENDINO
Journal: Circulation (1967)

Four critically ill infants aged 3, 5, 5, and 13 months; weighing 3.7, 4.6, 5.3, and 6.5 kg, respectively; with total anomalous pulmonary venous drainage, underwent complete correction of their lesions with the utilization of surface-induced deep hypothermia. Although this series is small, we are not aware of any other consecutive series in this age group with a comparable mortality rate. Rectal temperatures of 17.5 to 20.2 C were utilized, with periods of cardiac arrest and total circulatory interruption of 32 to 41 minutes. Important aspects of the technique are surface cooling, deep ether anesthesia, intravenous low-molecular-weight dextran, induced respiratory alkalosis during cooling, and electrical pacing during resuscitation. This method works well in the infant, in contrast with perfusion techniques in which surgical mortality is excessively high.
Characterization of human hepatocyte lines derived from normal liver tissue
Authors: Eve A. Roberts, Michelle Letarte, Jeremy Squire, Suyun Yang
Journal: Hepatology (1994)

Four separate continuous lines of human hepatocytes (HH01, HH02, HH09, HH25) were developed from normal liver tissue by subjecting cocultures of human hepatocytes with rat liver epithelial cells in a highly enriched medium to frequent subculturing. The addition of conditioned medium from either the human hepatoma line Hep G2 or one of these stable human hepatocyte lines (HH09) appeared to facilitate establishment of line HH25. These human hepatocyte lines have been in continuous culture for 2 to 5 yr and consist of approximately 95% human cells by analysis of cell surface antigens. Cytogenetic analysis also confirmed the human origin of these cells and showed clonal origin with abnormal ploidy. Cells in these human hepatocyte lines retain morphological features of hepatocytes by both light and electron microscopy. They also retain glucose-6-phosphatase activity and secrete proteins characteristic of hepatocytes, such as albumin, alpha-fetoprotein and transferrin. After incubation with 13 mumol/L dibenz(a,h) anthracene for 24 hr, each line had detectable activity of aryl hydrocarbon hydroxylase, ethoxyresorufin O-deethylase and methoxyresorufin O-demethylase. Thus, these human hepatocyte lines retain important differentiated characteristics of hepatocytes. Derived from normal liver tissue, they appear to be immortalized. They provide a new model system for studying human hepatocellular drug metabolism. These lines may also be useful for studying the regulation of synthesis of albumin, alpha-fetoprotein and other proteins in human hepatocytes, determining the effects of cytokines and growth factors and designing systems to effect gene transfer into human hepatocytes for the purpose of gene therapy.
P47 De-novo antiviral therapy with nucleos(t)ide analogues in 'real-life' patients with chronic hepatitis B infection: comparison of virological responses between lamivudine + adefovir vs entecavir vs tenofovir therapy
Authors: I. Carey, H. Nguyen DorothyJoe, M. Al-Freah, S. Knighton, M. Bruce, A. Suddle, P. M. Harrison, K. Agarwal
Journal: Gut (2011)

<h3>Introduction</h3> Several nucleos(t)ide analogues (NA) are approved for the treatment of chronic hepatitis B (CH-B); all aim to control HBV replication with minimal risk of drug-resistance and toxicity. Limited comparative data exist assessing differences between viral responses to different de-novo therapeutic regimens in real-life cohorts. <h3>Aim</h3> To assess and compare virological and serological responses in 3 real-life CH-B de-novo therapeutic cohorts—lamivudine 100 mg/d + adefovir 10 mg/d (LAM+ADV) combination therapy vs entecavir 0.5 mg/d (ETV) vs tenofovir 245 mg/d (TDF) monotherapies. <h3>Method</h3> <b> Patients:</b> NA therapy naive 406 CH-B patients treated at a single-centre practice [median 30 months (m), range 3–72] were split into three groups according therapy regimen: LAM+ADV (n=192, 78% males, median age 40 y, 35% HBeAg+, 34% cirrhosis, median duration 36 months), ETV (n=154, 79% males, median age 42 y, 31% HBeAg+, 34% cirrhosis, median duration 28 months) and TDF (n=60, 50% males, median age 40 y, 23%HBeAg+, 25% cirrhosis, median duration 9 months). HBV DNA viral load tested by real-time PCR [log10 IU/ml], serology for HBeAg/HBsAg were compared between baseline, months 3, 6, 9 and 12. Five responses, evaluated by change in serum HBV DNA, were recorded: (1) complete (CR) &lt;12 IU/ml; (2) partial (PR), fall &gt;3log10 but &gt;12 IU/ml; (3) slow (SR), fall 2–3 log10; (4) non-response (NR), fall &lt;1 log10; 5) viral breakthrough (VB), rise &gt;1 log10 from nadir. HBV genotypic resistance was tested pre-treatment and at the time of SR, NR or VB by direct sequencing. <h3>Results</h3> Baseline HBV DNA was similar in all cohorts (median log<sub>10</sub> 4.6 vs 4.4 vs 4.2 IU/ml), higher proportions achieved CR in TDF cohort than LAM+ADV and ETV (m3: 78%vs 48% and 53%, p&lt;0.01; m6: 82% vs 60% and 65%, p=0.02; m9: 86% vs 62% and 55%, p&lt;0.01), but were similar at m12: 80% vs 73% and 76% and there were no differences in PR, SR and NR in all groups. HBV DNA decreased in analogous rate in all groups. 2 patients in LAM+ADV and ETV groups developed VB. No viral mutations associated with drug resistance were detected in the LAM + ADV and TDFgroup, including those with VB, NR or SR; in contrast 1 ETV patient with SR at m12 (genotype C) developed mutation rtM204I. HBeAg seroconversion was more frequent in LAM + ADV cohort vs ETV and TDF (21% vs 8% and 7%, p=0.06) and HBsAg seroconversion occurred only in LAM + ADV and ETV patients (2% and 1%). <h3>Conclusion</h3> De-novo antiviral therapy with different therapeutic approaches of nucleos(t)ide analogues LAM+ADV, ETV and TDF achieves similar efficacy within 12 months of treatment in real-life patient cohorts with CH-B.
THE SOLUBLE SPECIFIC SUBSTANCE OF FRIEDLÄNDER'S BACILLUS
Authors: Oswald T. Avery, Michael Heidelberger, Walther F. Goebel
Journal: The Journal of Experimental Medicine (1925)

The chemical and immunological properties of the soluble specific substances of a strain of Friedländer's bacillus and Pneumococcus Type II are described and correlated, and the serological and antigenic similarity of these biologically unrelated organisms is discussed as an example of heterogenetic specificity among bacteria.
MARSILID (IPRONIAZID) AND ELECTROSHOCK
Authors: ALFRED GALLINEK
Journal: American Journal of Psychiatry (1959)

Marsilid (iproniazid), so far, is the only drug with powerful anti-depressive properties. Twenty-five out of 32 patients derived benefit from the drug. It is helpful [See TABLE-1 in source PDF] in depressive syndromes in which somatization and retardation predominate, particularly so, if strong neurotic features are present. In one severe chronic schizophrenic syndrome Marsilid had a powerful euphorizing, unblocking effect. It is ineffective in most agitated depressions. It requires considerable length of time before exerting effect. Half of the successfully treated patients relapsed and had to be kept on maintenance therapy. Toxic features are of considerable degree and frequency. Fifteen out of 32 patients showed serious complications, among them 7 cases of liver damage. The well-known minor complications occurred in the vast majority of patients. Indications for electroshock and Marsilid will rarely overlap since depressions with neurotic features were never a first choice indication for electroshock, and since the prevalent group of psychotic depressions, the agitated depressions, failed to respond to Marsilid. It appears that the anti-depressive effect of Marsilid is exerted over the sense of increased physical well-being and increased energy induced by the drug. A possibly important chance observation was the disappearance of the manifestations of psoriasis of 40 years uninterrupted duration and their reappearance after discontinuation of the drug. [See TABLE-2 in souce PDF]
The “Shadow Government” in Health Care
Authors: Samuel Y. Sessions
Journal: JAMA (2010)

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