tbuckley/cabot-search huggingface dataset:
Exposure of healthy volunteers to swine house dust increases formation of leukotrienes, prostaglandin D2, and bronchial responsiveness to methacholine
Authors: S. O'Sullivan, S.-E. Dahlen, K. Larsson, B.-M. Larsson, P. Malmberg, M. Kumlin, L. Palmberg
Journal: Thorax (1998)

<h3>BACKGROUND</h3> Acute exposure of healthy subjects to swine house dust causes increased bronchial responsiveness to methacholine but no acute bronchoconstriction. The role of cysteinyl leukotrienes and mast cells in increased bronchial responsiveness is unclear. <h3>METHODS</h3> Ten non-asthmatic subjects were exposed to swine dust for three hours while weighing pigs in a piggery. Urine was collected prior to and for up to 12 hours after entering the piggery and at the same times five days before and the day after exposure. As indices of whole body leukotriene production and mast cell activation, urinary levels of leukotriene E<sub>4</sub>(LTE<sub>4</sub>) and 9α,11β-PGF<sub>2</sub>, the earliest appearing urinary metabolite of prostaglandin D<sub>2</sub>(PGD<sub>2</sub>), were measured. Bronchial responsiveness to methacholine was determined five days before and the day after the exposure. <h3>RESULTS</h3> Methacholine PD<sub>20</sub>FEV<sub>1</sub> decreased from 1.32 mg (95% CI 0.22 to 10.25) before exposure to 0.38 mg (95% CI 0.11 to 1.3) after exposure (p&lt;0.01). Associated with the increase in bronchial responsiveness there was a significant mean difference between post- and pre-challenge levels of LTE<sub>4</sub> (difference 38.5 ng/mmol creatinine (95% CI 17.2 to 59.8); p&lt;0.01) and 9α,11β-PGF<sub>2</sub> (difference 69 ng/mmol creatinine (95% CI 3.7 to 134.3); p&lt;0.05) on the day of exposure to swine dust. Swine dust exposure induced a 24-fold increase in the total cell number and a 12-fold increase in IL-8 levels in the nasal lavage fluid. The levels of LTB<sub>4</sub> and LTE<sub>4</sub> in nasal lavage fluid following exposure also increased 5.5-fold and 2-fold, respectively. <h3>CONCLUSIONS</h3> The findings of this study indicate that cysteinyl leukotrienes and other mast cell mediators contribute to the development of increased bronchial responsiveness following inhalation of organic swine dust.
Factors That Affect Efficacy of Ultrasound Surveillance for Early Stage Hepatocellular Carcinoma in Patients With Cirrhosis
Authors: Paolo Del Poggio, Stefano Olmi, Francesca Ciccarese, Mariella Di Marco, Gian Ludovico Rapaccini, Luisa Benvegnù, Franco Borzio, Fabio Farinati, Marco Zoli, Edoardo Giovanni Giannini, Eugenio Caturelli, Maria Chiaramonte, Franco Trevisani
Journal: Clinical Gastroenterology and Hepatology (2014)
Experience with cardiac pacemaking.
Authors: A. B. Taylor
Journal: BMJ (1966)

Clinical Use of Cardiac PacemakingThe indications for pacemaking are becoming established in the management of heart-block and Stokes-Adams seizure.For other disorders of rhythm the possibilities are still under exploration.1. Complete heart-block with the low cardiac output syndrome, showing symptoms of fatigue, mental deterioration, and breathless-BRmSH
I hear the heartbeat, or things that go bump-bump in the night…
Authors: Laurence Drake
Journal: Thorax (2014)

A 47-year-old woman telephones your surgery and says, “I can hear my boyfriend's heartbeat—from three feet away!” Do you: 

1.  arrange an urgent psychiatric review for this obviously delusional woman?

2.  arrange an urgent psychiatric review for the Editors of Thorax for publishing a cardiology case report?

3.  or do something else?

On urgent review after the phone call, you can hear what sounds like his amplified heart sounds from over a metre away, especially if he leans backwards.

This …
Separation of helper and suppressor T lymphocytes on a ficoll velocity sedimentation gradient.
Authors: H Tse, R W Dutton
Journal: The Journal of Experimental Medicine (1976)

A 5-20% Ficoll velocity sedimentation gradient has been successfully applied to separate concanavalin A (Con A)-induced helper; and suppressor T cells. When titrated into a constant number of fresh normal spleen cells responding to sheep erythrocytes, cells from the top pool show stimulatory effects while those from the bottom pool show inhibitory activity. Both activities are found to be Con A dependent and anti-theta sensitive. We conclude that Con A-induced helper and suppressor T cells are distinct subpopulations and such separation will allow further characterization of these cell types.
Increased Erythrocyte Phosphatidylserine Exposure in Chronic Renal Failure
Authors: MARIO BONOMINI, VITTORIO SIROLLI, NICOLA SETTEFRATI, SECONDO DOTTORI, LORENZO DI LIBERATO, ARDUINO ARDUINI
Journal: Journal of the American Society of Nephrology (1999)

The appearance of phosphatidylserine, an aminophospholipid normally confined to the inner monolayer, at the outer leaflet of red cell membrane may have several pathophysiologic implications. This study examines erythrocyte phosphatidylserine exposure in chronic renal failure (CRF) patients on conservative treatment or on dialysis, to assess possible alterations to phospholipid asymmetry in a condition associated with a state of deranged red cell function. A significant increase in phosphatidylserine-expressing erythrocytes was found in undialyzed patients with CRF (2.32%) and patients on hemodialysis (3.06%) and on peritoneal dialysis (2.14%) compared with control subjects (0.68%). In undialyzed CRF patients, a strong correlation (r = 0.903) was found between the percentage of phosphatidylserine-expressing red cells and the serum creatinine concentration. The increased exposure of phosphatidylserine in uremic erythrocytes may be due to inhibition of phosphatidylserine transport from the outer to the inner leaflet of plasma membrane and may promote an increased erythrophagocytosis. In reconstitution experiments, normal erythrocytes showed an increase in phosphatidylserine-expressing cells when incubated in uremic plasma (3.2% after 2 h versus 1.1% at beginning of incubation), whereas phosphatidylserine-positive uremic erythrocytes decreased when resuspended in normal plasma (2.03% after 2 h and 1.65% after 8 h versus 2.9% at beginning of incubation). Preliminary characterization of the putative uremic compound(s) indicates a molecular weight between 10,000 and 20,000, as well as heat instability. These findings show an impairment of erythrocyte membrane phospholipid asymmetry in CRF patients, regardless of the dialysis treatment. Such abnormality seems related to the uremic state and could contribute to the red cell pathology present in CRF.
Drug-Induced Long-QT Syndrome Associated With a Subclinical <i>SCN5A</i> Mutation
Authors: Naomasa Makita, Minoru Horie, Takeshi Nakamura, Tomohiko Ai, Koji Sasaki, Hisataka Yokoi, Masayuki Sakurai, Ichiro Sakuma, Hideo Otani, Hirofumi Sawa, Akira Kitabatake
Journal: Circulation (2002)

Background— Subclinical mutations in genes associated with the congenital long-QT syndromes (LQTS) have been suggested as a risk factor for drug-induced LQTS and accompanying life-threatening arrhythmias. Recent studies have identified genetic variants of the cardiac K + channel genes predisposing affected individuals to acquired LQTS. We have identified a novel Na + channel mutation in an individual who exhibited drug-induced LQTS. Methods and Results— An elderly Japanese woman with documented QT prolongation and torsade de pointes during treatment with the prokinetic drug cisapride underwent mutational analysis of LQTS-related genes. A novel missense mutation (L1825P) was identified within the C-terminus region of the cardiac Na + channel ( SCN5A ). The L1825P channel heterologously expressed in tsA-201 cells showed Na + current with slow decay and a prominent tetrodotoxin-sensitive noninactivating component, similar to the gain-of-function phenotype most commonly observed for SCN5A -associated congenital LQTS (LQT3). In addition, L1825P exhibited loss of function Na + channel features characteristic of Brugada syndrome. Peak Na + current density observed in cells expressing L1825P was significantly diminished, and the voltage dependence of activation and inactivation was shifted toward more positive and negative potentials, respectively. Conclusions— This study demonstrates that subclinical mutations in the LQTS-related gene SCN5A may predispose certain individuals to drug-induced cardiac arrhythmias.
Depression of peripheral blood monocyte aryl hydrocarbon hydroxylase activity in patients with liver disease: Possible involvement of macrophage factors
Authors: Theresa C. Peterson, Noel C. Williams
Journal: Hepatology (1987)

Aryl hydrocarbon hydroxylase activity was detectable in cultured macrophage monolayers of peripheral blood monocyte origin. Peripheral blood monocytes were isolated from patients with biopsy-confirmed liver disease and healthy volunteers. Macrophage monolayers were prepared and incubated at 37°C. After 24 hr, the aryl hydrocarbon hydroxylase activity and cellular protein concentration were assayed on cell homogenates. The monocyte aryl hydrocarbon hydroxylase activity in cultured macrophages from normal volunteers was 1.23 ± 0.16 (n = 19). The aryl hydrocarbon hydroxylase activity in macrophage cultures from patients with biopsy-confirmed liver disease was 0.48 ± 0.05 (n = 20). This represents a significant (61%) decrease in monocyte aryl hydrocarbon hydroxylase compared to controls. The 20 patients have established cirrhosis or early stage liver disease. The established cirrhosis group includes α 1 -antitrypsin deficiency-associated cirrhosis; primary biliary cirrhosis; alcoholic (Laennec's) cirrhosis; cryptogenic cirrhosis, and hemochromatosis. Early stage liver disease is attributed to methotrexate (Stage III), early stage primary biliary cirrhosis and α 1 -antitrypsin deficiency. Our results indicate that the depression in monocyte aryl hydrocarbon hydroxylase activity is greater in patients with established cirrhosis than early stage liver disease. Our results further suggest that cultured monocytes from patients with liver disease spontaneously release soluble factors into the culture medium. Incubation of this medium, containing macrophage factors, with isolated hepatocytes significantly depress hepatocyte aryl hydrocarbon hydroxylase activity compared to medium obtained from cultures of monocytes from normal volunteers. We propose that cultured monocyte aryl hydrocarbon hydroxylase activity mimics the hepatic enzyme and reflects the status of the hepatic enzyme in severe liver disease. Consequently, monocyte aryl hydrocarbon hydroxylase activity may be a useful noninvasive measure of hepatic enzyme function.
Phase I and pharmacodynamic study of the topoisomerase I-inhibitor topotecan in patients with refractory acute leukemia.
Authors: E K Rowinsky, A Adjei, R C Donehower, S D Gore, R J Jones, P J Burke, Y C Cheng, L B Grochow, S H Kaufmann
Journal: Journal of Clinical Oncology (1994)

PURPOSE To determine the feasibility of escalating the hydrophilic topoisomerase I (topo I)-inhibitor topotecan (TPT) above myelosuppressive doses in adults with refractory or relapsed acute leukemias and to assess pharmacodynamic determinants of TPT action. PATIENTS AND METHODS Seventeen patients received 33 courses of TPT as a 5-day infusion at doses ranging from 0.70 to 2.7 mg/m2/d. Pharmacologic studies were performed to determine the TPT concentrations at steady-state (Css) and to examine parameters in the patients' leukemic blasts ex vivo that may be related to TPT sensitivity, eg, topo I content, p-glycoprotein (Pgp) expression, and the inhibitory effects of relevant TPT concentrations on the growth of blast colonies in clonogenic assays relative to the range of TPT Css values achieved. RESULTS Severe mucositis of the oropharynx and perianal tissues was intolerable at TPT doses greater than 2.1 mg/m2/d, the recommended dose for phase II studies in leukemia. One complete response (CR) in a patient with chronic myelogenous leukemia in blast crisis (CML-B) and one partial response (PR) in a patient with acute myelogenous leukemia (AML) were noted. Significant reductions in circulating blast-cell numbers occurred in all courses, and complete leukemia clearance from the peripheral blood, albeit transient, was noted in 11 courses. TPT Css values ranged from 4.8 to 72.5 nmol/L. Colony-forming assays showed that the TPT LD90 (dose that inhibits the growth of leukemia blast colonies by 90%) values for blasts varied from 6 to 22 nmol/L, a range that overlapped with TPT Css values. In view of these variations in TPT sensitivity, several aspects of topo I-mediated drug action were also studied. In 10 of 11 samples, the multi-drug resistance (Mdr) modulator quinidine altered nuclear daunorubicin (DNR) accumulation and whole-cell TPT accumulation by less than 15%, which suggests that Pgp-mediated effects on drug efflux are insufficient to explain the fourfold range of TPT sensitivities in the colony-forming assays. Immunohistochemistry showed that topo I was expressed in all of the blasts from individual patients without detectable cell-to-cell heterogeneity in each marrow. Western blots indicated that topo I content varied over a 10-fold range. Although the sample size was small, topo I content appeared to be higher in acute lymphoblastic leukemia (ALL), intermediate in AML, and lower in CML-B. Topo I content did not appear to be related to the proliferative status of the blasts. CONCLUSION These results indicate that substantial dose escalation of TPT above myelosuppressive doses reached in solid-tumor patients is feasible in patients with refractory leukemia, that biologically relevant TPT Css values are achievable, and that further developmental trials are warranted.
Osteoarthritis of the hip: the patient behind the disease.
Authors: L Solomon, C M Schnitzler, J P Browett
Journal: Annals of the Rheumatic Diseases (1982)

Previous epidemiological studies suggested that patients with osteoarthritis (OA) of the hip might constitute a definable subset of the population with characteristics that predispose them to joint failure. To investigate this possibility a comparative study of somatotype, bone density, disc degeneration, polyarticular joint degeneration, and soft-tissue calcification was carried out in 3 groups of individuals: (1) patients presenting with OA of the hip; (2) patients with acute femoral neck fracture; (3) healthy controls. OA of the hip was rare in patients with femoral neck fracture; conversely, patients with coxarthrosis did not have the low values for bone density seen in the fracture group. There were significant differences in somatotype in the 2 patient groups; 94% of those with OA were endomorphic mesomorphs. Polyarticular OA occurred with the same prevalence in the 2 groups of women, but among males there was a significantly greater involvement of knees and hands in the OA group than in the fracture group. The highest incidence of joint calcification was found in the fracture group and the lowest in the OA group. It was concluded that patients with OA of the hip form a definable subset of the general population. Within this group the appearances of hip OA are determined by 3 interacting factors: mechanical stress, cartilage degeneration, and bone response.
An allelic polymorphism within the human tumor necrosis factor alpha promoter region is strongly associated with HLA A1, B8, and DR3 alleles.
Authors: A G Wilson, N de Vries, F Pociot, F S di Giovine, L B van der Putte, G W Duff
Journal: The Journal of Experimental Medicine (1993)

The tumor necrosis factor (TNF) alpha gene lies within the class III region of the major histocompatibility complex (MHC), telomeric to the class II and centromeric to the class I region. We have recently described the first polymorphism within the human TNF-alpha locus. This is biallelic and lies within the promoter region. Frequency analysis of the TNF-alpha polymorphism, using the polymerase chain reaction and single-stranded conformational polymorphism, in HLA-typed individuals, reveals a very strong association between the uncommon TNF allele and HLA A1, B8, and DR3 alleles. This is the first association between TNF-alpha and other MHC alleles and raises the possibility that the uncommon TNF-alpha allele may contribute to the many autoimmune associations of the A1,B8,DR3 haplotype.
Long-term efficacy of single-dose radiofrequency-induced heat therapy vs. intralesional antimonials for cutaneous leishmaniasis in India
Authors: R.A. Bumb, N. Prasad, K. Khandelwal, N. Aara, R.D. Mehta, B.C. Ghiya, P. Salotra, L. Wei, S. Peters, A.R. Satoskar
Journal: British Journal of Dermatology (2013)

Radiofrequency-induced heat therapy (RFHT) has been found to be safe and effective against cutaneous leishmaniasis (CL) in the short term, but its long-term efficacy is unclear.To compare the long-term efficacy of RFHT vs. intralesional sodium stibogluconate (SSG) injections in the treatment of CL in India.One hundred patients with a confirmed diagnosis of CL were randomly assigned in a 1 : 1 ratio to receive topical RFHT for 30-60 s or seven intralesional injections of SSG (50 mg cm(-2) of lesion). Improvement and recurrence were monitored every 15 days after the initiation of treatment for 4 months and then at 5, 6, 9, 12 and 18 months post-treatment; the rates of complete cure were compared.Lesions were healed in 47 out of 50 patients (94%) in the RFHT group and in 46 out of 50 patients (92%) in the SSG group at week 12. Time to complete healing was comparable in the two groups. At 6 months post-treatment, cure rates in the RFHT and SSG groups were 98% [95% confidence interval (CI) 94-100%] and 94% (95% CI 86-100%), respectively. Age, sex and lesion size or number had no effect on cure rates. No relapse of infection was recorded in cured patients in either group up to 12-18 months after initiation of treatment. Skin biopsies of cured lesions in eight out of eight (100%) patients from the RFHT group and three of three from the SSG group at 12 months showed minimal fibrosis and were negative for Leishmania tropica by polymerase chain reaction test.A single application of RFHT is safe, cosmetically acceptable and effective in inducing a long-term cure of CL.
Calcium depletion in rabbit myocardium. Ultrastructure of the sarcolemma and correlation with the calcium paradox.
Authors: J S Frank, T L Rich, S Beydler, M Kreman
Journal: Circulation Research (1982)

The ultrastructure of the Ca-depleted myocardial sarcolemma (via Ca-free and Ca-free plus EGTA perfusion at 28 degree C and 37 degree C) was studied in the vascularly perfused interventricular septum of the rabbit. Thin-section and freeze-fracture electron microscopy was used. Two major structural defects in the sarcolemma were found. (1) Ninety percent of the Ca-depleted cells have between 30 and 40% of their glycocalyx separated from the bilayer. With tannic acid staining, the separation is seen to occur between the external lamina and the surface coat. (2) Freeze-fracture data showed an apparent decrease in intramembrane particles on the P face of unidirectionally shadowed replicas. Quantitation of rotary-shadowed replicas showed no decrease in density of intramembrane particles. It was concluded from this that there was no loss of intramembrane particles, but rather a reorientation in the plane of the bilayer after Ca depletion. Both glycocalyx and bilayer changes were present after perfusion of the heart for only 5 minutes (37 degree C) with Ca-free perfusate. With low temperature and Cd substitution, separation of the glycocalyx occurred in less than 1% of the cells. After Ca depletion at 18 degree C, the density of intramembrane particles on the P face was not significantly different from controls. Cd substitution did not prevent the decrease total intramembrane particles per square micron, but the larger intramembrane particles had similar densities (154/micrometer2) as control (181/micrometer2), and as Ca-depletion with hypothermia (180/micrometer2). These findings indicate that structural changes in the glycocalyx and the bilayer can be totally prevented by hypothermia. Cd, on the other hand, prevents glycocalyx separation and affords protection only to the large intramembrane particles. Upon reperfusion with Ca, the intramembrane particles undergo the further alteration of aggregation, while numerous vesicles can be seen in the fracture plane of the membrane.
1061-97 Efficacy of granulocyte-colony stimulating factor after coronary ligation in rats: Evaluation by echocardiographic acoustic quantification and myocardial contrast
Authors: Takashiro Hirano, Ryoko Azakami, Tomoko Kastuta, Kohei Okuda, Toshihiko Asanuma, Fuminobu Ishikura, Shintaro Beppu
Journal: Journal of the American College of Cardiology (2004)
Sustained, spontaneous disappearance of serum HCV-RNA under immunosuppression after liver transplantion for HCV cirrhosis
Authors: Dimitrios N. Samonakis, Evangelos Cholongitas, Christos K. Triantos, Paul Griffiths, Amar Paul Dhillon, Ulrich Thalheimer, David W. Patch, Andrew K. Burroughs
Journal: Journal of Hepatology (2005)
Initial clarithromycin monotherapy for Mycobacterium avium-intracellulare complex lung disease.
Authors: R J Wallace, B A Brown, D E Griffith, W M Girard, D T Murphy, G O Onyi, V A Steingrube, G H Mazurek
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

Sputum conversion rates in Mycobacterium avium-intracellulare (MAI) complex lung disease have ranged from only 50 to 80% despite the use of three to five antituberculosis agents. We initiated a prospective, open, noncomparative trial of initial clarithromycin monotherapy at 500 mg twice a day for 4 months in HIV-negative patients with MAI lung disease. The primary study end point was microbiologic improvement. Of 30 patients enrolled, 20 completed therapy. This latter group was predominantly male (60%), smokers (70%), older than 45 yr of age (90%), infected with Mycobacterium intracellulare (70%) and with bilateral disease (85%). Of 19 patients with pretreatment minimum inhibitory concentrations (MIC) for clarithromycin < 16 micrograms/ml, 58% became sputum-negative, and 21% showed significant reductions in sputum positivity. Heavily positive sputum cultures (> 200 colonies) were reduced from 30 to 47 samples pretherapy (64%) to three of 54 (6%) post-therapy (p < 0.0001); 18 of 19 patients (95%) showed an improvement in sputum cultures, chest radiographs, or both. Only two patients (7%) discontinued the drug because of adverse events. Only three (16%) of 19 isolates developed clarithromycin resistance (MIC > 32 micrograms/ml). Clarithromycin-susceptible and -resistant MAI isolates from the same patient had identical DNA large-restriction fragment patterns. Clarithromycin is the first single agent to be shown efficacious in the treatment of MAI lung disease.
Patterns of Drug Use in a Population of Youthful Psychiatric Patients
Authors: CHARLES R. SHEARN, DAVID J. FITZGIBBONS
Journal: American Journal of Psychiatry (1972)

The authors used a questionnaire to obtain information on drug use by a group of 167 young psychiatric inpatients and then compared their results with those of a survey of 26,000 college and university students. They found that their subjects showed far greater involvement with drugs, both in breadth and in depth. Since there were strong tendencies toward using a wide variety of drugs and toward repetitive long-term use, the life-style of a great many of these patients probably includes a chronic dependency on these drugs.