tbuckley/cabot-search huggingface dataset:
Effect of sulphasalazine and sulphapyridine on neutrophil superoxide production: role of cytosolic free calcium.
Authors: L Kanerud, I Hafstrom, B Ringertz
Journal: Annals of the Rheumatic Diseases (1990)

As the neutrophil granulocyte plays an important part in rheumatoid inflammation the effect of sulphasalazine on neutrophil function was studied. The results show that sulphasalazine, and its metabolite sulphapyridine, inhibit neutrophil superoxide production elicited by the receptor mediated stimulus N-formyl-methionyl-leucyl-phenyl-alanine (fMLP) and by the calcium ionophore A23187. This effect seems to be dependent on inhibition of intracellular Ca++ increase as both substances reduce this increase upon cell activation with fMLP and A23187. Sulphasalazine and sulphapyridine do not inhibit superoxide production after stimulation with the ester phorbol myristate acetate, a stimulus response coupling which is independent of intracellular Ca++ increase. The reported inhibition of superoxide generation may explain, at least partly, the antirheumatic property of sulphasalazine.
Identification of the fetal liver cytochrome CYP3A7 in human endometrium and placenta.
Authors: J D Schuetz, S Kauma, P S Guzelian
Journal: Journal of Clinical Investigation (1993)

Placenta and endometrium carry out steroidogenic biotransformation reactions such as 6-beta-hydroxylation of cortisol, a reaction characteristic of the dominant family of cytochromes P450 in human liver, CYP3A. To investigate the possible role in these extrahepatic tissues of the CYP3A microsomal hemoproteins, we analyzed placental and endometrial microsomes on Western blots developed with an anti-human CYP3A antibody. We found an immunoreactive 51,500 D protein that migrated between CYP3A3 (HLp) and CYP3A5 (HLp2) identical with CYP3A7 (HFLa). CYP3A7, a form found prominently in human fetal liver microsomes, was first isolated as a liver 16-alpha-dehydroepiandrosterone-sulfate hydroxylase. Northern blot analysis of total RNA isolated from placenta or from endometrium demonstrated a single band that cross-hybridized with a CYP3A7 cDNA. Amplification of the same RNA samples with the use of primers specific for CYP3A7, produced a 552-bp segment that had the predicted size and the same DNA sequence as does liver CYP3A7 cDNA. Hybridizable endometrial CYP3A7 mRNA was detected more frequently (six of seven samples) and in higher amounts (approximately 12-fold higher) in pregnant compared with nonpregnant women (4 of 12 samples). In addition, during the secretory phase of the menstrual cycle CYP3A7 expression was sixfold higher than in the one sample from the proliferative phase that had detectable CYP3A7 mRNA. Moreover, the amounts of placental and endometrial CYP3A7 mRNA and protein increased substantially from the first to the second trimester of pregnancy. We conclude that placenta and endometrium express the same P450 as is found in fetal liver. These tissues represent a previously unrecognized and quantitatively important site for 6-beta-hydroxylation and 16-alpha-hydroxylation of specific steroid precursors, possibly for protection of the fetus from the toxic effects of endogenous steroids and foreign substrates.
The Medical Expert Witness in Malpractice Suits
Authors: Alan Rosenberg
Journal: JAMA (1975)

To the Editor.—  I have just finished reading Dr Paul C. Bucy's article (232:1352, 1975) and find it well done. However, it seems to me that he was too cautious concerning the physician's duty to testify as an expert against another physician when the issue is malpractice.  We proudly consider ourselves a nation of laws, and rightly so. The physician in our society has reasonably high privileges and with that come equally high duties. An injured party ordinarily cannot sustain an action for malpractice without having an expert, ie, a physician, agreeing with him that malpractice did occur. The injured party cannot legally subpoena an expert, since only witnesses to fact can be subpoenaed, ergo, his entire case may turn on his ability to secure an expert for his cause, not on the issue of malpractice itself. In the past, a physician's refusal to testify was called conspiracy of silence.
Ivermectin for the Treatment of Wuchereria bancrofti Filariasis
Authors: V. Kumaraswami
Journal: JAMA (1988)

Ivermectin treatment was evaluated for efficacy and side effects in 40 patients in South India who had microfilaremia and bancroftian filariasis. Ivermectin was administered once orally at four dose levels (range, 25 to 200 micrograms/kg), and at each it was found to be completely effective in clearing blood microfilariae within five to 12 days. In most patients, microfilariae reappeared by three months; by six months the levels averaged 14% to 32% of pretreatment values in the four study groups, and all groups showed equivalent efficacy. Detailed monitoring identified some side effects in almost all patients: usually fever, headache, light-headedness, myalgia, sore throat, or cough that occurred most prominently 18 to 36 hours after treatment. These were most frequent and severe in patients with the greatest microfilaremia, but only when treated with the two higher doses of ivermectin (100 and 200 micrograms/kg). The low-dose (25 micrograms/kg) ivermectin group, despite equivalent efficacy in parasite killing, had clinical reaction scores that were minimal and that were not correlated with parasitemia. Since efficacy and side effects of ivermectin therapy compare favorably with those reported for treatment with the standard antifilarial drug diethylcarbamazine citrate, the major advantage of single-oral-dose administration makes ivermectin the best candidate to replace diethylcarbamazine as the treatment of choice for bancroftian filariasis.
Orbitofacial Wounds and Cerebral Artery Injuries Caused by Umbrella Tips
Authors: Andrew Carothers
Journal: JAMA (1978)

Penetrating orbitofacial wounds inflicted by the sharp metal tips of umbrellas may go unrecognized. This type of injury is not generally appreciated as having fatal consequences. Immediate neurologic and radiologic evaluations are diagnostic. The value of computerized tomography and cerebral angiography is stressed.
Nitrogen dioxide exposure enhances asthmatic reaction to inhaled allergen in subjects with asthma.
Authors: V Strand, S Rak, M Svartengren, G Bylin
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

We investigated whether exposure to a low level (490 micrograms/m3) of nitrogen dioxide (NO2) affects bronchial responsiveness to allergen and enhances allergen-induced increase in airway responsiveness to histamine. Eighteen subjects with asthma and allergy to pollen were exposed at rest to either purified air or NO2 for 30 min followed 4 h later by an allergen inhalation challenge. Responsiveness to histamine was measured the day after. Lung function during NO2 exposure and allergen challenge was measured by plethysmography and after exposure by a portable spirometer hourly. The order of exposure to NO2 and air was randomized and separated by at least 2 wk. The asthmatic reaction during the late phase was enhanced by NO2, and peak expiratory flow after allergen challenge was on average 6.6% lower (p = 0.02) after NO2 than after air exposure. The number of subjects having a late asthmatic reaction (fall in FEV1 > 15%) was seven after air and 10 after NO2 (NS). Peripheral blood samples were analyzed for differential cell counts before and after NO2/allergen and serum levels of eosinophil cationic protein (ECP). NO2 effect on lung function was neither associated with an increase in eosinophil numbers nor with ECP levels. NO2 did not affect lung function before allergen challenge, early asthmatic reaction, and allergen-induced increase in responsiveness to histamine. These results indicate that short exposure to an ambient level of NO2 followed several hours later by allergen inhalation enhances allergen-induced late asthmatic reaction.
John Collings-Wells
Authors: J. Collings-Wells
Journal: BMJ (2009)

John was born on the night of 5/6 June 1922 on the family coffee farm in Kenya. There were no clocks, so he never knew his true date of birth.

The family moved to England when John was 5 because he had a patent ductus arteriosus, and it was thought that the altitude would be detrimental to his health. Before this time, he was bilingual, speaking Swahili to his friends, and wore no shoes.

He grew up in Cheriton Bishop, Devon. With the help of his godfather, Reverend Darrol Smith, he built a wooden canoe in a workshop at the back of the rectory. John’s love of woodwork endured for the rest of his life. …
Transdermal Clonidine Therapy in Hypertensive Patients
Authors: Marie-Denise Schaller
Journal: JAMA (1985)

The antihypertensive effect of clonidine hydrochloride delivered at a constant rate for seven days by transdermal disks was evaluated in seven patients with essential hypertension. Blood pressure values measured at the physician's office were not significantly decreased by one month of treatment with one (n=2) or two (n=5) once-weekly applied clonidine transdermal disks. In contrast, blood pressure values recorded during patients' customary daily activities by means of a portable blood pressure recorder were considerably reduced, from 159/97±2/2 to 136/76±7/5 mm Hg. Plasma drug concentration at the end of the fourth week averaged 1.22±0.24 ng/mL. Plasma renin, vasopressin, and epinephrine levels were not modified by clonidine, whereas plasma norepinephrine level was significantly reduced. Local skin erythema developed in three patients and dry mouth in six. These findings suggest that clonidine transdermal disks lower blood pressure in hypertensive patients, but produce local skin lesions and general side effects. (<i>JAMA</i>1985;253:233-235)
Three-Dimensional Intraductal Ultrasonography: Preliminary Results of a New Technique for the Diagnosis of Diseases of the Pancreatobiliary System
Authors: N. Kanemaki, S. Nakazawa, K. Inui, J. Yoshino, K. Yamao, K. Okushima
Journal: Endoscopy (1997)

Intraductal ultrasonography (IDUS) is a useful method for the diagnosis of pancreatobiliary diseases, but the images obtained using the presently available ultrasonic probes are limited by their two-dimensional nature and are sometimes difficult to interpret. The possible application of three-dimensional intraductal ultrasonography (3 D-IDUS) to facilitate the diagnosis of pancreatobiliary disease was therefore studied using a newly developed system.3 D-IDUS of the biliary system was performed on 26 patients with benign (n = 100) or malignant pancreatobiliary diseases (n = 16), via percutaneous transhepatic or peroral approaches. Three-dimensional diagnoses were made using both radial and linear images generated on the monitor of this system along with a comparison with conventional IDUS (2 D-IDUS) findings.The courses of vessels surrounding the bile duct could be easily imaged in all cases, and accurate assessment of tumor extension and the relationship with surrounding organs could be achieved for all the malignancies. In four of six cases of bile duct cancers the whole outline of the tumor could be visualized so that the tumor volumes could be measured.These preliminary results of 3 D-IDUS in the pancreatobiliary system, the first to be reported in the English literature, indicate that this new system has clear advantages over the 2 D-IDUS approach for diagnostic purposes. Further technical improvements can be expected which will ensure a clinical role for 3 D-IDUS.
[74] MICRO-RNA GENE EXPRESSION PROFILE OF HCV-ASSOCIATED HEPATOCELLULAR CARCINOMA
Authors: M. Scheffler, E. Konze, V. Dries, U. Drebber, P. Schirmacher, F. Schulze, I. Wedemeyer, H.P. Dienes, M. Odenthal, H. Varnholt
Journal: Journal of Hepatology (2007)
A Novel Case of False-Positive I-131 Whole-Body Scan in Thyroid Carcinoma Caused by Subdural Hematoma
Authors: Seng Chuan Ong, David Ng Chee Eng, Felix X. Sundram, Ling Ling Chan
Journal: Clinical Nuclear Medicine (2004)

Iodine-131 whole-body scintigraphy has been used extensively to detect thyroid remnants as well as metastatic disease in thyroid carcinoma postthyroidectomy. Over the years, numerous causes of false-positive scans have been reported. The authors report a novel case of a false-positive result resulting from a subdural hematoma mimicking a skull or cerebral metastasis.
Cytokine-induced expression of a nitric oxide synthase in rat renal tubule cells.
Authors: B A Markewitz, J R Michael, D E Kohan
Journal: Journal of Clinical Investigation (1993)

Nitric oxide (NO.) has been implicated in the regulation of renal vascular tone and tubular sodium transport. While the endothelial cell is a well known source of NO(.), recent studies suggest that tubular epithelial cells may constitutively generate NO(.). An inducible isoform of nitric oxide synthase which produces far greater quantities of NO. exists in some cell types. We sought to determine whether kidney epithelial cells exposed to cytokines could express an inducible nitric oxide synthase. Primary cultures of rat proximal tubule and inner medullary collecting duct cells generated NO. on exposure to TNF-alpha and IFN-gamma. NO. production by both cell types was inhibited by NG-monomethyl-L-arginine; this inhibition was partially reversed by the addition of excess L-arginine. Stimulation of kidney epithelial cells with TNF-alpha and IFN-gamma dramatically increased the level of inducible nitric oxide synthase mRNA. In summary, renal proximal tubule and inner medullary collecting duct cells can produce NO. via expression of an inducible isoform of nitric oxide synthase.
Elevated Atypical Creatine Kinases
Authors: Jack D. Horton
Journal: JAMA (1986)

<h3>To the Editor.—</h3> We read with interest the CASE REPORT of a patient with metastatic adenocarcinoma of the lung and elevated serum CK isoenzyme with an electrophoretic pattern consistent with the MB fraction.<sup>1</sup> We have reported a similar case of a patient with metastatic oat cell carcinoma who had persistent elevation of the serum CK with isoenzyme fractionation showing CK-MB in the range of 47% to 53% and CK-BB in the range of 11% to 23%.<sup>2</sup>At postmortem examination, there was no evidence of myocardial injury. Of interest, however, was that measurement of CK isoenzymes in the patient's tumor tissue showed 46% MB, 44% BB, and only 9% MM, while the myocardium showed 93% MM and 7% MB fraction and skeletal muscle 97% MM and only 3% MB fraction. Although the nature and mechanisms of production of these CK isoenzymes by malignant tissue remain unclear, we demonstrated that
Human Homologue of Cement Gland Protein, a Novel Metastasis Inducer Associated with Breast Carcinomas
Authors: Dong Liu, Philip S. Rudland, D. Ross Sibson, Angela Platt-Higgins, Roger Barraclough
Journal: Cancer Research (2005)

A suppression subtractive cDNA library representing mRNAs expressed at a higher level in the malignant human breast cancer cell line, MCF-7, relative to a benign breast tumor-derived cell line, Huma 123, contained a cDNA, M36, which was expressed in estrogen receptor alpha (ERalpha)-positive breast carcinoma cell lines but not in cell lines from normal/benign/ERalpha-negative malignant breast lesions. M36 cDNA had an identical coding sequence to anterior gradient 2 (AGR2), the human homologue of the cement gland-specific gene (Xenopus laevis). Screening of breast tumor specimens using reverse transcription-PCR and immunocytochemistry with affinity-purified anti-AGR2 antibodies showed that the presence of AGR2 mRNA and protein were both statistically significantly associated with ERalpha-positive carcinomas (P = 0.007, Fisher's exact test) and with malignancy (P < or = 0.025). When an expression vector for AGR2 cDNA was introduced into benign nonmetastatic rat mammary tumor cells, and three separate clones and two pools of cells were transferred to the mammary glands of syngeneic hosts, there were no consistent differences in the mean latent periods of tumor formation. However, metastases occurred in the lungs of animals receiving the AGR2 transfectants in 77% to 92% of animals with primary tumors (P = 0.0001) compared with no metastases in the control groups. The AGR2 transfectants exhibited enhanced rates of adhesion to a plastic substratum and extracellular AGR2 enhanced the rate of attachment of AGR2-negative but not AGR2-positive cells. These experiments are the first to link mechanistically the developmental gene product, AGR2, with metastasis in vivo.
Indications for flexible versus rigid bronchoscopy in children with suspected foreign-body aspiration.
Authors: A Martinot, M Closset, C H Marquette, V Hue, A Deschildre, P Ramon, J Remy, F Leclerc
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

Diagnostic indications for flexible bronchoscopy in the initial investigation of children with suspected foreign-body (FB) aspiration have not been evaluated prospectively. We prospectively collected history, clinical, and radiologic findings at prebronchoscopic examination of all children referred for suspected FB aspiration between February 1993 and September 1995. Children with asphyxiating FB aspiration, requiring immediate rigid bronchoscopy, were excluded. If there was clear evidence of FB aspiration from the physical and radiographic findings, rigid bronchoscopy was directly performed. If the evidence was not convincing, children underwent diagnostic flexible bronchoscopy under local anesthesia. If an FB was found, rigid bronchoscopy was always performed for extraction. Eighty-three consecutive children (median age: 24 mo) were included. Among 28 who underwent rigid bronchoscopy first, 23 had an FB. Among the 55 children who underwent flexible bronchoscopy first, 17 had an FB. Predictive signs of a bronchial FB were a radiopaque FB, and associated unilaterally decreased breath sounds and obstructive emphysema (positive predictive value = 0.94). We propose the following management algorithm: Rigid bronchoscopy is performed first in case of asphyxia, a radiopaque FB, or association of unilaterally decreased breath sounds and obstructive emphysema. In any other case, flexible bronchoscopy is performed first for diagnostic purposes. If applied retrospectively to the 83 children in our study, this algorithm would have decreased the negative first rigid bronchoscopy rate to 4%. Flexible bronchoscopy is a safe and cost-saving diagnostic procedure in children with suspected FB aspiration.
Comparison of Clinical Interpretation With Visual Assessment and Quantitative Coronary Angiography in Patients Undergoing Percutaneous Coronary Intervention in Contemporary Practice
Authors: Brahmajee K. Nallamothu, John A. Spertus, Alexandra J. Lansky, David J. Cohen, Philip G. Jones, Faraz Kureshi, Gregory J. Dehmer, Joseph P. Drozda, Mary Norine Walsh, John E. Brush, Gerald C. Koenig, Thad F. Waites, D. Scott Gantt, George Kichura, Richard A. Chazal, Peter K. O’Brien, C. Michael Valentine, John S. Rumsfeld, Johan H.C. Reiber, Joann G. Elmore, Richard A. Krumholz, W. Douglas Weaver, Harlan M. Krumholz
Journal: Circulation (2013)

Studies conducted decades ago described substantial disagreement and errors in physicians' angiographic interpretation of coronary stenosis severity. Despite the potential implications of such findings, no large-scale efforts to measure or improve clinical interpretation were subsequently undertaken.We compared clinical interpretation of stenosis severity in coronary lesions with an independent assessment using quantitative coronary angiography (QCA) in 175 randomly selected patients undergoing elective percutaneous coronary intervention at 7 US hospitals in 2011. To assess agreement, we calculated mean difference in percent diameter stenosis between clinical interpretation and QCA and a Cohen weighted κ statistic. Of 216 treated lesions, median percent diameter stenosis was 80.0% (quartiles 1 and 3, 80.0% and 90.0%), with 213 (98.6%) assessed as ≥70%. Mean difference in percent diameter stenosis between clinical interpretation and QCA was 8.2±8.4%, reflecting an average higher percent diameter stenosis by clinical interpretation (P<0.001). A weighted κ of 0.27 (95% confidence interval, 0.18-0.36) was found between the 2 measurements. Of 213 lesions considered ≥70% by clinical interpretation, 56 (26.3%) were <70% by QCA, although none were <50%. Differences between the 2 measurements were largest for intermediate lesions by QCA (50% to <70%), with variation existing across sites.Physicians tended to assess coronary lesions treated with percutaneous coronary intervention as more severe than measurements by QCA. Almost all treated lesions were ≥70% by clinical interpretation, whereas approximately one quarter were <70% by QCA. These findings suggest opportunities to improve clinical interpretation of coronary angiography.
Applicability of Cardiac Troponin T and I for Early Risk Stratification in Unstable Coronary Artery Disease
Authors: Michael S. Lüscher, Kristian Thygesen, Jan Ravkilde, Lene Heickendorff
Journal: Circulation (1997)

Background Studies have demonstrated that troponin T is a strong independent indicator of a poor prognosis in patients with unstable coronary artery disease. Up to the present, no study has compared the prognostic value of troponin T with that of troponin I in the same cohort of patients. Methods and Results Patients (n=516) suspected of having unstable coronary artery disease were investigated. Follow-up was done after 30 days, and the occurrences of cardiac death, acute myocardial infarction, refractory angina pectoris, and recurrent angina pectoris were registered. Elevated levels of troponin T (≥0.10 μg/L) were associated with an increased risk of cardiac death at 30 days compared with patients with normal levels, 3.2% versus 0.4% ( P =.014). Troponin I values above the chosen cutoff (2.0 μg/L) were similarly found to be an indicator of increased risk of cardiac death, 3.2% versus 0.7% ( P =.026). With regard to the composite end point of cardiac death/acute myocardial infarction, the troponins were strong independent indicators of adverse outcome. Conclusions In patients suspected of having unstable coronary artery disease, both troponin T and troponin I provide independent prognostic information with regard to cardiac death and acute myocardial infarction.
THE OCCURRENCE AND PROPERTIES OF LEUKOCYTOSIS AND LYMPHOCYTOSIS-STIMULATING MATERIAL IN THE SUPERNATANT FLUIDS OF BORDETELLA PERTUSSIS CULTURES
Authors: Stephen I. Morse, Karen K. Bray
Journal: The Journal of Experimental Medicine (1969)

1. Leukocytosis- and lymphocytosis-stimulating activity was present in fluid cultures of B. pertussis. The activity was found primarily in the culture supernatant fluid. 2. The sequential changes in the leukocyte response were similar to those previously observed following injection of intact bacteria into mice. 3. Activity was destroyed by heat and was diminished, but not abolished, by prolonged treatment with proteolytic enzymes. 4. A water-insoluble fraction of the culture supernatant fluid was isolated which contained virtually all of the activity. The specific activity was more than 100-fold greater than that of the intact bacteria, and injection of microgram quantities produced a response. 5. The distribution of histamine-sensitizing factor followed that of leukocytosis-stimulating activity. In contrast, mouse protective antigen was localized to the bacterial pellet.