tbuckley/cabot-search huggingface dataset:
CULPRIT LESION REMODELING AND LONG-TERM MORTALITY IN PATIENTS WITH ACUTE CORONARY SYNDROME
Authors: Hiroyuki Okura, Nobuya Matsushita, Kenji Shimeno, Takeshi Ozaki, Hiroyuki Yamagishi, Iku Toda, Kiyoshi Yoshida
Journal: Journal of the American College of Cardiology (2011)
Physician-Assisted Death and Pharmacy Practice in the Netherlands
Authors: Anthonius de Boer, Hong Sang Lau, Arijan Porsius
Journal: New England Journal of Medicine (1997)

may be important in predicting later neurodevelopmental outcome.Finally, the authors actually found no significant difference in the Mental Development Index between the two groups.It was only after excluding babies with neuromotor impairment that a difference between the groups was found, but this removed most of the infants with an abnormal neurodevelopmental outcome.If aluminum is indeed an important cause of neurotoxicity, shouldn't the authors be concerned with all types of neurologic impairment?Given all these factors, then, the case for aluminum neurotoxicity in these infants seems weak.
Inhibition of Activator Protein 1 Activation, Vascular Endothelial Growth Factor, and Cyclooxygenase-2 Expression by 15-Deoxy-Δ12,14-Prostaglandin J2 in Colon Carcinoma Cells: Evidence for a Redox-Sensitive Peroxisome Proliferator-Activated Receptor-γ-Independent Mechanism
Authors: Raquel Grau, Miguel A. Iñiguez, Manuel Fresno
Journal: Cancer Research (2004)

Abstract Cyclooxygenase (COX)-2 and vascular endothelial growth factor (VEGF) are significantly associated with tumor growth and metastasis. Here we show that phorbol ester-mediated induction of VEGF and COX-2 expression in colon carcinoma cells is inhibited by 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2). This cyclopentenone was able to inhibit activator protein1 (AP-1)-dependent transcriptional induction of COX-2 and VEGF promoters induced by phorbol 12-myristate 13-acetate (PMA) or c-Jun overexpression. 15d-PGJ2 interfered with at least two steps within the signaling pathway leading to AP-1 activation. First, 15d-PGJ2 impaired AP-1 binding to a consensus DNA sequence. Second, 15d-PGJ2 selectively inhibited c-Jun NH2 terminal kinase (JNK) but not extracellular signal-regulated kinase or p38 mitogen-activated protein kinase activation induced by PMA. This led to a decreased ability of JNK to phosphorylate c-Jun and to activate its transactivating activity. Inhibition of AP-1 activation and COX-2 or VEGF transcriptional induction by this cyclopentenone was found to be independent of peroxisome proliferator-activated receptor-γ (PPARγ) because it was not affected by either expression of a dominant negative form of PPARγ or the use of a PPARγ antagonist. In contrast, we have found that the effects of 15d-PGJ2 on AP-1 activation may occur through its ability to induce intracellular oxidative stress. The antioxidant N-acetylcysteine significantly reversed the inhibition by 15d-PGJ2 of AP-1 activity and COX-2 or VEGF transcriptional induction. Together, these findings provide new insight into the antitumoral properties of 15d-PGJ2 through the inhibition of the induction of AP-1-dependent genes involved in tumor progression, such as COX-2 and VEGF.
MOUTH INFECTION IN VARIOUS DISEASES
Authors: Oliver T. Osborne
Journal: JAMA (1924)

To the Editor:  —Every physician and surgeon presenting clinical reports on diseases of the heart, diseases of the blood vessels, diseases of the blood, disturbances of the thyroid gland, diseases of the kidneys, especially infection of the kidneys, neuritis, joint inflammations, sacro-iliac pain, and mental disturbances should state the condition of the teeth, tonsils and accessory sinuses, as well as the very scientific reports on roentgen-ray examinations, blood examinations, blood pressure examinations, genito-urinary examinations, electrocardiographic examinations and similar studies.  From the point of view of etiologic value, of the results of treatment, of the pathology, and, in fact, from any standpoint, any report that does not declare the absence or the presence of mouth infection is incomplete and has its value greatly diminished.  The neglect of practicing physicians and surgeons in omitting a study of the mouths of their patients is inexcusable. Moreover, the neglect of laboratory experts in not
A simple algorithm to predict the development of radiological erosions in patients with early rheumatoid arthritis: prospective cohort study
Authors: P. Brennan, B. Harrison, E. Barrett, K. Chakravarty, D. Scott, A. Silman, D. Symmons
Journal: BMJ (1996)

<h3>Abstract</h3> <b>Objective</b>: To produce a practical algorithm to predict which patients with early rheumatoid arthritis will develop radiological erosions. <b>Design</b>: Primary care based prospective cohort study. <b>Setting</b>: All general practices in the Norwich Health Authority, Norfolk <b>Subjects</b>: 175 patients notified to the Norfolk Arthritis Register were visited by a metrologist soon after they had presented to their general practitioners with inflammatory polyarthritis, and again after a further 12 months. All the patients satisfied the American Rheumatism Association9s 1987 criteria for rheumatoid arthritis and were seen by a metrologist within six months of the onset of symptoms. The study population was randomly split into a prediction sample (n = 105) for generating the algorithm and a validation sample (n = 70) for testing it. <b>Main outcome measures</b>: Predictor variables measured at baseline included rheumatoid factor status, swelling of specific joint areas, duration of morning stiffness, nodules, disability score, age, sex, and disease duration when the patient first presented. The outcome variable was the presence of radiological erosions in the hands or feet, or both, after 12 months. <b>Results</b>: A simple algorithm based on a combination of three variables—a positive rheumatoid factor test, swelling of at least two large joints, and a disease duration of more than three months—was best able to predict erosions. When the accuracy of this algorithm was tested with the validation sample, the erosion status of 79% of patients was predicted correctly. <b>Conclusions</b>: A simple algorithm based on three easily measured items of information can predict which patients are at high risk and which are at low risk of developing radiological erosions.
Virologic diagnosis of HCV infection: Proposition of a diagnostic algorithm
Authors: P HALFON
Journal: Hepatology (1995)

Susceptibility of African buffalo, eland, waterbuck, N'Dama and Boran cattle to sequential Glossina morsitans centralis-transmitted infections of Trypanosoma congolense, T. brucei brucei and T. vivax was compared, and their possible role as reservoirs of these parasites for G. moristans centralis, G. pallidipes, G. austeni, G. brevipalpis and G. longipennis determined. The buffalo, eland, waterbuck and N'Dama controlled T. congolense parasitaemias and were able to prevent anaemia. By contrast, one Boran became severely anaemic whilst the other controlled parasitaemia and anaemia. When the above five species of Bovidae were rechallenged with T. brucei brucei they showed persistent parasitaemias but did not develop anaemia. The buffalo died of other causes. When the remaining four bovids were rechallenged with T. vivax they became infected with mixed T. vivax/T. b. brucei parasites. Eland, waterbuck and N'Dama controlled parasitaemias and anaemia whereas the Boran became anaemic. Cyclical development of T. congolense occurred in G. moristans centralis when fed on the bovid hosts, with buffalo being infective for tsetse flies for a much longer period. There was no relationship between the levels of T. congolense parasitaemia in the bovid hosts and the resultant infection rates in tsetse flies. Glossina m. centralis was more susceptible than G. pallidipes to T. brucei brucei whilst G. austeni the least; G. brevipalpis and G. longipennis were refractory to the mature infection. Again there was no relationship between T. brucei brucei parasitaemia levels in the hosts and infection rates in the flies. Glossina m. centralis and G. pallidipes showed mixed T. brucei brucei/T. vivax infections whilst G. austeni, G. brevipalpis and G. longipennis became infected with T. vivax alone. Tsetse flies showed higher T. vivax infection rates when fed on the hosts with high parasitaemias than those with low parasitaemias. Thus trypanotolerant African buffalo, eland, waterbuck, N'Dama as well as some trypanosusceptible Boran cattle can serve as reservoirs of single or mixed trypanosome infections for tsetse flies. This study has also shown that the Ag-ELISA on the sera from the five bovid hosts had low sensitivity and species-specificity. Examinations of thin wet blood films and buffy coats with a phase-contrast microscope were not sensitive enough to detect the parasites on all occasions. Xenodiagnosis using mice for T. brucei brucei and T. congolense infections, and tsetse flies for all the three trypanosome species were most sensitive for the detection of trypanosome infections in the bovid hosts.
Studies on the Mechanism of Oliguria in a Model of Unilateral Acute Renal Failure
Authors: John W. Cox, Richard W. Baehler, Hari Sharma, Thomas O'Dorisio, Richard W. Osgood, Jay H. Stein, Thomas F. Ferris
Journal: Journal of Clinical Investigation (1974)

To further evaluate the mechanism of the oliguria of acute renal failure, a model was utilized in which intense and prolonged vasoconstriction produced the unilateral cessation of urine flow. The radioactive microsphere method was used to measure total and regional blood flow before and after the intrarenal infusion of norepinephrine, 0.75 μg/kg/min, for 2 h in the dog. In the control kidney, renal blood flow increased 32% 48 h after norepinephrine in association with a fall in the fractional distribution of flow to the outer cortex. In the experimental kidney, total renal blood flow fell from 190 ml/min before norepinephrine to 116 ml/min at 48 h (P < 0.025) with a uniform reduction in cortical blood flow. After the administration of 10% body wt Ringer's solution, there was a marked redistribution of flow to inner cortical nephrons in both the control and experimental kidney. In addition, there was a marked increase in total blood flow in both kidneys. On the experimental side, flow rose to 235 ml/min, a value greater than in either the control period (P < 0.05) or at 48 h after norepinephrine (P < 0.001). However, in spite of this marked increase in blood flow, there was essentially no urine flow from the experimental kidney. In separate studies, the animals were prepared for micropuncture. In all studies, the surface tubules were collapsed, and there was no evidence of tubular obstruction or leakage of filtrate. Over 99% of the 15-μM spheres were extracted in one pass through the experimental kidney. An analysis of the forces affecting filtration suggested that an alteration in the ultrafiltration coefficient may be responsible, at least in part, for the anuria in this model. In this regard, transmission and scanning electron microscopy revealed a marked abnormality in the epithelial structure of the glomerulus. It is suggested that a decrease in glomerular capillary permeability may be present in this model of acute renal failure.
Echocardiographic analysis of mitral valve motion after acute myocardial infarction.
Authors: G A Bergeron, M V Cohen, L E Teichholz, R Gorlin
Journal: Circulation (1975)

To examine the effects of acute myocardial infarction on mitral valve diastolic velocity, echocardiograms were performed in 18 patients on admission, daily in the Coronary Care Unit, and at 3-day intervals during the remainder of hospitalization. These patients were divided into three groups based on the time interval between onset of symptoms and initial echocardiogram. Five of six patients admitted within 5 hours of onset of myocardial infarction had a triphasic response of mitral valve diastolic velocity with a transient rise above initial values, followed by a fall to below initial values, and then a slow rise during recovery. Seven of eight patients admitted 1-2 days after onset of myocardial infarction had a biphasic response, i.e., a fall from initial values and then a slow rise. Four patients admitted later in the course of myocardial infarction had a monophasic response, i.e. low initial velocity followed by a slow recovery. We conclude that in patients with myocardial infarction the mitral valve diastolic velocity following myocardial infarction shows a triphasic response which may appear biphasic or monophasic depending on the interval between myocardial infarction and admission. The temporal pattern of mitral valve diastolic velocity changes may reflect the dynamic alterations of myocardial function and compliance that are occurring after acute myocardial infarction and during the recovery period.
S116 MicroRNA Regulation of Toll-Like Receptor 7 Function in Severe Asthma: Relevance to Viral Responses
Authors: H Rupani, P Dennison, N Jayasekera, T Sanchez-Elsner, P H Howarth
Journal: Thorax (2012)

<h3>Background and Aims</h3> Viral-induced disease exacerbation is common in asthma and studies have identified that both bronchial epithelial cells and alveolar macrophages (AM) from asthmatics have a reduced interferon (IFN) response to rhinovirus infection. The mechanism behind this defect is unclear. As asthmatic peripheral blood mononuclear cells have been reported to have defective toll-like receptor (TLR) 7 function, we investigated the expression of microRNAs (miRNAs) in AM from healthy control (HC) and severe asthma (SA) volunteers with relevance to TLR7-viral interactions. MicroRNAs are non-coding RNAs that down-regulate gene expression by suppressing translation. We identified and focused on 3 miRNAs that could target TLR7. Additionally, we investigated if manipulating the expression of these miRNAs can ameliorate the defective IFN response in AM. <h3>Methods</h3> 26 HC and 30 patients with SA (BTS Step 4/5) were recruited for bronchoscopy. AM were isolated from bronchoalveolar lavage using the adherence to plastic technique. Expression of miRNAs and TLR7 was determined by qRT-PCR and western blotting. AM were transfected with a combination of antagomirs, specifically directed against the 3 miRNAs, and then treated with imiquimod (5ug/ml), a TLR7 agonist, or human rhinovirus-16 (HRV16) and IFN-β expression was determined after 24 hours using qRT-PCR and ELISA. <h3>Results</h3> Expression of all three miRNAs was significantly increased in SA compared to HC TLR7 mRNA was found to be significantly reduced in AM from volunteers with SA compared to HC. Western blotting confirmed reduced expression of TLR7 protein in AM from SA compared to HC. Compared to mock transfected AM, AM transfected with the 3 antagomirs showed significantly increased imiquimod-induced IFN-β mRNA and protein expression and significantly increased HRV16-induced IFN-β mRNA production. <h3>Conclusion</h3> TLR7 expression is significantly reduced in SA compared to HC. The differential expression of the miRNAs identified may lead to impaired viral sensing by asthmatic AM and contribute to the defective IFN response to rhinovirus. Importantly, TLR7 induced IFN-β production by human AM can be significantly augmented by inhibition of these miRNAs. The identification of these miRNAs and our ability to manipulate their expression in human AM offers the potential for future miRNA-based therapies in asthma.
Monoamine oxidase inhibitors and low alcohol or alcohol free drinks
Authors: M Sandler
Journal: BMJ (1990)

<h3>Background and objective</h3> Transcutaneous pulse oximetry saturation (<i>S</i><sub>pO<sub>2</sub></sub>) is widely used to diagnose severe hypoxaemia and to prescribe long-term oxygen therapy (LTOT) in COPD. This practice is not based on evidence. The primary objective of this study was to determine the accuracy (false positive and false negative rates) of oximetry for prescribing LTOT or for screening for severe hypoxaemia in patients with COPD. <h3>Methods</h3> In a cross-sectional study, we correlated arterial oxygen saturation (<i>S</i><sub>aO<sub>2</sub></sub>) and <i>S</i><sub>pO<sub>2</sub></sub> in patients with COPD and moderate hypoxaemia (n=240) and calculated the false positive and false negative rates of <i>S</i><sub>aO<sub>2</sub></sub> at the threshold of ≤88% to identify severe hypoxaemia (arterial oxygen tension (<i>P</i><sub>aO<sub>2</sub></sub>) ≤55 mmHg or <i>P</i><sub>aO<sub>2</sub></sub> &lt;60 mmHg) in 452 patients with COPD with moderate or severe hypoxaemia. <h3>Results</h3> The correlation between <i>S</i><sub>aO<sub>2</sub></sub> and <i>S</i><sub>pO<sub>2</sub></sub> was only moderate (intra-class coefficient of correlation: 0.43; 95% confidence interval: 0.32–0.53). LTOT would be denied in 40% of truly hypoxaemic patients on the basis of a <i>S</i><sub>aO<sub>2</sub></sub> &gt;88% (<i>i.e.,</i> false negative result). Conversely, LTOT would be prescribed on the basis of a <i>S</i><sub>aO<sub>2</sub></sub> ≤88% in 2% of patients who would not qualify for LTOT (<i>i.e.,</i> false positive result). Using a screening threshold of ≤92%, 5% of severely hypoxaemic patients would not be referred for further evaluation. <h3>Conclusions</h3> Several patients who qualify for LTOT would be denied treatment using a prescription threshold of saturation ≤88% or a screening threshold of ≤92%. Prescription of LTOT should be based on <i>P</i><sub>aO<sub>2</sub></sub> measurement.
Blunted serotonin response to fenfluramine challenge in premenstrual dysphoric disorder
Authors: M FitzGerald, K M Malone, S Li, W M Harrison, P A McBride, J Endicott, T Cooper, J J Mann
Journal: American Journal of Psychiatry (1997)

Indirect evidence suggests that abnormalities in serotonergic function may be involved in the pathogenesis of premenstrual dysphoric disorder. The goal of this study was to test the hypothesis of serotonergic deficiency in premenstrual dysphoric disorder by measuring the prolactin response to fenfluramine.The authors administered the serotonin-releasing drug dl-fenfluramine in a placebo-controlled protocol to nine women with premenstrual dysphoric disorder and 11 healthy female volunteers in the luteal phase of the menstrual cycle.Compared to the normal subjects, the women with premenstrual dysphoric disorder had a significantly blunted prolactin response to fenfluramine.Premenstrual dysphoric disorder appears to be associated with serotonergic deficiency.
Field Investigation of Diphtheria Outbreak
Authors: J. W. Webb, N. Macfadyen
Journal: BMJ (1947)

An outbreak of diphtheria imited to one house occurred at a boys' boarding-school.The history of the outbreak and the tracing of the source of infection may be of interest.The house contained 39 boys, a matron and her daughter (Mrs.T. and A.T), a house-master, his wife, and four children.The domestic staff consisted of five persons for the boys and three for the family.The population at risk therefore comprised 55 persons, con- sisting of 11 adults, 40 adolescents, and 4 young children.The house was roughly divided into a private side and a school side, but two of the private-side maids, Y.S. and M.R., waited at table on the boys and family.These maids occupied a bedroom opposite to A.T., the matron's daughter.district, and the following events occurred.March 3.-Arrival of M.R. and Y.S. at the inn.March 10.-A contact at the inn, S.B., developed a sore throat and was off work for a week.March 12.-An out-worker at the inn developed diphtheria.March 21.-A guest staying at the inn left for Brighton and was admitted into Brighton Isolation Hospital with diphtheria on March 24
Molecular and mutation trends analyses of omp1 alleles for serovar E of Chlamydia trachomatis. Implications for the immunopathogenesis of disease.
Authors: D Dean, K Millman
Journal: Journal of Clinical Investigation (1997)

Serovars E, F, and D are the most prevalent Chlamydia trachomatis strains worldwide. This prevalence may relate to epitopes that enhance infectivity and transmission. There are numerous major outer membrane protein (MOMP) gene (omp1) variants described for D and F but few for E. However, omp1 constant regions are rarely sequenced yet, they may contain mutations that affect the structure/function relationship of the protein. Further, differentiating variants that occur as a result of selection from variants that contain random mutations without biologic impact is difficult. We investigated 67 urogenital E serovars and found 11 (16%) variants which contained 16 (53%) nonconservative amino acid changes. Using signature-pattern analysis, 57 amino acids throughout MOMP differentiated the E sequence set from the non-E sequence set, thus defining E strains. Four E variants did not match this signature-pattern, and, by phenetic analyses, formed new phylogenetic branches, suggesting that they may be biologically distinct variants. Our analyses offer for the first time a unique approach for identifying variants that may occur from selection and may affect infectivity and transmission. Understanding the mutation trends, phylogeny, and molecular epidemiology of E variants is essential for designing public health control interventions and a vaccine.
The persistence and heterogeneity of factor VIII:C inhibitors as demonstrated by preparative isofocusing
Authors: Macie C. Coots, Helen I. Glueck
Journal: American Journal of Hematology (1990)

The purpose of this study was to determine if factor VIII:C inhibitors completely disappear during remission and if they recur on exacerbation, are they similar to or different from the original inhibitors? To answer these questions, isofocusing, which separates proteins on the basis of their pIs, was utilized to recover inhibitors from the plasmas of six patients, five nonhemophiliacs with acquired VIII:C inhibitors and the sixth with classic hemophilia. Initially, all plasmas were studied during the presenting hemorrhagic episodes and, subsequently, following the disappearance or recurrence of the inhibitors. Following isofocusing, each fraction was tested for inhibitory activity. The method enabled us to determine that inhibitors to factor VIII:C persisted even when they could not be demonstrated by conventional methods. The inhibitory activity resulted from a composite of inhibitors, each of the group identified by its own pI. In many patients, some peaks persisted throughout the entire interval of study, whereas others disappeared and new ones appeared, suggesting that various groups of cells were capable of producing the inhibitors.
WHO is urged to exclude alcohol industry from talks on reducing harms
Authors: A. Gulland
Journal: BMJ (2013)

A group of public health professionals from around the world is urging the World Health Organization to stop the alcohol industry influencing its strategy to reduce harmful use of alcohol.

The Global Alcohol Policy Alliance has issued a “statement of concern” to WHO.1 It warns that a commitment issued by 13 of the world’s largest alcohol producers last October to tackle harmful drinking misinterpreted the role of the drinks industry in WHO’s alcohol strategy. 

The alliance quotes the International Center for Alcohol Policies, a body funded by the drinks industry, which said that WHO’s global strategy had “legitimated industry’s ongoing efforts and has opened the door to the inclusion of producers as equal stakeholders.” 

However, the alliance said that this misinterpreted the role of …