tbuckley/cabot-search huggingface dataset:
Inorganic nitrite and chronic tissue ischaemia: a novel therapeutic modality for peripheral vascular diseases
Authors: C. B. Pattillo, S. Bir, V. Rajaram, C. G. Kevil
Journal: Cardiovascular Research (2010)

Ischaemic tissue damage represents the ultimate form of tissue pathophysiology due to cardiovascular disease, which is the leading cause of morbidity and mortality across the globe. A significant amount of basic research and clinical investigation has been focused on identifying cellular and molecular pathways to alleviate tissue damage and dysfunction due to ischaemia and subsequent reperfusion. Over many years, the gaseous molecule nitric oxide (NO) has emerged as an important regulator of cardiovascular health as well as protector against tissue ischaemia and reperfusion injury. However, clinical translation of NO therapy for these pathophysiological conditions has not been realized for various reasons. Work from our laboratory and several others suggests that a new form of NO-associated therapy may be possible through the use of nitrite anion (sodium nitrite), a prodrug which can be reduced to NO in ischaemic tissues. In this manner, nitrite anion serves as a highly selective NO donor in ischaemic tissues without substantially altering otherwise normal tissue. This surprising and novel discovery has reinvigorated hopes for effectively restoring NO bioavailability in vulnerable tissues while continuing to reveal the complexity of NO biology and metabolism within the cardiovascular system. However, some concerns may exist regarding the effect of nitrite on carcinogenesis. This review highlights the emergence of nitrite anion as a selective NO prodrug for ischaemic tissue disorders and discusses the potential therapeutic utility of this agent for peripheral vascular disease.
Comorbidities, complications, and coding bias. Does the number of diagnosis codes matter in predicting in-hospital mortality?
Authors: L I Iezzoni, S M Foley, J Daley, J Hughes, E S Fisher, T Heeren
Journal: JAMA (1992)

<h3>Objective.</h3> —Incomplete coding of secondary diagnoses may bias assessments of patient risks of poor outcomes using administrative health care databases, most of which allow only five diagnoses. The Medicare program is expanding the number of possible diagnoses from five to nine, aiming to improve coding completeness. We examined the impact of having more diagnosis codes available on assessments of risk of death. <h3>Design.</h3> —We used 1988 computerized hospital discharge abstract data from California, which allow up to 25 diagnoses per discharge, to select a sample of hospitalized patients and assessed the relationship between the presence of 29 specific secondary diagnoses and the risk of in-hospital death. <h3>Setting.</h3> —Nonfederal acute-care hospitals in California. <h3>Study Population.</h3> —All patients at least 65 years of age who were hospitalized for stroke, pneumonia, acute myocardial infarction, or congestive heart failure in California in 1988 (N = 162 790). <h3>Main Outcome Measures.</h3> —Relative risk of death for each specific secondary diagnosis. <h3>Results.</h3> —Many conditions that on a clinical basis would be expected to increase the risk of death, such as adult-onset diabetes mellitus, previous myocardial infarction, angina, and ventricular premature beats, were associated with a lower risk of in-hospital death. <h3>Conclusions.</h3> —Bias against coding of chronic or comorbid conditions on the computerized discharge abstracts of patients who die best explains these results. Efforts to improve diagnosis coding completeness solely by increasing the number of available coding spaces may not succeed. (<i>JAMA</i>. 1992;267:2197-2203)
Effects of Ketamine on Anterior Cingulate Glutamate Metabolism in Healthy Humans: A 4-T Proton MRS Study
Authors: Laura M Rowland, Juan R Bustillo, Paul G Mullins, Rex E Jung, Rhoshel Lenroot, Elma Landgraf, Ranee Barrow, Ronald Yeo, John Lauriello, William M Brooks
Journal: American Journal of Psychiatry (2005)

OBJECTIVE: The authors’ goal was to test in humans the hypothesis that N-methyl-d-aspartate receptor (NMDAR) antagonism results in increased cortical glutamate activity, as proposed by the NMDAR hypofunction model of schizophrenia. METHOD: 4-T 1H proton magnetic resonance spectroscopy (1H-MRS) was used to acquire in vivo spectra from the bilateral anterior cingulate of 10 healthy subjects while they received a subanesthetic dose of either placebo or ketamine, an NMDAR antagonist. Assessments given before and after ketamine or placebo administration included the Brief Rating Psychiatric Rating Scale, the Scale for the Assessment of Negative Symptoms, the Clinician-Administered Dissociative States Scale, and the Stroop task. RESULTS: As predicted, there was a significant increase in anterior cingulate glutamine, a putative marker of glutamate neurotransmitter release, with ketamine administration. This increase was not related to schizophrenia-like positive or negative symptoms but was marginally related to Stroop performance. CONCLUSIONS: In humans as in animals, an acute hypofunctional NMDAR state is associated with increased glutamatergic activity in the anterior cingulate.
Capillary growth in anemia-induced ventricular wall remodeling in the rat heart.
Authors: G Olivetti, C Lagrasta, F Quaini, R Ricci, G Moccia, J M Capasso, P Anversa
Journal: Circulation Research (1989)

To determine whether anemia-induced cardiac hypertrophy affects ventricular size and shape and the component structures of the capillary network of the left and right ventricles, young male rats were fed an iron- and copper-deficient diet for 7 weeks. By that time, blood hemoglobin content fell to 5 +/- 1 g/dl, and packed cell volume fell to 18 +/- 3%. To further characterize the implications of anemia, red blood cell number, hemoglobin corpuscular content, systemic arterial pressure, heart rate, and blood viscosity were measured. Moreover, the changes in ventricular weights were analyzed in terms of the alterations in ventricular wall area and ventricular wall thickness to establish the impact of the elevation in load associated with a high cardiac output state on ventricular remodeling. The quantitative properties of the capillary circulation were also examined biventricularly by low power electron microscopic morphometry to evaluate the adaptive growth potential of the coronary microcirculation in this form of cardiac hypertrophy. Anemia was found to interfere with the production of red blood cells and their mean corpuscular hemoglobin content and resulted in a 40% reduction in blood viscosity and a 12% and 27% decrease in systolic and diastolic blood pressure, respectively. The changes in heart rate were not statistically significant. In comparison with control animals, heart weight increased by 50%, but the enlargement in right ventricular mass (65%) was greater than that of the left ventricle (47%). Ventricular hypertrophy occurred with increases in wall area and wall thickness although the former increased consistently more than the latter in either ventricle. Tissue growth was accompanied by a 60% lengthening of the capillary network, which in combination with an increase in capillary diameter resulted in a 65% and 34% expansion in capillary luminal volume and 56% and 20% larger luminal surface density in the left and right sides of the heart, respectively. In conclusion, hypochromic microcytic anemia leads to eccentric ventricular hypertrophy with a significant amount of capillary proliferation that may tend to protect the myocardium from the increased potential for ischemic injury.
Untangling Differences in Cancer Mortality Rates: A Closer Look at Race and Education
Authors: S. Wacholder
Journal: JNCI Journal of the National Cancer Institute (2007)

JNCI Vol. 99, Issue 18 | September 19, 2007 In this issue of the Journal, Albano et al. ( 1 ) draw attention to the association between education and cancer mortality overall and for the most common sites among white men and women and among black men and women. Their effort to cull the information on educational level from death certificates adds to the wealth of descriptive data on racial disparities in cancer mortality in the United States. However, the authors are not able to address with confidence a question that many readers will ask: do differences in education explain racial differences in cancer mortality? Albano et al. ( 1 ) show age-adjusted cancer mortality rates by years of formal education within strata that are defi ned by sex and race for individuals aged 25 – 64 years using information from death certifi cates collected in 47 of the 50 states and the District of Columbia for the year 2001. These rates are broadly representative of those for individuals younger than 65 years in the US population. The age restriction excludes deaths in older people, which, for example, constitute more than 90% of deaths from prostate cancer ( 2 ). Two unrealistic assumptions are required to extrapolate from the data presented by Albano et al. ( 1 ) to a conclusion that education level explains some fraction of the difference in cancer mortality rates between blacks and whites: fi rst, that we can estimate the effect of race on educational achievement, and second, that we can estimate the effect of increasing a child’s educational level on his or her subsequent risk of death from cancer. Estimating these effects is challenging because educational level both refl ects and affects personal and family income in childhood and adulthood, health insurance coverage and the use of preventive measures, early detection of cancer and medical care, occupational choices, and behavioral, occupational, and environmental factors — all of which have an impact on mortality. How might comparisons of education-, sex-, and race-specifi c cancer mortality rates obtained from vital statistics records improve health? Unequal mortality rates between groups can sometimes provide hints about where a successful public health intervention might have the greatest potential impact. The extra detail about educational level provided in the study by Albano et al. ( 1 ) might help in the design of more intensive attempts at reducing cancer Untangling Differences in Cancer Mortality Rates: A Closer Look at Race and Education
Risk factors for noma disease: a 6-year, prospective, matched case-control study in Niger
Authors: Denise Baratti-Mayer, Angèle Gayet-Ageron, Stéphane Hugonnet, Patrice François, Brigitte Pittet-Cuenod, Antoine Huyghe, Jacques-Etienne Bornand, Alain Gervaix, Denys Montandon, Jacques Schrenzel, Andrea Mombelli, Didier Pittet
Journal: The Lancet Global Health (2013)

BackgroundNoma is a poorly studied disease that leads to severe facial tissue destruction in children in developing countries, but the cause remains unknown. We aimed to identify the epidemiological and microbiological risk factors associated with noma disease.MethodsWe did a prospective, matched, case-control study in Niger between Aug 1, 2001, and Oct 31, 2006, in children younger than 12 years to assess risk factors for acute noma. All acute noma cases were included and four controls for each case were matched by age and home village. Epidemiological and clinical data were obtained at study inclusion. We undertook matched-paired analyses with conditional logistic regression models.FindingsWe included 82 cases and 327 controls. Independent risk factors associated with noma were: severe stunting (odds ratio [OR] 4·87, 95% CI 2·35–10·09) or wasting (2·45, 1·25–4·83); a high number of previous pregnancies in the mother (1·16, 1·04–1·31); the presence of respiratory disease, diarrhoea, or fever in the past 3 months (2·70, 1·35–5·40); and the absence of chickens at home (1·90, 0·93–3·88). After inclusion of microbiological data, a reduced proportion of Fusobacterium (4·63, 1·61–13·35), Capnocytophaga (3·69, 1·48–9·17), Neisseria (3·24, 1·10–9·55), and Spirochaeta in the mouth (7·77, 2·12–28·42), and an increased proportion of Prevotella (2·53, 1·07–5·98), were associated with noma. We identified no specific single bacterial or viral pathogen in cases.InterpretationNoma is associated with indicators of severe poverty and altered oral microbiota. The predominance of specific bacterial commensals is indicative of a modification of the oral microbiota associated with reduced bacterial diversity.FundingGertrude Hirzel Foundation.
Capecitabine plus oxaliplatin and irinotecan regimen every other week: a phase I/II study in first-line treatment of metastatic colorectal cancer
Authors: E Bajetta, L Celio, E Ferrario, M Di Bartolomeo, A Denaro, K Dotti, M Mancin, R Bajetta, A Colombo, S Pusceddu
Journal: Annals of Oncology (2007)
In vitro antigen-induced, antigen-specific antibody production in man. Specific and polyclonal components, kinetics, and cellular requirements.
Authors: H C Lane, D J Volkman, G Whalen, A S Fauci
Journal: The Journal of Experimental Medicine (1981)

A highly specific and reproducible antigen-induced, antigen-specific culture and assay system for antibody production by human peripheral blood B lymphocytes has been developed. The system is clearly T cell and monocyte dependent and is independent of exogenous mitogens. The major factors in our ability to trigger specific antibody production with antigen alone have been the use of extremely low concentrations of antigen in vitro (doses several orders of magnitude below those inducing a peak blastogenic response), careful attention to in vitro cell density and culture vessel geometry, and appreciation of the kinetics of the circulating antigen-inducible B cell repertoire. A dichotomy and overlap between antigen-induced, antigen-specific and antigen-induced, polyclonal responses was observed in the study of doubly immunized individuals. Whereas antibody responses highly specific for the antigen in culture were observed under one set of culture conditions (flat-bottomed vessels, 1.5 x 10(6) cells), switching to another culture system (round-bottomed vessels, 5 x 10(5) cells) resulted in polyclonal responses to antigen. Despite these culture condition-related differences in the induction of antibody synthesis, the suppression of specific antibody production that occurred at high concentrations of antigen was specific only for the antigen in culture. The capability to easily and reproducibly look at truly antigen-induced, antigen specific antibody production should be a major tool in furthering the understanding of human B cell activation and immunoregulation.
Caspase 8 activation independent of Fas (CD95/APO-1) signaling may mediate killing of B-chronic lymphocytic leukemia cells by cytotoxic drugs or γ radiation
Authors: Dylan T. Jones, Kanagasabai Ganeshaguru, Andres E. Virchis, Najeem I. Folarin, Mark W. Lowdell, Atul B. Mehta, H. Grant Prentice, A. Victor Hoffbrand, R. Gitendra Wickremasinghe
Journal: Blood (2001)

Abstract Ligation of the cell-surface Fas molecule by its ligand (Fas-L) or agonistic anti-Fas monoclonal antibodies results in the cleavage and activation of the cysteine protease procaspase 8 followed by the activation of procaspase 3 and by apoptosis. In some leukemia cell lines, cytotoxic drugs induce expression of Fas-L, which may contribute to cell killing through the ligation of Fas. The involvement of Fas, Fas-L, and caspase 8 was studied in the killing of B-cell chronic lymphocytic leukemia (B-CLL) cells by chlorambucil, fludarabine, or γ radiation. Spontaneous apoptosis was observed at 24-hour incubation, with additional apoptosis induced by each of the cytotoxic treatments. Although Fas mRNA expression was elevated after exposure to chlorambucil, fludarabine, or γ radiation, Fas protein levels only increased after irradiation. Therefore, Fas expression may be regulated by multiple mechanisms that allow the translation of Fas mRNA only in response to restricted cytotoxic stimuli. None of the cytotoxic stimuli studied here induced Fas-L expression. An agonistic anti-Fas monoclonal antibody (CH-11) did not significantly augment apoptosis induction by any of the death stimuli. A Fas-blocking antibody (ZB4) did not inhibit spontaneous, chlorambucil-, fludarabine-, or radiation-induced apoptosis. However, procaspase 8 processing was induced by all cytotoxic stimuli. These data suggest that the Fas/Fas-L signaling system does not play a major role in the induction of apoptosis in B-CLL cells treated with cytotoxic drugs or radiation. However, Fas-independent activation of caspase 8 may play a crucial role in the regulation of apoptosis in these cells.
Proptosis can be the presenting feature of systemic lupus erythematosus
Authors: S Siebert
Journal: Annals of the Rheumatic Diseases (2004)

The patient, a 23 year old student, initially presented to another hospital with swelling of his left eye. Clinical examination showed only isolated proptosis of his left eye. A computed tomographic (CT) scan of his orbits was consistent with orbital pseudotumour, for which he was given a short course of oral steroids, with good clinical response. He was then lost to follow up as he returned home from his studies.

A few months later he presented to the physicians in our hospital with a 2 week history of painful swelling of his left eye, accompanied by polyarthralgia, fever with rigors, and lethargy. Further questioning showed he had mild photosensitivity and frequent mouth ulcers of several months’ duration. He had not been receiving any other drug before the onset of symptoms. At the time of admission he was clearly unwell and extremely lethargic, with a temperature of 37.4°C. He had no facial rash, but he did have tender proptosis of his left eye. There was no associated ophthalmoplegia. He …
A retrospective study of 69 patients with t(6;9)(p23;q34) AML emphasizes the need for a prospective, multicenter initiative for rare ‘poor prognosis’ myeloid malignancies
Authors: M L Slovak, H Gundacker, C D Bloomfield, G Dewald, F R Appelbaum, R A Larson, M S Tallman, J M Bennett, D L Stirewalt, S Meshinchi, C L Willman, Y Ravindranath, T A Alonzo, A J Carroll, S C Raimondi, N A Heerema
Journal: Leukemia (2006)
Type II alveolar epithelial cells and interstitial fibroblasts express connective tissue growth factor in IPF
Authors: L-H. Pan, K. Yamauchi, M. Uzuki, T. Nakanishi, M. Takigawa, H. Inoue, T. Sawai
Journal: European Respiratory Journal (2001)

Connective tissue growth factor (CTGF) is a growth and chemotactic factor for fibroblasts encoded by an immediate early gene that is transcriptionally activated by transforming growth factor-β. Previous studies have shown that both CTGF messenger ribonuclear acid (mRNA) and protein are expressed in renal fibrosis and bleomycin-induced pulmonary fibrosis in mice. The aim of the present study was to investigate the localization of CTGF protein and its mRNA expression in the fibrotic lung tissue of patients with idiopathic pulmonary fibrosis (IPF). Using human fibrotic lung tissue obtained from eight autopsy cases and four biopsy cases with IPF, immunohistochemical staining, in situ hybridization, and reverse transcription-polymerase chain reaction (RT-PCR) were performed. The cellular immunoreactivity for CTGF was markedly increased in the lung tissue of patients with IPF, compared to normal lungs. The immunolocalization of CTGF was confined predominantly to proliferating type II alveolar epithelial cells and activated fibroblasts. In the normal lung, type II alveolar epithelial cells stained for CTGF were sparsely distributed. CTGF mRNA was localized in proliferating type II alveolar epithelial cells and activated fibroblasts in the interstitium of fibrotic lung tissues. RT-PCR analysis showed that CTGF mRNA was expressed at a higher level in fibrotic lungs than in normal lungs. In both an autocrine and a paracrine manner, type II alveolar epithelial cells and activated fibroblasts may play a critical role in pulmonary fibrosis by producing connective tissue growth factor which modulates fibroblast proliferation and extracellular matrix production.
Skin bruising, adrenal function and markers of bone metabolism in asthmatics using inhaled beclomethasone and fluticasone
Authors: J.-L. Malo, A. Cartier, H. Ghezzo, S. Mark, J Brown, M Laviolette, L.-P Boulet
Journal: European Respiratory Journal (1999)

Fluticasone propionate (FP) is generally considered to have twice the efficacy of beclomethasone dipropionate (BDP) on a weight-to-weight basis for the control of asthma, and may have lesser effects on adrenal function. However, the effects of FP and BDP on skin integrity and bone metabolism markers require further examination. Sixty-nine asthmatic subjects were enrolled in a double-blind crossover study in which, after a baseline period, they received BDP or FP (at half the dose of BDP) for two 4-month periods each. A questionnaire on skin bruising, a skin examination, tests of adrenal function and of markers of bone metabolism were performed after 2 months of each period. The number of asthma exacerbations was not significantly different for the two treatment periods (eight for BDP and nine for FP), nor were various indices of asthma control. Whereas the frequency of bruising reported by the questionnaire was not different, there were more bruises on examination for BDP (1.6+/-2.5) than for FP (1.2+/-2.3) (p=0.04). Although baseline serum cortisol was not significantly different for the two drugs, the increase in cortisol after cortrosyn was lower for BDP (357+/-158 micromol x dL(-1)) than for FP (422+/-144 micromol x dL(-1)) (p<0.01). Serum osteocalcin levels were significantly lower in subject on BDP (2.8+/-1.7 microg x mL(-1)) than on FP (3.5+/-1.9 ng x mL(-1)) (p=0.003). Other markers of bone metabolism were not significantly altered. The three major side-effects were loosely, but significantly correlated with the periods on BDP and FP. However, skin bruises, increase in cortisol after Cortrosyn and osteocalcin were not significantly correlated for the period on either BDP or FP. In conclusion, whereas fluticasone propionate used at half the dose of beclomethasone dipropionate has a comparable effect on the control of asthma, fluticasone propionate demonstrated fewer side-effects in terms of skin bruising, adrenal suppression and bone metabolism.
Treatment of Basal Cell Epitheliomas And Actinic Keratoses
Authors: G. Thomas Jansen
Journal: JAMA (1976)

BASAL cell epithelioma is the most common skin carcinoma in the United States. Because these lesions rarely metastasize, their medical importance has been minimized by some, and others have approached treatment with a cavalier attitude. Fortunately, a majority of basal cell epitheliomas can be cured with a simple treatment approach, especially when the lesions are of the common "rodent ulcer" or<i>solid</i>type (Fig 1), containing only a small amount of fibrous stroma. However, the physician must realize that this carcinoma has an unusual number of clinical traits capable of invading cartilage and bone and extending along blood vessels and nerves, leading toward the recurrent, serious, and complicated cases (Fig'2). These variations include the<i>superficial erythematous</i>type (Fig 3), which may resemble psoriasis or eczema. Treatment may be delayed because of clinical misinterpretation. Another form may be<i>deeply pigmented</i>(Fig 4) and mistaken for a nevus, or malignant melanoma. The