tbuckley/cabot-search huggingface dataset:
Noninvasive Proportional Assist Ventilation for Acute Respiratory Insufficiency
Authors: PETER C. GAY, DEAN R. HESS, NICHOLAS S. HILL
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Noninvasive positive pressure ventilation (NPPV) is usually applied using pressure support ventilation (PSV). Proportional assist ventilation (PAV) is a newer mode that delivers assisted ventilation in proportion to patient effort. We hypothesized that PAV for NPPV would support gas exchange and avoid intubation as well as PSV and be more comfortable and tolerable for patients. Adult patients with acute respiratory insufficiency were randomized to receive NPPV with PAV delivered using the Respironics Vision ventilator or PSV using a Puritan-Bennett 7200ae critical care ventilator. Each mode was adjusted to relieve dyspnea and improve gas exchange until patients met weaning or intubation criteria, died, or refused to continue. Twenty-one and 23 patients were entered into the PAV and PSV groups, respectively, and had similar diagnoses and baseline characteristics, although pH was slightly lower in the PAV group (7.30 versus 7.35, p = 0.02). Mortality and intubation rates were similar, but refusal rate was lower, reduction in respiratory rate was more rapid, and there were fewer complications in the PAV group. We conclude that use of the PAV mode is feasible for noninvasive therapy of acute respiratory insufficiency. Compared with PSV delivered with the Puritan-Bennett 7200ae, PAV is associated with more rapid improvements in some physiologic variables and is better tolerated.
Once Daily Treatment with Beclomethasone Dipropionate Hydrofluoroalkane Nasal Aerosol Is Safe and Effective in Children (6-11 Years of Age) With Seasonal Allergic Rhinitis
Authors: N. Segall, L. Mansfield, N. Amar, P.M. Dorinsky, L. Kelley, Y. Ding, S.K. Tantry
Journal: Journal of Allergy and Clinical Immunology (2012)
Leptin attenuates cardiac apoptosis after chronic ischaemic injury
Authors: Kenneth R. McGaffin, Baobo Zou, Charles F. McTiernan, Christopher P. O’Donnell
Journal: Cardiovascular Research (2009)

We have previously shown that activation of leptin signalling in the heart reduces cardiac morbidity and mortality after myocardial infarction (MI). In the present study, we tested the hypothesis that leptin signalling limits cardiac apoptosis after MI through activation of signal transducer and activator of transcription (STAT)-3 responsive anti-apoptotic genes, including B-cell lymphoma (bcl)-2 and survivin, that serve to downregulate the activity of caspase-3. Hearts from C57BL/6J and three groups of leptin-deficient Ob/Ob mice (food-restricted, ad libitum, and leptin-repleted) were examined 4 weeks after permanent left coronary artery ligation or sham operation. Inflammatory and apoptotic cell number was determined in cardiac sections by immunostaining. Expression of cardiac bcl-2, survivin, and pro and active caspase-3 was determined and correlated with in vitro caspase-3 activity. In the absence of MI, both lean and obese leptin-deficient mice exhibited increased cardiac apoptosis compared with wild-type mice. After MI, the highest rates of apoptosis were seen in the infarcted tissue of lean and obese Ob/Ob mice. Further, leptin-deficient hearts, as well as hearts from wild-type mice treated with the STAT-3 inhibitor WP1066, exhibited blunted anti-apoptotic bcl-2 and survivin gene expression, and increased caspase-3 protein expression and activity. The increased caspase-3 activity and apoptosis in hearts of leptin-deficient mice after MI was significantly attenuated in Ob/Ob mice replete with leptin, reducing apoptosis to levels comparable to that observed in wild-type mice after MI. These results demonstrate that intact leptin signalling post-MI acts through STAT-3 to increase anti-apoptotic bcl-2 and survivin gene expression and reduces caspase-3 activity, consistent with a cardioprotective role of leptin in the setting of chronic ischaemic injury.
The effect of different doses of aerobic exercise training on endothelial function in postmenopausal women with elevated blood pressure: results from the DREW study
Authors: Damon L Swift, Conrad P Earnest, Steven N Blair, Timothy S Church
Journal: British Journal of Sports Medicine (2011)

Objectives The aim of this study was to examine the effect of three different doses of aerobic exercise training (corresponding to approximately 50%, 100% and 150% of the National Institutes of Health consensus guidelines) on endothelial function in sedentary obese postmenopausal women with elevated blood pressure. Aerobic exercise training improves endothelial function in individuals with cardiovascular risk; however, it is unknown whether these adaptations occur in a dose-dependent manner. Methods Obese postmenopausal women (n=155) with elevated blood pressure (systolic blood pressure between 120 and 159.0 mm Hg) were randomly assigned to one of four groups: 4, 8 or 12 kilocalories per kilogram of energy expenditure per week (kcal/kg/week) or a non-exercise control group for 6 months. Endothelial function was assessed via flow-mediated dilation (FMD) at baseline and post-intervention. Results After exercise training, there was a similar improvement (1.02–1.5%) in FMD in all three exercise groups (p&lt;0.05) compared with control (–0.5%). Change in FMD after exercise training was significantly correlated with FMD at baseline (r= –0.35, p&lt;0.001). Post hoc analyses found a significant improvement in FMD in exercisers (all exercise groups combined) with endothelial dysfunction (FMD &lt; 5.5%) at baseline (1.8%, 95% CI: 1.17 to 2.38; p&lt;0.001) compared with exercisers with normal endothelial function (FMD ≥ 5.5%) (–1.2%; 95% CI: –1.17 to 0.69; p=0.60). Conclusions Aerobic exercise training was associated with improved FMD in postmenopausal women with elevated blood pressure. In addition, exercise training may be more efficacious in improving endothelial function in postmenopausal women with endothelial dysfunction than individuals with normal endothelial function at baseline.
MULTIPLICATION AND SURVIVAL OF TUBERCLE BACILLI IN THE ORGANS OF MICE
Authors: Cynthia H. Pierce, René J. Dubos, Werner B. Schaefer
Journal: The Journal of Experimental Medicine (1953)

Cultures of tubercle bacilli (typical bovine and human strains) known to differ in the severity of the lesions they induce in experimental animals, were injected in various doses into the cerebrum, peritoneal cavity, or blood stream of mice. Quantitative determinations of the numbers of living bacilli present in the tissues at different intervals of time after infection led to the following classification of the cultures tested:— (a) Certain well known variant forms of tubercle bacilli were found to be unable to multiply in vivo, although they could survive for many weeks in the tissues of mice. These organisms proved to be truly avirulent. (b) Other variant forms underwent multiplication in vivo, even when extremely small infective doses were used, but could not give rise to progressive disease. It is proposed to designate these strains, which produce only abortive infections, as "attenuated." Different levels of attenuation could be detected. The maximum numbers of living bacilli that were recovered from the tissues corresponded directly to the severity and duration of the abortive lesions that could be produced by the strain in guinea pigs or in mice and were characteristic for each strain tested. The two BCG substrains tested were found to differ markedly in their level of attenuation. (c) The cultures virulent for guinea pigs were also capable of establishing a progressive infection in mice even when small infective doses were used. In the case of the attenuated and virulent strains, the population of living bacilli present in the lungs was at first much lower than that in the spleen, but it continued to increase in the former organs throughout the period of observation. This was notably true in the case of the virulent cultures. In contrast, the numbers of living bacilli in the spleen rapidly reached a maximum in the case of all cultures and then decreased progressively. For a given infective dose, and a given interval of time after inoculation, the maximum levels of living bacterial population attained in the spleen and in the lungs proved to be a direct expression of the virulence of the strain.
Immunologic Tolerance to the Insulin Analogue Glulisine
Authors: Nobuaki Ozaki, Yutaka Oiso
Journal: Diabetes Care (2010)

Systemic allergy to insulin is a rare but severe condition. The introduction of human insulin analogues lispro and aspart has considerably decreased the severity of a reaction to insulin (1). However, cases of an allergic reaction to these analogues have also been reported (2). We describe the case of a patient in which severe systemic allergy subsided after glulisine, the latest insulin analogue, was administered.

A 33-year-old man was referred to our hospital for the management of type 1 diabetes and insulin allergy. Previously, we showed that intravenous administration using a portable device …
Genetic Factors Influencing Irradiation Protection by Bone Marrow. V. Multiple Allogeneic Donors
Authors: Delta E. Uphoff, Louisa P. Press, Rose Lieberman
Journal: JNCI Journal of the National Cancer Institute (1965)

Under certain conditions, lethally irradiated strain A mice were protected against acute irradiation death by a marrow pool from several allogeneic donors without an increase of the total inoculum. The secondary disease syndrome was severe and lethal when the marrow pool consisted of only “incompatible” marrow. Addition of related hybrid marrow or H-2 “compatible” marrow to the pool decreased the severity of the syndrome. Survival was intermediate between that expected after the inoculation of the most compatible marrow and the least compatible marrow. Permanent marrow grafts, as indicated by acceptance of parental strain skin homografts and by presence of hybrid γ-globulin allotypes, were established with marrow from related F1 hybrids and H-2 compatible hybrids. Permanent skin homografts indicated mixed chimerism between related F1 hybrid and incompatible hybrid marrow when one parent of each hybrid was compatible. The γ-globulin allotype data suggest the possibility of other mixed chimerism, but absence of permanent skin homograft of the appropriate phenotype indicates the necessity for further investigation of the correlation of γ-globulin allotypes and skin homograft acceptance, or rejection, or both.
Correlation of Specific Amyloid-β Oligomers With Tau in Cerebrospinal Fluid From Cognitively Normal Older Adults
Authors: Maureen Handoko, Marianne Grant, Michael Kuskowski, Kathleen R. Zahs, Anders Wallin, Kaj Blennow, Karen H. Ashe
Journal: JAMA Neurology (2013)

To improve the ability to develop treatments that prevent incipient Alzheimer disease (AD) from progressing to overt AD, it is important to understand the molecular basis of the earliest pathophysiological abnormalities and to determine how amyloid-β (Aβ) is involved very early in its pathogenesis.To investigate 2 specific Aβ oligomers, Aβ trimers and Aβ*56, in human cerebrospinal fluid (CSF); evaluate the effects of aging and AD; and obtain support for the hypothesis that they may be pathogenic by determining their relationships to CSF tau.A CSF sampling study.The University of Minnesota Medical School in Minneapolis, Minnesota, and the Salhgrenska University Hospital, Sweden.Forty-eight older adults with mild cognitive impairment or AD (impaired group); 49 age-matched cognitively intact control subjects (unimpaired group); and 10 younger, normal control subjects.Measurements of CSF Aβ trimers, Aβ*56, the 42-amino acid Aβ isoform (Aβ1-42), total tau (T-tau), and phospho-tau 181 (p-tau(181)). The hypothesis being tested was formulated after data collection. RESULTS We observed that Aβ trimers and Aβ*56 levels increased with age; within the unimpaired group, they were elevated in subjects with T-tau/Aβ1-42 ratios greater than a cutoff that distinguished the unimpaired group from subjects with AD. In the unimpaired group, T-tau and p-tau(181) were found to correlate strongly with Aβ trimers and Aβ*56 (r > 0.63), but not with Aβ1-42 (-0.10 < r < -0.01). The strong correlations were found to be attenuated in the impaired group.In cognitively intact older adults, CSF Aβ trimers and Aβ*56 were elevated in individuals at risk for AD, and they showed stronger relationships with tau than did Aβ1-42, a surrogate for Aβ fibril deposition. These findings suggest that prior to overt symptoms, 1 or both of the Aβ oligomers, but not fibrillar Aβ, is coupled to tau; however, this coupling is weakened or broken when AD advances to symptomatic stages. The uncoupling is interesting in light of the failure of experimental Aβ therapies to improve mild cognitive impairment/AD, which has prompted a shift in the timing of Aβ therapies to asymptomatic subjects. Knowing which Aβ species to target in asymptomatic subjects may enhance the success of future treatments for AD.
Patients with Active Tuberculosis often Have Different Strains in the Same Sputum Specimen
Authors: Robin M. Warren, Thomas C. Victor, Elizabeth M. Streicher, Madalene Richardson, Nulda Beyers, Nicolaas C. Gey van Pittius, Paul D. van Helden
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

It is generally accepted that tuberculosis results from a single infection with a single Mycobacterium tuberculosis strain. Such infections are thought to confer protective immunity against exogenous reinfection. In this study, a novel polymerase chain reaction method was developed to specifically identify M. tuberculosis strains belonging to the Beijing and non-Beijing evolutionary lineages in sputum specimens collected from tuberculosis patients resident in an epidemiologic field site in Cape Town, South Africa. The sensitivity and specificity of the polymerase chain reaction–based strain classification method were 100% (95% confidence interval, 85–100%) when compared with DNA fingerprinting and spacer oligotyping (spoligotyping). Application of this method showed that 19% of all patients were simultaneously infected with Beijing and non-Beijing strains, and 57% of patients infected with a Beijing strain were also infected with a non-Beijing strain. Multiple infections were more frequent in retreatment cases (23%) as compared with new cases (17%), but were not associated with sex, age, or smear grading. These results suggest that multiple infections are frequent, implying high reinfection rates and the absence of efficient protective immunity conferred by the initial infection. This finding could influence our understanding of the epidemiology of disease in high-incidence regions and our understanding for vaccine development.
Serological evidence of infection with Chlamydia pneumoniae is related to the severity of asthma
Authors: P.N. Black, R. Scicchitano, C.R Jenkins, F Blasi, L Allegra, J Wlodarczyk, B.C Cooper
Journal: European Respiratory Journal (2000)

There is evidence that infection with Chlamydia pneumoniae is associated with asthma of recent onset and that it can influence the severity of asthma. This has led to the suggestion that macrolide antibiotics may be useful in the treatment of asthma in subjects infected with C. pneumoniae. This study examined the association between immunoglobulin (Ig)G and IgA titres to C. pneumoniae and the severity of asthma. IgG and IgA antibodies to C. pneumoniae were measured in 619 subjects with asthma (18-60 yrs), using the microimmunofluoresence method. Subjects were asked about their use of asthma medicines, symptoms, previous hospitalization for asthma, smoking status and age of onset of asthma. In subjects with IgG titres of > or =1:64 and/or IgA titres > or =1:16 (n=212), spirometry was performed and peak expiratory flow rate (PEFR) and symptoms were recorded twice daily for 4 weeks on a diary card. The use of high dose inhaled steroids was associated with an increase of 74.1% in the titre of IgG antibodies (p=0.04) and an increase of 70.6% in the titre of IgA antibodies (p=0.0001) when compared with the use of low dose inhaled steroids. There was an inverse association between IgG antibodies and forced expiratory volume in one second (FEV1) as a percentage of predicted in those subjects with elevated IgG and/or IgA (p=0.04). In this group IgA antibodies were also associated with a higher daytime symptom score (p=0.04). Higher titres of antibodies to Chlamydia pneumoniae appears to be associated with markers of asthma severity. This raises the possibility that chronic infection with Chlamydia pneumoniae leads to an increase in the severity of asthma. Studies aimed at eradicating chronic infection with Chlamydia pneumoniae are necessary to determine whether or not this is the case.
Antisecretory activity of pirenzepine versus cimetidine in man: a controlled study.
Authors: F Procacciante, G Citone, C Montesani, G Ribotta
Journal: Gut (1984)

Antisecretory effect of single oral therapeutic doses of pirenzepine (25 mg and 50 mg) and cimetidine (200 mg and 400 mg) was studied in 12 patients with duodenal ulcer. Gastric secretion was studied in basal condition and after stimulation with pentagastrin. Basal, maximum and peak acid output, basal and maximum acidity, and basal and maximum volume were calculated after computerised correction for pyloric loss and duodenal reflux. Both drugs showed dose-related inhibition of all facets of gastric secretion. Cimetidine (200 mg) had a greater inhibitory effect on gastric basal secretion, but a similar effect on pentagastrin stimulated secretion as with pirenzepine (50 mg). Cimetidine (400 mg) showed about twice the inhibitory activity of pirenzepine (50 mg) both on basal and stimulated secretion.
Development of Polycystic Kidney Disease in Juvenile Cystic Kidney Mice
Authors: Laurie A. Smith, Nikolay O. Bukanov, Hervé Husson, Ryan J. Russo, Tiffany C. Barry, Ava L. Taylor, David R. Beier, Oxana Ibraghimov-Beskrovnaya
Journal: Journal of the American Society of Nephrology (2006)

Significant progress in understanding the molecular mechanisms of polycystic kidney disease (PKD) has been made in recent years. Translating this understanding into effective therapeutics will require testing in animal models that closely resemble human PKD by multiple parameters. Similar to autosomal dominant PKD, juvenile cystic kidney (jck) mice develop cysts in multiple nephron segments, including cortical collecting ducts, distal tubules, and loop of Henle. The jck mice display gender dimorphism in kidney disease progression with more aggressive disease in male mice. Gonadectomy experiments show that testosterone aggravates the severity of the disease in jck male mice, while female gonadal hormones have protective effects. EGF receptor is overexpressed and mislocalized in jck cystic epithelia, a hallmark of human disease. Increased cAMP levels in jck kidneys and activation of the B-Raf/extracellular signal-regulated kinase pathway are demonstrated. The effect of jck mutation on the expression of Nek8, a NIMA-related (never in mitosis A) kinase, and polycystins in jck cilia is shown for the first time. Nek8 overexpression and loss of ciliary localization in jck epithelia are accompanied by enhanced expression of polycystins along the cilia. The primary cilia in jck kidneys are significantly more lengthened than the cilia in wild-type mice, suggesting a role for Nek8 in controlling ciliary length. Collectively, these data demonstrate that the jck mice should be useful for testing potential therapies and for studying the molecular mechanisms that link ciliary structure/function and cystogenesis.
Endomitosis and polyploidization of myocardial cells in the periphery of human acute myocardial infarction
Authors: P MECKERT, H RIVELLO, C VIGLIANO, P GONZALEZ, R FAVALORO, R LAGUENS
Journal: Cardiovascular Research (2005)

Although the genetic program for reinitiating DNA synthesis exists in post-mitotic cardiomyocytes, and it was reported that in human acute myocardial infarction (AMI) a significant proportion of myocytes enter mitosis, the rule is that the lost tissue is replaced by a collagen scar. The purpose of this study was to search for the basis of this discordance in order to devise future strategies to induce division of myocytes into daughter cells that may replace the lost tissue with contractile cells.In 15 human hearts with 1- to 21-day-old infarcts, the expression of the cell cycle proteins Ki67 antigen, cyclins D, A, and B1, the presence of mitotic bodies, and the ploidy status were investigated with immunoenzymatic methods, light and laser confocal microscopy, and densitometry in the myocytes surrounding the infarct area.In 7- to 13-day-old infarcts, 11.61+/-6.94% of the myocytes presented Ki67+ nuclei, and a lower proportion presented cyclins D, A, and B. At earlier and later times, the proportion of Ki67+ myocytes was significantly lower. Although under confocal microscopy and fluorescent labels, some of the Ki67+ myocytes appeared to be in different stages of mitosis, with Nomarski optics and hematoxylin counterstaining, the condensed chromosomes, although arranged in metaphase and anaphase plates or split in sister chromatids, were always located within a preserved nuclear envelope, indicating the presence of endomitosis. Conventional mitosis was exceptionally observed. In the 14- and 21-day-old infarcts, the ploidy of the myocytes adjacent to the infarct was significantly higher than in distant zones.These observations indicate that in human infarcts, entrance of cardiomyocytes into the cell cycle is transient and that endomitosis, leading to polyploidy, rather than mitosis, leading to karyokinesis, is the final fate of cycling cells. Both observations may account for the discordance between the regenerative ability of myocytes and the lack of an efficient reparative process in human AMI.
Potential role for magnetoencephalography in distinguishing low- and high-grade gliomas: a preliminary study with histopathological confirmation
Authors: T. W. Wilson, E. Heinrichs-Graham, M. R. Aizenberg
Journal: Neuro-Oncology (2012)

Gliomas are the most common form of tumor in the CNS and are exceptionally heterogeneous. Accurately characterizing gliomas, in terms of grade and type, is essential for predicting the rate of tumor progression. Histopathological grading and analysis based on biopsied tissue remains the gold standard, but non- and semi-invasive neuroimaging also plays a key role. Neuroimaging has been used to guide and optimize biopsies for several decades, but more recently molecular imaging and variants of MRI have shown promise in independently predicting glioma grade. Here we evaluated whether magnetoencephalographic (MEG) measurements of population-level physiology within the glioma space were predictive of the inherent grade of the tissue, based on definitive histopathological analyses. High-density MEG data were recorded from 11 patients who were undergoing functional mapping in preparation for resective surgery. The primary results indicated that glioma grade was positively correlated with the local amplitude of activity within the glioma space in the theta (4–7 Hz), alpha (8–14 Hz), and beta bands (14–30 Hz). Additionally, activity within the glioma was significantly elevated relative to the nonaffected homologue area in the same frequency bands. These results indicate that pathological levels of synchronization exist within the tumor space and that MEG may be a viable tool for noninvasively differentiating gliomas by their grade. Although these results should be considered preliminary and are only correlative in nature, these data suggest that MEG can potentially detect neurophysiological signatures or markers that predict the inherent grade of a glial tumor.