tbuckley/cabot-search huggingface dataset:
The thorax in history. 6. Circulation of the blood.
Authors: R K French
Journal: Thorax (1978)

Physicians and philosophersWe saw in the last article that the discovery that blood passes from the heart to the lungs and back again to the heart was the first break with the Galenic system of physiology.Galen's physiological scheme was the theoretical underpinning of his medical system and was directly related to his interpretation of the biological world.Both of these were still widely accepted at the end of the six- teenth century, and so to accept the pulmonary transit meant being based more firmly in theology than in Galenism, like Servetus, or modifying rather than rejecting the Galenic system, in the way that Colombo found Galenic answers to the brain.This allowed him to accept the neo- Aristotelian cardiac origin of the nerves and the
Seasonality of tuberculosis: the reverse of other respiratory diseases in the UK.
Authors: A. S. Douglas, D. P. Strachan, J. D. Maxwell
Journal: Thorax (1996)

BACKGROUND: In Western societies there is a winter peak in mortality, largely accounted for by respiratory and cardiovascular deaths. In view of the known seasonal variation in vitamin D, and of the postulated link between tuberculosis and vitamin D deficiency, a study was undertaken to examine whether the presentation of tuberculosis had the same seasonal rhythm as other pulmonary infections. METHODS: Using cosinor analysis the presence or absence of seasonality was determined for 57,313 tuberculosis notifications for England and Wales. OPCS data in four weekly notifications over a 10 year period (1983-92) were examined as two quinquential sets (1983-7 and 1988-92). These were compared with two groups of acute respiratory illness: 138,992 notifications to OPCS of pneumonia deaths for 1988-92 and all admissions to Scottish hospitals with respiratory disease (252,163 cases) during 1980-4. RESULTS: Analysis of notifications of tuberculosis revealed a summer peak with an amplitude of 10%. This pattern differs markedly from other respiratory disorders in which a winter peak and summer trough is observed. CONCLUSIONS: The unusual seasonality of tuberculosis is currently unexplained. One possibility is that low post-winter trough levels of vitamin D (which are known to affect macrophage function and cell mediated immunity) might result in impaired cellular immunity leading, after a latent period, to reactivation of dormant mycobacterial infection.
Mutations of hepatitis C virus 1b NS5A 2209–2248 amino acid sequence do not predict the response to recombinant interferon-alfa therapy in French patients
Authors: Hafida Khorsi, Sandrine Castelain, Ann Wyseur, Jacques Izopet, Valérie Canva, Annelies Rombout, Dominique Capron, Jean-Pierre Capron, Françoise Lunel, Lieven Stuyver, Gilles Duverlie
Journal: Journal of Hepatology (1997)
Abstract S1-10: Association between the 21-gene recurrence score (RS) and benefit from adjuvant paclitaxel (Pac) in node-positive (N+), ER-positive breast cancer patients (pts): Results from NSABP B-28
Authors: EP Mamounas, G Tang, S Paik, FL Baehner, Q Liu, J-H Jeong, S-R Kim, SM Butler, F Jamshidian, DB Cherbavaz, AP Sing, S Shak, TB Julian, BC Lembersky, DL Wickerham, JP Costantino, N Wolmark
Journal: Cancer Research (2012)

Abstract Background: The RS result predicts outcome in N- and N+, ER+ pts treated with adjuvant endocrine therapy. RS also predicts benefit from adjuvant chemotherapy (CT) and pts with a high RS result receive most of the benefit. We evaluated the association between RS and paclitaxel (Pac) benefit in N+, ER+ pts from NSABP B-28. Methods: B-28 compared 4 cycles of doxorubicin/cyclophosphamide (AC) vs. AC followed by Pac × 4 (AC→Pac). Pts ≥50 yrs and those&amp;lt;50 yrs with ER+ and/or PR+ tumors also received 5 yrs of tamoxifen starting with CT. From 8/95 to 5/98 3060 pts were accrued. The present study includes 1065 pts, ER+ by central tissue microarray IHC assay, tamoxifen-treated, and with a RS result from the Oncotype DX 21-gene assay by standard processes. Sub-distribution analyses were used for loco-regional recurrence (LRR) to account for competing risks, including distant recurrence (DR), second primary cancers, and death. Kaplan-Meier estimates and Cox models were used for other clinical outcomes. Results: Median follow-up time was 11.2 yrs. Of the 1065 pts, 386 (36%) had low RS (&amp;lt;18); 364 (34%) intermediate RS (18–30); and 315 (30%) high RS (≥31). RS was a significant predictor of LRR, DFS event, DR, and death in univariate analyses both in pts treated with AC and in those treated with AC→Pac (Table). Pts with low RS had similar outcomes at 10 yrs when treated with AC→Pac vs. AC (Table). The majority of Pac benefit was observed in pts with intermediate/high RS (Table). Interaction tests between RS and Pac benefit were not statistically significant (LRR: p = 0.75, DFS: p = 0.65, DR: p = 0.93, death: p = 0.30). Conclusions: RS significantly predicts risk for LRR, DR, DFS event, and death in N+, ER+ pts treated with AC or AC→Pac adjuvant CT. Pts with a low RS value have similar outcomes whether treated with AC or with AC→Pac and most of Pac benefit is evident in pts with intermediate/high RS. Although there was no significant interaction between RS and Pac benefit, these results support previous findings of lack of CT benefit in pts with a low RS result. Supported by: NCI grants U10-CA-12027, -69651, -37377, -69974, U24-CA-114732, and CA-75362; Susan G. Komen for the Cure® grants; and Bristol-Myers Squibb Pharmaceutical Research Institute Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr S1-10.
Alcoholism: A Statewide Program Evaluation
Authors: SHELDON MILLER, EDWARD HELMICK, LAWRENCE BERG, PAUL NUTTING, GREGORY SHORR
Journal: American Journal of Psychiatry (1974)

This paper describes an attempt to evaluate the mental health services offered to Alaskan Natives. The concern of the authors was not the outcome of treatment, but whether the delivery system was functioning efficiently. Restricting their study to a single problem—alcoholism—they describe how their method of evaluation was developed and applied to programs and agencies in Alaska.
Allergic rhinitis may impact the recovery of pulmonary function tests after moderate/severe asthma exacerbation in children
Authors: O. Yilmaz, A. Bakirtas, H. I. Ertoy Karagol, E. Topal, M. S. Demirsoy
Journal: Allergy (2014)

Abstract Background During an asthma exacerbation, pulmonary function test parameters ( PFT s) return to their baseline values within a few weeks. Factors affecting the recovery of PFT s other than the severity of exacerbation are not well known. Objective The primary aim of the study was to determine the risk factors for recovery of PFT s &gt; 7 days after a moderate to severe asthma exacerbation in children. Methods Children who had moderate to severe asthma exacerbation performed serial prebronchodilator PFT s on days 1, 3, 7 of the exacerbation and then once weekly until their PFT s reached a plateau. All children received systemic corticosteroid for 3 days and inhaled salbutamol as long as they needed. Results Fifty‐seven children were recruited. When all PFT s were considered, 42% and 74% of children recovered within 7 and 14 days, respectively. The last recovered PFT parameter was FEF 25–75 . Allergic rhinitis ( AR ) ( P = 0.016), persistent AR ( P = 0.005), and severe asthma exacerbation ( P = 0.009) were significantly higher in children whose PFT s recover &gt;7 days; only severe asthma exacerbation was different for recovery &gt;14 days ( P = 0.048). Logistic regression analysis revealed that AR and severe asthma exacerbation increase the recovery of PFT s &gt; 7 days by 4.3 (95% CI : 1.29–14.67) and 8.1 (95% CI : 1.51–44.43), respectively. Conclusions Recovery of PFT s during a moderate/severe asthma exacerbation may take up to 4 weeks. Apart from severity of the exacerbation, AR is a significant factor affecting the recovery time of PFT s and therefore may impact asthma management. This issue reinforces the combined treatment of AR and asthma.
Interferon gamma therapy and pulmonary fibrosis
Authors: A R L Medford
Journal: Thorax (2004)

▴ Hung CC, Chen MY, Hsiao CF, et al . Improved outcomes of HIV-1-infected adults with tuberculosis in the era of highly active antiretroviral therapy. AIDS2003;17:2615–22

[OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4]



In this prospective observational cohort study from Taiwan the outcome of HIV infected TB patients and HIV infected non-TB patients treated with highly active antiretroviral therapy (HAART) was compared.

A total of 46 TB and 230 non-TB antiretroviral naive patients were included between June 1994 and October 2002. The median duration of antituberculous therapy was 9 months (range …

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Induced sputum in adolescents with severe stable asthma. Safety and the relationship of cell counts and eosinophil cationic protein to clinical severity
Authors: DC Grootendorst, JW van den Bos, JJ Romeijn, M Veselic-Charvat, EJ Duiverman, EJ Vrijlandt, PJ Sterk, AC Roldaan
Journal: European Respiratory Journal (1999)

This study examined the safety of sputum induction and the relation between sputum cell counts and clinical parameters in adolescents with severe persistent asthma. Within 5 days, induced sputum and reversibility in forced expiratory volume in one second (FEV1), quality of life, provocative concentration causing a 20% fall in FEV1 (PC20) of adenosine monophosphate and histamine, exercise-induced bronchoconstriction, overall asthma severity index, and blood eosinophils were collected in 20 atopic adolescents with moderate-to-severe persistent asthma (12-18 yrs of age, FEV1 65-110% of predicted, on 500-2,000 microg inhaled steroids daily). FEV1 was reversible by 13.3-2.3% pred. After sputum induction, FEV1 was still increased by 9.0+/-2.6% pred as compared to the pre-salbutamol baseline. Sputum contained, median (range): 12.4 (0.4-59.5)% squamous cells, 47.3 (6.8-84.0)% macrophages, 39.0 (4.6-84.8)% neutrophils, 4.8 (1.0-12.4)% lymphocytes, 0.4 (0-10.8)% eosinophils and 3.6 (0-23.4)% bronchial epithelial cells. Sputum eosinophils showed a trend towards a significant association with the overall asthma severity index (r=0.46, p=0.06) and correlated inversely with baseline FEV1 (r=-0.51, p=0.03). In conclusion, sputum can be induced safely in adolescents with moderate-to-severe persistent asthma, if pretreated with beta2-agonists. Despite relatively low sputum eosinophil counts in these patients on inhaled steroids, the association of eosinophil numbers with baseline forced expiratory volume in one second and asthma severity index favours a role of induced sputum in monitoring adolescents with severe asthma.
COUNTERPOINT: Estrogen Effects on Calcitropic Hormones and Calcium Homeostasis
Authors: RICHARD LEWIS PRINCE
Journal: Endocrine Reviews (1994)

Aresearcher evaluating the relative importance of the various calcitropic hormones in bone and calcium disease might conclude that estrogen would be a good contender for the most clinically significant hormone in view of its role in the pathogenesis of osteoporosis. Paradoxically, it is not usually considered a calcitropic hormone because there are no rapid detectable effects on extracellular calcium homeostasis. It is this subtle nature of estrogen action that makes its study difficult. However, estrogen is recognized as a hormone with perhaps the most profound effect of any hormone on the female skeleton. Bone loss at the menopause is preventable for up to 10 yr by estrogen replacement (1). If estrogen treatment is not introduced, it has been estimated that 11% of the bone loss in a 70-yr-old woman is menopause related (2). If estrogen plays a substantial role in age-related bone loss, this could rise to 29% of the skeleton.
Value of serum magnesium estimation in diagnosing myocardial infarction and predicting dysrhythmias after coronary artery bypass grafting.
Authors: R W Bunton
Journal: Thorax (1983)

Serial serum magnesium estimations, beginning before operation, were performed on 200 patients who underwent coronary artery bypass grafting. The results indicate that serum magnesium concentration is of no value in the diagnosis of myocardial infarction in the postoperative patient or in predicting which patients are susceptible to postoperative dysrhythmias. There was no statistically significant difference in serum magnesium values between those patients who had an uncomplicated course and patients who had sustained either myocardial infarction or postoperative dysrhythmia or both.
Durable response of breast cancer leptomeningeal metastasis to capecitabine monotherapy
Authors: Lisa R. Rogers, Sandra E. Remer, Sheela Tejwani
Journal: Neuro-Oncology (2004)

We report a durable (12-month) response to capecitabine monotherapy, shown clinically, by MRI, and by cerebrospinal fluid analysis, in a patient with leptomeningeal metastasis from breast cancer.
High-dose erythropoietin has no effect on short- or long-term graft function following deceased donor kidney transplantation
Authors: Carsten Hafer, Thomas Becker, Jan T. Kielstein, Elisabeth Bahlmann, Anke Schwarz, Nikolai Grinzoff, Daria Drzymala, Isabelle Bonnard, Nicolas Richter, Frank Lehner, Juergen Klempnauer, Hermann Haller, Jana Traeder, Danilo Fliser
Journal: Kidney International (2011)
Cancer Cells Exploit eIF4E2-Directed Synthesis of Hypoxia Response Proteins to Drive Tumor Progression
Authors: James Uniacke, J. Kishan Perera, Gabriel Lachance, Camille B. Francisco, Stephen Lee
Journal: Cancer Research (2014)

Human tumors display considerable diversity in their genetic makeup but share common physiologic attributes such as a hypoxic microenvironment that contribute to the malignant phenotype. Hypoxic cells switch from eukaryotic initiation factor 4E (eIF4E) to eIF4E2 cap-dependent translation to synthesize a portion of their proteins. Here, we show that genetically distinct human cancer cells exploit eIF4E2-directed protein synthesis to form cellular masses larger than approximately 0.15 mm, the diffusion limit of oxygen. Cancer cells depleted of eIF4E2 are indistinguishable from control cells under normoxic conditions, but are unable to survive and proliferate in low oxygen conditions. Activation of eIF4E2-directed translation is essential for cancer cells to form a hypoxic tumor core in in vitro spheroids and to form detectable tumors in in vivo xenograft assays. In contrast, the eIF4E-directed protein synthesis pathway alone cannot sustain cellular adaptation to hypoxia in vitro or confer tumorigenic potential in xenograft assays. These data demonstrate that the phenotypic expression of the cancer genome requires translation by the eIF4E2-directed hypoxic protein synthesis machinery.
CCR5 promoter polymorphism and HIV-1 disease progression
Authors: David H McDermott, Peter A Zimmerman, Florence Guignard, Cynthia A Kleeberger, Susan F Leitman, Philip M Murphy
Journal: The Lancet (1998)

The rate of progression to AIDS varies among individuals infected with HIV-1. Factors responsible include two inherited human alleles, CCR5 delta32 and CCR2-641, which alter the protein-coding regions for the HIV-1 coreceptors/chemokine receptors CCR5 and CCR2b. We tested the hypothesis that polymorphisms of the CCR5 promoter might affect the rate of progression of HIV-1 infected people to AIDS.We used directed heteroduplex analysis to identify polymorphism in the CCR5 promoter. Promoter-variants were compared in vitro with a chloramphenicol acetyltransferase reporter gene, and in vivo by genotyping HIV-1 seroconvertors discordant at polymorphous loci.An A/G polymorphism was identified at basepair 59029 (Genbank U95626) in the CCR5 promoter. Both promoter alleles were common (43-68% allelic frequency for 59029-A depending on race). When in-vitro promoter activity was measured, 59029-G had 45% lower activity than 59029-A (p=0.05). In a cohort of HIV-1 seroconvertors lacking both CCR5 delta32 and CCR2-641, 59029-G/G individuals progressed to AIDS on average 3.8 years more slowly than 59029-A/A individuals (p=0.004). 59029-G/A discordance did not correlate with discordant rates of infection.Our results are consistent with the hypothesis that CCR5 is important in HIV-1 pathogenesis. CCR5 59029-G/G appears to be protective relative to CCR5 59029-A/A, and about twice as protective relative to CCR5 delta32 or CCR2-641. This effect may be the result of reduced CCR5 mRNA production. These results identify the first site in the CCR5 promoter that may be a useful target for treatment of HIV-1 infection.
EMOTIONAL AND PSYCHOLOGICAL FACTORS IN EPILEPSY: PHYSIOLOGICAL BACKGROUND
Authors: W. T. LIBERSON
Journal: American Journal of Psychiatry (1955)

1. An elementary seizure discharge is characterized by high amplitude, synchronized activity expressed by interlocking brain wave rhythms of different frequencies. Among various components of the electrical changes associated with convulsions, slow waves of polarization may play an important role during both ictal and postictal stages. 2. Rhinencephalic structures show the lowest threshold. Their epileptic discharges show the most intricate organization. Traveling slow waves of polarization are very easy to induce in the olfactory brain, particularly in the Ammon's Formation. Contrasting with the complexity and intensity of the electrical correlates of the seizure discharges, there is a meagerness of its "clinical" expression in animals in terms of motor activity. Awareness is impaired and certain manifestations of emotional disturbances are reported. Experiments with ablation and chemical stimulation confirm the role of the rhinencephalon in emotional control. Experiments with sensory stimulation which reveal a high level of intergration also show an unusual reaction of hypersynchronization under certain conditions. 3. An epileptogenic excitation of a limited extent may produce psychological manifestations by a dual mechanism: ( a) Only partial decrease of awareness may be experienced by the patient as a threat of ego dissolution and thus stir his emotional reactions. ( b) The involvement of certain specific areas ( for instance the rhinencephalon) may be expressed by disturbances of the emotional control. 4. Emotional stimuli may induce a convulsion through either ( a) a creation of a general excitatory state with an excessive formation of either acetylcholine or insulin; or ( b) a preliminary conditioning of certain stimuli which Set up epileptogenic states in those areas of the brain which participate in the control of emotional processes ("affectogenic" epilepsy).
Phase II Pilot Study of Vemurafenib in Patients With Metastatic <i>BRAF</i>-Mutated Colorectal Cancer
Authors: Scott Kopetz, Jayesh Desai, Emily Chan, Joel Randolph Hecht, Peter J. O'Dwyer, Dipen Maru, Van Morris, Filip Janku, Arvind Dasari, Woonbook Chung, Jean-Pierre J. Issa, Peter Gibbs, Brian James, Garth Powis, Keith B. Nolop, Suman Bhattacharya, Leonard Saltz
Journal: Journal of Clinical Oncology (2015)

Purpose BRAF V600E mutation is seen in 5% to 8% of patients with metastatic colorectal cancer (CRC) and is associated with poor prognosis. Vemurafenib, an oral BRAF V600 inhibitor, has pronounced activity in patients with metastatic melanoma, but its activity in patients with BRAF V600E–positive metastatic CRC was unknown. Patients and Methods In this multi-institutional, open-label study, patients with metastatic CRC with BRAF V600 mutations were recruited to an expansion cohort at the previously determined maximum-tolerated dose of 960 mg orally twice a day. Results Twenty-one patients were enrolled, of whom 20 had received at least one prior metastatic chemotherapy regimen. Grade 3 toxicities included keratoacanthomas, rash, fatigue, and arthralgia. Of the 21 patients treated, one patient had a confirmed partial response (5%; 95% CI, 1% to 24%) and seven other patients had stable disease by RECIST criteria. Median progression-free survival was 2.1 months. Patterns of concurrent mutations, microsatellite instability status, CpG island methylation status, PTEN loss, EGFR expression, and copy number alterations were not associated with clinical benefit. In contrast to prior expectations, concurrent KRAS and NRAS mutations were detected at low allele frequency in a subset of the patients' tumors (median, 0.21% allele frequency) and were apparent mechanisms of acquired resistance in vemurafenib-sensitive patient-derived xenograft models. Conclusion In marked contrast to the results seen in patients with BRAF V600E–mutant melanoma, single-agent vemurafenib did not show meaningful clinical activity in patients with BRAF V600E mutant CRC. Combination strategies are now under development and may be informed by the presence of intratumor heterogeneity of KRAS and NRAS mutations.
Using protein structural information in evolutionary inference: transmembrane proteins
Authors: P. Lio, N. Goldman
Journal: Molecular Biology and Evolution (1999)

We present a model of amino acid sequence evolution based on a hidden Markov model that extends to transmembrane proteins previous methods that incorporate protein structural information into phylogenetics. Our model aims to give a better understanding of processes of molecular evolution and to extract structural information from multiple alignments of transmembrane sequences and use such information to improve phylogenetic analyses. This should be of value in phylogenetic studies of transmembrane proteins: for example, mitochondrial proteins have acquired a special importance in phylogenetics and are mostly transmembrane proteins. The improvement in fit to example data sets of our new model relative to less complex models of amino acid sequence evolution is statistically tested. To further illustrate the potential utility of our method, phylogeny estimation is performed on primate CCR5 receptor sequences, sequences of l and m subunits of the light reaction center in purple bacteria, guinea pig sequences with respect to lagomorph and rodent sequences of calcitonin receptor and K-substance receptor, and cetacean sequences of cytochrome b.