tbuckley/cabot-search huggingface dataset:
P2-16-05: Delay of Adjuvant Chemotherapy after Elective Mastectomy and Immediate Reconstruction in Breast Conservation Candidates: A Matched-Pair Analysis.
Authors: PN Barry, EC Riley, J Pan, JB Crew, K Lee, D Jain, B Kruse, AR Quillo, S Rai, AE Dragun
Journal: Cancer Research (2011)

Abstract Background: To analyze factors that influence the timing of adjuvant chemotherapy in patients who are candidates for breast conservation therapy (BCT) but elect mastectomy with immediate reconstruction (M-IR). Methods: Using data from the University of Louisville Cancer Registry, we identified 35 consecutively-treated patients with stage I or II breast cancer between 2004 and 2009 who underwent M-IR and adjuvant chemotherapy. These were matched for age and AJCC stage to 35 controls who underwent BCT and adjuvant chemotherapy. We examined the timing of initiation of chemotherapy from the date of surgery and assessed the probability of therapeutic delay using univariate logistic regression and McNemar's test for matched pairs. Results: For the 70 patients included in this study, the median age was 46y (range: 30–65y), and the distribution for stage I, IIA and IIB was 22.9%, 65.7% and 11.4%, respectively. The two groups were well balanced in terms of race, rural/urban status, smoking, diabetes, insurance coverage, and histology. The median time to initiation of adjuvant chemotherapy was 38 days (range: 25–103 days) for BCT and 55 days (range: 30–165 days) for M-IR. Patients undergoing M-IR were more likely to experience any delay (&amp;gt; 45 days; 74.3% vs. 25.7%, p &amp;lt; 0.001) and/or significant delay (&amp;gt;90 days; 20.0% vs. 2.9%, p &amp;lt; 0.001) than those choosing BCT. On univariate logistic regression analysis, the extent of surgery had a major impact on the likelihood of any delay in chemotherapy (OR= 8.35, 95% C.I. = 2.86−24.3, p &amp;lt;0.001). None of the other aforementioned factors predicted for delay. Conclusion: The use of elective mastectomy with immediate reconstruction in breast conservation candidates independently predicts for delay in initiation of adjuvant chemotherapy. Further study is needed to qualify the underlying causes of and ultimate clinical significance of these delays. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-16-05.
Inhibition of the Bcl-x<sub>L</sub>Deamidation Pathway in Myeloproliferative Disorders
Authors: Rui Zhao, George A. Follows, Philip A. Beer, Linda M. Scott, Brian J.P. Huntly, Anthony R. Green, Denis R. Alexander
Journal: New England Journal of Medicine (2008)

The myeloproliferative disorders are clonal disorders with frequent somatic gain-of-function alterations affecting tyrosine kinases. In these diseases, there is an increase in DNA damage and a risk of progression to acute leukemia. The molecular mechanisms in myeloproliferative disorders that prevent apoptosis induced by damaged DNA are obscure.We searched for abnormalities of the proapoptotic Bcl-x(L) deamidation pathway in primary cells from patients with chronic myeloid leukemia (CML) or polycythemia vera, myeloproliferative disorders associated with the BCR-ABL fusion kinase and the Janus tyrosine kinase 2 (JAK2) V617F mutation, respectively.The Bcl-x(L) deamidation pathway was inhibited in myeloid cells, but not T cells, in patients with CML or polycythemia vera. DNA damage did not increase levels of the amiloride-sensitive sodium-hydrogen exchanger isoform 1 (NHE-1), intracellular pH, Bcl-x(L) deamidation, and apoptosis. Inhibition of the pathway was reversed by enforced alkalinization or overexpression of NHE-1, leading to a restoration of apoptosis. In patients with CML, the pathway was blocked in CD34+ progenitor cells and mature myeloid cells. Imatinib or JAK2 inhibitors reversed inhibition of the pathway in cells from patients with CML and polycythemia vera, respectively, but not in cells from a patient with resistance to imatinib because of a mutation in the BCR-ABL kinase domain.BCR-ABL and mutant JAK2 inhibit the Bcl-x(L) deamidation pathway and the apoptotic response to DNA damage in primary cells from patients with CML or polycythemia vera.
Case 46-1968
Authors: Conger Williams, Robert E. Scully
Journal: New England Journal of Medicine (1968)

Presentation of CaseA seventy-six-year-old woman was admitted to the hospital because of dyspnea.She had been well until a year previously, when there was the onset of episodes of wheezing respiration. A physician prescribed a bronchodilator medication as well as corticosteroid therapy on two occasions, with a good response. Four months before entry increasing dyspnea on exertion developed, accompanied by progressive pedal edema. Digitalis and a diuretic agent were prescribed. For several weeks before admission nocturnal dyspnea and orthopnea occurred intermittently. On the morning of entry, while she was using a bronchodilator, severe pain in the anterior portion of . . .
The Neglected Neglect
Authors: Sankalp Gokhale, Sourabh Lahoti, Louis R. Caplan
Journal: JAMA Neurology (2013)

Whereas visual and somatosensory forms of neglect are commonly recognized by clinicians, auditory neglect is often not assessed and therefore neglected. The auditory cortical processing system can be functionally classified into 2 distinct pathways. These 2 distinct functional pathways deal with recognition of sound ("what" pathway) and the directional attributes of the sound ("where" pathway). Lesions of higher auditory pathways produce distinct clinical features. Clinical bedside evaluation of auditory neglect is often difficult because of coexisting neurological deficits and the binaural nature of auditory inputs. In addition, auditory neglect and auditory extinction may show varying degrees of overlap, which makes the assessment even harder. Shielding one ear from the other as well as separating the ear from space is therefore critical for accurate assessment of auditory neglect. This can be achieved by use of specialized auditory tests (dichotic tasks and sound localization tests) for accurate interpretation of deficits. Herein, we have reviewed auditory neglect with an emphasis on the functional anatomy, clinical evaluation, and basic principles of specialized auditory tests.
WASP confers selective advantage for specific hematopoietic cell populations and serves a unique role in marginal zone B-cell homeostasis and function
Authors: Lisa S. Westerberg, Miguel A. de la Fuente, Fredrik Wermeling, Hans D. Ochs, Mikael C. I. Karlsson, Scott B. Snapper, Luigi D. Notarangelo
Journal: Blood (2008)
Meta-analysis: Procalcitonin-guided antibiotic therapy reduces treatment failure in acute respiratory infection
Authors: Liudvikas Jagminas
Journal: Annals of Internal Medicine (2013)

Source Citation Schuetz P, Müller B, Christ-Crain M, et al. Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections. Cochrane Database Syst Rev. 2012;(9):CD007498. 22972110
Association of Maternal Height With Child Mortality, Anthropometric Failure, and Anemia in India
Authors: S. V. Subramanian
Journal: JAMA (2009)

ORE THAN 2 MILLION children younger than 5 years died in India in 2006, more than in any other country, comprising onequarter of all child deaths in the world. 1 Most recent estimates also show very high prevalences of underweight (42.5%), stunting (48.0%), wasting (19.8%), and anemia (69.5%) among children younger than 5 years in India. 2 Prior research on the determinants of child mortality and nutritional outcomes have primarily focused on contemporaneous factors such as breastfeeding, medical care, 3 and birth spacing. 4Research on intergenerational factors that might also predispose a child to increased health adversity remains limited.Maternal height can be a useful marker for characterizing intergenerational linkages in health because adult height reflects a mother's health stock accumulated through her life course, especially the social and environmental exposures in her early childhood. 5lthough a few studies have shown associations between maternal height and mortality 6 and stunting, 7,8 studies conducted in India to date have investigated only the association between
Soluble TNF-α receptor 1 and IL-6 plasma levels in humans subjected to the sleep deprivation model of spaceflight
Authors: William T. Shearer, James M. Reuben, Janet M. Mullington, Nicholas J. Price, Bang-Ning Lee, E.O’Brian Smith, Martin P. Szuba, Hans P.A. Van Dongen, David F. Dinges
Journal: Journal of Allergy and Clinical Immunology (2001)
Psychometric Reaction to Milman's Report
Authors: John A. Schmitt
Journal: JAMA (1968)

<h3>To the Editor:—</h3> In a recent issue (<b>201</b>:821, 1967), Doris H. Milman, MD, described the results of psychological and physiological examinations of a 5-year-old girl over a period of nine months following accidental ingestion of LSD. These clinical data were collected post factum, precluding any but conjectural conclusions regarding a causal relationship between the accident and the findings. The background summary provided by Milman indicated a possibility that the girl's home environment may have been somewhat unusual from psychological, sociological, and nutritional standpoints. These remarks are related only to the five intelligence quotients obtained following the accidental ingestion which occurred on April 6,1966: All IQs were obtained with the Ammons Quick test (QT),<sup>1</sup>and the results led Milman to conclude that, "four months after ingestion, with an IQ of 121, [sic] could be stated with confidence that the drug had had a clearly depressing effect upon intellectual functioning."
Metabolomics Studies Show Dose‐Dependent Toxicity Induced by SiO<sub>2</sub> Nanoparticles in MRC‐5 Human Fetal Lung Fibroblasts
Authors: Shao‐Min Huang, Xinbing Zuo, Jasmine Jia'En Li, Sam Fong Yau Li, Boon Huat Bay, Choon Nam Ong
Journal: Advanced Healthcare Materials (2012)

Metabolomics measures a comprehensive range of metabolites and is applied here to understand cellular toxicity of nano-SiO2. Silica nanoparticles are assessed for their effects on MRC-5 lung fibroblasts and initial investigations reveal no significant alterations in cell viability and morphology. Further metabolomic analysis reveals dose-dependent alterations in cellular metabolism due to nano-SiO2 exposure. This methodology may be a potentially useful analytical platform to investigate nanotoxicity. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Ernest Herman Rainer
Authors: N. Ashford
Journal: BMJ (2003)

Former consultant ear, nose, and throat surgeon Dartford and Sevenoaks Hospitals, Kent (b Germany 1916; q Edinburgh 1941; FRCS Ed), d 11 Apri1 2003.​2003.




Figure 1




The son of a Dusseldorf businessman, he came from Germany in 1936 to study medicine at Edinburgh University. Following the outbreak of the second world war he was, as an “alien,” interned in Canada, but returned to complete his qualifications at Edinburgh and Glasgow. He then joined the Royal Army Medical Corps, where he served as a captain until the end of the war. Ernest had a wide experience in all branches of otolaryngology, mainly otology and neck surgery. He was an accomplished violinist and played in several local orchestras and music groups. He leaves two daughters and four grandchildren.
Peginterferon Alfa-2a plus Ribavirin versus Interferon Alfa-2a plus Ribavirin for Chronic Hepatitis C in HIV-Coinfected Persons
Authors: Raymond T. Chung, Janet Andersen, Paul Volberding, Gregory K. Robbins, Tun Liu, Kenneth E. Sherman, Marion G. Peters, Margaret J. Koziel, Atul K. Bhan, Beverly Alston, Dodi Colquhoun, Tom Nevin, George Harb, Charles van der Horst
Journal: New England Journal of Medicine (2004)

Chronic hepatitis C virus (HCV) infection is a cause of major complications in persons who are also infected with the human immunodeficiency virus (HIV). However, the treatment of HCV infection in such persons has been associated with a high rate of intolerance and a low rate of response. We conducted a multicenter, randomized trial comparing peginterferon plus ribavirin with interferon plus ribavirin for the treatment of chronic hepatitis C in persons coinfected with HIV.A total of 66 subjects were randomly assigned to receive 180 microg of peginterferon alfa-2a weekly for 48 weeks, and 67 subjects were assigned to receive 6 million IU of interferon alfa-2a three times weekly for 12 weeks followed by 3 million IU three times weekly for 36 weeks. Both groups received ribavirin according to a dose-escalation schedule. At week 24, subjects who did not have a virologic response (those who had an HCV RNA level greater than or equal to 60 IU per milliliter) underwent liver biopsy, and medications were continued in subjects with either a virologic response or histologic improvement.Treatment with peginterferon and ribavirin was associated with a significantly higher rate of sustained virologic response (an HCV RNA level of less than 60 IU per milliliter 24 weeks after completion of therapy) than was treatment with interferon and ribavirin (27 percent vs. 12 percent, P=0.03). In the group given peginterferon and ribavirin, only 14 percent of subjects with HCV genotype 1 infection had a sustained virologic response (7 of 51), as compared with 73 percent of subjects with an HCV genotype other than 1 (11 of 15, P<0.001). Histologic responses were observed in 35 percent of subjects with no virologic response who underwent liver biopsy.In persons infected with HIV, the combination of peginterferon and ribavirin is superior to the combination of interferon and ribavirin in the treatment of chronic hepatitis C. These regimens may provide clinical benefit even in the absence of virologic clearance. The marked discrepancy in the rates of sustained virologic response between HCV genotypes indicates that strategies are needed to improve the outcome in persons infected with HCV genotype 1.
Feeding Overstrength Cows' Milk to Babies
Authors: B. A. M. Smith
Journal: BMJ (1974)

The dangers of overstrength milk feeds have been emphasized in several reports during the last two years. They may even be a factor in unexpected death in infants. Samples of prepared dried milk feeds were obtained from 302 mothers who brought their 5- to 8-week-old infants to a special follow-up clinic. Determination of the sodium content of the milk indicated that 57% of the feeds were significantly overstrength. There is an urgent need to improve mothers9 knowledge of the importance of preparing dried cows9 milk infant feeds correctly.
New test for invalidity is accused of unfairness
Authors: N Craft
Journal: BMJ (1994)

Under a new scheme announced by the British government, general practitioners will no longer have to decide whether their patients should be given invalidity benefit. In future, claimants will complete a self assessment questionnaire and it will be up to doctors working for the Benefits Agency Medical Service to perform a full evaluation.

William Hague, minister of state for social security, said that …
Absence of receptor interacting protein kinase 3 prevents ethanol-induced liver injury
Authors: Sanjoy Roychowdhury, Megan R. McMullen, Sorana G. Pisano, Xiuli Liu, Laura E. Nagy
Journal: Hepatology (2012)

Hepatocyte cell death via apoptosis and necrosis are major hallmarks of ethanol-induced liver injury. However, inhibition of apoptosis is not sufficient to prevent ethanol-induced hepatocyte injury or inflammation. Because receptor-interacting protein kinase (RIP) 3–mediated necroptosis, a nonapoptotic cell death pathway, is implicated in a variety of pathological conditions, we tested the hypothesis that ethanol-induced liver injury is RIP3-dependent and RIP1-independent. Increased expression of RIP3 was detected in livers of mice after chronic ethanol feeding, as well as in liver biopsies from patients with alcoholic liver disease. Chronic ethanol feeding failed to induce RIP3 in the livers of cytochrome P450 2E1 (CYP2E1)-deficient mice, indicating CYP2E1-mediated ethanol metabolism is critical for RIP3 expression in response to ethanol feeding. Mice lacking RIP3 were protected from ethanol-induced steatosis, hepatocyte injury, and expression of proinflammatory cytokines. In contrast, RIP1 expression in mouse liver remained unchanged following ethanol feeding, and inhibition of RIP1 kinase by necrostatin-1 did not attenuate ethanol-induced hepatocyte injury. Ethanol-induced apoptosis, assessed by terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick-end labeling–positive nuclei and accumulation of cytokeratin-18 fragments in the liver, was independent of RIP3. Conclusion : CYP2E1-dependent RIP3 expression induces hepatocyte necroptosis during ethanol feeding. Ethanol-induced hepatocyte injury is RIP3-dependent, but independent of RIP1 kinase activity; intervention of this pathway could be targeted as a potential therapeutic strategy.
Analgesia in Labour
Authors: J. A. R. Cripps, B. Hall, W. F. T. Haultain
Journal: BMJ (1944)

hyperaemia by warming the leg up in any way; the worst cases occurred among those who, against instructions, had put their feet by a fire as soon as they took off their boots.The damage caused by the wet and chill leads to stagnation of the circula- tion and then hyperaemia, with oozing of fluid from the capillaries and diminished vitality of nerves, skin, and muscle; in severe cases irreparable loss of function may result, but in the milder cases the tingling, pains, and oedema subside in one or two weeks.The hyperaemic stage may last many weeks with sometimes intense hyperaesthesia, but in most of my cases full recovery occurred within 6 weeks.In some men there had been a lifelong tendency to cold hands or feet; and in the worst cases lasting sequelae, including hyperhidrosis and extreme sensitivity to cold, may persist.As a rule immersion for periods of many days is necessary to produce symptoms, as has been the case with numbers of men torpedoed at sea and remaining afloat for a long time in open boats; but sometimes minor degrees follow shorter periods.This occurred, for example, in the case of an officer who fell into the sea during the glider landings in Sicily and had to stand in the water hidden under a cliff for about 10 hours, after which he walked some 18 miles in a hot sun; later his feet swelled and became anaesthetic-symptoms which still persisted when I saw him 8 days later.No specific treatment was given, but strict avoidance of any artificial heat, as by hot-water bottles, was essential, and cooling by fans has often been adopted.Careful Buerger's exercises seemed to do good.Anxiety States In the fighting in North Africa, as in other theatres, many acute anxiety states and conditions of severe physical exhaus- t:on or terror occurred, as well as gross sensory and motor manifestations of hysteria.Few things in the future may be of more far-reaching importance than the development of personnel selection and the attempt to prevent psychological breakdowns under stress and strain.How far the art of selec- tion of men and women may go in education, industry, or
Muscle capillary basement membrane width in patients with vacor-induced diabetes mellitus.
Authors: K R Feingold, T H Lee, M Y Chung, M D Siperstein
Journal: Journal of Clinical Investigation (1986)

Muscle capillary basement membrane width is a sensitive marker for the presence of diabetic microangiopathy. Studies have indicated that genetic factors and alterations in glucose metabolism influence muscle capillary basement membrane width. To define the role of these factors we have measured muscle capillary basement membrane thickness in controls, insulin dependent diabetics, and individuals with diabetes secondary to the ingestion of Vacor, a rat poison, which results in hyperglycemia. Hemoglobin A1 concentrations were increased in both diabetic groups, but hemoglobin A1 levels and the duration of diabetes were similar in the two diabetic groups. The muscle capillary basement membrane width was increased to a similar extent in the insulin-dependent diabetics (control, 1,781 +/- 46 vs. IDD, 2,287 +/- 144 A, P less than 0.001) and in the Vacor diabetic group (2,320 +/- 149 A, P less than 0.001). In the insulin-dependent diabetic group, 63% of the patients had a muscle capillary basement membrane width greater than two standard deviations above the mean of the controls, while in the Vacor diabetic group this figure was 56%. Despite the relatively short duration of diabetes (6.2 +/- 0.3 yr), 44% of the Vacor diabetic patients had retinopathy and 28% had proteinuria. The present study provides strong evidence that even in the absence of genetic diabetes mellitus, hyperglycemia or some other abnormality related to insulin lack can cause microvascular changes.
The alveolar macrophage.
Authors: D H Bowden
Journal: Environmental Health Perspectives (1984)

The pulmonary macrophagic system is critical to the defense of the lung, keeping the alveoli clean and sterile and responding on demand with an adaptive outpouring of new cells into the air sacs. Under basal conditions alveolar macrophages, in common with other mononuclear phagocytes, are derived from the bone marrow. A population of macrophage precursors within the pulmonary interstitium provides a reserve pool capable of proliferation and delivery of phagocytes in response to unusually heavy loads of inhaled particles. This reserve system also produces macrophages when monocytic precursors in the bone marrow are depleted by diseases such as leukemia. The alveolar macrophage is destined to ingest particulate matter and to be eliminated along the mucociliary pathway; clearance by lymphatics is of minor importance and macrophages probably do not recross the alveolar epithelium to reach the pulmonary interstitial compartment. Although the protective role of the macrophage is dominant, this cell may participate, directly or indirectly, in the genesis of two major groups of chronic pulmonary disease, interstitial fibrosis and emphysema. Such inappropriate responses involve interactions with fibroblastic cells and tissue injury initiated by proteases secreted by the macrophage.