tbuckley/cabot-search huggingface dataset:
Immune changes associated with insulin dependent diabetes may remit without causing the disease: a study in identical twins.
Authors: B A Millward, L Alviggi, P J Hoskins, C Johnston, D Heaton, G F Bottazzo, D Vergani, R D Leslie, D A Pyke
Journal: BMJ (1986)

Activation of T lymphocytes and islet cell antibodies were studied in two groups of insulin dependent diabetics and their non-diabetic identical cotwins. Group 1 comprised 12 "short term" twin pairs (diabetic twin diagnosed less than five years previously) in whom only a third of the cotwins were likely to develop diabetes; 10 of the 12 non-diabetic cotwins showed increased values of activated T lymphocytes, islet cell antibodies, or both. Group 2 comprised 10 "long term" twin pairs (diabetic twin diagnosed more than 11 years previously) in whom none of the non-diabetic cotwins was likely to develop diabetes; these pairs were selected because all the non-diabetic cotwins had shown islet cell antibodies at some time in the past, but only two still did so (one with an increased value of activated T cells). There was relative glucose intolerance in the cotwins of the short term group but not in those of the long term group. Non-diabetic cotwins of diabetics may show the immune changes associated with insulin dependent diabetes and relative glucose intolerance, but these changes may remit without leading to diabetes.
Pacritinib (SB1518), a JAK2/FLT3 inhibitor for the treatment of acute myeloid leukemia
Authors: S Hart, K C Goh, V Novotny-Diermayr, Y C Tan, B Madan, C Amalini, L C Ong, B Kheng, A Cheong, J Zhou, W J Chng, J M Wood
Journal: Blood Cancer Journal (2011)

FMS-like tyrosine kinase 3 (FLT3) is the most commonly mutated gene found in acute myeloid leukemia (AML) patients and its activating mutations have been proven to be a negative prognostic marker for clinical outcome. Pacritinib (SB1518) is a tyrosine kinase inhibitor (TKI) with equipotent activity against FLT3 (IC(50)=22 n) and Janus kinase 2 (JAK2, IC(50)=23 n). Pacritinib inhibits FLT3 phosphorylation and downstream STAT, MAPK and PI3 K signaling in FLT3-internal-tandem duplication (ITD), FLT3-wt cells and primary AML blast cells. Oral administration of pacritinib in murine models of FLT3-ITD-driven AML led to significant inhibition of primary tumor growth and lung metastasis. Upregulation of JAK2 in FLT3-TKI-resistant AML cells was identified as a potential mechanism of resistance to selective FLT3 inhibition. This resistance could be overcome by the combined FLT3 and JAK2 activities of pacritinib in this cellular model. Our findings provide a rationale for the clinical evaluation of pacritinib in AML including patients resistant to FLT3-TKI therapy.
Hormonal Treatment of Cancer
Authors: Ira T. Nathanson, Rita M. Kelley
Journal: New England Journal of Medicine (1952)

AN INTIMATE relation between steroid hormones and the genesis and course of certain tumors may be regarded as established. Recent developments have stimulated extensive exploration of the potentialities of steroids in the etiology and treatment of cancer.1 2 3 4 5 6 7 8 9 10 11 12 It is generally acknowledged that induced alterations in the hormonal balance of patients with advanced stages of some neoplasms may significantly modify the anticipated behavior of the tumor. It should be emphasized that this modification can be in the direction of either temporary regression or distinct acceleration of the disease. This report is a summary of the extensive literature that has accumulated on . . .
Lidocaine: Antiarrhythmic Panacea or Cardiac Cosmetic Agent?
Authors: Bernard Lown
Journal: JAMA (1981)

At the very inception of the coronary care unit (CCU) era, lidocaine hydrochloride became the mainstay of antiarrhythmic drug therapy. Introduction of this agent was considered the basis for decrease in the 30% fatality rate recorded among hospitalized patients with acute myocardial infarction. 1 This fatality rate had prevailed unchanged over many decades. A number of studies, however, failed to provide convincing evidence demonstrating a lessened incidence of ventricular fibrillation after the use of lidocaine. Neither the expressed doubts of the academic world nor the absence of hard data quenched the enthusiasm or restrained CCU physicians from enfilading all comers with lidocaine. A Lancet editorial demurring of this practice recalled the injunction of Pasteur to keep your enthusiasm but let strict verification be its constant companion. 2   It is worth examining the basis for the widespread acceptance of lidocaine therapy. The focus of care in the early CCUs was on
Variant IRAK-1 Haplotype Is Associated with Increased Nuclear Factor–κB Activation and Worse Outcomes in Sepsis
Authors: John Arcaroli, Eliezer Silva, James P. Maloney, Qianbin He, Daiva Svetkauskaite, James R. Murphy, Edward Abraham
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

The IL-1 receptor-associated kinase (IRAK-1) plays a central role in TLR2- and TLR4-induced activation of nuclear factor (NF)-kappaB, a critical event in the transcriptional regulation of many sepsis-associated proinflammatory mediators. There are two haplotypes for the IRAK-1 gene in Caucasians, with the variant haplotype consisting of five intron single-nucleotide polymorphisms (SNPs) and three exon SNPs.To examine the functional significance of the IRAK-1 variant haplotype in modifying nuclear translocation of NF-kappaB and affecting outcomes from sepsis.One hundred fifty-five Caucasian patients with sepsis were included. Twenty-one (14%) were homozygous for the IRAK-1 variant haplotype as determined by a SNP in which T is replaced with C at nucleotide 1,595 within exon 12 of the IRAK-1 gene. The IRAK-1 variant haplotype was associated with increased nuclear levels of NF-kappaB in LPS-stimulated peripheral blood neutrophils from patients with sepsis compared with that found in patients with wild-type IRAK-1 haplotype (p=0.0009). There was an increased incidence of shock (p=0.047) (odds ratio [OR], 2.9; 95% confidence interval [CI], 1.1-7.7), greater requirement for more prolonged mechanical ventilator support (p=0.04) (OR, 2.7; 95% CI, 1.05-6.9), and higher 60-d mortality (p=0.05) (OR, 2.7; 95% CI, 1.0-6.8) in patients with the IRAK-1 variant haplotype compared with wild type.These results indicate that the IRAK-1 variant haplotype is functionally significant in patients with sepsis, being associated with increased nuclear translocation of NF-kappaB, more severe organ dysfunction, and higher mortality.
Terms and conditions of service for new specialist registrar grade are not yet established
Authors: P. Bennie
Journal: BMJ (1995)

the reduction was to only 83 hours a week.Furthermore, although we included some of the more benign comments of the trainees in our article, many of them, though entertaining, were unprintable.We agree that the Junior Doctors Committee (which allegedly disbelieved our data) is out of touch with the wishes of many junior staff, particularly surgical trainees.Perish the thought that we should shorten our hours to the levels in Europe.For example, in Denmark (where they have a 37 hour week), on a urological unit a little bigger than ours there are eight senior registrars.The trainee who covers a weekend has to have the whole of the next week off.Surely even the Junior Doctors Committee cannot believe that this is compatible with an adequate training programme.One of the great advantages of consultant practice in Britain is personal autonomy (though this also is under threat).This requires a higher level of exposure and experience than is needed by our counterparts in Europe, who are more protected.
THE CATABOLISM OF PROTEIN ANTIGENS IN THE NEWBORN AND MATURING RABBIT
Authors: John Robbins, Donald V. Eitzman, Richard T. Smith
Journal: The Journal of Experimental Medicine (1963)

The rate of degradation, organ deposition, and blood clearance of SBSA, SRSA, and IRSA has been measured in the newborn, 6-, and 30-day-old rabbits. When the animals were injected with a weight-graded dose of the 3 proteins, differences in their catabolism in the newborns were demonstrable as compared to the 6-, and 30-day-old animals. The capacity to degrade the azo compounds was shown to be incompletely developed at birth. At 6 days of age, however, the rabbits catabolized these proteins much at the same rate as the 30-day-old animals. Addition of the benzenesulfonate moiety determined the rate of degradation organ deposition and excretion rather than the carrier protein when the azo compounds were injected. The biosynthetically labeled S(25) rabbit serum albumin (IRSA) was catabolized at a slower rate than the azoproteins in all age groups. Very little difference in the metabolism and organ deposition of the IRSA was shown to exist between the newborn and maturing animals. A dosage schedule, therefore, designed to test the immunological capacity of developing animals may not be valid when calculated upon body weight. The low level of activity of enzyme systems present at birth which degrade anti-genic material may serve as an explanation as to why this period of development is so vulnerable to the induction of tolerance rather than immunity when compared to the adult.
Left Ventricular Performance Following Correction of Free Aortic Regurgitation
Authors: JAMES H. GAULT, JAMES W. COVELL, EUGENE BRAUNWALD, JOHN ROSS
Journal: Circulation (1970)

Left ventricular (LV) myocardial contractility, or inotropic state, was characterized in terms of the instantaneous relations between velocity of circumferential fiber shortening (V CF ), determined cineangiographically, and LV wall tension (hoop stress), calculated from LV dimensions and pressure, in five patients before and 7 to 10 mo after aortic valve replacement for free aortic regurgitation. Preoperatively the cardiac index was reduced or the LV end-diastolic pressure was markedly increased (or both occurred) in four patients, in each of whom depression of inotropic state was documented by a reduced V CF at maximum wall tension, ranging from 0.13 to 1.07 circumferences (circ)/sec (normal, &gt; 1.40 circ/sec) at wall tensions of 318 to 464 g/cm 2 (normal, 178 to 417 g/cm 2 ). In one patient in whom LV end-diastolic pressure and cardiac index were normal preoperatively, V CF was 1.66 circ/sec at a maximum tension of 440 g/cm 2 . Following operation, LV end-diastolic pressure fell in the four patients with depressed inotropic state (average decrease, 23 mm Hg) and cardiac index increased (average increase, 0.93 L/min/m 2 ). However, no change in the tension-velocity relation was observed postoperatively, V CF ranging from 0.27 to 1.14 circ/sec in these patients, indicating that no change had occurred in the inotropic state. In addition, a fixed abnormality in diastolic LV pressure-volume characteristics, determined from preoperative and postoperative measurements of pressure and radius during diastole, had occurred in patients with depressed myocardial function. In contrast, in the patient with normal myocardial function, LV end-diastolic radius was reduced by 33% postoperatively while end-diastolic pressure was unchanged, suggesting reversal of stress relaxation, or creep, following relief of volume overload.
Patterns, acts, and self-control: Rachlin's theory
Authors: Robert Kane
Journal: Behavioral and Brain Sciences (1995)

Abstract Regarding Rachlin's behavioral act/pattern theory of self-control, it is argued that some cases of self-control involve pattern/ pattern conflicts rather than merely act/pattern conflicts and that – if all cases of self-control are to be accounted for – some patterns must be viewed as internal representational states of mind (plans) rather than merely as patterns of actual overt behavior.
Regulating Physician-Assisted Death
Authors: Franklin G. Miller, Timothy E. Quill, Howard Brody, John C. Fletcher, Lawrence O. Gostin, Diane E. Meier
Journal: New England Journal of Medicine (1994)

Public-opinion polls have consistently shown that approximately 60 percent of the American public favors legal reform allowing physician-assisted death as a last resort to end the suffering of competent patients1. Yet the voters in Washington State in 1991 and California in 1992 narrowly defeated referendums that would have permitted physicians to prescribe or administer lethal treatment to terminally ill patients. The lack of adequate safeguards to protect vulnerable patients and prevent abuse may have been an important factor in the rejection of these legislative proposals2. In this article we describe a policy of legalized physician-assisted death restricted to . . .
Cell fusion is a physiological process in mouse liver
Authors: Francesca Faggioli, Maria Grazia Sacco, Lucia Susani, Cristina Montagna, Paolo Vezzoni
Journal: Hepatology (2008)

Abstract A large portion of hepatocytes are polyploid cells, thought to arise through endoduplication followed by aborted cytokinesis. However, several recent reports describing liver cell fusion with exogenously derived bone marrow cells have been published. The exact significance of this finding is unclear, because the adopted protocols involve ablation regimens, damaged livers and artificial injections of adult cells. By creating chimeric mice bearing distinct reporter genes (LacZ and GFP), we show that in an unperturbed setting, hepatocytes carrying both markers can be detected via immunohistochemistry and polymerase chain reaction analysis. To further corroborate these findings with a direct visualization of the chromosome content at the single-cell level, we performed genotype analysis via fluorescence in situ hybridization on XY/XX chimeric mice with a Y chromosome–specific paint and an X chromosome–specific bacterial artificial chromosome clone probes. Conclusion : This technique confirmed the occurrence of cell fusion in adult mouse liver. (Hepatology 2008.)
Relative efficacy of steroid therapy in immune thrombocytopenia mediated by anti‐platelet GPIIbIIIa versus GPIbα antibodies
Authors: Qingshu Zeng, Lingyan Zhu, Lili Tao, Jing Bao, Mingzhen Yang, Elisa K. Simpson, Conglei Li, Dianne E. van der Wal, Pingguo Chen, Christopher M. Spring, Mingli Wang, Lingjie Zhang, Changgeng Ruan, Ming Hou, Ruixiang Xia, Heyu Ni
Journal: American Journal of Hematology (2011)

Immune thrombocytopenia (ITP) is characterized by platelet clearance mediated primarily by autoantibodies against the platelet GPIIbIIIa and/or GPIbα. Steroid therapy is a first-line treatment for ITP. However, some patients are refractory to this therapy and currently no method can predict which patients will respond. To evaluate whether steroids are equally efficacious in treating patients with ITP caused by anti-GPIIbIIIa versus anti-GPIbα antibodies, we performed a retrospective study on 176 newly diagnosed patients with acute ITP who had severe bleeding symptoms and were admitted as resident patients to the hospital. The patients were treated first with intravenous administration of high-dose dexamethasone (DXM), followed by oral administration of prednisone. Response to therapy was observed in a majority of patients with antibodies specific for GPIIbIIIa (31/43) or without detectable antibodies against either GPIIbIIIa or GPIbα (36/45). In contrast, the steroid response was significantly lower in patients with anti-GPIbα antibodies (9/34) or with antibodies against both GPIbα and GPIIbIIIa (16/54). The preliminary findings of this study suggest that in future prospective clinical trials including corticosteroids, the anti-GPIbα, and -GPIIbIIIa status should be assessed in order to test its potential relevance in deciding future treatments.
The Relationship of Subtle Neurologic Impairments to Disturbances of Thinking
Authors: G.J. Tucker, E.W. Campion, P.A. Kelleher, P.M. Silberfarb
Journal: Psychotherapy and Psychosomatics (1974)

Consecutive admissions (58) to an acute psychiatric service were studied for the presence of thought disturbance and soft neurologic signs. Forty-three percent of the patients studied showed neurologic impairment and 63 % evidence of thought disturbance. Sixty percent of those diagnosed schizophrenic showed neurologic impairment versus 29 % of the nonschizophrenics. Fifty-nine percent with thought disorder had neurologic impairment while 21 % without thought disorder had neurologic impairment. It is hypothesized that schizophrenia be viewed as a dysfunction of the central nervous system and that the presence of thought disorder in schizophrenic patients may be a reflection of this neurologic dysfunction, thus the relation of thought disorder and neurologic impairment may transcend diagnostic categories.
Airflow limitation by the Global Lungs Initiative equations in a cohort of very old adults
Authors: Eralda Turkeshi, Bert Vaes, Elena Andreeva, Catharina Matheï, Wim Adriaensen, Gijs Van Pottelbergh, Jean-Marie Degryse
Journal: European Respiratory Journal (2015)

The cut-off for forced expiratory volume in 1 s (FEV 1 )/forced vital capacity (FVC) defining airflow limitation for chronic obstructive pulmonary disease (COPD) is still contested. We assessed airflow limitation prevalence by the lower limit of normal (LLN) of Global Lungs Initiative (GLI) 2012 reference values and its predictive ability for all-cause mortality and hospitalisation in very old adults (aged ≥80 years) compared with the fixed cut-off. In a Belgian population-based prospective cohort of 411 very old adults, airflow limitation prevalence by the 5th percentile of GLI 2012 z-scores (GLI-LLN) and fixed cut-off (0.70) were compared with COPD reported by general practitioners (GPs). Survival and Cox regression multivariable analysis assessed the association of airflow limitation by both cut-offs with 5-year all-cause mortality and first hospitalisation at 3 years. 9.2% had airflow limitation by GLI-LLN and 27% by fixed cut-off, without good agreement (kappa coefficient ≤0.40) with GP-reported COPD (9%). Only airflow limitation by GLI-LLN was independently associated with mortality (adjusted hazard ratio 2.10, 95% CI 1.30–3.38). FEV 1 /FVC &lt;0.70 but ≥GLI-LLN (17.8%) had no significantly higher risk for mortality or hospitalisation. In a cohort of very old adults, airflow limitation by GLI-LLN has lower prevalence than by fixed cut-off, independently predicts all-cause mortality and does not miss individuals with significantly higher all-cause mortality and hospitalisation.
Peer Review at JAMA—1985
Authors: George D. Lundberg
Journal: JAMA (1986)

A professional journal is distinguished from other publications by virtue of peer review. Few, if any, other methods of disseminating information can equally challenge such a process. Journal peer review is the assessment by experts (peers) of material submitted for publication in scientific and technical periodicals.<sup>1</sup>Through the process of peer review, judiciously applied, we can ensure that the information we provide you each week is as accurate as it is humanly possible to produce at that time. We believe that you trust us not to mislead you and we do our best to merit your trust. We have substantial resources to help sift out the bad and choose from the best and most important manuscripts submitted to us. Our consultant file holds the names of the best scientists, clinicians, statisticians, educators, economists, authors, administrators, and even poets to help guide us in manuscript review, rejection, revision, and selection.
Hippocrates in a World of Pagans and Christians
Authors: Ruben D. Rumbaut
Journal: JAMA (1991)

The old fabled dictum "Take me to your leader" is an excellent test of the essential character of human beings and human groups. Whenever individuals, professions, or societies recognize a specific person as their genuine leader, their own values, judgment, and worth are revealed distinctly. When we faithfully accept somebody as a role model and archetype, our acceptance speaks volumes. In that light, we, the practitioners of medicine, can be very secure and proud of our leader, the founder and historical guide of our profession: Hippocrates. We can get satisfaction not only in his oath, his teachings, his accomplishments, and his legend, but in the man himself. Twenty-five centuries have passed since his birth, yet his figure still commands respect and reverence. A Greek physician of ancient times from the small island of Cos, he remains so interesting to our contemporary world that Dr Owsei Temkin, a distinguished historian at
Small intestinal function and dietary status in dermatitis herpetiformis.
Authors: D J Gawkrodger, C McDonald, S O'Mahony, A Ferguson
Journal: Gut (1991)

Small intestinal morphology and function were assessed in 82 patients with dermatitis herpetiformis, 51 of whom were taking a normal diet and 31 a gluten free diet. Methods used were histopathological evaluation of jejunal mucosal biopsy specimens, quantitation of intraepithelial lymphocytes, cellobiose/mannitol permeability test, tissue disaccharidase values, serum antigliadin antibodies, and formal assessment of dietary gluten content by a dietician. There was no correlation between dietary gluten intake and the degree of enteropathy in the 51 patients taking a normal diet, whereas biopsy specimens were normal in 24 of the 31 patients on a gluten free diet, all previously having been abnormal. Eighteen patients on gluten containing diets had normal jejunal histology and in seven of these all tests of small intestinal morphology and function were entirely normal. Intestinal permeability was abnormal and serum antigliadin antibodies were present in most patients with enteropathy. Studies of acid secretion in seven patients showed that hypochlorhydria or achlorhydria did not lead to abnormal permeability in the absence of enteropathy. This study shows that a combination of objective tests of small intestinal architecture and function will detect abnormalities in most dermatitis herpetiformis patients, including some with histologically normal jejunal biopsy specimens. Nevertheless there is a small group in whom all conventional intestinal investigations are entirely normal.
Practical System for Determining Ventilatory Function
Authors: Jack D. Hackney
Journal: JAMA (1965)

Ventilatory failure can occur in a variety of conditions and may often go unrecognized clinically. A practical system has been developed for detecting ventilatory failure. The arterial carbon dioxide pressure (Paco<sub>2</sub>) as determined with this system was compared with the Paco<sub>2</sub>as measured directly in 107 tests on 63 patients with heart and lung disease (Paco<sub>2</sub>range of 22 to 103 mm Hg). With this system it was possible to make a reasonably accurate and useful estimate of Paco<sub>2</sub>(standard error of the estimate, 4.6 mm Hg). The test can be done quickly and the equipment is portable, inexpensive, and suitable for office and bedside use.
Connecting (C)-Peptide—A Spin-off of Insulin Secretion
Authors: Samuel Vaisrub
Journal: JAMA (1976)

Direct measurement of hormone concentrations, made possible by radioimmunoassay and other methods, has enhanced precision in estimating hormone secretion. No longer dependent on provocative or suppressive tests or on the evidence provided by serum electrolyte values, radioisotope studies, and other indirect indicators of hormone activity, assessment of glandular function can be made with greater confidence. Triidothyronine and tetraiodothyronine values are more reliable in diagnosing hyperthyroidism or hypothyroidism than is the basal metabolic rate; an elevated serum aldosterone level will dispel any doubts created by unexpectedly normal serum potassium levels in suspected aldosteronism; and high serum insulin levels are more diagnostic of insulinoma than is fasting hypoglycemia. Occasionally, however, serum hormone levels become fallible guides. Such is the case with immunoreactive insulin assays in patients receiving exogenous insulin. In vitro, circulating endogenous insulin antibodies compete with added antibodies for the labeled insulin, thus vitiating the insulin immunoassay. The latter then fails