tbuckley/cabot-search huggingface dataset:
Cut-off points defining normal and asthmatic bronchial reactivity to exercise and inhalation challenges in children and young adults
Authors: S Godfrey, C Springer, E Bar-Yishay, A Avital
Journal: European Respiratory Journal (1999)

An analysis was undertaken to determine the optimal cut-off separating an asthmatic from a normal response to a bronchial provocation challenge by exercise and the inhalation of methacholine or histamine in children and young adults. Data were extracted, after appropriate correction, from published studies available in Medline of large random populations that complied with preset criteria of suitability for analysis, and the distribution of bronchial reactivity in the healthy population for exercise and inhalation challenges were derived. Studies on the response to exercise and methacholine inhalation in 232 young asthmatics of varying severity were carried out by the authors and the distribution of bronchial reactivity of a young asthmatic population obtained. Comparisons of the sensitivity and specificity of the challenges were aided by the construction of receiver operating characteristic curves. The optimal cut-off point of the fall in forced expiratory volume in one second (FEV1) after exercise was 13%, with a sensitivity (power) of 63% and specificity of 94%. For inhalation challenges, the optimal cut-off point for the dose of methacholine or histamine causing a 20% fall in FEV1 was 6.6 micromol, with a sensitivity of 92% and a specificity of 89%. The cut-off values were not materially affected by the severity of the asthma and provide objective data with which to evaluate the results of bronchial provocation challenges in children and young adults.
Targeted therapy for HER2 positive breast cancer
Authors: Jason A Incorvati, Shilpan Shah, Ying Mu, Janice Lu
Journal: Journal of Hematology & Oncology (2013)

Breast cancer is the second most common cause of death for women behind lung cancer and the most common cause of cancer deaths for women aged 45-55 years old (CDC.gov 2012). Although there continue to be enormously large numbers of disease incidence, deaths have been declining due to the disease with two hallmark time frames. The first occurred during the mid to late 1980's when hormonal therapy was introduced as a treatment for ER/PR positive breast cancer. The second occurred in the late 1990's when trastuzumab was introduced in treating HER2 positive breast cancer. These remarkable accomplishments in developing novel targeted therapies for breast cancer, along with a better understanding of the disease biology have improved disease outcome over the past 20 years.This article reviews the data presented at 2012 American Society of Clinical Oncology and 2012 San Antonio Breast Cancer Symposium regarding progress made in the field of HER2 positive breast cancer and examines the future of HER2 targeted therapy.
Fish oil ameliorates renal injury and hyperlipidemia in the Milan normotensive rat model of focal glomerulosclerosis.
Authors: D J Goldstein, D C Wheeler, D J Sandstrom, H Kawachi, D J Salant
Journal: Journal of the American Society of Nephrology (1995)

Rats of the Milan normotensive rat strain (MNS) spontaneously develop severe proteinuria and excessive glomerular thromboxane (Tx)A2 production at a young age. These abnormalities are accompanied by podocyte alterations, progressive focal glomerulosclerosis (FGS), and interstitial fibrosis, resembling human FGS. Since it has been shown that pharmacologic Tx-synthase inhibition protects MNS rats from these changes, it was hypothesized that a fish oil (FO) enriched diet, by enhancing TxA3 production instead of TxA2, might afford similar protection, compared with diets enriched in safflower oil (SO) or lard (LD). Rats were pair-fed 11% fat diets from age of 1 to 11 months. Glomerular TxA2 at 11 months was significantly lower in PO-fed rats than in SO- and LD-fed rats (11 +/- 3.0, 69 +/- 3.0, 59 +/- 19.0 nanograms per min/mg, respectively; P < 0.001). At 3 months, urinary albumin excretion was similar among the groups. Over the course of the study, rats fed FO developed significantly less albuminuria than the SO and LD groups (P < 0.001 by analysis of variance for repeated measures), such that the values at 11 months were 25 +/- 5.8, 49 +/- 8.7, and 68 +/- 13.0 mg/24h, respectively. Serum cholesterol and triglycerides were also significantly lower in FO-fed rats than in SO- and LD-fed rats. The extent of FGS was similar in the three groups, but FO-fed rats had less interstitial injury than the other groups. It was observed that a fish-oil diet substantially alleviated albuminuria, normalized nephrotic hyperlipidemia, and reduced interstitial injury, but did not prevent the development of FGS in the MNS model.
Cerebral vein thrombosis in patients with <scp>P</scp>hiladelphia‐negative myeloproliferative neoplasms An <scp>E</scp>uropean <scp>L</scp>eukemia <scp>N</scp>et study
Authors: Ida Martinelli, Valerio De Stefano, Alessandra Carobbio, Maria L. Randi, Claudia Santarossa, Alessandro Rambaldi, Maria C. Finazzi, Francisco Cervantes, Eduardo Arellano‐Rodrigo, Serena Rupoli, Lucia Canafoglia, Alessia Tieghi, Luca Facchini, Silvia Betti, Alessandro M. Vannucchi, Lisa Pieri, Rossella Cacciola, Emma Cacciola, Agostino Cortelezzi, Alessandra Iurlo, Enrico M. Pogliani, Elena M. Elli, Antonio Spadea, Tiziano Barbui
Journal: American Journal of Hematology (2014)

To investigate the characteristics and clinical course of cerebral vein thrombosis (CVT) in patients with myeloproliferative neoplasms (MPN) we compared 48 patients with MPN and CVT (group MPN‐CVT) to 87 with MPN and other venous thrombosis (group MPN‐VT) and 178 with MPN and no thrombosis (group MPN‐NoT) matched by sex, age at diagnosis of MPN (±5 years) and type of MPN. The study population was identified among 5,500 patients with MPN, from January 1982 to June 2013. Thrombophilia abnormalities were significantly more prevalent in the MPN‐CVT and MPN‐VT than in MPN‐NoT group ( P = 0.015), as well as the JAK2 V617F mutation in patients with essential thrombocythemia ( P = 0.059). Compared to MPN‐VT, MPN‐CVT patients had a higher rate of recurrent thrombosis (42% vs. 25%, P = 0.049) despite a shorter median follow‐up period (6.1 vs. 10.3 years, P = 0.019), a higher long‐term antithrombotic (94% vs. 84%, P = 0.099) and a similar cytoreductive treatment (79% vs. 70%, P = 0.311). The incidence of recurrent thrombosis was double in MPN‐CVT than in MPN‐VT group (8.8% and 4.2% patient‐years, P = 0.022), and CVT and unprovoked event were the only predictive variables in a multivariate model including also sex, blood count, thrombophilia, cytoreductive, and antithrombotic treatment (HR 1.97, 95%CI 1.05–3.72 and 2.09, 1.09–4.00, respectively). Am. J. Hematol. 89:E200–E205, 2014. © 2014 Wiley Periodicals, Inc.
Implementation of Universal Microsatellite Instability and Immunohistochemistry Screening for Diagnosing Lynch Syndrome in a Large Academic Medical Center
Authors: Brandie Heald, Thomas Plesec, Xiuli Liu, Rish Pai, Deepa Patil, Jessica Moline, Richard R. Sharp, Carol A. Burke, Matthew F. Kalady, James Church, Charis Eng
Journal: Journal of Clinical Oncology (2013)

In 2009, the Evaluation of Genomic Applications in Practice and Prevention recommended that all colorectal cancers (CRCs) be screened for Lynch syndrome (LS) through microsatellite instability (MSI) or immunohistochemistry (IHC). No studies report how this process is implemented on a health system-wide basis.Since 2004, Cleveland Clinic has screened CRC specimens with MSI/IHC. Between January 2004 and July 2007, MSI/IHC results went only to the colorectal surgeon (approach 1). Between August 2007 and June 2008, colorectal surgeons and a genetic counselor received the MSI/IHC results, and the counselor e-mailed the colorectal surgeon regarding appropriate patients for genetic counseling (GC) referral (approach 2). After July 2008, the colorectal surgeon and counselor received MSI/IHC results, but the counselor contacted the patient to facilitate referral (approach 3). In approaches 2 and 3, patients were presumed to have sporadic CRC if the tumor lacked MLH1 expression and was also BRAF mutated or if the patient was diagnosed at age greater than 72 years and had no cancer family history.Abnormal MSI/IHC results occurred in 178 (16%) of 1,108 patients. In approach 1, 21 (55%) of 38 patients with abnormal MSI/IHC were referred for GC, 12 (32%) of 38 underwent GC, and 10 (26%) of 38 underwent genetic testing (GT). In approach 2, nine (82%) of 11 patients were referred for GC, seven (64%) of 11 underwent GC, and five (45%) of 11 underwent GT. In approach 3, 56 (100%) of 56 patients were referred for GC, 40 (71%) of 56 underwent GC, and 37 (66%) of 56 underwent GT. Time from referral to GC was 10-fold quicker in approach 3 than approach 1.Implementation of universal MSI/IHC with GC/GT, along with effective multidisciplinary communication and plans of responsibility for patient contact, resulted in increased identification of patients with LS.
"Prorenin" in human plasma?
Authors: J E Sealey, J H Laragh
Journal: Circulation Research (1975)

An increase in plasma renin activity was demonstrated in plasma from normal subjects and most patients with essential hypertension after prolonged storage of the plasma at -20 degrees C. No change in renin substrate concentration was observed after storage for 12 months, and the rate of angiotensin generation during incubation with a fixed amount of added human renin was not increased. It therefore seems unlikely that the observed increase in renin activity was due to changes in plasma activators or inhibitors. The data are consistent with the activation of an inactive form of renin, tentatively called "prorenin" in normal subjects averaged from 1 to 2 ng/ml/hr, and did not change during sodium deprivation. However, three of four patients studied who had low-renin essential hypertension secreted abnormally large amounts of "prorenin" in response to sodium depletion. In these patients, subsequent sodium administration was associated with a return of "prorenin" to baseline levels.
Lord, deliver us from pain
Authors: Francis Veyckemans, Daniel Rodenstein
Journal: European Respiratory Journal (2013)

Pain is a word every human being can understand. Except those with congenital insensitivity to pain there is probably no human being that has completely escaped the perception of pain. Pain is an unpleasant feeling related to a physical aggression compromising the integrity of the body. It also has an emotional component that may be weak or strong. The fear of pain may be as disturbing as pain itself, as many a torturer knows and uses.
Development and evaluation of evidence based risk assessment tool (STRATIFY) to predict which elderly inpatients will fall: case-control and cohort studies
Authors: D Oliver, M Britton, P Seed, F C Martin, A H Hopper
Journal: BMJ (1997)

To identify clinical characteristics of elderly inpatients that predict their chance of falling (phase 1) and to use these characteristics to derive a risk assessment tool and to evaluate its power in predicting falls (phases 2 and 3).Phase 1: a prospective case-control study. Phases 2 and 3: prospective evaluations of the derived risk assessment tool in predicting falls in two cohorts.Elderly care units of St Thomas's Hospital (phase 1 and 2) and Kent and Canterbury Hospital (phase 3).Elderly hospital inpatients (aged > or = 65 years): 116 cases and 116 controls in phase 1,217 patients in phase 2, and 331 in phase 3.21 separate clinical characteristics were assessed in phase 1, including the abbreviated mental test score, modified Barthel index, a transfer and mobility score obtained by combining the transfer and mobility sections of the Barthel index, and several nursing judgements.In phase 1 five factors were independently associated with a higher risk of falls: fall as a presenting complaint (odds ratio 4.64 (95% confidence interval 2.59 to 8.33); a transfer and mobility score of 3 or 4 (2.10 (1.22 to 3.61)); and primary nurses' judgment that a patient was agitated (20.9 (9.62 to 45.62)), needed frequent toileting (2.48 (1.08 to 5.70)), and was visually impaired (3.56 (1.26 to 10.05)). A risk assessment score (range 0-5) was derived by scoring one point for each of these five factors. In phases 2 and 3 a risk assessment score > 2 was used to define high risk: the sensitivity and specificity of the score to predict falls during the following week was 93% and 88% respectively in phase 2 and 92% and 68% respectively in phase 3.This simple risk assessment tool predicted with clinically useful sensitivity and specificity a high percentage of falls among elderly hospital inpatients.
A CONTRIBUTION TO THE BIOLOGY OF PERIPHERAL NERVES IN TRANSPLANTATION
Authors: Ragnvald Ingebrigtsen
Journal: The Journal of Experimental Medicine (1915)

In autoplastic transplanted nerves a degenerative process occurs which resembles the ordinary Wallerian degeneration, but appears a little more slowly than the latter. The cells of Schwann are in a condition of survival and are capable of multiplication after the transplantation. In homoplastic transplanted nerves I have found a degenerative process resembling a Wallerian degeneration, somewhat delayed. The cells of Schwann multiply, and for some time at least are in a condition of survival. After twelve to fourteen days an abundant and increasing immigration of lymphocytes is observed, and from the eighteenth day the cells of Schwann develop a necrobiotic appearance. In heteroplastic transplanted nerves numerous myelin ovoids are formed during the first four to five days, but there is no proliferation of the cells of Schwann, and no Wallerian degeneration is seen. The graft becomes necrotic within about two weeks. The formation of ovoids that occurs during the first four to five days after the performance of the heteroplastic transplantation does not reveal the condition of the life of the graft. This formation of myelin ovoids is found in the nerve fibers when they have been kept in an incubator for twenty-four hours in Ringer solution (Nageotte12) or in homologous or heterologous serum, but it is not found in the fibers after their incubation in isotonic salt solution (Nageotte), the presence of calcium being necessary for the occurrence of ovoid formation. Heteroplastic transplanted nerves become necrotic. They are unsuitable for bridges in cases of nerve defects, and my results explain the failure of the attempts at heteroplastic transplantation of nerves in human beings. If we wish to bridge a nerve defect by implantation we must use autoplastic or homoplastic grafts. The occurrence of a Wallerian degeneration in these grafts during the first two to three weeks after the transplantation should make bridging a promising operation; for in this period the grafts resemble the peripheral part of a divided nerve and must be assumed to be capable of regeneration, and thus are very different from dead material. I have studied the process of regeneration, and shall communicate in a future article my results of bridging defects, which are encouraging as far as the function is concerned. My results with homoplastic transplantation of nerves have a bearing on the homoplastic transplantation of limbs, which has been successfully performed in dogs by Carrel. None of his dogs lived long enough to show any function of the transplanted leg. The practical value of this operation is dependent, of course, upon the return of function, and especially on the regeneration of the nerves in the transplanted leg. The results with homoplastic transplantation of nerves seem to indicate the possibility of a regeneration of the nerves in a homoplastic transplanted leg.
STUDIES ON TYPHUS FEVER
Authors: M. Ruiz Castaneda, Hans Zinsser
Journal: The Journal of Experimental Medicine (1930)

Our experiments have shown that the Mooser bodies or Rickettsiae derived from guinea pigs with Mexican typhus fever can survive in bedbugs after intra-coelomic injection for 10 days, remaining capable of infection. We have also succeeded in similarly infecting bedbugs by allowing them to feed on benzolized rats in whose blood Rickettsiae had been shown to be present. Injection of the organs of such bedbugs 5 days after the last, 9 days after the first infectious feeding into guinea pigs produced typical Mexican typhus fever. Some of the guinea pigs infected with such bedbug organs and passing through a typical typhus proved to be immune to subsequent inoculation with the European disease. Attempts to infect normal guinea pigs by allowing infected bedbugs to feed on them or by rubbing the feces into the uninjured skin have, so far, been unsuccessful. We have not, therefore, completed the cycle proving that bedbugs can transmit the disease, but we have shown that this is a possibility when dealing with man, obviously more susceptible to the disease than any of our experimental animals. The ease with which the Rickettsiae seem to survive in the bedbugs suggests the desirability of investigating other common insects for a similar capacity of harboring the typhus Rickettsiae-experiments which we have not yet had the time to carry out.
THE RELATIONSHIP OF CERTAIN ORAL SIGNS IN NEUROPSYCHIATRIC PATIENTS TO DOSAGE OF ATARACTIC DRUGS
Authors: S. H. BLEICHER, A. I. ISHLER, M. B. PAUL, J. K. KEW, H. C. RICKARD
Journal: American Journal of Psychiatry (1962)

Thirty-one NP patients exhibiting the oral sign of black hairy tongue were identified by the dental service; 46 control subjects were selected at random from patients examined at that time who did not exhibit the sign. Records of ataractic drug treatment for the 6-month period prior to the examination were obtained for both groups. No significant relationship emerged between drug dosage and presence of the sign of any criteria examined.
Integration of Troponin I Phosphorylation With Cardiac Regulatory Networks
Authors: R. John Solaro, Marcus Henze, Tomoyoshi Kobayashi
Journal: Circulation Research (2013)

We focus here on the modulation of thin filament activity by cardiac troponin I phosphorylation as an integral and adaptive mechanism in cardiac homeostasis and as a mechanism vulnerable to maladaptive response to stress. We discuss a current concept of cardiac troponin I function in the A-band region of the sarcomere and potential signaling to cardiac troponin I in a network involving the ends of the thin filaments at the Z-disk and the M-band regions. The cardiac sarcomere represents a remarkable set of interacting proteins that functions not only as a molecular machine generating the heartbeat but also as a hub of signaling. We review how phosphorylation signaling to cardiac troponin I is integrated, with parallel signals controlling excitation–contraction coupling, hypertrophy, and metabolism.
Effect of High-Dose Vitamin E on Insulin Resistance and Associated Parameters in Overweight Subjects
Authors: Patrick J. Manning, Wayne H.F. Sutherland, Robert J. Walker, Sheila M. Williams, Sylvia A. de Jong, Anne R. Ryalls, Elizabeth A. Berry
Journal: Diabetes Care (2004)

Markers of oxidative stress and plasma alanine transferase (ALT) levels are increased and circulating antioxidant concentrations are reduced in individuals with insulin resistance. Vitamin E improves glycemic control in people with diabetes. We tested the hypothesis that vitamin E would decrease markers of oxidative stress and plasma ALT levels and improve insulin sensitivity in overweight individuals.Eighty overweight individuals (BMI >27 kg/m(2)) were randomly allocated to receive either 800 IU vitamin E per day or a matching placebo for 3 months. The dose of vitamin E was increased to 1,200 IU per day for a further 3 months.Plasma peroxides decreased by 27% at 3 months and by 29% at 6 months in the group that received vitamin E and were positively correlated with plasma vitamin E concentrations at the 6-month time point. At 3 months, fasting plasma glucose and insulin concentrations were significantly reduced and homeostasis model assessment increased. These changes were not apparent at 6 months. Plasma ALT concentrations declined significantly throughout the study period.In conclusion, these findings indicate that vitamin E improves oxidative stress and hepatocellular function. Although insulin resistance also improves, this effect appears transient.
Familial reactive perforating collagenosis and intolerance to cold
Authors: M. W. KANAN
Journal: British Journal of Dermatology (1974)

A clinico-pathological study of reactive perforating collagenosis (RPC) is reported in seven adult siblings of both sexes in two unrelated consanguineous families from Kuwait. Although the primary defect in the skin of these patients is genetically determined, superficial trauma seems to be a triggering factor in most of the lesions. However, the regular occurrence of spontaneous lesions on the face in two patients and perniosis of the hands and feet in four other patients, together with the increased incidence on the exposed areas during the cold season, suggest an additive role for atmospheric cold. Experimental reproduction of RPC lesions was successful on the dorsa of the wrist and right middle finger respectively in two patients, while it failed twice on the covered areas. A significant finding was the absence of such lesions following deep incisional wounds, which suggests that the primary defect is in the pars papillaris of the dermis where a post-traumatic necrobiotic change starts off an RPC lesion.
Genetic Basis of Pancreas Cancer Development and Progression: Insights from Whole-Exome and Whole-Genome Sequencing
Authors: Christine A. Iacobuzio-Donahue, Victor E. Velculescu, Christopher L. Wolfgang, Ralph H. Hruban
Journal: Clinical Cancer Research (2012)

Pancreatic cancer is caused by inherited and acquired mutations in specific cancer-associated genes. The discovery of the most common genetic alterations in pancreatic cancer has provided insight into the fundamental pathways that drive the progression from a normal cell to noninvasive precursor lesions and finally to widely metastatic disease. In addition, recent genetic discoveries have created new opportunities to develop gene-based approaches for early detection, personalized treatment, and molecular classification of pancreatic neoplasms.