tbuckley/cabot-search huggingface dataset:
Nilotinib is associated with minimal cross intolerance to imatinib in patients with imatinib-intolerant chronic myelogenous leukemia (CML) in chronic phase (CP)
Authors: E. Jabbour, P. le Coutre, M. Baccarani, K. Bhalla, G. J. Ossenkoppele, A. Hochhaus, N. Gattermann, A. Haque, A. Weitzman, H. Kantarjian
Journal: Journal of Clinical Oncology (2007)

7039 Background: Nilotinib is a highly selective Bcr-Abl tyrosine kinase inhibitor that is 30-fold more potent than imatinib and is an important therapeutic option for patients (pts) who have either imatinib-resistant or -intolerant CML disease. Results of a subset of pts with Ph+ CML-CP who received nilotinib for imatinib-intolerance are reported Methods: Pts were part of a phase II open-label study evaluating the safety and efficacy of nilotinib in imatinib-resistant or -intolerant CML-CP. Imatinib intolerance was defined as no MCyR and discontinuation of imatinib due to Grade 3/4 AEs or persistent (&gt; 1 mo) or recurrent Grade 2 AE (recurred &gt; 3 times) despite optimal supportive care. The proportion of pts achieving MCyR was the primary endpoint, and safety and toxicity were secondary endpoints. Planned starting dose was nilotinib 400mg BID. Results: Of the 316 pts with CML-CP enrolled, 95 (30%) pts had imatinib-intolerance for either non-hematologic and/or hematolgic AEs. Some pts had more then one AE satisfying the criteria for intolerance. The frequency of intolerant symptoms for imatinib and nilotinib is shown in the table below. Only 2/80 (3%) pts with non-hematologic imatinib-intolerance experienced a recurrence of similar symptoms during nilotinib therapy. 33 patients entered the study due to hematologic intolerance (neutropenia, thrombocytopenia) and only 7/33 (21%) developed similar problems. In 86 pts with intolerance and at least 6 mos of follow up, 55% of these patients achieved MCyR, similar to that previously reported for imatinib-resistant patients. Conclusions: These are the first reported results evaluating cross intolerance symptoms to TKIs. The results demonstrate that nilotinib is effective in imatinib-intolerant CML-CP and has a very low rate of cross- intolerance, further supporting the excellent tolerability of nilotinib No significant financial relationships to disclose. [Table: see text]
A Randomized Trial of Immediate versus Delayed Elective Angioplasty after Intravenous Tissue Plasminogen Activator in Acute Myocardial Infarction
Authors: Eric J. Topol, Robert M. Califf, Barry S. George, Dean J. Kereiakes, Charles W. Abbottsmith, Richard J. Candela, Kerry L. Lee, Bertram Pitt, Richard S. Stack, William W. O'Neill
Journal: New England Journal of Medicine (1987)

We compared the efficacy of immediate coronary angioplasty after acute myocardial infarction with that of elective angioplasty at 7 to 10 days in patients treated initially with intravenous tissue plasminogen activator. The plasminogen activator (150 mg) was administered 2.95±1.1 hours after the onset of symptoms, to 386 patients with acute myocardial infarction. Ninety minutes later, patency of the coronary artery serving the area of the infarct was demonstrated by coronary angiography in 288 patients (75 percent). Bleeding problems were frequently encountered, as evidenced by an average drop in hematocrit of 11.7±6.5 points from base line to nadir and by a need for transfusion not related to bypass surgery in 70 patients (18 percent). After successful thrombolysis, 197 patients with a patent but severely stenotic vessel suitable for angioplasty were randomly assigned to immediate angioplasty (n = 99) or, if indicated 7 to 10 days after infarction, to deferred (elective) angioplasty (n = 98). The incidence of reocclusion was similar in the two groups: 11 percent in the group assigned to immediate angioplasty and 13 percent in the group assigned to elective angioplasty. Neither group had a significant improvement in global left ventricular function, and regional wall motion in the infarct zone improved to a similar extent in the two groups. In the elective-angioplasty group, the rate of crossover to emergency angioplasty for recurrent ischemia was 16 percent (whereas 5 percent of the immediate-angioplasty group required emergency repeated angioplasty; P = 0.01). In 14 percent of the patients in the elective group, the stenosis was substantially reduced by the time of the seven-day follow-up angiography, obviating the need for angioplasty. We conclude that in patients with initially successful thrombolysis and suitable coronary-artery anatomy, immediate angioplasty offers no clear advantage over delayed elective angioplasty. (N Engl J Med 1987; 317: 581–8.)
Prevention of<i>Haemophilus influenzae</i>Type b Infections in High-Risk Infants Treated with Bacterial Polysaccharide Immune Globulin
Authors: Mathuram Santosham, Raymond Reid, Donna M. Ambrosino, Mark C. Wolff, Janne Almeido-Hill, Claudette Priehs, Kathy M. Aspery, Steve Garrett, Larry Croll, Stephan Foster, Gerald Burge, Peter Page, Bonnie Zacher, Richard Moxon, George R. Siber
Journal: New England Journal of Medicine (1987)

Apache Indian infants have a high frequency of Haemophilus influenzae type b (Hib) and pneumococcal infections. Forty percent of Hib infections in these infants occur before the age of six months, when active immunization may not be protective. To evaluate the efficacy of passive immunization with a human hyperimmune globulin (bacterial polysaccharide immune globulin [BPIG]) prepared from the plasma of immunized adult donors, we randomly assigned 703 infants in a double-blind fashion to receive 0.5 ml of BPIG per kilogram of body weight (n = 353) or 0.5 ml of saline (n = 350) intramuscularly at 2, 6, and 10 months of age. Hib-antibody levels were significantly higher in BPIG recipients than in placebo recipients at 4, 6, and 10 months of age (P less than 0.001). During the first 90 days after BPIG or placebo injection, no Hib or pneumococcal infections were detected in the BPIG group, whereas seven Hib infections (six cases of bacteremia and one of meningitis) and four pneumococcal infections (bacteremia) were detected in the placebo group (P = 0.007 and 0.06, respectively). During the fourth month, one case of Hib meningitis and two cases of pneumococcal bacteremia developed in the BPIG group, whereas there were no Hib or pneumococcal infections in the placebo group. We conclude that BPIG given at four-month intervals provided significant protection against serious Hib disease for three months, and that in high-risk infants it might be used alone, perhaps at three-month intervals, or together with active immunization.
Safety of Viaskin Milk Epicutaneous Immunotherapy (EPIT) in IgE-Mediated Cow's Milk Allergy (CMA) in Children (MILES Study)
Authors: Karine Rutault, Wence Agbotounou, Aurélie Peillon, Claude Thébault, Fanny Vincent, Laurent Martin, Ruban Charles, Christophe Dupont, Pierre-Henri Benhamou, Hugh A. Sampson
Journal: Journal of Allergy and Clinical Immunology (2016)
Promoting organisational justice in medicine and health science research and practice
Authors: Malcolm MacLachlan
Journal: BMJ (2016)

The BMJ ’s issue highlighting clinical and research malpractice is welcome,1 as is the recognition of trenchant resistance to change. Privileged groups seek to defend the indefensible.2 There is much privilege and profit to defend in health, including for health professional associations, corporations, and universities.

Once qualified, clinical professionals find …
Treatment Results in the Major Psychoses
Authors: J. Sanbourne Bockoven, Milton Greenblatt, Harry C. Solomon
Journal: New England Journal of Medicine (1951)

THE long-accepted view that persons attacked by psychosis are doomed to life-long custodial care is seriously challenged by present-day experience. The somatic therapies have revived hope for the ultimate curability of the most serious mental derangements, and concurrently a new enthusiasm for psychotherapy and social therapy has emerged.The statistics of the Boston Psychopathic Hospital provide a basis for evaluating the effectiveness of modern treatment. The Boston Psychopathic Hospital admits three classes of patients: Patients with gross abnormalities of thinking, feeling or behavior, admitted from the community on referral by practicing physicians. Some of these patients are discharged as not . . .
Lupus Diathesis and the Hydralazine Syndrome
Authors: Donato Alarcón-Segovia, John W. Worthington, L. Emmerson Ward, Khalil G. Wakim
Journal: New England Journal of Medicine (1965)

CERTAIN hypertensive patients treated with hydralazine hydrochloride acquire a clinical picture that, when fully manifested, is indistinguishable from that of systemic lupus erythematosus.1,2 The relation of this drug-induced disease to spontaneously occurring lupus erythematosus, as yet undetermined, is important because it may provide some clues to the pathogenesis and prevalence of systemic lupus erythematosus and related conditions.We believe that overt systemic lupus erythematosus as presently known is the end, stage of a long standing process, possibly genetically induced, that may remain latent until unmasked or exacerbated by one of various agents with this potential.3 4 5 This latency or the . . .
Mitochondrial Sirtuins in Cancer: Emerging Roles and Therapeutic Potential
Authors: Jasmine George, Nihal Ahmad
Journal: Cancer Research (2016)

Abstract The past few decades have witnessed a furious attention of scientific community toward identifying novel molecular factors and targets that could be exploited for drug development for cancer management. One such factor is the sirtuin (SIRT) family of nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases. The role of SIRTs in cancer is extremely complex, with dichotomous functions depending on cell contexts. Mammalian SIRTs (SIRT1–7) differ in their cellular localization and biologic functions. Among these, SIRT -3, -4, and -5 are located in the mitochondria and are being carefully investigated. These mitochondrial SIRTs (mtSIRT) regulate multiple cellular and physiologic processes, including cell cycle, gene expression, cell viability, stress response, metabolism, and energy homeostasis. Recent research suggests that mtSIRTs influence tumors by regulating the metabolic state of the cell. Although the research on the role of mtSIRTs in cancer is still in its infancy, studies have suggested tumor suppressor as well as tumor promoter roles for them. This review is focused on discussing up-to-date information about the roles and functional relevance of mtSIRTs (SIRT -3, -4, -5) in cancers. We have also provided a critical discussion and our perspective on their dual roles, as tumor promoter versus tumor suppressor, in cancer. Cancer Res; 76(9); 2500–6. ©2016 AACR.
DIVERGENT ACTIVITY OF AFATINIB (AFAT) AND CETUXIMAB (CET) IN PATIENT-DERIVED XENOGRAFT (PDX) MODELS OF ACQUIRED ERLOTINIB RESISTANCE.
Authors: Philip Mack, Neal Goodwin, William Holland, Karen Kelly, Tianhong Li, Primo Lara, David Gandara
Journal: Journal of Thoracic Oncology (2013)
Impaired Pulsatile Secretion of Insulin in Relatives of Patients with Non-Insulin-Dependent Diabetes
Authors: Stephen O'Rahilly, Robert C. Turner, David R. Matthews
Journal: New England Journal of Medicine (1988)

In fasting nondiabetic subjects, insulin is secreted in regular pulses every 12 to 15 minutes, but patients with non-insulin-dependent diabetes lack regular oscillatory insulin secretion. To investigate whether abnormal insulin oscillations are an early feature of diabetes, we studied 10 minimally glucose-intolerant first-degree relatives of patients with non-insulin-dependent diabetes and 10 controls matched for age and obesity. We performed a time-series analysis of fasting plasma insulin levels in blood samples obtained at 1-minute intervals for 150 minutes. Fasting plasma glucose levels were higher in the relatives than in the controls (mean +/- SD, 5.4 +/- 0.7 vs. 4.4 +/- 0.3 mmol per liter). Autocorrelation of pooled data showed no regular oscillatory activity in the relatives but a 13-minute cycle in the controls (r = 0.23, P less than 0.001). Similarly, Fourier transform analysis showed no significant peak in the relatives but the expected significant peak at 13 to 14 minutes in the controls (P less than 0.05). First-phase (0 to 10 minutes) insulin secretory responses to glucose administered intravenously were not significantly impaired in the relatives (geometric mean, 188 pmol per liter [26.2 mU per liter]; range of SD, +103 to -67 pmol per liter [+14.4 to -9.3 mU per liter]), as compared with the controls (geometric mean, 231 pmol per liter [32.2 mU per liter]; range of SD, +131 to -83 pmol per liter [+18.2 to -11.6 mU per liter]). We conclude that abnormal oscillatory insulin secretion may be an early phenomenon in the development of non-insulin-dependent diabetes.
Case 38-2007
Authors: Vincent Liu, Corey S. Cutler, Alison Z. Young
Journal: New England Journal of Medicine (2007)

A 44-year-old woman was admitted to this hospital because of generalized, painful, ulcerated skin lesions. Four years before admission, she had generalized hyperkeratotic lesions that responded poorly to treatment. Biopsy specimens had been interpreted as squamous-cell carcinoma. Three months before admission, mycophenolate mofetil was begun; some of the lesions regressed, but 1 month later, new painful nodules and plaques developed, with central necrosis and ulceration.
<scp>MP</scp>‐AzeFlu is more effective than fluticasone propionate for the treatment of allergic rhinitis in children
Authors: W. Berger, J. Bousquet, A. T. Fox, J. Just, A. Muraro, A. Nieto, E. Valovirta, M. Wickman, U. Wahn
Journal: Allergy (2016)

Abstract The objective was to evaluate the efficacy of MP ‐AzeFlu (Dymista ® ) vs fluticasone propionate ( FP ), (both 1 spray/nostril bid), in children with allergic rhinitis ( AR ). MP ‐AzeFlu combines azelastine hydrochloride, FP and a novel formulation in a single spray. Children were randomized in a 3 : 1 ratio to MP ‐AzeFlu or FP in this open‐label, 3‐month study. Efficacy was assessed in children aged ≥ 6 to &lt;12 years ( MP ‐AzeFlu: n = 264; FP : n = 89), using a 4‐point symptom severity rating scale from 0 to 3 (0 = no symptoms; 3 = severe symptoms). Over the 3‐month period, MP ‐AzeFlu‐treated children experienced significantly greater symptom relief than FP‐treated children (Diff: −0.14; 95% CI : −0.28, −0.01; P = 0.04), noted from the first day (particularly the first 7 days) and sustained for 90 days. More MP ‐AzeFlu children achieved symptom‐free or mild symptom severity status, and did so up to 16 days faster than FP . MP ‐AzeFlu provides significantly greater, more rapid and clinically relevant symptom relief than FP in children with AR .
Non-Diabetic Retinal Abnormalities in Chronic Pancreatitis
Authors: Phillip P. Toskes, William Dawson, Cheryl Curington, Norman S. Levy, Constance Fitzgerald
Journal: New England Journal of Medicine (1979)

To determine whether retinal abnormalities occur in patients with chronic pancreatitis, ophthalmoscopic and retinal-function evaluation was performed in 28 patients with chronic pancreatitis and 19 healthy subjects. The final threshold of dark adaptation was significantly increased 40 per cent (P less than 0.001) in patients with pancreatitis, whether or not they had steatorrhea. Patients with steatorrhea had a significant decrease of about 42 per cent (P less than 0.001) in the b-wave of the electroretinogram, a measure of both rod and cone function. Seven of the 28 patients complained of difficulty with hight vision; six of these seven had morphologic lesions on ophthalmoscopic examination, confirmed by fluorescein angiography. No correlation was found between any of the retinal abnormalities and the serum vitamin A or zinc levels or glucose tolerance. Non-diabetic retinal lesions and retinal-function abnormalities are common in patients with chronic pancreatitis, even in the absence of steatorrhea.
TMIC-12MODELING AND ESTIMATION OF TUMOR INTERSTITIAL FLUID PRESSURE AND NORMAL TISSUE COMPRESSION USING HYPERFOAM THEORY AND FINITE ELEMENT TECHNIQUE
Authors: Narsollah Goudarzi, Reza Faghihi, James Ewing, Brent Griffith, David Nathanson, Ali Arbab, Hassan Bagher-Ebadian
Journal: Neuro-Oncology (2015)

Recent studies have shown that mechanical stresses and interstitial fluid pressure (IFP) gradients of solid and embedded tumors directly contribute to their aggressiveness and response to therapy.Thus, studying and modeling these parameters play an important role in diagnosis and therapy of solid Overall survival
PWE-264 Laparoscopic versus open T4 colonic cancer resection
Authors: A King, J Dixon, D Harji, P Sagar
Journal: Gut (2015)

<h3>Introduction</h3> The role of laparoscopic resection in T4 colon cancer is controversial, with the early laparoscopic randomised trials reporting variable outcomes in this cohort of patients. We aim to examine the clinical and oncological outcomes between laparoscopic and open T4 colon cancer resections. <h3>Method</h3> All consecutive patients undergoing surgery for a radiological presumed T4 colon cancer between 2009 and 2012 from a prospectively maintained database were identified. Data were collected on patient demographics, operative detail, histological data and follow up status. <h3>Results</h3> 221 patients were identified, with 106 (48.0%) undergoing open surgery and 115 (52.0%) undergoing laparoscopic surgery. Conversation rate was 12.1%. The two groups were similar in pre-operative staging. R0 resection rate was achieved in 75.9% with similar rates in the laparoscopic and open group, 40.8% and 35.1% respectively, p = 0.74. Complication rates were similar between the two groups (laparoscopic 19% versus open 23.5%, p = 0.06). Median length of stay was shorter in the laparoscopic group compared to the open group (9 vs. 14 days, p = 0.05). Overall 3-year survival was similar in both groups, (laparoscopic 39% versus open 25%, p = 0.27). <h3>Conclusion</h3> Laparoscopic surgery is feasible in T4 colon cancers with comparable clinical and oncological outcomes, with the advantage of faster recovery. <h3>Disclosure of interest</h3> None Declared.
The gut-adherent microbiota of PSC–IBD is distinct to that of IBD
Authors: Mohammed Nabil Quraishi, Martin Sergeant, Gemma Kay, Tariq Iqbal, Jacqueline Chan, Chrystala Constantinidou, Palak Trivedi, James Ferguson, David H Adams, Mark Pallen, Gideon M Hirschfield
Journal: Gut (2016)

Primary sclerosing cholangitis–IBD (PSC–IBD) is an inflammatory autoimmune hepato–biliary–enteric disease in which it is predicted that gut microbiota have potential pathophysiological effects, relevant to disease initiation and outcome. The recent article by Kummen et al 1 who reported that the gut microbiota in PSC is distinct compared with those from healthy controls and patients with UC without liver disease, is therefore of interest. However, it remains unclear if these alterations in the gut microbiota are a cause or an effect of liver disease, and there remains a challenging task to link dysbiosis with disease pathogenesis, as well as clarify whether faecal microbiota are entirely representative of communities of mucosa-associated bacteria, which might uniquely interact with immune and epithelial cells.

Nevertheless Kummen et al notably demonstrated that the Veillonella genus showed a marked increase in PSC–IBD, in comparison with both healthy controls and patients with UC alone. Given interest in the mechanism of lymphocyte tracking between the bowel and liver …
Frequency of vitamin D (Vit D) deficiency at breast cancer (BC) diagnosis and association with risk of distant recurrence and death in a prospective cohort study of T1–3, N0–1, M0 B
Authors: P. J. Goodwin, M. Ennis, K. I. Pritchard, J. Koo, N. Hood
Journal: Journal of Clinical Oncology (2008)

511 Background: Vit D acts through a nuclear transcription factor to regulate many aspects of cellular growth and differentiation. Low levels have been associated with increased BC risk. We examined Vit D levels and prognostic effects in an existing BC cohort. Methods: 512 consecutive women with newly diagnosed BC were enrolled at 3 U of Toronto hospitals between 1989 and 1995. A blood specimen obtained at diagnosis was stored at −80°C. The Block questionnaire was used to measure diet intake. Clinical and pathology data were obtained from medical and pathology records. 25-OH Vit D was measured by radioimmunoassay. Women were followed prospectively to 2006. Results: Mean age was 50.4±9.7 yrs. 288 women had T1 tumors, 164 T2 and 24 T3/4. 356 tumors were N0. 342 were estrogen receptor (ER) positive. 73 tumors were grade 1, 202 grade 2 and 173 grade 3. 199 women received adjuvant chemotherapy (CXT) and 200 received tamoxifen. 116 women (22.7%) had distant recurrences and 106 (20.7%) died during a median follow-up of 11.6 yrs. Mean 25-OH Vit D was 58.1±23.4 nmol/L. Vit D levels were deficient (<50 nmol/L) in 192 (37.5%), insufficient (50–72 nmol/L) in 197 (38.5%) and adequate (>72 nmol/L) in 123 (24.0%). Low Vit D levels were associated with premenopausal status, high body mass index (BMI), high insulin and high tumor grade (all p≤0.03). Low Vit D levels were associated with low dietary intake of retinol, Vitamin E, grains and alcohol (all p<0.02). Vit D was marginally lower when drawn in winter (Oct-Mar) vs summer (Apr-Sept) months (56.7 vs 59.5 nmol/L, p=0.07). Distant disease-free survival (DDFS) was significantly worse in women with deficient (vs adequate) Vit D levels (HR 1.94, 95% CI 1.16–3.24, p=0.02) as was overall survival (OS) (HR 1.73, 95% CI 1.05–2.86, p=0.02). Vit D associations with DDFS were independent of age, BMI, insulin, T and N stage, ER and grade (all HR ≥1.55 Q1 vs Q4, all p ≤ 0.04); they were not significantly modified by ER, adjuvant CXT or tamoxifen. Vit D associations with OS were attenuated by grade and were absent in ER negative BC. Conclusions: Vit D deficiency is common at BC diagnosis and is associated with poor prognosis. This research was funded by the Breast Cancer Research Foundation. No significant financial relationships to disclose.