tbuckley/cabot-search huggingface dataset:
Genetic Prediction of Nonresponse to Hepatitis B Vaccine
Authors: Chester A. Alper, Margot S. Kruskall, Deborah Marcus-Bagley, Donald E. Craven, Aubrey J. Katz, Stuart J. Brink, Jules L. Dienstag, Zuheir Awdeh, Edmond J. Yunis
Journal: New England Journal of Medicine (1989)

In previous studies of the antibody response to hepatitis B vaccine in 598 subjects who received a full course of vaccination, we observed a bimodal response, with about 14 percent producing less than approximately 1000 radioimmunoassay (RIA) units. An analysis of the major histocompatibility complex (MHC) HLA and complement types of 20 of the subjects with the lowest responses indicated a greater-than-expected number of homozygotes for the extended or fixed MHC haplotype [HLA-B8,SC01,DR3]. This finding suggested that the lack of a normal response was a recessive MHC-linked trait. In this study, we prospectively vaccinated five homozygotes and nine heterozygotes for this haplotype in the expectation that the homozygotes would produce much lower levels of antibody than the heterozygotes. When the antibody response was assessed two months after the third injection, four of the five homozygotes had produced very low levels (approximately 1000 units or less) of antibody (mean, 467 RIA units; range, <8 to 1266), whereas all nine heterozygotes produced more than 2500 RIA units (mean, 15,608; range, 2655 to 28,900) (P<0.01). We conclude that the usual response to hepatitis B surface antigen is due to the presence of a dominant immune-response gene in the MHC and that a low response is due to the absence of such a gene and the presence on both chromosomes of MHC haplotypes (such as [HLA-B8,SC01,DR3]) that indicate such a response. (N Engl J Med 1989;321:708–12.)
OC-064 Damage control cholecystectomy: four years experience in a dgh
Authors: R Evans, N Malik, A Khan
Journal: Gut (2015)

<h3>Introduction</h3> Around 60,000 laparoscopic cholecystectomies are performed each year in the UK. Increasingly patients are being operated on during periods of active gallbladder inflammation. Identification of the anatomy can prove challenging during a “hot” cholecystectomy. Sub-total cholecystectomy is an increasingly accepted method of minimising operative complications for patients with complicated cholecystitis. The aim of the study is to determine whether complications can be kept to a minimum without needing to perform an open procedure. <h3>Method</h3> Retrospective analysis of 32 patients’ cases who underwent sub-total cholecystectomy in a District General hospital between 01/2011 and 12/2014. <h3>Results</h3> During the study period 840 cholecystectomies were performed in 664 women (79.0%) and 176 men (21.0%). 32 subtotal cholecystectomies were performed (3.8%, 31 laparoscopic, 1 lap converted to open). 808 total cholecystectomies were performed (96.2%, 1 open, 3 lap converted to open). 132 cases (15.7%) were performed as ‘hot’ emergency or urgent procedures. 155 patients (18.1%) underwent on table cholangiograms. No bile duct injuries and 1 bile leak occurred in the total cholecystectomy population. In the subtotal cholecystectomy cohort there were 21 men and 11 women with a median age of 69 (range 44–83). 25 patients presented with cholecystitis, 2 with biliary colic, 4 with cholangitis and one with pancreatitis. 11 were performed as ‘hot’ emergency or urgent procedures (34%). Despite this, active inflammation was present in 24 cases. Empyema was present in five patients. Four gallbladders’ were perforated. 30 pts had sub-hepatic drain insertion. Of these, 7 were removed in clinic post discharge. Median time to drain removal was 2 days (range 1–15 days). Median length of stay was 2 day (range 1–19). No bile duct injuries occurred. 1 bile leak occurred and required ERCP and stent. 3 patients developed post operative abscesses. One patients required laparoscopy and washout, one required a radiologically inserted drain and was managed conservatively with IV antibiotics. 8 patients received a single follow up in clinic (range 6 days – 3 months). 2 patients were re-referred to clinic from primary care with on-going symptoms. Of these, one required laparoscopic completion cholecystectomy 13 months following the original procedure. Another suffered cholangitis attributed to pre-operative ERCP and sphincterotomy, managed conservatively. <h3>Conclusion</h3> In the context of indefinable anatomy, laparoscopic sub-total cholecystectomy with retrograde dissection is a safe procedure with minimal complications. It is sufficient management in the majority patients. It allows for safer re-intervention in the small proportion of patients suffering from ongoing biliary symptoms. <h3>Disclosure of interest</h3> None Declared.
Ventilation and Oxygen Requirements during Prolonged Artificial Ventilation in Patients with Respiratory Failure
Authors: Henning Pontoppidan, John Hedley-Whyte, Henrik H. Bendixen, Myron B. Laver, Edward P. Radford
Journal: New England Journal of Medicine (1965)

IN a person with normal lungs the amount of ventilation that is sufficient to eliminate the carbon dioxide produced (and thus to maintain carbon dioxide homeostasis) is predictable with considerable accuracy, as shown by Radford and his associates.1 , 2 Such ventilation standards are based on the sex, weight and respiratory rate of the subject as well as predictable changes in basal metabolic rate caused by elevation in body temperature and moderate physical activity. Their accuracy when applied to the normal, anesthetized patient has been confirmed by others.3 , 4 In recent years the indications for use of artificial ventilation have broadened, and the . . .
Book: And When Did You Last See Your Father?
Authors: Tamara Rader
Journal: BMJ (2003)

Sooner or later we all die. And so do our parents. Blake Morrison has generously offered his insight into the experience of losing his father. This book met with critical acclaim on its publication almost 10 years ago and has inspired similar confessional memoirs. It is a testament to the quality of Morrison's writing that details of everyday family life and death, not sensational trauma or dysfunction, are what engage the reader. Between vivid descriptions of his father's death from cancer he recounts quirky, sometimes painfully funny anecdotes. His father's self centred impatience and interfering ways are tempered by true love and affection. It is this focus on ordinary details, such as a fondness for cars, practical jokes, and a series of dachshunds named Nikki, that give this book a wide appeal.​appeal.




Figure 1



Blake Morrison

Granta, £7.99, pp 224 ISBN 1 86207 093 8

Rating: ★★★★




Of course, there is no escaping the sad conclusion of this story. Dr Arthur Morrison had a good death, at home and surrounded by family. Perhaps because the author grew up with doctors as parents he has the ability to provide compassionate and rich details of scenes in hospital and at the deathbed. These unsentimental passages of a death at home are some of the most compelling in the book.

Modern life has a way of detaching us from the uncomfortable images, mixed emotions, and strange conversations of the final stage of life. Morrison writes, “I used to think the world divided between those who have children and those who don't; now I think it divides between those who've lost a parent and those whose parents are still alive.”

He cautions the reader against underestimating the strength of the grief of sons and daughters, no matter what relationships between parents and children are like. As much as I hate to, I have begun to contemplate this advice when it comes to my own mother, who in October 1998 was diagnosed as having heart failure, diabetes, and other health problems. I am grateful for this warm, nostalgic, but unsentimental book.
Reversible Protein-Losing Enteropathy with Intestinal Lymphangiectasia Secondary to Chronic Constrictive Pericarditis
Authors: Patricia Wilkinson, Benjamin Pinto, John R. Senior
Journal: New England Journal of Medicine (1965)

IT is now recognized that a considerable portion of the daily catabolism of serum albumin occurs in the gastrointestinal tract1 , 2 and that under some circumstances abnormally large amounts of protein may be lost in this way.3 When the magnitude of protein loss exceeds the patient's synthetic capacity, hypoproteinemia and depletion of body protein pools results. In many cases the gastrointestinal mucosa is disordered or damaged although sometimes no abnormality can be found. However, when hypoproteinemia can be shown to be caused by protein-losing gastroenteropathy,4 it is important to seek a specific cause in the hope of finding a situation that . . .
Analysis of HLA-DQ Genotypes and Susceptibility in Insulin-Dependent Diabetes Mellitus
Authors: Jeanine M. Baisch, Tracy Weeks, Robert Giles, Marie Hoover, Peter Stastny, J. Donald Capra
Journal: New England Journal of Medicine (1990)

There is evidence that certain alleles at the HLA-DQ locus are correlated with susceptibility to insulin-dependent diabetes mellitus (IDDM) and in particular that DQ beta-chain alleles containing aspartic acid at position 57 are protective. The availability of a large group of patients with IDDM enabled us to assess the role of HLA-DQ alleles in susceptibility to the disease in order to confirm and extend recent observations derived from studies of smaller numbers of patients. Using allele-specific oligonucleotide probes and the polymerase chain reaction, we studied 266 unrelated patients with IDDM and 203 unrelated normal subjects for eight HLA-DQ beta-chain alleles.
Temporary Amelioration of Primary Idiopathic Hypoparathyroidism by a Noncaseating Granulomatous Disease
Authors: Gary R. Joachim
Journal: New England Journal of Medicine (1964)

THE features of one disease seldom ameliorate the biochemical alterations of another occurring concurrently. Hasterick1 reported the case of a forty-nine-year-old Negro woman with sarcoid cutaneous lesions and bone involvement. Because the total twenty-four-hour urinary calcium was 60 mg. after three days on an Aub diet the author suggested that she might also have hypoparathyroidism. However, no further clinical data were given to support this assumption. A review of the literature indicates that the case reported below is the first well documented account of a patient simultaneously suffering from idiopathic hypoparathyroidism and a noncaseating granuloma consistent with sarcoidosis.Case Report . . .
Cefoxitin as a Single-Dose Treatment for Urethritis Caused by Penicillinase-Producing<i>Neisseria Gonorrhoeae</i>
Authors: S. William Berg, Michael E. Kilpatrick, William O. Harrison, J. Allen McCutchan
Journal: New England Journal of Medicine (1979)

Gonococci that resist standard penicillin regimens by production of a penicillinase are now well established in certain areas of the world. Because cefoxitin, a semisynthetic cephamycin, resists gonococcal penicillinase in vitro, we compared procaine penicillin G and cefoxitin in treatment of gonorrhea in an area where 40 per cent of isolates produce penicillinase. One hundred and seven men with culture-proved gonococcal urethritis were given a single dose of either procaine penicillin G, 4.8 million U, or cefoxitin, 2 g, intramuscularly. Both groups took 1 g of probenecid orally; cefoxitin was given with lidocaine to reduce pain at the injection site. In men infected with penicillinase-negative gonococci, both cefoxitin and penicillin were highly effective. Penicillin failed in 77 per cent of men with penicillinase-positive strains, whereas cefoxitin was completely successful. Cefoxitin is an effective alternative to spectinomycin for single-session therapy of urethritis caused by penicillinase-producing Neisseria gonorrhoeae.
Abstract P5-04-14: The covalent JNK inhibitor, JNK-IN-8, synergizes with lapatinib to cause cell death in basal-like breast cancer cell lines
Authors: ND Ebelt, CL Van Den Berg
Journal: Cancer Research (2016)

Abstract Basal-like and claudin-low breast cancers have the worst prognosis and represent 15-20% of breast cancers diagnosed each year. Endocrine and molecularly targeted therapies, such as trastuzumab, are ineffective due to lack of ER expression or HER2 amplification in the tumors. They also have a high frequency of p53 mutations, low BRCA1 expression and high EGFR expression. Our lab has shown that high expression of JNK2 in human basal-like breast cancers leads to significantly decreased disease-free survival. JNK2 also promotes basal-like tumor progression in mice by increasing EGFR-mediated migration through facilitating internalization of EGFR, upregulating EMT gene expression and promoting metastasis. The ATP-competitive JNK inhibitor SP600125 has been commonly used by researchers to elucidate JNK-specific mechanisms, but this inhibitor was found to have high affinity to many other intracellular kinases. A new JNK inhibitor, JNK-IN-8, has been developed that binds covalently to all three JNK gene products and is more selective than the SP600125 compound (Zhang, et al. 2012). Using this inhibitor, we have found that basal-like breast cancer cell lines can become sensitized to lapatinib. This combination is synergistic and causes apoptotic cell death, while as single agents at these concentrations, these drugs have little effect on cell viability. Treatment with either lapatinib or JNK-IN-8 decreases transcriptional activity of NF-κB significantly, but combination of the two drugs reduces NF-κB activity to an almost negligible amount compared to vehicle treatment. Combination treatment also led to a 6-fold increase in ROS production that may be activating apoptosis. We hypothesize that inhibition by both JNK-IN-8 and lapatinib cause independent decreases in NF-κB activation that, when combined, cause a synergistic decrease in NF-κB-mediated survival mechanisms. Use of the JNK-IN-8 inhibitor with lapatinib in humans may increase survival in patients with basal-like or claudin-low breast cancers. Zhang, T. et al. "Discovery of potent and selective covalent inhibitors of JNK". Chem Biol. 2012 Jan 27;19(1):140-54. Citation Format: Ebelt ND, Van Den Berg CL. The covalent JNK inhibitor, JNK-IN-8, synergizes with lapatinib to cause cell death in basal-like breast cancer cell lines. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-04-14.
LP02 : C-surfer: grazoprevir plus elbasvir in treatment-naive and treatment-experienced patients with hepatitis C virus genotype 1 infection and chronic kidney disease
Authors: D. Roth, D. Nelson, A. Bruchfeld, A. Liapakis, M. Silva, H. Monsour, P. Martin, S. Pol, M.-C. Londoño, T. Hassanein, P. Zamor, E. Zuckerman, Y. Zhao, S. Wan, B. Jackson, M. Robertson, J. Wahl, E. Barr, W. Greaves
Journal: Journal of Hepatology (2015)
An Interview Method for Obtaining Personal Histories
Authors: Clark W. Heath
Journal: New England Journal of Medicine (1946)

IN MEDICAL practice, knowledge of the patient's personality and social history is often essential for diagnosis and treatment. There is great need both in practice and teaching for well organized methods of obtaining this information. The interview is a powerful instrument if properly employed, yet most students and physicians have received little training in the art of interviewing.In recent years I have had personal experience with a short-interview method for the selection of officer candidates. This method, prepared by Woods1 and designed to reveal pertinent facts regarding the man's capacities, interests, personality traits, weaknesses and strengths, does not employ . . .
FRI0468 Long-Term Outcome of Pulmonary Function in the Anti-Synthetase Syndrome:
Authors: H. Andersson, M.B. Lund, T. Garen, Ø. Molberg
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Inflammatory myopathies including the Antisynthetase syndrome (ASS) is often complicated by interstitial lung disease (ILD), with impact on morbidity and mortality (1). There is increasing focus on the ILD component of the ASS, but knowledge about long term pulmonary outcome is still limited. <h3>Objectives</h3> To perform a longitudinal assessment of pulmonary function tests (PFT) in a well-defined cohort of ASS-patients with long term follow up. <h3>Methods</h3> The ASS-cohort at Oslo University Hospital includes 97 patients diagnosed from 1994-2011. Serial PFT data available for retrospective analyses were available in 94 of these patients. PFT measurements included Forced Vital Capacity (FVC), Forced Expiratory Volume in one second (FEV1) and diffusing capacity of the lung for Carbon monoxide (DLCO). PFT data were captured by systematic review of patient charts from symptom onset to study end (at December 31st 2014) or time of death. The earliest PFT identified was defined as the baseline PFT and the examination closest to study end or the time of death was defined as the follow-up PFT. The study was approved by the regional committee of health and medical research ethics in South-East Norway. Paired samples T-test and independent T-test were used to evaluate statistical significance (p&lt;0.05). <h3>Results</h3> The study cohort included 65 female and 29 male ASS patients (77 anti Jo-1, 7 anti-PL-7 and 10 anti-PL-12) with median age at diagnosis of 49 years. At the end of the study period 62 of the patients were alive and 32 (34%) had died. At the time of the follow-up PFT, 90/94 patients were on immunosuppressive therapy. The median time from baseline to follow up PFT was 61 months, but differed between the living and deceased subsets (Table). In the total cohort, there were no significant differences in PFT values from baseline to follow-up; FVC -0.008 (p&lt;0.933), FEV1 0.061 (p&lt;0.369) and DLCO -0.312 (p&lt;0.208). Subset analyses showed that the deceased patients, except for FVC at baseline, had consistently lower PFT values than the living patients (Table).We also observed a reduction in mean FVC and FEV1 values from baseline to follow-up in the deceased group, but not in the living group (Table). <h3>Conclusions</h3> In this study, on 94 ASS patients, we found no significant differences in pulmonary function parameters during a median follow up time of 61 months. These data indicate that pulmonary function may be rather stable in treated ASS-patients. The patients who died during the observation period had lower PFT values than the patients who survived, supporting the notion that PFTs have prognostic value in the ASS. Further analyses are required to fully evaluate the described data set. <h3>References</h3> Marie I et al. Short-term and long-term outcome of interstitial lung disease in polymyositis and dermatomyositis: a series of 107 patients. Arthritis Rheum Nov;63(11):3439-47 <h3>Disclosure of Interest</h3> None declared
Vaccines against Human Immunodeficiency Virus -- Progress and Prospects
Authors: Jeffrey S. Flier, Lisa H. Underhill, Norman L. Letvin
Journal: New England Journal of Medicine (1993)

The frightening pace of the worldwide spread of the human immunodeficiency virus (HIV) demands that priority be placed on the development of an effective vaccine1. Two distinct populations of viruses responsible for the acquired immunodeficiency syndrome (AIDS) have been defined: HIV type 2 (HIV-2), the viral group responsible for AIDS in West Africa, and HIV type 1 (HIV-1), the viral group that accounts for the AIDS epidemic in Central Africa and the rest of the world2. The genomes of both HIV groups encode for three structural proteins: an envelope glycoprotein that constitutes the viral outer coat, a core . . .
Detection of Familial Hypercholesterolemia by Assaying Functional Low-Density-Lipoprotein Receptors on Lymphocytes
Authors: Jennifer A. Cuthbert, Cara A. East, David W. Bilheimer, Peter E. Lipsky
Journal: New England Journal of Medicine (1986)

In familial hypercholesterolemia, structural and functional abnormalities of the receptor for low-density lipoprotein (LDL) lead to hypercholesterolemia and premature atherosclerosis. We have developed a simplified method to identify LDL-receptor defects in peripheral-blood lymphocytes. When lymphocytes are cultured in lipoprotein-depleted medium and endogenous sterol biosynthesis is suppressed with mevinolin, mitogen-stimulated proliferation of lymphocytes is dependent on an exogenous source of cholesterol. Whereas a small concentration of supplemental LDL cholesterol (3 to 4 μg per milliliter) permits a maximal response in normal lymphocytes, even high concentrations (10 to 50 μg per milliliter) are unable to support the proliferation of lymphocytes from patients with homozygous familial hypercholesterolemia. Thus, functional LDL receptors are necessary to allow lymphocyte proliferation in these cultures. The response of lymphocytes from patients with hyperlipidemia not caused by defective LDL receptors was like that of normal cells. In contrast, the response of lymphocytes from patients with heterozygous familial hypercholesterolemia was intermediate between that of homozygotes and that of normal or hyperlipidemic controls. Our method can therefore be used to identify persons who are heterozygous for abnormalities of LDL receptors. (N Engl J Med 1986; 314:879–83.)
Final results of a randomized controlled phase III trial (TAX 325) comparing docetaxel (T) combined with cisplatin (C) and 5-fluorouracil (F) to CF in patients (pts) with metastatic gastric adenocarcinoma (MGC)
Authors: V. M. Moiseyenko, J. Ajani, S. A. Tjulandin, A. Majlis, M. Constenla, C. Boni, A. Anelli, A. J. Yver, E. van Cutsem
Journal: Journal of Clinical Oncology (2005)

4002 Background: Locally advanced or MGC has a poor prognosis (2-year survival 11.5%). Different treatments are used with no evidence of survival benefit. Methods: Pts with chemotherapy-naive MGC were randomized to either TCF: T 75 mg/m2 day (d) 1, C 75 mg/m2 d 1, and F 750 mg/m2/d continuous infusion (c.i.) d 1–5 every (q) 3 weeks (w) or CF: C 100 mg/m2 d 1 and F 1000 mg/m2/d c.i. d 1–5 q 4 w. Pts with locally recurrent or metastatic gastric adenocarcinoma (including gastroesophageal junction in 22% pts) and measurable/evaluable disease were eligible. Biased-coin randomization was stratified for center, liver metastases, prior gastrectomy, 5% weight loss, and measurability. Tumor assessments were performed q 8 w and externally reviewed. Time to progression (TTP) was the primary endpoint; the trial was equally powered for overall survival (OS). Results: 457 pts (227/230 TCF/CF) were randomized between Nov 99-Jan 03. Median age was 55 yrs and 97% pts had metastatic cancer. Weight loss in prior 3 months [mo] was >5–10%: 29% pts and >10%: 27% pts. TTP was longer with TCF (5.6 mo) compared to CF (3.7 mo; risk reduction 32%; log-rank p=0.0004). With median follow-up of 23 mo, OS was longer with TCF (risk reduction 23%, log-rank p=0.0201). 2-year survival was 18% with TCF vs 9% with CF. Response rate to TCF (37%) was superior to CF (25%; chi-square p=0.0106); 17%/31% pts had disease progression as best response to TCF/CF. Grade 3–4 treatment-emergent adverse events occurred in 81% and 75% of TCF and CF pts, the most common of which included diarrhea and stomatitis (20%/8% and 21%/27% TCF/CF pts); neutropenia was more frequent with TCF while anemia was less. With TCF/CF, 60-day all-cause mortality was 7%/9%. The TCF benefit/risk ratio tended to be less in pts ≥65 years. Conclusions: Docetaxel is the first drug with a proven survival benefit in MGC. Tolerance of TCF and CF was limited in this sick patient population. Docetaxel combined with CF and appropriate risk management represents a new option for MGC. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration sanofi-aventis sanofi-aventis sanofi-aventis AstraZeneca, Aventis, Hoffmann-La Roche Bristol-Myers Squibb, Hoffmann-La Roche, Johnson & Johnson, tbc