tbuckley/cabot-search huggingface dataset:
EXPERIMENTAL REFERRED PAIN FROM THE GASTRO-INTESTINAL TRACT. PART I. THE ESOPHAGUS
Authors: W. S. Polland, A. L. Bloomfield
Journal: Journal of Clinical Investigation (1931)

Despite the development of modern diagnostic methods, the exact recognition of the disorders or lesions which are responsible for di- gestive syrmptoms remains a difficult problem.In practice the percentage of error in this domain of medicine is high and in many instances diagnosis is based more on the general clinical intuition of the examiner than on any very substantial basis.The interpretation of symptoms is especially difficult and it is with-this phase of the subject that the present studies are concerned.It is generally conceded that the first step in the analysis of a digestive disorder is a careful consideration of the patient's history, and symptom complexes have been built up which are believed by some to indicate with considerable certainty the existence of special lesions.Many physicians, for example, are quite dogmatic as to the significance of so-called "peptic ulcer indigestion" or "gallbladder indigestion"; some go even further and feel that such conditions as "duodenitis," "mobile cecum," etc., present themselves with characteristic com- plaints.The validity of such symptom complexes, however, still remains open to question and our own experience indicates that unless fortified by some highly specific phenomenon such as bleeding in the case of ulcer or colic or jaundice in the case of gallbladder disease, the digestive symptoms in themselves (gas, vague abdominal distress, burning or " indigestion ") have little, if any, specific mneaning.When one considers that the upper abdominal viscera have a common autonomic innervation and that their sensibility under ordinary conditions is of a crude protopathic type this conclusion is supported.Furthermore, when one interrogates patients with digestive dis-
Thomas Joseph Delaney
Authors: T P. Ormerod
Journal: BMJ (2003)

Consultant dermatologist Gloucestershire hospitals 1975-2000 (b Liverpool 1940; q Liverpool 1964; FRCP), died from a stroke, while in Vietnam with the Dowling Travelling Club, on 22 February 2003. 

Joe was registrar at Liverpool before becoming a senior registrar in London at St George's Hospital and St John's Hospital for Diseases of the Skin. As a consultant, he introduced several new techniques and established new clinics at three GP hospitals, as well as running busy outpatient clinics in Cheltenham and Gloucester hospitals, with inpatients latterly at Standish. He was joint honorary secretary of the Gloucestershire branch of the BMA for five years. He leaves a wife, Gill; and four children.
Pathologic Findings in the Retinal Pigment Epitheliopathy Associated with the Amyotrophic Lateral Sclerosis/Parkinsonism-dementia Complex of Guam
Authors: R. Jean Campbell, John C. Steele, Terry A. Cox, Arthur J. Loerzel, Martin Belli, Deanna D. Belli, Leonard T. Kurland
Journal: Ophthalmology (1993)
IMMUNOINHIBITION OF INTRACELLULAR PROTEIN DIGESTION IN MACROPHAGES
Authors: John T. Dingle, A. Robin Poole, Gerald S. Lazarus, Alan J. Barrett
Journal: The Journal of Experimental Medicine (1973)

Specific anti-(rabbit cathepsin D) serum, previously shown to inhibit cathepsin D, arrested the intracellular digestion of sheep IgG and radiochemically labeled hemoglobin and proteoglycan in rabbit alveolar macrophages. In the presence of antiserum, cells remained viable, but became very vacuolated. Both sheep IgG and hemoglobin were demonstrated immunocytochemically in vacuoles most of which could also be shown to contain cathepsin D. When the antiserum was removed, cells regained their normal morphology, and digestion of endocytosed proteins returned to normal. These results indicate that cathepsin D can be inhibited within lysosomes of viable cells, in which it plays a major role in the intracellular digestion of certain proteins.
Ultrasonography-Guided Endoscopic Stent Placement for Malignant Biliary Obstruction: A Preliminary Report of Four Cases
Authors: G. D. De Palma, A. Puzziello, M. Rega, L. Mastantuono, F. Persico, F. Patrone, G. Persico
Journal: Endoscopy (2004)

We present a new combination of transabdominal ultrasound (US) and biliary endoscopy, with endoscopic stent placement carried out under US guidance. Four patients (two men, two women; average age 66.2 years) underwent US-guided stent placement for palliation of ampullary carcinoma (n = 3) or pancreatic cancer (n = 1). A guide wire and a guiding catheter were endoscopically introduced and identified, by US in the common bile duct across the stricture. Hydromer-coated polyurethane angled stents (10 Fr) were finally inserted over the guide wire/guiding catheter by a pusher tube system. Successful drainage, with substantial reduction in bilirubin level, was achieved in all patients (14.2 +/- 9.5 vs. 4.2 +/- 2.9 mg/dl at 1 week). The present case series shows that endoscopic stent placement performed under US guidance is safe and effective. Further studies of larger series, including more proximal strictures, are warranted.
Abstract 3318: Using synthetic lethal screening to identify therapeutic targets for innately platinum resistant lung cancer
Authors: Kieren D. Marini, Fernando J. Rossello, Luciano G. Martelotto, D. Neil Watkins
Journal: Cancer Research (2014)

Abstract Although platinum-based chemotherapy is the standard of care for most cases of advanced lung adenocarcinoma, its effectiveness is limited by the frequent incidence of innate chemoresistance. As a result, response rates rarely exceed 20%, even though cis-platinum and carboplatin are highly effective in other settings such as small cell lung, ovarian and testicular cancers. We hypothesized that innate chemoresistance in lung adenocarcinoma is mediated by one or more signalling pathways dependent on the expression of a single gene, and that these pathways could ultimately be targeted therapeutically. To address this question, we developed a synthetic-lethal high throughput siRNA screen using the innately resistant A549 lung adenocarcinoma cell line. Optimisation of the screen was performed using a siRNA death control (PLK1), which induced cell death in the absence of platinum, and a sensitization control (MTOR), which enhanced cell death only in combination with a sublethal concentration of carboplatin. These independent controls revealed that the screening protocol performed within acceptable limits of variability, quality and reproducibility as determined by Z’ factor analysis. Screening was then performed using a pool of four siRNAs targeting a single gene in conjunction with vehicle treatment, or with carboplatin. After screening siRNAs targeting the 720 kinases, 256 phosphatases and 4794 “druggable” targets of the human genome, we identified 50 candidate targets based on fold change difference between platinum and vehicle treatments, and statistical significance determined by multiple t-test corrected for false discovery rate. Preliminary integrated pathway analysis of RNA expression array and screening datasets revealed a highly significant enrichment of sensitizing genes in previously identified pathways as well as novel pathways. These data demonstrate that a synthetic-lethal approach can be used to identify therapeutic targets that could potentially sensitize lung adenocarcinoma to platinum-based chemotherapy. Citation Format: Kieren D. Marini, Fernando J. Rossello, Luciano G. Martelotto, D. Neil Watkins. Using synthetic lethal screening to identify therapeutic targets for innately platinum resistant lung cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3318. doi:10.1158/1538-7445.AM2014-3318
Abstract B100: Genomic copy number alterations associated with the early brain metastasis of non-small cell lung cancer
Authors: Hye Won Lee, Se Jeong Lee, Mi Young Song, Kyeung Min Joo, Do-Hyun Nam
Journal: Cancer Research (2013)

Abstract Frequent early development of systemic metastasis leads unfavourable clinical prognosis of the non-small cell lung cancer (NSCLC). Although the brain metastasis (BM) contributes significantly to the morbidity and mortality of NSCLC, relevant driver mechanisms are largely unknown. To elucidate genetic alterations and prognostic markers associated with early BM of NSCLC, we retrospectively collected 18 NSCLC patients with BM (12 adenocarcinomas (ADC) and 6 squamous cell carcinomas (SQCC)) whose surgical tissues of primary and/or metastatic tumors were preserved as formaldehyde fixed and paraffin embedded (FFPE) pathologic samples. When chromosomal copy number alterations (CNAs) of those FFPE samples were analysed by the Molecular Inversion Probe (MIP) technology, the most frequent CNAs detected in primary ADCs were gains of 3q, 5p, 5q, 6p, 8q, 9p, 11p, 15q, 17q and losses of 10q and 22q whereas primary SQCCs revealed gains in 4q and 12q and loss in 9q. Moreover, comparative MIP analysis on 11 matched cases demonstrated the fact that the BM carried the majority of genetic alterations present in the corresponding primary tumor but with a slightly higher frequency including gain of 9p11 and loss of 2p11 in ADCs. Especially, when primary 12 ADCs were analyzed depending on the pattern of BM to uncover predetermining signatures that can predict the risk of BM, selectively amplified regions of primary lung ADCs (5q35, 10q23 and 17q23-24) were identified as significantly associated with the development of early BM within 3 months after first diagnosis of primary tumor. Small interfering RNA silencing of ACTA2, which is one of several candidate genes revealed in this study, reduced the in vitro migratory and invasive potential of human ADC cell line PC14PE6-GFP tagged cells without affecting on proliferation. Although more validation is needed, the genetic signatures elucidated in this study shed light on the molecular mechanisms involved in BM and help to identify prognostic markers stratifying the subgroup at high risk of developing recurrence or distant metastasis within heterogeneous NSCLC patients. Citation Format: Hye Won Lee, Se Jeong Lee, Mi Young Song, Kyeung Min Joo, Do-Hyun Nam. Genomic copy number alterations associated with the early brain metastasis of non-small cell lung cancer. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr B100.
Aid deal is "repackaged peanuts," says Oxfam
Authors: O. Dyer
Journal: BMJ (2002)

Aid agencies are accusing the world's richest countries of failing Africa once again, after the G8 summit in Kananaskis, Canada, ended with plenty of advice for the poorest continent but few financial commitments.

Britain's Prime Minister Tony Blair defended the G8 Africa Action Plan, saying: “This isn't old fashioned aid. It's a genuine partnership for the renewal of Africa. We are going to help Africa to help itself.”

The plan promised an annual $1bn (£650m; €1bn) top-up to the fund established to relieve the payments of the countries most heavily in debt. African …
Possession and Jinn
Authors: J. Hanley
Journal: Journal of the Royal Society of Medicine (2005)

Embryonic stem cells-sources and destinationsVats et al. (August 2005 JRSM 1 ) are correct in stating that embryonic stem cells (SCs) represent a unique opportunity to study cellular differentiation processes, and that progress in the related arena of tissue engineering depends on generation of suitable cells and their ability to perform specific biological functions.But, as the authors discussed, social and ethical discord has complicated the availability of human embryonic SCs.In the mouse, they have been produced from single blastomeres obtained from nondestructive biopsy of embryos destined for transfer, or from the isolation of karyotypically normal blastomeres from disaggregated ('dead') embryos regarded unsuitable for transfer. 2As neither of these laboratory techniques harms a viable source embryo, application of such methods to human embryos might satisfy some of the objections currently lodged against this research.Indeed, the successful translation of this work to humans could potentiate further advancements in tissue engineering, where preliminary experiments have shown promise for correction of severe organ pathology.
Historical Atlas of Dermatology and Dermatologists
Authors: Barry Monk
Journal: Journal of the Royal Society of Medicine (2002)

Dermatology remains a mystery to many doctors, and will do so increasingly as its toehold in the medical curriculum is eroded (in some medical schools it no longer features at all in the undergraduate curriculum). The history of the specialty, which began to develop as a distinct entity in the nineteenth century, is a fascinating subject. Skin disorders that we now regard as trivial—impetigo, head lice, scabies—were common and untreatable. Syphilis, with its protean cutaneous manifestations, was rampant and incurable. Simple bacterial infections of the skin could lead to septicaemia and death. The early descriptive dermatologists were remarkable clinical observers. Jonathan Hutchinson, for example, was the first person to describe sarcoidosis, lentigo maligna melanoma, melanoma of the nail bed, Peutz-Jegher syndrome (and its association with intussusception of the bowel), arsenical keratosis, Hutchinson's teeth (in congenital syphilis); the list is far from complete. Few doctors confined their interests to the skin alone; Erasmus Wilson, regarded by many as the leading dermatologist of his era, found time to bring Cleopatra's needle to London and amass a fortune on the stock exchange. The illustrations and clinical descriptions produced put many of our present-day efforts to shame. The changes that have occurred in therapy are also remarkable: much of the early therapeutic use of X ray was in the treatment of benign dermatological disorders (it continued to be widely used for childhood ringworm until 1958).

Dr Crissey and his coauthors, all distinguished dermatologists and collectors of ‘dermatological memorabilia’, have produced a book containing a remarkable collection of illustrations, of dermatologists, of their original papers, of their clinical cases, and related material. They have interlaced this with descriptions of their subjects, and the significance of their work. There is much to fascinate and enchant any dermatologist with any sense of history. The advertisement for do-it-yourself X-ray equipment and the illustration of the first picture of the scabies mite are just two examples among many. The text likewise has plenty to capture the imagination: Kaposi (of the eponymous vascular tumour) changed his name from Cohen, because he thought that it would help his career if he sounded less Jewish.

This is not a history of dermatology, and should not be bought by anyone expecting it to be so. There is no theme of progression from one topic to the next, and much is omitted (for example, there is no mention of penicillin). The work might best be described as a scrapbook assembled by three enthusiasts for their subject, whose love of dermatology shines through the pages. As such it is enormous fun, and would make a perfect Christmas or birthday present for your favourite dermatologist.
Tackling the problems of seriously challenged NHS providers
Authors: C. Ham, A. Dixon
Journal: BMJ (2012)

Requires moving away from the usual solutions and applying the right remedies

The experience of South London Healthcare NHS Trust highlights the inadequacies of existing approaches to dealing with failing healthcare providers.1 The trust, which was created from a merger between hospitals that had well known financial and quality challenges, had a deficit of £65m (€81m; $101m) in 2011-12, and a similar deficit is projected for the current financial year.

One of three remedies has usually been applied to NHS providers who face challenges in delivering care of an acceptable standard within budget. The first approach is often to appoint a new chief executive and senior team. The problem with this approach is that the causes of failure may not be a result of poor management or weak governance. The scale of the difficulties facing the most challenged providers today is without precedent, and even the most able leaders will struggle to overcome them. Only when the underlying causes are properly understood can appropriate interventions be developed.

The second approach is to merge challenged providers with organisations that are performing well. Although this may help in some situations, well performing organisations may find their own performance dragged down by the work involved in supporting providers with which they merge. The evidence on mergers suggests that caution is needed, …
Disruption of LDL but not VLDL clearance in autosomal recessive hypercholesterolemia
Authors: Christopher Jones, Rita Garuti, Peter Michaely, Wei-Ping Li, Nobuyo Maeda, Jonathan C. Cohen, Joachim Herz, Helen H. Hobbs
Journal: Journal of Clinical Investigation (2007)

Genetic defects in LDL clearance result in severe hypercholesterolemia and premature atherosclerosis. Mutations in the LDL receptor (LDLR) cause familial hypercholesterolemia (FH), the most severe form of genetic hypercholesterolemia. A phenocopy of FH, autosomal recessive hypercholesterolemia (ARH), is due to mutations in an adaptor protein involved in LDLR internalization. Despite comparable reductions in LDL clearance rates, plasma LDL levels are substantially lower in ARH than in FH. To determine the metabolic basis for this difference, we examined the synthesis and catabolism of VLDL in murine models of FH (Ldlr–/–) and ARH (Arh–/–). The hyperlipidemic response to a high-sucrose diet was greatly attenuated in Arh–/– mice compared with Ldlr–/– mice despite similar rates of VLDL secretion. The rate of VLDL clearance was significantly higher in Arh–/– mice than in Ldlr–/– mice, suggesting that LDLR-dependent uptake of VLDL is maintained in the absence of ARH. Consistent with these findings, hepatocytes from Arh–/– mice (but not Ldlr–/– mice) internalized β-migrating VLDL (β-VLDL). These results demonstrate that ARH is not required for LDLR-dependent uptake of VLDL by the liver. The preservation of VLDL remnant clearance attenuates the phenotype of ARH and likely contributes to greater responsiveness to statins in ARH compared with FH.
Abstract P5-14-06: Analysis of test-therapy concordance for biomarkers uPA and PAI-1 in primary breast cancer in clinical hospital routine: Results of a prospective multi-center study at Certified Breast Cancers in Germany
Authors: VR Jacobs, D Augustin, A Wischnik, M Kiechle, C Hoess, O Steinkohl, B Rack, T Kapitza, P Krase
Journal: Cancer Research (2012)

Abstract Objective: Biomarkers uPA and PAI-1 are guideline recommended by ASCO, USA, and AGO, Germany, to be used in primary breast cancer to avoid unnecessary CTX in medium risk recurrence patients [G2, N−, HR+, Her2neu−, &amp;gt;35 years]. For quality assurance of uPA/PAI-1 testing an analysis of test-therapy concordance was performed. Methods: Prospective, non-interventional, multi-center study over two years among six Certified Breast Centers in Germany to analyze application of uPA/PAI-1 and use of the result in consecutive decision making in Tumor Board decision and actual therapy in the clinical setting for AOK Bayern-insured patients. Concordance and discordance rates of uPA/PAI-1 testing in daily clinical setting were calculated and individual reasons for decision making analyzed. Results: Among n=93 uPA/PAI-1 tests evaluated n=42/93 (45.2%) were uPA+PAI-1 negative and n=51/93 (54.8%) uPA and/or PAI-1 positive. In the group of uPA+PAI-1 negative test result in n=35/42 (83.3%) CTX was avoided and and in n=7/42 (16.7%) CTX performed. In the group of uPA and/or PAI-1 positive test result in n=26/51 (51.0%) CTX was performed and in n=25/51 (49.0%) not. Concordance of uPA/PAI-1 test result vs. consecutive therapy was (35+26)/93=65.6% and discordance of uPA/PAI-1 test-therapy (7+25)/93 = 34.4%. However, discordance of uPA/PAI-1 test result vs. Tumor Board recommendation was only n=21/93 (22.6%). As reasons for discordance a variety of influencing and/or interference factors were indentified, affecting use of test and test results or even changing therapy decision, e.g. individual therapy decision by physician, parallel use of competitive biomarkers, study participation, missing CTX therapy option in advance (like advanced age), wrong target group, timing of uPA/PAI-1 test too early, test result in contradiction of physicians' expectations (expected negative result) and rejection of CTX recommended by patients despite uPA/PAI-1 test-proven benefit. Conclusions: Individual process optimization of uPA/PAI-1 test indication, performance and result assessment could improve quality of care, reduce costs and lead to an improved application of uPA/PAI-1 test results as well as more stringency and consistency of test-therapy decisions in daily clinical setting. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-14-06.
Points: Screening patients with retinitis pigmentosa for Refsum's disease
Authors: F B Gibberd, J M Goldman
Journal: BMJ (1985)

Mr P H Chapins and colleagues have provided information useful to practising physicians (25 May, p 1546).Although the authors viewed sigmoidoscopy as unhelpful in differentiating neoplastic (polyps, adenocarcinoma) from non-neoplastic sources (haemorrhoids, diverticula, etc), the data can be viewed as valuable in assessing the validity of rectal bleeding as a historical screening tool.Specifically, the simple characteristic of "no rectal bleeding" appears quite accurate in identifying those individuals without neoplastic disease.The 2 x 2 table is reconstructed from data in the article.The predictive value of a Relation between rectal bleeding and findings on siginoidoscopy Findings on sigmoidoscopy Carcinoma or No polyp or polyp >10cm carcinoma >10cm Rectal bleeding 4 44 No rectal bleeding 8 263positive finding, as described in the paper, is 4/48 or 8%-quite low.In contrast, the predictive value of a negative finding is 263/271 or 97%-that is, a history of no rectal bleeding accurately identified patients without neoplastic processes.While these results must be used cautiously when applied to a population different from that described in their study, it appears that a negative response to inquiry about rectal bleeding may be useful in identifying patients at low risk for rectosigmoid neoplasia.
Patient-controlled dose regimen of methadone for chronic cancer pain.
Authors: J Sawe, J Hansen, C Ginman, P Hartvig, P A Jakobsson, M I Nilsson, A Rane, E Anggard
Journal: BMJ (1981)

Fourteen patients with severe cancer pain participated in a trial of methadone given in a fixed dose (10 mg) but at intervals selected by the patients themselves during the loading phase. The aim was to achieve rapid pain relief while avoiding the risk of toxicity from accumulation of methadone. As expected, the dosage intervals increased gradually over the first few days of treatment, the daily dose decreasing from 30-80 mg on the first day to 10-40 mg at the end of the week. Plasma concentrations of methadone varied sevenfold after four to five days (0.24 to 1.75 mumol/1; 7.4 to 54.2 microgram/100 ml). Eleven patients reported complete or almost complete pain relief and elected to continue with methadone after the study. In no case was treatment withdrawn because of intoxication. From these findings a patient-controlled dosage regimen of oral methadone may be an effective and safe alternative to parenteral narcotic medication, adjusting both for individual variation in pain intensity and for pharmacokinetics.
Passive neutralizing antibody controls SHIV viremia and enhances B cell responses in infant macaques
Authors: Cherie T Ng, J Pablo Jaworski, Pushpa Jayaraman, William F Sutton, Patrick Delio, LaRene Kuller, David Anderson, Gary Landucci, Barbra A Richardson, Dennis R Burton, Donald N Forthal, Nancy L Haigwood
Journal: Nature Medicine (2010)