tbuckley/cabot-search huggingface dataset:
Robert Michael ("Sam") Forrester
Authors: I. FORRESTER
Journal: BMJ (2003)

Former consultant paediatrician Royal Albert Edward Infirmary, Wigan (b 1919; q Cambridge/Manchester 1943), died from acute myeloma on 21 June 2003.​2003.




Figure 1




After national service with the Inniskillen Dragoon Guards and training posts around Manchester—during which he strove for improved conditions for junior doctors via the BMA committee system—Sam was appointed to one of the earliest consultant paediatrician posts in the north west. He set about organising children's services for Wigan and Leigh from 1956 until retirement in 1980. A keen advocate of integrating disabled children into the community, he served on the Warnock committee of inquiry into the education of children with special needs, and was instrumental in developing centres and services for those with disabilities. Retirement in Ambleside allowed him to pursue a plethora of interests. He leaves a wife, Marion; three children; and six grandchildren.
THE THERAPEUTIC ACTION OF TONICA WATER. WITH THE HISTORY OF TWENTY-SIX CASES WHERE IT HAS BEEN USED.Read in the Section of Practice of Medicine and Physiology, at the Forty-second Annual Meeting of the American Medical Association, held at Washington, D. C., May, 1891.
Authors: J. W. SMALL
Journal: JAMA (1891)

Water, as an agent in the treatment of disease, is a remedy which should not be too lightly estimated, as it is more or less concerned in all those changes which take place in inorganic matter, and is essential to the life and growth of all living organisms, whether animal or vegetable. When taken into the stomach it acts by its temperature, its bulk, its absorption, and as a solvent for mineral and vegetable matters which otherwise could produce no beneficial action in the animal economy. When natural spring waters are so far impregnated with foreign substances as to have a decided taste and a peculiar therapeutic action, they are classed in the Pharmacopoeia as mineral waters, and are divided into five classes: the carbonated, alkaline, sulphuretted, saline (including magnesian, chalybeate and chlorinated), and silicious. The name of each of these classes suggests its peculiar impregnation; but analysis of the
Mechanism of γ-glutamyl transpeptidase release in serum during intrahepatic and extrahepatic cholestasis in the rat: A histochemical, biochemical and molecular approach
Authors: Frederique Bulle, Philippe Mavier, Elie Serge Zafrani, Anne-Marie Preaux, Marie-Claude Lescs, Sylvie Siegrist, Daniel Dhumeaux, Georges Guellaën
Journal: Hepatology (1990)

The mechanism of the elevation of serum γ–glutamyl transpeptidase activity in cholestasis is not clear. We therefore analyzed rat γ–glutamyl transpeptidase activities in liver, bile and serum during intrahepatic cholestasis induced by a single dose of α–naphthyl isothiocyanate (20 mg/100 gm body weight) and during extrahepatic cholestasis after bile duct ligation. At days 1 and 2 after α–naphthyl isothiocyanate ingestion, we saw a fivefold and a 60–fold increase in serum and bile γ–glutamyl transpeptidase activities, respectively. These increases were associated with a decrease in hepatic γ–glutamyl transpeptidase activity and of corresponding mRNA. Simultaneously, necrosis of the biliary epithelium appeared in portal tracts. From day 2 to day 14, γ–glutamyl transpeptidase activity in bile and serum progressively returned to basal levels; in the liver, cholangiolar proliferation was mild and was associated with moderate elevation of the γ–glutamyl transpeptidase activity and of its corresponding mRNA. In extrahepatic cholestasis, a 10–fold increase in serum γ–glutamyl transpeptidase activity was detected between day 0 and day 14. This increase was associated with major cholangiolar proliferation and with a progressive rise in hepatic γ–glutamyl transpeptidase activity and in specific mRNA; in bile, γ–glutamyl transpeptidase activity was slightly elevated. In these two models of cholestasis, histochemically detected γ–glutamyl transpeptidase activity was largely predominant in biliary cells. We found no significant induction of γ–glutamyl transpeptidase activity in hepatocytes. These results suggest that in these two models of cholestasis, the increase in serum γ–glutamyl transpeptidase activity is of biliary cell origin and does not originate from hepatocytes. This mechanism is quite different from the hepatocyte inductionhypothesized for alkaline phosphatase.(HEPATOLOGY 1990; 11:545:550.)
Limited Clinical Utility of Prognostic Gene Expression Profiles in Grade 3 Node-Negative Early Stage Breast Cancer.
Authors: P. Bedard, M. Ignatiadis, B. Haibe-Kains, B. Haibe-Kains, S. Loi, C. Criscitiello, C. Desmedt, G. Bontempi, M. Piccart, M. Piccart, C. Sotiriou, C. Sotiriou
Journal: Cancer Research (2009)

Abstract Background: There are a variety of commercially available prognostic gene expression profiles (GEPs) for early stage breast cancer. These have been shown to be highly concordant in their risk classification, as their prognostic performance is largely driven by an improved quantification of cellular proliferation in the ER+/HER2- (luminal) subtype. We hypothesized that the clinical utility of prognostic GEPs would be limited to the subset of tumors with an indeterminate assessment of proliferation by histological grading (grade 2).Methods: We computed five gene-expression signatures – genomic grade index (GGI), 70-gene signature (GENE70), 76-gene signature (GENE76), 21-gene recurrence score, and wound response signature – in 999 lymph node negative, untreated breast tumors (median follow-up of 7.8 years) from six publicly available datasets. We compared their performance against traditional clinicopathological risk classification using Adjuvant!Online (AOL) for each histological grading category.Results: All five GEPs demonstrated superior prognostication of 10-year distant metastasis free survival (DMFS) in grade 1 (range of area under the ROC curves (AUC)=0.63-0.75) and grade 2 (AUC=0.64-0.71) tumors than in grade 3 (AUC=0.48-0.53) tumors. For the GGI, GENE70, and GENE76 profiles, discordant risk classification with AOL was more frequent in grade 2 (53%) than grade 1 (38%) and grade 3 (26%) tumors (p&amp;lt;.001). In the event of discordant risk classification, GEP identified a low risk subgroup that might be spared chemotherapy in grade 2 (10-yr DFMS: 80% vs 66% (GGI); 81% vs 65% (GENE70); 80% vs 67% (GENE76)) and grade 1 (10-yr DFMS: 92% vs 69% (GGI); 84% vs 79% (GENE70); and 87% vs 70% (GENE76)) but not grade 3 (10-yr DFMS: 67% vs 47% (GGI); 75% vs 47% (GENE70); and 71% vs 52% (GENE76)). Even within the subset of all small (T&amp;lt;2cm), ER-positive, node-negative grade 3 tumors, low genomic risk patients did not experience a sufficiently favorable long-term outcome (10-yr DMFS: 60% (GGI), 69% (GENE70) and 64% (GENE76)) to justify the omission of adjuvant chemotherapy.Conclusion: There is limited clinical utility of prognostic GEPs in grade 3 early breast cancer. Histological grading should guide decision-making for assessment of genomic risk. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 103.
A Need for Determination
Authors: Charles A. Sanders
Journal: New England Journal of Medicine (1977)

Determination-of-need laws now exist in 33 states and the District of Columbia. The National Health Planning and Resources Development Act of 1974 (PL 93–641) mandates that such statutes must be adopted in every state by 1980. These laws have the laudable goals of controlling unnecessary proliferation of health-care facilities and capital equipment and of preventing the establishment of substantial new, but duplicative, clinical services. The national program is usually administered by delegation through state agencies. The way in which the law has been applied has depended largely upon the individual state. For example, in Massachusetts, applications of individual health-care providers . . .
Influence of specific dietary sugars on the jejunal mechanisms for glucose, galactose, and alpha-methyl glucoside absorption: evidence for multiple sugar carriers.
Authors: E S Debnam, R J Levin
Journal: Gut (1976)

The effects of feeding glucose, galactose, and alpha-methyl glucoside on the kinetics of absorption of these sugars in the jejunum of the fasting rat were assessed by recently developed chemical and electrical methods for characterizing the electrogenic active transfer mechanisms in vivo. The parameters of 9apparent Km9 (an index of carrier affinity) and Vmax (an index of the maximum jejunal transfer capacity) were obtained from the kinetic data to describe quantitatively the active transport mechanisms in rats fed their normal solid diet, in rats deprived of solid food for three days, and in rats deprived of solid food but allowed ad libitum access to isotonic solutions of glucose, galactose, or alpha-methyl glucoside for up to three days. Feeding the sugars to fasting rats produced complex differential effects on the 9apparent Km9s9 and Vmax9s of the various transport mechanisms. The changes, although complex, can best be explained by alterations in the transport mechanisms per se rather than by non-specific changes in intestinal morphology or metabolism. The differential effects induced by the feeding sugars are further evidence for the concept that jejunal enterocytes possess multiple carriers or mechansims for the absorption of actively transported sugars in vivo. The multiple forms of the sugar carriers (isocarriers?) MAY BE INVOLVED IN THE FACULTATIVE RESPONSES OF THE ENTEROCYTES TO CHANGES IN THE DIETARY LEVELS OF SUGAR AND MAY BE IMPORTANT IN UNDERSTANDING THE INFLUENCES OF DISEASE AND NUTRITIONAL STATUS ON ABSORPTION PROCESSES IN MAN.
The Hippocrates Prize
Authors: T. Dalrymple
Journal: BMJ (2012)

The Hippocrates Prize is an annual prize for poetry, awarded since 2010 and open to anyone who works, or has worked, in the NHS. There is also a category for poetry about a medical subject, open to anyone in the world writing in English. Altogether there are thousands of entries and the winning poems, the two runners up, and all the commended poems, are published in a slim but elegant volume. It is rather difficult to imagine a poetry prize open to people who have worked in accountancy, or to anyone who has …
Abstract 2244A: Prion protein cross-talks with Notch1 to promote pancreatic ductal adenocarcinoma progression
Authors: Yiwei Wang, Dan Huang, Lan Zhou, Wei Xin
Journal: Cancer Research (2014)

Abstract Human prion protein (PrP) is a glycosylphosphatidylino¬sitol (GPI)-anchored membrane protein and has been found to be up-regulated in some of the pancreatic ductal adenocarcinoma (PDAC). Current literature also suggests that over-expression of PrP induces inherent resistance to cancer therapeutics, while repression of PrP induces sensitization to cancer therapeutics. Our previous studies revealed the increased level of PrP expression associated with worse prognosis in PDAC patients. In PDACs, instead of forming normal GPI anchored protein, PrP exists as a pro-prion protein that binds Filamin A (FLNa) and exerts a cascade of activities subsequently augment the invasiveness of PDAC. In this study, we would like to investigate whether PrP also involves other signal transduction pathway in PDACs, especially Notch pathway. Using immunoprecipitation and immunocytometry, we investigated the binding partners for PrP in several PDAC cell lines and found that PrP associates with Notch1 but not with Notch2 or Notch3 in cytoplasm and cell membrane. The association of PrP and Notch1 was further validated by confocal microscopy. Silencing PrP by siRNA not only decreased PrP expression, but also decreased Notch1 in the cytoplasm and the nuclear localized cleaved Notch1. Knocking down PrP in PDAC cells with high levels of PrP led to decreased cell proliferation and tumor invasion and increased apoptosis. PDAC cells showed Increased tumor necrosis after inhibition of PrP in xenografts, which accompanied by down-regulation of intracellular domain of Notch1 (Notch1NTM). In comparison, over-expression of PrP in PDAC cells with lower levels of PrP increased Notch1NTM expression, cell proliferation, tumor invasion, and xenograft tumor growth which could be blocked by the gamma secretase inhibitor. These findings suggest that PrP cross talking Notch1 in PDAC cells regulates pancreatic cancer cell survival and invasion. Elucidating the mechanisms for PrP mediated Notch activation in PDAC will further our long-term goal of understanding the role of oncogenic PrP in conferring pancreatic cancer aggressiveness, and potentially will lead to novel therapeutic options for treatment of pancreatic cancer. Citation Format: Yiwei Wang, Dan Huang, Lan Zhou, Wei Xin. Prion protein cross-talks with Notch1 to promote pancreatic ductal adenocarcinoma progression. [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 2244A. doi:10.1158/1538-7445.AM2014-2244A
Impact of hepatitis C on health related quality of life
Authors: Brennan M.R. Spiegel, Zobair M. Younossi, Ron D. Hays, Dennis Revicki, Sean Robbins, Fasiha Kanwal
Journal: Hepatology (2005)

Hepatitis C virus (HCV) diminishes health related quality of life (HRQOL), and it is now common to measure HRQOL in clinical trials. We sought to summarize the HRQOL data in HCV, and to establish the minimally clinically important difference (MCID) in HRQOL scores in HCV. We performed a systematic review to identify relevant studies, and converted HRQOL data from each study into clinically interpretable statistics. An expert panel used a modified Delphi technique to estimate the MCID in HCV. We found that patients with HCV scored lower than controls across all scales of the SF-36. Patients achieving sustained virological response (SVR) scored higher across all scales versus patients without SVR, especially in the physical health domains. HRQOL differences did not correspond with differences in liver histology or ALT levels. Based upon the published data, the expert panel concluded that the SF-36 vitality scale was most relevant in patients with HCV, and generated a mean MCID of 4.2 points on this scale. In conclusion, patients with HCV have a clinically significant decrement in HRQOL versus controls, and physical HRQOL improves in patients achieving SVR but not in those without SVR. The data further suggest that traditional outcomes fail to capture the full spectrum of illness related to chronic HCV. A difference of 4.2 points on the SF-36 vitality scale can be used as an estimate of the MCID in HCV, and this value may be used as the basis for power calculations in clinical trials evaluating HRQOL. Supplementary material for this article can be found on the HEPATOLOGY website (http://www.interscience.wiley.com/jpages/0270-9139/suppmat/index.html). (HEPATOLOGY 2005;41:790–800.)
Actin organization and hepatocyte differentiation are regulated by extracellular matrix via PI-4,5-bisphosphate in the rat
Authors: Takayuki Kimata, Masahito Nagaki, Tomio Ogiso, Takafumi Naiki, Tomohiro Kato, Hisataka Moriwaki
Journal: Hepatology (2006)

Cell adhesion to the extracellular matrix (ECM) plays vital roles in both morphogenesis and regulation of gene expression in cells of adult organisms. How intracellular, cytoskeletal, and signaling factors connect and communicate with the ECM is a fundamental question. Using a cDNA microarray analysis, we identified phosphatidylinositol 4,5-bisphosphate (PI[4,5]P2) phosphatase mRNA as being up-regulated in hepatocytes cultured on a basement membrane matrix, Engelbreth-Holm-Swarm (EHS) gel, which led to the finding that the PI(4,5)P2 levels of hepatocytes decreased on EHS gel. These changes in hepatocytes on EHS gel were accompanied by promotion of actin depolymerization and differentiated phenotypes of the hepatocytes. Treatment with PI(4,5)P2 or a phospholipase C inhibitor, U73122, resulted in decreased mRNA expressions of albumin and hepatocyte nuclear factor 4 (HNF-4) in hepatocytes. In contrast, actin-disrupting agent gelsolin increased mRNA expressions of albumin and HNF-4. In conclusion, organization of the actin cytoskeleton via PI(4,5)P2 is involved in the regulation of hepatocyte differentiation by the ECM.
Adenoviral-mediated gene transfer to fetal pulmonary epithelia in vitro and in vivo.
Authors: P B McCray, K Armstrong, J Zabner, D W Miller, G A Koretzky, L Couture, J E Robillard, A E Smith, M J Welsh
Journal: Journal of Clinical Investigation (1995)

Vector-mediated gene transfer offers a direct method of correcting genetic pulmonary diseases and might also be used to correct temporary abnormalities associated with acquired, nongenetic disorders. Because the fetus or newborn may be a more immune tolerant host for gene transfer using viral vectors, we used replication defective recombinant adenoviral vectors to test the feasibility of gene transfer to the fetal pulmonary epithelium in vitro and in vivo. Both proximal and distal epithelial cells in cultured fetal lung tissues from rodents and humans diffusely expressed the lacZ transgene 3 d after viral infection. In vivo gene delivery experiments were performed in fetal mice and lambs. Delivery of Ad2/CMV-beta Gal to the amniotic fluid in mice produced intense transgene expression in the fetal epidermis and amniotic membranes, some gastrointestinal expression, but no significant airway epithelial expression. When we introduced the adenoviral vector directly into the trachea of fetal lambs, the lacZ gene was expressed in the tracheal, bronchial, and distal pulmonary epithelial cells 3 d after viral infection. Unexpectedly, reactive hyperplasia and squamous metaplasia were noted in epithelia expressing lacZ in the trachea, but not in the distal lung of fetal lambs. 1 wk after infection, adenovirus-treated fetuses developed inflammatory cell infiltrates in the lung tissue with CD4, CD8, IgM, and granulocyte/macrophage positive immune effector cells. Transgene expression faded coincident with inflammation and serologic evidence of antiadenoviral antibody production. While these studies document the feasibility of viral-mediated gene transfer in the prenatal lung, they indicate that immunologic responses to E1-deleted recombinant adenoviruses limit the duration of transgene expression.
Similar Postoperative Safety Between Primary and Revisional Gastric Bypass for Failed Gastric Banding
Authors: Jérémie Thereaux, Nicolas Veyrie, Charles Barsamian, Nicola Corigliano, Alain Beauchet, Christine Poitou, Jean-Michel Oppert, Sebastien Czernichow, Jean-Luc Bouillot
Journal: JAMA Surgery (2014)

IMPORTANCE Adjustable gastric bands are widely used because of low postoperative morbidity, but their long-term results are poor, often leading to revisional surgery.OBJECTIVE To assess the safety of revisional procedures by comparing the 30-day outcomes of primary gastric bypass vs revisions following failed adjustable gastric banding.DESIGN, SETTING, AND PARTICIPANTS Retrospective review using logistic regression models to compute odds ratios (95% CIs) across preoperative body mass index (calculated as weight in kilograms divided by height in meters squared) quartiles to evaluate the risk for major adverse outcomes at 30 days (death, venous thromboembolism, reinterventions, and failure to be discharged).The prospective database of a single university surgical center in Paris, France, was queried for clinical and other relevant data among all patients undergoing primary or revisional laparoscopic gastric bypass between January 1, 2004, and June 30, 2013. MAIN OUTCOMES AND MEASURESThe primary outcome was a comparison between 30-day outcomes of primary gastric bypass and procedures following failed adjustable gastric banding. RESULTSIn total, 831 patients had a primary procedure (group 1), and 177 patients had a secondary procedure after failed adjustable gastric banding (group 2).Overall, 78.7% of patients were female, the mean (SD) patient age was 42.6 (11.6) years, the mean (SD) body mass index was 47.6 (7.6), and mortality at 30 days was 0.5%.The rates of major adverse outcomes were similar in group 1 (7.8%) and group 2 (8.5%) (P = .77).In multivariate analyses, odds ratios for major adverse outcomes across preoperative body mass index quartiles (<42, 42-46, >46 to 52, and >52) were 1.00, 0.39 (95% CI, 0.20-0.77;P = .006),0.55 (95% CI, 0.30-1.02;P = .06),and 0.50 (95% CI, 0.27-0.94;P = .03),respectively.CONCLUSIONS AND RELEVANCE The 30-day major adverse outcome rates were similar for primary gastric bypass and for procedures following failed adjustable gastric banding.Long-term comparative studies are required to better understand the quadratic relationship between body mass index and early postoperative outcomes.
Effect of a Computer-Based Decision Aid on Knowledge, Perceptions, and Intentions About Genetic Testing for Breast Cancer Susceptibility
Authors: Michael J. Green, Susan K. Peterson, Maria Wagner Baker, Gregory R. Harper, Lois C. Friedman, Wendy S. Rubinstein, David T. Mauger
Journal: JAMA (2004)

As the availability of and demand for genetic testing for hereditary cancers increases in primary care and other clinical settings, alternative or adjunct educational methods to traditional genetic counseling will be needed.To compare the effectiveness of a computer-based decision aid with standard genetic counseling for educating women about BRCA1 and BRCA2 genetic testing.Randomized controlled trial conducted from May 2000 to September 2002.Outpatient clinics offering cancer genetic counseling at 6 US medical centers enrolled 211 women with personal or family histories of breast cancer.Standard one-on-one genetic counseling (n = 105) or education by a computer program followed by genetic counseling (n = 106).Participants' knowledge, risk perception, intention to undergo genetic testing, decisional conflict, satisfaction with decision, anxiety, and satisfaction with the intervention. Counselor group measures were administered at baseline and after counseling. Computer group measures were administered at baseline, after computer use, and after counseling. Testing decisions were assessed at 1 and 6 months. Outcomes were analyzed by high vs low risk of carrying a BRCA1 or BRCA2 mutation.Both groups had comparable demographics, prior computer experience, medical literacy, and baseline knowledge of breast cancer and genetic testing, and both counseling and computer use were rated highly. Knowledge scores increased in both groups (P<.001) regardless of risk status, and change in knowledge was greater in the computer group compared with the counselor group (P =.03) among women at low risk of carrying a mutation. Perception of absolute risk of breast cancer decreased significantly after either intervention among all participants. Intention to undergo testing decreased significantly after either intervention among low-risk but not high-risk women. The counselor group had lower mean scores on a decisional conflict scale (P =.04) and, in low-risk women, higher mean scores on a satisfaction-with-decision scale (P =.001). Mean state anxiety scores were reduced by counseling but were within normal ranges for both groups at baseline and after either intervention, regardless of risk status.An interactive computer program was more effective than standard genetic counseling for increasing knowledge of breast cancer and genetic testing among women at low risk of carrying a BRCA1 or BRCA2 mutation. However, genetic counseling was more effective than the computer at reducing women's anxiety and facilitating more accurate risk perceptions. These results suggest that this computer program has the potential to stand alone as an educational intervention for low-risk women but should be used as a supplement to genetic counseling for those at high risk.