tbuckley/cabot-search huggingface dataset:
European governments promise equal health rights for children with special needs
Authors: Z. Kmietowicz
Journal: BMJ (2010)

More than 50 countries in Europe have signed a declaration committing their governments to provide high quality healthcare for children and young people with learning disabilities and to end neglect, abuse, and discrimination.

The 53 countries from the World Health Organization Europe’s region are also committed to transferring care of children and young people with learning disabilities from institutions to the community. Families should be given support to allow parents to care for their children at home, says the declaration, which was signed at a WHO Europe conference on improving the lives of children and young people with intellectual disabilities and their families in Bucharest on 26 and 27 November. The conference believes that health underpins wellbeing and the capacity to enjoy life.

A review by …
B‐prolymphocytic leukemia cells that form rosettes with sheep red blood cells through monoclonal surface immunoglobulin
Authors: Atsuo Maruta, Shigeki Motomura, Koji Ogawa, Michio Matsuzaki, Hiroko Asada, Kenichi Takahashi, Motonori Fukumura, Masako Sakurai, Akira Ita, Takao Ookubo, Hiroshi Mouri, Shinichiro Watanabe
Journal: American Journal of Hematology (1985)

Abstract The neoplastic cells from a patient with B‐cell prolymphocytic leukemia exhibited sheep red blood cell (SRBC) rosette formation. Immunochemistries revealed no reactivity with T‐cell monoclonal antibodies OKT 3, 4, 8, and 11. However, the neoplastic cells expressed characteristics of B‐cells including surface IgM and IgD associated with lambda light chains, Ia‐like antigenicity, and reactivity to monoclonal antibodies against B‐cell antigens B1, B2, and B4. Inhibition procedures revealed that SRBC rosette formation was the result of binding activity of surface immunoglobulin to SRBC. Pretreatment of the leukemic cells with antihuman IgM or lambda antisera, or pronase or trypsin blocked rosette formation with SRBC. Circulating antibody to SRBC was also suspected by the fact that preincubation of SRBC with heat‐inactivated patient's serum resulted in agglutination of the SRBC.
Concerns about "lookback" exercise for hepatitis C
Authors: P. Scheuer, A. Rogers
Journal: BMJ (1996)

EDITOR,—Nigel Higson identifies two issues that we have raised with the deputy medical officer regarding the “lookback” exercise to detect recipients of blood products donated by donors found to be positive for hepatitis C.1 The first issue is the inappropriateness of counselling and advice being given by medical practitioners who do not have up to date knowledge about hepatitis C. Our experience …
Chromosome Studies in Patients With Diabetes Mellitus
Authors: Pen-Ming L. Ming
Journal: JAMA (1965)

It is well recognized that the predisposition to diabetes mellitus is genetically determined. The familial incidence of this disease was reported first in 1696 by Morton who observed four children of one family becoming diabetic at the age of dentition. The familial occurrence may be explained by assuming that susceptibility to diabetes is due to homozygosity for a recessive gene.<sup>1</sup>The genetic liability to this disease among children born to parents, both of whom are diabetic, is said to be 100%.<sup>2</sup>It is also known that there is a significantly higher incidence of spontaneous abortion, stillbirth, premature birth, and congenital anomalies in the offspring of the diabetic parents. Forbes and Engel reported recently on the high incidence of diabetes mellitus in patients with gonadal dysgenesis (Turner's syndrome) and in their close relatives.<sup>3</sup>The frequent association between chromosomal anomalies and abortuses, stillborn infants, and patients with gonadal dysgenesis
Principles and problems of environmental pollution of groundwater resources with case examples from developing countries.
Authors: B C Egboka, G I Nwankwor, I P Orajaka, A O Ejiofor
Journal: Environmental Health Perspectives (1989)

The principles and problems of environmental pollution and contamination are outlined. Emphasis is given to case examples from developing countries of Africa, Asia, and Latin America with a comparative analysis to developed countries. The problems of pollution/contamination are widespread in developed countries but are gradually spreading from the urban to rural areas in the developing countries. Great efforts in research and control programs to check pollution-loading into the environment have been made in the industrialized countries, but only negligible actions have been taken in developing countries. Pollutants emanate from both point and distributed sources and have adversely affected both surface water and groundwaters. The influences of the geologic and hydrologic cycles that exacerbate the incidences of pollution/contamination have not been well understood by environmental planners and managers. Professionals in the different areas of pollution control projects, particularly in developing countries, lack the integrated multiobjective approaches and techniques in problem solving. Such countries as Nigeria, Kenya, Brazil, and India are now menaced by pollution hazards. Appropriate methods of control are hereby suggested.
Risks and Benefits of Activated Protein C Treatment for Severe Sepsis
Authors: H Shaw Warren, Anthony F Suffredini, Peter Q Eichacker, Robert S Munford
Journal: New England Journal of Medicine (2002)

A new hypothesis with implications for the treatment of sepsis has recently been tested — the hypothesis that part of the pathophysiology of sepsis is caused by unrestricted or inappropriate coagulation in the microcirculation. Three agents that block coagulation at different stages have now been evaluated in large, multicenter trials as adjunctive therapy for sepsis. Neither antithrombin III nor tissue-factor-pathway inhibitor was effective in patients with severe sepsis or septic shock.1,2 In contrast, treatment with activated protein C (drotrecogin alfa [activated]) was associated with a significant reduction in 28-day mortality. Of the patients who received activated protein C, 24.7 . . .
The urinary proteome and metabonome differ from normal in adults with mitochondrial disease
Authors: Andrew M. Hall, Annalisa Vilasi, Isabel Garcia-Perez, Marta Lapsley, Charlotte L. Alston, Robert D.S. Pitceathly, Robert McFarland, Andrew M. Schaefer, Doug M. Turnbull, Nick J. Beaumont, Justin J. Hsuan, Pedro R. Cutillas, John C. Lindon, Elaine Holmes, Robert J. Unwin, Robert W. Taylor, Grainne S. Gorman, Shamima Rahman, Michael G. Hanna
Journal: Kidney International (2014)
Effects of plasmapheresis and of hypoproteinemia on lung liquid conductance in awake sheep.
Authors: P M Dodek, T W Rice, M R Bonsignore, S Yamada, N C Staub
Journal: Circulation Research (1986)

The Starling equation, which describes net transvascular liquid flow, does not include the possibility that a reduction in plasma protein concentration may have a direct effect on lung liquid conductance or microvascular protein permeability. Nevertheless, both effects have been reported. Since these results were not predictable, we wondered whether the changes were due to the decrease in plasma protein concentration or to the process by which protein depletion was accomplished (batch plasmapheresis which involves considerable handling of blood). To separate these factors, we did control (sham) and protein removal plasmapheresis in awake sheep by two plasmapheresis methods (batch and continuous-flow). We monitored pulmonary hemodynamics, measured lung lymph flow, and determined protein concentrations in lymph and plasma. We calculated or measured the protein osmotic pressures of plasma and lymph. After control plasmapheresis, lymph flow increased and lymph:plasma protein concentration decreased but had returned to baseline levels by 4 hours. After protein removal plasmapheresis, the changes persisted for 24 hours. However, lung microvascular conductance (filtration coefficient) was not increased, except during the first 4-hour period. The changes in lymph flow and protein concentration ratio are explained using a simple two-pore model. We conclude that, over the range studied, hypoproteinemia does not increase lung microvascular liquid conductance or protein permeability.
Acute type A aortic dissection in the elderly: clinical characteristics, management, and outcomes in the current era
Authors: Rajendra H. Mehta, Patrick T. O’Gara, Eduardo Bossone, Christoph A. Nienaber, Truls Myrmel, Jeanna V. Cooper, Dean E. Smith, William F. Armstrong, Eric M. Isselbacher, Linda A. Pape, Kim A. Eagle, Dan Gilon
Journal: Journal of the American College of Cardiology (2002)
Parenteral Ketorolac: The Risk for Acute Renal Failure
Authors: Harold I. Feldman
Journal: Annals of Internal Medicine (1997)

Background: Acute renal failure has been associated with parenteral ketorolac tromethamine, but the risk that is associated with this therapy has not been quantified. Objective: To compare the risk for acute renal failure associated with ketorolac with that associated with opioids. Design: Retrospective cohort study. Setting: 35 hospitals in or near Philadelphia. Patients: Patients receiving 10 219 courses of parenteral ketorolac and patients receiving 10 145 courses of parenteral opioids. Measurements: Acute renal failure was defined by 1) an increase in the serum creatinine concentration of 50% or more and 2) either an absolute increase of 44.2 µmol/L or more for concentrations that were less than 132.6 µmol/L at baseline or an absolute increase of 88.4 µmol/L or more for concentrations that were 132.6 µmol/L or more at baseline. In addition, a secondary definition required a diagnosis by a physician. Results: The overall incidence of acute renal failure was 1.1% after therapy with either ketorolac or opioids. Multivariate-adjusted rate ratios comparing ketorolac with opioids for acute renal failure were 1.09 (95% CI, 0.83 to 1.42) overall, 1.00 (CI, 0.76 to 1.33) for less than 5 days of therapy, and 2.08 (CI, 1.08 to 4.00; P = 0.03) for more than 5 days of therapy. Similar results were obtained when the secondary definition of acute renal failure was used. Conclusions: Overall, acute renal failure was uncommon in this hospitalized population. Compared with opioids, ketorolac administered for 5 days or less did not increase the rate of renal failure. However, among patients who were treated with analgesics for more than 5 days, ketorolac may be associated with an elevated rate of acute renal failure.
Calcium Release from the Skeletons of Rachitic Puppies
Authors: Jenifer Jowsey
Journal: Journal of Clinical Investigation (1972)

The experiment was carried out on 3-month old puppies. Control animals received a diet normal in calcium and vitamin D. The diet for one group of experimental animals was deficient in both calcium and vitamin D, while another experimental group was fed a diet deficient in calcium but with adequate vitamin D. The response of these animals to injected parathyroid extract was evaluated over a 4 month period. The serum calcium response fell after approximately 20 days in both the calcium-deficient (vitamin D-replete) and the calcium- and vitamin D-deficient animals. The effect on the parathyroid response of the addition of calcium or vitamin D in vitamin D- and calcium-deficient animals was also evaluated. The addition of vitamin D to rachitic animals did not restore the response to parathyroid extract; however, in calcium- and vitamin D-deficient animals with normal calcium levels there was a restored response to parathyroid extract. Morphologic studies were made of the bone at various times during the experimental period; the presence of osteoid tissue correlated with the absence of a response to injected parathyroid extract. The results suggest that parathyroid hormone acts independently and requires the presence of mineralized bone for its action in raising the serum calcium. Vitamin D appears to be important in the mineralization of new bone tissue.
Birth weight and risk of cardiovascular disease in a cohort of women followed up since 1976
Authors: J. W Rich-Edwards, M. J Stampfer, J. E Manson, B. Rosner, S. E Hankinson, G. A Colditz, C. H Hennekens, W. C Willet
Journal: BMJ (1997)

To examine the association between birth weight and non-fatal adult cardiovascular disease while controlling for potential confounders such as socioeconomic group and adult lifestyle.Retrospective self report of birth weight in an ongoing longitudinal cohort of nurses followed up by postal questionnaire every two years.Nurses' health study, a cohort of 121700 women followed up since 1976.Non-fatal cardiovascular disease, including myocardial infarction, coronary revascularisation, and stroke.Among the 70297 women free of cardiovascular disease at baseline who reported birth weight in the 1992 questionnaire there were 1309 first cases of non-fatal cardiovascular disease. Increasing birth weight was associated with decreasing risk of non-fatal cardiovascular disease. There were 1216 first cases of non-fatal cardiovascular disease among women who were singletons and had been born full term; their relative risks adjusted for several cardiovascular risk factors were 1.49 (95% confidence interval 1.05 to 2.10) for birth weight < 2268 g (< 5 lb 0 oz); 1.25 (0.98 to 1.61) for birth weight 2268-2495 g (5 lb 0 oz to 5 lb 8 oz); 1.12 (0.98 to 1.27) for birth weight > 2495-3175 g (> 5 lb 8 oz to 7 lb 0 oz); 1.00 (referent) for birth weight > 3175-3856 g (> 7 lb 0 oz to 8 lb 8 oz); 0.96 (0.80 to 1.15) for birth weight > 3856-4536 g (> 8 lb 8 oz to 10 lb 0 oz); and 0.68 (0.46 to 1.00) for birth weight > 4536 g (> 10 lb 0 oz) (P value for trend = 0.0004). The inverse trend was apparent for both coronary heart disease and stroke.These data provide strong evidence of an association between birth weight and adult coronary heart disease and stroke.
STK33 promotes hepatocellular carcinoma through binding to c-Myc
Authors: Tian Yang, Bin Song, Jin Zhang, Guang-Shun Yang, Han Zhang, Wei-Feng Yu, Meng-Chao Wu, Jun-Hua Lu, Feng Shen
Journal: Gut (2014)

<h3>Objective</h3> STK33 has been reported to play an important role in cancer cell proliferation. We investigated the role of STK33 in hepatocellular carcinoma (HCC) and its underlying mechanisms. <h3>Design</h3> 251 patients with HCC were analysed for association between STK33 expression and clinical stage and survival rate. Tamoxifen (TAM)-inducible, hepatocyte-specific STK33 transgenic and knockout mice models were used to study the role of STK33 in liver tumorigenesis. HCC cell lines were used to study the role of STK33 in cell proliferation in vitro and in vivo. <h3>Results</h3> STK33 expression was found to be frequently upregulated in patients with HCC. Significant associations were found between increased expression of STK33 and advanced HCC staging and shorter disease-free survival of patients. Overexpression of STK33 increased HCC cell proliferation both in vitro and in vivo, whereas suppression of STK33 inhibited this effect. Using a TAM-inducible, hepatocyte-specific STK33 transgenic mouse model, we found that overexpression of STK33 resulted in increased hepatocyte proliferation, leading to tumour cell burst. Using a TAM-inducible, hepatocyte-specific STK33 knockout mouse model, we found that, when subjected to the diethylnitrosamine (DEN) liver cancer bioassay, STK33KO<sup>flox/flox, Alb-ERT2-Cre</sup> mice exhibited a markedly lower incidence of tumour formation compared with control mice. The underlying mechanism may be that STK33 binds directly to c-Myc and increases its transcriptional activity. In particular, the C-terminus of STK33 blocks STK33/c-Myc association, downregulates HCC cell proliferation, and reduces DEN-induced liver tumour cell number and tumour size. <h3>Conclusions</h3> STK33 plays an essential role in hepatocellular proliferation and liver tumorigenesis. The C-terminus of STK33 could be a potential therapeutic target in the treatment of patients with STK33-overexpressed HCC.
Knock knees and bow legs.
Authors: W J Sharrard
Journal: BMJ (1976)

Background/Aim: We aimed to investigate the prognosis of patients who received radiofrequency ablation (RFA) for liver metastases of unresectable colorectal cancer (CRC). Patients and Methods: We retrospectively compared 147 patients treated for CRC liver metastases, who underwent RFA (n=26), resection (n=92), and chemotherapy (n=29) between 2001 and 2021. Results: RFA and chemotherapy were performed for unresectable or non-operable cases, and resection was performed for suitable cases. The median overall survival (OS) was 44.9, 49.5, and 11.6 months for patients who underwent RFA, resection, and chemotherapy, respectively. RFA led to a significantly shorter OS compared to resection (p=0.027) but to a longer OS compared to chemotherapy (p=0.003). The 5-year survival rates were 34.6% and 42.4% for patients who underwent RFA and resection, respectively (p=0.508). Conclusion: RFA has the potential to achieve long-term survival or radical cure, even for unresectable or non-operable cases of CRC with liver metastasis.
Abstract 753: Novel, potent and selective small molecule inhibitors of 3-phosphoinositide-dependent kinase (PDK1)
Authors: Sean T. Murphy, Gordon Alton, Simon Bailey, Sangita Baxi, Ben Burke, Jacques Ermolieff, Samantha Greasley, Natasha Kablaoui, John Kath, Darcy Kohls, Michael Kothe, Stan Kupchinsky, Laura Lingardo, Matthew A. Marx, Dan Richter, Khanh Tran, William Vernier, Min-Jean Yin
Journal: Cancer Research (2010)

Abstract The phosphatidylinositol 3-kinase (PI3K) signaling pathway plays a crucial role in cell growth, proliferation and survival. Genomic aberrations in the PI3K pathway, such as mutational activation of PI3Kα or loss-of-function of the tumor suppressor PTEN, have been closely linked to the development and progression of a wide range of cancers. Inhibition of the key targets in the pathway, PI3K, AKT, mTOR &amp; PDK1, may provide an effective treatment of cancer. In an effort to discover compounds that inhibit PDK1, we have developed a series of 3-Carbonyl-4-Amino-Pyrrolopyrimidine (CAP) compounds that are selective and potent PDK1 inhibitors. Early screening led to a viable starting point, PF-03772304, (4-amino-7-isopropyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-(6-methylamino-pyrazin-2-yl)-methanone, which has an IC50 of 94 nM for PDK1 and a ligand efficiency of 0.42. While potent, this lead was not selective against PI3K. Using structure-based drug design, this lead was modified to expand into the selectivity pocket of PDK1 (under the G-Loop), leading to the identification of a potent and pathway-selective compound, PF-05017255 ((4-Amino-7-isopropyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-{6-[(3S,4R)-4-(4-fluoro-phenyl)-tetrahydro-furan-3-ylamino]-pyrazin-2-yl}-methanone). PF-05017255 has a Ki of 0.6 nM for PDK1 and is more than 400-fold selective against other PI3K pathway kinases: PI3Kα, AKT, S6K and mTOR. For even greater kinase selectivity, we sought to lower the clogP of our lead (clogP for PF-05017255 is 3.0) to reduce the contribution from the hydrophobic effect. These efforts led to PF-05168899 (1-{(2R,3R)-3-[6-(4-Amino-7-isopropyl-7H-pyrrolo[2,3-d]pyrimidine-5-carbonyl)-pyrazin-2-ylamino]-2-phenyl-pyrrolidin-1-yl}-ethanone) with a Ki of 0.4 nM for PDK1, a clogP of 2.1, and greater than 1000-fold selectivity against PI3Kα, AKT, S6K, mTOR, CDK2, CHK1 and PAK4. PF-05168899 also showed little inhibitory effect (&amp;lt;50% at 1 uM) against 33 of 35 kinases in a broader panel, demonstrating significant inhibition only against CHK2 (94%) and AuroraB (54%). In addition, the most potent analogs (e.g. PF-05168889) inhibited the phosphorylation of AKT at the residue threonine 308 (IC50 40-200 nM) in a variety of cancer cell lines (e.g. H460, A549). The design, synthesis and SAR of this chemical series will be described. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 753.
A FILTERING ADAPTER FOR THE ADMINISTRATION OF NEO-ARSPHENAMIN
Authors: Jay F. Schamberg
Journal: JAMA (1922)

During the World War, the practice became common abroad of administering neo-arsphenamin in concentrated solutions in a small Luer syringe. This practice has likewise been adopted by many physicians in this country. It possesses the advantage of simplicity of administration and of time economy, factors which are important when large numbers of patients in clinics are treated. When concentrated solutions are used with a Luer syringe, and even when larger quantities of water are employed, it is quite possible for minute fragments of glass dust, dust in the water or undissolved particles of the drug to be carried through the needle. Such particles, while not large enough to be readily visible to the eye, may still be of sufficient size to cause an embolism in the minute capillaries of the lungs or possibly other organs. It is probable that the nitritoid and similar immediate reactions which follow the administrations of
The Kerr Symballophone
Authors: Arthur M. Master
Journal: JAMA (1965)

<h3>To the Editor:—</h3> For many years, I have used William J. Kerr's "Symballophone" which has been of great help in discerning the origin of murmurs. For example, if there is a systolic blow over the mitral and aortic areas and one must decide if it is the same murmur or two distinct murmurs, by placing one chest piece over each region, the ear perceives the differences in timing and quality. This stereophonic binaural stethoscope or the Symballophone might be used routinely whenever a murmur is audible, though the instrument is clumsy. Kerr showed illustrations of three stethoscopes, but favored the introduction of a "longer connecting-tube from each end piece to the opposite ear." Thus, the Symballophone is a little clumsier than Dr. Horowitz's stethoscope, in that altogether there are four rubber tubes instead of two.
Glucagon in Heart Failure and in Cardiogenic Shock
Authors: ROBERT LVOFF, DAVID E. L. WILCKEN
Journal: Circulation (1972)

Intravenous glucagon, in doses of 2.5-15 mg/hour, was administered to 50 patients for periods of 1-7 days. Forty patients had either intractable heart failure or cardiogenic shock or both; the remaining 10 had less severe heart disease. In all patients glucagon was added to conventional therapy. Twenty-two of the 40 with very severe heart failure showed a clinical improvement, and 18 were discharged from the hospital; 16 of the 18 patients who did not respond died in the hospital. Only two of the 10 with less severe heart disease improved with glucagon but all could be discharged from the hospital. Glucagon did not initiate or aggravate a tendency to arrhythmias in any of the 17 patients with acute myocardial infarction. In two patients with bradycardia and cardiac failure due to beta-adrenergic blocking drugs, glucagon increased heart rate and there was clinical improvement in heart failure. However, there was no effect in two patients with digitalis-induced nodal bradycardia and heart failure. Nausea was the most troublesome side effect and this could usually be controlled by intramuscular prochlorperazine (Stemetil) which was given routinely before the infusion in all except postoperative patients and repeated as required during the infusion. The results show that glucagon has a definite place in the management of patients with severe heart failure when used as an adjunct to conventional therapy.