tbuckley/cabot-search huggingface dataset:
Function and Immunochemistry of Prekallikrein-High Molecular Weight Kininogen Complex in Plasma
Authors: Cheryl F. Scott, Robert W. Colman
Journal: Journal of Clinical Investigation (1980)

Plasma from individuals with high molecular weight (HMW) kininogen deficiency has been reported to be deficient in prekallikrein as measured by radial immunodiffusion, prekallikrein coagulant activity, and/or kaolin-activated arginine esterase activity. The discovery that prekallikrein and HMW kininogen circulate as a complex in plasma led us to reevaluate the antigenic and functional properties of prekallikrein in HMW kininogen-deficient plasma as well as in normal plasma. The low prekallikrein antigen level in an individual with HMW kininogen deficiency was corrected to the normal range (80-95%) by the addition of 0.2 U/ml of purified HMW kininogen. A similar increase in apparent prekallikrein antigen was observed when purified prekallikrein and HMW kininogen were combined. The correction of the apparent prekallikrein defect in this HMW kininogen-deficient plasma coincided with the formation of a prekallikrein-HMW kininogen complex as demonstrated by immunoelectrophoresis. Similar findings were demonstrated with purified prekallikrein and HMW kininogen by immunoelectrophoresis as well as crossed immunoelectrophoresis. The coagulant activity in HMW kininogen-deficient plasma was increased in a dose-dependent manner by the addition of HMW kininogen, reaching 85% of normal level at a concentration of 0.2 U/ml. Kaolin-activated arginine esterase activity (kallikrein) in HMW kininogen-deficient plasma was fully corrected when HMW kininogen was added to the deficient plasma after depletion of kallikrein inhibitors. The functional and antigenic concentration of prekallikrein in plasma from four other HMW kininogen-deficient individuals was similarly corrected to normal after adding HMW kininogen. Addition of HMW kininogen increased the apparent prekallikrein activity in native normal plasma (as measured by esterase activity) but not in normal plasma in which inhibitors were inactivated. The apparent prekallikrein antigen concentration (as measured by radial immunodiffusion or electroimmunodiffusion) increased upon addition of HMW kininogen. Immunoelectrophoresis as well as gel filtration of normal plasma revealed the presence of free prekallikrein (17-38% of the total) in addition to the HMW kininogen-prekallikrein complex previously reported. This study emphasizes the influence of HMW kininogen on both functional and immunologic determinations of prekallikrein.
Extracorporeal liver support based on primary human liver cells and albumin dialysis – treatment of a patient with primary graft non-function
Authors: Igor M. Sauer, Katrin Zeilinger, Gesine Pless, Dimitrios Kardassis, Tom Theruvath, Andreas Pascher, Max Goetz, Peter Neuhaus, Joerg C. Gerlach
Journal: Journal of Hepatology (2003)
Scabies Successfully Treated with Coal-Tar Naphtha
Authors: S. Spratly
Journal: BMJ (1861)

TRASACTIONS OP BRAoHES rB"ua mmMap Jouxsu.rectum, runningalong the upper surface of the bowel.The boy was then put under the influence of chloroform, to allow of a inore thlorough examiination being made.Witlh one hand placed over the pubes, wllilst the leg was rotated, a distinct crepitus was detected.Auiotlier at- tempt was made to pass the catheter; andl, after some difficulty, Mr. Lawsoni succeeded in putting a silver oine into the bladdelr, whichl ho fastened in by tapes.Juily '26.He was doing well.A gum-clastic catheter was passed to-day, as thie lad had drawn the silver one out in the night.Thte bladder was qtuite paralysed, and tile uirine would oinly flow tliroughi the catlheter, when pressure withi the handl was alplied above the pubes.On this accotint, a long ltidia-rubber tube was couitiected with the end of tile cathieter, and cairied over tiie side of tbe bed into a chamber-pot, so as to form a siphon and thus keep the biladder empty.Fromii this time, the boy pro-ressed uuinter-uptedly towardls recovery, and was dischlarged from tlle hospital on August 20tlh to attend as an out-patient He was able to walk about, and had comnplete command over his bladder.
Isolated defect in postsecretory reabsorption of uric acid.
Authors: L B Sorensen, D J Levinson
Journal: Annals of the Rheumatic Diseases (1980)

A 26-year-old woman was found to have an abnormally sensitive excretory response to a rise in plasma urate with a markedly increased ratio of uric acid to creatinine clearance (exceeding 35%). Uric acid was studied before and after administration of pyrazinamide and benzbromarone. In the presence of pyrazinamide urinary uric acid decreased markedly just as in normal subjects. The uricosuric response to benzbromarone was reduced. No other renal tubular or metabolic abnormalities were found. It appears that the abnormality is related to an isolated defect in postsecretory reabsorption of urate.
Behavioral Skills in Self-Monitoring of Blood Glucose: Relationship to Accuracy
Authors: R R Wing, R Koeske, A New, D Lamparski, P Becker
Journal: Diabetes Care (1986)

Sixty-two children and adolescents with IDDM were observed while performing self-monitoring of blood glucose (SMBG) to determine which of the behaviors involved in SMBG were most likely to be performed incorrectly and which errors had the greatest effect on the accuracy bf SMBG readings. Behaviors related to cleanliness and timing were performed most poorly; only 60% of the subjects correctly timed the first minute, and 30–33% correctly timed the second interval. The duration of SMBG and frequency of monitoring were not related to proper performance of the behaviors involved in SMBG. Accuracy of SMBG was assessed by comparing subjects' readings to laboratory values obtained immediately afterward. The behavior that had the greatest effect on the accuracy of SMBG readings was that concerning whether the blood was adequately wiped from the Chemstrip bG. This behavior should receive more emphasis in SMBG training programs. The systematic observation procedure used in this study may help to identify errors made by patients while performing SMBG and may serve as the basis for training programs to improve SMBG accuracy.
ABC of major trauma. Paediatric trauma: secondary survey.
Authors: A R Lloyd-Thomas, I Anderson
Journal: BMJ (1990)

Principles for the secondary survey * Children should be assessed systematically according to a strict protocol * Finding an injury should not stop the remainder of the evaluation * Always be gentle and pay particular attention to manipulation of the spinal cord axis * Vital signs should be recorded repeatedly After the primary survey, initial stabilisation of the cardiorespiratory system, and treatment of shock a complete physical examination takes place.
Impaired Counterregulation of Glucose in a Patient with Hypothalamic Sarcoidosis
Authors: Françoise Féry, Laurence Plat, Philippe van de Borne, Elie Cogan, Jean Mockel
Journal: New England Journal of Medicine (1999)

Hypoglycemia stimulates rapid increases in the secretion of several hormones, including catecholamines, glucagon, cortisol, and growth hormone, that act in concert to increase the plasma glucose concentration. The chief role of the central nervous system in triggering the release of such counterregulatory hormones during hypoglycemia is well recognized. The specific region of the hypothalamus responsible for this process is probably the ventromedial region, because bilateral lesions or perfusion of d-glucose into this region reduces the increases in plasma glucagon and catecholamines in response to hypoglycemia in rats.1,2 We describe a patient with a hypothalamic sarcoid infiltrate who had complete . . .
In-frame Dystrophin Following Exon 51-Skipping Improves Muscle Pathology and Function in the Exon 52–Deficient mdx Mouse
Authors: Yoshitsugu Aoki, Akinori Nakamura, Toshifumi Yokota, Takashi Saito, Hitoshi Okazawa, Tetsuya Nagata, Shin'ichi Takeda
Journal: Molecular Therapy (2010)

A promising therapeutic approach for Duchenne muscular dystrophy (DMD) is exon skipping using antisense oligonucleotides (AOs). In-frame deletions of the hinge 3 region of the dystrophin protein, which is encoded by exons 50 and 51, are predicted to cause a variety of phenotypes. Here, we performed functional analyses of muscle in the exon 52-deleted mdx (mdx52) mouse, to predict the function of in-frame dystrophin following exon 51-skipping, which leads to a protein lacking most of hinge 3. A series of AOs based on phosphorodiamidate morpholino oligomers was screened by intramuscular injection into mdx52 mice. The highest splicing efficiency was generated by a two-oligonucleotide cocktail targeting both the 5' and 3' splice sites of exon 51. After a dose-escalation study, we systemically delivered this cocktail into mdx52 mice seven times at weekly intervals. This induced 20-30% of wild-type (WT) dystrophin expression levels in all muscles, and was accompanied by amelioration of the dystrophic pathology and improvement of skeletal muscle function. Because the structure of the restored in-frame dystrophin resembles human dystrophin following exon 51-skipping, our results are encouraging for the ongoing clinical trials for DMD. Moreover, the therapeutic dose required can provide a suggestion of the theoretical equivalent dose for humans.
1113-162 Geometric deformity of the saddle-shaped mitral annulus in patients with ischemic mitral regurgitation: Real-time three-dimensional echocardiographic study
Authors: Nozomi Watanabe, Yasuko Yamaura, Manabu Taniguchi, Takahiro Kawamoto, Yasuo Ogasawara, Takashi Akasaka, Kiyoshi Yoshida
Journal: Journal of the American College of Cardiology (2004)
Abstract 1532: Small-molecule Stat3 inhibitor sensitizes Cisplatin-resistant ovarian cancer cells to Cisplatin-induced apoptosis
Authors: Bhaswati Sengupta, A Startzman, J Turkson
Journal: Cancer Research (2011)

Abstract Ovarian Cancer causes the highest number of gynecologic neoplasm related deaths in the United States. The disease and its progression to drug resistance remain poorly understood. While the aberrant activation of the Signal Transducer and Activator of Transcription (Stat) 3 protein is prevalent in ovarian cancer and is detected in chemotherapy resistance, its exact role in the development and maintenance of the drug resistance phenotype remains poorly understood. We sought to investigate the molecular mechanisms by which constitutive Stat3 activity may support Cisplatin resistance in ovarian cancer. Compared to the sensitive A2780S ovarian cancer line, which does not harbor aberrant Stat3 activity, the SKOV3 line harboring constitutively-active Stat3 was partially sensitive to Cisplatin and showed evidence of moderate apoptosis in response to Cisplatin treatment. Compared to the sensitive A2780S cells, the partly-resistant, SKOV3 cells over-express c-Myc, Survivin, and Bcl-xL, and the XIAP anti-apoptotic factor, as well as VEGF pro-angiogenic factor and the matrix metalloproteinases, MMP-2 and MMP-9. The inhibition of constitutively-active Stat3 in SKOV3 cells by the small-molecule inhibitor, S3I-201 suppressed the expression of the anti-apoptotic and the pro-angiogenic factors, and induced moderate degree of apoptosis. Significantly, treatment with S3I-201 enhanced the sensitivity of SKOV3 cells to Cisplatin. Furthermore, the combined treatment of SKOV3 cells with Cisplatin and S3I-201 strongly inhibited colony formation and cell migration in vitro. Our study together identifies potential mechanisms by which aberrant Stat3 activity might support Cisplatin resistance in ovarian cancer, raising the potential that the combination therapy with Stat3 inhibitors would be effective therapeutic and chemo-sensitizing modalities for ovarian cancer and the recurrent disease. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1532. doi:10.1158/1538-7445.AM2011-1532
Margaret McCartney: We lack the tools to help patients decide about statins
Authors: M. McCartney
Journal: BMJ (2014)

The National Institute for Health and Care Excellence (NICE) recently approved atorvastatin for people in England and Wales who have a 10% risk of a cardiovascular event within 10 years; it had previously been a 20% risk.1 GPs are advised to treat such people—which includes everyone older than 85—and to continually review everyone else in case they pass the 10% threshold.

This decision on funding statins is based primarily on cost effectiveness to the NHS.2 The press release from NICE mentioned the potential benefit to the population (namely, it “could help prevent up to 28 000 heart attacks and 16 000 strokes each year”3) but not the absolute benefit to the …
Nerve growth factor may heal corneal ulcers
Authors: D. Josefson
Journal: BMJ (1998)

Topical application of eye drops containing nerve growth factor can heal corneal ulcers and restore damaged vision, according to a preliminary report by Italian researchers ( New England Journal of Medicine 1998;338: 1174-80).

The study, by Alessandro Lambiase and colleagues of the ophthalmology department of the University of Rome, involved 12 patients with 14 neurotrophic corneal ulcers. The patients were treated with eye drops containing 10 μg of murine nerve growth factor 10 times a day for …
Abstract B70: Modification of hematopoietic stem cells with CD19-specific chimeric antigen receptors as a novel approach for cancer immunotherapy
Authors: Satiro N. De Oliveira, Christine Ryan, Jennifer Wherley, Andy Tu, David Elashoff, Laurence JN Cooper, Roger P. Hollis, Donald B. Kohn
Journal: Cancer Research (2014)

Abstract Pediatric patients with recurrent B-lineage hematological malignancies have less than 50% of chance of cure, despite intensive therapy. Chimeric Antigen Receptors (CARs) redirect immune cells to tumor-associated antigens. CD19 is proposed as target because its B-lineage restriction and expression in the majority of hematological malignancies. Current clinical trials use CD19-specific CAR-modified T-cells, but the effector cells are only transiently present. The main hypothesis is that modification of hematopoietic stem cells (HSCs) with anti-CD19 CAR will generate persistent anti-leukemic activity through production of multilineage effectors. Gene transfer did not impair HSC differentiation and proliferation when transduced at 1-2 copies/cell. CAR-bearing myeloid and NK cells specifically lysed CD19-positive targets, with second-generation CAR including CD28 domains being more efficient in NK cells. CAR-modified human HSCs engrafted in NSG mice, producing functional cell progenies. Furthermore, ex vivo leukocytes presented antigen-specific target lysis, and animals engrafted with CAR-modified cells presented inhibition or elimination of CD19-positive tumors, and consequent survival advantage. First-generation CAR did not present tumor development inhibition or survival advantage when compared to non-modified HSCs, confirming that the addition of co-stimulatory moieties to the CAR construct is necessary for effectiveness. This approach is untested in cancer immunotherapy, implies the use of a patient's own cells, and can be applied to different cancers just by adjusting the target specificity. It bears the possibility of decreased morbidity and mortality, being desirable for vulnerable populations such as children, and offers alternative treatment for patients with no available HLA-matched sources for bone marrow transplantation, benefiting ethnic minorities. Citation Format: Satiro N. De Oliveira, Christine Ryan, Jennifer Wherley, Andy Tu, David Elashoff, Laurence JN Cooper, Roger P. Hollis, Donald B. Kohn. Modification of hematopoietic stem cells with CD19-specific chimeric antigen receptors as a novel approach for cancer immunotherapy. [abstract]. In: Proceedings of the AACR Special Conference on Pediatric Cancer at the Crossroads: Translating Discovery into Improved Outcomes; Nov 3-6, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;74(20 Suppl):Abstract nr B70.
Selected Vitamins and Minerals in Diabetes
Authors: Arshag D Mooradian, Mark Failla, Byron Hoogwerf, Melinda Maryniuk, Judith Wylie-Rosett
Journal: Diabetes Care (1994)

The interrelationship between diabetes and various vitamins and minerals is characterized by a high degree of reciprocity. Chronic uncontrolled hyperglycemia can cause significant alterations in the status of these nutrients, and conversely, some of these substances, especially those that have been characterized as micronutrients, can directly modulate glucose homeostasis (1). Differences in patient populations studied and methodological uncertainties account for the discrepancies in most reported studies. Certain subgroups of individuals with diabetes, such as elderly patients, vegans (who consume no animal products), and pregnant and lactating women, are at particular risk for deficiencies for such nutrients. Additionally, caloric restriction for obese patients and the effects of a high fiber diet and a host of drugs on the metabolism of vitamins and minerals are of concern (2,3).
Influenzal Meningitis Treated with Chloramphenicol
Authors: R. Green, D. S. Mankikar, J. S. Millett
Journal: BMJ (1950)

No pecuniary interest is attached by Togna to his concept, but he has a profound conviction of the benefit of exercises in the bath to his family, his friends, and himself, and a desire to make it known by publication of pamphlets and a book illustrated by photographs.I myself have acquired the habit of these exercises and found them of benefit at my age, now 84, in keeping my body supple and fit in all parts.There can be no doubt, I think, that these exercises offer a valuable means of bringing at bay the decadence of the ageing processes by keeping up bodily energy, and quite possibly warding off heart disease.Recently I have had a fresh series of observations carried out on Mr. Togna by the Clinical Research Association to ascertain: (a) the oxygen consumption under basal condi- tions; (b) the increase in oxygen consumption during three types of bath exercises; (c) the rate of oxygen consumption up to two hours after the exercises; and, for comparison, (d) the oxygen consumption while performing mild exercises (standing run) in the air.The values obtained and the physical conditions are shown in Table I.The results "of tests on three subjects exercising for the first time are shown in Table II.
Prolonged Bleeding Time Associated With 'Low-Dose' Moxalactam Therapy
Authors: Michael C. Bach
Journal: JAMA (1984)

<h3>To the Editor.—</h3> Recent reports have documented prolongation of prothrombin and bleeding times in patients receiving moxalactam disodium.<sup>1-3</sup>These reports have resulted in changes in the manufacturer's recommendations so that patients now should receive supplemental vitamin K. It is also recommended that bleeding times be monitored in patients receiving more than 4 g daily. Prolonged bleeding times developed in the cases of three patients receiving "low-dose" moxalactam. One patient experienced clinical bleeding, and a possible additive or synergistic effect of calcium channel-blocking agents is suggested in two of the cases. <h3>Report of Cases.—Case 1.—</h3> A 59-year-old man was treated with moxalactam for a<i>Serratia marcescens</i>bacteremia secondary to a urinary tract infection. His initial serum creatinine value was 2.2 mg/dL, and he received 1 g every 12 hours intravenously (IV) as well as supplemental vitamin K. The azotemia was prerenal, and his creatinine level fell to 1.1
Use of First- and Second-Generation Cyclooxygenase-2–Selective Nonsteroidal Antiinflammatory Drugs and Risk of Acute Myocardial Infarction
Authors: Frank Andersohn, Samy Suissa, Edeltraut Garbe
Journal: Circulation (2006)

Background— The cardiovascular safety of cyclooxygenase (COX)-2–selective nonsteroidal antiinflammatory drugs (NSAIDs) has come under scrutiny after the withdrawal of rofecoxib and halting of the Adenoma Prevention with Celecoxib trial. Whether the newer second-generation COX-2 inhibitors (etoricoxib, valdecoxib) also increase the cardiovascular risk is unknown. Methods and Results— We performed a nested case-control study in a cohort of 486 378 persons registered within the United Kingdom General Practice Research Database with at least 1 prescription of an NSAID between June 1, 2000, and October 31, 2004. A total of 3643 cases with acute myocardial infarction (AMI) were matched to 13 918 controls on age, sex, year of cohort entry, and general practice. Rate ratios (RRs) of AMI associated with use of COX-2–selective and –nonselective NSAIDs were calculated. Current use of etoricoxib was associated with a 2.09-fold (95% confidence interval [CI], 1.10 to 3.97) risk of AMI compared with no use of NSAIDs during the prior year. Current use of rofecoxib (RR=1.29; 95% CI, 1.02 to 1.63), celecoxib (RR=1.56; 95% CI, 1.22 to 2.00), and diclofenac (RR=1.37; 95% CI, 1.17 to 1.59) also significantly increased the AMI risk. For current use of valdecoxib, the RR was 4.60 (95% CI, 0.61 to 34.51). RRs appeared to increase with higher daily doses of COX-2 inhibitors and were also increased in patients without major cardiovascular risk factors. Conclusions— Our study supports the hypothesis that the elevated risk of AMI is a class effect of COX-2 inhibitors. The increase in risk appears to be dose dependent, but further data are needed to verify this observation.
Hepatoblastoma in Families With Polyposis Coli
Authors: Frederick P. Li
Journal: JAMA (1987)

We observed hepatoblastoma in four unrelated children who have a family history of polyposis coli and found this association in ten other kindreds in the literature. The one child in our series who has survived hepatoblastoma showed multiple colonic adenomas at 7 years of age. She and eight affected maternal relatives also had congenital hypertrophy of the retinal pigment epithelium, a new marker of gene carriers in some polyposis coli families. These findings suggest that childhood hepatoblastoma is an associated feature of familial polyposis coli. (<i>JAMA</i>1987;257:2475-2477)
Truth and evidence based medicine: spin is everything
Authors: Lokesh Tiwari, Jacob M Puliyel, Prerna Upadhyay
Journal: BMJ (2004)

EDITOR—Abbasi quotes Richard Smith saying, “Journals are in the debate business, not the truth business.”1 Evidence based medicine (EBM), on the other hand, is supposed to glean facts and is clearly in the truth business. It is disturbing when these truths become debatable. We would like …