tbuckley/cabot-search huggingface dataset:
RB-02 * PHASE I/II CLINICAL TRIAL USING TRANS SODIUM CROCETINATE AS A RADIOSENSITIZER FOR GLIOBLASTOMA
Authors: J. Gainer, J. Sheehan, J. Larner, D. Jones
Journal: Neuro-Oncology (2014)

BACKGROUND: Trans sodium crocetinate (TSC) was developed at UVA to increase tissue oxygenation. Since hypoxic tumors are more resistant to radiation therapy (RT), TSC was demonstrated to increase survival in a rat GBM model.TSC has been used in an open GBM clinical trial in conjunction with TMZ and RT. All patients have undergone at least one year of treatment/check-ups. METHODS: 59 patients with newly diagnosed GBM were enrolled between January 2012 and March 2013. Patients received standard of care RT and TMZ. TSC was also administered 3/week, prior to the RT sessions. The trial began with a Phase I portion to establish the safety of dosing TSC in 3 half-dose patients. Then 6 more patients received TSC for the full 6 weeks of RT. Since there were no dose-limiting toxicities, 50 more Phase II patients were enrolled at the higher dosage of TSC. Four weeks after completion of RT, patients resumed TMZ for 5 days every 4 weeks, but no further TSC was administered. The patients continued to receive bi-monthly check-ups for MRI, KPS scores and Quality of Life questions. The principal efficacy measurement is survival at 24 months as compared to a historical control (Stupp 2005). RESULTS: At a time of 12 months since the diagnosis of GBM: survival = 70% of the 56 full-dose patients are alive as compared to 61% in the Stupp 2005 trial; radiologic response shows 6 full-dose patients who began RT with partially-resected tumors now show no tumor, while another 13 show declining tumors. 7 patients who began RT following complete resections still show no detectable tumor. Thus, 46% of the patients exhibit decreased or zero tumor volumes; SAFETY: The patients tolerated the concurrent dosing of TMZ and TSC during RT extremely well. Only one patient experienced TMZ-induced thrombocytopenia.
Metformin and Heart Failure: Innocent Until Proven Guilty
Authors: Sergio Muntoni
Journal: Diabetes Care (2006)

The editorial by Inzucchi (1) in the October 2005 issue of Diabetes Care on the effects of metformin in type 2 diabetic patients with heart failure deals in a masterly manner with the choice of the most suitable treatment of this condition. Since both diabetic heart failure and mechanism of metformin action are not completely understood, it is difficult, in the author’s opinion, to …
677. Gene Delivery of TNFR:Fc by Adeno-Associated Virus Vector Blocks Progression of Periodontitis
Authors: Mario Taba, Heather H. Huffer, Charles E. Shelburne, Jaclynn M. Kriegl, Steven A. Goldstein, Kurt H. Lustig, Haim Burstein, William V. Giannobile
Journal: Molecular Therapy (2005)

Although periodontitis is initiated by specific oral pathogens that colonize and invade the oral tissues, the host inflammatory response is a major factor in disease progression. Soluble protein delivery of antagonists to tumor necrosis factor alpha (TNF-receptor:Fc fusion protein) inhibit alveolar bone resorption. However, the clinical use of recombinant p75-TNFR:Fc fusion protein raises several concerns, such as reoccurrence of disease activity after cessation of therapy. Objectives: This pilot study used adeno-associated virus (AAV) as a mode to deliver the TNFR:Fc transgene to periodontal lesions in an experimental model of P. gingivalis LPS-mediated bone loss. Methods: Three groups of Sprague-Dawley rats received one of three treatments: LPS delivered to the maxillary interdental gingivae thrice weekly for 8 weeks; vehicle alone (PBS) or LPS plus the single local delivery of pseudotyped AAV[2/5]-TNFR:Fc vector [6 sites|[times]|15uL of 8|[times]|1011 DNase I-resistant particles (DRP)] at baseline. Microcomputed tomography (MicroCT), systemic blood levels of TNFR:Fc protein and cytokine profiles were performed at various timepoints ranging from baseline to 8 weeks following TNFR:Fc transgene delivery. Results: TNFR protein serum levels were low to undetectable in all groups over the entire observation period indicating that local vector delivery did not result in systemic distribution of the soluble TNFR:Fc protein. Real-time PCR showed higher expression of both TNFR1 and TNFR2 than controls (p<0.05) for AAV[2/5]-TNFR-treated animals. In addition, local delivery of AAV[2/5]-TNFR:Fc resulted in protection against LPS-mediated bone loss (mean linear bone loss: AAV-TNFR:Fc=0.68mm similar to PBS=0.71mm) while the LPS alone group demonstrated severe alveolar bone resorption 70-100% of root length (LPS=1.27mm; p<0.05). Conclusion: This proof-of-principle investigation suggests that local delivery of AAV[2/5]-TNFR:Fc vector can block alveolar bone loss for extended periods of time in the face of continual challenge of P. gingivalis LPS.
A SUGGESTION AS TO THE CARE OF SILK SUTURES DURING OPERATIONS.
Authors: GEORGE F. KEIPER
Journal: JAMA (1894)

The ordinary method of sterilizing silk sutures is to put needles and silk in boiling water. Result, tangling of the different sutures and vexation in their separation. To overcome this, manufacturers have put before us reels of silk in bottles containing an antiseptic solution. The ends are brought out through rubber corks. They are thus always kept sterilized. The needle is supposed to be threaded by this sterilized silk, but it would be hazardous to use it in living tissues unless both are sterilized after threading. This puts us where we usually begin, and the result is, to be safe, we must again sterilize the silk. The accompanying photograph explains a method of caring for sutures; this I have used for two years. It is impossible for them to tangle. The needles are threaded and wound on an ordinary card, which is nicked the better to receive and hold the
The Power of Life or Death: A Critique of Medical Tyranny
Authors: U. Freudenstein
Journal: BMJ (1996)

Fabian Tassano Duckworth, pounds sterling12.95, pp 177 ISBN 0 7156 2697 3

Live footage of a NATO bombing of a Bosnian Serb artillery base is followed by two interviews on television. They are with a Bosnian Serb and his Muslim counterpart respectively. Their viewpoints on the meaning of the attack are diametrically opposed. My disagreement with Fabian Tassano's interpretation of the facts about doctors' relationships with their patients reaches similar proportions (although our lives are fortunately not at stake).

I agree that doctors in the NHS are not always courteous and do not …
De Novo Treatment of Diffuse Large B-Cell Lymphoma With Rituximab, Cyclophosphamide, Vincristine, Gemcitabine, and Prednisolone in Patients With Cardiac Comorbidity: A United Kingdom National Cancer Research Institute Trial
Authors: Paul A. Fields, William Townsend, Andrew Webb, Nicholas Counsell, Christopher Pocock, Paul Smith, Andrew Jack, Nadjet El-Mehidi, Peter W. Johnson, John Radford, David C. Linch, David Cunnningham
Journal: Journal of Clinical Oncology (2013)

The treatment of patients with diffuse large B-cell lymphoma (DLBCL) with cardiac comorbidity is problematic, because this group may not be able to receive anthracycline-containing chemoimmunotherapy. We designed a single-arm phase II multicenter trial of rituximab, gemcitabine, cyclophosphamide, vincristine, and prednisolone (R-GCVP) in patients considered unfit for anthracycline-containing chemoimmunotherapy because of cardiac comorbidity.
Polyuria in paroxysms of tachycardia
Authors: D Kohn
Journal: BMJ (1976)

extremely well, obviating the need for intrathecal administration.Also we are not aware of any evidence to suggest that penicillin allergy increases the risk of adverse reactions to chloramphenicol.Consequently it would appear that when the organism is sensitive to chloramphenicol this drug is the treatment of choice for bacterial meningitis in the penicillinallergic patient.
Detection of Mutant Hemoglobins with Altered Affinity for Oxygen
Authors: MARSHALL A. LICHTMAN
Journal: Annals of Internal Medicine (1976)

The detection of high- or low-affinity hemoglobins in subjects with polycythemia or anemia is difficult for most physicians because of the requirement for special equipment to do oxygen-hemoglobin dissociation curves. Measurement of the pH, oxygen tension, and oxygen saturation of antecubital venous blood with instruments present in most clinical chemistry laboratories permits an estimate of the strength of oxygen binding to hemoglobin. An equation can be used to convert the venous oxygen tension (standardized to pH 7.4) and the oxygen saturation to the P50 of the oxygen-hemoglobin dissociation curve on which the observed point falls. The data indicate that this method is a reliable initial step in the identification of a hemoglobin with abnormal affinity for oxygen and may be applied to population studies, since reliable results are obtained with venous blood stored at 4 °C for up to 24 hours.
Spontaneous Mutational and Standing Genetic (Co)variation at Dinucleotide Microsatellites in Caenorhabditis briggsae and Caenorhabditis elegans
Authors: N. Phillips, M. Salomon, A. Custer, D. Ostrow, C. F. Baer
Journal: Molecular Biology and Evolution (2008)

Understanding the evolutionary processes responsible for shaping genetic variation within and between species requires separating the effects of mutation and selection. Differences between the patterns of genetic variation observed in nature and when mutations are allowed to accumulate in the relative absence of selection can reveal biases imposed by selection. We characterize the genetic variation at dinucleotide microsatellite repeats in four sets of 250-generation mutation accumulation (MA) lines, two in the species Caenorhabditis briggsae and two in Caenorhabditis elegans, and compare the mutational variation with the standing variation in those species. We also compare the mutational properties of microsatellites with the cumulative effects of mutations on fitness in the same lines. Integrated over the whole genome, we infer that the mutation rate of C. briggsae is about twice that of C. elegans, consistent with the cumulative mutational effects on fitness. The mutational spectrum (ratio of insertions to deletions) differs between repeat types and, in some cases, between species. The per-locus mutation rate is significantly positively correlated with the standing genetic variation at the same locus in both species, providing justification for the common practice of using the standing genetic variance as a surrogate for the mutation rate.
Troglitazone Use in Insulin-Treated Type 2 Diabetic Patients
Authors: John B Buse, Barry Gumbiner, Nancy P Mathias, Debra M Nelson, Barbara W Faja, Randall W Whitcomb
Journal: Diabetes Care (1998)

To determine the ability of troglitazone to reduce requirements for injected insulin while maintaining blood glucose levels in insulin-treated patients with type 2 diabetes.This 26-week double-blind study with open-label extension included patients who had failed previous oral antidiabetic medication and took > or =30 but <150 U of insulin daily The 222 patients in the double-blind study received 200 or 400 mg troglitazone once daily or matching placebo. The primary end point was the proportion of patients meeting the target of > or =50% reduction in injected insulin and either a 15% reduction in fasting blood glucose or a blood glucose <7.8 mmol/l. Insulin dose was reduced 25% based on a study-specific algorithm whenever fasting blood glucose was reduced 5% from baseline. Also of interest were changes in insulin dose and HbA1c. The open-label extension included 173 patients. They received 200 mg of troglitazone with optional titration to 400 mg, and insulin dose was adjusted based on investigators' standards of care. Open-label measures were change in insulin dose, HbA1c, and fasting serum glucose (FSG).In the double-blind phase, 22 and 27% of the 200- and 400-mg troglitazone groups, respectively, reached target, compared with placebo (7%) (P < 0.01). Insulin dose reductions of 13 +/- 3, 30 +/- 3, and 41 +/- 3 U were observed for placebo, 200-, and 400-mg troglitazone groups, respectively HbA1c decreased 0.09 +/- 0.14% for placebo, 0.13 +/- 0.14% for 200 mg, and 0.41 +/- 0.14% for 400 mg (P < 0.05) troglitazone. In the open-label extension, troglitazone treatment resulted in >50% reduction from baseline in daily insulin dose and decreases in HbA1c of 1% and in FSG of >17%.Troglitazone decreases daily injected insulin dose requirements and improves glycemic control in insulin-treated patients with type 2 diabetes.
Further Remarks on the Natural History of Pulmonary Consumption
Authors: A. B. Shepherd
Journal: BMJ (1877)

IN the lectures which I had the honour to give before the Royal College of Physicians, now more than a year ago, I attempted to take, as far as I could do so, a general view of the various diseases which, leading by different means to a larger or smaller interference with the respiratory function, produce clinically the same symptoms of pulmonary consumption, but show by no means precisely similar post mortem appearances.The task of giving those lectures came upon me unexpectedly, and I made use of such materials as I had at hand or could easily lay hold of.Since then, in preparing the lectures for publication, though I have not found anything to withdraw, I have found much to support the views there stated, and I would supplement them by filling in more fully than I could do at the time the outlines I sketched.But it is impossible to avoid the conclusions that all indi- vidual experience only adds further proof to knowledge already well grounded, and that any originality to which a dissertation of this kind may be supposed to lay claim is, except in the handling of facts already observed, utterly out of the question.The points I would further touch upon here are these :-The mark- edly perivascular and peribronchial growth which accompanies, with few, if any, exceptions, the course of acute tuberculosis in the adult and the child; the catarrhal commencement of ordinary phthisis;and the condition of the lungs, to which more attention has been lately drawn, due, as I suggested in my Goulstonian lectures, to the poison of syphilis.I would also make a few remarks on one of the causes of hemoptysis.The drawings* to which I would first call attention are made from preparations taken from a child, Henry B., aged twelve months, who died about four months ago with the symptoms of tubercular meningitis, and presented post mortem the appearances found in general tuberculosis.If these drawings be compared with those made from the lungs of a woman who was admitted into one of the metropolitan hospitals for supposed delirium tremens, but died after a short period of illness from general tuberculosis, they will show a striking simi- larity.And if, again, they be compared with other drawings made from cases of ordinary pneumonia and ordinary phthisis, that similarity will appear more striking still.Whether you examine the lung of the child or the lung of the adult, you cannot but be astonished at the very small amount of intra-alveolar growth present in the shape of catarrhal or desquamated cells, while, at the same time, you find the alveoli themselves collapsed and the vessels running along their walls intensely congested.I am, of course, not referring to those much rarer cases, to the absolute certainty of accurately diagnosing which Niemeyer has already drawn attention, in which the naked-eye appearances, easily taken for those of acute tuberculosis, resolve themselves, under the microscope, into districts of acute catarihal pneumonia.And, in addition to this absence of catarrhal products and this col-
A STUDY OF HEMOLYTIC STREPTOCOCCI IN ACUTE RHEUMATIC FEVER, WITH AN ANALYSIS OF THE ANTIGENIC RELATIONSHIPS EXISTING AMONG CERTAIN STRAINS
Authors: Christopher H. Andrewes, Clifford L. Derick, Homer F. Swift
Journal: The Journal of Experimental Medicine (1926)

1. Thirteen strains of hemolytic streptococci isolated from patients with acute rheumatic fever did not show any evidence of being related serologically. 2. Strains of hemolytic streptococci exist which, although identical by the agglutination test, do not show complete reciprocal agglutinin absorption. Sera prepared from such related strains may show some protective power in mice against another member of the group. 3. Some strains of hemolytic streptococci may absorb agglutinins from a serum prepared against another strain, and yet may fail to be agglutinated by that serum. 4. None of 20 strains of hemolytic streptococci isolated in New York City in 1924, and 1925, corresponded serologically with Dochez, Avery, and Lancefield's 4 type strains or with Gordon's Type I strain.
High‐dose (40,000 IU twice/week) alpha recombinant human erythropoietin as single agent in low/intermediate risk myelodysplastic syndromes: A retrospective investigation on 133 patients treated in a single institution
Authors: Antonio Azzarà, Giovanni Carulli, Sara Galimberti, Claudia Baratè, Rita Fazzi, Giulia Cervetti, Mario Petrini
Journal: American Journal of Hematology (2011)

Abstract We investigated the efficacy of alpha recombinant human erythropoietin (α‐rHuEPO) administered as single agent to 133 patients affected by myelodysplastic syndromes referring to our Institution in the last 10 years. WPSS score was “very low” in 67%, “low” in 19%, “intermediate” in 14%. The starting schedule was: 40,000 IU bi‐weekly, with reduction or suspension, when necessary, in responsive patients. According to new IWG criteria, response rate (RR) was 75%, 66%, 59% after 8, 16, 24 weeks, respectively. Comparing “very low” and “low/intermediate” risk, RR was 81% vs. 43% ( P &lt; 0.001); 70% vs. 45% ( P = 0.040); 63% vs. 42% ( P = NS) after 8, 16, 24 weeks. RR was significantly influenced by transfusion dependence ( P = 0.039) and basal serum EPO level ( P &lt; 0.001). Mean Hb value was 94 ± 11 g/l before therapy; 114 ± 19 after 8 weeks ( P &lt; 0.001); 116 ± 18 after 16 weeks ( P &lt; 0.001); 114 ± 17 after 24 weeks ( P &lt; 0.001). Reduction or suspension of therapy significantly affected Hb level after 4 ( P &lt; 0.001) and 8 weeks ( P &lt; 0.01). Conversely, restart of full dosage significantly enhanced again Hb level after 4 ( P &lt; 0.01) and 8 weeks ( P &lt; 0.001). 65% patients are alive (mean survival: 74 weeks). Seventy percent are alive in the “very low risk” group and 38% in “low/intermediate risk” group ( P &lt; 0.001). Overall mean follow‐up was 69 weeks (range, 8–376): it was 80 weeks in responsive patients (max 376) and 38 weeks in patients who progressively became unresponsive (max 168) ( P &lt; 0.01). Median response was 36 weeks, with 33% of patients still responding after one year. Treatment was well tolerated. Am. J. Hematol. 86:762–767, 2011. © 2011 Wiley‐Liss, Inc.
A monoclonal antibody to a human neutrophil-specific plasma membrane antigen. Effect of the antibody on the C3bi-mediated adherence by neutrophils and expression of the antigen during myelopoiesis.
Authors: B Pytowski, T G Easton, J E Valinsky, T Calderon, T Sun, J K Christman, S D Wright, J Michl
Journal: The Journal of Experimental Medicine (1988)

We have used mice selectively tolerized to antigens of human lymphocytes by treatment with cyclophosphamide to raise an mAb, BH2-C6, that reacts with a plasma membrane antigen specific for human neutrophils. This specificity is demonstrated by indirect immunofluorescence microscopy, cytochemical analysis of fluorescence-positive and -negative cell populations separated by flow cytometry, and by the selective, complement-mediated killing of mAb BH2-C6-treated neutrophils. Additional evidence for the neutrophil specificity of mAb BH2-C6 is shown by immunoelectron microscopy, which demonstrates a lack of reactivity with human eosinophils. Immunoblotting of SDS-PAGE-separated proteins of polymorphonuclear leukocytes with 125I-labeled BH2-C6 identifies protein with an average molecular mass of 157 kD. Binding studies show that, at saturation, neutrophils bind 214,000 molecules of 125I-BH2-C6 per cell. Addition of mAb BH2-C6 to neutrophils significantly reduces the number of C3bi-opsonized sheep erythrocytes (EIgMC3bi) bound by these cells. This reduction is partly reversed by the presence of soybean trypsin inhibitor (SBTI), indicating that at least one part of this inhibition is due to BH2-C6-stimulated secretion of a serine protease that may affect ligand binding. Cytochemical analysis of normal human bone marrow cells sorted by cytofluorimetry identifies the promyelocyte as the precursor cell that first expresses BH2-Ag on the plasma membrane. Using the leukemic cell line HL-60, we demonstrate that only inducers of granulocytic differentiation, cis-retinoic acid, and dimethyloxazolidine stimulate the expression of BH2-Ag. These results show that the expression of BH2-Ag during myelomonocytic differentiation is a property uniquely possessed by cells committed to the neutrophilic lineage.
Braces in Spinal Curvature.
Authors: John Ridlon
Journal: JAMA (1898)

Chicago, Sept. 12, 1898. <h3>To the Editor:</h3> —In theJournalof Sept. 10, 1898, there appears an editorial entitled "Braces in Spinal Curvature" which contains so many half truths, to put it gently, that it should not pass without comment. The editorial writer says: "The two conditions of tubercular caries and spinal curvature differ so widely in their causation, symptomatology and treatment that each must have a clearcut picture in our mind when examining soinal caries." This is true in so far as causation and treatment go, but it is not true in all cases in so far as symptomatology is concerned. It is true that there are cases that distinctly differ, and there are other cases where those having the greatest experience can not at once differentiate. Lateral spinal curvature may not simulate tubercular caries, indeed there would be no serious harm done to the patient by the treatment
Prescribing Records and the First Amendment — New Hampshire's Data-Mining Statute
Authors: Robert Post
Journal: New England Journal of Medicine (2009)

In November 2008, the U.S. Court of Appeals for the First Circuit upheld against constitutional attack a New Hampshire statute that prohibits data miners from selling information about physicians' prescribing histories to pharmaceutical companies for use by sales representatives (“detailers”).1 Pharmaceutical companies annually spend billions of dollars on detailing, which entails visiting individual physicians to persuade them to prescribe specific brand-name drugs. A detailer who knows a physician's prescribing history can effectively tailor his or her promotional message.Although the statute prohibits data miners from transferring the prescribing history of individual physicians “for any commercial purpose,” including the “marketing, promotion, . . .
Inferior Vena Cava Obstruction with Hot Quadrate Lobe on Technetium-99m MAA Scintivenography
Authors: GREGORY R. WEAVER, JANET A. JOHNSON, MARTIN P. SANDLER
Journal: Clinical Nuclear Medicine (1986)

In the presence of inferior vena cava thrombosis, the venous blood return from the lower extremity is via collateral channels to the umbilical vein and into the left portal vein. This may result in the visualization of a hot spot in the region of the liver secondary to deposition of a relatively large amount of radionuclide in the quadrate lobe when venous angioscintigraphy of the lower extremity is performed.