tbuckley/cabot-search huggingface dataset:
Comparative Studies of Protoveratrine A and Protoveratrine B Intravenously in Hypertensive Man
Authors: BERTRAM M. WINER
Journal: Circulation (1960)

Comparative studies of intravenously administered protoveratrine A and protoveratrine B in hypertensive man indicate that the alkaloids have qualitatively similar hypotensive, bradycrotic, and emetic actions, but quantitatively different hypotensive and emetic potency. The relative hypotensive potencies of the two substances were determined by analyses of logarithmic dose-response curves in the same patients. On a weight basis protoveratrine B was slightly less potent than protoveratrine A. A favorable dissociation between hypotensive and emetic activity was found. Tolerance ratios were determined in which the largest doses of protoveratrine B given without nausea were compared with the doses of protoveratrine A producing nausea. These ratios were adjusted for the differences in hypotensive potency of the alkaloids. Protoveratrine B was better tolerated than protoveratrine A ( p &lt;.001). Indeed, protoveratrine B had little emetic activity when given intravenously in doses producing normotension. Protoveratrine B appears to have properties that warrant its preferential selection for parenteral administration. Its effective dosage range has been studied. The strong hypotensive activity of intravenously administered protoveratrine B, its development of maximal action within minutes, and its pulse-slowing effect favor its use in those hypertensive states in which almost immediate lowering of the blood pressure is indicated. Fixed hypertension lends itself to the application of biological assay technics. The use of such technics in human pharmacology fosters the perception of clinically significant differences among drugs that are chemically closely related.
Black Urinary Spherules and Hyperphosphatemic Renal Failure
Authors: DOUGLAS WEBSTER
Journal: Annals of Internal Medicine (1983)

Letters and Corrections1 August 1983Black Urinary Spherules and Hyperphosphatemic Renal FailureDOUGLAS WEBSTER, M.D., RICHARD A. ZAGER, PH.D., MARK RARICK, M.D.DOUGLAS WEBSTER, M.D.Search for more papers by this author, RICHARD A. ZAGER, PH.D.Search for more papers by this author, MARK RARICK, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-99-2-283_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editors: Several reports indicate that rapid killing of tumor cells during cancer chemotherapy can produce severe hyperphosphatemia and concomitant acute renal failure (1-5). We have seen a patient who developed hyperphosphatemic renal failure on two separate occasions during the course of cancer chemotherapy and who had no other discernable cause of renal failure. On both occasions, the patient had an unusual finding on urinalysis.A 54-year-old white woman with recently diagnosed diffuse lymphocytic lymphoma received MOPP chemotherapy (plus allopurinol) which produced a striking reduction in her lymphomatous masses. Four days later oliguria developed without prior sepsis, hypotension, or...References1. COHENBALOWMAGRATHPOPLACKZIEGLER LJIDJ. Acute tumor lysis syndrome: a review of 37 patients with Burkitt's lymphoma. Am J Med. 1980;68:486-91. CrossrefMedlineGoogle Scholar2. KAPLANHEBERTMORRELL BDR. Acute renal failure induced by hyperphosphatemia in acute lymphoblastic leukemia. CMA Journal. 1981;124:429-31. MedlineGoogle Scholar3. ETTINGERHARKERGERRYSANDERSSARAL DWHRR. Hyperphosphatemia, hypocalcemia and transient renal failure; result of cytotoxic treatment of acute lymphoblastic leukemia. JAMA. 1978;239:2472-4. CrossrefMedlineGoogle Scholar4. KANFERROLANDCHATELETRICHET AJRG. Hyperphosphatemic acute renal failure following therapy of lymphosarcoma. Kidney Int. 1979;15:450A. Google Scholar5. DUTELBOLESBRIEREGARREBRIERE JJJMJ. Severe hyperphosphatemia-induced nephrocalcinosis after chemotherapy of acute lymphoblastic leukemia. Kidney Int. 1982;22:235A. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Renal Diseases Department of Medicine Ohio State University 2-North Means Hall, 1655 Upham Drive; Columbus, OH 43210 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 August 1983Volume 99, Issue 2Page: 283-283KeywordsAcute renal failureAllopurinolCancer chemotherapyCellsChemotherapyHomicideHypotensionLymphomaRenal failureSepsis Issue Published: 1 August 1983 PDF DownloadLoading ...
Salmonella Osteomyelitis in an HLA-B27 Patient
Authors: ROBERT G. LECKIE, MARC DARROW, CALVIN B. DELAPLAIN
Journal: Clinical Nuclear Medicine (1993)

This is a case report of an 11-year-old boy who had right hip pain and intermittent fevers for several weeks. Plain radiographs were initially read as normal. The Tc-99m HDP bone scan revealed increased uptake in the right acetabulum. A CT scan of the pelvis demonstrated a lytic lesion in the right acetabulum. Open biopsy of the site cultured salmonella Group D. The patient was negative for sickle cell disease but was HLA-B27 positive. This may be the first report of salmonella osteomyelitis in a HLA-B27 patient, which raises the possibility of the HLA-B27 antigen being a predisposing factor for salmonella osteomyelitis. Review of the radiographs with a Pediatric Radiologist revealed subtle medial displacement of the obturator fat pad.
Lymphocyte phenotypes in chronic hepatitis C infection: A correlation with disease activity
Authors: S KHAKOO
Journal: Hepatology (1995)

Sequences of the HIV-2 envelope C2–C3 region were obtained after direct PCR amplification of proviral DNA from the brain and peripheral blood mononuclear cells of an HIV-2-infected AIDS patient. Tissue-specific sequences confirmed previous observations that HIV-2 is indeed present in the central nervous system of infected individuals. Distinct but related quasi-species were present in these two different tissues of the same individual. Residues at position 18 and 19 of the V3 loop and overall charge of the loop suggest that the brain virus was NSI/macrophage tropic; whereas the sequences from the two blood samples were indicative of a SI/T-cell tropic virus. This is the first description of these two genotypes in the same HIV-2-infected individual. Analysis of more samples from different compartments would help to better understand tissue-specific factors in quasi-species evolutionin vivo.
Relationship Between Patient’s Risk Profile and Benefits in Mortality From Adjunctive Abciximab to Mechanical Revascularization for ST-Segment Elevation Myocardial Infarction: A Meta-Regression Analysis of Randomized Trials
Authors: Giuseppe De Luca, Harry Suryapranata, Gregg W. Stone, David Antoniucci, James E. Tcheng, Franz-Josef Neumann, Erminio Bonizzoni, Eric J. Topol, Massimo Chiariello
Journal: Journal of the American College of Cardiology (2006)
Court of Appeal issues guidance on shaken baby syndrome
Authors: C. Dyer
Journal: BMJ (2010)

<h3>ABSTRACT</h3> <h3>Background</h3> Immune checkpoint inhibitors (ICIs) are now a therapeutic standard in advanced non-small cell lung cancer (NSCLC), but strong predictive markers for ICIs efficacy are still lacking. We evaluated machine learning models built on simple clinical and biological data to individually predict response to ICIs. <h3>Methods</h3> Patients with metastatic NSCLC who received ICI in second line or later were included. We collected clinical and hematological data and studied the association of this data with disease control rate (DCR), progression free survival (PFS) and overall survival (OS). Multiple machine learning (ML) algorithms were assessed for their ability to predict response. <h3>Results</h3> Overall, 298 patients were enrolled. The overall response rate and DCR were 15.3 % and 53%, respectively. Median PFS and OS were 3.3 and 11.4 months, respectively. In multivariable analysis, DCR was significantly associated with performance status (PS) and hemoglobin level (OR 0.58, p&lt;0.0001; OR 1.8, p&lt;0.001). These variables were also associated with PFS and OS and ranked top in random forest-based feature importance. Neutrophils-to-lymphocytes ratio was also associated with DCR, PFS and OS. The best ML algorithm was a random forest. It could predict DCR with satisfactory efficacy based on these three variables. Ten-fold cross-validated performances were: accuracy 0.68 ± 0.04, sensitivity 0.58 ± 0.08; specificity 0.78 ± 0.06; positive predictive value 0.70 ± 0.08; negative predictive value 0.68 ± 0.06; AUC 0.74 ± 0.03. <h3>Conclusion</h3> Combination of simple clinical and biological data could accurately predict disease control rate at the individual level. <h3>Highlights</h3> -Machine learning applied to a large set of NSCLC patients could predict efficacy of immunotherapy with a 69% accuracy using simple routine data -Hemoglobin levels and performance status were the strongest predictors and significantly associated with DCR, PFS and OS -Neutrophils-to-lymphocyte ratio was also associated with outcome -Benchmark of 8 machine learning models
Water fluoridation almost halves hospital admissions for dental caries, report finds
Authors: I. Torjesen
Journal: BMJ (2014)

Children living in local authorities in England with water fluoridation schemes have less tooth decay than those in local authorities without such schemes, and there is no evidence that fluoridation harms health, says a report by Public Health England.

Rates of tooth decay were significantly lower in both children’s milk teeth and adult teeth in fluoridated areas, with the effect most pronounced in deprived areas where tooth decay in children is a greater problem, said the agency’s first report on the health of people living in fluoridated water areas.1 Tooth decay was defined as decay into dentine.

In fluoridated water areas there were 45% fewer hospital admissions of children aged one to four for dental caries (mostly for extraction of decayed teeth under a general anaesthetic) than in non-fluoridated water areas. The rate of hospital admissions for children aged one to four with caries varied from 7 per 100 000 in Leicestershire to 1550 per 100 000 in Rotherham between 2009-12, figures showed.2

At age five years, 15% fewer children had tooth decay in …
Mutations in the Connexin 26 Gene (<i>GJB2</i>) among Ashkenazi Jews with Nonsyndromic Recessive Deafness
Authors: Robert J. Morell, Hung Jeff Kim, Linda J. Hood, Leah Goforth, Karen Friderici, Rachel Fisher, Guy Van Camp, Charles I. Berlin, Carole Oddoux, Harry Ostrer, Bronya Keats, Thomas B. Friedman, Theresa San Agustin, Jan Dumon
Journal: New England Journal of Medicine (1998)

Mutations in the GJB2 gene cause one form of nonsyndromic recessive deafness. Among Mediterranean Europeans, more than 80 percent of cases of nonsyndromic recessive deafness result from inheritance of the 30delG mutant allele of GJB2. We assessed the contribution of mutations in GJB2 to the prevalence of the condition among Ashkenazi Jews.
Immunohistochemical Analysis of the p16INK4 Cyclin-Dependent Kinase Inhibitor in Malignant Mesothelioma
Authors: R. A. Kratzke, G. A. Otterson, C. E. Lincoln, S. Ewing, H. Oie, J. Geradts, F. J. Kaye
Journal: JNCI Journal of the National Cancer Institute (1995)

The identification in 1994 of the CDKN2 gene as a target for mutations in a wide range of human cancers, including malignant mesothelioma, has been controversial because subsequent studies have detected a lower frequency of CDKN2 gene mutations in primary tumors than in cultured cell lines. These reports raised the hypothesis that another gene, distinct from CDKN2, might be the target of the chromosome 9p21 deletions frequently observed in these tumors.To address whether inactivation of CDKN2 function is an essential event in the etiology of malignant mesothelioma, we examined p16INK4 protein expression in primary thoracic mesotheliomas, in nonmalignant pleural tissues, and in independent mesothelioma cell lines. We also studied the growth rate of tumor cell lines following stable transfection of CDKN2 gene.Retinoblastoma (Rb) and p16INK4 protein expression was determined by immunohistochemical analysis from archival paraffin specimens of 12 primary thoracic mesotheliomas and a nonmalignant pleural biopsy specimen. In addition, protein immunoblot analysis for Rb and p16INK4 expression was conducted on 15 independent mesothelioma cell lines, and the ability of a transfected CDKN2 gene to suppress the growth of the mesothelioma cell lines H2373 and H2461 in vitro was examined.We demonstrated abnormal p16INK4 expression in 12 of 12 primary mesothelioma specimens and in 15 of 15 mesothelioma cell lines. All tumor specimens and the tumor cell lines showed expression of wild-type Rb protein. In addition, we have confirmed the ability of a transfected CDKN2 gene to suppress growth of two independent mesothelioma cell lines.Immunohistochemical analysis of the p16INK4 gene product is feasible in archival biopsy samples. With this analysis, CDKN2 gene inactivation can be determined in tumors that are contaminated with nonmalignant cells. Furthermore, since loss of p16INK4 protein expression can result from both genetic (gene mutations) and epigenetic (abnormal DNA hypermethylation) mechanisms, as we and others have shown recently, examination of protein expression is a highly sensitive method for analyzing the CDKN2 status in large numbers of tumor samples.This study suggests that inactivation of the CDKN2 gene is an essential step in the etiology of malignant mesotheliomas. Defining the role of the p16INK4:Rb tumor suppressor pathway and its immediate downstream substrates will be an important goal in designing future therapeutic strategies.
SENSITIZATION TO THIAMINE HYDROCHLORIDE
Authors: Clarence L. Laws
Journal: JAMA (1941)

The widespread use of thiamine hydrochloride parenterally makes this report of acquired sensitivity to the substance of some clinical interest. <h3>REPORT OF CASE</h3> A white married woman aged 72, who had no prior history of allergic symptoms, was advised by her physician in September 1940 to take thiamine hydrochloride subcutaneously each day for ten days. This was administered in 25 mg. doses, and at the expiration of the ten day period the interval was increased to seven days. Eight injections were given, one each week, when she was advised to discontinue medication. The patient felt so well that she consulted a physician in a different city and discussed the possibility of continuing thiamine, since she had had such definite benefits. He acquiesced and gave her weekly injections of 25 mg. for eight or ten more doses. The patient fell and fractured the left radius at this time, and the thiamine
Abstract P6-07-41: Sub classification of early stage hormone positive (HP) Her-2 negative breast cancer (BC) by immunohistochemistry (IHC) into intrinsic subtypes (IS) and their correlation with Oncotype Recurrence Score (RS)
Authors: S Mahesh, J Lane, P Ravichandran
Journal: Cancer Research (2012)

Abstract Background: Early stage HPBC is a heterogenous disease and various models of prognostication are available. Molecular profiling by IS i.e. Luminal A (LA) and Luminal B (LB) is one such attempt but is complex and expensive. Literature suggests a Ki-67 index of ≥14% as a cutoff between LA and LB tumors. LB subtype is associated with worse breast cancer outcomes. Oncotype RS is one of the most robust tools to assess prognosis and predict benefit from chemotherapy in HP Her-2 negative early BC. We sought to investigate the correlation between IHC classification of IS and RS. In addition, we also evaluated incidence of basal immunophenotype in this population. Methods: Early Stage Her-2 negative HPBC cases that had RS testing from 2007–2011 were found through our database. IHC for Ki-67, CK 5/6 and EGFR was performed if adequate tissue blocks were present. IHC classification of IS was as follows: Ki-67 ≥ 14%: LB; Ki-67 &amp;lt; 14%: LA; CK 5/6 and/or EGFR expression: Basal. An exploratory analysis using Ki-67 cutoff of 19% i.e. LA (&amp;lt;19%); LB (≥19%) was performed to evaluate its effect on correlation with RS. Results: We found 115 patients. Median age: 62 years. Stage 1: 79/115 (69%) Stage 2: 36/115 (31%). Using Ki-67 cutoff of 14%, LA: 42/115 (36.5%); LB: 72/115 (62.6%); Using Ki-67 cutoff of 19%, LA: 66/115 (57.4%); LB: 48/115 (41.7%); Basal: 1/115(0.9%). Characteristics of LA and LB and their comparison with Oncotype Dx are shown in the Table 1. Compared to LA, LB patients were younger (p = 0.004) and had higher oncotype scores (p = 0.007). However, range of RS in both subtypes was large. Among LB patients, 43% fell in low risk category and only 15% fell into high risk category. Among LA, results seemed to correlate more with expectations; 69% were in low risk category while 5% were in high risk category. When a cutoff of Ki-67 &amp;lt;/≥19% was used to classify LA/LB, 42% of LB were still in low risk category of Oncotype Dx. Only 1 patient had basal immunophenotype (Ki-67 25%, RS 42). Conclusion: Majority (85%) of LB patients were in Low or Intermediate category of RS. This did not change when a higher KI-67 cutoff was used. Thus, relying solely on Ki-67 to classify LA/LB and using it as a surrogate marker for obtaining benefit from chemotherapy would be inappropriate. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-07-41.
Natural Porcine Surfactant Augments Airway Inflammation after Allergen Challenge in Patients with Asthma
Authors: Veit J. Erpenbeck, Andreas Hagenberg, Yasmin Dulkys, Jörn Elsner, Ralf Bälder, Harald Krentel, Marc Discher, Armin Braun, Norbert Krug, Jens M. Hohlfeld
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

There is increasing evidence for a role of pulmonary surfactant in asthma and allergic inflammation. In murine asthma models, recent studies have demonstrated that surfactant components downregulate the allergic inflammation. Therefore, we tested the hypothesis that in individuals with mild asthma, a natural porcine surfactant preparation (Curosurf) given before segmental allergen challenge can reduce the allergic airway inflammation. Ten patients with asthma and five healthy control subjects were treated in two segments with either Curosurf or vehicle followed by local allergen challenge. Six additional patients with asthma received Curosurf before allergen challenge in one segment as above, but the second segment was instilled with Curosurf without allergen challenge. Unexpectedly, surfactant treatment augmented the eosinophilic inflammation 24 hours after allergen challenge. A direct chemotactic effect of Curosurf was excluded. However, levels of eotaxin and interleukin-5 were increased in bronchoalveolar lavage after Curosurf treatment, whereas IFN-γ-levels and numbers of IFN-γ+ T cells were decreased. Curosurf had no influence on spreading and retention of allergen determined by allergen uptake in mice. These findings demonstrate that treatment with a natural porcine surfactant results in an augmentation of the eosinophilic inflammation after allergen challenge that is more likely due to immunomodulatory effects than to biophysical properties of the surfactant.
Disparities in ST-Elevation Myocardial Infarction Management for the Young Goose and Young Gander
Authors: Nanette K. Wenger
Journal: Circulation (2015)

2][3] Sexbased differences in CHD outcomes are a compelling basis for enhancing the representation of women in CHD clinical trials.A robust literature specifically identifies that younger women have more adverse outcomes with myocardial infarction and coronary artery bypass graft surgery than do their male peers. 4 Article see p 1324This has obtained despite the data that, since 2000, there has been a steady decline in cardiovascular mortality for US women, narrowing the gender gap (Figure 1). 5 Half of this mortality decline is attributable to improved management of established cardiovascular disease, and the remainder, to preventive interventions.Sex-specific science (evidence) guides management decisions and has translated into these improved cardiovascular outcomes for women over the past decade, yet many important clinical outcomes differ by age, with young women selectively disadvantaged.Since 1984, more women than men continue to die annually of cardiovascular disease.Importantly, in recent years, there has been an increase in cardiovascular mortality for young women, those aged 35 to 54 years, reversing the favorable trend of the past 4 decades. 6Cardiovascular mortality continues to decline, albeit more slowly in women aged 55 to 64, 56 to 64, 65 to 74, 75 to 84, and >85 years (Figure 2).This highlights the prescience and creativity of the Variations in Recovery: Role of Gender on Outcomes of Young AMI Patients (VIRGO) investigators in designing, conducting, and analyzing this National Heart, Lung, and Blood Institute study 7 to fill the knowledge gap, examining the role of sex in the outcome of young patients (18-55 years) with acute myocardial infarction.The VIRGO protocol design is worthy of commendation.At each research site, after every 2 women enrolled, the next consecutive male patient presenting to the hospital who consented to participate was enrolled.Women were thus preferentially represented.
From Viols to Violons
Authors: Thomas E. Layman
Journal: JAMA (1974)

<h3>To the Editor.—</h3> In a recent letter (227:1260, 1974) Dr. Edward Parnall erred in his naming of the string musical instruments. Specifically, the violoncello (not violincello) is<i>not</i>a "little<i>little viol</i>." It is not a viol at all, in fact. The term<i>viol</i>was a generic name encompassing many different instruments. These were the predecessors of the violin family of instruments. They are to the violin family what the harpsichord is to the piano. About the 17th century, the viol group was superceded by the violin group. The latter have only four strings to the viol's six; the sounding holes are made in the shape of the letter "f" instead of the viol's "c"; and the attachment of the fingerboard to the body is different. All in all, a major metamorphosis was passed through in going from<i>viol to violin</i>. About the year 1600, the term "violino" or<i>violino</i>
The Costs of Doctoring, the Distribution of Physicians, and Caring for the Underinsured
Authors: Eric L. Book
Journal: JAMA (1991)

To the Editor.  — As illustrated by Dr Hughes, 1 the different Canadian provinces have attempted to control health care costs by placing various restrictions on that part of the cost equation represented by physicians. However, as long as there is a failure to analyze carefully all of the diverse factors contributing to the process, it is unlikely that any of the solutions will be effective. Unfortunately, the Canadian physicians themselves have contributed to the development of these remedies with self-serving attitudes compounded by poor public relations. The Canadian health care experiment is a noble attempt to provide the highest quality medical care to 100% of the population at a reasonable price. Have they succeeded? Not necessarily. Could they have done better? Definitely!  Canadian government bureaucrats have a vested interest in proving that the system, as it exists, provides outcomes that are at least as good, and possibly better, than