tbuckley/cabot-search huggingface dataset:
Serum Drug Concentrations as Therapeutic Guides
Authors: Jan Koch-Weser
Journal: New England Journal of Medicine (1972)

DRUG dosages needed for optimal therapeutic effects differ widely among patients. The "usual dose" of most potent drugs accomplishes little in some persons, causes serious toxicity in others, and is fully satisfactory in few. The inability of standard dosage schedules to exert a sufficiently intense pharmacologic effect in many patients is often misinterpreted as therapeutic ineffectiveness of drugs. Conversely, drug toxicity is often caused by the failure to reduce the usual dosage appropriately in other patients. The importance of the latter problem is pointed up by the frequency and severity of adverse reactions to drug therapy. More than half these . . .
Homocysteine and methionine metabolism in ESRD: A stable isotope study
Authors: Coen Van Guldener, Wim Kulik, Ruud Berger, Denise A. Dijkstra, Cornelis Jakobs, Dirk-Jan Reijngoud, Ab J.M. Donker, Coen D.A. Stehouwer, Kees De Meer
Journal: Kidney International (1999)
Improved pain relief after thoracotomy
Authors: E N S Fry
Journal: BMJ (1981)

<b>1592</b> <h3><b>Objectives:</b></h3> Neuroinflammation is known to be one of major pathological abnormalities of epilepsy. Translocator protein (TSPO) ligand PET imaging has been suggested as a functional imaging for detection of epileptogenic foci in patients with intractable epilepsy. Especially the second-generation TSPO radioligands like C-11 DPA713 are known to have high specific binding than prototypical agent PK11195. The utility of PET by such agents, however, has never be examined for pediatric patients with epilepsy. Although the distribution volume of the tracer is usually used as an index of specific binding, invasive arterial sampling and long duration of scanning are necessary to calculate the parameter. The purpose of this study is to suggest the minimum invasive scan protocol of C-11 DPA713 PET to identify the lesions in pediatric patients with intractable epilepsy. Seven patients (age: 8.9 ± 6.2 years old, male/female: 5/2) with intractable epilepsy whose foci or cause had already been diagnosed were included in this study. (The patients’ genotype affecting the affinity of radioligand binding to TSPO were all homozygous high-affinity binders.) For all the patients, C-11 DPA was intravenously injected over 30 seconds by the infusion pump and, at the same time as injection start, dynamic PET scan was started. Dynamic PET image of each patient was co-registered to MRI. In each patient, volume of interest were located on the epileptogenic foci resected by surgery or on the pathological lesion determined by MRI and on the corresponding region in the contralateral hemisphere. The difference in time activity curve between the ipsilateral and contralateral volume of interest (dTAC) was assessed. As the result, the dTACs reached a plateau and the maximum within 60 minutes after injection in all the patients irrespective of pathological features. As far as pediatric patients with epilepsy are concerned, static scanning of C-11 DPA713 PET should be performed around 60 minutes after injection.
Hepatic uptake of organic anions affects the plasma bilirubin level in subjects with Gilbert's syndrome mutations in UGT1A1
Authors: M Persico
Journal: Hepatology (2001)

Although in Gilbert's syndrome (GS), bilirubin glucuronidation is impaired due to an extra TA in the TATA box of the promoter of the gene for bilirubin UDP-glucuronosyltransferase 1 (UGT1A1), many GS homozygotes lack unconjugated hyperbilirubinemia. Accordingly, an additional defect in bilirubin transport might be required for phenotypic expression. Plasma bilirubin and the early fractional hepatic uptake rate (BSP K1) of a low dose of tetrabromosulfophthalein (0.59 μmol/kg) were determined in (1) 15 unrelated patients with unconjugated hyperbilirubinemia plus 12 random controls; (2) 4 unrelated GS probands and 15 of their first-degree relatives; (3) 7 unrelated patients with hemolysis due to β-Thalassemia minor. Subjects were classified by DNA sequencing of the promoter region of both UGT1A1 alleles. In group 1, GS homozygotes showed a highly significant negative linear correlation between plasma bilirubin levels and BSP K1. BSP K1 values overlapped considerably between GS and normal subjects, whereas, in group 2, they were clustered within, and sharply segregated among, families. Patients with hemolysis, despite elevated plasma bilirubin levels, had mean BSP K1 values similar to the normal subjects. Within each GS subgroup with defined UGT1A1 mutations, the plasma bilirubin level is in part determined by the organic anion uptake rate, assessed by early plasma disappearance of low-dose BSP. The lower BSP uptake in GS is not secondary to the hyperbilirubinemia, but probably caused by (an) independent, genetically determined defect(s) in hepatic transport mechanism(s), shared by BSP and bilirubin, that are likely necessary for phenotypic expression of GS.
Action and Reaction in Medical Research
Authors: ROBERT P. HUDSON
Journal: Annals of Internal Medicine (1967)

Special Article1 September 1967Action and Reaction in Medical ResearchROBERT P. HUDSON, M.D.ROBERT P. HUDSON, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-67-3-660 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptIn 1928 Alexander Fleming noticed the inhibitory effect of a fungal contaminant on the growth of a culture of staphylococci. For his exploitation of this "triumph of accident and shrewd observation," Fleming received the 1945 Nobel Prize in Medicine. In 1965 Lyndon B. Johnson affixed his signature to Public Law 89-97, setting in motion the experiment in social medicine known as Medicare. Mr. Johnson's recognition will have to await the judgment of history. From this near point in time, however, the discovery of penicillin can be connected causally to the passage of Public Law 89-97. Hopefully, the process of linking...References1. VAUGHN B: Starbeams. The Kansas City Star, March 25 1965. p. 32. Google Scholar2. MASON SF: A History of the Sciences. Collier Books, New York, 1962, p. 601. Google Scholar3. PRICE DK In this context, attributed to , quoted in KERR, C.: The Uses of the University. New York University Press, New York, 1964, p. 69. Google Scholar4. BURNET M: Speech in Sydney, Australia, quoted in Med. World News, December 2 1966, p. 58. Google Scholar5. BIERCE A: The Devil's Dictionary. American Century Series, New York, 1957, p. 80. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: ROBERT P. HUDSON, M.D.Affiliations: Kansas City, KansasFrom the Department of History of Medicine, University of Kansas Medical Center, Kansas City, Kan.Requests for reprints should be addressed to Robert P. Hudson, M.D., Department of History of Medicine, University of Kansas Medical Center, Kansas City, Kan. 66103. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byDeath, Dying, and the Zealous PhaseROBERT P. HUDSON, M.D., F.A.C.P. 1 September 1967Volume 67, Issue 3_Part_1Page: 660-667KeywordsHistory of medicineMedicarePenicillin ePublished: 1 December 2008 Issue Published: 1 September 1967 PDF downloadLoading ...
Immunotherapy using bispecific T cell engager (BiTE®) antibodies: preclinical and clinical experience in acute leukemia
Authors: Marion Subklewe, Max Topp, Christina Krupka, Peter Kufer, Roman Kischel, Thomas Köhnke, Patrick Baeuerle, Gerhard Zugmaier, Stanley Frankel, Tapan Maniar, Katie Newhall, Karsten Spiekermann, Gert Riethmueller, Dirk Nagorsen, Wolfgang Hiddemann
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts BiTE® antibodies are novel recombinant single chain Ig domain constructs that leverage the endogenous cytotoxic potential of polyclonal T cells to target malignant cells by utilizing the specific binding properties of variable domains from two different antibodies. Antibody-based
THE RELATION OF THE SPINAL CORD TO THE SPONTANEOUS LIBERATION OF EPINEPHRIN FROM THE ADRENALS
Authors: G. N. Stewart, J. M. Rogoff
Journal: The Journal of Experimental Medicine (1917)

1. After section of the spinal cord in cats in the cervical region, as low as the last cervical segment, epinephrin continues to be liberated from the adrenal glands. This liberation has all the characters of the normal secretion with intact central nervous system. It is sustained through the same nerve paths connecting the cord with the adrenals. 2. After section of the cord in the middorsal region the spontaneous liberation of epinephrin from the adrenals is abolished within the limits of detectability by the methods employed (denervated eye reactions of Meltzer, and rabbit intestine and uterus segments). 3. The portion of the cord concerned in the liberation of epinephrin does not appear to extend much below the third thoracic segment. 4. In acute experiments on cats under urethane anesthesia no change in the rate of liberation of epinephrin, which could be detected by the tests employed, was observed when the cord was severed in the cervical region.
Mechanism of Pulmonary Conversion of Anglotensin II to Angiotensin II in the Dog
Authors: Suzanne Oparil, Geoffery W. Tregear, Terry Koerner, Benjamin A. Barnes, Edgar Haber
Journal: Circulation Research (1971)

The mechanism of conversion of angiotensin I to angiotensin II was studied in vivo in the pulmonary circulation of the intact anesthetized dog and in vitro in plasma by using L-Leu-anglotensin I, D-Leu-angiotensin I, and des-Leu-angiotensin I which had been synthesized by the solid-phase technique. None of the peptides were active in the rabbit aortic strip preparation; D-Leu-angiotensin I and des-Leu-angiotensin I gave less than 5% of the pressor response of L-Leu-angiotensin I in the pentolinium-treated rat. D-Leu-angiotensin I and des-Leu-angiotensin I were not converted to angiotensin II when incubated with diluted human or dog plasma or partially purified converting enzyme from dog plasma. In a single pulmonary circulation time, following injection of a 20-nmole bolus of L-Leu-angiotensin I into the dog right ventricle, 56% of the material recovered had been converted to angiotensin II, as measured by radioimmunoassay. Conversion was accompanied by a rise in mean blood pressure of 30 mm Hg. After injection of equimolar amounts of D-Leu-angiotensin I and des-Leu-angiotensin I, no generation of angiotensin II and no pressor response occurred. These observations indicate that pulmonary conversion in vivo and plasma conversion in vitro occur via a dipepridylcarboxypeptidase and that a D-amino acid at the C-terminus prevents conversion.
Exome Sequencing in the Clinical Diagnosis of Sporadic or Familial Cerebellar Ataxia
Authors: Brent L. Fogel, Hane Lee, Joshua L. Deignan, Samuel P. Strom, Sibel Kantarci, Xizhe Wang, Fabiola Quintero-Rivera, Eric Vilain, Wayne W. Grody, Susan Perlman, Daniel H. Geschwind, Stanley F. Nelson
Journal: JAMA Neurology (2014)

<h3>Importance</h3> Cerebellar ataxias are a diverse collection of neurologic disorders with causes ranging from common acquired etiologies to rare genetic conditions. Numerous genetic disorders have been associated with chronic progressive ataxia and this consequently presents a diagnostic challenge for the clinician regarding how to approach and prioritize genetic testing in patients with such clinically heterogeneous phenotypes. Additionally, while the value of genetic testing in early-onset and/or familial cases seems clear, many patients with ataxia present sporadically with adult onset of symptoms and the contribution of genetic variation to the phenotype of these patients has not yet been established. <h3>Objective</h3> To investigate the contribution of genetic disease in a population of patients with predominantly adult- and sporadic-onset cerebellar ataxia. <h3>Design, Setting, and Participants</h3> We examined a consecutive series of 76 patients presenting to a tertiary referral center for evaluation of chronic progressive cerebellar ataxia. <h3>Main Outcomes and Measures</h3> Next-generation exome sequencing coupled with comprehensive bioinformatic analysis, phenotypic analysis, and clinical correlation. <h3>Results</h3> We identified clinically relevant genetic information in more than 60% of patients studied (n = 46), including diagnostic pathogenic gene variants in 21% (n = 16), a notable yield given the diverse genetics and clinical heterogeneity of the cerebellar ataxias. <h3>Conclusions and Relevance</h3> This study demonstrated that clinical exome sequencing in patients with adult-onset and sporadic presentations of ataxia is a high-yield test, providing a definitive diagnosis in more than one-fifth of patients and suggesting a potential diagnosis in more than one-third to guide additional phenotyping and diagnostic evaluation. Therefore, clinical exome sequencing is an appropriate consideration in the routine genetic evaluation of all patients presenting with chronic progressive cerebellar ataxia.
Reversal of Left Ventricular Dysfunction after Renal Transplantation
Authors: Richard K. Burt
Journal: Annals of Internal Medicine (1989)

We report the cases of four patients with end-stage renal disease and New York Heart Association class III or IV heart failure of nonischemic origin as documented by coronary angiography. Because of left ventricular dysfunction (left ventricular end-diastolic pressure, 23 to 30 mm Hg; ejection fraction, 20% to 35%), all four patients were initially considered poor surgical candidates for renal transplantation. These same four patients became asymptomatic, however, with markedly improved cardiac function (ejection fraction, 43% to 69%) detected as early as 6 and 14 days after renal engraftment. Therefore, there exists a subset of patients with end-stage renal disease in whom congestive heart failure should not be considered a contraindication to renal transplantation. We conclude that some dialysis-dependent patients who manifest symptomatic heart failure of nonischemic origin have a reversible cardiomyopathy and should not be denied renal transplantation.
Letter: Adjustment of plasma calcium measurements.
Authors: R W Marshall, B E Nordin
Journal: BMJ (1974)

clude the possibility of a direct effect of metoclopramide and propantheline on absorption across the intestinal mucosa.We have tested the effects of these compounds and of phenobarbitone on D-xylose absorption from rat small intestine in vitro.Everted sacs were used with Krebs phosphate buffer containing calci,um and glucose.' Transport of 50 mM xylose was measured with a concentration gradient- that is, with buffer only and no xylose initially within the sac.The drugs were added to the mucosal and serosal solutions of alternative sacs at a concentration of 1 rmnol/l.Phenobarbitone and metoclopramide significantly reduced xylose transport but propantheline had no such effect.Our finding of inhibition by metoclo- pramide agrees with the clinical findings of Kendall' in individuals with normal gastro- intestinal function.He also showed that propantheline increased urinary excretion, and presumably intestinal absorption, of xylose in one case of carcinoid syndrome.No such effect of propantheline was ob- served in our investigation in vitro.The in-situ intestinal loop preparation with anaesthetized rats has been used to study antibiotic absorption.This showed good correlation when predicting antibiotic absorption in man.By contrast, results with the everted sac as a model for gastro- intestinal absorption had to be interpreted with extreme caution.5Our results agree with this latter view.Thus phenobarbitone6 and metoclopramide show similar effects on xylose absorption both in vivo and in vitro but there is no such correlation with pro- pantheline.-Weare, etc.,
Renal handling of uric acid in normal and gouty subject: evidence for a 4-component system.
Authors: D J Levinson, L B Sorensen
Journal: Annals of the Rheumatic Diseases (1980)

Bidirectional renal urate tranport was studied in both control and gouty subjects. 99.3% of filtered urate undergoes reabsorption as assessed by pyrazinamide suppression of urate secretion. The maximum uricosuric response to benzbromarone, equated with the minimum secretory rate, amounted to 50% of the filtered load in normal persons and was lower in gouty normoproducers. Since benzbromarone selectively inhibits reabsorption of secreted urate, the difference between secreted and excreted uric acid becomes a valid measure of urate reabsorption distal to the secretory site and amounts to 80% of the secreted load in both groups. These data conform to a 4-component model of renal urate handling in man.
OSMOTIC ACTIVITY OF TISSUES DURING FETAL AND POSTNATAL GROWTH
Authors: Eugene L. Opie
Journal: The Journal of Experimental Medicine (1954)

The osmotic pressure maintained by liver tissue of the white rat preceding birth is less than that of the maternal blood serum and shortly after birth approximates this level. Following birth osmotic pressure of liver tissue, continuing to increase, reaches after about 60 to 90 days the level found in the liver of mature animals and is then isotonic with solutions of sodium chloride with concentration slightly more than twice that isotonic with blood serum. Osmotic pressure maintained by kidney tissue pursues with growth a similar course but at a lower level and about 35 to 60 days after birth reaches that found in the mature animal being represented by isotonicity with a concentration of sodium chloride slightly less than twice that isotonic with blood serum. The tissues of the whole fetus are isotonic with sodium chloride solutions less concentrated than that isotonic with the maternal blood serum.
Keratinocytes cultured from patients with Hailey-Hailey disease and Darier disease display distinct patterns of calcium regulation
Authors: P.T. Leinonen, R.M. Myllyla, P.M. Hagg, J. Tuukkanen, J. Koivunen, S. Peltonen, A. Oikarinen, T. Korkiamaki, J. Peltonen
Journal: British Journal of Dermatology (2005)

Hailey-Hailey disease (HHD) (OMIM 16960) and Darier disease (DD) (OMIM 124200) are dominantly inherited acantholytic skin diseases, respectively, caused by mutations in the genes encoding the Golgi secretory pathway Ca2+-ATPase (SPCA1, ATP2C1) and the sarco/endoplasmic reticulum Ca2+-ATPase type 2 (SERCA2, ATP2A2) genes.To investigate calcium regulation in keratinocytes cultured from patients with HHD and DD by measuring intracellular calcium resting levels and the cellular responses to ATP and thapsigargin.The study was carried out using keratinocyte cultures established from four patients with HHD and four with DD. Calcium concentrations were measured with fluorescence ratio imaging using fura-2 loading.Control and HHD keratinocytes displayed approximately the same Ca2+ levels in resting phase, while DD keratinocytes showed elevated Ca2+ levels. Application of ATP caused less pronounced elevation of intracellular calcium concentration ([Ca2+]i) in both HHD and DD keratinocytes than in control cells. HHD keratinocytes did not lower their [Ca2+]i as efficiently as control keratinocytes after treatment with thapsigargin. In addition, DD keratinocytes were practically incapable of lowering their [Ca2+]i after treatment with thapsigargin.The results demonstrate that the defects in SPCA1 and SERCA2 calcium ATPases result in distinct patterns of calcium metabolism. This is also supported by the different clinical features of the diseases.
IgE and IgG antibody responses to cat and dust mite allergen over the first five years: Influence of maternal immune responses
Authors: D.M. Riposo, E.A. Erwin, N.J. Custis, K. Blumenthal, M. Barr, D. Sredl, H.A. Burge, D.R. Gold, T.A.E. Platts-Mills
Journal: Journal of Allergy and Clinical Immunology (2003)
Visual analogue scores and urinary incontinence.
Authors: M I Frazer, J R Sutherst, E F Holland
Journal: BMJ (1987)

9-77 (5 20) and 5 57 (4 05) (t=2-18; p<005).A significant inverse correlation was found between the amount of tobacco used daily and the number of years preceding the onset of proteinuria in the uraemic patients (n=18; r=0 47; p<005) and controls (n=7; r=0-82; p<0-01).In the control group smokers more often than non-smokers had renal lesions (table).
DUTIES OF THE DERMATOLOGIST
Authors: H. H. HAZEN
Journal: JAMA (1918)

Under ordinary circumstances it would be both easy and proper to point out many duties that confront the specialist in general and the dermatologist in particular; but in these times it seems necessary to mention only a few. Accordingly, five phases will be considered, namely, the duties of the special societies, certain duties to the patient that have not been sufficiently recognized, the need for developing more and better dermatologic clinics, the arsphenamin situation, and lastly the duties to the country. <h3>THE WORK BEFORE DERMATOLOGISTS</h3> For years many of us have felt that the various societies composed of specialists, as well as many of the special sections of the American Medical Association, have not fulfilled all that might be reasonably expected of them. They are rather pleasant social meetings with a sprinkling of good papers and some valuable discussion, both public and private, rather than beacons in the progress of
Failing to Plan Is Planning to Fail: Improving the Quality of Care With Survivorship Care Plans
Authors: Craig C. Earle
Journal: Journal of Clinical Oncology (2006)

The recent Institute of Medicine report “From Cancer Patient to Cancer Survivor: Lost in Transition” recommended the creation of survivorship care plans for patients as they complete primary therapy for cancer to ensure clarity for all involved about patients’ diagnoses, treatments received, and surveillance plans. Any previously existing follow-up guidelines for cancer survivors have been largely restricted to surveillance for recurrence of the primary disease. An important message of the Institute of Medicine report is that survivorship care plans must surpass this and address the chronic effects of cancer (pain, fatigue, premature menopause, depression/anxiety), monitoring for and preventing late effects like osteoporosis, heart disease, and second malignancies, and promoting healthy lifestyles. It should explicitly identify the providers responsible for each aspect of ongoing care and provide information on resources available for psychosocial and other practical issues that may arise as a result of the prior cancer diagnosis. Although having some sort of a plan is clearly necessary to achieve high quality care, there are practical barriers to formal off-treatment consultations and the creation of written documents that may become part of the medical record. This article reviews the elements of the proposed survivorship care plan and discusses areas of research and development needed to make them part of standard oncology practice.