tbuckley/cabot-search huggingface dataset:
THE PASSING OF CHRONIC RHEUMATISM.
Authors: JAMES J. WALSH
Journal: JAMA (1903)

In response to the question, "Have you ever suffered from rheumatism?" addressed to the ordinary patient over 40 years of age, the physician seldom gets a negative answer. Even younger patients will tell of having had vague pains in their arms or shoulders, or in their knees or ankles, that they consider to have been rheumatic. Popularly, the notion is that rheumatism is one of the ills to which flesh is almost inevitably heir, and, in the course of time, practically every one is supposed to have some touches of it. It is not too much to say, then, that rheumatism is popularly considered to be practically, a universal disease. Physicians encouraged this idea, to a certain extent at least, by suggesting that vague pains are rheumatic in origin, or at least agreeing with patients when they say that probably they have rheumatism. As a matter of fact, many
A Patient with Cubilin Deficiency
Authors: Tina Storm, Francesco Emma, Pierre J. Verroust, Jens Michael Hertz, Rikke Nielsen, Erik Ilsø Christensen
Journal: New England Journal of Medicine (2011)

To the Editor: Imerslund–Grasbeck syndrome, or megaloblastic anemia 1, is a rare autosomal recessive disorder characterized by selective intestinal malabsorption of intrinsic factor–vitamin B12; it...
Risk characterization framework for noncancer end points.
Authors: T K Pierson, R G Hetes, D F Naugle
Journal: Environmental Health Perspectives (1991)

The nature of both indoor air exposures and noncancer end points present significant issues for risk characterization. Noncancer end points are multidimensional, affecting various organs, and are assumed to have thresholds. Symptoms also vary in severity within a population. In addition to the complexity of noncancer risk assessment, indoor air exposures are typified by the presence of complex mixtures, which further complicates the complex nature of noncancer risk characterization. Most noncancer risk assessment efforts have focused on defining acceptable daily intakes or reference doses (RfD) rather than estimating incidence and severity of the wide range of effects within an exposed population. The risk characterization framework has been developed to accommodate the RfD approach but, more importantly, to address the multidimensional nature of noncancer risk characterization. Newly emerging methods and standard EPA risk assessment guidelines for noncancer effects and complex mixtures were used as guides for developing the framework. Information and data needs have been identified from the framework. Peak, average, and cumulative doses from indoor air exposures are highly dependent on variable indoor air concentrations and affected by time-activity patterns. Susceptibility also plays a significant role in noncancer end points and, unlike susceptibility in cancer risk assessment, is quantifiable. This paper highlights the risk characterization framework for noncancer health risks that we developed in cooperation with the U.S. Environmental Protection Agency Environmental Criteria and Assessment Office. Additionally, a preliminary application of the framework to a complex mixture of volatile organic compounds from indoor sources is illustrated.
13-year renal outcomes varied in patients with type 1 diabetes and new-onset microalbuminuria
Authors: David R. Gutknecht
Journal: Annals of Internal Medicine (2011)

Source Citation de Boer IH, Rue TC, Cleary PA, et al. Long-term renal outcomes of patients with type 1 diabetes mellitus and microalbuminuria: an analysis of the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications cohort. Arch Intern Med. 2011;171:412-20. 21403038
Immunogenicity and safety of a two-dose schedule of whole-virion and AS03A-adjuvanted 2009 influenza A (H1N1) vaccines: a randomised, multicentre, age-stratified, head-to-head trial
Authors: Karl G Nicholson, Keith R Abrams, Sally Batham, Tristan W Clark, Katja Hoschler, Wei Shen Lim, Marie-Jo Medina, Jonathan S Nguyen-Van-Tam, Robert C Read, Fiona C Warren, Maria Zambon
Journal: The Lancet Infectious Diseases (2010)
Renal fibrosis: not just PAI-1 in the sky
Authors: Agnes B. Fogo
Journal: Journal of Clinical Investigation (2003)

A delicate balance exists between ECM synthesis and degradation such that interruption of the corresponding pathways results in increased plasminogen activator inhibitor-1 (PAI-1), pathological matrix accumulation, and glomerulosclerosis. A new study demonstrates that therapy with a mutant PAI-1 increases matrix turnover and reduces glomerulosclerosis by competing with endogenous PAI-1, suggesting therapeutic utility in the treatment of fibrotic renal disease.
Advances in the Neuropharmacology of Parkinsonism
Authors: Donald B. Calne, John Kebabian, Ellen Silbergeld, Edward Evarts
Journal: Annals of Internal Medicine (1979)

Advances through basic research have elucidated the disturbances of neurotransmitter function in Parkinson's disease, with findings directly applicable to drug therapy. Dopamine has replaced acetylcholine and norepinephrine as the most studied neurotransmitter, with both conceptual and practical developments, exemplified by the hypothesis of cyclic adenosine monophosphate as a "second messenger," and new therapeutic agents. We now have rationally designed in-vitro and in-vivo tests for the evaluation of dopaminergic compounds instead of entirely empiric screening procedures. We are starting to identify different categories of dopaminergic receptors and to manipulate them selectively, with gains in understanding the physiologic input to the striatum. Crucial questions remain, including how dopamine modulates striatal output and what causes the parkinsonian degeneration of the nigrostriatal pathway. Developing knowledge on synaptic physiology and pharmacology may lead to better therapy.
Diurnal variation of urinary histamine and 1‐methylhistamine excretion in healthy children
Authors: S. Schulze, B. Niggemann, A. N. Savaser, U. Wahn
Journal: Allergy (1992)

In order to establish a noninvasive method of monitoring immediate hypersensitivity reactions in children, we studied the diurnal variation of urinary histamine and 1‐methylhistamine excretion and the influence of food intake in a group of 14 healthy nonatopic children (aged 2–16 years). Histamine and 1‐methylhistamine in spontaneous urine samples were determined by radioimmunoassay. Mean variation of 2–h intervals was much higher for urinary histamine than for 1‐methylhistarnine (45% of base‐line level versus 24%). There was no circadian rhythm or influence of food intake. The short half‐life of histamine released into blood circulation may be the main reason for the higher variation of histamine excretion. In children, urinary 1‐methylhistamine is less influenced by diurnal variation and is therefore more suited to monitor immediate hypersensitivity reactions than urinary histamine itself.
Haplotype analysis andAγ gene polymorphism associated with the Brazilian type of hereditary persistence of fetal hemoglobin
Authors: Silvana Bordin, Juliana T. Martins, Marilda S. Gonçalves, Mônica B. Melo, Sara T. O. Saad, Fernando F. Costa
Journal: American Journal of Hematology (1998)

We have identified three unrelated individuals and three members of a family with the non-deletion form of Aγ–hereditary persistence of fetal hemoglobin (HPFH). Molecular analysis showed that each individual is a heterozygote for a previously described −195 Aγ (C→G) mutation. The β-globin gene cluster was studied using the polymerase chain reaction and related techniques. Haplotyping using nine restriction sites identified two closely related chromosomes with the −195 Aγ mutation, differing only in a single site 3′ to the β-globin gene. Further analysis of β-globin framework indicated that the HPFH allele segregates with haplotype V, according to Orkin's classification. The second haplotype probably originated by a point mutation or DNA rearrangement of a pre-existing −195Aγ chromosome. We also determined the sequences from −622 to +55 bp upstream to the Aγ gene and part of the Aγ IVS-2. We found four polymorphisms associated to the −195Aγ promoter region. All −195A γ chromosomes had a G at positions −588 and +25 relative to the Aγ gene. One individual was also homozygous for polymorphisms at −398 (G→A), and another at −369 (C→G). Cloning and sequencing of the polymorphic patterns of the 3′ region of Aγ IVS-2 showed that the mutated allele is linked to β-globin chromosome B. Some correlations between chromosome characteristics and Aγ point mutations were also observed. Am. J. Hematol. 58:49–54, 1998. © 1998 Wiley-Liss, Inc.
Enterotoxigenic<i>Escherichia coli</i>— An Emerging Pathogen
Authors: R. Bradley Sack
Journal: New England Journal of Medicine (1976)

The past eight years have witnessed the emergence of a new era in the understanding of diarrheal diseases. The characterization of the biochemical lesion induced by the protein enterotoxin of Vibrio cholerae makes cholera probably the best understood, at the molecular level, of all infectious diseases. Benign-appearing but enterotoxin-producing Escherichia coli have been recognized as important worldwide etiologic agents in diarrheal illness of children and adults,1 and more recently reovirus-like agents were found to account for a major portion of diarrheal illness in early childhood.2 Whereas 10 years ago recognizable pathogens could be identified in only 25 per cent of . . .
A comparison of 2 weeks of terbinafine 250 mg/day with 4 weeks of itraconazole 1OO mg/day in plantar-type tinea pedis
Authors: R.J. HAY, J.M. McGREGOR, J. WUITE, K.S. RYATT, C.Z. EGLER, Y.M. CLAYTON
Journal: British Journal of Dermatology (2006)

This double-blind, parallel group study compared a 2-week course of terbinafine 250 mg/day with a 4-week course of itraconazole 100 mg/day. A total of 190 patients were enrolled, of whom 129 were evaluable for efficacy. At week 8, 69% of patients treated with terbinafine were classified as effectively treated (mycological cure, and clinical assessment total score < or = 2) vs. 67% in the itraconazole group. At week 16, however, the rating for effective treatment increased to 71% of the terbinafine group, but decreased to 55% of the itraconazole group. This difference was of borderline statistical significance (P = 0.06). The results of this study demonstrate that both drugs can be used safely, and that 2 weeks' treatment with terbinafine 250 mg daily is as effective as 4 weeks' treatment with itraconazole 100 mg daily, but with fewer long-term relapses.
Determination of numbers of lead-exposed women of childbearing age and pregnant women: an integrated summary of a report to the U.S. Congress on childhood lead poisoning.
Authors: A F Crocetti, P Mushak, J Schwartz
Journal: Environmental Health Perspectives (1990)

In a Congressionally mandated study carried out under the aegis of the U.S. Agency for Toxic Substances and Disease Registry (ATSDR) and summarized in this article, the authors have provided estimates of the numbers of American women of childbearing age and the numbers of American pregnant women whose lead exposure is sufficiently elevated to pose an intrauterine toxicity risk. Exposures associated with such risk were defined as blood lead (PbB) levels greater than 10, greater than 15, greater than 20, and greater than 25 micrograms/dL. Using PbB prevalence projection techniques based on the Second National Health and Nutrition Examination Survey (NHANES II), we first generated projected 1984 prevalences of these PbB levels in white and black women of childbearing age, ages 15 to 19 and 20 to 44. White women in the two age bands had rates of PbBs greater than 10 micrograms/dL of 9.2 and 9.7%, respectively. For black women, the corresponding rates were 8.2 and 19.7%, respectively. Combining these rates with standard metropolitan statistical areas (SMSAs) based 1980 Census and other population enumerations show, for example, that 4.4 million U.S. women of childbearing age are estimated to have had PbBs greater than 10 micrograms/dL. Pregnant black and white women in U.S. SMSAs are approximately 9% of the U.S. black and white childbearing age total, i.e. 3.6 million out of a 41.3 million SMSA total. Of these, 403,200 pregnant women were estimated to have PbB levels greater than 10 micrograms/dL.(ABSTRACT TRUNCATED AT 250 WORDS)
A piece of my mind. Cold feet
Authors: P. D. Danielson
Journal: JAMA (1991)

Slush was common in March. The upstate New York snow could never accomplish its task of melting. Instead it would linger for a month and quietly aggravate everything. People tracked it into buildings and dripped it onto car floormats. Nothing short of rubber boots would protect one's feet, but that was an empty victory since trouser legs collected the splatter anyway. For those fated to live in the city, slush was the unavoidable precursor to spring. The medical center housekeeping staff saw a challenge in this winter morass. However, their custodial efforts never stopped the seepage of another inclemency. No one could sufficiently define it or explain it, but everyone recognized the "blahs." The attendings grew more critical, the nurses more exacting, the residents more exhausted, and the patients more difficult. The affliction struck medical students in similar form. I was slouched in the second-year lecture hall as slide after
Methylprednisolone and Cyclophosphamide, Alone or in Combination, in Patients with Lupus Nephritis
Authors: Mark F. Gourley
Journal: Annals of Internal Medicine (1996)

Background: Uncertainty exists about the efficacy and toxicity of bolus therapy with methylprednisolone or of the combination of methylprednisolone and cyclophosphamide in the treatment of lupus nephritis. Objective: To determine 1) whether intensive bolus therapy with methylprednisolone is an adequate substitute for bolus therapy with cyclophosphamide and 2) whether the combination of methylprednisolone and cyclophosphamide is superior to bolus therapy with methylprednisolone or cyclophosphamide alone. Design: Randomized, controlled trial with at least 5 years of follow-up. Setting: Government referral-based research hospital. Patients: 82 patients with lupus nephritis who had 10 or more erythrocytes per high-power field, cellular casts, proteinuria (>1 g of protein per day), and a renal biopsy specimen that showed proliferative nephritis. Interventions: Bolus therapy with methylprednisolone (1 g/m2 body surface area), given monthly for at least 1 year; bolus therapy with cyclophosphamide (0.5 to 1.0 g/m2 body surface area), given monthly for 6 months and then quarterly; or bolus therapy with both methylprednisolone and cyclophosphamide. Measurements: 1) Renal remission (defined as <10 dysmorphic erythrocytes per high-power field, the absence of cellular casts, and excretion of <1 g of protein per day without doubling of the serum creatinine level), 2) prevention of doubling of the serum creatinine level, and 3) prevention of renal failure requiring dialysis. Results: Renal remission occurred in 17 of 20 patients in the combination therapy group (85%), 13 of 21 patients in the cyclophosphamide group (62%), and 7 of 24 patients in the methylprednisolone group (29%) (P < 0.001). Twenty-eight patients (43%) did not achieve renal remission. By life-table analysis, the likelihood of remission during the study period was greater in the combination therapy group than in the methylprednisolone group (P = 0.028). Combination therapy and cyclophosphamide therapy were not statistically different. Adverse events were amenorrhea (seen in 41% of the cyclophosphamide group, 43% of the combination therapy group, and 7.4% of the methylprednisolone group), cervical dysplasia (seen in 11% of the cyclophosphamide group, 7.1% of the combination therapy group, and 0% of the methylprednisolone group), avascular necrosis (seen in 11% of the cyclophosphamide group, 18% of the combination therapy group, and 22% of the methylprednisolone group), herpes zoster (seen in 15% of the cyclophosphamide group, 21% of the combination therapy group, and 3.7% of the methylprednisolone group) and at least one infection (seen in 26% of the cyclophosphamide group, 32% of the combination therapy group, and 7.4% of the methylprednisolone group). Conclusions: Monthly bolus therapy with methylprednisolone was less effective than monthly bolus therapy with cyclophosphamide. A trend toward greater efficacy with combination therapy was seen.
Enhanced atrioventricular conduction in patients without preexcitation syndrome: relation to heart rate in paroxysmal reciprocating tachycardia.
Authors: D G Benditt, M L Epstein, C E Arentzen, J M Kriett, G J Klein
Journal: Circulation (1982)

We studied the electrophysiologic characteristics of atrioventricular (AV) nodal conduction in patients with reciprocating tachycardia (RT) without ventricular preexcitation, and the relation of these characteristics to RT cycle length (CL). Thirty-five symptomatic patients who had a normal PR interval (0.13-0.20 second) during sinus rhythm underwent detailed intracardiac electrophysiologic study during which ventricular preexcitation was excluded, and the RT mechanism was determined. RT was due to reentry using an accessory AV pathway capable of conduction only in the retrograde direction (concealed AP) in 13 patients (37%) and to reentry within the AV node in 22 (63%). Dynamic properties of AV conduction (assessed by degree of AH prolongation during progressive increase in atrial pacing rate) were normally distributed (p less then 0.005); 12 patients (34%) fulfilled the criteria for enhanced AV conduction (EAVC). The patients with EAVC had a shorter RT CL than did patients without EAVC (294 +/- 43.3 msec vs 360 +/- 68.1 msec, p less than 0.01). However, CL differences were primarily due to the influence of EAVC in the subgroup of patients with RT using a concealed AP (EAVC CL, 274 +/- 35.1 msec; without EAVC, 326 +/- 15.7 msec, p less than 0.005). The RT CL in patients with reentry within AV node was not measureable influenced by concomitant EAVC (EAVC, 314 +/- 43.8 msec; without EAVC, 376 +/- 76.8 msec) (NS). This study suggests that despite the presence of a normal PR interval during sinus rhythm, dynamic AV conduction responses can vary widely in patients with RT. In patients with RT using a concealed AP, but not in those with reentry within the AV node, coexisting diminished physiologic AV conduction slowing may be associated with more rapid tachycardia rates.
Targeted mutation of mouse skeletal muscle sodium channel produces myotonia and potassium-sensitive weakness
Authors: Lawrence J. Hayward, Joanna S. Kim, Ming-Yang Lee, Hongru Zhou, Ji W. Kim, Kumudini Misra, Mohammad Salajegheh, Fen-fen Wu, Chie Matsuda, Valerie Reid, Didier Cros, Eric P. Hoffman, Jean-Marc Renaud, Stephen C. Cannon, Robert H. Brown
Journal: Journal of Clinical Investigation (2008)

Hyperkalemic periodic paralysis (HyperKPP) produces myotonia and attacks of muscle weakness triggered by rest after exercise or by K+ ingestion. We introduced a missense substitution corresponding to a human familial HyperKPP mutation (Met1592Val) into the mouse gene encoding the skeletal muscle voltage-gated Na+ channel NaV1.4. Mice heterozygous for this mutation exhibited prominent myotonia at rest and muscle fiber-type switching to a more oxidative phenotype compared with controls. Isolated mutant extensor digitorum longus muscles were abnormally sensitive to the Na+/K+ pump inhibitor ouabain and exhibited age-dependent changes, including delayed relaxation and altered generation of tetanic force. Moreover, rapid and sustained weakness of isolated mutant muscles was induced when the extracellular K+ concentration was increased from 4 mM to 10 mM, a level observed in the muscle interstitium of humans during exercise. Mutant muscle recovered from stimulation-induced fatigue more slowly than did control muscle, and the extent of recovery was decreased in the presence of high extracellular K+ levels. These findings demonstrate that expression of the Met1592ValNa+ channel in mouse muscle is sufficient to produce important features of HyperKPP, including myotonia, K+-sensitive paralysis, and susceptibility to delayed weakness during recovery from fatigue.
Recovery of the Immune System With Antiretroviral Therapy
Authors: William G. Powderly, Alan Landay, Michael M. Lederman
Journal: JAMA (1998)

Objective.—Clinical care of people infected with human immunodeficiency virus (HIV) has been substantially affected by the introduction of potent antiretroviral therapy. Changes in the immune system after such therapy and the clinical consequences are important issues for clinicians treating patients with HIV.Data Sources.—A systematic review of MEDLINE, 1993 to January 1998, of peer-reviewed publications, abstracts from national and international conferences, and product registration information through January 1998.Study Selection and Data Extraction.—Criteria used to select studies include relevance to immune reconstitution with potent antiretroviral therapy and having been published in the English language. Assessment of data quality and validity included consideration of venue of the publication and relevance to practice.Data Synthesis.—Suppression of viral replication after administration of potent antiretroviral therapy that includes inhibitors of the HIV-1 protease is associated with quantitative and qualitative changes in the immune system. In patients with relatively advanced disease, there is a first-phase rise (during the initial 3 months) in both naive and memory CD4+ and CD8+ T lymphocytes and B lymphocytes. This is followed by a slower second-phase increase (after 3 months) in cells primarily of the naive CD4+ and CD8+ phenotypes. These quantitative changes are associated with qualitative improvements in host immune responses, best characterized by dramatically reduced risk of opportunistic infection. Restoration of the immune system during the first year of potent antiretroviral therapy is partial at best.Conclusions.—Potent antiretroviral therapy has become the standard of care for people with HIV infection, and its use has led to significant reductions in the incidence of the acquired immunodeficiency syndrome (AIDS) and in mortality from HIV infection. Although incomplete, considerable immune recovery occurs, sufficient, in most cases, to provide adequate protection against most AIDS-associated opportunistic infections.
A Case of Congenital Cyanosis, in which a Patent Foramen Ovale was Associated with a Presystolic Basic Murmur
Authors: G. Johnson
Journal: BMJ (1878)

such physical signs, when in association, are evidence of aneurism, and of no other kind of tumour, let it be glandular, cancerous, hydatid or other, or of psoas or iliac abscess.Situation of the Aneurism.-Inboth, it was looked upon as of the abdominal aorta, near its bifurcation.The position and the immo- bility of the pulsating tumour, together with the neuralgic pains in the spine, pointed to the correctness of the supposition; while the fact that the cure of the aneurism, in Case No. ii, was accompanied by the disappearance of the pulse in the femoral arteries, rendered the possi- bility of the aneurism being situated in the inferior mesenteric artery, or in one of its branches, as highly improbable.Etiology.-Both patients were under thirty years of age.The history of previous syphilis in the second was clear.The supposition, there- fore, that in both the lesion of the arterial coats was inflammatory in nature, and not atheromatous, was rendered very certain.If it be true that, in this lesion, an inflammatory process commences just external to the lining membrane, leading to a deposition of lymph there, producing elevation of the internal surface, and, as a consequence of the pressure and of the interruption of the nutrient supply, atrophy and erosion of the endarterial membrane, it may readily be understood how easily the already thinned arterial wall will dilate, and become in time converted into a lateral sacculated aneurism.Anatomical or Specific Character of the Aneurism.-Inbotlh, it was