tbuckley/cabot-search huggingface dataset:
Behcet's Syndrome with Neurological Involvement
Authors: R. T. Williams
Journal: BMJ (1958)

fever or acute rheumatoid arthritis, and stresses its brief duration in the tuberculous cases.The case reported here would appear to fulfil these criteria.It is interesting to recall in this connexion the well-authenticated syndrome of erythema nodosum, arthralgia, and hilar lymph-node enlarge- ment, which is a common presentation of sarcoidosis (James et al., 1956).The association between pleurisy and " tuber- culous rheumatism " has been described by Poncet (1902) and Schneider (1903).As in the case of tuberculous rheumatism itself, it is not possible to evaluate many of these older reports in the light of the stricter diagnostic concepts of to-day.
Delivering Bad News-Reply
Authors: J. T. Ptacek
Journal: JAMA (1996)

In Reply.  —The thoughtful comments made by the authors of the letters in response to our article prompted several thoughts of our own. First, it was encouraging to be provided with information about the apparently effective use of SPs in the training of medical personnel. Such an approach will be most effective when integrated with other training experiences that help explicate the personal, interpersonal, and institutional processes that make bad news transactions potentially problematic for giver and receiver. Without this integration, trainees may be left with a heightened sense of anxiety, as they recognize that such transactions are important enough to warrant a workshop, but have an insufficient theoretical or social context in which to place their new skills. More detailed aspects of various training programs also have been reported.1-2  Second, some evidence suggests that for certain medical conditions, such as cancer, social support can have lasting positive effects.3Conversely,
Medical and ethical issues in genetic screening--an academic view.
Authors: N A Holtzman
Journal: Environmental Health Perspectives (1996)

This article is intended to acquaint those whose principal concerns are the health and safety of workers with genetic screening and some of the medical and ethical issues it raises. Population-based genetic screening increasingly is being considered for predicting future disease in the person being screened. A major problem in screening for alleles that contribute to the development of common, multifactorial disorders is low sensitivity and positive predictive value. In many instances, no demonstrably effective prophylaxis or treatment is available to help those with positive test results. This creates ethical problems of assuring that testing is in the person's best interest and raises in turn issues of autonomy, discrimination, and privacy. Instead of screening for genetic predispositions to harm from workplace exposures, other means of improving the health of workers may bring greater benefits to a higher proportion of workers. The current state of genetic tests for chronic beryllium disease are considered. None are suitable for screening.
Myocardial Perfusion Imaging Is a Strong Predictor of Death in Women
Authors: Mario Sergio Julio Cerci, Juliano Julio Cerci, Rodrigo Julio Cerci, Carlos Cunha Pereira Neto, Evelinda Trindade, Dominique Delbeke, Claudio L. Pereira da Cunha, João Vicente Vitola
Journal: JACC. Cardiovascular imaging (2011)
TARGETED MYBPC3 KNOCK-OUT MICE WITH NON-OBSTRUCTIVE HYPERTROPHIC CARDIOMYOPATHY EXHIBIT STRUCTURAL MITRAL VALVE ABNORMALITIES
Authors: Hani Nematalla, Nicolas Vignier, Daniel P. Judge, Robert A. Levine, Michel Desnos, Emmanuel Messas, Lucie Carrier, Albert A. Hagege
Journal: Journal of the American College of Cardiology (2011)
ECONOMIC MODELING OF COST-EFFECTIVENESS FOR NEW STENT PLATFORM DESIGNS: THE TAXUS ELEMENT (ION) STENT COMPARED TO THE BARE METAL EXPRESS STENT IN SMALL VESSELS MODELED TO DETERMINE COST EFFICACY
Authors: Mark A. Turco, Louis A. Cannon, Stacey L. Amorosi, Sean Stern, Timothy M. Stivland, Paul Underwood, Greg de Lissovoy, Anuraag R. Kansal
Journal: Journal of the American College of Cardiology (2011)
Points: Big versus small maternity units
Authors: J E U Moxon
Journal: BMJ (1982)

A Ledermann and colleagues (12 June, p 1784) reporting thrombocytopenia following benoxaprofen therapy.They state that thrombocytopenia associated with benoxaprofen has not been reported before.We reported thrombocytopenia in association with leucopenia and toxic epidermal necrolysis in a 62- year-old woman after only nine days' treatment with benoxaprofen, and this was published in May 1982.
Computer-Based Interview for Screening Blood Donors for Risk of HIV Transmission
Authors: Steven E. Locke
Journal: JAMA (1992)

To test the ability of a computer-based interview to detect factors related to the risk of the human immunodeficiency virus (HIV) among potential blood donors and to determine donor reactions to the use of the interview.A comparison of the rate of detection of HIV-related factors elicited by a computer interview with that obtained by standard American Red Cross procedures for assessment of donor suitability, including a randomized crossover trial in which the order of the two methods was reversed. Information obtained by the computer was not available to influence the use of blood components for transfusion.The computer interview was administered to donors at an American Red Cross blood donor center and at a mobile blood drive at a hospital.Consecutive sample of 294 male and female blood donors 18 to 75 years of age.Subjects' responses to the computer-based interview as well as responses to the standard Red Cross written questionnaires and face-to-face interviews were used for donor assessment.The interview took an average of 8 minutes to complete. From among 272 donors who provided complete data, the computer identified 12 donors who reported either behaviors associated with a risk of HIV acquisition or symptoms compatible with the acquired immunodeficiency syndrome; none of these donors had been so identified either by routine written questionnaires or by face-to-face interviews used to screen potential blood donors. Only one of the 12 identified donors used the confidential unit exclusion procedure to prevent use of his donated unit. The rate of elicitation of HIV-related factors by the computer interview was 12 (4.4%) of 272 (95% confidence interval [CI], 2.3% to 7.6%), compared with two (0.13%) of 1536 (95% confidence upper bound, 0.28%) using the standard Red Cross procedure (P less than .0001). Tests for antibodies to HIV were negative in blood samples from all of the 272 subjects studied. The subjects enjoyed the computer interview and judged it to be more private than the standard donor assessment method. They also predicted that donors would be more honest with the computer interview than with a human interviewer.Computer-based screening elicits more HIV-related factors in the health histories of blood donors than do the standard questionnaire and interviewing methods currently in use. Computer-based screening is also acceptable to blood donors.
Predictive tests in Huntington's chorea.
Authors: M Segal
Journal: BMJ (1978)

with angina pectoris, especially for patients unable to tolerate beta-blockers.Even if the occasional patient does develop side effects such as those described, the fact that these are easily recognised and, in our experience to date, have always been reversible should provide reassurance to those who have doubts about prescribing this drug because of the development of neuropathy.
Hot flashes are associated with CYP2D6 genotype in breast cancer survivors taking tamoxifen.
Authors: L Madlensky, SW Flatt, L Natarajan, H Lawrence, D Nikoloff, M Fontecha, S Hao, G Hillman, A Johnson, BA Parker, JP Pierce
Journal: Cancer Research (2009)

Abstract Abstract #6045 Background: We have previously shown that participants in the Women's Healthy Eating and Living (WHEL) study comparison group who reported hot flashes after breast cancer treatment had more favorable disease-free survival than women who did not report hot flashes. However, this was not the case in the intervention group. The polymorphic CYP450 enzyme CYP2D6 catalyzes the conversion of tamoxifen (TAM) to one of its key active metabolites, endoxifen. Some studies have suggested that certain genetic variants of CYP2D6 are associated with a decreased likelihood of hot flashes, reduced endoxifen levels and an increased risk of disease recurrence in women receiving adjuvant TAM therapy. This analysis was performed to estimate the association between CYP2D6 genotype and hot flashes in early stage breast cancer survivors who took adjuvant TAM in the WHEL study.&amp;#x2028; Methods: The WHEL study was a randomized trial of a dietary intervention in breast cancer survivors, who enrolled in the study within 4 years of diagnosis from 1995-2000. Participants self-reported TAM use, hot flash severity and menopausal status at study entry. Clinical characteristics (tumor stage, estrogen receptor status, chemotherapy) were extracted from medical records. Blood samples were obtained by venipuncture, separated and stored at -80 deg. DNA was extracted from stored buffy coat and analyzed using the Roche AmpliChip CYP450 Test. Women were classified according to their predicted CYP2D6 phenotype as Extensive (EM), Heterozygous Extensive (Het EM), Intermediate (IM), Poor (PM), or Ultrarapid (UM) Metabolizers.&amp;#x2028; Results: Overall, 1434 WHEL participants had verified estrogen receptor-positive stage I or II breast cancers and reported taking TAM at baseline for at least 4 months. A total of 1411 women were successfully genotyped and their CYP2D6 phenotypes were classified as follows: 468 EM (33.2%); 665 Het EM(47.1%), 164 IM (11.6%), 86 PM (6.1%) and 28 UM (2.0%). In univariate analyses, there was a significant difference among CYP2D6 genotype in relation to hot flashes reported at baseline: 79.8% of EMs, 76.3% of Het EMs, 80.1% of IMs, 63.9% of PMs, and 75% of UMs reported hot flashes (χ2= 11.3, p=0.02). After controlling for age, menopausal status, and time since diagnosis, the PM group was half as likely to report hot flashes as the referent EM group (OR= 0.46; 95% CI= 0.28-0.78; p=0.003). Additional analyses of serum endoxifen levels and associations with disease outcome are underway.&amp;#x2028; Conclusion: In the WHEL study, women who were classified as Poor Metabolizers of TAM, based on their CYP2D6 genotype, were half as likely as Extensive Metabolizers to report experiencing hot flashes while receiving adjuvant TAM treatment for early stage breast cancer. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6045.
Inborn Errors of the Complement System of Man
Authors: K. Frank Austen
Journal: New England Journal of Medicine (1967)

TWO inborn errors of the complement system of man have been well documented: hereditary deficiency of the serum inhibitor of the activated first component of complement (C′1a) and hereditary deficiency of the second component of complement (C′2). To appreciate both the nature of the inborn errors and their possible consequences, it is necessary to review very briefly certain basic aspects of the complement system.The sequence in which the components of complement act in immune hemolysis is depicted in Figure 1; this scheme is based on studies by many investigators using both guinea pig and human complement (reviewed by Rapp and . . .
Dissection of Regenerating T-Cell Responses against Tuberculosis in HIV-infected Adults Sensitized by <i>Mycobacterium tuberculosis</i>
Authors: Katalin A. Wilkinson, Ronnett Seldon, Graeme Meintjes, Molebogeng X. Rangaka, Willem A. Hanekom, Gary Maartens, Robert J. Wilkinson
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

Combination antiretroviral treatment (cART) reduces the risk of tuberculosis in HIV-infected people. Therefore a novel approach to gain insight into protection against tuberculosis is to analyze the T cells that expand in people sensitized by Mycobacterium tuberculosis (MTB) during cART.To longitudinally analyze CD4 T-cell subsets during the first year of cART, from the time of starting cART (Day 0), in 19 HIV-infected, MTB-sensitized adults.Peripheral blood mononuclear cells were obtained on Day 0, Weeks 2, 4, 12, 24, 36, and 48 of cART and were stimulated with purified protein derivative (PPD) followed by flow cytometry to analyze surface markers and intracellular cytokines.CD4(+) T cells significantly increased during follow-up and the viral load fell to undetectable levels in each patient, indicating successful immune restoration. Central memory CD27(+)CD45RA(-) and CD27(+)CCR5(-) CD4(+) cells expanded by 12 weeks (P < 0.02) followed by naive CD27(+)CD45RA(+) cells at 36 weeks (P = 0.02). Terminally differentiated effector CD4(+)CD27(-)CCR7(-) cells decreased by 12 weeks (P = 0.02), paralleled by a proportional decline of PPD-specific CD4(+)IFN-gamma(+) cells (P = 0.02). However, the absolute numbers of PPD-specific IFN-gamma-producing cells, determined by enzyme-linked immunospot assay, increased (P = 0.02).Rapid effector responses are often measured when evaluating immunity. We show that although cART is associated with an absolute increase in effector function, the proportional response decreased and the strongest correlate of increased cART-mediated immunity in this study was the central memory response.
[187] PORTAL HYPERTENSION CONTRIBUTES TO SPATIAL REFERENCE MEMORY DEFICIT IN THE RAT
Authors: M.A. Aller, M. Mendez, M. Mendez-Lopez, F. Sanchez-Patan, L. Lopez, R. Anchuelo, I. Mejia, J. Arias, J.L. Arias
Journal: Journal of Hepatology (2007)
750 Is PDC-E3BP (protein X) a T-cell autoantigen in primary biliary cirrhosis?
Authors: A MCHUGH, J PALMER, S YEAMAN, D JONES
Journal: Hepatology (2003)

Primary biliary cirrhosis (PBC) is an autoimmune disease of liver associated with a unique serologic response to mitochondrial autoantigens. Many of the autoantigens recognized by autoantibodies in PBC are members of the 2-oxo-acid dehydrogenase complex. The two major autoantigens are the E2 component of the pyruvate dehydrogenase complex (PDC-E2) and the E2 component of the branched chain 2-oxo-acid dehydrogenase complex (BCOADC-E2). The autoantibody response to PDCE2 has been mapped to one immunodominant epitope, which consists of both linear and conformational components. The presence of a single immunodominant epitope in PDC-E2 is unusual when contrasted to the immune response to autoantigens in other human autoimmune diseases. We have mapped the epitope recognized by antimitochondrial autoantibodies (AMA) specific to BCOADC-E2 in patients with PBC by taking advantage of the full-length bovine BCOADC-E2 complementary DNA (cDNA) and a series of expression clones spanning the entire molecule. Reactivity to the various expression clones was studied by immunoblotting, enzyme-linked immunosorbent assay (ELISA), as well as selective absorption of patient sera by expressed protein fragments. Autoantibodies to BCOADC-E2 map within peptides spanning amino acid residues 1 to 227 of the mature protein; our data demonstrate that the epitope is dependent on conformation and includes the lipoic acid binding region. However, only the full-length clone (amino acid residue 1 to 421) is sufficient to remove all detectable BCOADC-E2 reactivity. Moreover, the absence of lipoic acid on the recombinant polypeptides used in this study indicates that antibody binding to BCOADC-E2 is not dependent on the presence of lipoic acid.
The Rich Specialist.
Authors: E. N. Palmer
Journal: JAMA (1900)

<h3>Dear Doctor:</h3> —Can you give me, without too much trouble, the number of hysterectomies and laparotomies you performed during the year 1899, in which you received no fees? I am preparing a reply to the speech of the Hon. L. D. Watkins at the Association of Farmers Clubs, at Lansing, in which he uses your charges in Culver and Dunn cases as an argument—"to regulate the fees of physicians by law." Yours truly,
No way to start a space program: Associationism as a launch pad for analogical reasoning
Authors: Keith J. Holyoak, John E. Hummel
Journal: Behavioral and Brain Sciences (2008)

Abstract Humans, including preschool children, exhibit role-based relational reasoning, of which analogical reasoning is a canonical example. The “role-less” connectionist model proposed in the target article is only capable of conditional paired-associate learning.
Abstract 135: Phosphorylation and furin-mediated processing are critical posttranslational modifications of the KISS1 metastasis suppressor
Authors: Sitaram Harihar, Kelsey R. Hampton, Tomoo Iwakuma, Nabil G. Seidah, Danny R. Welch
Journal: Cancer Research (2014)

Abstract Originally discovered as a metastasis suppressor, KISS1 has since been defined as a neurotransmittor and regulator of diverse cellular functions and has been implicated in pathologies such as hypogonadism and Alzheimer's disease. Several laboratories are actively developing therapies based upon KISS1 biology. KISS1 is secreted and processed into small peptides (called kisspeptins (KP)) in the extracellular milieu. However, the enzyme(s) responsible for generation of KP from nascent KISS1 is unknown, although sequence analysis (cleavage at KR or RR dibasic sites) suggests that proprotein convertases (PC) are responsible. We hypothesized that enzyme(s) belonging to the PC family processes KISS1 to generate KP. KISS1 processing was completely inhibited by treatment with PC inhibitors Dec-RVKR-CMK and a1-PDX in these cells multiple tumor cell lines. Further, mRNA expression of the seven members of the PC family showed consistent expression of only three proteases - furin, PCSK5 and PCSK7 narrowing the candidate proteases. Only shRNA-mediated knockdown of furin (i.e., not PCSK5 or PCSK7) blocked KISS1 processing. Thus furin is the essential enzyme responsible for KP generation. Even when cells were exposed to Dec-RVKR-CMK or shRNA targeting furin, two bands (Mr∼15.9 kDa and Mr ∼17 kDa) were consistently detected in SDS-PAGE of conditioned medium. This observation suggested KISS1 could either be alternatively post-translationally modified or that another protease (family) might also cleave KISS1. To investigate the possibility that KISS1 may be post-translationally modified, potential sites of O-glycosylation (NetOGlyc 4.0) or serine/threonine phosphorylation (NetPhos 2.0) were analyzed in silico. Three amino acid residues (T69, S70, and S72)of the native KISS1 protein showed highest scores as being either O-glycosylated or phosphorylated. Further, mutation of these three residues to alanine resulted in the loss of the higher molecular weight band which was co-localized to a band detected using anti-phospho Ser/Thr strongly suggesting that KISS1 is indeed phosphorylated. This is the first report of phosphorylation of KISS1. Studies are underway to identify the kinase(s) and phosphatase(s) involved as well as the functional significance of the phosphorylation. Support: CA134981, National Foundation for Cancer Research, Steiner Family Fellowship in Metastasis Research, Susan G. Komen for the Cure SAC110037. Citation Format: Sitaram Harihar, Kelsey R. Hampton, Tomoo Iwakuma, Nabil G. Seidah, Danny R. Welch. Phosphorylation and furin-mediated processing are critical posttranslational modifications of the KISS1 metastasis suppressor. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 135. doi:10.1158/1538-7445.AM2014-135
458 HBsAg level in serum and liver in genotype B and C infected chinese chronic hepatitis B patients and their changes under peginterferon-alpha-2a treatment
Authors: J.J. Chen, J.L. Hou, S.W. Ma, Z.H. Wang, Y.E. Zhu, K.X. Luo,, N.V Naoumov
Journal: Journal of Hepatology (2006)
Fluorouracil-Associated Dermatitis of the Hands and Feet
Authors: Lorne D. Feldman
Journal: JAMA (1985)

Continuous intravenous infusion has recently been investigated as a method of improving the therapeutic index of cancer chemotherapy. Theoretical advantages of this schedule include (1) a reduction or modification in drug toxicity owing to a lower peak concentration of the drug and (2) an enhanced therapeutic effect owing to a prolonged tumor cell exposure to the drug in various phases of the cell cycle. This approach has been investigated using fluorouracil, a pyrimidine antimetabolite that is frequently used in chemotherapy programs for gastrointestinal and breast malignant neoplasms. After fluorouracil undergoes activation, it interferes with both RNA and DNA synthesis in the cancer cell, but its plasma half-life is only ten minutes because it undergoes rapid inactivation in the liver and other tissues. The schedule-dependent nature of fluorouracil toxicity has long been known: myelosuppression predominates in patients who receive intravenous bolus administration, and stomatitis is prevalent in patients who receive short-term
Diagnosis of cobalamin deficiency: II. Relative sensitivities of serum cobalamin, methylmalonic acid, and total homocysteine concentrations
Authors: John Lindenbaum, David G. Savage, Sally P. Stabler, Robert H. Allen
Journal: American Journal of Hematology (1990)

Abstract The serum cobalamin level has been generally considered to be essentially 100% sensitive in the detection of the clinical disorders caused by cobalamin deficiency. We tested this hypothesis in two groups of patients. In patients with pernicious anemia or previous gastrectomy who received less than monthly maintenance therapy, early hematologic relapse was associated with elevation of the serum methylmalonic acid, total homocysteine, or both metabolites in 95% of instances, although the serum cobalamin was low in only 69%. In the absence of hematologic relapse, the methylmalonic acid was abnormal more than twice as frequently as the serum cobalamin. We also reviewed the records of 419 consecutive patients with recognized clinically significant cobalamin deficiency. Twelve patients were identified in whom deficiency was clearly present although the serum cobalamin was greater than 200 pg/ml. Anemia was usually absent or mild, but 5 had prominent neurological involvement that subsequently responded to cobalamin. Both the serum methylmalonic acid and total homocysteine were increased in each patient. The serum cobalamin was normal in 9 (5.2%) of 173 patients with recognized cobalamin deficiency seen in the last 5 years. Antibiotic treatment lowered the serum methylmalonic acid but not the total homocysteine level in two cobalamin‐deficient patients, suggesting that propionic acid generated by the anaerobic gut flora may be a precursor of methylmalonic acid in deficient patients. We conclude that the serum cobalamin is normal in a significant minority of patients with cobalamin deficiency and that the measurement of serum metabolite concentrations facilitates the identification of such patients.
The Meaning of a New Marker for Coronary-Artery Disease
Authors: Henry Blackburn
Journal: New England Journal of Medicine (1983)

A strong, almost perfectly predictive association between apolipoprotein A-I levels and the presence of obstructive coronary-artery disease is reported by a Mayo Clinic group in this issue.1 The report induces love at first sight, but quick romance does not a marriage make. The finding, and how it was achieved, raises important questions.First of all, is the association real and causal — what can be inferred from a cross-sectional, descriptive analysis of a case series? Is the closer correlation found between coronary-artery disease and apolipoprotein A-I than between the disease and high-density lipoprotein (HDL) or low-density lipoprotein (LDL) due to . . .