tbuckley/cabot-search huggingface dataset:
Letter from Indonesia
Authors: Raden Soeharto
Journal: New England Journal of Medicine (1954)

BECAUSE most American physicians have not had the opportunity of visting Indonesia I should like to offer some information about my country, its population and its history in brief lines, some data regarding historical developments of what is called western medicine and concerning general conditions. It is believed that this information will help readers understand Indonesian problems in general and medical problems in particular.The Republik Indonesia (Republic of Indonesia) was recognized as a sovereign and independent country as a result of the Round Table Conference at the Hague from August 23 to November 2, 1949, and was admitted to . . .
Survival of the ischemic brain: a progress report.
Authors: P Scheinberg
Journal: Circulation (1979)

The number of patients with cerebral infarctions increases as the population ages, despite campaigns against hypertension, the greatest risk factor. Cerebral ischemia initiates events that are presumed to defer the stage of irreversible injury. These events cause an increase of perfusion around the central ischemic zone and trigger the Bohr effect, both of which preserve tissue viability. Almost simultaneously, mitochondrial function fails, resulting in insufficient energy for the enzyme systems to control Na and K ion equilibrium. At the same time, protein synthesis slows and cellular respiratory enzymes decrease their activity, initiating an irreversible state of tissue change. Tissue fatty acids increase as a result of dissolution of cell membrane lipoprotein structure. Barbiturates reduce the extent of experimental infarction. Resperine and aminophylline are also effective, but there are no corroborative clinical trials. That ischemic brain damage may be the result of toxic substances in the ischemic tissue represents a new concept.
Health put at risk by insurers' demands for gene test results
Authors: Z. Kmietowicz
Journal: BMJ (1997)

Medical ethicists are concerned about the new ruling by insurance companies that results of genetic tests have to be disclosed by people seeking new policies worth more than £100000 ($160000). They warn that the move may deter people from having tests that could save or prolong their lives and jeopardise future research into genetic testing.

In a statement issued last week the Association of British Insurers confirmed that member companies will not ask people to take genetic tests when applying for life insurance and that they will ignore any adverse test results of new applicants seeking mortgage linked cover of up to £100000. However, the results of those who require higher …
Epinephrine is a Hypophosphatemic Hormone in Man. PHYSIOLOGICAL EFFECTS OF CIRCULATING EPINEPHRINE ON PLASMA CALCIUM, MAGNESIUM, PHOSPHORUS, PARATHYROID HORMONE, AND CALCITONIN
Authors: Jean-Jacques Body, Philip E. Cryer, Kenneth P. Offord, Hunter Heath
Journal: Journal of Clinical Investigation (1983)

The physiologic effects of epinephrine on mineral metabolism are not known. In six healthy men, insulin-induced hypoglycemia, a potent stimulus to endogenous epinephrine secretion, resulted in a decrement of 0.9±0.1 mg/dl (mean±SE, P < 0.001) in serum inorganic phosphorus and smaller increments in magnesium and total and ionized calcium. Plasma immunoreactive parathyroid hormone (iPTH) decreased and plasma immunoreactive calcitonin (iCT) increased appropriately with the increments in calcium and magnesium. We wished to determine to what extent these changes in mineral metabolism might be attributable to epinephrine. Therefore, in the same protocol, we infused the hormone over 60 min in these six men, in doses that resulted in steady-state plasma epinephrine concentrations ranging from 52 to 945 pg/ml (levels that span the physiologic range), for a total of 25 studies. Serum ionized calcium, iPTH, and iCT concentrations were unaltered by these physiologic elevations of plasma epinephrine. However, epinephrine resulted in dose-dependent decrements in serum inorganic phosphorus of 0.6±0.1 mg/dl (P < 0.005) for the highest epinephrine infusion rate. The plasma epinephrine concentration threshold for this hypophosphatemic effect was ∼50-100 pg/ml. Thus, the sensitivity of the hypophosphatemic response to epinephrine is comparable to that of the cardiac chronotropic, systolic pressor, and lipolytic responses to epinephrine, and considerably greater than that of the diastolic depressor, glycogenolytic, glycolytic, and ketogenic responses to the hormone in human beings. In view of its rapidity, the hypophosphatemic effect of epinephrine is probably the result of a net shift of phosphate from the extracellular compartment to intracellular compartments. We suggest that it is a direct effect of epinephrine, in that it is not mediated by changes in availability of the primary regulatory hormones PTH and CT, although indirect effects mediated by changes in other hormones, such as insulin, cannot be excluded. The hypophosphatemic response is also not attributable to increments in plasma calcium. These data indicate that epinephrine in physiologic concentrations is a hypophosphatemic hormone in man.
Effects of Sorafenib Dose on Acquired Reversible Resistance and Toxicity in Hepatocellular Carcinoma
Authors: Elizabeth A. Kuczynski, Christina R. Lee, Shan Man, Eric Chen, Robert S. Kerbel
Journal: Cancer Research (2015)

Acquired evasive resistance is a major limitation of hepatocellular carcinoma (HCC) treatment with the tyrosine kinase inhibitor (TKI) sorafenib. Recent findings suggest that resistance to sorafenib may have a reversible phenotype. In addition, loss of responsiveness has been proposed to be due to a gradual decrease in sorafenib plasma levels in patients. Here, the possible mechanisms underlying reversible sorafenib resistance were investigated using a Hep3B-hCG orthotopic human xenograft model of locally advanced HCC. Tissue and plasma sorafenib and metabolite levels, downstream antitumor targets, and toxicity were assessed during standard and dose-escalated sorafenib treatment. Drug levels were found to decline significantly over time in mice treated with 30 mg/kg sorafenib, coinciding with the onset of resistance but a greater magnitude of change was observed in tissues compared with plasma. Skin rash also correlated with drug levels and tended to decrease in severity over time. Drug level changes appeared to be partially tumor dependent involving induction of tumoral CYP3A4 metabolism, with host pretreatment alone unable to generate resistance. Escalation from 30 to 60 mg/kg sorafenib improved antitumor efficacy but worsened survival due to excessive body weight loss. Microvessel density was inhibited by sorafenib treatment but remained suppressed over time and dose increase. In conclusion, tumor CYP3A4 induction by sorafenib is a novel mechanism to account for variability in systemic drug levels; however, declining systemic sorafenib levels may only be a minor resistance mechanism. Escalating the dose may be an effective treatment strategy, provided toxicity can be controlled.
Diet Quality Declines Despite Increase in Healthy Food Consumption
Authors: M. J. Friedrich
Journal: JAMA (2015)

Over the last 2 decades, adults around the world modestly increased their intake of healthy dietary items, but this trend was exceeded by increases in consumption of unhealthy items, according to an analysis of global dietary patterns (Imamura F et al. Lancet Glob Health. 2015;3[3]:e132-e142).
The debate on statins must stay in the public domain
Authors: J. Burne
Journal: BMJ (2014)

As a medical journalist, I’m concerned about the recommendation of the independent panel considering the retraction of two BMJ papers that the ongoing statin debate “be conducted primarily in medical journals rather than in the lay media.”1

How could this be enforced? Could I be fined or imprisoned for reporting dissenting data? And what about The BMJ ’s support for transparency? Debate behind closed …
Configuration of Unipolar Atrial Electrograms During Electrically Induced Atrial Fibrillation in Humans
Authors: Karen T.S. Konings, Joep L.R.M. Smeets, Olaf C. Penn, Hein J.J. Wellens, Maurits A. Allessie
Journal: Circulation (1997)

Background During atrial fibrillation (AF), the atrium is activated by multiple wavelets that continuously change in size and direction. The aim of this study was to correlate the temporal variation in AF electrogram configuration with the varying spatial patterns of activation. Methods and Results In a group of 25 Wolff-Parkinson-White patients undergoing cardiac surgery, the free wall of the right atrium was mapped (244 points) during electrically induced AF. The unipolar electrograms recorded during 4 seconds of AF were classified into four categories: (1) single deflections, (2) short-double potentials, (3) long-double potentials, and (4) fragmented potentials. The proportion of these four types of electrograms during AF was as follows: singles, 77±12%; short-doubles, 7±3%; long-doubles, 10±7%; and fragmented, 6±4%. Electrogram morphology was an indicator for rapid uniform conduction (single potentials; positive predictive value [PPV] of 0.96), collision (short-double potentials; PPV of 0.33), conduction block (long-double potentials; PPV of 0.84), and pivoting points or slow conduction (fragmented potentials; PPV of 0.87). In type I, II, and III AF, the proportion of long-double potentials was 4±2%, 12±3%, and 18±7% ( P &lt;.05); the proportion of fragmented complexes was 2±2%, 6±3%, and 10±4% ( P &lt;.05), respectively. During electrically induced and self-terminating episodes of AF, no preferential anatomic sites for double or fragmented potentials were found in the right atrium. Conclusions The morphology of single unipolar electrograms during AF reflects the occurrence of various specific patterns of conduction. This might be used to differentiate between different types of AF and to identify regions with structural conduction disturbances involved in perpetuation of chronic AF.
Routine Serological Tests for Syphilis
Authors: A. E. W. McLachlan
Journal: BMJ (1947)

emergencies is seldom in the patient's best interest, and an obstetric emergency service should consist primarily of an ambulance equipped as an efficient resuscitation unit with unlimited blood at its disposal.The obstetrician can thus ensure that he is not forced by circumstances to perform opera- tions at home that would have a wider margin of safety in hospital.-Iam, etc., Birmingham.W. G. MILLS. Child-bearing and TuberculosisSIR,-Child-bearing and tuberculosis is still a subject which arouses strong feelings.We are grateful to your correspondents for their interest in our work and for some very appreciative remarks.We have endeavoured to make an objective judgment on this difficult subject, but we hope our figures are a sufficient basis for an opinion.It cannot be denied that the tuberculous disease in some patients becomes worse in association with pregnancy.This is a habit of tuberculous disease in nonpregnant women too, and in our experience equally common in both groups.We too wish to emphasize the importance of the environment of the tuberculous woman who has borne a child.Efficient
Medical malpractice in perspective. II--The implications for Britain.
Authors: L Quam, P Fenn, R Dingwall
Journal: BMJ (1987)

The "malpractice crisis" in the United States cannot be understood in isolation. Litigation is precipitated by features of the American health care and social security systems. Relative to the United Kingdom, there are fewer barriers of access to the courts, although the role of contingency fees has probably been exaggerated. Given the great institutional differences between the UK and the USA, the crisis seems unlikely to be replicated here unless there are further moves towards privatising both the costs of providing health care and the costs of its failures. It is concluded that a marginal change in the frequency or average cost of claims could have a serious impact on National Health Service resources, the medical defence societies, recruitment to specialties, and clinical practice. Debate over possible reforms is compromised by the dearth of good empirical data. Any changes, however, must address both the deterrence of bad practice and the compensation of injured patients.
Stromal Gene Signatures in Large-B-Cell Lymphomas
Authors: G Lenz, G Wright, S S Dave, W Xiao, J Powell, H Zhao, W Xu, B Tan, N Goldschmidt, Javeed Iqbal, Julie M. Vose, M Bast, Kai Fu, D D. Weisenburger, T C Greiner, James O. Armitage, A Kyle, L May, R D Gascoyne, J M Connors, G Troen, H Holte, S Kvaloy, D Dierickx, G Verhoef, J Delabie, E B Smeland, P Jares, A Martinez, A Lopez-Guillermo, E Montserrat, E Campo, R M Braziel, T P Miller, L M Rimsza, J R Cook, B Pohlman, J Sweetenham, R R Tubbs, R I Fisher, E Hartmann, A Rosenwald, G Ott, H-K Muller-Hermelink, D Wrench, T A Lister, E S Jaffe, W H Wilson, W C. Chan, L M Staudt
Journal: New England Journal of Medicine (2008)

The addition of rituximab to combination chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), or R-CHOP, has significantly improved the survival of patients with diffuse large-B-cell lymphoma. Whether gene-expression signatures correlate with survival after treatment of diffuse large-B-cell lymphoma is unclear.We profiled gene expression in pretreatment biopsy specimens from 181 patients with diffuse large-B-cell lymphoma who received CHOP and 233 patients with this disease who received R-CHOP. A multivariate gene-expression-based survival-predictor model derived from a training group was tested in a validation group.A multivariate model created from three gene-expression signatures--termed "germinal-center B-cell," "stromal-1," and "stromal-2"--predicted survival both in patients who received CHOP and patients who received R-CHOP. The prognostically favorable stromal-1 signature reflected extracellular-matrix deposition and histiocytic infiltration. By contrast, the prognostically unfavorable stromal-2 signature reflected tumor blood-vessel density.Survival after treatment of diffuse large-B-cell lymphoma is influenced by differences in immune cells, fibrosis, and angiogenesis in the tumor microenvironment.
Regional myocardial downregulation of the inhibitory guanosine triphosphate-binding protein (Gi alpha 2) and beta-adrenergic receptors in a porcine model of chronic episodic myocardial ischemia.
Authors: H K Hammond, D A Roth, M D McKirnan, P Ping
Journal: Journal of Clinical Investigation (1993)

Regional myocardial ischemia is associated with increased levels of adenosine and norepinephrine, factors that may alter activation of the beta-adrenergic receptor (beta AR)-G protein-adenylyl cyclase pathway in the heart. We have used the ameroid constrictor model to determine whether alterations in myocardial signal transduction through the beta AR-G protein-adenylyl cyclase pathway occur in the setting of chronic episodes of reversible ischemia. Pigs were instrumented with ameroid occluders placed around the left circumflex coronary artery. 5 wk later, after ameroid closure, flow and function were normal in the ischemic bed, but flow (P = 0.001) and function (P < 0.03) were abnormal when metabolic demands were increased. The ischemic bed showed a reduction in myocardial beta AR number (P < 0.005). Despite regional downregulation of myocardial beta AR number, adenylyl cyclase activity was similar in the ischemic and control beds. Quantitative immunoblotting showed that the cardiac inhibitory GTP-binding protein, Gi alpha 2, was decreased in the ischemic bed (P = 0.02). In contrast, the cardiac stimulatory GTP-binding protein, Gs alpha, was increased in endocardial sections from the ischemic bed (P = < 0.05). Decreased Gi alpha 2 content was associated with decreased inhibition of adenylyl cyclase. Reduced Gi alpha 2 content, in conjunction with increased Gs alpha content in the endocardium, may provide a means by which adrenergic activation is maintained in the setting of chronic episodic myocardial ischemia.
Reviews and Notes: Cardiology: Coronary Heart Disease Prevention
Authors: Michael V. Cohen
Journal: Annals of Internal Medicine (1994)

Literature of Medicine1 January 1994Reviews and Notes: Cardiology: Coronary Heart Disease PreventionMichael V. Cohen, MDMichael V. Cohen, MDUniversity of South Alabama College of Medicine, Mobile, AL 36688Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-120-1-199401010-00035 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Coronary Heart Disease PreventionFrank Yanowitz; ed. 488 pages. New York: Marcel Dekker; 1992. $69.75.It is nearly impossible to evaluate or treat a patient with heart disease without at some point considering the significance and implications of past and present risk factors. Despite the obvious central importance of risk factors to the overall care of a patient, few health care professionals, save epidemiologists, seem to appreciate the rewards that may follow successful risk factor modification; fewer still acknowledge by deed the value of attention to risk factors in patients with cardiac maladies. To be sure, physician and patient awareness ... Author, Article, and Disclosure InformationAffiliations: University of South Alabama College of Medicine, Mobile, AL 36688 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 January 1994Volume 120, Issue 1Page: 94KeywordsCardiovascular therapyExerciseHealth careHeart diseasesHypertensionLipidsMedical risk factorsObesityStable coronary artery diseaseTreatment guidelines ePublished: 15 August 2000 Issue Published: 1 January 1994 Copyright & PermissionsCopyright © 1994 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
P101The effect of rapamycin in cardiac mTORC2-deficient mice under pressure overload conditions
Authors: M Brink, L Xu, C Morandi
Journal: Cardiovascular Research (2014)

Aims: Mammalian target of rapamycin (mTOR) is a central regulator of cellular growth and metabolism and has distinct substrates with tissue-specific functions depending on whether it is part of the multiprotein complex mTORC1 or mTORC2. Rapamycin has been reported to attenuate the development of cardiac hypertrophy and regress established hypertrophy in aortic-banded mice without reducing cardiac function. Short-term rapamycin treatment increases Akt phosphorylation via mTORC2, which may promote cell survival. The molecular effects and involvement of mTORC2 in long-term rapamycin treatment are not known in the heart. Methods: Rictor, an essential and specific component of mTORC2, was deleted in 10 weeks-old male mice homozygous for floxed rictor and expressing cre-recombinase (MerCreMer) under control of the α-MHC-promoter (rictor-cKO mice). Three weeks after tamoxifen, the aorta was ligated (TAC). Rapamycin (2 mg×kg-1×d-1) or vehicle was administered daily from the day before until 7 days after surgery. Echocardiography was performed before and 7 days after surgery. Mice were sacrificed after the last echo and the hearts harvested for histology, protein and RNA analysis. Results: TAC led to significant increases in left ventricular mass and decreases in cardiac function. Post-mortem analysis revealed that all rapamycin-treated mice had lower ventricular weight/body weight ratios than the corresponding vehicle-treated groups. However, only rapamycin-treated control mice showed improved cardiac function after TAC (EF: 48.6±2.0% for rapamycin and 30.8±3.1% for vehicle, p<0.001). The effect of rapamycin in rictor-cKO mice was less pronounced (EF: 37.0±3.6% for rapamycin and 25.8±3.7% for vehicle, p=0.06). The inhibition of mTORC1 by rapamycin was confirmed as phosphorylation of p70-S6K was suppressed. Rictor deficiency reduced the phosphorylation of the mTORC2 target Akt at S473, and rapamycin treatment further decreased its phosphorylation. In the control group, phosphorylation of Akt at S473 was also blocked by rapamycin. Conclusions: Rapamycin attenuated pressure overload-induced hypertrophy in both control and rictor-deficient mice, but cardiac function was significantly improved only in the control group. Prolonged rapamycin treatment not only inhibited mTORC1 activities but also blocked mTORC2-mediated Akt phosphorylation. Despite blockade of several mTOR targets by rapamycin, some rapamycin-insensitive activities of mTOR appear to be cardioprotective.
A role for associated transition metals in the immunotoxicity of inhaled ambient particulate matter.
Authors: Judith T Zelikoff, Kimberly R Schermerhorn, Kaijie Fang, Mitchell D Cohen, Richard B Schlesinger
Journal: Environmental Health Perspectives (2002)

Epidemiologic studies demonstrate that infection, specifically pneumonia, contributes substantially to the increased morbidity and mortality among elderly individuals following exposure to ambient particulate matter (PM). This laboratory has previously demonstrated that a single inhalation exposure of Streptococcus pneumoniae-infected rats to concentrated ambient PM(2.5) (particulate matter with aerodynamic diameter < or =2.5 microm) from New York City (NYC) air exacerbates the infection process and alters pulmonary and systemic immunity. Although these results provide some basis for explaining the epidemiologic findings, the identity of specific PM constituents that might have been responsible for the worsening pneumonia in exposed hosts remains unclear. Thus, studies were performed to correlate the physicochemical attributes of ambient PM(2.5) with its in vivo immunotoxicity to identify and characterize the role of constitutive transition metals in exacerbating an ongoing streptococcal infection. Uninfected or previously infected rats were exposed in the laboratory to soluble divalent Fe, Mn, or Ni chloride salts. After exposure, uninfected rats were sacrificed and their lungs were lavaged. Lungs from infected hosts were used to evaluate changes in bacterial clearance and effects of exposure on the extent/severity of infection. Results demonstrated that inhalation of Fe altered innate and adaptive immunity in uninfected hosts, and both Fe and Ni reduced pulmonary bacterial clearance in previously infected rats. The effects on clearance produced in infected Fe-exposed rats were similar to those seen in infected rats exposed to ambient NYC PM. Taken together, these studies demonstrate that inhaled ambient PM can worsen the outcome of an ongoing pulmonary infection and that associated Fe may play some role in the immunotoxicity.
Effect of recent health and social service policy reforms on Britain's mental health system
Authors: T. R Hadley, H. Goldman
Journal: BMJ (1995)

The introduction of new policies in health and social services in Britain has changed the way community care is provided to seriously mentally ill people. Britain is creating the same problems that have existed in the United States, whereby clinicians struggle to provide services in an environment with multiple payers and perverse incentives. A simple system in Britain has been replaced with complicated organisational and financial structures that require almost impossible feats by local health and social service staff to coordinate care for patients for whom continuity of care is critical for their survival in the community and their wellbeing. Seriously mentally ill people are in the middle of these complicated problems. The creation of a local mental health authority that could be held responsible for community care, as exists in some American states, may be one solution.
Comparison of chromosome banding analysis, interphase- and hypermetaphase-FISH, qualitative and quantitative PCR for diagnosis and for follow-up in chronic myeloid leukemia: a study on 350 cases
Authors: C Schoch, S Schnittger, S Bursch, D Gerstner, A Hochhaus, U Berger, R Hehlmann, W Hiddemann, T Haferlach
Journal: Leukemia (2002)