tbuckley/cabot-search huggingface dataset:
Prevalence and predictors of audible physiological third heart sound in a population sample aged 36 to 37 years.
Authors: M Kupari, P Koskinen, J Virolainen, P Hekali, P Keto
Journal: Circulation (1994)

BACKGROUND A physiological third heart sound (S3) is common in youth but allegedly very rare after the age of 40 years. The mechanism of its disappearance is not known. The aim of this work was to study the prevalence and predictors of physiological S3 in a population-based sample of persons approaching 40 years of age. METHODS AND RESULTS A random sample of 120 persons born in 1954 was invited; 93 (42 men) entered the study. Their physical activity, alcohol and tobacco consumption, and salt intake were quantified by diary follow-up. The presence of an S3 was determined by auscultation and confirmed by phonocardiography. Left ventricular (LV) size, mass, and systolic function were assessed by M-mode echocardiography and LV filling by Doppler velocimetry of transmitral flow. An audible S3 was detected in 22 subjects, 1 of whom had heart disease. The prevalence of physiological S3 was 23.1%. Subjects with physiological S3 had a lower body mass index (22.3 +/- 2.8 versus 24.6 +/- 4.1 kg/m2 [mean +/- SD], P = .005), lower heart rate (63 +/- 7 versus 68 +/- 10 beats per minute, P = .015), higher peak early diastolic transmitral velocity (67 +/- 10 versus 58 +/- 8 cm/s, P = .002), and higher acceleration of early diastolic velocity (717 +/- 148 versus 622 +/- 122 cm/s2, P = .012) than those without S3. No differences were noted in the lifestyle characteristics, blood pressure, or LV mass and systolic function. Body mass index and peak early diastolic transmitral velocity were independent predictors of physiological S3 in logistic regression analysis. CONCLUSIONS Nearly one fourth of persons approaching their forties still have an audible physiological S3. The presence of S3 is predicted by leanness and a high early diastolic LV inflow velocity; the disappearance of S3 is unlikely to be secondary to increasing blood pressure and relative LV hypertrophy, as is widely presented, but reflects a more primary age-related alteration of LV early diastolic function.
Zinc Gluconate Lozenges for Treating the Common Cold in Children
Authors: Michael L. Macknin, Marion Piedmonte, Cory Calendine, Janine Janosky, Ellen Wald
Journal: JAMA (1998)

Context.—The common cold is one of the most frequently occurring illnesses and is responsible for substantial morbidity and economic loss. Biochemical evidence suggests that zinc may be an effective treatment, and zinc gluconate glycine (ZGG) lozenges have been shown to reduce the duration of cold symptoms in adults.Objective.—To determine the efficacy of ZGG treatment of colds in children and adolescents.Design.—A randomized, double-masked, placebo-controlled study.Setting.—Two suburban school districts in Cleveland, Ohio.Patients.—A total of 249 students in grades 1 through 12 were enrolled within the first 24 hours of experiencing at least 2 of 9 symptoms of the common cold.Intervention.—Zinc lozenges, 10 mg, orally dissolved, 5 times a day (in grades 1-6) or 6 times a day (in grades 7-12).Main Outcome Measures.—Time to resolution of cold symptoms based on subjective daily symptom scores for cough, headache, hoarseness, muscle ache, nasal congestion, nasal drainage, scratchy throat, sore throat, and sneezing.Results.—Time to resolution of all cold symptoms did not differ significantly between students receiving zinc (n=124) and those receiving placebo (n=125) (median, 9 days; 95% confidence interval [CI], 8-9 days; median, 9 days, 95% CI, 7-10 days, respectively; P=.71). There were no significant differences in the time to resolution of any of the 9 symptoms studied. Compared with controls, more students in the zinc group reported adverse effects (88.6% vs 79.8%; P=.06); bad taste (60.2% vs 37.9%; P=.001); nausea (29.3% vs 16.1%; P=.01); mouth, tongue, or throat discomfort (36.6% vs 24.2%; P=.03); and diarrhea (10.6% vs 4.0%; P=.05).Conclusions.—In this community-based, randomized controlled trial, ZGG lozenges were not effective in treating cold symptoms in children and adolescents. Further studies with virologic testing are needed to clarify what role, if any, zinc may play in treating cold symptoms.
Radiography for ankle injuries
Authors: R. Hatch
Journal: JAMA (1993)

To the Editor.  —I found the decision rules described by Stiell et al 1 potentially very useful. However, it is difficult to assess their true value because some potentially important information was not included in the article. The abstract states that the decision rules had sensitivities of 1.0 for ankle and foot fractures. However, it is apparent from the body of the article and from Tables 1 and 5 that these sensitivities are actually based on the ability of the rules to predict what the authors consider  significant fractures. It would be very helpful to know how the authors define clinical significance, as well as how sensitive the rules were for detecting the 31 clinically insignificant fractures.
One thing leads to another
Authors: Jules Hirsch
Journal: Journal of Clinical Investigation (2004)

In 1956, the JCI published an article by Vincent Dole on a method for titrating plasma fatty acids that uncovered the importance of fatty acids as a substrate for glucose metabolism. When asked to prepare a historical perspective on this very popular paper, I paid Dole a visit and we reminisced. His answer to my question of how he came to do this work on plasma fatty acids was: “Well, one thing leads to another.” Let me remind the reader of what “things” were like in 1956 and how they might have related to Dole’s important contribution.
Privilege and Health -- What Is the Connection?
Authors: Marcia Angell
Journal: New England Journal of Medicine (1993)

Anyone who follows the medical literature knows that “socioeconomic status” is a powerful determinant of health. In current jargon, socioeconomic status refers to a mix of factors that shape a person's relative social advantage. It is usually gauged by income, education, profession, or some combination of the three, but no one knows exactly which factors determine health, much less how they do so. It does not seem to be simply a matter of the privileged having better access to health care. Nevertheless, in study after study socioeconomic status emerges as one of the most important influences on mortality and morbidity. . . .
THE NONTUBERCULOUS CHILD
Authors: JOSEPH BRENNEMANN
Journal: JAMA (1928)

The pediatrician is a general practitioner to the young, a chronologic, and not a regional specialist. We have not, therefore, that incisive special knowledge concerning the diagnosis of pulmonary tuberculosis that the specialist in tuberculosis has. We sit in proper awe, possibly a little skeptical at times, but only wholesomely so, as you unravel the mysteries of a suspected chest with that peculiar precision that you have acquired and that we, and I might include not a few internists, frankly do not possess. If we sometimes feel that an immediate autopsy might be instructive it is only because of that reasonable skepticism that is imposed on every intelligent clinician by the still existing limitations to unfailing diagnosis in chest conditions, that makes it still rather an art than a science. I shall not therefore "bring coals to Newcastle" by dwelling on finer points of diagnosis but will attempt as a
The Harvard Medical School, 1906–1956
Authors: Edward D. Churchill
Journal: New England Journal of Medicine (1956)

EARLY in the autumn of 1868 two young Boston doctors met in Paris almost as it were by chance. One was J. Collins Warren, who had spent a summer vacation mountain climbing in Switzerland and was looking toward a return to Berlin to continue his studies in the laboratory of Julius Cohnheim. Shortly before, Cohnheim had demonstrated the ability of the white cells of the blood to pass through the capillary vessels, thus affording a fresh and dynamic insight into the behavior of living tissues in inflammation. Cellular pathology was the keynote of the new medical science in Germany, and . . .
THERAPEUTIC USES AND DANGERS OF THE ROENTGEN RAYS.
Authors: CHARLES LESTER LEONARD
Journal: JAMA (1907)

The value and power of therapeutic agents and methods are determined by the results obtained by those competent to use them. Judged by this standard, the Roentgen rays have established their value as a powerful therapeutic agent. A distinction must always be made in judging results between deficiencies in the method and defects in the technic of its employment. As a therapeutic agent, the rays have proved themselves to be potent stimulants, alteratives and even destroyers of tissue. They produce results, that can not otherwise be obtained, by influencing metabolism. They stop pathologic processes, cause the absorption of pathologic tissue, stimulate normal processes of growth and repair and restore the tissues to their normal state. These effects were first recognized by their injurious action, but their therapeutic value has been carefully studied and determined. Efficient methods have been developed for guarding against their injurious effect, while a breadth of therapeutic
Neurobehavioral aspects of developmental toxicity testing.
Authors: B Ulbrich, A K Palmer
Journal: Environmental Health Perspectives (1996)

Tests for detection of neurobehavioral changes in the offspring have been a regulatory requirement in developmental toxicity testing of drugs for almost 20 years. Keeping their purpose of hazard identification and risk assessment for humans in mind, investigators and agency reviewers have become deeply ingrained with some stereotyped behaviors with respect to such relevant issues as choice of animal species and data evaluation. Other problematic areas of study design and conduct, selection of litter representatives for testing, what methods to combine in a testing battery, and statistical treatment of results and their interpretation, will need more research and discussion in the future.
Pressure-Flow Studies in Man: Effect of Respiration on Left Ventricular Stroke Volume
Authors: JEROME RUSKIN, ROBERT J. BACHE, JUDITH C. REMBERT, JOSEPH C. GREENFIELD
Journal: Circulation (1973)

The pressure gradient technique was used to evaluate effects of respiration on left ventricular stroke volume in 22 patients: 11 normal patients; eight patients with airway obstruction; and three patients with pericardial tamponade. In normals, stroke volume, systolic pressure, and pulse pressure fell an average of 7, 3 and 11% ( P &lt; 0.01), respectively, during inspiration. In patients with airway obstruction, these parameters decreased by 25, 12 and 23% ( P &lt; 0.001), respectively. After breath-holding, stroke volume also fell immediately with the onset of inspiration in both groups. These results are consistent with a reduction in left ventricular filling during inspiration as the factor primarily responsible for the fall in stroke volume. In patients with pericardial tamponade, variations in left ventricular stroke volume, systolic pressure and pulse pressure were related to: (1) an immediate fall in stroke volume with the onset of inspiration; and (2) a subsequent increase in stroke volume presumably due to an inspiratory increase in right ventricular stroke volume.
Complex Partial Seizures vs Schizophrenia
Authors: Jon Brillman
Journal: JAMA (1977)

<h3>To the Editor.—</h3> The report by Adebimpe concerning a man who was thought to have complex partial seizures simulating schizophrenia underscores a trend among many psychiatrists to ascribe organic causes for apparent emotionally aberrant behavior. The report also supports my feeling, however, that this trend often leads one into a confusing area that is neither psychiatric or neurologic. Based on the case report, the evidence to support complex partial epilepsy is much less than satisfactory. The episodes last approximately three hours and as long as 24 hours, rather long for seizures. They are said to have "aura-like" phases that last as long as four hours. They are not followed by any confusion, and they are characterized by goal-directed destructive behavior as part of the ictal period. These features are all highly atypical of temporal lobe seizures. Further, the inability to obtain an abnormal EEG and the response of these "seizures"
Pregnancy-Associated Plasma Protein A as Predictor of Outcome in Patients With Suspected Acute Coronary Syndromes
Authors: Elena Conti, Felicita Andreotti, Cecilia Zuppi
Journal: Circulation (2004)

We read with interest the article by Lund et al 1 on circulating pregnancy-associated plasma protein A (PAPP-A) in 136 patients evaluated for suspected acute coronary syndrome without cardiac troponin I elevation.PAPP-A concentrations above 2.9 mIU/L during the first 24 hours independently predicted cardiovascular death, nonfatal myocardial infarction, or revascularization over the following 6 months.The risk ratio of PAPP-A Ͼ2.9 mIU/L, adjusted for C-reactive protein (CRP), age, gender, diabetes, current smoking, hypertension, previous myocardial infarction, and congestive heart failure was superior to that of CRP Ͼ2 mg/L: 4.6 for PAPP-A (95% confidence interval 1.8 to 11.8, Pϭ0.002) versus 2.6 for CRP (95% confidence interval 1.1 to 6.5, Pϭ0.03).The cumulative risk of an event, graded by increasing PAPP-A values, was 8% in the lowest group and 37.9% in the highest (Pϭ0.0012).PAPP-A and CRP levels were independent of each other (rϭϪ0.03,Pϭ0.7 on admission; rϭ0.02,Pϭ0.8 for peak values).These striking data are discussed only briefly by the authors, who, despite showing a lack of correlation between PAPP-A and CRP, propose PAPP-A as a mediator of the inflammatory reactions that would lead to plaque rupture and clinical instability.We would like to propose an alternative interpretation, based on the main activity of PAPP-A, which is to cleave insulin-like growth factor-1 (IGF-1) from its binding protein-4, thereby increasing the accessibility of free IGF-1 to tissues. 2 Several lines of evidence indicate that PAPP-A is induced in response to, and within, damaged tissues, as a promoter of repair, in virtue of its IGF-1-dependent actions on vasculogenesis, vasodilation, cell preconditioning, cell survival, and insulin-sensitivity. 3,4 Even mild damage, such as brief ischemia, would activate this pathway, 2 thus explaining the higher sensitivity of PAPP-A compared with cardiac troponins as predictors of outcome.In response to necrosis, the broad-ranging fluctuations of PAPP-A justify its correlation with cardiac enzymes 1 and inflammatory markers.The remission of rheumatoid arthritis and other inflammatory states during pregnancy 5 (the prototype of increased PAPP-A) denotes PAPP-A as a suppressor, rather than mediator, of inflammation and tissue damage.
Stimulus-induced critical point. Mechanism for electrical initiation of reentry in normal canine myocardium.
Authors: D W Frazier, P D Wolf, J M Wharton, A S Tang, W M Smith, R E Ideker
Journal: Journal of Clinical Investigation (1989)

The hypothesis was tested that the field of a premature (S2) stimulus, interacting with relatively refractory tissue, can create unidirectional block and reentry in the absence of nonuniform dispersion of recovery. Simultaneous recordings from a small region of normal right ventricular (RV) myocardium were made from 117 to 120 transmural or epicardial electrodes in 14 dogs. S1 pacing from a row of electrodes on one side of the mapped area generated parallel activation isochrones followed by uniform parallel isorecovery lines. Cathodal S2 shocks of 25 to 250 V lasting 3 ms were delivered from a mesh electrode along one side of the mapped area to scan the recovery period, creating isogradient electric field lines perpendicular to the isorecovery lines. Circus reentry was created following S2 stimulation; initial conduction was distant from the S2 site and spread towards more refractory tissue. Reentry was clockwise for right S1 (near the septum) with top S2 (near the pulmonary valve) and for left S1 with bottom S2; and counterclockwise for right S1 with bottom S2 and left S1 with top S2. The center of the reentrant circuit for all S2 voltages and coupling intervals occurred at potential gradients of 5.1 +/- 0.6 V/cm (mean +/- standard deviation) and at preshock intervals 1 +/- 3 ms longer than refractory periods determined locally for a 2 mA stimulus. Thus, when S2 field strengths and tissue refractoriness are uniformally dispersed at an angle to each other, circus reentry occurs around a "critical point" where an S2 field of approximately 5 V/cm intersects tissue approximately at the end of its refractory period.
In vivo measurement of neuronal uptake of norepinephrine in the human heart.
Authors: D S Goldstein, J E Brush, G Eisenhofer, R Stull, M Esler
Journal: Circulation (1988)

Neuronal uptake (Uptake-1) of the sympathetic neurotransmitter norepinephrine from the circulation in the human heart was assessed in vivo with three techniques. 1) Cardiac removal of intravenously infused tracer-labeled norepinephrine was measured before and after Uptake-1 blockade with desipramine; 2) the difference between the fractional extraction of radioactive norepinephrine and of radioactive isoproterenol, which is not a substrate for neuronal uptake, was used to estimate the removal of norepinephrine by Uptake-1 in the heart compared with other vascular beds (arm, leg, brain, and lungs); and 3) regional arteriovenous differences in radioactive and endogenous dihydroxyphenylglycol (DHPG), an exclusively intraneuronal metabolite of norepinephrine, were compared in these beds. In untreated patients, cardiac removal of radioactive norepinephrine averaged 79%, whereas in desipramine-treated patients, cardiac removal of radioactive norepinephrine averaged 19%, a value similar to that of isoproterenol in untreated patients (14%), confirming that in the heart the non-neuronal removals of isoproterenol and norepinephrine were similar. In the heart, 69% of delivered norepinephrine was estimated to be removed by Uptake-1, a much higher percentage than that in the arm (14%), leg (7%), brain (10%), and lungs (4%). The cardiac arteriovenous increment in endogenous DHPG (137%) far exceeded that of the other beds (49%, 26%, 39%, and -19%, respectively), and radioactive DHPG in the great cardiac vein exceeded arterial levels by 113%, whereas in the other beds, arterial radioactive DHPG exceeded venous levels. The results indicate that the human heart is exceptionally dependent on neuronal uptake for in vivo removal of circulating norepinephrine.
Pathophysiology and pathogenesis of stunned myocardium. Depressed Ca2+ activation of contraction as a consequence of reperfusion-induced cellular calcium overload in ferret hearts.
Authors: H Kusuoka, J K Porterfield, H F Weisman, M L Weisfeldt, E Marban
Journal: Journal of Clinical Investigation (1987)

Contractile dysfunction in stunned myocardium could result from a decrease in the intracellular free [Ca2+] transient during each beat, a decrease in maximal Ca2+-activated force, or a shift in myofilament Ca2+ sensitivity. We measured developed pressure (DP) at several [Ca]0 (0.5-7.5 mM) in isovolumic Langendorff-perfused ferret hearts at 37 degrees C after 15 min of global ischemia (stunned group, n = 13) or in a nonischemic control group (n = 6). At all [Ca]0, DP was depressed in the stunned group (P less than 0.001). Maximal Ca2+-activated pressure (MCAP), measured from tetani after exposure to ryanodine, was decreased after stunning (P less than 0.05). Normalization of the DP-[Ca]0 relationship by corresponding MCAP (Ca0 sensitivity) revealed a shift to higher [Ca]0 in stunned hearts. To test whether cellular Ca overload initiates stunning, we reperfused with low-[Ca]0 solution (0.1-0.5 mM; n = 8). DP and MCAP in the low-[Ca]0 group were comparable to control (P greater than 0.05), and higher than in the stunned group (P less than 0.05). Myocardial [ATP] observed by phosphorus NMR failed to correlate with functional recovery. In conclusion, contractile dysfunction in stunned myocardium is due to a decline in maximal force, and a shift in Ca0 sensitivity (which may reflect either decreased myofilament Ca2+ sensitivity or a decrease in the [Ca2+] transient). Our results also indicate that calcium entry upon reperfusion plays a major role in the pathogenesis of myocardial stunning.
Histamine suppresses epidermal keratinocyte differentiation and impairs skin barrier function in a human skin model
Authors: M. Gschwandtner, M. Mildner, V. Mlitz, F. Gruber, L. Eckhart, T. Werfel, R. Gutzmer, P. M. Elias, E. Tschachler
Journal: Allergy (2012)

Abstract Background Defects in keratinocyte differentiation and skin barrier are important features of inflammatory skin diseases like atopic dermatitis. Mast cells and their main mediator histamine are abundant in inflamed skin and thus may contribute to disease pathogenesis. Methods Human primary keratinocytes were cultured under differentiation‐promoting conditions in the presence and absence of histamine, histamine receptor agonists and antagonists. The expression of differentiation‐associated genes and epidermal junction proteins was quantified by real‐time PCR , W estern blot, and immunofluorescence labeling. The barrier function of human skin models was tested by the application of biotin as tracer molecule. Results The addition of histamine to human keratinocyte cultures and organotypic skin models reduced the expression of the differentiation‐associated proteins keratin 1/10, filaggrin, and loricrin by 80–95%. Moreover, the addition of histamine to skin models resulted in the loss of the granular layer and thinning of the epidermis and stratum corneum by 50%. The histamine receptor H1R agonist, 2‐pyridylethylamine, suppressed keratinocyte differentiation to the same extent as did histamine. Correspondingly, cetirizine, an antagonist of H1R, virtually abrogated the effect of histamine. The expression of tight junction proteins zona occludens‐1, occludin, claudin‐1, and claudin‐4, as well as that of desmosomal junction proteins corneodesmosin and desmoglein‐1, was down‐regulated by histamine. The tracer molecule biotin readily penetrated the tight junction barrier of skin cultures grown in the presence of histamine, while their diffusion was completely blocked in nontreated controls. Conclusions Our findings suggest a new mechanism by which mast cell activation and histamine release contribute to skin barrier defects in inflammatory skin diseases.
The Future of the Department of Veterans Affairs-Reply
Authors: James A. Pittman
Journal: JAMA (1995)

<h3>In Reply.</h3> —The proposal by Dr Moskowitz is an old one with a new twist—combine the USPHS, Medicare, and Medicaid with existing VA hospitals and clinics into a federal health care system for those too poor to afford the "first tier" of private care. When I worked in the VA Central Office in Washington, DC, across from the White House between 1971 and 1973, years when President Lyndon Johnson's Great Society still lingered and presidential woes increased, the air was rife with talk of making the VA the framework for a new federal system like Britain's National Health Service. It didn't happen in the 1970s, as President Clinton's system didn't happen in the 1990s. The VA system is already the nation's county hospital. The average income of employed VA patients is below $16 000 annually (69% unemployed),<sup>1</sup>and the maximum allowable is $20 469.<sup>2</sup>As emphasized by Fisher