tbuckley/cabot-search huggingface dataset:
The Meaning of the Patient to the Hospital
Authors: Ida M. Cannon
Journal: New England Journal of Medicine (1947)

THOSE of us to whom the old Ether Dome and its furnishings are familiar, need little imagination to picture the scene just a hundred years ago today, when the first public demonstration of anesthesia for a major surgical operation took place. From all descriptions that I have seen, the focus of attention was on the great surgeon, in his frock coat, who dared accept responsibility for operating under untried conditions, on Morton, the dentist, who produced the mysterious stuff, or on the skeptics in the amphitheater. The atmosphere must have been charged as courage and determination met incredulity and suspended . . .
Hebbian Synapses: Biophysical Mechanisms and Algorithms
Authors: T H Brown, E W Kairiss, C L Keenan
Journal: Annual Review of Neuroscience (1990)

The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, nonhuman primate, cat, and rodent brains. Its ...Read More
Hepatic cytochrome P450 2E1 is increased in patients with nonalcoholic steatohepatitis
Authors: Martin D. Weltman, Geoffrey C. Farrell, Pauline Hall, Magnus Ingelman-Sundberg, Christopher Liddle
Journal: Hepatology (1998)

Nonalcoholic steatohepatitis (NASH) has multiple etiologic associations, but the pathogenesis is poorly understood. Cytochrome P450 (CYP) 2E1 is induced in the liver of patients who drink alcohol to excess and is important in the pathogenesis of alcoholic liver disease (ALD). We have previously shown that hepatic CYP2E1 is also increased in a rat dietary model of steatohepatitis. The aim of the present study was to test the hypothesis that hepatic CYP2E1 is induced in the liver of patients with NASH, defined on the basis of compatible liver histology and the exclusion of excessive alcohol intake. Sections of paraffin-embedded liver biopsy material from 31 subjects with NASH were evaluated and compared with sections from 10 histologically normal livers and 6 patients with ALD. Hepatic CYP2E1 and CYP3A were detected in liver sections by immunohistochemistry using specific anti-human CYP2E1 and CYP3A antibodies. As expected, normal livers showed CYP2E1 immunostaining confined to a rim, two to three cells thick, around terminal hepatic venule, while livers from alcoholic hepatitis patients showed increased CYP2E1 staining. CYP2E1 immunostaining was also increased in livers from patients with NASH, irrespective of the etiologic association. Further, the pattern of CYP2E1 distribution was similar to ALD, with increased perivenular intensity and more extensive acinar distribution of staining. As in the rat model, the hepatic distribution of CYP2E1 corresponded to that of steatosis. In contrast to CYP2E1, CYP3A immunostaining was decreased in patients with NASH. We conclude that hepatic CYP2E1 is increased in patients with NASH compared with normal livers. Thus, despite many possible etiologic factors for NASH, the pathogenetic mechanisms may be similar and, like alcoholic steatohepatitis, may involve induction of CYP2E1.
C-Reactive Protein and Other Circulating Markers of Inflammation in the Prediction of Coronary Heart Disease
Authors: John Danesh, Jeremy G. Wheeler, Gideon M. Hirschfield, Shinichi Eda, Gudny Eiriksdottir, Ann Rumley, Gordon D.O. Lowe, Mark B. Pepys, Vilmundur Gudnason
Journal: New England Journal of Medicine (2004)

C-reactive protein is an inflammatory marker believed to be of value in the prediction of coronary events. We report data from a large study of C-reactive protein and other circulating inflammatory markers, as well as updated meta-analyses, to evaluate their relevance to the prediction of coronary heart disease.Measurements were made in samples obtained at base line from up to 2459 patients who had a nonfatal myocardial infarction or died of coronary heart disease during the study and from up to 3969 controls without a coronary heart disease event in the Reykjavik prospective study of 18,569 participants. Measurements were made in paired samples obtained an average of 12 years apart from 379 of these participants in order to quantify within-person fluctuations in inflammatory marker levels.The long-term stability of C-reactive protein values (within-person correlation coefficient, 0.59; 95 percent confidence interval, 0.52 to 0.66) was similar to that of both blood pressure and total serum cholesterol. After adjustment for base-line values for established risk factors, the odds ratio for coronary heart disease was 1.45 (95 percent confidence interval, 1.25 to 1.68) in a comparison of participants in the top third of the group with respect to base-line C-reactive protein values with those in the bottom third, and similar overall findings were observed in an updated meta-analysis involving a total of 7068 patients with coronary heart disease. By comparison, the odds ratios in the Reykjavik Study for coronary heart disease were somewhat weaker for the erythrocyte sedimentation rate (1.30; 95 percent confidence interval, 1.13 to 1.51) and the von Willebrand factor concentration (1.11; 95 percent confidence interval, 0.97 to 1.27) but generally stronger for established risk factors, such as an increased total cholesterol concentration (2.35; 95 percent confidence interval, 2.03 to 2.74) and cigarette smoking (1.87; 95 percent confidence interval, 1.62 to 2.16).C-reactive protein is a relatively moderate predictor of coronary heart disease. Recommendations regarding its use in predicting the likelihood of coronary heart disease may need to be reviewed.
The Chest-Pain Unit — Ready for Prime Time?
Authors: L. Kristin Newby, Daniel B. Mark
Journal: New England Journal of Medicine (1998)

For much of this decade, managed care has led a private, market-driven “reform” of the U.S. health care system. The introduction of late-20th-century business practices into the cottage industry of medicine has not always been pleasant or productive. It has, however, created strong incentives to improve the efficiency of the delivery of care. The chest-pain unit (CPU) is largely a product of those incentives.As recently as 10 years ago, cardiologists were routinely taught that a diagnosis of myocardial infarction could not be ruled out in the emergency department. If the possibility of myocardial infarction was great enough, the patient . . .
THE RATIONAL USE AND LIMITATIONS OF THERAPEUTIC MEASURES INTENDED TO PROMOTE THE ABSORPTION OF EXUDATES WITHIN THE EYEBALL. MEDICINAL MEASURES.
Authors: RANDOLPH BRUNSON
Journal: JAMA (1901)

If there has been one branch of ophthalmology which has been neglected in our study and research, it is the general therapeutic measures. I know of only two works on the subject of general therapeutics in relation to the eye, which treat exhaustively—one is a little book called "Ocular Therapeutics," by Ohlemann, the other by Carl Ferdinand Graefe, father of the great Albrecht v. Graefe, and published in 1817. Ohlemann, in his preface says: "Since 1817 when Ferdinand Graefe wrote his 'Repertorium Augenärztlicher Heilmittel,' no attempt has been made to treat the remedial agents used in ophthalmology exhaustively, and to supply a treatise on the subject that might serve as a guide to the practicing physician. This is the more interesting when it is remembered that C. F. Graefe made the assertion that in no branch of therapeutics is the value so worthy of consideration as in ophthalmology." We are
The effect of thyroid hormone on bile salt-independent bile flow and Na+, K+ -ATPase activity in liver plasma membranes enriched in bile canaliculi.
Authors: T J Layden, J L Boyer
Journal: Journal of Clinical Investigation (1976)

The relationship between bile salt-independent canalicular flow and ATPase activity in liver plasma membranes (LPM) enriched in bile canaliculi, was studied in control, hyperthyroid, and hypothyroid rats. Canalicular bile production was significantly increased in hyperthyroid rats (3.19 +/- 0.23 mul/min per g liver) compared to controls (2.27 +/- 0.24 mul/min per g liver), while it diminished in hypothyroid animals (1.58 +/- 0.17 mul/min per g liver). Although bile salt excretion was also increased in hyperthyroid animals (62.4 +/- 13.3 vs. 41.2 +/- 8.4 nmol/min per g liver), the stimulation in canalicular secretion was primarily related to enhancement of the bile salt-independent fraction of flow (2.47 mul/min per g liver in hyperthyroid rats vs. 1.67 mul/min per g liver in controls). LPM Na+, K+-ATPase activity doubled in hyperthyroid animals (21.5 +/- 5.8 vs. 10.7 +/- 3.1 mumol Pi/mg protein per h) while Mg++-ATPase activity remained unchanged and 5'-nucleotidase activity increased to a small but significant extent. In hypothyroid rats, bile salt excretion remained unchanged from control values so that the reduced secretion was entirely secondary to an inhibition of bile salt-independent secretion (1.19 mul/min per g liver). Na+, K+-ATPase activity in the LPMs from hypothyroid animals decreased by nearly 50% (5.4 +/- 1.6 mumol Pi/mg protein per h), although comparable reductions in the specific activity of Mg++-ATPase and 5'-nucleotidase were also observed. Administration of L-thyroxine to hypothyroid animals restored both bile salt-independent canalicular secretion and membrane enzymes to control values within 2 and 4 days, respectively. Sodium dodecyl sulfate gel electrophoresis demonstrated no significant changes in LPM protein fractions from any of the treatment groups. These studies indicate that thyroid hormone has a parallel effect on bile salt-independent canalicular secretion and LPM Na+, K+-ATPase activity, supporting the hypothesis that Na+ transport and Na+, K+-ATPase may be determinants of bile salt-independent canalicular flow.
Insulin Responses to Glucose in Non-insulin-dependent Diabetic Subjects With and Without the Chlorpropamide-Alcohol Flush: Effect of Salicylate and Naloxone
Authors: Kenneth S Hershon, Edwin L Bierman, Carole M Bruzzone, John W Ensinck
Journal: Diabetes Care (1982)

We examined the role of endogenous opiates and/or prostaglandins on the abnormal insulin secretion characteristic of some non-insulin-dependent diabetic subjects. A group of chlorpropamide-alcohol flush positive (CPAF +) and a group of flush negative (CPAF −) non-insulin-dependent subjects were compared as to their pancreatic beta-cell responses to intravenous glucose tolerance tests before and after sodium salicylate infusion, and before and after naloxone infusion. There was no difference in mean insulin secretion (either first or second phase) between CPAF+ versus CPAF− groups. Both groups increased their insulin secretion with salicylate infusion, and both had a small decrease with naloxone infusion. There was no correlation between chlorpropamide-alcohol flushing and beta-cell response tO glucose.
Gonadal function in young adults after surgical treatment of cryptorchidism.
Authors: E A Werder, R Illig, T Torresani, M Zachmann, P Baumann, F Ott, A Prader
Journal: BMJ (1976)

In a follow-up study of 48 young men who had been surgically treated for cryptorchidism before puberty testicular function was assessed by examining the genitalia, testicular volume, secondary sex characteristics, semen, plasma luteinising hormone (LH) and follicle-stimulating hormone (FSH) concentrations after luteinising hormone-releasing hormone stimulation, and plasma testosterone concentrations. Clinical androgen effects were normal. The mean testicular volume of both testes was in the low normal range in those who had had unilateral cryptorchidism and below normal in those who had had bilateral cryptorchidism. Of 37 patients whose sperm counts were recorded (14 bilateral) six showed azoospermia (all bilateral), five had severe oligospermia (four bilateral), and 10 had moderate oligospermia (one bilateral). In nearly all those who had had bilateral cryptorchidism and most of those who had had unilateral cryptorchidism plasma gonadotrophin levels were increased. Four cases of possible partial LH deficiency were identified. Plasma testosterone concentrations were normal in all except two patients.
Vitamin A and Malaria
Authors: Rebecca Voelker
Journal: JAMA (1999)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Philosophy, Prescriptions, and Politics
Authors: Douglas R. Bess
Journal: JAMA (1980)

<h3>Philosophy</h3> SINCE the 1960s, the complex topic of so-called "substitution, drug product selection, or generic dispensing"<sup>1</sup>has evoked much<i>stürm und drang</i>("storm and stress") in both lay and professional articles. To the detriment of patient, physician, and pharmacist, the issue of generic substitution has been more obfuscated with rhetoric than enlightened by fact. Even exactly what is debated is often unclear, as "positions have had time to harden into symbolic and rigid polarities: Free Enterprise vs. Government, Big Business vs. Consumer Groups, and—especially today—Quality Assurance vs. Cost Containment."<sup>2</sup> Basic concepts of pharmacokinetics (the study of the absorption, distribution, metabolism, and excretion of a drug) have been reviewed elsewhere<sup>3</sup>and will not be covered in this article. The reader, however, is strongly urged to acquaint himself with the basic concepts of bioavailability—such as disintegration and dissolution rates, single-dose and steady-state study designs, blood concentration-time curves, and the
Keratinocyte gene therapy for systemic diseases. Circulating interleukin 10 released from gene-transferred keratinocytes inhibits contact hypersensitivity at distant areas of the skin.
Authors: X Meng, D Sawamura, K Tamai, K Hanada, H Ishida, I Hashimoto
Journal: Journal of Clinical Investigation (1998)

This study has examined the systemic effects of a circulating gene product, human interleukin 10 (IL-10), released from transduced keratinocytes. IL-10 is an anti-inflammatory cytokine which has an inhibitory effect on contact hypersensitivity (CHS). An expression vector (phIL-10) was constructed for human IL-10 and was injected into the dorsal skin of hairless rats. Local expression of IL-10 mRNA and protein was detected by reverse-transcriptase polymerase chain reaction and immunohistochemical staining, respectively. Enzyme-linked immunosorbent assay showed that the amount of IL-10 in the local keratinocytes and in the circulation increased with the dose of phIL-10 transferred. To determine whether circulating IL-10 could inhibit the effector phase of CHS at a distant area of the skin, various doses of phIL-10 were injected into the dorsal skin of sensitized rats before challenge on the ears. Our results showed that the degree of swelling of the ears of phIL-10- treated rats was significantly lower than that in the negative control animals. These results suggest that IL-10 released from transduced keratinocytes can enter the bloodstream and cause biological effects at distant areas of the skin. This study demonstrates that it may be possible to treat systemic disease using keratinocyte gene therapy.
Absence of skin sensitivity to oxides of aluminium, silicon, titanium or zirconium in patients with Crohn's disease.
Authors: J C Lee, S Halpern, D G Lowe, A Forbes, J E Lennard-Jones
Journal: Gut (1996)

Some metallic compounds, especially of zirconium, can cause cell mediated granulomatous inflammation of the skin. Pigment granules containing compounds of aluminium, silicon, and titanium have been observed within macrophages in the wall of the small intestine in health and in Crohn's disease. Zirconium compounds can be ingested in toothpaste.To determine in a pilot study if granulomatous sensitivity can be detected to compounds of these metals or silicon after injection into the skin of patients with Crohn's disease.Eight patients with Crohn's disease known to have had granulomata in the intestine and not currently treated with corticosteroids, and two healthy controls.Two intradermal injections each of 0.1 ml of a 0.02% suspension of one of the compounds made in the abdominal wall of each subject. The site was marked and full thickness skin biopsy performed six weeks later.A foreign body granuloma was observed on histological examination of two biopsy specimens but no evidence of a cell mediated response in any subject.No support was found for the hypothesis that Crohn's disease is due to a specific sensitivity to ingested metallic or silicon compounds.
Therapeutic manipulation of peroxynitrite attenuates the development of opiate-induced antinociceptive tolerance in mice
Authors: Carolina Muscoli, Salvatore Cuzzocrea, Michael M. Ndengele, Vincenzo Mollace, Frank Porreca, Francesca Fabrizi, Emanuela Esposito, Emanuela Masini, George M. Matuschak, Daniela Salvemini
Journal: Journal of Clinical Investigation (2007)

Severe pain syndromes reduce quality of life in patients with inflammatory and neoplastic diseases, often because chronic opiate therapy results in reduced analgesic effectiveness, or tolerance, leading to escalating doses and distressing side effects. The mechanisms leading to tolerance are poorly understood. Our studies revealed that development of antinociceptive tolerance to repeated doses of morphine in mice was consistently associated with the appearance of several tyrosine-nitrated proteins in the dorsal horn of the spinal cord, including the mitochondrial isoform of superoxide (O2–) dismutase, the glutamate transporter GLT-1, and the enzyme glutamine synthase. Furthermore, antinociceptive tolerance was associated with increased formation of several proinflammatory cytokines, oxidative DNA damage, and activation of the nuclear factor poly(ADP-ribose) polymerase. Inhibition of NO synthesis or removal of O2– blocked these biochemical changes and inhibited the development of tolerance, pointing to peroxynitrite (ONOO–), the product of the interaction between O2– and NO, as a signaling mediator in this setting. Indeed, coadministration of morphine with the ONOO– decomposition catalyst, Fe(III) 5,10,15,20-tetrakis(N-methylpyridinium-4-yl)porphyrin, blocked protein nitration, attenuated the observed biochemical changes, and prevented the development of tolerance in a dose-dependent manner. Collectively, these data suggest a causal role for ONOO– in pathways culminating in antinociceptive tolerance to opiates. Peroxynitrite (ONOO–) decomposition catalysts may have therapeutic potential as adjuncts to opiates in relieving suffering from chronic pain.
Novel nonsense mutation in the platelet glycoprotein Ibβ gene associated with Bernard‐Soulier syndrome
Authors: Shinji Kunishima, Tadashi Matsushita, Takahiko Ito, Tadashi Kamiya, Hidehiko Saito
Journal: American Journal of Hematology (2002)

Abstract Bernard‐Soulier syndrome (BSS) is an autosomal recessive bleeding disorder caused by quantitative or qualitative abnormalities in the glycoprotein (GP) Ib/IX/V complex, the platelet receptor for von Willebrand factor. This complex is composed of four subunits, GPIbα, GPIbβ, GPIX, and GPV, and the coordinated assembly of GPIbα, GPIbβ, and GPIX is required for the efficient surface expression of a functional complex. We report here a novel nonsense mutation of the GPIbβ gene associated with BSS. Flow cytometric analysis of the patient's platelets showed markedly reduced GPIbα and absent GPIX surface expression. Immunoblot analysis of solubilized platelets showed that a small amount of GPIbα was detected; however, GPIbβ and GPIX were undetectable. DNA sequencing analysis revealed a novel nonsense mutation of the GPIbβ gene that converts Trp (TGG) to a stop codon (TAG) at residue 123. Transient transfection studies revealed that the mutant GPIbβ polypeptide was not detected in the transfected 293T cells, suggesting that null expression of the mutant GPIbβ impairs expression of the GPIbα and GPIX subunits and results in a BSS phenotype in the patient. Am. J. Hematol. 71:279–284, 2002. © 2002 Wiley‐Liss, Inc.
α-2 macroglobulin gene and Alzheimer disease
Authors: Varuni Rudrasingham, Fabienne Wavrant-De Vrièze, Jean-Charles Lambert, Sumi Chakraverty, Patrick Kehoe, Richard Crook, Philippe Amouyel, William Wu, Frances Rice, Jordi Pérez-Tur, Bernard Frigard, John C. Morris, Stephanie Carty, Ronald Petersen, Dominique Cottel, Nigel Tunstall, Peter Holmans, Simon Lovestone, Marie-Christine Chartier-Harlin, Alison Goate, John Hardy, Michael J. Owen, Julie Williams
Journal: Nature Genetics (1999)
A pilot study of urinary estrogen metabolites (16alpha-OHE1 and 2-OHE1) in postmenopausal women with and without breast cancer.
Authors: G Ursin, S London, F Z Stanczyk, E Gentzschein, A Paganini-Hill, R K Ross, M C Pike
Journal: Environmental Health Perspectives (1997)

The two main pathways for metabolizing estrogen are via 16alpha-hydroxylation and 2-hydroxylation. The 16alpha-hydroxy metabolites are biologically active; the 2-hydroxy metabolites are not. It is suggested that women who metabolize a larger proportion of their endogenous estrogen via the 16alpha-hydroxy pathway may be at significantly elevated risk of breast cancer compared with women who metabolize proportionally more estrogen via the 2-hydroxy pathway. In particular, it is suggested that the ratio of urinary 2-hydroxyestrone (2-OHE1) to 16alpha-hydroxyestrone (16alpha-OHE1) is an index of reduced breast cancer risk. This pilot study compared this ratio in postmenopausal women diagnosed with breast cancer to those of healthy controls. Urinary concentrations of estrone (E1), 17beta-estradiol (E2) and estriol (E3) were also quantified. White women who were subjects in a previous breast cancer case-control study at our institution were eligible for inclusion. All participants provided a sample of their first morning urine. The results from the first 25 cases and 23 controls are presented here. The ratio of 2-OHE1 to 16alpha-OHE1 was 12% lower in the cases (p=0.58). However, urinary E1 was 30% higher (p=0.10), E2 was 58% higher (p=0.07), E3 was 15% higher (p=0.48), and the sum of E1, E2, and E3 was 22% higher (p=0.16) in the cases. These preliminary results do not support the hypothesis that the ratio of the two hydroxylation metabolites (2-OHE1/16alpha-OHE1) is an important risk factor for breast cancer or that it is a better predictor of breast cancer risk than levels of E1, E2 and E3 measured in urine.