tbuckley/cabot-search huggingface dataset:
Kinetics of Salicylate Elimination by Anephric Patients
Authors: David T. Lowenthal, William A. Briggs, Gerhard Levy
Journal: Journal of Clinical Investigation (1974)

The objectives of this research were to determine the kinetics of salicylate elimination in anephric patients and particularly to establish if these patients form the major metabolite of salicylic acid, salicyluric acid, at a normal rate. This investigation was initiated because of conflicting reports concerning the contribution of the kidneys to the formation of salicyluric acid in man. Six patients, 20-44 yr old, three of whom were anatomically anephric while the other three were physiologically anephric, received an intravenous injection of 500 mg salicylic acid (as sodium salicylate)/1.73 m2 body surface area on an interdialysis day. Serial blood samples were obtained for 12 or 16 h after injection and the plasma was assayed for salicylic acid, salicyluric acid, total protein, albumin, and creatinine. Detailed pharmacokinetic analysis based on an open, two-compartment linear model revealed no significant differences in apparent volume of distribution and apparent first-order distribution and elimination rate constants between the anephric patients and normal adult subjects. An estimate of salicyluric acid formation rate by the anephric patients, based on the initial rate of increase of salicylurate concentrations in plasma, indicates that the metabolite is formed at a normal rate. These results suggest that the kidneys do not contribute significantly to the formation of salicyluric acid from salicylic acid in man.
Remarkable Response to Radioiodine Therapy in a Case of Metastatic Macrofollicular Variant of Papillary Thyroid Carcinoma
Authors: Pedro Marques, Valeriano Leite, Maria João Bugalho
Journal: Clinical Nuclear Medicine (2013)

Macrofollicular variant is a rare variant of papillary thyroid carcinoma. Although they are usually associated with a good prognosis, aggressive forms have been described. Distinction from an adenomatous goiter or follicular adenoma is often difficult and can lead to misdiagnosis. We report a metastatic macrofollicular variant of papillary thyroid carcinoma with a remarkable clinical, biochemical, and structural response to radioiodine treatment.
Bim regulation may determine hippocampal vulnerability after injurious seizures and in temporal lobe epilepsy
Authors: Sachiko Shinoda, Clara K. Schindler, Robert Meller, Norman K. So, Tomohiro Araki, Akitaka Yamamoto, Jing-Quan Lan, Waro Taki, Roger P. Simon, David C. Henshall
Journal: Journal of Clinical Investigation (2004)

Programmed cell death pathways have been implicated in the mechanism by which neurons die following brief and prolonged seizures, but the significance of proapoptotic Bcl-2 family proteins in the process remains poorly defined. Expression of the death agonist Bcl-2–interacting mediator of cell death (Bim) is under the control of the forkhead in rhabdomyosarcoma (FKHR) transcription factors. This prompted us to examine the response of this pathway to experimental seizures and in hippocampi from patients with intractable temporal lobe epilepsy. A short period of status epilepticus in rats that damaged the hippocampus activated FKHR/FKHRL-1 and induced a significant increase in expression of Bim. Blocking of FKHR/FKHRL-1 dephosphorylation after seizures improved hippocampal neuronal survival in vivo, and Bim antisense oligonucleotides were neuroprotective against seizures in vitro. Inhibition of Akt increased the FKHR/Bim response and DNA fragmentation within the normally resistant cortex. Analysis of hippocampi from patients with intractable epilepsy revealed that Bim levels were significantly lower than in controls and FKHR was inhibited; we were able to reproduce these results experimentally in rats by evoking multiple brief, noninjurious electroshock seizures. We conclude that Bim expression may be a critical determinant of whether seizures damage the brain, and that its control may be neuroprotective in status epilepticus and epilepsy.
The pharmacological properties of corticosteroids in relation to clinical efficacy
Authors: E. S. SNELL
Journal: British Journal of Dermatology (1976)

The pharmacological properties of cortisol (and cortisol-like drugs) are divided into several distinct activities according to the type and cellular site of action of the hormone. To each of these discrete properties is allotted the separate clinical beneficial responses and the adverse effects that probably arise from them. For any one patient only one, or two, of these pharmacological properties are desirable and the remainder are undesirable. Therapy aims to separate the wanted from unwanted effects and this can be attempted in three ways: firstly, by adjustment of dose, frequency and duration of corticosteroid administration; secondly by delivery of the drug directly only to the site of disease– if this is possible; and thirdly, by using analogues which have been synthesized with ‘tailor-made’ selective actions. Synthetic analogues have not yet offered much selectivity of action of value for systemic use, but for local use (as on the skin and in the respiratory tract) such analogues have provided a considerable therapeutic advance. It is suggested that the several distinctive pharmacological properties of cortisol (as well as the existence of other steroids closely related chemically but with widely different biological activities, such as progestagens and anaesthetics) offer hope for the synthesis of cortisol-like compounds with much greater selectivity in systemic action.
Viruses in Carcinogenesis
Authors: RENATO DULBECCO
Journal: Annals of Internal Medicine (1969)

This article reviews the role of viruses in cancer. Oncogenic viruses may contain either ribonucleic acid (RNA) or deoxyribonucleic acid (DNA). The small DNA viruses, polyoma virus and SV40, are best known in terms of genetics and molecular biology. Cell transformation by these viruses includes two steps: first, the integration of the viral DNA in the cellular DNA; and secondly, the expression of viral transforming functions. If integration fails, the cells undergo abortive transformation and then return to normality. In the transformed cell only some of the viral genes are transcribed into messenger RNA, and this accounts for the survival of the cells. The RNA viruses are less well known. They produce either leukemias with very low efficiency or (sometimes) sarcomas with a high efficiency. The sarcoma viruses often have complex biology. An extensive search is going on for viruses as possible agents of human cancer. The most interesting virus is the one found in the Burkitt's lymphoma cells and, in all likelihood, the agent of infectious mononucleosis. The search for human cancer viruses is beset by great difficulties, both methodological and conceptual.
Textbook of Medicine
Authors: Lester S. King
Journal: JAMA (1975)

How can any one person review the new edition of Beeson-McDermott, with its 200 contributors (over a third of them new); its 1,892 pages of text, together with much accessory material; with its coverage of conditions and diseases, causes and remedies, from "abdomen, actinomycosis of" to "zyloprim (see allopurinol)"? No reviewer, regardless of his training or background, is competent to evaluate the total medical knowledge involved. But he can provide a personal reaction. First, a few superficial comments, comparing this to the previous edition. The new volume is slightly larger overall. Although there are fewer actual text pages, the margins are smaller. The index is vastly more detailed, covering 78 pages compared with the previous 51. If you want, you can look up O'Nyong-Nyong fever or Psathyrosis, which you could not do in the 13th edition. The table of contents is vastly improved in regard to organization, arrangement, clarity, and
Globular and full-length forms of adiponectin mediate specific changes in glucose and fatty acid uptake and metabolism in cardiomyocytes
Authors: R PALANIVEL, X FANG, M PARK, M EGUCHI, S PALLAN, S DEGIROLAMO, Y LIU, Y WANG, A XU, G SWEENEY
Journal: Cardiovascular Research (2007)

Our aim was to investigate the regulation of glucose and fatty acid metabolism in cardiomyocytes by the globular (gAd) and full-length (fAd) forms of adiponectin.We produced fAd (consisting of high, medium and low molecular weight oligomers) in a mammalian expression system and gAd in bacteria. These were used to treat primary neonatal rat cardiomyocytes (up to 48 h), and we employed 3H- or 14C-labeled substrates to monitor glucose uptake and subsequent metabolism via oxidation, glycogen synthesis or lactate production and fatty acid uptake and oxidation. Enzymatic assay for acetyl CoA carboxylase activity was employed, and protein phosphorylation and expression was determined by immunoblotting cell lysates. The role of adiponectin receptor (AdipoR) isoforms was determined via siRNA-mediated knockdown.There was an initial (1 h) increase in glucose uptake and oxidation in response to gAd or fAd. Fatty acid uptake was stimulated by gAd or fAd, and by 24 h a decrease in acetyl CoA carboxylase activity and elevated fatty acid oxidation were observed. After 48 h increased fatty acid oxidation correlated with decreased glucose oxidation and pyruvate dehydrogenase activity, while glycogen synthesis and lactate production increased. Both gAd and fAd elicited phosphorylation of AMP kinase, insulin receptor substrate-1, Akt and glycogen synthase kinase-3beta. Knockdown of AdipoR1 or AdipoR2 attenuated the effect of both gAd and fAd on fatty acid uptake and oxidation. Only AdipoR1 knockdown prevented the ability of gAd (1 h) to increase glucose uptake and oxidation; however, reducing either AdipoR1 or AdipoR2 expression attenuated the long-term (24 h) effects of gAd.These results clearly demonstrate that gAd and fAd mediate distinct and time-dependent effects on cardiomyocyte energy metabolism via AdipoR1 and AdipoR2.
Encounters With Aging: Mythologies of Menopause in Japan and North America
Authors: Johanna F. Perlmutter
Journal: JAMA (1995)

The author has done a Herculean job of interviewing more than 1000 Japanese women over 20 years. The inquiries were to establish what knowledge these women had about the menopause and the symptoms they experienced. Women from all walks of life were included. Each chapter has a theme, and narratives from selected women are included to describe and emphasize the point being made. Statistics are detailed in one chapter, and the rest of the book is devoted to narrative description. A detailed picture of life in Japan evolves from this. Changes in society are well outlined, allowing one to better understand how the nuclear family is evolving and the problems that have resulted. Information is given about the position of various members of the family and the extended family. Emphasis is placed in this narrative on the role of women—their work habits and daily living experiences, particularly during the midlife
MPs are urged to end inaction on social care reform
Authors: M. Limb
Journal: BMJ (2012)

<h3>Objectives</h3> To derive priority weights for access to bariatric surgery for obese adults, from the perspective of the public. <h3>Setting</h3> Australian public hospital system. <h3>Participants</h3> Adults (N=1994), reflecting the age and gender distribution of Queensland and South Australia. <h3>Primary and secondary outcome measures</h3> A discrete choice experiment in which respondents indicated which of two individuals with different characteristics should be prioritised for surgery in repeated hypothetical choices. Potential surgery recipients were described by seven key characteristics or attributes: body mass index (BMI), presence of comorbid conditions, age, family history, commitment to lifestyle change, time on the surgical wait list and chance of maintaining weight loss following surgery. A multinomial logit model was used to evaluate preferences and derive priority weights (primary analysis), with a latent class model used to explore respondent characteristics that were associated with variation in preference across the sample (see online supplementary analysis). <h3>Results</h3> A preference was observed to prioritise individuals who demonstrated a strong commitment to maintaining a healthy lifestyle as well as individuals categorised with very severe (BMI≥50 kg/m<sup>2</sup>) or (to a lesser extent) severe (BMI≥40 kg/m<sup>2</sup>) obesity, those who already have obesity-related comorbidity, with a family history of obesity, with a greater chance of maintaining weight loss or who had spent a longer time on the wait list. Lifestyle commitment was considered to be more than twice as important as any other criterion. There was little tendency to prioritise according to the age of the recipient. Respondent preferences were dependent on their BMI, previous experience with weight management surgery, current health state and education level. <h3>Conclusions</h3> This study extends our understanding of the publics’ preferences for priority setting to the context of bariatric surgery, and derives priority weights that could be used to assist bodies responsible for commissioning bariatric services.
Inorganic mercury and methylmercury in placentas of Swedish women.
Authors: Karolin Ask, Agneta Akesson, Marika Berglund, Marie Vahter
Journal: Environmental Health Perspectives (2002)

We determined levels of inorganic mercury (I-Hg) and methylmercury in placentas from 119 Swedish women, not selected with respect to high exposure of mercury. Our objective was to relate placental Hg species with maternal and fetal blood concentrations and to evaluate possible associations with selenium. We performed the analyses using automated alkaline solubilization/reduction and cold-vapor atomic fluorescence spectrophotometry. I-Hg levels in placenta increased with an increasing number of maternal dental amalgam fillings (p < 0.001). Despite placental accumulation (median, 1.3 microg/kg; range, 0.18-6.7 microg/kg wet weight), a substantial fraction of maternal blood I-Hg, probably as Hg(0), reached the fetus. Although MeHg transferred easily to the fetus, it also accumulated in the placenta. On average, 60% of placental Hg was in the form of MeHg. The median concentration was 1.8 microg/kg (range, 0-6.2 microg/kg wet weight), more than twice the maternal blood concentration. We found significant associations between MeHg and selenium in both maternal and umbilical cord blood but not in the placenta. The associations were particularly obvious in freshwater fish consumers, probably reflecting that fish is a source of both MeHg and selenium. We found no correlations between I-Hg and selenium. This study increases the understanding of Hg, in its different forms, in human placenta and how they are related to maternal and fetal exposure.
Conceptualizing Physician Professionalism
Authors: Arthur H. Gale
Journal: JAMA (2011)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
Frailty and type of death among older adults in China: prospective cohort study
Authors: M. E Dupre, D. Gu, D. F Warner, Z. Yi
Journal: BMJ (2009)

<b>Objective</b> To examine the association between frailty and type of death among the world's largest oldest-old population in China. <b>Design</b> Prospective cohort study. <b>Setting</b> 2002 and 2005 waves of the Chinese longitudinal healthy longevity survey carried out in 22 provinces throughout China. <b>Participants</b> 13 717 older adults (aged ≥65). <b>Main outcome measures</b> Type of death, categorised as being bedridden for fewer than 30 days with or without suffering and being bedridden for 30 or more days with or without suffering. <b>Results</b> Multinomial analyses showed that higher levels of frailty significantly increased the relative risk ratios of mortality for all types of death. Of those with the highest levels of frailty, men were most likely to experience 30 or more bedridden days with suffering before death (relative risk ratio 8.70, 95% confidence interval 6.31 to 12.00) and women 30 or more bedridden days with no suffering (11.53, 17.84 to 16.96). Regardless of frailty, centenarians and nonagenarians were most likely to experience fewer than 30 bedridden days with no suffering, whereas those aged 65-79 and 80-89 were more likely to experience fewer than 30 bedridden days with suffering. Adjusting for compositional differences had little impact on the link between frailty and type of death for both sexes and age groups. <b>Conclusions</b> The association between frailty and type of death differs by sex and age. Health scholars and clinical practitioners should consider age and sex differences in frailty to develop more effective measures to reduce preventable suffering before death.
A Phase I and Pharmacokinetic Study of Irinotecan Given as a 7-Day Continuous Infusion in Metastatic Colorectal Cancer Patients Pretreated with 5-Fluorouracil or Raltitrexed
Authors: Gianluca Masi, Alfredo Falcone, Antonello Di Paolo, Giacomo Allegrini, Romano Danesi, Cecilia Barbara, Samanta Cupini, Mario Del Tacca
Journal: Clinical Cancer Research (2004)

The purpose is to determine the plasma pharmacokinetics, the maximum-tolerable dose and to preliminary evaluate the antitumor activity of irinotecan administered as a 7-day continuous infusion every 21 days in metastatic colorectal cancer patients pretreated with 5-fluorouracil or raltitrexed.A total of 13 patients entered the study. Three received irinotecan at 20 mg/m(2)/day (dose level I), 6 at 25 mg/m(2)/day (dose level II), and 4 at 22.5 mg/m(2)/day (dose level III). In 8 patients, plasma levels of irinotecan and its metabolites SN-38 and SN-38 glucuronide (SN-38glu) were measured by high-performance liquid chromatography and main pharmacokinetic parameters, including steady-state concentration, area under the time-concentration curve, and clearance, were calculated and normalized to the dose level of 22.5 mg/m(2)/day.Dose-limiting toxicity was grade 3-4 diarrhea, which occurred in 4 of 6 patients at dose level II and in 2 of 4 patients at dose level III. Therefore, we defined 22.5 mg/m(2)/day the maximum-tolerable dose and 20.0 mg/m(2)/day the recommended dose for Phase II studies. Hematological toxicity was rare. The pharmacokinetic data provided evidence that continuous infusion increased the metabolism of irinotecan to SN-38 with respect to standard 30/90-min administration. Indeed, the steady-state concentration of irinotecan, SN-38, and SN-38glu were 42.7 +/- 25.2, 14.9 +/- 1.9, and 31.7 +/- 3.5 nmol/liter, respectively, and the area under the time-concentration curves of irinotecan, SN-38, and SN-38glu were 6.94 +/- 0.41, 1.92 +/- 0.30, and 4.23 +/- 0.52 hx micro mol/liter, respectively. Twelve patients were evaluable for activity, and we observed 3 (25%) partial responses, 2 (17%) minor responses, and 4 (33%) disease stabilizations.The administration of irinotecan as a 7-day continuous infusion every 21 days is feasible with diarrhea being the dose-limiting toxicity; recommended dose for Phase II studies is 20.0 mg/m(2)/day. The comparison of the present data with those obtained after a standard 30-90 min. i.v. infusion of irinotecan demonstrates that continuous infusion improves the transformation of irinotecan to SN-38 and also results in increased glucuronidation of the active metabolite. Antitumor activity in pretreated metastatic colorectal cancer patients is encouraging.
What is a good death?: A good death follows a good life
Authors: A. A Syed
Journal: BMJ (2003)

Editor—A good death is like the final chapter of a good book: it wraps up the story of life with panache; is physically, emotionally, and spiritually satisfying to the author (the deceased) and the readers (kith and kin); and leaves no loose ends to be explained in a sequel.1​1




Figure 1
The International Hippocratic Foundation of Cos
Authors: Spyridion Oeconomos
Journal: JAMA (1962)

To the Editor:—  The appearance of Chauncey D. Leake's letter (JAMA177:813 [Sept. 16] 1961) has been a most valuable support to the cause of the International Hippocratic Foundation of Cos, and we appreciated it very much indeed. Pending the establishment of a special fund, would-be members of the foundation are kindly asked to send their contributions through the local agencies of the American Express Company which is properly represented in Greece. Owing to various difficulties, contributions are more easily collected, instead of by subscriptions or otherwise, the conference of the membership not being disturbed by the procedure mentioned.
Orthopaedic surgeons and flaccid liberals
Authors: K. Barraclough
Journal: BMJ (2003)

It is easy to forget to be in awe of what our colleagues do everyday. As a physician and flaccid liberal I have spent my working life disparaging, in a humorous way (I assumed), the labours of orthopaedic surgeons. But being on the receiving end of their ministrations rekindles a sense of wonder. Injuries that once would have crippled a person for life are now merely minor. Thanks to steel and titanium (and, in my case, …
Cytoprotection by Jun Kinase During Nitric Oxide–Induced Cardiac Myocyte Apoptosis
Authors: Peter Andreka, Jie Zang, Christopher Dougherty, Tatiana I. Slepak, Keith A. Webster, Nanette H. Bishopric
Journal: Circulation Research (2001)

Nitric oxide (NO) induces apoptosis in cardiac myocytes through an oxidant-sensitive mechanism. However, additional factors appear to modulate the exact timing and rate of NO-dependent apoptosis. In this study, we investigated the role of mitogen-activated protein kinases (MAPKs) (extracellular signal-regulated kinase [ERK] 1/2, c-Jun N-terminal kinase [JNK] 1/2, and p38MAPK) in NO-mediated apoptotic signaling. The NO donor S:-nitrosoglutathione (GSNO) induced caspase-dependent apoptosis in neonatal rat cardiac myocytes, preceded by a rapid (<10-minute) and significant (approximately 50-fold) activation of JNK1/2. Activation of JNK was cGMP dependent and was inversely related to NO concentration; it was maximal at the lowest dose of GSNO (10 micromol/L) and negligible at 1 mmol/L. NO slightly increased ERK1/2 beginning at 2 hours but did not affect p38MAPK activity. Inhibitors of ERK and p38MAPK activation did not affect cell death rates. In contrast, expression of dominant-negative JNK1 or MKK4 mutants significantly increased NO-induced apoptosis at 5 hours (56.77% and 57.37%, respectively, versus control, 40.5%), whereas MEKK1, an upstream activator of JNK, sharply reduced apoptosis in a JNK-dependent manner. Adenovirus-mediated expression of dominant-negative JNK1 both eliminated the rapid activation of JNK by NO and accelerated NO-mediated apoptosis by approximately 2 hours. These data indicate that NO activates JNK as part of a cytoprotective response, concurrent with initiation of apoptotic signaling. Early, transient activation of JNK serves both to delay and to reduce the total extent of apoptosis in cardiac myocytes.