tbuckley/cabot-search huggingface dataset:
Progressive Multifocal Leukoencephalopathy in AIDS
Authors: Richard E. Chaisson
Journal: JAMA (1990)

<h3>CASE PRESENTATION</h3> —John Williams, MD A 42-YEAR-OLD bisexual, white man presented complaining of progressive memory loss, confusion, and difficulty speaking for 1 week. The patient had been diagnosed with acquired immunodeficiency syndrome (AIDS) a year earlier when he developed cutaneous Kaposi's sarcoma. Three months before admission,<i>Pneumocystis</i>pneumonia was diagnosed and treated. At that time, radiation therapy for his cutaneous Kaposi's lesions was performed. A month prior to admission, he was found to have Kaposi's sarcoma of the upper gastrointestinal tract. On admission he denied fever, sweats, headache, stiff neck, photophobia, seizures, or focal weakness. His medications were a combination product of sulfamethoxazale and trimethoprim and clotrimazole troches. Physical examination showed a temperature of 37°C; pulse rate, 82 beats per minute; blood pressure, 127/79 mm Hg; and respirations, 18/min. Notable physical findings included the cutaneous lesions of Kaposi's sarcoma, a 2/6 systolic ejection murmur at the left sternal border, and
Advanced Maternal Age — How Old Is Too Old?
Authors: Linda J. Heffner
Journal: New England Journal of Medicine (2004)

The past decade has seen a remarkable shift in the demographics of childbearing in the United States. The number of first births per 1000 women 35 to 39 years of age increased by 36 percent between 1991 and 2001, and the rate among women 40 to 44 years of age leaped by a remarkable 70 percent. In 2002, 263 births were reported in women between 50 and 54 years of age. Most media attention paid to older moms has been favorable, inspiring a female business-school student to declare on a nationally televised segment of CBS's 60 Minutes (entitled "The Biological . . .
Health Care Reform in Action — Calorie Labeling Goes National
Authors: Marion Nestle
Journal: New England Journal of Medicine (2010)

Tucked away on page 455 of the 906-page health care reform act (Public Law 111-148) is a provision for listing calorie counts on the menu boards of chain restaurants or adjacent to each food offered in vending machines and in retail stores. Establishments with 20 or more locations nationwide must post calories "in a clear and conspicuous manner," along with "a succinct statement concerning suggested daily caloric intake" — presumably the 2000-kcal-per-day standard that the Food and Drug Administration (FDA) uses for the "Nutrition Facts" on packaged foods. When the Nutrition Labeling and Education Act of 1990 went into effect . . .
Timing and sampling in surveillance of premalignant gastric lesions
Authors: G. Capurso, E. Lahner, G. Delle Fave, Bruno Annibale
Journal: Gut (2002)

We read with interest the paper by Whiting et al ( Gut 2002; 50 :378–81) regarding the surveillance of premalignant gastric lesions. The authors reported that over 10 years, 12 cancers (11.5%) were diagnosed in 104 patients with intestinal metaplasia and/or atrophic gastritis. Therefore, they suggest that these patients have an increased risk of developing gastric cancer, and benefit from annual endoscopic follow up.

Although we agree with the major conclusions of the study, our experience is somehow different. In fact, we have recently investigated the timing of first endoscopic-histological follow up of patients with body predominant atrophic gastritis and demonstrated that four years seems a satisfactory interval for the first follow up of these patients.1 The timing of surveillance …
Bruce's Choice
Authors: Charlie Goldberg
Journal: Annals of Internal Medicine (2002)

On Being a Doctor21 May 2002Bruce's ChoiceCharlie Goldberg, MDCharlie Goldberg, MDSan Diego VA Medical Center; San Diego, CA 92037Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-136-10-200205210-00014 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Bruce was a pain in the ass. I'm sure that his premorbid state bore little resemblance to his current condition. He had been a construction worker. Decades of smoking, however, left him tethered to an oxygen tank and in a wheelchair. His brittle and collapsed bones, washed out from years of prednisone use, supported a chronic morphine requirement but little else. He was angry and tired, our periodic encounters focusing on the difficulties of his day-to-day existence.I was surprised to receive a message that Bruce really needed to talk with me. In the past, he would frequently call to ... Author, Article, and Disclosure InformationAffiliations: San Diego VA Medical Center; San Diego, CA 92037Corresponding Author: Charlie Goldberg, MD, San Diego VA Medical Center, Department of Internal Medicine, 3350 La Jolla Village Drive, San Diego, CA 92101; e-mail, charles.[email protected]va.gov. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByThe choices, choosing model of quality of life: linkages to a science base 21 May 2002Volume 136, Issue 10Page: 777-778KeywordsColonoscopyHead and neck cancersLiverPelvisPerceptionReasoningRectumTouchVomitingWheelchairs ePublished: 21 May 2002 Issue Published: 21 May 2002 CopyrightCopyright © 2002 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Endothelial Function in Deoxycorticosterone-NaCl Hypertension
Authors: Heikki Mäkynen, Mika Kähönen, Xiumin Wu, Pertti Arvola, Ilkka Pörsti
Journal: Circulation (1996)

Background Dietary calcium intake has been suggested to correlate inversely with blood pressure in humans and experimental animals. However, the effects of calcium supplementation on hypertensive disturbances of the endothelium have not been well characterized. Methods and Results Wistar-Kyoto rats were made hypertensive by deoxycorticosterone (DOC)-NaCl treatment, but a concurrent increase in chow calcium content from 1.1% to 2.5% markedly attenuated the rise in blood pressure. The function of isolated mesenteric arterial rings in vitro was investigated at the close of the 10-week study. In norepinephrine-precontracted rings, the relaxations to acetylcholine (ACh) and ADP, as well as to nitroprusside, 3-morpholinosydnonimine, and isoproterenol were attenuated in hypertensive rats on 1.1% calcium, but these responses were improved by calcium supplementation. In the presence of N G -nitro- l -arginine methyl ester (L-NAME), the relaxations to ACh in hypertensive animals on normal calcium were practically absent, whereas in normotensive rats and calcium-supplemented hypertensive rats, distinct relaxations to higher concentrations of ACh were still present. These responses were reduced by 30% to 50% with apamin, a blocker of Ca 2+ -activated K + channels, and were further inhibited by blockade of ATP-dependent K + channels with glyburide. Interestingly, relaxations elicited by ACh and ADP during precontraction with 60 mmol/L KCl (preventing endothelium-dependent hyperpolarization) were not impaired in hypertensive animals. The contractile sensitivity of endothelium-intact arterial rings to 5-hydroxytryptamine and norepinephrine was higher in hypertensive rats on either normal or high-calcium diet, whereas the increase in contractile sensitivity caused by L-NAME corresponded in all groups. Conclusions High-calcium diet markedly opposed experimental DOC-NaCl hypertension, an effect associated with improved arterial relaxation, while abnormalities of vascular contractile properties remained unaffected. In particular, the hyperpolarization-related component of endothelium-dependent arterial relaxation, mediated via opening of arterial K + channels, could be augmented by calcium supplementation in DOC-NaCl hypertension.
Detection of Double Meckel Diverticulum by Meckel Scan
Authors: Ji-Gang Yang, Da-Qing Ma, Rui-Rui Hao, Chun-Lin Li, Lan-Fang Zou
Journal: Clinical Nuclear Medicine (2008)

Meckel scan with Tc-99m pertechnetate is commonly used for detection of Meckel diverticulum by localization within ectopic gastric mucosa. An 8-year-old boy had a 2-week history of constant right abdomen pain associated with bright red bleeding and anemia. Clinical examination revealed pallor but nothing else of note. Meckel scan was performed without any pharmacologic pretreatment, and double abnormal foci were demonstrated in the right upper and lower quadrants. The patient underwent laparoscopy, and double Meckel diverticulum was removed. The patient recovered fully after operation.
Relationship Between Mitochondrial Matrix Volume and Cellular Volume in Response to Stress and the Role of ATP-Sensitive Potassium Channel
Authors: Melissa M. Anastacio, Evelyn M. Kanter, Carol M. Makepeace, Angela D. Keith, Haixia Zhang, Richard B. Schuessler, Colin G. Nichols, Jennifer S. Lawton
Journal: Circulation (2013)

Background— Cardiac myocytes demonstrate significant swelling and associated reduced contractility in response to stress that is prevented by the ATP-sensitive potassium channel opener, diazoxide (DZX) via an unknown mechanism. One proposed mechanism of cardioprotection is mitochondrial matrix swelling. To establish the relationship between mitochondrial and cellular volume during stress, this study examined the effect of DZX on mitochondrial volume. Methods and Results— Isolated mouse mitochondria were exposed to the following solutions: Tyrode, isolation buffer, cardioplegia (CPG)±DZX±ATP-sensitive potassium channel inhibitor, 5-hydroxydecanoate, and metabolic inhibition (MI)±DZX±5-hydroxydecanoate. Mitochondrial volume was measured. DZX resulted in significant mitochondrial swelling ( P &lt;0.0001 versus Tyrode). MI and CPG resulted in significant mitochondrial swelling compared with baseline volume. The addition of DZX did not alter the response of mitochondrial volume to CPG ( P =0.912) but increased swelling in response to MI ( P =0.036). The addition of 5-hydroxydecanoate to MI+DZX or CPG+DZX significantly reduced mitochondrial swelling ( P &lt;0.003 MI+DZX versus MI+DZX+5HD; P &lt;0.001 CPG+DZX versus CPG+DZX+5HD). Conclusions— Both cellular and mitochondrial volume increased during exposure to MI and CPG. DZX did not alter mitochondrial volume during CPG; however, it was associated with an increase in mitochondrial volume during MI. 5-Hydroxydecanoate reduced mitochondrial volume during exposure to both stresses with DZX, supporting a role for a mitochondrial ATP-sensitive potassium channel in the mechanism of cardioprotection by DZX.
A Phase I Pilot Study of the Oral mTOR Inhibitor RAD001 in Combination with Capecitabine for Metastatic Breast Cancer.
Authors: C. Chen, M. Chen, R. Imaoka, T. Svahn, A. Guardino
Journal: Cancer Research (2009)

Abstract Background:RAD001 is an oral inhibitor of mTOR, an intracellular protein kinase downstream of the PI3K/Akt signaling pathway. There is evidence to suggest that Akt promotes breast cancer resistance to cytotoxic treatment and thus targeting this pathway with RAD001 may increase the efficacy of standard chemotherapy. We combined RAD001 in a Phase I dose escalation study with Capecitabine (oral fluorpyrimidine), as treatment of metastatic breast cancer. This study evaluated the oral combination for tolerability and safety. Pharmacokinetics of RAD001 was examined in all dosing cohorts.Methods:This was a single center, Phase I trial. Eligible patients had stage IV breast cancer, have not received endocrine or chemotherapy for 3 weeks prior to initiation and not receiving concurrent endocrine therapy. Patients must not have received prior therapy with capecitabine or an mTOR inhibitor and up to 3 prior chemotherapy regimens were allowable. Pharmacokinetic data are collected weekly for first 2 cycles.All patients received capecitabine (825 mg PO BID) and RAD001 in 3 dose-escalation cohorts: 2.5 mg every other day (Cohort 1), 2.5 mg daily (Cohort 2) and 5 mg daily (cohort 3). The primary endpoint is to determine the DLT of RAD001 + capecitabine, secondary endpoints include tumor response. Treatment continues until disease progression or unacceptable toxicity. Efficacy assessed every 6 weeks for first 4 cycles, then every 9 weeks until end of the 1st year of treatment, then every 12 weeks after.Results: As of April 2009, 12 patients with a median age of 58 years (range 34-75) have been treated at 3 dose levels: 3 in the 1st cohort, 6 in the 2nd cohort and 3 in the 3rd cohort. Toxicities in cohort 1 were generally manageable and expected. They most commonly consisted of nausea, hand-foot syndrome and elevated LFTs. 2 patients in cohort 2 had a grade 3/4 neutropenia and responded to dose reduction. 1 patient had a grade 3/4 elevated lipid panel. Other adverse events (all grade 1/2) included leukopenia, neutropenia, anemia, hypoalbuminemia, elevated LFTs, nausea, hand-foot syndrome, fatigue, sensory neuropathy, and thrombocytopenia. Of the 9 evaluable patients, the clinical benefit rate (CR+PR+SD ≥ 24 weeks) in this heavily pretreated group is 44%. No patient had DLT during cycle 1. 3 patients remain on treatment. Enrollment to the 3rd cohort continues.Conclusion:The all-oral regimen of RAD001 with capecitabine is well tolerated. The maximal tolerated dose (MTD) after 3 dose escalations was not reached. The maximal dose of 5 mg per day of RAD001 was well tolerated. Final toxicity data and preliminary efficacy will be presented at the meeting. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6112.
Abstract LB-16: Altered circadian rhythm components are resynchronized by melatonin in human prostate cancer
Authors: Brittney D. Jung, Wei Huang, Nihal Ahmad
Journal: Cancer Research (2010)

Abstract Prostate cancer (PCa) is a major age-related malignancy as increasing age correlates with increased risk for developing this neoplasm. Similarly, alterations in circadian rhythms, because of modifications in various core clock components, have also been associated with the aging population and cancer risk. The pineal hormone melatonin is known to regulate circadian rhythm, which is under the control of a core set of genes: Per-, Clock- and Bmal-family members. The circulating serum levels of melatonin have been shown to decrease in patients with cancer including PCa. Interestingly, melatonin has been shown to have anti-proliferative effects in certain cancers. We have recently found that melatonin imparts anti-proliferative effects in vitro and in vivo via inhibiting Sirt1 that is a class III histone deacetylase and involved in the regulation of aging and several other metabolic processed. In this study, we challenged the hypothesis that melatonin imparts anti-proliferative effects in prostate cancer via resynchronization of deregulated core clock circuitry at the cellular level. First, we determined if the core clock genes circuitry is disrupted in PCa. Interestingly, we found that Clock and Per2 protein levels were downregulated whereas Bmal1 protein levels were up regulated in PCa cells (LNCaP, 22R 1, DU145, PC3), compared to normal prostate epithelial cells as assessed by Western blot analysis. Further, we employed the automated quantitative analysis (AQUA) system to asses the levels of Clock, Per2 and Bmal1 in a tissue microarray (TMA) containing clinical specimens of benign prostate hyperplasia (BPH), high-grade intraepithelial neoplasias (HGPIN), localized PCa, aggressive PCa with metastases as well as benign prostate tissue. We found that compared to benign tissues, in all proliferative prostate diseases Clock and Per2 levels were downregulated whereas Bmal1 levels were up regulated. In addition, a forced over-expression of Per2 was found to result in a significant loss of viability of PCa cells. Further, we found that melatonin (1mM and 2mM; 48 h) treatment causes an increase in Per2 and Clock and decrease in Bmal1 (at the protein and mRNA levels) in human PCa cells. Furthermore, as shown by the COSOPT algorithm, we found that melatonin treatment resulted in a resynchronization of oscillatory circadian rhythm genes (Dbp and Per2) while having no effect on non-oscillatory genes. Our data support our hypothesis and suggest that melatonin should be thoroughly investigated as an agent for the management of PCa and other age-related malignancies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-16.
Transfusion in the absence of inflammation induces antigen-specific tolerance to murine RBCs
Authors: Nicole H. Smith, Eldad A. Hod, Steven L. Spitalnik, James C. Zimring, Jeanne E. Hendrickson
Journal: Blood (2011)

Most human transfusion recipients fail to make detectable alloantibodies to foreign RBC antigens ("nonresponders"). Herein, we use a murine model to test the hypothesis that nonresponders may be immunologically tolerant. FVB mice transfused with RBCs expressing transgenic human glycophorin A (hGPA) antigen in the absence of inflammation produced undetectable levels of anti-hGPA immunoglobulins, unlike those transfused in the presence of polyinosinic:polycytidylic acid-induced inflammation. Mice in the nonresponder group failed to produce anti-hGPA after subsequent transfusions in the presence of polyinosinic:polycytidylic acid, whereas anti-hGPA levels increased in the responder group. This tolerance was antigen specific, because nonresponders to hGPA produced alloantibodies to RBCs that expressed a different transgenic antigen. This tolerance was not an idiosyncrasy of the hGPA antigen nor of the recipient strain, because B10.BR mice transfused with membrane-bound hen egg lysozyme antigen-transgenic RBCs also demonstrated induced nonresponsiveness. These data demonstrate that RBCs transfused in the absence of inflammation can induce tolerance.
EFFECT OF ROSUVASTATIN ON CORONARY FIBROUS CAP THICKNESS IN PATIENTS WITH ACUTE CORONARY SYNDROME: SERIAL OPTICAL COHERENCE TOMOGRAPHY STUDY
Authors: Hironori Kitabata, Shigeho Takarada, Hiroto Tsujioka, Manabu Kashiwagi, Yasutsugu Shiono, Kunihiro Shimamura, Makoto Orii, Kohei Ishibashi, Kenichi Komukai, Takashi Tanimoto, Yasushi Ino, Kazushi Takemoto, Kenichi Ishigami, Tsunenari Soeda, Keizo Kimura, Kumiko Hirata, Masato Mizukoshi, Toshio Imanishi, Shiro Uemura, Yoshihiko Saito
Journal: Journal of the American College of Cardiology (2011)
beta Blockade after myocardial infarction: systematic review and meta regression analysis
Authors: N. Freemantle, J. Cleland, P. Young, J. Mason, J. Harrison
Journal: BMJ (1999)

<h3>Abstract</h3> <b>Objectives</b>: To assess the effectiveness of β blockers in short term treatment for acute myocardial infarction and in longer term secondary prevention; to examine predictive factors that may influence outcome and therefore choice of drug; and to examine the clinical importance of the results in the light of current treatment. <b>Design</b>:Systematic review of randomised controlled trials. <b>Setting</b>: Randomised controlled trials. <b>Subjects</b>: Patients with acute or past myocardial infarction. <b>Intervention</b>: βBlockers compared with control. <b>Main</b>:outcome measures All cause mortality and non-fatal reinfarction. <b>Results</b>: Overall, 5477 of 54 234 patients (10.1%) randomised to β blockers or control died. We identified a 23% reduction in the odds of death in long term trials (95% confidence interval 15% to 31%), but only a 4% reduction in the odds of death in short term trials (−8% to 15%). Meta regression in long term trials did not identify a significant reduction in effectiveness in drugs with cardioselectivity but did identify a near significant trend towards decreased benefit in drugs with intrinsic sympathomimetic activity. Most evidence is available for propranolol, timolol, and metoprolol. In long term trials, the number needed to treat for 2 years to avoid a death is 42, which compares favourably with other treatments for patients with acute or past myocardial infarction. <b>Conclusions</b>: β Blockers are effective in long term secondary prevention after myocardial infarction, but they are underused in such cases and lead to avoidable mortality and morbidity.
Somatic deletions of genes regulating MSH2 protein stability cause DNA mismatch repair deficiency and drug resistance in human leukemia cells
Authors: Barthelemy Diouf, Qing Cheng, Natalia F Krynetskaia, Wenjian Yang, Meyling Cheok, Deqing Pei, Yiping Fan, Cheng Cheng, Evgeny Y Krynetskiy, Hui Geng, Siying Chen, William E Thierfelder, Charles G Mullighan, James R Downing, Peggy Hsieh, Ching-Hon Pui, Mary V Relling, William E Evans
Journal: Nature Medicine (2011)
Mercury levels in high-end consumers of fish.
Authors: Jane M Hightower, Dan Moore
Journal: Environmental Health Perspectives (2002)

Consumption of food containing mercury has been identified as a health risk. The U.S. Environmental Protection Agency (U.S. EPA) and the National Academy of Sciences recommend keeping the whole blood mercury level < 5.0 microg/L or the hair level < 1.0 microg/g. This corresponds to a reference dose (RfD) of 0.1 microg/kg body weight per day. All patients in a 1-year period (n = 720) who came for an office visit in a private internal medicine practice in San Francisco, California, were evaluated for mercury excess using the current RfD. One hundred twenty-three patients were tested (93 females, 30 males). Of these, data were statistically analyzed for 89 subjects. Mercury levels ranged from 2.0 to 89.5 microg/L for the 89 subjects. The mean for 66 women was 15 microg/L [standard deviation (SD) = 15], and for 23 men was 13 microg/L (SD = 5); 89% had levels exceeding the RfD. Subjects consumed 30 different forms or types of fish. Swordfish had the highest correlation with mercury level. Sixty-seven patients with serial blood levels over time after stopping fish showed a decline in mercury levels; reduction was significant (p < 0.0001). A substantial fraction of patients had diets high in fish consumption; of these, a high proportion had blood mercury levels exceeding the maximum level recommended by the U.S. EPA and National Academy of Sciences. The mean level for women in this survey was 10 times that of mercury levels found in a recent population survey by the U.S. Centers for Disease Control and Prevention. Some children were > 40 times the national mean.
Varied assembly and RNA editing efficiencies between genotypes I and II hepatitis D virus and their implications
Authors: Sheng-Chieh Hsu, Wan-Jr Syu, I-Jane Sheen, Hui-Ting Liu, King-Song Jeng, Jaw-Ching Wu
Journal: Hepatology (2002)

The mechanisms that link genotypes of hepatitis D virus (HDV) with clinical outcomes have not yet been elucidated. Genotypic variations are unevenly distributed along the sequences of hepatitis delta antigens (HDAgs). Of these variations, the packaging signal at the C-terminus has a divergence of 74% between genotypes I and II. In this report, we address the issue of whether these high variations between genotypes affect assembly efficiency of HDV particles and editing efficiency of RNA. Viral package systems of transfection with expression plasmids of hepatitis B surface antigen and HDAgs or whole genomes of HDV consistently indicate that the package efficiency of genotype I HDV is higher than that of genotype II. Segment swapping of large-form HDAg indicates that the C-terminal 19-residue region plays a key role for the varied assembly efficiencies. Also, the editing efficiency of genotype I HDV is higher than that of genotype II. The nucleotide and structural changes surrounding the editing site may explain why genotype II HDV has a low RNA editing efficiency. The findings of in vitro assembly systems were further supported by the observations that patients infected with genotype II had significantly lower alanine transaminase (ALT) levels, more favorable outcomes ( P &lt; .05), and a trend to have lower serum HDV RNA levels as compared with those infected with genotype I HDV ( P = .094). In conclusion, genotype II HDV secretes fewer viral particles than genotype I HDV does, which in turn may reduce the extent of infection of hepatocytes and result in less severe hepatic inflammation.