tbuckley/cabot-search huggingface dataset:
Limitations and Future Treatment Options in Type 2 Diabetes With Renal Impairment
Authors: Eberhard Ritz
Journal: Diabetes Care (2011)

In the past two decades, nephropathy in type 2 diabetes has emerged as a major public health issue. The purpose of this presentation is to review the epidemiology of diabetic nephropathy, the controversy surrounding HbA1c and blood pressure as targets for treatment, the efficacy of blocking the renin-angiotensin system (RAS) pathway, and finally the available add-on therapies in patients with “escape.”

Diabetic nephropathy in type 1 and type 2 diabetes emerged as a major issue in the 1970s, but knowledge of albuminuria in patients without primary kidney disease goes back to the work of Senator (1), who found albumin excretion in the urine of roughly 10% of the general population, including individuals with diabetes. In 1891, Schmitz (2) found albuminuria in 10–26% of diabetic patients and discussed its etiology and prognostic implications.

Renal failure in patients with diabetes became a major issue when continuously increasing numbers of diabetic patients were admitted for renal replacement therapy—a veritable “medical catastrophe of worldwide dimension” (3). According to the U.S. Renal Data System report, diabetes accounted for 54% of new patients in 2007. The incidence of end-stage renal disease (ESRD) in diabetic patients is currently 155 patients per million per year; it decreased by 3.3% between 2006 and 2007. In recent years, the prevalence was ∼600 patients per million per year, illustrating the dimension of the problem.

In our own local experience in Heidelberg (4), 49%, or 98 patients per million per year, admitted for renal replacement therapy had diabetes; of these patients, 6% had type 1 diabetes, and 94% had type 2 diabetes.

Recently, however, the rate of admission of type 2 diabetic patients for renal replacement therapy reached its plateau (5) in Denmark and in Europe in general. Observations in the Pima Indian population show that there is a significant decrease …
Plastic Surgeon/Greek Amphora
Authors: B. A. St. Andrews
Journal: JAMA (2002)

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
Promoter Hypermethylation of Mismatch Repair Gene <i>hMLH1</i> Predicts the Clinical Response of Malignant Astrocytomas to Nitrosourea
Authors: Takao Fukushima, Yoichi Katayama, Takao Watanabe, Atsuo Yoshino, Akiyoshi Ogino, Takashi Ohta, Chiaki Komine
Journal: Clinical Cancer Research (2005)

Abstract Purpose: In certain types of human cancers, transcriptional inactivation of hMLH1 by promoter hypermethylation plays a causal role in the loss of mismatch repair functions that modulate cytotoxic pathways in response to DNA-damaging agents. The aim of the present study was to investigate the role of promoter methylation of the hMLH1 gene in malignant astrocytomas. Experimental Design: We examined the hMLH1 promoter methylation in a homogeneous cohort of patients with 41 malignant astrocytomas treated by 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-2(2-chloroethyl)-3-nitrosourea chemotherapy in combination with radiation and interferon therapy, and assessed the correlation of such methylation with clinical outcome. Results: hMLH1 promoter methylation was found in 6 (15%) of the 41 newly diagnosed malignant astrocytomas. Hypermethylation of the hMLH1 promoter corresponded closely with a loss of immunohistochemical staining for hMLH1 protein (P = 0.0013). Patients with hMLH1-methylated tumors displayed a greater chance of responding to adjuvant therapy as compared with those with hMLH1-unmethylated tumors (P = 0.0150). The presence of hMLH1 hypermethylation was significantly associated with a longer progression-free survival on both univariate analysis (P = 0.0340) and multivariate analysis (P = 0.0161). Conclusions: The present study identified hMLH1 methylation status as a predictor of the clinical response of malignant astrocytomas to chloroethylnitrosourea-based adjuvant therapy. The findings obtained suggest that determination of the methylation status of hMLH1 could provide a potential basis for designing rational chemotherapeutic strategies, as well as for predicting prognosis.
Link Between Smoking and Mental Illness May Lead to Treatments
Authors: Bridget M Kuehn
Journal: JAMA (2006)

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
Five Years of Letrozole Compared With Tamoxifen As Initial Adjuvant Therapy for Postmenopausal Women With Endocrine-Responsive Early Breast Cancer: Update of Study BIG 1-98
Authors: Alan S. Coates, Aparna Keshaviah, Beat Thürlimann, Henning Mouridsen, Louis Mauriac, John F. Forbes, Robert Paridaens, Monica Castiglione-Gertsch, Richard D. Gelber, Marco Colleoni, István Láng, Lucia Del Mastro, Ian Smith, Jacquie Chirgwin, Jean-Marie Nogaret, Tadeusz Pienkowski, Andrew Wardley, Erik H. Jakobsen, Karen N. Price, Aron Goldhirsch
Journal: Journal of Clinical Oncology (2007)

Previous analyses of the Breast International Group (BIG) 1-98 four-arm study compared initial therapy with letrozole or tamoxifen including patients randomly assigned to sequential treatment whose information was censored at the time of therapy change. Because this presentation may unduly reflect early events, the present analysis is limited to patients randomly assigned to the continuous therapy arms and includes protocol-defined updated results.Four thousand nine hundred twenty-two of the 8,028 postmenopausal women with receptor-positive early breast cancer randomly assigned (double-blind) to the BIG 1-98 trial were assigned to 5 years of continuous adjuvant therapy with either letrozole or tamoxifen; the remainder of women were assigned to receive the agents in sequence. Disease-free survival (DFS) was the primary end point.At a median follow-up time of 51 months, we observed 352 DFS events among 2,463 women receiving letrozole and 418 events among 2,459 women receiving tamoxifen. This reflected an 18% reduction in the risk of an event (hazard ratio, 0.82; 95% CI, 0.71 to 0.95; P = .007). No predefined subsets showed differential benefit. Adverse events were similar to previous reports. Patients on tamoxifen experienced more thromboembolic events, endometrial pathology, hot flashes, night sweats, and vaginal bleeding. Patients on letrozole experienced more bone fractures, arthralgia, low-grade hypercholesterolemia, and cardiovascular events other than ischemia and cardiac failure.The present updated analysis, which was limited to patients on monotherapy arms in BIG 1-98, yields results similar to those from the previous primary analysis but more directly comparable with results from other trials of continuous therapy using a single endocrine agent.
Outcomes of Iris-Claw Anterior Chamber versus Iris-Fixated Foldable Intraocular Lens in Subluxated Lens Secondary to Marfan Syndrome
Authors: Denise E. Hirashima, Eduardo S. Soriano, Rodrigo L. Meirelles, Gustave N. Alberti, Walton Nosé
Journal: Ophthalmology (2010)
Activated mesangial cells produce vascular permeability factor in early-stage mesangial proliferative glomerulonephritis.
Authors: K Noguchi, N Yoshikawa, S Ito-Kariya, Y Inoue, Y Hayashi, H Ito, H Nakamura, K Iijima
Journal: Journal of the American Society of Nephrology (1998)

Vascular permeability factor (VPF), also known as vascular endothelial growth factor (VEGF), is a multifunctional cytokine involved in angiogenesis, inflammation, and wound healing. Although VPF/VEGF has been reported to be produced only by glomerular podocytes in glomeruli, it was found that it is produced by human cultured mesangial cells (MC). Therefore, immunohistochemical analysis (using indirect immunofluorescence and in situ hybridization) of VPF/VEGF in normal kidneys (n = 7) and biopsy specimens taken from 83 patients with renal diseases, including mesangial proliferative glomerulonephritis (PGN) (n = 58), was performed to examine whether VPF/VEGF is produced by MC in human PGN. In all of the healthy subjects and all of the patients except those with PGN (disease control subjects), VPF/VEGF protein and mRNA were detected mainly in podocytes. However, in some PGN patients, VPF/VEGF protein was demonstrated clearly in MC as well as in podocytes, as some of the VPF/VEGF was colocalized with alpha-smooth muscle actin, a marker of activated MC, and VPF/VEGF mRNA was expressed by MC and podocytes. Mesangial VPF/VEGF expression level increased significantly in PGN patients with early lesions (P < 0.01 versus healthy subjects or disease control subjects, P < 0.05 versus PGN with later lesions). The time between biopsy and disease onset was significantly shorter in PGN patients with than in those without mesangial VPF/VEGF expression (P < 0.01). These findings provide the first evidence that activated MC are a source of VPF/VEGF in human PGN, and indicate that mesangial VPF/VEGF expression is characteristic of early lesions of PGN. Because VPF/ VEGF plays a pivotal role in tissue repair, MC-produced VPF/VEGF may play pathophysiologic roles, including promoting recovery from glomerular injuries, in early-stage PGN.
Mechanisms of Insulin Resistance in Aging
Authors: Raymond I. Fink, Orville G. Kolterman, Jennifer Griffin, Jerrold M. Olefsky
Journal: Journal of Clinical Investigation (1983)

We have studied 17 elderly and 27 non-elderly, nonobese subjects (mean age 69±1 and 37±2 yr, respectively) to assess the mechanisms responsible for the abnormal carbohydrate tolerance associated with aging. Serum glucose and insulin levels were significantly elevated in the elderly subjects compared with the nonelderly subjects during a 75-g oral glucose tolerance test, suggesting an insulin resistant state. Peripheral insulin sensitivity was assessed in both groups using the euglycemic glucose clamp technique during an insulin infusion rate of 40 mU/m2 per min. Similar steady-state serum insulin levels led to a peripheral glucose disposal rate of 151±17 mg/m2 per min in the elderly compared with a value of 247±12 mg/m2 per min in the nonelderly, thus documenting the presence of insulin resistance in the elderly subjects. Insulin binding to isolated adipocytes and monocytes was similar in the elderly and nonelderly groups (2.34±0.33 vs. 2.62±0.24% and 5.04±1.10 vs. 5.12±1.07%), respectively. Thus, insulin resistance in the presence of normal insulin binding suggests the presence of a postreceptor defect in insulin action. This was confirmed by performing additional euglycemic clamp studies using infusion rates of 15 and 1,200 mU/m2 per min to assess the contours of the dose-response relationship. These studies revealed a 39 and 25% decrease in the glucose disposal rate in the elderly subjects, respectively. The results confirm the presence of a postreceptor defect as well as a rightward shift in the dose-response curve. Insulin's ability to suppress hepatic glucose output was less in the elderly subjects during the 15 mU/m2 per min insulin infusion (77±5 vs. 89±4% suppression), but hepatic glucose output was fully and equally suppressed in both groups during the 40 and 1,200 mU/m2 per min infusion. Finally, a significant inverse relationship was observed between the degree of glucose intolerance in the individual elderly subjects, as reflected by the 2-h serum glucose level during the oral glucose tolerance test, and the degree of peripheral insulin resistance as assessed by the glucose disposal rate during the 40 mU/m2 per min insulin infusion (r = 0.59, P < 0.01).
Bisphosphonate-Related Osteonecrosis of the Jaw: Diagnosis, Prevention, and Management
Authors: Salvatore L. Ruggiero, Bhoomi Mehrotra
Journal: Annual Review of Medicine (2008)

Bisphosphonate therapy has been considered standard therapy in the management and care of cancer patients with metastatic bone disease and patients with osteoporosis. The efficacy of these drugs is due to their ability to inhibit osteoclast-mediated bone resorption. However, the postmarketing experience with intravenous and, to a much lesser extent, oral bisphosphonates has raised concerns about potential side effects related to profound bone remodeling inhibition and osteonecrosis isolated to the jaws. We review the risk factors, incidence, pathogenesis, prevention strategies, and management of this new complication.
Acute upper gastrointestinal bleeding in the UK: patient characteristics, diagnoses and outcomes in the 2007 UK audit
Authors: S. A. Hearnshaw, R. F. A. Logan, D. Lowe, S. P. L. Travis, M. F. Murphy, K. R. Palmer
Journal: Gut (2011)

To describe the patient characteristics, diagnoses and clinical outcomes of patients presenting with acute upper gastrointestinal bleeding (AUGIB) in the 2007 UK Audit.Multi-centre survey.All UK hospitals admitting patients with AUGIB.All adults (>16 years) presenting in or to UK hospitals with AUGIB between 1 May and 30 June 2007.Data on 6750 patients (median age 68 years) was collected from 208 participating hospitals. New admissions (n=5550) were younger (median age 65 years) than inpatients (n=1107, median age 71 years), with less co-morbidity (any co-morbidity 46% vs 71%, respectively). At presentation 9% (599/6750) had known cirrhosis, 26% a history of alcohol excess, 11% were taking non-steroidal anti-inflammatory drugs and 28% aspirin. Peptic ulcer disease accounted for 36% of AUGIB and bleeding varices 11%. In 13% there was evidence of further bleeding after the first endoscopy. 1.9% underwent surgery and 1.2% interventional radiology for AUGIB. Median length of stay was 5 days. Overall mortality in hospital was 10% (675/6750, 95% CI 9.3 to 10.7), 7% in new admissions and 26% among inpatients. Mortality was highest in those with variceal bleeding (15%) and with malignancy (17%).AUGIB continues to result in substantial mortality although it appears to be lower than in 1993. Mortality is particularly high among inpatients and those bleeding from varices or upper gastrointestinal malignancy. Surgical or radiological interventions are little used currently.
Time to Treatment Response in Patients with Follicular Lymphoma Treated with Bortezomib Is Longer Compared with Other Histologic Subtypes
Authors: Owen A. O'Connor, Carol Portlock, Craig Moskowitz, Paul Hamlin, David Straus, John Gerecitano, Mithat Gonen, Otilia Dumitrescu, Debra Sarasohn, John Butos, Ellen Neylon, Barbara Mac-Gregor Cortelli, Susan Blumel, Andrew M. Evens, Andrew D. Zelenetz, John Wright, Brenda Cooper, Jane Winter, Julie Vose
Journal: Clinical Cancer Research (2010)

To determine the antitumor activity of the novel proteasome inhibitor bortezomib in patients with indolent non-Hodgkin's lymphoma.Patients with follicular lymphoma (FL), marginal zone lymphoma, mantle cell lymphoma, small lymphocytic lymphoma/chronic lymphocytic leukemia, and Waldenstrom's macroglobulinemia were eligible for study. Bortezomib was given at a dose of 1.5 mg/m(2) as an i.v. push on days 1, 4, 8, and 11 of a 21-day cycle. Eligibility included the following: (a) no more than three prior therapies, (b) at least 1 month since prior chemotherapy, (c) measurable disease, and (d) an absolute neutrophil count of >1,000/microL and a platelet count >50,000/microL for the first dose of any cycle.Seventy-seven patients were registered, of which 69 were assessable for response based on the completion of two cycles of therapy. Subtypes included FL (59.5%), mantle cell lymphoma (52%), small lymphocytic lymphoma/chronic lymphocytic leukemia (16.2%), marginal zone lymphoma (21.6%), and one Waldenstrom's macroglobulinemia. The median number of prior therapies was three. The most common grade 3 toxicity was lymphopenia (35%) and thrombocytopenia (31%). Twenty-five patients experienced grade <or=2 sensory neuropathy (32), and 8% experienced grade 3 neurosensory toxicity. The overall response rate was 45% (40% on an intention to treat) including 10 complete remissions. Of 18 patients with FL, 9 responded with 4 complete response. The median time to treatment response for FL was 12 weeks, whereas the median time to treatment response for other subtypes of non-Hodgkin's lymphoma was only 4 weeks.These data suggest that bortezomib has significant single agent activity in patients with FL, and that longer durations of treatment may improve overall response.
Effect of red blood cells from patients with sickle cell disease on platelet factor 3 release
Authors: Constantine A. Toumbis, Istvan Stadler, Julian L. Ambrus
Journal: American Journal of Hematology (1992)

Abstract Red cells from two SS genotype and two SA genotype patients were sampled. When the samples were deoxygenated and mixed with platelet‐rich plasma, they caused the release of platelet factor 3 as recorded in a coagulometer. This phenomenon was not present in control blood samples from normal individuals. Membrane changes in abnormal red cells during hypoxia may be responsible in part for platelet activation and its role in vasoocclusive crisis. Vasoocclusive crisis could be prevented by increasing the red cell membrane fluidity and inhibiting the platelet aggregation with pentoxifylline. © 1992 Wiley‐Liss, Inc.
Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies
Authors: Josep Dalmau, Amy J Gleichman, Ethan G Hughes, Jeffrey E Rossi, Xiaoyu Peng, Meizan Lai, Scott K Dessain, Myrna R Rosenfeld, Rita Balice-Gordon, David R Lynch
Journal: The Lancet Neurology (2008)
Radioisotope determination of regional colonic transit in severe constipation: comparison with radio opaque markers.
Authors: J R van der Sijp, M A Kamm, J M Nightingale, K E Britton, S J Mather, G P Morris, L M Akkermans, J E Lennard-Jones
Journal: Gut (1993)

Radio-opaque markers have a well established role in distinguishing between patients with normal and those with slow intestinal transit, but in the latter group their accuracy in defining the region of delay has not been established. To study regional colonic transit accurately the transit of a radioisotope labelled meal was determined and findings were compared with those of simultaneously ingested radio-opaque markers. Twelve healthy controls (mean age 33 years) and 12 severely constipated women (mean age 36 years, bowel frequency &lt; once per week) were studied On day 1, a meal containing 10 MBq 111In bound to 0.7 mm resin microspheres was ingested. Subjects also ingested a set of radiologically distinguishable markers on three successive days. Abdominal scans were obtained three times daily for 7 days. Abdominal radiographs were obtained after 72 or 96 hours and again at 144 or 168 hours. Eight 9regions of interest9 were created--one for the small bowel, six for the colon, and one for excreted stool. The constipated patients all showed colonic transit outside the normal range, with a variable site of delay demonstrated by time activity curves for each region. To provide a different measure of the effectiveness of colonic transport, the movement of the 9centre of mass9 for the radioisotope and for the markers was then determined. The radioisotope and radiopaque marker methods gave similar results. At all times between 24 and 144 hours there was no significant difference for the position of the centre of mass between the radio-opaque and marker methods. At all times, however, the mean difference between the markers and the radioisotopes was positive, indicating that the center of mass of the markers was always head of that of the radioisotope. The mean difference between the methods was never greater than one region of interest, and ranged from 12 to 72% of one region of interest in the colon. The difference between these two methods could reach up to two colonic segments in certain patients at one time. Radioisotope ingestion provides accurate information about the transit through individual colonic regions because of the possibility of frequent observations and the clear delineation of the entire colon. Although these features were not obtained with radio-opaque markers, they are suitable as a screening test for the presence and pattern of colonic delay.
A randomized phase II study of the telomerase inhibitor imetelstat as maintenance therapy for advanced non-small-cell lung cancer
Authors: A.A. Chiappori, T. Kolevska, D.R. Spigel, S. Hager, M. Rarick, S. Gadgeel, N. Blais, J. Von Pawel, L. Hart, M. Reck, E. Bassett, B. Burington, J.H. Schiller
Journal: Annals of Oncology (2014)
Phase II study of pemetrexed disodium (Alimta®) administered with oral folic acid in patients with advanced gastric cancer
Authors: E. Bajetta, L. Celio, R. Buzzoni, L. Ferrari, A. Marchianò, A. Martinetti, R. Longarini, C. Becerra, C. Ilardi, W. John
Journal: Annals of Oncology (2003)
Role of immune complexes in hypertrophic osteoarthropathy and nonmetastatic polyarthritis.
Authors: M S Awerbuch, P M Brooks
Journal: Annals of the Rheumatic Diseases (1981)

Three case histories of patients with histologically proved malignant disease and an associated nonmetastatic symmetrical polyarthropathy are analysed. No evidence of a pathogenetic role for immune complexes was found in hypertrophic osteoarthropathy, whereas there is considerable evidence suggesting that the nonmetastatic polyarthritis associated with malignant lymphoma is an immune complex phenomenon.