tbuckley/cabot-search huggingface dataset:
Population based screening for chronic kidney disease: cost effectiveness study
Authors: B. Manns, B. Hemmelgarn, M. Tonelli, F. Au, T. C. Chiasson, J. Dong, S. Klarenbach
Journal: BMJ (2010)

<b>Objective</b> To determine the cost effectiveness of one-off population based screening for chronic kidney disease based on estimated glomerular filtration rate. <b>Design</b> Cost utility analysis of screening with estimated glomerular filtration rate alone compared with no screening (with allowance for incidental finding of cases of chronic kidney disease). Analyses were stratified by age, diabetes, and the presence or absence of proteinuria. Scenario and sensitivity analyses, including probabilistic sensitivity analysis, were performed. Costs were estimated in all adults and in subgroups defined by age, diabetes, and hypertension. <b>Setting</b> Publicly funded Canadian healthcare system. <b>Participants</b> Large population based laboratory cohort used to estimate mortality rates and incidence of end stage renal disease for patients with chronic kidney disease over a five year follow-up period. Patients had not previously undergone assessment of glomerular filtration rate. <b>Main outcome measures</b> Lifetime costs, end stage renal disease, quality adjusted life years (QALYs) gained, and incremental cost per QALY gained. <b>Results</b> Compared with no screening, population based screening for chronic kidney disease was associated with an incremental cost of $C463 (Canadian dollars in 2009; equivalent to about £275, €308, US $382) and a gain of 0.0044 QALYs per patient overall, representing a cost per QALY gained of $C104 900. In a cohort of 100 000 people, screening for chronic kidney disease would be expected to reduce the number of people who develop end stage renal disease over their lifetime from 675 to 657. In subgroups of people with and without diabetes, the cost per QALY gained was $C22 600 and $C572 000, respectively. In a cohort of 100 000 people with diabetes, screening would be expected to reduce the number of people who develop end stage renal disease over their lifetime from 1796 to 1741. In people without diabetes with and without hypertension, the cost per QALY gained was $C334 000 and $C1 411 100, respectively. <b>Conclusions</b> Population based screening for chronic kidney disease with assessment of estimated glomerular filtration rate is not cost effective overall or in subgroups of people with hypertension or older people. Targeted screening of people with diabetes is associated with a cost per QALY that is similar to that accepted in other interventions funded by public healthcare systems.
Glutamine Depletion in Phenylketonuria
Authors: Thomas L. Perry, Shirley Hansen, Bluma Tischler, Rosamund Bunting, Sheila Diamond
Journal: New England Journal of Medicine (1970)

Two adult brothers with untreated phenylketonuria, one with a severe mental defect and the other with superior intelligence, were compared biochemically. No significant differences were found in their degree of hyperphenylalaninemia, nor in their urinary excretion of phenylalanine metabolites. A striking difference between the two, however, was a significant reduction in concentration of glutamine in the plasma of the defective brother, but not in the intelligent brother. A second adult with untreated phenylketonuria and normal intelligence, as well as a group of phenylketonuric children who were receiving a low-phenylalanine diet, also had plasma glutamine concentrations within the normal range. Twelve mentally defective untreated patients with phenylketonuria all showed a significant reduction in plasma glutamine. These findings cast doubt on some proposed mechanisms for the mental defect in phenylketonuria, and suggest that chronic insufficiency of glutamine may play a part in damaging the growing human brain.
Relationship of Deep White Matter Hyperintensities and Apolipoprotein E Genotype to Depressive Symptoms in Older Adults Without Clinical Depression
Authors: Robert D. Nebes, Illa J. Vora, Carolyn C. Meltzer, Melanie B. Fukui, Robert L. Williams, M. Ilyas Kamboh, Judith Saxton, Patricia R. Houck, Steven T. DeKosky, Charles F. Reynolds
Journal: American Journal of Psychiatry (2001)

OBJECTIVE: This study examined whether evidence of cerebrovascular disease in the form of magnetic resonance imaging (MRI) signal hyperintensities in white matter was associated with depressive symptoms in a high-functioning group of normal elderly volunteers. METHOD: Ninety-two community-dwelling elderly individuals participating in a study of white matter hyperintensities (WMHs) in normal aging whose apolipoprotein E (APOE) genotype had been determined completed the Geriatric Depression Scale and received an MRI scan. Univariate analyses of variance were used to examine the relationship between depressive symptoms and the location of WMHs (in deep white matter versus in periventricular white matter) and to determine whether WMHs were more likely to be associated with symptoms of impaired motivation and concentration or with mood symptoms. The effect on depressive symptoms of the interaction between severity of cerebrovascular disease as evidenced by WMHs and APOE genotype was also examined. RESULTS: Hyperintensities in the deep white matter, but not in the periventricular white matter, were associated with depressive symptoms, especially symptoms of impaired motivation, concentration, and decision making. The relationship between deep WMHs and depressive symptoms was especially strong in individuals carrying the APOE-4 allele. CONCLUSIONS: The pattern of depressive symptoms associated with WMHs in this study was similar to the pattern described in the literature as characterizing "vascular" depression in older persons with major depression. The results suggest that cerebrovascular disease may also underlie the depressive symptoms often found in older individuals who are not clinically depressed.
COMPARATIVE ANALYSIS OF THE ACTION OF BUTYRYLPERAZINE AT MANHATTAN STATE HOSPITAL AND THE UNIVERSITY PSYCHIATRIC CLINIC AT ERLANGEN
Authors: HERMAN C. B. DENBER, D. BENTE, PAUL RAJOTTE
Journal: American Journal of Psychiatry (1962)

1. Butyrylperazine was administered to 20 patients at Manhattan State Hospital, New York City, and 26 patients at the University Psychiatric Clinic of Erlangen, West Germany. 2. There were significant differences between both groups in (a) dosage requirements, (b) side effects, and (c) clinical results. 3. It is suggested that genetic factors may play some role in explaining at least two of these findings (2a and b).
Effect of warming up on knee proprioception before sporting activity
Authors: M J Bartlett, P J Warren
Journal: British Journal of Sports Medicine (2002)

Background: It is now generally accepted that the ligamentous structures of the knee not only act as mechanical restraints but also have a neurophysiological role in joint function and protection. A report that knee joint laxity increases with exercise raised the question as to whether there is any compensatory change in joint position appreciation. Objective: To test whether there is a compensatory mechanism for increased ligamentous laxity during normal levels of activity. Methods: Joint position appreciation was measured, using a previously reported technique, in the knees of sportsmen at rest and after warm up. Results: Joint position appreciation was found to be significantly more sensitive after warm up (p = 0.005). Conclusions: These findings indicate that joint position appreciation within the knee accommodates physiological changes within the ligaments and muscles after exercise.
mTOR Inhibition Specifically Sensitizes Colorectal Cancers with <i>KRAS</i> or <i>BRAF</i> Mutations to BCL-2/BCL-XL Inhibition by Suppressing MCL-1
Authors: Anthony C. Faber, Erin M. Coffee, Carlotta Costa, Anahita Dastur, Hiromichi Ebi, Aaron N. Hata, Alan T. Yeo, Elena J. Edelman, Youngchul Song, Ah Ting Tam, Jessica L. Boisvert, Randy J. Milano, Jatin Roper, David P. Kodack, Rakesh K. Jain, Ryan B. Corcoran, Miguel N. Rivera, Sridhar Ramaswamy, Kenneth E. Hung, Cyril H. Benes, Jeffrey A. Engelman
Journal: Cancer Discovery (2013)

Abstract Colorectal cancers harboring KRAS or BRAF mutations are refractory to current targeted therapies. Using data from a high-throughput drug screen, we have developed a novel therapeutic strategy that targets the apoptotic machinery using the BCL-2 family inhibitor ABT-263 (navitoclax) in combination with a TORC1/2 inhibitor, AZD8055. This combination leads to efficient apoptosis specifically in KRAS- and BRAF-mutant but not wild-type (WT) colorectal cancer cells. This specific susceptibility results from TORC1/2 inhibition leading to suppression of MCL-1 expression in mutant, but not WT, colorectal cancers, leading to abrogation of BIM/MCL-1 complexes. This combination strategy leads to tumor regressions in both KRAS-mutant colorectal cancer xenograft and genetically engineered mouse models of colorectal cancer, but not in the corresponding KRAS-WT colorectal cancer models. These data suggest that the combination of BCL-2/BCL-XL inhibitors with TORC1/2 inhibitors constitutes a promising targeted therapy strategy to treat these recalcitrant cancers. Significance: Effective targeted therapies directed against colorectal cancer with activating mutations in KRAS remain elusive. We have leveraged drug-screen data from a large panel of human colorectal cancers to uncover an effective, rational targeted therapy strategy that has preferential activity in colorectal cancers with KRAS or BRAF mutations. This combination may be developed for clinical testing. Cancer Discov; 4(1); 42–52. ©2013 AACR. See related commentary by Russo et al., p. 19 This article is highlighted in the In This Issue feature, p. 1
Leukemic Diffuse Large B-Cell Lymphoma in a Patient With Myeloproliferative Disorder
Authors: Vijaya Raj Bhatt, R. Gregory Bociek, Ji Yuan, Kai Fu, Timothy C. Greiner, Bhavana J. Dave, Sandeep K. Rajan, James O. Armitage
Journal: Journal of the National Comprehensive Cancer Network (2015)

Essential thrombocythemia is well-known to transform to other myeloid disorders, such as leukemia; however, the risk for development of lymphoma is not as well studied. This case report discusses a 76-year-old man with a history of prefibrotic post-essential thrombocythemia myelofibrosis on ruxolitinib, who developed anemia, thrombocytopenia, and leukocytosis with peripheral blasts. Results of a bone marrow biopsy and PET and CT scans revealed stage IV leukemic diffuse large B-cell lymphoma. Several days after cessation of ruxolitinib, the patient developed fevers, hypotension, and low-grade disseminated intravascular coagulation, and subsequently developed spontaneous tumor lysis syndrome, which resulted in death. This case is unique in several aspects: it highlights the rare possibility of lymphomatous transformation of myeloproliferative disorders, an unusual presentation of lymphoma masquerading as leukemia, and the possibility of ruxolitinib withdrawal syndrome. Additionally, this case serves as a reminder that the use of novel therapies should be adopted after a thorough assessment of long-term risks, including those associated with abrupt withdrawal.
The role of hemoglobin heme loss in Heinz body formation: studies with a partially heme-deficient hemoglobin and with genetically unstable hemoglobins
Authors: Harry S. Jacob, Kaspar H. Winterhalter
Journal: Journal of Clinical Investigation (1970)

A number of mutant hemoglobins are inordinately unstable, denaturing in circulating red cells into Heinz bodies, resulting in congenital Heinz body hemolytic anemia (CHBHA). We have emphasized that most such hemoglobins involve amino acid substitutions at sites neighboring the heme group of the beta-polypeptide chain, and have shown that heme binding to globin is diminished thereby. Thus, hemes were progressively lost from four unstable hemoglobins (Köln, Hammersmith, San Francisco, and Zürich) as they precipitated into Heinz bodies at 50 degrees C. The role of heme loss, especially from beta chains, in Heinz body formation was supported by studies with a hemoglobin synthesized to contain hemes only on its alpha chains (alpha(2) (heme)beta(2) (0)). The behavior of this compound, postulated to be an intermediary in the formation of Heinz bodies, mimicked that of the genetically unstable hemoglobins in several ways: (a) it precipitated at 50 degrees C into typical coccoid Heinz bodies; (b) as also observed with CHBHA hemoglobins this denaturation was virtually prevented by the heme ligands, cyanide or carbon monoxide, which inhibit further heme loss; it was potentiated by oxidation of hemes to the ferri- state, which accentuates heme loss; (c) the thiol groups of alpha(2) (heme)beta(2) (0) were hyperreactive, forming mixed disulfides with glutathione and membrane sulfhydryls at rates similar to those of CHBHA hemoglobins and 10 or more times that of normal hemoglobin A; (d) heme repletion of the protein molecules by the addition of crystalline hemin to either alpha(2) (heme)beta(2) (0) or to the genetically unstable hemoglobins, prevented their precipitation into Heinz bodies and normalized their aberrant electrophoretic behaviors; and (e) during Heinz body formation at 50 degrees C both alpha(2) (heme)beta(2) (0) and the genetically unstable hemoglobins released free alpha(heme)-chains into solution, suggesting that the bulk of the whitish, Heinz body precipitate is naked beta(8)-chains. We conclude that heme loss from mutant beta chains is an early step in Heinz body formation in several of the unstable hemoglobinopathies. The resulting hemedepleted compounds, of which synthetic alpha(2) (heme)beta(2) (0) is a prototype, are unstable, cleaving into beta(0)-chain precipitates (the bulk of the Heinz body material) and soluble, free alpha(heme)-chains (demonstrated previously in hemolysates from many patients with CHBHA).
Antihypertensive drugs and risk of cancer: network meta-analyses and trial sequential analyses of 324 168 participants from randomised trials
Authors: Sripal Bangalore, Sunil Kumar, Sverre E Kjeldsen, Harikrishna Makani, Ehud Grossman, Jørn Wetterslev, Ajay K Gupta, Peter S Sever, Christian Gluud, Franz H Messerli
Journal: The Lancet Oncology (2010)
Glucose-Lowering Effects of Sulfasalazine in Type 2 Diabetes
Authors: Romana M. Haas, Phoebe Li, James W. Chu
Journal: Diabetes Care (2005)

Salicylates are therapeutic agents clinically useful in treating inflammatory bowel diseases and arthropathies. These drugs have also demonstrated glucose-lowering effects in type 2 diabetes (1–2). Sulfasalazine (SSZ) is a compound that is cleaved in vivo to 5-aminosalicylic acid (a salicylate) and sulfapyridine (a sulfonamide antibiotic). We report a case of a patient with systemic lupus erythematosus (SLE) and type 2 diabetes on high-dose insulin therapy, who after initiating SSZ experienced recurrent severe hypoglycemia and eventually achieved normoglycemia without the need for diabetes medications. After caring for the index patient, and then two others manifesting similar metabolic responses to SSZ, we conducted a systematic chart review to evaluate glycemic effects of SSZ in a cohort of diabetic patients.

A 37-year-old woman with SLE, iron-deficiency anemia, metamphetamine usage, and a 1-year history of type 2 diabetes was referred to the Santa Clara Valley Medical Center (SCVMC) diabetes clinic for treatment of severe hyperglycemia. She took 100 units of insulin daily (NPH 35 units b.i.d., regular 10 units t.i.d.), yet her self-monitored blood glucose (SMBG) values consistently exceeded 16.7 mmol/l, and she experienced polyuria/dipsia and blurry vision. Other medications were prednisone 7.5 mg/day and hydroxychloroquine. On examination, the patient was cachexic, weighing 44 kg. Laboratory evaluation revealed normal …
Trials and tribulations in pursuing an MD
Authors: J R. Sneyd
Journal: BMJ (1992)

to them to set up strong audit structures in their units (£42 1 million in 1992-3)' they have only themselves to blame for a remarkable lack of initiative.But then effective audit requires not only hard work but also the active participation and commitment of senior doctors.On the other hand, picking up the telephone and complaining to the press is so much simpler and avoids the rather tedious business of systematic and critical analysis.For all that, it is time that we recognised and used the right whistle.
Second Cancers Following Oral and Pharyngeal Cancers: Role of Tobacco and Alcohol
Authors: G. L. Day, W. J. Blot, R. E. Shore, J. K. McLauglin, D. F. Austin, R. S. Greenberg, J. M. Liff, S. Preston-Martin, S. Sarkar, J. B. Schoenberg, J. F. Fraumeni
Journal: JNCI Journal of the National Cancer Institute (1994)

The exceptionally high rate of second primary cancers among patients with oral and pharyngeal cancers is well recognized, yet there has been limited epidemiologic study of risk factors for second tumors.To evaluate the relation of smoking and alcohol consumption to the development of second cancers among this high-risk patient group, we conducted a nested case-control study.A total of 1090 patients enrolled in a 1984-1985 population-based, case-control study of oral cancer in four areas of the United States were followed through June 1989 for the occurrence of second primary cancers. Information on tobacco and alcohol consumption was obtained from the original interviews and was updated by follow-up interviews obtained for 80 case patients with second cancers and 189 sex-, study area-, and survival-matched cancer patients free of second cancers (control subjects).Tobacco smoking and alcohol drinking each contributed to risk of second cancers, with the effects of smoking more pronounced than those of alcohol. The odds ratios (ORs) for smoking (adjusted for alcohol) rose with duration and intensity of smoking and were strongest for tumors of the aerodigestive tract (oral cavity, pharynx, esophagus, larynx, and lungs), with ORs reaching 4.7 (95% confidence interval [CI] = 1.4-16) among smokers of 40 or more cigarettes per day for 20 or more years. Current smokers as of the baseline survey experienced a fourfold increased risk of a second aerodigestive tract cancer relative to nonsmokers and former smokers. No reduction in risk was associated with cessation of smoking or drinking at or after the index diagnosis, although the short median interval (27 months) between tumor diagnoses limited observation of the effects due to recent cessation. Risk was significantly reduced, however, 5 years after smoking cessation. Among drinkers, second cancer risk was greatest for beer intake, with an OR for a second aerodigestive tract cancer of 3.8 (95% CI = 1.2-12) for 15 or more beers per week.Oral and pharyngeal cancer patients with the highest intakes of tobacco and alcohol are the ones most prone to develop second primary cancers.Avoidance of tobacco smoking and alcohol drinking is the most desirable way not only to prevent primary oral cancers, but also to reduce risk of second cancers of the aerodigestive system.
A 61-Year-Old Man With Parkinson's Disease
Authors: C. Warren Olanow
Journal: JAMA (1996)

Dr Delbanco: Dr H, a 61-year-old dentist, was diagnosed with Parkinson's disease (PD) in August 1990 by one of his patients, a neurologist, who noticed a change in his gait and difficulty in swallowing and speech. There was no tremor. Married and the father of three children living close to his home in the Boston, Mass, suburbs, Dr H has individual health insurance through a private managed care plan. Dr H's patient encouraged him to seek a formal opinion, and a consulting neurologist confirmed that Dr H had PD; his condition was considered to be in the early stages. In retrospect, his primary care doctor, Dr C, now believes that earlier episodes of drooling and voice changes were due to PD. Of note in his medical history is mild hypertension and a resection of a right frontal meningioma in 1978, which has not recurred and left no neurologic residua. His
Efficacy and Tolerability of Carbamazepine for Agitation and Aggression in Dementia
Authors: Pierre N. Tariot, Rosemary Erb, Carol Ann Podgorski, Christopher Cox, Shirish Patel, Laura Jakimovich, Carrie Irvine
Journal: American Journal of Psychiatry (1998)

The efficacy, safety, and tolerability of carbamazepine in the treatment of agitation and aggression associated with dementia were assessed.In a 6-week, randomized, multisite, parallel-group study of 51 nursing home patients with agitation and dementia, individualized doses of carbamazepine were compared with placebo. Except for a physician monitor and a pharmacist, all participants were blind to treatment. The primary outcome measures were the Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression (CGI) global improvement rating. Secondary measures included measures of behavior, aggression, cognition, functional status, staff time, safety, and tolerability. Intent-to-treat analysis was performed.The modal carbamazepine dose at 6 weeks was 300 mg/day, and a mean serum level of 5.3 micrograms/ml was achieved. The study was terminated after a planned interim analysis showed that carbamazepine provided more benefit than did placebo. Over 6 weeks the mean total BPRS score decreased 7.7 points for the carbamazepine group and 0.9 for the placebo group, and the weekly scores showed a gradual divergence between the two groups. CGI ratings showed global improvement in 77% of the patients taking carbamazepine and 21% of those taking placebo. Secondary analyses confirmed that the positive changes were due to decreased agitation and aggression. The drug was generally well tolerated, and no change in cognition or functional status occurred. The perception of staff time needed to manage agitation showed a decrease for carbamazepine but not placebo.This controlled study showed significant short-term efficacy of carbamazepine for agitation with generally good safety and tolerability.
BCL-2/JH rearrangements in circulating B cells of healthy blood donors and patients with nonmalignant diseases.
Authors: G Dölken, G Illerhaus, C Hirt, R Mertelsmann
Journal: Journal of Clinical Oncology (1996)

PURPOSE To answer the question whether t(14;18)-positive cells can be detected by polymerase chain reaction (PCR) in the peripheral blood of healthy blood donors and patients with nonmalignant diseases. PATIENTS AND METHODS Peripheral-blood mononuclear cells (PBMNC) from healthy donors (n = 36) and patients with nonmalignant diseases (n = 21) were examined by two-step PCR for the detection of t(14;18)-positive cells with a breakpoint within the major breakpoint region (MBR). Approximate numbers of t(14;18)-positive cells were determined using limiting dilution assays, as well as the stochastic multiple-tube approach. RESULTS We were able to detect t(14;18)-positive cells in PBMNC of approximately 50% of healthy donors and patients with nonmalignant diseases if DNA amounts up to 10 microg were tested. Compared with 17 t(14;18)-positive patients being in complete remission after radiotherapy for low-stage malignant follicular lymphoma, the majority of 26 healthy donors were found to have significantly lower numbers of t(14;18)-positive cells circulating in the peripheral blood. In the case of six healthy donors, more than one t(14;18) DNA fragment based on size and nucleotide sequence analysis was detected. In one healthy individual, four different t(14;18)-positive cell clones were found in nine samples found over 5 years. CONCLUSION The occurrence of the t(14;18) translocation is not restricted to follicular lymphoma cells. In healthy donors, long-lived t(14;18)-positive cells can be detected by PCR if the sensitivity is high enough. Based on nucleotide sequence analysis, the t(14;18) DNA fragments detected in healthy donors cannot be distinguished from those found in follicular lymphomas.
Triple Therapy for Atrial Fibrillation and Percutaneous Coronary Intervention
Authors: Willem J.M. Dewilde, Paul W.A. Janssen, Freek W.A. Verheugt, Robert F. Storey, Tom Adriaenssens, Morten L. Hansen, Morten Lamberts, Jurriën M. ten Berg
Journal: Journal of the American College of Cardiology (2014)