tbuckley/cabot-search huggingface dataset:
Risk Factors for Progression of Peripheral Arterial Disease in Large and Small Vessels
Authors: Victor Aboyans, Michael H. Criqui, Julie O. Denenberg, James D. Knoke, Paul M Ridker, Arnost Fronek
Journal: Circulation (2006)

Data on the natural history of peripheral arterial disease (PAD) are scarce and are focused primarily on clinical symptoms. Using noninvasive tests, we assessed the role of traditional and novel risk factors on PAD progression. We hypothesized that the risk factors for large-vessel PAD (LV-PAD) progression might differ from small-vessel PAD (SV-PAD).Between 1990 and 1994, patients seen during the prior 10 years in our vascular laboratories were invited for a new vascular examination. The first assessment provided baseline data, with follow-up data obtained at this study. The highest decile of decline was considered major progression, which was a -0.30 ankle brachial index decrease for LV-PAD and a -0.27 toe brachial index decrease for SV-PAD progression. In addition to traditional risk factors, the roles of high-sensitivity C-reactive protein, serum amyloid-A, lipoprotein(a), and homocysteine were assessed. Over the average follow-up interval of 4.6+/-2.5 years, the 403 patients showed a significant ankle brachial index and toe brachial index deterioration. In multivariable analysis, current smoking, ratio of total to HDL cholesterol, lipoprotein(a), and high-sensitivity C-reactive protein were related to LV-PAD progression, whereas only diabetes was associated with SV-PAD progression.Risk factors contribute differentially to the progression of LV-PAD and SV-PAD. Cigarette smoking, lipids, and inflammation contribute to LV-PAD progression, whereas diabetes was the only significant predictor of SV-PAD progression.
Improved detection of abnormal respiratory function using forced expiration from raised lung volume in infants with cystic fibrosis
Authors: DJ Turner, CJ Lanteri, PN LeSouef, PD Sly
Journal: European Respiratory Journal (1994)

The raised volume rapid thoracic compression (RVRTC) technique is a recently developed method of measuring lung function in infants. The measurements of forced expiratory volume-time (FEVt) parameters from raised lung volumes have been shown to be less variable than maximal flow at functional residual capacity (VmaxFRC), obtained from the conventional rapid thoracic compression (RTC) technique. Measurements of VmaxFRC are highly variable, and may not be sensitive enough to detect a difference between normal infants and infants with cystic fibrosis (CF). The aim of this study was to determine whether the raised volume rapid thoracic compression technique could detect abnormal lung function in a group of CF infants with no current respiratory symptoms. Twelve CF infants were studied (median age 10.5 months, range 3-18 months), and compared to normative data collected previously on 26 healthy infants (median age 14 months, range 3-23 months). We found that VmaxFRC failed to detect any difference between the two groups. CF infants had significantly smaller FEV0.5 and FEV0.75 measurements at a lung volume set by 17.5 cmH2O predetermined inflation pressure (PP) both as raw values and when expressed as percentage predicted. We conclude that the raised volume rapid thoracic compression technique is a sensitive tool, able to detect abnormal lung function in infants with cystic fibrosis. This abnormality was not demonstrated by measurements derived from the conventional rapid thoracic compression technique in the tidal volume range.
NEW THORACIC MURMURS, WITH TWO NEW INSTRUMENTS, THE REFRACTOSCOPE AND THE PARTIAL STETHOSCOPE
Authors: Frederick D. Parker
Journal: The Journal of Experimental Medicine (1918)

1. An understanding of the physics of sound is essential for a better comprehension of refined auscultation, tone analysis, and the use of these instruments. 2. The detection of variations of the third heart sound should prove a valuable aid in predicting mitral disease. 3. The variations of the outflow sound should prove a valuable aid in determining early aortic lesions with the type of accompanying intimal changes. 4. The character of chamber timbre as distinct from loudness heard as the first and second heart sounds denotes more often the condition of heart muscle, and must not be confounded with valvular disease. 5. The full significance of sound shadows is uncertain. Cardiac sound shadows appear normally in the right axilla and below the left clavicle. Their mode of production is quite clear. 6. Both the third heart sound and the outflow sound may be heard with the ordinary stethoscope.
Treatment of acute myelogenous leukemia in patients over 50 years of age with V‐TAD: A southwest oncology group study
Authors: Carolyn L. Bigelow, Kenneth Kopecky, Joe C. Files, David Head, David A. Lipschitz, Michael Grever, Frederick R. Appelbaum
Journal: American Journal of Hematology (1995)

Abstract Acute myelogenous leukemia (AML) in the elderly continues to have a poor prognosis and new treatment approaches are needed. This Phase II trial was undertaken to evaluate the complete remission rate and toxicity of a chemotherapeutic regimen including etoposide and 6‐thioguanine, combined with reduced doses of cytosine arabinoside and daunorubicin (V‐TAD) in individuals greater than 50 years of age with AML. Thirty‐five patients, ranging in age from 51 to 80 years (median, 66 years), were registered onto the study. Twenty‐nine patients were entered at the first dose level (daunomycin 20 mg/m 2 days 1 and 2, ara‐C 75 mg/m 2 days 1‐5, 6‐thioguanine 75 mg/m 2 every 12 hr days 1‐5, and etoposide 50 mg/m 2 days 1, 2, and 3) and six patients underwent therapy at the second dose level (ara‐C 75 mg/m 2 days 1‐7 with the remainder of the regimen unchanged). After achieving a complete remission, patients underwent two to three consolidation cycles of chemotherapy. Thirty‐one patients were evaluable for response. Thirteen patients (ten of twenty‐five at the first dose level and three of six at the second dose level) achieved a complete remission (42%). Median remission duration was 6 months (range 1‐21 months). The current regimen, while tolerated, did not result in improved survival compared with prior treatment regimens because of a high incidence of resistant and recurrent leukemia. © 1995 Wiley‐Liss, Inc.
Safety and Immunogenicity Study of NY-ESO-1b Peptide and Montanide ISA-51 Vaccination of Patients with Epithelial Ovarian Cancer in High-Risk First Remission
Authors: Catherine S.M. Diefenbach, Sacha Gnjatic, Paul Sabbatini, Carol Aghajanian, Martee L. Hensley, David R. Spriggs, Alexia Iasonos, Helen Lee, Bo Dupont, Sandra Pezzulli, Achim A. Jungbluth, Lloyd J. Old, Jakob Dupont
Journal: Clinical Cancer Research (2008)

Abstract Purpose: The cancer-testis antigen NY-ESO-1 is expressed by &amp;gt;40% of advanced epithelial ovarian cancers and is a promising immunotherapeutic target. In this study, we describe the effects of vaccination with the HLA-A*0201–restricted NY-ESO-1b peptide on patients with epithelial ovarian cancer in high-risk first remission. Experimental Design: After primary surgery and chemotherapy, high-risk epithelial ovarian cancer patients in first clinical remission received NY-ESO-1b peptide and Montanide every 3 weeks for five vaccinations. Tumor expression was evaluated by immunohistochemistry. Toxicity was monitored using National Cancer Institute Common Toxicity Criteria Scale Version 2. NY-ESO-1 specific humoral immunity (ELISA), T-cell immunity (tetramer and ELISPOT), and delayed-type hypersensitivity were assessed on weeks 0, 1, 4, 7, 10, 13, and 16. Results: Treatment-related adverse events included grade 1 fatigue, anemia, pruritus, myalgias, and hyperthyroidism and grade 2 hypothyroidism. There were no grade 3/grade 4 adverse events. Three of four patients (75%) with NY-ESO-1–positive tumor showed T-cell immunity by tetramer (0.6-9.5%) and ELISPOT (range, 35-260 spots). Four of five patients (80%) with NY-ESO-1–negative tumor showed T-cell immunity by tetramer (1.0-12.1%) and/or ELISPOT (range, 35-400 spots). With a median follow-up of 11.3 months, six of nine patients (67%) have recurred, with a median progression-free survival of 13 months (95% confidence interval, 11.2 months–not reached). Three of nine patients remain in complete clinical remission at 25, 38, and 52 months. Conclusion: Vaccination of high-risk HLA-A*0201–positive epithelial ovarian cancer patients with NY-ESO-1b and Montanide has minimal toxicity and induces specific T-cell immunity in patients with both NY-ESO-1–positive and NY-ESO-1–negative tumors. Additional study is warranted.
Revised International Staging System for Multiple Myeloma: A Report From International Myeloma Working Group
Authors: Antonio Palumbo, Hervé Avet-Loiseau, Stefania Oliva, Henk M. Lokhorst, Hartmut Goldschmidt, Laura Rosinol, Paul Richardson, Simona Caltagirone, Juan José Lahuerta, Thierry Facon, Sara Bringhen, Francesca Gay, Michel Attal, Roberto Passera, Andrew Spencer, Massimo Offidani, Shaji Kumar, Pellegrino Musto, Sagar Lonial, Maria T. Petrucci, Robert Z. Orlowski, Elena Zamagni, Gareth Morgan, Meletios A. Dimopoulos, Brian G.M. Durie, Kenneth C. Anderson, Pieter Sonneveld, Jésus San Miguel, Michele Cavo, S. Vincent Rajkumar, Philippe Moreau
Journal: Journal of Clinical Oncology (2015)

The clinical outcome of multiple myeloma (MM) is heterogeneous. A simple and reliable tool is needed to stratify patients with MM. We combined the International Staging System (ISS) with chromosomal abnormalities (CA) detected by interphase fluorescent in situ hybridization after CD138 plasma cell purification and serum lactate dehydrogenase (LDH) to evaluate their prognostic value in newly diagnosed MM (NDMM).Clinical and laboratory data from 4,445 patients with NDMM enrolled onto 11 international trials were pooled together. The K-adaptive partitioning algorithm was used to define the most appropriate subgroups with homogeneous survival.ISS, CA, and LDH data were simultaneously available in 3,060 of 4,445 patients. We defined the following three groups: revised ISS (R-ISS) I (n = 871), including ISS stage I (serum β2-microglobulin level < 3.5 mg/L and serum albumin level ≥ 3.5 g/dL), no high-risk CA [del(17p) and/or t(4;14) and/or t(14;16)], and normal LDH level (less than the upper limit of normal range); R-ISS III (n = 295), including ISS stage III (serum β2-microglobulin level > 5.5 mg/L) and high-risk CA or high LDH level; and R-ISS II (n = 1,894), including all the other possible combinations. At a median follow-up of 46 months, the 5-year OS rate was 82% in the R-ISS I, 62% in the R-ISS II, and 40% in the R-ISS III groups; the 5-year PFS rates were 55%, 36%, and 24%, respectively.The R-ISS is a simple and powerful prognostic staging system, and we recommend its use in future clinical studies to stratify patients with NDMM effectively with respect to the relative risk to their survival.
Serial evaluation of vasopressin release and thirst in human pregnancy. Role of human chorionic gonadotrophin in the osmoregulatory changes of gestation.
Authors: J M Davison, E A Shiells, P R Philips, M D Lindheimer
Journal: Journal of Clinical Investigation (1988)

Serial studies were designed to characterized changes in osmoregulation throughout gestation. Eight women underwent a 2-h infusion of hypertonic saline before conception, during gestational weeks 5-8, 10-12, and 28-33, and then 10-12 wk postpartum. Basal plasma osmolality (Posmol) was already significantly decreased by 5-8 wk (P less than 0.001) and remained 10 mosmol.kg-1 below nonpregnant values throughout pregnancy. The apparent threshold for AVP release (defined as the abscissal intercept of the regression line relating plasma AVP [PAVP] to Posmol) was also decreased significantly throughout gestation, as was the osmotic threshold for thirst (derived from analogue scales relating desire to drink to Posmol). The decrement in osmotic thirst threshold appeared to precede that for AVP release, and consistent with this 24-h urine volumes were significantly greater at 5-8 wk gestation (P less than 0.05). The slopes of each regression equation defining PAVP vs. Posmol (whose r values ranged from 0.79 to 0.99), very reproducible before and after pregnancy, were similar at 5-8 and 10-12 wk, but were markedly reduced in the third trimester (P less than 0.001). These volunteers had randomly undergone an additional infusion before conception (both tests in the luteal phase of the menstrual cycle) when 10,000 IU of human chorionic gonadotrophin (hCG) had been given intramuscularly over a 5-d period. Serum hCG values between 0.2 and 3.3 U.ml-1 were lower than usually seen in pregnancy, but the osmotic thresholds for AVP release and thirst decreased by 3 and 4 mosmol.kg-1, respectively (P less than 0.05). Finally we studied a patient with a molar pregnancy in whom thresholds for hormone release and thirst were both decreased to values resembling normal gestation and remained so for approximately 6 wk postevacuation, only normalizing when hCG had virtually disappeared from her serum. In contrast, thresholds increased within the first two puerperal weeks in two women with normal pregnancies. These data demonstrate (a) osmotic thresholds for both AVP release and thirst decrease within the very first gestational weeks; (b) increment in PAVP per unit increase in Posmol is reduced late in gestation; and (c) hCG may be involved in the osmoregulatory changes of pregnancy.
Radioimmunoassay of somatomedin B. Application to clinical and physiologic studies.
Authors: R S Yalow, K Hall, R Luft
Journal: Journal of Clinical Investigation (1975)

A radioimmunoassay has been developed for Somatomedin B, a growth hormone-dependent factor that stimulates DNA synthesis in human glia-like cells. The sensitivity permits detection of this factor in human plasma diluted 1: 20,000 and in monkey plasma diluted 1: 5,000. It is not measurable in nonprimate plasma diluted 1: 20. The concentration in growth hormone-deficient adult patients is equivalent to 6.6plus or minus0.5 ug/ml of a highly purified somatomedin preparation. In acromegaly the concentration is 19.3plus or minus2.3 ug/ml and falls after definitive therapy that results in a decrease in plasma growth hormone. In unextracted human plasma the immunoreactive Somatomedin B is associated with a plasma protein at least as large as gamma-globulin and with an electrophoretic mobility on paper resembling the alpha-globulins. The level of Somatomedin B in the bound form in human plasma under steady-state conditions may depend on the rate of production of the peptide and/or the concentration of the plasma-binding protein. At present there is no information concerning which of these is modulated by growth hormone. Immunoreactive Somatomedin B is found predominantly in Cohn plasma fractions III and IV, largely dissociated from the plasma-binding protein. The disappearance curves of labeled purified Somatomedin B and of immunoreactive Somatomedin B from acromegalic plasma administered intravenously to a dog were superposable; the terminal portion of the disappearance curve having a half time of almost an hour.
Randomised trial of Haemophilus influenzae type-b tetanus protein conjugate for prevention of pneumonia and meningitis in Gambian infants
Authors: Kim Mulholland, Stephen Hilton, Richard Adegbola, Stanley Usen, Anslem Oparaugo, Charles Omosigho, Martin Weber, Ayo Palmer, Gisela Schneider, Kebba Jobe, George Lahai, Shabbar Jaffar, Ousman Secka, Kimi Lin, Chantal Ethevenaux, Brian Greenwood
Journal: The Lancet (1997)
The Audible Sounds of Atrial Tachyarrhythmia (Flutter?)
Authors: R. A. MASSUMI, T. HERNANDEZ, G. JUST, A. A. TAWAKKOL
Journal: Circulation (1966)

A patient with a rapid atrial mechanism (rate approximately 225), categorized as atrial flutter, had audible sounds correlated with the atrial cycle. Second degree heart block was present and the intensity of the sounds increased sequentially during the ventricular diastolic period. Phonocatheter records revealed prominent vibrations related to the atrial cycle in the right atrium, but not in the right ventricle, left atrium, or left ventricle. It is suggested that the flutter sounds represent tension of the atrial wall or the atrioventricular valve at the time of atrial systole and are unrelated to ventricular filling.
Prognostic Utility of Anti-EBV Antibody Testing for Defining NPC Risk among Individuals from High-Risk NPC Families
Authors: Kelly J. Yu, Wan-Lun Hsu, Ruth M. Pfeiffer, Chun-Ju Chiang, Cheng-Ping Wang, Pei-Jen Lou, Yu-Juen Cheng, Patti Gravitt, Scott R. Diehl, Alisa M. Goldstein, Chien-Jen Chen, Allan Hildesheim
Journal: Clinical Cancer Research (2011)

Epstein-Barr virus (EBV) infection and a family history of nasopharyngeal carcinoma (NPC) are associated with NPC risk. We examined the risk associated with EBV markers and their clinical utility to identify NPC susceptibles within high-risk NPC families.We evaluated antibody titers against viral capsid antigen (VCA) IgA, EBV nuclear antigen-1 (EBNA1) IgA, and DNase among unaffected relatives of NPC cases from 358 multiplex families in Taiwan. Incident NPC cases were identified via linkage to the National Cancer Registry. Clinical examinations of 924 individuals were also done to identify occult, asymptomatic NPC. Baseline EBV serology was used to estimate NPC risk using rate ratios with 95% CI. Associated sensitivity/specificity and receiver operating characteristic (ROC) curves were calculated.A total of 2,444 unaffected individuals with 15,519 person-years (6.5 years median follow-up) yielded 14 incident NPC cases (nearly 11 times the general population rate). The absolute rate of NPC among anti-EBV EBNA1 IgA seropositives using a standard positivity cutoff versus an optimized cutoff point defined by ROC analyses was 265/100,000 person-years with a 4.7-fold increased risk of NPC (95% CI: 1.4-16) and 166/100,000 person-years with a 6.6-fold increase (95% CI: 1.5-61), respectively. Sensitivity and specificity using the optimized positivity cutoff points were 85.7% and 51.2%, respectively. It is estimated that active evaluation of 49% of individuals from high-risk NPC families seropositive for this marker could lead to earlier detection of up to 86% of NPC cases. Risks associated with the other three EBV markers were weaker.Future efforts are needed to identify susceptibility markers among high-risk NPC families that maximize both sensitivity and specificity.
Vitamin D Status and Outcomes After Renal Transplantation
Authors: Frank Bienaimé, Delphine Girard, Dany Anglicheau, Guillaume Canaud, Jean Claude Souberbielle, Henri Kreis, Laure Hélène Noël, Gérard Friedlander, Caroline Elie, Christophe Legendre, Dominique Prié
Journal: Journal of the American Society of Nephrology (2013)

Kidney transplant recipients usually have low vitamin D levels, especially in the early posttransplantation period, but the association between vitamin D status with renal outcomes is not well described in this population. Here, we studied a prospective cohort of 634 kidney recipients who underwent transplantation at a single institution between January 2005 and June 2010. In this cohort, low 25-hydroxyvitamin D concentrations 3 months after transplantation did not predict early death or graft loss but were independently associated with lower measured GFR at 12 months (P=0.001) and higher risk for interstitial fibrosis and tubular atrophy (P=0.01). In contrast, levels of calcium, phosphorus, calcitriol, parathyroid hormone, or fibroblast growth factor-23 were not consistently associated with any of the studied outcomes. In conclusion, low 25-hydroxyvitamin D concentration measured 3 months after transplantation is an independent risk factor for interstitial fibrosis progression and is associated with a lower GFR 1 year after transplantation.
Measurement of kinetic parameters for urea in end-stage renal disease patients using a two-compartment model.
Authors: P Pearson, S Lew, F Abramson, J Bosch
Journal: Journal of the American Society of Nephrology (1994)

Urea kinetic modeling depends critically on the parameters of the model used. When urea is removed during hemodialysis, the kinetic model is quite complex. This experiment describes for the first time the use of injected stable isotope-labeled urea to define kinetics in ESRD patients and compares the magnitude of the two urea compartments in these patients with those of control subjects. Such an experimental approach provides the kinetic data in the most direct manner. A gas chromatograph/mass spectrometer-based assay provided quantitation to as little as 0.2 mol% excess urea. The rapidly equilibrating fraction of the two urea compartments is quantified as 41.2% in ESRD patients and 33.4% in controls (P = 0.24). The rest is in a more slowly equilibrating pool. The urea clearances between these two compartments were near 1 L/min for both sets of subjects. The elimination of urea was due to the metabolic removal of the 15N label in both groups of subjects as well as renal elimination in the controls. The nearly threefold larger clearance (Cl) of labeled urea removal in controls (Cl = 74.6 mL/min) than in ESRD patients (Cl = 25.4 mL/min; P = 0.015) shows the extent to which renal clearance is more important than metabolism. These direct analyses of the fractional volumes and intercompartmental clearances for urea agree closely with previous measurements during high-efficiency hemodialysis and indicate that ESRD patients do not differ significantly from control subjects in these parameters.
The Relationship Between Depressive Personality Disorder and Major Depressive Disorder: A Population-Based Twin Study
Authors: Ragnhild E. Ørstavik, Kenneth S. Kendler, Nikolai Czajkowski, Kristian Tambs, Ted Reichborn-Kjennerud
Journal: American Journal of Psychiatry (2007)

Objective: One of the most important controversies regarding depressive personality disorder is the overlap with mood disorders. The aim of this study was to estimate the genetic and environmental sources of covariance between depressive personality disorder and major depressive disorder and to what extent genetic, shared, and unique environmental factors are specific to each disorder. Method: A total of 2,801 young adult twins from the Norwegian Institute of Public Health Twin Panel were assessed at personal interview for depressive personality disorder and major depressive disorder with the Structured Interview for DSM-IV Personality and the Composite International Diagnostic Interview. Bivariate Cholesky models were fitted to the data by using the Mx statistical program. Results: In the best-fitting model, the covariation between depressive personality disorder and major depressive disorder were accounted for by genetic and unique environmental factors only. A model that did not include genetic factors specific to major depressive disorder was rejected. The authors found no clear evidence for gender differences in sources of comorbidity of depressive personality disorder and major depressive disorder. Conclusions: Although depressive personality disorder and major depressive disorder share a substantial proportion of genetic and environmental risk factors, the results from this study support the hypothesis that the two disorders are distinct entities with overlapping, but not identical, etiologies.