tbuckley/cabot-search huggingface dataset:
Diabetes and Mortality in Men With Locally Advanced Prostate Cancer: RTOG 92-02
Authors: Matthew R. Smith, Kyounghwa Bae, Jason A. Efstathiou, Gerald E. Hanks, Miljenko V. Pilepich, Howard M. Sandler, William U. Shipley
Journal: Journal of Clinical Oncology (2008)

Purpose Diabetes is associated with lower risk of prostate cancer. Most men with diabetes are obese, and obesity is associated with greater prostate cancer mortality. Whether diabetes influences outcomes after prostate cancer diagnosis is unknown. Patients and Methods We assessed the relationship between prevalent diabetes and mortality using data from Radiation Therapy Oncology Group Protocol 92-02, a large randomized trial of men (N = 1,554) treated with radiation therapy and short-term versus long-term adjuvant goserelin for locally advanced prostate cancer. Regression and proportional hazard models were performed to evaluate relationships between prevalent diabetes and all-cause mortality, prostate cancer mortality, and non–prostate cancer mortality. Covariates included age, race, tumor stage, Gleason score, prostate-specific antigen, weight, and treatment arm. Results There were a total of 765 deaths; 210 (27%) were attributed to prostate cancer. In univariate analyses, prevalent diabetes was associated with greater all-cause mortality and non–prostate cancer mortality but not prostate cancer mortality. After controlling for other covariates, prevalent diabetes remained significantly associated with greater all-cause mortality and non–prostate cancer mortality (hazard ratio [HR] = 2.12; 95% CI, 1.69 to 2.66; P &lt; .0001) but not prostate cancer mortality (HR = 0.80; 95% CI, 0.51 to 1.25; P = .34). In contrast, weight was associated with greater prostate cancer mortality (HR = 1.77; 95% CI, 1.22 to 2.55; P = .002) but not all-cause or non–prostate cancer mortality. Conclusion Weight but not prevalent diabetes is associated with greater prostate cancer mortality in men receiving combined modality treatment for locally advanced disease. These observations suggest that the association between obesity and greater prostate cancer mortality is mediated by mechanism(s) other than the characteristic metabolic alterations of diabetes.
Functional organization of the hematopoietic stem cell compartment: implications for cancer and its therapy.
Authors: S Hellman, U Reincke, L Botnick, P Mauch
Journal: Journal of Clinical Oncology (1983)

Recent discoveries indicate that hematopoietic stem cells have limits on their proliferative capacity and are unable to divide indefinitely. There is great heterogeneity within the compartment as to the extent of this proliferative limitation. At any given time it appears that hematopoiesis is maintained by the progeny of only a few stem cells. When these are exhausted the progeny from other stem cells take their place. The observations of proliferative limitation, heterogeneity, and clonal succession must be incorporated into any model of stem cell organization. These new discoveries and the models incorporating them have important clinical implications. They may explain the inability of normal tissues to develop drug resistance and they also offer a mechanism by which cell renewal systems decrease the development of malignancies. In the selection of chemotherapeutic agents not only the effectiveness of the drug upon the tumor must be considered, but also how specific agents affect the stem cell compartment. These data have important implications in the use of bone marrow transplantation for both malignant and nonmalignant disease.
Lawyers will appeal ruling that cleared Guantanamo doctor of ethics violations
Authors: Janice Hopkins Tanne
Journal: BMJ (2005)

Lawyers representing four Yemeni detainees at the US Guantanamo naval base in Cuba have said that they would appeal a ruling of the Medical Board of California. The board dismissed a complaint made on behalf of the detainees against John Edmondson, who is the US army doctor in charge of medical care at the base. More than 500 detainees are being held there.

Doctors who serve in the US military must hold valid state licences, as Dr Edmondson does in California. State boards have responsibility for investigating allegations of unprofessional conduct.

Lawyers for the international firm of Allen & Overy, working pro bono, complained to the medical board about Dr Edmondson, who is commander of the US Navy Hospital at Guantanamo. They alleged that Dr Edmondson and the personnel he supervised engaged in …
High-Dose Antiangiogenic Therapy for Glioblastoma: Less May Be More?
Authors: John F. de Groot
Journal: Clinical Cancer Research (2011)

Abstract Targeting angiogenesis in glioblastoma rapidly reduces vascular permeability and contrast enhancement on MRI and prolongs progression-free survival. The long-term efficacy of bevacizumab and other antiangiogenic agents is limited, however, because of the rapid development of resistance. Alternative dosing approaches may be one mechanism of prolonging therapeutic efficacy. Clin Cancer Res; 17(19); 6109–11. ©2011 AACR.
Abnormal Adrenal Responsiveness and Angiotensin II Dependency in High Renin Essential Hypertension
Authors: Robert G. Dluhy, Sam Z. Bavli, Frank K. Leung, Harold S. Solomon, Thomas J. Moore, Norman K. Hollenberg, Gordon H. Williams
Journal: Journal of Clinical Investigation (1979)

Adrenal responsiveness to angiotensin II (AII) and the diastolic blood pressure responses to saralasin were studied in 19 patients with high renin essential hypertension (HREH) on a 10-meq Na+/100 meq K+ diet. The increment in plasma renin activity (PRA) between supine and upright positions was used as an estimate of the acute stimulation of the adrenal gland by endogenous AII; the normal increment in plasma aldosterone divided by the increment in PRA was >3.8. 7 of 19 had abnormal upright posture responses with significantly greater mean PRA increments (24±6 ng/ml per h) and significantly smaller plasma aldosterone increments 47 ± 16 ng/dl) (P < 0.036) compared to the increments observed in HREH patients with normal adrenal responsiveness (PRA = 15 ± 1 ng/ml per h; plasma aldosterone = 87 ± 17 ng/dl). When AII was infused at doses of 0.1-3 ng/kg per min, only patients with normal posture responses had normal plasma aldosterone increments; plasma aldosterone levels failed to significantly increase even at the highest infusion rate in the patients with the abnormal upright posture responses. The AII competitive inhibitor, saralasin (0.3-30 μg/kg per min) was then infused to study the occurrence of angiotensinogenic hypertension in both HREH subgroups. The mean decline in diastolic blood pressure to saralasin in the subnormal adrenal responsive patients (−15 ± 3 mm Hg) was significantly greater than in the normal adrenal responsive group (−3 ± 2 mm Hg) (P < 0.02).
Body mass index and breast cancer risk in Japan: a pooled analysis of eight population-based cohort studies
Authors: K. Wada, C. Nagata, A. Tamakoshi, K. Matsuo, I. Oze, K. Wakai, I. Tsuji, Y. Sugawara, T. Mizoue, K. Tanaka, M. Iwasaki, M. Inoue, S. Tsugane, S. Sasazuki
Journal: Annals of Oncology (2014)

A positive association between body mass index (BMI) and breast cancer risk among postmenopausal women has been reported, and a weak inverse association has been suggested among premenopausal women from studies in the Western population. The effects of BMI on breast cancer have remained unclear among the Asian population, especially in premenopausal women.We assessed the associations between BMI and breast cancer incidence by a pooled analysis from eight representative large-scale cohort studies in Japan. Cancer incidence was mainly confirmed through regional population-based cancer registries and/or through active patient notification from major local hospitals. Breast cancer was defined as code C50 according to ICD10. Pooled estimates of the hazard ratios (HRs) and 95% confidence interval (CIs) for breast cancer were calculated using random-effects models.Analytic subjects were 183 940 women, 1783 of whom had breast cancer during 2 194 211 person-years of follow-up. A positive association between BMI and the risk of postmenopausal breast cancer was observed (trend P<0.001). The HRs for premenopausal breast cancer were 1.05 (95% CI 0.56-1.99), 1.07 (95% CI 0.76-1.52), 0.91 (95% CI 0.64-1.30), 1.15 (95% CI 0.76-1.73), 1.45 (95% CI 0.71-2.94), and 2.25 (95% CI 1.10-4.60), respectively, in BMIs of <19, 19 to <21, 21 to <23, 25 to <27, 27 to <30, and ≥30 kg/m2. These results were not substantially altered after excluding the patients who were diagnosed with breast cancer in the first 2 years of follow-up.The increased risk of postmenopausal breast cancer among women with higher BMIs was confirmed in Japanese. A borderline-significant positive association between BMI and premenopausal breast cancer was observed, suggesting that body mass in Asian women might have opposite effects on breast cancer compared with Western women.
CBX7 is a tumor suppressor in mice and humans
Authors: Floriana Forzati, Antonella Federico, Pierlorenzo Pallante, Adele Abbate, Francesco Esposito, Umberto Malapelle, Romina Sepe, Giuseppe Palma, Giancarlo Troncone, Marzia Scarfò, Claudio Arra, Monica Fedele, Alfredo Fusco
Journal: Journal of Clinical Investigation (2012)

The CBX7 gene encodes a polycomb group protein that is known to be downregulated in many types of human cancers, although the role of this protein in carcinogenesis remains unclear. To shed light on this issue, we generated mice null for Cbx7. Mouse embryonic fibroblasts derived from these mice had a higher growth rate and reduced susceptibility to senescence compared with their WT counterparts. This was associated with upregulated expression of multiple cell cycle components, including cyclin E, which is known to play a key role in lung carcinogenesis in humans. Adult Cbx7-KO mice developed liver and lung adenomas and carcinomas. In in vivo and in vitro experiments, we demonstrated that CBX7 bound to the CCNE1 promoter in a complex that included HDAC2 and negatively regulated CCNE1 expression. Finally, we found that the lack of CBX7 protein expression in human lung carcinomas correlated with CCNE1 overexpression. These data suggest that CBX7 is a tumor suppressor and that its loss plays a key role in the pathogenesis of cancer.
The potent bone-resorbing mediator of Actinobacillus actinomycetemcomitans is homologous to the molecular chaperone GroEL.
Authors: A C Kirby, S Meghji, S P Nair, P White, K Reddi, T Nishihara, K Nakashima, A C Willis, R Sim, M Wilson
Journal: Journal of Clinical Investigation (1995)

Actinobacillus actinomycetemcomitans is a Gram-negative bacterium implicated in the pathology of localized juvenile periodontitis, a condition involving rapid destruction of alveolar bone. We have established that gentle extraction of this bacterium in saline releases a proteinaceous fraction (which we have termed surface-associated material [SAM] which has potent osteolytic activity in the murine calvarial bone resorption assay. Fractionation of the SAM has now revealed that activity is associated with a 62-kD protein. This bone-resorbing activity can be blocked by a monoclonal antibody (raised to the whole bacterium) that is claimed to recognize a protein homologous to the Escherichia coli molecular chaperone GroEL. Purification of this bone-resorbing protein to homogeneity has been achieved by a combination of anion exchange, gel filtration, and ATP-affinity chromatography and the NH2-terminal sequence shows > 95% homology to E. coli GroEL. This GroEL homologue is found in the SAM of A. actinomycetemcomitans but is not found in the osteolytically active SAM from other Gram-negative or Gram-positive bacteria. The GroEL protein from E. coli, but not from Mycobacterium tuberculosis and Mycobacterium leprae, also showed activity in the bone resorption assay. We believe this to be the first observation that a molecular chaperone has the capacity to stimulate the breakdown of connective tissue.
An Early Pregnancy HbA1c ≥5.9% (41 mmol/mol) Is Optimal for Detecting Diabetes and Identifies Women at Increased Risk of Adverse Pregnancy Outcomes
Authors: Ruth C.E. Hughes, M. Peter Moore, Joanna E. Gullam, Khadeeja Mohamed, Janet Rowan
Journal: Diabetes Care (2014)

OBJECTIVE Pregnant women with undiagnosed diabetes are a high-risk group that may benefit from early intervention. Extrapolating from nonpregnancy data, HbA1c ≥6.5% (48 mmol/mol) is recommended to define diabetes in pregnancy. Our aims were to determine the optimal HbA1c threshold for detecting diabetes in early pregnancy as defined by an early oral glucose tolerance test (OGTT) at &amp;lt;20 weeks’ gestation and to examine pregnancy outcomes relating to this threshold. RESEARCH DESIGN AND METHODS During 2008–2010 in Christchurch, New Zealand, women were offered an HbA1c measurement with their first antenatal bloods. Pregnancy outcome data were collected. A subset completed an early OGTT, and HbA1c performance was assessed using World Health Organization criteria. RESULTS HbA1c was measured at a median 47 days’ gestation in 16,122 women. Of those invited, 974/4,201 (23%) undertook an early OGTT. In this subset, HbA1c ≥5.9% (41 mmol/mol) captured all 15 cases of diabetes, 7 with HbA1c &amp;lt;6.5% (&amp;lt;48 mmol/mol). This HbA1c threshold was also 98.4% (95% CI 97–99.9%) specific for gestational diabetes mellitus (GDM) before 20 weeks (positive predictive value = 52.9%). In the total cohort, excluding women referred for GDM management, women with HbA1c of 5.9–6.4% (41–46 mmol/mol; n = 200) had poorer pregnancy outcomes than those with HbA1c &amp;lt;5.9% (&amp;lt;41 mmol/mol; n = 8,174): relative risk (95% CI) of major congenital anomaly was 2.67 (1.28–5.53), preeclampsia was 2.42 (1.34–4.38), shoulder dystocia was 2.47 (1.05–5.85), and perinatal death was 3.96 (1.54–10.16). CONCLUSIONS HbA1c measurements were readily performed in contrast to the low uptake of early OGTTs. HbA1c ≥5.9% (≥41 mmol/mol) identified all women with diabetes and a group at significantly increased risk of adverse pregnancy outcomes.
Incidence and predictors of secondary fibromyalgia in an early arthritis cohort
Authors: Yvonne C Lee, Bing Lu, Gilles Boire, Boulos (Paul) Haraoui, Carol A Hitchon, Janet E Pope, J Carter Thorne, Edward Clark Keystone, Daniel H Solomon, Vivian P Bykerk
Journal: Annals of the Rheumatic Diseases (2012)

Objectives Secondary fibromyalgia (FM) is common among patients with inflammatory arthritis, but little is known about its incidence and the factors leading to its development. The authors examined the incidence of secondary FM in an early inflammatory arthritis cohort, and assessed the association between pain, inflammation, psychosocial variables and the clinical diagnosis of FM. Methods Data from 1487 patients in the Canadian Early Arthritis Cohort, a prospective, observational Canadian cohort of early inflammatory arthritis patients were analysed. Diagnoses of FM were determined by rheumatologists. Incidence rates were calculated, and Cox regression models were used to determine HRs for FM risk. Results The cumulative incidence rate was 6.77 (95% CI 5.19 to 8.64) per 100 person-years during the first 12 months after inflammatory arthritis diagnosis, and decreased to 3.58 (95% CI 1.86 to 6.17) per 100 person-years 12–24 months after arthritis diagnosis. Pain severity (HR 2.01, 95% CI 1.17 to 3.46) and poor mental health (HR 1.99, 95% CI 1.09 to 3.62) predicted FM risk. Citrullinated peptide positivity (HR 0.48, 95% CI 0.26 to 0.88) was associated with decreased FM risk. Serum inflammatory markers and swollen joint count were not significantly associated with FM risk. Conclusions The incidence of FM was from 3.58 to 6.77 cases per 100 person-years, and was highest during the first 12 months after diagnosis of inflammatory arthritis. Although inflammation was not associated with the clinical diagnosis of FM, pain severity and poor mental health were associated with the clinical diagnosis of FM. Seropositivity was inversely associated with the clinical diagnosis of FM.
Effect of vitamins C and E on progression of transplant-associated arteriosclerosis: a randomised trial
Authors: James C Fang, Scott Kinlay, John Beltrame, Hiroyuki Hikiti, Marco Wainstein, Dominik Behrendt, Jung Suh, Balz Frei, Gilbert H Mudge, Andrew P Selwyn, Peter Ganz
Journal: The Lancet (2002)
Detection of early neoplastic changes in experimentally induced colorectal cancer using scanning electron microscopy and cell kinetic studies.
Authors: T Cooke, N Kirkham, D H Stainthorp, C Inman, N Goeting, I Taylor
Journal: Gut (1984)

Colonic tumours were induced in Wistar rats using 12 consecutive subcutaneous injections of azoxymethane at a dose of 10 mg/kg/week. Pairs of rats were killed at five weekly intervals after initial injection until 25 weeks. Colonic mucosa was sampled from five standard areas along the length of the colon and examined by both scanning electron microscopy and conventional light microscopy. The crypt cell production rate was measured by stathmokinetic techniques. Scanning electron microscopy showed microadenomas as early as five weeks and consistently after 15 weeks. They were found predominantly in the distal colon and increased in size with time. The lesions showed a progressive increase in the number of crypts per adenoma and increasingly disorganised slit shaped crypt orifices. The presence of epithelial dysplasia in the microadenomas and of invasion of the colonic wall by carcinoma was confirmed histologically, although fewer lesions were identified in tissue sections than by scanning electron microscopy. Crypt cell production rate increased with time, particularly in the distal colon. This increase was significant between five and 25 weeks. The results of these observations suggest that there is an adenoma-carcinoma sequence in this animal model. The value of scanning electron microscopy in identifying and quantifying the mucosal changes during carcinogenesis is emphasised.
Iron uptake and increased intracellular enzyme activity follow host lactoferrin binding by Trichomonas vaginalis receptors.
Authors: K M Peterson, J F Alderete
Journal: The Journal of Experimental Medicine (1984)

Lactoferrin acquisition and iron uptake by pathogenic Trichomonas vaginalis was examined. Saturation binding kinetics were obtained for trichomonads using increasing amounts of radioiodinated lactoferrin, while no significant binding by transferrin under similar conditions was achieved. Only unlabeled lactoferrin successfully and stoichiometrically competed with 125I-labeled lactoferrin binding. Time course studies showed maximal lactoferrin binding by 30 min at 37 degrees C. Data suggest no internalization of bound lactoferrin. The accumulation of radioactivity in supernatants after incubation of T. vaginalis with 125I-labeled lactoferrin and washing in PBS suggested the presence of low affinity sites for this host macromolecule. Scatchard analysis indicated the presence of 90,000 receptors per trichomonad with an apparent Kd of 1.0 microM. Two trichomonad lactoferrin binding proteins were identified by affinity chromatography and immunoprecipitation of receptor-ligand complexes. A 30-fold accumulation of iron was achieved using 59Fe-lactoferrin when compared to the steady state concentration of bound lactoferrin. The activity of pyruvate/ferrodoxin oxidoreductase, an enzyme involved in trichomonal energy metabolism, increased more than sixfold following exposure of the parasites to lactoferrin, demonstrating a biologic response to the receptor-mediated binding of lactoferrin. These data suggest that T. vaginalis possesses specific receptors for biologically relevant host proteins and that these receptors contribute to the metabolic processes of the parasites.
Increased Synthesis and AVP Unresponsiveness of Na,K-ATPase in Collecting Duct from Nephrotic Rats
Authors: GEORGES DESCHÊNES, SANDRINE GONIN, EINATH ZOLTY, LYDIE CHEVAL, MARTINE ROUSSELOT, PIERRE-YVES MARTIN, JEAN-MARC VERBAVATZ, ERIC FÉRAILLE, ALAIN DOUCET
Journal: Journal of the American Society of Nephrology (2001)

Renal sodium retention is responsible for ascites and edema in nephrotic syndrome. In puromycin aminonucleoside (PAN)—induced nephrosis, sodium retention originates in part from the collecting duct, and it is associated with increased Na,K-ATPase activity in the cortical collecting duct (CCD). The aims of this study were to evaluate whether the outer medullary collecting duct (OMCD) also participates to sodium retention and to determine the mechanisms responsible for stimulation of Na,K-ATPase in CCD. PAN nephrosis increased Na,K-ATPase activity in the CCD but not in OMCD. The two-fold increase of Na,K-ATPase activity in CCD was associated with two-fold increases in the number of α and β Na,K-ATPase subunits mRNA determined by quantitative RT-PCR and of the total amount of Na,K-ATPase α subunits estimated by Western blotting. PAN nephrosis also increased two-fold the amount of Na,K-ATPase α subunit at the basolateral membrane of CCD principal cells, as determined by Western blotting after biotinylation and streptavidin precipitation and by immunofluorescence. The intracellular pool of latent Na,K-ATPase units also increased in size and was no longer recruitable by vasopressin and cAMP. This unresponsiveness of the intracellular pool of Na,K-ATPase to vasopressin was not the result of any alteration of the molecular and functional expression of the vasopressin V2 receptor/adenylyl cyclase (AC) complex. It is concluded that PAN nephrosis (1) does not alter sodium reabsorption in OMCD, (2) is associated with increased synthesis and membrane expression of Na,K-ATPase in the CCD, and (3) alters the normal trafficking of intracellular Na,K-ATPase units to the basolateral membrane.
Human physiology: the basis of medicine
Authors: V Higgins
Journal: British Journal of Sports Medicine (2006)

<h3>Background</h3> The neonatal intensive care unit (NICU) can be one of the most stressful hospital environments. Alongside providing intensive clinical care, it is important that parents have the opportunity for regular physical contact with their babies because the neonatal period is critical for parent–child bonding. At present, monitoring technology in the NICU requires multiple wired sensors to track each baby9s vital signs. This study describes the experiences that parents and nurses have with the current monitoring methods, and reports on their responses to the concept of a wireless monitoring system. <h3>Methods</h3> Semistructured interviews were conducted with six parents, each of whom had babies on the unit, and seven nurses who cared for those babies. The interviews initially focused on the participants’ experiences of the current wired system and then on their responses to the concept of a wireless system. The transcripts were analysed using a general inductive approach to identify relevant themes. <h3>Results</h3> Participants reported on physical and psychological barriers to parental care, the ways in which the current system obstructed the efficient delivery of clinical care and the perceived benefits and risks of a wireless system. The parents and nurses identified that the wires impeded baby–parent bonding; physically and psychologically. While a wireless system was viewed as potentially enabling greater interaction, staff and parents highlighted potential concerns, including the size, weight and battery life of any new device. <h3>Conclusions</h3> The many wires required to safely monitor babies within the NICU creates a negative environment for parents at a critical developmental period, in terms of physical and psychological interactions. Nurses also experience challenges with the existing system, which could negatively impact the clinical care delivery. Developing a wireless system could overcome these barriers, but there remain challenges in designing a device suitable for this unique environment.