tbuckley/cabot-search huggingface dataset:
Mortality after Parental Death in Childhood: A Nationwide Cohort Study from Three Nordic Countries
Authors: Jiong Li, Mogens Vestergaard, Sven Cnattingius, Mika Gissler, Bodil Hammer Bech, Carsten Obel, Jørn Olsen
Journal: PLoS Medicine (2014)

Bereavement by spousal death and child death in adulthood has been shown to lead to an increased risk of mortality. Maternal death in infancy or parental death in early childhood may have an impact on mortality but evidence has been limited to short-term or selected causes of death. Little is known about long-term or cause-specific mortality after parental death in childhood.This cohort study included all persons born in Denmark from 1968 to 2008 (n = 2,789,807) and in Sweden from 1973 to 2006 (n = 3,380,301), and a random sample of 89.3% of all born in Finland from 1987 to 2007 (n = 1,131,905). A total of 189,094 persons were included in the exposed cohort when they lost a parent before 18 years old. Log-linear Poisson regression was used to estimate mortality rate ratio (MRR). Parental death was associated with a 50% increased all-cause mortality (MRR = 1.50, 95% CI 1.43-1.58). The risks were increased for most specific cause groups and the highest MRRs were observed when the cause of child death and the cause of parental death were in the same category. Parental unnatural death was associated with a higher mortality risk (MRR = 1.84, 95% CI 1.71-2.00) than parental natural death (MRR = 1.33, 95% CI 1.24-1.41). The magnitude of the associations varied according to type of death and age at bereavement over different follow-up periods. The main limitation of the study is the lack of data on post-bereavement information on the quality of the parent-child relationship, lifestyles, and common physical environment.Parental death in childhood or adolescence is associated with increased all-cause mortality into early adulthood. Since an increased mortality reflects both genetic susceptibility and long-term impacts of parental death on health and social well-being, our findings have implications in clinical responses and public health strategies. Please see later in the article for the Editors' Summary.
GENE CONTROL OF HEMATOPOIESIS
Authors: Beatrice Mintz, Joy Palm
Journal: The Journal of Experimental Medicine (1969)

Erythropoietic cells of two unrelated strains, C3H (or C3Hf) and C57BL/6, can coexist throughout hematopoiesis in allophenic mice experimentally produced from aggregated, undifferentiated blastomeres of separate genotypes. The presence of two red cell genotypes in these circumstances signifies that the erythroid population must normally be multiclonal, i.e., derived mitotically from at least two genetically determined cells. The two strains were detected by hemagglutination and absorption tests of erythrocytes for the specific histocompatibility antigens dictated by the H-2(k) and H-2(b) alleles. Of 34 C3H(f) <--> C57BL/6 allophenics tested, 16 had both red cell types; the remaining 18 showed only C3H or C57 red cells and included 12 mice with both cell strains present in some other tissues. All animals with evidence of two H-2 phenotypes among circulating erythrocytes were permanently immunologically tolerant of both antigenic types and remained free of runt disease. They lived a full lifespan, up to 2 yr 7(1/2) months of age. The data suggest a possible specific selective advantage of C57BL/6 over C3H erythropoietic tissue. There is considerable individual variability, not only in proportions of antigenically distinct erythrocytes, but also in strain composition of other tissues in the same animals. A broad spectrum of distinctive situations is found, in which parameters are varied within or outside of the circulatory system. Allophenic mice can therefore serve as investigative tools for entirely new kinds of experimental studies of gene control mechanisms and blood physiology in normal hematopoiesis and in a number of hereditary blood diseases.
Abstract P6-07-26: Prognostic significance of the maximal value of the baseline standardized uptake value on fluorine 18 fluorodeoxyglucose positron emission tomography/computed tomography for predicting pathologic malignancy of operable breast cancer with neoadjuvant chemotherapy
Authors: T Kadoya, E Akimoto, A Emi, H Shigematsu, N Masumoto, M Okada
Journal: Cancer Research (2012)

Abstract PURPOSE: [18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) is potentially useful in predicting pathological complete response (pCR), disease free survival (DFS) and overall survival (OS) of breast cancer patients with neoadjuvant chemotherapy. MATERIALS AND METHODS: 77 breast cancer patients (mean age ± SD: 52.6 ± 11.2 years) with clinical Stage I∼III between January 2006 and December 2011, were prospectively evaluated (median follow up period:26.5 months). Neoadjuvant chemotherapy of an anthracycline-based regimen and taxane was performed, and patients underwent a whole-body FDG PET/CT before and after chemotherapy. The maximal value of the baseline standardized uptake values (SUVmax) were assessed for predicting pCR, DFS and OS. For the evaluation of relationship between SUVmax values and prognosticators such as hormone receptors, human epidermal growth factor receptor 2 (HER2), nuclear grade, lymph node metastasis and tumor size, statistical analyses were performed using Student t test and log-rank test, and p values of less than 0.05 were considered to indicate statistically significant differences. RESULTS: Clinical Stage included were I (n = 2, 2.6%), II (n = 62, 80.5%) and III (n = 12, 15.6%). Tumors with estrogen receptor positive were 52 (67.5%) and negative were 24 (31.2%). Therapeutic response by neoadjuvant chemotherapy was obtained in 15 patients (19.5%) with pCR and 60 (77.9%) without pCR. Patients were divided into two groups according to cut-off SUVmax established on the basis of receiver operating characteristic (ROC) analysis (&amp;lt;6.0 vs. ≥6.0, AUC=0.721). When related to the biologic parameters, estrogen receptor (OR:3.75, 95%Cl:1.36–10.35, p = 0.02), but not progesterone receptor (OR:2.31, 95%Cl:0.89–6.00, p = 0.08) nor HER2 status (OR:1.51, 95%Cl:0.47–4.85, p = 0.70) were found strong relation to SUVmax values. There was a significant difference in OS between two groups (p = 0.05), but, pCR (OR:1.07, 95%Cl:0.34–3.40, p = 0.86) and DFS (p = 0.07) did not show strong relationship with SUVmax values. CONCLUSION: SUVmax on FDG PET/CT before neoadjuvant chemotherapy have a predictive value for high-grade malignancy and prognosis in clinical Stage I∼III breast cancer. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-07-26.
Intercellular canaliculi in eccrine sweat glands: an immunoperoxidase study
Authors: R.M. GRAHAM, P.H. MCKEE, D.V. CHAPMAN, T.C. RICHARDSON, M.R. STOKOE, E. HEYDERMAN
Journal: British Journal of Dermatology (1985)

Using an indirect immunoperoxidase technique, both epithelial membrane antigen and carcinoembryonic antigen were identified within the ducts and secretory coils of the eccrine sweat gland. Antibodies to epithelial membrane antigen stained the intercellular canaliculi of the secretory coils, as did those antisera to CEA which showed activity against normal cross-reacting antigen (CEX, NCA). Those without such activity showed minimal or no staining of intercellular canaliculi. There is a difference in antigenic expression between the acinar cells and their intercellular canaliculi, and the cells of eccrine ducts.
Ovarian Transplantation in a Series of Monozygotic Twins Discordant for Ovarian Failure
Authors: Sherman J. Silber, Roger G. Gosden
Journal: New England Journal of Medicine (2007)

To the Editor: We previously reported in the Journal a case of a successful ovarian transplantation between 25-year-old monozygotic twins. One had undergone menopause at the age of 14 years, wherea...
Modulation of rat hepatocyte proliferation by bile salts: In vitro and In vivo studies
Authors: M Barone
Journal: Hepatology (1996)

In this study, the stimulatory effect of bile salts (BS) was evaluated both In vitro, using hepatocyte primary cultures, and In vivo, in normal and 40% partially hepatectomized rats previously fed on BS- enriched diets for 4 weeks. In vitro results show that conjugated cholate (CA) and chenodeoxycholate (CDCA) augmented proliferative activity in rat hepatocytes cultured in absence of mitogens, whereas conjugated deoxycholate (DCA), and ursodeoxycholate (UDCA) did not have any significant effect. None of these BSs increased significantly the replicative response induced by submaximal concentrations of epidermal growth factor (EGF). In vivo, at the end of dietary treatment all animals fed on CA or DCA but not those fed on either CDCA, or UDCA, or tauroursodeoxycholate (TUDCA) developed cholestatic hepatitis and a burst of damage-induced hepatocyte proliferation. After 40% partial hepatectomy (PH), CA- and DCA-treated groups underwent a deterioration of cholestatic hepatitis. On the other hand, in CDCA-, and UDCA-, and TUDCA-treated groups liver histology, serum glutamic pyruvic transaminase (SGPT) and cholestasis indices did not change significantly compared with controls. As far as the proliferative activity, a significant increase was observed not only in CA and DCA but also in UDCA- and TUDCA-fed groups compared with controls, whereas a slight decrease was observed in CDCA-treated animals. In conclusion, our data indicate that conjugated BSs had only a modest stimulatory effect on hepatocyte proliferation In vitro. However, In vivo, in PH rats, UDCA or TUDCA treatment determined a further increase of hepatocellular proliferation not attributable to hepatotoxic effects. Our result suggest that modifications of bile acid pool could modulate hepatocellular proliferation. (Hepatology 1996 May;23(5):1159-66)
Endoscopic appearance of irradiated gastric mucosa
Authors: L. De Sagher, B. Van den Heule, P. Van Houtte, L. Engelholm, D. Balikdjan, H. Bleiberg
Journal: Endoscopy (1979)

Irradiation of the epigastric area for gastric cancer may induce actinic lesions of the stomach characterized on endoscopic examination by ulcerations, haemorrhagic gastritis, fragility of the mucosa, thickening and congestion of the gastric folds.
Exercise Training Attenuates MuRF-1 Expression in the Skeletal Muscle of Patients With Chronic Heart Failure Independent of Age
Authors: Stephan Gielen, Marcus Sandri, Irina Kozarez, Jürgen Kratzsch, Daniel Teupser, Joachim Thiery, Sandra Erbs, Norman Mangner, Karsten Lenk, Rainer Hambrecht, Gerhard Schuler, Volker Adams
Journal: Circulation (2012)

Background— Muscle wasting occurs in both chronic heart failure (CHF) and normal aging and contributes to exercise intolerance and increased morbidity/mortality. However, the molecular mechanisms of muscle atrophy in CHF and their interaction with aging are still largely unknown. We therefore measured the activation of the ubiquitin-proteasome system and the lysosomal pathway of intracellular proteolysis in muscle biopsies of CHF patients and healthy controls in two age strata and assessed the age-dependent effects of a 4-week endurance training program on the catabolic-anabolic balance. Methods and Results— Sixty CHF patients (30 patients aged ≤55 years, mean age 46±5 years; 30 patients aged ≥65 years, mean age 72±5 years) and 60 healthy controls (30 subjects aged ≤55 years, mean age 50±5 years; 30 subjects aged ≥65 years, mean age 72±4 years) were randomized to 4 weeks of supervised endurance training or to a control group. Before and after the intervention, vastus lateralis muscle biopsies were obtained. The expressions of cathepsin-L and the muscle-specific E3 ligases MuRF-1 and MAFbx were measured by real-time polymerase chain reaction and confirmed by Western blot. At baseline, MuRF-1 expression was significantly higher in CHF patients versus healthy controls (mRNA: 624±59 versus 401±25 relative units; P =0.007). After 4 weeks of exercise training, MuRF-1 mRNA expression was reduced by −32.8% ( P =0.02) in CHF patients aged ≤55 years and by −37.0% ( P &lt;0.05) in CHF patients aged ≥65 years. Conclusions— MuRF-1, a component of the ubiquitin-proteasome system involved in muscle proteolysis, is increased in the skeletal muscle of patients with heart failure. Exercise training results in reduced MuRF-1 levels, suggesting that it blocks ubiquitin-proteasome system activation and does so in both younger and older CHF patients. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00176319.
The Diabetogenic Activity of Benzothiadiazines
Authors: Frederick W. Wolff, William W. Parmley
Journal: JAMA (1964)

To the Editor:—  Because benzothiadiazines have been used so widely for many diverse conditions—including even obesity—any comment on the diabetogenic effect of this class of compounds is important.  It is not surprising that a respected senior investigator such as Dr. Edward Freis ( JAMA  187 :462 [Feb 8] 1964) is disturbed at the increasingly reported side effects of  agents. Everyone will agree with him as he states that these agents are quite effective and often irreplaceable, either alone or as an adjunct in the treatment of hypertension.... Though sufficient details of studies cannot be supplied in a letter, we feel compelled nonetheless to question certain points in Dr. Freis's argument.  He states that the two groups were similar in regard to race distribution and family history of diabetes, but he does not mention sex, and we believe that the Veterans Administration Cooperative Study is limited to male patients. This may
Book Review Pediatric Endocrinology and Inborn Errors of Metabolism Edited by Kyriakie Sarafoglou, Georg F. Hoffmann, and Karl S. Roth. 949 pp., illustrated. New York, McGraw-Hill, 2009. $99. 978-0-07-143915-2
Authors: Kristina I. Rother
Journal: New England Journal of Medicine (2009)
Cancer of the Breast
Authors: Curtis P. Artz
Journal: JAMA (1968)

This slim volume is a summary of current methods of managing carcinoma of the breast. It is well written and adequately covers the current status. It has as its chief virtues, discussions in depth on several controversial issues, such as super radical and modified surgical approaches, mammography, preand postoperative irradiation, nipple discharge, and cystosarcoma phyllodes. The conclusions reached concerning these entities arc drawn from careful consideration of a particular experience at the Ellis Fischel State Cancer Hospital together with a conscientious survey of the published data from other centers. These conclusions are presented clearly and derived logically. The sections on pathology and anatomy would appear to be somewhat superfluous in a book whose main service is that of bringing the reader up to date rather than introducing him to the subject.
Regulation of glucocorticoid receptor in nasal polyps by systemic and intranasal glucocorticoids
Authors: L. Pujols, I. Alobid, P. Benítez, A. Martínez‐Antón, J. Roca‐Ferrer, W. J. Fokkens, J. Mullol, C. Picado
Journal: Allergy (2008)

Background: Poor response of nasal polyps to glucocorticoids (GCs) may be because of abnormal expression of GC receptors (GR) α and β or to downregulation of GRα. We aimed to evaluate the in vivo regulation of GR isoforms in GC‐treated nasal polyps and to assess the relationship between clinical response to GCs and GR levels. Methods: Patients with nasal polyps were randomly (3:1) treated ( n = 51) or not ( n = 14) with oral prednisone and intranasal budesonide for 2 weeks, plus intranasal budesonide for 10 additional weeks. Nasal symptoms were evaluated. Biopsies were obtained before (w0) and after 2 (w2) and 12 (w12) weeks of treatment, and analysed for their inflammatory content and GR mRNA (10 2 cDNA copies/μg total RNA) and protein (% immunoreactive inflammatory cells) expression. Healthy nasal mucosa ( n = 11) was also investigated. Data are presented as median and 25–75th percentile. Results: At w0, nasal polyps expressed less GRα mRNA (1343;683–2263; P &lt; 0.05) and GR protein (41;29–54; P &lt; 0.05) than nasal mucosa (2474;1346–2933; 60;51–72, respectively). GRβ immunoreactivity was higher in nasal polyps (11;4–19; P &lt; 0.05) than in nasal mucosa (5;2–5). At w2, increased GRα mRNA (2010;1037–2732; P &lt; 0.01) and GR protein (56;27–71; P = 0.056) were found compared with w0 (1177;759–2058; 37;29–55, respectively). At w12, GRα mRNA and GR protein were similar to w0. GRβ expression was unaltered by treatment. Neither GRα nor GRβ correlated with nasal symptoms. GR immunoreactivity negatively correlated with eosinophils ( r = −0.478; P &lt; 0.001). Conclusions: GRα is downregulated in nasal polyps and upregulated by GC treatment. Neither GRα nor GRβ appear to determine the sensitivity to GCs in nasal polyposis.
Prestone Gallstone Disease — Is Therapy Safe?
Authors: Donald M. Small
Journal: New England Journal of Medicine (1971)

The pathogenesis of cholesterol gallstones has been divided into three stages.1 The first stage involves the formation of abnormal bile supersaturated with cholesterol, the second stage, the nucleation and precipitation of the excess cholesterol as cholesterol crystals, and the third the growth or conglomeration of these crystals into macroscopic stones capable of producing clinical gallstone disease.Recently, Sampliner et al.2 showed that the true age-specific prevalence of gallstones in Pima Indian men increased only gradually between the ages of 15 and 65 but in women jumped from less than 1 per cent at 18 to greater than 75 per . . .
Is physiologic sympathoadrenal catecholamine release exocytotic in humans?
Authors: M A Takiyyuddin, J H Cervenka, P A Sullivan, M R Pandian, R J Parmer, J A Barbosa, D T O'Connor
Journal: Circulation (1990)

In cultured cells and isolated perfused organs, catecholamines are coreleased with chromogranin A (CgA) from adrenal chromaffin cells and sympathetic neurons. The corelease suggests that exocytosis is the mechanism of catecholamine secretion. To investigate whether physiologic catecholamine secretion is exocytotic in humans, we measured plasma norepinephrine, epinephrine, and CgA responses to differentiated stimuli of sympathoadrenal discharge. The CgA radioimmunoassay antibody recognized authentic CgA in normal human adrenal chromaffin vesicles. Insulin-induced hypoglycemia and caffeine ingestion, in decreasing order of potency, selectively stimulated epinephrine release from the adrenal medulla. During hypoglycemia, plasma levels of epinephrine and CgA rose, and peak plasma levels of epinephrine and CgA correlated, suggesting that gradations in epinephrine release represented gradations in exocytosis. However, significant increments in plasma CgA were not observed after caffeine ingestion. Furthermore, the rise of CgA levels during hypoglycemia lagged 60 minutes behind those of epinephrine. A less-pronounced temporal dissociation between CgA and epinephrine release was also shown in isolated chromaffin cells in vitro. Selective adrenal vein catheterization suggested a barrier to CgA transport across the adrenal capillary wall. Short-term, high-intensity dynamic exercise, assumption of the upright posture, prolonged low-intensity dynamic exercise, and smoking, in decreasing order of potency, stimulated norepinephrine release from sympathetic nerve endings. Only the first sympathetic neuronal stimulus resulted in significant increments in plasma CgA, increments considerably less than those attained during adrenal medullary activation by insulin hypoglycemia. During high-intensity exercise, peak plasma norepinephrine and CgA levels correlated, suggesting that gradations in norepinephrine release represented gradations in exocytosis. The human adrenal medulla was a far more prominent tissue source of CgA than human sympathetic nerves--adrenal medullary homogenates contained 97-fold more CgA (micrograms/g) than sympathetic nerve homogenates. In conclusion, catecholamine secretion during selective stimulation of either sympathetic nerves or the adrenal medulla is, at least in part, exocytotic. Furthermore, stimulation of the former results in comparatively modest changes in plasma CgA compared with changes attained during stimulation of the latter. CgA appears to be transported by a route different from that of catecholamines from adrenal medullary chromaffin cells to the circulation in vivo.
PWE-045 Has Colonoscopy Become A Test To Find Incidentalomas?
Authors: J George, K Manoj
Journal: Gut (2014)

<h3>Introduction</h3> Demand for colonoscopy has risen over the years and many hospital trusts in the UK are struggling to cope with the demand. This causes many deserving patients waiting longer for the procedure resulting in increasing patient anxiety along with potential clinical risks of delayed diagnosis. We were interested in looking at the correlation between indications and findings at colonoscopy and to explore the possibility of refining the referral criteria to improve diagnostic yield and to reduce demand. We had a specific interest in rectal bleeding as a symptom. <h3>Methods</h3> Colonoscopy data for 2013 was sought giving us a total of 2021 porcedures which was retrospectively analysed by using the reporting software. This number was then filtered by indications for colonoscopy which included rectal bleeding with or without associated factors which left 378. We analysed all the pathology in particular that which was proximal to the splenic flexure and whether the findings showed a causal link to the indication. <h3>Results</h3> There were 52 (13.8%) procedures among these which found pathology proximal to splenic flexure and therefore beyond the extent of examination of flexible sigmoidoscopy that can directly be linked to the symptoms. Of these 52, 12 (3.2%) were attributed to the indication for the referral. 86.2% of colonic pathology could be found potentially using flexible sigmoidoscopy. Looking at the indications in detail in relation to significant pathology proximal to the splenic flexure only; diarrhoea (8/69) 11.6%, iron deficiency anaemia (1/30) 3.3% and bleeding only (2/89) 2.2% had significance. <h3>Conclusion</h3> Colonic pathology proximal to splenic flexure with a causal link to the indication is rare when investigating rectal bleeding unless associated with diarrhoea. Flexible sigmoidoscopy may be more appropriate in other instances. <h3>Disclosure of Interest</h3> None Declared.
Unstable Angina
Authors: Jose A. Silva, Alvaro Escobar, Tyrone J. Collins, Stephen R. Ramee, Christopher J. White
Journal: Circulation (1995)

Background Patients with diabetes mellitus have a higher prevalence of atherosclerotic heart disease and a higher incidence of myocardial infarction than the general population. Diabetic patients also have several hematologic, rheologic, and metabolic abnormalities not present in their nondiabetic counterparts that may predispose them to atherosclerotic plaque rupture and intraluminal thrombosis and consequently may lead to the formation of morphologically complex plaques and the development of acute coronary syndromes. Methods and Results Percutaneous coronary angioscopy was performed in 55 consecutive patients with unstable angina. We observed plaque color, texture, and the incidence of intracoronary thrombus associated with the culprit lesions of these patients. The population consisted of 17 (31%) diabetic and 38 (69%) nondiabetic patients. The presence of coronary risk factors was not significantly different between the two populations. Ulcerated plaque was found in 16 of 17 (94%) diabetic patients versus 23 of 38 (60%) nondiabetic patients ( P =.01). Intracoronary thrombi were seen in 16 of 17 (94%) diabetic patients versus 21 of 38 (55%) nondiabetic patients ( P =.004). Conclusions The results of the angioscopic examination show that diabetic patients with unstable angina have a higher incidence of plaque ulceration and intracoronary thrombus formation than nondiabetic patients. This increased frequency of complex lesion morphology is consistent with the disproportionately higher risk for development of acute coronary syndromes in these patients.