tbuckley/cabot-search huggingface dataset:
Quality of Life End Points in Cancer Clinical Trials: Review and Recommendations
Authors: C. M. Moinpour, P. Feigl, B. Metch, K. A. Hayden, F. L. Meyskens, J. Crowley
Journal: JNCI Journal of the National Cancer Institute (1989)

In this presentation, issues that influenced the developmentof policies for inclusion of quality of life end points in cer-tain Southwest Oncology Group clinical trials are reviewed. The key policies recommended by us and adopted by the Cancer Control Research Committee of the Southwest On-cology Group are as follows: (a) Begin assessment of qualityof life in specific types of phase III protocols, (b) Alwaysmeasure physical functioning, emotional functioning, symp-toms (general and protocol specific), and global quality oflife separately, (c) Include measures of social functioningand additional protocol-specific measures if resources per-mit, (d) Use patient-based questionnaires with psychometric properties that have been documented in published studies. In this review, we also recommend specific questionnaires. Our recommendations may prove useful for other cancerclinical trials groups and for multi-institution trials of treat-ment for chronic diseases. [J Natl Cancer Inst 81:485-495,1989]
Abstract 169: Activation of the Phosphoinositide 3-Kinase/Akt Pathway is Responsible for Cardioprotection Induced by Modulation of TLR2
Authors: Chuanfu Li, Fang Hua, Tuanzhu Ha, Jing Ma, Jim Kelley, I W Browder, Race L Kao, David L Williams
Journal: Circulation (2007)

Activation of the phosphoinositide-3 kinase/Akt (PI3K/Akt) signaling pathway protects cells from ischemic injury. We have reported that the immune modulator, glucan, rapidly induces cardioprotection. Dectin-1 is a specific receptor for glucan and Toll-like receptor 2 (TLR2) is required for transmitting the signal from Dectin-1 into cells. However, the role of modulation of TLR2 in cardioprotection has not been investigated. We hypothesized that modulation of TLR2 will induce cardioprotection through a PI3K/Akt-dependent mechanism. To evaluate our hypothesis, we examined the effect of modulation of TLR2 on myocardial ischemic injury. TLR2 knockout (KO) (n=8) and wild type mice (n=8) were treated with glucan (1 mg/25g) or peptidoglycan (PDG, 75 μg/25g), a specific TLR2 ligand, one hr before the hearts were subjected to ischemia (1 hr)/reperfusion (4 hrs). Untreated mice (n=8) were also subjected to I/R. Myocardial infarction was determined by TTC staining. Infarct size was significantly reduced in glucan (11.6 ± 2.38% vs 36.1 ± 3.48%, p&lt;0.01) and PDG (10.5 ± 3.03% vs 30.1 ± 7.59%, p&lt;0.01) treated mice vs untreated mice. The levels of phospho-Akt (0.80 ± 0.10 vs 0.45 ± 0.09) and phospho-GSK3β (0.66 ± 0.14 vs 0.33 ± 0.10) were significantly increased in the myocardium of glucan treated mice compared with untreated mice. However, both glucan and PDG-induced cardioprotection were completely abolished in TLR2 KO mice. To investigate whether PI3K/Akt signaling is involved in cardioprotection induced by modulation of TLR2, we administered glucan (1 mg/25g) or PDG (75 μg/25g) to kdAkt (kinase deficient Akt) transgenic mice (n=8) one hr before myocardial I/R. Both glucan and PDG-induced cardioprotection were completely abolished in kdAkt mice. The results suggest that modulation of TLR2, either directly or indirectly, will induce cardioprotection through a PI3K/Akt dependent mechanism and that there is a critical link between TLR2 and PI3K/Akt signaling during myocardial I/R.
Expression Levels of B Cell Surface Immunoglobulin Regulate Efficiency of Allelic Exclusion and Size of Autoreactive B-1 Cell Compartment
Authors: Norihiko Watanabe, Sazuku Nisitani, Koichi Ikuta, Misao Suzuki, Tsutomu Chiba, Tasuku Honjo
Journal: The Journal of Experimental Medicine (1999)

Surface-expressed immunoglobulin (Ig) has been shown to have a critical role in allelic exclusion of Ig heavy (H) and light (L) chains. Although various degrees of suppression of endogenous Ig expression are observed in Ig transgenic (Tg) mice, it was not clear whether this difference is due to different onsets of Tg expression or to different levels of Tg expression, which are obviously affected by integration sites of the transgene. In this study we generated antierythrocyte antibody Tg mice that carry tandem joined H and L chain transgenes (H+L) and confirmed that homozygosity of the transgene loci enhances the level of transgene expression as compared with heterozygosity. Suppression of endogenous H and L chain gene expression was stronger in homozygous than in heterozygous Tg mice. Similar results were obtained in control Tg mice carrying the H chain only. These results suggest that there is a threshold of the B cell receptor expression level that induces allelic exclusion. In addition, despite the same B cell receptor specificity, the size of Tg autoreactive B-1 cell compartment in the peritoneal cavity is larger in homozygous than in heterozygous mice, although the number of the Tg B-2 cell subset decreased in the spleen and bone marrow of homozygous Tg mice as compared with heterozygous Tg mice. By contrast, homozygosity of the H chain alone Tg line, which does not recognize self-antigens, did not increase the size of the peritoneal B-1 subset. These results suggest that the size of the B-1 cell subset in the Tg mice may depend on strength of signals through B cell receptors triggered by self-antigens.
Breast Tumor Localization Using Sestamibi
Authors: LEONARD R. COOVER, PAUL J. MALASPINA
Journal: Clinical Nuclear Medicine (2002)

Purpose The sensitivity of sestamibi scanning is 85% for breast lesions that measure ≥1 cm in diameter. This detection technique complements mammography and clinical examination and can benefit patients with very dense breast tissue. An innovation in nuclear imaging uses a lead marker for localization. Materials and Methods A 53-year-old woman underwent scintigraphy to clarify the indeterminate findings of a mammogram. Left breast biopsies 7 and 8 years earlier had yielded benign results. Mammography revealed a somewhat asymmetric stromal pattern, but the tissue appeared stable compared with results of previous studies. No focal abnormalities were identified. The original sestamibi breast scan revealed focally increased sestamibi uptake in the left breast. She was referred for another sestamibi scan because no radiographic or palpable abnormality correlated with the scintigraphic findings, and the lesion was believed to be nonlocalizable. Histologic examination revealed high-grade, poorly differentiated infiltrating ductal adenocarcinoma. Results After intravenous administration of Tc-99m sestamibi, the site of the lesion was identified using a lead marker, the persistence scope, and localization needles. This facilitated surgical removal. Conclusion Using a lead marker allows placement of localization wires to guide surgical breast biopsy in patients whose lesions are visible by scintigraphy but not via mammography or palpation.
Reversal of angiotensin II effect on the cyclic adenosine 3',5' monophosphate response to isoprenaline in cardiac hypertrophy
Authors: P. S Sunga, S. W Rabkin
Journal: Cardiovascular Research (1991)

The aim was to examine the effect of angiotensin II on the response of hypertrophic cardiac myocytes to the beta adrenergic receptor agonist isoprenaline.Viable ventricular myocytes were isolated from hypertrophic hearts of Dahl S rats and hearts of Dahl R rats. Myocytes were stimulated with isoprenaline. cAMP content was measured by competitive binding radioimmunoassay.Hypertrophic Dahl S myocytes had smaller cAMP response to isoprenaline than Dahl R myocytes (p less than 0.05). Angiotensin II inhibited cAMP stimulation in Dahl R myocytes. In contrast, angiotensin II increased cAMP accumulation in hypertrophic Dahl S myocytes compared to the effect of isoprenaline alone (p less than 0.05). Enhancement of isoprenaline stimulation of cAMP accumulation by angiotensin II was positively related to the degree of cardiac hypertrophy. Angiotensin II treatment in the absence of isoprenaline had no effect on cAMP levels.The reversal of the normal inhibitory action of angiotensin II is evidence of a unique alteration in the signal transduction of beta receptor stimulation and is of potential importance in defining the role of angiotensin II in cardiac hypertrophy.
Haemoptysis as the sole presenting symptom of dissection of the aorta.
Authors: A S Guidetti, A Pik, A Peer, S Shikiar, D Ben-Yaakov
Journal: Thorax (1989)

Abstract A 75 year old man who had had haemoptysis for 24 hours was found to have his left lower lobe compressed by a dissection of the aorta, which was otherwise symptomless.
Large scale isolation, growth, and function of porcine neonatal islet cells.
Authors: G S Korbutt, J F Elliott, Z Ao, D K Smith, G L Warnock, R V Rajotte
Journal: Journal of Clinical Investigation (1996)

Based upon existing methods of isolating fetal porcine islet tissue, a simple, reliable procedure was developed for the preparation of porcine neonatal islet cell aggregates with a reproducible and defined cellular composition. After 9 d of in vitro culture, tissue from one neonatal pig pancreas yielded approximately 50,000 islet cell aggregates, consisting of primarily epithelial cells (57%) and pancreatic endocrine cells (35%). During the culture period, the total beta cell mass decreased initially, but subsequently increased 1.5-fold between days 3 and 9. Transplantation of grafts consisting of 3 x 10(5) beta cells (1,000 aggregated) under the kidney capsule of alloxan-diabetic nude mice corrected hyperglycemia in 75% (10/13) of the animals, whereas, 100% (20/20) of recipients implanted with 6 x 10(5) beta cells (2,000 aggregates) achieved euglycemia within 8 wk posttransplantation. Nephrectomy of the graft bearing kidney at 14 wk posttransplantation resulted in hyperglycemia in all recipients, and examination of the grafts revealed the presence of numerous well-granulated insulin- and glucagon-containing cells. The cellular insulin content of these grafts was 20 to 30-fold higher than at the time of transplantation. These results indicate that the neonatal porcine pancrease can be used as a source of large numbers of viable islet cells, which have the potential for growth both in vitro and in vivo, and exhibit the metabolic capacity to correct diabetes in nude mice.
Results of Elective Aortocoronary Saphenous Vein Graft Surgery in a Community Hospital
Authors: ALAN D. FORKER, HERBERT E. REESE, WALT F. WEAVER, CHARLES S. WILSON, ROBERT BUCHMAN, STEPHEN W. CARVETH
Journal: Circulation (1974)

In a community hospital setting, without academic affiliation or house staff coverage, 145 patients had elective saphenous vein graft surgery between January 1970 and January 1973. Patients with good left ventricular function, with or without associated procedures, had an operative mortality of 2.4%. The surgical mortality of patients who had associated procedures was 9.5%. The overall operative mortality was 6.2% with an immediate postoperative myocardial infarction rate of 17%. Results in 38 patients with pre-infarction angina were no different from the group as a whole. The risk of surgery is best categorized by a combination of angiographic severity of coronary artery disease plus severity of left ventricular dysfunction estimated by left ventriculogram.
Lymphocyte dysfunction in congenital hypoplastic anemia.
Authors: J L Finlay, N T Shahidi, S Horowitz, W Borcherding, R Hong
Journal: Journal of Clinical Investigation (1982)

Congenital hypoplastic anemia (Diamond-Blackfan syndrome) is thought to involve the erythropoietic cell line alone. In this study, the evaluation of lymphocyte function in five patients with this syndrome revealed a number of abnormalities. Peripheral blood T lymphocyte percentages as assessed by monoclonal antibodies were decreased in three patients. T-helper/T-suppressor cell (OKT4:OKT8) ratios were almost unity in four of the five patients. We usually find a ratio of 2:1 in normal populations. Studies of lymphocyte-mediated suppression of lymphoproliferation demonstrated an inability to generate concanavalin A-induced suppressor cells in the same four patients and impaired prostaglandin-mediated suppression in two patients. Co-culture studies revealed a T lymphocyte-mediated suppression of erythropoiesis in a single patient, who also showed suppression of the mixed lymphocyte reaction. The four remaining patients showed no excessive suppressor effects either upon erythropoiesis or lymphoproliferation. These studies demonstrate that in congenital hypoplastic anemia, the cellular defect is not restricted to the erythroid progenitor cells, but extends to the lymphocytes.
The sudden death of a child
Authors: Richard Smith
Journal: BMJ (2004)

“The sudden unexpected death of an infant or child is one of the worst events to happen to any family.” This is the opening line of a review by authors from Bristol of how best to investigate such deaths and care for bereaved families (p 331). Such a death presents great difficulties to doctors, social workers, and the police, and the difficulties have been increased by the publicity surrounding wrongful conviction of parents of murder. Every primary care trust is supposed to have a “designated doctor” to serve on child protection teams, but a third of these posts are unfilled (p …
Insulin Binding and Degradation by Luminal and Basolateral Tubular Membranes from Rabbit Kidney
Authors: Zvi Talor, Dimitrios S. Emmanouel, Adrian I. Katz
Journal: Journal of Clinical Investigation (1982)

Insulin influences certain metabolic and transport renal functions and is avidly degraded by the kidney, but the relative contribution of the luminal and basolateral tubular membranes to these events remains controversial. We studied 125I-insulin degradation [TCA and immunoprecipitation (IP) methods] and the specific binding of the hormone by purified luminal (L) and basolateral (BL) tubular membranes. These were prepared from rabbit kidney cortical homogenates by differential and gradient centrifugation and ionic precipitation steps in sequence, which resulted in enrichment vs. homogenate of marker enzymes' activities (sodium-potassium-activated adenosine triphosphatase for BL and maltase for L) of 8- and 12-fold, respectively. Both fractions degraded insulin avidly and bound the hormone specifically without saturation even at pharmacologic concentrations (10 μM). At physiologic insulin concentrations (0.157 nM) BL membranes degraded substantial amounts of insulin (44.2±2.6 and 40.7±2.2 pg/mg protein per min by the TCA and IP methods, respectively), even though at lesser rates (P < 0.001) than the luminal fraction (67.2±2.3 and 75±6.2 pg/mg protein per min, respectively); the rate of insulin catabolism by BL membranes was significantly higher (P < 0.001) than that which could be attributed to their contamination by luminal components [12.2±1.9 pg/mg per min (TCA method), or 13.7±1.9 pg/mg per min (IP method)]. Competition experiments suggested that insulin-degrading activity in both fractions includes both specific and nonspecific components. In contrast to degradation, insulin binding by both membranes was highly specific for native insulin and was severalfold higher in BL than L membranes [17.5±1.3 vs. 4.5±0.4 fmol/mg protein (P < 0.001) at physiologic insulin concentrations]. Despite the marked difference in the binding capacity for insulin by the two membranes, the patterns of labeled insulin displacement by increasing amounts of unlabeled hormone were superimposable (50% displacement required ∼3 nM), suggesting that their receptors' affinity for insulin was similar. These observations provide direct evidence that interaction of insulin with the kidney involves binding and degradation of the hormone at the peritubular cell membrane.
TOTAL ANOMALOUS PULMONARY VENOUS RETURN–IMPACT OF PREOPERATIVE OBSTRUCTION AND EARLY ELECTIVE REPAIR ON OUTCOME AND NEED FOR PROLONGED MECHANICAL VENTILATORY SUPPORT
Authors: Peter C. Frommelt, David Sheridan, Michele A. Frommelt, S. Bert Litwin, James S. Tweddell
Journal: Journal of the American College of Cardiology (2010)
Monoclonal endothelial cell proliferation is present in primary but not secondary pulmonary hypertension.
Authors: S D Lee, K R Shroyer, N E Markham, C D Cool, N F Voelkel, R M Tuder
Journal: Journal of Clinical Investigation (1998)

The etiology and pathogenesis of the vascular lesions characterizing primary pulmonary hypertension (PPH), an often fatal pulmonary vascular disease, are largely unknown. Plexiform lesions composed of proliferating endothelial cells occur in between 20 and 80% of the cases of this irreversible pulmonary vascular disease. Recently, technology to assess monoclonality has allowed the distinction between cellular proliferation present in neoplasms from that in reactive nonneoplastic tissue. To determine whether the endothelial cell proliferation in plexiform lesions in PPH is monoclonal or polyclonal, we assessed the methylation pattern of the human androgen receptor gene by PCR (HUMARA) in proliferated endothelial cells in plexiform lesions from female PPH patients (n = 4) compared with secondary pulmonary hypertension (PH) patients (n = 4). In PPH, 17 of 22 lesions (77%) were monoclonal. However, in secondary PH, all 19 lesions examined were polyclonal. Smooth muscle cell hyperplasia in pulmonary vessels (n = 11) in PPH and secondary PH was polyclonal in all but one of the examined vessels. The monoclonal expansion of endothelial cells provides the first marker that allows the distinction between primary and secondary PH. Our data of a frequent monoclonal endothelial cell proliferation in PPH suggests that a somatic genetic alteration similar to that present in neoplastic processes may be responsible for the pathogenesis of PPH.
Measurement of Blood Volume with a New Apparatus
Authors: John A. Williams, Jacob Fine
Journal: New England Journal of Medicine (1961)

THE prevailing methods for measuring blood volume have failed to find widespread clinical application. This is because the technics are cumbersome, and because accurate, repeated measurements cannot be made with sufficient frequency to be of value in the management of persisting derangements of blood volume. The need for an accurate, freely repetitive and, if possible, semiautomatic method is obvious. Appraisals of blood volume during major surgical procedures, after extensive burns and during therapy for cardiac decompensation, acute renal failure and other major disorders as a rule are based upon data that at best allow only rough approximations. These are often . . .
Evaluation of Carcinoma of the Uterine Cervix Before Radiotherapy
Authors: Jay S. Cooper
Journal: JAMA (1979)

In 1974 the Patterns of Care Study began a prospective nationwide survey of radiotherapeutic cancer care in the United States. Cancer of the uterine cervix was one of the diseases surveyed. Pretreatment evaluation data were collected from 170 randomly chosen radiation therapy facilities. The frequency of use of tests in workup varied substantially according, for example, to the severity of disease and the availability of tests. For carcinoma of the uterine cervix, we found that the following tests were used routinely: physical examination, including taking a history; complete blood cell count; serum chemistry analysis; chest roentgenogram; and intravenous pyelogram. Frequent but not routine tests included dilation and curettage and evaluation of the involvement of the bladder and rectum. Other tests were used infrequently. (<i>JAMA</i>242:1996-1997, 1979)
Obstetric outcome in homeless women.
Authors: C M Paterson, P Roderick
Journal: BMJ (1990)

OBJECTIVE--To characterise the pregnant homeless population booking and delivering at St Mary9s Hospital, London, and ascertain whether their obstetric outcome was adversely affected by their homeless condition. DESIGN--Retrospective comparison of demographic characteristics of 185 homeless women booking for delivery with those of housed women booking in the same period and with the population of North West Thames region; comparison of obstetric performance of homeless women with subgroup of the housed population (group matched for age, parity, and ethnic origin). SETTING--Consultant obstetric unit, St Mary9s Hospital, London. SUBJECTS--All women booking between April 1987 and March 1988 who subsequently had a registrable birth. MAIN RESULTS--185 (8%) Of the 2308 women studied were homeless. Compared with the housed population, they had a larger proportion of young women, women of high parity, and Indo-Pakistani women and a smaller proportion of primiparas. Homeless women booked later and had had more previous obstetric problems than housed women. Pregnancy outcome (assessed by birth weight and prematurity rates) was worse than that of both women housed locally and the regional population. Antenatal attendance, complications, intrapartum performance, and perinatal outcome of homeless women did not differ from those in the control group. CONCLUSIONS--This study has been unable to show any significant differences in the outcome of pregnancy in homeless women that can be directly attributed to living in bed and breakfast accommodation, but these women have sociodemographic characteristics and obstetric risk factors that contribute to a poorer outcome in pregnancy than for the general population.
Groin Hernia with Inguinoscrotal Hemiation of the Urinary Bladder
Authors: JOSEPH E. BERNSTEIN, KAREN MEYER
Journal: Clinical Nuclear Medicine (1987)

Inguinal herniation of the urinary bladder is not uncommon. However, bladder herniation extending into the scrotum has been previously described as unusual, if not rare. Presented here is a case of recurrent inguinoscrotal hernia containing urinary bladder producing a “double sac” in the scrotum identified on a routine bone scan.
THE ASSOCIATION BETWEEN GALL-BLADDER LESIONS AND HEPATITIS IN THE HUMAN SUBJECT
Authors: E. R. Flint
Journal: BMJ (1930)

lhave beeni written by others corroborating hlis coniteiitioii.T'hle present investigatioll was begnLn about three years ago to (letermine, if possible, tlhe extent the hepatitis, the type, and the route by which thie liver beconiesMys method has been muclh the same as that used-bv others- namnely, to obtain segments of liver at operation and: subject them to microscopic and bacteriological scrui-tiny- but I think my investigation has this advantage oktie ayii other within my knowledge, that sectionshlave taken from both lobes of the liver, in the riglt lobe at a distance of at least1 inch the gall-bladderl fossa, so that the whole liver should ,not judgedl the condition of that part of it in the imiiiediate neighbour- lhood of an inflamed gall-bladder.The method employed to obtainl thle liver sectionis follows: A triangular piece w-ith a base aboout half anl inch and sides rather longer was taken edge of the lright lobe under strictly precautions antid placed in a sterile tuibe; the sides of the gal) were brought together by one or more miattress sutuires fine cattgut and tied with juist slfficient tenisionl bleed-.inig.A similar proceeding was conducted side.In miost of the cases the gall-bladder wwas senit examinatiol, care being taken to prevent bile contact with the exterior.-Inmany cases the separately removed.A fresh set of instrumiiiienits was ised for each prroceeding, each specimiein being separ ate sterile tube; all were sent immiiecediately the labor atory for culture and later for Iiistolorical exaniiia- tion Thiere was never any difficulty in arriesting liaciiior- rhage, and the procedure did not seem disturl b tIme pr-ogress of the patients in the least.Th'here are 50 cases in this series, buit for-various rlea-sonis it has been possible to get a complete histological reeport of only 34.Of the 34 eases the gall-bladder xvas lpathio- logiical in 20 and normal in 14. h hese cases regardled as controls, and were operated oni i n n g conditions: 1 for subacute, appendicitis, chironic appeiidiciti.s, 2 for visceroptosis, 4 f'or duodenal ulcer, 3 for jjejunal ulcer, for gastric ulcce, for a coidlit ion miegeding laparot-oniiv T