tbuckley/cabot-search huggingface dataset:
Mobile patients in an inner London practice.
Authors: F Hanson, M Wilks
Journal: BMJ (1984)

In an area with the most highly mobile population in Britain 10% of the consultations in one practice were with temporary residents and a further 10% with newly registered patients. We analysed data gathered in 1980 about these two groups and about established patients that included demographic characteristics, the diagnoses made, and the actions taken by the doctors. Temporary residents caused a considerable amount of administration, but they were relatively straightforward to deal with medically and the practice received compensation for the work; with new patients problems were more time consuming, both clinically and administratively, and there was no financial compensation. A practice with a high turnover of its registered patients is at a considerable disadvantage compared with one in a more settled area.
Enhancement of Regression of Cervical Intraepithelial Neoplasia II (Moderate Dysplasia) With Topically Applied All- trans -Retinoic Acid: a Randomized Trial
Authors: Frank L. Meyskens, Earl Surwit, Thomas E. Moon, Joel M. Childers, John R. Davis, Robert T. Dorr, Cynthia S. Johnson, David S. Alberts
Journal: JNCI Journal of the National Cancer Institute (1994)

Retinoids enhance differentiation of most epithelial tissues. Epidemiologic studies have shown an inverse relationship between dietary intake or serum levels of vitamin A and the development of cervical dysplasia and/or cervical cancer. Pilot and phase I investigations demonstrated the feasibility of the local delivery of all-trans-retinoic acid (RA) to the cervix using a collagen sponge insert and cervical cap. A phase II trial produced a clinical complete response rate of 50%.This randomized phase III trial was designed to determine whether topically applied RA reversed moderate cervical intraepithelial neoplasia (CIN) II or severe CIN.Analyses were based on 301 women with CIN (moderate dysplasia, 151 women; severe dysplasia, 150 women), evaluated by serial colposcopy, Papanicolaou cytology, and cervical biopsy. Cervical caps with sponges containing either 1.0 mL of 0.372% beta-trans-RA or a placebo were inserted daily for 4 days when women entered the trial, and for 2 days at months 3 and 6. Patients receiving treatment and those receiving placebo were similar with respect to age, ethnicity, birth-control methods, histologic features of the endocervical biopsy specimen and koilocytotic atypia, and percentage of involvement of the cervix at study. Treatment effects were compared using Fisher's exact test and logistic regression methods. Side effects were recorded, and differences were compared using Fisher's exact test.RA increased the complete histologic regression rate of CIN II from 27% in the placebo group to 43% in the retinoic acid treatment group (P = .041). No treatment difference between the two arms was evident in the severe dysplasia group. More vaginal and vulvar side effects were seen in the patients receiving RA, but these effects were mild and reversible.A short course of locally applied RA can reverse CIN II, but not more advanced dysplasia, with acceptable local side effects.A derivative of vitamin A can reverse or suppress an epithelial preneoplasia, lending further support to the notion that chemoprevention of human cancer is feasible.
Artificial Antigen-Presenting Cells Transduced with Telomerase Efficiently Expand Epitope-Specific, Human Leukocyte Antigen–Restricted Cytotoxic T Cells
Authors: Jakob Dupont, Jean-Baptiste Latouche, Chia Ma, Michel Sadelain
Journal: Cancer Research (2005)

Abstract Human telomerase reverse transcriptase (hTERT) is overexpressed in most human tumors, making it a potential target for cancer immunotherapy. hTERT-derived CTL epitopes have been identified previously, including p865 (RLVDDFLLV) and p540 (ILAKFLHWL), which are restricted by the human leukocyte antigen (HLA) class I A*0201 allele. However, it remains a major challenge to efficiently and consistently expand hTERT-specific CTLs from donor peripheral blood T lymphocytes. To bypass the need for generating conventional antigen-presenting cells (APC) on an autologous basis, we investigated the potential ability of fibroblast-derived artificial APCs (AAPC) to activate and expand HLA-A*0201-restricted CTLs. We show here that AAPCs stably expressing HLA-A*0201, human β2-microglobulin, B7.1, intercellular adhesion molecule-1, and LFA-3, together with either p540 and p865 minigenes or the full-length hTERT, effectively stimulate tumoricidal, hTERT-specific CTLs. hTERT-expressing AAPCs stimulated both p540 and p865 CTLs as shown by peptide-specific cytolysis and tetramer staining, indicating that hTERT is processed by the AAPCs and that the two peptides are presented as codominant epitopes. The level of cytotoxic activity against a panel of tumors comprising hematologic and epithelial malignancies varied, correlating overall with the level of HLA-A2 and hTERT expression by the target cell. Starting from 100 mL blood, ∼100 million hTERT-specific CTLs could be generated over the course of five sequential stimulations, representing an expansion of ∼1 × 105. Our data show that AAPCs process hTERT antigen and efficiently stimulate hTERT-specific CTLs from human peripheral blood T lymphocytes and suggest that sufficient expansion could be achieved to be clinically useful for adoptive cell therapy.
TECHNIQUE OF SURGERY OF THE UTERUS AND ADNEXAE PER VAGINAM.
Authors: WILLIAM H. WATHEN
Journal: JAMA (1899)

When I gave the title of my paper I supposed that it would be read before this Section separately from other papers, but I am associated in the program with several other persons in a "symposium" intended to present all questions of practical significance in relation to the advantages of the infrapubic and the suprapublic methods in treating diseases of the uterus and its adnexæ. The popular belief that there is any antagonism between the scientific celiotomist and the vaginal hysterectomist is not justified by facts, for there are many cases that may be successfully treated by either method, and the preference that one surgeon may have for the vaginal route and another for the abdominal route, is often largely the result of experience. However, we may refer to some of the arguments against vaginal hysterectomy and the treatment of the uterine adnexæ, and show that there is no justification
CIRCULATING ADIPONECTIN AS A PREDICTOR OF VASCULAR SUPEROXIDE GENERATION AND NITRIC OXIDE BIOAVAILABILITY IN HUMAN ARTERIES AND VEINS
Authors: Charalambos A. Antoniades, Cheerag Shirodaria, Paul Leeson, Constantinos Bakogiannis, Michael Dimosthenous, Alexis S. Antonopoulos, Dimitris Tousoulis, Nikolaos Sfyras, Christodoulos Stefanadis, Keith M. Channon
Journal: Journal of the American College of Cardiology (2010)
Microanatomy of the human liver?exploring the hidden interfaces
Authors: Romil Saxena, Neil D. Theise, James M. Crawford
Journal: Hepatology (1999)

The functional unit of an organ may be defined as the smallest, structurally distinct, ''self-sufficient'' unit that can independently subserve all known functions of that organ.The nephron is exemplary of such a concept, for it is both a well-defined functional and structural unit.A similar hepatic unit that can reconcile the dual vascular supply and the dual outflow tracts (vascular and biliary) with all known liver functions has not been identified.This reflects the functional complexity of the liver and the sophistication of its microarchitectural interfaces.This review addresses the recent resurgence of investigation into the microanatomy of the liver, emphasizes studies in humans, and highlights the ''grey'' zones in our existing knowledge.
Abstract A4: Guanylate binding protein-1 promotes glioma cell invasion through induction of MMP1 expression
Authors: Ming Li, Frank B. Furnari, Webster K. Cavenee
Journal: Cancer Research (2009)

Abstract Glioma is the most common and deadly human brain tumor. Epidermal growth factor receptor (EGFR) amplification or constitutively active mutation (EGFRVIII) is one of the most frequent genetic lesions in gliomas. To identify target genes regulated by EGFR signaling, we performed expression array analysis and found that human guanylate binding protein-1 (GBP-1), a large GTPase that is induced by inflammatory cytokines, is one of the predominant genes induced by EGFR/EGF or EGFR VIII kinase activity. Our results demonstrate that EGF/EGFR signaling could dramatically induce Gbp-1 expression at both the mRNA and protein level through the p38 kinase signaling cascade that is distinct from Stat1 signaling used by interferon gamma. Interestingly, we show that Gbp-1 is required for EGFR-mediated matrix metallopeptidase-1 (MMP1) expression, and plays a role in glioma cell invasion in vitro. Overexpression of Gbp-1 induced MMP1 expression in glioma cells, which was independent of Gbp-1 GTPase activity. In contrast, siRNA-mediated knockdown of Gbp-1 inhibited MMP1 expression and in turn blocked cell invasion as well. Consistently, we found that GBP-1 is overexpressed and positively correlated with EGFR/EGFRVIII and MMP1 expression in human glioma clinical samples and glioma cell lines. Therefore, this study suggests that Gbp-1 may be a novel therapeutic target in glioma. Citation Information: Cancer Res 2009;69(23 Suppl):A4.
Allogeneic hematopoietic stem cell transplantation versus hypomethylating agents in patients with myelodysplastic syndrome: A retrospective case–control study
Authors: Elias Jabbour, Michael S. Mathisen, Guillermo Garcia‐Manero, Richard Champlin, Uday Popat, Issa Khouri, Sergio Giralt, Tapan Kadia, Julianne Chen, Sherry Pierce, Ebru Koca, Naval Daver, Maria Tanaka, Gabriela Rondon, Betul Oran, Simrit Parmar, Hagop Kantarjian, Marcos de Lima
Journal: American Journal of Hematology (2012)

Allogeneic stem cell transplantation (allo-SCT) is the only potentially curative treatment for myelodysplastic syndrome (MDS). Recently, hypomethylating agents (HMAs) have been shown to improve survival in patients with high-risk MDS. We conducted a retrospective case-control study to compare survival with these treatment modalities in patients with untreated MDS. Controls were identified using a departmental database and transplant patients were matched in at least three of the following five criteria: year of diagnosis, age, blast percentage, International Prognostic Scoring System cytogenetic risk, and time from diagnosis to treatment. Median overall survival (OS) was 26 and 25 months for, respectively, allo-SCT [(n = 53); range, 2-210 months] and HMA [(n = 40); range, 2-98 months] (P = 0.89). Four-year survival rates were 24 and 23% for allo-SCT patients and the nontransplant cohort, respectively. Patients undergoing allo-SCT after 2000 had longer median OS compared with those transplanted before 2000 (41 versus 7 months, P=0.001). These results would suggest that prospective studies are needed to delineate the timing and efficacy of allo-SCT in the HMA era.
Infant and Toddler Type 1 Diabetes
Authors: Silvana Salardi, Massimo Porta, Giulio Maltoni, Flavia Rubbi, Silvia Rovere, Franco Cerutti, Dario Iafusco, Stefano Tumini, Vittoria Cauvin
Journal: Diabetes Care (2012)

To compare the effect of the prepubertal duration of diabetes on the occurrence of complications in two groups of patients after the same number of years of the disease.This multicenter study enrolled 105 patients aged 16-40.3 years; 53 were prepubertal at diagnosis (aged 0-3) and 52 were pubertal (Tanner stage) and aged 9-14.9. The mean duration of disease was 19.8 and 19.5 years for prepubertal and pubertal patients, respectively. In all patients, retinal photographs were taken and centrally graded. Urinary albumin excretion (UAE; 86 case subjects), blood pressure (BP; 89 case subjects), and lifetime HbA(1c) (72 case subjects) were also evaluated.The prevalence of diabetic retinopathy (DR) was higher in pubertal than in prepubertal patients, both for any grade DR (71 vs. 40%, P = 0.002) and for mild or more severe DR (P = 0.005). The prevalence of abnormal UAE was not different in the two groups. Hypertension was found only in three patients, all pubertal at diagnosis. In the small group with moderate-to-severe DR, lifetime HbA(1c) levels, as percentages above the upper normal reference value, were higher (P < 0.01) in prepubertal than in pubertal patients.If diabetes is diagnosed in infants or toddlers and the prepubertal duration of diabetes is very long, the patients seem to be protected against DR. This protection disappears if lifetime metabolic control is bad. Instead, when onset is at puberty, the DR risk is higher and less dependent on metabolic control and may be influenced by age-related factors, such as BP.
Pheochromocytoma of the Urinary Bladder
Authors: Franz H. Messerli
Journal: JAMA (1982)

PHEOCHROMOCYTOMA is an uncommon lesion of the urinary bladder, accounting for less than 0.06% of all vesical tumors.<sup>1</sup>However, its classic symptoms—sharp headaches, hypertension, and fainting immediately after voiding—often present a diagnostic puzzle, especially since the entity is not widely known.<sup>2,3</sup>The present report describes a patient with both normal resting BP and 24-hour urinary catecholamine levels, in whom systemic hemodynamics and plasma catecholamine levels were measured before and after voiding. <h3>Report of a Case</h3> A 38-year-old man was admitted to the hospital for evaluation of piercing headaches, which lasted a few minutes and occurred immediately after emptying the bladder. This symptom had been present for about a year. The patient turned pallid and sweated profusely during these episodes and felt as though he was going to pass out. To avoid the symptoms, the patient preferred to empty his bladder only partially. Medical history was not significant, but
Long-term patency of the ductus arteriosus after balloon dilatation: an experimental study.
Authors: G Lund, J Rysavy, A Cragg, E Salomonowitz, Z Vlodaver, W C Zuniga, K Amplatz
Journal: Circulation (1984)

Balloon dilatation of the ductus arteriosus was carried out in vivo in eight piglets that were 12 to 16 days old. The ductus was functionally closed in all animals before dilatation. Long-term patency for periods of up to 6 months after the procedure was demonstrated in six animals by angiography, Doppler ultrasound examination, and at autopsy. The presence of hemodynamically significant shunts was indicated by clinical development of heart failure, pulmonary infections, and left ventricular hypertrophy. These results confirm the value of this laboratory preparation to create left-to-right shunts at the ductus level.
Freud: Living and Dying
Authors: Nathan G. Hale
Journal: JAMA (1972)

The late Max Schur, Freud's internist from 1928 to 1939 and a psychoanalyst, has written both an informative medical memoir and a pretentious, bumbling psychobiography of Freud. Perhaps one fifth of the text adds to Freud's medical history. A cardiac episode of the 1890s, dismissed by Ernest Jones as anxiety neurosis, is diagnosed as a minor thrombosis. An account of Freud's first surgery for cancer of the maxilla emphasizes Freud's initial reluctance to seek treatment, although he himself had diagnosed an epithelioma. Schur includes extensive notes by Freud's second surgeon, Hans Pichler, who followed the case almost to the end. Despite repeated warnings, as well as surgery for a new cancer and for recurring leukoplakias, Freud refused to give up cigars. He also refused sedatives and narcotics, despite increasing pain. At the last, Schur induced a terminal coma with two injections of two centigrams of morphine, at twelve-hour intervals. In
Determination of Benzo[a]pyrene Diol Epoxide--DNA Adducts in White Blood Cell DNA From Coke-Oven Workers: The Impact of Smoking
Authors: F. J. van Schooten, F. E. van Leeuwen, M. J. X. Hillebrand, M. E. de Rijke, A. A. M. Hart, H. G. van Veen, S. Oosterink, E. Kriek
Journal: JNCI Journal of the National Cancer Institute (1990)

We have undertaken a study among coke-oven workers to test the feasibility of an enzyme-linked immunosorbent assay with anti-trans-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahy-dro-benzo[ a ]pyrene-DNA antibodies for monitoring occupational exposure to poly cyclic aromatic hydrocarbons (PAH). Coke-oven workers are occupationally exposed to relatively high levels of PAH and are at increased risk for lung cancer. Three blood samples were collected from each of the 56 coke-oven workers exposed to PAH and 44 unexposed workers employed in a steel-rolling factory of the same plant. In addition, PAH levels were measured in ambient air by personal sampling, and the excretion of 1-hydroxypyrene in urine was also measured on 3 consecutive working days. All participants were interviewed regarding working conditions, personal hygiene, and smoking habits. The results showed that the coke-oven workers were exposed to substantial concentrations of atmospheric PAH [1–186 μg/m 3 ), including benzo[ a ]pyrene (0.1–7.8 μg/m 3 ) and pyrene (0.6–23.6 μg/m 3 ). Both benzo[ a ]pyrene and pyrene were shown to be representative for the whole group of PAH. Forty-seven percent of the coke-oven workers had detectable levels of PAH–DNA adducts in their white blood cells, compared with 30% of the controls. In both groups, smokers had significantly higher levels of PAH-DNA adducts than did nonsmokers. At one site, we found the correlation positive between DNA adducts and the duration of exposure ( r = .47, p = .005). Generally, the correlation was not significant between PAH–DNA adducts in blood and the concentration of PAH in the air and 1-hydroxypyrene in urine. [J Natl Cancer Inst 82: 927–933, 1990]
Ascorbic Acid and Vitamin B12 Deficiency
Authors: John D. Hines
Journal: JAMA (1975)

<h3>To the Editor.—</h3> Drs Herbert and Jacob made the observation that ascorbic acid (vitamin C) in quantities in excess of 0.5 gm will destroy between 50% and 95% of vitamin B<sub>12</sub>content in food (230:241, 1974). During the past six months, we have been able to assess the vitamin B<sub>12</sub>concentrations in serum as well as in the peripheral blood smears in 90 subjects at Cleveland Metropolitan General Hospital, all taking more than 500 mg of ascorbic acid daily. These subjects responded to publicity concerning the possible danger of megadose ascorbic acid ingestion. Three subjects, aged 50 to 60 years, had been taking a minimum of 1,000 mg of ascorbic acid with each meal for more than three years. These three subjects did show subnormal serum vitamin B<sub>12</sub>concentrations ranging from 65 to 100 pg/ml. Two of the three had hypersegmented neutrophils and occasional ovalomacrocytes, although none
Detection of Lung Cancer-Reply
Authors: Robert S. Fontana
Journal: JAMA (1981)

<h3>In Reply.—</h3> The editorial cited by Dr Eddy was provoked by the February 1980 ACS report on "The Cancer-Related Health Checkup."<sup>1</sup>That report, prepared for the ACS by Dr Eddy, emphasized that its recommendations pertained only to early detection of cancer on an individual basis and not to "mass screening programs at public expense."<sup>1</sup> Our editorial comment was likewise confined to individual case-finding initiated by patients.<sup>2</sup>We are on record as being opposed to noncontrolled large-scale screening programs initiated by any organization. Our concern is that Dr Eddy seems to use "screening" and "early detection" interchangeably. In his letter he writes: the ACS is aware that x-ray films can detect cancers in asymptomatic persons and that the cancers often appear to be detected in early stages. The Society is also aware, however, of the many biases that can cause an interpretation of staging information and case-survival rates
An Unfortunate Precedent
Authors: H. H. Bashford
Journal: BMJ (1949)

Natural and synthetic lipid A as well as natural and synthetic oligosaccharide partial structures of LPS were examined in dose-response experiments to define the minimal structure necessary for IL-1 induction and release in cultures of human mononuclear cells. Wild type LPS (S. abortus equi) and rough mutant LPS was active in minimal-doses of 1 to 100 pg/ml, whereas synthetic heptaacyl and hexaacyl lipid A (Salmonella minnesota and Escherichia coli lipid A, respectively) induced IL-1 in minimal-doses of 100 to 1,000 pg/ml and 10 to 1,000 pg/ml, respectively. Nanogram amounts (0.1 to 10 ng/ml) of synthetic monodephospho partial structures of E. coli lipid A were necessary for IL-1 induction. Synthetic pentaacyl partial structures induced IL-1 very weakly. Synthetic tetraacyl and bisacyl partial structures lacking non-hydroxylated fatty acids were not active. Compared to LPS million-fold higher doses of natural and synthetic 3-deoxy-D-manno-octulosonic acid containing core oligosaccharides were necessary for IL-1 induction. Dose-response investigations with LPS and natural or synthetic partial structures established the following hierarchy in IL-1 induction-capacity: LPS greater than lipid A much greater than lipid A partial structures greater than core oligosaccharides greater than oligoacyl lipid A. Lipid A was shown here to be the portion of LPS mainly responsible for induction of IL-1 activity. The high potency of lipid A in inducing IL-1 release and the failure of the precursor Ia of lipid A to induce IL-1 production and release was also observed measuring intracellular IL-1 activity after freeze-thawing the cells. Levels of IL-1 beta mRNA in extracts of mononuclear cells correlated with biologic activity. In co-incubation experiments, precursor Ia of lipid A produced dose-dependent inhibition of production and release of IL-1 activity induced by lipid A or LPS, but not by Staphylococcus epidermidis or PHA. Incubation of cells with precursor Ia for 1h, followed by a medium change and further incubation of stimulus without precursor Ia of lipid A also resulted in inhibition. We conclude that lipid A is the main portion of LPS responsible for induction of IL-1, and that specific activation- and/or binding-mechanisms are involved in stimulation of cells with LPS and/or lipid A.
Long-Term Survival of Participants in the Prostate Cancer Prevention Trial
Authors: Ian M. Thompson, Phyllis J. Goodman, Catherine M. Tangen, Howard L. Parnes, Lori M. Minasian, Paul A. Godley, M. Scott Lucia, Leslie G. Ford
Journal: New England Journal of Medicine (2013)

In the Prostate Cancer Prevention Trial (PCPT), finasteride significantly reduced the risk of prostate cancer but was associated with an increased risk of high-grade disease. With up to 18 years of follow-up, we analyzed rates of survival among all study participants and among those with prostate cancer.We collected data on the incidence of prostate cancer among PCPT participants for an additional year after our first report was published in 2003 and searched the Social Security Death Index to assess survival status through October 31, 2011.Among 18,880 eligible men who underwent randomization, prostate cancer was diagnosed in 989 of 9423 (10.5%) in the finasteride group and 1412 of 9457 (14.9%) in the placebo group (relative risk in the finasteride group, 0.70; 95% confidence interval [CI], 0.65 to 0.76; P<0.001). Of the men who were evaluated, 333 (3.5%) in the finasteride group and 286 (3.0%) in the placebo group had high-grade cancer (Gleason score, 7 to 10) (relative risk, 1.17; 95% CI, 1.00 to 1.37; P=0.05). Of the men who died, 2538 were in the finasteride group and 2496 were in the placebo group, for 15-year survival rates of 78.0% and 78.2%, respectively. The unadjusted hazard ratio for death in the finasteride group was 1.02 (95% CI, 0.97 to 1.08; P=0.46). Ten-year survival rates were 83.0% in the finasteride group and 80.9% in the placebo group for men with low-grade prostate cancer and 73.0% and 73.6%, respectively, for those with high-grade prostate cancer.Finasteride reduced the risk of prostate cancer by about one third. High-grade prostate cancer was more common in the finasteride group than in the placebo group, but after 18 years of follow-up, there was no significant between-group difference in the rates of overall survival or survival after the diagnosis of prostate cancer. (Funded by the National Cancer Institute.).