tbuckley/cabot-search huggingface dataset:
Risk Assessment Among Prostate Cancer Patients Receiving Primary Androgen Deprivation Therapy
Authors: Matthew R. Cooperberg, Shiro Hinotsu, Mikio Namiki, Kazuto Ito, Jeanette Broering, Peter R. Carroll, Hideyuki Akaza
Journal: Journal of Clinical Oncology (2009)

Prostate cancer epidemiology has been marked overall by a downward risk migration over time. However, in some populations, both in the United States and abroad, many men are still diagnosed with high-risk and/or advanced disease. Primary androgen deprivation therapy (PADT) is frequently offered to these patients, and disease risk prediction is not well-established in this context. We compared risk features between large disease registries from the United States and Japan, and aimed to build and validate a risk prediction model applicable to PADT patients.Data were analyzed from 13,740 men in the United States community-based Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) registry and 19,265 men in the Japan Study Group of Prostate Cancer (J-CaP) database, a national Japanese registry of men receiving androgen deprivation therapy. Risk distribution was compared between the two datasets using three well-described multivariable instruments. A novel instrument (Japan Cancer of the Prostate Risk Assessment [J-CAPRA]) was designed and validated to be specifically applicable to PADT patients, and more relevant to high-risk patients than existing instruments.J-CaP patients are more likely than CaPSURE patients to be diagnosed with high-risk features; 43% of J-CaP versus 5% of CaPSURE patients had locally advanced or metastatic disease that could not be stratified with the standard risk assessment tools. J-CAPRA--scored 0 to 12 based on Gleason score, prostate-specific antigen level, and clinical stage--predicts progression-free survival among PADT patients in J-CaP with a c-index of 0.71, and cancer-specific survival among PADT patients in CaPSURE with a c-index of 0.84.The novel J-CAPRA is the first risk instrument developed and validated for patients undergoing PADT. It is applicable to those with both localized and advanced disease, and performs well in diverse populations.
Sex practice correlates of human immunodeficiency virus transmission and acquired immunodeficiency syndrome incidence in heterosexual partners and offspring of U.S. hemophilic men
Authors: Dale N. Lawrence, Janine M. Jason, Robert C. Holman, Peggy Heine, Bruce L. Evatt
Journal: American Journal of Hematology (1989)

Abstract We assessed the risk of human immunodeficiency virus (HIV) transmission from heterosexual seropositive hemophilic men to their female sex partners through an HIV sero‐survey and questionnaire study conducted during 1984–1987. Five percent of 21 female partners of asymptomatic men and 11% of 35 partners of HIV‐symptomatic (acquired immunodeficiency syndrome [AIDS], AIDS‐related complex [ARC], peripheral generalized lymphadenopathy [PGL]) hemophilic men had been infected when first tested. One of 19 seronegative women tested about 1 year later reportedly seroconverted. Only 18% of a sample of the serosurvey women responding to sex practices questions said their partners used condoms “nearly always.” Over 60% engaged in oral/genital sex in addition to vaginal intercourse. Only 12% of still‐seronegative women followed the preventive strategy of consistent avoidance of oral/genital sex, together with consistent condom use by the male partner. Further evidence for heterosexual transmission comes from the CDC national AIDS surveillance reports showing 25 women who acquired HIV infection through heterosexual contact with U.S. hemophilic men (September 6, 1988). Seven (28%) were diagnosed and reported in the first 6 months of 1988. Their ages range from 20 years to more than 70 years. The dates of infection for the women are unknown but must have been at least 5 years before AIDS diagnosis for at least one. Only approximately 30% of their male partners had already manifested any HIV‐assodaied illness. Through May 18, 1988, six cases of AIDS have occurred in children whose infection was acquired through exposure of the mother to a hemophific partner. Four were diagnosed in latter 1987. The median age at diagnosis was 4.5 months. Four had died. None of their mothers is as yet diagnosed.
Dipterous Larvae and Wound Treatment
Authors: A. D. Imms
Journal: BMJ (1939)

DURING the war of 1914–18, W. S. Baer1, in the United States, noticed that when troops wounded in battle had been lying out on the ground unattended for some time, their wounds very commonly became infested with larvae of certain kinds of flies. He noticed specially that when the wounds had acquired about their maximum maggot population they did not exhibit dangerous after-effects. On the other hand, men whose wounds had received prompt early treatment often developed infection. It was found that the presence of these larvae was especially beneficial in cases of osteomyelitis. It was discovered that the larvae were eating the necrotic tissue which was supporting the main bacterial infection, and at the same time these larvae were inhibiting further bacterial growth. Stewart2 claimed that the scavenging larvae play an important part in clearing the necrotic tissue, but that calcium carbonate, which is constantly excreted by the larvae, is also important in alkalizing the medium (the wound) in which the bacteria live, and of increasing phagocytie activity.
Abdominal coarctation in a hypertensive female collegiate basketball player
Authors: B Sloan, S Simons, A Stromwall
Journal: British Journal of Sports Medicine (2004)

The purpose of the preparticipation examination is to identify health conditions that might adversely affect an athlete while participating in sport. Hypertension is the most common. This case report details a female basketball player found to be hypertensive, and complaining of fatigue, at her preparticipation physical examination. Presentation, diagnostics, treatment, and final outcome of coarctation involving the abdominal aorta are summarised.
Effect of KRAS Oncogene Substitutions on Protein Behavior: Implications for Signaling and Clinical Outcome
Authors: Nathan T. Ihle, Lauren A. Byers, Edward S. Kim, Pierre Saintigny, J. Jack Lee, George R. Blumenschein, Anne Tsao, Suyu Liu, Jill E. Larsen, Jing Wang, Lixia Diao, Kevin R. Coombes, Lu Chen, Shuxing Zhang, Mena F. Abdelmelek, Ximing Tang, Vassiliki Papadimitrakopoulou, John D. Minna, Scott M. Lippman, Waun K. Hong, Roy S. Herbst, Ignacio I. Wistuba, John V. Heymach, Garth Powis
Journal: JNCI Journal of the National Cancer Institute (2012)

Mutations in the v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) play a critical role in cancer cell growth and resistance to therapy. Most mutations occur at codons 12 and 13. In colorectal cancer, the presence of any mutant KRas amino acid substitution is a negative predictor of patient response to targeted therapy. However, in non–small cell lung cancer (NSCLC), the evidence that KRAS mutation is a predictive factor is conflicting. We used data from a molecularly targeted clinical trial for 215 patients with tissues available out of 268 evaluable patients with refractory NSCLC to examine associations between specific mutant KRas proteins and progression-free survival and tumor gene expression. Transcriptome microarray studies of patient tumor samples and reverse-phase protein array studies of a panel of 67 NSCLC cell lines with known substitutions in KRas and in immortalized human bronchial epithelial cells stably expressing different mutant KRas proteins were used to investigate signaling pathway activation. Molecular modeling was used to study the conformations of wild-type and mutant KRas proteins. Kaplan–Meier curves and Cox regression were used to analyze survival data. All statistical tests were two-sided. Patients whose tumors had either mutant KRas-Gly12Cys or mutant KRas-Gly12Val had worse progression-free survival compared with patients whose tumors had other mutant KRas proteins or wild-type KRas (P = .046, median survival = 1.84 months) compared with all other mutant KRas (median survival = 3.35 months) or wild-type KRas (median survival = 1.95 months). NSCLC cell lines with mutant KRas-Gly12Asp had activated phosphatidylinositol 3-kinase (PI-3-K) and mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK) signaling, whereas those with mutant KRas-Gly12Cys or mutant KRas-Gly12Val had activated Ral signaling and decreased growth factor–dependent Akt activation. Molecular modeling studies showed that different conformations imposed by mutant KRas may lead to altered association with downstream signaling transducers. Not all mutant KRas proteins affect patient survival or downstream signaling in a similar way. The heterogeneous behavior of mutant KRas proteins implies that therapeutic interventions may need to take into account the specific mutant KRas expressed by the tumor.
GPR18 is required for a normal CD8αα intestinal intraepithelial lymphocyte compartment
Authors: Xiaoming Wang, Hayakazu Sumida, Jason G. Cyster
Journal: The Journal of Experimental Medicine (2014)

Intraepithelial lymphocytes (IELs) play an important role in maintaining the physiology of the small intestine. The majority of mouse IELs express CD8αα and are either γδ or αβ T cells. Although the development and homing of CD8αα IELs have been studied in some detail, the factors controlling their homeostasis and positioning are incompletely understood. Here we demonstrate that G protein–coupled receptor 18 (GPR18) is abundantly expressed in CD8αα IELs and that mice lacking this orphan receptor have reduced numbers of γδT IELs. Mixed bone marrow chimera experiments reveal a markedly reduced contribution of GPR18-deficient cells to the CD8αα IEL compartment and a reduction in the CD8αβ T cell subset. These defects could be rescued by transduction with a GPR18-expressing retrovirus. The GPR18-deficient γδT IELs that remained in mixed chimeras had elevated Thy1, and there were less granzyme B+ and Vγ7+ cells, indicating a greater reduction in effector-type cells. Flow cytometric analysis indicated GPR18 deficiency more strongly affected the CD8αα cells in the intraepithelial compared with the adjacent lamina propria compartment. These findings establish a requirement for GPR18 in CD8αα and CD8αβ IELs, and we suggest the receptor has a role in augmenting the accumulation of CD8 T cells in the intraepithelial versus lamina propria compartment.
The Incidence and Severity of Atherosclerosis in Estrogen-Treated Males, and in Females with a Hypoestrogenic or a Hyperestrogenic State
Authors: ARTHUR U. RIVIN, SIM P. DIMITROFF
Journal: Circulation (1954)

Autopsy records of estrogen-treated men, castrated women, and women with breast carcinoma were analyzed with reference to the degree of atherosclerotic disease. Findings were then compared with those in similar groups of men and women whose estrogen supply was considered normal. Results obtained suggest: (1) that the male treated with estrogen has less atherosclerosis than the normal male; (2) that the oophorectomized female has an incidence of severe atherosclerosis approaching that of the male; and (3) that the hyperestrogenic female with breast carcinoma has less atherosclerosis than the normal female.
Osteonecrosis of the Jaw in Multiple Myeloma Patients: Clinical Features and Risk Factors
Authors: Ashraf Badros, Dianna Weikel, Andrew Salama, Olga Goloubeva, Abraham Schneider, Aaron Rapoport, Robert Fenton, Natalie Gahres, Edward Sausville, Robert Ord, Timothy Meiller
Journal: Journal of Clinical Oncology (2006)

To describe the clinical, radiologic, and pathologic features and risk factors for osteonecrosis of the jaw (ONJ) in multiple myeloma (MM) patients.A retrospective review of 90 MM patients who had dental assessments, including 22 patients with ONJ. There were 62 men; the median age was 61 years in ONJ patients and 58 years among the rest. Prior MM therapy included thalidomide (n = 67) and stem-cell transplantation (n = 72). Bisphosphonate therapy included zoledronate (n = 34) or pamidronate (n = 17) and pamidronate followed by zoledronate (n = 33). Twenty-seven patients had recent dental extraction, including 12 patients in the ONJ group. Median time from MM diagnosis to ONJ was 8.4 years for the whole group.Patients usually presented with pain. ONJ occurred posterior to the cuspids (n = 20) mostly in the mandible. Debridement and sequestrectomy with primary closure were performed in 14 patients; of these, four patients had major infections and four patients had recurrent ONJ. Bone histology revealed necrosis and osteomyelitis. Microbiology showed actinomycetes (n = 7) and mixed bacteria (n = 9). More than a third of ONJ patients also suffered from long bone fractures (n = 4) and/or avascular necrosis of the hip (n = 4). The variables predictive of developing ONJ were dental extraction (P = .009), treatment with pamidronate/zoledronate (P = .009), longer follow-up time (P = .03), and older age at diagnosis of MM (P = .006).ONJ appears to be time-dependent with higher risk after long-term use of bisphosphonates in older MM patients often after dental extractions. No satisfactory therapy is currently available. Trials addressing the benefits/risks of continuing bisphosphonate therapy are needed.
How to Turn Pennies Into Dollars
Authors: M. Siraj Uddin
Journal: JAMA (1980)

To the Editor.—  Tossing specie of base or precious metal into fountains such as the Trevi is a practice of ancient vintage, usually performed in a state of gay abandon by some romantics or for mystical reasons by others. We report the case of a patient, who was impelled neither by romance nor by any impulse, other than the most practical reasons, to place copper pennies in a jar used to measure his 24-hour urine copper output. He apparently hoped the pennies would gain him greater pension benefits.  We report this incident because of the need to repeat an old story in new garb. We all are tempted at times to engage in deception. Sometimes the deception is subtle and imaginative; at other times, it is pedestrian and amateurish. We leave it to the reader to decide which kind this story illustrates.  Report of a Case.—  A 32-year-old man was
Individualized treatment with combination of Peg-interferon alpha 2b and ribavirin in patients infected with HCV genotype 3
Authors: Alessandra Mangia, Franco Bandiera, Giuseppe Montalto, Leonardo Mottola, Valeria Piazzolla, Nicola Minerva, Adriano Pellicelli, Giovanni L. Ricci, Marina Cela, Vito Carretta, Gaetano Scotto, Donato Bacca, Brigida Annicchiarico, Mario Romano, Maurizio Russello, Giorgio Barbarini, Ernesto Agostinacchio, Angelo Andriulli
Journal: Journal of Hepatology (2010)
T cell responses and virus evolution: loss of HLA A11-restricted CTL epitopes in Epstein-Barr virus isolates from highly A11-positive populations by selective mutation of anchor residues.
Authors: P O de Campos-Lima, V Levitsky, J Brooks, S P Lee, L F Hu, A B Rickinson, M G Masucci
Journal: The Journal of Experimental Medicine (1994)

Epstein-Barr virus (EBV) is a B lymphotropic herpesvirus of humans that elicits strong HLA class I-restricted cytotoxic T lymphocyte (CTL) responses. An influence of such responses on virus evolution was first suggested by our finding that EBV isolates from the highly HLA A11-positive Papua New Guinea (PNG) population carried a lys-thr mutation at residue 424 of the nuclear antigen EBV-encoded nuclear antigen (EBNA4) that destroyed the immunodominant target epitope for A11-restricted CTL recognition. Here we turn to a much larger population, Southern Chinese, where the A11 allele is again present in over 50% of the individuals. Each of 23 EBV isolates analyzed from this population were also mutated in the EBNA4 416-424 epitope, the mutations selectively involving one of the two anchor residues in positions 2 (417 val-leu) or 9 (424 lys-asp, -arg or -thr) that are critical for A11-peptide interaction. The majority of the Chinese isolates and all 10 PNG isolates also carried mutations affecting positions 1 and 2 of the next most immunodominant A11-restricted epitope, EBNA4 residues 399-408. These changes clearly affected antigenicity since A11-positive lymphoblastoid cell lines (LCLs) carrying these mutant EBV strains were not recognized by A11-restricted CTLs raised against the prototype B95.8 virus. Furthermore, Chinese donors naturally infected with these mutant viruses did not mount detectable A11-restricted CTL responses on in vitro stimulation with autologous LCL cells carrying either the B95.8 or their endogenous EBV strain. In two different highly A11-positive populations, therefore, immune pressure appears to have selected for resident EBV strains lacking immunodominant A11-restricted CTL epitopes.
Etiology of Hyperparathyroidism and Bone Disease during Chronic Hemodialysis. III. EVALUATION OF PARATHYROID SUPPRESSIBILITY
Authors: Ralph S. Goldsmith, Jacob Furszyfer, William J. Johnson, Albert E. Fournier, Glen W. Sizemore, Claude D. Arnaud
Journal: Journal of Clinical Investigation (1973)

Parathyroid function was assessed by calcium infusions (4-8 h) in 16 patients with chronic renal insufficiency being treated by long-term hemodialysis. The concentrations of two immunoreactive species of parathyroid hormone in plasma (iPTH-9, mol wt 9500; iPTH-7, mol wt 7000) were estimated by radioimmunoassays utilizing two relatively specific antisera. Control values of the smaller species, iPTH-7, were uniformly high, whereas values of iPTH-9 were normal in 12 of 19 studies. Response of iPTH-7 to calcium infusions was variable, with significant decreases occurring only five times in 27 infusions. Concentrations of iPTH-9, however, decreased during every calcium infusion. In contrast to these acute responses, five of six patients studied during periods of dialysis against both low (< 6 mg/100 ml) and high (7-8 mg/100 ml) calcium concentrations in the dialyzate showed a decrease in values of iPTH-7 during the period of dialysis against the higher calcium concentration. It is concluded that plasma concentrations of iPTH-9 reflect primarily the moment-to-moment secretory status of the parathyroid glands, while concentrations of iPTH-7 reflect more closely chronic parathyroid functional status. It is further concluded that the failure of iPTH-7 to decrease during induced hypercalcemia should not be equated with autonomy of parathyroid gland function.
Acute bronchial obstruction following inhalation of PAF in asthmatic and normal subjects: comparison with methacholine
Authors: R.E. Louis, M.F. Radermecker
Journal: European Respiratory Journal (1996)

Platelet-activating factor (PAF) may play a role in the pathophysiology of asthma but controversies exist about bronchial responsiveness toward this mediator in asthma. We have compared the variations in the specific conductance (sGaw) and forced expiratory volume in one second (FEV1) in 12 asthmatics and 12 normal subjects after inhalation of doubling doses of PAF (15-120 micrograms) and methacholine (18 to at least 144 micrograms). In order to take into account a possible tachyphylaxis, we compared PAF dose-response curves performed on one day with the curves obtained by giving the same doses separately on different days. Repeated inhalations of doubling doses of PAF caused sGaw and FEV1 to plateau after the second dose in each group, whereas methacholine provoked a dose-related decrease in sGaw and FEV1. A dose-dependent decrease in the functional indices was restored when the different doses of PAF were administered on separate days. In both groups, the fall in sGaw after inhalation of 60 micrograms as a single dose was higher than that achieved when this dose was given during a full bronchial challenge. The falls in sGaw and FEV1 after PAF inhalation were significantly higher in the asthmatics than in the normal subjects. The provocative dose of PAF causing a 35% fall in sGaw (PD35,sGaw) PAF was only twofold lower in the asthmatics than in the normal subjects (p < 0.05), while it was 11 fold lower for methacholine (p < 0.001). When the PD35,sGaw values were compared, PAF was found on a molar basis to be 33 fold more potent than methacholine in the normal subjects, but only fivefold more potent in the asthmatics (p < 0.05). The percentage falls in FEV1 (calculated by interpolation) for a 35% fall in sGaw, were greater in asthmatics than in normals both for methacholine (p < 0.05) and PAF (p = 0.09). Our results demonstrate a tachyphylaxis after inhalation of platelet-activating factor in normal subjects and asthmatics, and show that asthmatics develop a greater bronchial obstruction than normal subjects even if methacholine is more sensitive than platelet-activating factor at discriminating between the two groups.
Sudden cardiac arrest in children and young athletes: the importance of a detailed personal and family history in the pre-participation evaluation
Authors: R M Campbell, S Berger, J Drezner
Journal: British Journal of Sports Medicine (2008)

Healthcare providers have become more aware of and concerned about paediatric sudden cardiac arrest. The diseases predisposing a patient to sudden cardiac arrest are all infrequently encountered. However, a detailed and comprehensive patient and family history may reveal warning signs and symptoms that identify a patient at higher risk for sudden cardiac arrest. Since many of these diseases are genetic, extensive family evaluation may uncover a previously undetected cardiac disease process and as well direct the development of a complete family evaluation and treatment plan. Published data document that in many cases preceding warning symptoms and signs are present, but may be misinterpreted or disregarded by medical staff. Attention to the details of patient history, family history and physical exam is critical to the success of any detection strategy, which can and should be widely applied.