tbuckley/cabot-search huggingface dataset:
Profile of the malignant melanoma excised in general practice
Authors: M.M.C. BOSCH, M.E. BOON
Journal: British Journal of Dermatology (1994)

An analysis of 27 malignant melanomas diagnosed in a Dutch laboratory specializing in the provision of a cytology and pathology service to general practitioners is reported. The median age of the patients was 39 years, and was lower in women (30 years) than in men (54 years). In the national data the mean age was 52 years for both sexes. There were twice as many women as men. There were no tumours from the head and neck region. The ratio of tumours on the limbs to those on the trunk was 3:2. The melanomas were very small (74% with a diameter of < or = 6.0 mm), and they were also very thin (74% with a Breslow thickness < or = 1.0 mm), compared with the national data in which 62% were < or = 1.0 mm. Not surprisingly, the estimated mean 5-year survival was favourable (95% for women and 76% for men). After a period of follow-up ranging from 2 to 32 months, none of the patients had any evidence of residual disease. This study demonstrates that in skin biopsies performed by general practitioners melanomas are mainly detected by chance, and have a very good prognosis.
The evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer: recommendations by an International TILs Working Group 2014
Authors: R. Salgado, C. Denkert, S. Demaria, N. Sirtaine, F. Klauschen, G. Pruneri, S. Wienert, G. Van den Eynden, F.L. Baehner, F. Penault-Llorca, E.A. Perez, E.A. Thompson, W.F. Symmans, A.L. Richardson, J. Brock, C. Criscitiello, H. Bailey, M. Ignatiadis, G. Floris, J. Sparano, Z. Kos, T. Nielsen, D.L. Rimm, K.H. Allison, J.S. Reis-Filho, S. Loibl, C. Sotiriou, G. Viale, S. Badve, S. Adams, K. Willard-Gallo, S. Loi
Journal: Annals of Oncology (2014)
Initial Phase 2 Trial of a Nicotinic Agonist in Schizophrenia
Authors: Robert Freedman, Ann Olincy, Robert W. Buchanan, Josette G. Harris, James M. Gold, Lynn Johnson, Diana Allensworth, Alejandrina Guzman-Bonilla, Bettye Clement, M. Patricia Ball, Jay Kutnick, Vicki Pender, Laura F. Martin, Karen E. Stevens, Brandie D. Wagner, Gary O. Zerbe, Ferenc Soti, William R. Kem
Journal: American Journal of Psychiatry (2008)

Objective: Nicotinic acetylcholine receptors are possible therapeutic targets for schizophrenia, as shown by neurobiological and molecular evidence for deficiencies in expression of α 7 -nicotinic receptors. Patients’ heavy smoking suggests attempted self-medication through this mechanism. The agent 3-(2,4-dimethoxybenzylidene) anabaseine (DMXB-A) is a partial α 7 -nicotinic agonist and can be taken orally. A phase 1 trial showed evidence for cognitive enhancement in schizophrenia. Method: Thirty-one subjects with schizophrenia received DMXB-A at two different doses and placebo for periods of 4 weeks in a three-arm, two-site, double-blind, crossover phase 2 trial. The MATRICS Consensus Cognitive Battery assessed cognitive effects, and the Scale for the Assessment of Negative Symptoms (SANS) and Brief Psychiatric Rating Scale (BPRS) assessed clinical effects. Subjects continued their current antipsychotic drug during the trial and were nonsmokers. Results: There were no significant differences in the MATRICS cognitive measures between DMXB-A and placebo over the three treatment arms, but the patients experienced significant improvement at the higher DMXB-A dose on the SANS total score and nearly significant improvement on the BPRS total score. Improvement was most notable on the SANS anhedonia and alogia subscales. Examination of the first treatment arm showed effects of DMXB-A on the attention/vigilance and working memory MATRICS domains, compared to baseline. Five subjects developed mild tremor, and nearly half had mild nausea while taking DMXB-A. Conclusion: DMXB-A, a nicotinic agonist that activates α 7 -nicotinic receptors, improved clinical ratings of negative symptoms that are generally resistant to treatment with dopamine antagonist antipsychotic drugs. The clinical utility of this treatment is not yet determined.
When Should Patients with Lethal Ventricular Arrhythmia Resume Driving?
Authors: S. Adam Strickberger, Catherine O. Cantillon, Peter L. Friedman
Journal: Annals of Internal Medicine (1991)

Most states have specific laws governing whether patients with seizure disorders can drive. To learn whether similar laws exist for patients with lethal ventricular arrhythmias, we surveyed the Departments of Motor Vehicles in all 50 states. In addition, either an arrhythmia specialist (n = 25) or a general cardiologist (n = 25) was chosen randomly from each state and interviewed to study physician awareness of such laws and physician attitudes toward driving by patients with arrhythmias. Forty-two states (84%) have laws restricting driving by patients who have seizures; only 8 states (16%) have specific laws for patients with arrhythmias. No state makes a distinction between driving by patients with arrhythmias who are managed with an implantable cardioverter-defibrillator (ICD) compared with patients who are managed medically. Seventy-four percent of physicians did not know their own state's laws about driving by patients who have ventricular arrhythmias. Cardiologists were more likely to advise no driving restriction for medically treated patients than for ICD-treated patients. Cardiologists were also more likely to advise permanent restriction for patients with ICDs than for patients treated medically. We conclude that greater legal and medical consensus is needed to guide physicians in advising patients with lethal ventricular arrhythmias about driving restrictions.
Total prosthetic replacement of atrioventricular valves in the dog: Part I. Development of a free-floating cone valve for the right atrioventricular ostium
Authors: G. Den Otter
Journal: Thorax (1968)

A free-floating cone valve to be used as a prosthesis for the tricuspid valve of the heart is described. It consists of a stainless steel flat cage with a Lucite cone inside. The experience and reasoning that led to its construction are presented and the results obtained with it in a series of 32 dogs are given.
Advance directives are associated with "good deaths" in chronic dialysis patients.
Authors: R D Swartz, E Perry
Journal: Journal of the American Society of Nephrology (1993)

The effect of prior advance directives (AD) on the outcome when chronic dialysis patients died was evaluated in a retrospective review of consecutive deaths over a period of more than 6 yr in a large academic dialysis center. Among 182 patients who died during the period under review, 74 (41%) had previously stated their AD verbally or in writing and the prevalence of AD was highest among patients with age-related or chronically debilitating diseases. Previous statement of AD was significantly more prevalent (P < 0.001) among patients who withdrew from treatment in reconciled fashion than among patients who died suddenly and unexpectedly or who died without a reconciled decision to forego life-sustaining intervention (e.g., dialysis, intubation, emergency surgery). Further analysis shows that patients stating prior AD and patients withdrawing from treatment were most often those who made their own medical decisions ("internal" locus of decision making), rather than relying on relatives or other agents ("external" locus), and tended to be those with a definite spouse or spouse-equivalent relationship. Finally, retrospective assessment suggests that cases in which patients stated prior AD and cases in which patients withdrew from treatment were associated more frequently with a favorable outcome. It was concluded that addressing AD before a medical crisis ensues may increase the likelihood of a "good death" when complications bring the course of chronic dialysis to termination.(ABSTRACT TRUNCATED AT 250 WORDS)
Pyrimidine base degradation in cultured murine C-1300 neuroblastoma cells and in situ tumors.
Authors: M Tuchman, R F O'Dea, M L Ramnaraine, B L Mirkin
Journal: Journal of Clinical Investigation (1988)

Dihydropyrimidine dehydrogenase (DPD), the initial, rate-limiting step in pyrimidine degradation, was studied in two cell lines of murine neuroblastoma (MNB-T1 and MNB-T2) that were derived from C-1300 MNB tumor carried in A/J mice. The MNB-T2 (low malignancy) cell line was originally derived from the in situ tumor and carried in tissue culture for more than 100 passages; the MNB-T1 (high malignancy) line consisted of a new sub-culture that was also established from the in situ MNB tumor. DPD activity was determined in cytosolic preparations of MNB utilizing high performance liquid chromatography to separate the radiolabeled substrate ([2-14C]thymine) from [2-14C]dihydrothymine. The apparent affinity of DPD for NADPH in MNB cells (Km approximately 0.08 mM) was identical to that of A/J mouse brain and liver. The DPD activity of the high malignancy (MNB-T1) cell line was 14.3% of that observed in the low malignancy (MNB-T2) line. In situ tumors formed after implantation of high malignancy (MNB-T1) cells into A/J mice had only 25.2% of the DPD activity observed in tumors derived from low malignancy (MNB-T2) cells. When MNB-T2 cells were injected into naive A/J mice, tumors developed in only 68% of animals, the tumor growth rate was slow and a mortality of 20% was observed. In contrast, tumors derived from injected MNB-T1 cells showed a faster growth rate and 100% mortality. Most MNB-T2 derived tumors were not lethal and ultimately resolved while the MNB-T1 derived tumors were invariably lethal. These studies support the concept that the levels of DPD activity in neoplastic cells are inversely related to their malignant expression and also provide a model to study differences between neuroblastoma cell lines derived from the same in situ tumor but which manifest different neoplastic behavior.
<i>In Silico</i> Cloning of Mouse <i>Muc5b</i> Gene and Upregulation of Its Expression in Mouse Asthma Model
Authors: YIN CHEN, YU HUA ZHAO, REEN WU
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Using a BLAST-searching approach, we identified a mouse expressed sequence tag (EST) clone (AA038672) showing great similarity to the 3 ′ end of the human MUC5B gene. The clone was named “3pmmuc5b-1” after complete nucleotide sequencing (Genbank Accession, AF369933). A subsequent search of the mouse genome database with the 3pmmuc5b-1 sequence identified two overlapping genomic clones (AC020817 and AC020794) that contained the sequence of both 3pmmuc5b-1 and the mouse Muc5ac gene. Like their human homologs, the genomic order of the mouse Muc genes is 5 ′ -Muc5ac-Muc5b-3 ′ . These results suggest that the newly identified EST clone, 3pmmuc5b-1, is part of the 3 ′ portion of the mouse Muc5b gene. In situ hybridization demonstrated that this putative mouse Muc5b message was expressed in a restricted manner in the sublingual gland region of the tongue and the submucosal gland region of the mouse trachea in a normal animal. However, the gene expression was greatly enhanced in airway surface epithelium and the submucosal gland region in ovalbumin-induced asthmatic mice. These results were consistent with previous studies of human airway tissues. We therefore conclude that this newly cloned mouse Muc5b gene could be used as a marker for studying aberrant mucin gene expression in mouse models of various airway diseases.
Quality of Life in Patients With Gastroenteropancreatic Tumors Treated With [<sup>177</sup>Lu-DOTA<sup>0</sup>,Tyr<sup>3</sup>]octreotate
Authors: Jaap J.M. Teunissen, Dik J. Kwekkeboom, Eric P. Krenning
Journal: Journal of Clinical Oncology (2004)

Purpose To evaluate the quality of life (QoL) in patients with metastatic somatostatin receptor positive gastroenteropancreatic tumors treated with [ 177 Lu-DOTA 0 ,Tyr 3 ]octreotate ( 177 Lu-octreotate) therapy. Patients and Methods Fifty patients who had been treated with 600 to 800 mCi of 177 Lu-octreotate and had a follow-up of at least 3 months were studied. The patients completed the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire C30 before therapy and at follow-up visit 6 weeks after the last cycle. Overall QoL and specific QoL domains of both the total group of patients and subgroups according to treatment outcome were analyzed. Twenty-four patients had regression, 19 had stable disease, six had progressive disease, and one had nonassessable disease status. Analysis of variance was used for statistical comparison. Results A significant improvement in the global health status/QoL scale was observed after therapy with 177 Lu-octreotate (P &lt; .01). The score increased significantly six weeks after therapy to a mean of 78.2, up from 69.0 (scale range, 0 to 100). Furthermore, significant improvement was observed in the role, emotional, and social function scales. The symptom scores for fatigue, insomnia, and pain were significantly decreased. Patients with proven tumor regression most frequently had an improvement of QoL domains. Unexpectedly, patients with progressive disease also indicated an improvement in their global health/QoL score. Conclusion 177 Lu-octreotate therapy significantly improved the global health/QoL and several function and symptom scales in patients with metastasized gastroenteropancreatic tumors, but especially in those patients with proven tumor regression.
The influence of INK4 proteins on growth and self-renewal kinetics of hematopoietic progenitor cells
Authors: John L. Lewis, Wimol Chinswangwatanakul, Bo Zheng, Stephen B. Marley, Dao X. Nguyen, Nicholas C. P. Cross, Lolita Banerji, Janet Glassford, N. Shaun B. Thomas, John M. Goldman, Eric W.-F. Lam, Myrtle Y. Gordon
Journal: Blood (2001)
p53 Protein Accumulation and Gene Mutation in the Progression of Human Prostate Carcinoma
Authors: Nora M. Navone, Patricia Troncoso, Louis L. Pisters, Tamra L. Goodrow, Judy L. Palmer, Warren W. Nichols, Andrew C. von Eschenbach, Claudio J. Conti
Journal: JNCI Journal of the National Cancer Institute (1993)

Nuclear accumulation of p53 protein has been shown to be strongly associated with missense p53 mutations. Studies of nuclear accumulation of p53 protein in prostate carcinoma cells have to date been confined to material from primary tumors.We studied the accumulation of p53 protein in specimens obtained from primary and metastatic sites of prostate carcinoma. By examining the accumulation of this protein as a function of stage, histologic grade, and androgen responsiveness of the tumor, we hoped to determine the role of p53 mutation in the progression of prostate carcinoma.The accumulation of the p53 protein in the cell nuclei was determined by immunohistochemical methods using polyclonal antibody to human p53 CM-1. The material studied consisted of formalin-fixed, paraffin-embedded tissue obtained from primary tumors and metastases of 92 patients with prostate carcinoma. Twelve samples from 11 patients were analyzed for the presence of mutations within exons 5-8 of the p53 gene (also known as TP53) by polymerase chain reaction-single-stranded conformation polymorphism (PCR-SSCP) analysis. Sequence analysis was subsequently performed on DNA obtained by polymerase chain reaction amplification of PCR-SSCP reactions produced from six different specimens. The chi-square test, Fisher's exact test, and the Freeman Halton test were used for statistical analyses of the results.All tumors with p53 accumulation were metastatic (stage D), poorly differentiated, and androgen independent. Nuclear accumulation of p53 protein was strongly associated with stage (D2 versus D1 versus A-C, P < .0001), grade (Gleason score 8-10 versus 5-7, P < .003), and androgen sensitivity (androgen independent versus dependent, P < .0001). Logistic regression analysis demonstrated that androgen sensitivity predicted p53 outcome better than did stage (P < .0001) or grade alone (P < .006). There was a perfect concordance between the results obtained by PCR-SSCP analysis and the p53 protein accumulation determined by immunohistochemistry in the 12 samples studied. Mutation of the p53 gene was confirmed by sequencing DNA obtained from six specimens positive in the PCR-SSCP assay.p53 gene mutation is a late event in the progression of prostate cancer and is associated with advanced (metastatic) stage, loss of differentiation, and the transition from androgen-dependent to androgen-independent growth.Testing of prostate cancer biopsy specimens from metastatic sites for p53 protein accumulation and gene mutation may provide useful prognostic information and could influence the recommended course of treatment.
Randomized Phase II Trial of Single-Agent Amrubicin or Topotecan as Second-Line Treatment in Patients With Small-Cell Lung Cancer Sensitive to First-Line Platinum-Based Chemotherapy
Authors: Robert Jotte, Paul Conkling, Craig Reynolds, Matthew D. Galsky, Leonard Klein, James F. Fitzgibbons, Richard McNally, Markus F. Renschler, Jennifer W. Oliver
Journal: Journal of Clinical Oncology (2010)

Purpose This phase II study evaluated the safety and efficacy of single-agent amrubicin versus topotecan in patients with small-cell lung cancer (SCLC) sensitive to first-line platinum-based chemotherapy. Patients and Methods Patients were randomly assigned 2:1 to amrubicin (40 mg/m 2 /d in a 5-minute intravenous [IV] infusion, days 1 through 3, every 21 days) or topotecan (1.5 mg/m 2 /d in a 30-minute IV infusion, days 1 through 5, every 21 days). The primary efficacy end point was overall response rate (ORR) for amrubicin. Secondary end points included time to progression, median progression-free survival (PFS), and median overall survival (OS). Results Of 76 patients enrolled, 50 patients were randomly assigned to amrubicin, and 26 patients were randomly assigned to topotecan. Amrubicin treatment resulted in a significantly higher ORR than topotecan (44% v 15%; P = .021). Median PFS and median OS were 4.5 months and 9.2 months with amrubicin and 3.3 months and 7.6 months with topotecan, respectively. Tolerability was similar with both agents. However, grade 3 or worse neutropenia and thrombocytopenia seemed to be more frequent in the topotecan group as compared with the amrubicin group (78% and 61% v 61% and 39%, respectively). Conclusion Amrubicin shows promising activity, with an ORR of 44% compared with an ORR of 15% for topotecan as second-line treatment in patients with SCLC sensitive to first-line platinum-based chemotherapy. In addition, the safety profiles were comparable; however, a trend was noted for more frequent grade 3 or worse neutropenia and thrombocytopenia in the topotecan group as compared with the amrubicin group. Additional studies are ongoing.
Anaphylactic reaction to ranitidine
Authors: M. Lázaro, J. A. Compaired, B. De La Hoz, J. M. Igea, C. Marcos, I. Dávila, E. Losada
Journal: Allergy (1993)

Ranitidine is a well‐tolerated H 2 ‐receptor antagonist with a furan ring a nucleus. Anaphylactic reactions are seldom reported despite the wide use the drug. We report a patient who presented an anaphylactic reaction with ranitidine (Zantac). The positive skin prick test and oral challenge suggest type I hypersensitivity. Specific IgE determination by RAST technique and histamine release test with ranitidine were negative. The patient did not react to other H 2 ‐receptor antagonists or to another furan‐derivative (nitrofurantoin).
Deficiency of Splicing Factor 1 Suppresses the Occurrence of Testicular Germ Cell Tumors
Authors: Rui Zhu, Jason Heaney, Joseph H. Nadeau, Sara Ali, Angabin Matin
Journal: Cancer Research (2010)

Abstract Testicular germ cell tumors (TGCT) originate from germ cells. The 129-Ter and M19 (129.MOLF-Chr19 consomic) mouse strains have extremely high incidences of TGCTs. We found that the expression levels of Sf1-encoded splicing factor 1 (SF1) can modulate the incidence of TGCTs. We generated mice with inactivated Sf1. Sf1 null mice (Sf1−/−) died before birth. Mice with one intact allele of Sf1 (Sf1+/−) were viable but expressed reduced levels of Sf1. When Sf1-deficient mice (Sf1+/−) were crossed to the 129-Ter and M19 strains, we observed decreased incidence of TGCTs in Sf1+/−;Ter and Sf1+/−;M19/+ mice compared with that in control cohorts. Therefore, Sf1 deficiency protects against TGCT development in both strains. Sf1 is expressed in the testes. We found that Sf1 levels vary significantly in the testes of inbred strains such as 129 and MOLF, and as such Sf1 is an oncogenic tumor-susceptibility factor from 129. Our results also highlight the complications involved in evaluating Sf1 levels and TGCT incidences. When a large number of tumor-promoting factors are present in a strain, the protective effect of lower Sf1 levels is masked. However, when the dosage of tumor-promoting factors is reduced, the protective effect of lower Sf1 levels becomes apparent. SF1 is involved in splicing of specific pre-mRNAs in cells. Alternate splicing generates the complex proteosome in eukaryotic cells. Our data indicate that Sf1 levels in mouse strains correlate with their incidences of TGCTs and implicate the importance of splicing mechanisms in germ cell tumorigenesis. Cancer Res; 70(18); 7264–72. ©2010 AACR.
Special features of the clinical use of oral terbinafine in the treatment of fungal diseases
Authors: V.V. VILLARS, T.C. JONES
Journal: British Journal of Dermatology (1992)

Terbinafine (Lamisil) is an antifungal drug, belonging to a class of drugs called the allylamines, which has recently become available for clinical use. This is a report of four special features which emerged during evaluation of the systemic use of orally administered terbinafine in the treatment of 2500 patients during the last 5 years. These features include: (i) distribution of terbinafine in skin, hair and nail tissue; (ii) use in short-duration treatment of chronic tinea pedis and onychomycosis; (iii) use in patients with serious infections often associated with local or generalized immunological defects; and (iv) tolerability and safety of the drug. The diffusion of terbinafine into thickened, chronically infected tissue and into nails, and its recognized fungicidal action are the most likely features responsible for its success in the treatment of chronic fungal diseases, including those with immunological defects. Terbinafine is well tolerated, particularly when compared with other available systemic antifungal drugs.