tbuckley/cabot-search huggingface dataset:
p53 Status predicts survival in breast cancer patients treated with or without postoperative radiotherapy: a novel hypothesis based on clinical findings.
Authors: T Jansson, M Inganäs, S Sjögren, T Norberg, A Lindgren, L Holmberg, J Bergh
Journal: Journal of Clinical Oncology (1995)

PURPOSE AND METHODS Primary breast cancer tumors without axillary metastases from 206 consecutive patients in a population-based cohort were investigated with regard to the presence of an intact p53 gene using a cDNA-based sequencing method. Clinical follow-up data and outcome of node-negative patients without any adjuvant systemic therapy (n = 168) were related to locoregional radiotherapy and p53 status. RESULTS Mutations in p53 occurred in 31 node-negative breast cancer patients who did not receive any systemic adjuvant treatment, but were treated with postoperative locoregional radiotherapy or nothing. Node-negative breast cancer patients with p53 mutations had significantly improved relapse-free survival (P = .0007), breast cancer-corrected survival (P = .01), and overall survival (P = .02) rates when treated with locoregional radiotherapy. In node-negative breast cancer patients with wild-type p53, there was no statistically significant difference in outcome between patients who received locoregional radiotherapy and those who did not. Cox proportional hazards models indicate that mutant p53 is associated with worse prognosis independent of response to radiotherapy and that response to radiotherapy is qualitatively different in tumors with p53 mutations compared with those with wild-type p53. CONCLUSION Our clinical findings define a group of breast cancer patients in whom locoregional radiotherapy improves relapse-free, breast cancer-corrected, and overall survival. The outcome for irradiated node-negative breast cancer patients with p53 alterations indicates that irradiation can induce cell death even in the presence of p53 mutations.
Treatment of Schizoaffective Disorder and Schizophrenia With Mood Symptoms
Authors: Douglas F. Levinson, C. Umapathy, Mohamado Musthaq
Journal: American Journal of Psychiatry (1999)

Patients with concurrent schizophrenic and mood symptoms are often treated with antipsychotics plus antidepressant or thymoleptic drugs. The authors review the literature on treatment of two overlapping groups of patients: those with schizoaffective disorder and those with schizophrenia and concurrent mood symptoms.MEDLINE searches (from 1976 onward) were undertaken to identify treatment studies of both groups, and references in these reports were checked. Selection of studies for review was based on the use of specified diagnostic criteria and of parallel-group, double-blind design (or, where few such studies addressed a particular issue, large open studies). A total of 18 treatment studies of schizoaffective disorder and 15 of schizophrenia with mood symptoms were selected for review.For acute exacerbations of schizoaffective disorder or of schizophrenia with mood symptoms, antipsychotics appeared to be as effective as combination treatments, and there was some evidence for superior efficacy of atypical antipsychotics. There was evidence supporting adjunctive antidepressant treatment for schizophrenic and schizoaffective patients who develop a major depressive syndrome after remission of acute psychosis, but there were mixed results for treatment of subsyndromal depression. There was little evidence to support adjunctive lithium for depressive symptoms and no evidence concerning its use for manic symptoms in patients with schizophrenia.Empirical data suggest that both groups of patients are best treated by optimizing antipsychotic treatment and that atypical antipsychotics may prove to be most effective. Adjunctive antidepressants may be useful for patients with major depression who are not acutely ill. Careful longitudinal assessment is required to ensure identification of primary mood disorders.
Abstract 4398: Native Endothelium Mimicking Self-Assembled Nanomatrix for Drug Eluting Stents
Authors: Ho-Wook Jun, Meenakshi Kushwaha, Joel Anderson Anderson, Adinarayana Andukuri, Brigitta Brott, Peter Anderson
Journal: Circulation (2009)

Introduction: Drug eluting stents (DES) is one of major therapeutic methods for treatment of cardiovascular diseases. However, recent reports suggest that DES has been associated with a higher risk of late thrombosis which may be related to inadequate endothelialization. Therefore, the main goal of this project is to develop the next generation of DES using a native endothelium mimicking self-assembled nanomatrix which will inhibit both restenosis and thrombosis while enhancing endothelialization from surrounding endothelium and endothelial progenitor cells circulating in the blood stream. Results: The nanomatrix is formed by self-assembly of peptide amphiphiles (PAs) which contain a nitric oxide (NO) producing donor and an endothelial cell adhesive ligand, YIGSR along with enzyme-mediated degradable sites. NO was successfully released from the nanomatrix rapidly within 48 hours followed by sustained release over period of 30 days. The NO releasing nanomatrix demonstrated a significantly enhanced prolifer...
High BCR-ABL/GUSIS Levels At Diagnosis Are Associated With Unfavorable Responses To Imatinib
Authors: Paolo G Vigneri, Fabio Stagno, Stefania Stella, Alessandra Cupri, Stefano Forte, Michele Massimino, Agostino Antolino, Clementina Caracciolo, Laura Nocilli, Stefana Impera, Caterina Musolino, Diamante Turri, Mario Russo, Carmen Tomaselli, Michele Rizzo, Maurizio Musso, Fortunato Morabito, Luciano Levato, Livia Manzella, Martin C Muller, Andreas Hochhaus, Francesco Di Raimondo
Journal: Blood (2013)
An etiologic model of alcoholism
Authors: J M Donovan
Journal: American Journal of Psychiatry (1986)

As we await a successful model of the etiology of alcoholism, research and intervention strategies founder. The author critically reviews the present etiologic models, particularly those bearing on alcoholic personality. The central shortcoming of these models is that they pay only lip service to the multidimensional etiology of alcoholism. Hereditary, environmental, and psychostructural risk factors have never been adequately integrated into any one design. The author explains the difficulties that this problem and others have introduced into the previous etiologic research. In the conclusion, he constructs a new model from the positive findings thus far. This, in turn, suggests the studies needed next and has definite diagnostic and therapeutic implications.
Abstract 15855: Cardiovascular Benefits of Beta Blocker Therapy in Patients With Acute Coronary Syndrome Without Heart Failure: A Meta-Analysis of Randomized Controlled Trials
Authors: Mukesh Singh, Tejaskumar Shah, Rohit Arora
Journal: Circulation (2011)

Background: Current guidelines recommend early use of beta blockers in acute coronary syndrome (ACS). Beta blocker therapy in ACS with previous heart failure (HF) is well established but benefit of...
Imaging of epithelial repair processes in the mouse trachea after laser-induced injury
Authors: Sarah Kretschmer, Mario Pieper, Peter König
Journal: European Respiratory Journal (2014)

Small lesions in the airway epithelium occur frequently and offer an entry for pathogens. Therefore injuries have to be repaired to prevent prolonged disruption of epithelial integrity. The mechanism of the repair process of small lesions in the airways is largely unknown.  To better understand this repair process we used two-photon microscopy and an  ex-vivo  murine trachea model. The explanted trachea was cut longitudinally and then imaged with the epithelium facing up. Epithelial lesions were induced by focussing Ti-sapphire femtosecond laser pulses to single epithelial cells for 1-8 seconds. Staining with propidium iodide (PI) allowed identification of damaged cells. Phalloidin was used to stain actin filaments after the experiment.  Depending on the irradiation time a specific area of 1-12 epithelial cells was damaged. Hyperfluorescence around the beam focus and loss of autofluorescence in adjacent cells was observed. Within the lesion nuclei were stained with PI. Small lesions of 1-3 cells were closed within 3 h. Lesions of 5-8 cells needed 4 h or did not close within the observation time of up to 6 h. Epithelial cells around the lesion changed their shape. Especially the cells immediately adjacent to the wound margin protracted notably to close the lesion. During this process damaged cells were expelled into the lumen. Staining with phalloidin after two-photon microscopy showed a transepithelial actin ring formed in the cells around the wound.  Healing of small lesions in the airways depends on an active coordinated movement of adjacent epithelial cells. Further studies will focus on the molecular mechanisms of repair that might be impaired in airway diseases.
Cetuximab maintenance therapy – How long should we proceed? A case report
Authors: Stefan Rüdiger, Cornelia Kropf, Gerald Schmid-Bindert, Thomas Wibmer, Martin Lanzinger, Kathrin Stoiber, Joanna Blanta, Wolfgang Rottbauer, Christian Schumann
Journal: European Respiratory Journal (2011)

The continuation of an active therapeutic agent for extended duration following frontline induction chemotherapy as maintenance therapy can improve overall survival. The Gemtax IV trial compares a platinum-containing doublet vs. a platinum-free sequential chemotherapy with docetaxel and gemcitabine, both arms in combination with cetuximab until progression. However, a useful predictive marker for maintaining an EGFR antibody treatment still not exists.  We report about a 56-year-old female Caucasian patient with multiple pulmonary lesions and diagnosis of a bronchioloalveolar carcinoma. She was at good performance status (ECOG 0), without relevant comorbidities with a smoking history of 35 packyears. EGFR mutation analysis showed an insertion in exon 20 of the EGFR-gene. Within the Gemtax IV trial 4 cycles of carboplatin/gemcitabine/cetuximab were given. Toxicity was a grade III neutropenia and a grade I rash without itching. A total number of 16 cycles cetuximab were completed until therapy was stopped on patient9s request. After six weeks, tumor progression was documented, resulting in a PFS of 12.5 months. In the course, the patient did benefit from another chemotherapy, but not from an EGFR-TKI (erlotinib). OS was 32 month.  In our case a rapid tumor progression was seen after stopping cetuximab maintenance therapy. This could indicate a significant antitumor activity of the EGFR antibody in this patient. Biomarkers or clinical selection criteria should be identified that allow to predict patients benefit from cetuximab maintenance therapy and avoid such “rebound phenomenon” or unneeded maintenance treatment.
Identification and characterisation of seven novel SERPINA1 null mutations
Authors: Stefania Ottaviani, Tomás P. Carroll, Ilaria Ferrarotti, Anna M. Fra, Geraldine O'Brien, Kevin Molloy, Luciano Corda, Noel G. McElvaney, Maurizio Luisetti
Journal: European Respiratory Journal (2014)

Background Alpha-1 antitrypsin (AAT) is a serine protease inhibitor, encoded by the highly polymorphic  SERPINA1  gene. Mutations in this gene can lead to AAT deficiency (AATD) which is associated with a substantially increased risk of lung and liver disease. A group of rare mutations causing AATD, termed Null, are characterised by a complete absence of AAT in the plasma, that confer a particularly high risk of emphysema.   Objective  s Here we reported the novel Null AAT mutations that we discovered during the Italian and Irish targeted detection programs of AATD.   Methods We performed the determination of AAT serum levels by a rate immune nephelometric method or by immune turbidimetry. The phenotype was determined by isoelectric focusing analysis.DNA was isolated from whole peripheral blood or dried blood spot (DBS) samples using a commercial extraction kit. The new mutations were identified by sequencing all coding exons of the  SERPINA1  gene.   Results We identified seven previously unidentified  SERPINA1  Null mutations. Three are nonsense mutations, the others are frameshift mutations caused by deletion of one or two nucleotides. We also performed familial screening. Analysis of the clinical characteristics revealed the recurrence of lung symptoms and lung diseases in M/Null subjects, over 45 years-old, irrespective of their smoking habit.   Conclusions  We added seven more mutations to the list of  SERPINA1  Null alleles. Moreover, we underlined that the laboratory diagnosis of AATD is not just a matter of degree, because the precise determination of the deficiency and Null alleles carried by an AATD individual may help to evaluate the risk for the lung disease.
Subcutaneous injections of 2-chlorodeoxyadenosine for symptomatic hairy cell leukemia.
Authors: G Juliusson, D Heldal, E Hippe, M Hedenus, C Malm, K Wallman, C M Stolt, S A Evensen, F Albertioni, G Tjønnfjord
Journal: Journal of Clinical Oncology (1995)

PURPOSE To evaluate the clinical efficacy and safety of 2-chlorodeoxyadenosine (CdA) when administered by subcutaneous injection to patients with symptomatic hairy cell leukemia (HCL), and to evaluate predictive factors for response. PATIENTS AND METHODS Seventy-three patients were given CdA as a subcutaneous injection once daily for 7 days. Complete remission (CR) required normalized blood counts and the absence of B-ly 7-positive bone marrow cells by flow cytometry. CdA concentrations in plasma following the first injection were analyzed by high-pressure liquid chromatography. RESULTS Fifty-nine patients (81%) achieved a durable CR after one (n = 55) or two courses, and 10 had a partial remission (PR). With a median follow-up duration of 20 months, no patient had a clinical relapse. Neutropenic fever that required intravenous antibiotics occurred in 28 patients (38%). No toxicity at injection sites was observed. Incomplete response was predicted by an elevated lymphocyte count and serum beta 2-microglobulin level, and by a high percentage of hairy cells in the bone marrow. Plasma CdA levels were similar to those achieved from intravenous administration. CONCLUSION Subcutaneous injection of CdA is safe and as effective as continuous infusion without problems associated with the mode of administration. Our schedule simplifies CdA treatment and can be generally recommended.
Male menopause after unilateral inguinal herniorrhaphy
Authors: M P J Vanderpump
Journal: Journal of the Royal Society of Medicine (1998)

A man aged 56 began to experience severe episodic flushing and sweating one month after a right inguinal herniorrhaphy. These episodes lasted several minutes and were described as sudden drenching perspiration occurring twenty or more times a day and severe enough to wake him at least ten times every night. There was no relation to food or exercise, he had no history of chest pain or syncope and there were no ictal phenomena; he was on no regular medication, was a non-smoker and drank little alcohol; he was married with two children. During a witnessed episode no abnormalities were observed in pulse, blood pressure or temperature. Routine blood investigations, including thyroid function tests, were normal and screening for phaeochromocytoma and carcinoid syndrome was negative. Although the herniorrhaphy had apparently been uncomplicated the patient reported that the right testis had become swollen and painful postoperatively (he had believed this to be the expected discomfort after a hernia repair). Once the pain had subsided, the right testis seemed to him smaller than it had been before surgery. He also disclosed that, as a child, he had experienced an episode of acute pain in the left testis which had resolved spontaneously. Examination of the scrotum revealed an atrophic left testis and a soft right testis, volumes 3 mL and 15 mL, respectively, when measured by Prader's orchidometer. Biochemical investigations confirmed the presence of hypogonadism: serum testosterone 1.0 nmol/L (normal range 10.5-31.0), luteinizing hormone 27.5 mU/mL (212 mU/mL) and follicle stimulating hormone 54.4 mU/mL (1-12). On direct questioning he said there had been no change in shaving frequency or loss of body hair but his libido had declined and he complained of lethargy. Within 4 hours after receiving testosterone replacement via intramuscular injection (Sustanon 250 mg), the sweating episodes had resolved and they did not recur for two weeks. Lifelong testosterone replacement is to be provided by subcutaneous testosterone implants.
Purine Nucleoside Phosphorylase Deficiency
Authors: William R. A. Osborne, Shi-Han Chen, Eloise R. Giblett, W. Douglas Biggar, Arthur A. Ammann, C. Ronald Scott
Journal: Journal of Clinical Investigation (1977)

Purine-nucleoside phosphorylase (NP) deficiency is associated with severely defective thymus-derived (T)-cell and normally functioning bone marrow-derived (B)-cell immunity. In this study, two unrelated families with a total of three NP deficient members were investigated.
Association of the severe, frequent exacerbation phenotype with exercise capacity, sputum bacteriology and copeptin circulating levels in COPD
Authors: Daiana Stolz, Wim Boersma, Renaud Louis, Francesco Blasi, Branislava Milenkovic, Alicia Lacoma, Joachim Aerts, Vincent Heinen, Marilena Pappalettera, Kostantinos Kostikas, Cristina Prat, Emiel Wouters, Antoni Torres, Tobias Welte, Michael Tamm
Journal: European Respiratory Journal (2011)

Background: There is growing interest in the determinants of the frequency of exacerbation in COPD, leading to the definition of a frequent exacerbation phenotype. We have assessed variables associated with a history of frequent, severe exacerbation according to the ERS definition in a well characterized cohort of COPD patients.

Methods: Data of 598 patients with stable COPD (GOLD II-IV) for > 6 weeks, and seeking care in pulmonary tertiary hospitals in 10 European centers were analyzed. Assessment included history, systemic biomarkers (procalcitonin, proANP, copeptin, proadrenomedullin), lung function, SF-36, SGRQ, MMRC dyspnea score, and 6MWD test.

Results: Patients had a mean age of 66 yo ± 12, 448 were male. Mean FEV1% pred was 48.2% ± 18.5. A total of 387 patients (64.7%) reported no severe exacerbation, 170 (28.4%) reported one severe exacerbation, and 41 (6.9%) patients reported two or more severe exacerbations requiring hospitalization in previous year. ICU care was required in 45 (7.6%) of the cases. In the multivariate analysis, OR [95% CI] age 1.218 [1.043-1.422, p=0.013], positive sputum bacteriology at the stable state 8.88 [1.57-50.19, p=0.014], FEV1% pred 0.946 [0.902-0.992, p=0.021], MMRC 3.240 [1.021-10.281, p=0.046], 6MWD 1.014 [1.002-1.026, p=0.026], Borg 1.607 [1.010-2.558, p=0.045], and copeptin 0.305 [0.140-0.664, p=0.003] were independently associated with the severe, recurrent exacerbations phenotype.

Conclusions: Age, sputum bacteriology, lung function, dyspnea, exercise capacity and copeptin circulating levels are independently associated with the severe, frequent exacerbation phenotype.
A New Dimension for the JRSM
Authors: Robin Fox
Journal: Journal of the Royal Society of Medicine (2001)

On the matter of electronic publication the world of medical journals is split—opportunity or threat? Since I lean strongly towards opportunity, I am much heartened by the RSM's decision to put our Journal on the World Wide Web. The current issue of the JRSM, and its successors, will be found on a site run by High Wire Press, which already serves numerous medical publications including the BMJ, Circulation, Gut and the Quarterly Journal of Medicine.

Not many readers of the JRSM, I think, will now entirely forsake print-on-paper for the screen. What the website offers is a plus. When an article excites your special attention, you can now pursue the subject to your heart's content via hyperlinks to other journals. For JRSM authors a considerable attraction is that the reverse applies: readers of other online journals will gain instant access to your work, and so too can those whose attention is drawn to it by mention in a newspaper or on television.

The barriers to communication in medicine are collapsing one by one. Try the website—www.jrsm.org
US oncologists call for government regulation to curb drug price rises
Authors: Michael McCarthy
Journal: BMJ (2015)

The US government must act to curb the soaring cost of anticancer drugs, 118 US oncologists have argued in a commentary published on 23 July in Mayo Clinic Proceedings .1

The authors include leading oncologists from such institutions as the University of Texas MD Anderson Cancer Center in Houston, Memorial Sloan Kettering Cancer Center in New York City, and Dana-Farber Cancer Institute and Harvard Medical School in Boston, Massachusetts.

“High cancer drug prices are affecting the care of patients with cancer and our healthcare system,” said the lead author, Ayalew Tefferi, a hematologist at the Mayo Clinic in Rochester, Minnesota. “The average gross household income in the US is about $52 000 [£33 000; €47 000] per year. For an insured patient with cancer who needs a drug that costs $120 000 per year, …
Efficacy of Docetaxel 60 mg/m<sup>2</sup> in Patients With Metastatic Breast Cancer According to the Status of Anthracycline Resistance
Authors: Masashi Ando, Toru Watanabe, Kazuhiro Nagata, Masaru Narabayashi, Isamu Adachi, Noriyuki Katsumata
Journal: Journal of Clinical Oncology (2001)

PURPOSE: To evaluate the efficacy of docetaxel 60 mg/m 2 in metastatic breast cancer (MBC) according to the status of anthracycline resistance. PATIENTS AND METHODS: Ninety-nine patients with anthracycline-resistant MBC were treated with docetaxel 60 mg/m 2 intravenously for a 90-minute period every 3 to 4 weeks. Anthracycline resistance was defined as primary and secondary resistance. Primary resistance was defined as progression during or within 6 months after completion of adjuvant anthracycline, and no MBC response to a first-line regimen that contained anthracycline. Secondary resistance was defined as progression after a documented clinical response to a first-line anthracycline treatment for MBC. Secondary resistance was further divided into three categories: (1) absolute resistance, or progression during treatment with anthracycline after a period of response; (2) relative resistance, or progression within 6 months after anthracycline administration ended; and (3) sensitive regrowth, or progression more than 6 months after the conclusion of anthracycline administration. RESULTS: The response rate in the 99 patients was 35.4% (95% confidence interval, 30.1% to 44.8%). The response rates according to the status of anthracycline resistance were as follows: primary resistance (n = 46), 19.6%; secondary resistance (n = 53), 49.1% (absolute resistance [n = 16], 56.3%); relative resistance (n = 17), 47.1%; and sensitive regrowth (n = 20), 45.0%. The median time to treatment failure in patients with primary resistance was 2.9 months, compared with 5.2 months in patients with secondary resistance (P = .0022). CONCLUSION: Docetaxel at a dose of 60 mg/m 2 seemed to be effective in MBC with secondary resistance to anthracycline. The status of anthracycline resistance is important for the prediction of response to second-line treatment with docetaxel.
Abstract 13617: Bone Morphogenetic Protein Signaling is a Regulator of Hepatic Cholesterol Biosynthesis in vitro and in vivo
Authors: Matthias Derwall, Rajeev Malhotra, Yuko Beppu, Warren M Zapol, Paul B Yu, Kenneth D Bloch
Journal: Circulation (2011)

Introduction: We have previously found that Inhibition of bone morphogenetic protein (BMP) signaling reduces atherosclerosis and vascular calcification in mouse models, but the mechanisms by which ...
Folate Deficiency Delays the Onset But Increases the Incidence of Leukemia in Friend Virus-Infected Mice
Authors: Mark J. Koury, Don J. Park, Danko Martincic, Donald W. Horne, Vladimir Kravtsov, James A. Whitlock, Maria del Pilar Aguinaga, Prapaporn Kopsombut
Journal: Blood (1997)