tbuckley/cabot-search huggingface dataset:
High-dose chemotherapy with hematopoietic rescue as primary treatment for metastatic breast cancer: a randomized trial.
Authors: W R Bezwoda, L Seymour, R D Dansey
Journal: Journal of Clinical Oncology (1995)

PURPOSE The aims of this study were to compare in a randomized trial the results of high-dose versus conventional-dose chemotherapy as first-line treatment for metastatic breast cancer. The comparison included complete response (CR) rate, duration of response, and duration of survival. PATIENTS AND METHODS Ninety patients were entered onto a study to compare two cycles of high-dose cyclophosphamide 2.4 g/m2, mitoxantrone 35 to 45 mg/m2, and etoposide (VP16) 2.5 g/m2 (HD-CNV) versus six to eight cycles of conventional-dose cyclophosphamide 600 mg/m2, mitoxantrone 12 mg/m2, and vincristine 1.4 mg/m2 (CNV) as first-line treatment for metastatic breast cancer. The high-dose regimen included either autologous bone marrow or peripheral-blood stem-cell rescue. All 90 patients are assessable. RESULTS The response rates were significantly different. The overall response rate for HD-CNV was 43 of 45 (95%), with 23 of 45 patients (51%) achieving CR. Twenty-four of 45 patients (53%) who received conventional CNV have responded, with only two patients achieving CR. Both duration of response and duration of survival were significantly longer for patients, who received HD-CNV. Toxicity of the high-dose therapy was moderate in most patients. Grade 2 to 3 mucositis and hematologic suppression that required supportive treatment was universal, but hematologic recovery to a neutrophil count more than 500/microL and platelet count more than 40,000/microL occurred at day 18 (median) after therapy. CONCLUSION HD-CNV appears to be a promising schedule that results in a significant proportion of CRs and increased survival in patients with metastatic breast cancer.
Alternating combination VCMP/VBAP chemotherapy versus melphalan/prednisone in the treatment of multiple myeloma: a randomized multicentric study of 487 patients.
Authors: J Bladé, J F San Miguel, A Alcalá, J Maldonado, M A Sanz, J García-Conde, M J Moro, C Alonso, J Besalduch, A Zubizarreta
Journal: Journal of Clinical Oncology (1993)

PURPOSE To determine whether combination chemotherapy with alternating cycles of vincristine, cyclophosphamide, melphalan, and prednisone (VCMP) and vincristine, carmustine (BCNU), Adriamycin (doxorubicin; Farmitalia, Carlo-Erba Laboratories, Spain), and prednisone (VBAP) is better than the standard melphalan-prednisone (MP) regimen in multiple myeloma (MM). PATIENTS AND METHODS From January 1985 to December 1989, 28 institutions of the Spanish Cooperative Group for Hematological Malignancies Treatment, Spanish Society of Hematology (PETHEMA) entered 487 eligible patients with symptomatic MM into the study. Patients were randomized to receive either MP or alternating courses of VCMP and VBAP. Logistic regression and the Cox proportional hazards models were used to assess the association between patients' characteristics and response rate and survival, respectively. RESULTS Among 449 patients who were assessable for response, the overall response rate to MP was 51.8% (31.5% objective response plus 20.3% partial response) as compared with 62.7% (45.2% objective response plus 17.5% partial response) to VCMP/VBAP (P = .025). Also, a significantly higher proportion of objective responses was observed with combination chemotherapy (45.2% v 31.5%; P = .004). The factors associated with an unfavorable response rate in the overall series were low platelet count, treatment with MP, high creatinine level and immunoglobulin, (IgG) monoclonal (M)-component. No significant differences were found when survival rates of both groups of patients were compared. However, patients with IgA myeloma treated with VCMP/VBAP survived significantly longer than those who received MP (median, 20.2 v 38.4 months; P &lt; .005). CONCLUSION These results indicate that combination chemotherapy improves response rate in MM. However, this does not result in a significantly different survival rate, except for patients with IgA myeloma, who survive significantly longer with combination chemotherapy.
Congenital insensitivity to pain with anhidrosis: a case with preserved itch sensation to histamine and partial pain sensation
Authors: T. Tanaka, T. Satoh, A. Tanaka, H. Yokozeki
Journal: British Journal of Dermatology (2011)

Congenital insensitivity to pain with anhidrosis is a rare autosomal recessive hereditary disorder that is characterized by having both sensory neuropathy and anhidrosis. A 6-year-old Japanese boy presented with recurrent fever, lack of sweating, occult bone fractures and impaired pain sensation without mental retardation. Genetic analyses revealed compound heterozygous mutations in the NTRK1 gene that encodes TrkA, which is a receptor for nerve growth factor. While there were no apparent changes in the patient's dermal eccrine glands, the quantitative sudomotor axon reflex test with acetylcholine chloride revealed a complete loss of both the axon reflex-mediated and the directly activated sweat responses. On the other hand, the histamine prick test induced a normal weal response surrounded by a flare phenomenon. Notably, the patient felt both an itch sensation after histamine and a burning sensation after topical capsaicin application. Consistent with these findings, PGP9.5+ nerve fibre innervation of the papillary dermis was observed, although the fibres were completely absent around the eccrine glands. These findings suggest that there was a partial preservation of the nerve endings that express the H(1) receptor and/or TRPV1 in the upper dermis, even though there were mutations of the NTRK1 gene in this case.
Erythropoietin (EPO) attenuates the expression of its receptor (EPO-R) in bleomycin (BLM)-induced pulmonary fibrosis (PF) in rats
Authors: Drosos Tsavlis, Anna Tzoumaka, Georgia Kokaraki, Kokkona Kouzi-Koliakou, Anastasia Tektonidou, Afroditi Papadopoulou, Evangelia Spandou
Journal: European Respiratory Journal (2012)

PURPOSE:PF is characterized by apoptosis as well as by inflammation, excessive collagen deposition and fibroplasts' proliferation.The EPO-R is well known to play an important role in the fibrotic-apoptotic pathway. EPO is a multiple functional cytokine with anti-apoptotic, anti-oxidative and anti-inflammatory properties.We looked for the effect of EPO on BLM-induced lung fibrosis, by examining the expression of EPO-R in the lung tissue of rats.

MATERIAL AND METHODS: Fifty Wistar rats (300gr) were divided into five groups of 10 animals each:1)control animals,2)intratracheal (i.t) and intraperitoneal (i.p) injection of saline (0.5ml/kg),3)BLM hydrochloride (7.5mg/kg) i.t injection,4)BLM hydrochloride (7.5mg/kg) i.t injection followed by EPO i.p injection (2000 iu/kg),5)saline (0.5ml/kg) i.t injection followed by EPO i.p injection (2000 iu/kg). All rats were sacrified after 14 days.Immunohistochemical evaluation was performed for the expression of EPO-R.A scale of 4 grades was used for the evaluation of the results: 0-25% (A),25-50% (B),50-75% (C),75-100% (D).

RESULTS: In groups 1,2 and 5 (control groups), EPO-R was expressed in the lower grades A (80%) and B (20%). In group 3 (BLM group), EPO-R was expressed in the high grades B (20%), C (70%) and D (10%). In group 4 (EPO group), EPO-R was expressed only in the low grades A (50%) and B (50%). The expression of EPO-R took place in the high grades for BLM group and in the lower grades for BLM+EPO group (p<0.05).

CONCLUSION: BLM injection followed by EPO resulted in significant lower expression of EPO-R compared with BLM group. The protective mechanisms of EPO on PF must be further clarified.
Subcutaneous versus intravenous granulocyte colony stimulating factor for the treatment of neutropenia in hospitalized hemato‐oncological patients: Randomized controlled trial
Authors: Mical Paul, Ron Ram, Eitan Kugler, Laura Farbman, Anat Peck, Leonard Leibovici, Meir Lahav, Moshe Yeshurun, Ofer Shpilberg, Corina Herscovici, Ofir Wolach, Gilad Itchaki, Michal Bar‐Natan, Liat Vidal, Anat Gafter‐Gvili, Pia Raanani
Journal: American Journal of Hematology (2013)

Intravenous (IV) granulocyte colony stimulating factor (G-CSF) might be safer and more convenient than subcutaneous (SC) administration to hospitalized hemato-oncological patients receiving chemotherapy. To compare IV vs. SC G-CSF administration, we conducted a randomized, open-label trial. We included inpatients receiving chemotherapy for acute myeloid leukemia, acute lymphoblastic leukemia, lymphoma or multiple myeloma, and allogeneic or autologous hematopoietic cell transplantation (HCT). Patients were randomized to 5 mcg/kg single daily dose of IV bolus versus SC filgrastim given for its clinical indications. Patients were crossed-over to the alternate study arm on the subsequent chemotherapy course. The primary outcomes were time from initiation of filgrastim to recovery of stable neutrophil count of >500 cells/µL and a composite clinical outcome of infection or death assessed for the first course post-randomization. The study was stopped on the second interim analysis. Of 120 patients randomized, 118 were evaluated in the first treatment course. The mean time to neutropenia resolution was longer with IV G-CSF [7.9 days, 95% confidence interval (CI) 6.6-9.1] compared with SC G-CSF (5.4 days, 95% CI 4.6-6.2), log-rank P = 0.001. Longer neutropenia duration was observed in all patient subgroups, except for patients undergoing autologous HCT. There was no significant difference between groups in the occurrence of infection or death, but more deaths were observed with IV (4/57, 7%) versus SC (1/61, 1.6%) G-CSF administration, P = 0.196. Similar results were observed when all 158 courses following cross-over were analyzed. Patients reported similar pain and satisfaction scores in both groups. Bolus IV administration of G-CSF results in longer neutropenia duration than SC administration, with no difference in clinical or quality-of-life measures.
Does allergens influence resistin levels in children with allergic rhinitis
Authors: Maria Palma Carbone, Anna Maria Zicari, Bonci Enea, Francesca Occasi, Ilaria Ernesti, Giovanna De Castro, Paolo Del Greco, Marzia Duse
Journal: European Respiratory Journal (2012)

BACKGROUND: Resistin, a serum protein produced by adipocytes and circulating macrophages, seems to be associated with inflammatory states. Many authors reported high levels of this serum adipokine in respiratory diseases such as allergic rhinitis(AR).

AIM: The purpose of this study was to confirm the relationship between resistin levels and atopy and to assess whether these levels were influenced by Skin Prick Test (SPT) patterns in children with nasal obstruction.

METHODS: 35 children (15 males; mean age 9 yr) were selected for nasal obstruction: 12 monosensitized to house dust mites (HDM), 10 to grass pollens (GP) and 13 with negative SPT to airborne allergens.

A blood sampling to evaluate resistin serum values was performed in all subjects.

RESULTS: Atopic patients showed significantly higher levels of serum resistin than non atopic children (4.6ng/ml vs 5.7ng/ml; p<0.05). Moreover resistin mean values were 5.5 ng/ml in children sensitized to HDM and 3.6 ng/ml in those sensitized to GP. This difference was statistically significant (0.001<p<0.01).

CONCLUSIONS: Our results confirm that serum resistin levels are associated with the allergic inflammatory process in children. Among patients with AR higher resistin serum levels also showed a stronger association with HDM monosensitization. Thus, resistin, as a proinflammatory protein, may be influenced also by the persistence of the allergic trigger and perennial allergens may increase its levels more than seasonal allergens.
Sevuparin Reduces Adhesion Of Both Sickle Red Cells and Leukocytes To Endothelial Cells In Vitro and Inhibits Vaso-Occlusion In Vivo
Authors: Milena Batchvarova, Siqing Shan, Rahima Zennadi, Maria Lindgren, Anna Leitgeb, Pirkko Sulila Tamsen, Marilyn J. Telen
Journal: Blood (2013)
Tumor Characteristics and Clinical Outcome of Tubular and Mucinous Breast Carcinomas
Authors: Sami G. Diab, Gary M. Clark, C. Kent Osborne, Arlene Libby, D. Craig Allred, Richard M. Elledge
Journal: Journal of Clinical Oncology (1999)

PURPOSE: To comprehensively characterize the clinical and biologic features of tubular and mucinous carcinomas in a large cohort of patients and to relate this to clinical outcome and management. PATIENTS AND METHODS: The clinical and biologic features of 444 patients with tubular and 1,221 patients with mucinous carcinomas were compared with those of 43,587 patients with infiltrating ductal carcinoma, not otherwise specified (NOS). Disease-free survival (DFS) and overall survival (OS) for patients with tubular and mucinous carcinomas were compared with those of patients with NOS carcinomas and with age-matched sets from the general population. RESULTS: Tubular and mucinous carcinomas were more likely to occur in older patients, be smaller in size (tubular only), have substantially less nodal involvement, be estrogen receptor– and progesterone receptor–positive, have a lower S-phase fraction, be diploid, and be c-erbB-2– and epidermal growth factor receptor–negative compared with NOS carcinomas. Axillary node involvement was a poor prognostic feature in mucinous but not tubular carcinomas. Mucinous carcinomas ≤ 1 cm had a ≤ 5% incidence of node involvement. The 5-year DFS and OS were 94% and 88% for tubular, 90% and 80% for mucinous, and 80% and 77% for NOS carcinoma, respectively (P &lt; .001 for differences among all three types for both DFS and OS). The 5-year OS of females from the general population age-matched to the patients with tubular and mucinous carcinomas was 89% and 82%, respectively, which is not different from the OS of patients with tubular or mucinous carcinomas. CONCLUSION: The biologic phenotype of tubular and mucinous carcinomas is quite favorable. Consistent with this observation, the survival of patients with tubular and mucinous carcinomas is similar to that of the general population. Systemic adjuvant therapy and node dissection may be avoided in many patients with these special types of carcinoma.
Non-communication between ophthalmologists and optometrists
Authors: Karl W Whittaker, Khalid Ikram, David F Anderson, Andrew W Kiel, Andrew J Luff
Journal: Journal of the Royal Society of Medicine (1999)

Many patients seen in the British hospital eye service are referred by high-street optometrists; and, if the optometrist is to receive feedback from the ophthalmologist, the patient should consent to disclosure of medical information. On the referral form (revised GOS 18) there is a space for this purpose. We investigated the level of communication by asking optometrists in our hospital catchment area about their use of the GOS 18 form and by examining the medical records of all new patients seen in the eye outpatient department in one month. 79 optometrists (55%) returned the questionnaire. 54 routinely used the GOS 18; and, of these, 10 said they obtained patient consent always, 23 sometimes and 21 never. 158 of 555 sets of medical notes contained an optometrist's referral, 107 of them on the revised GOS 18; and patient consent had been recorded on 17 of these forms. Ophthalmologists responded to the optometrist in 2/17 (12%) cases where consent had been obtained and 15/90 (17%) where it had not. Ophthalmologists could provide much better feedback to optometrists. The GOS 18 form could be used more effectively; and there is no reason why patient consent to disclosure of medical information should not be obtained by ophthalmologists as well as by optometrists.
Petition calling for health secretary’s resignation exceeds 200 000 supporters
Authors: Abi Rimmer
Journal: BMJ (2015)

<h3>Background</h3> Neurological examination in children presenting with upper limb fractures is often poorly performed in the Emergency Department (ED). We aimed to assess the improvement in documented neurological examination for children presenting with upper limb fractures following introduction of a simple guideline. <h3>Methods</h3> We developed and introduced a simple guideline for upper limb neurological assessment in children (‘rock, paper, scissors, OK’). We compared documentation of neurological examination and nerve injury detection at our hospital before and after introduction of this guideline, as well as for children admitted from external hospitals (where the guideline had not been introduced). <h3>Results</h3> In the period following guideline introduction, 97 children with upper limb fractures were admitted (46% presenting directly to our ED and 54% admitted from external hospitals). This cohort was similar in number and distribution to the cohort reviewed prior to the guideline. Documentation of neurological examination in our ED increased from 92% to 98% after guideline introduction. Documented information on nerves examined also increased from 2% to 68% (p&lt;0.01). Prior to the guideline, there were six nerve injuries, all of which were missed in our ED. After guideline introduction, there were four nerve injuries, all of which were detected in our ED. Documentation and nerve injury detection at external hospitals over the same time period showed no improvement. <h3>Conclusions</h3> A simple guideline to assist neurological examination in children with upper limb fractures can significantly improve the quality of documented neurological assessment and nerve injury detection.
A mechanism for acceleration of GM-CSF autoantibody (GMAb) production in autoimmune pulmonary alveolar proteinosis (aPAP)
Authors: Koh Nakata, Takahiro Tanaka, Ryushi Tazawa
Journal: European Respiratory Journal (2014)

Background :IgG type GMAb is the etiologic agent for aPAP, although low concentration of the antibody is present in healthy subjects. To elucidate whether the acceleration of IgG-GMAb production by B cells in aPAP is caused by expansion/maturation of the corresponding B cells, we evaluated the frequencies and sequence of IgG-BCR +  B cell clones in aPAP and normal subjects (control).  Methods : Memory B cells were sorted using anti-CD27 magnetic beads from blood cells,inoculated with Epstein Barr virus (EBV), and GMAb producing B cells were detected by ELISPOT and ELISA.GMAb BCR +  were sorted magnetically followed by RNA extraction and cDNA generation. IgH cDNA V region were amplified by PCR and were applied to the next generation sequencing (GS FLX and GS Junior Systems, Roche ® ). The sequence data were analyzed using a bioinformatics software.  Results:  ELISA and ELISPOT data demonstrated that GMAb producing cells was less frequently in the controls than aPAP. The next generation sequencing of membrane-GMAb positice B cells revealed that the number of productive IgG sequences was much larger in aPAP than the controls. CDR2 sequences tended to form cluster by phylogenic analysis especially in severe aPAP, suggesting that clonal expansion and selection may proceed in the disease process. Thus, our present data suggest that the accelerated IgG-GMAb BCR +  B cell clones are expanding in aPAP.
Effectiveness of trained nurses in preoperative assessment
Authors: R. K Kerridge
Journal: BMJ (2003)

Self reported patterns of sexual activity in 4624 British men Age group (years) Men with self reported activity greater than once weekly (n=4624) Men with self reported activity greater than once weekly minus men with no sexual activity over 4 week study period (n=4316) No (%) 95% CI No (%) 95% CI 40-44 742 (51) 48 to 55 687 (55) 52 to 59 45-49 545 (41) 37 to 45
Intermittent Vismodegib Therapy in Basal Cell Nevus Syndrome
Authors: Xinyi Yang, Scott M. Dinehart
Journal: JAMA Dermatology (2015)

approximately 20% to 30% of patients. 1,2Characteristically, HFSR presents as painful, hyperkeratotic, erythematous plaques on the palms and soles in areas subject to increased pressure.Other mucocutaneous effects described with anti-VEGF agents include keratoacanthoma, squamous cell carcinoma, splinter subungual hemorrhages, hair depigmentation, and stomatitis. 2 Both systemic and cutaneous toxic effects of axitinib are consistent with other agents in the same class, with a significant incidence of HFSR. 3,4Hand-foot skin reaction has been proposed to result from blockade of VEGF receptor and plateletderived growth factor receptor in areas repeatedly subject to subclinical trauma, disrupting normal vascular repair processes in fibroblasts and endothelial cells. 4While the acral lesions in the present patient were distinct from HFSR, it is possible that a similar process was responsible.Inhibition of VEGF leads to increased vascular tone, 1 and so dysregulated vasoconstriction in the skin may disrupt normal tissue repair. 4Indeed, hypertension in patients treated with concurrent sorafenib and bevacizumab, a monoclonal antibody against VEGF, was found to be a risk factor for developing HFSR. 5 Vasodilatory agents such as nifedipine may therefore be useful for both hypertension and cutaneous lesions.One patient treated with bevacizumab developed hemorrhagic ulcers and purpuric patches on the lower legs, termed thrombogenic vasculopathy, 6 further supporting a direct VEGF-mediated effect.In the midst of continued characterization of toxic effects profiles of newer oncologic agents, our case represents a distinct cutaneous vasculopathy associated with the anti-VEGF agent axitinib.
Chromatin in 3D: progress and prospects for plants
Authors: Chang Liu, Detlef Weigel
Journal: Genome biology (2015)

Methods that use high-throughput sequencing have begun to reveal features of the three-dimensional structure of genomes at a resolution that goes far beyond that of traditional microscopy. Integration of these methods with other molecular tools has advanced our knowledge of both global and local chromatin packing in plants, and has revealed how patterns of chromatin packing correlate with the genomic and epigenomic landscapes. This update reports recent progress made in this area in plants, and suggests new research directions.