tbuckley/cabot-search huggingface dataset:
Outcomes 18 Months after the First Human Partial Face Transplantation
Authors: Jean-Michel Dubernard, Benoit Lengelé, Emmanuel Morelon, Sylvie Testelin, Lionel Badet, Christophe Moure, Jean-Luc Beziat, Stéphanie Dakpé, Jean Kanitakis, Cédric D'Hauthuille, Assia El Jaafari, Palmina Petruzzo, Nicole Lefrancois, Farid Taha, Angela Sirigu, Giovanni Di Marco, Esther Carmi, Danielle Bachmann, Sophie Cremades, Pascal Giraux, Gabriel Burloux, Olivier Hequet, Nathalie Parquet, Camille Francès, Mauricette Michallet, Xavier Martin, Bernard Devauchelle
Journal: New England Journal of Medicine (2007)

We performed the first human partial face allograft on November 27, 2005. Here we report outcomes up to 18 months after transplantation.The postsurgical induction immunosuppression protocol included thymoglobulins combined with tacrolimus, mycophenolate mofetil, and prednisone. Donor hematopoietic stem cells were infused on postoperative days 4 and 11. Sequential biopsy specimens were taken from a sentinel skin graft, the facial skin, and the oral mucosa. Functional progress was assessed by tests of sensory and motor function performed monthly. Psychological support was provided before and after transplantation.Sensitivity to light touch, as assessed with the use of static monofilaments, and sensitivity to heat and cold had returned to normal at 6 months after transplantation. Motor recovery was slower, and labial contact allowing complete mouth closure was achieved at 10 months. Psychological acceptance of the graft progressed as function improved. Rejection episodes occurred on days 18 and 214 after transplantation and were reversed. A decrease in inulin clearance led to a change in immunosuppressive regimen from tacrolimus to sirolimus at 14 months. Extracorporeal photochemotherapy was introduced at 10 months to prevent recurrence of rejection. There have been no subsequent rejection episodes. At 18 months, the patient is satisfied with the aesthetic result.In this patient who underwent the first partial face transplantation, the functional and aesthetic results 18 months after transplantation are satisfactory.
Induction of λ-glutamylcysteine synthetase gene expression by platinum drugs in peripheral mononuclear cells of lung cancer patients
Authors: T. Oguri, Y. Fujiwara, M. Miyazaki, T. Takahashi, T. Kurata, M. Yokozaki, N. Ohashi, T. Isobe, O. Katoh, M. Yamakido
Journal: Annals of Oncology (1999)

To investigate in vivo the roles of gamma-glutamylcysteine synthetase (gamma-GCS), multidrug resistance-associated protein (MRP), human canalicular multispecific organic anion transporter (cMOAT) and DNA topoisomerase I (topo I) in relation to platinum drug resistance, we monitored the changes of the steady-state levels of the mRNAs for these factors in peripheral mononuclear cells (PMN) after completing platinum drug administration.PMN from 46 subjects were studied. We obtained PMN from 14 previously untreated lung cancer patients and 14 normal volunteers to measure the baseline gene expression levels. We then obtained PMN from 18 patients with previously untreated advanced lung cancer before and after they received platinum drug treatment. We analyzed the gene expression levels by using the quantitative reverse transcription polymerase chain reaction (RT-PCR).There were no differences in the baseline expression levels between normal volunteers and lung cancer patients in any of the genes. After platinum drug administration, the heavy subunit of gamma-GCS (gamma-GCSh) expression level increased 2.5-fold within 24 hours and the increase persisted for a month, whereas the light subunit of gamma-GCS (gamma-GCSl) expression level did not show an early response but had increased after a month. By contrast, the MRP, cMOAT and topo I expression levels were similar before, during and after chemotherapy.These results suggest that the gene expression levels of both subunits of gamma-GCS play an important in vivo role in platinum drug resistance.
H2 antagonists for gastric cancer: small numbers are not beautiful
Authors: J W L FIELDING
Journal: Gut (1998)

See article on page 17 

The study reported on page 17 illustrates some of the frustrations of clinical trials. The rationale for undertaking a prospective trial of the use of ranitidine in gastric cancer was appropriate. A previous study from Tonnesen et al 1 had demonstrated a survival benefit using cimetidine in patients with gastric cancer. This group of authors argued that cimetidine had an immunological effect which included inhibition of T suppresser activity and increased interleukin 2 production by lymphocytes.2 3 

Ranitidine has a similar effect: the Yorkshire GI tumour group began this study in 1989 to evaluate the potential effect of this …
Respiratory Syncytial Virus in Allergic Lung Inflammation Increases Muc5ac and Gob-5
Authors: Koichi Hashimoto, Barney S. Graham, Samuel B. Ho, Kenneth B. Adler, Robert D. Collins, Sandra J. Olson, Weisong Zhou, Tatsuo Suzutani, Phillip W. Jones, Kasia Goleniewska, Jamye F. O'Neal, R. Stokes Peebles
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

Respiratory syncytial virus (RSV) is associated with wheezing and childhood asthma. We previously reported that RSV infection prolongs methacholine-induced airway hyperresponsiveness in ovalbumin (OVA)-sensitized mice. In addition, allergically sensitized RSV-infected (OVA/RSV) mice had more abundant airway epithelial mucus production compared with OVA mice 14 days after infection, whereas there was almost no mucus in mice that were only RSV infected. We hypothesized that this increased mucus was associated with mucosal expression of Muc5ac, a mucus gene expression in airways, and gob-5, a member of the Ca2+-activated chloride channel family. By histochemical analysis, we found that there was significantly increased staining for gob-5 and Muc5ac in the airways of OVA/RSV mice compared with either OVA mice or allergically sensitized mice that were challenged with inactivated RSV, and virtually no detectable staining in the RSV group. These findings were confirmed by Western blot analysis. The increased mucus expression in the OVA/RSV group was associated with increased lung levels of interleukin-17, a factor known to stimulate airway mucin gene expression. The impact of virus infection combined with allergic inflammation on mucus production may partially explain the more severe disease and airway hyperresponsiveness associated with RSV in the setting of atopy.
Quality of Life in Long-Term, Disease-Free Survivors of Breast Cancer: a Follow-up Study
Authors: P. A. Ganz
Journal: JNCI Journal of the National Cancer Institute (2002)

Background: Women with breast cancer are the largest group of female survivors of cancer. There is limited information about the long-term quality of life (QOL) in disease-free breast cancer survivors. Methods: Letters of invitation were mailed to 1336 breast cancer survivors who had participated in an earlier survey and now were between 5 and 10 years after their initial diagnosis. The 914 respondents interested in participating were then sent a survey booklet that assessed a broad range of QOL and survivorship concerns. All P values were two-sided. Results: A total of 817 women completed the follow-up survey (61% response rate), and the 763 disease-free survivors in that group, who had been diagnosed an average of 6.3 years earlier, are the focus of this article. Physical well-being and emotional well-being were excellent; the minimal changes between the baseline and follow-up assessments reflected expected age-related changes. Energy level and social functioning were unchanged. Hot flashes, night sweats, vaginal discharge, and breast sensitivity were less frequent. Symptoms of vaginal dryness and urinary incontinence were increased. Sexual activity with a partner declined statistically significantly between the two assessments (from 65% to 55%, P = .001). Survivors with no past systemic adjuvant therapy had a better QOL than those who had received systemic adjuvant therapy (chemotherapy, tamoxifen, or both together) (physical functioning, P = .003; physical role function, P = .02; bodily pain, P = .01; social functioning, P = .02; and general health, P = .03). In a multivariate analysis, past chemotherapy was a statistically significant predictor of a poorer current QOL (P = .003). Conclusions: Long-term, disease-free breast cancer survivors reported high levels of functioning and QOL many years after primary treatment. However, past systemic adjuvant treatment was associated with poorer functioning on several dimensions of QOL. This information may be useful to patients and physicians who are engaging in discussion of the risks and benefits of systemic adjuvant therapy.
Phase II study of methotrexate, vincristine, pegylated-asparaginase, and dexamethasone (MOpAD) in patients with relapsed/refractory acute lymphoblastic leukemia
Authors: Tapan M. Kadia, Hagop M. Kantarjian, Deborah A. Thomas, Susan O'Brien, Zeev Estrov, Farhad Ravandi, Elias Jabbour, Naveen Pemmaraju, Naval Daver, Xuemei Wang, Preetesh Jain, Sherry Pierce, Mark Brandt, Guillermo Garcia‐Manero, Jorge Cortes, Gautam Borthakur
Journal: American Journal of Hematology (2014)

Newer approaches are needed for the treatment of relapsed and refractory acute lymphoblastic leukemia (ALL). Asparaginase-based regimens are active in the treatment of pediatric ALL and may be important in salvage therapy for adult patients. We conducted a pilot trial combining methotrexate, vincristine, PEGylated-asparaginase, and dexamethasone (MOpAD) in adults with relapsed or refractory ALL. We added tyrosine kinase inhibitors in patients with Philadelphia chromosome positive (Ph+) ALL and rituximab in patients with CD20 positive B-cell ALL. Among 37 patients treated (median age 42 years; median 2 prior therapies), the complete remission (CR) rate was 28% and an overall response rate (ORR) was 39%. The median CR duration was 4.3 months. Patients with Ph+ ALL had CR and ORR of 50% and 67%, respectively and the CR and ORR in patients with T-cell leukemia were 45% and 56%, respectively. The median survival in patients with CR/CRp was 10.4 versus 3.4 months in nonresponders (P = 0.02). The most common grade 3 or 4 nonhematologic toxicities were elevations in bilirubin and transaminases, nausea, peripheral neuropathy, and hyperglycemia, which were managed with supportive care, dose adjustments, and interruptions.
Selective inhibition of mucosal serotonin as treatment for IBD?
Authors: Alon D Levin, Gijs R van den Brink
Journal: Gut (2013)

Serotonin (5-HT) has extensively been studied in the central and enteric nervous system. Altered levels of 5-HT play a role in many central nervous system (CNS) disorders and can be treated with specific 5-HT receptor agonists and antagonists. Interestingly, 95% of the bodies 5-HT is located outside central neuronal regions and in the intestine. The discovery of 5-HT secreting cells in the intestinal epithelium has resulted in a fruitful area of research that is focused on the function of intestinal epithelium-derived 5-HT.1 The subsequent discovery that 5-HT may play an important role in driving intestinal inflammation has generated interest in the potential of 5-HT antagonists for treatment of inflammatory bowel disease (IBD). However, side effects related to the important role of 5-HT in the enteric and central nervous system have precluded drug development in this field. In this issue of Gut , Margolis et al 2 use mouse models to demonstrate that it may be possible to selectively inhibit intestinal mucosal 5-HT signalling and suppress intestinal inflammation without such side effects. 

In the intestine, 5-HT is produced by a subset of enteroendrocrine cells called enterochromaffin (EC) …
Non–Islet-Cell Tumor Induced Hypoglycemia in Patients With Advanced Gastrointestinal Stromal Tumor Possibly Worsened By Imatinib
Authors: Paul Hamberg, Floris A. de Jong, Joke G. Boonstra, Jaap van Doorn, Jaap Verweij, Stefan Sleijfer
Journal: Journal of Clinical Oncology (2006)

Numerous causes for hypoglycemia exist including hepatic, renal, or adrenal dysfunction, toxins such as alcohol and drugs, congestive heart failure, sepsis, malnutrition, prolonged exercise, hypopituitarism, autoimmune disorders, and increased insulin production by islet-cell tumors or small-cell carcinomas.Next to these causes, hypoglycemic episodes in cancer patients can be caused by non-islet-cell tumor induced hypoglycemia (NICTH).NICTH results from overproduction of incompletely processed forms of proinsulin-like growth factor-II (pro-IGF-II), which may lead to an excessive stimulation of the insulin receptors at various target tissues.NICTH is predominantly encountered in patients with large mesenchymal tumors, including gastrointestinal stromal tumors (GISTs), 1-4 but epithelial tumors have also been reported to be associated with NICTH. 5,6We describe two GIST patients with hypoglycemia related to a raised concentration of pro-IGF-II; in one case imatinib (Gleevec; Novartis Pharma, Basel, Switzerland) is likely to have contributed to the severity of the hypoglycemia.A 57-year-old male GIST patient with liver metastases had previously been treated with imatinib and subsequently with SU 11248 (sunitinib) because of progressive disease.Later he participated in a phase I study with a nuclear factor-kappa B inhibitor, but showed further disease progression shortly after treatment initiation.Two weeks after his last treatment, he was admitted because of hypoglycemic coma (glucose, Ͻ 1.0 mmol/L; reference value fasting glucose, 4.0 mmol/L to 6.4 mmol/L).Additional laboratory investigation showed no abnormalities except pre-existing, slightly increased liver enzyme concentrations while bilirubin was normal.He did not use medication and repeatedly measured glucose concentrations before admission were normal.After intravenous glucose administration all symptoms disappeared.Additional evaluation revealed reduced serum concentrations of IGF-I, and IGF-binding protein (IGFBP)-3, a slightly increased serum concentration of total IGF-II, and considerably elevated concentrations of pro-IGF-II and IGFBP-2 (Table 1)-characteristic of NICTH.Concentrations of other mediators known to affect glucose concentrations were normal.After a few days he did not need any glucose infusions to retain a normal glucose concentration and no more hypoglycemic episodes were detected despite extensive monitoring.The concentration of pro-IGF-II decreased spontaneously but remained elevated at 13.7 nmol/L (reference value, 3.8 nmol/L to 10.7 nmol/L).The second patient was a 52-year-old woman diagnosed with intra-abdominal metastases of GIST without liver involvement.She was treated with 400 mg of imatinib once daily.She had no other medical history.Seven weeks after initiation of imatinib, she was admitted to the hospital because of abdominal pain, which was con-
Locoregional Failure 10 Years After Mastectomy and Adjuvant Chemotherapy With or Without Tamoxifen Without Irradiation: Experience of the Eastern Cooperative Oncology Group
Authors: Abram Recht, Robert Gray, Nancy E. Davidson, Barbara L. Fowble, Lawrence J. Solin, Frank J. Cummings, Geoffrey Falkson, Hendrika C. Falkson, Samuel G. Taylor, Douglass C. Tormey
Journal: Journal of Clinical Oncology (1999)

PURPOSE: To assess patterns of failure and how selected prognostic and treatment factors affect the risks of locoregional failure (LRF) after mastectomy in breast cancer patients with histologically involved axillary nodes treated with chemotherapy with or without tamoxifen without irradiation. PATIENTS AND METHODS: The study population consisted of 2,016 patients entered onto four randomized trials conducted by the Eastern Cooperative Oncology Group. The median follow-up time for patients without recurrence was 12.1 years (range, 0.07 to 19.1 years). RESULTS: A total of 1,099 patients (55%) experienced disease recurrence. The first sites of failure were as follows: isolated LRF, 254 (13%); LRF with simultaneous distant failure (DF), 166 (8%); and distant only, 679 (34%). The risk of LRF with or without simultaneous DF at 10 years was 12.9% in patients with one to three positive nodes and 28.7% for patients with four or more positive nodes. Multivariate analysis showed that increasing tumor size, increasing numbers of involved nodes, negative estrogen receptor protein status, and decreasing number of nodes examined were significant for increasing the rate of LRF with or without simultaneous DF. CONCLUSION: LRF after mastectomy is a substantial clinical problem, despite the use of chemotherapy with or without tamoxifen. Prospective randomized trials will be necessary to estimate accurately the potential disease-free and overall survival benefits of postmastectomy radiotherapy for patients in particular prognostic subgroups treated with presently used and future systemic therapy regimens.
The Effect of Benign Lower Urinary Tract Symptoms on Subsequent Prostate Cancer Testing and Diagnosis
Authors: Christopher J. Weight, Simon P. Kim, Debra J. Jacobson, Michaela E. McGree, Stephen A. Boorjian, R. Houston Thompson, Bradley C. Leibovich, R. Jeffrey Karnes, Jennifer St. Sauver
Journal: European Urology (2013)
Cooperative inhibitory effect of ZD1839 (Iressa) in combination with trastuzumab (Herceptin) on human breast cancer cell growth
Authors: N. Normanno, M. Campiglio, A. De Luca, G. Somenzi, M. Maiello, F. Ciardiello, L. Gianni, D.S. Salomon, S. Menard
Journal: Annals of Oncology (2002)
COPD dashboard: about official Documents, Authors, Science, Health status and BOARDs
Authors: H. J. Schünemann
Journal: European Respiratory Journal (2008)

Readers of this issue of the European Respiratory Journal ( ERJ ) should review the important document that it features, which is a result of a continuing and successful tradition of joint Task Forces of the European Respiratory Society (ERS) and the American Thoracic Society (ATS) 1. The document will guide investigators and others making decisions about the use and application of outcome measures in order to reduce the burden of chronic obstructive pulmonary disease (COPD) in individual patients and groups of patients alike. The purpose of this editorial is to describe some general aspects related to document development for joint Task Forces and to comment on the content of the document by Cazzola et al. 1. While the opinion, expertise and experiences described here have led me to apply for the position of documents editor for the ATS and perhaps influenced, at least in part, my selection for this position, they should not be equated with official ATS policy. This editorial reflects an individual's view on documents including those that guide clinical practice.

Given the standing of the ATS and the ERS in the field of respiratory, critical care and sleep medicine, the document featured in this issue of the ERJ is an approved statement of the Societies and, thus, becomes official and authoritative by default. As a result of the responsibility that the Societies therefore carry, but also just by nature of their stature, the principle aim of these official documents must be to provide evidence-based information to support evidence-based decision-making in healthcare. In the current climate of increased scrutiny of clinical practice guidelines and other official statements, what are the best strategies to ensure that documents are indeed based on the best available evidence?

Evidence can be of very low-to-high quality, which is determined by the risk …
CD24 Controls Expansion and Persistence of Autoreactive T Cells in the Central Nervous System during Experimental Autoimmune Encephalomyelitis
Authors: Xue-Feng Bai, Ou Li, Qunmin Zhou, Huiming Zhang, Pramod S. Joshi, Xincheng Zheng, Yan Liu, Yin Wang, Pan Zheng, Yang Liu
Journal: The Journal of Experimental Medicine (2004)

In the development of experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis (MS), autoreactive T cells must be activated and clonally expand in the lymphoid organs, and then migrate into the central nervous system (CNS) where they undergo further activation. It is unclear whether the autoreactive T cells further expand in the CNS and if so, what interactions are required for this process. We have demonstrated previously that expression by the host cells of the heat-stable antigen (CD24), which was recently identified as a genetic modifier for MS, is essential for their susceptibility to EAE. Here we show that CD24 is essential for local clonal expansion and persistence of T cells after their migration into the CNS, and that expression of CD24 on either hematopoietic cells or nonhematopoietic antigen-presenting cells in the recipient is sufficient to confer susceptibility to EAE.
A 4-year follow-up study of atopic dermatitis therapy with 0·1% tacrolimus ointment in children and adult patients
Authors: S. Reitamo, M. Rustin, J. Harper, K. Kalimo, A. Rubins, F. Cambazard, E.E.A. Brenninkmeijer, C. Smith, J. Berth-Jones, T. Ruzicka, G. Sharpe, A. Taieb
Journal: British Journal of Dermatology (2008)

For the treatment of a chronic disease like atopic dermatitis, sustained tolerability and efficacy of the applied medication are essential.The present open-label, noncomparative study was conducted to obtain information on the long-term safety and efficacy of 0.1% tacrolimus ointment.Patients aged 2 years or older with an affected body surface area of more than 5%, who previously participated in a clinical trial on tacrolimus ointment, were eligible for this study. The treatment area was defined by the investigator at study entry. Both children and adults applied continuously or intermittently 0.1% tacrolimus ointment twice daily during episodes of active disease plus an additional week after remission over a follow-up period of up to 4 years.The intent-to-treat population comprised 782 patients, with a median age of 22 years (range 2-72). Patients remained in the study for up to 4 years. Approximately half of the patients discontinued the study prematurely; the median follow-up was 1422 days. Median tacrolimus ointment use was 31.2 g during the first week; ointment use decreased during the first year and then remained stable for the remainder of the study. The median cumulative tacrolimus use was 271.5 g at month 6, 462.5 g at month 12, 739.9 g at month 24, 1029.3 g at month 36 and 1320.8 g at month 48. Altogether 51.8% of patients discontinued the study prematurely; the main reasons were withdrawal of consent (13.3%), loss to follow-up (11.3%) and lack of efficacy (9.4%). Adverse events led to study discontinuation in 3.7% of the patients. The most frequent application site events were skin burning and pruritus. These events were most often reported in adult patients during the initial treatment period; prevalence decreased after the first week and remained at a low level throughout the study. Nonapplication site events occurred with stable incidences throughout the study period. In general, calculated daily hazard rates did not indicate an increased risk of adverse events with prolonged treatment. The total affected body surface area decreased substantially upon onset of treatment and efficacy of treatment was maintained until the end of the study with smaller but continuous improvements throughout the follow-up period. Overall, 75% of the patients and 76% of the investigators rated their satisfaction with the treatment as excellent, very good or good at the end of the study or at the time of premature discontinuation.The safety profile of intermittent or continuous long-term application of 0.1% tacrolimus ointment for up to 4 years was consistent with that which has been established from shorter studies and gave no reason for concern. In addition, 0.1% tacrolimus ointment demonstrated sustained efficacy as reflected by the expression of high satisfaction with treatment by both patients and investigators.
Spatiotemporal Control of Opioid Signaling and Behavior
Authors: Edward R. Siuda, Bryan A. Copits, Martin J. Schmidt, Madison A. Baird, Ream Al-Hasani, William J. Planer, Samuel C. Funderburk, Jordan G. McCall, Robert W. Gereau, Michael R. Bruchas
Journal: Neuron (2015)