tbuckley/cabot-search huggingface dataset:
Multidisciplinary Management of Patients with Advanced Rectal Cancer
Authors: Robert W. Beart
Journal: Clinical Cancer Research (2007)

Abstract The chance of lymph node involvement in T3 and T4 rectal cancers is 20% to 60%, a risk sufficiently high that most clinicians favor mesorectal excision rather than less aggressive approaches. Patients who have a complete clinical response of the primary lesions to neoadjuvant therapy may represent a special case. Total mesorectal excision can be accomplished without sacrifice of the anal sphincters, and continence can be preserved. Evolving understanding of patterns of tumor spread and mechanisms of anal continence have resulted in increased use of continence-preserving procedures. Removal of the anal sphincters seems to be advantageous only if the sphincters are directly involved. A few small series suggest that a segmental sphincter resection could result in good local control and continence preservation, even if the sphincters are involved. Areas of controversy currently include the role of neoadjuvant therapy for high rectal lesions, the role of lateral lymph node dissection, and methods of improving anal continence after rectal resection.
When a Patient Chooses Wisely
Authors: Anna Petroni
Journal: JAMA Internal Medicine (2013)

I was diagnosed as having progressive multiple sclerosis more than 30 years ago, and now I am almost 77 years old. My legs have been affected, and I lose my balance occasionally. I use a walker to get around but not for long distances. When I go to the grocery store, I use one of the electric carts.
Metabolic substrates alter attachment and differentiated functions of proximal tubule cell culture.
Authors: M J Tang, R L Tannen
Journal: Journal of the American Society of Nephrology (1994)

Proximal tubules cultured in vitro gradually lose their differentiated functions. Because standard culture media lacks several substrates important for renal proximal tubule oxidative metabolism, whether a mixture of substrates including butyrate, alanine, and lactate (BAL) would modify growth and/or differentiated function of proximal tubular cells in culture was examined. Tubules cultured in media supplemented with 2 mM butyrate, alanine, and lactate exhibited enhanced attachment but did not exhibit an altered growth rate. Higher levels of phosphoenolpyruvate carboxykinase and leucine-amino peptidase were sustained, although these activities were still diminished in comparison with that in fresh tubules. Sodium-dependent glucose uptake and dome formation--other reflections of epithelial cell differentiated function--also were enhanced. These studies demonstrate that the substrates used to culture proximal tubules can modify both their attachment and their manifestation of differentiated function in culture.
Hemoglobin-Independent Organ Protection by EPO in Humans
Authors: H. Ehrenreich, D. Hinze-Selch, S. Stawicki, C. Aust, S. Knolle-Veentjer, S. Wilms, G. Heinz, S. Erdag, H. Jahn, D. Degner, M. Ritzen, A. Mohr, M. Wagner, U. Schneider, M. Bohn, M. Huber, A. Czernik, T. Pollma[Combining Diaeresis]cher, W. Maier, A.-L. Sire[Combining Acute Accent]n, J. Klosterko[Combining Diaeresis]tter, P. Falkai, E. Ru[Combining Diaeresis]ther, J.B. Aldenhoff, H. Krampe
Journal: Journal of the American Society of Nephrology (2006)

Improvement of Cognitive Functions in Chronic Schizophrenic Patients by Recombinant Human Erythropoietin.
PTCH codon 1315 polymorphism and risk for nonmelanoma skin cancer
Authors: A. Asplund, A.C. Gustafsson, N.M. Wikonkal, A. Sela, D.J. Leffell, K. Kidd, J. Lundeberg, D.E. Brash, F. Ponten
Journal: British Journal of Dermatology (2005)

The PTCH tumour suppressor gene is involved in the development of nearly all basal cell carcinomas (BCCs) of the skin and a fraction of squamous cell carcinomas (SCCs). A nonconservative Pro/Leu nucleotide polymorphism within PTCH exon 23 at codon 1315 was recently reported to be potentially important for the development of breast epithelial cell cancers. Objectives Accordingly, the status of PTCH codon 1315 was analysed for a possible association with the development of nonmelanoma skin cancers (NMSCs) in a pilot study. Because skin cancer risk is affected by specific population-dependent phenotypes such as skin and hair colour, codon 1315 was also analysed for normal allele frequency variation in human populations having differing extents of eumelanin vs. phaeomelanin.The single nucleotide polymorphism in codon 1315 of the human PTCH gene was analysed in genomic DNA from six different populations comprising 472 blood samples and from 170 patients in four different categories with NMSC. Polymerase chain reaction and pyrosequencing were used to determine the allele frequencies. Allelic loss was furthermore determined in tumours following microdissection.The Pro/Pro genotype frequency ranged from 30% to 65% between populations, with a significant trend for a reduced frequency of the Pro/Pro genotype in populations having lighter pigmentation (P = 0.020). Pro/Pro frequency showed an increasing trend with increasing tumour case severity (P = 0.027). In 260 samples from 180 Swedish patients with NMSC and a control group of 96 healthy ethnically matched volunteers, no statistically significant pairwise differences between groups were detected in the PTCH codon 1315 allelic distribution, neither was a difference seen for multiple or early onset cases of BCC in the Swedish population. In Swedish patients with single tumours, allelic loss (loss of heterozygosity) was observed in 20 of 30 (67%) patients with BCC and four of 22 (18%) patients with SCC, with no preference in the allele lost. In contrast, the Pro/Pro genotype was frequent in seven U.S. patients having multiple independent BCCs. One of these patients was heterozygous, enabling allelic loss studies. Of 20 independent tumours, 11 had lost an allele; 10 of the 11 had lost Leu, suggesting nonrandom loss that favoured retention of Pro (P = 0.0059).Our results indicate an association between the eumelanin-to-phaeomelanin shift and a shift from the Pro/Pro genotype to Leu-containing genotypes. Failure to lose Pro during the shift to phaeomelanin may be associated with an increased population risk for BCC and increased individual risk for multiple BCC. During development of a tumour, the effect of Pro may be magnified by loss of the Leu allele.
Surfactant Protein D Regulates Airway Function and Allergic Inflammation through Modulation of Macrophage Function
Authors: Katsuyuki Takeda, Nobuaki Miyahara, Yeong-Ho Rha, Christian Taube, Eun-Seok Yang, Anthony Joetham, Taku Kodama, Annette M. Balhorn, Azzeddine Dakhama, Catherine Duez, Amanda J. Evans, Dennis R. Voelker, Erwin W. Gelfand
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

The lung collectin surfactant protein D (SP-D) is an important component of the innate immune response but is also believed to play a role in other regulatory aspects of immune and inflammatory responses within the lung. The role of SP-D in the development of allergen-induced airway inflammation and hyperresponsiveness (AHR) is not well defined. SP-D levels progressively increased up to 48 hours after allergen challenge of sensitized mice and then subsequently decreased. The levels of SP-D paralleled the development of airway eosinophilia and AHR. To determine if this association was functionally relevant, mice were administered rat SP-D (rSP-D) intratracheally. When given to sensitized mice before challenge, AHR and eosinophilia were reduced by rSP-D in a dose-dependent manner but not by mutant rSP-D. rSP-D administration resulted in increased levels of interleukin (IL)-10, IL-12, and IFN-gamma in bronchoalveolar lavage fluid and reduced goblet cell hyperplasia. Culture of alveolar macrophages together with SP-D and allergen resulted in increased production of IL-10, IL-12, and IFN-gamma. These results indicate that SP-D can (negatively) regulate the development of AHR and airway inflammation after airway challenge of sensitized mice, at least in part, by modulating the function of alveolar macrophages.
A British Medical Association Lecture on THE LOCALIZATION OF ABDOMINAL PAIN
Authors: V. Z. Cope
Journal: BMJ (1930)

ECA_."G_3A_ 6 then perforce we shall have to limit our ambitions and discover more economiical.methods of attaininig 0111 eiic(.s.As yet w-e ar-e niot within siglht of such a crisis.(o-ordhiacftion is a Necessary Con stititelit of Pro qrelss.'Up to tlis poinit I have beeni discussinig tlle imianifesta- tions of p)rogress as seeni in tlhe Hailey Street quiarters of ouir grgeater cities, in our medical schlools anid hosl)itals, and InI ouir subsidize(d laboratories.In all thr ee qiua.-rterswie finid meidical ineai pressing forward.s; in seareli of new souIrces of knowN-ledge, anid as they pres.sbecom1inig sulbdiid(led iliole anid milore inlto separate groups.We lhave, in thlese in- stances, been studying oniil one of the factors of miiedical p)rogress; tlhere is aniother wlich Spencer perceived w^-as eqiually inievitable.Specialization, if it work(ed unclhecke(l, w-ould tenid to break ul) our medical forces anid dissipate their strength in confusionl.Henicew,e finid, ill the proogress of ouir profession, just as in the evolultioni of the e-arlier aiiiinial organizations, there como into play certain unifv- inig inifluences, exeited by a crude foirmii of nervous systemll.Ani astuite student of the evolutioln of medeicinie, if lie had v-isited London in 1880, would ldave l)erceived that this nieirve centre lhad already come inito being in the form of a Delp)artment of State, situated in Whlitehlall-the Local Government Board.He wouild hlave founiid London already div-ided into fifty-two districts-each with a miiedical officer of health-controlled more or less indirectly by tlle niervous centre in Whlitelhall.All EMiland, 'Yales, and Scotland hiad thein become so div-ided, anid a muitiltitude of inedical m11en1, MO-St of whom, wlhile still continutiing to attenid to their patienits served also as members of a htealth airmy, and cari-ied out a policv formliated or suiggested in Wh'liitehall.Tihe Pr ocess of lnte jttieao).ITnification or initegrationi is just as niecessar-y ani inigr-e-(lient of " proclress ' as specializationt or sep)aration.The influtences wAhich teiid to bring about the unification of our medical armiiy, like mnost of the inivenitionis which alter
Obstructive sleep disorders in children with allergic rhinitis
Authors: Mirjana Turkalj, Davor Plavec, Daria Kucic, Romana Gjergja-juraski
Journal: European Respiratory Journal (2012)

Background:  Allergic rhinitis (AR) is the most prevalent chronic disease in children, associated with impairments in quality of life, sleep disorders, emotional problems, and impairment in activities. AR can induce medical complications, learning problems and sleep-related complaints, such as obstructive sleep apnea syndrome (OSAS). OSAS is characterized by repeated events of partial or complete upper airway obstruction during sleep. The aim of this study was to estimate the prevalence of obstructive sleep apnea in children with seasonal and perennial allergic rhinitis together with predictive factors.   Methods: We studied children (age 5-17 yrs, N=47) with allergic rhinitis that underwent sleep study using complete polysomnography (PSG) according to standardized protocol. All patients underwent detailed medical and family history, physical examination including ENT examination, and an array of diagnostic tests (skin-prick test, total and specific IgE, cytology of the nasal mucosa, complete and differential blood counts) and Children9s Sleep Habits Questionnaire.   Results  from our study showed that almost half (46%) of the examined children with allergic rhinitis suffer from obstructive sleep apnea (88% had obstructive hypopnea). Obstructive sleep apnea was significantly associated with: perennial allergies (p=0.018) and nasal congestion (p=0.026), showing a significantly higher apnea/hypopnea index (AHI) in the group with perennial allergy (p   Conclusion:  Results of this study indicate that significant number of children with allergic rhinitis may develop obstructive sleep apnea. Perennial AR is an independent risk factor for OSAS in children probably because nasal congestion is the most prevalent symptom of it.
Recombinant Leukocyte A Interferon: Pharmacokinetics, Single-Dose Tolerance, and Biologic Effects in Cancer Patients
Authors: Jordan U. Gutterman, Seymour Fine, Jorge Quesada, Sandra J. Horning, Jedd F. Levine, Raymond Alexanian, Leon Bernhardt, Michael Kramer, Herbert Spiegel, Wayne Colburn, Patrick Trown, Thomas Merigan, Zofia Dziewanowski
Journal: Annals of Internal Medicine (1982)

Sixteen patients with advanced cancer were treated with recombinant-DNA-produced pure leukocyte A interferon (IFLrA) intramuscularly in doses ranging from 3 to 198 X 10(6) units. with interval periods of 72 to 96 hours between doses. At the two lowest doses of 3 and 9 million units, there was a cross-over evaluation between IFLrA and partially pure leukocyte interferon (IFN-C) produced from human cells. THe maximum observed serum concentration of IFLrA measured by enzyme immunoassay and bioassay increased with increasing doses. The mean serum concentrations of IFLrA and IFN-C were similar. Clinical effects produced by IFLrA and IFN-C were similar, including fever, chills, myalgias, headache fatigue, and reversible leukopenia and granulocytopenia. Eight patients had transient and mild numbness of the hands or feet, or both. Three patients developed low titers of antibody to IFLrA, Seven of 16 patients showed objective evidence of tumor regression during the study.
Insulin Therapy in People With Type 2 Diabetes: Opportunities and Challenges?
Authors: Philip Home, Matthew Riddle, William T. Cefalu, Clifford J. Bailey, Reinhard G. Bretzel, Stefano del Prato, Derek Leroith, Guntram Schernthaner, Luc van Gaal, Itamar Raz
Journal: Diabetes Care (2014)

Given the continued interest in defining the optimal management of individuals with type 2 diabetes, the Editor of Diabetes Care convened a working party of diabetes specialists to examine this topic in the context of insulin therapy. This was prompted by recent new evidence on the use of insulin in such people. The group was aware of evidence that the benefits of insulin therapy are still usually offered late, and thus the aim of the discussion was how to define the optimal timing and basis for decisions regarding insulin and to apply these concepts in practice. It was noted that recent evidence had built upon that of the previous decades, together confirming the benefits and safety of insulin therapy, albeit with concerns about the potential for hypoglycemia and gain in body weight. Insulin offers a unique ability to control hyperglycemia, being used from the time of diagnosis in some circumstances, when metabolic control is disturbed by medical illness, procedures, or therapy, as well as in the longer term in ambulatory care. For those previously starting insulin, various other forms of therapy can be added later, which offer complementary effects appropriate to individual needs. Here we review current evidence and circumstances in which insulin can be used, consider individualized choices of alternatives and combination regimens, and offer some guidance on personalized targets and tactics for glycemic control in type 2 diabetes.
Memories of Childhood Abuse: Dissociation, Amnesia, and Corroboration
Authors: James A. Chu, Lisa M. Frey, Barbara L. Ganzel, Julia A. Matthews
Journal: American Journal of Psychiatry (1999)

This study investigated the relationship between self-reported childhood abuse and dissociative symptoms and amnesia. The presence or absence of corroboration of recovered memories of childhood abuse was also studied.Participants were 90 female patients admitted to a unit specializing in the treatment of trauma-related disorders. Participants completed instruments that measured dissociative symptoms and elicited details concerning childhood physical abuse, sexual abuse, and witnessing abuse. Participants also underwent a structured interview that asked about amnesia for traumatic experiences, the circumstances of recovered memory, the role of suggestion in recovered memories, and independent corroboration of the memories.Participants reporting any type of childhood abuse demonstrated elevated levels of dissociative symptoms that were significantly higher than those in subjects not reporting abuse. Higher dissociative symptoms were correlated with early age at onset of physical and sexual abuse and more frequent sexual abuse. A substantial proportion of participants with all types of abuse reported partial or complete amnesia for abuse memories. For physical and sexual abuse, early age at onset was correlated with greater levels of amnesia. Participants who reported recovering memories of abuse generally recalled these experiences while at home, alone, or with family or friends. Although some participants were in treatment at the time, very few were in therapy sessions during their first memory recovery. Suggestion was generally denied as a factor in memory recovery. A majority of participants were able to find strong corroboration of their recovered memories.Childhood abuse, particularly chronic abuse beginning at early ages, is related to the development of high levels of dissociative symptoms including amnesia for abuse memories. This study strongly suggests that psychotherapy usually is not associated with memory recovery and that independent corroboration of recovered memories of abuse is often present.
The PDL1-PD1 Axis Converts Human T <sub>H</sub> 1 Cells into Regulatory T Cells
Authors: Shoba Amarnath, Courtney W. Mangus, James C. M. Wang, Fang Wei, Alice He, Veena Kapoor, Jason E. Foley, Paul R. Massey, Tania C. Felizardo, James L. Riley, Bruce L. Levine, Carl H. June, Jeffrey A. Medin, Daniel H. Fowler
Journal: Science Translational Medicine (2011)

The inhibitory ligand PDL1 transforms immune cells from attackers into regulators.
Phase III Trial Comparing Oral S-1 Plus Carboplatin With Paclitaxel Plus Carboplatin in Chemotherapy-Naïve Patients With Advanced Non–Small-Cell Lung Cancer: Results of a West Japan Oncology Group Study
Authors: Isamu Okamoto, Hiroshige Yoshioka, Satoshi Morita, Masahiko Ando, Koji Takeda, Takashi Seto, Nobuyuki Yamamoto, Hideo Saka, Kazuhiro Asami, Tomonori Hirashima, Shinzoh Kudoh, Miyako Satouchi, Norihiko Ikeda, Yasuo Iwamoto, Toshiyuki Sawa, Masaki Miyazaki, Kenji Tamura, Takayasu Kurata, Masahiro Fukuoka, Kazuhiko Nakagawa
Journal: Journal of Clinical Oncology (2010)

Purpose The primary goal of this open-label, multicenter, randomized phase III trial was to determine whether treatment with carboplatin plus the oral fluoropyrimidine derivative S-1 was noninferior versus that with carboplatin plus paclitaxel with regard to overall survival (OS) in chemotherapy-naive patients with advanced non–small-cell lung cancer (NSCLC). Patients and Methods A total of 564 patients were randomly assigned to receive either carboplatin (area under the curve, 5) on day 1 plus oral S-1 (40 mg/m 2 twice per day) on days 1 to 14 or carboplatin (area under the curve, 6) plus paclitaxel (200 mg/m 2 ) on day 1 every 21 days. Results At the planned interim analysis, with a total of 268 death events available, the study passed the O'Brien-Fleming boundary of 0.0080 for a positive result and noninferiority of carboplatin and S-1 compared with carboplatin and paclitaxel was confirmed for OS (hazard ratio, 0.928; 99.2% CI, 0.671 to 1.283). Median OS was 15.2 months in the carboplatin and S-1 arm and 13.3 months in the carboplatin and paclitaxel arm, with 1-year survival rates of 57.3% and 55.5%, respectively. Rates of leukopenia or neutropenia of grade 3/4, febrile neutropenia, alopecia, and neuropathy were more frequent in the carboplatin and paclitaxel arm, whereas thrombocytopenia, nausea, vomiting, and diarrhea were more common in the carboplatin and S-1 arm. The carboplatin and S-1 arm had significantly more dose delays than the carboplatin and paclitaxel arm. Conclusion Oral S-1 with carboplatin was noninferior in terms of OS compared with carboplatin and paclitaxel in patients with advanced NSCLC, and is thus a valid treatment option.
Comorbidities in patients with COPD and their impact on COPD course
Authors: Izabela Kuprys-Lipinska, Piotr Kuna
Journal: European Respiratory Journal (2014)

In 2012 the nationwide survey of COPD subjects was conducted in Poland. The purpose of the analysis presented here is to assess the prevalence and the type of comorbidities and their impact on patients9 health and COPD course in Polish population. Data were collected from patients by their physicians during routine visit with usage of questionnaire specifically prepared for this study. The study involved 10,365 outpatients over 35 years of age, with diagnosed COPD, current or past smokers. Representative sample of 2,967 questionnaires were randomly drawn for the statistical analysis. The mean age of responders was 61.15 ± 10.25 years, 33.98% of participants were women, 56.73% were current smokers. COPD grade A was recognized in 52.67%, B — 10.72%, C — 16.16% and D — 20 45%. Most subjects (73.89%) had at least one additional disease, more frequently ex-smokers. Average of comorbidities was 1,61 and increase with age, ex-smoker status, COPD grade, number of exacerbation and hospitalization due to COPD. Successively cardiovascular diseases (HA), diabetes mellitus,gastroesophageal reflux and neoplastic diseases were the most frequent. Two or more comorbidities increase the probability of COPD exacerbations and hospitalizations more than 3 times (respectively OR=3.265 and 3.445, p Study funded by Polpharma .
In the academic game, a higher degree is the qualifying standard, and every paper is a personal best
Authors: Domhnall Macauley
Journal: British Journal of Sports Medicine (2000)

Warm upWhere we are, how we do it, where we are going, and what others do.This issue sets out to create a benchmark in education.With many important recent developments in sports medicine education in the UK, we invited experts to address some of the current issues, look at methods of delivery, and give a vision of the future.To put these developments in context we present snapshots from Finland, Canada, Germany, and Australia (pages 235-244).The final stage of our educational odyssey is a survey of teaching in undergraduate medical schools (page 244) and a short paper describing the qualities required in a sports medicine specialist (page 243).Elsewhere in this issue, we look at common sporting topics from unusual angles.Running and relaxation seem to fit well together but research into runners who practise relaxation techniques is unexpected (page 268).Osteoporosis and oestrogen are often linked but examining bone mineral density and testosterone in male runners is a new