tbuckley/cabot-search huggingface dataset:
Can continuous positive airway pressure reduce the incidence of cardiovascular disease in non-sleepy patients with obstructive sleep apnoea?
Authors: Abiramy Jeyabalan
Journal: Thorax (2012)

Can continuous positive airway pressure reduce the incidence of cardiovascular disease in non-sleepy patients with obstructive sleep apnoea?An association has been demonstrated between obstructive sleep apnoea (OSA) and both hypertension and cardiovascular events.Although observational studies suggest that treatment with continuous positive airways pressure (CPAP) can reduce blood pressure and the incidence of fatal and non-fatal cardiovascular events in patients with severe and moderate OSA, short term randomised controlled trials have failed to demonstrate a similar effect in non-sleepy patients.The primary objective of this large, multicentre randomised controlled trial was to investigate the effect of CPAP on the incidence of hypertension and cardiovascular events in nonsleepy patients (Epworth Sleepiness Score of ≤10, range 0-24) with OSA (apnoea-hypopnoea index of 20 h -1 or greater).The secondary objective was to assess an association between OSA severity and the incidence of hypertension or cardiovascular events.Although a statistically significant reduction in the incidence of hypertension and cardiovascular events was not observed in the treatment group, there was a reduction in the incidence density ratio in a subgroup of patients with better adherence to treatment.The study adds to the debate regarding potential cardiovascular benefits of CPAP in OSA and suggests that adequate adherence to treatment may result in a reduction in the incidence of hypertension or cardiovascular events in non-sleepy patients.Further larger studies with longer follow up should be conducted to confirm the results.
Studies of Experimental Bladder Carcinoma in Fischer 344 Female Rats. I. Induction of Tumors With Diet Low in Vitamin B&lt;sub&gt;6&lt;/sub&gt; Containing &lt;italic&gt;N&lt;/italic&gt;-2-Fluorenylacetamide After Single Dose of Cyclophosphamide&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Leopold G. Koss, Pedro Lavin
Journal: JNCI Journal of the National Cancer Institute (1971)

Carcinomas of the bladder were induced in Fischer 344 female rats pretreated with a single intraperitoneal dose of cyclophosphamide and then fed a pyridoxine-deficient diet containing 600 mg/kg of N-2-fluorenylacetamide (FAA). Bladder carcinomas were first observed after 6¾ months on this diet; there was no correlation between the dose of cyclophosphamide (from 100–200 mg/kg) and the timing of the beginning of the diet (72 hr or 2 wk after injection). Carcinoma in situ comparable to that in man was not observed as a stage before formation of invasive carcinoma. However, it was noted later in the experiment in the surface epithelium adjacent to the invasive carcinoma. Transitional cell carcinomas originated from hyperplastic epithelium, squamous carcinomas from metaplastic squamous epithelium, and the infrequent papillary carcinomas from papillomas. Formation of papillomas was triggered by epithelial hyperplasia. The role of cyclophosphamide in the genesis of bladder cancer and reasons for absence of carcinoma in situ during the early stages of cancerogenesis are discussed.
Should Sulfonylureas Remain an Acceptable First-Line Add-on to Metformin Therapy in Patients With Type 2 Diabetes? No, It’s Time to Move On!
Authors: Saul Genuth
Journal: Diabetes Care (2014)

Since their introduction to clinical practice in the 1950s, sulfonylureas have been widely prescribed for use in patients with type 2 diabetes. Of all the other medications currently available for clinical use, only metformin has been used more frequently. However, several new drug classes have emerged that are reported to have equal glucose-lowering efficacy and greater safety when added to treatment of patients in whom metformin monotherapy is no longer sufficient. Moreover, current arguments also suggest that the alternative drugs may be superior to sulfonylureas with regard to the risk of cardiovascular complications. Thus, while there is universal agreement that metformin should remain the first-line pharmacologic therapy for those in whom lifestyle modification is insufficient to control hyperglycemia, there is no consensus as to which drug should be added to metformin. Therefore, given the current controversy, we provide a Point-Counterpoint on this issue. In the preceding point narrative, Dr. Abrahamson provides his argument suggesting that avoiding use of sulfonylureas as a class of medication as an add-on to metformin is not appropriate as there are many patients whose glycemic control would improve with use of these drugs with minimal risk of adverse events. In the counterpoint narrative below, Dr. Genuth suggests there is no longer a need for sulfonylureas to remain a first-line addition to metformin for those patients whose clinical characteristics are appropriate and whose health insurance and/or financial resources make an alternative drug affordable. —William T. Cefalu Editor in Chief, Diabetes Care
CARRIER FUNCTION IN ANTI-HAPTEN IMMUNE RESPONSES
Authors: William E. Paul, David H. Katz, Edmond A. Goidl, Baruj Benacerraf
Journal: The Journal of Experimental Medicine (1970)

Transfer of live lymphoid cells from BGG-immunized strain 2 guinea pigs into syngeneic animals primed with DNP-OVA prepares the recipients for a markedly enhanced secondary anti-DNP antibody response upon challenge with DNP-BGG. This phenomenon has been demonstrated when the recipients were challenged 1 day after cell transfer, but it was considerably more striking when an interval of 6 days was allowed between transfer of cells and challenge with antigen. As demonstrated in the preceding paper (6), BGG preimmunization enhanced anti-DNP antibody responses to challenge with DNP-BGG. An analysis of the characteristics of substances to which preimmunization was effective in enhancing subsequent anti-hapten responses was made. It was shown that preimmunization of strain 13 guinea pigs with a copolymer of glutamic acid and lysine (GL), to which these animals are genetically unable to accord an immune response, failed to prepare them for an enhanced anti-DNP response to DNP-GL. Tolerance to BGG specifically abrogated the capacity of subsequent BGG immunization to prepare DNP-OVA primed rabbits for an enhanced anti-DNP response to DNP-BGG. Sensitization of animals to haptens by preimmunization with hapten-protein conjugates failed to prepare them for enhanced primary or secondary antibody responses to other determinants associated with that hapten on a different carrier. These studies indicate that the enhancing effect of carrier preimmunization reflects a cooperative interaction between lymphoid cells specific for carrier and cells specialized for haptenic determinants. Furthermore, the capacity of a substance to behave as a carrier requires more than its possession of a variety of antigenic determinants.
Use of mesalazine slow release suppositories 1 g three times per week to maintain remission of ulcerative proctitis: a randomised double blind placebo controlled multicentre study
Authors: P Marteau, J Crand, M Foucault, J-C Rambaud
Journal: Gut (1998)

Background —Daily administration of rectal formulations of mesalazine is effective in preventing relapse of ulcerative proctitis. Maintenance of remission with lower doses would be an advantage. Aim —The efficacy of mesalazine suppositories (Pentasa) 1 g three times a week v placebo to maintain remission in patients with cryptogenetic proctitis was studied. Methods —Ninety five patients with cryptogenetic proctitis were randomised within two weeks of remission to receive for one year or until relapse three suppositories per week of either Pentasa (n=48) or placebo (n=47). In the case of a relapse, the patients received one suppository/day. Results —It was found that 25 of 48 subjects v 18 of 47 remained in remission in the mesalazine and placebo groups respectively. The relapse rate was lower in the mesalazine group for the following time intervals: 0–90 days (19% v 38%, p=0.035), 0–180 days (29% v 54%, p=0.017), 0–270 days (38% v 60%, p=0.031), and 0–365 days (48% v 62%, p=0.18). Treatment of relapse with one suppository/day induced remission in 11 of 18 and 2 of 26 patients in the mesalazine and placebo groups respectively (p=0.001). Overall, 61% v 28% patients remained in the protocol and were in remission at one year (p=0.001). Tolerance was good. Conclusion —Mesalazine suppositories 1 g three times a week are effective for preventing relapses of cryptogenetic proctitis. Increasing the dose to 1 g/day is effective in a high proportion of subjects who relapsed.
Points: Human trypanosomiasis in Africa
Authors: N M. Davidson
Journal: BMJ (1981)

liams's letter (10 October, p 987) about the management of gastrointestinal bleeding, and agree entirely with your comment.I would take exception, however, to his last sentence, which implies that an "alcoholic binge" may lead to an upper gastrointestinal haemorrhage and that this does not require investigation.It is our experience that when alcoholic excess leads to a massive bleed there is usually a chronic underlying cause, and I would suggest that these patients most certainly should be investigated.
Mitochondrial Topoisomerase I (Top1mt) Is a Novel Limiting Factor of Doxorubicin Cardiotoxicity
Authors: Salim Khiati, Ilaria Dalla Rosa, Carole Sourbier, Xuefei Ma, V. Ashutosh Rao, Leonard M. Neckers, Hongliang Zhang, Yves Pommier
Journal: Clinical Cancer Research (2014)

Abstract Purpose: Doxorubicin is one of the most effective chemotherapeutic agents. However, up to 30% of the patients treated with doxorubicin suffer from congestive heart failure. The mechanism of doxorubicin cardiotoxicity is likely multifactorial and most importantly, the genetic factors predisposing to doxorubicin cardiotoxicity are unknown. On the basis of the fact that mtDNA lesions and mitochondrial dysfunctions have been found in human hearts exposed to doxorubicin and that mitochondrial topoisomerase 1 (Top1mt) specifically controls mtDNA homeostasis, we hypothesized that Top1mt knockout (KO) mice might exhibit hypersensitivity to doxorubicin. Experimental Design: Wild-type (WT) and KO Top1mt mice were treated once a week with 4 mg/kg doxorubicin for 8 weeks. Heart tissues were analyzed one week after the last treatment. Results: Genetic inactivation of Top1mt in mice accentuates mtDNA copy number loss and mtDNA damage in heart tissue following doxorubicin treatment. Top1mt KO mice also fail to maintain respiratory chain protein production and mitochondrial cristae ultrastructure organization. These mitochondrial defects result in decreased O2 consumption, increased reactive oxygen species production, and enhanced heart muscle damage in animals treated with doxorubicin. Accordingly, Top1mt KO mice die within 45 days after the last doxorubicin injection, whereas the WT mice survive. Conclusions: Our results provide evidence that Top1mt, which is conserved across vertebrates, is critical for cardiac tolerance to doxorubicin and adaptive response to doxorubicin cardiotoxicity. They also suggest the potential of Top1mt single-nucleotide polymorphisms testing to investigate patient susceptibility to doxorubicin-induced cardiotoxicity. Clin Cancer Res; 20(18); 4873–81. ©2014 AACR.
Natural Killer Receptors on CD8 T Cells and Natural Killer Cells from Different HLA-C Phenotypes in Melanoma Patients
Authors: José A. Campillo, Jorge A. Martínez-Escribano, M. Rosa Moya-Quiles, Luis A. Marín, Manuel Muro, Natalia Guerra, Antonio Parrado, Matilde Campos, José F. Frías, Alfredo Minguela, Ana M. García-Alonso, María Rocío Álvarez-López
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Because immune mechanisms involved in cutaneous melanoma have not been fully elucidated, efforts have been made to achieve prognosis markers and potential targets for immune therapies, but they have not been entirely fruitful thus far. Therefore, the goal of this study was to investigate the involvement of early changes in CD8 T cells and CD56 natural killer (NK) cells expressing NK receptors in different HLA-C dimorphism groups of melanoma patients. Experimental Design: CD8 T cells and CD56 NK cells were analyzed in 41 patients and 39 sex- and age-matched controls with different HLA-C genotypes by flow cytometry. HLA-C dimorphism at position 80 was tested by PCR sequence-specific primers and PCR sequence-specific oligonucleotide to examine whether it could mediate in the emergence of cells expressing killer cell immunoglobulin-like receptors. Results: Thirty-five of 41 patients had benign sentinel node, and showed an imbalance in the absolute number of CD8+DR+ or CD8+CD161+ peripheral blood T cells according to the CD28 coexpression compared with controls. CD8+CD28−CD158a+ T and CD56+CD158a+ NK cells were significantly increased in HLA-CLys80 homozygous nonmetastatic patients, whereas only CD56+CD158a+ NK cells increased in heterozygous ones. An up-regulation of the CD158a KIR receptor was also seen on NK cells but not in T cells of patients at advanced disease stages. Conclusions: This work provides, for the first time, evidence of immune activation in early stages of cutaneous melanoma, together with an increase of cells expressing CD158a in patients bearing the corresponding HLA-C ligand, which may be important to evaluate the disease progression and to use individualized immune therapeutic approaches.
Dissociation of neutrophil emigration and metabolic activity in lobar pneumonia and bronchiectasis
Authors: HA Jones, S Sriskandan, AM Peters, NB Pride, T Krausz, AR Boobis, C Haslett
Journal: European Respiratory Journal (1997)

In animal models of pulmonary inflammation, neutrophils exhibit a dramatic influx of glucose in periods of high metabolic activity. This information was utilized to develop a technique, involving positron emission tomography (PET) of 2-[18F]-fluoro-2-deoxy-D-glucose (18FDG), which measures neutrophil activity in situ. This technique was applied in a comparative study of neutrophil function in patients with acute lobar pneumonia or bronchiectasis. Neutrophil emigration was measured by gamma-scintigraphy of intravenously injected 111In-labelled granulocytes and neutrophil activity determined by PET of 18FDG. Neutrophil emigration was evident in 4 out of 5 bronchiectasis patients, whilst no emigration was apparent in the two pneumonia patients studied, consistent with animal studies showing maximum emigration soon after challenge. In contrast, 18FDG uptake was markedly increased in 4 out of 5 pneumonia patients but not in the patients with bronchiectasis. Localization of radioactivity to neutrophils was confirmed by microautoradiography of lavage fluid in a patient with pneumonia. These results suggest that the elevated uptake of glucose by neutrophils during the inflammatory response is a postmigratory event, most likely reflecting the respiratory burst, and that high levels of neutrophil emigration are not necessarily associated with significantly increased metabolic activity of these cells.
Polyomavirus Infection of Renal Allograft Recipients
Authors: VOLKER NICKELEIT, HANS H. HIRSCH, ISABELLE F. BINET, FRED GUDAT, OLIVER PRINCE, PETER DALQUEN, GILBERT THIEL, MICHAEL J. MIHATSCH
Journal: Journal of the American Society of Nephrology (1999)

Abstract. Polyomavirus (PV) exceptionally causes a morphologically manifest renal allograft infection. Five such cases were encountered in this study, and were followed between 40 and 330 d during persistent PV renal allograft infection. Transplant (Tx) control groups without PV graft infection were analyzed for comparison. Tissue and urine samples were evaluated by light microscopy, immunohistochemistry, electron microscopy, and PCR. The initial diagnosis of PV infection with the BK strain was made in biopsies 9 ± 2 mo (mean ± SD) post-Tx after prior rejection episodes and rescue therapy with tacrolimus. All subsequent biopsies showed persistent PV infection. Intranuclear viral inclusion bodies in epithelial cells along the entire nephron and the transitional cell layer were histologic hallmarks of infection. Affected tubular cells were enlarged and often necrotic. In two patients, small glomerular crescents were found. In 54% of biopsies, infection was associated with pronounced inflammation, which had features of cellular rejection. All patients were excreting PV-infected cells in the urine. PV infection was associated with 40% graft loss (2 of 5) and a serum creatinine of 484 ± 326 μmol/L (mean ± SD; 11 mo post-Tx). Tx control groups showed PV-infected cells in the urine in 5%. Control subjects had fewer rejection episodes ( P &lt; 0.05) and stable graft function ( P = 0.01). It is concluded that a manifest renal allograft infection with PV (BK strain) can persist in heavily immunosuppressed patients with recurrent rejection episodes. PV mainly affects tubular cells and causes necrosis, a major reason for functional deterioration. A biopsy is required for diagnosis. Urine cytology can serve as an adjunct diagnostic tool.
Voltage-Gated Na+ Channel <i>SCN5A</i> Is a Key Regulator of a Gene Transcriptional Network That Controls Colon Cancer Invasion
Authors: Carrie D. House, Charles J. Vaske, Arnold M. Schwartz, Vincent Obias, Bryan Frank, Truong Luu, Narine Sarvazyan, Rosalyn Irby, Robert L. Strausberg, Tim G. Hales, Joshua M. Stuart, Norman H. Lee
Journal: Cancer Research (2010)

Voltage-gated Na(+) channels (VGSC) have been implicated in the metastatic potential of human breast, prostate, and lung cancer cells. Specifically, the SCN5A gene encoding the VGSC isotype Na(v)1.5 has been defined as a key driver of human cancer cell invasion. In this study, we examined the expression and function of VGSCs in a panel of colon cancer cell lines by electrophysiologic recordings. Na(+) channel activity and invasive potential were inhibited pharmacologically by tetrodotoxin or genetically by small interfering RNAs (siRNA) specifically targeting SCN5A. Clinical relevance was established by immunohistochemistry of patient biopsies, with strong Na(v)1.5 protein staining found in colon cancer specimens but little to no staining in matched-paired normal colon tissues. We explored the mechanism of VGSC-mediated invasive potential on the basis of reported links between VGSC activity and gene expression in excitable cells. Probabilistic modeling of loss-of-function screens and microarray data established an unequivocal role of VGSC SCN5A as a high level regulator of a colon cancer invasion network, involving genes that encompass Wnt signaling, cell migration, ectoderm development, response to biotic stimulus, steroid metabolic process, and cell cycle control. siRNA-mediated knockdown of predicted downstream network components caused a loss of invasive behavior, demonstrating network connectivity and its function in driving colon cancer invasion.
Bone mineral density and nutritional status in children with chronic inflammatory bowel disease
Authors: A M Boot, J Bouquet, E P Krenning, S M P F de Muinck Keizer-Schrama
Journal: Gut (1998)

Background —Osteoporosis has been reported in adult patients with inflammatory bowel disease. Aims —To evaluate bone mineral density (BMD), nutritional status, and determinants of BMD in children with inflammatory bowel disease. Patients —Fifty five patients (34 boys and 21 girls, age range 4–18) were studied; 22 had Crohn’s disease and 33 ulcerative colitis. Methods —Lumbar spine and total body BMD, and body composition were assessed by dual energy x ray absorptiometry (DXA). Results were expressed as standard deviation scores (SDS). Lean body mass was also assessed by bioelectrical impedance analysis (BIA). Yearly measurements during two years were performed in 21 patients. Results —The mean SDS of lumbar spine BMD and total body BMD were significantly lower than normal (−0.75 and −0.95, both p&lt;0.001). Height SDS and body mass index SDS were also decreased. The decrease in BMD SDS could not be explained by delay in bone maturation. The cumulative dose of prednisolone correlated negatively with lumbar spine BMD SDS ( r =−0.32, p&lt;0.02). Body mass index SDS correlated positively with total body BMD SDS ( r =0.36, p&lt;0.02). Patients with Crohn’s disease had significantly lower lumbar spine and total body BMD SDS than patients with ulcerative colitis, even after adjustment for cumulative dose of prednisolone. In the longitudinal data cumulative dose of prednisolone between the measurements correlated negatively with the change in lumbar spine and total body BMD SDS. Lean tissue mass measured by DXA had a strong correlation with lean body mass measured by BIA ( r =0.98). Conclusions —Children with inflammatory bowel disease have a decreased BMD. Children with Crohn’s disease have a higher risk of developing osteopaenia than children with ulcerative colitis. Corticosteroid therapy and nutritional status are important determinants of BMD in these patients.
GATA-3 promotes T-cell specification by repressing B-cell potential in pro–T cells in mice
Authors: Marcos E. García-Ojeda, Roel G. J. Klein Wolterink, Fabrice Lemaître, Odile Richard-Le Goff, Milena Hasan, Rudolf W. Hendriks, Ana Cumano, James P. Di Santo
Journal: Blood (2013)
Safety of Intracavernous Bone Marrow-Mononuclear Cells for Postradical Prostatectomy Erectile Dysfunction: An Open Dose-Escalation Pilot Study
Authors: René Yiou, Leila Hamidou, Brigitte Birebent, Dalila Bitari, Philippe Lecorvoisier, Isabelle Contremoulins, Muhieddine Khodari, Anne-Marie Rodriguez, Déborah Augustin, Françoise Roudot-Thoraval, Alexandre de la Taille, Hélène Rouard
Journal: European Urology (2015)
Light-activated tissue bonding for excisional wound closure: a split-lesion clinical trial
Authors: S. Tsao, M. Yao, H. Tsao, F.P. Henry, Y. Zhao, J.J. Kochevar, R.W. Redmond, I.E. Kochevar
Journal: British Journal of Dermatology (2011)

Apposition of wound edges by sutures provides a temporary scaffold and tension support for healing. We have developed a novel tissue-sealing technology, photoactivated tissue bonding (PTB), which immediately crosslinks proteins between tissue planes, thereby sealing on a molecular scale.To determine the effectiveness of PTB for superficial closure of skin excisions and to compare the results with standard epidermal suturing.A split-lesion, paired comparison study of 31 skin excisions was performed. Following deep closure with absorbable sutures, one-half of each wound was superficially closed with nonabsorbable nylon sutures while the other half was stained with Rose Bengal dye and treated with green light. Overall appearance and scar characteristics were rated at 2weeks and 6months in a blinded manner by three dermatologists viewing photographs, by two onsite physicians and by patients.At 2weeks, neither sutured nor PTB-treated segments showed dehiscence; however, PTB-sealed segments showed less erythema than sutured segments as determined by photographic (P=0·001) and onsite evaluations (P=0·005). Overall appearance after PTB was judged better than after sutures (P=0·002). At 6months, scars produced by PTB were deemed superior to scars resulting from sutures in terms of appearance (P<0·001), width (P=0·002) and healing (P=0·003). Patients were more satisfied with the appearance of the PTB-sealed wound half after 2weeks and 6months (P=0·013 and P=0·003, respectively).A novel molecular suturing technique produces effective wound sealing and less scarring than closure with nylon interrupted epidermal sutures. Comparisons with better suturing techniques are warranted.
Mental Health Act 1983: guardianship order and definition of mental impairment.
Authors: T. H. Singh
Journal: BMJ (1989)

this does not mean that I avoid the peer review process, as was implied.Dr Lawrence and col- leagues also choose to disregard the evidence I put forward in favour of transcutaneous electrical nerve stimulation but raise the controversial (and again not physical) point of drug treatment.In summary, they are mistaken to state that there is no evidence for benefit from physical treatments.In my view the BMJ7 rightly and courageously took up the much neglected subject of physical therapy.