tbuckley/cabot-search huggingface dataset:
Nuclear Factor-kB Tumor Expression Predicts Response and Survival in Irinotecan-Refractory Metastatic Colorectal Cancer Treated With Cetuximab-Irinotecan Therapy
Authors: Mario Scartozzi, Italo Bearzi, Chiara Pierantoni, Alessandra Mandolesi, Fotios Loupakis, Alberto Zaniboni, Vincenzo Catalano, Antonello Quadri, Fausto Zorzi, Rossana Berardi, Tommasina Biscotti, Roberto Labianca, Alfredo Falcone, Stefano Cascinu
Journal: Journal of Clinical Oncology (2007)

Purpose NF-kB expression has been shown to be responsible for resistance to antineoplastic agents and it also plays a part in the activation of the epidermal growth factor receptor downstream signaling pathway in colorectal tumors. The aim of our analysis was to investigate a correlation between NF-kB expression, response rate, time to progression, and survival in advanced colorectal cancer patients receiving cetuximab and irinotecan. Patients and Methods We analyzed retrospectively the immunoreactivity for NF-kB in irinotecan-refractory patients receiving cetuximab and irinotecan. Results Seventy-six patients were analyzed. Cetuximab and irinotecan were administered as second-line chemotherapy in 19 patients and after ≥ two lines of chemotherapy in the remaining 57 patients. We observed a partial response (PR) in 16 patients for an overall response rate of 24%. Thirty-two patients (48%) experienced progressive disease; median time to progression (TTP) was 3.6 months and median overall survival was 10.3 months. NF-kB was positive in 46 patients (60%). All main clinical characteristics were well balanced between NF-kB–positive and NF-kB–negative patients. The response rate was 10% (four PRs) versus 48% (12 PRs; P = .0007) in NF-kB–positive and NF-kB–negative tumors, respectively. Median TTP in NF-kB–positive patients was 3 v 6.4 months in the remaining patients (P = .021). Median overall survival was 9.5 v 15.8 months for NF-kB–positive and NF-kB–negative patients, respectively (P = .036) Conclusion The difference in median TTP, overall survival, and response rate seem to confirm that NF-kB may play a crucial role in predicting the efficacy of cetuximab and irinotecan in advanced colorectal tumors.
Intratumor Heterogeneity of Cancer/Testis Antigens Expression in Human Cutaneous Melanoma Is Methylation-Regulated and Functionally Reverted by 5-Aza-2′-deoxycytidine
Authors: Luca Sigalotti, Elisabetta Fratta, Sandra Coral, Silvia Tanzarella, Riccardo Danielli, Francesca Colizzi, Ester Fonsatti, Catia Traversari, Maresa Altomonte, Michele Maio
Journal: Cancer Research (2004)

Abstract Cancer/testis antigens (CTA) are suitable targets for immunotherapy of human malignancies, and clinical trials are mainly focusing on MAGE-A3. However, the heterogeneous intratumor expression of CTA may hamper the effectiveness of CTA-directed vaccination through the emergence of CTA-negative neoplastic clones. We investigated the intratumor heterogeneity of CTA in human melanoma and the underlying molecular mechanism(s) at clonal level using 14 single cell clones generated from the melanoma lesion Mel 313. Reverse transcription-PCR revealed a highly heterogeneous expression of MAGE-A1, -A2, -A3, -A4, -A6, GAGE 1–6, SSX 1–5, and PRAME among melanoma clones. Only nine clones expressed MAGE-A3 and competitive reverse transcription-PCR identified relative differences in the number of mRNA molecules of up to 130-fold between clones 5 and 14. This clonal heterogeneity of MAGE-A3 expression correlated with the methylation status of specific CpG dinucleotides in MAGE-A3 promoter: i.e., hypomethylated CpG dinucleotides at positions −321, −151, −19, −16, −5, −2, +21, and +42 were found in clones expressing high but not low levels of MAGE-A3. Supporting the role of DNA methylation in generating the intratumor heterogeneity of CTA, the DNA hypomethylating agent 5-aza-2′-deoxycytidine (5-AZA-dCyd) invariably induced their expression in all CTA-negative clones. Furthermore, 5-AZA-dCyd–treatment reduced to 6 folds the differential expression of MAGE-A3 between clones 5 and 14, which became recognized to a similar extent by T cells specific for a MAGE-A–encoded peptide. These findings identify promoter methylation as directly responsible for the intratumoral heterogeneity of therapeutic CTA in melanoma and foresee the use of 5-AZA-dCyd to overcome the limitations set by their intratumor heterogeneous expression to CTA-based vaccine therapy.
High frequency of vitamin D deficiency among patients with cutaneous lupus erythemathosus
Authors: J. Renne, T. Werfel, M. Wittmann
Journal: British Journal of Dermatology (2008)

Journal Article High frequency of vitamin D deficiency among patients with cutaneous lupus erythemathosus Get access J. Renne, J. Renne Department of Dermatology, Hannover Medical School, Ricklinger Str. 5, 30449 Hannover, Germany E‐mail: renne.julius@mh‐hannover.de Search for other works by this author on: Oxford Academic Google Scholar T. Werfel, T. Werfel Department of Dermatology, Hannover Medical School, Ricklinger Str. 5, 30449 Hannover, Germany Search for other works by this author on: Oxford Academic Google Scholar M. Wittmann M. Wittmann Department of Dermatology, Hannover Medical School, Ricklinger Str. 5, 30449 Hannover, Germany Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 159, Issue 2, 1 August 2008, Pages 485–486, https://doi.org/10.1111/j.1365-2133.2008.08632.x Published: 01 August 2008
Letter: Snake bite in Britain.
Authors: R V Jones
Journal: BMJ (1976)

investigated 30 fatal cases in which we are convinced that dextropropoxyphene played the major part in the death.All these patients had taken Distalgesic tablets, some with suicidal intent and many in association with alcohol.The combined cerebral depressant effect of dextropropoxyphene and alcohol seems particularly hazardous, although all the victims had apparently ingested the analgesic in doses exceeding the therapeutic range.It appears to us from the absence of published material in Britain that the problem has not yet been fully recognised, although recent information, not at variance with our own experience, is now reaching us from the USA.2We are at present in the process of collating our detailed results for publication, but feel that the time is opportune to highlight what we feel is an increasingly serious problem.
Tissue Engineering: Current State and Prospects
Authors: Ulrich A. Stock, Joseph P. Vacanti
Journal: Annual Review of Medicine (2001)

▪ Abstract Organ shortage and suboptimal prosthetic or biological materials for repair or replacement of diseased or destroyed human organs and tissues are the main motivation for increasing research in the emerging field of tissue engineering. No organ or tissue is excluded from this multidisciplinary research field, which aims to provide vital tissues with the abilities to function, grow, repair, and remodel. There are several approaches to tissue engineering, including the use of cells, scaffolds, and the combination of the two. The most common approach is biodegradable or resorbable scaffolds configured to the shape of the new tissue (e.g. a heart valve). This scaffold is seeded with cells, potentially derived from either biopsies or stem cells. The seeded cells proliferate, organize, and produce cellular and extracellular matrix. During this matrix formation, the starter matrix is degraded, resorbed, or metabolized. First clinical trials using skin or cartilage substitutes are currently under way. Both the current state of the field and future prospects are discussed.
Commensal Oral Candida in Asian Cohorts
Authors: Lakshman Samaranayake
Journal: International Journal of Oral Science (2009)

The oral carriage rate of Candida in healthy humans ranges from 40% to 60%. However for a prolonged period, the oral candidal prevalence in humans was documented essentially using data from studies in the West as their prevalence in inhabitants in different regions of the world, including Asia was not known. Yet, recent reports from a number of studies indicate the quality, quantity and prevalence of oral yeasts differ between Asia and other regions for reason that are still unclear. This mini review on such data from Asian studies on oral carriage of Candida provides another intriguing facet of the behavior of this ubiquitous yeast.
Movement discrimination after intra-articular local anaesthetic of the ankle joint
Authors: Stuart Down, Gordon Waddington, Roger Adams, Malcolm Thomson
Journal: British Journal of Sports Medicine (2007)

Background: The effect on clinical safety of dampening articular mechanoreceptor feedback at the ankle is unknown. Injection of the ankle joint for pain control may result in such dampening. Athletes receiving intra-articular local anaesthetic may therefore be at increased risk of sustaining ankle injuries, which are a common reason for missed sporting participation. Objective: To determine the effect of intra-articular local anaesthetic on movement discrimination at the ankle joint. Design: Prospective, randomised, double-blinded, placebo-controlled, cross-over trial. Setting: Australian Institute of Sport Medical Centre, Canberra, Australia. Patients: Twenty two healthy subjects (44 ankles) aged 18–26 were recruited for the three visits of the study. Interventions: Subjects were tested for their initial movement discrimination scores using the active movement extent discrimination apparatus (AMEDA). They then received ultrasound-guided intra-articular injections of local anaesthetic (2% lignocaine hydrochloride) or normal saline, on two separate later occasions, before further AMEDA assessment. Main outcome measures: Change in movement discrimination scores after intra-articular injection of local anaesthetic or saline. Results: Movement discrimination scores were not significantly different from control ankles after injection of either local anaesthetic or saline into the ankle joint. Conclusions: The intra-articular injection of neither 2 ml lignocaine nor an equivalent amount of normal saline resulted in significant effects on movement discrimination at the ankle joint. These results suggest that injections of local anaesthetic into the ankle joint are unlikely to significantly affect proprioception and thereby increase injury risk.
Targeted treatment for sonic hedgehog-dependent medulloblastoma
Authors: M. W. Kieran
Journal: Neuro-Oncology (2014)

Novel treatment options, including targeted therapies, are needed for patients with medulloblastoma (MB), especially for those with high-risk or recurrent/relapsed disease. Four major molecular subgroups of MB have been identified, one of which is characterized by activation of the sonic hedgehog (SHH) pathway. Preclinical data suggest that inhibitors of the hedgehog (Hh) pathway could become valuable treatment options for patients with this subgroup of MB. Indeed, agents targeting the positive regulator of the pathway, smoothened (SMO), have demonstrated efficacy in a subset of patients with SHH MB. However, because of resistance and the presence of mutations downstream of SMO, not all patients with SHH MB respond to SMO inhibitors. The development of agents that target these resistance mechanisms and the potential for their combination with traditional chemotherapy and SHH inhibitors will be discussed. Due to its extensive molecular heterogeneity, the future of MB treatment is in personalized therapy, which may lead to improved efficacy and reduced toxicity. This will include the development of clinically available tests that can efficiently discern the SHH subgroup. The preliminary use of these tests in clinical trials is also discussed herein.
Use of biofeedback in treating chronic hyperhidrosis: a preliminary report
Authors: P. DULLER, W. DOYLE GENTRY
Journal: British Journal of Dermatology (1980)

Preliminary findings attesting to the successful therapeutic use of biofeedback training in reducing symptoms of chronic hyperhidrosis are reported. Eleven of the fourteen adult patients trained with biofeedback were able to demonstrate clinical improvement in their excessive sweating 6 weeks after termination of treatment. Relaxation was suggested as the active ingredient in the biofeedback treatment effect. These findings support a recent report of the successful use of biofeedback in treating patients with dyshidrotic eczema.
Pharmacotherapy and Pharmacogenetics of Nicotine Dependence
Authors: Wade H Berrettini, Caryn E Lerman
Journal: American Journal of Psychiatry (2005)

The authors review recent advances in the pharmacotherapy and pharmacogenetics of nicotine dependence. Despite the negative health consequences of smoking, approximately 23% of adults in the United States are daily tobacco smokers and approximately 13% are nicotine dependent. Data for development of new medications for nicotine dependence are likely to come from animal models of the reinforcing value of nicotine, studies to identify proteins in transgenic rodents, and pharmacological studies of nicotine withdrawal. The initial pharmacogenetic studies of pharmacotherapies approved by the United States Food and Drug Administration for treatment of nicotine dependence-nicotine replacement (nicotine gum, nicotine nasal spray, and transdermal nicotine) and bupropion-have identified candidate alleles at the dopamine D2 receptor gene and mu opioid receptor gene that may predict therapeutic response. Because no one medication is likely to be safe and efficacious for a majority of persons with nicotine dependence, it will be useful to develop genetics-based methods and other tools to predict therapeutic response in subgroups of nicotine-dependent persons.
Acute generalized exanthematous pustular dermatitis induced by diltiazem
Authors: D.G. Lambert, S. Dalac, F. Beer, P. Chavannet, H. Portier
Journal: British Journal of Dermatology (1988)

Journal Article Acute generalized exanthematous pustular dermatitis induced by diltiazem Get access D.G. Lambert, D.G. Lambert Departments of Dermatology, Diseases University of Dijon, C.H.U. du Bocage, 21034 Dijon Cedex, France Search for other works by this author on: Oxford Academic Google Scholar S. Dalac, S. Dalac Departments of Dermatology, Diseases University of Dijon, C.H.U. du Bocage, 21034 Dijon Cedex, France Search for other works by this author on: Oxford Academic Google Scholar F. Beer, F. Beer Departments of Dermatology, Diseases University of Dijon, C.H.U. du Bocage, 21034 Dijon Cedex, France Search for other works by this author on: Oxford Academic Google Scholar P. Chavannet, P. Chavannet Departments of Infections, Diseases University of Dijon, C.H.U. du Bocage, 21034 Dijon Cedex, France Search for other works by this author on: Oxford Academic Google Scholar H. Portier H. Portier Departments of Infections, Diseases University of Dijon, C.H.U. du Bocage, 21034 Dijon Cedex, France Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 118, Issue 2, 1 February 1988, Page 308, https://doi.org/10.1111/j.1365-2133.1988.tb01789.x Published: 01 February 1988
Prognostic value of iterative lung function testing in amyotrophic lateral sclerosis (ALS)
Authors: Monique Oswald-Mammosser, Marie Fleury, Irina Enache, Cristina Pistea, Christine Tranchant, Anne Charloux
Journal: European Respiratory Journal (2013)

We hypothesized that, in addition to baseline values, changes in lung function values measured during the 6 first mo of follow-up may be prognostic in ALS.  Methods  113 patients from the Strasbourg ALS Centre completed follow-up of slow vital capacity (VC), maximal inspiratory pressure (MIP) and sniff nasal pressure (SNIP) till death. The best of either MIP or SNIP (called S/MIP) was used. Parameters were measured every 3 mo.  Results  Patients’ characteristics are presented in Table 1.  Mean survival was 20 (+/-19) months.  Baseline values were related to survival. A VC  2 O had a PPV of survival  60 cmH 2 O was associated with survival >6 mo in 97% of patients.  Considering changes in VC, a decrease >40% at 3 mo had a PPV of survival  40% at 6 mo had a PPV of survival  6 mo in 91% of patients, and >12 mo in 80% of patients.  Conclusions  This first study of changes in VC and S/MIP at 3 and 6 mo of follow-up show they are highly predictive of death in ALS.
Evidence of a Role of Tumor Necrosis Factor α in Refractory Asthma
Authors: Mike A. Berry, Beverley Hargadon, Maria Shelley, Debbie Parker, Dominick E. Shaw, Ruth H. Green, Peter Bradding, Christopher E. Brightling, Andrew J. Wardlaw, Ian D. Pavord
Journal: New England Journal of Medicine (2006)

The development of tumor necrosis factor alpha (TNF-alpha) antagonists has made it feasible to investigate the role of this cytokine in refractory asthma.We measured markers of TNF-alpha activity on peripheral-blood monocytes in 10 patients with refractory asthma, 10 patients with mild-to-moderate asthma, and 10 control subjects. We also investigated the effects of treatment with the soluble TNF-alpha receptor etanercept (25 mg twice weekly) in the patients with refractory asthma in a placebo-controlled, double-blind, crossover pilot study.As compared with patients with mild-to-moderate asthma and controls, patients with refractory asthma had increased expression of membrane-bound TNF-alpha, TNF-alpha receptor 1, and TNF-alpha-converting enzyme by peripheral-blood monocytes. In the clinical trial, as compared with placebo, 10 weeks of treatment with etanercept was associated with a significant increase in the concentration of methacholine required to provoke a 20 percent decrease in the forced expiratory volume in one second (FEV1) (mean difference in doubling concentration changes between etanercept and placebo, 3.5; 95 percent confidence interval, 0.07 to 7.0; P=0.05), an improvement in the asthma-related quality-of-life score (by 0.85 point; 95 percent confidence interval, 0.16 to 1.54 on a 7-point scale; P=0.02), and a 0.32-liter increase in post-bronchodilator FEV1 (95 percent confidence interval, 0.08 to 0.55; P=0.01).Patients with refractory asthma have evidence of up-regulation of the TNF-alpha axis. (ClinicalTrials.gov number, NCT00276029.).
Cryoglobulinemia and hepatatrophic viruses
Authors: Alfred L. Baker
Journal: Hepatology (1993)

Essential mixed cryoglobulinemia is frequently associated with chronic hepatitis. This report presents four cases of cryoglobulinemia with vasculitis associated with chronic hepatitis related to hepatitis C virus infection. Hepatitis C virus infection was ascertained in the four patients by both the presence in the serum of anti-HCV antibodies detected by the fourantigen recombinant immunoblot assay and of HCV RNA detected by polymerase chain reaction. In two patients tested, anti-HCV antibodies were not detected after centrifugation in the purified cryoglobulin but were detected in the supernatant. HCV RNA was detected in the purified cryoglobulin in all four patients and was detected in the supernatant in three patients. In one patient receiving recombinant interferon alfa, serum aminotransferases normalized and cryoglobulin disappeared; in another patient receiving recombinant interferon alfa, serum aminotransferases remained high and the cryoglobulin persisted. The presence of HCV RNA in the cryoglobulin and the parallelism of the changes of the cryoglobulinemia and of the serum aminotransferases during recombinant interferon alfa administration suggest that HCV infection is responsible for the production of cryoglobulinemia and vasculitis. It is proposed that HCV infection is a cause of cryoglobulinemia associated with chronic hepatitis. Background. Type II cryoglobulinemia is a vasculitis characterized by cryoglobulins consisting of complexes of polyclonal IgG and monoclonal IgM rheumatoid factors. The cause of these immune complexes is unknown, though both the hepatitis B (HBV) and C (HCV) viruses have been suspected. Methods. We studied 19 patients with Type II cryoglobulinemia for markers of HCV and HBV infection. Quantitative HCV antibody and RNA studies were performed on whole serum, cryoprecipitates, and supernatants. Results. Eight patients (42 percent) had HCV antibodies, and 16 (84 percent) had HCV RNA. Of the 19 patients, 5 (26 percent) had HBV markers, but only 1 had evidence of active HBV infection. Control serum samples from nine patients with Type I cryoglobulinemia were negative for HCV antibody and HCVRNA. There was a close, although not exclusive, association of one type of rheumatoid factor (WA) with HCV RNA. HCV antibody and HCV RNA were concentrated approximately 10-fold and 1000-fold, respectively, in the Type II cryoglobulins examined. Conclusions. Type II cryoglobulinemia is strongly associated with concomitant HCV infection and a high rate of false negative serologic tests. HCV virions and HCV antigen-antibody complexes are concentrated in the cryoprecipitates, most commonly in association with the WA type of rheumatoid factor, suggesting a role for HCV in the pathogenesis of mixed cryoglobulinemia.
Long-term results of 2-mm punch grafting in patients with vitiligo vulgaris and segmental vitiligo: effect of disease activity
Authors: A. Fongers, A. Wolkerstorfer, L. Nieuweboer-Krobotova, P. Krawczyk, G.G. Tóth, J.P.W. van der Veen
Journal: British Journal of Dermatology (2009)

Punch grafting is a simple and frequently used technique for the treatment of stable vitiligo, resistant to medical therapy. However, studies reporting long-term results are exceptional.To evaluate the long-term results of 2-mm punch grafting in patients with vitiligo vulgaris and segmental vitiligo.We studied a prospective cohort study involving 61 patients (25 male, 36 female) with vitiligo vulgaris and nine patients (all male) with segmental vitiligo who underwent 2-mm punch grafting more than 3 years ago. The main outcome measure was the degree of repigmentation of a single transplanted lesion as measured with a digital image analysis system with a mean follow-up of 5.2 years.In patients with vitiligo vulgaris, 17 lesions (28%) showed excellent, 14 lesions (23%) showed good, 14 lesions (23%) showed fair and 16 lesions (26%) showed poor repigmentation. In patients with segmental vitiligo, seven of nine lesions (78%) showed excellent repigmentation. A cobblestone-like effect was observed in 19 of 70 patients (27%). Disease activity after punch grafting was reported in 94% of patients with poor repigmentation but in only 18% of patients with excellent repigmentation (chi(2) test, P < 0.0005). Patients who reported disease activity after transplantation had a lower mean repigmentation than those who did not report disease activity (77% vs. 39%, P < 0.05).Two-millimetre punch grafting in vitiligo is an effective surgical procedure with long-lasting effect. To prevent a cobblestone-like effect, we advise the use of smaller grafts (1-1.2 mm). Disease activity after grafting, localization and type of vitiligo, prior ultraviolet B treatment and a Koebnerized donor site influence the long-term outcome of punch grafting and should be taken into account in the selection of patients eligible for this treatment.
Skewed T-cell receptor repertoire, decreased thymic output, and predominance of terminally differentiated T cells in ataxia telangiectasia
Authors: Antonello Giovannetti, Francesca Mazzetta, Elisabetta Caprini, Alessandro Aiuti, Marco Marziali, Marina Pierdominici, Andrea Cossarizza, Luciana Chessa, Enrico Scala, Isabella Quinti, Giandomenico Russo, Massimo Fiorilli
Journal: Blood (2002)