tbuckley/cabot-search huggingface dataset:
A prospective study of cisplatin-based combination chemotherapy in advanced germ cell malignancy: role of maintenance and long-term follow-up.
Authors: J A Levi, D Thomson, T Sandeman, M Tattersall, D Raghavan, M Byrne, G Gill, V Harvey, I Burns, R Snyder
Journal: Journal of Clinical Oncology (1988)

Two hundred fifty-three patients with advanced germ cell malignancy received initial chemotherapy with cisplatin, vinblastine, and bleomycin followed by surgical resection of residual masses if possible. Patients achieving complete remission (CR) were prospectively randomized to receive 6 months maintenance therapy with vinblastine or no further treatment. CR was achieved in 183 patients (72%) and a further eight patients (4%) had complete resection of residual viable malignancy (no evidence of disease [NED]). Pretreatment factors having a significant adverse influence on response by univariate analysis included extragonadal origin of the tumor, poor performance status, advanced lung or lung and abdominal disease, and elevated serum levels of human chorionic gonadotropin (HCG) and alpha-fetoprotein (AFP) greater than 1,000 ng/mL. Multivariate regression analysis indicated the independent prognostic factors of significance were advanced lung or advanced lung and abdominal disease, total tumor diameter greater than 10 cm, and a serum level of HCG greater than 1,000 ng/mL. Of the toxicities encountered, myelosuppression was significant, being exacerbated by radiotherapy, and seven deaths occurred from septicemia. Bleomycin pulmonary toxicity occurred in 46% of patients and was severe in 4%, resulting in eight deaths. With a median follow-up of 64 months, relapses have occurred in 25 patients with no significant difference between those patients receiving or not receiving maintenance vinblastine. Eight of these relapses occurred beyond 1 year and four beyond 2 years of follow-up. Presently, 68% of the total patient population is alive and disease-free, with 84% of the CR and NED patients alive and 81% alive and disease-free. It is concluded that with prolonged follow-up, vinblastine maintenance therapy does not improve treatment outcome. Moreover, late relapses occur, cautioning against premature pronouncements of cure.
Loss of lymphocyte modulatory control by surfactant lipid extracts from acute hypersensitivity pneumonitis: comparison with sarcoidosis and idiopathic pulmonary fibrosis
Authors: O Lesur, NM Mancini, C Janot, F Chabot, A Boitout, JM Polu, H Gerard
Journal: European Respiratory Journal (1994)

Surfactant components are recognized to exert a regulatory control on lymphocytes in physiological conditions, as testified by in vitro studies. However, what happens following lung injury has not been established. As surfactant composition is altered in interstitial lung diseases, this work was carried out to compare the modulatory impact of normal human alveolar fluids on lymphocyte proliferation, with that from inflammatory lung diseases which are characterized by distinct patterns of immunologically-mediated alterations (i.e. sarcoidosis, acute hypersensitivity pneumonitis, idiopathic pulmonary fibrosis). Thymidine incorporation of allogeneic normal human blood lymphocytes was studied in the presence of total alveolar fluids or lipid extracts from 37 subjects, and phytohaemagglutinin (PHA) as T-cell mitogen. The results show that: 1) total alveolar fluids and lipid extracts from normal subjects share a concentration-dependent suppressive activity on T-cell proliferation; 2) total alveolar fluids from diseased patients have lost this property, either by a lack of suppressive activity (i.e. idiopathic pulmonary fibrosis) or even by enhanced activity (i.e. sarcoidosis and hypersensitivity pneumonitis); 3) lipid extracts from diseased patients still retain the suppressive activity of normal subjects, except for hypersensitivity; and 4) an imbalance in surfactant phospholipids with an increase in the inducers to suppressors ratio is more likely to explain this alteration in hypersensitivity pnuemonitis than changes in total lipid content. In conclusion, alveolar lipid extracts from acute hypersensitivity pnuemonitis have lost the modulatory control normally exerted by surfactant lipids on lymphocyte proliferation in vitro. This alteration may contribute to the invasion of the lung by lymphocytes in acute hypersensitivity pnuemonitis in vivo.
Thymidylate synthase inhibitors in cancer therapy: direct and indirect inhibitors.
Authors: Y M Rustum, A Harstrick, S Cao, U Vanhoefer, M B Yin, H Wilke, S Seeber
Journal: Journal of Clinical Oncology (1997)

PURPOSE AND METHODS Although fluoropyrimidines, in particular, fluorouracil (5-FU) and fluorodeoxyuridine (FdUrd), are active alone and in combination with other agents in a variety of human malignancies, therapeutic selectivity, resistance, and efficacy have been a major limitation in cancer therapy. Preclinical and clinical results in advanced and adjuvant colorectal cancers confirmed that the therapeutic efficacy of fluoropyrimidines, with thymidylate synthase (TS) as a primary target, can be improved significantly with leucovorin (LV) modulation. With the recognition that TS is an important therapeutic target, direct and specific inhibitors have been developed and are under intensive preclinical and clinical evaluation, primarily in patients with colorectal cancer, with demonstrable activity. The direct TS inhibitors have been shown to be potent, with a high level of specificity under therapeutic conditions for TS. This includes ZD1694, AG337, and LY231514. To date, although the therapeutic activity of both direct and indirect inhibitors of TS is similar, differences in the magnitude and profile of toxicity have been observed. A phase III comparative evaluation of a direct inhibitor of TS (ZD1694) with an indirect inhibitor (5-FU/LV) has been completed and showed similar activity but reduced toxicity in favor of ZD1694. RESULTS Recognition that greater than 95% of the injected dose of 5-FU is rapidly inactivated by dihydropyrimidine dehydrogenase (DPD) to therapeutically inactive products, but with toxicity to normal tissues, led to the development of inhibitors of this enzyme with the aim to modify the therapeutic index of 5-FU. Several inhibitors in combination with 5-FU are under preclinical and clinical evaluation, including uracil and 5-chloro-2,4-dihydroxy pyridine, as modulators of 5-FU derived from its prodrug tegafur and 5-ethynyluracil as a modulator of 5-FU. CONCLUSION In this review, an update of the present status of direct and indirect inhibitors of TS is discussed, as well as the future prospect for new drugs alone and in combination.
Occurrence of Hepatomas in Rats Fed Diets Containing Peanut Meal as a Major Source of Protein
Authors: W. D. Salmon, Paul M. Newberne
Journal: Cancer Research (1963)

Summary  When Charles River CD strain rats were fed diets containing 33.3 per cent of commercial peanut meal, 7.9 per cent of dried lean beef or commercial casein, and 20 per of fat, 64/73 rats developed hepatomas. Kidney tubule adenomas were observed in 16/73 rats fed these diets. When similar diets were fed in which the peanut meal had been subjected to 72 hours of continuous extraction with methanol, hepatomas developed in only 15 of 88 rats. Kidney adenomas were not observed in rats fed the diets that contained extracted peanut meal. Of 50 rats receiving a similar level of total dietary protein in the form of dried beef, no hepatoma or kidney adenoma was observed. The results indicate that the commercial peanut meal used was the source of a carcinogenic agent and that the carcinogenic effect of the meal was markedly decreased by prolonged extraction with hot methanol. The nature of the carcinogenic agent has not yet been determined.
Increase in Hormonal Activation of Adenylate Cyclase by Treatment of Cultured Cells With &lt;italic&gt;N&lt;/italic&gt;-Alkyl,&lt;italic&gt;N&lt;/italic&gt;-nitrosourea
Authors: G S Johnson, W B Anderson
Journal: JNCI Journal of the National Cancer Institute (1979)

Treatment of cultured normal rat kidney cells with the nitrosourea-containing compounds streptozotocin, chlorozotocin, or 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea resulted in a time-dependent potentiation in the ability of prostaglandin E1 and (-)-isoproterenol to elevate intracellular cAMP levels. This hormone response increased at 4 hours and reached a maximum at 15--25 hours after addition of the nitrosoureas. Basal cAMP levels were not affected. The greater response was apparently due to an increase in the GTP-dependent step in hormonal activation of adenylate cyclase, inasmuch as GTP- and GTP plus hormone-stimulated adenylate cyclase activities were enhanced twofold to threefold in crude membranes prepared from nitrosourea-treated cells. Fluoride-stimulated adenylate cyclase activity was increased only 10--25%. Nicotinamide did not prevent the elevated response, and NAD+ plus NADH levels were not appreciably altered after 42 hours; treatment with streptozotocin. The results suggest a possible involvement of cAMP in the biologic actions of nitrosoureas.
Cyclic AMP and Sodium Transport
Authors: Victor S. Sapirstein, Walter N. Scott
Journal: Journal of Clinical Investigation (1973)

The effects of oxytocin upon tissue cAMP content and short-circuit current (SCC) were measured in the urinary bladder of the toad, Bufo marinus. Tissue cAMP levels doubled before any increment in SCC was observed, the two hormone responses were quantitatively related, and a threshold level for an effect of cAMP upon sodium transport was demonstrated. The period of time over which cAMP levels continued to rise after the threshold level had been attained seemed invariant with hormone concentration. The rate at which cAMP levels rose increased with hormone concentration yielding hormone concentration-dependent maximal levels. The decay of cAMP levels was delayed when sodium influx was curtailed, suggesting a sodium-regulatory effect upon tissue cAMP levels.
Outbreak of pneumocystis jiroveci pneumonia among renal transplant patients
Authors: Sayaka Tachibana, Koji Inoue, Masaaki Siojiri, Norihiko Nakanishi, Tomonori Moritaka
Journal: European Respiratory Journal (2013)

Pneumocystis jiroveci  pneumonia(PJP) is an important cause of morbidity and mortality in renal transplant recipients (RTRs). The epidermiology and pathogenesis of this infection are poorly understood, and the exact mode of transmission remains unclear. In general, reactivation of latent infection was considered the mechanism of infection. However, recent studies reported clusters or outbreaks of PJP among immunocompromised patients as RTRs, interhuman transmission has been suggested.  We experienced 9 consecutive development cases with PJP from May to December 2012 despite no occurrence of PJP in the past 10 years. These 9 cases consisted of 7 males and 2 females. The age range of patients was 30–74 years (mean age: 54.7 years). The interval from the renal transplantation was 1.3–11.5 years (mean: 5.8 years). In all cases, patients visited our hospital due to symptoms such as fever, cough, and shortness of breath. CT images shows diffuse ground-glass opacity in both lung. In blood examination, β-d glucan was 37-1319 (mean: 376) pg/ml. In 8 patients, on admission we had bronchial endoscopy and investigated with segmental alveolar lavage.  Pneumocystis  carinii -PCR was positive in all cases. Among these, 4 cases were established a diagnosis using cytology by Grocott methanamine silver staining. Trimethoprim-Sulfamethoxazole was administered to all patients, 8 patients were discharged, but 1 patient died. The route of  Pneumocystis jiroveci  infection remains uncertain. The clustering of PJP suggests that possibility of nosocomial transmission.
Endoscopy Posters
Authors: K. Ragunath, L.A. Thomas, P.D. Duane
Journal: Gut (2001)

Background: Achalasia in children is a rare disorder of oesophageal motility characterised by abnormal relaxation of the Lower Oesophageal Sphincter (LOS) and peristalsis.Among all ages the incidence is estimated to be between 0.03 -1.1 per 100 000 population / year.In this review we report 6 children who presented within a period of 18 months.Methods: Retrospective case review.Results: 6 children presented with achalasia over an 18/12 period (5 over 1 year), comprising 3 males and 3 females with ages ranging from 7/12 to 14 yrs (median 10 yrs).Prior to diagnosis there was a median 2 month duration of symptoms (range 2-12/12) including dysphagia, vomiting, feeding problems, pain and weight loss.On presentation a diagnosis of achalasia was made on barium swallow, and oesophageal perfusion manometry performed on all cases.Mean LOS pressure ranged from 37.5-70 mmHg (mean 50) with typical loss of LOS relaxation and absent peristalsis.Nifedipine was used as the first line agent with symptomatic improvement in 2 of the 6 for 2-4 weeks.Botulinum Toxin (BTX) was used as second line (endoscopic injection into LOS; <2 years-50 units / quadrant, >2 years-100 units /quadrant).All 6 had good clinical response within one week, lasting up to 3 months (median 8 weeks).4 had repeat BTX injection (2 awaiting) with similar response.Of these 3 had repeat oesophageal manometry showing a mean reduction in LOS pressure of 40mmHg (35-50) from diagnosis but no improvement in peristalsis.One has had successful surgery and the other two referred.Discussion: This yearly incidence of achalasia is considerably higher than the 1 -2 expected from the centre's referral population.This may be partly explained by underdiagnosis, and we suggest barium studies as a first line investigation for recurrent or acquired vomiting, dysphagia or feeding diYculties.If available, oesophageal manometry is a valuable tool for diagnosis and monitoring treatment response.Nifedipine has no benefit.To our knowledge this is the first report of the use of Botulinum Toxin in children with achalasia in the UK, and the biggest single centre use.The short lived eVects warrant repeat dosage at shorter intervals or combination with other therapy e.g.balloon dilatation.Surgery remains the definitive treatment.
Abstract 16089: Epidemiology and Outcomes of Peripartum Cardiomyopathy in United States From 2009-2010
Authors: Parasuram Krishnamoorthy, Jalaj Garg, Chandrasekar Palaniswamy, Gregg Lanier
Journal: Circulation (2013)

Objective: Peripartum cardiomyopathy (PPCM) is defined as systolic heart failure within the last month of pregnancy or 5 months after delivery in the absence of any identifiable etiology of heart f...
A novel fibrotic disorder associated with increased dermal fibroblast proliferation and downregulation of genes of the microfibrillar network
Authors: K.M. Szauter, A. Ordas, R.M. Laxer, E. Pope, D. Wherrett, B. Alman, M. Mink, C.D. Boyd, K. Csiszar, A. Hinek
Journal: British Journal of Dermatology (2010)

Clinical evaluation of a young woman with subcutaneous fibrotic nodules, progressive distal joint contractures and marfanoid stature revealed a previously unrecognized fibrotic disorder characterized by several unique phenotypic features and some features overlapping with known disorders. Mutational analysis of the FBN1 and FBN2 genes excluded Marfan syndrome and congenital contractural arachnodactyly. MMP2 gene sequence analysis excluded multicentric osteolysis, nodulosis and arthropathy. The lack of mutations within the MAGP2 gene also excluded an MAGP2‐associated disorder. In order to establish the mechanistic basis for the severe skin pathology noted in this patient, we performed transcriptional profiling of dermal fibroblasts, and candidate gene expression studies in conjunction with immunocytochemistry and cell‐based and functional assays. Data from these experiments have further excluded any previously recognized fibrotic disorder and identified a unique pattern of gene expression in this patient consistent with progressive fibrosis. The pathogenic mechanisms included persistent proliferation of dermal fibroblasts in coexistence with a disarray of the microfibrillar network. Collagen accumulation, moreover, could be linked to extensive crosslinking resulting from increased activities of lysyl oxidases (LOX and LOXL), and lack of remodelling due to deficiencies in collagenolytic matrix metalloproteinases. The disorder may represent a novel syndrome in which transforming growth factor‐β1‐independent dermal fibrosis, unlike known microfibrillar disorders caused by single gene deficiencies, associates with a disarray of the microfibrillar network.
AIDS: Neurological Opportunist Infections in Central London
Authors: R J Guiloff
Journal: Journal of the Royal Society of Medicine (1989)

Twenty six (41%) of 64 central London cases of AIDS with nervous system involvement during the course of the illness had neurological opportunist infection. Cytomegalovirus and Toxoplasma gondii were the commonest agents in 22 cases with central nervous system (CNS) infection. Eight cases had herpes zoster radiculopathy. Other infections included those caused by Cryptococcus neoformans, Mycobacterium tuberculosis and papova JC virus. Prognosis was generally poor, irrespective of whether the opportunist infection was treatable.
Abstract 14365: 320-Row Cardiac Computed Tomography Angiography With Small Amount of Contrast and Hydration Can Prevent Contrast Induced Nephropathy
Authors: Atsushi Mizuno, Hiroyuki Niinuma, Koichiro Niwa
Journal: Circulation (2011)

Introduction; 320-row multi-detector computed tomography (MDCT) enables one beat acquisition for cardiac computed tomography angiography (CCTA) and can reduce both radiation dose and contrast agent...
Prediction of response to bortezomib and dexamethasone resistance in myeloma (MM) by novel mutations in the NFKB pathway
Authors: W. J. Chng, J. J. Keats, M. Chesi, A. Baker, L. K. Bruhn, A. Dispenzieri, A. K. Stewart, J. Carpten, R. Fonseca, P. L. Bergsagel
Journal: Journal of Clinical Oncology (2007)

8007 Background: We recently described mutations in multiple genes in MM patients that lead to the activation of the non- canonical NF-KB pathway. Among the mutated genes, TRAF3 is the most commonly affected, and is inactivated in about 20% of patients. In this study, we further defined the clinical significance of TRAF3 inactivation in MM. Methods: Deletion of TRAF3 was identified by array- based comparative genomic hybridization using Agilent Human Genome CGH 44k oligonucleotide array and confirmed by fluorescent in situ hybridization. Mutations were detected by sequencing. We use a TRAF3 gene expression cut-off (derived from 127 Mayo clinic patients) as a surrogate for TRAF3 inactivation to investigate its association with Translocations and Cyclin D genetic subtypes, response rates, and survival using 2 large gene expression dataset: UAMS dataset (559 newly diagnosed patients treated with Total therapy II and III) and Millenium datasets (213 relapsed patients entered into randomized study of bortezomib versus dexamethasone). Results: A normalized expression level of less than 0.6 identified all but three of the known TRAF3 inactivated cases in the Mayo dataset (p&lt;0.0001). Using this cut-off, TRAF3 inactivated cases were enriched for t(4;14) (26%, p=0.00002) and rarely D1 (mostly hyperdiploid) (9%, p=9.6E-10) in all 3 datasets. TRAF3 inactivation did not affect survival of patients treated with transplant-based therapy (UAMS and Mayo dataset) but was strongly associated with bortezomib response (89% TRAF3 low versus 40% TRAF3 normal, p0.6 had similar PFS with the two treatment. Conclusion: Mutations resulting in TRAF3 inactivation are common, particularly in non-hyperdiploid MM, and predict for response to bortezomib and resistance to dexamethasone suggesting that inhibition of the non-canonical NF-KB pathway may be one of the principle mechanisms of action of proteasome inhibitors in MM. No significant financial relationships to disclose.
The performance of COPD assessment test (CAT) in mustard lung patients
Authors: Shahrzad Mohammadzadeh Lari, Hassan Ghobadi Marallu, Davood Attaran, Mohammad Towhidi, Afsoun Mahmoudpour
Journal: European Respiratory Journal (2012)

Introduction 

Mustard lung is a form of chronic obstructive pulmonary disease (COPD) due to sulfur mustard exposure. Health-related quality of life (QOL) is an important part of management in mustard lung patients. The properties of COPD assessment test (CAT), in COPD patients have been well documented. The aim of this study was to determine the role of CAT in evaluating the QOL in mustard lung patients.

Methods and materials 

Eighty- six consecutively patients with stable COPD with all levels of severity were enrolled into this study. The QOL was evaluated by CAT and ST George Respiratory Questionnaires (SGRQ).Also standard spirometry, 6 minute walk test (6MWT), and pulse oxymetry were performed in patients. Severity of COPD was evaluated by GOLD (Global initiative for chronic Obstructive Lung Disease) and BODE (body mass index, obstruction, dyspnea, exercise) index.

Results 

The mean age of the patients was 47.30± 7.08 SD years. The mean CAT score was26.03±8.28SD. Thirty-five (43%) patients were in CAT stage 3.There was statistically significant correlation between CAT with SGRQ (p= 0.001) and BODE index (p=0.001) respectively. Also statistically significant inverse correlation was found between CAT score with FEV1 (p=0.03) and 6MWT (p=0.001) respectively. There was statistically significant difference in mean CAT score between patients in GOLD stages ≥3 and those with <3 (p=0.02).

Conclusion 

The findings of this study revealed that CAT questionnaire as a simple tool for assessment of QOL in mustard lung patients is valuable and can be used in clinical practice.
Chemo-Immunotherapy With Hyper-CVAD/MA and Rituximab For B-Cell Lymphomas Leads To Prolonged Immune Suppression Compared To Conventional Treatment With R-CHOP
Authors: Eri Matsuki, Taku Kikuchi, Norisato Hashimoto, Shunsuke Souma, Sumiko Kohashi, Takaaki Toyama, Masatoshi Sakurai, Daiki Karigane, Daichi Abe, Takayuki Shimizu, Kenji Yokoyama, Hideaki Nakajima, Shinichiro Okamoto
Journal: Blood (2013)