tbuckley/cabot-search huggingface dataset:
Human Botulism Immune Globulin for the Treatment of Infant Botulism
Authors: Stephen S. Arnon, Robert Schechter, Susan E. Maslanka, Nicholas P. Jewell, Charles L. Hatheway
Journal: New England Journal of Medicine (2006)

We created the orphan drug Human Botulism Immune Globulin Intravenous (Human) (BIG-IV), which neutralizes botulinum toxin, and evaluated its safety and efficacy in treating infant botulism, the intestinal-toxemia form of human botulism.We performed a five-year, randomized, double-blind, placebo-controlled trial statewide, in California, of BIG-IV in 122 infants with suspected (and subsequently laboratory-confirmed) infant botulism (75 caused by type A Clostridium botulinum toxin, and 47 by type B toxin); treatment was given within three days after hospital admission. We subsequently performed a 6-year nationwide, open-label study of 382 laboratory-confirmed cases of infant botulism treated within 18 days after hospital admission.As compared with the control group in the randomized trial, infants treated with BIG-IV had a reduction in the mean length of the hospital stay, the primary efficacy outcome measure, from 5.7 weeks to 2.6 weeks (P<0.001). BIG-IV treatment also reduced the mean duration of intensive care by 3.2 weeks (P<0.001), the mean duration of mechanical ventilation by 2.6 weeks (P=0.01), the mean duration of tube or intravenous feeding by 6.4 weeks (P<0.001), and the mean hospital charges per patient by 88,600 dollars (in 2004 U.S. dollars; P<0.001). There were no serious adverse events attributable to BIG-IV. In the open-label study, infants treated with BIG-IV within seven days of admission had a mean length of hospital stay of 2.2 weeks, and early treatment with BIG-IV shortened the mean length of stay significantly more than did later treatment.Prompt treatment of infant botulism type A or type B with BIG-IV was safe and effective in shortening the length and cost of the hospital stay and the severity of illness.
Molecular Mechanisms Underlying Effects of Epidermal Growth Factor Receptor Inhibition on Invasion, Proliferation, and Angiogenesis in Experimental Glioma
Authors: Jean-Sébastien Guillamo, Sophie de Boüard, Samuel Valable, Lena Marteau, Pascal Leuraud, Yannick Marie, Marie-France Poupon, Jean-Jacques Parienti, Eric Raymond, Marc Peschanski
Journal: Clinical Cancer Research (2009)

Epidermal growth factor receptor (EGFR) signal transduction pathways are implicated in malignant glioma aggressiveness and promote tumor cell invasion, proliferation, and angiogenesis. Nevertheless, response to EGFR tyrosine kinase inhibitor gefitinib (Iressa, ZD1839) has been disappointing in clinical trials. One potential explanation may come from the diversity of molecular alterations seen in gliomas. To validate that hypothesis, we have investigated responses to gefitinib on various tumor parameters in human malignant gliomas that exhibited different molecular alterations.We used a panel of six human malignant gliomas from established xenografts characterized for their genetic (EGFR, PTEN, TP53, and CDKN2A) and molecular (EGFR, PTEN, ERK, and Akt) alterations. Tumors were treated with gefitinib (1 or 10 micromol/L) for prolonged periods (8 or 16 days) in an organotypic brain slice model that allowed quantification of invasion, proliferation, and angiogenesis.In nontreated tumors, EGFR amplification was associated with profuse tumor cell invasion. After treatment, invasion was inhibited in tumors with EGFR amplification in a dose-dependent manner. Treatment had only antiproliferative effect in two of three tumors with EGFR amplification. Tumors with PTEN loss were resistant to treatment. We did not observe shrinkage of the tumors after treatment. None of the tumors had mutations of the EGFR kinase domain. Gefitinib had similar antiangiogenic effect in all of the tumors.Gefitinib reduces cell invasion in EGFR amplified tumors. PTEN loss of expression seems to be a determinant of resistance. Interestingly, inhibition of angiogenesis by gefitinib seems independent on the EGFR genetic status of the tumors.
Smoking among children and young people in Japan.
Authors: H Kawane
Journal: Thorax (1993)

Smoking among children and young people in Japan I read with great interest the editorial on children and smoking (July 1992;47:485-8).The increase in the number of under age smokers and of young women smoking is one of Japan's most important problems.'There seems to be no doubt that cigarette advertis- ing (especially on television) and the sale of tobacco through vending machines in the street are responsible for the increase of smoking among youngsters.23It is believed that about 30% of primary school pupils, 50% of junior high school students, and 70% of senior high school students in Japan have tried smoking at least once or twice.According to a recent survey by the Japan Know Your Body Study, 8% of boys and 3% of girls among third year students at junior high school (14-15 year olds) said that they smoked occasionally or regularly, but only 1% of sixth grade pupils at primary school (11-12 year olds).The survey also showed that the prevalance of smoking among third year students at senior high school (17-18 year olds) increased to 37% for boys and 15% for girls.
Rituximab maintenance improves progression-free and overall survival rates after combined immuno-chemotherapy (R-FCM) in patients with relapsed follicular and mantle cell lymphoma: Final results of a prospective randomized trial of the German Low Grade Lymphoma Study Group (GLSG)
Authors: M. Dreyling, R. Forstpointner, M. Gramatzki, H. Böck, M. Hänel, J. Seymour, M. Planker, U. Dührsen, K. Wilms, M. Unterhalt, W. Hiddemann
Journal: Journal of Clinical Oncology (2006)

7502 Background: Rituximab (R) prolongs the progression-free survival (PFS) in patients with follicular lymphoma (FL) when given either simultaneously with or as maintenance after chemotherapy only. Methods: In the current study the impact of R maintenance after remission induction with an R-containing combined immuno-chemotherapy (R-FCM) was evaluated. Patients with advanced stage relapsed or refractory FL and mantle cell lymphoma (MCL) were eligible. The study design comprized 4 courses of chemotherapy with Fludarabine (25 mg/m 2 /d days 1–3), Cyclophosphamide (200 mg/m 2 /d days 1–3) and Mitoxantrone (8 mg/m 2 /d day 1) (FCM) ± Rituximab (375 mg/m 2 /d day 0). Patients entering a complete (CR) or partial remission (PR) underwent a second randomization for R maintenance (4 weekly doses (375 mg/m 2 /d) at three and nine months after end of induction) or observation only. Randomization was stratified for histology, prior therapies (up to 2 lines vs. &gt;2), induction (±R), and response (CR vs. PR). After improved outcome of the R-FCM arm had been observed in the initial 147 randomized patients, all subsequent patients received a combined immuno-chemotherapy induction. Results: 176 of 195 randomized cases are evaluable, 138 of whom had received an R-containing induction. In these patients (as well as the total group) the median PFS after end of induction has not been reached in the R-maintenance arm in contrast to 17 months in patients with no further treatment (p = 0.001). This improvement was seen both in FL (n = 81; p = 0,035) and MCL (n = 47; p = 0,049). More importantly, overall survival rate was also improved after R maintenance with borderline significance (3 y rate 82% vs. 55%; p = 0,056). No major sided effects of R maintenance have been observed and the rate of serious infections was similar in both study arms (p = 0.72). Conclusions: The final analysis of this study confirms that R maintenance after combined immuno-chemotherapy (R-FCM) is highly effective and improves the progression-free survival—with a strong trend towards improved overall survival—of patients with relapsed FL and MCL. [Table: see text]
CpG oligodeoxynucleotides do not require TH1 cytokines to prevent eosinophilic airway inflammation in a murine model of asthma☆☆☆★
Authors: Joel N. Kline, Arthur M. Krieg, Thomas J. Waldschmidt, Zuhair K. Ballas, Vipul Jain, Thomas R. Businga
Journal: Journal of Allergy and Clinical Immunology (1999)
Acute effect of oral steroids on muscle function in chronic obstructive pulmonary disease
Authors: N.S. Hopkinson, W.D‐C. Man, M.J. Dayer, E.T. Ross, A.H. Nickol, N. Hart, J. Moxham, M.I. Polkey
Journal: European Respiratory Journal (2004)

Prospective data to support the hypothesis that corticosteroids are a significant cause of muscle weakness in patients with chronic obstructive pulmonary disease (COPD) are lacking. The authors studied respiratory and quadriceps muscle function, using both volitional techniques and magnetic nerve stimulation, as well as measuring metabolic parameters during incremental cycle ergometry, in 25 stable COPD patients. The forced expiratory volume in one second was 37.6±21.4 % predicted, before and after a 2‐week course of o.d. prednisolone 30 mg. Quadriceps strength was also assessed in 15 control patients on two occasions. Only two patients met the British Thoracic Society definition of steroid responsiveness. There was no change either in sniff transdiaphragmatic pressure (pre: 96.8±19.7 cmH 2 O; post: 98.6±22.4 cmH 2 O) or in twitch transdiaphragmatic pressure elicited by bilateral anterolateral magnetic phrenic-nerve stimulation (pre: 16.8±9.1 cmH 2 O; post: 17.9±10 cmH 2 O). Quadriceps twitch force did not change significantly either in the steroid group (pre: 9.5±3.1 kg; post: 8.9±3.7 kg) or in the control patients (pre: 8.1±2.7 kg; post: 7.9±2.2 kg). There were no changes in either peak or isotime ventilatory and metabolic parameters during exercise. In conclusion, in stable patients with chronic obstructive pulmonary disease, a 2‐week course of 30 mg prednisolone daily does not cause significant skeletal muscle dysfunction or alter metabolic parameters during exercise.
Aldara<sup>®</sup>-induced skin inflammation: studies of patients with psoriasis
Authors: H. Vinter, L. Iversen, T. Steiniche, K. Kragballe, C. Johansen
Journal: British Journal of Dermatology (2014)

The application of Aldara(®) cream containing 5% imiquimod stimulates Toll-like receptor 7/8 on plasmacytoid dendritic cells, thereby producing a potent immunomodulatory effect. This has been reported to trigger psoriasis.To establish a human model of Aldara-induced psoriasis-like skin inflammation in patients with psoriasis.Nonlesional psoriatic skin of 13 patients was treated with Aldara for 2 or 7 days. The skin was evaluated clinically and histologically on days 2, 4 and 7. Cytokine expression in Aldara-treated, lesional and nonlesional psoriatic skin was compared using reverse-transcription quantitative polymerase chain reaction.Nine of the 10 patients receiving application of Aldara under occlusion for 2 days developed redness, induration and scaling. Histological analysis revealed focal parakeratosis, acanthosis and perivascular mononuclear infiltration. On days 4 and 7 both clinical and histological signs of inflammation subsided. Two of the three patients treated with Aldara for 7 days developed erosions leading to psoriasis on day 21. Cytokine markers of activation of the innate immune system [interferon-α, interferon regulatory factor-7 and interleukin (IL)-1β] were equally expressed in lesional and Aldara-treated skin (n = 6). IL-6 and tumour necrosis factor-α were preferentially expressed in Aldara-treated skin. Adaptive immune system activation occurred only partially: IL-23p19 and IL-22 were similarly overexpressed in Aldara-treated and lesional psoriatic skin, but IL-17A and IL-12p40 were significantly underexpressed in Aldara-treated skin compared with lesional psoriatic skin. IL-10 was significantly overexpressed in Aldara-treated skin.We were able to induce psoriasis-like skin inflammation although typical psoriasis did not develop, possibly due to incomplete adaptive immune system recruitment and the powerful stimulation of IL-10 counter-regulation.
Renal tubular dysfunction in patients with inflammatory bowel disease treated with aminosalicylate.
Authors: S Schreiber, J Hamling, E Zehnter, S Howaldt, W Daerr, A Raedler, W Kruis
Journal: Gut (1997)

BACKGROUND: An increasing number of case reports indicate potential nephrotoxicity of 5-aminosalicylic acid (5-ASA), which shares similarities with the chemical structures of both phenacetin and acetylsalicylic acid. AIM: In a point prevalence study the occurrence of sensitive indices indicative of early kidney malfunction was assessed in outpatients with inflammatory bowel disease. METHODS: Routine indices of kidney function (creatinine clearance, urinary protein content, pH, electrolytes, and microscopy) were investigated in 223 patients with inflammatory bowel disease as well as sensitive markers of glomerular or tubular dysfunction (microproteinuria by SDS polyacrylamide gel electrophoresis (SDS-PAGE), urinary concentrations of N-acetyl-beta-D-glucosaminidase, alpha 1-microglobulin, gamma-glutamyltransferase (GGT), alkaline phosphatase (AP), and albumin). Histories of exposure to 5-ASA were assessed by questionnaire. RESULTS: Patients receiving high amounts of 5-ASA, both actual as well as on a lifetime basis, showed an increased prevalence of tubular proteinuria by SDS-PAGE. Raised values for urinary AP and GGT indicate proximal tubular epithelial cells as the source. All other kidney function tests were normal. Analysis of covariates indicated strong associations between disease activity and size of 5-ASA doses as well as alterations in kidney tubular function. CONCLUSION: The possibility exists that high doses of 5-ASA may be associated with proximal tubular proteinuria. This point prevalence study cannot dissect the possible impact of chronic inflammation from high dose 5-ASA treatment and further prospective studies are warranted.
Serum alpha interferon and lymphocyte inclusions in systemic lupus erythematosus.
Authors: J H Klippel, S Carette, O T Preble, R M Friedman, P M Grimley
Journal: Annals of the Rheumatic Diseases (1985)

The relationship between serum acid-labile alpha interferon and tubuloreticular inclusions within the cytoplasm of circulating lymphocytes was studied in 46 patients with systemic lupus erythematosus. Elevated levels of interferon (greater than or equal to 8 IU/ml) were found in 17 patients and lymphocyte inclusions in 35. The mean serum interferon concentration in patients with lymphocyte inclusions was significantly higher than in patients without inclusions (17.2 versus 2.4 IU/ml, p less than 0.01). Inclusions were found in 16 of 17 patients with elevated interferon and also in 19 of 29 patients without interferon (p = 0.026). In lupus, serum interferon appears to be a sufficient though not an essential marker for the presence of lymphocyte inclusions.
The relationship between cancer and medication exposures in systemic lupus erythaematosus: a case-cohort study
Authors: S Bernatsky, L Joseph, J-F Boivin, C Gordon, M Urowitz, D Gladman, P R Fortin, E Ginzler, S-C Bae, S Barr, S Edworthy, D Isenberg, A Rahman, M Petri, G S Alarcon, C Aranow, M-A Dooley, R Rajan, J-L Senecal, M Zummer, S Manzi, R Ramsey-Goldman, A E Clarke
Journal: Annals of the Rheumatic Diseases (2007)

To examine if, in systemic lupus erythaematosus (SLE), exposure to immunosuppressive therapy (cyclophosphamide, azathioprine, methotrexate) increases cancer risk.A case-cohort study was performed within a multi-site international SLE cohort; subjects were linked to regional tumour registries to determine cancer cases occurring after entry into the cohort. We calculated the hazard ratio (HR) for cancer after exposure to an immunosuppressive drug, in models that controlled for other medications (anti-malarial drugs, systemic glucocorticoids, non-steroidal anti-inflammatory drugs (NSAIDs), aspirin), smoking, age, sex, race/ethnicity, geographic location, calendar year, SLE duration, and lupus damage scores. In the primary analyses, exposures were treated categorically (ever/never) and as time-dependent.Results are presented from 246 cancer cases and 538 controls without cancer. The adjusted HR for overall cancer risk after any immunosuppressive drug was 0.82 (95% CI 0.50-1.36). Age > or = 65, and the presence of non-malignancy damage were associated with overall cancer risk. For lung cancer (n = 35 cases), smoking was also a prominent risk factor. When looking at haematological cancers specifically (n = 46 cases), there was a suggestion of an increased risk after immunosuppressive drug exposures, particularly when these were lagged by a period of 5 years (adjusted HR 2.29, 95% CI 1.02-5.15).In our SLE sample, age > or = 65, damage, and tobacco exposure were associated with cancer risk. Though immunosuppressive therapy may not be the principal driving factor for overall cancer risk, it may contribute to an increased risk of haematological malignancies. Future studies are in progress to evaluate independent influence of medication exposures and disease activity on risk of malignancy.
Chromosome assignment of the tumor-specific antigen of a 3-methylcholanthrene-induced mouse sarcoma.
Authors: D D Pravtcheva, A B DeLeo, F H Ruddle, L J Old
Journal: The Journal of Experimental Medicine (1981)

Chemically induced sarcomas of inbred mice express antigens that are distinct and specific for each individual tumor. Chromosome assignment of tumor-specific antigens would help to elucidate the genetic basis of their diversity. Expression of the serologically defined Meth A sarcoma antigen is not suppressed in hybrid cells containing a complete foreign (Chinese hamster) genome. Chromosome and serologic analysis of microcell hybrids between Meth A sarcoma cells and Chinese hamster cells shows a clear correlation of Meth A antigen expression with the presence of the distal region of chromosome 12 (bands F1 and F2). Chromosome 16 may also be implicated. The significance of the close linkage of genes determining Meth A antigen expression with the immunoglobulin heavy chain gene cluster (on chromosome 12) and the lambda light chain genes (on chromosome 16) is discussed.
CONTRACT PRACTICE: THE EVIL AND ITS REMEDY
Authors: A. B. McKee
Journal: BMJ (1902)

The chances against five of the positive cases being found in the first six case-s by mere coineidence have been calculated out for me by the Calculus of Probabilities and amount to 2,583 to I. Hence the probability is very strong that the Penang beri-bpri is arsenical, especially wthen we know that the people there largely work 1n tin manufacturies and are brought closely into contact witlh arsenic.RvFE RENCE.
Letter From Ipoh
Authors: Rosalie Bertell
Journal: JAMA (1990)

To the Editor.—  In August 1988, JAMA published a Letter From Ipoh by Dr Wagner, 1 expert witness for the Asian Rare Earth Company (ARE), Malaysia. We have also been involved with the Ipoh court case. Dr Wagner was incorrect in claiming citizen protests were a result of nuclear panic imported from the developed countries.  The Malaysian people were alerted to the radioactive waste at the ARE facility when two women employees gave birth to children with severe neurological damage. Concentrated thorium hydroxide was found on-site in drums with a surface radiation dose rate of 0.1 mSv/h. Workers, including pregnant women, were never warned.  Radioactive waste was also dumped carelessly in open trenches near a public road. During its cleanup, there were high dust levels and the miscarriage rate doubled. A pregnancy ended with a neurologically damaged child. These effects have a well-documented relationship with radiation exposure. 2 We also
Metabolic acidosis stimulates muscle protein degradation by activating the adenosine triphosphate-dependent pathway involving ubiquitin and proteasomes.
Authors: W E Mitch, R Medina, S Grieber, R C May, B K England, S R Price, J L Bailey, A L Goldberg
Journal: Journal of Clinical Investigation (1994)

Metabolic acidosis often leads to loss of body protein due mainly to accelerated protein breakdown in muscle. To identify which proteolytic pathway is activated, we measured protein degradation in incubated epitrochlearis muscles from acidotic (NH4Cl-treated) and pair-fed rats under conditions that block different proteolytic systems. Inhibiting lysosomal and calcium-activated proteases did not reduce the acidosis-induced increase in muscle proteolysis. However, when ATP production was also blocked, proteolysis fell to the same low level in muscles of acidotic and control rats. Acidosis, therefore, stimulates selectively an ATP-dependent, nonlysosomal, proteolytic process. We also examined whether the activated pathway involves ubiquitin and proteasomes (multicatalytic proteinases). Acidosis was associated with a 2.5- to 4-fold increase in ubiquitin mRNA in muscle. There was no increase in muscle heat shock protein 70 mRNA or in kidney ubiquitin mRNA, suggesting specificity of the response. Ubiquitin mRNA in muscle returned to control levels within 24 h after cessation of acidosis. mRNA for subunits of the proteasome (C2 and C3) in muscle were also increased 4-fold and 2.5-fold, respectively, with acidosis; mRNA for cathepsin B did not change. These results are consistent with, but do not prove that acidosis stimulates muscle proteolysis by activating the ATP-ubiquitin-proteasome-dependent, proteolytic pathway.
Serving researchers, the impact factor and other conflicts of interest
Authors: P. J. Sterk, K. F. Rabe
Journal: European Respiratory Journal (2005)

wo years in office, 3,000 manuscripts down the line, a bit wiser, somewhat more strict, very much enjoying it, yet still beginning: it is time to give you our yearly reflections and projections regarding the European Respiratory Journal.Are we on the right track?Do clinical readers like our journal?Is the ERJ recruiting and publishing better science?And are we up to standard with regard to transparency of potential conflicts of interest by our authors, editors and reviewers?Well, for those of you reading the journal electronically, it is time to get your hard copy.How else could you fully enjoy the new cover of the ERJ! Linda Arnold and her crew should be proud in presenting the new look for the in-and outside of the Journal.Our sincere thanks should also go to Ganesh Raghu for his creativity and flair in providing the outstanding digital image of the lung that can be seen adorning the new front cover.It symbolises modern pulmonary medicine as one of the front-runners in the medical field.