tbuckley/cabot-search huggingface dataset:
Combined Interferon-Alfa, 13-<i>cis</i>-Retinoic Acid, and Alpha-Tocopherol in Locally Advanced Head and Neck Squamous Cell Carcinoma: Novel Bioadjuvant Phase II Trial
Authors: Dong M. Shin, Fadlo R. Khuri, Barbara Murphy, Adam S. Garden, Gary Clayman, Marites Francisco, Diane Liu, Bonnie S. Glisson, Lawrence Ginsberg, Vassiliki Papadimitrakopoulou, Jeffrey Myers, William Morrison, Ann Gillenwater, K. Kian Ang, Scott M. Lippman, Helmuth Goepfert, Waun Ki Hong
Journal: Journal of Clinical Oncology (2001)

PURPOSE: Retinoids and interferons (IFNs) have single-agent and synergistic combined effects in modulating cell proliferation, differentiation, and apoptosis in vitro and clinical activity in vivo in the head and neck and other sites. Alpha-tocopherol has chemopreventive activity in the head and neck and may decrease 13-cis-retinoic acid (13-cRA) toxicity. We designed the present phase II adjuvant trial to prevent recurrence or second primary tumors (SPTs) using 13-cRA, IFN-α, and α-tocopherol in locally advanced-stage head and neck cancer. PATIENTS AND METHODS: After definitive local treatment with surgery, radiotherapy, or both, patients with locally advanced SCCHN were treated with 13-cRA (50 mg/m 2 /d, orally, daily), IFN-α (3 × 10 6 IU/m 2 , subcutaneous injection, three times a week), and α-tocopherol (1,200 IU/d, orally, daily) for 12 months, with a dose modification. Screening for recurrence or SPTs was performed every 3 months. RESULTS: Tumors of 11 (24%) of the 45 treated patients were stage III, and 34 (76%) were stage IV. Thirty-eight (86%) of 44 patients completed the full 12-month treatment (doses modified as needed). Toxicity generally was consistent with previous IFN and 13-cRA reports and included mild to moderate mucocutaneous and flu-like symptoms; occasional significant fatigue (grade 3 in 7% of patients), mild to moderate hypertriglyceridemia in 30% of patients who continued treatment along with antilipid therapy, and mild hematologic side effects. Six patients did not complete the planned treatment because of intolerable toxicity or social problems. At a median 24-months of follow-up, our clinical end point rates were 9% for local/regional recurrence (four patients), 5% for local/regional recurrence and distant metastases (two patients), and 2% for SPT (one patient), which was acute promyelocytic leukemia (ie, not of the upper aerodigestive tract). Median 1- and 2-year rates of overall survival were 98% and 91%, respectively, and of disease-free survival were 91% and 84%, respectively. CONCLUSION: The novel biologic agent combination of IFN-α, 13-cRA, and α-tocopherol was generally well tolerated and promising as adjuvant therapy for locally advanced squamous cell carcinoma of the head and neck. We are currently conducting a phase III randomized study of this combination (v no treatment) to confirm these phase II study results.
Childhood origins of self-destructive behavior
Authors: B A van der Kolk, J C Perry, J L Herman
Journal: American Journal of Psychiatry (1991)

Clinical reports suggest that many adults who engage in self-destructive behavior have childhood histories of trauma and disrupted parental care. This study explored the relations between childhood trauma, disrupted attachment, and self-destruction, using both historical and prospective data.Seventy-four subjects with personality disorders or bipolar II disorder were followed for an average of 4 years and monitored for self-destructive behavior such as suicide attempts, self-injury, and eating disorders. These behaviors were then correlated with independently obtained self-reports of childhood trauma, disruptions of parental care, and dissociative phenomena.Histories of childhood sexual and physical abuse were highly significant predictors of self-cutting and suicide attempts. During follow-up, the subjects with the most severe histories of separation and neglect and those with past sexual abuse continued being self-destructive. The nature of the trauma and the subjects' age at the time of the trauma affected the character and the severity of the self-destructive behavior. Cutting was also specifically related to dissociation.Childhood trauma contributes to the initiation of self-destructive behavior, but lack of secure attachments helps maintain it. Patients who repetitively attempt suicide or engage in chronic self-cutting are prone to react to current stresses as a return of childhood trauma, neglect, and abandonment. Experiences related to interpersonal safety, anger, and emotional needs may precipitate dissociative episodes and self-destructive behavior.
Epigenome-wide association of DNA methylation markers in peripheral blood from Indian Asians and Europeans with incident type 2 diabetes: a nested case-control study
Authors: John C Chambers, Marie Loh, Benjamin Lehne, Alexander Drong, Jennifer Kriebel, Valeria Motta, Simone Wahl, Hannah R Elliott, Federica Rota, William R Scott, Weihua Zhang, Sian-Tsung Tan, Gianluca Campanella, Marc Chadeau-Hyam, Loic Yengo, Rebecca C Richmond, Martyna Adamowicz-Brice, Uzma Afzal, Kiymet Bozaoglu, Zuan Yu Mok, Hong Kiat Ng, François Pattou, Holger Prokisch, Michelle Ann Rozario, Letizia Tarantini, James Abbott, Mika Ala-Korpela, Benedetta Albetti, Ole Ammerpohl, Pier Alberto Bertazzi, Christine Blancher, Robert Caiazzo, John Danesh, Tom R Gaunt, Simon de Lusignan, Christian Gieger, Thomas Illig, Sujeet Jha, Simon Jones, Jeremy Jowett, Antti J Kangas, Anuradhani Kasturiratne, Norihiro Kato, Navaratnam Kotea, Sudhir Kowlessur, Janne Pitkäniemi, Prakash Punjabi, Danish Saleheen, Clemens Schafmayer, Pasi Soininen, E-Shyong Tai, Barbara Thorand, Jaakko Tuomilehto, Ananda Rajitha Wickremasinghe, Soterios A Kyrtopoulos, Timothy J Aitman, Christian Herder, Jochen Hampe, Stéphane Cauchi, Caroline L Relton, Philippe Froguel, Richie Soong, Paolo Vineis, Marjo-Riitta Jarvelin, James Scott, Harald Grallert, Valentina Bollati, Paul Elliott, Mark I McCarthy, Jaspal S Kooner
Journal: The Lancet Diabetes & Endocrinology (2015)
Raising the Bar for Failure to Rescue
Authors: Elliot Wakeam, Joseph A. Hyder
Journal: JAMA Surgery (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Abstract 4120: Pause Dependent Torsade de Pointes - Does the Cause of Bradycardia Matter?
Authors: preety chawla, Prahlad Gadhavi, Sam Hanon, Paul Schweitzer
Journal: Circulation (2008)

Background: Pause dependent torsades de pointes (TdP) is an important complication of heart block. However, reports linking sinus bradycardia to TdP are uncommon. One potential mechanism of TdP is ...
Efficient transduction and oncolysis of multi-focal hepatocellular carcinoma in the rat liver by hepatic arterial infusion with vesicular stomatitis virus
Authors: K. Shinozaki, O. Ebert, C. Kournioti, Y.-S. Tai, S. L. C. Woo
Journal: Journal of Clinical Oncology (2004)

3178 Background: Vesicular Stomatitis Virus that replicate selectively in cancer cells hold considerable promise as novel therapeutic agents for the treatment of malignancy. Clinically, advanced HCC is a multi-focal disease in the liver and systemic or local-regional administration of the oncolytic virus may be required to be an effective treatment. To this end, we studied the potential of VSV, administered via the hepatic artery, to treat multi-focal HCC in the rat liver. Methods: Visible multi-focal HCC nodules of 1–6 mm in diameters developed in the livers of immune-competent Buffalo rats by inoculation of syngeneic McA-RH7777 cells via the portal vein 15 days later. These rats were infused with rVSV-Β-gal via the hepatic artery. X-gal staining of liver sections was performed to evaluate the kinetic profiles of viral transduction and spread within the lesions. In addition, viral replication was estimated by plaque assay using tumor and liver tissues. Serum chemistry and pro-inflammatory cytokines were analyzed. PBS or VSV treated tumor-bearing rats were followed for survival and the results were analyzed by the Kaplan-Meier method and the log-rank test. Results: Hepatic arterial infusion of rVSV-Β-gal at the maximal tolerable resulted in efficient transduction of multi-focal HCC, tumor-selective viral replication, and oncolysis. Importantly, no significant VSV-associated toxicities were noted, and in particular, no damage to the hepatic parenchyma was seen. Moreover, the survival of VSV-treated rats was significantly improved over that of animals in the control group (p=0.028). Conclusions: Hepatic arterial administration of VSV is both effective and safe in the treatment of multi-focal HCC in the livers of rats, suggesting that it can be developed into an effective therapeutic agent for multi-focal HCC in patients in the future. No significant financial relationships to disclose.
Etiology of hyperparathyroidism and bone disease during chronic hemodialysis
Authors: Albert E. Fournier, William J. Johnson, Donald R. Taves, John W. Beabout, Claude D. Arnaud, Ralph S. Goldsmith
Journal: Journal of Clinical Investigation (1971)

The present study was prompted by the observation that, in patients with chronic renal failure being followed at this center, renal osteodystrophy developed almost exclusively in those who were treated by chronic hemodialysis at home rather than in our center. A systematic comparison was made between the 10 patients with roentgenographic evidence of the bone disease and 18 patients without demonstrable bone disease. The two groups were similar in age, sex, nature of renal disease, and duration of dialysis. The mean duration of kidney disease was almost 2 yr longer in the patients without bone disease than in those with bone disease. Other significant differences related to where the hemodialysis was performed and to the calcium concentration in the dialysate (6.0-7.4 mg/100 ml in the hospital and 4.9-5.6 mg/100 ml at home). If the unknown factors related to where the dialysis was performed were of no consequence, the major factor contributing to the production of bone disease observed in these patients was the use of a dialysate with a calcium concentration less than 5.7 mg/100 ml.
Genetic and clinical implications of alcoholism and affective disorder
Authors: Marc A. Schuckit
Journal: American Journal of Psychiatry (1986)

The association between alcoholism and affective disorders is complex and has fomented much debate. Problems occur because of confusion in definitions (e.g., the distinction between drinking and alcoholism on the one hand and sadness and major affective disorders on the other) and because sadness and even intense temporary secondary affective episodes are often seen in the course of alcoholism. The author notes five possible factors contributing to the confusion between these two disorders and points out several ways to approach the problems of patients who have more than one concurrent clinical syndrome. Using the data from a literature review, he concludes that alcoholism and affective disorder appear to be independent diseases with some overlap in clinical symptoms.
Airway bacteria and respiratory symptoms are common in ambulatory HIV-positive UK adults
Authors: Camus Nimmo, Santino Capocci, Isobella Honeyborne, James Brown, Janey Sewell, Sarah Thurston, Margaret Johnson, Timothy D. McHugh, Marc Lipman
Journal: European Respiratory Journal (2015)

The widespread use of antiretroviral therapy (ART) and Pneumocystis pneumonia prophylaxis has led to significant declines in opportunistic infection rates in people with chronic HIV infection. Despite this, pulmonary disease is more common in these patients than HIV-negative individuals [1]. Observational studies suggest that while bacterial pneumonia is reduced by ART, it still occurs relatively frequently even after CD4 T-cell reconstitution [2, 3]. Non-recurrent HIV-associated bacterial pneumonia is 10 times more likely than in uninfected individuals [3, 4], and is now the most common infection and the leading cause of death after sepsis [5]. Airway bacterial colonisation and respiratory symptoms are common in ambulatory HIV-positive UK adults <http://ow.ly/Nug5A>
Mechanism of immune suppression by ultraviolet irradiation in vivo. I. Evidence for the existence of a unique photoreceptor in skin and its role in photoimmunology.
Authors: E C De Fabo, F P Noonan
Journal: The Journal of Experimental Medicine (1983)

UV irradiation of mice causes a systemic immune alteration that can be detected either by suppression of the immunologic rejection of UV-induced tumors, or by suppression of contact hypersensitivity (CHS). Suppression of these two immunologic responses has similar photobiologic characteristics and in both cases is associated with the generation of antigen-specific suppressor T cells. To identify whether a specific photoreceptor for this effect exists, the relative wavelength effectiveness (action spectrum) was determined for the UV-induced suppression of CHS. Narrow bands of UV (half bandwidth 3 nm) were used at 10 wavelengths from 250 to 320 nm to obtain dose-response curves. Irradiation with each of these bands of UV caused dose-dependent immunosuppression of CHS, but with differing effectiveness. Immunosuppression was clearly separable from the generation of gross skin damage and inflammation. Further, immunosuppression by the most effective wavelength (270 nm) was associated with the generation of antigen-specific suppressor cells. The action spectrum derived from the dose-response curves has a maximum between 260 and 270 nm, a shoulder at 280-290 nm, and declines steadily to approximately 3% of maximum at 320 nm. The finding of such a clearly defined wavelength dependence implies the presence of a specific photoreceptor for this effect. Removing the stratum corneum by tape stripping before UV irradiation prevented the suppression of CHS using 254-nm radiation, suggesting the photoreceptor is superficially located in the skin. A number of epidermal compounds with absorption spectra similar to the action spectrum are discussed and evaluated with respect to their potential for being the photoreceptor. Based on (a) the close fit of its absorption spectrum to the action spectrum, (b) its superficial location in the stratum corneum, and (c) its photochemical properties, the hypothesis is advanced that the photoreceptor for systemic UV-induced immunosuppression of contact hypersensitivity may be urocanic acid. As such, it may also play a role in UV-induced carcinogenesis via the production of tumor-specific suppressor cells.
ABC of Asthma
Journal: Thorax (1995)

Letters to the editor look at first glance as though ICI 118 551 has no effect on exercise-induced hyperkalaemia compared with placebo.However, the base- line potassium concentration was significantly lower in the ICI 118 551 group than in the placebo group, and this may explain the ap- parent lack of effect on exercise response.Furthermore, in that study atenolol had no effect on the exercise-induced potassium re- sponse, suggesting that ,13 receptors are not involved.Indeed, in our own study sal- butamol had no effect on the exercise heart rate response, showing that PI3 blockade did not occur.It has also been shown that a low dose of nadolol (5 mg), which has a minimal P, blockade, exhibits marked P2 blockade as assessed by exercise-induced hyperkalaemia.3Thus, the fact that in our study both sal- butamol and propranolol significantly aug- mented the exercise-induced potassium response is in keeping with a P2 receptor mediator mechanism linked to the Na/K-ATPase pump.This hypothesis is further sup- ported by the enhancement of exercise-induced hyperkalaemia by digitalis which directly inhibits the Na/K-ATPase pump.4We therefore remain of the firm opinion that, in the presence of high adrenergic tone, salbutamol exhibits 12 antagonist activity as demonstrated by augmentation of exerciseinduced hyperkalaemia.This would be in keeping with the known pharmacological properties ofsalbutamol as a partial P2 agonist along with in vitro data showing salbutamol to antagonise the relaxant effect of isoprenaline in the presence of carbachol- induced bronchoconstriction.5 Whilst we agree that salbutamol is of great value in treating acute bronchospasm, it may be that a P2 agonist with greater intrinsic activity may be preferable in certain situations where airway tone is increased.
Phosphofructokinase Regulation in Some Transplantable Thyroid Tumors
Authors: Maria-Fiore Meldolesi, Paolo Laccetti
Journal: Cancer Research (1979)

Some kinetic, molecular, and rate-limiting properties of partially purified phosphofructokinase from normal rat thyroid and three transplantable rat thyroid tumors have been studied, and interesting differences have been found. Citrate inhibition of tumor phosphofructokinase and its reversal by cyclic adenosine 3′:5′-monophosphate were lower than those of the normal enzyme. A direct relationship between tumor growth rate and the decrease of citrate inhibition was observed. The diethylaminoethyl cellulose affinity properties of the rat thyroid phosphofructokinase were slightly but consistently different from those of the three tumors; differences observed among the tumor enzymes with regard to these properties were likewise related to their respective growth rates. When the amounts of lactate, pyruvate, and glycerol 3-phosphate produced from each of the substrates of the glycolytic pathway were measured, it was found that, in contrast to results obtained with normal thyroid extracts, no rate-limiting function was associated with phosphofructokinase activity in tumor extracts. It was concluded that the modulation of phosphofructokinase by its allosteric effectors was similar in all three tumors, although different from that of the enzyme from normal rat thyroid; it was proportional to tumor growth rate and probably related to molecular and regulatory modifications.
Determining Role of “Mammotropins” in Induction of Mammary Tumors in Mice by Virus&lt;xref ref-type="fn" rid="fn1"&gt;2&lt;/xref&gt;
Authors: Kenjiro Yokoro, Jacob Furth
Journal: JNCI Journal of the National Cancer Institute (1962)

Mammary tumors were induced in 16 of 37 (43%) adult female C57L/J × A/HeJ mice treated with mammarytumor virus (Bittner's MTA) and “mammotropins” (administered by means of a mammotropie pituitary tumor graft). In contrast, no mammary tumors developed in 159 female C57L/J × A/HeJ mice when treated with either “mammotropin,” virus, or diethylstilbestrol alone or a combination of diethylstilbestrol and virus, or diethylstilbestrol and mammotropins. The mammarytumor incidence was higher (61%) in mice given diluted milk (0.1 ml, 1 : 20) than in those given undiluted milk (26%). The hormone responsiveness of 4 mammary tumors induced by virus plus mammotropin was tested by transplantation. One of these tumors was highly responsive to mammotropins; 3 were fully autonomous. The responsive tumor retained its full hormone dependency in the frozen state at −70° C. The latency period of hormone-responsive mammary tumor was related to the level of mammotropins. These findings support the concept that mammotropins are powerful promoters of mammary tumors but are not primary carcinogens. Induction of mammary tumors and their progressive growth are influenced by mammotropin levels, irrespective of whether the initiation is a chemical or ionizing radiation, as previously shown, or a virus, as shown in the present study.
Induction of Polyploidy by Histone Deacetylase Inhibitor: A Pathway for Antitumor Effects
Authors: Wei-Sheng Xu, Gisela Perez, Lang Ngo, Chang-Yun Gui, Paul A. Marks
Journal: Cancer Research (2005)

Abstract Histone deacetylase (HDAC) inhibitors can induce various transformed cells to undergo growth arrest and/or death. Suberoylanilide hydroxamic acid (SAHA) is an HDAC inhibitor which is in phase I/II clinical trials and has shown antitumor activity in hematologic and solid tumors at doses well tolerated by patients. HDAC is the target for SAHA, but the mechanisms of the consequent induced death of transformed cells are not completely understood. In this study, we report that SAHA induced polyploidy in human colon cancer cell line HCT116 and human breast cancer cell lines, MCF-7, MDA-MB-231, and MBA-MD-468, but not in normal human embryonic fibroblast SW-38 and normal mouse embryonic fibroblasts. The polyploid cells lost the capacity for proliferation and committed to senescence. The induction of polyploidy was more marked in HCT116 p21WAF1−/− or HCT116 p53−/− cells than in wild-type HCT116. The development of senescence of SAHA-induced polyploidy cells was similar in all colon cell lines. The present findings indicate that the HDAC inhibitor could exert antitumor effects by inducing polyploidy, and this effect is more marked in transformed cells with nonfunctioning p21WAF1 or p53 genes.
Effects of self-administered chest physiotherapy (SA-CP) in patients with non-cystic fibrosis bronchiectasis
Authors: Ana Balañá, Juana Martínez LLorens, Pilar Ausin, Mireia Admetllo, Angela Roig, Joaquim Gea
Journal: European Respiratory Journal (2013)

Bronchiectasis is a disorder characterized by the abnormal dilation of the bronchi caused by different diseasses. SA-CP is considered an essential part of the treatment of these patients. There are still controversial issues on the most appropriate techniques to be applied. Aim: To analyze the effects of SA-CP program in non-cystic fibrosis bronchiectasis (BCH) patients. Method: Although the study initially included 19 BCH patients (73±9ys), only 14(72±10ys) finished it. They were evaluated at baseline, 3 months later, and again at the end of 3 months SA-CP. This program consisted of a 1 day training period in-hospital followed by in-home sessions (2times/day/3months) of expiration with the glottis open in the lateral posture(ELTGOL)and active cycle of breathing technique(ACTB). Anthropometry, lung and respiratory muscle function, quality of life (QoL), and systemic inflammation were assessed. Result: Baseline: Stable BCH patients showed mild inspiratory muscle dysfunction (MIP73±11%); poor QoL (SGRQ51±18), elevated systemic inflammation (ESR31±17mm/h, nv   Conclusion:  Stable BCH patients have inspiratory muscle dysfunction, systemic inflammation and poor QoL. SA-CP techniques (ETGOL&ACBT) reduce systemic inflammation, improve inspiratory muscle function and QoL.