tbuckley/cabot-search huggingface dataset:
High-dose ifosfamide: circumvention of resistance to standard-dose ifosfamide in advanced soft tissue sarcomas.
Authors: A Le Cesne, E Antoine, M Spielmann, T Le Chevalier, E Brain, C Toussaint, N Janin, L Kayitalire, F Fontaine, J Genin
Journal: Journal of Clinical Oncology (1995)

PURPOSE The study was designed to assess the toxicity and activity of high-dose ifosfamide (HDI) administered by continuous infusion at a dose of 4 g/m2/d over 3 days every 4 weeks in adult patients with advanced soft tissue sarcomas (ASTS) pretreated with doxorubicin and/or a standard-dose ifosfamide (SDI)-containing regimen. PATIENTS AND METHODS Between January 1991 and November 1993, 40 patients with progressive ASTS were entered onto the study. Twenty-eight patients had been pretreated with a multidrug regimen that contained SDI and were classified as follows: SDI-refractory (n = 21), SDI-resistant (n = 2), and indeterminate SDI-sensitive (n = 5). Patients were treated until progression or major toxicity. RESULTS One hundred forty-seven cycles of HDI were administered. Neutropenia was dose-limiting, with 100% of patients experiencing grade 3 to 4 toxicity and 12 admissions for febrile neutropenia (30% of patients). Neurotoxicity (17% of patients) was significantly associated with acute renal failure (n = 4) (P &lt; .001), grade 4 thrombocytopenia (P &lt; .01) and febrile neutropenia (P = .048). Chronic renal toxicity (n = 4) was significantly associated with retroperitoneal masses and/or prior nephrectomy (P = .008). Partial responses (PRs) were observed in 12 of 36 assessable patients (33%) and eight patients (22%) experienced disease stabilization. All but one response occurred in patients pretreated with SDI, with five PRs among SDI-refractory patients. Leiomyosarcomas appear resistant to HDI. The median response duration was 8 months (range, 6 to 13+) and the median overall survival time was 12 months. CONCLUSION The activity of HDI in these pretreated ASTS patients and the apparent circumvention of SDI resistance suggest a real dose-response relationship for ifosfamide and deserve further evaluation. Although toxic, this treatment appears feasible and manageable using routine clinical support. Since prophylaxis of ifosfamide-induced renal damage remains unknown, frequent monitoring of renal and tubular functions during therapy is highly recommended.
Notch signaling via hairy/enhancer of Split-5 (Hes5) & paired-box containing gene 6 (Pax6) controls progenitor cell reservoir for repair of airway injury
Authors: Parviz Minoo, Yiming Xing
Journal: European Respiratory Journal (2012)

Background: The airways of the mammalian lung are lined with specialized epithelial cell types that are the target of airborne toxicants and injury. Notch signaling plays an important role in the ontogeny of these cells, but its contributions to recruitment, expansion or differentiation of resident progenitor/stem cells in repair of injured airways remains unknown.

Aims & Objective: To elucidate the role of Notch signaling in repair of injured airway epithelium.

Methods: We used targeted inactivation of, Notch1, via the epithelial-specific Gata5-cre line in the embryonic lung epithelium.

Results: Notch1(-/-) mice are viable with intact pulmonary epithelial cell fate determination/differentiation. However, Notch1 was found to be required for normal repair of the injured airway epithelium. Absence of Notch1 reduced the ability of cells distinguished by expression of PGP9.5, a marker of pulmonary neuroendocrine cells, which serve as a reservoir for regeneration of Clara cells. Hairy/Enhancer of Split-5 (Hes5) and a paired-box containing gene 6 (Pax6) were found to be downstream targets of Notch1. Both Hes5 and Pax6 expression were significantly increased in association with Clara cell regeneration in wild type lungs. Ablation of Notch1 reduced Hes5 and Pax6 and inhibited airway epithelial repair. Thus, although dispensable in developmental ontogeny of airway epithelial cells, normal activity of Notch1 is required for repair of the airway epithelium. The signaling pathway by which Notch1 regulates the repair process also includes stimulation of Hes5 and Pax6 gene expression.

Supported by NIH, NHLBI & The Hastings Foundation.
Phenylethylamine Hypothesis of Affective Behavior
Authors: HECTOR C. SABELLI, A. DAVID MOSNAIM
Journal: American Journal of Psychiatry (1974)

The authors present experimental evidence to support the hypothesis that 2-phenylethylamine (PEA) and its metabolites modulate affective behavior. Values for the urinary excretion of PEA were lower for 71 percent of a group of depressed patients than the lowest values obtained from control subjects, which suggests that a large percentage of endogenous depressions may be due to a deficit of PEA in the brain. Animal studies indicate that an increase in the levels of PEA in the brain may be partly responsible for the elation induced by marijuana and for the therapeutic action of antidepressant agents.
Hypercalcemia and neuroendocrine carcinoma of the prostate: a report of three cases and a review of the literature.
Authors: D C Smith, J A Tucker, D L Trump
Journal: Journal of Clinical Oncology (1992)

PURPOSE Hypercalcemia is a rare complication of prostate cancer, and no definite association with any histologic subtype of prostatic malignancy has been documented. We have recently seen three patients who developed hypercalcemia in the setting of prostate cancer. All had neuroendocrine carcinoma of the prostate (NCPs), which prompted an exploration of the potential association of hypercalcemia with NCP. DESIGN An extensive review of literature published in the English-language was conducted to identify cases of hypercalcemia associated with prostate cancer and well-documented cases of NCP. RESULTS We found 17 reported cases of hypercalcemia clearly associated with prostate cancer and a total of 61 cases of well-documented NCP. Including our cases, 11 of the 20 reported cases of hypercalcemia associated with prostate carcinoma were in patients with neuroendocrine carcinomas. CONCLUSION Hypercalcemia in the setting of prostate cancer should prompt a search for unusual histologies.
Medical thoracoscopy: Learning curve of a new service
Authors: Arun Khanna, Sanjay Adlakha, George Mabeza, Irfan Wahedna, Robert Berg, Chris Whale
Journal: European Respiratory Journal (2012)

Introduction : Many hospitals have, or plan to establish, a Medical Thoracoscopy (MT) service. Whilst high diagnostic yields and low adverse event rates are widely reported 1 , little is known about the learning curve attributed to the procedure.   Aims : To examine the diagnostic rate per annum (9hit rate9) and learning curve of a Medical Thoracoscopy service in a large District General Hospital.   Methods : We retrospectively analysed data from our first 100 consecutive MT9s since November 2008. Procedures were carried out by three Consultants with experience of Medical Thoracoscopy, one Consultant learning the technique and trainees under close supervision. 9Hit-rate9 per year was calculated and trend analysed to determine the learning curve.   Results : 9Hit-rate9 was 65% in year 1, 79% in year 2 and 89% in year 3, demonstrating a steep learning curve for this skill. Histologically confirmed diagnosis included mesothelioma (n=34), metastatic lung cancer (n=20; predominantly non-small cell lung cancer), other metastatic malignancy (n=16;predominantly Ca Breast), pleural Tuberculosis (n=4), chronic inflammation (n=13) and fibrous pleural plague (n=1).Five MT9s were performed for palliative purposes, one had to be abandoned and six failed to achieve a diagnostic yield. No major procedure related adverse events were noted during the study period.   Conclusions : This data provides insight into the diagnostic learning curve of a new MT service. Improved patient selection and enhanced operator skills should produce a diagnosis rate of over 90% in year 4.The study also re-confirms the safety and high diagnostic yield of this procedure, even outside the settings of mesothelioma.   Reference   1) Casal RF  et al ; Curr Opin Pulm Med 2009.
Chronic kidney disease
Authors: Prabir Kumar Mitra, Peter R W Tasker, M S Ell
Journal: BMJ (2007)

A 68 year old man sees you after you sent him a letter saying that the results of blood tests done over the past year to monitor hypertension show that he has chronic kidney disease (CKD). He is worried, as he thought that high blood pressure was his only medical problem. #### Useful resources
Astro-Lab project: Assessment of the safety of long-acting beta agonists (LABAs) in asthma by combining health-care databases and direct patient follow-up: Description of the patient pattern in France and in the United-Kingdom (UK)
Authors: Eric Van Ganse
Journal: European Respiratory Journal (2013)

Background: The efficacy of long-acting -β agonists (LABAs) in asthma has been demonstrated but their safety remains an issue, particularly in children.  Objectives : The main objective of the Astro-Lab project is to assess the safety of LABAs in children and adults taking in account patient adherence.  Methods: A prospective observational cohort of 3000 patients, 1500 children (6-17 yrs) and 1500 adults (18-40 yrs) with persistent asthma, will be followed-up during 2 years. In the UK, patients are pre-selected in the THIN database. In France, an online register built by a network of 550 general practitioners will allow to pre-select patients. Patients are pre-selected based on prescription data: at least 6 months with the same prescribed therapy pattern during the 12-months period prior enrolment.  Results: Descriptive data of the patient profile (6000 in France and 20 000 in the UK) will be presented.  Same table will be presented for France.  Conclusions: These data will provide information about the different patterns of use of LABAs and ICs within children and adults populations in France and in the UK.  The research leading to these results has received funding from the European Community’s Seventh Framework Programme (FP7/2007-2013) under grant agreement #282593.
Usefulness of biodegradable polydioxanone stents in the treatment of postsurgical colorectal strictures and fistulas
Authors: F. Pérez Roldán, P. González Carro, M. Villafáñez García, S. Aoufi Rabih, M. Legaz Huidobro, N. Sánchez-Manjavacas Múñoz, O. Roncero García-Escribano, M. Ynfante Ferrús, E. Bernardos Martín, F. Ruiz Carrillo
Journal: Endoscopy (2012)

Benign colonic strictures and fistulas are a growing problem presenting most commonly after bowel resection. Standard treatment is with endoscopic bougies or, more usually, balloon dilation. When these approaches are not successful, other solutions are available and different endoscopic and surgical approaches have been used to treat fistulas. We present an additional option--biodegradable stents--for the treatment of colonic strictures and fistulas that have proven refractory to other endoscopic interventions. We analyzed the results from 10 patients with either a postsurgical colorectal stricture (n =7) or rectocutaneous fistula (n =3) treated with the biodegradable SX-ELLA esophageal stent (covered or uncovered). Stents were successfully placed in nine patients, although early migration subsequently occurred in one. Placement was impossible in one patient due to deformity of the area and the fact that the stricture was approximately 30cm from the anus. The fistulas were successfully closed in all patients, although symptoms reappeared in one patient. In the six patients who received stents for strictures, symptoms resolved in five; in the remaining patient, the stent migrated shortly after the endoscopy. Treatment of colonic strictures and rectocutaneous fistulas with biodegradable stents is an effective alternative in the short-to-medium term. The stent does not have to be removed and is subject to very few complications. The drawbacks of this approach are the need to repeat the procedure in some patients and the lack of published series on efficacy.
Chikungunya fever in two German tourists returning from the Maldives, September, 2009
Authors: M Pfeffer, I Hanus, T Löscher, T Homeier, G Dobler
Journal: Eurosurveillance (2010)

This report describes the first isolation and molecular characterisation of a chikungunya virus from two German tourists who became ill after a visit to the Maldives in September 2009. The virus contained the E1 A226V mutation, shown to be responsible for an adaptation to the Asian tiger mosquito Aedes albopictus. The E1 coding sequence was identical to chikungunya virus isolates from Sri Lanka and showed three nt-mismatches to the only available E1 nt sequence from the Maldives.
Randomized trial of hyperfractionated radiation therapy with or without concurrent chemotherapy for stage III non-small-cell lung cancer.
Authors: B Jeremic, Y Shibamoto, L Acimovic, L Djuric
Journal: Journal of Clinical Oncology (1995)

PURPOSE To investigate the efficacy of combined hyperfractionated radiation therapy (HFX RT) and concurrent chemotherapy (CHT) in stage IIIA or IIIB non-small-cell lung cancer (NSCLC) compared with that of HFX RT alone. PATIENTS AND METHODS Between January 1988 and December 1989, 169 patients were divided randomly into the following groups: group I, HFX RT with 1.2 Gy twice daily to a total dose of 64.8 Gy (n = 61); group II, same HFX RT with CHT consisting of 100 mg of carboplatin (CBDCA) on days 1 and 2 and 100 mg of etoposide (VP-16) on days 1 to 3 of each week during the RT course (n = 52); and group III, same HFX RT with CHT consisting of 200 mg of CBDCA on days 1 and 2 and 100 mg of VP-16 on days 1 to 5 of the first, third, and fifth weeks of the RT course (n = 56). RESULTS The median survival time (MST) was 8 months for group I, 18 months for group II, and 13 months for group III. The 3-year survival rates were 6.6%, 23%, and 16%, respectively. There was a significant difference in the survival rate between groups I and II (P = .0027, log-rank test), but not between groups I and III (P = .17) or between groups II and III (P = .14). The relapse-free survival rate in group II was also higher than that in group I (P = .0024), which was largely due to improved local control in group II patients. Patients in groups II and III showed a higher incidence of acute and/or late high-grade toxicity compared with group I patients, but no patient died of treatment-related toxicity. CONCLUSION The combination of HFX RT and continuous CBDCA/VP-16 CHT was tolerable and substantially increased the survival rate.
Effect of nebulized salbutamol in preterm infants during the first year of life
Authors: B Yuksel, A Greenough
Journal: European Respiratory Journal (1991)

The acute effect on lung function of nebulized salbutamol and saline (placebo) has been investigated in preterm infants at follow-up. Twenty two premature infants, median gestational age 29 weeks (range 26-32 weeks) and birthweight 1,264 g (720-1,800 g), were studied at a median postnatal age of 7 months (range 6-9 months). Nine of the infants had recurrent respiratory symptoms; they coughed and/or wheezed at least 3 days per week for the previous 4 weeks. The remaining 13 infants were free from recurrent or persistent respiratory symptoms. Thoracic gas volume (TGV) and airways resistance (Raw) were measured and specific airway conductance sGaw calculated before and 10 min after salbutamol and normal saline given via a nebulizer. Amongst the symptomatic infants administration of nebulized salbutamol was associated with a median reduction in Raw of 25% (p less than 0.01) and also a significant improvement in sGaw (p less than 0.01). In the asymptomatic infants neither Raw nor sGaw changed significantly. Nebulized saline caused no significant change in lung mechanics in either the symptomatic or asymptomatic infants. We conclude that nebulized salbutamol is an effective bronchodilator for symptomatic preterm infants less than one year of age.
Advances in Supportive Care for Multiple Myeloma
Authors: Noopur S. Raje, Andrew J. Yee, G. David Roodman
Journal: Journal of the National Comprehensive Cancer Network (2014)

As patients with multiple myeloma live longer, helping them live better through improvements in supportive care is equally as vital. Intrinsic to the disease are bone-related complications at presentation and over the course of illness. Bisphosphonates have been an important therapy for ameliorating the risk of skeletal-related events, and work is ongoing to determine their optimal schedule. Patients with multiple myeloma also encounter several challenges related to their treatment, including peripheral neuropathy, thrombotic complications, and infections. These challenges are being addressed through a better understanding of the risk factors for developing these complications and by mitigating these risks through better dosing schemas and prophylaxis.
Effects of Oxygen Depletion on In Vitro Metabolism of Dimethylnitrosamine in Microsomes From Rat Liver and Human Tissues&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Hsiang Ju Lin, Louise Y. Y. Fong
Journal: JNCI Journal of the National Cancer Institute (1980)
Comparative Effectiveness Research in Lung Diseases and Sleep Disorders
Authors: Tracy A. Lieu, David Au, Jerry A. Krishnan, Marc Moss, Harry Selker, Andrea Harabin, Virginia Taggart, Alfred Connors, Andrea Apter, Carol Blaisdell, Thomas F. Boat, Noreen Clark, Dennis Drotar, Daniel Lewin, Bruce C. Marshall, Antonello Punturieri, Susan Redline, Shelby D. Reed, Michael Schatz, Robert Smith, Stephen B. Soumerai, B. Taylor Thompson
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

The Division of Lung Diseases of the National Heart, Lung, and Blood Institute (NHLBI) held a workshop to develop recommendations on topics, methodologies, and resources for comparative effectiveness research (CER) that will guide clinical decision making about available treatment options for lung diseases and sleep disorders. A multidisciplinary group of experts with experience in efficacy, effectiveness, implementation, and economic research identified (a) what types of studies the domain of CER in lung diseases and sleep disorders should include, (b) the criteria and process for setting priorities, and (c) current resources for and barriers to CER in lung diseases. Key recommendations were to (1) increase efforts to engage stakeholders in developing CER questions and study designs; (2) invest in further development of databases and other infrastructure, including efficient methods for data sharing; (3) make full use of a broad range of study designs; (4) increase the appropriate use of observational designs and the support of methodologic research; (5) ensure that committees that review CER grant applications include persons with appropriate perspective and expertise; and (6) further develop the workforce for CER by supporting training opportunities that focus on the methodologic and practical skills needed.
Clinicians demonstrate substantial uncertainty in antibiotic management of HCAP and CAP with immunosuppression- a survey study
Authors: Kirsty Brown, James Chalmers
Journal: European Respiratory Journal (2014)

Introduction: UK Community-acquired pneumonia (CAP) guidelines do not address the antibiotic management of Healthcare associated pneumonia (HCAP) HCAP or CAP with immunosuppression, potentially causing uncertainty in antibiotic management.  Methods:A survey was distributed to junior and senior clinicians describing 5 clinical scenarios: a case of mild CAP (case 1), a case of HAP (case 2), a case of HCAP (nursing home resident, recently hospitalised- case 3), a case of pneumonia with immunosuppression (case 4) and a case of neutropenic sepsis after chemotherapy (case 5). Respondents could choose from 5 antibiotic regimens and could refer to available guidelines.  Results:There were 81 respondents. In case 1 77(95%) gave amoxicillin, the guideline recommendation for mild CAP. For case 2, 51(63%) suggested regional guidelines for severe HAP, with 21 choosing treatment for mild HAP. For HCAP (case 3), 55(68%) managed the case according to CAP guidelines, 14(17%) recommended broader spectrum therapy but without P. aeruginosa/MRSA coverage and 0 respondents suggested MRSA and P. aeruginosa coverage.  Case 4 showed the greatest variation: 44 (54%) managed the patient as a severe CAP, 22 (27%) used the broadest available regime including coverage of P.aeruginosa. 6(8%) managed this patient as HAP.  For case 5, 53(65%) recommended broad spectrum therapy including P.aeruginosa coverage. Only 7(9%) managed the patients according to CAP guidelines.  Conclusion: There is substantial uncertainty in the choice of antibiotic therapy for HCAP and CAP with immunosuppression, which may direct the need for specific guidelines for patients with these classifications of pneumonia.
Spontaneous Hepatomas in Mice Inbred From Ha:ICR Swiss Stock: Effects of Sex, Cedar Shavings in Bedding, and Immunization With Fetal Liver or Hepatoma Cells&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Barbara B. Jacobs, Diane K. Dieter
Journal: JNCI Journal of the National Cancer Institute (1978)

Mice from Ha:ICR noninbred Swiss stock were mated brother X sister for 21--25 generations and then maintained up to the age of 33 months. Hepatomas developed in 62.8% of 86 males autopsied at 349--999 days of age (mean age = 21.1 mo). Of 130 females, 6.9% had hepatomas when autopsied at 328-825 days of age (mean age = 18.7 mo). Hepatoma incidence in males at 18 months of age was not affected by the presence or absence of cedar shavings in the bedding or by immunization of 3-month-old males with 2 weekly inoculations of 150 microgram (protein) sonicate of fetal liver or spontaneous hepatoma cells.
Survivorship: Fatigue, Version 1.2014
Authors: Crystal S. Denlinger, Jennifer A. Ligibel, Madhuri Are, K. Scott Baker, Wendy Demark-Wahnefried, Debra L. Friedman, Mindy Goldman, Lee Jones, Allison King, Grace H. Ku, Elizabeth Kvale, Terry S. Langbaum, Kristin Leonardi-Warren, Mary S. McCabe, Michelle Melisko, Jose G. Montoya, Kathi Mooney, Mary Ann Morgan, Javid J. Moslehi, Tracey O’Connor, Linda Overholser, Electra D. Paskett, Muhammad Raza, Karen L. Syrjala, Susan G. Urba, Mark T. Wakabayashi, Phyllis Zee, Nicole McMillian, Deborah Freedman-Cass
Journal: Journal of the National Comprehensive Cancer Network (2014)

Many cancer survivors report that fatigue is a disruptive symptom even after treatment ends. Persistent cancer-related fatigue affects quality of life, because individuals become too tired to fully participate in the roles and activities that make life meaningful. Identification and management of fatigue remains an unmet need for many cancer survivors. This section of the NCCN Guidelines for Survivorship provides screening, evaluation, and management recommendations for fatigue in survivors. Management includes education and counseling, physical activity, psychosocial interventions, and pharmacologic treatments.