tbuckley/cabot-search huggingface dataset:
19-Nor-1-alpha-25-dihydroxyvitamin D2 (Paricalcitol) safely and effectively reduces the levels of intact parathyroid hormone in patients on hemodialysis.
Authors: K J Martin, E A González, M Gellens, L L Hamm, H Abboud, J Lindberg
Journal: Journal of the American Society of Nephrology (1998)

Paricalcitol (19-nor-1alpha-25-dihydroxyvitamin D2), a new vitamin D analog developed for the treatment of secondary hyperparathyroidism, was evaluated in three double-blind, placebo-controlled, dose-escalating, randomized multicenter trials. A total of 78 patients (40 Paricalcitol injection, 38 placebo) achieved treatment phase eligibility, which included intact parathyroid hormone (iPTH) > or = 400 pg/ml, normalized serum calcium levels between 8.0 and 10.0 mg/dl, and calcium x phosphorus product values less than 75. Study end points included a decrease in iPTH of at least 30% or a maximum of five dose escalations. After a 4-wk washout, paricalcitol or placebo was administered intravenously three times per week after dialysis for 12 wk. Study drug was started at a dose of 0.04 microg/kg and was increased by 0.04 microg/kg every 2 wk to a maximal allowable dose of 0.24 microg/kg or until at least a 30% decrease in serum iPTH was achieved. The dose of paricalcitol that decreased iPTH by at least 30% became the maintenance dose. Of 40 patients receiving paricalcitol, 27 (68%) had at least a 30% decrease in serum iPTH for 4 consecutive weeks, compared with three of 38 patients (8%) receiving placebo (P < 0.001). For patients who received 12 wk of treatment with paricalcitol, the levels of iPTH decreased significantly from 795+/-86 to 406+/-106 pg/ml (P < 0.001), whereas the values for PTH were 679+/-41 pg/ml before and 592+/-41 pg/ml after 12 wk of therapy in patients receiving placebo (P=NS). Also, there was a significant difference between treatment groups for the change from baseline PTH levels (P < 0.001). Paricalcitol treatment resulted in a significant reduction in serum alkaline phosphatase from 148+/-23 U/L to 101+/-14 U/L (P < 0.001) in patients treated for 12 wk compared with 120+/-9 U/L to 130+/-11 U/L (P=NS) in patients receiving placebo for 12 wk. Importantly, hypercalcemia did not occur before achieving target serum iPTH levels in any of the paricalcitol-treated patients. There was no significant difference for the change from baseline in serum phosphorus within or between treatment groups. There was no significant difference in adverse events between the paricalcitol and placebo-treated groups. These studies demonstrate that paricalcitol safely and effectively suppresses iPTH levels in hemodialysis patients. This second generation vitamin D analog may have a wider therapeutic window than current vitamin D preparations, and thus may allow reduction in PTH with less hypercalcemia.
Prospectively randomized trial of postoperative adjuvant chemotherapy in patients with high-risk colon cancer.
Authors: M J O'Connell, J A Laurie, M Kahn, R J Fitzgibbons, C Erlichman, L Shepherd, C G Moertel, W I Kocha, R Pazdur, H S Wieand, J Rubin, A M Vukov, J H Donohue, J E Krook, A Figueredo
Journal: Journal of Clinical Oncology (1998)

PURPOSE This study had two major goals: (1) to assess the effectiveness of a regimen of fluorouracil (5-FU) plus levamisole plus leucovorin as postoperative surgical adjuvant therapy for patients with high-risk colon cancer, and (2) to evaluate 6 months versus 12 months of chemotherapy. PATIENTS AND METHODS Patients with poor-prognosis stage II or III colon cancer were randomly assigned to receive adjuvant chemotherapy with either intensive-course 5-FU and leucovorin combined with levamisole, or a standard regimen of 5-FU plus levamisole. Patients were also randomly assigned to receive either 12 months or 6 months of chemotherapy, which resulted in four treatment groups. RESULTS Eight hundred ninety-one of 915 patients entered (97.4%) were eligible. The median follow-up duration is 5.1 years for patients still alive. There was a difference among the four treatment groups with respect to patient survival, and a significant duration-by-regimen interaction was observed. Specifically, standard 5-FU plus levamisole was inferior to 5-FU plus leucovorin plus levamisole when treatment was given for 6 months (5-year survival rate, 60% v 70%; P &lt; .01). CONCLUSION There was no significant improvement in patient survival when chemotherapy was given for 12 months compared with 6 months. When chemotherapy was given for 6 months, standard 5-FU plus levamisole was associated with inferior patient survival compared with intensive-course 5-FU plus leucovorin plus levamisole. These data suggest that 5-FU plus levamisole for 6 months should not be used in clinical practice, whereas 6 months of treatment with 5-FU plus leucovorin plus levamisole is effective.
Follow-Up Management of Patients With Testicular Cancer: A Multidisciplinary Consensus-Based Approach
Authors: Clair J. Beard, Shilpa Gupta, Robert J. Motzer, Elizabeth K. O'Donnell, Elizabeth R. Plimack, Kim A. Margolin, Charles J. Ryan, Joel Sheinfeld, Darren R. Feldman
Journal: Journal of the National Comprehensive Cancer Network (2015)

Testicular cancer is the most common cancer in men aged 15 to 40 years in the United States, Canada, and many European countries. Given the excellent prognosis of most men with testicular cancer, updates in care after treatment have become very important. This article provides a review of the available evidence, integrated with expert medical judgment, in the area of testicular cancer follow-up.
Nephrotoxicity in the Elderly Due to Co-Prescription of ACE Inhibitors and NSAIDs
Authors: O M P Jolobe
Journal: Journal of the Royal Society of Medicine (2001)

The report by Dr Adhiyaman and others (October 2001 JRSM, pp. 512-514) of renal failure after co-prescription of angiotensin converting enzyme (ACE) inhibitors and nonsteroidal anti-inflammatory drugs (NSAIDs), together with findings on renal function in elderly heart failure patients1, should invoke even greater vigilance in the era following the RALES study (which reported survival benefit from co-prescription of spironolactone and ACE inhibitors in heart failure). Already there are reports not only of deterioration in renal function but also of hyperkalaemia complicating co-prescription of ACE inhibitors, spironolactone, and NSAIDs3,4. Spironolactone aggravates the impairment of potassium excretion in renal failure. NSAIDs are liable to impair potassium excretion in their own right, because they can induce hyporeninaemic hypoaldosteronism, which, in turn, impairs renal potassium excretion5. Selective cyclo-oxygenase-2 (COX-2) inhibitors also seem to carry some risk of nephrotoxicity, as judged by anecdotal reports of acute renal failure associated with rofecoxib6 and celecoxib7, so these drugs may differ little in this respect from conventional NSAIDs. Perhaps the time has come for indiscriminate prescription of NSAIDs to be used as an indicator of clinical underperformance.
Changes in PH of exhaled breath condensate after specific inhalation challenge test, in patients with hypersensitivity pneumonitis
Authors: Iñigo Ojanguren, María Jesus Cruz, Ana Villar, Ferran Morell, Xavier Muñoz
Journal: European Respiratory Journal (2014)

INTRODUCTION:  The measurement of pH in exhaled breath condensate (EBC) has proven to be useful for monitoring pulmonary inflammation. The aim of this study was to investigate possible changes in the pH values of EBC in patients with hypersensitivity pneumonitis (NH) after specific inhalation challenge (SIC).  METHODS:  The study population consisted of 99 patients with suspected NH induced by exposure to avian antigens or fungi. 52 patients had a positive SIC and 47 patients had negative. EBC samples were collected before and after performing the SIC in all patients. In all samples the pH values were determined after degassing with helium. ROC curves were performed to calculate the more significant decrease of pH value to predict the positivity of SIC.  RESULTS:  In patients with a positive SIC, the pH of EBC post-SIC was significantly lower (median: 8.04 range: 3.91) than in patients with a negative SIC (median: 8.26 range: 2.49), (p = 0.046). The ROC curve showed that a decrease in the pH of the EBC of 0.4 after the SIC had a sensitivity of 20% (CI: 7-29%) and specificity of 83% (CI: 81-98%). In patients exposed to fungal antigens, 0.4 decrease of the pH in the EBC, showed a sensitivity of 31% (CI: 12-58%) and a specificity of 100% (CI: 77-100 %).  CONCLUSION:  The pH of the EBC, in conjunction with the SIC, could be useful for the diagnosis of NH.
Gender differences in adult-onset asthma: results from the Swiss SAPALDIA cohort study
Authors: Sofie Hansen, Nicole Probst-Hensch, Dirk Keidel, Julia Dratva, Robert Bettschart, Marco Pons, Luc Burdet, Pierre-Olivier Bridevaux, Tamara Schikowski, Christian Schindler, Thierry Rochat, Elisabeth Zemp
Journal: European Respiratory Journal (2015)

A higher incidence of asthma is reported in women compared with men, but evidence in later adulthood is limited. We aimed to determine the 20-year cumulative incidence of adult asthma in Switzerland and its relation to sex, taking into account age and allergic sensitisation. We assessed incidence of self-report of doctor-diagnosed asthma between 1991/1992 and 2010/2011 in 5128 subjects without asthma, aged 18–60 years at baseline. The age-related probability of asthma onset was analysed by logistic regression adjusting for potential confounders and stratified by sex and allergic sensitisation at baseline. Over 20 years, 128 (5.1%) men and 198 (7.5%) women newly reported doctor-diagnosed asthma. The adjusted odds ratio for female sex was 1.99 (95% CI 1.54–2.57) overall, 3.21 (95% CI 2.12–4.85) among nonsensitised subjects, and 1.43 (95% CI 1.02–2.02) in sensitised subjects. The probability of asthma onset decreased with increasing baseline age in women but not in men. The higher probability of new asthma in sensitised compared with nonsensitised men was unrelated to age, whereas in women it decreased with age. Asthma incidence was higher in women than in men but decreased with increasing age. The female predominance was considerably stronger in nonsensitised adults compared with those with allergic sensitisation.
Differences in Resistance of Metastatic Tumor Cells and Cells From Local Tumor Growth to Cytotoxicity of Natural Killer Cells&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: E Gorelik, M Fogel, M Feldman, S Segal
Journal: JNCI Journal of the National Cancer Institute (1979)

Cells from local tumor growth (L-3LL) were compared to metastatic tumor cells (M-3LL) for their susceptibility to the cytotoxicity of natural killer (NK) cells. M-3LL cells were more resistant in vitro to NK cells from normal spleens than were L-3LL cells. A similar phenomenon of relative resistance of metastatic cells to NK activity was found when L-3LL and M-3LL cells were admixed with normal spleen cells and then inoculated into syngeneic mice. Because hybrid resistance was shown to be based on mechanisms that in principle are similar to mechanisms involved in NK activity, we tested the growth of M-3LL and L-3LL cells in semiallogeneic F1 mice. The in vitro effect of NK cells from semiallogeneic mice on M-3LL and L-3LL cells was tested in parallel. In vitro tests showed that irrespective of the haplotype of the spleen cell donors, L-3LL cells were more susceptible to NK activity than were M-3LL cells. In vivo experiments indicated that whereas M-3LL and L-3LL cells grew similarly in syngeneic recipients, M-3LL cells grew far more in F1 mice than did L-3LL cells. Thus metastatic cells are more resistant to NK activity than are cells of the local tumor growth. This relative resistance may determine, among other factors, the metastatic spread and progression of tumor cells.
An evaluation of outpatient bone marrow harvesting.
Authors: J M Brandwein, J Callum, M Rubinger, J G Scott, A Keating
Journal: Journal of Clinical Oncology (1989)

In order to avoid the difficulties in scheduling and cost involved in admitting patients to hospital to undergo bone marrow harvests, we assessed outpatient marrow harvesting for autologous bone marrow transplant (BMT) candidates. Over a 13-month period, 39 consecutive patients with hematologic malignancies underwent bone marrow harvests as outpatients. For comparison we also evaluated 20 consecutive patients with similar disease status who had undergone bone marrow harvests as inpatients over the preceding 6 months. The mean hemoglobin value prior to harvest the mean volume of marrow harvested, and the mean nucleated cell count in the outpatient group were not significantly different from those of the inpatient group. There were no intraoperative complications. Of these 39 patients, 36 were discharged later the same day on oral iron supplements, with no adverse sequelae. Local pain was well controlled at home with mild oral analgesics. Two patients required admission due to postoperative hypotension--both responded promptly to intravenous (IV) fluids and blood and were discharged the following day. One patient was admitted postoperatively due to fever. There was a trend for the outpatients to receive less intra- and postoperative blood transfusions, but this did not reach statistical significance. The results suggest that most candidates for autologous BMT can safely undergo bone marrow harvesting as outpatients, thereby relieving pressure for hospital beds, potentially reducing costs and improving bed utilization. The study also raises the possibility of safely performing outpatient harvests on allogeneic BMT donors.
Abstract 349: Signal Transducer and Activator of Transcription 3 (Stat3) in the Matrix of Cardiomyocyte Mitochondria
Authors: Kerstin Boengler, Ina Konietzka, Anita van de Sand, Denise Hilfiker-Kleiner, Gerd Heusch, Rainer Schulz
Journal: Circulation (2008)

STAT3 (signal transducer and activator of transcription 3) transduces signals from the plasma membrane to the nucleus and is central for the cardioprotection by ischemic pre- and postconditioning. However, preliminary data suggest that STAT3 is also located in mitochondria. The aim of the present study was to confirm the presence of STAT3 in cardiomyocyte mitochondria, to elucidate its submitochondrial localization and to identify interacting proteins and the import mechanism of STAT3. STAT3 was detected by Western blot analysis in mitochondrial preparations from rat left ventricle (LV), which were negative for marker proteins of other subcellular compartments (sarcolemma, sarcoplasmic reticulum, nucleus, and cytosol). This finding was confirmed by confocal laser scan microscopy on mouse LV mitochondria (n=4). In contrast, no STAT3 was detected in mitochondria isolated from the LV of mice with a cardiomyocyte-specific deletion of STAT3 (n=3). Immunoprecipitation and confocal laser scan microscopy showed that, apart from total STAT3, also Ser727- and Tyr705-phosphorylated STAT3 was present in rat mitochondria. The analysis of subfractionated mitochondria by Western blot displayed STAT3 predominantly in the fraction negative for marker proteins of the outer membrane (voltage dependent anion channel), inner membrane (ATP synthase alpha), and the intermembrane space (cytochrome c), but positive for marker proteins of the matrix such as cyclophilin D (n=4). Immunoprecipitation of STAT3 from right ventricular and mitochondrial proteins showed a co-precipitation of connexin 43 (Cx43), which is present both at the sarcolemma and at the inner mitochondrial membrane and is also involved in cardioprotection, but not with GSK3β, MnSOD or cytochrome c. Furthermore, STAT3 co-precipitated with Tom20 (translocase of the outer membrane 20), which regulates the import of proteins into the mitochondria. Taken together, total and phosphorylated STAT3 are present in the matrix of cardiomyocyte mitochondria, STAT3 is possibly imported via a Tom20-dependent pathway, and STAT3 interacts with mitochondrial Cx43, and is thus possibly involved in Cx43-mediated cardioprotection.
Within-breath changes in respiratory impedance in healthy neonates
Authors: Bence Radics, Zita Gyurkovits, Hajnalka Szabó, Balázs Maár, Hajnalka Orvos, Peter Sly, Zoltán Hantos
Journal: European Respiratory Journal (2012)

There are limited data on respiratory impedance (Zrs) in healthy newborns and infants and the within-breath changes of Zrs are not known.  We aimed to measure Zrs and the cyclic changes of resistance (R) and reactance (X) as functions of lung volume (V) and respiratory flow (V9) in healthy term newborns.  Neonates (n=37) were measured during natural sleep. Forced oscillations at 16 Hz were superimposed on breathing via the face mask. Zrs was estimated with the wave tube technique and V9 was measured with a pneumotachograph. Steady-state breathing cycles were selected for the analysis of R and X which were compared at minimum (Vmin) and maximum volume (Vmax), peak inspiratory (V9in) and expiratory (V9ex) flow.  The V9 dependence of R was much more marked than the influence of V (see Figure). The difference between R at Vmin (29.0±10.9 cmH 2 O.s/l) and Vmax (28.9±10.7) was negligible, whereas R at V9ex (53.3±22.4) and V9in (45.1±26.2) were far higher than the zero-flow values in the corresponding breathing phase (P 2 O.s/l) was significantly more negative (P 2 O.s/l).  We conclude that the marked changes in Zrs during tidal breathing in healthy newborns are due to flow nonlinearities in the narrow nasal and glottal pathways. The absence of the V dependence of R may be a result of opposing changes in tissue resistance and airway resistance at Vmax.
Asia-Pacific Primary Liver Cancer Expert Meetings
Authors: Ye Sheng-Long
Journal: Liver Cancer (2012)

Asia-Pacific Primary Liver Cancer Expert MeetingsPrimary liver cancer (PLC) is the sixth most common malignancy and the third leading cause of death worldwide.Eighty percent of PLC patients are found in Asian countries.Therefore, it is of paramount importance that all healthcare professionals in the Asia-Pacific region, especially those in China, Korea, and Japan, examine new methods to counteract this highly prevalent disease.The Asia-Pacific Primary Liver Cancer Expert (APPLE) Meeting provides an excellent platform to exchange information regarding the latest advancements in PLC treatment.The APPLE meeting is organized as an academic program, where medical experts (both regional and international) are given an opportunity to share their updated knowledge of PLC and its clinical management.This meeting is aimed at bridging gaps in the basic science and clinical aspects of liver cancer among professionals.The ultimate aim is dissemination of the results of laboratory research and clinical trials in liver cancer among professionals.Such exchange of ideas will enable professionals to reach a consensus about the urgent and unresolved areas of liver cancer in the Asia-Pacific region.The first APPLE meeting was hosted by the Korean Liver Cancer Study Group (KLCSG) on July 3-4, 2010 in Incheon, Korea.The second APPLE meeting was hosted by the Liver Cancer Study Group of Japan (LCSGJ) on July 1-3, 2011 in Osaka, Japan.The third APPLE meeting was hosted by the Chinese Liver Cancer Study Group (CLCSG) on July 6-8, 2012 in Shanghai, China.A total of 489 participants registered to attend this meeting.Following the tradition of the previous two APPLE meetings, medical experts (both regional and international), exchanged and discussed their opinions, and research results on most aspects of liver cancer.This forum will hopefully enable the latest consensus findings on the treatment of liver cancer to be put into clinical practice.This academic meeting is not a one-off event.We shall continue to have APPLE meetings in China, Korea, and Japan, each hosting the event in rotation, and maintaining good relationships with the International Liver Cancer Association and Asia Pacific Association for the Study of Liver.The fourth APPLE meeting will be hosted by KLCSG on July 5-7, 2013 in Busan, Korea.Once again, we extend a warm welcome to those participating in this meeting.We hope you have a stimulating time and be primed with new enthusiasm for your work.Moreover, Liver Cancer, the first international peer-reviewed journal focusing exclusively on basic and clinical research in liver cancer, is officially affiliated with APPLE.This association will play an important role in contributing and updating knowledge in all aspects of liver cancer.The most valuable, novel, and thought-provoking articles on the basic and advanced clinical research of PLC should be submitted for publication to this exciting and well-regarded journal.
Effect of inhalation exposure to an occupational allergen on sputum levels of brain-derived neurotrophic factor
Authors: Roberto Castano, Melanie Welman, Lucero Castellanos, Carole Trudeau, Karim Maghni, Jean-Luc Malo
Journal: European Respiratory Journal (2013)

Background: There is raising interest on the potential role of neurotrophins in pathogenic mechanisms and clinical manifestations of respiratory allergic diseases. The neurotrophin brain-derived neurotrophic factor (BDNF) seems to play a role in the pathophysiology of asthma. However, there are not data on changes in sputum levels of BDNF after inhalation challenge with occupational allergens. Thus, we sought to assess the effect of inhalation challenge with a high-molecular-weight agent on levels of BDNF in induced sputum in patients with allergic occupational asthma.  Methods: Eight patients sensitized to flour underwent control and active challenge on consecutive days. Bronchial response to challenge was monitored by measuring FEV1 before the challenge and then serially for 7 h afterwards. Induced sputum was performed at the end of control and active challenge days.  Results: In contrast to control day, flour challenge induced clinically significant bronchial reactions in all subjects. After flour challenge, the levels of BDNF in induced sputum were significantly increased as compared to levels after control challenge (p=0.02). Also, a nonsignificant increase in the number of eosinophils as compared to control challenge levels (p=0.07) was observed. No correlation between BDNF levels and inflammatory cells in induce sputum was noted.  Conclusions: We showed that BDNF increases in induced sputum after inhalation challenge with flour. The results support the suggestion that neurotrophins may be involved in the pathogenesis of allergic occupational asthma.
Preference of the inhaler device and assessment of the technique among the asthmatic and COPD patients
Authors: Walid Tarsin, Ishraq Alshamli, Mokhthar Soussi
Journal: European Respiratory Journal (2011)

Different inhaler devices (IDs) are available for delivering treatments to patients with asthma & COPD. They have different technique which can easily confuse patients, resulting in incorrect use. The aim of this study was to evaluate the preference of the IDs and assessment of inhaler technique among the asthmatic and COPD Patients. 300 patients (117 male&183 female) included in this study. Their mean (SD) age was 44.6 (16.9) years. Manly three different inhaler devices; Metered dose inhaler (MDI), Accuhaler (ACH) and Turbuhaler (TUR) were used. 205 patient preferred the ACH while 82 & 13 preferred the TUR & MDI respectively. The assessment of inhaler technique according to the manufacturer instruction shows that 156 patients were having a good technique when using MDI, while 278 and 210 patients were having a good technique when using TUR & ACH respectively. Table 1 highlights that some patients were inhaling with either very low or very high rates.  Thus they need to be trained but this may not be successful, because studies have shown that patient soon revert back to the pre counselling technique. Even after counselling some patients may not have sufficient inspiratory effort to achieve the most desirable inhalation rate for the DPI they have been prescribed. From the results obtained we can conclude that the ACH is the most desirable ID by the patients followed by the TUR & MDI. All patients were using MDI, where nearly all of them having a high flow rate through it.