tbuckley/cabot-search huggingface dataset:
Pituitary-adrenal-system regulation and psychopathology during amitriptyline treatment in elderly depressed patients and normal comparison subjects
Authors: I J Heuser, U Schweiger, U Gotthardt, J Schmider, C H Lammers, M Dettling, A Yassouridis, F Holsboer
Journal: American Journal of Psychiatry (1996)

This study was done to compare the effects of 6-week treatment with amitriptyline on hypothalamic-pituitary-adrenocortical (HPA) regulation in elderly depressed patients and age-matched comparison subjects.A combined dexamethasone-suppression/CRH-stimulation (dexamethasone/CRH) test was administered before initiation of amitriptyline treatment and at the end of weeks 1, 3, and 6 of treatment. Thirty-nine depressed inpatients, mean age = 69 years, completed the study. Fourteen normal volunteers, mean age = 67 years, served as comparison subjects.In relation to the comparison subjects, the depressed patients had a profoundly abnormal HPA response, in particular an exaggerated cortisol release in the dexamethasone/CRH test. This abnormality began to disappear after 1 week of treatment with amitriptyline. In contrast, amitriptyline did not affect neuroendocrine regulation in the comparison subjects at any time during the test period.The data suggest that amitriptyline affects HPA regulation in hypercortisolemic depression only, and they raise the possibility that normalization of its feedback control is related to the antidepressive effect of amitriptyline.
Development and validation of a pharmacokinetically based fixed dosing scheme for suramin.
Authors: L M Reyno, M J Egorin, M A Eisenberger, V J Sinibaldi, E G Zuhowski, R Sridhara
Journal: Journal of Clinical Oncology (1995)

PURPOSE We used population pharmacokinetic-parameter estimates and designed a fixed dosing schedule to maintain plasma suramin concentrations between 100 and 300 micrograms/mL and then evaluated its performance. MATERIALS AND METHODS On day 1, patients received a 200-mg test dose and 1,000-mg/m2 loading dose. On days 2, 3, 4, and 5, patients received 1-hour infusions of 400, 300, 250, and 200 mg/m2, respectively. Subsequent 1-hour infusions of 275 mg/m2 were given on days 8, 11, 15, 19, 22, 29, 36, 43, 50, 57, 67, and 78. Therapy was discontinued for dose-limiting toxicity (DLT) or progressive disease (PD). Patients were to be removed from the fixed dosing schedule if, after day 5, three consecutive peak plasma suramin concentrations were greater than 300 micrograms/mL. RESULTS Forty-two patients, including 40 with hormone-refractory prostate cancer (HRPC), received 700 infusions. Forty patients were assessable for toxicity; 38 were assessable for response. Two patients with preexisting pulmonary disease died early of respiratory insufficiency. Treatment was discontinued in five patients due to DLT and in seven due to PD. No patient had treatment discontinued due to repeated peak plasma suramin concentrations &gt; or = 300 micrograms/mL. The fixed dosing schedule was precise, unbiased, and well tolerated. DLT consisted of grade 4 nephrotoxicity (n = 2), neurotoxicity (n = 2), and corticosteroid-induced psychosis (n = 1). Three patients, who received all 18 doses of suramin per protocol, developed severe, but not dose-limiting, malaise, fatigue, and lethargy. Twenty-four of 36 assessable patients with elevated serum prostate-specific antigen (PSA) levels had a &gt; or = 50% reduction, lasting more than 4 weeks, and 18 had a &gt; or = 75% reduction, lasting more than 4 weeks. Twelve of 23 (52%) symptomatic HRPC patients noted a subjective improvement in pain. There were no measurable responses in four patients with measurable disease. The estimated median survival time in 38 assessable patients with HRPC was 18.8 months. The estimated median time to progression in 35 patients, for whom data were available, was 10.1 months. CONCLUSION This easily implemented schedule allowed suramin to be administered safely as an intermittent bolus injection. Toxicity was manageable and reversible.
Intergroup study of fluorouracil plus levamisole as adjuvant therapy for stage II/Dukes' B2 colon cancer.
Authors: C G Moertel, T R Fleming, J S Macdonald, D G Haller, J A Laurie, C M Tangen, J S Ungerleider, W A Emerson, D C Tormey, J H Glick
Journal: Journal of Clinical Oncology (1995)

PURPOSE To determine the effectiveness of fluorouracil plus levamisole administered postoperatively to patients with resected stage II (Dukes' B2) colon cancer. PATIENTS AND METHODS This randomized controlled clinical trial (INT-0035) was performed by National Cancer Institute-sponsored cancer clinical trials cooperative groups. Patients were assigned to observation only or to fluorouracil (450 mg/m2 intravenously [IV] daily for 5 days and, beginning at 28 days, weekly for 48 weeks) plus levamisole (50 mg orally three times daily for 3 days repeated every 2 weeks for 1 year). Cancer recurrence, survival, and treatment side effects were assessed. RESULTS Three hundred eighteen eligible patients were analyzed with a median follow-up time of 7 years. Fluorouracil plus levamisole reduced the recurrence rate by 31%, although this trend was not statistically significant (P = .10). A total of 87 patients died: 43 on observation and 44 on fluorouracil plus levamisole. Disparity between effects on recurrence rate and overall survival is partially explained by a higher rate of non-colon cancer-related deaths on fluorouracil plus levamisole (15 v seven) and by the effects of salvage surgery with curative intent. Of seven patients with recurrence who were rendered disease-free by salvage surgery, six were on the observation arm. As was observed in patients treated with fluorouracil plus levamisole for stage III disease, toxicity was acceptable and compliance was excellent. CONCLUSION Fluorouracil plus levamisole is tolerable and accepted as standard surgical adjuvant therapy for patients with stage III colon cancer, but the data from this study in stage II patients suggest a decreased relapse rate without a significant improvement in survival.
Minimal Residual Disease Status Before Allogeneic Bone Marrow Transplantation Is an Important Determinant of Successful Outcome for Children and Adolescents With Acute Lymphoblastic Leukemia
Authors: Christopher J.C. Knechtli, Nicholas J. Goulden, Jeremy P. Hancock, Victoria L.G. Grandage, Emma L. Harris, Russell J. Garland, Claire G. Jones, Anthony W. Rowbottom, Linda P. Hunt, Ann F. Green, Emer Clarke, Alan W. Lankester, Jacqueline M. Cornish, Derwood H. Pamphilon, Colin G. Steward, Anthony Oakhill
Journal: Blood (1998)
Blood flow conditioning reduces kidney injury in high risk cardiac surgery patients
Authors: S. Mayor
Journal: BMJ (2015)

Remote ischaemic preconditioning, which involves alternately inflating and deflating a blood pressure cuff around a limb to restrict and restore blood flow, reduces kidney injury and the need for dialysis in high risk patients undergoing cardiac surgery, a study reported in JAMA has shown.1

As many as 30% of patients develop acute kidney injury after cardiac surgery, and no interventions investigated so far have been shown to reduce this risk. Research has shown that remote ischaemic preconditioning from brief episodes of …
Accuracy of the indirect hemagglutination test in the differential diagnosis of lung cancer and complicated hydatid cyst
Authors: Bayram Altuntas, Yener Aydin, Atilla Eroglu
Journal: European Respiratory Journal (2014)

Objective:  When the cyst ruptures and become complicated, clinical and radiological distinction from lung cancer is not possible. In this study, the differential diagnosis of complicated hydatid cyst and lung cancer was investigated with the indirect hemogglutination test.   Methods:  In our clinic between January 2010 and December 2013, we studied the indirect test hemogglutination in 28 cases whose clinical and radiological distinction could not be diagnosed as hydatid disease or lung cancer and in 28 cases whose lung cancer was diagnosed as histopathological in a prospective study.   Results:  The indirect hemagglutination test was positive in 25 of 28 cases (90%) and was negative in 3 of 28 cases (10%) whose histopathological and differential diagnosis could not be made. In all of these cases, histopathological diagnosis of hydatid cyst was diagnosed with the operation. In two of 28 lung cancer patients in the control group, the indirect hemogglutination test was found to be positive (7%), while it was negative in 26 (93%).   Conclusions:  Our findings revealed that indirect hemagglutination contributes to differential diagnosis of complicated hydatid cyst confused with primary lung cancer.
Modification of Methylation Level Dna Promoter in Serum of a Panel of Gene Before and After Treatment and Impact in Prognostic Factor in Patients with Breast Cancer
Authors: J. Martinez-Galan, C. Gonzalez-Rivas, J. Ruiz Vozmediano, L. Castillo, L. Ochoa, J.R. Delgado
Journal: Annals of Oncology (2014)
UK scientists reject call for moratorium on gene editing
Authors: N. Hawkes
Journal: BMJ (2015)

New techniques for editing genes, used for the first time in human embryos by researchers in China, have considerable potential as a research tool and are already being used in animals, UK experts told a briefing at the Science Media Centre in London on 12 May.

Clinical applications in humans are far more problematical and much further off, and the use of the technique has raised ethical concerns, because such changes are heritable and could have unpredictable effects on future generations. The UK scientists, however, rejected calls for a moratorium. Tony Perry of the University of Bath said it would be unenforceable and would risk driving research underground, and Robin Lovell-Badge of the Francis Crick Institute called a moratorium “pointless.”

The disclosure that a group led by Junjiu Huang at Sun Yat-sen University in Guangzhou had edited human embryonic genes caused a …
Pulmonary rehabilitation decreases dynamic hyperinflation during activities of daily life in patients with COPD
Authors: H.A.C. Van Helvoort, L.M. Willems, P.N.R. Dekhuijzen, Y.F. Heijdra
Journal: European Respiratory Journal (2014)

Background   Dynamic hyperinflation (DH) is an important contributor to dyspnea in patients with COPD and has been shown to occur during different kind of activities of daily life (ADL). It is known that pulmonary rehabilitation (PR) reduces DH during (sub)maximal exercises. However, from patient perspective it is important to study whether PR is also effective to reduce DH during ADL.   Aim   To study the effect of PR on DH during ADL in patients with COPD.   Methods   Eleven patients with COPD (FEV 1 = 52 ± 11% of predicted (mean ± stdev)) who started a PR program were included into the study if they showed DH (at least 10% decrease of IC) during ADL. As a control group, 11 COPD patients (FEV1= 58 ± 16% of predicted) who also hyperinflated during ADL but who received no PR, were included. Before and after 10-12 weeks PR or a control period with usual patient care, DH was measured as change in IC during a standardized ADL reflecting unloading their groceries where patients displaced products of 1 kg one by one from the ground shelve to a shelve at shoulder height and back at their own pace for 3 minutes or until symptom limitation.  DH pre and post PR or control were compared within both groups with paired t-tests.   Results   Mean and stdev DH (in L and as % of resting IC) after ADL are shown in table 1. DH significantly decreased after PR but not in the control group.   Conclusion   Within COPD patients who hyperinflate during ADL, PR has shown to be effective in decreasing DH during ADL.
Prognostic value of ventricular volumes and function in patients with pulmonary hypertension due to chronic obstructive pulmonary disease
Authors: Andrew Swift, Smitha Rajaram, Dave Capener, Sproson Tom, Charlie Elliot, Robin Condliffe, David Kiely, Jim Wild
Journal: European Respiratory Journal (2012)

Background   This study investigated the relationship between ventricular structure and function and survival in patients with pulmonary hypertension due to COPD (PH-COPD).   Methods    55 patients were evaluated with cardiac magnetic resonance imaging, right heart catheterization, lung function and CT emphysema scoring. Cardiac gated CINE MR and phase contrast imaging sequences were acquired in all patients. During follow-up of 42 months, 16 patients died. Cardiac volumes and function were analysed as predictors of mortality.   Results   Low SV measured by phase contrast MRI predicted mortality independent of demographic, haemodynamic, lung function and emphysema severity data (p=0.029). LVEF predicted mortality from univariate analysis (p=0.017), but did not reach significance at multivariate analysis (p=0.573). According to Kaplan–Meier survival curves, outcome was less favourable for patients with an inframedian SV index  2  (log rank; p=0.007), and worse outcome was associated with a LVEF    Right ventricular end-diastolic and systolic volume and left ventricular end-diastolic and end-systolic did not significantly predict mortality at Cox proportional hazards regression or Kaplan -Meier analysis.   Conclusions   Low SV is a strong predictor of adverse outcome in patients with PH-COPD. Static ventricular volumes did not aid the prediction of adverse outcome.
Heritable connective tissue disorders as factor modifying asthma symptoms in pediatric patients
Authors: Zoia Nesterenko, Olena Ivanina
Journal: European Respiratory Journal (2012)

Background:  High prevalence of heritable connective tissue disorders (HCTD) among children changes clinical manifestations of common childhood diseases, leading to diagnostic and therapeutic errors.   Aim:  To study clinical features of asthma (A) in children with HCTD.   Methods:  80 patients aged 3-18 years with moderate allergic A (GINA Guidelines 2009) were followed up for two years. 33(41.6%) patients had mild persistent A, 37(49.5%) – moderate persistent A and 10(8.9%) – severe persistent A. 55(68,8%) patients had clinically, serologically and radiographically diagnosed CAP. All children had phenotypic manifestations of HCTD.   Results:  CAP caused by Mycoplasma pneumonia was in 80% of asthmatic patients with CAP, by Cytomegalovirus – in 36.3%, by Chlamydophila pneumonia - in 29.1%. 47.3% of patients with A and CAP had recurrent episodes of CAP that caused A exacerbation. Pulmonary hypertension (PH) was in 28.8% of patients with A and in 32.7% of patients with CAP and A, 33.3% of the latter had severe persistent A with CT evidence of pulmonary fibrosis (PF) and emphysematous bullae (EB). Patients with A exacerbation due to CAP received antibiotic treatment (macrolides) (ABT) besides controller therapy, and this provided the achievement of A control.   Conclusions:  1. A exacerbation in 80% of asthmatic patients was due to CAP caused by Mycoplasma pneumonia. 2. Recurrent episodes of CAP were in 47.3% of asthmatic patients with HCTD. 3. 28.8% of patients with A and HCTD, and 37.2% of patients with A, HCTD and CAP had evidence of PH, with PF and EB in 33.3% of the latter. 4. Basic therapy of asthmatic patients with CAP included ABT to achieve A control.
Military medical services to be restored
Authors: John Warden
Journal: BMJ (1998)

Reinforcement of the defence medical services is a key theme of Britain's strategic defence review announced by the government last week. It is to include the recruitment of 250 hospital specialists, nurses, and technicians as well as a series of operational changes to restore the medical capability of the armed forces.

In a statement to the Commons, the defence secretary, George Robertson, spoke of “serious weaknesses in our hollowed out and demoralised defence medical services.” Last year the Commons defence committee said that Britain's military medical …
Manual of Clinical Problems in Pulmonary Medicine
Journal: Thorax (1992)

ABSTRACT This study evaluated the influence of receptor/G-protein (R:G) stoichiometry on constitutive activity and the efficacy of agonists, partial agonists, and inverse agonists at human (h) 5-hydroxytryphamine 1B (5-HT<sub>1B</sub>) receptors. Two Chinese hamster ovary cell lines were used; they expressed 8.5 versus 0.4 pmol h5-HT<sub>1B</sub> receptors/mg (determined by [<sup>3</sup>H]GR125,743 saturation analysis) and 3.0 versus 1.5 pmol receptor-activated G-proteins/mg [determined by guanosine-5′-<i>O</i>-(3-[<sup>35</sup>S]thio)-triphosphate ([<sup>35</sup>S]GTPγS) isotopic dilution], respectively. Thus, they displayed R:G ratios of ∼3.0 (RGhigh) and ∼0.3 (RGlow), respectively. In competition-binding experiments, the agonists, 5-HT and sumatriptan, displayed fewer high-affinity (HA)-binding sites and the partial agonists, BMS181,101 and L775,606, displayed decreased affinity in RGhigh versus RGlow membranes. In contrast, the inverse agonists, SB224,289 and, to a lesser extent, methiothepin, showed increased affinity. In G-protein activation experiments, both basal and 5-HT-activated [<sup>35</sup>S]GTPγS binding were higher in RGhigh than in RGlow membranes. Constitutive activity (determined by inhibition of basal [<sup>35</sup>S]GTPγS binding with GTPγS in the absence of receptor ligands) was more pronounced in RGhigh versus RGlow membranes, as revealed by the &gt;5-fold greater proportion of HA sites. Correspondingly, the negative efficacy of inverse agonists was strikingly augmented, inasmuch as they suppressed approximately two-thirds of HA [<sup>35</sup>S]GTPγS binding in RGhigh membranes, but only approximately one-third in RGlow membranes. Furthermore, the efficacy of partial agonists was greater at RGhigh versus RGlow membranes, as estimated by their ability to enhance [<sup>35</sup>S]GTPγS binding. In conclusion, an increase in R:G ratios at h5-HT<sub>1B</sub> receptors was associated with an increase in relative efficacy of partial agonists and, most notably, an increase in both constitutive G-protein activation and negative efficacy of inverse agonists.
Differential Susceptibility of Inbred Mouse Strains Forecast by Acute Colonic Proliferative Response to Methylazoxymethanol23
Authors: Eleanor E. Deschner, Florence C. Long, Mary Hakissian, Susan H. Cupo
Journal: JNCI Journal of the National Cancer Institute (1984)

The proliferative response of colonic epithelial cells to methylazoxymethanol (MAM) was followed in 1,2-dimethylhydrazine (DMH)-sensitive SWR/J, moderately resistant C57BL/6J, and resistant AKR/J strains. Untreated AKR mice had a significantly lower labeling index (LI) a shorter proliferative compartment (PC), and a smaller percentage of DNA synthesizing cells in the middle third of the crypts than did the SWR strain. SWR had the highest LI, the widest PC, and the largest percentage of DNA synthesizing cells in the middle third of the crypts. C57BL/6 mice had characteristics that lay between the sensitive and resistant strains. Pooled data from 1 week after the fifth and sixth injections and 12 weeks after the first MAM injection revealed that extension of the PC had occurred in all strains, but it was only the DMH-sensitive SWR strain that showed extension of the PC to the upper third of the crypt, the greatest shift of proliferating cells to the middle and upper third of crypts, and the greatest increase in LI. The AKR strain demonstrated these proliferative alterations least, and the C57BL/6 strain fell between them. This differential response to MAM among the strains mimicked that previously reported by us when DMH was investigated. The similarity in response of the colonie epithelial cells of each strain to either a direct-acting (MAM) or indirect-acting carcinogen (DMH) would support the concept that susceptability to this family of carcinogens is directly related to the genetically controlled indigenous proliferative characteristics of the colon.
Abstract 122: A Novel Mutation in a X-linked Gene Causes Human Congenital Dilated Cardiomyopathy
Authors: Young Wook Chun, Tromondae K Feaster, Charles H Williams, Calvin C Sheng, Audrey Y Frist, Yan Ru Su, David P Bichell, Charles C Hong
Journal: Circulation Research (2014)

Congenital dilated cardiomyopathy (cDCM) is a rare but often fatal disease. In most cases, there is no family history, and its etiology is unknown. A major hurdle to elucidating a mechanistic understanding of congenital cardiomyopathy, and primary cardiomyopathies in general, has been a lack of access to diseased human cardiac tissues. Recent advances in patient-derived induced pluripotent stem cells (iPSCs) now enable production of human cardiomyocytes (iPSC-CMs) and allows for a systematic study of normal and diseased cardiomyocytes. We hypothesize that cardiomyocytes generated from iPSCs derived from cDCM patients will exhibit cellular and molecular differences from those generated from healthy donor iPSCs and that a rare genetic mutation, or a collection of mutations, plays a critical role in cDCM pathogenesis. To test these hypotheses, we generated cardiomyocytes from iPSCs derived from a 7-month old male with cDCM using a robust cardiac induction protocol based on the “matrigel sandwich” method of Kamp and colleagues. With this remarkably robust induction method, iPSC-CMs from the cDCM patient and a healthy control donor exhibited proteomic profiles that were 99.7% superimposable. Despite the close similarity at the global proteome level, iPSC-CMs from the cDCM patient showed greatly reduced contractility and dramatic structural defects in the sarcomere and the mitochondria. Finally, bioinformatics analyses of the RNAseq data of the patient’s iPSC-CMs discovered a putative causal mutation in an evolutionarily conserved site in a X-linked gene with unknown function. In summary, our work demonstrates that iPSC-based approaches are particularly useful for the study of human congenital heart diseases. We plan to confirm the causality of this mutation using gene editing techniques such as CRISPR/Cas9 and explore the role of this novel gene in cardiomyocyte structure and function.
Is T-SPOT.TB performance in bronchoalveolar lavage usuful in differential diagnosis between sarcoidosis and tuberculosis? - Pilot study
Authors: Anna Kempisty, Piotr Radwan-Rohrenschef, Dagmara Borkowska, Ewa Augustynowicz-Kopec, Jan Kus
Journal: European Respiratory Journal (2012)

Introduction: Both sarcoidosis and tuberculosis are similar in their radiological and histological pictures. Sometimes it is difficult to distinguish between these two diseases. The only reliable diagnostic tool for M. tuberculosis (MTB) are cultures. Unfortunately we have to wait for several weeks for culture results to make final diagnosis.

Object and rationale: IGRAs in peripheral blood detect MTB infection but do not discriminate latent from active TB. The aim of this study was to evaluate utility of T-SPOT.TB test in BAL and its advantages over T-SPOT.TB test in peripheral blood in differential diagnosis between sarcoidosis and tuberculosis.

Material and method: 11 subjects (4 female, 7 male; mean aged 45,8±12) suspected for sarcoidosis were included in this study. 1 was withdrew because of bronchial obstruction which made the BAL impossible. T-SPOT.TB tests in peripheral blood and in BAL were performed in 10 subjects.

Results: All 10 patients were AFB and MTB DNA negative in BAL. T-SPOT.TB test was positive in peripheral blood in 2/10 and in BAL in 1/10. The culture of BAL was positive for MTB only in the case who had positive T-SPOT.TB test both in BAL and in peripheral blood.

Conclusion : Positive T-SPOT.TB performed in BAL could be helpful in differential diagnosis between sarcoidosis and tuberculosis. Further studies are needed.