tbuckley/cabot-search huggingface dataset:
Acute Efficacy of ECT in the Treatment of Major Depression in the Old-Old
Authors: James D. Tew, Benoit H. Mulsant, Roger F. Haskett, Joan Prudic, Michael E. Thase, Raymond R. Crowe, Diane Dolata, Amy E. Begley, Charles F. Reynolds, Harold A. Sackeim
Journal: American Journal of Psychiatry (1999)

There are few data addressing the outcome of ECT for persons over 75 years of age. In a prospective, multisite study, the authors compared characteristics and treatment outcomes of adult (59 and younger), young-old (60 to 74 years), and old-old (75 and older) patients treated with ECT for major depression.At four hospitals, 268 patients with primary unipolar major depression and scores of at least 20 on the 24-item Hamilton Depression Rating Scale were treated with suprathreshold right unilateral or bilateral ECT in a standardized manner. Demographic variables, clinical characteristics, and short-term outcomes of the three groups were compared.The demographic and clinical characteristics of the old-old patients were similar to those of the young-old patients, whereas both groups differed from the adult patients on these variables. Both older groups had significantly greater burdens from physical illness and global cognitive impairment at baseline than the adult subjects. Both older groups had shorter index depressive episodes and were less likely to have had inadequate responses to adequate medication trials before ECT. The older groups had higher seizure thresholds, but the three groups received similar courses of treatment. The adult patients experienced a significantly lower rate of ECT response (54%) than the young-old patients (73%), while the old-old patients had an intermediate rate of response (67%).Despite a higher level of physical illness and cognitive impairment, even the oldest patients with severe major depression tolerate ECT in a manner similar to that for younger patients and demonstrate similar or better acute response.
Home NIV for patients with stable COPD
Authors: Kasper Ankjærgaartd, Sophia Maibom, Jon Torgny Wilcke
Journal: European Respiratory Journal (2012)

Background: Non invasive ventilation (NIV) is shown to be effective in the treatment of acute respiratory failure in patients with chronic obstructive pulmonary disease (COPD) and as treatment at home in patients with chronic respiratory failure due to e.g. neuromuscular disease. Previous studies in patients with COPD have shown conflicting results of home NIV.  Aim: Audit of home NIV treatment initiated due to repeated admissions with NIV treated acute hypercapnic respiratory failure (AHRF).  Method: Retrospective study of acutely NIV treated patients in our dept. of lung medicine. Frequency and duration of hospital admissions respectively 12 and 6 months before and 6 months after the initiation of home NIV were compared.  Results: Fig. shows a significant reduction in number of admissions 6 months after initiation of home NIV compared to 12 (avg 2,4 to 0,75 (p = 0,05)) and 6 months before initiation (avg. 4 to 0.75 (p = 0,0046))  Conclusion: The study shows that home NIV is effective to reduce admissions with respiratory problems in a highly selected group of COPD patients with previous repeated AHRF and need of acute NIV treatment.
High cure rate with a moderately intensive treatment regimen in non-high-risk childhood acute lymphoblastic leukemia. Results of protocol ALL VI from the Dutch Childhood Leukemia Study Group.
Authors: A J Veerman, K Hählen, W A Kamps, E F Van Leeuwen, G A De Vaan, G Solbu, S Suciu, E R Van Wering, A Van der Does-Van der Berg
Journal: Journal of Clinical Oncology (1996)

PURPOSE Here we report the results of a nationwide cooperative study in the Netherlands on acute lymphoblastic leukemia (ALL) in children. The aim of the study was to improve the cure rate and to minimize side effects in a group of non-high-risk ALL patients, especially with regard to the CNS. A second aim was to study potential prognostic factors. METHODS Children (age 0 to 15 years) with non-high-risk ALL (WBC count &lt; 50 x 10(9)/L, no mediastinal mass, no B-cell phenotype, and no CNS involvement) were treated with a uniform protocol, ALL VI. The treatment protocol used 6-week induction regimen with three drugs (vincristine, dexamethasone, and asparaginase), three weekly doses of intravenous (IV) medium high-dose methotrexate (2 g/m2), and 2-year maintenance therapy that consisted of alternating 5-week periods of methotrexate and mercaptopurine and 2-week periods of vincristine and dexamethasone. In the first year of maintenance, triple intrathecal therapy was administered every 7 weeks. RESULTS From December 1, 1984 until July 1, 1988, 291 children with ALL were diagnosed; 206 were categorized as non-high-risk (71%), and 190 were treated according to protocol ALL VI. At 8 years, the event-free survival (EFS) rate was 81% (SE = 3%) and survival rate 85% (SE = 2.9%); the median follow-up time was 7.3 years (range, 36 to 117 months). The CNS relapse rate was 1.1% (two of 184 patients who achieved a complete remission [CR]). The only factor found to be of negative prognostic importance in terms of EFS (P = .05) was a positive acid phosphatase reaction. CONCLUSION For children with non-high-risk ALL, the combination of IV medium high-dose methotrexate (2 g/m2 times three), triple intrathecal therapy in the first year of maintenance treatment, and the use of dexamethasone for induction and pulses during maintenance treatment has proved to be highly effective, especially in the prevention of CNS relapse. A high cure rate was achieved without the use of anthracyclines, alkylating agents, and cranial irradiation.
PCD with normal ultrastructure is not rare
Authors: Mieke Boon, Anne Smits, Mark Jorissen, Lieven Dupont, Francois Vermeulen, Marijke Proesmans, Frans De Baets, Véronique Godding, Anne Malfroot, Martine Jaspers, Kris De Boeck
Journal: European Respiratory Journal (2012)

Introduction:  The presence of ultrastructural abnormalities (UA) on transmission electron microscopy (TEM) is proposed as gold standard for the diagnosis of Primary Ciliary Dyskinesia (PCD). Functional evaluation after ciliogenesis in culture (CC) is only proposed if the diagnosis is doubted. Because secondary changes are frequent, all samples are evaluated by CC at our centre. Since the detection of a  DNAH11  mutation, the existence of the subtype normal ultrastructure but abnormal motility (NU) is proven. Using CC, we show that this subtype is not as rare as thought.   Methods : Over 22 years, the CC procedure was used in 3077 subjects, of which 200 were diagnosed as PCD. Epithelial cells are isolated from nasal biopsies and cultured as a monolayer. After losing all the cilia they are brought into suspension, to gain cilia  de novo .   Results : UA was found in 133 subjects, NU in 67. In only 35 of the NU, ciliary beat frequency (CBF) could be measured before CC. It was abnormal in 22 and normal in 13, with absent ciliary coordination in 7 of these 13. After CC, all the samples lacked coordination, pathognomonic for PCD. CBF was abnormal in 50 and normal in 17 subjects. Repeat biopsy in 18 patients was identical. CC was the only technique to make the diagnosis of PCD in 39 subjects.  nNO did not significantly differ from the UA group. There was familial occurrence of NU in 4 sibling pairs, consanguinity in 13.6%, situs inversus in 34%. The clinical characteristics (bronchiectasis, nasal secretions, hearing loss, draining ears, polyposis nasi, infertility) were similar in UA and NA.   Conclusion : CC is the most reliable tool to diagnose PCD and unambigouosly detect patients with PCD and NA who might be missed when using other diagnostic methods.
Mechanisms of bone destruction in multiple myeloma: the importance of an unbalanced process in determining the severity of lytic bone disease.
Authors: R Bataille, D Chappard, C Marcelli, P Dessauw, J Sany, P Baldet, C Alexandre
Journal: Journal of Clinical Oncology (1989)

In order to clarify the mechanisms involved in the occurrence of lytic bone lesions (BL) in multiple myeloma (MM), we have compared the presenting myeloma-induced histological bone changes of 14 previously untreated MM patients with lytic BL with those of seven MM patients lacking lytic BL at presentation despite similar myeloma cell mass. A major unbalanced bone remodeling (increased bone resorption with normal to low bone formation) was the characteristic feature of patients presenting lytic BL. Furthermore, this unbalanced process was associated with a significant reduction of bone mass. Unexpectedly, a balanced bone remodeling (increase of both bone resorption and bone formation, without bone mass reduction) rather than a true lack of an excessive bone resorption was the usual feature of patients lacking lytic BL. Our current work clearly shows that a majority (72%) of patients with MM present an important unbalanced bone remodeling at diagnosis, leading to bone mass reduction and bone destruction (unbalanced MM). Some patients (20%) retain a balanced bone remodeling with initial absence of bone destruction (balanced MM). Few (8%) patients have pure osteoblastic MM without bone destruction.
Length of hospital stay and 30‐day readmission following heart failure hospitalization: insights from the <scp>EVEREST</scp> trial
Authors: Hassan Khan, Stephen J. Greene, Gregg C. Fonarow, Andreas P. Kalogeropoulos, Andrew P. Ambrosy, Aldo P. Maggioni, Faiez Zannad, Marvin A. Konstam, Karl Swedberg, Clyde W. Yancy, Mihai Gheorghiade, Javed Butler
Journal: European Journal of Heart Failure (2015)
Human Signal-Regulatory Protein Is Expressed on Normal, But Not on Subsets of Leukemic Myeloid Cells and Mediates Cellular Adhesion Involving Its Counterreceptor CD47
Authors: Martina Seiffert, Charles Cant, Zhengjun Chen, Irene Rappold, Wolfram Brugger, Lothar Kanz, Eric J. Brown, Axel Ullrich, Hans-Jörg Bühring
Journal: Blood (1999)
More brickbats than bouquets?
Authors: John Appleby, Kambiz Boomia, Jane Dacre, Peter Davies, Jacky Davis, Andy Haines, David Haslam, David J. Hunter, Bart Johnson, Robert Lechler, Judith Lindeck, Ann McPherson, Allyson Pollock, Gayathri Rabindra, Simon Stevens, Richard Thompson, Jonathan Waxman
Journal: BMJ (2010)
Analysis of a Pathology Review of Patients With Lung Tumors2, 3
Authors: Kenneth E. Stanley, Mary J. Matthews
Journal: JNCI Journal of the National Cancer Institute (1981)

The rates of agreement and patterns of disagreement in the classification of lung tumors were evaluated for a pathology panel review of 476 patients with lung cancer. The panel review consisted of three independent diagnoses made in accordance with the criteria of the Working Party for Therapy of lung Cancer. At least two of the three pathologists agreed as to the major cell classification in 94% of the patients. In 67% of the evaluations, there was agreement among the three pathologists. Small-cell carcinoma and epidermoid carcinoma were the most consistently evaluated classes, followed by adenocarcinoma and large-cell carcinoma. The poorly differentiated categories provided the greatest source of difficulty in discriminating among major histologic classes. For an initial diagnosis of large-cell carcinoma, 14% of the second classifications were poorly differentiated epidermoid carcinoma, and 20% were poorly differentiated adenocarcinoma. For an initial diagnosis of small-cell carcinoma, 11% of the second independent evaluations classified the carcinoma as other than small-cell. The most likely alternative diagnosis was large-cell carcinoma (5%).
Effect of Protracted High-Dose <scp>l</scp>-Asparaginase Given as a Second Exposure in a Berlin-Frankfurt-Münster–Based Treatment: Results of the Randomized 9102 Intermediate-Risk Childhood Acute Lymphoblastic Leukemia Study—A Report From the Associazione Italiana Ematologia Oncologia Pediatrica
Authors: C. Rizzari, M.G. Valsecchi, M. Aricò, V. Conter, A. Testi, E. Barisone, F. Casale, L. Lo Nigro, R. Rondelli, G. Basso, N. Santoro, G. Masera
Journal: Journal of Clinical Oncology (2001)

To assess in a randomized study the therapeutic effect of the addition of high-dose L-asparaginase (HD ASP) in the context of a Berlin-Frankfurt-Münster (BFM)-based chemotherapy regimen for intermediate risk (IR) childhood acute lymphoblastic leukemia (ALL).From March 1991 to April 1995, a total of 705 patients, with 59% of the cohort of patients fewer than 15 years old, with newly diagnosed non-B ALL, enrolled onto the Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) ALL-91 study, were assigned to the IR group. Patients in remission at the beginning of the reinduction phase were randomized either to the standard treatment (SD ASP arm) or the experimental treatment (HD ASP arm; weekly intramuscular administration of HD ASP 25,000 IU/m(2) repeated for a total of 20 weeks). Most of the patients (90%) were treated with Erwinia chrysanthemi L-asparaginase product.Among the 610 patients randomized to the SD ASP arm (n = 322) or to the HD ASP arm (n = 288), relapse occurred at a median time of 24 months after randomization in 76 (24%) and in 64 children (22%), respectively. Most of the relapses occurred in the marrow (100 isolated, 21 combined). There was no significant difference between the disease-free survival in the two treatment arms (P =.64), with estimated values at 7 years from randomization of 72.4% (SE 3.1) v 75.7% (SE 2.6) in the SD ASP and HD ASP arms, respectively.No advantage was observed for IR ALL children treated with BFM-based intensive chemotherapy who received protracted E chrysanthemi HD ASP during reinduction and the early continuation phase.
U.S. Centralized Cancer Patient Data System for Uniform Communication Among Cancer Centers&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Polly Feigl, Norman E. Breslow, John Laszlo, Roger L. Priore, William F. Taylor
Journal: JNCI Journal of the National Cancer Institute (1981)

The evolution of the Centralized Cancer Patient Data System, a cooperative venture of the 21 comprehensive cancer centers in the United States, and its structure at the end of 3 years of data collection are described. Functions of the data system are detailed in terms of input and output. It is concluded that the short-run objective of establishing a data system to provide high-quality patient data that ae 21 comprehensive cancer centers in the United States, and its structure at the end of 3 years of data collection are described. Functions of the data system are detailed in terms of input and output. It is concluded that the short-run objective of establishing a data system to provide high-quality patient data that ae 21 comprehensive cancer centers in the United States, and its structure at the end of 3 years of data collection are described. Functions of the data system are detailed in terms of input and output. It is concluded that the short-run objective of establishing a data system to provide high-quality patient data that are comparable among cancer centers has been largely accomplished. Moreover, the very process of setting up the national data system has benefited the participating centers by upgrading their individual cancer registries. For the future, the goal is to realize the research potential of this new cooperative data collection mechanism, as well as the accumulating data themselves. Progress toward the long-term goal is just beginning.
Perigranuloma Localization and Abnormal Maturation of B Cells
Authors: Lieke S. Kamphuis, Menno C. van Zelm, King H. Lam, Guus F. Rimmelzwaan, G. Seerp Baarsma, Willem A. Dik, H. Bing Thio, Paul L. van Daele, Mirjam E. van Velthoven, Manou R. Batstra, P. Martin van Hagen, Jan A. van Laar
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Recent observations of abnormal immunoglobulin responses and case reports describing successful B-cell ablative therapy suggest involvement of B cells in the pathogenesis of sarcoidosis.To investigate how abnormal B-cell maturation and function in patients with sarcoidosis contribute to disease.Patients with sarcoidosis (n = 32) were included for detailed analysis by immunohistochemistry of tissue, flow cytometry of blood B-cell subsets, and serum immunoglobulin levels. Vaccination responses in patients with sarcoidosis to influenza virus and encapsulated bacteria and molecular analysis of immunoglobulin heavy chain transcripts were studied for functional analysis of immunoglobulin responses.Perigranuloma localization of IgA-producing plasma cells and numerous B cells were found in affected tissues. Total blood B-cell numbers were normal, CD27(+) memory B cells were significantly reduced, and CD27(-)IgA(+) B cells were significantly increased; the results are normalized in patients treated with TNF-α blockers. Despite this, patients had normal serum immunoglobulin levels and normal antigen-specific immunoglobulin responses. IgA and IgG transcripts, however, showed high frequencies of somatic hypermutations and increased usage of downstream IgG subclasses, suggestive for prolonged or repetitive responses.The large B-cell infiltrates in granulomatous tissue and increased molecular signs of antibody maturation are indicative of direct involvement of B cells in local inflammatory processes in patients with sarcoidosis. Moreover, CD27(-)IgA(+) B cells could be a marker for treatment with TNF-α blockers. These findings of B cells as emerging key players provide a rationale for a systematic study on B-cell ablative therapy in patients with sarcoidosis.
Phase I/II study to assess safety, pharmacokinetics, and efficacy of the oral MEK 1/2 inhibitor GSK1120212 (GSK212) dosed in combination with the oral BRAF inhibitor GSK2118436 (GSK436).
Authors: J. R. Infante, G. S. Falchook, D. P. Lawrence, J. S. Weber, R. F. Kefford, J. C. Bendell, R. Kurzrock, G. Shapiro, R. R. Kudchadkar, G. V. Long, H. A. Burris, K. B. Kim, A. Clements, S. Peng, B. Yi, A. J. Allred, D. Ouellet, K. Patel, P. F. Lebowitz, K. T. Flaherty
Journal: Journal of Clinical Oncology (2011)

CRA8503 Background: In preclinical models, the BRAF/MEK inhibitor (i) combination GSK436/GSK212 has demonstrated enhanced activity against BRAF-mutant cancer cells compared to either drug alone, delayed emergence of GSK436 resistance, and prevented proliferative skin lesions attributable to BRAFi exposure. Methods: Eligible patients (pts) had BRAF V600 mutation positive solid tumors. Part 1: pharmacokinetic (PK) drug-drug interaction (DDI) study. Part 2: Dose escalation of continuous daily dosing of the combination followed by expansion cohorts; Part 3: Randomized phase II trial in untreated stage IV melanoma. Results: 45 pts have received ≥ 1 dose of GSK212 + GSK436, including 43 melanoma (all BRAFi naïve), 1 NSCLC and 1 salivary duct carcinoma. PK results of 7 pts in Part 1 showed no effect of GSK212 on single dose of GSK436. There was no clinically meaningful DDI between GSK436 and GSK212 after repeat dosing of the combination (Part 2). GSK436 was dosed 75-150 mg BID in combination with GSK212 1.0, 1.5, 2.0 mg QD. The recommended dose was 2 mg QD GSK212 in combination with 150 mg BID GSK436. At 1.5 mg GSK212, there was one DLT, a recurrent grade (G) 2 neutrophilic panniculitis. The only G4 adverse event (AE) was a sepsis-like syndrome with fever/hypotension. G3 AEs included generalized rash (n=2, 4%) and neutropenia (n=2, 4%). Skin toxicity ≥ G2 occurred in 9 (20%) pts; of these, G2 rash (n=4, 8%) and G2 macular rash (n=1, 2%). No cutaneous squamous cell carcinoma (SCC) or hyperproliferative skin lesions have occurred at any dose level. Other common G2 toxicities were pyrexia (n=5, 11%), vomiting (n=2, 4%) and fatigue (n=2, 4%). Of 16 evaluable pts in Part 2, 13 pts had PR and 3 SD for an ORR of 81% (95% CI 54.4%-96.0%) and all but 2 pts remain on study. In 10 evaluable pts who received 150 mg BID GSK436 + ≥1 mg QD GSK212, 9 pts had PR and 1 SD. Conclusions: GSK212 at 2 mg QD combines safely with GSK436 150 mg BID, no SCC thus far and decreased frequency of rash compared to previous trials of single agent GSK436 and GSK212, respectively. The preliminary anti-tumor activity warrants further investigation; the randomized phase II trial (Part 3) is accruing.
EFFECTS OF DRUGS ON VERTEBRATE MECHANORECEPTORS
Authors: A.S. PAINTAL
Journal: Pharmacological Reviews (1964)

By using the results of experiments  in vitro  on the effects of procaine on sensory endings for interpreting the effects of procaine  in vivo , it has become clear that there is practically no diffusion barrier in the terminal parts of sensory nerve fibres. Nature has thereby exposed the regenerative region of the sensory ending to the influence of substances circulating in the blood stream. The generator region is probably equally exposed but is apparently more resistant to the effects of drugs. The central parts of the sensory fibres are not easily exposed to the drugs because of the protection afforded by the nerve sheath, which is known to act as a strong diffusion barrier. This barrier can be overcome (equilibrium approached) by infusion of drugs.  The effects of all intravenously injected drugs on sensory endings can be explained by their effects on the regenerative region, which has practically the same properties as the rest of the nerve fibre. Since non-medullated fibres are more susceptible to drugs than medullated fibres, it follows that the regenerative regions of the endings of non-medullated fibres must be more susceptible to drugs. This explains why the endings of non-medullated fibres are more readily stimulated by a variety of substances that leave the endings of medullated fibres unaffected.  The effects of local anaesthetics have revealed that only in higher doses, or after longer action, do such drugs act on the generator region, but when this occurs, the regenerative region is already totally blocked. It may be assumed that the same applies to other drugs.
Clinical use of the fatigue severity scale on obstructive sleep apnoea patients
Authors: Mafalda van Zeller, Marta Drummond, João Almeida, João Carlos Winck
Journal: European Respiratory Journal (2013)

Introduction-Current obstructive sleep apnoea (OSA) definition includes daytime fatigue as a relevant symptom. The use of scales might be of help characterizing these subjective symptom allowing quantification and standardization as well as evaluation of treatment response.

Aim-To evaluate the relation between fatigue scores and apnoea-hypopnoea index(AHI) and the impact of APAP treatment in that symptom.

Methods-All patients with suspected OSA referred to our center between Feb-Mar 2012 were considered eligible. During first the appointment patients completed Fatigue Severity Scale (FSS) and Epworth Severity Scale (ESS) questionnaires, clinical history was collected and a polygraphic cardiorespiratory sleep study performed.

If patients were started on APAP treatment with good compliance (>70%/days, >4hours/night) after 3 months of treatment the FSS and ESS questionnaires were repeated.

Results-88 patients were included, 71.6% were male, with a mean age of 51.9±13.4 years. Mean values of FSS and ESS questionnaires were 34.64±14.5 and 8.47±5.0, respectively.

In 24 (27.3%) patients OSA was excluded, OSA was diagnosed in 64 patients being mild in 25 patients (28.6%), moderate in 20 (22.7%) and severe in 19 (21.6%) patients. A statistically significant correlation was found between FSS score and AHI (r-0.263; p=0.05). Those patients with confirmed OSA but without excessive daytime sleepiness (ESS 36. After 3 months of adequate APAP therapy (n=27) a significant reduction of FSS (p=0.004) and ESS (p=0.035) scores was found.

Conclusion-The Portuguese version of the Fatigue Severity Scale seems to be helpful evaluating symptoms related to OSA, specially monitoring the impact of APAP treatment.