tbuckley/cabot-search huggingface dataset:
Alveolitis: the key to the interstitial lung disorders.
Authors: B A Keogh, R G Crystal
Journal: Thorax (1982)

Alveolitis: the key to the interstitial lung disordersThe interstitial lung diseases are a heterogeneous group of chronic, non-infectious, non-malignant dis- orders that affect primarily the alveolar structures.1-5The spectrum of disease included under this heading is enormous-at least 130 different interstitial lung diseases have been described (see references 1, 5 for the current list).Most of these diseases, however, are relatively rare; the common interstitial disorders are those resulting from inhalation of inorganic or organic dusts, sarcoidosis, idiopathic pulmonary fibrosis, and the interstitial lung diseases associated with the collagen-vascular disorders.'While diagnosis is not usually a major problem, the management of patients with interstitial lung disease presents a difficult challenge.These diseases are generally progressive, but in a baffling, often intermittent, stop-start fashion.More importantly, it is now apparent that conventional, clinical, radio- logical, and physiological assessments bear little relationship to staging the activity of these disorders, thus frustrating the clinician's attempt to make rational therapeutic decisions.1 5 6All this is changing, however.Through the work of many laboratories throughout the world, it is now recognised that, independent of the type of disease or specific aetiology, the earliest manifestation of inter- stitial disease is an "alveolitis"-the accumulation of inflammatory and immune effector cells within the alveolar structures.1 3-5 7-10 The importance of the alveolitis is simply stated: while it is clear that the interstitial lung diseases are characterised by a variety of derangements to the cells and connective tissue matrix that comprise the alveolar structures, it is now recognised that it is the alveolitis that causes these derangements.As we will see, the con- cept of "alveolitis" has caused a revolution in think- ing that has completely changed the clinical approach to staging and treating patients with interstitial lung disease. Lessons from morphologyWhile the concept of alveolitis may appear "new",
DNA Methylation Profiling Defines Clinically Relevant Biological Subsets of Non–Small Cell Lung Cancer
Authors: Kim Walter, Thomas Holcomb, Tom Januario, Pan Du, Marie Evangelista, Nithya Kartha, Leonardo Iniguez, Robert Soriano, Ling Huw, Howard Stern, Zora Modrusan, Somasekar Seshagiri, Garret M. Hampton, Lukas C. Amler, Richard Bourgon, Robert L. Yauch, David S. Shames
Journal: Clinical Cancer Research (2012)

Non-small cell lung cancers (NSCLC) comprise multiple distinct biologic groups with different prognoses. For example, patients with epithelial-like tumors have a better prognosis and exhibit greater sensitivity to inhibitors of the epidermal growth factor receptor (EGFR) pathway than patients with mesenchymal-like tumors. Here, we test the hypothesis that epithelial-like NSCLCs can be distinguished from mesenchymal-like NSCLCs on the basis of global DNA methylation patterns.To determine whether phenotypic subsets of NSCLCs can be defined on the basis of their DNA methylation patterns, we combined microfluidics-based gene expression analysis and genome-wide methylation profiling. We derived robust classifiers for both gene expression and methylation in cell lines and tested these classifiers in surgically resected NSCLC tumors. We validate our approach using quantitative reverse transcriptase PCR and methylation-specific PCR in formalin-fixed biopsies from patients with NSCLC who went on to fail front-line chemotherapy.We show that patterns of methylation divide NSCLCs into epithelial-like and mesenchymal-like subsets as defined by gene expression and that these signatures are similarly correlated in NSCLC cell lines and tumors. We identify multiple differentially methylated regions, including one in ERBB2 and one in ZEB2, whose methylation status is strongly associated with an epithelial phenotype in NSCLC cell lines, surgically resected tumors, and formalin-fixed biopsies from patients with NSCLC who went on to fail front-line chemotherapy.Our data show that patterns of DNA methylation can divide NSCLCs into two phenotypically distinct subtypes of tumors and provide proof of principle that differences in DNA methylation can be used as a platform for predictive biomarker discovery and development.
Assessing the Shape of the Glucose Curve During an Oral Glucose Tolerance Test
Authors: Otto Tschritter, Andreas Fritsche, Fatemeh Shirkavand, Fausto Machicao, Hans Häring, Michael Stumvoll
Journal: Diabetes Care (2003)

OBJECTIVE—The oral glucose tolerance test (OGTT) is used to define the status of glucose tolerance based on the plasma glucose level at 120 min. The purpose of the present study was to identify parameters that determine the shape of the plasma glucose course measured at 0, 30, 60, 90, and 120 min during an OGTT. RESEARCH DESIGN AND METHODS—OGTT data from 551 subjects (485 with normal glucose tolerance [NGT] and 66 with impaired glucose tolerance [IGT]) were analyzed. We distinguished between “monophasic,” “biphasic,” and unclassified glucose shapes. A “shape” index based on the extent and the direction of the plasma glucose change in the second hour allowed us to treat shape as a continuous variable. RESULTS—In the biphasic group, the NGT-to-IGT ratio was slightly higher (173/20 vs. 209/40, P = 0.08) and the male-to-female ratio was lower (60/133 vs. 120/129, P = 0.0003). Subjects with a biphasic shape had significantly lower age, BMI, waist-to-hip ratio (WHR), HbA1c, plasma glucose, and area under the insulin curve (insulinAUC) and a better estimated insulin sensitivity and secretion (using validated indexes) than monophasic subjects (all P &amp;lt; 0.05). By adjusting this shape index for glucoseAUC (as continuous measure of glucose tolerance), correlations with age, BMI, WHR, HbA1c, and insulinAUC were completely abolished. The adjusted shape index was still higher in female than in male subjects but lower in IGT than in NGT subjects (both P = 0.0003). Finally, we tested common polymorphisms in insulin receptor substrate (IRS)-1, IRS-2, calpain-10, hepatic lipase, and peroxisome proliferator-activated receptor-γ for association with the shape index. CONCLUSIONS—We conclude that the plasma glucose shape during an OGTT depends on glucose tolerance and sex. In addition, genetic factors seem to play a role. The shape index may be a useful metabolic screening parameter in epidemiological and genetic association studies.
Prevalence of metabolic syndrome with obstructive sleep apnea in a Korean population
Authors: Hyeon Hui Kang, Ki Hoon Park, Woo Ho Ban, Sang Haak Lee, Ki Bum Won
Journal: European Respiratory Journal (2013)

Background  Obstructive sleep apnea (OSA) is known to be associated with cardiovascular risk factors and metabolic syndrome (MS). We investigated the prevalence of MS and its risk factor in a cross-sectional study in patients with and without OSA in a sleep clinic population.  Methods  Consecutive patients undergoing full overnight polysomnography in our sleep lab, were studied. Anthropometric and polysmonograpic data were measured. MS was defined using the National Cholesterol Education Program Adult treatment panel III criteria, with asian cut-off values for abdominal obesity. The patients whose apnea-hypopnea index was ≥5 were determined as OSA group.  Results  Of the 194 subjects recruited, 158 (81%) was diagnosed as OSA. Prevalence of MS in OSA patients was 67 % compared to 33 % in non-OSA subjets [OR 4.07, (1.89-8.79),  P  P  P =0.009]. Cutoff point value for neck circumference as OSA determiner in patients with MS was revealed ≥36.5 cm.  ConclusionIn  In this study, OSA is associated with 4-fold higher risk of MS than patients without OSA. The prevalence of MS is correlated with the severity of OSA. Neck circumference is an independent risk factor for OSA in patients with MS.
PIP2 Activates KCNQ Channels, and Its Hydrolysis Underlies Receptor-Mediated Inhibition of M Currents
Authors: Hailin Zhang, Liviu C Craciun, Tooraj Mirshahi, Tibor Rohács, Coeli M.B Lopes, Taihao Jin, Diomedes E Logothetis
Journal: Neuron (2003)
Polyamine and Nucleic Acid Concentrations in Ehrlich Ascites Carcinoma Cells and Liver of Tumor-Bearing Mice at Various Stages of Tumor Growth&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Gunnar Andersson, Olle Heby
Journal: JNCI Journal of the National Cancer Institute (1972)

The concentrations of putrescine, spermidine, spermine, DNA, and RNA in Ehrlich mouse ascites carcinoma cells were determined at various stages of tumor growth. The putrescine concentration was markedly elevated in the latter phases of rapid multiplication, but declined considerably with increasing tumor mass. The changes in the concentration of spermidine, spermine, and nucleic acids were similar to each other. There were concomitant maxima in the polyamine-N/nucleic acid-P ratio and the number of prophases during tumor growth. The concentrations of polyamines and nucleic acids were also studied in the livers of tumorbearing mice. The results clearly demonstrated that the transplanted ascites tumor greatly influenced the spermidine concentration in the liver. After a precipitous drop, it progressively increased to a value considerably higher than the initial value. However, the presence of the tumor did not markedly alter the DNA and RNA concentrations.
Changes in gastric secretion with time after vagotomy and the relationship to recurrent duodenal ulcer.
Authors: D J Butterfield, P F Whitfield, M Hobsley
Journal: Gut (1982)

We studied 29 patients who had gastric secretion tests after a vagotomy for duodenal ulcer. There were 14 patients who developed a recurrent duodenal ulcer during the follow-up period and 15 patients who remained free from recurrence. Insulin-stimulated gastric secretion increased with time in the recurrent ulcer group, but not in the group with a satisfactory outcome. On the basis of our results, post-vagotomy patients could be divided into three groups. The first group had a high secretion immediately after the operation and it remained high. The risk of recurrent ulcer in that group was about 50%. The second group had an initially low secretion which increased with time, and the risk of recurrent ulcer in that group was the same as for the first group. The third group had an early low secretion which did not increase with time and the risk of recurrence in this group was less than 5%.
Risk of fatal cerebrovascular accident in patients on peritoneal dialysis versus hemodialysis.
Authors: J Mattana, C Effiong, R Gooneratne, P C Singhal
Journal: Journal of the American Society of Nephrology (1997)

Several reports have suggested that the incidence of hemorrhagic stroke may be greater on hemodialysis as compared with that among the general population and that patients with intracranial hemorrhage should be treated with peritoneal dialysis rather than hemodialysis. However, whether the risk of fatal stroke is greater on hemodialysis versus peritoneal dialysis has not been systematically examined. In this study, the case of a diabetic patient with extensive peripheral vascular disease who, after 7 years on hemodialysis, was changed to peritoneal dialysis and subsequently suffered two strokes over a 5-month period, is reported. Recent data from the United States Renal Data System, which allow a comparison of death rates from stroke in large numbers of hemodialysis versus peritoneal dialysis patients, are reviewed. These data suggest that the risk of death from stroke may actually be greater for patients on peritoneal dialysis versus hemodialysis in spite of their having a lesser prevalence of preexisting cerebrovascular disease. This risk was greatest for elderly diabetic black patients and women, who experienced a nearly twofold-greater odds favoring death from stroke on peritoneal dialysis versus hemodialysis. Selection of a dialysis modality for a patient beginning renal replacement therapy may require the consideration of such data, particularly in those patients with extensive preexisting vascular disease.
Interleukin 7 receptor α chain ( IL7R ) shows allelic and functional association with multiple sclerosis
Authors: Simon G Gregory, Silke Schmidt, Puneet Seth, Jorge R Oksenberg, John Hart, Angela Prokop, Stacy J Caillier, Maria Ban, An Goris, Lisa F Barcellos, Robin Lincoln, Jacob L McCauley, Stephen J Sawcer, D A S Compston, Benedicte Dubois, Stephen L Hauser, Mariano A Garcia-Blanco, Margaret A Pericak-Vance
Journal: Nature Genetics (2007)
Why castration-resistant prostate cancer patients with neuroendocrine differentiation should be addressed to a cisplatin-based regimen
Authors: F. Vignani, L. Russo, M. Tucci, M. Motta, G. Vellani, M. Tampellini, M. Papotti, L. Dogliotti, A. Berruti
Journal: Annals of Oncology (2009)
Partners of patients with sleep apnoea/hypopnoea syndrome: effect of CPAP treatment on sleep quality and quality of life
Authors: N McArdle
Journal: Thorax (2001)

Background-The sleep apnoea/ hypopnoea syndrome (SAHS) causes snoring, apnoeas, and restlessness during sleep which partners frequently complain about.A study was undertaken to determine the impact on partners of SAHS and of treatment of the patient with continuous positive airway pressure (CPAP).Methods-Forty nine partners and patients with SAHS booked for CPAP treatment completed in house and validated questionnaires (Pittsburgh sleep quality index, Short Form 36 self-reported health status) before the patient started treatment.Twenty three couples in whom the index SAHS patient had no driving problems were recruited to a randomised crossover trial with 1 month limbs of CPAP and placebo capsule.At the end of each limb the partners' sleep was monitored by home polysomnography (PSG) and questionnaires were completed.Results-Before treatment partners frequently reported moderate to severe disturbance from patient snoring/apnoeas/ restlessness and had poor sleep quality and self-reported health status.In the crossover study (22 completed) the partners' objective sleep quality did not diVer between CPAP and placebo, but they reported benefit from treatment of the patients with CPAP in subjective sleep quality (p=0.05) and disturbance to sleep (p=0.03).The reported change in partners' sleep quality between pre-study and following CPAP treatment correlated positively with CPAP use (r=0.5, p=0.01).Conclusions-Partners of patients with SAHS have poor sleep quality and selfreported health status but only subjective sleep quality benefits from treatment of the patient with CPAP.
Beneficial response to rituximab in a patient with haemolysis and refractory Felty syndrome
Authors: A Salama, U Schneider, T Dorner
Journal: Annals of the Rheumatic Diseases (2008)

Felty syndrome is characterised by chronic arthritis, splenomegaly and leucopenia. Although anaemia is present in many affected patients, significant haemolysis has not yet been described. While disease-modifying agents do not seem to improve leucopenia and anaemia, splenectomy results in a prompt relief of the haematological manifestations in most cases.1–3 To date, rituximab has been used in the treatment of three patients with Felty syndrome, and the haematological manifestation was improved in one patient only.4 5

We report on an improvement of both arthritis and haemolysis, but not of neutropenia and thrombocytopenia, …
Cell surface marker studies in a patient with cutaneous multilobated T-cell lymphoma
Authors: A. FATTOROSSI, S. MORETTI, A. PALERMO, M. SANTUCCI, R. BONDI, B. GIANNOTTI
Journal: British Journal of Dermatology (1985)

The phenotypic profile of atypical cells from a patient with cutaneous multilobated T-cell lymphoma was investigated using a multiparameter approach including evaluation of membrane markers, cytochemistry, and functional activity. Retroviral sequence restriction analysis was also used to investigate the presence of human T-cell leukaemia/lymphoma virus type I (HTLV-I) in atypical cells infiltrating the skin and in otherwise normal peripheral blood lymphocytes. The atypical cells appeared to belong to the T-lineage demonstrating OKT11 positivity, E-rosette formation, tartrte-sensitive acid phosphatase and β-glucuronidase activity, and consistent negativity for cytoplasmic and/or surface monoclonal immunoglobulins. However, they failed to stain for other T-lymphocyte-associated antigens, such as those defined by OKT3, OKT4, OKT6, OKT8, OKT9, OKT10, Leu-2a and Leu-3a monoclonal antibodies, and did not express a definite α-naphthyl-acetate esterase pattern. Additional studies including phagocytosis tests and a series of monoclonal antibodies against phagocytic and natural killer cell associated antigens were all negative. No HTLV-I related sequences were found in either the cells infiltrating the skin or in circulating lymphocytes. To our knowlege, in previously reported cases of cutaneous multilobated cell lymphoma a clear T-lymphocyte phenotypic profile was demonstrated. Our present data indicate that this is not always necessarily the case. The peculair phenotype we found might represent a transitional state between different T-cell subsets or an as yet unrecognized phenotype of a neoplastic T-lymphocyte which lacks a normal counterpart.
Respiratory function changes after asbestos pleurisy.
Authors: P H Wright, A Hanson, L Kreel, L H Capel
Journal: Thorax (1980)

Six patients with radiographic evidence of diffuse pleural thickening after industrial asbestos exposure are described. Five had computed tomography of the thorax. All the scans showed marked circumferential pleural thickening often with calcification, and four showed no significant evidence of intrapulmonary fibrosis (asbestosis). Lung function testing showed reduction of the inspiratory capacity and the single-breath carbon monoxide transfer factor (TLCO). The transfer coefficient, calculated as the TLCO divided by the alveolar volume determined by helium dilution during the measurement of TLCO, was increased. Pseudo-static compliance curves showed markedly more negative intrapleural pressures at all lung volumes than found in normal people. These results suggest that the circumferential pleural thickening was preventing normal lung expansion despite abnormally great distending pressures. The pattern of lung function tests is sufficiently distinctive for it to be recognised in clinical practice, and suggests that the lungs are held rigidly within an abnormal pleura. The pleural thickening in our patients may have been related to the condition described as "benign asbestos pleurisy" rather than the interstitial fibrosis of asbestosis.
Report of a Multicenter Phase II Trial Testing a Combination of Biweekly Bevacizumab and Daily Erlotinib in Patients With Unresectable Biliary Cancer: A Phase II Consortium Study
Authors: Sam J. Lubner, Michelle R. Mahoney, Jill L. Kolesar, Noelle K. LoConte, George P. Kim, Henry C. Pitot, Philip A. Philip, Joel Picus, Wei-Peng Yong, Lisa Horvath, Guy Van Hazel, Charles E. Erlichman, Kyle D. Holen
Journal: Journal of Clinical Oncology (2010)

Purpose Biliary cancers overexpress epidermal growth factor receptor (EGFR), and angiogenesis has been correlated with poor outcome. Erlotinib, an EGFR tyrosine kinase inhibitor, and bevacizumab, a vascular endothelial growth factor (VEGF) inhibitor have each been shown to have activity in biliary cancer. The primary objective of this study was to evaluate the response rate by Response Evaluation Criteria in Solid Tumors (RECIST). Secondary end points included overall survival (OS), time to progression (TTP), VEGF levels, and molecular studies of EGFR and k-ras. Patients and Methods Eligible patients had advanced cholangiocarcinoma or gallbladder cancer. Patients were treated with bevacizumab 5 mg/kg intravenously on days 1 and 15 and erlotinib 150 mg by mouth daily on days 1 through 28. Responses were evaluated by RECIST. VEGF levels were collected, and samples were analyzed for EGFR mutation by polymerase chain reaction. Results Fifty-three eligible patients were enrolled at eight sites. Of 49 evaluable patients, six (12%; 95% CI, 6% to 27%) had a confirmed partial response. Stable disease was documented in another 25 patients (51%). Rash was the most common grade 3 toxicity. Four patients had grade 4 toxicities. Median OS was 9.9 months, and TTP was 4.4 months. Low repeats (&lt; 16) in EGFR intron 1 polymorphism and G&gt;G k-ras Q38 genotype (wild type) were associated with improved outcomes. Conclusion Combination chemotherapy with bevacizumab and erlotinib showed clinical activity with infrequent grade 3 and 4 adverse effects in patients with advanced biliary cancers. On the basis of preliminary molecular analysis, presence of a k-ras mutation may alter erlotinib efficacy. The combination of bevacizumab and erlotinib may be a therapeutic alternative in patients with advanced biliary cancer.
Vpr R77Q is associated with long-term nonprogressive HIV infection and impaired induction of apoptosis
Authors: Julian J. Lum, Oren J. Cohen, Zilin Nie, Joel G. Weaver, Timothy S. Gomez, Xiao-Jian Yao, David Lynch, André A. Pilon, Nanci Hawley, John E. Kim, Zhaoxia Chen, Michael Montpetit, Jaime Sanchez-Dardon, Eric A. Cohen, Andrew D. Badley
Journal: Journal of Clinical Investigation (2003)

The absence of immune defects that occurs in the syndrome of long-term nonprogressive (LTNP) HIV infection offers insights into the pathophysiology of HIV-induced immune disease. The (H[F/S]RIG)(2) domain of viral protein R (Vpr) induces apoptosis and may contribute to HIV-induced T cell depletion. We demonstrate a higher frequency of R77Q Vpr mutations in patients with LTNP than in patients with progressive disease. In addition, T cell infections using vesicular stomatitis virus G (VSV-G) pseudotyped HIV-1 Vpr R77Q result in less (P = 0.01) T cell death than infections using wild-type Vpr, despite similar levels of viral replication. Wild-type Vpr-associated events, including procaspase-8 and -3 cleavage, loss of mitochondrial transmembrane potential (deltapsi(m)), and DNA fragmentation factor activation are attenuated by R77Q Vpr. These data highlight the pathophysiologic role of Vpr in HIV-induced immune disease and suggest a novel mechanism of LTNP.
Angiotensin-Converting Enzyme Inhibitors versus AT1 Receptor Antagonist in Cardiovascular and Renal Protection
Authors: Tomas Berl
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. The development of pharmacologic agents that directly inhibit the angiotensin II receptor (angiotensin receptor blocker [ARB]) has provided clinicians with an alternative to the previously available angiotensin-converting enzyme inhibitors (ACEI) to downregulate the renin-angiotensin system. This review focuses on the available data that can guide the clinician to the use of these two classes of agents vis à vis their ability to provide cardiovascular (CV) and renal protection. Although the CV protective effect of ACEI in high-risk populations is widely appreciated, whether such an effect is entirely BP independent can be questioned. Most head-to-head comparisons between ACEI and ARB have yielded comparable CV protective effects, with ARB being associated with fewer adverse effects. Likewise, several—but not all—studies have demonstrated a CV protective effect of ACEI when compared with other active agents in patients with type 2 diabetes. One study demonstrated a similar protection with ARB when compared with a β blocker. In terms of renal protection, there are ample data to support a role for both ACEI and ARB to prevent the progression from microalbuminuria to overt albuminuria in both type 1 and type 2 diabetes. However, when progression of renal disease is used as an end point, protection has been demonstrated with ACEI only for type 1 but not type 2 diabetes. In this latter group, only ARB have been shown to slow progression to ESRD.