tbuckley/cabot-search huggingface dataset:
The effect of postrehabilitation programmes among individuals with chronic obstructive pulmonary disease
Authors: D. Brooks, B. Krip, S. Mangovski-Alzamora, R.S. Goldstein
Journal: European Respiratory Journal (2002)

The purpose of this study was to examine the effects of two postrehabilitation programmes on functional exercise tolerance and health-related quality of life in patients with chronic obstructive pulmonary disease (COPD). Subjects with COPD (n=109) were randomised to receive either enhanced follow-up (EF) or conventional follow-up (CF). Subjects in the EF group attended a monthly support group and received a telephone call from a staff member at the midpoint (2 weeks) between their visits. Both groups had scheduled appointments with a physical therapist and physician at 3‐monthly intervals after discharge. Longitudinal data were recorded in 85 subjects (37 EF and 48 CF). Over the course of the study, there was no difference in distance walked in 6 min between the two groups but a significant difference for time and a group-time interaction. There was no difference in total chronic respiratory disease questionnaire score between groups at baseline or at any time interval despite a significant difference with time. There was a clear deterioration in functional exercise capacity and health-related quality of life after completion of respiratory rehabilitation but no difference between the groups.
Reduced forced expiratory flow but not increased exhaled nitric oxide or airway responsiveness to methacholine characterises paediatric sickle cell airway disease
Authors: Rifat A Chaudry, Mark Rosenthal, Andrew Bush, Suzanne Crowley
Journal: Thorax (2014)

<h3>Background</h3> Asthma and airway hyper-responsiveness are reportedly more common in children with sickle cell disease (SCD). <h3>Aim</h3> To determine airway responsiveness, airway inflammation and clinical features of asthma in SCD. <h3>Methods</h3> A prospective, single-centre study of 50 SCD children without overt pulmonary vascular disease and 50 controls. Exhaled nitric oxide (FeNO) and total serum IgE were measured and spirometry and methacholine challenge were performed. The methacholine dose–response slope (DRS) was calculated. <h3>Results</h3> Doctor diagnosis of asthma was made in 7 (14%) SCD versus 12 (24%) control subjects (p=0.203). FeNO levels were similar in SCD and controls (p=0.250), and were higher in those with atopy and an asthma diagnosis (OR 4.33, 95% CI 1.7 to 11.1; p&lt;0.05). zFEV<sub>1</sub> (p=0.002) and zFEV<sub>1</sub>/FVC (p=0.003) but not zFVC (p=0.098) were lower in SCD versus controls. DRS was higher in those with asthma (p=0.006) but not in SCD versus controls (p=0.403). DRS correlated with FeNO and blood eosinophil count in controls but not SCD. In SCD, DRS was higher in those admitted to hospital with respiratory symptoms (n=27) versus those never admitted (n=23) (p=0.046). DRS was similar in those with at least one acute chest syndrome episode (n=12) versus those with none (n=35) (p=0.247). <h3>Conclusions</h3> SCD children have airflow obstruction despite having minimal evidence of pulmonary vascular disease. Airflow obstruction is not associated with increased methacholine sensitivity or eosinophilic inflammation, at least as judged by FeNO. Airflow obstruction in SCD does not appear to be related to childhood eosinophilic asthma, but its pathophysiology remains ill understood.
Long-Term Results of Mitral Valve Repair in Active Endocarditis
Authors: Rachid Zegdi, Mohamed Debièche, Christian Latrémouille, Djoulène Lebied, Catherine Chardigny, Jean-Michel Grinda, Sylvain Chauvaud, Alain Deloche, Alain Carpentier, Jean-Noël Fabiani
Journal: Circulation (2005)

Several investigators have reported the feasibility of mitral valve repair in active endocarditis, but the long-term results are still unknown.We reviewed 37 consecutive patients who underwent mitral valve repair with the Carpentier technique for active endocarditis in our center between 1989 and 1994. This repair involved prosthetic annuloplasty in 31 patients (84%), valve resection in 31 (84%), chordal shortening or transposition in 19 (51%), pericardial patch in 16 (43%), and direct suture of leaflet perforation in 4 (11%). Associated procedures were primarily aortic valve repair or replacement in 11 (30%) and tricuspid repair in 2 (6%). Early complications included 1 operative death (3%; 95% CI, 0 to 15.5) and 1 reoperation for pericardial patch dehiscence. Recurrence of endocarditis was observed in 1 patient (3%; 95% CI, 0 to 16). The 10-year survival rate and freedom from mitral valve reoperation were 80% (95% CI, 66 to 94) and 91% (95% CI, 81 to 100), respectively. At 10 years, most patients (96%) were in good functional status (NYHA class I to II) with no or trivial mitral regurgitation (92%) on echocardiography.Mitral valve repair using Carpentier's techniques in patients with active endocarditis offers very good long-term results with a low rate of recurrence or reoperation.
<i>TP53</i> Mutations and Pathologic Complete Response to Neoadjuvant Cisplatin and Fluorouracil Chemotherapy in Resected Oral Cavity Squamous Cell Carcinoma
Authors: Federica Perrone, Paolo Bossi, Barbara Cortelazzi, Laura Locati, Pasquale Quattrone, Marco A. Pierotti, Silvana Pilotti, Lisa Licitra
Journal: Journal of Clinical Oncology (2010)

PURPOSE To find out if TP53 functional status predicts response to neoadjuvant chemotherapy and thus may be helpful during treatment decision making of oral cavity squamous cell carcinoma (SCC) patients. PATIENTS AND METHODS We analyzed the predictive value of TP53 mutations and their functional status on the basis of the transactivation activity of p53 mutant proteins in 53 pretreatment biopsies of oral cavity SCC patients receiving primary cisplatin and fluorouracil chemotherapy followed by surgery. Results The surgical specimens showed that 15 patients (28%) achieved a pathologic complete remission (pCR) at both T and N sites, and 38 patients had residual tumor cells. Among the 53 pretreatment biopsies, 24 (45%) displayed TP53 mutations: 22 single-nucleotide substitutions and two deletions. According to functional status that could be determined only for the 22 substitutions, 21 mutations were nonfunctional and one was partially functional. TP53 mutation was found in four (27%) of 15 patients who achieved a pCR and in 20 (53%) of 38 nonresponder patients; the difference was not statistically significant (P = .12). In contrast, two (14%) of 14 cases with pCR carried a nonfunctional TP53 mutation, a frequency significantly less than that found in the nonresponders (19 [51%] of 37; P = .02). TP53 mutation predicted pCR in four (17%) of 24 patients and a nonfunctional mutation in only two (9%) of 22 patients. CONCLUSION The results indicate that the loss of function (transactivation activities) of p53 mutant proteins may predict a significant low pCR rate and suboptimal response to cisplatin-based neoadjuvant chemotherapy in patients with oral cavity SCC.
Lung Cancer in Chronic Obstructive Pulmonary Disease
Authors: Stacy Raviv, Keenan A. Hawkins, Malcolm M. DeCamp, Ravi Kalhan
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Patients with chronic obstructive pulmonary disease (COPD) are at increased risk for both the development of primary lung cancer, as well as poor outcome after lung cancer diagnosis and treatment. Because of existing impairments in lung function, patients with COPD often do not meet traditional criteria for tolerance of definitive surgical lung cancer therapy. Emerging information regarding the physiology of lung resection in COPD indicates that postoperative decrements in lung function may be less than anticipated by traditional prediction tools. In patients with COPD, more inclusive consideration for surgical resection with curative intent may be appropriate as limited surgical resections or nonsurgical therapeutic options provide inferior survival. Furthermore, optimizing perioperative COPD medical care according to clinical practice guidelines including smoking cessation can potentially minimize morbidity and improve functional status in this often severely impaired patient population.
IMMUNITY REACTIONS OF HUMAN SUBJECTS TO STRAINS OF PNEUMOCOCCI OTHER THAN TYPES I, II AND III
Authors: Maxwell Finland, W. D. Sutliff
Journal: The Journal of Experimental Medicine (1933)

1. A group of 72 human subjects were studied with respect to the immune reactions of their blood and sera to Types I, II and III pneumococci and to 4 other types (V, VI, VIII and IX) previously included in Group IV. 2. The same general relationships were observed for all of these types as were previously demonstrated for Types I, II and III. Each type was specific in relation to the bactericidal action of normal human blood and the protective action of normal human serum. 3. The frequency with which pneumococcidal action for any pair of types was present for both or absent for both in the same blood samples was slightly greater than that calculated from the frequencies with which each of the types was killed separately. 4. No closer correlation could be demonstrated between the reaction of the blood of these subjects to Types II and V or between Types III and VIII pneumococci, types related in their reaction with artificially prepared immune sera, than was observed between unrelated strains.
Circulating Adiponectin and Resistin Levels in Relation to Metabolic Factors, Inflammatory Markers, and Vascular Reactivity in Diabetic Patients and Subjects at Risk for Diabetes
Authors: Greeshma K. Shetty, Panayiotis A. Economides, Edward S. Horton, Christos S. Mantzoros, Aristidis Veves
Journal: Diabetes Care (2004)

OBJECTIVE—Adiponectin and resistin, two recently discovered adipocyte-secreted hormones, may link obesity with insulin resistance and/or metabolic and cardiovascular risk factors. We performed a cross-sectional study to investigate the association of adiponectin and resistin with inflammatory markers, hyperlipidemia, and vascular reactivity and an interventional study to investigate whether atorvastatin mediates its beneficial effects by altering adiponectin or resistin levels. RESEARCH DESIGN AND METHODS—Associations among vascular reactivity, inflammatory markers, resistin, and adiponectin were assessed cross-sectionally using fasting blood samples obtained from 77 subjects who had diabetes or were at high risk to develop diabetes. The effect of atorvastatin on adiponectin and resistin levels was investigated in a 12-week-long randomized, double-blind, placebo-controlled study. RESULTS—In the cross-sectional study, we confirm prior positive correlations of adiponectin with HDL and negative correlations with BMI, triglycerides, C-reactive protein (CRP), and plasma activator inhibitor (PAI)-1 and report a negative correlation with tissue plasminogen activator. The positive association with HDL and the negative association with PAI-1 remained significant after adjusting for sex and BMI. We also confirm prior findings of a negative correlation of resistin with HDL and report for the first time a positive correlation with CRP. All of these associations remained significant after adjusting for sex and BMI. No associations of adiponectin or resistin with any aspects of vascular reactivity were detected. In the interventional study, atorvastatin decreased lipid and CRP levels, but adiponectin and resistin were not specifically altered. CONCLUSIONS—We conclude that adiponectin is significantly associated with inflammatory markers, in part, through an underlying association with obesity, whereas resistin’s associations with inflammatory markers appear to be independent of BMI. Lipid profile and inflammatory marker changes produced by atorvastatin cannot be attributed to changes of either adiponectin or resistin.
Treatment of aggressive Non‐Hodgkin's lymphoma in the elderly
Authors: Nicolas Novitzky, Helen S. King, Carol Johnson, Peter Jacobs
Journal: American Journal of Hematology (1995)

Abstract A nonanthracycline‐containing chemotherapeutic combination for the treatment of intermediate and high‐grade non‐Hodgkin's lymphoma was evaluated. Thirty‐four consecutive and previously untreated patients, with a median age of 75 (range 54‐86) years, with aggressive lymphoma, received daily etoposide (60 mg/m 2 intravenous infusion [IVI]), cytosine arabinoside (50 mg/m 2 subcutaneously), and methylprednisolone (60 mg/m 2 IVI) on each of 5 consecutive days. Individuals with limited disease (stages I and II) (n = 9) received six, 3‐day cycles of the same therapy and involved field radiation (36 Gy in 20 fractions) between the third and fourth courses. Patients with disseminated lymphoma (n = 25) received 10 cycles over 8 months of the same combination, with the addition of methotrexate (200 mg/m 2 on days 8 and 15), followed by leucovorin rescue (10 mg/m 2 orally every 6 hr for 8 doses). Of the 34 patients, 44% entered complete remission (CR), and 7 died before completing the first cycle of chemotherapy. Fifty‐six percent of the patients with limited disease and 40% with disseminated lymphoma ( P &gt; 0.05) achieved CR. For all patients, median survival was 14 months (range 3 days‐&gt;54 months), this being 12 and 15 months, respectively. For the entire population of responding patients, median survival has not been reached at a median follow‐up of 39 months, while the median CR duration is 21 months. Ten of the 15 responders are alive in unmaintained CR at a median of 41 (range 30‐54) months. Myelotoxicity was the major side effect, leading to adjustments in dose and schedule in two‐thirds of the patients, although treatment changes did not affect outcome. Of the 15 deaths that occurred in this trial, in 53.3% it was unrelated to lymphoma or its therapy. Four patients that had achieved CR died of cardiovascular events (n = 2) or of progressive second malignancies (n = 2). It is concluded that cytosine arabinoside in combination regimens is effective in selected patients; this is particularly relevant in the elderly. © 1995 Wiley‐Liss, Inc.
Short-Term Breast Cancer Prediction by Random Periareolar Fine-Needle Aspiration Cytology and the Gail Risk Model
Authors: C. J. Fabian, B. F. Kimler, C. M. Zalles, J. R. Klemp, S. Kamel, S. Zeiger, M. S. Mayo
Journal: JNCI Journal of the National Cancer Institute (2000)

Background: Biomarkers are needed to refine short-term breast cancer risk estimates from epidemiologic models and to measure response to prevention interventions. The purpose of our study was to determine whether the cytologic appearance of epithelial cells obtained from breast random periareolar fine-needle aspirates or molecular marker expression in these cells was associated with later breast cancer development. Methods: Four hundred eighty women who were eligible on the basis of a family history of breast cancer, prior precancerous biopsy, and/or prior invasive cancer were enrolled in a single-institution, prospective trial. Their risk of breast cancer according to the Gail model was calculated, and random periareolar fine-needle aspiration was performed at study entry. Cells were characterized morphologically and analyzed for DNA aneuploidy by image analysis and for the expression of epidermal growth factor receptor, estrogen receptor, p53 protein, and HER2/NEU protein by immunocytochemistry. All statistical tests are two-sided. Results: At a median follow-up time of 45 months after initial aspiration, 20 women have developed breast cancer (invasive disease in 13 and ductal carcinoma in situ in seven). With the use of multiple logistic regression and Cox proportional hazards analysis, subsequent cancer was predicted by evidence of hyperplasia with atypia in the initial fine-needle aspirate and a 10-year Gail projected probability of developing breast cancer. Although expression of epidermal growth factor receptor, estrogen receptor, p53, and HER2/NEU was statistically significantly associated with hyperplasia with atypia, it did not predict the development of breast cancer in multivariable analysis. Conclusion: Cytomorphology from breast random periareolar fine-needle aspirates can be used with the Gail risk model to identify a cohort of women at very high short-term risk for developing breast cancer. We recommend that cytomorphology be studied for use as a potential surrogate end point in prevention trials.
Leptin, polycystic ovaries and polycystic ovary syndrome
Authors: H S Jacobs, G S Conway
Journal: Human Reproduction Update (1999)

As soon as leptin was discovered four years ago, its potential as a player in the polycystic ovary syndrome (PCOS) was explored in a primitive way, though little light was shed on the enigma that is PCOS. As a second wave of leptin research is now available, we review how the expanded role of the cytokine in reproduction might yet impact upon our understanding of PCOS.
Evaluating Three Treatments for Borderline Personality Disorder: A Multiwave Study
Authors: John F. Clarkin, Kenneth N. Levy, Mark F. Lenzenweger, Otto F. Kernberg
Journal: American Journal of Psychiatry (2007)

The authors examined three yearlong outpatient treatments for borderline personality disorder: dialectical behavior therapy, transference-focused psychotherapy, and a dynamic supportive treatment.Ninety patients who were diagnosed with borderline personality disorder were randomly assigned to transference-focused psychotherapy, dialectical behavior therapy, or supportive treatment and received medication when indicated. Prior to treatment and at 4-month intervals during a 1-year period, blind raters assessed the domains of suicidal behavior, aggression, impulsivity, anxiety, depression, and social adjustment in a multiwave study design.Individual growth curve analysis revealed that patients in all three treatment groups showed significant positive change in depression, anxiety, global functioning, and social adjustment across 1 year of treatment. Both transference-focused psychotherapy and dialectical behavior therapy were significantly associated with improvement in suicidality. Only transference-focused psychotherapy and supportive treatment were associated with improvement in anger. Transference-focused psychotherapy and supportive treatment were each associated with improvement in facets of impulsivity. Only transference-focused psychotherapy was significantly predictive of change in irritability and verbal and direct assault.Patients with borderline personality disorder respond to structured treatments in an outpatient setting with change in multiple domains of outcome. A structured dynamic treatment, transference-focused psychotherapy was associated with change in multiple constructs across six domains; dialectical behavior therapy and supportive treatment were associated with fewer changes. Future research is needed to examine the specific mechanisms of change in these treatments beyond common structures.
Comparison of Ovariectomy and Retinyl Acetate on the Growth of Established 7,12-Dimethylbenz[&lt;italic&gt;a&lt;/italic&gt;]anthracene-Induced Mammary Tumors in the Rat&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn3"&gt;3&lt;/xref&gt;
Authors: P Gandilhon, R Melancon, J Djiane, P A Kelly
Journal: JNCI Journal of the National Cancer Institute (1982)

Prolonged exposure to retinyl acetate (RA) in the diet inhibits the development of 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary cancers in rats. The effectiveness of RA was examined when given 6 months after the administration of DMBA. Non-inbred female Sprague-Dawley rats with DMBA-induced mammary tumors were divided into 3 groups and treated for 4 weeks as follows: Group 1 served as controls, group 2 was ovariectomized, and group 3 received 328 mg RA/kg diet. Ovariectomy (OVX) markedly reduced both the number and size of the tumors. RA administration failed to induce any significant regression in tumor number but significantly retarded tumor growth when compared to tumor growth in group 1 controls. The levels of estradiol, progestin, and prolactin (PRL) receptors were significantly reduced after OVX, whereas only the levels of PRL receptors declined significantly after RA administration. Circulating progesterone concentrations were not affected in the RA-treated group but the plasma PRL level was significantly increased. The present studies show that if treatment with RA is delayed until 6 months after carcinogen administration, the protective effect of RA can still be observed although its effectiveness is less dramatic than when it is administered earlier.
Generation in plasma of a fast-acting inhibitor of plasminogen activator in response to endotoxin stimulation.
Authors: M Colucci, J A Paramo, D Collen
Journal: Journal of Clinical Investigation (1985)

Endotoxin producing bacteria cause disseminated intravascular coagulation (DIC); however, the mechanism of endotoxin action in man is still unclear. Impairment of the fibrinolytic system has been suggested as a contributing mechanism. A single injection of Escherichia coli lipopolysaccharide in rabbits resulted in a marked and prolonged increase of the levels of a fast-acting inhibitor of plasminogen activator (PA-inhibitor) in plasma (from 3.9 +/- 0.7 to 41 +/- 13.2 U/ml after 3 h). Gel filtration studies indicated that inhibition of human tissue-type plasminogen activator (t-PA) by rabbit plasma is accompanied by a change in the elution profile of the activator compatible with the formation of an enzyme-inhibitor complex with an apparent molecular weight of 100,000. Injection of human t-PA (1,500 IU/kg body wt) in endotoxin treated animals resulted in very fast inhibition of t-PA and formation of a similar complex. The half-life of circulating PA-inhibitor activity in rabbits was about 7 min as estimated by donor receiver plasma transfusion experiments. Stimulation of cultured human endothelial cells with endotoxin resulted in enhanced rate of accumulation of PA-inhibitor activity in the culture medium (two- to sevenfold increase). In five patients with septicemia, markedly increased levels of PA-inhibitor (14.3 +/- 15.5 U/ml) as compared with control subjects (1.3 +/- 0.7 U/ml) were observed in plasma. A very strong correlation (r = 0.98) was found between inhibition of t-PA and of urokinase in all conditions, suggesting that this fast-acting inhibitor reacts with both plasminogen activators. These data suggest that the appearance of this fast-acting PA-inhibitor is very sensitive to endotoxin stimulation. The marked increase in the level of PA-inhibitor in blood may contribute to the pathogenesis of DIC in septicemia.
Antitumor Immunity: Easy as 1, 2, 3 with Monoclonal Bispecific Trifunctional Antibodies?
Authors: John Maher, Antonella A. Adami
Journal: Cancer Research (2013)

Monoclonal antibodies occupy an increasing niche in the arsenal available to treat cancer. Several developments have rendered this the fastest growing sector in the pharmaceutical industry. Traditionally, antibodies were developed to block key signaling molecules implicated in tumor progression. However, antibodies also recruit additional immune effector mechanisms against tumors, a property that may be exploited for clinical benefit. Bispecific antibodies represent one such strategy in which elements derived from two monoclonal antibodies are incorporated into a single molecular species. Commonly, the bispecific approach is used to achieve simultaneous cross-linking of CD3 and a tumor antigen such as epithelial cell adhesion molecule (EpCAM), thereby recruiting T-cell activation to the tumor cell surface. A further sophistication involves the engineering of trifunctional derivatives such as the clinically approved agent, catumaxomab. Catumaxomab has antigen-binding arms that engage CD3 and EpCAM and a constant domain that recruits Fc receptor-bearing cells, notably monocytes, dendritic cells, and natural killer cells. Owing to this triangular binding capability, catumaxomab can activate both innate and adaptive immune effector mechanisms in addition to promoting immunologic memory. Recent data indicate that this agent can also promote immunogenic cell death, particularly when used in combination with selected chemotherapeutic agents such as oxaliplatin.