tbuckley/cabot-search huggingface dataset:
Preclinical Symptoms of Major Depression in Very Old Age: A Prospective Longitudinal Study
Authors: Anna-Karin Berger, Brent J. Small, Yvonne Forsell, Bengt Winblad, Lars Bäckman
Journal: American Journal of Psychiatry (1998)

The authors' goal was to examine whether individuals diagnosed as having major depression experienced greater levels of depressive symptoms and cognitive dysfunction up to 3 years before the clinical diagnosis was rendered.The study included 185 subjects 75 years old or older who participated in a population-based longitudinal survey in Stockholm. Ten of the subjects were diagnosed as depressed up to 3 years after initial screening, and these individuals were compared with the 175 subjects who were not depressed at 3-year follow-up. Depression was diagnosed according to DSM-III-R and DSM-IV criteria. Psychiatric signs and symptoms were assessed by physicians using a structured interview. Cognitive functioning was assessed with the Mini-Mental State.At the initial screening, the patients later diagnosed as depressed had a greater number of depressive symptoms, such as dysphoria and appetite disturbance, and their symptoms were also more severe than those of the nondepressed subjects. Moreover, the depressed subjects suffered from a more severe lack of interest and psychomotor disturbance and had lower Mini-Mental State scores.There are preclinical markers for individuals who will become depressed after a 3-year interval. Major depression may have a more chronic nature in very old age, in contrast to the relatively short clinical onset of depression seen in younger adults. The authors conclude that standard diagnostic instruments such as DSM-IV may have to take this lengthy course of impairment into consideration when dealing with very old adults.
Use of Oral<i>N</i>-Acetylcysteine for Protection of Melanocytic Nevi against UV-Induced Oxidative Stress: Towards a Novel Paradigm for Melanoma Chemoprevention
Authors: Agnessa Gadeliya Goodson, Murray A. Cotter, Pamela Cassidy, Mark Wade, Scott R. Florell, Tong Liu, Kenneth M. Boucher, Douglas Grossman
Journal: Clinical Cancer Research (2009)

Induction of oxidative stress has been implicated in UV-induced melanoma. We sought to determine whether the antioxidant N-acetylcysteine (NAC) could be safely administered to protect melanocytic nevi from the oxidative stress resulting from acute UV exposure.Patients at increased risk for melanoma were recruited from a screening clinic. Induction and detection of oxidative stress (reactive oxygen species and glutathione depletion) was optimized in nevi following ex vivo UV irradiation. Nevi were removed from patients before, and following, oral ingestion of a single (1,200 mg) dose of NAC, and then these nevi were UV irradiated (4,000 J/m(2)).Oxidative stress was induced in nevi 24 to 48 hours following ex vivo UV irradiation. A single oral dose of NAC was well tolerated in all patients (n = 72). Basal levels of reduced glutathione and the NAC metabolite cysteine were well correlated between similar-appearing nevi from the same patient and were significantly increased in nevi removed 3 hours after NAC ingestion compared with nevi removed before drug ingestion. In approximately half (9 of 19) of patients tested, UV-induced glutathione depletion was attenuated in the postdrug (compared with predrug) nevus.NAC can be safely administered to patients for the purpose of modulating UV-induced oxidative stress in nevi. This study suggests the feasibility of patients taking NAC prophylactically before acute UV exposure, to prevent pro-oncogenic oxidative stress in nevi and ultimately reduce long-term melanoma risk.
IFN-β Down-Regulates the Expression of DNA Repair Gene <i>MGMT</i> and Sensitizes Resistant Glioma Cells to Temozolomide
Authors: Atsushi Natsume, Dai Ishii, Toshihiko Wakabayashi, Takaya Tsuno, Hisashi Hatano, Masaaki Mizuno, Jun Yoshida
Journal: Cancer Research (2005)

Alkylating agents, such as temozolomide, are among the most effective cytotoxic agents used for malignant gliomas, but responses remain very poor. The DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) plays an important role in cellular resistance to alkylating agents. IFN-beta can act as a drug sensitizer, enhancing toxicity against a variety of neoplasias, and is widely used in combination with other antitumor agents such as nitrosoureas. Here, we show that IFN-beta sensitizes glioma cells that harbor the unmethylated MGMT promoter and are resistant to temozolomide. By means of oligonucleotide microarray and RNA interference, we reveal that the sensitizing effect of IFN-beta was possibly due to attenuation of MGMT expression via induction of the protein p53. Our study suggests that clinical efficacy of temozolomide might be improved by combination with IFN-beta using appropriate doses and schedules of administration.
Effect of airway clearance techniques on the efficacy of the sputum induction procedure
Authors: M. R. Elkins, T. Lane, H. Goldberg, J. Pagliuso, L. A. Garske, E. Hector, L. Marchetto, J. A. Alison, P. T. P. Bye
Journal: European Respiratory Journal (2005)

Sputum induction is used in the early identification of tuberculosis (TB) and pneumocystis infections of the lung. Although manual physiotherapy techniques to clear the airways are often incorporated in the sputum induction procedure, their efficacy in this setting is unknown. This randomised, crossover trial enrolled adults referred for sputum induction for suspected TB and pneumocystis infections of the lung. All participants underwent two sputum induction procedures, inhaling 3% saline via ultrasonic nebuliser. During one randomly allocated procedure, airway clearance techniques (chest wall percussion, vibration, huffing) were incorporated. In total, 59 participants completed the trial. The airway clearance techniques had no significant effect on how the test was tolerated, the volume expectorated or the quality of the sample obtained (assessed by the presence of alveolar macrophages). The techniques did not significantly affect how often the test identified a suspected organism, nor the sensitivity or specificity of sputum induction. In conclusion, the study was unable to demonstrate any effect of airway clearance techniques on the sputum induction procedure. The results provide some justification for not including airway clearance techniques as part of the sputum induction procedure.
Human Immunodeficiency Virus Type 1 (HIV-1) Infection a Median of 18 Months before a Diagnostic Western Blot
Authors: Steven M. Wolinsky
Journal: Annals of Internal Medicine (1989)

Study Objective: To study the natural history of human immunodeficiency virus type 1 (HIV-1) infection, we used an in-vitro amplification technique to detect HIV-1 nucleic acid sequences in sequential aliquots of peripheral blood mononuclear cells from homosexual men enrolled in the Multicenter AIDS Cohort Study. Design and Patients: Blinded, longitudinal study of 24 homosexual men who were positive for HIV-1 antibodies at a recent follow-up visit. Measurements and Main Results: Coded clinical samples were evaluated using two enzyme-linked immunosorbent assays (whole virus and gp120-gp41 fragment), Western blot, a p24 antigen capture assay, virus cocultivation, and in-vitro amplification of conserved regions from the HIV-1 gag and env open-reading frames. In 20 of the 24 men an HIV-1 enzymatically amplified product was detected before HIV-1 antibody seroconversion: at 42 months before seroconversion in two cases; at 36 months in one case; at 30 months in one case; at 24 months in four cases; at 18 months in eight cases; at 12 months in one case; and at 6 months in three cases (median, 18 months). In the four other men, detection of an HIV-1 enzymatically amplified product was concurrent with confirmation of antibody seroconversion by Western blot. Conclusions: There is a long and variable interval between virus acquisition and a diagnostic serum antibody response, perhaps due to the prolonged, persistent infection characteristic of the lentiviruses (family Retroviridae).
Right Ventricular Function After Pulmonary Autograft Replacement of the Aortic Valve
Authors: G. S. Carr-White, M. Kon, T. W. Koh, S. Glennan, F. D. Ferdinand, A. C. De Souza, J. R. Pepper, D. J. Pennell, D. G. Gibson, M. H. Yacoub
Journal: Circulation (1999)

The pulmonary autograft operation (the Ross procedure) involves excision of a portion of the right ventricular (RV) outflow tract, prolonged cross-clamp times, and insertion of a pulmonary homograft. There is concern about the effect of such operations on right ventricular function.Twenty-five patients undergoing either pulmonary autograft or homograft replacement of the aortic valve as part of a prospective randomized trial had echocardiographic RV long-axis measurements performed before surgery and 6 months (range 3 to 12 months) after surgery. In all patients, systolic excursion (SE) and both shortening and lengthening rates (SR and LR, respectively) were reduced postoperatively (P<0.05) (homografts: SE 1.5+/-0.4 versus 2.3+/-0.6 cm, SR 6.8+/-2.1 versus 9. 6+/-3.1 cm/s, LR 6.0+/-1.8 versus 8.9+/-3.0 cm/s; autografts: SE 1. 4+/-0.4 versus 2.2+/-0.4 cm, SR 5.8+/-3.0 versus 8.2+/-3.0 cm/s, LR 5.7+/-1.9 versus 8.5+/-3.7 cm/s). There were no differences between the 2 groups. Eighteen patients who had undergone either aortic homograft or pulmonary autograft surgery were studied between 6 and 35 months after surgery. RV volumes were assessed with the use of MRI in addition to echocardiographic RV long-axis measurements. Global volumes were increased to a similar amount in both groups (homografts: end-diastolic volume 145+/-34 mL, end-systolic volume 78+/-23 mL; autografts: end-diastolic volume 157+/-33 mL, end-systolic volume 89+/-25 mL; P=NS), whereas stroke volumes were maintained in both groups (homografts 67+/-15 mL, autografts 67+/-16 mL; P=NS). RV SE was depressed in both groups to a similar degree to that seen with the previous group (homografts 1.5+/-0.3 cm, autografts 1.4+/-0.2 cm).Aortic valve replacement with either a pulmonary autograft or an aortic homograft leads to a degree of persistent RV longitudinal dysfunction that is not more pronounced in those undergoing the Ross procedure. The mechanisms and long-term effects of these changes must be further studied.
Measurement of Platelet-Activating Factor in a Canine Model of Coronary Thrombosis and in Endarterectomy Samples From Patients With Advanced Coronary Artery Disease
Authors: Howard W. Mueller, Courtney A. Haught, Janice M. McNatt, Kexin Cui, Simon J. Gaskell, Dennis A. Johnston, James T. Willerson
Journal: Circulation Research (1995)

Abstract Platelet-activating factor (PAF, 1- O -alkyl-2-acetyl- sn -glycero-3-phosphocholine) is a potent phospholipid mediator of numerous inflammatory and thrombotic responses. The purpose of this study was to determine if PAF synthesis is elevated in damaged coronary arteries after a sustained period of cyclic flow variation (CFV), a phenomenon caused by alternating periods of thrombosis and reperfusion at sites of endothelial injury. Cyclic flow was established and maintained in the left anterior descending coronary arteries (LADs) of 10 dogs. After 8 hours of CFV, the section of damaged LAD containing the thrombus and control sections of the circumflex artery, carotid artery, and saphenous vein was excised, and the total lipids were extracted. The PAF was then purified by silica column chromatography and high-performance liquid chromatography and assayed by both a rabbit platelet bioassay and a PAF radioimmunoassay. With the platelet bioassay, PAF levels of 8.9±4.0 (range, 4.8 to 15.5) pg/mg wet wt were found in the damaged LADs from the 10 dogs. This PAF bioactivity was completely inhibited by a PAF receptor antagonist. When the radioimmunoassay was used, slightly higher PAF levels of 16.3±12.9 (range, 4.5 to 41.8) pg/mg wet wt were observed in the LADs. Overall, these PAF levels were 3- to 64-fold higher than in the control vessels when either assay method was used. Although increases in PAF were observed in the damaged LADs, measurements of PAF in blood samples taken from the LAD and the aorta (control) failed to demonstrate any site-specific increase of PAF in the blood. In related experiments, PAF was also measured in 23 endarterectomy samples taken from the coronary arteries of 16 patients with severe atherosclerosis. The PAF levels in these samples were highly variable (2.9±2.2 [range, 0.3 to 8.5] pg/mg wet wt) and showed no correlation with tissue mass, suggesting that PAF is affected by factors other than the simple presence of atherosclerotic tissue in the vessel. These findings provide direct evidence that PAF is synthesized locally at the site of endothelial injury during thrombosis and that PAF accumulates in the atherosclerotic plaque of some patients with advanced coronary artery disease.
Sphincter-Sparing Local Excision and Adjuvant Radiation for Anal-Rectal Melanoma
Authors: Matthew T. Ballo, Jeffrey E. Gershenwald, Gunar K. Zagars, Jeffrey E. Lee, Paul F. Mansfield, Eric A. Strom, Agop Y. Bedikian, Kevin B.S. Kim, Nicholas E. Papadopoulos, Victor G. Prieto, Merrick I. Ross
Journal: Journal of Clinical Oncology (2002)

To evaluate the outcome and toxicity of a sphincter-sparing treatment strategy in the management of patients with anal-rectal melanoma.Between 1989 and 2000, 23 patients with invasive anal-rectal melanoma were managed with sphincter-sparing surgical resection and adjuvant radiation. Surgery consisted of primary local excision, as well as dissection for patients with documented regional nodal disease. Adjuvant radiation was delivered using a hypofractionated regimen of 30 Gy in five fractions over 2.5 weeks. Adjuvant systemic therapy was delivered to nine patients: cytotoxic chemotherapy in seven and immunotherapy in two.After a median follow-up of 32 months, 15 patients had relapsed and 15 patients had died. The actuarial 5-year overall, disease-specific, disease-free, and distant metastasis-free survival rates were 31%, 36%, 37%, and 35%, respectively. The actuarial 5-year local and regional nodal control rates were 74% and 84%, respectively. No patient had locoregional failure as the sole site of failure and no patient required salvage abdominoperineal resection (APR). By univariate analysis, patients with nodal disease at presentation had a decreased actuarial 5-year disease-specific (0% v 45%, P =.004), disease-free (0% v 45%, P <.001), and distant metastasis-free survival (0% v 42%, P <.001). The actuarial complication-free survival rate was 71%. Two patients developed mild scrotal edema (grade 1), and four patients developed moderate proctitis requiring prolonged medical management (grade 2).Sphincter-sparing local excision and adjuvant radiation is well tolerated and can effectively control local-regional disease while avoiding the functional morbidity of APR.
A CASE OF STRANGULATED FEMORAL HERNIA, WITH PROTRUSION OF THE INTESTINE ON THE FIFTH DAY: RECOVERY
Authors: T. M. Ward
Journal: BMJ (1856)

for while abdominal aneurism in the female is of very rare ocurrence, inorganic aortic pulsation is very common.ju l accumulatioa and impaction has been mistaken i# aneurism of the abdominal aorta.The oval shape of the tumour, with its doughy, inelastic feel, and the result of free purgation, will, in general, suffice to clear up the gos.Enlarged glands, or organic disease of the abdominal Tiscea, either lying over, or pressing laterally upon the artery, will sometimes closely simulate aneurism.The history of the cases, and especially the existence of malig-
Hodgkin’s Disease and Lymphomas
Authors: L. Kostakoglu, M. Coleman, S. J. Goldsmith
Journal: Clinical Nuclear Medicine (2008)

Lymphomas represent a diverse range of diseases with evolving pathologic classification and therapy strategies. Essentially, the lymphomas are classified into two main groups, Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL). For both disease entities accurate determination of extent of disease at initial staging and restaging is key for optimal management. More than 75% of all newly diagnosed patients with adult HD can be cured with combination chemotherapy and/ or radiation therapy. As for NHL, effective drug combinations can produce prolonged disease-free survival in the majority of patients. A functional or metabolic diagnostic imaging modality can contribute to the assessment of a patient in various ways. Functional imaging can complement anatomic imaging modalities, mainly CT, and thereby enhances the accuracy of defining the extent of disease prior to therapy. In the posttherapy setting, the ability to differentiate residual viable disease from benign post-therapy changes could impact patient management and outcome, particularly if it helps to select patients who would require additional therapy or a change in treatment regimen.
Complement Factor H Autoantibodies Are Associated with Early Stage NSCLC
Authors: Nita Amornsiripanitch, Shaolin Hong, Michael J. Campa, Michael M. Frank, Elizabeth B. Gottlin, Edward F. Patz
Journal: Clinical Cancer Research (2010)

Abstract Purpose: To discover diagnostic biomarkers associated with early-stage non–small cell lung cancer (NSCLC), we searched for autoantibodies preferentially present in stage I patients compared with patients with advanced-stage disease. Here we describe an autoantibody against complement factor H (CFH) and this autoantibody's association with early-stage NSCLC. Experimental Design: Immunoblots were used to detect autoantibodies in the sera of stage I NSCLC patients. An autoantibody recognizing a 150 kDa protein was discovered, and the protein was identified by mass spectrometry. The association of the autoantibody with early-stage disease was suggested by the results of immunoblot analysis with sera from 28 stage I patients and 28 stage III/IV patients. This association was confirmed by protein microarray of sera from 125 NSCLC patients of all stages as well as 125 controls matched by age, gender, and smoking history. Results: The immunoreactive protein was identified as CFH. By immunoblot analysis, anti-CFH autoantibody was found in 50% of stage I NSCLC patients and 11% of late-stage NSCLC patients (P = 0.003). By protein microarray analysis, patients with stage I NSCLC had a significantly higher incidence of anti-CFH antibody than those with late-stage NSCLC (P = 0.0051). The percentage of sera with a positive level of CFH autoantibody was 30.4% in stage I, 21.1% in stage II, 12.5% in stage III, 7.4% in stage IV, and 8.0% in the control group. Conclusions: These findings suggest that in patients with NSCLC, CFH autoantibody is a molecular marker associated with early-stage disease. Clin Cancer Res; 16(12); 3226–31. ©2010 AACR.
Role of neutrophil elastase in ozone-induced airway responses in guinea-pigs
Authors: K Matsumoto, H Aizawa, H Inoue, H Koto, H Nakano, N Hara
Journal: European Respiratory Journal (1999)

Ozone-induced airway hyperresponsiveness occurs concurrently with neutrophilic inflammation and epithelial injury in various species including humans. The mechanism of neutrophil-induced airway hyperresponsiveness, however, has not yet been fully clarified. Neutrophil elastase (NE) is a multipotent protease released from activated neutrophils, which may play a role in ozone-induced airway hyperresponsiveness. In order to address this issue, the effects of ONO-5046, a specific NE inhibitor, were investigated in ozone-exposed guinea-pigs. Awake animals were exposed to ozone at 3 parts per million for 2 h, airway responsiveness to acetylcholine (ACh) measured and examination of bronchoalveolar lavage fluid (BALF) performed. Ozone exposure increased airway responsiveness to both inhaled and intravenous ACh, the concentration of NE in BALF and the number of neutrophils and airway epithelial cells in BALF. Although pretreatment with ONO-5046 (200 mg x kg(-1), i.p.) had no effect on these changes immediately after the exposure, it significantly inhibited airway hyperresponsiveness to inhaled ACh, whilst decreasing the number of neutrophils and epithelial cells in BALF 3-5 h after the exposure. In contrast, ONO-5046 showed no significant effect on airway hyperresponsiveness to intravenous ACh at any time. These results suggest that neutrophil elastase contributes to ozone-induced airway hyperresponsiveness developing during the hours after exposure, presumably by means of inducing epithelial injury.
Interrelations Between Brachial Endothelial Function and Carotid Intima-Media Thickness in Young Adults
Authors: Markus Juonala, Jorma S.A. Viikari, Tomi Laitinen, Jukka Marniemi, Hans Helenius, Tapani Rönnemaa, Olli T. Raitakari
Journal: Circulation (2004)

Endothelial vasodilator dysfunction and carotid intima-media thickening (IMT) are 2 indicators of subclinical cardiovascular disease. We examined their correlation and interaction with risk factors in a large, community-based cohort of young adults.As part of the longitudinal Cardiovascular Risk in Young Finns Study, we measured endothelium-dependent brachial artery flow-mediated dilatation (FMD) and carotid artery IMT by ultrasound in 2109 healthy adults aged 24 to 39 years. FMD was inversely associated with IMT (P< or =0.001) in a multivariate model adjusted for age, sex, brachial vessel size, and several risk variables. The subjects with age- and sex-specific FMD values in the extreme deciles were classified into groups of impaired (n=204, FMD=1.1+/-1.4%, mean+/-SD) and enhanced (n=204, FMD=16.3+/-2.9%) FMD response. The number of risk factors was correlated with increased IMT in subjects with an impaired FMD response (P<0.05) but not in subjects with an enhanced FMD response (P>0.2).Brachial FMD is inversely associated with carotid IMT. The number of risk factors in young adults is correlated with increased IMT in subjects with evidence of endothelial dysfunction, but not in subjects with preserved endothelial function. These observations suggest that endothelial dysfunction is an early event in atherosclerosis and that the status of systemic endothelial function may modify the association between risk factors and atherosclerosis.