tbuckley/cabot-search huggingface dataset:
Is vitamin D deficiency important in the natural history of COPD?
Authors: J K Quint, J A Wedzicha
Journal: Thorax (2010)

cultures.Up to 22% of patients intubated for >48 h had evidence of virus recoverable from tracheobronchial secretions in one study. 12Whether viruses in VAP contribute to an actual pneumonic process remains unclear.Very interestingly, IL-1b and IL-8 concentrations were similar in the patients with VAP with typical pathogenic microbes and those with microbes usually considered to be less pathogenic, for example coagulase-negative staphylococci or Candida species.It is not clear how many of these patients had simultaneous positive cultures for other microbes.If these are the sole isolates, the cytokine data suggest that these microbes do in fact induce an inflammatory response: by extrapolation, therefore, they may require treatment.Isolated Candida cultures, for example, are not routinely treated in clinical practice.This article raises the possibility that such "non-pathogenic" microbes are in fact true pathogens in the setting of VAP.Finally, the use of a bronchoscopically derived biomarker for clinical practice presents certain practical considerations.BAL is labour intense, and cannot be performed safely in all ICU patients (and as in the methods described, the sicker patients with higher ventilatory support requirements were excluded).This study was carried out by one investigator across two clinical sites.Highly precise methods were used to perform BAL by the investigator, and it is unlikely that this methodological rigour could be easily reproduced by multiple clinicians in different ICUs in clinical practice.Although the authors have previously demonstrated that BAL-based microbiological techniques can improve the diagnosis of VAP 8 there remains widespread high variability in the use of bronchoscopic sampling across ICUs throughout Europe. 19evertheless this study adds significantly to the diagnosis and understanding of VAP.The utility of these biomarkers for VAP in BAL now requires further evaluation in larger multicentre studies.It will be particularly interesting to see if the application of biomarker-based decisions could safely reduce antibiotic prescription, and whether biomarker measurements help our understanding of the role of atypical or "non-pathogenic" microbes in VAP.
Incidence of Types of Cancer among HIV-Infected Persons Compared with the General Population in the United States, 1992–2003
Authors: Pragna Patel, Debra L. Hanson, Patrick S. Sullivan, Richard M. Novak, Anne C. Moorman, Tony C. Tong, Scott D. Holmberg, John T. Brooks
Journal: Annals of Internal Medicine (2008)

Background: Persons who are HIV-infected may be at higher risk for certain types of cancer than the general population. Objective: To compare cancer incidence among HIV-infected persons with incidence in the general population from 1992 to 2003. Design: Prospective observational cohort studies. Setting: United States. Patients: 54 780 HIV-infected persons in the Adult and Adolescent Spectrum of HIV Disease Project (47 832 patients) and the HIV Outpatient Study (6948 patients), who contributed 157 819 person-years of follow-up from 1992 to 2003, and 334 802 121 records from the Surveillance, Epidemiology, and End Results program of 13 geographically defined, population-based, central cancer registries. Measurements: Standardized rate ratios (SRRs) to compare cancer incidence in the HIV-infected population with standardized cancer incidence in the general population. Results: The incidence of the following types of non–AIDS-defining cancer was significantly higher in the HIV-infected population than in the general population: anal (SRR, 42.9 [95% CI, 34.1 to 53.3]), vaginal (21.0 [CI, 11.2 to 35.9]), Hodgkin lymphoma (14.7 [CI, 11.6 to 18.2]), liver (7.7 [CI, 5.7 to 10.1]), lung (3.3 [CI, 2.8 to 3.9]), melanoma (2.6 [CI, 1.9 to 3.6]), oropharyngeal (2.6 [CI, 1.9 to 3.4]), leukemia (2.5 [CI, 1.6 to 3.8]), colorectal (2.3 [CI, 1.8 to 2.9]), and renal (1.8 [CI, 1.1 to 2.7]). The incidence of prostate cancer was significantly lower among HIV-infected persons than the general population (SRR, 0.6 [CI, 0.4 to 0.8]). Only the relative incidence of anal cancer increased over time. Limitations: Lower ascertainment of cancer in the HIV cohorts may result in a potential bias to underestimate rate disparities. Tobacco use as a risk factor and the effect of changes in cancer screening practices could not be evaluated. Conclusion: The incidence of many types of non–AIDS-defining cancer was higher among HIV-infected persons than among the general population from 1992 to 2003.
Changes of lymphocyte membrane fluidity in rheumatoid arthritis: a fluorescence polarisation study.
Authors: E Beccerica, G Piergiacomi, G Curatola, G Ferretti
Journal: Annals of the Rheumatic Diseases (1988)

Fluorescence polarisation of 1,6-diphenyl-1,3,5-hexatriene was used to study the lymphocyte membrane in rheumatoid arthritis. The increase of polarisation value in the patients (n = 27) compared with healthy controls (n = 32) suggests a decrease of membrane fluidity. Moreover, erythrocyte sedimentation rate (ESR) and plasma fibrinogen concentrations were positively correlated with lymphocyte fluorescence polarisation values (r = 0.66 and r = 0.76 respectively). The results suggest that the changes in lymphocyte membrane fluidity could be involved in the pathogenetic mechanism of rheumatoid arthritis.
Selection of Patients for Resection of Hepatic Colorectal Metastases: 18F-Fluorodeoxyglucose/Positron Emission Tomography
Authors: Rebecca Auer, Yuman Fong
Journal: Liver Cancer (2009)

The selection of appropriate patients for surgical resection of colorectal liver metas-tases is a central clinical dilemma. Using conventional imaging, up to one quarter of patients scheduled for surgical resection will be determined to have unresectable or metastatic disease at the time of surgery. Of the patients who do undergo a resection with curative intent, ~ 60% will develop a recurrence within 3 years, either within the liver or in an extrahepatic location (Bines et al., 1996). It is clear that a more effective preoperative staging modality is needed to avoid unsuccessful or ineffective surgeries. Positron emission tomography (PET) using [18F]fluorodeoxyglucose (FDG) is emerging as a promising diagnostic modality in metastatic colorectal cancer. [18F] fluorodeoxyglucose-positron emission tomography (FDG-PET) has the potential to differentiate between patients with resectable and unresectable hepatic colorectal cancer metastases and therefore improve patient selection for surgery with a positive effect on surgical treatment outcomes, including survival. Positron emission tomography may improve the survival time in patients undergoing hepatic resection for metastatic colorectal cancer for three reasons. First, if preop-erative workup with PET scanning detects more extrahepatic disease than conventional imaging alone, surgery would not be undertaken in these patients, and the group of patients undergoing surgery would have a more favorable prognosis; a concept similar to the Will-Rogers effect, which is used to describe stage migration. Second, if hepatic recurrences are detected earlier in patients screened with PET scanning as compared to conventional imaging alone, surgery would be performed earlier and survival, as defined from the time of metastasectomy, would be longer, a concept termed lead-time bias. Third, if hepatic recurrences are detected earlier with PET scan, surgery might be undertaken prior to the development of additional systemic micrometastases. Based on tumor biology, this results in a true improvement in survival.
PELLAGRA-LIKE SKIN LESIONS DUE TO THE KETOGENIC DIET
Authors: Alvis E. Greer
Journal: JAMA (1930)

It is my belief that the following case report constitutes an illustration of one of the dangers in the use of the ketogenic diet in the treatment of idiopathic epilepsy:  REPORT OF CASE  Mrs. H. E. R., an American, aged 33, 5 feet 4 inches (163 cm.) tall, weighing 112 pounds (50.8 Kg.), came to the clinic complaining of attacks of convulsions, lasting from fifteen to twenty minutes, followed by stupor. She cried easily and was nervous and excitable; her memory was poor and she was not able to concentrate. The attacks of convulsions had begun four years before, appearing three weeks after the birth of a child. Following the first convulsion she had been unconscious for six hours. She had had these attacks frequently, having as many as two or three a day, until she became pregnant again a little more than two years before; during this pregnancy she
Does Increased Oxidative Stress Cause Hypertension?
Authors: Ehud Grossman
Journal: Diabetes Care (2008)

Hypertension is associated with increased vascular oxidative stress; however, there is still a debate whether oxidative stress is a cause or a result of hypertension. Animal studies have generally supported the hypothesis that increased blood pressure is associated with increased oxidative stress; however, human studies have been inconsistent. Oxidative stress promotes vascular smooth muscle cell proliferation and hypertrophy and collagen deposition, leading to thickening of the vascular media and narrowing of the vascular lumen. In addition, increased oxidative stress may damage the endothelium and impair endothelium-dependent vascular relaxation and increases vascular contractile activity. All these effects on the vasculature may explain how increased oxidative stress can cause hypertension. Treatment with antioxidants has been suggested to lower oxidative stress and therefore blood pressure. However, to date, clinical studies investigating antioxidant supplements have failed to show any consistent benefit. It is noteworthy that lowering blood pressure with antihypertensive medications is associated with reduced oxidative stress. Therefore, it seems that oxygen stress is not the cause, but rather a consequence, of hypertension.
IgA1 and IgA2 subclass antibodies against Klebsiella pneumoniae in the sera of patients with peripheral and axial types of ankylosing spondylitis.
Authors: O Maki-Ikola, M Nissila, K Lehtinen, M Leirisalo-Repo, K Granfors
Journal: Annals of the Rheumatic Diseases (1995)

OBJECTIVE--To study further the Klebsiella specific serum antibody response in patients with axial and peripheral types of ankylosing spondylitis (AS). METHODS--IgA1 and IgA2 subclass antibodies to Klebsiella pneumoniae were measured by enzyme linked immunosorbent assay in the sera of 171 patients with axial or peripheral type AS, and in sera of 100 healthy controls. The effect of 26 weeks of sulphasalazine treatment on the antibody levels in the two types of AS was also analysed. RESULTS--K pneumoniae specific antibody levels of both IgA1 and IgA2 subclasses were increased in the sera of patients with AS compared with healthy controls. The increased levels were present in patients with axial and with peripheral AS, and there were no statistically significant differences in the antibody levels between these two groups. Sulphasalazine treatment decreased the Klebsiella specific antibody level of IgA1 subclass in patients with axial AS, but there were no statistically significant changes in the IgA2 subclass, or in the patients with peripheral type AS. CONCLUSIONS--These results agree with earlier published findings suggesting that IgA (especially Klebsiella specific IgA) may have a role in the pathogenetic mechanisms of both peripheral and axial types of AS. In addition, it seems that both IgA1 and IgA2 subclasses are involved in the disease process.
Mechanisms of proteinuria in human glomerulonephritis.
Authors: B D Myers, T B Okarma, S Friedman, C Bridges, J Ross, S Asseff, W M Deen
Journal: Journal of Clinical Investigation (1982)

We evaluated glomerular barrier function in 28 patients with glomerulonephritis. Neutral dextrans of graded size were used to characterize the size-selective properties of the barrier. Charge selectivity was characterized by electrofocusing excreted urinary proteins. A fractional IgG clearance (relative to freely permeable inulin), smaller or greater than 100 x 10(-5) was used to distinguish patients with minor (group I, n = 13) and major (group II, n = 15) urinary IgG leakage, respectively. Fractional clearances of smaller dextrans (radii 20-50 A) were similar, but those of larger dextrans (radii 52-60 A) were elevated in group II relative to group I patients. A model of solute transport through a bimodal pore size distribution revealed the values for pore radius in the lower mode to approximate 51-55 A in both group I and group II patients. Pore radius in the upper mode, by contrast, was much larger in group II than in group I patients, approximating 87-97 vs. 72-77 A, respectively. Electrofocusing of urinary protein from group I patients revealed mostly albumin (isoelectric point 5.2). In group II patients, however, immunoglobulin excretion was copious. Moreover, the distribution of anionic, neutral, and cationic species (isoelectric points 5.5-8.5) in urinary and plasma eluates of IgG2 and IgG4 was similar. We conclude that when glomerulonephritis is associated with selective albuminuria, as in group I,, there is an isolated reduction of electrostatic retardation of relatively small anionic proteins. Major urinary IgG leakage (group II), however, appears to result from the development in the glomerular membrane of a subpopulation of enlarged pores that are highly permeable towards proteins of large size and varying charge.
1,25(OH) <sub>2</sub> Vitamin D Inhibits Foam Cell Formation and Suppresses Macrophage Cholesterol Uptake in Patients With Type 2 Diabetes Mellitus
Authors: Jisu Oh, Sherry Weng, Shaili K. Felton, Sweety Bhandare, Amy Riek, Boyd Butler, Brandon M. Proctor, Marvin Petty, Zhouji Chen, Kenneth B. Schechtman, Leon Bernal-Mizrachi, Carlos Bernal-Mizrachi
Journal: Circulation (2009)

Background— Cardiovascular disease is the leading cause of death among those with diabetes mellitus. Vitamin D deficiency is associated with an increased risk of cardiovascular disease in this population. To determine the mechanism by which vitamin D deficiency mediates accelerated cardiovascular disease in patients with diabetes mellitus, we investigated the effects of active vitamin D on macrophage cholesterol deposition. Methods and Results— We obtained macrophages from 76 obese, diabetic, hypertensive patients with vitamin D deficiency (25-hydroxyvitamin D &lt;80 nmol/L; group A) and 4 control groups: obese, diabetic, hypertensive patients with normal vitamin D (group B; n=15); obese, nondiabetic, hypertensive patients with vitamin D deficiency (group C; n=25); and nonobese, nondiabetic, nonhypertensive patients with vitamin D deficiency (group D; n=10) or sufficiency (group E; n=10). Macrophages from the same patients in all groups were cultured in vitamin D—deficient or 1,25-dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ] –supplemented media and exposed to modified low-density lipoprotein cholesterol. 1,25(OH) 2 D 3 suppressed foam cell formation by reducing acetylated or oxidized low-density lipoprotein cholesterol uptake in diabetic subjects only. Conversely, deletion of the vitamin D receptor in macrophages from diabetic patients accelerated foam cell formation induced by modified LDL. 1,25(OH) 2 D 3 downregulation of c-Jun N-terminal kinase activation reduced peroxisome proliferated–activated receptor-γ expression, suppressed CD36 expression, and prevented oxidized low-density lipoprotein–derived cholesterol uptake. In addition, 1,25(OH) 2 D 3 suppression of macrophage endoplasmic reticulum stress improved insulin signaling, downregulated SR-A1 expression, and prevented oxidized and acetylated low-density lipoprotein–derived cholesterol uptake. Conclusion— These results identify reduced vitamin D receptor signaling as a potential mechanism underlying increased foam cell formation and accelerated cardiovascular disease in diabetic subjects.
Baseline C-Reactive Protein Is Associated With Incident Cancer and Survival in Patients With Cancer
Authors: Kristine H. Allin, Stig E. Bojesen, Børge G. Nordestgaard
Journal: Journal of Clinical Oncology (2009)

We tested the hypothesis that baseline plasma levels of C-reactive protein (CRP) are associated with risk of incident cancer in the general population and early death in patients with cancer.A total of 10,408 individuals from the Danish general population who had CRP measured at baseline were observed for up to 16 years; 1,624 developed cancer, and of these, 998 patients died during follow-up. Follow-up was 100% complete. We excluded individuals with a cancer diagnosis at baseline.Baseline CRP levels more than 3 versus less than 1 mg/L were associated with multifactorially adjusted hazard ratios of 1.3 (95% CI, 1.0 to 1.6) for cancer of any type, 2.2 (95% CI, 1.0 to 4.6) for lung cancer, 1.9 (95% CI, 0.8 to 4.6) for colorectal cancer, and 0.7 (95% CI, 0.4 to 1.4) for breast cancer. Corresponding hazard ratios for the highest versus the lowest quintile of baseline CRP levels were 1.3 (95% CI, 1.0 to 1.6), 2.1 (95% CI, 1.2 to 3.8), 1.7 (95% CI, 0.8 to 3.2), and 0.9 (95% CI, 0.5 to 1.7), respectively. Multifactorially adjusted hazard ratios for early death in patients with cancer were 1.8 (95% CI, 1.2 to 2.7) for CRP more than 3 versus less than 1 mg/L and 1.4 (95% CI, 1.1 to 1.7) for the highest versus the lowest quintile. Elevated CRP levels were associated with early death in patients with cancer having localized disease, but not in those with metastases (interaction; P = .03).Elevated levels of CRP in cancer-free individuals are associated with increased risk of cancer of any type, of lung cancer, and possibly of colorectal cancer. Moreover, elevated levels of baseline CRP associate with early death after a diagnosis of any cancer, particularly in patients without metastases.
A non-invasive method for testing neural circulatory control in man
Authors: A. LINDQVIST, P. PARVIAINEN, P. KOLARI, J. TUOMINEN, I. VALIMAKI, K. ANTILA, L. A LAITINEN
Journal: Cardiovascular Research (1989)

Exaggerated cardiovascular responsiveness is common in young men and may cause non-specific symptoms and poor performance. Conventional autonomic function tests are not clinically useful. We have therefore designed a thermal entrainment method to evaluate sympathetic and parasympathetic cardiovascular function in subjects with dystonic symptoms and orthostatic intolerance. Oscillations of thermal gradient in the skin were produced by standardised periodic stimulation of the lower part of the arm with warm and cool water. Vasomotor activity of the skin induced oscillations of arterial blood pressure which were thought to be regulated by sympathetic and parasympathetic heart rate control and by oscillation of the sympathetically controlled peripheral vascular resistance. We tested the method in subjects with cardiovascular symptoms (n=7) and controls (n=7). At supine rest, the frequency response of the heart rate variability to the thermal stimulation at frequencies of 0.01, 0.02, 0.03 and 0.1 Hz was significantly different (p=0.008) between symptomatic subjects and controls. The gain of the heart rate control was increased to 0.03 Hz [−1.3(SEM 0.5)dB v −3.8(0.8) dB, p=0.068] and decreased at 0.1 Hz [−3.9(1.l) dB v −1.5(0.6) dB, p=0.076] in the test group compared to the control group. At stimulus frequencies of less than 0.03 Hz the individual overall heart rate variability of the subjects with symptoms stayed below the mean control value, at 60(6) ms v 79(15) ms, p=0.16. The cutaneous temperature oscillations at the site of stimulation, frequency response of the oscillations of the skin blood flow and respiration to the thermal stimulation, and mean heart rate were similar in the both groups. The results show that this thermal entrainment method quantifies the increased sympathetic and decreased parasympathetic cardiac control of subjects with dystonic symptoms.
Identification of genes regulated by 2-methoxyestradiol (2ME2) in multiple myeloma cells using oligonucleotide arrays
Authors: Dharminder Chauhan, Guilan Li, Daniel Auclair, Teru Hideshima, Paul Richardson, Klaus Podar, Nicholas Mitsiades, Constantine Mitsiades, Cheng Li, Ryung Suk Kim, Nikhil Munshi, Lan Bo Chen, Wing Wong, Kenneth C. Anderson
Journal: Blood (2003)
HDM2 antagonist MI-219 (spiro-oxindole), but not Nutlin-3 (cis-imidazoline), regulates p53 through enhanced HDM2 autoubiquitination and degradation in human malignant B-cell lymphomas
Authors: Angela M Sosin, Angelika M Burger, Aisha Siddiqi, Judith Abrams, Ramzi M Mohammad, Ayad M Al-Katib
Journal: Journal of Hematology & Oncology (2012)

Abstract Background Lymphomas frequently retain wild-type (wt) p53 function but overexpress HDM2, thereby compromising p53 activity. Therefore, lymphoma is a suitable model for studying the therapeutic value of disrupting the HDM2-p53 interaction by small-molecule inhibitors (SMIs). HDM2 have been developed and are under various stages of preclinical and clinical investigation. Previously, we examined the anti-lymphoma activity of MI-319, the laboratory grade of a new class of HDM2 SMI, the spiro-oxindole, in follicular lymphoma. Since then, MI-219, the clinical grade has become readily available. This study further examines the preclinical effects and mechanisms of MI-219 in a panel of human lymphoma cell lines as well as a cohort of patient-derived B-lymphcytes for its potential clinical use. Results Preclinical assessment of MI-219 was evaluated by means of an in vitro and ex vivo approach and compared to Nutlin-3, the gold standard. Characterization of p53 activity and stability were assessed by quantitative PCR, Western blot, and immunoprecipitation. Biological outcome was measured using Trypan blue exclusion assay, Annexin V/PI, PARP and caspase-3 cleavage. Surprisingly, the overall biological effects of Nutlin-3 were more delayed (48 h) while MI-219 triggered an earlier response (12-24 h), predominantly in the form of apoptotic cell death. Using a cell free autoubiquitination assay, neither agent interfered with HDM2 E3 ligase function. MI-219 was more effective in upregulating wt-p53 stabilization compared to Nutlin-3. MI-219, but not Nutlin-3, enhanced the autoubiquitination and degradation of HDM2. Conclusions Our data reveals unexpected differences between MI-219 and the well-studied Nutlin-3 in lymphoma cell lines and patient samples. We suggest a novel mechanism for MI-219 that alters the functional activity of HDM2 through enhanced autoubiquitination and degradation. Additionally, this mechanism appears to correspond to biological outcome. Our results provide evidence that different classes of HDM2 SMIs elicit molecular events that extend beyond HDM2-p53 dissociation which may be of biological and potentially therapeutic importance.