tbuckley/cabot-search huggingface dataset:
Genotyping for disease associated HLA DR beta 1 alleles and the need for early joint surgery in rheumatoid arthritis: a quantitative evaluation
Authors: A. Crilly, N. Maiden, H. A Capell, R. Madhok
Journal: Annals of the Rheumatic Diseases (1999)

<h3>OBJECTIVE</h3> To determine the value of HLA DR β1 disease associated epitope (DAE) and erythrocyte sedimentation (ESR) in predicting the need for major joint replacement in rheumatoid arthritis (RA). <h3>METHODS</h3> Sixty five RA patients who had undergone hip, knee or shoulder arthroplasty within 15 years of disease onset and 65 who had not. HLA DR β1 genotype was determined by polymerase chain reaction. ESR at first hospital visit was noted. <h3>RESULTS</h3> Significantly more patients with two DAE required surgery, (32%<i>v</i> 9%), χ<sup>2</sup> = 13.9, p=0.001, odds ratio=5.4 (95% CI: 1.8, 16). Sensitivity was poor, 32%, specificity high, 91%. Presentation ESR was higher in surgery patients compared with non-surgery patients, 52 mm 1st h<i>v</i> 25 mm 1st h, p&lt; 0.001, but was independent of DAE status. Sensitivity of an ESR of 30 mm 1st h was 75%, specificity 53%. <h3>CONCLUSION</h3> The presence of two DAE is a risk factor for major joint surgery in RA and is independent of ESR, whereas in those with one or no DAE, a high ESR is an important predictor.
Diabetes Screening With Hemoglobin A1c Versus Fasting Plasma Glucose in a Multiethnic Middle-School Cohort
Authors: John B. Buse, Francine R. Kaufman, Barbara Linder, Kathryn Hirst, Laure El ghormli, Steven Willi
Journal: Diabetes Care (2012)

OBJECTIVE To characterize middle-school students from the HEALTHY study with glycemic abnormalities, specifically high-risk hemoglobin A1c (A1C) (hrA1C; A1C = 5.7–6.4%) and impaired fasting glucose (IFG; fasting plasma glucose [FPG] = 100–125 mg/dL). RESEARCH DESIGN AND METHODS History was collected by self-report, physical measurement was collected by trained study staff, and fasting blood was drawn by trained phlebotomists and analyzed centrally. RESULTS At baseline, among 3,980 sixth graders, 128 (3.2%) had hrA1C and 635 (16.0%) had IFG. Compared with A1C &amp;lt;5.7%, hrA1C was associated with non-Hispanic black race/ethnicity, family history of diabetes, and higher measurements of BMI, waist circumference, and fasting insulin. Compared with FPG &amp;lt;100 mg/dL, IFG was associated with Hispanic ethnicity; increased BMI, waist circumference, and fasting insulin; higher frequency of high blood pressure; and higher mean triglycerides. Two years later, children with hrA1C persisted as hrA1C in 59.4%, and one child (0.8%) developed A1C ≥6.5%; children with IFG persisted with IFG in 46.9%, and seven children (1.1%) developed FPG ≥126 mg/dL. Those with hrA1C compared with IFG had a higher BMI in sixth grade, which persisted to eighth grade. CONCLUSIONS In the HEALTHY study cohort, hrA1C and IFG define different groups of youth with differentially increased diabetes risk markers. IFG is approximately fivefold more common, but hrA1C is more persistent over time. Optimal screening strategies for diabetes in youth remain unresolved.
Use of Methadone for the Treatment of Diabetic Neuropathy
Authors: Lewis Hays, Coleen Reid, Michelle Doran, Karyn Geary
Journal: Diabetes Care (2005)

Editor's comment: This is the second Commentary of those that will appear from time to time describing treatments that may not have been validated by appropriate clinical trials but seem to be effective in diabetic patients based on small studies and/or extensive clinical experience. This one describes effective opioid treatment for those diabetic patients failing nonopioid therapies for painful neuropathy.
A QUANTITATIVE STUEY OF ERYTHRASMA LESIONS
Authors: DOROTHY A. SOMERVILLE
Journal: British Journal of Dermatology (1972)

Journal Article A QUANTITATIVE STUEY OF ERYTHRASMA LESIONS Get access DOROTHY A. SOMERVILLE DOROTHY A. SOMERVILLE Department of Bacteriology, St John's Hospital for Diseases of the Skin, London, E.9 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 87, Issue 2, 1 August 1972, Pages 130–137, https://doi.org/10.1111/j.1365-2133.1972.tb16187.x Published: 01 August 1972 Article history Accepted: 10 March 1972 Published: 01 August 1972
C4 concentrations and C4 deficiency alleles in systemic lupus erythematosus.
Authors: W A Wilson, P E Armatis, M C Perez
Journal: Annals of the Rheumatic Diseases (1989)

In a study of 66 patients with systemic lupus erythematosus (SLE) and 80 controls it was found that the presence of two deficiency (null) alleles of C4 had a significant effect on mean C4 concentrations in serum. In six controls who each had two C4 null alleles the mean C4 concentration in serum was 56% lower than in 43 controls without C4 null alleles; the nadir of the C4 concentration in four patients with SLE with two null alleles was also lower by a mean of 55% than in 32 patients who did not have null alleles. Reduced production of C4 allotypes in subjects with two null alleles may be an important determinant of total C4 concentration in patients with SLE. For optimal interpretation of C4 concentrations in SLE, C4 allotyping appears to be indicated, particularly to identify patients who have two null alleles of C4.
Anti–LAMP-2 Antibodies Are Not Prevalent in Patients With Antineutrophil Cytoplasmic Autoantibody Glomerulonephritis
Authors: Aleeza J. Roth, Michael C. Brown, Rex Neal Smith, Anshul K. Badhwar, Oscar Parente, Hyun chul Chung, Donna O’Dell, None Bunch, JulieAnne G. McGregor, Susan L. Hogan, Yichun Hu, Jia-Jin Yang, Elisabeth A. Berg, John Niles, J. Charles Jennette, Gloria A. Preston, Ronald J. Falk
Journal: Journal of the American Society of Nephrology (2011)

Lysosomal membrane protein 2 (LAMP-2) is a target of antineutrophil cytoplasmic autoantibodies (ANCA) in addition to the more commonly known targets proteinase 3 and myeloperoxidase. The prevalence of anti–LAMP-2 antibodies and their relationship to disease in ANCA glomerulonephritis are not well described. We measured anti–LAMP-2 reactivity in 680 sera samples (two academic centers) from patients with ANCA glomerulonephritis (n=329); those with ANCA-negative glomerulonephritis (n=104); those with fimbriated, gram-negative Escherichia coli urinary tract infection (n=104); disease controls (n=19); and healthy volunteers (n=124). With levels in healthy controls used to define a reference range, anti–LAMP-2 reactivity was present in 21% of ANCA sera from two of the centers; reactivity was present in 16% of the control group with urinary tract infection. Western blotting and immunofluorescence microscopy did not verify positivity. Titers of anti-myeloperoxidase and anti–proteinase 3 antibodies were 1500-fold and 10,000-fold higher than anti–LAMP-2 titers, respectively. There was no correlation between anti–LAMP-2 antibodies and disease activity. Furthermore, Wistar Kyoto rats injected with anti–LAMP-2 antibodies did not develop glomerulonephritis. In conclusion, antibodies that react with LAMP-2 may exist at very low titers in a minority of patients with ANCA disease. These data do not support a mechanistic relationship between anti–LAMP-2 antibodies and ANCA glomerulonephritis.
Mobitz type II second-degree atrioventricular block in athletes: true or false?
Authors: S Serge Barold, Luigi Padeletti
Journal: British Journal of Sports Medicine (2008)

The electro cardiographic patterns of type I and type II second-degree atrioventricular ( AV) block during sinus rhythm describe the behaviour of the PR intervals (in sinus rhythm) in sequences (with at least two consecutive conducted PR intervals) where a single P wave fails to conduct to the ventricles.1 Unfortunately, the diagnosis of Mobitz type II second-degree AV block continues to be an important clinical problem because the standard definitions of second-degree AV block are often misinterpreted.1 The literature is replete with cases of type I second-degree AV block labelled as type II block, and similar errors have crept into the sports literature with claims that narrow QRS type II AV block can also occur in otherwise healthy young athletes2,–,7 and less commonly after exercise in the form of vasovagal syncope (table 1).8 These reports of type II block in athletes provided either no ECG or misdiagnosed ones. Furthermore, when stated, the definitions of type II block were inappropriate. The occurrence of type II block in young athletes is counterintuitive because it would imply serious disease of the His–Purkinje system and an absolute indication for a permanent pacemaker regardless of symptoms.1 We were unable to find a single case of precisely documented type II block in young athletes. Yet, many review articles continue to list type II block as one of the manifestations of the athlete's heart.9,–,12 Accurate diagnosis of type II block in athletes is critical and will affect treatment recommendations. Based on these considerations, there is a need for reviewing the pitfalls surrounding the diagnosis of type II block with emphasis on how errors can be avoided by strict adherence to definitions.

View this table:

Table 1 
Incidence of reported type II second-degree atrioventricular block (AVB) in athletes



Type …
“OA02” Peptide Facilitates the Precise Targeting of Paclitaxel-Loaded Micellar Nanoparticles to Ovarian Cancer <i>In Vivo</i>
Authors: Kai Xiao, Yuanpei Li, Joyce S. Lee, Abby M. Gonik, Tiffany Dong, Gabriel Fung, Eduardo Sanchez, Li Xing, Holland R. Cheng, Juntao Luo, Kit S. Lam
Journal: Cancer Research (2012)

Micellar nanoparticles based on linear polyethylene glycol (PEG) block dendritic cholic acids (CA) copolymers (telodendrimers), for the targeted delivery of chemotherapeutic drugs in the treatment of cancers, are reported. The micellar nanoparticles have been decorated with a high-affinity "OA02" peptide against α-3 integrin receptor to improve the tumor-targeting specificity which is overexpressed on the surface of ovarian cancer cells. "Click chemistry" was used to conjugate alkyne-containing OA02 peptide to the azide group at the distal terminus of the PEG chain in a representative PEG(5k)-CA(8) telodendrimer (micelle-forming unit). The conjugation of OA02 peptide had negligible influence on the physicochemical properties of PEG(5k)-CA(8) nanoparticles and as hypothesized, OA02 peptide dramatically enhanced the uptake efficiency of PEG(5k)-CA(8) nanoparticles (NP) in SKOV-3 and ES-2 ovarian cancer cells via receptor-mediated endocytosis, but not in α-3 integrin-negative K562 leukemia cells. When loaded with paclitaxel, OA02-NPs had significantly higher in vitro cytotoxicity against both SKOV-3 and ES-2 ovarian cancer cells as compared with nontargeted nanoparticles. Furthermore, the in vivo biodistribution study showed OA02 peptide greatly facilitated tumor localization and the intracellular uptake of PEG(5k)-CA(8) nanoparticles into ovarian cancer cells as validated in SKOV3-luc tumor-bearing mice. Finally, paclitaxel (PTX)-loaded OA02-NPs exhibited superior antitumor efficacy and lower systemic toxicity profile in nude mice bearing SKOV-3 tumor xenografts, when compared with equivalent doses of nontargeted PTX-NPs as well as clinical paclitaxel formulation (Taxol). Therefore, OA02-targeted telodendrimers loaded with paclitaxel have great potential as a new therapeutic approach for patients with ovarian cancer.
Increase in exhaled carbon monoxide during exacerbations of cystic fibrosis
Authors: J. D Antuni
Journal: Thorax (2000)

Non-invasive assessment of inflammation is likely to be useful in the management of cystic fibrosis (CF). Exhaled carbon monoxide (CO) concentrations are increased in patients with clinically stable CF. A study was undertaken to determine whether this marker of oxidative damage is further increased during exacerbations of the disease.Exhaled CO concentrations were measured in 12 healthy non-smoking control subjects (six men) of mean (SE) age 37 (2) years with forced expiratory volume in one second (FEV(1)) 95 (1)% predicted and in 44 patients with CF (20 men) of mean (SE) age 29 (1) years with FEV(1) 56 (3)% predicted using an on-line CO analyser.Twenty nine patients were in a stable condition while 15 had clinically defined respiratory exacerbations (increased cough and production of sputum, change in the quality of the sputum, shortness of breath, sensation of chest congestion, and deterioration of FEV(1)) and represented the unstable group. Exhaled CO concentrations were 2.0 (0.15) ppm in the control group, were increased in the stable CF group to 2.7 (0.13) ppm (differences between means -0.67 (0.22), 95% confidence interval (CI) 0.22 to 1.12, p<0.01) and further increased in the unstable group to 4.8 (0.3) ppm (differences between means -2.15 (0.32), 95% CI 1.50 to 2.79, p<0.001). A significant correlation was found between the deterioration in FEV(1) and exhaled CO concentrations.This study shows that the measurement of exhaled CO is of potential value as an indicator of exacerbations in patients with CF and could be used as a simple method to monitor the course of the disease.
Role of macrophage-derived hypoxia-inducible factor (HIF)-1α as a mediator of vascular remodelling
Authors: Taisuke Nakayama, Hirotsugu Kurobe, Noriko Sugasawa, Hajime Kinoshita, Mayuko Higashida, Yuki Matsuoka, Yasushi Yoshida, Yoichiro Hirata, Mie Sakata, Mark W. Maxfield, Michio Shimabukuro, Yousuke Takahama, Masataka Sata, Toshiaki Tamaki, Tetsuya Kitagawa, Shuhei Tomita
Journal: Cardiovascular Research (2013)

Excessive vascular remodelling leads to progression of a wide range of vasculopathies, and the immune response to intimal injuries is crucial in this process. This vascular remodelling occurs in the hypoxic microenvironment and is closely related to the immune system. Macrophages play a key role in immunological-cell-mediated arterial remodelling. In this study, we clarified the role of macrophage-derived hypoxia-inducible factor (HIF-1α) in vascular remodelling. Wire-induced femoral arterial injury was inflicted in mice lacking the macrophage-specific HIF-1α gene and in their wild-type counterparts. The mutant mice showed both suppressed wire-induced neointimal thickening and decreased infiltration of inflammatory cells in the adventitia, compared with wild-type mice. Studies to clarify the mechanism of restrained vascular remodelling in the mutant mice revealed decreased production of pro-inflammatory cytokines by the activated macrophages and suppressed macrophage migration activity in the mutant mice. Gene expressions of the HIF-1α-deficient macrophages positively correlated with the phenotypic profile of M2 macrophages and negatively correlated with that of M1 macrophages. Our results show that HIF-1α in macrophages plays a crucial role in promoting vascular inflammation and remodelling. As decreasing HIF-1α activity in macrophages may prevent the progression of vascular remodelling, HIF-1α may be a possible therapeutic target in vascular diseases.
Bacteraemic Haemophilus influenzae pneumonia
Authors: MB Allen, K Prowse
Journal: European Respiratory Journal (1988)

Bacteraemia with Haemophilus pneumonia is uncommon. To determine its incidence and features case notes of patients in whom Haemophilus spp. were isolated from blood and pleural fluid over a five-year period were reviewed. Eight adult patients with H. influenzae bacteraemia were identified, five of whom had pneumonia on clinical and radiographic criteria. Only one patient had a predisposing factor, chronic obstructive lung disease. Two patients had beta-lactamase producing isolates, one of whom developed an empyema, following treatment with ampicillin, which required surgical drainage. Four patients were elderly, aged 69-80 yrs and were clinically in shock at the time of diagnosis. Seven of the eight patients survived.
Does This Child Have a Urinary Tract Infection?
Authors: Nader Shaikh, Natalia E Morone, John Lopez, Jennifer Chianese, Shilpa Sangvai, Frank D'Amico, Alejandro Hoberman, Ellen R Wald
Journal: JAMA (2007)

Urinary tract infection (UTI) is a frequently occurring pediatric illness that, if left untreated, can lead to permanent renal injury. Accordingly, accurate diagnosis of UTI is important.To review the diagnostic accuracy of symptoms and signs for the diagnosis of UTI in infants and children.A search of MEDLINE and EMBASE databases was conducted for articles published between 1966 and October 2007, as well as a manual review of bibliographies of all articles meeting inclusion criteria, 1 previously published systematic review, 3 clinical skills textbooks, and 2 experts in the field, yielding 6988 potentially relevant articles.Studies were included if they contained data on signs or symptoms of UTI in children through age 18 years. Of 337 articles examined, 12 met all inclusion criteria.Two evaluators independently reviewed, rated, and abstracted data from each article.In infants with fever, history of a previous UTI (likelihood ratio [LR] range, 2.3-2.9), temperature higher than 40 degrees C (LR range, 3.2-3.3), and suprapubic tenderness (LR, 4.4; 95% confidence interval [CI], 1.6-12.4) were the findings most useful for identifying those with a UTI. Among male infants, lack of circumcision increased the likelihood of a UTI (summary LR, 2.8; 95% CI, 1.9-4.3); and the presence of circumcision was the only finding with an LR of less than 0.5 (summary LR, 0.33; 95% CI, 0.18-0.63). Combinations of findings were more useful than individual findings in identifying infants with a UTI (for temperature >39 degrees C for >48 hours without another potential source for fever on examination, the LR for all findings present was 4.0; 95% CI, 1.2-13.0; and for temperature <39 degrees C with another source for fever, the LR was 0.37; 95% CI, 0.16-0.85). In verbal children, abdominal pain (LR, 6.3; 95% CI, 2.5-16.0), back pain (LR, 3.6; 95% CI, 2.1-6.1), dysuria, frequency, or both (LR range, 2.2-2.8), and new-onset urinary incontinence (LR, 4.6; 95% CI, 2.8-7.6) increased the likelihood of a UTI.Although individual signs and symptoms were helpful in the diagnosis of a UTI, they were not sufficiently accurate to definitively diagnose UTIs. Combination of findings can identify infants with a low likelihood of a UTI.
Association of Depression With Viral Load, CD8 T Lymphocytes, and Natural Killer Cells in Women With HIV Infection
Authors: Dwight L Evans, Thomas R Ten Have, Steven D Douglas, David R Gettes, Mary Morrison, Margaret S Chiappini, Priscilla Brinker-Spence, Carla Job, Delinda E Mercer, Yan Lin Wang, Dean Cruess, Benoit Dube, Erik A Dalen, Tiffany Brown, Russell Bauer, John M Petitto
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: Clinical and epidemiology studies have implicated depression as a risk factor in the morbidity and mortality of many human diseases. This study sought to determine if depression was associated with alterations in cellular immunity variables—specifically, natural killer (NK) cells and CD8 T lymphocytes—in women with HIV infection. METHOD: Ninety-three women (63 HIV-seropositive, 30 HIV-seronegative) were studied as part of an ongoing longitudinal study conducted at two sites. Subjects underwent extensive clinical, psychiatric, and immunological evaluations. CBC counts and flow cytometry panels were conducted and NK cell activity assayed for all subjects; viral load was determined for HIV-seropositive subjects. RESULTS: The overall rate of major depression in the HIV-seropositive and HIV-seronegative women was 15.87% (N=10 of 63) and 10.00% (N=3 of 30), respectively. HIV-seropositive women had higher depressive symptom scores than did the comparison subjects (Hamilton depression scale: mean=8.62 [SD=7.26] versus mean=5.67 [SD=7.33], respectively). Both groups had similar anxiety scores. Depressive and anxiety symptoms were significantly associated with higher activated CD8 T lymphocyte counts and higher viral load levels. Major depression was associated with significantly lower natural killer cell activity, and depressive and anxiety symptom scores showed a similar correlation. CONCLUSIONS: Our findings provide the first evidence that depression may alter the function of killer lymphocytes in HIV-infected women and suggest that depression may decrease natural killer cell activity and lead to an increase in activated CD8 T lymphocytes and viral load. The rate of current major depression in these HIV-seropositive women (none of whom had current substance abuse) is approximately twice that reported for HIV-seropositive men. The rate is also consistent with studies of women with other medical illnesses and with a recent epidemiology study that associated depression with mortality in HIV-infected women with chronic depressive symptoms. Depression may have a negative impact on innate immunity. Examination of killer lymphocytes may prove useful in assessing the potential relationship between depression, immunity, and HIV disease progression in women.
miRNA-491-5p and GIT1 Serve as Modulators and Biomarkers for Oral Squamous Cell Carcinoma Invasion and Metastasis
Authors: Wei-Chieh Huang, Shih-Hsuan Chan, Te-Hsuan Jang, Jer-Wei Chang, Ying-Chin Ko, Tzu-Chen Yen, Shang-Lun Chiang, Wei-Fan Chiang, Tien-Yu Shieh, Chun-Ta Liao, Jyh-Lyh Juang, Hsueh-Chun Wang, Ann-Joy Cheng, Ya-Ching Lu, Lu-Hai Wang
Journal: Cancer Research (2013)

Abstract MicroRNAs offer tools to identify and treat invasive cancers. Using highly invasive isogenic oral squamous cell carcinoma (OSCC) cells, established using in vitro and in vivo selection protocols from poorly invasive parental cell populations, we used microarray expression analysis to identify a relative and specific decrease in miR-491-5p in invasive cells. Lower expression of miR-491-5p correlated with poor overall survival of patients with OSCCs. miR-491-5p overexpression in invasive OSCC cells suppressed their migratory behavior in vitro and lung metastatic behavior in vivo. We defined the G-protein—coupled receptor kinase-interacting protein 1 (GIT1)—as a direct target gene for miR-491-5p control. GIT1 overexpression was sufficient to rescue miR-491-5p–mediated inhibition of migration/invasion and lung metastasis. Conversely, GIT1 silencing phenocopied the ability of miR-491-5p to inhibit migration/invasion and metastasis of OSCC cells. Mechanistic investigations indicated that miR-491-5p overexpression or GIT1 attenuation reduced focal adhesions, with a concurrent decrease in steady-state levels of paxillin, phospho-paxillin, phospho-FAK, EGF/EGFR-mediated extracellular signal–regulated kinase (ERK1/2) activation, and MMP2/9 levels and activities. In clinical specimens of OSCCs, GIT1 levels were elevated relative to paired normal tissues and were correlated with lymph node metastasis, with expression levels of miR-491-5p and GIT1 correlated inversely in OSCCs, where they informed tumor grade. Together, our findings identify a functional axis for OSCC invasion that suggests miR-491-5p and GIT1 as biomarkers for prognosis in this cancer. Cancer Res; 74(3); 751–64. ©2013 AACR.