tbuckley/cabot-search huggingface dataset:
Identification of Upper Airway Anatomic Risk Factors for Obstructive Sleep Apnea with Volumetric Magnetic Resonance Imaging
Authors: Richard J. Schwab, Michael Pasirstein, Robert Pierson, Adonna Mackley, Robert Hachadoorian, Raanan Arens, Greg Maislin, Allan I. Pack
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

We used sophisticated volumetric analysis techniques with magnetic resonance imaging in a case–control design to study the upper airway soft tissue structures in 48 control subjects (apnea–hypopnea index, 2.0 ± 1.6 events/hour) and 48 patients with sleep apnea (apnea–hypopnea index, 43.8 ± 25.4 events/hour). Our design used exact matching on sex and ethnicity, frequency matching on age, and statistical control for craniofacial size and visceral neck fat. The data support our a priori hypotheses that the volume of the soft tissue structures surrounding the upper airway is enlarged in patients with sleep apnea and that this enlargement is a significant risk factor for sleep apnea. After covariate adjustments the volume of the lateral pharyngeal walls (p < 0.0001), tongue (p < 0.0001), and total soft tissue (p < 0.0001) was significantly larger in subjects with sleep apnea than in normal subjects. These data also demonstrated, after covariate adjustments, significantly increased risk of sleep apnea the larger the volume of the tongue, lateral pharyngeal walls, and total soft tissue: (1) total lateral pharyngeal wall (odds ratio [OR], 6.01; 95% confidence interval [CI], 2.62–17.14); (2) total tongue (OR, 4.66; 95% CI, 2.31–10.95); and (3) total soft tissue (OR, 6.95; 95% CI, 3.08–19.11). In a multivariable logistic regression analysis the volume of the tongue and lateral walls was shown to independently increase the risk of sleep apnea.
Reply to Hervé Baumert's Letter to the Editor re: Matthew N. Simmons, Benjamin I. Chung, Inderbir S. Gill. Perioperative Efficacy of Laparoscopic Partial Nephrectomy for Tumors Larger than 4cm. Eur Urol 2009;55:199–208
Authors: Matthew N. Simmons, Benjamin I. Chung, Inderbir S. Gill
Journal: European Urology (2009)
Surveillance programme of cirrhotic patients for early diagnosis and treatment of hepatocellular carcinoma: a cost effectiveness analysis
Authors: L Bolondi
Journal: Gut (2001)

<h3>BACKGROUND</h3> Hepatocellular carcinoma (HCC) is a major cause of death in cirrhotic patients. This neoplasm is associated with liver cirrhosis (LC) in more than 90% of cases. Early diagnosis and treatment of HCC are expected to improve survival of patients. <h3>AIMS</h3> To assess the cost effectiveness of a surveillance programme of patients with LC for the early diagnosis and treatment of HCC. <h3>PATIENTS</h3> A cohort of 313 Italian patients with LC were enrolled in the surveillance programme between March 1989 and November 1991. In the same period, 104 consecutive patients with incidentally detected HCC were referred to our centre and served as a control group. <h3>METHODS</h3> Surveillance was based on ultrasonography (US) and α fetoprotein (AFP) determinations repeated at six month intervals. Risk factors for HCC were assessed by multivariate analysis (Cox model). Outcome measures analysed were: (1) number and size of tumours; (2) eligibility for treatment; and (3) survival of patients. Economic issues were: (1) overall cost of surveillance programme; (2) cost per treatable HCC; and (3) cost per year of life saved (if any). Costs were assessed according to charges for procedures at our university hospital. <h3>RESULTS</h3> Surveillance lasted a mean of 56 (31) months (range 6–100). During the follow up, 61 patients (19.5%) developed HCC (unifocal at US in 49 cases), with an incidence of 4.1% per year of follow up. AFP, Child-Pugh classes B and C, and male sex were detected as independent risk factors for developing HCC. Only 42 (68.9%) of 61 liver tumours were treated by surgical resection, orthotopic liver transplantation, or local therapy. The cumulative survival rate of the 61 patients with liver tumours detected in the surveillance programme was significantly longer than that of controls (p=0.02) and multivariate analysis showed an association between surveillance and survival. The overall cost of the surveillance programme was US$753 226, the cost per treatable HCC was US$17 934, and the cost for year of life saved was US$112 993. <h3>CONCLUSION</h3> Our surveillance policy of patients with LC requires a large number of resources and offers little benefit in terms of patient survival. The decision whether to adopt a surveillance policy towards HCC should rely on the prevalence of the disease in the population and on the resources of a particular country.
Oct-3/4 Expression Reflects Tumor Progression and Regulates Motility of Bladder Cancer Cells
Authors: Chao-Ching Chang, Gia-Shing Shieh, Pensee Wu, Chia-Cheng Lin, Ai-Li Shiau, Chao-Liang Wu
Journal: Cancer Research (2008)

Abstract Cancer and embryonic stem cells exhibit similar behavior, including immortal, undifferentiated, and invasive activities. Here, we show that in clinical samples bladder tumors with intense expression of stem cell marker Oct-3/4 (also known as POU5F1) are associated with further disease progression, greater metastasis, and shorter cancer-related survival compared with those with moderate and low expressions. Expression of Oct-3/4 is detected in human bladder transitional cell carcinoma samples and cell lines. Overexpression of Oct-3/4 enhances, whereas knockdown of Oct-3/4 expression by RNA interference reduces, migration and invasion of bladder cancer cells. Oct-3/4 can up-regulate fibroblast growth factor-4 and matrix metalloproteinase-2 (MMP-2), MMP-9, and MMP-13 production, which may contribute to tumor metastasis. Finally, we show that Ad5WS4, an E1B-55 kD–deleted adenovirus driven by the Oct-3/4 promoter, exerts potent antitumor activity against bladder cancer in a syngeneic murine tumor model. Therefore, our results implicate that Oct-3/4 may be useful as a novel tumor biological and prognostic marker and probably as a potential therapeutic target for bladder cancer. [Cancer Res 2008;68(15):6281–91]
Determinants of the Exercise Endurance Capacity in Patients with Chronic Obstructive Pulmonary Disease
Authors: J. ALBERTO NEDER, PAUL W. JONES, LUIZ E. NERY, BRIAN J. WHIPP
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

To characterize the determinants of the power-duration (W-t) relationship in patients with chronic obstructive pulmonary disease (COPD), we evaluated 8 nonhypoxemic patients (FEV(1) = 1.27 +/- 0.26 L) and 10 healthy controls. After an initial maximum-incremental exercise test on cycle ergometer (peak), the subjects underwent four high-intensity constant-load tests to the limit of tolerance (t), each on different days. The W-t relationship was found to be hyperbolic in both groups. Absolute values of both the critical power asymptote (theta(F)) and the curvature constant (W') were lower in patients than in control subjects. However, when expressed as percentage of peak work rate theta(F) was significantly higher in patients compared with control subjects (81.8 +/- 3.3% versus 67.5 +/- 3.7%, respectively, p < 0.01). There were severe reductions in t in the patients that were consistently associated with higher breathlessness scores and V E/MVV ratios. Interestingly, all patients were able to sustain exercise at theta(F) for 20 min despite near-maximum physiological and subjective stresses. We conclude that the reductions of both parameters of the hyperbolic W-t relationship (theta(F) and W') in patients with COPD were due to the ventilatory constraints and their sensory consequences. Importantly, theta(F) separated a "sustainable" from a "nonsustainable" exercise-intensity domain: this parameter consistently occurred closer to peak work rate in patients than the healthy control subjects.
Metastatic papillary craniopharyngioma: Case study and study of tumorangiogenesis
Authors: L. Elmaci, O. Kurtkaya-Yapicier, G. Ekinci, A. Sav, M. N. Pamir, S. Vidal, K. Kovacs, B. W. Scheithauer
Journal: Neuro-Oncology (2002)

We report a case of suprasellar papillary craniopharyngioma metastatic to the temporoparietal region 2 years after its initial resection. The literature documents examples of craniopharyngioma recurrences along the surgical tract, as well as remote ipsi- and contralateral metastases via cerebrospinal fluid seeding. Ours is the second report of a craniopharyngioma of papillary type to exhibit metastatic behavior. The tumor spread opposite the side of craniotomy. Although a rare occurrence, it confirms the limited capacity of histologically benign craniopharyngiomas to undergo meningeal seeding, likely the result of surgical manipulation. Immunohistochemical demonstration of increased microvascular density and vascular endothelial growth factor expression, as well as a high vascular endothelial growth receptor (VEGFR2) signal by in situ hybridization, suggests that tumor vascularity facilitated angiogenesis and may have been involved in the establishment and growth of the metastatic deposit.
Cathepsin B inhibition interferes with metastatic potential of human melanoma: an in vitro and in vivo study
Authors: Paola Matarrese, Barbara Ascione, Laura Ciarlo, Rosa Vona, Carlo Leonetti, Marco Scarsella, Anna M Mileo, Caterina Catricalà, Marco G Paggi, Walter Malorni
Journal: Molecular Cancer (2010)

Cathepsins represent a group of proteases involved in determining the metastatic potential of cancer cells. Among these are cysteinyl- (e.g. cathepsin B and cathepsin L) and aspartyl-proteases (e.g. cathepsin D), normally present inside the lysosomes as inactive proenzymes. Once released in the extracellular space, cathepsins contribute to metastatic potential by facilitating cell migration and invasiveness. In the present work we first evaluated, by in vitro procedures, the role of cathepsins B, L and D, in the remodeling, spreading and invasiveness of eight different cell lines: four primary and four metastatic melanoma cell lines. Among these, we considered two cell lines derived from a primary cutaneous melanoma and from a supraclavicular lymph node metastasis of the same patient. To this purpose, the effects of specific chemical inhibitors of these proteases, i.e. CA-074 and CA-074Me for cathepsin B, Cathepsin inhibitor II for cathepsin L, and Pepstatin A for cathepsin D, were evaluated. In addition, we also analyzed the effects of the biological inhibitors of these cathepsins, i.e. specific antibodies, on cell invasiveness. We found that i) cathepsin B, but not cathepsins L and D, was highly expressed at the surface of metastatic but not of primary melanoma cell lines and that ii) CA-074, or specific antibodies to cathepsin B, hindered metastatic cell spreading and dissemination, whereas neither chemical nor biological inhibitors of cathepsins D and L had significant effects. Accordingly, in vivo studies, i.e. in murine xenografts, demonstrated that CA-074 significantly reduced human melanoma growth and the number of artificial lung metastases. These results suggest a reappraisal of the use of cathepsin B inhibitors (either chemical or biological) as innovative strategy in the management of metastatic melanoma disease.
Antibodies to histones in systemic lupus erythematosus: prevalence, specificity, and relationship to clinical and laboratory features.
Authors: M G Cohen, K M Pollard, J Webb
Journal: Annals of the Rheumatic Diseases (1992)

Antibodies to histones (AHA) are commonly found in patients with systemic lupus erythematosus (SLE). However, the full profile of AHA and their clinical associations remains unclear. A total of 111 patients with SLE were studied, including 13 patients in whom multiple serum samples were available over several years. IgM, IgG, and IgA antibodies to total core histones, histone complexes, and individual histones were determined by highly sensitive enzyme linked immunosorbent assays (ELISAs). Antibodies to histones were detected in 74% of serum samples, though only at low levels in half of these. Antibodies to each of the individual histones (H1, H2A, H2B, H3, H4) occurred with similar frequencies except for IgG and IgA antibodies to H4, which were uncommon. In contrast, antibodies to the histone complexes H2A-H2B and H3-H4 were detected in only two serum samples and thus do not appear to be a feature of SLE. All three major isotypes of AHA were common and usually occurred with similar frequencies to one another for the various histone specificities. There were few clinical or laboratory associations with AHA; the strongest was between IgG antibodies to total core histones and antibodies to native DNA. Similarly, there was no association between the presence of AHA and disease activity. However, for the patients as a group and in one patient alone, periods of SLE disease activity were associated with higher levels of AHA. Although the profile of antibodies to individual histones varied with time, no profile was identified that corresponded with any specific disease manifestations. It is concluded from this study that although AHA are common in patients with SLE, their clinical value in this syndrome must, at present, be considered limited.
The centenary (2015) of the transfer factor for carbon monoxide (TLCO): Marie Krogh's legacy
Authors: J. M. B. Hughes, C. D. R. Borland
Journal: Thorax (2014)

Whether or not the lungs actively secreted oxygen, particularly under stressful conditions (severe exertion, alveolar hypoxia), was an argument which continued for more than 50 years (1870–1923), and involved some of the most distinguished respiratory physiologists of that era, such as JS Haldane, Christian Bohr and August Krogh. The denouement, as told by Krogh's daughter, Bodil Schmidt-Neilsen,1 began 11 years earlier in 1904 when a Danish medical student, Marie Jorgensen, attended a class taught by August Krogh, an instructor in physiology in Christian Bohr's department. They were attracted to each other and married in 1905, and Marie (figure 1) joined August (a Nobel Prize winner in physiology and medicine in 1920) in some aspects of his research. The subsequent publication of a paper in 1915, 100 years ago this year, by Marie Krogh in the Journal of Physiology 2 was the pivotal moment in the story. The influence of this paper “The diffusion of gases through the lungs of man”2 continues to this day, long after the oxygen secretion question was settled (in Marie Krogh's favour). Nowadays, pulmonary function laboratories throughout the world use a modification of her single breath transfer factor for carbon monoxide (TLCO.sb) test, known in North America as the DLCO.sb (carbon monoxide diffusing capacity); it is an essential part of routine lung function screening, and the only non-invasive test (apart from pulse oximetry) of the gas exchanging efficiency of the lung.



Figure 1 
Marie Krogh (nee Jorgenson), born Christmas day 1874 on the island of Fyn, Denmark, married August Krogh in Copenhagen, March 1905, died 1943 in Copenhagen, aged 69 years.



The oxygen secretion story has been told many times.1 ,3 ,4 A century ago, the idea that Claude Bernard's milieu interieur might be stabilised by alveolar cells secreting oxygen at times …
Polymorphism of the human complement C4 and steroid 21-hydroxylase genes. Restriction fragment length polymorphisms revealing structural deletions, homoduplications, and size variants.
Authors: P M Schneider, M C Carroll, C A Alper, C Rittner, A S Whitehead, E J Yunis, H R Colten
Journal: Journal of Clinical Investigation (1986)

Several autoimmune disorders as well as congenital adrenal hyperplasia (CAH) are either associated or closely linked with genetic variants of the fourth component of complement (C4A and C4B) and the enzyme steroid 21-hydroxylase (21-OH). These proteins are encoded by genes that are located downstream from the genes for complement proteins, C2 and factor B (BF) between HLA-B and -DR in the major histocompatibility complex (MHC). Previous studies of variants and null alleles were based on electrophoretic mobility of C4 protein and linkage with disease phenotypes. These data did not permit analysis of the basis for the observed null alleles and duplicated variants. We studied this region of the MHC in 126 haplotypes for a structural analysis of the four adjacent loci, C4A, 21-OHA, C4B, and 21-OHB. About half of the C4 genes typed as C4 null are deleted and several unrecognized homoduplicated C4 alleles were detected. Hence the frequencies of different C4 structural variants must be recalculated based on a direct analysis of the genes. Analysis of the C4/21-OH genes of patients with the classical (salt-wasting) form of CAH showed that some involve a deletion of the C4B and 21-OHB genes; whereas for two only the 21-OHB gene is deleted, i.e., the C4B gene is present. Together, these data provide a better understanding of the mechanisms generating and importance of deleted C4 and 21-OH null alleles in human disease.
The C-type lectin receptor CLEC9A mediates antigen uptake and (cross-)presentation by human blood BDCA3+ myeloid dendritic cells
Authors: Gerty Schreibelt, Lieke J. J. Klinkenberg, Luis J. Cruz, Paul J. Tacken, Jurjen Tel, Martin Kreutz, Gosse J. Adema, Gordon D. Brown, Carl G. Figdor, I. Jolanda M. de Vries
Journal: Blood (2012)
Asymptomatic muscle metastasis from pulmonary adenocarcinoma
Authors: I. Banzo, I. Martinez-Rodriguez, R. Quirce, J. Jimenez-Bonilla, J. M. Carril
Journal: Thorax (2011)

Asymptomatic muscle metastasis from pulmonary adenocarcinomaA 62-year-old never-smoker woman was admitted with a 2-month history of progressive dyspnoea.Her CT scan showed a 334 cm lung mass in the right upper lobe.Tumour biopsy revealed an adenocarcinoma.Integrated [ 18 F] fluorodeoxyglucose positron emission tomography (FDG-PET)/CT scan for staging demonstrated hypermetabolic FDG uptake in the lung mass (figure 1A) and an unexpectedly focal FDG uptake in the left paraspinal muscle (figure 1B).Physical examination was normal.Biopsy from the muscle showed infiltration with cells of adenocarcinoma.A revision of the initial CT scan revealed a mass in the left paraspinal muscle which had not been reported (figure 2, arrow).
Delayed Thrombocytopenic Purpura After Diminutive Gold Therapy
Authors: J. Robin Saphir
Journal: JAMA (1966)

OF THE VARIOUS forms of gold toxicity, thrombocytopenia is among the most dreaded. Occasionally, small amounts of gold have been found to produce purpura, or this manifestation could be delayed many weeks or months from time of injection.<sup>1</sup>It thus seems appropriate to report the case of the patient who developed thrombocytopenia seven months after having received a total gold dose of 50 mg. (For uniformity, all dosages of gold salts reported in this paper are in terms of metallic, or elemental, gold.) <h3>Report of a Case</h3> A 57-year-old white bus driver was admitted to the Buffalo General Hospital on Dec 29, 1964, with severe epistaxis. He had been well until two years previously, when his extremities became painful and swollen. Ten months prior to admission, four 12.5-mg gold doses (in the form of 25 mg gold sodium thiomalate) were administered at 14-day intervals, for a total of 50
Comparison of Early Surgery Versus Conventional Treatment in Asymptomatic Severe Mitral Regurgitation
Authors: Duk-Hyun Kang, Jeong Hoon Kim, Ji Hye Rim, Mi-Jeong Kim, Sung-Cheol Yun, Jong-Min Song, Hyun Song, Kee-Joon Choi, Jae-Kwan Song, Jae-Won Lee
Journal: Circulation (2009)

Background— The optimal timing of surgical intervention in asymptomatic patients with severe mitral regurgitation is unclear. We therefore compared the long-term results of early surgery with a conventional treatment strategy. Methods and Results— From 1996 to 2005, 447 consecutive asymptomatic patients (253 men, age 50±15 years) with severe degenerative mitral regurgitation and preserved left ventricular function were evaluated prospectively. The end point was defined as the composite of operative mortality, cardiac death, repeat mitral valve surgery, and urgent admission due to congestive heart failure during follow-up. Early surgery was performed on 161 patients (operated group), and the conventional treatment strategy was used for 286 patients (conventional treatment group). There were no significant differences between the 2 groups in terms of age, gender, euroSCORE (European System for Cardiac Operative Risk Evaluation), or ejection fraction. During a median follow-up of 1988 days, there were 2 repeat surgeries and no cardiac deaths or operative mortality in the operated group compared with 12 cardiac deaths, 1 repeat surgery, and 22 admissions for congestive heart failure in the conventional treatment group. The estimated actuarial 7-year cardiac mortality rate was 0% in the operated group and 5±2% in the conventional treatment group ( P =0.008), and for 127 propensity score-matched pairs, the estimated actuarial 7-year event-free survival rate was significantly higher in the operated than in the conventional treatment group (99±1% versus 85±4%, P =0.007). In the conventional treatment group, baseline grade of pulmonary hypertension (hazard ratio 1.87, 95% CI 1.22 to 2.87, P =0.003), age (hazard ratio 1.02, 95% CI 1.01 to 1.04, P =0.005), and effective regurgitant orifice area (hazard ratio 2.06, 95% CI 1.11 to 3.82, P =0.02) were independent variables that predicted late development of surgical indications or congestive heart failure on Cox multivariate analysis. Conclusions— Compared with conservative management, the strategy of early surgery was associated with an improved long-term event rate by decreasing cardiac mortality and congestive heart failure hospitalization more effectively in patients with severe degenerative mitral regurgitation. Early surgery may therefore further improve clinical outcomes in asymptomatic severe mitral regurgitation with preserved left ventricular systolic function and a high likelihood of mitral valve repair.
Survivin safeguards chromosome numbers and protects from aneuploidy independently from p53
Authors: Ralf Wiedemuth, Barbara Klink, Katrin Töpfer, Evelin Schröck, Gabriele Schackert, Masaaki Tatsuka, Achim Temme
Journal: Molecular Cancer (2014)

Survivin, a member of the inhibitor of apoptosis (IAP) gene family, has a dual role in mitosis and in apoptosis. It is abundantly expressed in every human tumor, compared with normal tissues. During mitosis Survivin assembles with the chromosomal passenger complex and regulates chromosomal segregation. Here, we aim to explore whether interference with the mitotic function of Survivin is linked to p53-mediated G1 cell cycle arrest and affects chromosomal stability. In this study, we used HCT116, SBC-2, and U87-MG and generated corresponding isogenic p53-deficient cells. Retroviral vectors were used to stably knockdown Survivin. The resulting phenotype, in particular the mechanisms of cell cycle arrest and of initiation of aneuploidy, were investigated by Western Blot analysis, confocal laser scan microscopy, proliferation assays, spectral karyotyping and RNAi. In all cell lines Survivin-RNAi did not induce instant apoptosis but caused polyplodization irrespective of p53 status. Strikingly, polyploidization after knockdown of Survivin resulted in merotelic kinetochore spindle assemblies, γH2AX-foci, and DNA damage response (DDR), which was accompanied by a transient p53-mediated G1-arrest. That p53 wild type cells specifically arrest due to DNA damage was shown by simultaneous inhibition of ATM and DNA-PK, which abolished induction of p21waf/cip. Cytogenetic analysis revealed chromosomal aberrations indicative for DNA double strand break repair by the mechanism of non-homologous end joining (NHEJ), only in Survivin-depleted cells. Our findings suggest that Survivin plays an essential role in proper amphitelic kinetochore-spindle assembly and that constraining Survivin's mitotic function results in polyploidy and aneuploidy which cannot be controlled by p53. Therefore, Survivin critically safeguards chromosomal stability independently from p53.