tbuckley/cabot-search huggingface dataset:
Adrenomedullin induces lymphangiogenesis and ameliorates secondary lymphoedema
Authors: D. Jin, K. Harada, S. Ohnishi, K. Yamahara, K. Kangawa, N. Nagaya
Journal: Cardiovascular Research (2008)

Adrenomedullin (AM) is a multifunctional peptide hormone that plays a significant role in vasodilation and angiogenesis. Lymphoedema is a common but refractory disorder that is difficult to be treated with conventional therapy. We therefore investigated whether AM promotes lymphangiogenesis and improves lymphoedema. The effects of AM on lymphatic endothelial cells (LEC) were investigated. AM promoted proliferation, migration, and network formation of cultured human lymphatic microvascular endothelial cells (HLMVEC). AM increased intracellular cyclic adenosine monophosphate (cAMP) level in HLMVEC. The cell proliferation induced by AM was inhibited by a cAMP antagonist and mitogen-activated protein kinase kinase (MEK) inhibitors. Phosphorylated extracellular signal-regulated kinase (ERK) in HLMVEC was increased by AM. Continuous administration of AM (0.05 µg/kg/min) to BALB/c mice with tail lymphoedema resulted in a decrease in lymphoedema thickness. AM treatment increased the number of lymphatic vessels and blood vessels in the injury site. AM promoted LEC proliferation at least in part through the cAMP/MEK/ERK pathway, and infusion of AM induced lymphangiogenesis and improved lymphoedema in mice.
A syndrome of lymphoblastic lymphoma, eosinophilia, and myeloid hyperplasia/malignancy associated with t(8;13)(p11;q11): description of a distinctive clinicopathologic entity [see comments]
Authors: RC Inhorn, JC Aster, SA Roach, CA Slapak, R Soiffer, R Tantravahi, RM Stone
Journal: Blood (1995)
Trends in rates of different forms of diagnosed coronary heart disease, 1978 to 2000: prospective, population based study of British men
Authors: Fiona C Lampe, Richard W Morris, Mary Walker, A Gerald Shaper, Peter H Whincup
Journal: BMJ (2005)

<h3>Abstract</h3> <b>Objective</b> To examine trends over time in rates of different forms of diagnosed coronary heart disease among British men, during a period in which mortality due to coronary heart disease has been declining. <b>Design</b> Prospective cohort study covering the period 1978-80 to 1998-2000. <b>Participants</b> 7735 men, aged 40-59 at entry, randomly selected from one general practice in each of 24 British towns. <b>Main outcome measures</b> Trends in the rates of major coronary events, first diagnosed angina and first diagnosed coronary heart disease (any fatal or non-fatal documented event or diagnosis). Events were ascertained from NHS central registers and reviews of medical records from general practices. <b>Results</b> Over the 20 year period, 1561 major coronary events occurred; 1087 and 1816 men had new diagnoses of angina and coronary heart disease, respectively. The age adjusted annual relative changes were -3.6% (95% confidence interval -4.8% to -2.4%, P &lt; 0.001) for all major coronary events, 2.6% (1.1% to 4.0%, P &lt; 0.001) for first diagnosed angina and -0.8% (-1.8% to 0.3%, P = 0.18) for first diagnosed coronary heart disease. The fall in major coronary events occurred across all categories of event (fatal and non-fatal, first and recurrent). Similarly, first diagnosed angina increased for both uncomplicated angina and angina after myocardial infarction. The age adjusted annual relative change in case fatality at 28 days of first major coronary events was -1.4% (-3.1% to 0.4%, P = 0.12). <b>Conclusions</b> Among British middle aged men, a substantial decline in the rate of major coronary events over the past two decades seems to have been largely offset by an increase in the incidence of diagnosed angina. Overall there was little change in the incidence of first diagnosed coronary heart disease. A continuing need exists for resources and services for coronary heart disease in general, and for new angina in particular.
Tyrosine Kinase Inhibitors in Renal Cell Carcinoma
Authors: Anil Potti, Daniel J. George
Journal: Clinical Cancer Research (2004)

Abstract Current standard treatments for patients with metastatic (stage IV) renal cell carcinoma involve both surgical removal of tumors and treatment with biological agents such as interleukin 2 and/or IFN-α. Unfortunately, such approaches are inadequate for most patients with stage IV disease; the result is a median time to progression of 2 to 4 months and an overall survival of 6 to 17 months. Standard chemotherapy has been uniformly disappointing in this disorder. It is clear that new therapies are needed to approach these patients. Recently, a greater understanding of cancer genetics has led to the successful development of novel therapeutics directed against targets linked to specific types of cancer. During the past decade, researchers have identified the von Hippel-Lindau (VHL) gene as an important tumor suppressor in clear cell carcinoma of the kidney. Elucidation of the VHL gene product (pVHL) and its regulation of hypoxia-inducible factor signaling have created a potential genetic basis for growth factor-targeted strategies in this disease. This review will focus on the potential growth factor targets in clear cell carcinoma, their relation to VHL and hypoxia-inducible factor, and the clinical challenges that face their development.
Patient-Controlled Subcutaneous Hydromorphone Verus Continuous Subcutaneous Infusion for the Treatment Cancer Pain
Authors: E. bruera, C. Brenneis, M. Michaud, k. MacMillan, J. Hanson, R. N. MacDonald
Journal: JNCI Journal of the National Cancer Institute (1988)

Twenty-five patients with pain due to advanced cancer were randomized to receive patient-controlled so injections (PCLS) of Hydromorphone (HM) versus continuous so infusion (CSCI) of HM by means of a Pharmacla 5200 Pump. Each self-Infusion (CSCI) of HM by means of a Pharmacia 5200 pump. Each self-injection of HM during Pci was equlavent to 4 hours of CSCI After 3days a crossover occurred, and patients received the alternate treatment for 3 days. During both phases of the study, patients could request extra doses of HM from their nurses. In 22 patients able to be evaluated, pain intensity (visual analogue, o-100mm) at 9.00 a.m.and 4.00 p.m. was 31±23 and 28±18 and 27± on PCI versus 28 ± 18 and 27± respectively on PCI versus 23±18 and 27 ±17mm, respectively, on CSCI (p=not significant (NS), The total dose of Hm was 168±197 and 181±234 mg on PCI and CSCI, respectively 9p=Ns), No significant difference was found in nausea, drowiness, or number of hours of sleep. The total number of extra doses of Hm was 6±7 on CSCI versus 2±3 on PCI (p=.007). At the end of the study, patients chose PCI and CSCI in seven and 10 case, respectively (p=NS; 55 patients expressed no preference), We conclude the both methods were similar in re-gard to effectiveness and taxic effects in short-term hospital use. [J Natl cancer Inst 1988;801152–1154]
Diagnosis and management of organic ovarian cysts: indications and procedures for laparoscopy
Authors: C Chapron
Journal: Human Reproduction Update (1996)

In the field of gynaecological surgery, the past few years have been significant due to the development of operative laparoscopy. Originally recommended for the diagnosis of female infertility, over the past 15 years laparoscopy has acquired the standing of a surgical discipline in its own right. Laparoscopic surgical treatment of ovarian cysts, whether conservative or radical, has now been completely standardized. The aim of this work is to specify the indications, procedures and risks involved with this surgery as applied to organic ovarian cysts. Only benign ovarian cysts are suitable for treatment by laparoscopic surgery; ovarian cancer must always be handled by classic surgery using a mid-line laparotomy. Given that clinical and other pre-operative investigations can give only an indication, ovarian lesions require surgical investigation to diagnose the histological type. Laparoscopy appears to be as reliable as laparotomy when assessing whether an ovarian tumour is malignant. The risk of parietal contamination and peritoneal dissemination if a malignancy is not recognized means that, if there are no signs of extra-ovarian extension, adnexectomy is mandatory whenever there is the slightest doubt. This adnexectomy must obey two important rules: it must be accomplished without rupturing the cyst, and the cyst must be placed, intact, inside an endoscopic bag before being extracted. Provided that all stages of the procedure, from pre-operative work-up to the initial diagnostic phase of the laparoscopy, are carried out meticulously, laparoscopic surgery is reliable for both the diagnosis and the management of benign organic-ovarian cysts.
KIT mutation analysis in mast cell neoplasms: recommendations of the European Competence Network on Mastocytosis
Authors: M Arock, K Sotlar, C Akin, S Broesby-Olsen, G Hoermann, L Escribano, T K Kristensen, H C Kluin-Nelemans, O Hermine, P Dubreuil, W R Sperr, K Hartmann, J Gotlib, N C P Cross, T Haferlach, A Garcia-Montero, A Orfao, J Schwaab, M Triggiani, H-P Horny, D D Metcalfe, A Reiter, P Valent
Journal: Leukemia (2015)
In vivo biological response to recombinant interferon-gamma during a phase I dose-response trial in patients with metastatic melanoma.
Authors: J M Kirkwood, M S Ernstoff, T Trautman, G Hebert, Y Nishida, C A Davis, J Balzer, S Reich, J Schindler, S A Rudnick
Journal: Journal of Clinical Oncology (1990)

Interferon-gamma (IFN gamma), as produced by recombinant DNA technology, has shown a wide range of immunomodulatory activity in vitro and in vivo. Clinical studies have attempted to establish a dose-response relationship to define optimal dosage ranges for induction of effector cell function and host response in patients with cancer. We conducted a randomized trial to test the in vivo biologic activity of five daily dosages ranging from 3 to 3,000 micrograms/m2, administered by daily 2-hour bolus injection or by continuous infusion for 14 days. We demonstrate comparable immunobiologic effects of recombinant IFN gamma (rIFN gamma; Biogen, Inc, Cambridge, MA) administered by these two schedules at the various dosages tested, and have defined a relationship of dose to biologic response over this 3-log10 dose range. Oligo 2'5' adenylate synthetase (2'5'As) induction, natural-killer (NK) cell activity, and T-cell subset distribution (heightened T helper/suppressor ratio) showed the most consistent treatment-associated changes and the greatest immunobiologic effects at dosages of 300 to 1,000 micrograms/m2. Mononuclear cell DR and DQ antigen expression showed no consistent dose-related treatment effect. The relevance of the phenotypic, functional, and enzymologic effects observed in this trial to any clinical antitumor effects of IFN gamma in cancer therapy must now be established.
Multilevel Whole-Genome Analysis Reveals Candidate Biomarkers in Clear Cell Renal Cell Carcinoma
Authors: Andrew H. Girgis, Vladimir V. Iakovlev, Ben Beheshti, Jane Bayani, Jeremy A. Squire, Anna Bui, Marina Mankaruos, Youssef Youssef, Bishoy Khalil, Heba Khella, Maria Pasic, George M. Yousef
Journal: Cancer Research (2012)

Renal cell carcinoma (RCC) is the most common neoplasm of the kidney. We conducted an integrated analysis of copy number, gene expression (mRNA and miRNA), protein expression, and methylation changes in clear cell renal cell carcinoma (ccRCC). We used a stepwise approach to identify the most significant copy number aberrations (CNA) and identified regions of peak and broad copy number gain and loss, including peak gains (3q21, 5q32, 5q34-q35, 7p11, 7q21, 8q24, 11q13, and 12q14) and deletions (1p36, 2q34-q37, 3p25, 4q33-q35, 6q23-q27, and 9p21). These regions harbor novel tumor-related genes and miRNAs not previously reported in renal carcinoma. Integration of genome-wide expression data and gene set enrichment analysis revealed 75 gene sets significantly altered in tumors with CNAs compared with tumors without aberration. We also identified genes located in peak CNAs with concordant methylation changes (hypomethylated in copy number gains such as STC2 and CCND1 and hypermethylated in deletions such as CLCNKB, VHL, and CDKN2A/2B). For other genes, such as CA9, expression represents the net outcome of opposing forces (deletion and hypomethylation) that also significantly influences patient survival. We also validated the prognostic value of miRNA let-7i in RCCs. miR-138, located in chromosome 3p deletion, was also found to have suppressive effects on tumor proliferation and migration abilities. Our findings provide a significant advance in the delineation of the ccRCC genome by better defining the impact of CNAs in conjunction with methylation changes on the expression of cancer-related genes, miRNAs, and proteins and their influence on patient survival.
Gene expression analyses of grade II gliomas and identification of rPTPβ/ζ as a candidate oligodendroglioma marker
Authors: Daniel Hägerstrand, Anja Smits, Anna Eriksson, Sunna Sigurdardottir, Tommie Olofsson, Magdalena Hartman, Monica Nistér, Hannu Kalimo, Arne Östman
Journal: Neuro-Oncology (2007)

Grade II gliomas are morphologically and clinically heterogeneous tumors for which histopathological typing remains the major tool for clinical classification. To what extent the major histological subtypes - astrocytomas, oligodendrogliomas, and oligoastrocytomas - constitute true biological entities is largely unresolved. Furthermore, morphological classification is often ambiguous and would be facilitated by specific subtype markers. In this study, 23 grade II gliomas were expression-profiled and subjected to hierarchical clustering. All six oligodendrogliomas were grouped together in one of two major clusters; a significant correlation was thus observed between gene expression and histopathological subtype. Supervised analyses were performed to identify genes differentiating oligodendrogliomas from other grade II tumors. In a leave-one-out test using 10 features for classification, 20 out of 23 tumors were correctly classified. Among the most differentially expressed genes was rPTPbeta/zeta. The expression of the rPTP beta/zeta protein in oligodendrogliomas and astrocytomas was further validated by immunohistochemistry in an independent set of tumors. All 11 oligodendrogliomas of this set displayed strong staining. In contrast, neoplastic astrocytes were mostly negative for rPTPbeta/zeta staining. In summary, this study demonstrates a correlation between gene expression pattern and histological subtype in grade II gliomas. Furthermore, the results from the immunohistochemical analyses of rPTPbeta/zeta expression should prompt further evaluation of this protein as a novel oligodendroglioma marker.
Occurrence of Thrombocytopenia in Psychiatric Patients Taking Valproate
Authors: Thomas J. Trannel, Iqbal Ahmed, Deborah Goebert
Journal: American Journal of Psychiatry (2001)

Few studies, with conflicting results, have examined the occurrence of thrombocytopenia with valproate administration. This study assessed whether the platelet-lowering effects of valproate are increased among elderly psychiatric patients.The charts of 39 psychiatric inpatients taking valproate were reviewed. Information on hematologic function and on doses and serum levels of valproate at sequential intervals over a 12-month period was abstracted. Data for subjects age <60 years (nonelderly subjects) and those age >/=60 years (elderly subjects) were compared.More than half (53.8%) of the elderly patients but only 13.0% of the nonelderly patients had at least one episode of thrombocytopenia. This difference corresponded to a significantly greater lowering of platelet counts among elderly patients than among nonelderly patients.The high rate of thrombocytopenia in our study suggests the need for routine monitoring of platelet counts among patients taking valproate, particularly among elderly patients.
Late-breaking abstract: When is pleural fluid microbiology useful?
Authors: Kerry Woolnough, Imran Hussain
Journal: European Respiratory Journal (2011)

Introduction:  It is routine clinical practice, and recommended by the British Thoracic Society, that fluid is sent for culture following diagnostic thoracocentesis.  Few studies have evaluated the yield from sending all pleural fluid specimens for culture in day to day practice. Culture yield has, however, been studied in cohorts of patients where pleural infection is suspected - with a sensitivity of 54%.  We wished to ascertain what our yield is from pleural fluid culture when used as part of a routine workup for an undiagnosed pleural effusion and whether positive cultures were associated with raised inflammatory markers (WCC and CRP).   Methods:  We retrospectively analysed all pleural fluid samples sent for culture over the previous 12 months. All specimens were cultured for aerobic and anaerobic bacteria, fungi and mycobacterium. Pleural fluid protein, LDH content, serum CRP and WCC were also recorded.   Results:  485 samples were sent for culture over the 12 month period. There were 42 (8.7%) positive cultures, of which 4 were excluded as contaminants.  20 different organisms were isolated.  Streptococcus anginosus  and  Mycobacterium tuberculosis  were the most common. 47% of these positive samples were exudates, none were transudates. The remainder of these specimens (53%) had no pleural fluid biochemistry performed.  We found a positive yield of 7.8% out of the 485 pleural fluid samples studied. A clear association was found between yield and a raised CRP and WCC with a raised CRP found in 97% of positive cultures and an increased WCC in 75%.   Conclusions:  Routine culture of pleural fluid is neither cost-effective nor clinically useful and should only be requested when pleural infection is suspected, both clinically and biochemically.
Cerebral white matter integrity and executive function in adult survivors of childhood medulloblastoma
Authors: T. M. Brinkman, W. E. Reddick, J. Luxton, J. O. Glass, N. D. Sabin, D. K. Srivastava, L. L. Robison, M. M. Hudson, K. R. Krull
Journal: Neuro-Oncology (2012)

Survivors of pediatric medulloblastoma are at risk for neurocognitive dysfunction. Reduced white matter integrity has been correlated with lower intelligence in child survivors, yet associations between specific cognitive processes and white matter have not been examined in long-term adult survivors. Twenty adult survivors of medulloblastoma were randomly recruited from a larger institutional cohort of adult survivors of childhood cancer. Survivors underwent comprehensive neurocognitive evaluations and MRI. Data on brain volume and cortical thickness and diffusion tensor imaging were acquired, including measures of fractional anisotropy, apparent diffusion coefficient, and axial and radial diffusivity. Observed neurocognitive scores were compared with population norms and correlated to MRI indices. Survivors were, on average, 29 years of age and 18 years postdiagnosis. Mean full-scale intelligence quotient was nearly 1 SD below the normative mean (86.3 vs 100, P = .004). Seventy-five percent of survivors were impaired on at least one measure of executive function. Radial diffusivity in the frontal lobe of both hemispheres was correlated with shifting attention (left: rs = −0.67, P = .001; right: rs = −0.64, P = .002) and cognitive flexibility (left: rs = −0.56, P = .01; right: rs = −0.54, P = .01). Volume and cortical thickness were not correlated with neurocognitive function. Neurocognitive impairment was common and involved many domains. Reduced white matter integrity in multiple brain regions correlated with poorer performance on tasks of executive function. Future research integrating diffusion tensor imaging should be a priority to more rigorously evaluate long-term consequences of cancer treatment and to inform cognitive intervention trials in this high-risk population.
Prediction of major clinical response (ACR50) to infliximab in psoriatic arthritis refractory to methotrexate
Authors: J Gratacos, E Casado, J Real, J C Torre-Alonso
Journal: Annals of the Rheumatic Diseases (2006)

<b>Objectives:</b> To determine the predictive factors of clinical response to infliximab in patients with refractory psoriatic polyarthritis. <b>Methods:</b> A multicentre open study which included 69 patients with psoriatic polyarthritis refractory to methotrexate (15 mg/week at least for 8 weeks). Patients were treated with infliximab 5 mg/kg every 8 weeks in addition to their stable doses of methotrexate. A major clinical response was defined by the ACR50 at week 38. Logistic regression analysis was performed to analyse which of the following measures at the start of treatment were associated with an ACR50 response: demographic and clinical characteristics, duration of disease, tender and swollen joint counts, involvement of large joints (knee or hip, or both), erythrocyte sedimentation rate, C reactive protein (CRP), Health Assessment Questionnaire disability index, axial involvement, and the presence of erosions at baseline. <b>Results:</b> In an intention to treat analysis 30/69 (44%) patients achieved an ACR50 response. In the univariate analysis both the presence of large joint involvement and severe disability were associated with a poor clinical response. In a multivariate logistic regression analysis high CRP values were independently associated with a good therapeutic response (odds ratio (OR) = 18.7; 95% confidence interval (CI) 1.8 to 181.6; p = 0.011). In contrast, large joint involvement and severe disability were associated with a poor response, which reached significance for large joint involvement (OR = 29.3; 95% CI 3.2 to 266.3; p = 0.003). <b>Conclusion:</b> A lower disability and, in particular, the absence of large joint involvement and higher CRP serum levels at the start of infliximab treatment are factors that seem to influence the probability of achieving a good therapeutic response in patients with psoriatic arthritis.
The Prevalence of Adrenal Cortical Hyperplasia at Autopsy and Its Association with Hypertension
Authors: R P Russell, A T Masi
Journal: Annals of Internal Medicine (1970)

Review of the autopsy indexes of the Johns Hopkins Hospital, Baltimore, Md., between 1889 and 1966 provided 180 cases of adrenal cortical hyperplasia among 35,000 examinations (0.51%). The total prevalence of adrenal cortical hyperplasia at autopsy increased with age, and the age-adjusted prevalence among negro males exceeded (P < 0.05) that of the other race-sex groups. A highly significant excess (P < 0.001) of all forms of hypertension was found in the cases compared with carefully matched controls. Males tended to contribute more significantly (P < 0.01) than females (P < 0.025) to the excess. An excess of essential hypertension significant at the 5% probability level was found in the total case series. Further analyses by race of cases and controls showed that recognized secondary forms of hypertension correlated significantly (P < 0.025) with the cases in whites; whereas "essential" accelerated hypertension correlated significantly (P < 0.025) with the cases in negroes. Unequivocally documented Cushing's syndrome was found in seven of the cases and in none of the controls (P < 0.025). The excess of essential and essential-accelerated hypertension among the cases could not be accounted for by the presence of nonbasophilic pituitary adenomas, use of benzothiadiazine diuretics, concommitant renal disease, or carcinomatosis.