Showing papers by "St Bartholomew's Hospital published in 2004"
National Institutes of Health1, University of Würzburg2, University of British Columbia3, University of Nebraska Medical Center4, University of Rochester5, Oregon Health & Science University6, University of Arizona7, Fred Hutchinson Cancer Research Center8, University of Oslo9, St Bartholomew's Hospital10, University of Barcelona11
TL;DR: The length of survival among patients with follicular lymphoma correlates with the molecular features of nonmalignant immune cells present in the tumor at diagnosis.
Abstract: background Patients with follicular lymphoma may survive for periods of less than 1 year to more than 20 years after diagnosis. We used gene-expression profiles of tumor-biopsy specimens obtained at diagnosis to develop a molecular predictor of the length of survival. methods Gene-expression profiling was performed on 191 biopsy specimens obtained from patients with untreated follicular lymphoma. Supervised methods were used to discover expression patterns associated with the length of survival in a training set of 95 specimens. A molecular predictor of survival was constructed from these genes and validated in an independent test set of 96 specimens. results Individual genes that predicted the length of survival were grouped into gene-expression signatures on the basis of their expression in the training set, and two such signatures were used to construct a survival predictor. The two signatures allowed patients with specimens in the test set to be divided into four quartiles with widely disparate median lengths of survival (13.6, 11.1, 10.8, and 3.9 years), independently of clinical prognostic variables. Flow cytometry showed that these signatures reflected gene expression by nonmalignant tumor-infiltrating immune cells. conclusions The length of survival among patients with follicular lymphoma correlates with the molecular features of nonmalignant immune cells present in the tumor at diagnosis.
1,336 citations
TL;DR: Assessment of specific or general tumor markers offers high sensitivity in establishing the diagnosis and can also have prognostic significance, and therapy with radionuclides may be used for tumors exhibiting uptake to a diagnostic scan, either after surgery to eradicate microscopic residual disease or later if conventional treatment or biotherapy fails.
Abstract: Neuroendocrine tumors (NETs) constitute a heterogeneous group of neoplasms that originate from endocrine glands such as the pituitary, the parathyroids, and the (neuroendocrine) adrenal, as well as endocrine islets within glandular tissue (thyroid or pancreatic) and cells dispersed between exocrine cells, such as endocrine cells of the digestive (gastroenteropancreatic) and respiratory tracts. Conventionally, NETs may present with a wide variety of functional or nonfunctional endocrine syndromes and may be familial and have other associated tumors. Assessment of specific or general tumor markers offers high sensitivity in establishing the diagnosis and can also have prognostic significance. Imaging modalities include endoscopic ultrasonography, computed tomography and magnetic resonance imaging, and particularly, scintigraphy with somatostatin analogs and metaiodobenzylguanidine. Successful treatment of disseminated NETs requires a multimodal approach; radical tumor surgery may be curative but is rarely possible. Well-differentiated and slow-growing gastroenteropancreatic tumors should be treated with somatostatin analogs or alpha-interferon, with chemotherapy being reserved for poorly differentiated and progressive tumors. Therapy with radionuclides may be used for tumors exhibiting uptake to a diagnostic scan, either after surgery to eradicate microscopic residual disease or later if conventional treatment or biotherapy fails. Maintenance of the quality of life should be a priority, particularly because patients with disseminated disease may experience prolonged survival.
644 citations
TL;DR: Patient recognition of exacerbation symptoms and prompt treatment improves exacerbation recovery, reduces risks of hospitalization, and is associated with a better health-related quality of life.
Abstract: Treatment of chronic obstructive pulmonary disease (COPD) exacerbations improves outcomes; however, responses to treatment are variable, and patients with COPD often delay presentation or fail to seek therapy. The impact on exacerbation outcomes, hospitalization, and health status of delaying or failing to seek treatment is poorly understood. We studied between 1996 and 2002 a cohort of 128 patients with COPD, mean (SD) FEV(1) of 1.07 (0.43) L. Patients recorded respiratory symptoms daily and reported exacerbations to the outpatient-based study team or to their primary care physician; 1,099 exacerbations were recorded by the patients, of which 658 were reported to a physician. The time between exacerbation onset and treatment was a median (interquartile range) of 3.69 (2.0-5.57) days, and the exacerbation recovery time was 10.7 (7.0-14.0) days. Earlier treatment was associated with a faster recovery (regression coefficient 0.42 days/day delay) (confidence interval, 0.19-0.65; p < 0.001). Patients who reported a higher proportion of exacerbations for treatment had better health-related quality of life than those patients with more untreated exacerbations (rho = -0.22, p = 0.018). Failure to report exacerbations was associated with an increased risk of emergency hospitalization (rho = 0.21, p = 0.04). Patient recognition of exacerbation symptoms and prompt treatment improves exacerbation recovery, reduces risks of hospitalization, and is associated with a better health-related quality of life.
614 citations
TL;DR: Ghrelin is a brain-gut peptide with growth hormone-releasing and appetite-inducing activities as mentioned in this paper, which is mainly secreted from the stomach mucosa but it is also expressed widely in different tissues and therefore may have both endocrine and paracrine effects.
580 citations
TL;DR: Evidence of moderate lower lobe bronchiectasis on HRCT is common in COPD and is associated with more severe COPD exacerbations, lower airway bacterial colonization, and increased sputum inflammatory markers.
Abstract: Relationships between high-resolution computed tomography (HRCT) findings in chronic obstructive pulmonary disease (COPD) and bacterial colonization, airway inflammation, or exacerbation indices are unknown. Fifty-four patients with COPD (mean [SD]: age, 69 [7] years; FEV(1), 0.96 [0.33] L; FEV(1) [percent predicted], 38.1 [13.9]%; FEV(1)/forced vital capacity [percent predicted], 40.9 [11.8]%; arterial partial pressure of oxygen, 8.77 [1.11] kPa; history of smoking, 50.5 [33.5] smoking pack-years) underwent HRCT scans of the chest to quantify the presence and extent of bronchiectasis or emphysema. Exacerbation indices were determined from diary cards over 2 years. Quantitative sputum bacteriology and cytokine measurements were performed. Twenty-seven of 54 patients (50%) had bronchiectasis on HRCT, most frequently in the lower lobes (18 of 54, 33.3%). Patients with bronchiectasis had higher levels of airway inflammatory cytokines (p = 0.001). Lower lobe bronchiectasis was associated with lower airway bacterial colonization (p = 0.004), higher sputum interleukin-8 levels (p = 0.001), and longer symptom recovery time at exacerbation (p = 0.001). No relationship was seen between exacerbation frequency and HRCT changes. Evidence of moderate lower lobe bronchiectasis on HRCT is common in COPD and is associated with more severe COPD exacerbations, lower airway bacterial colonization, and increased sputum inflammatory markers.
427 citations
TL;DR: This review focuses on the chromosomal region and candidate genes associated with PWS, and the possible links with individual PWS phenotypes identified using mouse models; the metabolic and hormonal phenotypes in PWS; and current and potential advances in the management of PWS and its complications.
Abstract: Prader-Willi syndrome (PWS) is a complex human genetic disease that arises from lack of expression of paternally inherited imprinted genes on chromosome 15q11-q13 Identification of the imprinting control centre, novel imprinted genes and distinct phenotypes in PWS patients and mouse models has increased interest in this human obesity syndrome In this review I focus on: (i) the chromosomal region and candidate genes associated with PWS, and the possible links with individual PWS phenotypes identified using mouse models; (ii) the metabolic and hormonal phenotypes in PWS; (iii) postmortem studies of human PWS hypothalami; and (iv) current and potential advances in the management of PWS and its complications This could have benefits for a wide spectrum of endocrine, paediatric and neuropsychiatric diseases
395 citations
01 Jan 2004
TL;DR: Sputum inflammatory markers were found to be higher in those patients with symptoms of a common cold or where rhinovirus was detected at exacerbation, thus suggesting that viral infections lead to greater airway inflammation and thus more severe exacerbations.
Abstract: Exacerbations of chronic obstructive pulmonary disease (COPD) are a major cause of morbidity and mortality and hospital admission. Respiratory viral infections, especially rhinoviruses, are a major cause of COPD exacerbations, with upper respiratory tract infections being associated with over 50% of COPD exacerbations. The presence of an upper respiratory tract infection leads to a more severe exacerbation and a longer symptom recovery time at exacerbation. Respiratory viral infections occurring during COPD exacerbations are more likely to lead to hospitalization. Sputum inflammatory markers were found to be higher in those patients with symptoms of a common cold or where rhinovirus was detected at exacerbation, thus suggesting that viral infections lead to greater airway inflammation and thus more severe exacerbations. COPD exacerbations are associated also with systemic inflammatory effects with increases in markers such as plasma fibrinogen and interleukin-6. Respiratory viruses have also been detected when the patients are stable, and this suggests that chronic viral infection may occur. Strategies to prevent viral infection will have a significant effect on the morbidity of COPD and will improve quality of life.
249 citations
TL;DR: For hepatoblastoma, total hepatectomy with orthotopic liver transplantation (LTX) has been advocated as the best treatment option and the role of LTX in the overall management of HB is still, however, unclear.
Abstract: BACKGROUND: For hepatoblastoma (HB) that remains unresectable by partial hepatectomy after chemotherapy, total hepatectomy with orthotopic liver transplantation (LTX) has been advocated as the best treatment option. The role of LTX in the overall management of HB is still, however, unclear. PROCEDURE: The results of LTX from the first study of HB by the International Society of Pediatric Oncology, SIOPEL-1, were analyzed. In addition, the world experience of LTX for HB was extensively reviewed. Twelve patients in the SIOPEL-1 study underwent a LTX. Median (range) follow-up at Dec. 31, 2001 was 117 months (52-125) since LTX. RESULTS: Overall survival at 10 years post-LTX was 85% for the seven children who received a "primary LTX" and 40% for the 5 children who underwent a "rescue LTX" after previous partial hepatectomy. In the world experience (147 cases), the overall survival rate at 6 year post-LTX was 82% for 106 patients who received a "primary LTX" and 30% for 41 patients who underwent a "rescue LTX." Multivariate analysis of patients undergoing primary LTX showed that only macroscopic venous invasion had a significant impact (P-value: 0.045 with a hazard ratio of 2.96) on overall survival. CONCLUSIONS: Orthotopic LTX has added a new dimension to the treatment of HB unresectable by partial hepatectomy. Because of the rarity of the disease and to optimize results, children with extensive HB should be treated in centers with surgical expertise in pediatric major liver resection and LTX, in close collaboration with pediatric oncologists, radiologists, and histopathologists.
248 citations
TL;DR: Diary data from 155 women were analyzed and confirmed that migraine at menstruation is different from nonmenstrual attacks, even within individuals.
Abstract: Diary data from 155 women were analyzed using within-woman analysis. Compared with all other times of the cycle, migraine was 1.7 times more likely to occur during the 2 days before menstruation and 2.1 times more likely to be severe and 2.5 times more likely to occur during the first 3 days of menstruation and 3.4 times more likely to be severe. This confirms that migraine at menstruation is different from nonmenstrual attacks, even within individuals.
232 citations
TL;DR: It is suggested that autoantibodies to IFN-gamma can induce susceptibility to disseminated mycobacterial infection, which may be refractory to chemotherapy.
Abstract: We evaluated a patient with disseminated Mycobacterium tuberculosis and Mycobacterium chelonae infection, of which he died. He also developed autoimmune (type I) diabetes and primary hypothyroidism. His serum contained a high titer of immunoglobulin G autoantibody to interferon-gamma (IFN-gamma) capable of blocking in vitro responses to this cytokine by peripheral blood mononuclear cells from normal donors. These results suggest that autoantibodies to IFN-gamma can induce susceptibility to disseminated mycobacterial infection, which may be refractory to chemotherapy.
224 citations
TL;DR: It is suggested that aspirin triggers the synthesis of 15-epi-lipoxin A4, which increases NO synthesis through eNOS and iNOS, which exerts antiinflammatory effects in the microcirculation by inhibiting leukocyte–endothelium interactions.
Abstract: The established model for the mechanism of action of aspirin is the inhibition of prostaglandin synthesis. However, this has never fully explained aspirin's repertoire of antiinflammatory properties. We found in acute pleuritis that aspirin, but not salicylate, indomethacin, or piroxicam, increased plasma nitric oxide (NO), which correlated with a reduction in inflammation. Inhibiting aspirin-elicited NO pharmacologically in this model nullified the antiinflammatory effects of aspirin. Moreover, aspirin was not antiinflammatory in either constitutive (eNOS) or inducible NO synthase (iNOS) knockout mice with IL-1β–induced peritonitis. It transpires that aspirin generates NO through its unique ability to trigger the synthesis of 15-epi-lipoxin A4. Aspirin and 15-epi-lipoxin A4 were shown to inhibit leukocyte trafficking in an NO-dependent manner using intravital microscopy on IL-1β–stimulated mouse mesentery. Not only did aspirin inhibit leukocyte–endothelial interaction in a manner similar to NO in wild-type mice but both aspirin and 15-epi-lipoxin A4 had markedly reduced effects on leukocyte–endothelial cell adherence in eNOS- and iNOS-deficient mice compared with wild type. Collectively, these data suggest that aspirin triggers the synthesis of 15-epi-lipoxin A4, which increases NO synthesis through eNOS and iNOS. This aspirin-elicited NO exerts antiinflammatory effects in the microcirculation by inhibiting leukocyte–endothelium interactions.
TL;DR: The evidence for an association between oestrogen "withdrawal" and attacks of migraine without aura is presented, as well as evidence for a association between high oestrogens states and attacksof migraine with aura.
Abstract: Summary During women's reproductive years, migraine is three times more common than in men of a similar age. Although this female preponderance is commonly assumed to be associated with the additional trigger of fluctuating sex hormones of the menstrual cycle, few studies have been done to confirm or refute this. This review is confined to the relation between oestrogen and attacks of migraine. The evidence for an association between oestrogen "withdrawal" and attacks of migraine without aura is presented, as well as evidence for an association between high oestrogen states and attacks of migraine with aura. Only clinical data are presented here.
TL;DR: Neuroendocrine tumours constitute a heterogeneous group of tumours that are able to express cell membrane neuroamine uptake mechanisms and/or specific receptors, which can be of great value in the localization and treatment of these tumours.
Abstract: Neuroendocrine tumours (NETs) constitute a heterogeneous group of tumours that are able to express cell membrane neuroamine uptake mechanisms and/or specific receptors, such as somatostatin receptors, which can be of great value in the localization and treatment of these tumours. Scintigraphy with 111 In-pentetreotide has become one of the most important imaging investigations in the initial identification and staging of gastro-enteropancreatic (GEP) tumours, whereas helical computed tomography (CT), magnetic resonance imaging (MRI), endoscopic and/or peri-operative ultrasonography are used for the precise localization of GEPs and in monitoring their response to treatment. Scintigraphy with 123 I-MIBG (meta-iodobenzylguanidine) is sensitive in the identification of chromaffin cell tumours, although scintigraphy with 111 In-pentetreotide may also have a role in the localization of malignant chromaffin cell tumours and medullary thyroid carcinoma; for further localization and monitoring of the response to treatment both CT and MRI are used with high diagnostic accuracy. More recently, positron emission tomography (PET) scanning is being increasingly used for the localization of NETs, particularly when other imaging modalities have failed, although its precise role and utility remain to be defined. Surgery is still the usual initial therapeutic, and only curative, modality of choice; however, the majority of NETs will require further treatment with somatostatin analogues and/or interferon; chemotherapy may be used for progressive and highly aggressive NETs, but its role has not been clearly defined. For those NETs that demonstrate uptake to a diagnostic scan with 123 I-MIBG or 111 In-octreotide, therapy with radionuclides such as 131 I-MIBG or 111 In/ 90 Y-octreotide or other isotopes, presents a further evolving therapeutic modality.
TL;DR: These proportions had increased to 26% and 22%, respectively, with 55% of women and 66% of men being overweight (BMI > 25 kg/m 2 ; Health Survey for England, 2001), reflecting a worldwide trend which is most marked in, but not restricted to, the developed world.
Abstract: these proportions had increased to 26% and 22%, respectively, with 55% of women and 66% of men being overweight (BMI > 25 kg/m 2 ; Health Survey for England, 2001), reflecting a worldwide trend which is most marked in, but not restricted to, the developed world. Most of us in affluent countries live in a privileged land of plenty where high calorie foods are easily available and in which we have a limited need for exercise. The rising prevalence of obesity in children is of particular concern (Chinn & Rona, 2001).
TL;DR: The first demonstration of a functional relationship between brain ghrelin and endocannabinoid systems is demonstrated and, although it needs to be further investigated, the effect of gh Relin on food intake when injected into the PVN seems to be mediated by stimulation of cannabinoid release.
Abstract: The paraventricular nucleus (PVN) of the hypothalamus plays a key role in the control of appetite and energy balance Both ghrelin and cannabinoid receptor agonists increase food intake when administered into this nucleus: this study investigated possible interactions between the two systems in relation to eating The orexigenic effect of ghrelin (100 pmol) when infused in to the PVN was reversed by a small, systemic dose of the CB1 cannabinoid receptor antagonist SR141716 (1 mg kg−1) This is the first demonstration of a functional relationship between brain ghrelin and endocannabinoid systems, and, although it needs to be further investigated, the effect of ghrelin on food intake when injected into the PVN seems to be mediated by stimulation of cannabinoid release
TL;DR: By transperitoneal laparoscopic lymphadenectomy, an adequate number of lymph nodes can be removed in an adequate time and independent from body mass index, and the complication rate is low and can be minimized by standardization of the procedure.
TL;DR: A new, stable, aqueous extract of allicin (extracted from garlic) is tested on 30 clinical isolates of MRSA that show a range of susceptibilities to mupirocin, and it is shown that a concentration of 500 µg/mL in an aqueously cream base was required to produce an activity equivalent to 256 µG/mL allicIn liquid.
Abstract: The increasing prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in hospitals and the community has led to a demand for new agents that could be used to decrease the spread of these bacteria. Topical agents such as mupirocin have been used to reduce nasal carriage and spread and to treat skin infections; however, resistance to mupirocin in MRSAs is increasing. Allicin is the main antibacterial agent isolated from garlic, but natural extracts can be unstable. In this study, a new, stable, aqueous extract of allicin (extracted from garlic) is tested on 30 clinical isolates of MRSA that show a range of susceptibilities to mupirocin. Strains were tested using agar diffusion tests, minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). Diffusion tests showed that allicin liquids produced zone diameters >33 mm when the proposed therapeutic concentration of 500 µg/mL (0.0005% w/v) was used. The selection of this concentration was based on evidence from the MIC, MBC and agar diffusion tests in this study. Of the strains tested, 88% had MICs for allicin liquids of 16 µg/mL, and all strains were inhibited at 32 µg/mL. Furthermore, 88% of clinical isolates had MBCs of 128 µg/mL, and all were killed at 256 µg/mL. Of these strains, 82% showed intermediate or full resistance to mupirocin; however, this study showed that a concentration of 500 µg/mL in an aqueous cream base was required to produce an activity equivalent to 256 µg/mL allicin liquid.
University of Porto1, University of Florence2, University of Münster3, University of Geneva4, National University of Ireland, Galway5, University College Dublin6, Katholieke Universiteit Leuven7, Nottingham City Hospital8, University of Bologna9, University of Helsinki10, Radboud University Nijmegen11, Rambam Health Care Campus12, Semmelweis University13, University of Navarra14, Netherlands Cancer Institute15, University of Copenhagen16, Medical University of Graz17, Research Institute of Molecular Pathology18, University of Turin19, Curie Institute20, St Bartholomew's Hospital21
TL;DR: Evaluated aspects of the current practice of sentinel lymph node (SLN) pathology in breast cancer via a questionnaire based survey to recognise major issues that the European guidelines for mammography screening should address in the next revision.
Abstract: Aims: To evaluate aspects of the current practice of sentinel lymph node (SLN) pathology in breast cancer via a questionnaire based survey, to recognise major issues that the European guidelines for mammography screening should address in the next revision.
Methods: A questionnaire was circulated by mail or electronically by the authors in their respective countries. Replies from pathology units dealing with SLN specimens were evaluated further.
Results: Of the 382 respondents, 240 European pathology units were dealing with SLN specimens. Sixty per cent of these units carried out intraoperative assessment, most commonly consisting of frozen sections. Most units slice larger SLNs into pieces and only 12% assess these slices on a single haematoxylin and eosin (HE) stained slide. Seventy one per cent of the units routinely use immunohistochemistry in all cases negative by HE. The terms micrometastasis, submicrometastasis, and isolated tumour cells (ITCs) are used in 93%, 22%, and 71% of units, respectively, but have a rather heterogeneous interpretation. Molecular SLN staging was reported by only 10 units (4%). Most institutions have their own guidelines for SLN processing, but some countries also have well recognised national guidelines.
Conclusions: Pathological examination of SLNs throughout Europe varies considerably and is not standardised. The European guidelines should focus on standardising examination. They should recommend techniques that identify metastases > 2 mm as a minimum standard. Uniform reporting of additional findings may also be important, because micrometastases and ITCs may in the future be shown to have clinical relevance.
TL;DR: Evidence is accumulating to indicate an improved therapeutic trend over the years, with the notable exception of older (>55 years) patients with adverse-risk chromosomal aberrations and/or leukemia secondary to myelodysplasia or prior cancer-related chemotherapy and/ or radiotherapy.
Abstract: The curability of acute myeloid leukaemia (AML) in a fraction of adult patients was demonstrated a long time ago. Currently, the probability of cure is consistently above fifty per cent in patients with de novo disease expressing favourable-risk associated cytogenetic features. Even better, the cure rate exceeds 75% in the acute promyelocytic subtype since the introduction of retinoic acid-containing regimens. In the meantime, continuing progress in supportive care systems and stem cell transplant procedures is making myeloablative therapies, when needed, somewhat less toxic-and thereby more effective-than in the recent past. Therefore, evidence is accumulating to indicate an improved therapeutic trend over the years, with the notable exception of older (>55 years) patients with adverse-risk chromosomal aberrations and/or leukemia secondary to myelodysplasia or prior cancer-related chemotherapy and/or radiotherapy. This review conveys the many facets of this progress, focusing on diagnostic subsets, risk classes, newer biological issues and conventional as well as innovative therapeutic interventions with or without autologous/allogeneic stem cell transplantation.
TL;DR: This consensus statement from the International Cancer Imaging Society (ICIS) reviews the RECIST criteria and addresses several challenges regarding tumour measurement and recommends a multimodality approach to monitoring response.
Abstract: New guidelines to evaluate the response to treatment in solid tumors using imaging techniques have major limitations and important implications for radiological workload. This consensus statement from the International Cancer Imaging Society (ICIS) reviews the RECIST criteria and addresses several challenges regarding tumour measurement. Recommendations are made regarding tumour measurement and other issues are raised. The growing need to introduce a multimodality approach to monitoring response is recognized. ICIS welcomes a dialogue with the authors of RECIST to address issues raised in this review.
TL;DR: Ghrelin has been shown to have anti-proliferative effects on breast, lung and thyroid cell lines as discussed by the authors, and the effect of ghrelin on the rat pituitary cell line GH3 was studied using immunoblotting and inhibitors of the extracellular signal-regulated kinase 1 and 2 (ERK 1/2), protein kinase C (PKC) and tyrosine phosphatase pathways.
Abstract: OBJECTIVES Ghrelin is a brain-gut peptide with GH-releasing and appetite-inducing activities and a widespread tissue distribution. Ghrelin is the endogenous ligand of the GH secretagogue receptor type 1a (GHS-R1a), and both ghrelin and the GHS-R1a are expressed in the pituitary. There are conflicting data regarding the effects of ghrelin on cell proliferation. A positive effect on proliferation and activation of the mitogen-activated protein kinase (MAPK) pathway has been found in hepatoma, adipose, cardiomyocyte and prostate cell lines. However, ghrelin has also been shown to have anti-proliferative effects on breast, lung and thyroid cell lines. We therefore examined the effect of ghrelin on the rat pituitary cell line GH3. METHODS RT-PCR was used for the detection of GHS-R1a and pre-proghrelin mRNA expression in GH3 cells. The effect of ghrelin on cell proliferation was studied using [(3)H]thymidine incorporation; cell counting and the activation of the MAPK pathway were studied using immunoblotting and inhibitors of the extracellular signal-regulated kinase 1 and 2 (ERK 1/2), protein kinase C (PKC) and tyrosine phosphatase pathways. RESULTS GHS-R1a and ghrelin mRNA expression were detected in GH3 cells. Ghrelin, at 10(-10) to 10(-6) M concentrations, significantly increased [(3)H]thymidine incorporation (at 10(-9) M, 183+/-13% (means+/-s.e.m.) compared with untreated controls), while 12-phorbol 13-myristate acetate (PMA) at 10(-7) M (used as a positive control) caused a 212+/-14% increase. A reproducible stimulatory effect of desoctanoyl ghrelin was also observed on [(3)H]thymidine incorporation (135+/-5%; P<0.01 at 10(-9) M compared with control), as well as on the cell count (control 6.8 x 10(4)+/-8.7 x 10(3) cells/ml vs desoctanoyl ghrelin (10(-9) M) 1.04 x 10(5)+/-7.5 x 10(3) cells/ml; P<0.01). Ghrelin caused a significant increase in phosphorylated ERK 1/2 in immunoblotting, while desoctanoyl ghrelin showed a smaller but also significant stimulatory effect. The positive effect of ghrelin and desoctanoyl ghrelin on [(3)H]thymidine incorporation was abolished by the MAPK kinase inhibitor U0126, the PKC inhibitor GF109203X and the tyrosine kinase inhibitor tyrphostin 23, suggesting that the ghrelin-induced cell proliferation of GH3 cells is mediated both via a PKC-MAPK-dependent pathway and via a tyrosine kinase-dependent pathway. This could also be clearly demonstrated by Western blot analysis, where a transient increase in ERK 1/2 phosphorylation by ghrelin was attenuated by all three inhibitors. CONCLUSION We have shown a novel role for ghrelin in stimulating the proliferation of a somatotroph pituitary tumour cell line, suggesting that ERK activation is involved in mediating the effects of ghrelin on cell proliferation. Desoctanoyl ghrelin showed a similar effect. As ghrelin has been shown to be expressed in both normal and adenomatous pituitary tissue, locally produced ghrelin may play a role in pituitary tumorigenesis via an autocrine/paracrine pathway.
TL;DR: 28-day PR lanreotide was effective in reducing the symptoms and biochemical markers associated with carcinoid syndrome and was well tolerated.
Abstract: This 6-month, open, non-controlled, multicenter, dose-titration study evaluated the efficacy and safety of 28-day prolonged-release (PR) lanreotide in the treatment of carcinoid syndrome. Eligible patients had a carcinoid tumor with > or =3 stools/day and/or > or =1 moderate/severe flushing episodes/day. Six treatments of 28-day PR lanreotide were administered by deep subcutaneous injection. The dose for the first two injections was 90 mg. Subsequent doses could be titrated (60, 90, 120 mg) according to symptom response. Seventy-one patients were treated. Flushing decreased from a mean of 3.0 at baseline to 2.3 on day 1, and 2.0 on day 2, with a daily mean of 2.1 for the first week post-treatment (p or =50% reduction from baseline. Median urinary 5-hydroxyindoleacetic acid and chromogranin A levels decreased by 24 and 38%, respectively. Treatment was well tolerated. 28-day PR lanreotide was effective in reducing the symptoms and biochemical markers associated with carcinoid syndrome.
TL;DR: The illness biographies and daily lives of HIV-positive African women receiving treatment in London are explored, revealing marked similarities and differences which need to be properly understood by health and social care professionals to offer the most appropriate care for this growing population of patients.
Abstract: There are no studies that have examined the particular needs and experiences of African women living with HIV in the UK at a time when they represent an increasingly large proportion of the UK HIV epidemic. This study explores the illness biographies and daily lives of HIV-positive African women receiving treatment in London. Sixty-two women from 11 African countries attending HIV specialist clinics in five London hospitals participated in self-completion questionnaires and in depth semi-structured interviews. Using a narrative approach, women were asked to talk about their HIV status in the broader context of their life history. Important differences exist within this group based mainly on nationality, income, education level and legal status in the UK. However, marked similarities also emerged which were related in part to their situation as migrants and were compounded by their illness. Stigma, both actual and perceived, had a profound impact on women's lives, making control of information about their situation a matter of acute concern. This had an effect on how women accessed health services and voluntary sector agencies. The resilience of women in dealing with difficulties in their lives was strengthened by religious belief. Such similarities and differences need to be properly understood by health and social care professionals if they are to offer the most appropriate care for this growing population of patients.
TL;DR: Coronary artery calcification measured by EBCT is not an accurate marker of the degree of vessel stenosis in coronary artery disease in uremic patients and should not be used as a single screening test for atherosclerotic coronary disease.
TL;DR: It is concluded that either hyperghrelinemia may not contribute to hyperphagia in PWS adults, or perhaps concomitant reductions in anorexigenic gastrointestinal hormones by somatostatin counteracted any anoreXigenic effect of lowering orexigenic ghrelin.
Abstract: Prader-Willi syndrome (PWS) is characterized by life-threatening childhood-onset hyperphagia, obesity and, uniquely, high plasma levels of ghrelin, the orexigenic gastric hormone. Somatostatin suppresses ghrelin secretion in normal subjects. We therefore examined the effect of somatostatin on plasma ghrelin and appetite in four male PWS adults fasted overnight in a double-blind, placebo-controlled, randomized cross-over study. Subjects received an intravenous infusion of somatostatin (250 microg/hr) or saline for 300 min, and had blood samples taken every 30 min for measurement of plasma ghrelin and PYY3-36 (anorexigenic intestinal hormone) by radio-immunoassay, and glucose. Appetite was measured by counting sandwiches eaten over a 60 min free food access period from +120 min. Despite somatostatin lowering fasting plasma ghrelin by 60 +/- 2% (P = 0.04) to levels seen in non-PWS men, there was no associated reduction in food intake (105 +/- 9% of food intake during saline infusion, P = 0.6). Somatostatin also lowered plasma PYY levels by 45 +/- 16% (P = 0.04), and produced post-prandial hyperglycemia (P = 0.04). We conclude that either hyperghrelinemia may not contribute to hyperphagia in PWS adults, or perhaps concomitant reductions in anorexigenic gastrointestinal hormones by somatostatin counteracted any anorexigenic effect of lowering orexigenic ghrelin. Somatostatin analogues may therefore not be an effective therapy for obesity in PWS. Larger chronic studies with long-acting somatostatin analogues will be needed to determine their benefits and risks in treating PWS obesity.
TL;DR: Tumor type, grade, vascular invasion, pattern of invasion, and depth are all extremely important prognostic indicators when used individually or as a part of a scoring system.
Abstract: Apart from clinical stage and lymph node status, acknowledged to be among the most powerful predictors of outcome in cervical cancer, the determination of prognosis and thereby the need for adjuvant therapy in surgically treated patients currently relies on a variety of histopathologic factors. The role of many of these is controversial. This may be because histopathology is genuinely lacking in sensitivity for predicting tumor behavior in vivo. There is, however, wide variation in histopathologic definitions and criteria. This is probably the major reason for both the lack of reproducibility in the reporting of certain factors and in their diminished value in predicting behavior. Tumor type, grade, vascular invasion, pattern of invasion, and depth are all extremely important prognostic indicators when used individually or as a part of a scoring system.
TL;DR: The hyperghrelinemia in PWS adults is therefore not solely explained by their reduced visceral adiposity and relative hypoinsulinemia, and its cause and consequences await further elucidation.
Abstract: Plasma ghrelin is elevated in Prader-Willi syndrome (PWS). This might contribute to obesity or GH deficiency in such patients. Visceral adiposity and insulin resistance are reduced in PWS, which might lead to hyperghrelinemia. We measured fasting plasma ghrelin in control female (n = 39), PWS female (n = 12), and PWS male (n = 6) adults. In controls and PWS, ghrelin was negatively correlated with visceral adiposity, fasting insulin, and homeostasis model insulin resistance index. There was no significant correlation with serum IGF-I in PWS. In stepwise linear regression, visceral adiposity (P < 0.02) had a stronger inverse correlation with ghrelin than sc fat depots in controls and PWS, possibly through hyperinsulinemia, as the correlations with insulin resistance were even stronger (P < 0.01). PWS females had significantly (P < 0.001) elevated ghrelin (mean ± sd, 661 ± 360 pg/ml), compared with both nonobese (363 ± 163) and obese (191 ± 66) controls. Ghrelin was increased 3.4- to 3.6-fold in PWS females ...
TL;DR: Nitrate preserves, rather than threatens, health, because it is reduced by microbes on the tongue to nitrite, which generates nitric oxide when acidified in an antibacterial defence mechanism vital to the authors' well‐being.
Abstract: . Nitrate is widely and mistakenly perceived to threaten human health by causing methaemoglobinaemia in infants and stomach cancer in adults, but it does cause environmental problems. Methaemoglobinaemia is a side-effect of gastroenteritis and is not caused by nitrate but by nitric oxide, which is produced in a defensive reaction stimulated by gastroenteritis. The latter may be caused by a bacterium or a virus. The association of methaemoglobinaemia with nitrate may have arisen because early cases of the condition were often associated with wells polluted with bacteria, and the same pollution increased the nitrate concentration. Four epidemiological studies sought a link between stomach cancer and nitrate but did not find one. The incidence of this cancer has also declined during the last 30 years, while nitrate concentrations in water have increased. Nitrate preserves, rather than threatens, health. It is reduced by microbes on the tongue to nitrite, which generates nitric oxide when acidified in an antibacterial defence mechanism vital to our well-being. This mechanism acts with great effectiveness in the stomach against Salmonella, Escherichia coli and other organisms that cause gastroenteritis. It also acts in our mouths against dental caries and even on our skin against fungal pathogens such as Tinea pedis (athlete's foot). This mechanism is the basis of the centuries-old practice of adding nitrate or nitrite to stored meat to protect against botulism, caused by the most lethal toxin known to mankind.
TL;DR: The basic principles of IMRT in comparison to other planning techniques are explained and the current clinical data are presented and future lines of research are discussed.
Abstract: Intensity-modulated radiotherapy (IMRT) is one of the most important recent developments in oncology. It enables precise conformation of the radiation dose to the target volume. It has the potential to significantly reduce long-term morbidity and improve local control. This article explains the basic principles of IMRT in comparison to other planning techniques. The current clinical data are presented and future lines of research are discussed.
TL;DR: High overall and CR rates were observed after a single dose of tositumomab and iodine I 131 tosituomab in this patient group, and Therapy was well tolerated; hematologic toxicity was the principal adverse event.
Abstract: Purpose An open-label phase II study was conducted at two centers to establish the efficacy and safety of tositumomab and iodine I 131 tositumomab at first or second recurrence of indolent or transformed indolent B-cell lymphoma. Patients and Methods A single dosimetric dose was followed at 7 to 14 days by the patient-specific administered radioactivity required to deliver a total body dose of 0.75 Gy (reduced to 0.65 Gy for patients with platelets counts of 100 to 149 × 109/L). Forty of 41 patients received both infusions. Results Thirty-one of 41 patients (76%) responded, with 20 patients (49%) achieving either a complete (CR) or unconfirmed complete remission [CR(u)] and 11 patients (27%) achieving a partial remission. Response rates were similar in both indolent (76%) and transformed disease (71%). The overall median duration of remission was 1.3 years. The median duration of remission has not yet been reached for those patients who achieved a CR or CR(u). Eleven patients continue in CR or CR(u) betwe...