bluuebunny/crossref_metadata_2025_split huggingface dataset:
How patients manage gastrointestinal symptoms after pelvic radiotherapy
Authors: Gami B. , Harrington K. , Blake P. , Dearnaley D. , Tait D. , Davies J. , Norman A. R. , Andreyev H. J. N. 
Published: November 2003

SummaryBackground : Approximately 13 000 patients undergo pelvic radiotherapy annually in the UK. It is not clear how frequently patients develop a permanent change in bowel habit after pelvic radiotherapy that affects their quality of life because the measures of gastrointestinal toxicity used in trials in the past have generally been inadequate. It has been suggested that patients who are symptomatic are only rarely referred to a gastroenterologist and it is not known how patients manage their symptoms.Methods : Patients who had completed radiotherapy for pelvic cancer at least 1 year previously were invited to answer 30 structured questions in a face‐to‐face interview to determine the frequency of gastrointestinal symptoms and what orthodox, dietary and complementary therapies they used to deal with them. They were also asked to score the effectiveness of the measures they had taken.Results : One hundred and seven patients were recruited [35 males; median age, 65 years (range, 35–80 years); 72 females; median age, 67.5 years (range, 31–87 years)]. Eight had been treated for a gastrointestinal primary tumour, 34 for a urological tumour and 65 for gynaecological tumours. Eighty‐seven patients (81%) described new‐onset gastrointestinal problems starting after radiotherapy. These symptoms affected the quality of life in 56 patients (52%). Significant effects on the quality of life were caused by diarrhoea or constipation (n = 53), faecal leakage (n = 19), abdominal, rectal or perineal pain (n = 14) and rectal bleeding (n = 6). Fifty‐nine patients had seen a doctor for their symptoms (86% found this helpful), 12 had seen a dietician or nurse (50% found this helpful) and 14 had seen alternative practitioners (88% found this helpful). Dietary manipulation generally did not improve symptoms, except in a small group of patients (14/15) who avoided raw vegetables to great benefit.Conclusions : At least 1 year after pelvic radiotherapy, gastrointestinal symptoms which have an adverse effect on the quality of life may be more common than generally reported. Patients found that advice from doctors and alternative practitioners was equally valuable. Dietary manipulation was generally unhelpful for gastrointestinal symptoms after pelvic radiotherapy, although the role of eliminating raw vegetables may benefit from further evaluation.
Oral ulceration – aetiopathogenesis, clinical diagnosis and management in the gastrointestinal clinic
Authors: Field E. A. , Allan R. B. 
Published: November 2003

SummaryOral ulceration is a common complaint of patients attending out‐patient clinics. The aim of this review is to provide the gastroenterologist with a differential diagnosis of oral ulceration, and a practical guide for the management of recurrent aphthous stomatitis, including topical and systemic therapy. The association of recurrent aphthous stomatitis with Behçet's disease and other systemic disorders, including coeliac disease, is discussed. Recent evidence concerning the immunopathogenesis of Behçet's disease is reviewed, including renewed interest in the role of Streptococcus sanguis and possible infectious triggering of an inappropriate immunoinflammatory response, resulting in tissue damage. The efficacy and limitations of conventional treatment for this mutisystem disorder are outlined together with the potential role of novel biological agents, such as anti‐tumour necrosis factor‐α therapy. Oral ulceration, as a manifestation of inflammatory bowel disease and a complication of drug therapy, is described. Guidance is given concerning indications for referral of patients with oral ulceration to an oral physician/surgeon for further investigations, including biopsy if appropriate.
The impact of current tobacco use on the outcome of paracetamol poisoning
Authors: Schmidt L. E. , Dalhoff K. 
Published: November 2003

SummaryBackground : Tobacco smoke contains a number of substances that are capable of inducing cytochrome P450. Consequently, current tobacco use may enhance the hepatotoxicity from a paracetamol overdose by increasing the oxidative metabolism of paracetamol.Aim : To evaluate, by multivariate analysis, the effect of current tobacco use on the morbidity and mortality from paracetamol‐induced hepatotoxicity.Methods : A retrospective study was carried out on the basis of the hospital charts of 602 patients admitted with single‐dose paracetamol poisoning for whom information on current tobacco use was available.Results : In patients admitted with paracetamol poisoning, the rate of current daily tobacco use of 70% (424 of 602 patients) was considerably higher than the rate of 31% in the background population (chi‐squared test: P < 0.0001). Current tobacco use was an independent risk factor for the development of hepatic encephalopathy (odds ratio, 2.68; 95% confidence interval, 1.28–5.62) and mortality (odds ratio, 3.64; 95% confidence interval, 1.23–10.75). Current tobacco use was independently associated with high peak values of alanine transaminase and the international normalized ratio.Conclusions : Current tobacco use was very frequent in patients admitted with paracetamol poisoning. It was an independent risk factor of severe hepatotoxicity, acute liver failure and death following paracetamol overdose.
Role of early ultrasound in detecting inflammatory intestinal disorders and identifying their anatomical location within the bowel
Authors: Parente F. , Greco S. , Molteni M. , Cucino C. , Maconi G. , Sampietro G. M. , Danelli P. G. , Cristaldi M. , Bianco R. , Gallus S. , Bianchi Porro G. 
Published: November 2003

SummaryBackground : Although bowel ultrasound is a widely accepted diagnostic tool in bowel diseases, its value as the primary imaging procedure in patients with symptoms/signs suggestive of inflammatory bowel disorders is still unclear.Aim : To investigate the accuracy of bowel ultrasound compared with barium X‐ray studies, computed tomography, endoscopy and bowel surgery in the initial assessment of inflammatory bowel disorders.Methods : Four hundred and eighty‐seven patients hospitalized consecutively for symptoms or signs suggestive of a bowel disorder between December 1999 and March 2002 were initially enrolled in the study. All patients underwent bowel ultrasound as the first imaging procedure within 36 h of admission; radiographic evaluations, endoscopy and/or surgery were then performed as appropriate and the results of these investigations were used as the gold standard.Results : Three hundred and thirty‐six patients had pathological findings of the bowel detectable at ultrasound as the final diagnosis. The main organic disorders found were Crohn's disease (56%), ulcerative/indeterminate colitis (30%), bowel tumours (5%), appendicitis/diverticulitis (2%) and other inflammatory conditions (8%). The overall sensitivity and specificity of bowel ultrasound were 85% and 95%, respectively, whereas the positive and negative predictive values were 98% and 75%, respectively. Comparisons of ultrasound with X‐ray or endoscopic results by disease localization showed that the diagnostic performance of ultrasound was higher for inflammatory conditions of the ileum and sigmoid/descending colon (sensitivity of 92% and 87%, respectively), whereas abnormalities localized in the rectum, duodenum and proximal jejunum were often missed by ultrasound.Conclusions : In expert hands, bowel ultrasound is highly predictive of inflammatory disease localized in the ileum or colon, and may well be used as the primary imaging method when Crohn's disease or ulcerative colitis is suspected on a clinical basis.
Intermediate‐dose melphalan (IDM) combined with G‐CSF (filgrastim) is an effective and safe induction therapy for autologous stem cell transplantation in multiple myeloma
Authors: Lokhorst Henk , Sonneveld Pieter , Wijermans Pierre , Van Marwijk Kooy Marinus , Th. Meuwissen Otger , Van Oers Rien , Van Der Griend René , Dekker Adriaan 
Published: November 2003

Twenty‐one previously untreated multiple myeloma (MM) patients and 10 previously treated patients with refractory or relapsed disease received two or three cycles of intermediate‐dose melphalan (70 mg/m2) (IDM), administered intravenously every 6 weeks. Seven previously untreated patients received three and all other patients received two courses of IDM. The objective of the study was to reduce the toxicity of high‐dose melphalan (140 mg/m2) (HDM) while maintaining its cytotoxic efficacy and secondly to ensure the possibility of collecting sufficient numbers of peripheral blood stem cells (PBSC) for transplantation. 18 (85%) previously untreated patients responded, of whom four achieved CR (18%). In addition five out of 10 previously treated patients with refractory or relapsed disease responded although bone marrow toxicity in this category was a major drawback. Toxicity was moderate, consisting of alopecia and moderate bone marrow suppression: the granulocyte count dropped below 0.5 × 109/l and platelets below 25 × 109/l for a median of 8 and 6 d, respectively. No serious infections occurred and the majority of patients attended the out‐patient clinic. In 12/14 previously untreated patients sufficient peripheral blood CD34+ cells for harvest were present in the repopulation phase after the first IDM. In nine patients peripheral blood stem cells were collected and eight patients have undergone succesful transplantation.Repeated IDM followed by filgrastim is highly effective in untreated MM and may be safely administered to reduce tumour load prior to PBSC collection. Autologous stem cells harvested after repeated IDM have a full long‐term repopulating capacity.
Richter's syndrome in a case of atypical chronic lymphocytic leukaemia with the t(11;14)(q13;q32): role for a p53 exon 7 gene mutation
Authors: Cuneo Antonio , De Angeli Cristiano , Grazia Roberti Maria , Piva Nadia , Bigoni Renato , Gan dini Domenica , Matteo Rigolin Gian , Moretti Sabrina , Cavaz zini Pierluigi , Del Senno Laura , C ASTOLDI GIANLUIGI 
Published: November 2003

Clinicobiological, histological, cytogenetic and molecular genetic studies were performed in a case of atypical B‐cell chronic lymphocytic leukaemia (B‐CLL) with the t(11;14)(q13;q32) evolving into Richter's syndrome (RS) in order (a) to determine the clonal relationship between the cell of origin for B‐CLL and RS, and (b) to analyse genetic events underlying the disease progression in this patient.After 4 years following diagnosis, a rapid deterioration of the clinical picture occurred, concomitant with the appearance of large lymphoid blasts in peripheral blood (PB), bone marrow (BM) and ascites samples. A diagnosis of RS was made and cytogenetic analysis revealed karyotype evolution with trisomy 7 and del(17p) in addition to t(11;14). Fluorescence in situ hybridization showed 78% lymphoid blast cells obtained from ascites sample to be trisomic using a chromosome‐7‐specific pericentromeric probe. Whereas no rearrangement of the c‐myc proto‐oncogene was detected at disease progression, direct sequencing of p53 gene exon 5–9 revealed an exon 7 missense point mutation. This abnormality was not present in the CLL phase. Immunological staining with the monoclonal antibody PAb‐1801, detecting the p53 protein product, revealed a negative pattern in the CLL phase, whereas 24% positivity was documented in representative samples obtained at RS.It is concluded that RS was cytogenetically related with B‐CLL in this patient, suggesting the occurrence of a bona fide transformation and that the mutation of p53 exon 7, in association with the development of 17p deletion, possibly played a role in the development of RS.
Analysis of the κ light chain variable region in multiple myeloma
Authors: Kosmas Christos , Viniou Nora‐Athina , Stamato poulos Kostas , Courtenay‐Luck Nigel S. , Papadaki Theodora , Kollia Panagoula , Paterakis George , Anagnostou Dimitra , Yataganas Xenophon , Loukopoulos Dimitris 
Published: November 2003

The study of immunoglobulin heavy chain gene rearrangements in multiple myeloma has revealed extensive divergence from the germline sequences, but no intraclonal diversity with disease evolution. Our study investigated the state of the rearranged κ light chain variable region (Vκ) gene segments, as well as abortive Vκ family gene usage in cases of multiple myeloma expressing λ light chain. We studied 11 cases of κ and five cases of λ light chain‐expressing multiple myeloma. Total cellular RNA was extracted from the bone marrow of patients with overt disease and subjected to reverse transcription‐polymerase chain reaction (RT‐PCR) analysis to amplify clonally rearranged variable region sequences. Direct nucleotide sequencing by the dideoxy‐chain termination method was performed on the RT‐PCR products. We did not observe preferential usage of certain Vκ gene families. Mutation frequencies of the Vκ segments varied in number. In the majority of cases, extensive somatic mutations occurred within the complementarity determining regions (CDRs) of Vκ, whereas only a limited degree of divergence from the germline was observed in others. In all cases studied, replacement mutations tended to cluster in the CDRs, a finding compatible with an antigen‐driven somatic hypermutation process. In 3/5 cases of λ light‐chain expressing multiple myeloma, abortively rearranged Vκ gene segments were amplified from genomic DNA; in two cases a non‐templated nucleotide insertion rendering the Vκ sequences out‐of‐frame was observed, and in the third a stop codon was identified in the open reading frame of the Vκ sequence. Somatic mutations were observed in all cases of abortive Vκ genes studied; however, their distribution does not suggest selection by antigen.We conclude that somatic mutations observed in the Vκ regions of myeloma cells are of variable extent and suggest operation of the antigen selection process. Lack of or minimal somatic hypermutation in a few cases may be in some way implicated in the biological heterogeneity of the disease.
Continuing (maintenance) therapy in lymphoblastic leukaemia: lessons from MRC UKALL X
Authors: Chessells J. M. , Harrison G. , Lilleyman J. S. , Bailey C. C. , Richards S. M. 
Published: November 2003

The relationship between the prescribed dose of drugs during continuing (maintenance) therapy, the degree of marrow suppression caused, and subsequent event‐free survival was examined in a cohort of 740 children with lymphoblastic leukaemia treated on MRC UKALL X. Girls, younger children, and patients who had received intensification treatment, were prescribed lower doses of mercaptopurine, became neutropenic more readily, and had more interruptions of treatment. Children who had one or more episodes of neutropenia with a count of < 0.5 × 109/l had a better prognosis than those who never became neutropenic.We conclude that early intensification treatment influences the probability of neutropenia during continuing treatment and that patients exhibiting myelosuppression during this phase of treatment have a better chance of prolonged remission.
HLA-dependent peripheral T cell receptor (TCR) repertoire formation and its modification by rheumatoid arthritis (RA)
Authors: MIZUSHIMA N , KOHSAKA H , NANKI T , OLLIER W E R , CARSON D A , MIYASAKA N 
Published: November 2003

SUMMARY
Our previous studies have disclosed that the peripheral T cell receptor β (TCRB) gene repertoires of RA monozygotic twins were similar. This suggested that the TCRBV repertoire is controlled primarily by genetic factors. Here, we examine how the combination of HLA and presence of RA influence the peripheral TCRB repertoire. Peripheral blood mononuclear cells from six pairs of healthy monozygotic twins, six pairs of monozygotic twins discordant for RA, and nine siblings of a large family, including three RA patients, were examined for their TCRB gene repertoires. Among healthy twins and siblings, the BV repertoires between HLA-identical pairs were significantly more similar than those of HLA-non-identical pairs. When RA-affected members were included, the repertoires of the HLA-identical pairs discordant for RA were dissimilar compared with those of healthy pairs. TCRBV–BJ combination repertoire analysis of CD4 and CD8 T cell subsets from the twins showed that the dissimilarity was primarily confined to CD8 T cells in the healthy identical twins, whereas it was seen in both CD4 and CD8 T cell subsets in the RA-discordant twins. These results suggest (i) the presence of RA modifies the genetically controlled TCR repertoire of peripheral T cells, and (ii) the RA-associated alterations appear to occur more frequently in CD4 T cells than in CD8 T cells.
The avidity of allospecific cytotoxic T lymphocytes (CTL) determines their cytokine production profile
Authors: VAN EMMERIK N E M , DAANE C R , KNOOP C J , HESSE C , VAESSEN L M B , BALK A H M M , MOCHTAR B , CLAAS F H J , WEIMAR W 
Published: November 2003

SUMMARY
Donor-specific CTL present within the cardiac allograft during a rejection episode are distinct from those that populate the cardiac allograft in the absence of rejection. Whereas the former generally have a high avidity for donor cells, the latter mainly have a low avidity for donor cells. This observation made us reason that high-avidity CTL are implicated in transplant rejection, whereas low-avidity CTL are not. In the present study, we analyse whether both CTL subsets were distinct with respect to their IL-2, IL-4, IL-6 and interferon-gamma (IFN-γ) secretion pattern. CTL clones with either a high or a low avidity for donor antigens were stimulated with donor cells, third party cells, or immobilized anti-CD3 MoAb and the amount of cytokine released was measured. High- and low-avidity CTL clones were found to differ with respect to their IFN-γ production profile. Stimulation with donor cells resulted in IFN-γ secretion by high-avidity CTL clones, but not by low-avidity CTL clones. CD3 stimulation, in contrast, led to secretion of equivalent amounts of IFN-γ by both CTL subsets. These observations indicate that low-avidity CTL are fully capable of producing IFN-γ, but, in contrast to high avidity CTL, fail to do so when they encounter donor cells. As IFN-γ favours the occurrence of transplant rejection, this observation emphasizes the relevance of high-avidity CTL in the rejection process. Additionally, the data show that the cytokine production profile of CTL depends on the nature of the stimulus.
Human peripheral eosinophils express functional interferon-gamma receptors (IFN-γR)
Authors: ISHIHARA C , OCHIAI K , KAGAMI M , TAKASHAHI H , MATSUYAMA G , YOSHIDA S , TOMIOKA H , KOYA N 
Published: November 2003

SUMMARY
In order to determine whether or not IFN-γR is associated with regulatory mechanisms on human eosinophil function, we examined the expression of functional IFN-γR on human peripheral eosinophils. In this study, peripheral blood eosinophils were obtained from seven normal controls and 12 patients (bronchial asthma, n = 9, and hypereosinophilic syndrome (HES), n = 3), and the purity of eosinophils was 97·11 ± 2·31%, n = 19. We first showed that anti-IFN-γR α-chain MoAb reacted with all tested eosinophils of both normal controls and patients by flow cytometry analysis. We also showed expression of mRNA for the α-chain of IFN-γR in all purified eosinophils of six individuals. Further, to characterize IFN-γR on eosinophils, we did binding experiments with 125I-IFN-γ on purified peripheral eosinophils. The linear Scatchard plot indicated a single type of high-affinity binding sites (dissociation constant (Kd) = 3·89–4·95 × 10−10 m, numbers of binding sites = 183–233/cell, n = 3). To determine whether IFN-γR on eosinophils is functional, we examined surface eosinophilic cationic protein (ECP) and CD69 induction after IFN-γR ligation with recombinant human IFN-γ (rhIFN-γ) on eosinophils by flow cytometry. rhIFN-γ stimulation significantly induced both ECP and CD69 expression on the 2–18 h-cultured eosinophils in a dose-dependent manner. Further, the effects of rhIFN-γ stimulation were significantly blocked by both a neutralizing anti-IFN-γ MoAb and a blocking anti-IFN-γR MoAb. These results suggest that human peripheral eosinophils express functional IFN-γR.
Inhibitory effects of low molecular weight heparin on mediator release by mast cells: preferential inhibition of cytokine production and mast cell-dependent cutaneous inflammation
Authors: BARAM D , RASHKOVSKY M , HERSHKOVIZ R , DRUCKER I , RESHEF T , BEN-SHITRIT S , MEKORI Y A 
Published: November 2003

SUMMARY
There has been substantial evidence that suggests that heparin may modulate various aspects of immune function and inflammation in addition to its well known anticoagulant activity. In this regard heparin was found to suppress cell-mediated immune responses or asthmatic reactions to allergen challenge. In the present study we analyse the effects of low molecular weight heparin (LMWH) on mast cell degranulation and cytokine production in vitro and on the elicitation of IgE-mediated mast cell-dependent late cutaneous allergic inflammation in vivo. We have established that LMWH preferentially inhibited tumour necrosis factor-alpha (TNF-α) and IL-4 production without having any significant effect on mast cell degranulation. These effects have been observed in mast cells derived from three different origins that were activated by either immunological or non-immunological stimuli. We have shown that there is inhibition of TNF-α production (and not neutralization of activity), as elimination of the drug after a short preincubation and addition of LMWH to rTNF-α had no effect on TNF-α-mediated cytotoxic activity. These results were also confirmed by ELISA. In vivo, s.c. injection of the LMWH inhibited the leucocyte infiltration associated with the late cutaneous response which followed passive cutaneous anaphylaxis (PCA) reaction, without affecting mast cell numbers or degranulation. These data suggest that LMWH may have an inhibitory role in mast cell-mediated allergic inflammation, and thus might be considered as a possible therapeutic modality.
Low density lipoprotein receptor expression and function in human polymorphonuclear leucocytes
Authors: Lara L L , Rivera H , Perez-P C , Blanca I , Bianco N E , De Sanctis J B 
Published: November 2003

Abstract
Low density lipoprotein receptors (LDLR), capable of internalizing LDL, are expressed in polymorphonuclear neutrophils (PMN). The expression was assessed using anti-LDLR antibody by flow cytometry. The internalization of LDL was assessed by: (i) quantification of the uptake of labelled LDL with 1,1′-dioctadecyl-3,3,3′,3′ tetramethyl-indocarboxycyanine perchlorate (DiI) by flow cytometry; and (ii) the binding of LDL-125I. In fresh purified cells, Lineweaver–Burk analysis of LDL binding (LDL-DiI) revealed that the calculated Kd (internalized LDL) for PMN (15.0 × 10−9 m) is lower than the Kd for monocytes (1.1 × 10−7 m) and the Kd for lymphocytes (3.2 × 10−7 m). Scatchard analysis (LDL-125I) revealed 25 000 binding sites and a Kd of 9.6 × 10−9 m for PMN. The interaction of LDL with its receptor caused a two-fold fast (peak at 1 min) and transient increase in the oxidative burst, measured by the formation of 2′,7′ dicholoflurescein (DCF) by flow cytometry. This effect was not observed in monocytes or lymphocytes, and it was blocked by anti-LDLR antibody. The stimulation of LDL was optimal at 10 μg of protein/ml. LDL was able to suppress DCF formation induced by phorbol myristate acetate (PMA) and PMA was unable to further stimulate LDL-treated cells, suggesting protein kinase-C (PKC) involvement in LDL effects. Using a PKC assay, LDL was shown to induce a two-fold increase in PKC translocation to the membrane. Thus, LDL increases PMN oxidative burst through a PKC-dependent pathway.