bluuebunny/crossref_metadata_2025 huggingface dataset:
Ill‐health reported by schoolchildren during questionnaire surveys in Ghana, Mozambique and Tanzania
Authors: Moestue Helen , Mahumane Bonifacio , Zacher Anna , Issae Wahab , Kihamia Charles M. , Wen Su‐Tung , Adjei Sam , Bundy Donald A. P. , Hall Andrew
Published: October 2003

Background Insufficient attention has been paid to the health problems of school‐age children in sub‐Saharan Africa. A questionnaire administered to schoolchildren about their ill‐health has been developed to identify schools in which urinary schistosomiasis occurs. The data collected during the interviews can also be used to assess other common health problems.

Objectives To analyse data collected during health questionnaires in schools to assess how schoolchildren perceive their own health, and to compare the findings between three countries in sub‐Saharan Africa.

Methods Questionnaires asking about recent health problems were administered by teachers to schoolchildren in 120 primary schools in Mozambique, 52 primary schools in Tanzania and 298 primary schools in Ghana. A total of 67 002 children aged 8–15 years took part.

Results Of the 10 health problems asked about in all questionnaires, the average number reported by each child was 3.9 in Ghana, 3.4 in Mozambique and 3.1 in Tanzania. The distributions of the prevalence of each condition among schools were similar and the prevalence of all conditions showed a similar ranking. For most conditions a greater percentage of girls than boys reported each health problem.

Conclusions Schoolchildren in Ghana, Mozambique and Tanzania do not perceive themselves to be healthy. The pattern of reported health problems was similar in each country. School health questionnaires are worthy of further study and validation.
Short communication: Low risk of transmission of severe acute respiratory syndrome on airplanes: the Singapore experience
Authors: Wilder‐Smith Annelies , Paton Nicholas I. , Goh Kee Tai
Published: October 2003

The risk of transmission of severe acute respiratory syndrome (SARS) on airplanes is of major concern to the public and airline industry. We examined data from flights to Singapore with SARS patients on board in order to assess this risk. In‐flight transmission occurred only in one of the three flights with symptomatic SARS patients on board. The incidence was estimated to be 1 out of 156 passengers. The risk of in‐flight transmission of SARS appears to be far lower than that reported for influenza, but may be increased with superspreaders on board.
Pharmacological characteristics and side effects of a new galenic formulation of propofol without soyabean oil*
Authors: Paul M. , Dueck M. , Kampe S. , Fruendt H. , Kasper S. M.
Published: October 2003

We compared the pharmacokinetics, pharmacodynamics and safety profile of a new galenic formulation of propofol (AM149 1%), which does not contain soyabean oil, with a standard formulation of propofol (Disoprivan® 1%). In a randomised, double‐blind, cross‐over study, 30 healthy volunteers received a single intravenous bolus injection of 2.5 mg.kg−1 propofol. Plasma propofol levels were measured for 48 h following drug administration and evaluated according to a three‐compartment model. The pharmacodynamic parameters assessed included induction and emergence times, respiratory and cardiovascular effects, and pain on injection. Patients were monitored for side effects over 48 h. Owing to a high incidence of thrombophlebitis, the study was terminated prematurely and only the data of the two parallel treatment groups (15 patients in each group) were analysed. Plasma concentrations did not differ significantly between the two formulations. Anaesthesia induction and emergence times, respiratory and cardiovascular variables showed no significant differences between the two treatment groups. Pain on injection (80 vs. 20%, p < 0.01) and thrombophlebitis (93.3 vs. 6.6%, p < 0.001) occurred more frequently with AM149 than with Disoprivan®. Although both formulations had similar pharmacokinetic and pharmacodynamic profiles the new formulation is not suitable for clinical use due to the high incidence of thrombophlebitis produced.
Making monitoring ‘work’: human–machine interaction and patient safety in anaesthesia
Authors: Smith A. F. , Mort M. , Goodwin D. , Pope C.
Published: October 2003

This study aimed to explore the use of electronic monitoring within the context of anaesthetic practice. We conducted workplace observation of, and interviews with, anaesthetists and other anaesthetic staff in two UK hospitals. Transcripts were analysed inductively for recurrent themes. Whilst formal sources of knowledge in anaesthesia deal with the issue of monitoring in terms of theoretical principles and performance specifications of devices, anaesthetists in practice often ‘disbelieve’ monitoring information. They call on and integrate other sources of knowledge about the patient, especially from their clinical assessment. The ability to distinguish ‘normal’ and ‘abnormal’ findings is vital. Confidence in electronic information varies with experience, as does the degree to which electronic information may be considered ‘redundant’. We conclude that electronic monitoring brings new dimensions of understanding but also the potential for new ways of misunderstanding. The tacit knowledge underlying the safe use of monitoring deserves greater acknowledgement in training and practice.
A web‐based system for teaching, assessment and examination of the undergraduate peri‐operative medicine curriculum
Authors: Wheeler D. W. , Whittlestone K. D. , Smith H. L. , Gupta A. K. , Menon D. K. ,   on behalf of the East Anglian Peri‐operative Medicine Undergraduate Teaching Forum
Published: October 2003

Today's students are generally computer literate and have high expectations of university information technology resources. Most United Kingdom medical schools now provide networked computers for learning, research, communication and accessing the worldwide web. We have exploited these advances to augment and improve the teaching of peri‐operative medicine and anaesthesia to medical students in our university, who are taught in several hospitals over a wide geographical area. Course material such as departmental induction information, lecture notes and assessment sheets can be accessed online, contributing to the smooth running of the course. Streamed videos and simulations allow students to familiarise themselves with common practical procedures in advance. Development of a web‐based end of course assessment has resulted in substantially less administration and bureaucracy for course organisers and proved to be a valuable research tool. Students' and teachers' opinions of the new course structure have been overwhelmingly positive.
Assessment of postsurgical recovery after discharge using a pen computer diary*
Authors: Begg A. , Drummond G. , Tiplady B.
Published: October 2003

We assessed patients after their return home following gynaecological surgery, using a daily electronic diary. Thirty‐two females aged 27–77 years took part. After a hospital stay of 1–6 days (mean 2.3), they were given a pen‐based electronic diary and asked to record symptoms and other data over one month. They also completed a questionnaire at the end of the study. Substantial effects on quality and duration of sleep, pain during both the night and day, interference with daily activities, energy, and ability to concentrate were recorded, mostly during the first week of treatment. Symptoms reported in the final questionnaire correlated significantly with diary data. Most patients found the electronic diary easy to use, and none found it difficult. Daily electronic diaries are an acceptable method of obtaining better information on the extent and duration of symptoms and other difficulties after discharge following surgery.
A clinical evaluation of the Bonfils Intubation Fibrescope*
Authors: Halligan M. , Charters P.
Published: October 2003

The Bonfils Intubation Fibrescope is a rigid optical instrument for performing orotracheal intubation. We describe its introduction into our clinical practice in 60 patients with normal airways who required orotracheal intubation for elective surgery. Two anaesthetists each performed 30 attempts to intubate, in turn, in patients who received a standard general anaesthetic with neuromuscular blockade. Intubation was successful in 59 out of 60 cases. The median (IQR [range]) time to intubation was 33 s (24–50 [13–180] s). Median (IQR [range]) verbal rating score for difficulty was 2 (1–3 [0–10]). There was a significant correlation between the intubation times and the verbal rating score (p < 0.01). There was evidence of airway trauma in the single patient in whom intubation failed. The Bonfils Intubation Fibrescope is an effective instrument for orotracheal intubation in normal subjects.
Prediction of difficult laryngoscopy in obese patients by ultrasound quantification of anterior neck soft tissue*
Authors: Ezri T. , Gewürtz G. , Sessler D. I. , Medalion B. , Szmuk P. , Hagberg C. , Susmallian S.
Published: October 2003

In 50 morbidly obese patients, we quantified the soft tissue of the neck from the skin to the anterior aspect of the trachea at the vocal cords using ultrasound. Thyromental distance, mouth opening, limited neck mobility, modified Mallampati score, abnormal upper teeth, neck circumference and sleep apnoea were assessed as predictors of difficult laryngoscopy. Of the nine (18%) cases of difficult laryngoscopy, seven (78%) had a history of obstructive sleep apnoea, compared with two of the 41 patients (5%) in whom laryngoscopy was easy (p < 0.001). Patients in whom laryngoscopy was difficult had more pretracheal soft tissue (mean (SD) 28 (2.7) mm vs. 17.5 (1.8) mm; p < 0.001) and a greater neck circumference (50 (3.8) vs. 43.5 (2.2) cm; p < 0.001). None of the other predictors correlated with difficult laryngoscopy. We conclude that an abundance of pretracheal soft tissue at the level of the vocal cords is a good predictor of difficult laryngoscopy in obese patients.
Post‐splenectomy thrombocytopenia: implications for regional analgesia
Authors: McLure H. A. , Trenfield S. , Quereshi A. , Williams J.
Published: October 2003

Hospital computerised records were reviewed to identify patients who had undergone splenectomy, then chart their platelet count before and for the 5 days after the operation. A pre‐operative platelet count less than 100 × 109.l−1 occurred in 66% of leukaemia (n = 35), 56% of lymphoma (n = 41) and 5% of solid tumour (n = 39) patients. Platelet supplementation prior to epidural catheter insertion may reduce the risks of spinal bleeding. However, accidental catheter removal during a postoperative period of thrombocytopenia may lead to formation of an epidural haematoma. The lowest postoperative platelet count was less than 100 × 109.l−1 in 66% of leukaemia, 27% of lymphoma and 13% of solid tumour patients. Platelet counts varied considerably, so predicting an individual patient's postoperative nadir from the pre‐operative count would be impossible. Consequently, placement of an epidural catheter in many of these patients could expose them to an increased risk of spinal bleeding if the catheter is removed accidentally.
Anaesthetic considerations in a parturient with varicella presenting for Caesarean section
Authors: Brown N. W. , Parsons A. P. R. , Kam P. C. A.
Published: October 2003

A parturient with varicella (chickenpox) presented for an elective Caesarean section and spinal anaesthesia was employed for surgery. A review of the literature is presented and the anaesthetic issues are discussed.
Pre‐operative hepatitis in a woman treated with Chinese medicines
Authors: Critchley L. A. H. , Chen D. Q. , Chu T. T. , Fok B. S. , Yeung C.
Published: October 2003

A 37‐year‐old Hong Kong Chinese female with cervical cancer was scheduled for radical hysterectomy and lymphadenectomy. Her past health was good. Pre‐operatively, she was found to have a fatty liver, prolonged prothrombin time and abnormal liver function tests. Surgery was not postponed and she was anaesthetised uneventfully, using a general anaesthetic technique. The procedure lasted 4 h. Postoperatively, she developed a large pelvic haematoma and a wound infection. Her coagulation and liver function tests gradually returned to normal. No obvious medical cause for her liver dysfunction could be found. However, it emerged that she had received a 6‐week course of traditional Chinese medicines prior to admission. The prescriptions contained over 60 different ingredients, some of which were known to be hepatotoxic, cytotoxic or to cause bleeding. This was the most likely explanation for her liver dysfunction.
Anaesthesia for Caesarean section: a survey in a UK region from 1992 to 2002
Authors: Jenkins J. G. , Khan M. M.
Published: October 2003

Summary Data are presented for anaesthesia for Caesarean section (CS) in the South‐west Thames region of the UK. The CS rate rose from 12.7% in 1987 to 24.2% in 2002. The rate of increase shows no sign of slowing. The rate of regional anaesthesia (RA) for elective CS rose from 69.4% in 1992 to 94.9% in 2002, when spinal anaesthesia was used for 86.6% of cases. This may limit the opportunities to teach other anaesthetic techniques. The rate of RA for emergency CS rose from 49.3% in 1992 to 86.7% in 2002. There is an unacceptable rate of failure of RA for both elective and emergency CS, 1.3% of RAs for elective CS and 4.9% of RAs for emergency CS were converted to general anaesthesia.
The provision and practice of renal replacement therapy on adult intensive care units in the United Kingdom
Authors: Wright S. E. , Bodenham A. , Short A. I. K. , Turney J. H.
Published: October 2003

This study surveyed the availability and current practice of renal replacement therapy on adult general intensive care units in the United Kingdom. Questionnaires were returned from 236 units (89%). Renal replacement therapy was provided by 212 (90%) of responding units, treating 9442 patients per year. Renal physicians were involved in the initiation and prescription of treatment in 22 (11%) units. Ninety‐one units (43%) had no step down facility on‐site for those patients still requiring renal replacement therapy but no longer requiring intensive care. Continuous techniques are used by the majority of units, most commonly, continuous veno‐venous haemofiltration, with an ultrafiltration rate of 2000 ml.h−1. Fifty‐eight units (28%) use haemofiltration as adjuvant treatment in septic shock. The provision and practice of renal replacement therapy is now an integral part of intensive care medicine in the United Kingdom.
Effect of the second‐generation antihistamine, fexofenadine, on cough reflex sensitivity and pulmonary function
Authors: Dicpinigaitis Peter V. , Gayle Yvonne E.
Published: October 2003

Aims  Current guidelines recommend the use of first‐generation antihistamines for the treatment of cough due to rhinitis/postnasal drip syndrome. The antitussive activity of the second‐generation antihistamine, fexofenadine, has not been investigated. Therefore, we evaluated the effect of fexofenadine on capsaicin‐induced cough in healthy volunteers and in subjects with acute viral upper respiratory tract infection (URI).

Methods  Twelve healthy volunteers and 12 subjects with URI underwent pulmonary function testing and capsaicin cough challenge on two separate days, 2 h after ingesting 180 mg fexofenadine or matched placebo. Subjects inhaled single, vital‐capacity breaths of capsaicin aerosol, administered in incremental doubling concentrations, until the concentration inducing five or more coughs (C5) was determined.

Results  In both subject groups, C5 was not significantly different after fexofenadine compared to placebo. In subjects with URI, pulmonary function studies were also similar. In healthy volunteers, however, FEV1 and FEF25−75, pulmonary function parameters reflecting the degree of airway dilatation, were significantly increased after fexofenadine. Mean (95% CI) values for FEV1(L) after fexofenadine and placebo were 3.16 (2.77, 3.55) and 3.08 (2.69, 3.47), respectively (P = 0.017). Mean values for FEF25−75(L/s) were 3.49 (3.10, 3.88) and 3.26 (2.79, 3.72), respectively (P = 0.029).

Conclusions  Fexofenadine demonstrated no antitussive activity against capsaicin‐induced cough in healthy volunteers and subjects with URI. The ineffectiveness of fexofenadine in suppressing cough probably reflects the lack of anticholinergic activity and central nervous system penetrance that is characteristic of first‐generation antihistamines. The mild bronchodilation induced by fexofenadine in healthy volunteers is of unclear clinical significance and requires further investigation.
Long‐term evaluation of 164 patients with essential thrombocythaemia treated with pipobroman: occurrence of leukaemic evolution
Authors: De Sanctis Vitaliana , Mazzucconi Maria Gabriella , Spadea Antonio , Alfò Marco , Mancini Marco , Bizzoni Luisa , Peraino Monica , Mandelli Franco
Published: October 2003

Summary.Essential thrombocythaemia (ET) is usually considered an indolent disease, but it may progress during its natural course into acute leukaemia (AL); however, an influence of myelosuppressive agents in the blastic transformation of ET cannot be excluded. We performed a retrospective study to assess the incidence of AL in ET patients treated with pipobroman (PB) as first‐line therapy. One hundred and sixty‐four patients with ET were managed with PB at a dose of 1 mg/kg/d until a stable platelet count below 400 × 109/l was achieved. Maintenance therapy was given at a planned dose ranging between 0·2 and 1 mg/kg/d according to platelet count, in all cases, with a median daily dose of 25 mg (range 7–75 mg/d). The median treatment time was 100 months (range 25–243 months). The patients were evaluated for the occurrence of AL and/or secondary malignancies and survival end‐points. AL was observed in nine patients (5·5%) after a median treatment time of 153 months (range 79–227 months). The overall survival (OS) and the event‐free survival (EFS) at 120 months were 95% and 97%, whereas at 180 months, they were 84% and 76% respectively. In conclusion, this retrospective analysis shows a low incidence of AL in a large group of patients consecutively treated with PB as first‐line chemotherapy. Therefore, an investigation of the role of myelosuppressive agents in the blastic transformation of ET would be of interest.
Adult T‐cell leukaemia/lymphoma‐like human T‐cell leukaemia virus‐1 replication in infective dermatitis
Authors: Gabet Anne‐Sophie , Kazanji Mirdad , Couppie Pierre , Clity Emmanuel , Pouliquen Jean‐François , Sainte‐Marie Dominique , Aznar Christine , Wattel Eric
Published: October 2003

Summary. Adult T‐cell leukaemia/lymphoma (ATLL) is a malignant T‐cell proliferation that occurs in 3–5% of individuals infected with human T‐cell leukaemia virus‐1 (HTLV‐1). HTLV‐1 infection is also linked to the development of infective dermatitis (ID), an exudative dermatitis of children that has been proposed as a cofactor of ATLL. Here, HTLV‐1 replication was investigated over time in a girl with ID and multiparasitic infestation including strongyloidiasis, a disease also known to predispose HTLV‐1 carriers to ATLL. Quantitative polymerase chain reaction (PCR) revealed extremely high proviral loads. During the 2‐year period of the present study, the proportion of circulating infected cells ranged between 12% and 36%. Quadruplicate linker‐mediated PCR amplification of HTLV‐1 flanking sequences identified a pattern of extensive and persistent oligoclonal expansion of infected lymphocytes. As viral loads, both the number and the degree of infected T‐cell expansion were independent of treatment or clinical signs. However, the temporal fluctuation of proviral loads correlated significantly with the degree of infected T‐cell expansion, but not with the overall number of detected clones. This pattern of HTLV‐1 replication over time is very different from that observed in asymptomatic carriers and reminiscent of that observed in ATLL, a result consistent with the proposal of ID as an ATLL cofactor.
Long‐term follow‐up of relapsed childhood acute lymphoblastic leukaemia
Authors: Chessells Judith M. , Veys Paul , Kempski Helena , Henley Patricia , Leiper Ali , Webb David , Hann Ian M.
Published: October 2003

Summary. We have reviewed the outcome after relapse in a cohort of 505 children with acute lymphoblastic leukaemia (ALL) seen at a single institution. The majority of relapses (74%) occurred within 3 years from diagnosis, and most involved the bone marrow alone or with overt extramedullary relapse. Early relapse was more common in children with T‐ALL and those with unfavourable cytogenetics. Factors influencing second remission included length of first remission and type of relapse. Children who had not received previous cranial irradiation had a superior survival. The German relapse score involving length of first remission, site of relapse and immunophenotype was highly predictive of outcome: event‐free survival with 95% confidence intervals at 6 years for patients who received modern treatment [intensive chemotherapy or bone marrow transplantation (BMT)] was 78% (51–92%) for standard risk, 41% (33–49%) for intermediate risk and 19% (10–31%) for highest risk. Retrospective comparison of BMT with chemotherapy showed no difference in the intermediate‐risk group but a possible advantage in the highest risk group. Follow‐up of 235 patients who relapsed after chemotherapy and received a third course of treatment showed an extremely high early attrition rate, but a small number of patients survived in third remission. We conclude that new approaches are needed to individualize therapy in intermediate‐risk patients and to improve the outcome for those in the highest risk group. Only a small number of children can be treated effectively in third remission.
Evaluation of the haemopoietic reservoir in de novo haemolytic paroxysmal nocturnal haemoglobinuria
Authors: Elebute Modupe O. , Rizzo Sian , Tooze Jennifer A. , Marsh Judith C. W. , Gordon‐Smith Edward C. , Gibson Frances. M.
Published: October 2003

Summary. Paroxysmal nocturnal haemoglobinuria (PNH) is an acquired clonal disorder of the haemopoietic stem cell (HSC). The pathogenetic link with bone marrow failure is well recognized; however, the process of clonal expansion of the glycosylphosphatidylinositol (GPI)‐deficient cells over normal haemopoiesis remains unclear. We have carried out detailed analysis of the stem cell population in 10 patients with de novo haemolytic PNH using the long‐term culture‐initiating cells (LTC‐IC) assay in parallel with measurements of CD34+ cells and mature haemopoietic progenitors, granulocyte–macrophage colony‐forming unit (CFU‐GM) and CFU‐erythroid [burst‐forming units erythroid (BFU‐E) + CFU granulocyte/erythroid/macrophage/megakaryocyte (GEMM)]. All patients had hypercellular bone marrows with erythroid hyperplasia, normal blood counts or mild peripheral blood cytopenias, increased reticulocyte counts and evidence of deficient GPI‐anchored proteins. We found a significant reduction in the LTC‐IC frequency in the CD34+ compartment of PNH patients (mean 2, range 1·3–3·0; n = 6) compared with normal donors (mean 13, range 5·2–45·5; n = 21) (P < 0·0001). Furthermore, there was a significant reduction in the erythroid compartment [CFU‐E/105 bone marrow mononuclear cells (BMMC) and CFU‐E/105 CD34+ cells] of PNH patients, but no significant difference in the granulocyte–monocyte precursors (CFU‐GM/105 BMMC or CFU‐GM/105 CD34+ cells) compared with normal donors, suggesting that there is a defect in the early stem cell pool in PNH patients without clinical or haematological evidence of bone marrow failure.
Is the determination of anti‐beta2 glycoprotein I antibodies useful in patients with venous thromboembolism without the antiphospholipid syndrome?
Authors: Hsieh Kety , Knöbl Paul , Rintelen Claudia , Kyrle Paul A. , Quehenberger Peter , Bialonczyk Christine , Partsch Hugo , Lechner Klaus , Pabinger Ingrid
Published: October 2003

Summary. Anti‐beta2‐glycoprotein I (beta2GPI) antibodies are frequently found in patients with lupus anticoagulant (LA). To investigate the prevalence of antibeta2GPI antibodies and their clinical impact in patients with a history of venous thromboembolism (VTE) without LA/anticardiolipin antibodies (ACA), we studied 503 patients [128 (36·2%) men, median age 41 years (interquartile range, IQR 28–54 years)] with previous thrombosis. A group of 113 individuals without VTE [43 (38·1%) men, age 46·7 years (IQR 38–52 years)] served as a control group. Among 418 patients without LA/ACA, anti‐beta2GPI‐IgG levels were elevated in seven (1·7%), ‐IgM in 15 (3·6%) and ‐IgA in 14 (3·3%) cases; in 58 patients with ACA, anti‐beta2GPI‐IgG levels were elevated in two (3·4%), six (10·3%) and three (5·2%), and in 27 with LA, they were elevated in 18 (66·7%), 19 (70·4%) and 10 (37%) respectively. Thus, the prevalence of elevated anti‐beta2GPI antibodies was not increased in patients without LA/ACA but was strongly associated with LA. Patients without ACA/LA who had a recurrent event did not have higher prevalence of elevated anti‐beta2GPI‐IgG, ‐IgM or ‐IgA antibodies than those without a recurrent event. Thus, elevated antibeta2GPI antibodies are not likely to be a predictor of recurrent events in patients without LA. We conclude that determination of anti‐beta2GPI antibodies does not improve the clinical management of patients with a history of VTE without LA/ACA.
Angiotensin I‐converting enzyme is expressed by erythropoietic cells of normal and myeloproliferative bone marrow
Authors: Marusic‐Vrsalovic Maruska , Dominis Mara , Jaksic Branimir , Kusec Rajko
Published: October 2003

Summary. It is proposed that a locally active, intrinsic renin–angiotensin system (RAS) exists in the bone marrow (BM) and plays a role in regulating haematopoiesis. Angiotensin II type I receptor has been detected on erythroid burst‐forming unit‐derived cells; its antagonist losartan and angiotensin I‐converting enzyme (ACE) inhibitors can suppress erythropoiesis. The possible role of ACE/RAS in BM was investigated by evaluating ACE expression in normal BM, several myeloproliferative disorders and myelodysplasia. Immunohistochemical studies showed that erythroid elements expressed ACE protein in both normal and disturbed haematopoiesis. The presence of ACE in erythroid cells suggests another mechanism for direct ACE inhibitor activity in erythropoiesis.
Mobilization of Ph chromosome‐negative peripheral blood stem cells in chronic myeloid leukaemia patients with imatinib mesylate‐induced complete cytogenetic remission
Authors: Drummond Mark W. , Marin David , Clark Richard E. , Byrne Jenny L. , Holyoake Tessa L. , Lennard Anne ,   on behalf of the United Kingdom Chronic Myeloid Leukaemia (UK CML) Working Party
Published: October 2003

Summary. Imatinib mesylate (IM, STI 571, Glivec®) can induce a high rate of complete cytogenetic response (CCR) in chronic myeloid leukaemia (CML) patients, although to date the majority of patients continue to have detectable disease by sensitive reverse transcription polymerase chain reaction (RT‐PCR). It is therefore possible that these patients may ultimately relapse and require treatment such as autologous peripheral blood stem cell transplant (APBSCT). We attempted mobilization of haemopoietic progenitor cells from 58 patients in CCR using recombinant human granulocyte colony‐stimulating factor [rHu‐G‐CSF; 10 µg/kg/d subcutaneously (s.c.) for at least 4 d] alone, while continuing IM treatment. The median d 5 (peak) CD34+ count was 11·5/µl (range 0–108/µl), and 43/58 (74%) patients underwent a median of two (range 1–3) apheresis procedures. A median dose of 2·1 × 106/kg CD34+ cells (range 0·1–6·5 × 106/kg) was collected. Some 84% of 31 collections analysed were negative for the Philadelphia (Ph) chromosome or breakpoint cluster region and Abelson murine leukaemia viral oncogene homologue (BCR‐ABL) translocation by cytogenetics or fluorescent in situ hybridization respectively. No toxicity was reported with the regimen. Overall, the target CD34+ dose (2 × 106/kg CD34+) was attained in 23/58 (40%) patients who entered the study. In summary, we have demonstrated that successful mobilization of Ph– CD34+ cells from IM‐treated patients in CCR is possible using rHu‐G‐CSF alone.
Neutrophil myeloperoxidase activity and the influence of two single‐nucleotide promoter polymorphisms
Authors: Rutgers Abraham , Heeringa Peter , Giesen Joyce E. H. M. , Theunissen Ruud T. , Jacobs Heinz , Tervaert Jan Willem Cohen
Published: October 2003

Summary.  Myeloperoxidase (MPO) catalyses the formation of hypochlorous acid and is involved in many (patho)physiological processes. The present study was designed to determine the effect of two MPO promoter polymorphisms (463G/A and 129G/A) on enzyme activity. In 243 healthy controls, genotypes were determined and MPO activity was measured on a single‐cell level using a haematological analyser. The 129G/A polymorphism reduces MPO activity in neutrophils, whereas for the 463G/A polymorphism, only gender‐dependent differences in MPO activity in older age groups could be found. When studying these polymorphisms in disease, therefore, age and gender should be included in the analysis.
Double Philadelphia masquerading as chromosome 20q deletion – a new recurrent abnormality in chronic myeloid leukaemia blast crisis
Authors: Reid Alistair G. , Swanton Soheila , Grace Colin , Campbell Lynda J. , Green Anthony R. , Nacheva Ellie P. ,   Together with the United Kingdom Cancer Cytogenetics Group (UKCCG)
Published: October 2003

Summary. The most common abnormality of chromosome 20 in haematological malignancy is deletion of the long arm [del(20q)]. These interstitial deletions are variable in size and are seen in both premalignant haematological conditions and acute myeloid neoplasia. A commonly deleted region (CDR), mapped within the 20q11.2/q13.1 segment with an estimated size of 1·7 Mbp, is considered to present a primary genetic lesion marking a gene(s), the loss of which is responsible for the pathogenesis of these haematological disorders. While a small number of recurrent translocations involving chromosome 20 have also been reported, no recurrent aberration of this chromosome has been associated with myeloid disease progression. We present nine cases of Philadelphia (Ph)‐positive chronic myeloid leukaemia (CML) in which deletions of chromosome 20 were also detected by conventional karyotyping. In six cases, fluorescent in situ hybridization (FISH) mapping confirmed a del(20q) which corresponded to the myeloid CDR. In the remaining three cases however, the presumed del(20q) marker was shown to be the result of an unbalanced translocation between band 20p11 and a second copy of the Ph chromosome. This new abnormality, termed dic(20;Ph) for short, was identical to a del(20)q by G‐banding, and combined duplication of the breakpoint cluster region and Abelson murine leukaemia viral oncogene homologue (BCR‐ABL) fusion with loss of the 20p11‐pter segment. In all three cases, the dic(20;Ph) was associated with disease progression and therefore represents a new recurrent abnormality in CML blast crisis.
HLA‐DR4 predicts haematological response to cyclosporine in T‐large granular lymphocyte lymphoproliferative disorders
Authors: Battiwalla Minoo , Melenhorst Jos , Saunthararajah Yogen , Nakamura Ryotaro , Molldrem Jeffrey , Young Neal S. , Barrett A. John
Published: October 2003

Summary. T‐cell large granular lymphocytic lymphoproliferative disease (T‐LGL) is often associated with life‐threatening cytopenias. Twenty‐five subjects with anaemia and/or neutropenia caused by T‐LGL were treated with cyclosporin A (CSA) 5–10 mg/kg/d for at least 3 months. Eighteen patients survived between 35 and 77 months after starting treatment. Fourteen patients [56%; 95% confidence interval (CI) 35–76%] responded to CSA with sustained improvement in the neutrophil count or transfusion independence. Seven had complete normalization of blood counts, and four achieved a durable response only after the addition of erythropoietin. Sustained response required continued low‐dose CSA. In a multivariate analysis, HLA‐DR4 was highly predictive of CSA responsiveness (odds ratio 18; 95% CI 1·8–184). T‐LGL subtype, LGL counts after therapy, lymphocytic marrow infiltration and bone marrow cellularity did not significantly affect the probability of response. We conclude that CSA is effective in inducing haematological responses in HLA‐DR4‐positive patients and that T‐LGL is likely to have an immune pathogenesis.
18FDG positron emission tomography versus 67Ga scintigraphy as prognostic test during chemotherapy for non‐Hodgkin's lymphoma
Authors: Zijlstra Josée M. , Hoekstra Otto S. , Raijmakers Pieter G. H. M. , Comans Emile F. I. , Van Der Hoeven Jacobus J.M. , Teule Gerrit J. J. , Jonkhoff A. Roelof , V Tinteren Harm , Lammertsma Adriaan A. , Huijgens Peter C.
Published: October 2003

Summary. A prospective study was performed, comparing gallium scintigraphy (67Ga) and positron emission tomography (PET) using fluorine‐18 fluorodeoxyglucose (18FDG), to monitor the response of aggressive non‐Hodgkin's lymphoma during treatment. 67Ga and 18FDG scans were performed in 26 patients after two cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) therapy. The scans were reviewed independently by four experienced nuclear physicians, who were blinded for the alternative scan technique and follow‐up. Eleven out of 26 patients remained free from progression with a mean follow up of 25 ± 5 months, whereas 14 patients relapsed, and one died of lung cancer. Interobserver variation was significantly greater for 67Ga than for 18FDG PET. Some 64% of patients who had a negative early restaging 18FDG PET remained free from progression versus 50% of patients with negative 67Ga scans. Only 25% of patients with a positive PET remained disease free versus 42% of 67Ga‐positive patients. Time to progression was associated with 18FDG PET results, but not with those by 67Ga. 18FDG PET had better test characteristics than 67Ga for the evaluation of early response in aggressive non‐Hodgkin's lymphoma patients.
Evidence for allelic evolution of C/EBPalpha mutations in acute myeloid leukaemia
Authors: Tiesmeier Jens , Czwalinna Andreas , Müller‐Tidow Carsten , Krauter Jürgen , Serve Hubert , Heil Gerhard , Ganser Arnold , Verbeek Walter
Published: October 2003

Summary. Transcription factor CCAAT/enhancer binding protein α (C/EBPα) is mutated in 6–10% of patients with acute myeloid leukaemia (AML). Recently, we reported the emergence of an N‐terminal C/EBPα mutation after chemotherapy in a patient with secondary AML. The clone carrying the mutation became the dominant clone at relapse. This observation prompted us to compare the C/EBPα mutational status of 26 de novo non‐core binding factor AML patients at diagnosis and at relapse after induction and consolidation chemotherapy. Four mutations in the C/EBPα gene were identified in two out of 26 patients. In both these cases, a biallelic mutation was present at diagnosis and at relapse: an amino‐terminal frameshift mutation and a mutation of the fork/leucine finger 1 region. In patient 1, the amino‐terminal frameshift mutation was duplicated and found on both alleles at relapse. In patient 2, the amino‐terminal frameshift mutation and a mutation in the fork region were found either alone or combined on the same allele, suggesting a subclone formation. None of the patients without a C/EBPα mutation at diagnosis showed a mutation at relapse. This is the first report of an evolution of the C/EBPα gene between diagnosis and relapse in AML.
Lamin B‐receptor mutations in Pelger–Huët anomaly
Authors: Best Steve , Salvati Filippo , Kallo Juraj , Garner Chad , Height Sue , Thein Swee Lay , Rees David C
Published: October 2003

Summary. Pelger–Huët anomaly is an inherited abnormality of neutrophils, characterized by reduced nuclear segementation and an apparently looser chromatin structure. Following linkage studies in two families, the lamin B‐receptor (LBR) was sequenced and mutations found: CCG→CTG causing proline→leucine in codon 119 of exon 3, and IVS11‐9 A→G, disrupting the splice acceptor site. The LBR gene (LBR) was also sequenced from a single English man with Pelger–Huët anomaly and a heterozygous C→G mutation was found in codon 569 of exon 14, predicted to cause a proline→arginine. Our results confirm recently published findings that LBR mutations cause Pelger–Huët.
Factor V I359T: a novel mutation associated with thrombosis and resistance to activated protein C
Authors: Mumford A. D. , McVey J. H. , Morse C. V. , Gomez K. , Steen M. , Norstrom E. A. , Tuddenham E. G. D. , Dahlback B. , Bolton‐Maggs P. H. B.
Published: October 2003

Summary. We report a kindred in which two siblings suffered spontaneous venous thromboses in the second decade of life. Further investigation showed reduced coagulation factor V (FV) activity and activated protein C resistance (APCR) ratio but no other thrombophilic abnormalities. The reduction in APCR ratio persisted in a modified APCR assay in which FV activity was normalized between test and control plasmas. Analysis of the FV gene showed that the thrombotic individuals had a complex genotype that included two novel point mutations c.529G>T and c.1250T>C resulting in FV E119X and FV I359T substitutions inherited on different alleles. Individuals in the kindred with FV E119X or FV I359T substitutions alone were asymptomatic. We suggest that the FV I359T substitution confers pro‐thrombotic risk and APCR, but that this is only clinically manifest when co‐inherited with the FV E119X allele. The FV I359T substitution creates a new consensus sequence for N‐linked glycosylation within the FV heavy chain and we speculate that this abnormal glycosylation may disrupt activated protein C‐mediated proteolysis of the variant FV and FVa.
Identification of the CD33‐related Siglec receptor, Siglec‐5 (CD170), as a useful marker in both normal myelopoiesis and acute myeloid leukaemias
Authors: Virgo Paul , Denning‐Kendall Patricia A. , Erickson‐Miller Connie L. , Singha Sakon , Evely Roger , Hows Jill M. , Freeman Sylvie D.
Published: October 2003

Summary. Sialic acid‐binding immunoglobulin‐like lectin (Siglec)‐5 or CD170 is a CD33‐related receptor, containing cytoplasmic immune receptor‐based tyrosine signalling motifs, that has previously been reported to be myeloid‐specific like CD33 and thus may be useful in the characterization of both normal and malignant haemopoiesis. This study showed that Siglec‐5 had a distinct expression pattern to CD33 both on normal myeloid cells and in acute myeloid leukaemia (AML). In normal bone marrow and cord blood, myeloid cells predominantly expressed Siglec‐5 at the later stages of granulocytic differentiation. Siglec‐5 was not expressed at significant levels by CD34+ progenitors either from bone marrow or mobilized peripheral blood. During in vitro myeloid differentiation of cord blood purified CD34+ cells, Siglec‐5 was upregulated later than CD33. Siglec‐5 expression remained absent or very low on cultured CD34+ cells, unlike CD33, which was present on almost all CD34+ cells by day 4. However, analysis of blasts from 23 patients with AML revealed aberrant expression of Siglec‐5 with CD34 in 50% (seven of 14) of patients with CD34+ AML; 61% (14 of 23) of AML cases were positive for Siglec‐5 with an increased frequency in the French–American–British subtypes M3‐5 (80%) compared with M0‐2 (25%). All 13 acute lymphoblastic leukaemic (ALL) samples tested, including a CD33+ ALL, were Siglec‐5 negative. These results support the further evaluation of Siglec‐5 antibodies in the diagnosis and monitoring of AML.
The clinical impact of expert pathological review on lymphoma management: a regional experience
Authors: Lester Jason F. , Dojcinov Stefan D. , Attanoos Richard L. , O'Brien Ciaran J. , Maughan Tim S. , Toy Elizabeth T. , Poynton Chris H.
Published: October 2003

Summary. The All Wales Lymphoma Panel (AWLP) was established in January 1998 to provide a central expert pathological review service for district general hospital pathologists. A discordance rate of 20% between the submitted and reviewed diagnosis has previously been identified. It has not been known whether this change in diagnosis affects clinical management. Ninety‐nine patients whose diagnosis was changed as a result of central pathological review are presented. Between January 1998 and August 2000, 125 of 745 (17%) specimens submitted for AWLP review had a consequent change in pathological diagnosis. Of these 125 specimens, 99 (79%) complete case notes were recovered. In all 99 cases, a hypothetical management plan was generated using collected data, clinical protocols and the submitted pathological diagnosis. These plans were compared with the actual management patients received based on the reviewed diagnosis proffered by the AWLP. Forty‐six of 99 (46%) cases had a change in management as a result of central pathological review. Overall, management was changed in 8% of cases referred for central pathological review. In conclusion, expert central pathological review has a direct effect on patient management.
Long‐term safety and feasibility of arteriovenous fistulae as vascular accesses in children with haemophilia: a prospective study
Authors: Santagostino Elena , Gringeri Alessandro , Berardinelli Luisa , Beretta Claudio , Muça‐Perja Myrvet , Mannucci Pier Mannuccio
Published: October 2003

Summary. Infectious and thrombotic complications limit the long‐term use of subcutaneous ports as venous accesses for children with haemophilia. This study has evaluated for the first time the safety and feasibility of internal arteriovenous fistulae (AVF) as alternative accesses. During the 3‐year study period, 27 severe haemophiliacs, 14 with factor VIII inhibitors (52%), underwent the creation of 31 proximal AVF in the forearm. Mild forearm haematomas were observed after five procedures (16%) in five patients who had or developed inhibitors after surgery. Inadequate AVF maturation was observed after five of 31 procedures (16%) in four children. AVF were first accessed after a median of 42 d and regularly used at home by 26 patients (96%) for a median follow‐up period of 29 months. Thrombosis of a venous branch occurred in one AVF (3%) after 9 months of uncomplicated use in a child with inhibitor who spontaneously recovered from the symptoms and still used AVF for nine additional months. Mild symptoms, referable to distal ischaemia, were transiently reported by two children (7%) who needed no remedial intervention. This study demonstrates that the use of AVF in haemophiliacs enabled long‐term treatment at home in all patients but one.
Progenitor cell involvement is predictive of response to induction chemotherapy in paediatric acute myeloid leukaemia
Authors: Johnston Donna L. , Meshinchi Soheil , Opheim Kent E. , Pallavicini Maria G. , Feusner James , Woods William G. , Lange Beverly J. , Radich Jerald P. , Bernstein Irwin D.
Published: October 2003

Summary. In acute myeloid leukaemia (AML), involvement of early progenitor cells may predict poor response to induction chemotherapy. We evaluated the involvement of early progenitor cells in two AML subtypes with a favourable prognosis [t(8;21) and t(15;17)], and a subtype with poor prognosis (monosomy  7). CD34+CD33− cells were isolated by fluorescence‐activated cell sorting, grown in liquid medium followed by culture in semi‐solid medium, and the colonies that were formed were analysed for the identifiable genetic markers. Two of 136 colonies from six t(8;21) AML patients expressed the AML1‐ETO transcript, and all six patients achieved remission after induction. None of 192 colonies from five t(15;17) AML patients expressed the RARα‐PML transcript and all achieved remission. In contrast, in three of 10 cases of monosomy  7 AML, colonies were positive for monosomy  7, and all three patients failed to enter remission. However, five of six evaluable patients with colonies negative for monosomy  7 entered remission. These data support the hypothesis that leukaemic involvement of early progenitor cells affects the response to induction chemotherapy.
Increased risk for vascular complications in PRV‐1 positive patients with essential thrombocythaemia
Authors: Johansson Peter , Ricksten Anne , Wennström Lovisa , Palmqvist Lars , Kutti Jack , Andréasson Björn
Published: October 2003

Summary. Essential thrombocythaemia (ET) is a heterogeneous disorder with respect to plasma erythropoietin concentration at diagnosis and clonality of haematopoiesis. Polycythaemia rubra vera‐1 (PRV‐1) positivity, i.e. PRV‐1 mRNA overexpression, is known to be present in the vast majority of patients with polycythaemia vera and also in some patients with ET. In the present study, PRV‐1 expression was quantified by real‐time polymerase chain reaction in 70 ET patients; 17 of them (24%) were found to be PRV‐1 positive. Ten of the 17 PRV‐1 positive ET patients had experienced thromboembolic complications compared with 14 of 53 PRV‐1 negative patients, the difference between the two groups being statistically significant (P = 0·02). In addition, the frequency of total vascular complications, thromboembolic events and major bleedings, was significantly higher in the group of PRV‐1 positive as compared with PRV‐1 negative ET patients (P = 0·03). The time from diagnosis of ET to the requirement of platelet‐lowering therapy was significantly shorter in PRV‐1 positive compared with PRV‐1 negative ET patients (P = 0·014). It can be concluded that PRV‐1 positive patients appear to suffer from a more aggressive disorder with increased risk for vascular complications and a greater need for platelet‐lowering therapy, compared with PRV‐1 negative ET patients.
Central venous catheter related thrombosis in haematology patients and prediction of risk by screening with Doppler‐ultrasound
Authors: Van Rooden Cornelis J. , Rosendaal Frits R. , Barge Renée M. Y. , Van Oostayen Jacques A. , Van Der Meer Felix J.M. , Meinders A. Edo , Huisman Menno V.
Published: October 2003

Summary. Patients with a central venous catheter (CVC) who receive intensive chemotherapy or a stem cell transplantation for haematological disease are at risk for developing CVC‐related thrombosis. To study the incidence of thrombosis, 105 consecutive patients underwent serial Doppler‐ultrasound and we evaluated whether clinically manifest thrombosis could be predicted by screening with Doppler‐ultrasound. Patients with subclavian or jugular inserted CVCs were clinically assessed each day for signs and symptoms of thrombosis. Additional Doppler‐ultrasound screens were performed weekly by an independent physician in all patients until CVC removal. Doppler‐ultrasound recordings were assessed by two blinded observers. In cases of clinically suspected thrombosis, the attending physicians followed routine diagnostic and therapeutic procedures. The overall cumulative incidence of CVC‐related thrombosis was 28·6% (30 of 105 patients). Of the 30 patients with thrombosis, 26 had subclinical thrombosis by Doppler‐ultrasound, nine of whom developed clinically manifest thrombosis later. Four patients had clinically manifest thrombosis without prior abnormal Doppler‐ultrasound. In cases of subclinical thrombosis the risk of developing symptomatic disease increased sevenfold (34·6% vs. 5·1%). Doppler‐ultrasound screening may be useful to identify those patients that are at high and low risk for clinically manifest CVC‐related thrombosis.