bluuebunny/crossref_metadata_2025 huggingface dataset:
Co‐administration of Flt‐3 ligand counteracts the actions of thrombopoietin in myelosuppressed rhesus monkeys
Authors: Hartong Simone C. C. , Neelis Karen J. , Wagemaker Gerard
Published: December 2004

Summary. This placebo‐controlled study evaluated the efficacy of Flt‐3 ligand (FL) combined with TPO in myelosuppressed rhesus monkeys. The monkeys were subjected to 5 Gy total body irradiation (TBI), resulting in 3 weeks of profound pancytopenia, and received either 5 µg/kg of rhesus TPO i.v. on d 1 (n = 4) and 100 µg/kg/d s.c. human FL (n = 4) or FL alone (n = 4) for 14 consecutive days and were compared with results from a concomitant study involving the administration of TPO alone (n = 4) or placebo (carrier; n = 4). The TPO/FL combination was considerably less effective than TPO alone, with a more profound nadir and a slower recovery to thrombocyte counts > 100 × 109/l, approaching recovery patterns of placebo controls. Leucocyte regeneration was similar in all animals. Monkeys treated with FL alone displayed a regeneration of reticulocytes and thrombocytes in the lower range of those of the placebo controls. Recovery of bone marrow (BM) cellularity was slightly accelerated in the TPO/FL‐treated monkeys, but was not reflected by an increase in progenitor cells, in contrast to TPO alone. Monkeys treated with FL alone showed a BM reconstitution similar to placebo‐treated controls. FL by itself was not effective as a therapeutic agent in this model for myelosuppression. As FL also suppressed BM CD34+ cell reconstitution, we concluded that FL competed with TPO at the level of immature cell differentiation.
Adult bone marrow is a rich source of human mesenchymal ‘stem’ cells but umbilical cord and mobilized adult blood are not
Authors: Wexler Sarah A. , Donaldson Craig , Denning‐Kendall Patricia , Rice Claire , Bradley Ben , Hows Jill M.
Published: December 2004

Summary. In postnatal life, mesenchymal stem cells (MSC) self‐replicate, proliferate and differentiate into mesenchymal tissues, including bone, fat, tendon, muscle and bone marrow (BM) stroma. Possible clinical applications for MSC in stem cell transplantation have been proposed. We have evaluated the frequency, phenotype and differentiation potential of MSC in adult BM, cord blood (CB) and peripheral blood stem cell collections (PBSC). During culture, BM MSC proliferated to confluence in 10–14 d, maintaining a stable non‐haemopoietic phenotype, HLA class‐1+, CD29+, CD44+, CD90+, CD45–, CD34– and CD14 through subsequent passages. Using the colony forming unit fibroblasts assay, the estimated frequency of MSC in the BM nucleated cell population was 1 in 3·4 × 104 cells. Both adipogenic and osteogenic differentiation of BM MSC was demonstrated. In contrast, CB and PBSC mononuclear cells cultured in MSC conditions for two passages produced a population of adherent, non‐confluent fibroblast‐like cells with a haemopoietic phenotype, CD45+, CD14+, CD34–, CD44–, CD90– and CD29–. In paired experiments, cultured BM MSC and mature BM stroma were seeded with CB cells enriched for CD34+. Similar numbers of colony‐forming units of granulocytes–macrophages were produced by MSC‐based and standard stroma cultures over 10 weeks. We conclude that adult BM is a reliable source of functional cultured MSC, but CB and PBSC are not.
Relationships between the N‐glycan structures and biological activities of recombinant human erythropoietins produced using different culture conditions and purification procedures
Authors: Yuen Chun‐Ting , Storring Patrick L , Tiplady Richard J. , Izquierdo Mabel , Wait Robin , Gee Christopher K. , Gerson Peter , Lloyd Pauline , Cremata Jos A.
Published: December 2004

Summary. Eight preparations of recombinant human erythropoietin (EPO) with differing isoform compositions were produced by using different culture conditions and purification procedures. The N‐glycan structures of these EPOs were analysed using a recently developed profiling procedure and identified using matrix‐assisted laser desorption ionization mass spectrometry. The specific activities of each of the EPOs were estimated by in vivo and in vitro mouse bioassays. The eight EPOs were found to differ in their isoform compositions (as judged by isoelectric focusing), their N‐glycan profiles, and in their in vivo and in vitro bioactivities. N‐glycan analyses identified at least 23 different structures among these EPOs, including bi‐, tri‐ and tetra‐antennary N‐glycans, with or without fucosylation or N‐acetyllactosamine extensions, and sialylated to varying degrees. Mass spectrometry also indicated the presence of N‐glycans with incomplete outer chains, terminating in N‐acetylglucosamine residues, and of molecular masses consistent with phosphorylated or sulphated oligomannoside structures. The tetrasialylated tetra‐antennary N‐glycan contents of the eight rEPOs were found to be significantly and positively correlated with their specific activities as estimated by mouse in vivo bioassay, and significantly and negatively correlated with their specific activities as estimated by mouse in vitro bioassay. It was concluded that the tetrasialylated tetra‐antennary N‐glycan content of EPO is a major determinant for its in vivo biological activity in the mouse.
Galactomannan detection in computerized tomography‐based broncho‐alveolar lavage fluid and serum in haematological patients at risk for invasive pulmonary aspergillosis
Authors: Becker Martin J. , Lugtenburg Elly J. , Cornelissen Jan J. , Van Der Schee Cindy , Hoogsteden Henk C. , De Marie Siem
Published: December 2004

Summary. We determined the value of galactomannan (GM) detection in computerized tomography (CT)‐based broncho‐alveolar lavage (BAL) fluid and serum for the diagnosis of invasive pulmonary aspergillosis (IPA) in haemato‐oncological patients with neutropenia. CT of the thorax and BAL were performed systematically at predefined clinical indications. GM was determined by sandwich enzyme‐linked immunosorbent assay; the clinicians were unaware of the results. Of 160 patients, 17 patients (10·6%) presented with proven, probable or suspected IPA. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of GM detection in CT‐based BAL fluid were all 100%. For GM detection in serially sampled serum, the sensitivity was 47%, the specificity 93%, the PPV 73% and the NPV 82%. A non‐blinded follow‐up study was performed to validate these results. In this study, 22 of 198 patients (11·1%) presented with IPA, and the sensitivity, specificity, PPV and NPV of GM detection in CT‐based BAL fluid were 85%, 100%, 100% and 88% respectively. None of BAL fluids obtained after antifungal treatment of 3 d or more were positive. These results indicate that, when CT is used systematically and at an early stage, GM detection in CT‐based BAL fluid has a high PPV for diagnosing IPA early in untreated patients.
Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group
Authors:   The International Myeloma Working Group
Published: December 2004

Summary. The monoclonal gammopathies are a group of disorders associated with monoclonal proliferation of plasma cells. The characterization of specific entities is an area of difficulty in clinical practice. The International Myeloma Working Group has reviewed the criteria for diagnosis and classification with the aim of producing simple, easily used definitions based on routinely available investigations. In monoclonal gammopathy of undetermined significance (MGUS) or monoclonal gammopathy, unattributed/unassociated (MG[u]), the monoclonal protein is < 30 g/l and the bone marrow clonal cells < 10% with no evidence of multiple myeloma, other B‐cell proliferative disorders or amyloidosis. In asymptomatic (smouldering) myeloma the M‐protein is ≥ 30 g/l and/or bone marrow clonal cells ≥ 10% but no related organ or tissue impairment (ROTI)(end‐organ damage), which is typically manifested by increased calcium, renal insufficiency, anaemia, or bone lesions (CRAB) attributed to the plasma cell proliferative process. Symptomatic myeloma requires evidence of ROTI. Non‐secretory myeloma is characterized by the absence of an M‐protein in the serum and urine, bone marrow plasmacytosis and ROTI. Solitary plasmacytoma of bone, extramedullary plasmacytoma and multiple solitary plasmacytomas (± recurrent) are also defined as distinct entities. The use of these criteria will facilitate comparison of therapeutic trial data. Evaluation of currently available prognostic factors may allow better definition of prognosis in multiple myeloma.
Clinical relevance of balance between type 1 and type 2 immune responses of lymphocyte subpopulations in aplastic anaemia patients
Authors: Giannakoulas Nikolaos C. , Karakantza Marina , Theodorou Georgios L. , Pagoni Maria , Galanopoulos Athanasios , Kakagianni Theodora , Kouraklis‐Symeonidis Alexandra , Matsouka Panagiota , Maniatis Alice , Zoumbos Nicholas C.
Published: December 2004

Immune dysfunction, which leads to the suppression of haemopoiesis by cytokines that are secreted by activated T lymphocytes, is considered to play a key role in the pathogenesis of acquired aplastic anaemia (AAA).

We investigated the intracytoplasmic expression of type‐1 [interferon γ (IFN‐γ), interleukin (IL)‐2] and type‐2 (IL‐4, IL‐10) cytokines in CD4+ and CD8+ T cells before and after in vitro activation in 16 patients with AAA and 17 normal controls. Untreated or refractory patients had a significantly higher proportion of unstimulated CD4+ and CD8+ T cells that produced IFN‐γ and IL‐2 whereas the IL‐4 and IL‐10 producing T cells did not differ from that of controls, resulting in a shift of IFN‐γ/IL‐4 ratio towards a type‐1 response. Patients in remission had also increased proportion of IFN‐γ‐producing unstimulated CD4+ and CD8+ cells, with a parallel rise of IL‐4‐ and IL‐10‐producing cells and normal IFN‐γ/IL‐4 ratio. These data indicate that, in newly diagnosed and refractory patients with AAA, CD4+ cells are polarized towards a type‐1 response that in turn leads to activation of cytotoxic CD8+ cells and finally to haemopoietic stem cell destruction. The type‐1 response persists in patients in remission although this effect is compensated by the increase of IL‐4 and IL‐10 production.
A population based, unselected, consecutive cohort of patients with acquired haemophilia A
Authors: Collins Peter , Macartney Nicola , Davies Richard , Lees Steven , Giddings John , Majer Ray
Published: December 2004

Previous studies in acquired haemophilia A have reported on cohorts of patients referred to specialist centres or were retrospective surveys of specialist centre experience. This may have resulted in the literature representing a more severe group of patients than seen in routine haematological practice. We report on a consecutive, unselected cohort of all patients in south and west Wales who presented with acquired haemophilia A between 1996 and 2002. There were 18 patients, an incidence of 1·34/million/year. Compared with previously reported cohorts our patients were older, with a median age of 70 years, and less likely to have an underlying diagnosis (27%). The bleeding phenotype was less severe, with only 27% having life or limb threatening bleeds and 41% required no haemostatic treatment. One patient died of bleeding, but three died of complications related to immunosuppression. Response to immunosuppression was high compared with other series, with 88% of treated patients attaining an undetectable inhibitor and normal factor VIII level. These data suggest that previously reported cohorts may represent more severely affected patients and, whilst guidelines for treatment based on these assumptions may be valid for severely affected patients, they may not be universally applicable.
Hepatocellular carcinoma in the thalassaemia syndromes
Authors: Borgna‐Pignatti Caterina , Vergine Gianluca , Lombardo Turi , Cappellini Maria Domenica , Cianciulli Paolo , Maggio Aurelio , Renda Disma , Lai Maria Eliana , Mandas Antonella , Forni Gianluca , Piga Antonio , Bisconte Maria Grazia
Published: December 2004

Hepatocellular carcinoma (HCC) frequently complicates hepatic cirrhosis secondary to viral infection or iron overload. Therefore, patients affected by thalassaemia syndromes have a theoretically high risk of developing the tumour. We collected data on patients attending Italian centres for the treatment of thalassaemia. Twenty‐two cases of HCC were identified; 15 were male. At diagnosis, the mean age was 45 ± 11 years and the mean serum ferritin was 1764 ± 1448 μg/l. Eighty‐six percent had been infected by hepatitis C virus. Nineteen of 22 cases were diagnosed after 1993, suggesting that this problem is becoming more frequent with the aging population of thalassaemia patients.
Molecular mimicry by Helicobacter pylori CagA protein may be involved in the pathogenesis of H. pylori‐associated chronic idiopathic thrombocytopenic purpura
Authors: Takahashi Toru , Yujiri Toshiaki , Shinohara Kenji , Inoue Yusuke , Sato Yutaka , Fujii Yasuhiko , Okubo Masashi , Zaitsu Yuzuru , Ariyoshi Koichi , Nakamura Yukinori , Nawata Ryouhei , Oka Yoshitomo , Shirai Mutsunori , Tanizawa Yukio
Published: December 2004

The eradication of Helicobacter pylori often leads to platelet recovery in patients with chronic idiopathic thrombocytopenic purpura (cITP). Although this clinical observation suggests the involvement of H. pylori, little is known about the pathogenesis of cITP. We initially examined the effect of H. pylori eradication on platelet counts in 20 adult Japanese cITP patients. Then, using platelet eluates as the probe in immunoblot analyses, we examined the role of molecular mimicry in the pathogenesis of cITP. Helicobacter pylori infection was detected in 75% (15 of 20) of cITP patients. Eradication was achieved in 13 (87%) of the H. pylori‐positive patients, seven (54%) of which showed increased platelet counts within the 4 months following treatment. Completely responsive patients also showed significant declines in platelet‐associated immunoglobulin G (PAIgG) levels. Platelet eluates from 12 (nine H. pylori‐positive and three H. pylori‐negative) patients recognized H. pylori cytotoxin‐associated gene A (CagA) protein, and in three completely responsive patients, levels of anti‐CagA antibody in platelet eluates declined after eradication therapy. Cross‐reactivity between PAIgG and H. pylori CagA protein suggests that molecular mimicry by CagA plays a key role in the pathogenesis of a subset of cITP patients.
FcγRIIB is differentially expressed during B cell maturation and in B‐cell lymphomas
Authors: Camilleri‐Broët Sophie , Cassard Lydie , Broët Philippe , Delmer Alain , Touneau Agnès Le , Diebold Jacques , Fridman Wolf Herman , Molina Thierry Jo , Sautès‐Fridman Catherine
Published: December 2004

FcγRIIB, a low affinity receptor for the Fc portion of immunoglobulin G (IgG), is thought to drive negative selection of B cells in germinal centers (GC) by inducing apoptosis upon interaction with immune complexes. Its expression was investigated by immunohistochemistry in 22 reactive lymphoid tissues and 112 B‐cell lymphomas. Pre‐GC mantle cells, marginal zone cells and their neoplastic counterparts expressed FcγRIIB. The B chronic lymphocytic leukaemia (B‐CLL)/small lymphocytic lymphomas were also positive. Not detected in GC, FcγRIIB was expressed in 52% of follicular lymphomas and in 20% of diffuse large B cell lymphomas (DLBCL). In DLBCL, FcγRIIB expression was linked to transformation (P < 0·001). Re‐analysis of a gene profile data set from the Lymphochip microarrays showed that FcγRIIB expression in the activated B‐like DLBCL subgroup was higher than in the GC‐like one (P < 0·04), and was associated with an adverse prognostic both in univariate (P < 0·003) and in multivariate analysis including the International Prognostic Indicator (IPI) (P < 0·01). Thus these results challenge the potential role of FcγRIIB during B‐cell selection in GC, and suggest a prognostic value of FcγRIIB expression in DLBCL.
Investigating the proximal limit of lymphadenectomy in patients with adenocarcinoma of the oesophagus in the mid-thoracic region
Authors: Vickery C W , Hollowood A D , Barham C P , Hardwick R H , Alderson D
Published: December 2004

Aims

The benefit of extended lymphadenectomy in patients with squamous cell carcinoma of the oesophagus is established, but there is little evidence to support this in patients with adenocarcinoma. The aim of this study was to investigate the extent of lymphatic spread of oesophageal adenocarcinomas, and particularly the proximal spread in tumours located in the mid thorax.

Methods

Twenty-six consecutive patients with tumours arising between 29 and 35 cm from the incisor teeth underwent three-stage oesophagectomy with two-field lymphadenectomy, including nodes in the recurrent laryngeal chains. The proximal extent was measured by endoscopic ultrasonography and confirmed at operation, with division of the lymph node harvest into anatomical sites according to the Japanese classification of oesophageal cancer.

Results

There were 21 men and five women, with a mean age of 64 (range 42–78) years; seven patients were lymph node negative in both the mediastinal and abdominal fields. Six patients had nodal metastases more than 2 cm above the tumour and all had extensive involvement of other nodes at the level of the tumour or below, with 7, 7, 9, 12, 15 and 18 nodes positive. There were no patients in whom nodes above the tumour contained metastases while those at the level or below were clear.

Conclusions

Dissection of proximal lymph nodes along the recurrent laryngeal nerve chains in patients with adenocarcinoma of the oesophagus is not warranted. Lymphatic spread above the level of the tumour occurs in association with extensive lymph node involvement elsewhere and removal of proximal nodes from difficult locations is not warranted as a means of improving staging or survival.
Exercise in claudicants is associated with systemic fibrinolysis
Authors: Evans S M , Haggart P C , Ludlam C A , Bradbury A W
Published: December 2004

Background

Claudicants have been shown to mount a potentially harmful systemic inflammatory response to exercise, characterized by vascular endothelial activation and thrombin generation. However, the fibrinolytic response to exercise remains unknown. This study aimed to determine the nature of the fibrinolytic response to exercise in claudicants and normal controls.

Methods

Peripheral venous blood was drawn from 18 claudicants and eight age- and sex-matched controls before, immediately and 1, 5, 10, 20, 40 and 60 min after treadmill exercise (Gardner protocol). Claudicants exercised to the point of maximal ischaemic pain and controls to the point of fatigue. Plasma tissue plasminogen activator (tPA) activity and plasminogen activator inhibitor (PAI) 1 activity were measured by ‘Coaset’ PAI and ‘Coatest’ tPA assays (Chromogenix, Sweden).

Results

There was no significant difference in tPA or PAI-1 activity between the groups at baseline. tPA activity increased significantly immediately after exercise in all claudicants (median (interquartile range) 2·8 (1·6–4·0) versus 5·6 (3·5–7·7) units ml−1; P = 0·003, Wilcoxon test) and remained significantly raised for 10 min. This was accompanied by an immediate significant fall in PAI-1 activity (8·5 (4·3–12·7) versus 8·3 (5·0–11·6) units ml−1; P = 0·04) which normalized by 10 min. Neither tPA activity or PAI-1 levels changed significantly in the control group.

Conclusion

These data indicate that exercise in claudicants is associated with systemic fibrinolysis. The immediacy and short-lived nature of the response suggests that it occurs as a consequence of muscle ischaemia rather than reperfusion.
Relationship between lower limb symptoms and patterns of deep and superficial venous reflux on duplex ultrasonography
Authors: Bradbury A W , Evans C J , Allan P L , Lee A J , Ruckley C V , Fowkes F G R
Published: December 2004

Background

There are inconsistent and sex-dependent relationships between lower limb symptoms and the presence and severity of trunk varicose veins on clinical examination. The relationship between lower limb symptoms and patterns of venous reflux on duplex ultrasonography were investigated.

Methods

This was a cross-sectional study of an age-stratified random sample of 1566 subjects (699 men and 867 women) aged 18–64 years selected from 12 family practices. Subjects completed a self-administered questionnaire regarding symptoms (heaviness/tension, a feeling of swelling, aching, restless legs, cramps, itching, tingling) and underwent duplex ultrasonographic examination of both legs. Reflux greater than 0·5 s was considered pathological.

Results

Isolated superficial reflux was significantly related to the presence of heaviness/tension (P < 0·025, both legs) and itching (P = 0·002, left leg only) in women. Isolated deep venous reflux was not significantly related to any symptom in either leg in either sex. Combined superficial and deep reflux was related to a feeling of swelling (P = 0·02, both legs), cramps (P < 0·005, left leg only) and itching (P < 0·005, left leg only) in men, and aching (P = 0·03, right leg only) and cramps (P = 0·026, left leg only) in women.

Conclusion

Duplex ultrasonography may be superior to clinical examination alone in identifying patients whose lower limb symptoms are truly of venous origin and thus most likely to benefit from surgery.
Prospective, multicentre audit of complex vascular wound and graft infections: the impact of methicillin-resistant Staphylococcus aureus
Authors: Hayes P D , Darke S , Naylor A R
Published: December 2004

Background

A number of studies have looked at the outcome of vascular graft infections, but these often include small numbers of patients collected over a prolonged period of changing practice. Many of these studies do not contain cases of methicillin-resistant Staphylococcus aureus (MRSA).

Methods

Between February 1998 and January 1999, a prospective, multicentre audit was performed in order to examine the outcome of complex wound and graft infections in vascular surgery, with particular reference to MRSA.

Results

Some 66 grade II or III Szilagyi wound infections occurred. Overall, 23 per cent of type II infections progressed to graft infection. Of those with type III infections, 83 per cent had an adverse outcome (death, major amputation or ongoing infection). No vein graft became infected, but 12 of 38 prosthetic grafts were affected. MRSA accounted for 42 per cent of infections and was present in 67 per cent of patients with an adverse outcome. Adverse events occurred in 32 per cent of MRSA cases and in 10 per cent of non-MRSA cases (P = 0·04). Wound infection proceeded to graft infection in 58 per cent of MRSA cases and in 32 per cent of non-MRSA cases (P = 0·08). Seven of eight patients with MRSA before operation developed postoperative MRSA infection. Median length of stay was 31 days for MRSA versus 18 days for non-MRSA infections (P = 0·001). Forty-three graft infections occurred; 12 were associated with a complex wound infection. Median time to presentation was 39 (range 2–2450) days. There were 16 deaths, nine major limb amputations and three ongoing infections among patients with a graft infection. The median length of stay was 36 days. MRSA was present in 36 per cent of all graft infections. Only one of these infections involved a vein graft (P = 0·001). MRSA infection occurred more frequently where the primary procedure had been urgent rather than elective (P = 0·03). MRSA graft infection accounted for seven of the nine major limb amputations. The median length of stay in patients with MRSA graft infection was 25 days longer (P = 0·001).

Conclusion

Complex wound and graft infections continue to be associated with postoperative deaths and amputations. MRSA infection is now the most common organism involved in complex infections following vascular procedures. It is associated with an increase in the number of adverse outcomes and a significant increase in length of stay.
Effect of carotid endarterectomy on cognitive function: long-term follow-up
Authors: Lloyd A J , Hayes P D , Naylor A R , Bell P R F
Published: December 2004

Background

Long-term effects of carotid endarterectomy (CEA) on cognitive function are not known. Evidence suggests that perioperative embolization may disrupt cognitive function in the short term.

Methods

A controlled study was conducted to examine the cognitive function of 109 patients undergoing CEA before and at 6 months after operation (n = 100). The objective validated psychometric tests assessed attention, memory, language and visuospatial skills. Perioperative embolization was determined using transcranial Doppler ultrasonography.

Results

Patients who were spontaneously embolizing before operation had significant preoperative cognitive impairment (P = 0·03). The controlled cognitive function tests showed no evidence of a cognitive deficit 6 months after CEA. The total number of emboli detected for each patient ranged from 0 to 700 (mean 32). There was no evidence of a significant correlation between the number of emboli detected during CEA and change in cognitive function (r = 0·07).

Conclusion

CEA is not associated with worsening cognitive impairment. Asymptomatic perioperative microembolization has no long-term effect on cognitive function.
Synergistic effects of tumour necrosis factor α and lymphotoxin α during lethal endotoxaemia
Authors: Netea M G , Kullberg B J , Verschueren I , Van der Meer J W M
Published: December 2004

Background

Tumour necrosis factor (TNF) α and lymphotoxin (LT) α are members of the TNF family which bind to the same receptors and which play a crucial role in the modulation of the immune response. Their differential and possible redundant roles during lethal endotoxaemia have been investigated in mice deficient in either TNF-α (TNF–/–) or TNF-α and LT-α (TNF–/– LT–/– double knockout) mice.

Methods

TNF–/– or TNF–/– LT–/– mice were injected intravenously with Escherichia coli lipopolysaccharide (LPS) 1 or 2 mg per mouse. Circulating levels of interleukin (IL) 1α and 1β were measured 3 h after the LPS challenge, and mortality rates were calculated.

Results

When LPS 1 mg per mouse was used, 80 per cent of the wild-type mice succumbed, whereas none of the TNF–/– or TNF–/– LT–/– mice died (P < 0·01). However, when LPS 2 mg per mouse was administered, the mortality rate in the control and TNF–/– mice was 100 per cent, whereas none of the TNF–/– LT–/–mice died (P < 0·01), suggesting that the absence of LT-α has an additional protective effect in lethal endotoxaemia. In comparison to the wild-type control mice, 3 h after the LPS challenge, the circulating concentrations of IL-1α were 47 and 55 per cent lower in the TNF–/– and TNF–/– LT–/–mice respectively. Moreover, circulating concentrations of IL-1β were 40 per cent lower in the TNF–/– mice, but 71 per cent lower in the TNF–/– LT–/– mice compared with the wild-type controls.

Conclusion

TNF-α and LT-α act synergistically during lethal endotoxaemia, and immunomodulation of both TNF-α and LT-α should be considered in experimental and clinical settings.
Infrainguinal reconstruction with endoscopically harvested saphenous vein
Authors: Holdsworth R J
Published: December 2004

Background

Endoscopic saphenous vein harvesting is gaining popularity in cardiac units because of a perceived reduction in lower limb wound complications. The requirements of the cardiac surgeon for saphenous vein differ from that of the peripheral vascular surgeon in that longer individual vein grafts are required for peripheral reconstruction.

Methods

Endoscopic vein harvest has been evaluated in the reconstruction of 36 legs. Vein was harvested successfully in all cases, although major vein damage occurred in one patient. All veins were reversed and routed through a new tunnel, and used for 18 above-knee femoropopliteal bypasses, 12 below-knee femoropopliteal bypasses, four distal and two pedal grafts. Mean follow-up was 20 (range 3–36) months.

Results

There were six graft occlusions, two in the immediate postoperative period, two at 1 month and two late closures at 1 year. Three patients had wound infections, two had significant haematomas and four had problematic oedema after operation. Postoperative stay was 2–18 days, with 17 patients being discharged within 5 days and 28 within 9 days.

Conclusion

Although this technique can be used successfully for vein harvesting, the immediate impact on patient morbidity and postoperative stay is only marginal and probably does not justify the increased cost of the procedure.
Midterm follow-up of 1000 patients in the Registry of Endovascular Treatment of Abdominal Aortic Aneurysms (RETA)
Authors: Thomas S M , Gaines P A , Beard J D
Published: December 2004

Background

The aim was to present the midterm follow-up data of patients in the Registry of Endovascular Treatment of Abdominal Aortic Aneurysms (RETA).

Methods

RETA now has a cohort of 1000 registered patients. Follow-up data are available for 483 patients at 1 year (80·8 per cent follow-up rate), 191 at 2 years (78·0 per cent follow-up rate) and 64 at 3 years (64·0 per cent follow-up rate).

Results

The mortality rates were 10·8, 12·6 and 6·3 per cent at 1, 2 and 3 years' follow-up respectively. The majority of deaths at follow-up were unrelated to the endovascular aneurysm repair. However, ruptures have occurred, with five (1·0 per cent) occurring in the first year of follow-up and three (1·6 per cent) reported in the second year of follow-up. This gives a cumulative risk of rupture of 1·0 per cent at 1 year and 2·6 per cent at 2 and 3 years. Three of the ruptures had persisting primary proximal endoleaks and two had documented secondary endoleaks. Complications related to the aneurysm or device occurred in 11·1, 14·8 and 12·8 per cent of cases at 1, 2 and 3 years' follow-up. The commonest problems were secondary endoleaks, although most of these had successful endovascular treatment. Graft or limb occlusions were the next most common problems. Follow-up of patients having secondary procedures with endovascular treatment suggests these treatments are durable, although the numbers at present are small. The cumulative endoleak-free survival rate was 73·4, 57·9 and 49·9 per cent, and the cumulative freedom from endoleak rate was 88·3, 81·2 and 75·6 per cent at 1, 2 and 3 years' follow-up respectively.

Conclusion

Most deaths occurring at follow-up are not related to the aortic aneursyms. Ruptures have occurred, some related to primary proximal type I endoleaks. Others may be related to secondary endoleaks that have not been detected. Late complications related to the device or aneurysm occur at a rate of about 10 per cent per year. Most frequently these are new endoleaks and are amenable to endovascular treatment, but recurrence may occur, so continued surveillance is necessary.
Successful subintimal angioplasty for leg ischaemia is dependent on length of occlusion, not site of lesion
Authors: Boyle J R , Perry D , Gonem N , Cowan A R , Sutton G L , Pemberton R M
Published: December 2004

Background

The development of subintimal angioplasty offers an endovascular approach to the treatment of long occlusions not suitable for conventional transluminal angioplasty; it remains, however, the remit of relatively few radiologists in specialist centres. The authors have adopted the technique in view of promising published results.

Methods

Between May 1997 and July 2000, 50 patients had attempted subintimal angioplasty (median age 71 (interquartile range (i.q.r.) 61–80) years). Patients were divided into two groups by length of occlusion; 26 patients (group 1) had occlusions greater than 10 cm in length (iliac, one; superficial femory artery (SFA), 24; crural, one) and 24 patients (group 2) had occlusions of less than 10 cm (iliac, five; SFA, five; popliteal, nine; crural, five). The primary technical success rate, ankle: brachial pressure index (ABPI) before and after the procedure, complication rate and symptomatic improvement were recorded for both groups.

Results

The groups were well matched for age and indication for intervention. Primary technical success was significantly better for occlusions of less than 10 cm than for the longer lesions (83 versus 50 per cent; P < 0·01) with corresponding significantly greater rises in ABPI (P < 0·05). Complications included one death in each group, one amputation in group 2 and six in group 1, all after failed salvage grafts.

Conclusion

Subintimal angioplasty gives excellent results for occlusions of less than 10 cm in length irrespective of arterial site. Results for longer lesions are poor, with failed subintimal angioplasty often precipitating urgent distal vascular reconstruction and associated high risk of major amputation.
Thoracic stent grafts
Authors: Gerrard D J , McGuinness C L , Sabharwal T , Reidy J F , Taylor P R
Published: December 2004

Background

The Endovascular Aneurysm Repair trial of infrarenal aortic aneurysm repair requires 20 operations to be performed at each centre to eliminate learning curve errors. An analysis was undertaken of the authors' learning curve experience of commercially made thoracic stent grafts.

Methods

Stent grafting was attempted in 26 patients. Aortic pathology included 13 atheromatous aneurysms, six dissections, one coarctation, three false aneurysms and three transections. Successful deployment was performed in 24 patients (92 per cent), but failed in two women due to small iliac arteries. Stent grafts used were Gore Excluder (16 patients), AneuRx (six), Vanguard (one) and Stenford (one). Four patients required two stents, two needed three stents, and 18 had a single stent.

Results

Thirteen elective procedures were uneventful. Two deaths occurred in 11 urgent procedures, from pulmonary embolism and aortic rupture of an unsuspected false aneurysm. The overall in-hospital mortality rate was 8 per cent (two of 24 patients). One graft with a persistent endoleak was removed at open repair at 6 weeks. The subclavian artery origin was covered in three elderly patients, resulting in minor distal ischaemia. No spinal cord problems were seen. One patient died from pneumonia at 8 weeks, and another died from rupture at 28 months as a result of prolapse of the stent into the aneurysm sac.

Conclusion

Assessment of the diameter of the iliac arteries is important, especially in women, to ensure that they accommodate the size of the sheath. Patients with false aneurysms have a poor outcome, and treatment by stent grafting may not be durable. Covering the origin of the left subclavian artery can be undertaken in elderly patients with transient minor symptoms. The use of stent grafts in acute type B dissection should be the subject of a randomized trial. Continued surveillance is essential.
Assessment of degree of internal carotid artery stenosis based on duplex velocity measurements using an artificial neural network
Authors: Mofidi R , Brabazon A , Powell T , Hurson C , Sheehan S , Mehigan D , MacErlaine D , Keaveny T V
Published: December 2004

Background

Duplex imaging is increasingly used as a stand-alone investigation before carotid endarterectomy. There is concern regarding the wide variation in diagnostic methods of grading internal carotid artery (ICA) stenosis using duplex velocity criteria. The aim of the study was to design an artificial neural network (ANN) that is able to provide a measure of the degree of ICA stenosis based on the four most commonly used duplex velocity profiles.

Methods

One hundred and four consecutive patients who were admitted for assessment of carotid occlusive disease were included. All patients underwent arch injection digital subtraction angiography and carotid duplex ultrasonography. Peak systolic velocity (PSV) and end-diastolic velocity (EDV) in the ICA and common carotid artery (CCA) were measured. The degree of angiographic stenosis was measured by two blinded investigators. A three-layered perceptron ANN was constructed using the NeuroSolutionsTM version 1 software program (NeuroDimension, Gainesville, FL, USA). The accuracy of the model in predicting the degree of ICA stenosis was expressed as the mean squared error (MSE) of the actual degree of angiographic stenosis. The performance of the neural network model was compared with that of the linear regression model at predicting the degree of ICA stenosis and classifying a degree of ICA stenosis greater than 50 per cent.

Results

One hundred and sixty-eight carotid bifurcations were available for analysis. The MSE of the ANN at predicting the degree of ICA stenosis was 0·096 (overall accuracy of 84 per cent), which was superior to a linear regression model (MSE 0·132; overall accuracy 73 per cent) (P < 0·001). Both models were equally accurate at identifying a degree of ICA stenosis greater than 50 per cent (ANN accuracy 0·91 versus regression model accuracy 0·89; P = 0·09).

Conclusion

Neural network algorithms are able to predict the degree of ICA stenosis with reasonable accuracy and outperform linear regression analysis on the basis of a limited set of duplex velocity measurements. With further refinement, ANN models could replace duplex criteria in assessment of the degree of ICA stenosis.
A carotid POSSUM model for predicting death
Authors: Kuhan G , Prytherch D , Sutton G L , Payne S P , Chetter I , Abidia A , McCollum P T
Published: December 2004

Background

Risk adjustment to allow for differences in case mix aids comparative audit of carotid endarterectomy (CEA). The aim of this study was to test the predictive accuracy of P-POSSUM (Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity – Portsmouth predictor equation for mortality) and V-POSSUM (P-POSSUM-based model for vascular surgery) and to develop a procedure-specific model for CEA.

Methods

A total of 709 CEAs performed in two vascular units from 1992 to 2000 were analysed. The physiological and the operative severity scores were calculated; the outcome used was 30-day mortality. Predicted mortality was calculated using P-POSSUM, V-POSSUM and V-POSSUM (physiology only = PS) equations. The observed and the predicted mortality were compared. The new model was developed on a set of 350 CEAs and validated on 359 CEAs. The data sets of the two units were combined and split into two by the procedure date order. The predictive accuracy of the model was analysed with the χ2 test.

Results

P-POSSUM and V-POSSUM models showed lack of fit in predicting death.

There was no evidence of any lack of fit in the new model.

Conclusion

P-POSSUM and V-POSSUM overpredict mortality and are unsuitable for the comparative audit of CEA. Procedure-specific models based on P-POSSUM can accurately predict death.
Length of the antral segment in pylorus-preserving gastrectomy
Authors: Nakane Y , Michiura T , Inoue K , Sato M , Nakai K , Yamamichi K
Published: December 2004

Background

Pylorus-preserving gastrectomy (PPG) has the advantages of preventing dumping syndrome and duodenogastric reflux. However, time was required to reduce symptoms of gastric fullness or to improve food intake after surgery. The aim of this study was to investigate whether the length of the retained antral segment influenced the postoperative symptoms in patients who underwent PPG.

Methods

Thirty patients with early gastric cancer who underwent PPG were divided into two groups according to the length of the retained antrum. In group 1 (n = 20) the transection was 1·5 cm and in group 2 (n = 10) it was 2·5 cm proximal to the oral edge of the pyloric ring. The subjects were interviewed and examined periodically to assess symptoms, food intake, body-weight and serum nutritional variables. Endoscopy and a radioisotope gastric emptying test were performed 1 year after the operation.

Results

In group 1 gastric fullness after meals was common, resulting in poor food intake and poor recovery of body-weight. A high incidence of food residue in the remnant stomach was found in group 1. With regard to gastric emptying, seven of 20 patients in group 1 and one of ten in group 2 had a delayed emptying curve 1 year after operation.

Conclusion

Group 2 was superior to group 1 in terms of postprandial symptoms, food intake, recovery of body-weight and gastric emptying. The length of the retained antrum may play an important role in the motility of the pyloric ring following PPG.
Abnormal expression of E-cadherin and β-catenin may be a molecular marker of submucosal invasion and lymph node metastasis in early gastric cancer
Authors: Tanaka M , Kitajima Y , Edakuni G , Sato S , Miyazaki K
Published: December 2004

Background

Impaired expression of E-cadherin and α- and β-catenin is frequently observed in several human cancers. The aim of this study was to examine immunohistochemical expression of these adhesion molecules, focusing on early gastric carcinomas, and to investigate differences between differentiated and undifferentiated gastric cancer at the early phase of carcinogenesis.

Methods

Immunohistochemical staining of E-cadherin and α- and β-catenin was performed using specimens from 143 patients with early gastric cancer.

Results

Abnormal E-cadherin and β-catenin staining correlated with depth of tumour invasion in differentiated-type tumours. In contrast, abnormal staining was frequently found even in intramucosal carcinoma of undifferentiated-type tumours, suggesting an apparent difference in the onset of E-cadherin–catenin complex abnormality between the two cancer types. Absent staining of β-catenin was associated with lymph node metastasis. Multivariate analysis revealed abnormal E-cadherin expression as an independent factor that correlated with submucosal invasion in early gastric cancer.

Conclusion

Abnormal E-cadherin expression is a possible marker of submucosal invasion in differentiated-type early gastric cancer and absent β-catenin staining could be used as a predictor of lymph node metastasis in both types.
Evidence for separate disease phenotypes in intestinal Crohn's disease
Authors: Borley N R , Mortensen N J McC , Chaudry M A , Mohammed S , Clarke T , Jewell D P
Published: December 2004

Background

This study investigated the hypothesis that separate phenotypes of Crohn's disease exist which display differing patterns of recurrence with a tendency to preservation of phenotype between serial operations.

Methods

Some 483 abdominal operations (278 patients) were identified from a prospectively compiled database. Patterns of recurrence (reoperation) were analysed by Kaplan–Meier plots and log rank tests according to disease phenotype (perforated, stenosed or ulcerated). Serial operations were analysed by agreement of phenotype and microscopic features of disease using kappa statistics and correlation coefficients.

Results

There was no significant difference in recurrence according to disease phenotype (median reoperation-free survival time 43·0, 50·2 and 47·9 months for perforated, stenosed and ulcerated types respectively; log rank χ2 = 3·5, P = 0·18). There was poor agreement in phenotype between serial operations (κ = 0·22 for first/second operation and κ = 0·15 for second/third operation) and no significant correlation between pathological features was identified (r between −0·19 and 0·48).

Conclusion

No evidence was found for the existence of separate disease phenotypes with differing natural histories or underlying pathological characteristics.
Long-term results of bilateral thoracoscopic splanchnicectomy in patients with chronic pancreatitis
Authors: Buscher H C J L , Jansen J B M J , van Dongen R , Bleichrodt R P , van Goor H
Published: December 2004

Background

The management of pain in patients with chronic pancreatitis is difficult. The aim of this prospective study was to evaluate the early and long-term pain relief provided by bilateral thoracoscopic splanchnicectomy.

Methods

From August 1995 to August 1999, 44 patients with chronic pancreatitis underwent bilateral thoracoscopic splanchnicectomy. Data were collected prospectively. Thirty-six patients required opioids. Pain intensity was registered before operation and at regular intervals after surgery by means of a visual analogue scale (VAS). Use of analgesics (opioids; non-steroidal anti-inflammatory drugs and acetaminophen; no analgesics or aminocetophen) was noted before and after splanchnicectomy. Median follow-up was 36 (range 12–60) months.

Results

The procedure was technically successful in 40 patients. Thirty-six patients had no complications. Eleven of 24 patients who have been followed up for 24 months or more had a significantly reduced VAS score at 2 years (median (range) 8·5 (7–10) versus 2·5 (0–5); P < 0·01). The cumulative rate of pain relief was 46 per cent 48 months after splanchnicectomy.

Conclusion

Bilateral thoracoscopic splanchnicectomy alleviated pain in patients with chronic pancreatitis. It was associated with a low morbidity rate and no deaths. Pain eventually recurred in approximately 50 per cent.
Role of mast cells in the development of pancreatitis-induced multiple organ dysfunction
Authors: Dib M , Zhao X , Wang X D , Andersson R
Published: December 2004

Background

Activated mast cells can produce and release a number of inflammatory mediators involved in the pathophysiology of acute conditions. The aim of the present study was to evaluate the role of activated tissue mast cells in the pathogenesis of multiple organ dysfunction syndrome following acute pancreatitis (AP).

Methods

AP was induced by the intraductal infusion of 5 per cent sodium taurodeoxycholate in the rat. Some 30 min before induction of AP, a mast cell stabilizer (sodium cromoglycate (SCG)) or antihistamines (pyrilamine, cyproheptadine, meclizine and amitriptyline) were administered intra peritoneally. Plasma exudation of radiolabelled albumin, histamine, myeloperoxidase (MPO), monocyte chemoattractant protein (MCP) 1 and adhesion molecules (platelet endothelial cell adhesion molecule (PECAM) 1 and L-selectin) were measured.

Results

The mast cell stabilizer significantly reduced plasma exudation in the pancreas, colon and lungs (P < 0·05), decreased the release of histamine at 1 h (P < 0·05), and reduced MPO activity and MCP-1 levels in the colon and lungs (P < 0·05) but not in the pancreas. Expression of PECAM-1 and L-selectin on total circulating leucocytes in rats with AP and SCG pretreatment did not differ from that in sham controls, while levels in animals that had AP and saline pretreatment were half of those seen following sham operation.

Conclusion

Activation of mast cells after induction of AP is involved in the development of endothelial barrier dysfunction in both the pancreas and extrapancreatic organs/tissues, particularly in the lungs and colon. This may, at least partly, contribute to the sequential development of multiple organ dysfunction and organ/tissue-specific endothelial barrier dysfunction.
Randomized clinical trial of Ligasure™versus open haemorrhoidectomy
Authors: Palazzo F F , Francis D L , Clifton M A
Published: December 2004

Background

Postoperative pain associated with open haemorrhoidectomy remains problematic. Haemorrhoidectomy performed using bloodless bipolar diathermy – Ligasure™ – may have advantages over conventional open haemorrhoidectomy in terms of operating time and postoperative pain.

Methods

Thirty-four patients were randomized to undergo Ligasure™ (18 patients) or diathermy (16) haemorrhoidectomy. The operating time, amount of pain and postoperative analgesic requirement, postoperative complications and overall patient satisfaction were documented.

Results

The median duration of operation was shorter in the Ligasure™ haemorrhoidectomy group (5·1 versus 9·2 min; P < 0·001). There was no statistically significant difference in the postoperative pain score, but the median analgesic requirement was lower in the Ligasure™ group (850 versus 1600 mg tramadol; P = 0·013). Patient satisfaction was similar in both groups.

Conclusion

Ligasure™ haemorrhoidectomy is quick and bloodless and, although as painful as diathermy haemorrhoidectomy, is associated with a reduced analgesic requirement.