bluuebunny/crossref_metadata_2025 huggingface dataset:
Tissue factor and tissue factor pathway inhibitor levels in unstable angina patients during short‐term low‐molecular‐weight heparin administration
Authors: Gori A. M. , Fedi S. , Pepe G. , Falciani M. , Rogolino A. , Prisco D. , Gensini G. F. , Abbate R.
Published: March 2003

Summary. High tissue factor (TF), tissue factor pathway inhibitor (TFPI) levels and a hypercoagulability state have been documented in unstable angina patients. We evaluated whether short‐term enoxaparin administration (100 IU/kg b.i.d. for 3 d) reduces the high TF levels and the hypercoagulability state, and whether it influences the fibrinolytic system in 20 unstable angina patients. On d 3, we observed a significant reduction in TF levels both 1 h and 4 h after the morning injection (−25·6% and −21·7%; P < 0·001 respectively) in comparison with the base‐line levels. Both 1 and 4 h after the morning injection on the d 3, TFPI levels significantly (P < 0·001) increased (+96·4%, +96·9% respectively) with respect to the base‐line values. After enoxaparin administration, at all observation times, thrombin–antithrombin complexes and prothrombin fragment F1 + 2 levels were significantly (P < 0·001) lower with respect to base‐line levels. We observed a slight but significant increase in tissue plasminogen activator antigen levels in preinjection samples, as well as 1 h and 4 h after enoxaparin administration, in comparison with the base‐line values. This study provides evidence that low‐molecular‐weight heparin (LMWH) administration, in addition to a reduction of hypercoagulability and a mild fibrinolytic activation, is associated with decreased TF levels, so indicating a novel mechanism of interference of LMWH with the haemostatic system.
The frequency of bleeding complications in patients with haematological malignancy following the introduction of a stringent prophylactic platelet transfusion policy
Authors: Callow Colin R. , Swindell Ric , Randall William , Chopra Rajesh
Published: March 2003

Summary. Indications for platelet transfusion remain controversial and are frequently based on arbitrary numerical criteria. In October 2000, we introduced a stringent prophylactic‐platelet transfusion policy < 10 × 109/l for stable patients and < 20 × 109/l in the presence of major bleeding or additional risk factors. A trigger of < 50 × 109/l was introduced for patients undergoing invasive procedures. A prospective analysis was performed measuring the frequency of minor and major bleeding events, morbidity, mortality and duration of pancytopenia. Blood product usage was assessed and health care savings measured. A total of 98 patients were evaluated on 2147 patient study days and 271 bleeding episodes were recorded. Major bleeding occurred on 1·39% (30/2147) of the study days when platelet counts were < 10 × 109/l and 2·3% (50/2147) of the study days when platelet counts were 10–20 × 109/l. In patients with platelets > 20 × 109/l, there were 117 major bleeding episodes observed on 5·4% of the study days. In patients with no identified additional risk factors present, major haemorrhages were recorded in 0·51% (11/2147) of the study days in patients with platelet counts ≥ 10 × 109/l. There was a 36% reduction in platelet units transfused compared with retrospective data when an arbitrary transfusion trigger of 20 × 109/l was in place (P = < 0·02). Of note, a 16% reduction in red cell transfusions was recorded. These data confirm that the introduction of a transfusion trigger of < 10 × 109/l in the absence of fresh bleeding and sepsis (> 38°C) is safe and has a significant impact on overall hospital transfusion costs.
Immunodeficiency‐related lymphoproliferative disorders: prospective data from the United Kingdom Children's Cancer Study Group Registry
Authors: Pinkerton C. R. , Hann I. , Weston C. L. , Mapp T. , Wotherspoon A. , Hobson R. , Kelly D. A. , Vergani D. , Hadzic D. , Rees L. , Burke M. , Alero Thomas J.
Published: March 2003

Summary. Clinical data and biological samples were prospectively collected in 42 children with lymphoproliferative disease (LPD) secondary to organ/bone marrow transplant‐related immunosuppression (30: 11 liver, 10 heart/lung, 8 kidney and 1 bone marrow), other drug‐induced immunosuppression (2), congenital immunodeficiency (8) or human immunodeficiency virus (HIV)‐related immune dysfunction (2). Ages ranged from 10 months to 17 years and there were 15 girls. Pathology was centrally reviewed and showed polymorphic features in 5 cases, monomorphic in 23, mixed pattern in 5 patients and 9 other types. Using the Revised European–American Classification of Lymphoid Neoplasms, 5 were B lymphoblastoid, 24 were high‐grade B and 14 were other subtypes. Using the Pittsburgh classification, 9 were lymphadenopathic, 10 were systemic, 25 were lymphomatous and, with the Murphy grouping for non‐Hodgkin's lymphoma (NHL), 10 were localized and 32 non‐localized. Twenty‐four out of 38 evaluable cases were Epstein–Barr virus positive. Thirty‐five patients were evaluable for clonality; 24 were monoclonal and 11 were polyclonal. Reduced immunosuppression in solid organ transplant patients resulted in resolution of disease in 14/24, which was sustained in 11. Nineteen patients received chemotherapy, 14/18 evaluable responded, which was sustained in 8 cases. Seven out of 29 solid organ transplant and 10/13 other immune‐deficient patients died. In the largest group of patients, solid organ transplants, no significant clinical or biological characteristics that predicted outcome were identified. In the transplant group close monitoring of response during reduction in immunosuppression is essential and the early use of B NHL chemotherapy may be effective.
Myelofibrosis with myeloid metaplasia following essential thrombocythaemia: actuarial probability, presenting characteristics and evolution in a series of 195 patients
Authors: Cervantes Francisco , Alvarez‐Larrán Alberto , Talarn Carme , Gómez Marta , Montserrat Emilio
Published: March 2003

Summary. Myelofibrotic transformation is a known complication of essential thrombocythaemia (ET), but information on its incidence, presenting features and evolution is scarce. In a series of 195 patients with ET followed for a median of 7·2 years (range: 1·9–24), evolution into myelofibrosis with myeloid metaplasia (MMM) occurred in 13 cases, a median of 8 years (range: 3·6–20·2) from diagnosis. The actuarial probability of this complication was 2·7% (95% CI: 2·4–2·9) at 5 years, 8·3% (95% CI: 7·8–8·9) at 10 years, and 15·3% (95% CI: 6·1–24·5) at 15 years. Four patients had not been treated before developing MMM. The main features indicating this condition were the appearance of immature myeloid precursors in the peripheral blood, a decrease in the Hb value not related to treatment and increased serum lactate dehydrogenase levels, followed by a progressive decrease in the platelet count, increasing leucocytosis and progressive splenomegaly. No patient had constitutional symptoms, and none of five evaluable cases showed chromosome abnormalities in bone marrow or unstimulated blood. After a median the myelofibrotic transformation, three patients have died and four have not required treatment for MMM as yet.
Serial monitoring of BCR–ABL by peripheral blood real‐time polymerase chain reaction predicts the marrow cytogenetic response to imatinib mesylate in chronic myeloid leukaemia
Authors: Wang Lihui , Pearson Kevin , Pillitteri Lynne , Ferguson Julia E. , Clark Richard E.
Published: March 2003

Summary. Imatinib mesylate (trade name Glivec® or Gleevec) is emerging as an important therapy in the management of chronic myeloid leukaemia (CML). It is clinically useful to monitor the cytogenetic response to imatinib, although frequent marrow examinations are inconvenient. We have used serial real‐time reverse transcription–polymerase chain reaction (RT‐PCR) to monitor the ratio of peripheral blood BCR–ABL to normal ABL transcripts in 43 patients receiving imatinib, and compared the results to concurrent conventional bone marrow (BM) cytogenetics. After 6 months of treatment, 13 cases were complete cytogenetic responders, defined as all BM metaphases negative for the Philadelphia (Ph) chromosome. In these patients, the BCR–ABL/ABL ratio was less than 0·08%. Six cases achieved a partial cytogenetic response (1–35% Ph‐positive BM metaphases) and their BCR–ABL/ABL ratio was between 0·08 and 10%. In total, 24 cases were cytogenetic non‐responders, and their BCR–ABL/ABL ratio exceeded 11%. The data suggested that the 6‐month BCR–ABL/ABL ratio may reliably predict the contemporary marrow cytogenetic response. It was concluded that serial real‐time RT‐PCR may offer a convenient surrogate assessment of the marrow cytogenetic response to imatinib therapy in CML.
Gender‐specific phenotypic expression and screening strategies in C282Y‐linked haemochromatosis: a study of 9396 French people
Authors: Deugnier Yves , Jouanolle Anne‐Marie , Chaperon Jacques , Moirand Romain , Pithois Catherine , Meyer Jean‐François , Pouchard Michel , Lafraise Bernard , Brigand Alain , Caserio‐Schoenemann Céline , Mosser Jean , Adams Paul , Le Gall Jean‐Yves , David Véronique
Published: March 2003

Summary. Most features of C282Y‐linked haemochromatosis support the implementation of population screening of the disorder in Caucasians. However, the penetrance of C282Y homozygosity is poorly documented and the strategy for population screening remains debated. Nine thousand three hundred and ninety‐six subjects (3367 men, aged 25–40 years, and 6029 women, aged 35–50 years), attending three Health Appraisal Centres, were genotyped and assessed with respect to clinical and biochemical signs of haemochromatosis. Discriminant, logistic regression and graphic analysis were used to predict homozygosity. Results were validated in 135 homozygotes detected through other family and population studies. Fifty‐four subjects (10 men and 44 women) were homozygous for C282Y. All men had abnormal iron status and most had mild clinical symptoms compatible with haemochromatosis. Identification of all homozygous men required a transferrin saturation (TS) threshold of 50% in the study group (90% specificity) and of 40% in the validation group. Homozygous women differed clinically from non‐homozygotes for the presence of distal arthralgias only (18%vs 6%, P < 0·03). Thirteen (29%) were iron‐deficient (serum ferritin < 13 µg/l) and undetectable by biochemical tests. Although the population studied was not fully representative of the general population, our data strongly suggests that, in young men, large‐scale screening for C282Y homozygosity is justified and can be achieved by using TS prescreening. However, in premenopausal women, large‐scale screening remains to be justified with respect to the natural history of haemochromatosis and should be directly genotypic.
Methylation is an inactivating mechanism of the p16 gene in multiple myeloma associated with high plasma cell proliferation and short survival
Authors: Mateos Maria V. , García‐Sanz Ramón , López‐Pérez Ricardo , Moro Maria J. , Ocio Enrique , Hernández Jose , Megido Marta , Caballero Maria D. , Fernández‐Calvo Javier , Bárez Abelardo , Almeida Julia , Orfão Alberto , González Marcos , San Miguel Jesús F
Published: March 2003

Summary. In order to gain further insights into the role of the p16 gene in cell cycle regulation and the prognostic implications of its inactivation, we investigated the methylation status of the p16 gene in 98 untreated patients using a polymerase chain reaction assay based on the inability of some restriction enzymes to digest methylated sequences. Forty‐one patients showed a p16 methylated gene (42%). The percentage of S‐phase plasma cells (PC) in these patients was almost three times higher than in those with an unmethylated p16 gene (4·16% ± 3·37%vs 1·5% ± 1·41%, P < 0·001). The presence of p16 methylation also correlated with both elevated β2‐microglobulin serum levels and high C‐reactive protein values. Patients with a p16 methylated gene had shorter overall and progression‐free survival than those patients without p16 methylation. However, this feature did not retain independent prognostic influence on multivariate analysis, probably due to its association with the S‐phase PC, which had more potent statistical significance in the Cox model. These findings showed methylation of the p16 gene was a frequent event inMM patients at diagnosis, and was associated with an increased proliferative rate of plasma cells and a poor prognosis, indicating an important role for p16 gene in the cell cycle regulation of multiple myeloma tumour cells, and thus in the clinical outcome of the disease.
Bone marrow failure in Shwachman–Diamond syndrome does not select for clonal haematopoiesis of the paroxysmal nocturnal haemoglobinuria phenotype
Authors: Keller Peter , Debaun Michael R. , Rothbaum Robert J. , Bessler Monica
Published: March 2003

Summary. Bone marrow failure is believed to be the underlying condition that drives the expansion of the paroxysmal nocturnal haemoglobinuria (PNH) clone. Indeed, circulating PNH blood cells have been identified in patients with acquired aplastic anaemia and with hypoplastic myelodysplasia. Whether PNH blood cells are also present in patients with inherited aplastic anaemia has not been reported. We screened a large group of patients diagnosed with Shwachman–Diamond Syndrome (SDS) for PNH blood cells. None of the patients analysed had detectable circulating PNH blood cells, indicating that bone marrow failure in SDS does not select for PNH progenitor cells.
Histone deacetylase inhibitors potently repress CXCR4 chemokine receptor expression and function in acute lymphoblastic leukaemia
Authors: Crazzolara Roman , Jöhrer Karin , Johnstone Ricky W. , Greil Richard , Ofler Reinhard K , Meister Bernhard , Bernhard David
Published: March 2003

Summary. The chemokine receptor CXCR4 plays a crucial role in the survival and trafficking of leukaemia cells and requires further attention as human immunodeficiency virus type I (HIV‐I) utilises CXCR4 as the major coreceptor for cellular entry. We demonstrated that inhibitors of histone deacetylases, currently being tested in clinical trials for the treatment of various tumours, extensively downregulated CXCR4 protein and mRNA levels in leukaemia cell lines and lymphoblasts from patients with childhood acute leukaemia. As a result, the ability of stromal cell‐derived factor‐1 to induce cellular migration was impaired. Repression of CXCR4 transcription by inhibitors of histone deacetylases might therefore represent a promising novel approach in the treatment of acute leukaemias.
Phenotypic and functional deficiencies of leukaemic dendritic cells from patients with chronic myeloid leukaemia
Authors: Eisendle Klaus , Lang Alois , Eibl Brigitte , Nachbaur David , Glassl Herta , Fiegl Michael , Thaler Joseph , Gastl Guenther
Published: March 2003

Summary. Chronic myeloid leukaemia (CML) dendritic cells (DC) are possible candidates for inducing antileukaemic immunity. This study aimed to investigate the frequency, phenotype and function of blood‐derived leukaemic DC in comparison with DC from healthy donors using flow cytometric assays and mixed leucocyte reaction (MLR). Immature leukaemic DC displayed a reduced endocytotic capacity as compared with healthy controls. Moreover, in vitro maturation of leukaemic DC was found to be deficient. Expression of CD80, CD83, CD86, and major histocompatibility complex class I and class II antigens were reduced on lipopolysaccharide (LPS)‐matured leukaemic DC but were enhanced by a mixture of interleukin 1β (IL‐1β), IL‐6, tumour necrosis factor‐α (TNF‐α) and prostaglandin E2 (PGE2). Upon stimulation with bacterial LPS, intracellular TNF‐α and IL‐8 production was diminished in maturing DC from CML patients. This distinct cytokine deficiency was overcome when leukaemic DC were stimulated with cytokines/PGE2. MLR showed fully functional leukaemic DC after TNF‐α‐induced maturation, but a reduced proliferative alloresponse of leukaemic peripheral blood mononuclear cells. Further, intracellular production of cytokines in CML‐derived T cells was markedly reduced. These data indicated that, in CML, the maturation response of leukaemic monocyte‐derived DC to a natural stimulus like LPS is abnormal and may be caused by an aberrant TNF‐α response in these cells. Thus, TNF‐α alone or in combination with pro‐inflammatory and T‐cell stimulatory cytokines should be considered as an adjuvant for DC‐based immunotherapy in CML.
Cell surface CD43 determination improves diagnostic precision in late B‐cell diseases
Authors: Jung Georges , Eisenmann Jean‐Claude , Thiébault Sylvie , Hénon Philippe
Published: March 2003

Summary. Panels of immunological markers are useful in refining diagnosis in view of certain variability between B‐cell leukaemias. A statistical multivariate approach was used on 100 B leukaemias (preliminary sample) to explore the potential value of the combination of CD43, and the classical markers CD5, CD23, CD79b, FMC7, CD22 and surface immunoglobulin to differentiate chronic lymphoid leukaemia (CLL) from lymphoma (non‐CLL). CD43 was highly effective (P < 0·00001) and its inclusion in the panels improved the accuracy of discrimination in a ‘control’ sample of 74 B leukaemias to 98·6%. Inclusion of CD43 facilitates the diagnosis of B‐lymphoproliferative disorders and improves their classification.
Standardization of activated protein C resistance testing: effect of residual platelets in frozen plasmas assessed by commercial and home‐made methods
Authors: Tripodi Armando , Valsecchi Carla , Chantarangkul Veena , Battaglioli Tullia , Mannucci Pier Mannuccio
Published: March 2003

Summary.  We investigated 42 plasmas prepared at different centrifugation speeds with three activated protein C (APC) resistance methods. The APC ratio for fresh platelet‐poor plasma declined significantly after freezing and thawing. This effect was more evident with the original method (average reduction 11·3%) than with either the home‐made (3·8%) or the modified method (3·2%). No significant decrease in the APC ratio was observed after freezing and thawing of platelet‐free plasmas from the same patients. When frozen platelet‐poor plasma was centrifuged at high speed after thawing and before testing, there was no significant decrease in the APC ratio, in comparison with fresh platelet‐poor plasma using the home‐made and modified methods.
Quality of life in patients with benign anorectal disorders
Authors: Sailer M , Bussen D , Debus E S , Fuchs K H , Thiede A
Published: March 2003

Background

Benign proctological conditions are very common in Western civilization. However, to date quality of life in these patients has not been evaluated comprehensively. The aim of this study was to investigate whether the Gastrointestinal Quality of Life Index (GIQLI) is a useful instrument for measuring quality of life in these patients, and subsequently to establish baseline values for different anorectal disorders.

Methods

The questionnaire was completed by 325 consecutive patients (182 men; mean age 49 years) seen at the proctology outpatient clinic. For further analysis patients were classified into nine subgroups according to the primary diagnosis: group 1, haemorrhoids (n = 96); group 2, anal fissure (n = 38); group 3, fistula in ano (n = 22); group 4, severe constipation (n = 14); group 5, faecal incontinence (n = 35); group 6, symptomatic anterior rectocele (n = 12); group 7, perianal abscess (n =7); group 8, perianal thrombosis (n = 7); and group 9, miscellaneous conditions (e.g. skin tags, anal papillomas, mild constipation, rectal polyps) (n = 94). The GIQLI scores were compared between the subgroups. In addition the GIQLI scores of age-matched healthy controls, derived from data in the literature, were compared with the patients' scores.

Results

The mean GIQLI score for all patients was 113 (78·5 per cent of the maximum score of 144). Mean scores for the nine diagnostic subgroups were: group 1, 120; group 2, 104; group 3, 119; group 4, 94; group 5, 93; group 6, 112; group 7, 115; group 8, 129; and group 9, 117. Age-matched controls from a series published previously had a significantly higher GIQLI score compared with all patients (P < 0·0001). However, only the subgroups of patients with miscellaneous conditions, fissures, severe constipation and faecal incontinence had a significantly poorer quality of life than age-matched healthy individuals.

Conclusion

The GIQLI is a valuable instrument for measuring quality of life in patients with benign anorectal disorders. Although certain diseases do not seem to affect quality of life profoundly, certain subgroups of patients, most notably those with incontinence and severe constipation, are extremely compromised. Severely constipated individuals exhibit the same poor quality of life as patients with faecal incontinence.
Smoking and alcohol abuse are major risk factors for anastomotic leakage in colorectal surgery
Authors: Sørensen L T , Jørgensen T , Kirkeby L T , Skovdal J , Vennits B , Wille-Jørgensen P
Published: March 2003

Background

Several studies have examined the association between anastomotic leakage and intraoperative risk factors in colorectal surgery, but only a few have taken patients' lifestyle into account. The aim of this study was to assess the association between anastomotic leakage and lifestyle factors such as smoking habits and alcohol consumption.

Methods

Between January 1993 and October 1996, 333 unselected consecutive patients in one surgical department underwent colonic or rectal resection with anastomosis. The association between clinical anastomotic leakage and 24 variables related to patient history, diagnosis and surgery was assessed retrospectively and analysed by logistic regression.

Results

The rate of clinical anastomotic leakage was 15·9 per cent (53 of 333 patients). Multiple regression analysis showed that smokers, compared with non-smokers, had an increased risk of anastomotic leakage (relative risk (RR) 3·18 (95 per cent confidence interval (c.i.) 1·44–7·00)), as did alcohol abusers compared with abstainers (RR 7·18 (95 per cent c.i. 1·20–43·01)). In the analysis, well known risk factors for anastomotic leakage such as site of anastomosis, age and stage of training of the surgeon were taken into account.

Conclusion

Smoking and alcohol abuse are important predictive factors for anastomotic leakage after colonic and rectal resection.
Systematic review of the use of fibrin sealant to minimize perioperative allogeneic blood transfusion
Authors: Carless P A , Anthony D M , Henry D A
Published: March 2003

Background

Fibrin sealants have become popular in improving perioperative haemostasis and reducing the need for allogeneic red cell transfusion.

Methods

A systematic review of randomized controlled trials was conducted to examine the efficacy of fibrin sealants in reducing perioperative blood loss and allogeneic red blood cell transfusion. Studies were identified by computer searches of Medline, Embase, Current Contents, the Cochrane Library, manufacturer websites (to January 2001), and bibliographic searches of published articles. Trials were eligible for inclusion if they involved adult elective surgery and reported quantitative data on blood loss, the proportion of patients exposed to allogeneic red cell transfusion and/or the volume of blood transfused.

Results

Twelve trials met the criteria for inclusion. Fibrin sealants reduced the rate of allogeneic blood transfusion (relative risk 0·40 (95 per cent confidence interval (c.i.) 0·26 to 0·61); five trials with 275 subjects) and reduced blood loss (weighted mean difference −151·68 (95 per cent c.i. −251·91 to −51·46) ml; seven trials with 391 subjects). Generally, the trials were small and of poor methodological quality.

Conclusion

Overall the results suggest that fibrin sealants are efficacious. Owing to lack of blinding, transfusion practices may have been influenced by knowledge of the patient's treatment status. This raises concern about blood transfusion practice as a response variable. Large methodologically rigorous trials of fibrin sealants with clinical outcomes are needed.
Botulinum neurotoxin and other treatments for fissure-in-anoand pelvic floor disorders
Authors: Maria G , Sganga G , Civello I M , Brisinda G
Published: March 2003

Background

The management of disorders of the lower gastrointestinal tract, such as chronic anal fissure and pelvic floor dysfunction, has undergone re-evaluation recently. To a large extent this is due to the advent of neurochemical treatments, such as botulinum neurotoxin injections and topical nitrate ointment.

Methods and results

This review presents, inter alia, current data on the use of botulinum neurotoxin to treat lower gastrointestinal tract diseases, such as chronic anal fissure for which it promotes healing and symptom relief in up to 70 per cent of cases. This agent has also been used selectively to weaken the external anal sphincter and puborectalis muscle in constipation and in Parkinson's disease. Symptomatic improvement can also be induced in anterior rectocele by botulinum neurotoxin injections.

Conclusion

Botulinum neurotoxin appears to be a safe therapy for anal fissure. It is more efficacious than nitrate application and does not require patient compliance to complete treatment. While it may also be a promising approach for the treatment of chronic constipation due to pelvic floor dysfunction, further investigation of its efficacy and safety in this role is needed before general usage can be advocated.
Revascularization of the superior mesenteric artery after acute thromboembolic occlusion
Authors: Björck M , Acosta S , Lindberg F , Troëng T , Bergqvist D
Published: March 2003

Background

The outcome and prognostic factors after revascularization of acute thromboembolic occlusion of the superior mesenteric artery (SMA) are poorly documented.

Methods

Sixty patients with acute thromboembolic occlusion of the SMA had revascularization procedures at 21 hospitals from 1987 to 1998. They were registered prospectively in the Swedish Vascular Registry. Patient files were analysed retrospectively.

Results

The median age of the patients was 76 years; 73 per cent suffered from cardiac disease and 23 per cent had previous vascular surgery. Onset of symptoms was classified as sudden (30 per cent), acute (33 per cent) or insidious (37 per cent). The occlusions were thought to be either embolic (67 per cent) or thrombotic (33 per cent). The diagnosis was suspected on first examination in 32 per cent of patients, a group whose median time to operation was shorter (P = 0·01). Fifty-eight patients had an exploratory laparotomy and subsequent revascularization, and two were treated with thrombolysis alone. Second-look laparotomy was performed in 41, and third look in eight patients; 19 required an additional bowel resection. The overall mortality rates were 43, 52, 60 and 67 per cent at 30 days, discharge, 1 and 5 years, respectively. No patient was dependent on intravenous nutrition after 1 year. Previous vascular surgery resulted in a higher institutional mortality rate (79 per cent; P = 0·02). Patients who had a sudden onset of symptoms outside hospital had a better outcome (mortality rate 27 per cent; P = 0·02).

Conclusion

Many non-diagnostic radiological examinations were performed and a routine second-look is warranted. The results suggest that attempts at revascularization procedures for acute mesenteric ischaemia may improve the outcome.
The mystery of liver regeneration
Authors: Court F G , Wemyss-Holden S A , Dennison A R , Maddern G J
Published: March 2003

Background

Partial hepatectomy is the strongest stimulator of hepatic regeneration. The process of initiation and the control of the final size of the regenerated liver have been the subject of research for many years. A better understanding of this process and the effect of disease may allow better selection of patients for partial hepatectomy. It may also allow an insight into the possible application of clinical stimulation of regeneration.

Methods

Data were reviewed from the published literature using the Medline database.

Results

Most knowledge comes from in vitro studies and the study of resection in the rat model. A variety of cytokines, hormones and growth factors are involved in regeneration but very few have been found capable of stimulating regeneration in vitro. The exact interactions are not known, but there is probably a cascade involving different factors at differing stages of regeneration.

Conclusion

Further in vivo research should allow greater understanding of liver regeneration, thereby providing a potential therapeutic tool in patients for whom regeneration has failed, or is likely to fail. Such research is also important in respect of liver support devices, which may inhibit liver regeneration by filtration of many of the factors involved.
Experience in the management of conjoined twins
Authors: Spitz L , Kiely E M
Published: March 2003

Background

Conjoined twins occur in approximately one in 200 000 live births. Their management is often extremely complex and experience with large numbers is restricted to a few centres worldwide.

Methods

An analysis of 17 sets of symmetrical conjoined twins managed by a single team of surgeons over a 16-year period was undertaken.

Results

Management could be divided into three groups. Those in group 1 (n = 5) had non-operative management, owing to cardiac fusion or gross anatomical union, and all died. Those in group 2 (n = 7) underwent emergency separation, when one twin was dead or threatening the survival of the sibling or where there was a correctable life-threatening associated anomaly (four of 14 survived). Twins in group 3 (n = 5) underwent elective separation, allowing time for detailed preoperative investigation and planning (eight of ten survived).

Conclusion

Accurate preoperative investigation, a team approach, previous experience, and meticulous operative and postoperative management contributed to the success rate achieved in this series.
Outcome of patients with severe chronic pain following repair of groin hernia
Authors: Courtney C A , Duffy K , Serpell M G , O'Dwyer P J
Published: March 2003

Background

Chronic pain is the most serious long-term complication that can occur after repair of a groin hernia. The aim of this study was to assess the outcome of patients who report severe or very severe pain 3 months after groin hernia repair.

Methods

This was a population-based study of all patients who underwent repair of a groin hernia between April 1998 and March 1999 in Scotland. All received a postal questionnaire 3 months after hernia repair and those who reported severe or very severe pain at the operation site were asked to complete a further questionnaire 2·5 years later. The main outcome measure included the number of patients with persistent pain and the effect of pain on daily activities and quality of life.

Results

Of 5506 patients who underwent repair of a groin hernia, 4062 (74 per cent) returned the first questionnaire and 125 (3 per cent) reported severe or very severe pain. Eight-six (72 per cent) of 120 patients (five had died or could not be contacted at the original address) replied to the second questionnaire; 61 (71 per cent) still reported pain, which was severe or very severe pain in 22 (26 per cent) and mild or very mild in 39 (45 per cent). Twenty-nine (48 per cent) sought further medical help from their general practitioner or surgeon. Nine (15 per cent) attended a pain clinic while five (8 per cent) had further surgery. Chronic pain had significant effects (P < 0·001) on all daily activities including walking, work, sleep, relationships with other people, mood and general enjoyment of life.

Conclusion

Chronic pain persists in most patients who report severe or very severe pain at 3 months after hernia repair, and has a significant effect on the patients' daily activities and quality of life.
Tumour thickness as a predictor of occult lymph node metastases in patients with stage I and II melanoma undergoing sentinel lymph node biopsy
Authors: Lens M B , Dawes M , Newton-Bishop J A , Goodacre T
Published: March 2003

Background

Sentinel lymph node biopsy (SLNB) is a minimally invasive procedure used accurately to stage nodal basins at risk of occult metastases. There are no data as yet to show a survival benefit from SLNB and its use remains controversial. If Breslow thickness of the tumour correlates well with positive SLNB, it could be used to select patients for SLNB.

Methods

A quantitative systematic review of published studies on SLNB in patients with melanoma available by September 2001 was performed.

Results

Twelve studies containing 4218 patients with stage I and II melanoma were identified; 17·8 (95 per cent confidence interval 16·7 to 19·0) per cent of patients had nodal micrometastases detected by SLNB. The incidence of micrometastasis in sentinel nodes correlated directly with Breslow tumour thickness; it was 1·0 per cent for lesions of less than or equal to 0·75 mm, 8·3 per cent for 0·76–1·50 mm, 22·7 per cent for 1·51–4·0 mm and 35·5 per cent for more than 4·0 mm.

Conclusion

The Breslow thickness of primary melanoma predicts the presence of a sentinel node metastasis. The published data are not sufficient to demonstrate a correlation between other known prognostic indicators and a positive SLNB.
Meta-analysis of relaparotomy for secondary peritonitis
Authors: Lamme B , Boermeester M A , Reitsma J B , Mahler C W , Obertop H , Gouma D J
Published: March 2003

Background

Planned relaparotomy and relaparotomy on demand are two frequently employed surgical treatment strategies for patients with abdominal sepsis.

Methods

The available literature was evaluated to compare the efficacy of both surgical treatment strategies. A systematic search for studies comparing planned and on-demand relaparotomy strategies in adult patients with secondary peritonitis was employed. Studies were reviewed independently for design features, inclusion and exclusion criteria, and outcomes. The primary outcome measure was in-hospital mortality.

Results

No randomized studies were found; eight observational studies with a total of 1266 patients (planned relaparotomy, 286; relaparotomy on demand, 980) met the inclusion criteria and were included in the meta-analysis. These eight studies were heterogeneous on clinical and statistical grounds (χ2 = 40·7, d.f. = 7, P < 0·001). Using a random-effects approach, the combined odds ratio for in-hospital mortality was 0·70 (95 per cent confidence interval 0·27 to 1·80) in favour of the on-demand strategy.

Conclusion

The combined results of observational studies show a statistically non-significant reduction in mortality for the on-demand relaparotomy strategy compared with the planned relaparotomy strategy when corrected for heterogeneity in a random-effects model. Owing to the non-randomized nature of the studies, the limited number of patients per study, and the heterogeneity between studies, the overall evidence generated by the eight studies was inconclusive.
Influence on antiproliferative activity of structural modification and conjugation of gonadotropin‐releasing hormone (GnRH) analogues
Authors: Kálnay A. , Pályi I. , Vincze B. , Mihalik R. , Mezõ I. , Pató J. , Seprõdi J. , Lovas S. , Murphy R.F.
Published: March 2003

The effect of various GnRH analogues, and their conjugates on proliferation, clonogenicity and cell cycle phase distribution of MCF‐7 and Ishikawa human cancer cell lines was studied. GnRH‐III, a sea lamprey GnRH analogue reduced cell proliferation by 35% and clonogenicity by 55%. Structural modifications either decreased, or did not alter biological activity. Conjugation of GnRH analogues including MI‐1544, MI‐1892, and GnRH‐III with poly(N‐vinylpyrrolidone‐co‐maleic acid) (P) through a tetrapeptide spacer GFLG(X) substantially increased the inhibitory effect of the GnRH analogues. The conjugate P‐X‐GnRH‐III induced significant accumulation of cells in the G2/M phase; from 8% to 15.6% at 24 h and 9.8% to 15% at 48 h. It was concluded that conjugation of various GnRH analogues substantially enhanced their antiproliferative activity, strongly reduced cell clonogenicity and retarded cell progression through the cell division cycle at the G2/M phase.
In vitro proliferation of achondroplastic and normal mouse chondrocytes, before and after basic fibroblast growth factor stimulation
Authors: Argentin G. , Cicchetti R.
Published: March 2003

Achondroplasia in mice is a recessive genetic disorder, characterized by disproportionate dwarfism with reduced bone growth. The cause of this chondrodystrophy is unknown.

In this study normal and achondroplastic mouse chondrocytes were cultured in monolayer primary culture, their differentiation was verified by immunofluorescence and their growth was compared.

The results showed that achondroplastic cells exhibited a higher proliferative activity than control cells of the same age, confirmed also by a thymidine incorporation assay. Furthermore, basic fibroblast growth factor treatment was found to induce a strong increase in growth of normal mouse chondrocytes, while it did not stimulate statistically significant proliferation of achondroplastic mouse cells.

We suppose that this different growth rate could play a role in achondroplastic phenotype development.
The geometry of proliferating dicot cells
Authors: Korn R.W.
Published: March 2003

The distributions of cell size and cell cycle duration were studied in two‐dimensional expanding plant tissues. Plastic imprints of the leaf epidermis of three dicot plants, jade (Crassula argentae), impatiens (Impatiens wallerana), and the common begonia (Begonia semperflorens) were made and cell outlines analysed. The average, standard deviation and coefficient of variance (CV = 100 × standard deviation/average) of cell size were determined with the CV of mother cells less than the CV for daughter cells and both are less than that for all cells. An equation was devised as a simple description of the probability distribution of sizes for all cells of a tissue. Cell cycle durations as measured in arbitrary time units were determined by reconstructing the initial and final sizes of cells and they collectively give the expected asymmetric bell‐shaped probability distribution. Given the features of unequal cell division (an average of 11.6% difference in size of daughter cells) and the size variation of dividing cells, it appears that the range of cell size is more critically regulated than the size of a cell at any particular time.
Blast colony‐forming cell binding from CML bone marrow, or blood, on stromal layers pretreated with G‐CSF or SCF
Authors: Gidáli J. , László E. , Halm G. , Fehér I.
Published: March 2003

Blast colony‐forming cells (CFU‐BL) represent a specific subpopulation of special primitive progenitors characterized by colony formation only in close contact with a preformed stromal layer. CFU‐BL derived from bone marrow of chronic myeloid leukaemia (CML) patients have been proved to adhere poorly to bone marrow derived stromal layers suggesting that the appearance of progenitors and precursors in the circulation is due to a defective adhesion of these cells to the bone marrow microenvironment. In the present experiments the effect of short‐term incubation of preformed normal bone marrow stroma on the adherence of CML derived CFU‐BL was studied. For stroma cultures bone marrow cells were cultured in microplates in the presence of hydrocortisone. Cultures were used when stromal layers became confluent and no sign of haemopoiesis could be observed. CFU‐BL were studied by panning plastic non‐adherent mononuclear (PNAMNC) bone marrow or blood cells. 8.9 ± 2.4 colonies/103 PNAMNC (six experiments) were formed from normal bone marrow on stromal layers and 4.8 ± 2.1 colonies/103 PNAMNC (five experiments) from CML bone marrow. Colony formation from normal bone marrow was not increased if stromal layers were incubated with 100 ng/mL granulocyte colony‐stimulating factor (G‐CSF) or stem cell factor (SCF). Incubation of stroma with G‐CSF or SCF, however, increased the colony formation of PNAMNC from CML bone marrow or blood significantly. These findings suggest that local concentration of haemopoietic growth factors at the time of panning may influence the attachment of CML progenitors to the stroma.
Transforming growth factor β1 dysregulation in a human oral carcinoma tumour progression model
Authors: Hsu S. , Borke J. L. , Lewis J. B. , Singh B. , Aiken A. C. , Huynh C. T. , Schuster G. S. , Caughman G. B. , Dickinson D. P. , Smith A. K. , Osaki T. , Wang X. F.
Published: March 2003

Abstract. A human oral tumour progression model was established that consists of normal epithelial cells and three cell lines representing stages from dysplastic to metastatic cells. To investigate the impact of exogenous transforming growth factor‐β1 on this model system, we analysed the responsiveness of those cells to transforming growth factor‐β1 and explored the potential mechanism underlying the transforming growth factor‐β1 activity. We found that the growth of all cell types, regardless of their stage of tumour progression, is inhibited by transforming growth factor‐β1, although to different degrees. Transforming growth factor‐β1 induced the expression of cyclin‐dependent kinase inhibitors p15INK4B, p21WAF1/CIP1 and p27KIP1. In contrast, transforming growth factor‐β1 was found to stimulate the invasive potential of one cell type that represents the most advanced stage of tumour phenotype, suggesting that the impact of transforming growth factor‐β1 on functional features of tumour cells other than cellular proliferation may play a significant role in the process of oral tumour progression.
Expression of RB C pocket fragments in HSF induces delayed cell cycle progression and sensitizes to apoptosis upon cellular stresses
Authors: Chung Junah , Cho Jae‐We , Baek Won‐Ki , Suh Seong‐Il , Kwon Taeg Kyu , Park Jong‐Wook , Suh Min‐Ho
Published: March 2003

Abstract. The retinoblastoma protein (RB) plays an important role in growth suppression through the formation of multiple protein complexes with its target proteins using A/B and C pockets. Even though the A/B and C pockets co‐operate for growth suppression, the function of RB in growth arrest is inhibited by the coexpression of RB C fragments with full length RB in the absence of p53, which implies that C pocket fragments are likely to act as a dominant‐negative inhibitor of RB function. In contrast, the loss of the RB functions in the presence of p53 triggers a cell cycle arrest or apoptosis by p53‐dependent pathways. Thus, it still remains to be elucidated whether the expression of RB C pocket fragments in the presence of p53 induces delayed cell cycle progression and sensitizes cells to apoptosis through p53‐dependent pathways. Our results show that the expression of RB C pocket fragments not only induces delayed cell cycle progression, which is mediated by the down‐regulation of cyclin A, cyclin E, and E2F‐1, but also sensitizes cells to apoptosis through p53‐dependent pathways.
A mathematical model of the impact of infused targeted cytotoxic agents on brain tumours: implications for detection, design and delivery
Authors: Wein Lawrence M. , Wu Joseph T. , Ianculescu Alexandra G. , Puri Raj K.
Published: March 2003

Abstract. Motivated by the recent development of highly specific agents for brain tumours, we develop a mathematical model of the spatio‐temporal dynamics of a brain tumour that receives an infusion of a highly specific cytotoxic agent (e.g. IL‐4‐PE, a cytotoxin comprised of IL‐4 and a mutated form of Pseudomonas exotoxin). We derive an approximate but accurate mathematical formula for the tumour cure probability in terms of the tumour characteristics (size at time of detection, proliferation rate, diffusion coefficient), drug design (killing rate, loss rate and convection constants for tumour and tissue), and drug delivery (infusion rate, infusion duration). Our results suggest that high specificity is necessary but not sufficient to cure malignant gliomas; a nondispersed spatial profile of pretreatment tumour cells and/or good drug penetration are also required. The most important levers to improve tumour cure appear to be earlier detection, higher infusion rate, lower drug clearance rate and better convection into tumour, but not tissue. In contrast, the tumour cure probability is less sensitive to a longer infusion duration and enhancements in drug potency and drug specificity.
Sucrose inhibits vascular smooth muscle cell proliferation/migration – protein synthesis is maintained
Authors: Schousboe P.
Published: March 2003

Abstract.  We have previously shown that the onset of smooth muscle cell proliferation in tissue cultures is triggered independently of serum. The aim of the present study was to investigate if this process was affected by osmotic stress. Vascular explants from 8‐month‐old male rats were cultured under serum‐free conditions using collagen I as migration substrate. Sucrose was added to the culture medium in concentrations varying from 1 to 3% (30–90 mOsM). Cell migration from aortic explants onto the culture dishes was totally inhibited at a sucrose concentration of 90 mOsM. A significant dose‐dependent decline in proliferation was shown for cells in explants pulse labelled with 3H‐thymidine. In contrast, pulse labelling with 35S‐methionine revealed that protein synthesis was maintained in the presence of sucrose. The results indicate that osmotic pressure affects smooth muscle cell protein synthesis, proliferation and migration.
Tales of transition: self‐narrative and direct scribing in exploring care‐leaving
Authors: Martin Fay E.
Published: March 2003

Direct scribing is a technique that transforms oral discourse into written text, basically by typing oral material verbatim. It was developed in practice with youth in child welfare care and adapted for research data collection. The technique flattens the power imbalance in the interview situation and between oral speech and written text, supports self‐reflection, democratizes the ownership of written material, is potentially empowering, and is an efficient means to produce high‐quality text. The origins in practice are reviewed and a research application is discussed in detail. Thirty youths aged 18/19 from child welfare constructed self‐narratives about how they conceptualized and managed the adolescent transition, and collaborated with the researcher in analysing the narrative as a story. Each interview was direct scribed and printed copy given to the participant. Participants were introduced to direct scribing by completing a questionnaire presented on a note‐book computer, and some took part in a gender‐specific group discussion as a final data‐collection event, which was audio‐taped and transcribed. The value of direct scribing and self‐narrative in this research project and possibilities for other applications are discussed.
The reduction of problem behaviours and school exclusion in at‐risk youth: an experimental study of school social work with cost–benefit analyses
Authors: Bagley  , Pritchard
Published: March 2003

A three‐year experimental programme of school social work involving 2.5 workers was introduced into a primary school and a linked secondary school serving deprived council estates with high rates of unemployment, poverty and crime and high rates of exclusions from school. In comparison with two similar schools which acted as controls, the experiment was reflected in a stat‐istically significant reduction in rates of self‐reported theft, truancy, bullying, hard‐drug use and net exclusions. Analysis of reduction in school exclusions showed that the experiment was highly cost‐effective. Qualitative evaluations supported findings from stat‐istical comparisons, suggesting that school social work can be effective in both preventing children coming into care and im‐proving school climate and teacher morale.