bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cost‐effectiveness and quality‐of‐life assessment of GM‐CSF as an adjunct to intensive remission induction chemotherapy in elderly patients with acute myeloid leukaemia
Authors: Uyl‐DE Groot  , LÖwenberg  , Vellenga  , Suciu  , Willemze  , Rutten  
Published: March 2003

We conducted a prospective, randomized, multicentre clinical trial comparing the effects and costs of GM‐CSF as an adjunct to intensive chemotherapy in elderly patients with acute myeloid leukaemia (AML). The patients were randomized to either daunomycin–cytosine arabinoside (control arm: n = 161) or daunomycin–cytosine arabinoside with GM‐CSF (GM‐CSF arm: n = 157). The primary end‐point was the effect of GM‐CSF on the percentage of complete remissions (CR). Survival duration, disease‐free survival, quality of life and costs were evaluated separately.CR after remission induction treatment was achieved in 55% of the patients in the control group and in 56% of the patients in the GM‐CSF group (P = NS). The duration of survival and disease‐free survival at 2 years after randomization were estimated at 22% and 19% for the control group and 22% and 14% for the GM‐CSF group (P = NS). Considering the short‐term quality of life, the administration of GM‐CSF resulted in more problems with regard to depressed mood, diarrhoea and rash/eczema. With regard to the long‐term quality of life there were no significant differences between the two groups. The average costs of the primary treatment were higher in GM‐CSF‐treated patients than in the control group, i.e. US$40782 and US$34465, respectively (P < 0.01). The costs during the follow‐up period did not differ between the two groups.The results of this randomized clinical trial indicate that daunomycin–cytosine arabinoside plus GM‐CSF is not a cost‐effective treatment strategy when compared with daunomycin–cytosine arabinoside alone.
Functional analysis of the p53 protein in AIDS‐related non‐Hodgkin's lymphomas and polymorphic lymphoproliferations
Authors: Martin Antoine , Flaman Jean‐Michel , Frebourg Thierry , Davi FRÉDÉric , EL Mansouri Said , Amouroux Jacques , RaphaËL Martine 
Published: March 2003

Alteration of the tumour suppressor gene p53 is frequent in AIDS‐related non‐Hodgkin's lymphomas (AIDS‐NHL), particularly in Burkitt's or Burkitt's‐like lymphomas (BL/BLL). Since mechanisms of inactivation other than mutations have been advanced, the transcriptional activity of the p53 protein was studied in a functional assay in yeast in a series of AIDS‐NHL lesions and compared with their morphology, immunohistochemistry (IHC) and single‐strand conformation polymorphism (SSCP) analysis detection of other p53 abnormalities, Epstein‐Barr virus (EBV) status, MDM‐2 oncoprotein expression and c‐MYC rearrangement. Polymorphic lymphoproliferations (PL), identified as precursors of NHL in HIV‐patients, were also analysed in attempt to detect p53 modifications related to clonal progression.The functional assay detected p53 mutants in 40% (12/30) of the tumours: 50% (6/12) of BL/BLL, 40% (4/10) of diffuse large cell lymphomas (DLCL) and 25% (2/8) of PL. An oligoclonal or monoclonal population was identified in the two PL cases with mutant p53. An accumulation of the p53 protein was detected by IHC in 26% (8/30) of the tumours (five BL/BLL and three DLCL) and was associated with positive functional assay. In the 20 lesions tested by both of the screening methods for mutations, a p53 mutant pattern was detected in 55% of cases (11/20) and in 25% of cases (5/20) respectively with the functional assay and SSCP analysis of exons 5–8. There was no inverse correlation between the detection of EBV genome and the presence of p53 mutations and no overexpression of MDM‐2 protein for the whole series. In conclusion, the functional assay was more sensitive than IHC and SSCP for the detection of p53 mutations in tumour samples. The mutations identified in AIDS‐NHL lesions inactivate the p53 protein and in PL they could represent a selection of an aggressive clone.
Mapping the prevalence of sickle cell and beta thalassaemia in England: estimating and validating ethnic‐specific rates
Authors: Hickman M. , Modell B. , Greengross P. , Chapman C. , Layton M. , Falconer S. , Davies S. C. 
Published: March 2003

A range of estimates for sickle cell and β thalassaemia have been derived for the different ethnic groups living in the U.K., reflecting uncertainty over the true population value in certain countries and the heterogeneity within and between countries of origin comprising the same ethnic group. These were validated against six community screening programmes, with the estimated range correctly predicting the number of affected births observed by the programmes.In England approximately 3000 affected babies (0.47%) carry sickle cell trait and 2800 (0.44%) carry β thalassaemia trait annually; with approximately 178 (0.28 per 1000 conceptions) affected by sickle cell disease (SCD) and 43 (0.07 per 1000) by β thalassaemia major/intermedia. Allowing for termination, about 140–175 (0.22–0.28 per 1000) affected infants are born annually with SCD and from 10 to 25 (0.02–0.04 per 1000) with β thalassaemia major/intermedia.These are the first evidence‐based rates for sickle cell and β thalassaemia for use in the U.K., and should underpin the future planning of services. The long‐term solution to monitoring changes in the rates of trait and disease in the population is to introduce a standardized instrument for collecting ethnicity for all community screening programmes.
Thrombosis and bleeding in myeloproliferative disorders: identification of at‐risk patients with whole blood platelet aggregation studies
Authors: Manoharan A. , Gemmell R. , Brighton T. , Dunkley S. , Lopez K. , Kyle P. 
Published: March 2003

Seventy‐five patients with chronic myeloproliferative disorders were studied to investigate platelet function by simultaneous measurement of platelet aggregation by the impedance method and ATP dense granule release using a whole blood platelet lumi‐aggregometer, in an attempt to identify patients at risk for thrombosis and bleeding.Thirty‐nine patients had at least one abnormal result indicating platelet hyperactivity (i.e. impedance or release with one agonist being above the reference range); 16 patients had platelet hypoactivity (i.e. at least one result was below the reference range), whilst 14 had co‐existence of hyper‐ and hypoactivity. Six patients had normal results. 20/53 patients with platelet hyperactivity (alone or mixed) had a positive history of venous and/or arterial thrombosis; in comparison, only two of the other 22 patients had a positive history. During a median follow‐up of 33 months, nine patients with and one patient without platelet hyperactivity respectively developed new thrombotic events before the addition of specific therapy. A total of 50 patients with and eight patients without platelet hyperactivity respectively received specific treatment including aspirin and/or cytotoxic therapy. All but one elderly patient with platelet hyperactivity have remained free of new thrombotic events on specific therapy. Two of the 17 patients with platelet hypoactivity had major clinical bleeding.These observations highlight the need to test platelets for hyper‐ as well as hypo‐function and suggest a useful role for routine whole blood platelet aggregation studies to identify the patients at risk for thrombosis or bleeding.
Standardization of the PFA‐100® platelet function test in 105 mmol/l buffered citrate: effect of gender, smoking, and oral contraceptives
Authors: Böck  , De Haan  , Beck  , Gutensohn  , Hertfelder  , Karger  , Heim  , Beeser  , Weber  , Kretschmer  
Published: March 2003

The PFA‐100® (PFA) diagnostic system for the detection of platelet dysfunction was evaluated to determine reference ranges in a normal population. The PFA determines the primary haemostasis capacity (PHC) of anticoagulated whole blood, expressed by the system's closure time (CT). In this study the CT reference ranges were determined for blood samples collected in 105 mmol/l (3.2%) buffered citrate and the effect of gender, smoking, and use of oral contraceptives on reference ranges was assessed. Each of the 309 healthy blood donors from five blood centres was confirmed to have normal platelet function before inclusion in the study. Blood samples were tested in duplicate with both the collagen/epinephrine (Col/Epi) and collagen/ADP (Col/ADP) test cartridges.PFA reference ranges (90% central intervals of measured closure times) for both cartridge types were similar for all groups. Subgroup analysis showed that neither gender nor oral contraceptive usage had any effect on PHC. The 95% cut‐off value for the Col/Epi CT was slightly higher for smokers than for non‐smokers, an effect more pronounced in female than in male donors. However, the small difference did not justify establishment of specific reference ranges for smokers. Data from all included subjects were pooled to calculate the CT reference ranges for blood samples collected in 105 mmol/l buffered citrate (Col/Epi 82–150 s; Col/ADP 62–100 s). Normal levels of fibrinogen, as well as normal platelet counts and normal haematocrit levels, appeared not to influence the PHC. Because slight but significant differences of the reference ranges were observed between some of the participating sites, in‐house confirmation of these reference range guidelines is recommended.
VH gene usage by family members affected with chronic lymphocytic leukaemia
Authors: Pritsch Otto , Troussard Xavier , Magnac Christian , Mauro Francesca R. , Davi Frederic , Payelle‐Brogard Beatrice , Dumas Gerard , Pulik Marc , Clerget Françoise , Mandelli Franco , Chiorazzi Nicholas , Schroeder Jr Harry W. , Leporrier Michel , Dighiero Guillaume 
Published: March 2003

The excess risk of chronic lymphocytic leukaemia (CLL) in the first‐degree relatives of affected patients suggests that familial CLL might constitute a useful model to study the pathogenesis of this disease, as has been demonstrated in numerous other neoplastic disorders. Previous studies have shown non‐random utilization of immunoglobulin genes in CLL, some germline in sequence and others containing numerous somatic mutations. To investigate whether familial cases of CLL exhibit similarities in the composition of the B‐cell receptor repertoire to the pattern expressed by CLL patients as a whole, we have studied 25 CLL patients belonging to 12 different families (four French and eight Italian), each of which contained at least two affected members.Among familial cases, VH gene segment utilization proved non‐random and diverged from the frequencies previously reported among unrelated patients with CLL. Specifically, although the 4‐34 and 5‐51 gene segments were found repeatedly, the 1‐69 and 4‐39 gene segments were used sparingly and the 3‐23 gene segment presented with increased frequency. Following the pattern detected in studies of unrelated patients, the single 1‐69 expressing CLL contained an unmutated H chain sequence and included a long HCDR3 interval. In contrast, 3‐23 containing H chains all used JH4, retained at most 93% homology with germline sequence, and included only short HCDR3 intervals. The vast majority of the CLL variable domains contained a high degree of somatic mutation and exhibited an excess of replacement mutations in the CDR intervals. These findings suggest that familial CLL cases may preferentially derive from B‐cell progenitors that have responded to antigen.
Treatment of infants with lymphoblastic leukaemia: results of the UK Infant Protocols 1987–1999
Authors: Chessells J. M. , Harrison C. J. , Watson S. L. , Vora A. J. , Richards S. M. ,   for the Medical Research Council Working Party on Childhood Leukaemia*
Published: March 2003

Summary.  One hundred and twenty‐six infants with acute lymphoblastic leukaemia (ALL) were treated on two consecutive protocols, Infant 87 (n = 40) and Infant 92 (n = 86), in an attempt to improve the poor prognosis of this disease. Both included intensive induction and consolidation with intrathecal and high‐dose systemic therapy for central nervous system (CNS) protection. Intensification therapy was modified and high‐dose chemotherapy with bone marrow transplantation in first remission was permitted in Infant 92. Four‐year event‐free survival was superior in Infant 92 (33%; 95% CI 23–44%) compared with Infant 87 (22·5%; 95% CI 12–37%) (P = 0·04) and survival at 4 years was also superior, 46% (95% CI	35–57%) c.f. 32·5% (95% CI 20–48%) (P = 0·01), largely as a result of a significant reduction in remission deaths. Twelve patients in Infant 92 underwent bone marrow transplantation (BMT) in first remission, but their survival was no better than that of patients receiving chemotherapy. Multivariate analysis of prognostic factors showed the adverse influence of younger age, CNS involvement at diagnosis and a high initial leucocyte count, but not of CD10 expression. Cytogenetic analysis, available in 93% of patients in Infant 92, showed that 67% had chromosomal rearrangements involving 11q23 of which 39% had the translocation t(4;11) (q21;q23). There was no significant difference in event‐free survival between cytogenetic subgroups, although no children under 6 months of age with 11q23 abnormalities, other than the t(4;11), survived. In conclusion, infants with lymphoblastic leukaemia remain a high‐risk group, but it is unclear whether their adverse prognosis can be attributed to unfavourable cytogenetics alone. The role of high‐dose therapy and BMT in first remission remains uncertain.
Laparoscopic cholangiography: a prospective study
Authors: Sabharwal A J , Minford E J , Marson L P , Muir I M , Hill D , Auld C D 
Published: March 2003

Abstract

Background
The place of cholangiography has been controversial in the conventional and now in the laparoscopic setting. The aim of this study was to evaluate laparoscopic cholangiography and compare use of a portable C-arm image intensifier with conventional radiography.

Methods
One hundred and ninety-seven consecutive patients undergoing laparoscopic cholecystectomy were randomized before operation to cholangiography by either C-arm image intensifier or conventional radiography. Data were collected on a pro forma completed immediately after the operation.

Results
Cholangiography was successful in 93·0 per cent of patients. Cholangiography with an image intensifier was significantly faster. In 19 patients the ductal system was obscured by a cannula; in 17 of these cases a metal cannula was used. In 31·6 per cent of patients the clip on the cystic duct was within 1 cm or less of the common bile duct (CBD).

Conclusion
Laparoscopic cholangiography is a safe procedure. Use of an image intensifier should be the preferred method of obtaining images. Metal cannulas are more likely to obscure the ductal system. The proximity of the clip on the cystic duct to the CBD highlights the potential for injury caused by electrocautery or erroneous clip application.
Role of saphenous vein surgery in the treatment of venous ulceration
Authors: Scriven J M , Hartshorne T , Thrush A J , Bell P R F , Naylor A R , London N J M 
Published: March 2003

Abstract

Background
This paper describes local anaesthetic saphenous disconnection in elderly patients for the treatment of venous ulceration in legs with either saphenous venous reflux alone or in combination with deep venous reflux.

Methods
Ambulatory venous pressure was measured in 16 legs with saphenous vein reflux alone and in nine legs with combined deep and saphenous venous reflux before, immediately after and 3 months after saphenofemoral or popliteal disconnection. Ulcer area was measured by computerized planimetry before surgery and at 1 and 3 months after operation. No compression bandages or hose were applied after surgery unless the ulcers had not begun to heal after 1 month.

Results
In legs with saphenous reflux alone all ulcers healed without compression bandages at a median of 81 (range 14–253) days and the pressure relief index (PRI) improved significantly both after surgery and at follow-up. None of the ulcers in the nine limbs with saphenous and deep venous reflux healed without compression bandaging and the PRI was unchanged immediately following surgery and at follow-up.

Conclusion
Saphenous vein disconnection improves venous function and heals venous ulcers without compression bandaging if the deep veins are normal. This procedure under local anaesthetic may be particularly suitable for elderly patients, but long saphenous vein stripping should be added in young patients.
Raised endothelin 1 levels in patients with colorectal liver metastases
Authors: Shankar A , Loizidou M , Aliev G , Fredericks S , Holt D , Boulos P B , Burnstock G , Taylor I 
Published: March 2003

Abstract

Background
Endothelin 1 (ET-1), a vasoconstrictor peptide, has been implicated as a tumour growth stimulator and an angiogenesis factor.

Methods
To assess the involvement of ET-1 in colorectal cancer, immunoelectron microscopy for ET-1 was performed in colorectal liver metastases and normal liver (n = 6). ET-1 plasma levels were measured by radioimmunoassay in patients with colorectal cancer, with (n = 18) and without (n = 12) liver metastases, and in controls (n = 22).

Results
In normal liver, ET-1 was present in endothelial cells; in tumour, it was observed in endothelial cells, tumour cells and myofibroblasts. Mean(s.d.) plasma ET-1 levels were 2·75 (1·37) pg/ml in controls, 4·53(1·61) pg/ml in patients with colorectal liver metastases (P = 0·001) and 3·92(1·32) pg/ml in patients without metastases (P = 0·02).

Conclusion
ET-1 was present in various cell types within colorectal liver metastases and raised levels were found in the plasma of patients with colorectal cancer. ET-1 may not only modulate tumour vascular tone but also act on tumour growth and angiogenesis, both locally and systemically.
J ileal pouch–anal anastomosis for chronic ulcerative colitis: complications and long-term outcome in 1310 patients
Authors: Meagher A P , Farouk R , Dozois R R , Kelly K A , Pemberton J H 
Published: March 2003

Abstract

Aim
The purpose of the study was to determine the risk of postoperative complications and the functional outcome after a hand-sewn ileal pouch–anal anastomosis (IPAA) for ulcerative colitis using a single J-shaped pouch design.

Methods
Preoperative function, operative morbidity and long-term functional outcome were assessed prospectively in 1310 patients who underwent IPAA between 1981 and 1994 for ulcerative colitis.

Results
Three patients died after operation. Postoperative pelvic sepsis rates decreased from 7 per cent in 1981–1985 to 3 per cent in 1991–1994 (P=0·02). After mean follow-up of 6·5 (range 2–15) years, the mean number of stools was 5 per day and 1 per night. Frequent daytime and night-time incontinence occurred in 7 and 12 per cent of patients respectively, and did not change over a 10-year period. The cumulative probability of suffering at least one episode of ‘clinical’ pouchitis was 18 and 48 per cent at 1 and 10 years and the cumulative probability of pouch failure at 1 and 10 years was 2 and 9 per cent respectively.

Conclusion
These results indicate that increased experience decreases the risk of pouch-related complications and that with time the functional results remain stable, but the failure rate increases.
Oral colonization is unlikely to play an important role in Helicobacter pylori infection
Authors: Oshowo A , Tunio M , Gillam D , Botha A J , Holton J , Boulos P , Hobsley M 
Published: March 2003

Abstract

Background
This clinical and microbiological study investigated whether Helicobacter pylori colonizes the mouth en route to the pyloric antrum. It has been suggested that oral colonies are a source of reinfection after eradication of gastric infection.

Methods
Some 208 patients attending for routine diagnostic endoscopy for dyspepsia were recruited. Before endoscopy, samples were collected of saliva, supragingival and infragingival plaque, and swabs were taken from the tongue, mouth and pharynx. At endoscopy, gastric antral biopsies were taken for the rapid urease test, culture and histological examination. Gastric and duodenal juice samples were aspirated. Restriction nuclease digestion with HaeIII was employed on all specimens from patients in whom there was evidence of the organism in the mouth.

Results
H. pylori was observed in dental plaque in only 15 patients, all from the 116 who had evidence of the organism in the stomach. Restriction endonuclease digestion demonstrated that in 13 of the 15 patients the strains were identical in mouth and stomach.

Conclusion
Oral colonization is a rare event, but does occur. Its rarity suggests that it is not an important factor in reinfection.
Metachronous colorectal cancers
Authors: Fajobi O , Yiu C-Y , Sen-Gupta S B , Boulos P B 
Published: March 2003

Abstract

Background
Up to 9 per cent of patients who undergo resection for colorectal cancer develop metachronous cancers. There is no consensus on the detection and management of such cancers.

Methods
The literature was reviewed exhaustively regarding the incidence, clinical characteristics, detection, treatment and molecular genetics of metachronous colorectal cancers. This was based on a Medline search from 1966 to December 1997 for articles on metachronous colorectal cancers. A manual search was also performed on references quoted in these articles. All publications relevant to this study were included.

Results
Although the underlying causes for metachronous colorectal cancers are yet to be elucidated, risk factors for the disease have been identified. These include the presence of synchronous polyps or cancers, a history of metachronous cancers, and hereditary non-polyposis colorectal cancer (HNPCC).

Conclusion
Preoperative colonoscopy and postoperative colonoscopic surveillance are essential in identifying patients at risk of metachronous colorectal cancer. A total colectomy and ileorectal anastomosis should be considered for some patients, certainly for those with HNPCC.