bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of thiopurine methyltransferase variant alleles in childhood acute lymphoblastic leukaemia
Authors: McLeod Howard L. , Coulthard Sally , Thomas Angela E. , Pritchard Stuart C. , King Derek J. , Richards Susan M. , Eden O. B. , Hall Andrew G. , Gibson Brenda E. S. 
Published: March 2003

The role of 6‐mercaptopurine (6MP) in the treatment of childhood acute lymphoblastic leukaemia (ALL) is well established. However, the efficacy of 6MP is significantly influenced by inactivation by the polymorphic enzyme thiopurine methyltransferase (TPMT). In the general population 89–94% have high TPMT activity, 6–11% have intermediate activity, and approximately 0.3% have low activity. Individuals with low‐activity experience severe or fatal toxicity with standard 6MP doses. Prospective identification of this group of patients might prevent this problem.Recent identification of the molecular basis for low TPMT activity enabled rapid assessment of altered 6MP metabolism by PCR methods. This study evaluated the frequency of mutant TPMT alleles in 147 children with ALL. One patient was homozygous mutant (0.7%), and 16 patients were heterozygous for variant TPMT alleles (10.9%). The majority of mutant alleles were TPMT*3A. Both the allele frequency and the pattern of TPMT mutations were similar to that observed in an adult British population.The number of weeks when 6MP therapy was administered at full dose was determined in patients on MRC UKALL X and XI. The 94 patients spent a median 11% of the maintenance period receiving no therapy as a result of haematological toxicity. There was no significant difference in the number of weeks when no therapy could be administered among patients with a wild‐type or heterozygous genotype. However, the one patient with a homozygous mutant genotype had severe haematological toxicity and no therapy could be administered for 53% of the maintenance period.This study demonstrates that 11.6% of the children had variant TPMT alleles. Prospective identification of TPMT genotype may be a promising tool for decreasing excessive haematological toxicity in individuals with low activity.
Detection of different Ikaros isoforms in human leukaemias using real‐time quantitative polymerase chain reaction
Authors: Olivero S. , Maroc C. , Beillard E. , Gabert J. , Nietfeld W. , Chabannon C. , Tonnelle C. 
Published: March 2003

The Ikaros gene is an essential regulator in development and haematopoiesis. Dysregulated Ikaros gene expression participates in leukaemic processes, as evidenced in animal models, and by analyses of blast‐cell populations from leukaemic patients. We used real‐time quantitative polymerase chain reaction (PCR) to evaluate the relative abundance of several Ikaros transcript isoforms in a variety of leukaemic‐cell samples. Total RNA was isolated from bone‐marrow or blood‐cell samples collected at diagnosis in children or adult patients, 18 of whom had acute myeloblastic leukaemia (AML), 61 of whom had acute lymphoblastic leukaemia (ALL) and 11 of whom had chronic myeloid leukaemia (CML). The ratio (Ik1 + Ik2)/(Ik1 + Ik2 + Ik4 + Ik7 + Ik8) ranged from 13·5% to 85% and was lower (P < 0·05) in samples from patients with m‐bcr‐abl ALL. An alternative splicing resulting in the deletion of 30 nucleotides at the end of exon 6 was observed in leukaemic samples, and in normal thymus and bone marrow.Our results are consistent with previous reports and suggest that the pattern of expression of the different human Ikaros isoforms are not homogeneous among different subsets of leukaemias.
bcl‐2 and immunoglobulin gene rearrangement in patients with hepatitis C virus infection
Authors: Zuckerman Eli , Zuckerman Tsila , Sahar Dvora , Streichman Sara , Attias Dina , Sabo Edmond , Yeshurun Daniel , Rowe Jacob M. 
Published: March 2003

An association between chronic hepatitis C virus (HCV) infection and clonal proliferation of B cells, including B cell lymphoma, has recently been demonstrated. However, the mechanism of malignant transformation is still unknown. It has been shown that B cells from patients with type II mixed cryoglobulinaemia (MC), strongly express the antiapoptotic bcl‐2 oncogene product. Therefore, we investigated a possible mechanism of lymphomagenesis, the occurrence of bcl‐2 and immunoglobulin gene rearrangement (IgH) in HCV‐infected patients. Three groups of patients were studied: (1) 44 patients with HCV and MC (anti‐HCV and HCV RNA positive); (2) 59 patients with chronic HCV infection without MC; (3) 50 patients with chronic liver disease (CLD) not related to HCV infection. The t(14;18) translocation (MBR bcl‐2–JH) and IgH rearrangement (FR3/JH) were detected by polymerase chain reaction (PCR) in peripheral mononuclear cells. bcl‐2 translocation was detected in 17/44 (39%), 7/59 (12%) and in none of the patients of groups 1, 2 and 3 respectively (P < 0·01). Monoclonal IgH rearrangement was detected in 15/44 (34%), 5/59 (8·5%) and 2/50 (4%) patients of groups 1, 2 and 3 respectively (P < 0·05). HCV‐infected patients had a higher prevalence of monoclonal IgH rearrangement and bcl‐2 translocation than patients with CLD of other aetiologies. These data suggest that HCV may play a role in the multistep mechanism of lymphomagenesis by inducing clonal proliferation of B cells and inhibition of apoptosis.
Massive immune haemolysis after allogeneic peripheral blood stem cell transplantation with minor ABO incompatibility
Authors: Bolan Charles D. , Childs Richard W. , Procter Jo Lynn , Barrett A. John , Leitman Susan F. 
Published: March 2003

Immune haemolysis as a result of minor ABO incompatibility is an underappreciated complication of haematopoietic transplantation. The increased lymphoid content of peripheral blood stem cell (PBSC) transplants may increase the incidence and severity of this event. We observed massive immune haemolysis in 3 out of 10 consecutive patients undergoing HLA‐identical, related‐donor PBSC transplants with minor ABO incompatibility. Non‐ablative conditioning had been given in 9 of these 10 cases, including two with haemolysis. Cyclosporin alone was used as prophylaxis against graft‐vs.‐host disease (GVHD). Catastrophic haemolysis of 78% of the circulating red cell mass led to anoxic death in the first case seen, but severe consequences were avoided by early, vigorous donor‐compatible red cell transfusions in the subsequent two cases. Haemolysis began 7–11 d after PBSC infusion and all patients with haemolysis had a positive direct antiglobulin test (DAT), with eluate reactivity against the relevant recipient antigen. However, neither the intensity of the DAT, the donor isohaemagglutinin titre, nor other factors could reliably be used to predict the occurrence of haemolysis. Our data indicate that haemolysis may be frequent and severe after transplantation of minor ABO‐incompatible PBSCs when utilizing cyclosporin alone to prevent GVHD. Meticulous clinical monitoring and early, vigorous donor‐compatible red cell transfusions should be practiced in all instances.
Primary prophylaxis with lamivudine of hepatitis B virus reactivation in chronic HbsAg carriers with lymphoid malignancies treated with chemotherapy
Authors: Rossi Giuseppe , Pelizzari Annamaria , Motta Maddalena , Puoti Massimo 
Published: March 2003

Hepatitis B virus (HBV) reactivation of various degrees of severity, including fulminant hepatitis, may develop in 20–50% of hepatitis B virus surface antigen (HbsAg)‐positive patients undergoing immunosuppressive or cytostatic treatment. Lamivudine is a nucleoside analogue that can directly suppress HBV replication. We have performed a pilot study to test the efficacy and tolerability of lamivudine as a primary prophylaxis of HBV reactivation in 20 consecutive patients treated for haematological malignancies, mainly of lymphoid origin. Lamivudine, 100 mg/d, was given orally from the start until 1 month after the end of chemotherapy, which included corticosteroids and/or purine analogues in 85% of cases. It was well tolerated and did not cause any unexpected reduction of cytostatic drugs dosages. The chemotherapy programme was completed in all patients without modifications. A transient threefold increase in serum amylase was observed in one case. HBV‐DNA levels decreased in six out of six patients (P = 0·039) and ALT levels in five out of six patients (P = 0·057) whose serum levels were abnormal at the onset of therapy. Two patients developed transient hepatitis. HBV reactivation was documented in only one of these patients who had stopped lamivudine 1 month before. No signs of HBV reactivation were detected both during and after treatment in 18 patients with a median follow‐up of 6 months (range 3–12). Thus, primary prophylaxis with lamivudine may be a well tolerated and effective method to reduce the frequency of chemotherapy‐induced HBV reactivation in chronic HBsAg carriers.
Laparoscopic management of acute peritonitis
Authors: Navez B , Tassetti V , Scohy J J , Mutter D , Guiot P , Evrard S , Marescaux J 
Published: March 2003

Abstract

Background
The presence of peritonitis has previously been considered to be a contraindication for the laparoscopic approach because of the theoretical risk of malignant hypercapnia and toxic shock syndrome. The aim of this retrospective study was to demonstrate that laparoscopy is feasible, safe and efficient in cases of peritonitis.

Methods
From January 1990 to July 1995, 231 patients had a laparoscopy for acute peritonitis in two centres (91 appendicular peritonitis, 69 gastroduodenal perforated ulcers, 35 perforations of the colon, 36 miscellaneous).

Results
The diagnostic accuracy of laparoscopic exploration was 84·8 per cent. The clinical preoperative diagnosis was changed by laparoscopic exploration in 25·1 per cent of patients. An unnecessary laparotomy was avoided in 6·5 per cent of patients and the site of traditional incision was modified in 8·7 per cent. Conversion rates were 25 per cent for appendicular peritonitis, 16 per cent for gastroduodenal perforation and 83 per cent (29 of 35 patients) for colonic perforation. The overall mortality rate was 3·9 per cent. No malignant hypercapnia occurred. Two patients (0·9 per cent) had postoperative septic shock but survived.

Conclusion
Laparoscopy is feasible and safe in cases of peritonitis. Laparoscopic treatment is particularly effective in the case of appendicular and gastroduodenal perforation. In the case of colonic perforation, the conversion rate remains high but with growing experience and surgical skill, more of these cases will be treated laparoscopically in the future.
Results of pancreatogastrostomy after pancreatoduodenectomy in 160 consecutive patients
Authors: Fabre J M , Arnaud J P , Navarro F , Bergamaschi R , Cervi C , Marrel E , Domergue J 
Published: March 2003

Abstract

Background
The advantages of pancreatogastrostomy over pancreatojejunostomy after pancreaticoduodenectomy are still debated. This study analyses the results of pancreatogastrostomy to identify factors that could influence immediate outcome.

Methods
During a 10-year period, 160 consecutive patients underwent a pancreatogastrostomy. There were 109 men (68 per cent) and 51 women (32 per cent) with a mean(s.d.) age of 59(10) (range 22–82) years; 27 patients were older than 70 years. The following parameters were assessed: mortality rate, morbidity, reasons for reoperation, length of hospital stay, duration of nasogastric tube and drainage.

Results
Hospital mortality rate was 3 per cent; overall morbidity rate was 30 per cent. The reoperation rate was 12 per cent, mainly because of bleeding at the pancreatic margin. Delayed gastric emptying occurred in 36 patients. The overall rate of pancreatic fistula was 2·5 per cent. Age, sex, indications for pancreatoduodenectomy, and the texture of the pancreatic remnant did not influence the occurrence of pancreatic fistula or delayed gastric emptying.

Conclusion
This study confirmed that pancreatogastrostomy is a safe procedure with low mortality and morbidity rates.
Risk factors for rebleeding and death from peptic ulcer in the very elderly
Authors: Chow L W , Gertsch P , Poon R T P , Branicki F J 
Published: March 2003

Abstract

Background
Ageing populations are increasing in many countries and bleeding peptic ulcers in patients older than 60 years carry a greater risk of rebleeding and death. This study aimed to identify the risk factors for rebleeding and death in very elderly patients with peptic ulcer bleeding. The efficacy of treatment in preventing recurrent bleeding and death in this group of patients was also studied by means of prospective data collection and analysis.

Methods
Data relating to 1744 patients treated between September 1985 and January 1994 for peptic ulcer bleeding were collected prospectively and analysed. Patients were stratified by age to one of three groups: group 1 (less than 60 years, n = 833), group 2 (60–79 years, n = 706) and group 3 (80 or more years, n = 205).

Results
Univariate and multivariate analyses of 21 factors possibly affecting either rebleeding or death identified age greater than 80 years as one of the factors significantly affecting rebleeding and death. In a comparison of groups 1, 2 and 3, the likelihood of rebleeding and death was significantly greater in group 3. Univariate and multivariate analyses for rebleeding and death were performed for each group. The severity of initial bleeding had a marked bearing on subsequent rebleeding rates for all three groups. In group 3, however, large ulcer size and impaired liver function were additional factors which correlated significantly with final outcome. No rebleeding or morbidity occurred when endoscopic treatment was performed early for patients in group 3 but there was a significantly greater risk of further recurrent haemorrhage and treatment-related morbidity when treatment was performed after the onset of rebleeding.

Conclusion
Patients aged 80 years or greater had the highest risk of rebleeding and death. For patients below 80 years of age, significant factors related to a fatal outcome included co-morbid illness, complications and the need for mechanical ventilation. For patients aged 80 years or older, the significant factors were ulcer size greater than 2 cm and admission with serum bilirubin level above 20 mmol/l. Endoscopic treatment for the very elderly was effective if carried out early.
Role of magnetic resonance angiography for assessment of abdominal aortic aneurysm before endoluminal repair
Authors: Nasim A , Thompson M M , Sayers R D , Boyle J R , Hartshorne T , Moody A R , Bell P R F 
Published: March 2003

Abstract

Background
A detailed knowledge of the morphology of the aorta and iliac arteries is an important prerequisite for successful endoluminal abdominal aortic aneurysm (AAA) repair. The best method of preoperative evaluation remains to be determined.

Methods
A prospective study was undertaken between January 1994 and July 1995 to assess the ability of computed tomography (CT), magnetic resonance angiography (MRA), colour duplex imaging and intra-arterial digital subtraction angiography (IA-DSA) to visualize AAA morphology.

Results
Eighty-two consecutive patients (64 men, 18 women) with AAA were assessed with MRA, contrast-enhanced CT, colour duplex imaging and IA-DSA. Median age was 74 (range 59–87) years and median AAA diameter was 5·7 (range 3·5–9·7) cm. Five patients were unable to tolerate CT or MRA examination. Seventy-seven patients underwent both CT and MRA. Of these, 55 also had a colour duplex scan and 32 underwent arteriography. The scans were assessed by an independent blinded observer. MRA was significantly better (P &lt; 0·01) at visualizing AAA morphology compared with CT and colour duplex imaging. There was no statistically significant difference between MRA and arteriography.

Conclusion
MRA is useful in patient selection for endoluminal AAA repair, as it avoids use of iodinated contrast medium and ionizing radiation.
Lichtenstein inguinal hernia repair in a primary healthcare setting
Authors: Lafferty P M , Malinowska A , Pelta D 
Published: March 2003

Abstract

Background
Given the generally accepted poor outcome of inguinal hernia repair when using nylon darn, and the recent interest in low-tension mesh repair, an attempt was made to demonstrate the feasibility, outcome and patient perception of providing Lichtenstein inguinal hernia repair, using local anaesthesia, wholly within the primary healthcare sector.

Methods
A prospective study reviewed clinical outcome and patient perception in 100 adults referred with inguinal hernia only. No selection was made regarding age, sex, American Society of Anesthesiologists status or previous repairs. Recurrence, pain, infection, return to full function and associated complications were assessed at 24 h, 1 and 6 weeks, and 1 year. Local Community Health Councils assessed patient perception.

Results
In the first 100 patients (age range 21–83 (mean(s.d.) 60(14·7)) years; 58 of employable age; 92 men; ten recurrent hernias), no recurrences have occurred at 1 year. Infection rate was 3 per cent. Pain was maximal in the first 24–48 h (median visual analogue scale 5, range 0–10) and reduced rapidly (median 1) at 1 week. Mean time to return to work or full normal activity was 8 days. Some 85 operations were performed within 1 month of diagnosis. In all, 86 patients returned the patient satisfaction questionnaire and 98 per cent of these were ‘very pleased’ with the service.

Conclusion
In highly motivated primary healthcare centres, inguinal hernia repair can be undertaken effectively, providing high patient satisfaction, minimal complications and low recurrence rates using the Lichtenstein technique.
Randomized trial of early versus delayed laparoscopic cholecystectomy for acute cholecystitis
Authors: Lai P B S , Kwong K H , Leung K L , Kwok S P Y , Chan A C W , Chung S C S , Lau W Y 
Published: March 2003

Abstract

Background
The aim of this prospective randomized study was to define the optimum management between early and delayed laparoscopic cholecystectomy for patients with acute cholecystitis.

Methods
Patients were randomized to receive either early laparoscopic cholecystectomy within 24 h of randomization or initial conservative treatment followed by delayed laparoscopic cholecystectomy 6–8 weeks later.

Results
There were 53 patients in the early group and 51 in the delayed group. There was no significant difference in conversion rate (early 21 per cent versus delayed 24 per cent), postoperative analgesic requirement (1 versus 2 doses) and postoperative complications. However, the early group had significantly longer operating time (122·8 versus 106·6 min, P = 0·04) and shorter total hospital stay (7·6 versus 11·6 days, P &lt; 0·001).

Conclusion
Early laparoscopic cholecystectomy is safe and feasible for acute cholecystitis with the additional benefit of shorter total hospital stay. Apart from a shorter operating time, treating patients with delayed laparoscopic cholecystectomy does not offer additional benefit.
Lack of telomerase in desmoids occurring sporadically and in association with familial adenomatous polyposis
Authors: Scates D K , Clark S K , Phillips R K S , Venitt S 
Published: March 2003

Abstract

Background
Telomerase activity may be required for unlimited growth of cells and is repressed in most somatic tissues, but is detectable in immortal cell lines, germ cells, many malignancies and some benign lesions. Desmoids are proliferative, locally invasive, non-metastasizing fibromatous tumours which rarely regress. They occur frequently in familial adenomatous polyposis (FAP), causing significant morbidity and death. Telomerase activity was assayed in desmoids from patients with and without FAP to assess the role of telomerase in the development of these lesions, and its potential as a prognostic marker and possible target for treatment.

Methods
Protein extracts from 11 desmoids from nine patients with FAP, and ten desmoids from ten patients without FAP, were analysed for telomerase activity by the telomeric repeat amplification protocol, a sensitive polymerase chain reaction-based assay. Six fibrosarcomas and a fibrosarcoma cell line were used as positive controls; all displayed telomerase activity.

Results
No telomerase activity was detected in any of the 21 desmoids studied.

Conclusion
These results indicate that desmoid tumours are one of the intriguing exceptions to the emerging view that re-expression of telomerase activity accompanies the development of preneoplastic and neoplastic tissues, and suggest that alternative mechanisms may operate in these proliferative neoplasms.
Antibiotic prophylaxis in the initial management of severe acute pancreatitis
Authors: Powell J J , Miles R , Siriwardena A K 
Published: March 2003

Abstract

Background
The role of antibiotic prophylaxis in the initial management of patients with acute pancreatitis is an area of major controversy. Contrary to earlier clinical trials, recent experimental and clinical studies have accrued evidence that warrants reappraisal of current clinical practice. This article reviews these recent advances in knowledge.

Methods
All papers derived from a Medline search for the years 1990–1997 inclusive using the text words ‘acute’, ‘pancreatitis’, ‘antibiotic’ and ‘antibiotics’ were studied. Additional papers were derived from reference lists within papers identified by the Medline search. Only experimental and clinical papers relevant to the issue of prophylactic antibiotic therapy in acute pancreatitis are included in the review.

Results and conclusion
Current experimental evidence favours the use of prophylactic antibiotics in severe acute pancreatitis. The results of contemporary randomized clinical trials restricted to patients with prognostically severe acute pancreatitis have demonstrated improvement in outcome associated with antibiotic treatment.
Port-site metastases following laparoscopic surgery
Authors: Neuhaus S J , Texler M , Hewett P J , Watson D I 
Published: March 2003

Abstract

Background
Application of laparoscopy to the resection of malignancy has been followed by a literature describing cases of metastatic involvement at laparoscopic port sites. These include patients who underwent surgery for early stage carcinoma and instances following laparoscopic procedures during which tumours were not dissected.

Methods
Recently published clinical and experimental studies, and case reports related to this problem are reviewed; their relevance is discussed.

Results
Experimental studies incorporating bench top and large animal models have confirmed that tumour cells may be redistributed to port sites during laparoscopic surgery either directly from contaminated instruments or indirectly via the insufflation gas. Small animal models suggest that the incidence of wound metastasis is increased following conventional laparoscopic surgery, and that it may be decreased by gasless laparoscopy or helium insufflation. This evidence suggests that the development of port-site metastases depends not only on the physical redistribution of tumour cells but also on the specific insufflation gas used, possibly because of influences on local metabolic or immune factors acting at the wound site.

Conclusion
Further research in this area is urgent. Until the issue is better understood, patients undergoing laparoscopic surgery for malignancy should be entered into clinical trials.