Showing papers by "Royal London Hospital published in 2005"

Local recurrence of colorectal cancer: The problem, mechanisms, management and adjuvant therapy

Abstract: Local recurrence of colorectal cancer after 'curative' surgery is a major clinical problem. Typically, 50-70 per cent of patients presenting to a surgical clinic will undergo apparently curative surgery for disease and of these about 10-25 per cent will develop local recurrence, in either the tumour bed or bowel wall. The wide differences in local recurrence rate both between and within institutions is probably caused by variation in surgical technique. The main causes of local recurrence are inadequate excision of the primary tumour or the draining lymph nodes, and intraoperative tumour cell implantation. The most significant single factor prognostic of local recurrence is Dukes' tumour stage. Other important factors include tumour grade and fixity, level of the tumour in the rectum, blood and lymphatic vessel invasion, inadvertent perforation of the tumour during resection, and the surgeon's experience. The prognosis of patients with local recurrence is poor. Prevention of recurrence by adequate surgery and adjuvant therapy as well as its early detection offer the best prospect of improving results.

Mutations in ABCA12 underlie the severe congenital skin disease harlequin ichthyosis.

Abstract: Harlequin ichthyosis (HI) is the most severe and frequently lethal form of recessive congenital ichthyosis. Although defects in lipid transport, protein phosphatase activity, and differentiation have been described, the genetic basis underlying the clinical and cellular phenotypes of HI has yet to be determined. By use of single-nucleotide–polymorphism chip technology and homozygosity mapping, a common region of homozygosity was observed in five patients with HI in the chromosomal region 2q35. Sequencing of the ABCA12 gene, which maps within the minimal region defined by homozygosity mapping, revealed disease-associated mutations, including large intragenic deletions and frameshift deletions in 11 of the 12 screened individuals with HI. Since HI epidermis displays abnormal lamellar granule formation, ABCA12 may play a critical role in the formation of lamellar granules and the discharge of lipids into the intercellular spaces, which would explain the epidermal barrier defect seen in this disorder. This finding paves the way for early prenatal diagnosis. In addition, functional studies of ABCA12 will lead to a better understanding of epidermal differentiation and barrier formation.

Benefit of dexamethasone compared with prednisolone for childhood acute lymphoblastic leukaemia: results of the UK Medical Research Council ALL97 randomized trial.

Abstract: Summary Corticosteroids are an essential component of treatment for acute lymphoblastic leukaemia (ALL). Prednisolone is the most commonly used steroid, particularly in the maintenance phase of therapy. There is increasing evidence that, even in equipotent dosage for glucocorticoid effect, dexamethasone has enhanced lymphoblast cytotoxicity and penetration of the central nervous system (CNS) compared with prednisolone. Substitution of dexamethasone for prednisolone in the treatment of ALL might, therefore, result in improved event-free and overall survival. Children with newly diagnosed ALL were randomly assigned to receive either dexamethasone or prednisolone in the induction, consolidation (all received dexamethasone in intensification) and continuation phases of treatment. Among 1603 eligible randomized patients, those receiving dexamethasone had half the risk of isolated CNS relapse (P = 0·0007). Event-free survival was significantly improved with dexamethasone (84·2% vs. 75·6% at 5 years; P = 0·01), with no evidence of differing effects in any subgroup of patients. The use of 6·5 mg/m2 dexamethasone throughout treatment for ALL led to a significant decrease in the risk of relapse for all risk-groups of patients and, despite the increased toxicity, should now be regarded as part of standard therapy for childhood ALL.

Syphilis in adults

Abstract: Syphilis is a sexually transmitted disease with protean manifestations resulting from infection by Treponema pallidum. It is systemic early from the outset, the primary pathology being vasculitis. Acquired syphilis can be divided into primary, secondary, latent, and tertiary stages. The infection can also be transmitted vertically resulting in congenital syphilis, and occasionally by blood transfusion and non-sexual contact. Diagnosis is mainly by dark field microscopy in early syphilis and by serological tests. The management in the tropics depends on the diagnostic facilities available: in resource poor countries, primary syphilis is managed syndromically as for anogenital ulcer. The introduction of rapid "desktop" serological tests may simplify and promote widespread screening for syphilis. The mainstay of treatment is with long acting penicillin. Syphilis promotes the transmission of HIV and both infections can simulate and interact with each other. Treponemes may persist despite effective treatment and may have a role in reactivation in immunosuppressed patients. Partner notification, health education, and screening in high risk populations and pregnant women to prevent congenital syphilis are essential aspects in controlling the infection.

Real-time, fluorescence-based quantitative PCR: a snapshot of current procedures and preferences

Abstract: Real-time fluorescence-based quantitative PCR has become established as the benchmark technology for the quantification of nucleic acids, offering an immense choice of protocols, chemistries and instruments. However, whilst there are comparatively few technical problems associated with DNA-targeted quantitative PCR, this is not the case for real-time reverse transcription PCR assays, and there is considerable uncertainty regarding biological or clinical relevance of many real-time reverse transcription PCR results. A survey of working practices of nearly 100 delegates carried out prior to the Third qPCR Symposium held in London, UK, April 25-26, 2005, reveals some of the reasons underlying the variability of reported real-time reverse transcription PCR results. Specifically, the survey reveals extensive interlaboratory variation in assay design, validation and analysis that, together with other dubious practices, are the likely cause for the publication of variable results. These results emphasize the urgent need for the establishment of best practice guidelines for this technology, particularly in the context of its mounting adaptation as a high-throughput clinical diagnostic assay.

Right thoracoscopically assisted oesophagectomy for cancer.

Abstract: Thoracoscopic mobilization was performed in nine patients with oesophageal cancer. Five principles emerged as essential for successful dissection: (1) the selection of patients with mobile oesophageal tumours without evidence of local invasion; (2) double-lumen anaesthesia and complete collapse of the right lung during surgery; (3) simultaneous use of a flexible gastroscope; (4) high-quality illumination; and (5) minimal blood loss during dissection. The surgeon should have adequate training in thoracic operations. Further experience should permit mediastinal lymph node dissection. Postoperative pulmonary complications were common, requiring prolonged intensive care management. Widespread adoption of the technique cannot be recommended.

Quality of life in thalassemia.

Abstract: Morbidity and mortality related to thalassemia have been reduced significantly with modern medical treatment, and quality of life (QOL) should now be considered an important index of effective health care. An assessment of QOL differs from other forms of medical assessment in that it focuses on the individuals' own views of their well-being and assesses other aspects of life, giving a more holistic view of well-being. There is very little published work on evaluation of QOL in thalassemia. A suitable tool should be reproducible, sensitive to the major features of the condition that affect patients' lives, and applicable in the range of different cultural, age, and social settings. Such an instrument would be valuable in evaluating new forms of treatment and in comparing health outcomes between different clinics. Two instruments have been assessed, one derived from the WHOQOL-100 questionnaire, and one designed specifically for thalassemia, which assesses psychosocial and clinical burden, as they affect adult patients, parents, and children. Further studies are required to develop and assess such tools for use in thalassemia. Another approach is to seek patients' own views of their routine treatment and the extent to which medical treatment affects QOL. Results from patient questionnaires in the United Kingdom and Cyprus are consistent in finding problems with organization of transfusions, insufficient options with chelation therapy, and poor communication. Practical measures could be taken to address these issues.

Helical computed tomographic scanning for the evaluation of the cervical spine in the unconscious, intubated trauma patient.

Abstract: Background:Assessment of the spine in the unconscious trauma patient is limited by an inadequate clinical examination. The potential of a missed unstable disc or ligamentous injury results in many patients remaining immobilized in critical care units for prolonged periods.Methods:This study evaluate

Emergency thoracotomy: "how to do it".

Abstract: This paper describes a simple approach to emergency thoracotomy that can be used by a doctor in the prehospital environment and in the resuscitation room.

A comparison of the Twin Block and Herbst mandibular advancement splints in the treatment of patients with obstructive sleep apnoea: a prospective study.

Abstract: This prospective, randomized, crossover study of 16 patients with obstructive sleep apnoea (OSA) [12 males, four females; median body mass index (BMI) 29.2 kg/m(2) (range 23.8-51.1); median age 44.8 years (range 24.0-68.4)] analysed the efficacy of the Twin Block (TB) in relation to the Herbst appliance as a mandibular advancement splint (MAS). Each subject was fitted with a TB and Herbst MAS in a random order with a washout period of 2 weeks between appliances. Once each patient was subjectively happy with the performance of each appliance, questionnaires and a visual analogue scale (VAS) were used to determine differences in snoring, daytime sleepiness, quality of life, side-effects of the appliances and patient preference. All patients underwent overnight domiciliary sleep recordings prior to and after fitting each appliance in order to objectively assess sleep quality in terms of the apnoea-hypopnoea index (AHI), snoring frequency and arterial oxygen saturation. The results suggested that there was no difference in the treatment performance of the TB and Herbst MAS for AHI (P = 0.71), snoring frequency (P = 0.49), arterial blood oxygen saturation (P = 0.97), quality of life and side-effects. The Herbst MAS proved to be the more effective appliance for reducing daytime sleepiness (P = 0.04) and was the more popular appliance among the patients. Side-effects with both appliances were minor and improved in the longer term. The TB MAS represents a viable alternative to the Herbst MAS in the treatment of patients with OSA.

Fatty tumours of the large intestine: a clinicopathological review of 13 cases.

Abstract: Thirteen cases of benign fatty tumours of the colon have been reviewed There were ten instances of submucosal lipoma, two of which were multiple, and three of lipohyperplasia of the ileocaecal valve Abdominal pain and gastrointestinal bleeding were the commonest symptoms Barium enema and angiography were misleading, the former in confusing polypoid lipomas and protruberant ileocaecal valves with carcinoma, the latter in misinterpreting fatty tissue vasculature as angiodysplasia in three patients Most lesions were in the right side of the colon, and many were treated by limited colectomy as if for carcinoma or angiodysplasia No patient has died as a result of their disease Awareness of the possibility of colonic lipomas and knowledge of the normal ileocaecal valve anatomy are of importance to radiologists and endoscopists, particularly now that angiography is localizing the smaller fatty lesions

Systemic pyoderma gangrenosum responding to infliximab and adalimumab

Abstract: Pyoderma gangrenosum (PG) is frequently associated with constitutional symptoms as part of a nonspecific inflammatory response. However, extracutaneous discrete aseptic neutrophilic infiltrates are extremely rare. We report a patient with idiopathic PG with splenic and psoas muscle involvement. His disease was extremely aggressive and was unresponsive to conventional immunosuppressive therapy. His cutaneous and extracutaneous PG cleared with infliximab and adalimumab.

Rectal intussusception in symptomatic patients is different from that in asymptomatic volunteers

Abstract: Background: Rectal intussusception is a common finding at evacuation proctography in both symptomatic and asymptomatic individuals. Little information exists, however, as to whether intussusception morphology differs between patients with evacuatory dysfunction and healthy volunteers. Methods: Thirty patients (19 women; median age 44 (range 21–76) years) with disordered rectal evacuation, in whom an isolated intussusception was seen on proctography, were studied. Various morphological parameters were measured, and compared with those from 11 asymptomatic controls (six women; median age 30 (range 24–38) years) found, from 31 volunteers, to have rectal intussusception. Intussusceptum thickness greater than 3 mm was designated as full thickness. Intussuscepta impeding evacuation were deemed to be occluding. Results: Twenty-two patients had full-thickness intussusception, compared with two controls (P = 0·003). Intussusceptum thickness was significantly greater in the symptomatic group (anterior component: P = 0·004; posterior: P = 0·011). Twenty patients in the symptomatic group, but only three subjects in the control group, had a mechanically occluding intussusception (P = 0·043), although only three patients demonstrated evacuatory dynamics outside the normal range. Conclusion: Rectal intussusception in patients with evacuatory dysfunction is more advanced morphologically than that seen in asymptomatic controls; it is predominantly full thickness in patients and mucosal in controls. However, caution is required when selecting patients for intervention based solely on radiological findings. Copyright © 2005 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.

Adenovirus infection after pediatric bone marrow transplantation: Is treatment always necessary?

Abstract: Background Adenovirus infections are associated with significant rates of morbidity and mortality among children after bone marrow transplantation (BMT). Many transplantation units use molecular virological methods, such as polymerase chain reaction (PCR), for surveillance for adenovirus infection and give preemptive antiviral therapy to children with evidence of disseminated adenovirus infection. This treatment strategy has never been evaluated in clinical trials. Methods We retrospectively tested blood samples obtained from a cohort of children who had undergone BMT before the introduction of regular weekly surveillance for adenovirus infection. A total of 273 samples collected from 26 patients between May 1998 and June 2002 were tested for adenovirus infection by quantitative PCR. Virus load was quantified for each sample yielding positive test results, and the clinical notes and virological records of each child were reviewed. Results Evidence of adenovirus infection was found in 11 children (42%), 7 of whom had not previously had positive test results. Receipt of T cell-depleted transplants was associated with a significantly higher incidence of adenovirus infection during the posttransplantation period. The 2 children who died from adenovirus disease developed infection within 2 weeks after transplantation, and both had very low absolute lymphocyte counts at the time of diagnosis. Seven of 11 children with blood samples that were found to be positive for adenovirus by PCR cleared the virus without antiviral therapy. Conclusions Surveillance for adenovirus by PCR is better than symptomatic testing for detecting adenovirus infection. Antiviral therapy may not be necessary for all children who develop adenovirus viremia after BMT.

Pre-hospital fluid therapy in the critically injured patient--a clinical update.

Abstract: Venous access and fluid therapy should still be considered to be essential elements of pre-hospital advanced life support (ALS) in the critically injured patient Initiation of fluid therapy should be based on a clinical assessment, most importantly the presence, or otherwise, of a radial pulse The goal in penetrating injury is to avoid hypovolaemic cardiac arrest during transport, but at the same time not to delay transport, or increase systolic blood pressure The goal in blunt injury is to secure safe perfusion of the injured brain through an adequate cerebral perfusion pressure, which generally requires a systolic blood pressure well above 100 mmHg Patients without severe brain injury tolerate lower blood pressures (hypotensive resuscitation) Importantly, using systolic blood pressure targets to titrate therapy is not as easy as it seems Automated (oscillometric) blood pressure measurement devices frequently give erroneously high values The concept of hypotensive resuscitation has not been validated in the few studies done in humans Hence, the suggested targeted systolic blood pressures should only provide a mental framework for the decision-making The ideal pre-hospital fluid regimen may be a combination of an initial hypertonic solution given as a 10-20 minutes infusion, followed by crystalloids and, in some cases, artificial colloids This review is intended to help the clinician to balance the pros and cons of fluid therapy in the individual patient

Rectal Intussusception: Characterization of Symptomatology

Abstract: Rectal intussusception is a common finding at evacuation proctography; however, its significance has been debated. This study was designed to characterize clinically and physiologically a large group of patients with rectal intussusception and test the hypothesis that certain symptoms are predictive of this finding on evacuation proctography. A total of 896 patients underwent evacuation proctography from which three groups were identified: those with isolated rectal intussusception (n = 125), those with isolated rectocele (n = 100), and those with both abnormalities (n = 152). Multivariate analyses were used to identify symptoms predictive of findings by evacuation proctography. The symptoms of anorectal pain and prolapse were highly predictive of the finding of isolated intussusception over rectocele (odds ratio, 3.6, P = 0.006; odds ratio, 4.9, P < 0.001) or combined intussusception and rectocele (odds ratio, 2.9, P = 0.02; odds ratio, 2.4, P = 0.03). The symptom of “toilet revisiting” was associated with the finding of rectoanal intussusception (odds ratio, 3.55, P = 0.04). Although patients with mechanically obstructing intussuscepta evacuated slower and less completely (P < 0.001) than those with nonobstructing intussuscepta, no symptom was predictive of this finding on evacuation proctography. Although certain symptoms are predictive of the finding of rectal intussusception, there is a wide overlap with symptoms of rectocele, another common cause of evacuatory dysfunction. Furthermore, the observation that “obstruction to evacuation” made on proctography had no impact on the incidence of evacuatory symptoms suggests that beyond simply demonstrating the presence of an intussusception, analysis of proctography and subclassifying intussusception morphology seems of little clinical significance, and selection for surgical intervention on the basis of proctographic findings may be illogical.

The impact of PET scanning on management of paediatric oncology patients

Abstract: Limited information is available on the use of positron emission tomography (PET) in paediatric oncology. The aim of this study was to review the impact of PET on the management of paediatric patients scanned over a 10-year period. One hundred and sixty-five consecutive oncology patients aged 11 months to 17 years were included. Two hundred and thirty-seven scans were performed. Diagnoses included lymphoma (60 patients), central nervous system (CNS) tumour (59), sarcoma (19), plexiform neurofibroma with suspected malignant change (13) and other tumours (14). A questionnaire was sent to the referring clinician to determine whether the PET scan had altered management and whether overall the PET scan was thought to be helpful. One hundred and eighty-nine (80%) questionnaires for 126 patients were returned (63 relating to lymphoma, 62 to CNS tumours, 30 to sarcoma, 16 to plexiform neurofibroma and 18 to other tumours). PET changed disease management in 46 (24%) cases and was helpful in 141 (75%) cases. PET findings were verified by histology, clinical follow-up or other investigations in 141 cases (75%). The returned questionnaires indicated that PET had led to a management change in 20 (32%) lymphoma cases, nine (15%) CNS tumours, four (13%) sarcomas, nine (56%) plexiform neurofibromas and four (22%) cases of other tumours. PET was thought to be helpful in 47 (75%) lymphoma cases, 48 (77%) CNS tumours, 24 (80%) sarcomas, 11 (69%) neurofibromas and 11 (61%) cases of other tumours. PET findings were verified in 44 (70%) lymphoma cases, 53 (85%) CNS tumours, 21 (70%) sarcomas, 12 (75%) neurofibromas and 11 (61%) other tumour cases. PET imaging of children with cancer is accurate and practical. PET alters management and is deemed helpful (with or without management change) in a significant number of patients, and the results are comparable with the figures published for the adult oncology population.

The Epsin 4 gene on chromosome 5q, which encodes the clathrin-associated protein enthoprotin, is involved in the genetic susceptibility to schizophrenia.

Abstract: Chromosome 5q33 is a region that has previously shown good evidence of linkage to schizophrenia, with four LOD scores >3.00 in independent linkage studies. We studied 450 unrelated white English, Irish, Welsh, and Scottish research subjects with schizophrenia and 450 ancestrally matched supernormal controls. Four adjacent markers at the 5′ end of the Epsin 4 gene showed significant evidence of linkage disequilibrium with schizophrenia. These included two microsatellite markers, D5S1403 (P=.01) and AAAT11 (P=.009), and two single-nucleotide–polymorphism markers within the Epsin 4 gene, rs10046055 (P=.007) and rs254664 (P=.01). A series of different two- and three-marker haplotypes were also significantly associated with schizophrenia, as confirmed with a permutation test (HapA, P=.004; HapB, P=.0005; HapC, P=.007; and HapD, P=.01). The Epsin 4 gene encodes the clathrin-associated protein enthoprotin, which has a role in transport and stability of neurotransmitter vesicles at the synapses and within neurons. A genetically determined abnormality in the structure, function, or expression of enthoprotin is likely to be responsible for genetic susceptibility to a subtype of schizophrenia on chromosome 5q33.3.

Butyrate metabolism in the terminal ileal mucosa of patients with ulcerative colitis

Abstract: The rate of oxidation of butyrate, glutamine and glucose was investigated in terminal ileal mucosal biopsy samples from nine patients with ulcerative colitis undergoing restorative proctocolectomy and from 12 patients undergoing laparotomy for reasons other than ulcerative colitis. Substrate oxidation was assayed using a radiolabelled isotope technique. Butyrate was the preferred fuel substrate, followed by glutamine and then glucose (median (95 per cent confidence interval) 567 (262-894), 63 (35-123) and 8.1 (5.1-18) pmol micrograms-1 h-1 respectively; P < 0.01, Mann-Whitney U test) in normal terminal ileal mucosa. The patients with ulcerative colitis had a significantly reduced rate of butyrate oxidation compared with the control group (194 (81-321) versus 567 (262-894) pmol micrograms-1 h-1, P < 0.05). Normal terminal ileal mucosa oxidized butyrate in greater quantities than glucose and glutamine. Ulcerative colitic terminal ileal mucosa exhibited an impaired rate of butyrate oxidation.

Expression of p53 in colorectal cancer and dysplasia complicating ulcerative colitis.

Abstract: An immunohistochemicac method using Pab1801, a monoclonal antibody specific to the human p53 protein, was applied to detect p53 expression in colorectal cancer and dysplasia complicating ulcerative colitis. Of 20 issue samples with dysplasia, six showed positive immunoreactivity. Archival paraffin-embedded tissue blocks from 21 colitic cancers were analysed; 11 showed positive immunoreactivity, compared with ten of 21 samples from matched sporadic colorectal cancers (P not significant). Previous data suggesting that colorectal carcinoma complicating ulcerative colitis has a reduced frequency of c-Ki-ras mutation compared with sporadic cancer have led to the hypothesis that different genetic lesions underlie colitic and sporadic colorectal carcinoma

Physiological and histochemical adaptation of the electrically stimulated gracilis muscle to neoanal sphincter function

Abstract: The physiological and histochemical characteristics of the gracilis muscle were studied in 19 patients undergoing electrically stimulated gracilis neosphincter construction. Indications for surgery were faecal incontinence (n = 11) and reconstruction following sphincter excision or congenital absence (n = 8). Transposition of the gracilis muscle around the anal canal followed by chronic low-frequency electrical stimulation was associated with a shift in the frequency-response curve and a prolongation of the time-course of individual muscle twitches suggestive of transformation to a slow-twitch fatigue-resistant type. Temporary cessation of electrical stimulation resulted in a reversal of the frequency-response changes. Muscle biopsies taken before and a median of 80 (range 49-137) days after transposition and low-frequency electrical stimulation indicated a significant increase in the proportion of type 1 fibres and a significant decrease in their diameter. These results show that the human gracilis muscle is capable of physiological and histochemical adaptation to long-term neosphincter function.

Mechanisms of Disease: cell death in acute renal failure and emerging evidence for a protective role of erythropoietin

Abstract: Acute renal failure--characterized by a sudden loss of the ability of the kidneys to excrete nitrogenous waste, and to maintain electrolyte homeostasis and fluid balance--is a frequently encountered clinical problem, particularly in the intensive care unit. Unfortunately, advances in supportive interventions have done little to reduce the high mortality associated with this condition. Might erythropoietin (EPO) have utility as a therapeutic agent in acute renal failure? This hormone mediates anti-apoptotic effects in the bone marrow, facilitating maturation and differentiation of erythroid progenitors. New evidence indicates that EPO also exerts anti-apoptotic effects in the brain, heart and vasculature, which can limit the degree of organ damage. Here, we review the emerging biological role of EPO in the kidney and the pathophysiology of ischemia-reperfusion injury in an attempt to understand the therapeutic potential of EPO in acute renal failure.

The role of the maxillofacial surgeon in the initial 48 h following a terrorist attack.

Abstract: On 7 July 2005 there were four explosions in central London, three almost synchronously and a fourth within an hour. The Royal London Hospital received 208 casualties and the Hospital Major Incident Plan was put into action. We report on the events of that day and the role of the maxillofacial surgeons immediately and in the subsequent 48 h.