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Biomedical subjects

G J Toogood

Publications and source records attributed to G J Toogood.

12 recordsLinked to original sources
PubMed1997

The immune response following small bowel transplantation. II. A very early cytokine response in the gut-associated lymphoid tissue.

The small bowel has a unique amount of closely associated lymphoid tissue in the form of mesenteric lymph nodes (MLNs) and Peyer's patches (PPs). It is rather unclear how this may affect the immune response to transplants involving small bowel. It is clear, however, that host-derived leukocytes infiltrate this lymphoid tissue very rapidly after transplantation of small bowel, which suggests the possibility of an early immune response within this compartment. To investigate this possibility, we analyzed, using a semiquantitative reverse transcriptase-polymerase chain reaction, the level of cytokine transcripts within isolated MLNs and PPs for the first 7 days after small bowel transplantation. Heterotopic small bowel (n=32) transplants were performed using the following rat strain combinations: syngeneic Lewis (Lew)-->Lew (n=8), blood group D Agouti (DA)-->DA (n=8), allogeneic Lew-->DA (n=8), and allogeneic DA-->Lew (n=8). Two rats from each group were killed at 1, 3, 5, and 7 days after transplantation. RNA was prepared separately from PPs and MLNs before analysis of transcripts for interleukin (IL) 2, IL-4, IL-10, IL-6, IL-1alpha, and interferon (IFN) gamma. No increase in transcripts for IL-2 or IL-10 was observed in either PPs or MLNs of syngeneic grafts. A small rise in IL-6, IL-1alpha, and IFN-gamma transcripts was seen in MLNs and IFN-gamma transcripts in PPs of syngeneic grafts. In contrast, in allografts an extremely early increase in cytokine transcripts was observed; all cytokine transcripts tested were elevated within the first 24 hr after transplantation. Indeed, the peak response of both IL-2 and IL-10 occurred within 1 to 3 days after grafting. This early immune response in the lymphoid tissue may not be controlled by immunosuppression delivered only at the time of transplantation, and therefore may be responsible for the difficulty in achieving adequate immunosuppression in small bowel transplantation.

Animals↗
PubMed1997

Control of fecal incontinence: continued success with the Malone procedure.

BACKGROUND: Our center has previously reported the use of the Malone antegrade continence enema procedure in children. The procedure involves bringing the appendix to the surface of the abdominal wall to provide a nonrefluxing catheterizable channel that enables antegrade colonic lavage for the control of fecal incontinence. METHODS: This report critically evaluates 23 patients treated for fecal incontinence with up to 6 years of follow-up. After operation, specific scoring criteria were used for assessment. Success in surgical technique, control of fecal soiling, and improvement in quality of life were evaluated. RESULTS: More than 85% of patients achieved maximal or near-maximal scores in all three categories. Postoperative complications remain a relevant concern when this procedure is undertaken, but we have found that significant postoperative complications are few and can be minimized by meticulous follow-up. CONCLUSIONS: Overall, the Malone antegrade continence enema procedure has been shown to be safe and highly effective. There is the potential for wider application in older age groups where sphincter and pelvic floor muscles have been compromised as a result of trauma or cancer surgery.

Adolescent↗
PubMed1996

The immune response following small bowel transplantation: I. An unusual pattern of cytokine expression.

Acute cell mediated graft rejection is frequently associated with an immune response dominated by cytokines like IL-2 and IFNgamma. While small bowel grafts are rejected acutely, there is little information on the type of immune response generated following transplantation and, in particular, whether the cytokine profile resembles that seen during the rejection of other solid organ grafts. In this paper we compare the expression of cytokines in isolated gut tissue following experimental small bowel transplantation with that in heart grafts. Heterotopic small bowel (n=32) and cardiac (n=32) transplants were performed using the following rat strain combinations: syngeneic Lewis (Lew) > Lew (n=8), blood group D Agouti (DA) > Lew (n=8) and allogeneic Lew > DA (n=8), DA > Lew (n=8). Two rats from each group were sacrificed at 1, 3, 5, or 7 days after transplantation. RNA was prepared separately from gut wall, after removing the Peyer's patches (PPs) and mesenteric lymph nodes (MLNs) and from heart. Cytokine (IL-1alpha, IL-2, IL-4, IL-6, IL-10 and IFNgamma) transcripts were analyzed using semiquantitative RT-PCR. Most notably, transcripts of only a single cytokine, IFNgamma, became progressively elevated with time in the rejecting small bowel grafts. This is in marked contrast to the findings presented here for rat cardiac grafts in which transcripts of all cytokines tested show an increase with rejection. This significant and steady increase in IFNgamma expression occurred before there was any clinical or histological evidence of rejection. These data demonstrate that the mechanisms of rejection in small bowel and other solid organ grafts are likely to be different. Further, the unique rise in IFNgamma expression in the gut wall may be a valuable and early indicator of graft rejection.

Animals↗
PubMed1996

Cytomegalovirus infection and colonic perforation in renal transplant patients.

Cytomegalovirus (CMV) infection in immunocompromised patients is a major cause of morbidity and mortality. A well-documented manifestation of gastrointestinal CMV infection is gastrointestinal haemorrhage. In contrast, CMV-associated intestinal perforation has rarely been reported after transplantation, although it is well documented in AIDS patients. Three patients are reported who received their first cadaveric renal transplant in 1994 and subsequently developed CMV disease. During the course of their CMV illness, which was treated with ganciclovir, each presented with clinical suspicion of peritonitis and proceeded to laparotomy. All three were found to have sigmoid colon perforations with histological evidence of CMV infection. Following bowel resection and defunctioning, two patients made an uneventful recovery and have had the continuity of their bowel restored, but one died of overwhelming sepsis within hours of surgery. The explanation for the apparent clustering of this rare condition in transplant patients is uncertain.

Aged↗
PubMed1996

Hepatic cystic disease in an adult polycystic kidney disease transplant population.

BACKGROUND: A study of the incidence of polycystic liver in a transplant population and an assessment of the impact of this disease on the group was undertaken. Clinical presentation, investigation and treatment of hepatic polycystic disease are explored. METHODS: The study examined the morbidity incurred by polycystic liver disease in patients, patient and graft survival, incidence of hepatic cysts and presentation, investigation and management of morbid hepatic cystic disease. One hundred and eleven patients were studied. RESULTS: It was found that hepatic cysts occurred in the majority of patients that underwent transplants for renal failure because of polycystic kidney disease at this institution. Symptomatic hepatic cystic disease was found to be primarily responsible for three deaths and affected between 15 and 20% of the group. Gall bladder disease was found to be associated with highly symptomatic hepatic cystic disease. CONCLUSION: Hepatic cystic disease is common in patients that have had kidney transplants because of polycystic kidney disease. Morbidity is likely to increase as patients survive for longer periods. Cholecystectomy should be considered in patients with significant hepatic cystic disease.

Adult↗
PubMed1996

Surgical skills of pre-registration house surgeons.

As demands on house surgeons increase and junior doctors' hours are reduced, the opportunity for learning surgical skills during the pre-registration period is threatened. An increasing number of medical specialties, including general practice, now require a proficiency in these skills. For many doctors the pre-registration period may be the last occasion when formal training from experienced surgeons is available. Fifteen house surgeons were tested and asked to perform three basic surgical drills on artificial skin and answer 10 questions relevant to minor surgery during the final week of their house surgical post. Four (27 per cent) house surgeons were unable to complete any of the surgical drills, no one could calculate the dose of lignocaine in 10 ml of a 1% solution, and only two (13 per cent) knew the safe maximum dose of subcutaneous plain lignocaine. This study highlights deficiencies in basic surgical skills amongst house surgeons and suggests that this opportunity for training is being missed.

Clinical Competence↗
PubMed1995

Twenty-seven years of liver transplantation at Addenbrooke's Hospital, Cambridge.

Twenty-seven years ago, liver transplantation at Addenbrooke's Hospital was a very experimental procedure. It is now recognized as an accepted mode of treatment for end-stage liver failure. In the coming year, over 600 liver transplants will take place in the United Kingdom. All western European countries now have an active liver transplantation program and more than 17,000 liver transplants have already been performed. As results improve and the procedure becomes more readily and widely accepted, the donor shortage is likely to get worse, and will be only partially met by the introduction of split livers and living-related donors.

Adolescent↗
PubMed1994

The relationship between fever and acute rejection or infection following renal transplantation in the cyclosporin era.

In the past, fever has been considered to be an important sign of rejection in renal transplant patients but since the introduction and widespread use of cyclosporin this relationship has become less clear. We have studied the relationship between fever defined as a single temperature reading > or = 38.5 degrees C or recordings > or = 38.0 degrees C over 2 consecutive days, and acute rejection or infection in 99 consecutive renal transplants. Within the first 6 months after transplantation 90 acute rejection episodes were recorded in 61 patients and most (83%) were not associated with fever. Forty-seven episodes of fever were documented in 37 patients and ascribed to acute rejection (15), infection (17), antibody therapy (11) or other causes (4). Fever in the first 16 days was significantly more likely to be due to rejection than to infection (chi 2 = 24.47, p = < 0.001). Episodes of fever due to infection tended to occur after the 1st month, coincident with the peak incidence of cytomegalovirus (CMV) infection. However, with the exception of CMV disease, fever was not a reliable guide for the presence of infection, including septicemia.

Acute Disease↗
PubMed1993

Bilateral knee replacements: simultaneous or staged?

Approximately one-third of primary knee replacements are performed on patients with bilateral symptomatic disease. This retrospective study compared the complication rate, functional outcome and cost implications of performing bilateral total knee replacements under a single anaesthetic or as staged procedures with a control group of unilateral cases. There was no significant difference in the complications or outcome. There was a significant reduction in the mean hospital admission time of 7 days per knee replacement (P < 0.001, Student's t test) by performing bilateral knee replacements for osteoarthritis under the same anaesthetic. However, a survey of practising knee surgeons in three health regions in the United Kingdom shows that only 24% would regularly perform bilateral knee replacements under one anaesthetic.

Adult↗