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Biomedical subjects

M E Allison

Publications and source records attributed to M E Allison.

At least 19 recordsLinked to original sources

The Colorectal Development Unit: impact on functional outcome for the electrically stimulated gracilis neoanal sphincter.

OBJECTIVE: A Colorectal Development Unit (CDU) was established to treat patients with end stage faecal incontinence with the electrically stimulated gracilis neoanal sphincter (ESGN). The aim of this study was to investigate the impact of the CDU on functional outcome and complications. METHODS: From March 1997 to March 2003, 53 patients underwent ESGN formation. Results were compared with 65 patients undergoing ESGN surgery prior to the establishment of the unit (pre-CDU) between 1988 and 1997, which were similar with regard to age, sex, aetiology and follow-up. RESULTS: Thirty-three (70%) CDU patients had a good functional outcome defined as continence to solid and liquid stool, a significant improvement when compared to the pre-CDU group, successful in 29 (45%) (P = 0.01). Episodes of technical complications leading to stimulator replacement were significantly reduced, from 25 to 3 over time (P < 0.001). Severe septic episodes were significantly reduced from 21 to four (P = 0.003) but there was no significant change in the incidence of postoperative evacuatory dysfunction. CONCLUSION: Since setting up a CDU, a successful outcome has been achieved in 33 (70%) of 47 patients undergoing ESGN surgery, which represents a significant improvement over time. This is probably related to improved patient assessment and selection, more reliable equipment and increased operative and peri-operative experience that come with a multidisciplinary team approach.

Adolescent↗

EXternal Pelvic REctal SuSpension (Express procedure) for rectal intussusception, with and without rectocele repair.

BACKGROUND: The results of conventional treatment for rectal intussusception and rectocele are unpredictable. The aim was to develop a less invasive surgical approach and to evaluate outcome in selected patients. METHODS: Seventeen patients (13 women; median age 47 (range 20-67) years) with rectal evacuatory dysfunction and rectal intussusception, 13 of whom had a rectocele, were selected. The intussusception was corrected by external pelvic suspension of the rectum, using collagen strips attached to the rectal wall and pubis. The rectocele was repaired with a collagen patch. Patients were assessed before and 6 months after surgery by symptom and quality of life questionnaires, anorectal physiological investigation and proctography, and were followed up for a median of 12 months. RESULTS: Sepsis requiring exploration occurred in two patients but there was no extrusion or need to remove the collagen. Of the 15 patients assessed after surgery, total symptom scores were significantly decreased (P < 0.001) and quality of life scores improved (P < 0.001). Proctographically, the degree of intussusception was improved in ten patients; six patients had normal postoperative proctograms. The rectocele was reduced in size in all patients, and was not demonstrable in eight. CONCLUSION: An effective procedure for rectal intussusception and rectocele has been developed in a selected group of patients with marked evacuatory symptoms.

Adult↗

Intraplatelet calcium levels in patients with acute renal failure before and after the administration of loop diuretics.

BACKGROUND: Intracellular calcium [Ca](i) has been found to be elevated in hypoxic cells in vitro and in erythrocytes and lymphocytes from patients who are septic. Loop diuretics decrease [Ca](i) in platelets from patients with hypertension and in red blood cells from normal volunteers. We report the results of a study designed to measure [Ca](i) in platelets from patients with acute renal failure (ARF) before and after the administration of loop diuretics. METHODS: Sixteen healthy adults and seven patients with ARF were enrolled into the study. Intraplatelet calcium was measured using a fluorescent probe (quin2). Patients with ARF all received intravenous (i.v.) dopamine, 2 microg/kg body weight, and 20% mannitol, 100 ml every 6 h and, in double-blind manner, either torasemide, frusemide, or placebo, 3 mg/kg body weight i.v. every 6 h. Data from subjects given either frusemide or torasemide have been considered together and termed the diuretic group. RESULTS: Basal levels of [Ca](i) in platelets from patients with ARF were significantly higher than in controls (126.9 +/-3 5.7 nmol/l vs 85.7 +/- 22.2 nmol/l, P = 0.02), but were not affected by the administration of loop diuretic (126.9 +/- 35.7 nmol/l vs 165.9 +/- 49.7 nmol/l, P = 0.09, pre- vs post-diuretic). CONCLUSIONS: Intraplatelet calcium is raised in patients with ARF. Loop diuretics have no significant effect on intraplatelet calcium in these patients.

Acute Kidney Injury↗

Enhanced immunogenicity of aldehyde-bearing antigens: a possible link between innate and adaptive immunity.

Innate immunity directs the adaptive immune response by identifying antigens that are associated with infectious agents. Although some microbial antigens can be recognized by innate immune receptors, most cannot, and these require identification by some other means. The introduction of aldehydes into antigens by glycolaldehyde, which can be produced by activated neutrophils reacting with serine, or by the oxidation of an N-linked oligosaccharide with NaIO4, enhances by several orders of magnitude their immunogenicity in mice. The augmented immunogenicity requires the presence of an aldehyde on the antigen, and is not dependent on protein aggregation. An in vitro correlate of augmented immunogenicity is the enhanced presentation of glycolaldehyde-modified antigen to T cells by macrophages and bone marrow-derived dendritic cells. The potential clinical importance of this form of antigen modification is twofold: glycolaldehyde renders a model self antigen immunogenic, and it converts a relatively non-immunogenic malaria antigen, merozoite surface protein-1, into an effective immunogen. Thus, the tagging of antigens by the addition of aldehydes, which may be an innate immune mechanism to facilitate their recognition by the adaptive immune system, may have a role in the genesis of autoimmunity and the development of vaccines.

Acetaldehyde↗

An artificial neural network can select patients at high risk of developing progressive IgA nephropathy more accurately than experienced nephrologists.

BACKGROUND: The object of the study was to develop an artificial neural network (ANN) to identify patients with IgA nephropathy (IgAN) with a poor prognosis and to compare the predictions of the ANN with the predictions of six experienced nephrologists. METHODS: The following data from the time of renal biopsy were retrieved from the records of 54 patients with IgAN: age, sex, systolic and diastolic blood pressure, number of prescribed antihypertensive drugs, 24-h urine protein excretion, and serum creatinine. Patients aged less than 14 years, or who had serum creatinine > 350 mumol/l at presentation, liver disease or concomitant kidney disease were excluded. Outcome was assigned as 'stable' if serum creatinine was < 150 mumol/l after 7 years and 'non-stable' if serum creatinine was > or = 150 mumol/l. The ANN was trained and tested using a 'jack-knife' sampling technique and performance evaluated in terms of number of correct predictions, sensitivity and specificity. The six nephrologists were asked to predict outcome at 7 years for each patient using the same data as the ANN and their performance was assessed in the same manner. RESULTS: The ANN assigned the correct outcome to 47/54 (87.0%) patients: sensitivity 19/22 (86.4%), specificity 28/32 (87.5%). The mean score for nephrologists was 37.5/54 (69.4%, range 35-40), mean sensitivity 72% and mean specificity 66%. CONCLUSIONS: An ANN trained using routine clinical information obtained at the time of diagnosis can potentially predict 7-year outcome for renal function in IgAN more accurately than experienced nephrologists, and can therefore identify a group of high-risk patients requiring close follow-up.

Adolescent↗

Loop diuretics in the management of acute renal failure: a prospective, double-blind, placebo-controlled, randomized study.

BACKGROUND: Studies on the role of loop diuretics in patients with acute renal failure (ARF) are largely retrospective, anecdotal, and poorly controlled. We report the results of a prospective, randomized, placebo-controlled, double-blind study examining the effect of loop diuretics on renal recovery, dialysis, and death in patients with ARF. METHODS: Ninety-two patients with ARF were enrolled into the study. All received intravenous dopamine, 2 micrograms/kg body weight/min throughout, 20% mannitol, 100 ml every 6 h for the first 3 days, and, in a double-blind manner, either torasemide, frusemide, or placebo, 3 mg/kg body weight i.v. every 6 h for 21 days or until renal recovery or death. RESULTS: Renal recovery, the need for dialysis, and death were no different in the three groups. Patients given a loop diuretic had a significant rise in urine flow rate in the first 24 h compared to placebo (P = 0.02). Based on the urine flow rate during the first post-medication day patients were divided into two groups--oliguric (< 50 ml/h) and non-oliguric (> or = 50 ml/h). Non-oliguric patients had a significantly lower mortality than oliguric patients (43% vs 69%, P = 0.01). However, they were less ill (APACHE II score 17.2 vs 20.6, P = 0.008) and had less severe renal failure at entry (creatinine clearance 14 ml/min vs 4 ml/min, P < 0.0001). CONCLUSION: The use of loop diuretics in oliguric patients with ARF can result in a diuresis. There is no evidence that these drugs can alter outcome.

Acute Kidney Injury↗

C3d of complement as a molecular adjuvant: bridging innate and acquired immunity.

An optimal immune response should differentiate between harmful and innocuous antigens. Primitive systems of innate immunity, such as the complement system, may play a role in this distinction. When activated, the C3 component of complement attaches to potential antigens on microorganisms. To determine whether this alters acquired immune recognition, mice were immunized with a recombinant model antigen, hen egg lysozyme (HEL), fused to murine C3d. HEL bearing two and three copies of C3d was 1000- and 10,000-fold more immunogenic, respectively, than HEL alone. Thus, C3d is a molecular adjuvant of innate immunity that profoundly influences an acquired immune response.

Adjuvants, Immunologic↗

Non-invasive measurement of azygos venous blood flow using magnetic resonance.

Monitoring treatment efficacy in patients with portal venous hypertension has been limited by the difficulty of direct or indirect assessment of portal vein pressure. The majority of currently available haemodynamic tests, such as hepatic vein wedge pressure or azygos vein flow measurement by thermodilution catheter, are invasive which has restricted their application. We describe a non-invasive cine phase contrast magnetic resonance technique for quantitative measurements of bulk volume flow and for demonstrating flow changes during the cardiac cycle in the azygos vein. The technique was used to analyse the azygos vein flow in seven adult volunteers and five patients with biopsy-confirmed chronic liver disease, portal hypertension and endoscopically proven oesophageal varices. In the volunteers the mean volume flow rates varied between 81 and 241 ml/min with a mean for the group of 171 ml/min. The patients had a significantly higher mean volume flow rate of 628 ml/min (p < 0.01), with a range of 339 to 945 ml/min. These preliminary results suggest that cine phase contrast magnetic resonance angiography is a practical non-invasive method for measuring absolute azygos vein flow, and may provide a non-invasive method of monitoring portal hypertension.

Adult↗

Evidence for a link between hepatitis C virus infection and diabetes mellitus in a cirrhotic population.

Abnormalities of carbohydrate metabolism, including hyperinsulinaemia and insulin resistance, are well recognised complications of cirrhosis. While diabetes mellitus can be explained in many instances on the basis of coincident pancreatic disease, in most the characteristic glucose intolerance of cirrhosis is not readily explicable. A previous clinical observation that hepatitis C virus infection and diabetes mellitus appeared to be associated was formally tested by a retrospective review of 100 consecutive adult patients with cirrhosis undergoing assessment for liver transplantation. Hepatitis C virus was diagnosed by conventional serological and histological criteria. Twenty-three patients had diabetes mellitus, of whom 18 were being treated with insulin. Of the 34 patients with hepatitis C virus-related cirrhosis, 17 (50%) had diabetes mellitus, in contrast to just six (9%) of the 66 patients with cirrhosis unrelated to hepatitis C virus (chi2 = 19.1, p < 0.0001) with an odds ratio for hepatitis C virus by diabetes mellitus status 10.0 (95% confidence interval 3.4 to 29.3). Hierarchical loglinear model analysis of those factors of potential relevance to the development of diabetes mellitus revealed that only hepatitis C virus interacted significantly with diabetes mellitus while the relation between diabetes mellitus and origin, sex, body mass index and severity of cirrhosis was conditional. By multiple logistic regression analysis of diabetes mellitus status in relation to the same variables, only hepatitis C virus status was statistically significant (p < 0.0001). Origin, sex, severity of cirrhosis, body mass index and therapy were not significantly associated.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Diuretics in acute renal failure.

Studies on the ability of loop diuretics, mannitol, dopamine, and atrial natriuretic peptide to ameliorate or reverse human acute renal failure are reviewed. A precise role for diuretic therapy in this clinical setting has not been established. Most reports are retrospective, poorly controlled, or simply anecdotal. There is a need for prospective, randomly allocated studies on adequate numbers of patients. While the use of diuretic agents may improve fluid balance management in patients at risk of developing acute renal failure, maintenance of adequate effective circulating volume and oxygen delivery probably provides the best-proven protection.

Acute Kidney Injury↗

Hepatitis C virus infection in renal dialysis patients in Glasgow.

A survey of all 483 adult dialysis patients in the three renal units in Glasgow using second-generation ELISA was carried out to determine hepatitis C virus (HCV) seroprevalence in the summer of 1991 before the introduction of blood donor screening for antibody to HCV in the UK. Supplementary testing of ELISA positive sera was by second-generation immunoblot assay (RIBA-2, Chiron). Retrospective case note analysis and testing of stored sera were performed to assess liver function and the risk factors for acquisition of the virus. Nineteen of the 483 patients (3.9%) were seropositive. Sixteen patients had been transfused and 12 had previous transplants. Seropositivity was associated with current haemodialysis (P < 0.01) rather than continuous ambulatory peritoneal dialysis (CAPD). Of those on haemodialysis, the time since first dialysis was longer for seropositives (13.6 years) than for seronegatives (6.3 years) (P < 0.01) but this did not apply to those on CAPD. Twelve of 19 (63.2%) seropositives had persistent elevations of alanine transferase compared to seven of 38 (18%) seronegative controls (P < 0.01). This large group of dialysis patients is at special risk of HCV infection but the seroprevalence is less than that reported from outside the UK despite the use of more sensitive techniques. The risk is associated with haemodialysis and is probably largely due to blood transfusion. The introduction of screening of donated blood for HCV antibody should reduce the incidence of new infection in dialysis patients.

Adolescent↗

Loop diuretic therapy in acute and chronic renal failure.

The development of the powerful loop diuretics over the past 30 years has significantly improved the quality of life for patients with advanced chronic renal failure (CRF). The most recent of these drugs is torasemide. This review outlines its mode of action and its pharmacokinetics and pharmacodynamics in CRF. A personal view of the efficacy and usefulness of these drugs in CRF, CRF on dialysis, and in nephrotic syndrome is given. The role of loop diuretics in potential and/or established acute renal failure is unknown. Theoretical advantages are described, current knowledge reviewed, and an outline of a prospective study presently underway is given.

Acute Kidney Injury↗

Which comes first, Kt/V or PCR--chicken or egg?

We previously hypothesized that PCR is dependent on Kt/V (urea). To test the hypothesis, 30 patients from two hemodialysis (HD) units with PCR values consistently less than 1 regardless of the Kt/V (urea) without an obvious cause (such as malignancy, peptic ulceration, etc.) were identified. These patients were randomized into an experimental group where an increase in the Kt/V (urea) was made or into a control group where a Kt/V (urea) remained unchanged. In the experimental group the minimal increment in Kt/V (urea) was 0.3 plus a minimum requirement of a Kt/V (urea) greater than or equal to 1. The control group were to maintain the existing Kt/V (urea) within +/- 0.2. Urea kinetic modeling was monitored monthly and the patients followed for three months. Of 30 patients, 18 fulfilled the criteria (9 experimental; 9 controls). In the experimental group, the initial Kt/V (urea) was 0.82 +/- 0.19 (means +/- SD); the final Kt/V (urea) was 1.32 +/- 0.21 (P = 0.000). These patients had an initial PCR of 0.81 +/- 0.08. This increased to 1.02 +/- 0.15 (P = 0.005). The control group had an initial Kt/V (urea) of 0.82 +/- 0.16. The final Kt/V (urea) was 0.87 +/- 0.15. Their initial PCR was 0.87 +/- 0.14 and the final PCR was 0.86 +/- 0.087 (P = NS). In the experimental group, the mean increments in Kt/V (urea) and PCR were 0.49 +/- 0.17 and 0.21 +/- 0.16 (P less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗

Successful use of cisplatin to treat metastatic seminoma during cisplatin-induced acute renal failure.

A chemotherapeutic regimen including cisplatin was administered to a man with extragonadal seminoma and cisplatin-induced acute renal failure. Three doses of cisplatin (30, 50, and 100 mg/m2) were given in conjunction with hemodialysis. Pharmacokinetic data for free and total plasma platinum were obtained. The patient also received one dose of carboplatin and a course of radiation therapy. Complete remission was achieved, and useful renal function returned. Cisplatin can be used successfully during acute renal failure.

Acute Kidney Injury↗

Wilson's disease presenting as acute fulminant hepatic failure.

A fatal case of fulminant hepatic failure in an adolescent is described. Post-mortem examination revealed the cause to be Wilson's Disease. This rare presentation is characterised by apparently atypical changes in copper metabolism. Wilson's Disease should be a differential diagnosis of any adolescent presenting in liver failure.

Adolescent↗