Biomedical subjects

A G Morgan

Publications and source records attributed to A G Morgan.

At least 19 recordsLinked to original sources

PubMed2004

Treatment of renal amyloidosis with etanercept in tumour necrosis factor receptor-associated periodic syndrome.

OBJECTIVE: To describe the effect of Etanercept treatment in systemic AA amyloidosis in tumour necrosis factor receptor-associated periodic syndrome (TRAPS). METHODS: Etanercept therapy was given to a 27 year old woman, with systemic amyloidosis and nephrotic syndrome, and to her 51 year old father, also affected by TRAPS, who had previously undergone renal transplant for amyloidosis. Serum SAA levels, plasma cytokines, glomerular filtration rate and serum amyloid P scanning were monitored. RESULTS: Etanercept treatment resulted in initial clinical resolution of nephrotic syndrome in the 27 year old female. Both subjects demonstrated improvements in GFR and initial reduction or stabilisation of amyloid deposits on SAP scanning. CONCLUSION: Etanercept may reverse or slow the progression of systemic AA amyloidosis in subjects with C33Y TNFRSF1A mutation. Treatment may however need to be continuous and life-long to prevent progression to end stage disease.

Adult↗

PubMed1999

The effect of long, slow haemodialysis on patient survival.

BACKGROUND: Long, slow haemodialysis (24 h/week) has been associated with excellent patient survival and reduced cardiovascular mortality. Comparisons of patient survival have only been possible with registry data and other published series which do not control for individual patient characteristics. This retrospective study compares actuarial patient survival between a unit using long, slow haemodialysis (Tassin) and one employing 'conventional' haemodialysis (Nottingham). METHODS: All patients undergoing haemodialysis at each centre since 1980 were included (Tassin, 452 patients; Nottingham, 282 patients). Actuarial curves of patient survival were calculated by the life-table method and log rank test was used to compare data. Patients were grouped as follows: standard (SRD) and non-standard (NSRD) renal diseases; diabetics and non-diabetics; patients with and without cardiovascular antecedents; risk stratification based on age and comorbidity. RESULTS: Overall survival was significantly better in Tassin. This difference was also noted for patients with SRD and non-diabetics (both P < 0.001) and for those with (P = 0.007) and without (P < 0.001) cardiovascular antecedents. Survival did not differ significantly for NSRD and diabetics. Survival was better in Tassin in low-risk (P < 0.001) and medium-risk (P < 0.001) groups, but not for high-risk (risk stratification). CONCLUSIONS: Overall survival is increased on long, slow haemodialysis. Although the benefits are seen in the most favourable prognostic categories, they are also present in patients with comorbid illness (medium-risk group) and pre-existing cardiovascular disease.

Adolescent↗

PubMed1997

Impaired bacterial killing and hydrogen peroxide production by polymorphonuclear neutrophils in end-stage renal failure.

Polymorphonuclear leukocytes (PMN) isolated from a sub-population of patients with end-stage renal failure (ESRF) who were identified because they demonstrated impaired intracellular bacterial killing, were assayed for hydrogen peroxide activity using two different techniques capable of distinguishing between total and intracellular hydrogen peroxide generation. In an attempt to elucidate the mechanism of impaired intracellular bacterial killing further, hydrogen peroxide activity was compared to PMN isolated from patients receiving continuous ambulatory peritoneal dialysis and a control group of healthy normal volunteers. PMN from conservatively treated ESRF patients demonstrated reduced production of intracellular hydrogen peroxide (mean 37.7 +/- 4.3 fluorescence units), compared to PMN from both ESRF patients treated with continuous ambulatory peritoneal dialysis (mean 57.9 +/- 6.6 fluorescence units) and normal controls (mean 60.4 +/- 3.5 fluorescence units). This suggests that the probable mechanism of impaired bacterial intracellular killing by the PMN of conservatively treated ESRF patients involves the production of intracellular hydrogen peroxide.

Adult↗

PubMed1997

Urea kinetic modelling in two groups of patients on continuous ambulatory peritoneal dialysis.

Dialysis adequacy (Kt/V) was investigated in two groups of patients on continuous ambulatory peritoneal dialysis (CAPD). Group I consisted of patients with serum creatinine concentration above 1200 mumol/l and Group II comprised patients with serum creatinine concentration of 600 mumol/l and less. The mean Kt/V was significantly higher in Group II (Kt/V, 2.0) than in Group I (Kt/V, 1.59; p < 0.01) patients. The mean duration of CAPD was significantly longer in Group I (3.12 years) than in Group II (1.32 years; (p < 0.01) patients, and the mean total creatinine clearance for Group II patients was significantly higher than for Group I (p < 0.001) patients. There was good correlation between Kt/V and total creatinine clearance (r = 0.73; p < 0.001); and between Kt/V and normalized protein catabolic rate (NPCR, r = 0.6; p < 0.001). There was weak correlation between Kt/V and duration on dialysis, but this was statistically significant. There was no significant difference between mean NPCR and mean mid-arm muscle circumference (MAMC) in the two groups and no significant association between Kt/V and dietary inventory. Group II patients had a significantly better residual renal clearance (p < 0.0001). Pruritus was a troublesome feature in Group I patients but in both groups patients were distressed by loss of libido, insomnia and tiredness. This study revealed that Group II patients with lower creatinine concentrations had better dialysis adequacy but were on CAPD for a shorter duration than Group I and had significantly better residual renal clearance and total clearance. Muscle mass does not appear to have contributed significantly to the differences in creatinine concentration between the groups. Additional studies on peritoneal membrane function vis-à-vis solute transfer are in progress.

Adult↗

PubMed1996

Glycated proteins as indices of glycaemic control in diabetic patients with chronic renal failure.

This study investigates the reliability of glycated haemoglobin, measured by electroendosmosis or by affinity chromatography, fructosamine, and albumin adjusted fructosamine, as indices of glycaemic control in Type 1 diabetes complicated by chronic renal failure. Twenty uraemic diabetic patients took part in the study, including 5 patients managed conservatively, 6 on CAPD, 3 on haemodialysis, and 6 renal transplant recipients. Results were compared with those from 15 diabetic subjects with normal renal function. In renal patients, there was significant correlation between glycated haemoglobin measured by electroendosmosis (r = 0.45; p = 0.04) or by affinity chromatography (r = 0.57; p = 0.01) and mean capillary blood glucose concentrations over the previous 6 weeks. The regression equations did not differ significantly between subjects with renal failure and those with normal renal function, suggesting that similar ranges can be used in interpreting glycated haemoglobin results from each group of patients. Patients on haemodialysis may be an exception; there was evidence that glycated haemoglobin may be misleadingly low in such subjects. Fructosamine correlated significantly with mean blood glucose concentrations measured over the previous week in patients with normal renal function (r = 0.75; p = 0.001), but not in patients with chronic renal failure (r = -0.1; p = 0.71). Calculation of an albumin adjusted fructosamine result failed to improve the correlation with blood glucose concentrations. The use of fructosamine cannot be recommended as an index of glycaemic control in uraemic patients.

Blood Glucose↗

PubMed1996

Free and esterified carnitine in continuous ambulatory peritoneal dialysis patients.

Free, acetyl-, medium- and long-chain acylcarnitine and total plasma carnitine concentrations were measured in eight continuous ambulatory peritoneal dialysis (CAPD) patients and eight age- and sex-matched healthy controls. Daily loss of carnitine was also quantified in both groups, by analysis of urine and dialysis fluid. Plasma total carnitine concentration in CAPD patients was not significantly different from controls (42.8 +/- 1.6 and 43.1 +/- 2.3 mumol/liter, respectively). However, the plasma free carnitine concentration of CAPD patients was significantly lower than that of controls (28.5 +/- 1.4 and 36.2 +/- 2.5 mumol/liter, respectively; P < 0.05). No difference in the daily loss of total carnitine was found between CAPD patients and controls (269.7 +/- 30.0 and 240.5 +/-33.0 mumol/liter, respectively), but the daily loss of free carnitine was significantly greater in CAPD patients (175.8 +/- 17.3 and 105.8 +/- 16.4 mumol/liter, respectively; P < 0.05). The ratio of total acylcarnitine (acetyl-, medium- and long-chain acylcarnitine) to free carnitine was significantly greater in plasma of CAPD patients than in controls (P < 0.01) and was lower in daily fluid losses (P < 0.001). These ratio differences suggests that an alteration in acyl group metabolism is occurring in CAPD patients. This may be attributable to an accumulation of medium- and long-chain acylcarnitine in liver of CAPD patients which would be exchanged for plasma free carnitine and/or to a differential loss of free and acylcarnitine across the peritoneal cavity.

Adult↗

PubMed1996

Pharmacokinetic behavior of intraperitoneal teicoplanin during treatment of peritonitis complicating continuous ambulatory peritoneal dialysis.

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Anti-Bacterial Agents↗

PubMed1996

Hydrogen peroxide generation by polymorphonuclear leukocytes exposed to peritoneal dialysis effluent.

In the presence of peritoneal dialysis effluent (PDE), human polymorphonuclear leukocytes (PMN) showed reduced production of hydrogen peroxide and hypochlorous acid (H2O2 and HOCl, respectively) when at rest and when stimulated with both soluble (formylmethionyl-leucyl-phenylalanine and phorbol myristate acetate) and particulate (Staphylococcus epidermidis) agonists. This effect occurred in a concentration-dependent manner between 0 and 70%. (vol/vol) dialysis effluent. The inhibition of H2O2 and HOCl observed in resting, formy-methionylleucyphenyalanine-stimulated, and S. epidermidis-stimulated PMN was confined to a low-molecular-mass (< 10,000-Da) fraction of PDE, whereas the inhibition of the PMA response was equally dispersed throughout both low (< 10,000-Da)- and high-molecular-mass (> 10,000-Da) fractions. Human serum albumin, a major component of PDE, also inhibited H2O2 and HOCl production by PMN; however, results from cell-free systems suggested that human serum albumin was not wholly responsible for the inhibition of PMN function seen with PDE. The solute(s) responsible did not affect myloperoxidase but very rapidly scavenged H2O2 and HOCl. These data suggest that the factors capable of affecting H2O2 and HOCl production by PMN accumulate in uremia and are removed from the circulation into dialysis effluent.

Ascitic Fluid↗

PubMed1996

Regular low-dose intravenous iron therapy improves response to erythropoietin in haemodialysis patients.

BACKGROUND: Erythropoietin (Epo) is an effective but expensive treatment for anaemia in patients with chronic renal failure. Hyporesponsiveness to Epo, particularly in haemodialysis patients, is most commonly due to a functional iron deficiency, which is difficult to monitor reliably. METHODS: Forty-six stable haemodialysis patients, receiving Epo therapy, were commenced on regular low-dose intravenous iron (sodium ferric gluconate complex) at a dose of 62.5 mg/5 ml given as a slow injection post-dialysis twice weekly, weekly, or fortnightly, according to their serum ferritin levels. Haemoglobin, serum ferritin, Epo dose, and iron dose were measured at 6-weekly intervals over a 6-month period. RESULTS: At the beginning of the study, 12 patients in the group had ferritin levels of less than 100 microg/l, and were thus considered to potentially have an absolute iron deficiency. The study group was therefore split into two subgroups for the purpose of analysis, i.e. the 12 patients with ferritin levels of less than 100 microg/l at the start of the study or 'low ferritin group', and the remaining 34 patients with ferritin levels of greater than 100 microg/l at the start of the study or 'normal ferritin group'. In the low ferritin group (n=12), intravenous iron therapy increased serum ferritin levels, and produced a significant rise in haemoglobin, and a significant reduction in Epo dose. (Ferritin pre-iron, median (range) 68 (20-96) microg/l; post-iron, 210.5 (91-447) microg/l, P<0. 003, Wilcoxon. Haemoglobin pre-iron, 10.05 (8.2-11.9) g/dl; post-iron, 11.0 (9.9-11.9) g/dl, P<0.03. Epo dose pre-iron, 9000 (4000-30 000)-i.u./week, P<0.05). Similar results were obtained in the normal ferritin group (n=34) following intravenous iron therapy, with significant increases in serum ferritin levels and haemoglobin concentrations, and a significant reduction in Epo dose. (Ferritin pre-iron, 176 (103-519) microg/l; post-iron, 304.5 (121-792) microg/l, P<0.0001. Haemoglobin pre-iron, 9.85 (6.5-12.8) g/dl; post-iron: 11.25 (9.9-13.3) g/dl, P<0.0001. Epo dose pre-iron, 6000 (2000-15 000) i.u./week; post-iron, 4000 (0-15 000)-i.u./week, P<0. 005). CONCLUSION: Regular intravenous iron supplementation in haemodialysis patients improves the response to Epo therapy.

Adult↗

PubMed1996

A prospective study of ward referrals for renal disease at a Jamaican and a United Kingdom hospital.

Seventy ward referrals for renal disease were prospectively studied at each of two tertiary hospitals: University Hospital of the West Indies (UHWI), Kingston, Jamaica and Nottingham City Hospital (NCH), England. At UHWI, the referral population was significantly younger, 89% being less than 60 years of age compared to 40% at NCH (p < 0.05). The leading cause of acute renal failure (ARF) at UHWI was systemic lupus erythematosus (SLE) followed by acute tubular necrosis (ATN). The leading causes of ARF at NCH were ATN and obstructive uropathy. Primary renal disease and diabetes mellitus were the major causes of end-stage renal disease (ESRD) at both centres, followed by SLE and hypertension at UHWI and renovascular disease and chronic pyelonephritis at NCH. Nephrotic syndrome occurred more frequently at UHWI than at NCH but the numbers were small (p < 0.05). Mortality rates were similar among patients with ARF and nephrotic syndrome at both centres, but were higher for patients with chronic renal failure (CRF) at UHWI than at NCH (p < 0.05). Continuous ambulatory peritoneal dialysis (CAPD) was a frequent mode of renal replacement therapy at NCH (76% v 19% on haemodialysis). At UHWI, CAPD was not available and 45% of patients with ESRD were not offered maintenance dialysis because of inadequate facilities. The major difference in management and outcome between the two centres occurred in cases with CRF, suggesting that survival in patients with CRF in Jamaica could be improved if this therapeutic modality was available.

Adult↗

PubMed1995

A randomized placebo-controlled study of enalapril in the treatment of erythrocytosis after renal transplantation.

BACKGROUND: Erythrocytosis is a common complication of renal transplantation with an incidence of up to 17%. It is associated with an increased risk of complications due to thromboembolic events and has traditionally been treated by intermittent venesection. More recently, angiotensin-converting enzyme inhibitors have been shown to cause a fall in haematocrit in a number of groups of subjects and some uncontrolled studies have shown these drugs to be of possible therapeutic benefit in post renal transplant erythrocytosis. METHODS: We performed a randomized double-blind placebo-controlled study in 25 patients with post-transplant erythrocytosis. Subjects received either 2.5 mg of enalapril daily or a placebo for 4 months and all patients completed the study period without any serious adverse effects. RESULTS: Haematocrit fell from 52.7 (+/- SEM 0.7) to 47.1 (+/- 1.8) at 1 month and 46.1 (+/- 1.2) after 4 months in patients receiving enalapril, with no change in the placebo group (P = 0.004). We did not demonstrate any change in serum erythropoietin in either group. CONCLUSIONS: Angiotensin-converting enzyme inhibitors are a safe and effective form of treatment for erythrocytosis developing after renal transplantation. The mechanism of action, however, is not mediated by changes in erythropoietin production and remains uncertain.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1995

Lansoprazole versus ranitidine for the treatment of reflux oesophagitis. UK Lansoprazole Clinical Research Group.

BACKGROUND: Lansoprazole is a H+.K(+)-ATPase (proton pump) inhibitor with an anti-secretory action and is therefore potentially useful in the treatment of gastro-oesophageal reflux. METHODS: This study was conducted to determine the efficacy and short-term safety of lansoprazole at doses of 30 mg or 60 mg once daily, compared with ranitidine 150 mg twice daily, in the treatment of patients with reflux oesophagitis. This was a double-blind, stratified, randomized, comparative, parallel group study conducted in five centres in the UK. A total of 229 patients (155 men) aged 18-79 years with endoscopically-confirmed oesophagitis were randomized to receive lansoprazole 30 mg p.o. daily, lansoprazole 60 mg p.o. daily, or ranitidine 150 mg p.o. b.d. Efficacy was assessed by endoscopic examination at 4 weeks and 8 weeks, together with symptom relief and antacid usage. RESULTS: Lansoprazole 30 mg and 60 mg were superior at 4 and 8 weeks (P < 0.01) to ranitidine in healing reflux oesophagitis: respective healing rates being 84%, 72% and 39% after 4 weeks and 92%, 91% and 53% after 8 weeks. Relief of heartburn with lansoprazole 30 mg and 60 mg was superior to that achieved with ranitidine at both week 4 (P < 0.01) and week 8 (P < 0.02). Sixty-four patients experienced a total of 85 adverse events, one-third of which were considered drug-related. The incidence and severity were similar in the three groups. CONCLUSION: Lansoprazole 30 mg and 60 mg once daily are more effective than ranitidine 150 mg twice daily in the short-term treatment of reflux oesophagitis.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed1995

Impaired polymorphonuclear neutrophil function in end-stage renal failure and its correction by continuous ambulatory peritoneal dialysis.

The polymorphonuclear neutrophil (PMN) function of 22 patients with end-stage renal failure (ESRF) was studied immediately before and 3 months after starting continuous ambulatory peritoneal dialysis (CAPD) and compared with a control group of healthy normal volunteers. The PMN functions studied were phagocytosis and killing of Staphylococcus epidermidis and respiratory burst activity. The results show that in the presence of normal pooled human serum PMN from patients with ESRF before CAPD treatment phagocytose bacteria normally, but have impaired killing. Before treatment, the PMN from patients with ESRF also showed an increase in both unstimulated and stimulated superoxide anion production. Abnormal PMN function was corrected by CAPD treatment, suggesting the involvement of a dialyzable toxin.

Acridines↗

PubMed1995

Cytomegalovirus infection in renal transplantation.

Three case reports of Cytomegalovirus (CMV) disease in seronegative renal transplant recipients of seropositive donor kidneys are presented. Clinicians need to have a high index of suspicion for CMV disease in such patients. Early diagnosis and treatment are essential to decrease morbidity and mortality. Prophylaxis with antiviral and/or CMV-hyperimmunoglobulin may decrease the incidence of serious infection.

Adolescent↗

PubMed1994

The use of DNA typing to clarify the origin of metastatic carcinoma after renal transplantation. A clinical and medico-legal problem.

We present an unusual diagnostic problem in a transplant patient whose failed renal transplant was found to contain undifferentiated carcinoma. When the patient later developed metastatic renal carcinoma, he began legal proceedings against the hospital for the transmission of a tumour with his renal transplant. He subsequently died of carcinomatosis. Post-mortem examination revealed acquired renal cystic disease in his native kidneys with a 1-cm adenocarcinoma arising from the wall of one of the cysts. We used DNA typing to determine the origin of the metastatic tumour and resolve the medico-legal problem.

Adenocarcinoma, Clear Cell↗

PubMed1994

Rapid healing of gastric ulcers with lansoprazole.

BACKGROUND: Lansoprazole is a new proton pump inhibitor which powerfully decreases acid secretion. METHODS: We compared the efficacy and short-term safety of lansoprazole against ranitidine in the healing of gastric ulcer. This was a parallel group, comparative multicentre, prospectively randomized, double-blind study which included 250 patients with gastric ulcer, 219 of whom had follow-up endoscopic data. RESULTS: Both lansoprazole 30 mg and 60 mg daily produced significantly more rapid healing of gastric ulcer than ranitidine 300 mg nightly with healing rates after 4 weeks of 78% (P < 0.05), 84% (P < 0.01) and 61%, respectively. After 8 weeks, the corresponding healing rates were 99%, 97% and 91% (P = 0.08). Symptom relief was similar for all treatment groups, but fewer antacids were used by patients receiving lansoprazole. Sixty-nine patients experienced 91 adverse events; the incidence, pattern and severity was similar across all three treatment groups. CONCLUSIONS: Lansoprazole 30 mg and 60 mg once daily had similar efficacy. Both were superior to ranitidine 300 mg nocte in healing gastric ulcer. The short-term safety profile of lansoprazole was similar to ranitidine. These data indicate that lansoprazole should be used at a dose of 30 mg once daily for the treatment of gastric ulcers.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed1994

Intensive treatment of renal failure in patients with myeloma.

We have reviewed our experience in the management of myeloma patients who present with features of severe renal impairment, to examine the role of intensive treatment of the renal failure, and to assess the role of renal biopsy. Between March 1983 and August 1991, 16 patients, who were subsequently diagnosed as having myeloma, presented to the Department of Renal Medicine for investigation of renal failure; nine with symptoms of uraemia and seven with pneumonia, bone pain, emphysema, or ischaemic heart disease. Renal biopsy was performed on 14 patients. Eleven patients had myeloma cast nephropathy, two of whom had concurrent hypertensive nephropathy, two patients had light chain deposition disease, and one patient had interstitial nephritis. Renal function improved in six patients with aggressive rehydration, but three of them subsequently required dialysis. In all 11 patients required dialysis, two short-term and nine long-term. Seven patients were given conventional melphalan and prednisolone and nine patients received VAMP as induction cytotoxic chemotherapy. Five of the VAMP sub-group received interferon alpha 2b as maintenance therapy. The median renal survival was five months (range 0-36 months) and median overall survival was 20 months (range 1-54 months). We conclude that intensive treatment, including dialysis, in myeloma patients with renal failure may result in survival durations approaching those of unselected myeloma patients, and a significant proportion will enjoy a reasonable quality of life.

Adult↗

PubMed1994

Primary and secondary granule release by polymorphonuclear leukocytes exposed to peritoneal dialysis effluent.

Peritoneal dialysis effluent from patients with end-stage renal failure contains a low-molecular-weight solute that inhibits the killing of phagocytosed Staphylococcus epidermidis by polymorphonuclear leukocytes (PMN). This observation has been investigated by using luciginen-enhanced chemiluminescence to measure PMN NADPH oxidase activity, CD11b/CD18 expression and lactoferrin release to measure secondary granule discharge, and cellular levels of beta-glucuronidase (EC 3.2.1.31) to measure changes in primary granules. Peritoneal dialysis effluent had no effect on the loss of intracellular beta-glucuronidase from normal unstimulated PMN or from PMN stimulated with S. epidermidis. It did, however, cause a concentration-dependent (0 to 70%; vol/vol) increase in expression of CD11b/CD18 and NADPH oxidase activity. CD11b/CD18 expression increased over 20 min before starting to plateau. Release of lactoferrin by the same cells demonstrated a strong positive correlation with integrin expression (P < 0.001, Spearman's rank correlation coefficient). When dialysis effluent-treated PMN were stimulated with formyl-methionylleucylphenylalanine, integrin expression, release of lactoferrin, and NADPH oxidase activity were greater than in PMN treated with formyl-methionylleucylphenylalanine alone. Under these conditions, a concentration-dependent increase in CD11b/ CD18 and lactoferrin release were observed only at a concentration between 0 and 30% (vol/vol) dialysis effluent, while a concentration-dependent increase in oxidase activity was seen at a concentration between 0 and 70% (vol/vol). The results suggest that dialysis effluent does not affect PMN primary granule release but does cause increased release of secondary granules and an increase in NADPH oxidase activity in both unstimulated and stimulated PMN.

CD11 Antigens↗