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Biomedical subjects

A G Morgan

Publications and source records attributed to A G Morgan.

At least 37 records · Page 2Linked to original sources
PubMed1994

Complement activation by cellulosic dialysis membranes.

AIMS: To assess the effect of cellulosic dialysis membranes on the production of complement degradation products to determine to the role of the classical pathway. METHOD: Complement activation was studied in 33 patients during a single haemodialysis session using cellulosic membranes. Pre- and post-dialysis plasma EDTA valves of C3, C4, C3dg, C4d and C reactive protein (CRP) were measured. Statistical analysis was done using the Wilcoxon signed rank test. RESULTS: Post-dialysis C4 (p = 0.0003), C3dg (p < 0.0001), and C4d (p = 0.003) concentrations were increased compared with pre-dialysis values. There was no significant change in C3 (p = 0.095) and CRP (p = 0.13) values. Post-dialysis C3dg and C4d concentrations correlated significantly (p = 0.007). IgG, an undialysed molecule, was quantified and post-dialysis valves were significantly higher than those before dialysis (p = 0.0002), indicating a degree of haemoconcentration. To remove this effect, the C3:IgG, C4:IgG, C3dg:IgG, C4d:IgG and CRP:IgG ratios were calculated. Compared with pre-dialysis values, post-dialysis C3dg:IgG and C4d:IgG ratios were increased and C3:IgG decreased significantly. No change was observed in C4:IgG and CRP:IgG ratios. CONCLUSION: This study confirms that significant complement activation takes place following dialysis with cellulosic membranes. This is denoted by an increase in C3dg. This was paralleled by a rise in C4d, implying a contributory role for the classical pathway. Concomitant post-dialysis increases in IgG and C4 indicate a degree of haemoconcentration; but removal of this effect shows that C3dg and C4d are increased following dialysis--suggesting classical, in addition to alternative, pathway activation.

Adult↗
PubMed1994

Treatment of resistant peritonitis in continuous ambulatory peritoneal dialysis with intraperitoneal urokinase: a double-blind clinical trial.

Resistant peritonitis in continuous ambulatory peritoneal dialysis (CAPD) is an indication for catheter removal, followed by interim haemodialysis and subsequent catheter replacement. This involves two surgical procedures using general anaesthetic and the availability of adequate hospital haemodialysis facilities. Urokinase is an alternative therapy but evidence of its effect is anecdotal and it has not been studied in a double-blind manner. Patients with resistant peritonitis (either no resolution of peritonitis within 4 days of appropriate antibiotic therapy or a third episode of peritonitis within 6 months) were randomized to receive intraperitoneal urokinase or placebo (saline) followed by 14 days of antibiotics in this double-blind prospective study. Treatment success was resolution of peritonitis within 4 days of giving urokinase/placebo (persistent infection) and no recurrence with the same organism for 6 months (recurrent infection). Twelve patients received urokinase and 12 placebo. Treatment was successful in 8/12 in the urokinase group and 1/12 in the placebo group (Fisher's exact test; P = 0.0047). Urokinase was successful in 8/12 patients with resistant peritonitis and significantly better than placebo. Urokinase is an effective and simple treatment that may avoid the need for catheter removal and interim haemodialysis in patients with resistant CAPD peritonitis.

Adult↗
PubMed1993

Copper-resistant enteric bacteria from United Kingdom and Australian piggeries.

Thirty-three enteric isolates from Australian (Escherichia coli only) and United Kingdom (U.K.) (Salmonella sp., Citrobacter spp., and E. coli) piggeries were characterized with respect to their copper resistance. The copper resistance phenotypes of four new Australian E. coli isolates were comparable with that of the previously studied E. coli K-12 strain ED8739(pRJ1004), in that the resistance level in rich media was high (up to 18 mM CuSO4) and resistance was inducible. Copper resistance was transferable by conjugation from the new Australian isolates to E. coli K-12 recipients. DNA similarity between the new Australian isolates and the pco copper resistance determinant located on plasmid pRJ1004 was strong as measured by DNA-DNA hybridization; however, the copper resistance plasmids were nonidentical as indicated by the presence of restriction fragment length polymorphisms between the plasmids. DNA-DNA hybridization and polymerase chain reaction analysis demonstrated DNA homology between the pco determinant and DNA from the U.K.E. coli, Salmonella sp., and Citrobacter freundii isolates. However, the copper resistance level and inducibility were variable among the U.K. strains. Of the U.K. E. coli isolates, 1 demonstrated a high level of copper resistance, 4 exhibited intermediate resistance, and 16 showed a low level of copper resistance; all of these resistances were expressed constitutively. A single U.K. C. freundii isolate, had a high level of copper resistance, inducible by subtoxic levels of copper. Transconjugants from one E. coli and one C. freundii donor, with E. coli K-12 strain UB1637 as a recipient, showed copper resistance levels and inducibility of resistance which differed from that expressed from plasmid pRJ1004.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Husbandry↗
PubMed1993

Systemic and mucosal humoral responses to Helicobacter pylori in gastric cancer.

The systemic IgG response to Helicobacter pylori was examined in 70 patients with gastric cancer. H pylori IgG antibodies were assayed by enzyme linked immunosorbent assay (ELISA), and serological recognition of H pylori antigens was characterised by western blotting. A percentage of 78.5 were seropositive by ELISA. Two of five patients under age 50 were seronegative. Positivity was unrelated to age, sex, tumour type, or site. Ninety one per cent of ELISA positive cancer patients recognised the H pylori cytotoxin associated 120 kilodalton (kD) protein, significantly more than a control group of 47 ELISA positive patients with non-ulcer dyspepsia (72%). Four of 15 ELISA negative cancer patients also showed recognition of this protein in western blots. Mucosal IgA responses to H pylori were examined by immunoblotting supernatants of in vitro cultured resected antral mucosa in an overlapping group of 19 gastric cancer patients. Eighteen had a positive response, including 10 of 11 negative for H pylori by biopsy urease testing. The systemic and local immunoblotting results show that the high seroprevalence of H pylori antibodies detected by ELISA is nevertheless an underestimate of past infection. Dyspepsia screening policies based solely on H pylori ELISA would miss some young patients with gastric cancer. Further study of the relation of the H pylori cytotoxin to gastric precancerous lesions is warranted.

Adenocarcinoma↗
PubMed1993

Asymptomatic acute pyelonephritis as a cause of acute renal failure in the elderly.

Urinary tract infections in the elderly are common, often asymptomatic and usually benign. We report three patients who presented with acute renal failure due to acute pyelonephritis in the absence of clinical findings of infection or urinary tract obstruction. Blood and urine cultures grew Escherichia coli in two of the patients and in two patients renal biopsy confirmed acute pyogenic pyelonephritis. Antimicrobial therapy and haemodialysis led to improvement, though one patient subsequently died from an unrelated cause. We suggest that acute bacterial pyelonephritis should be considered as a cause of acute renal failure in the elderly. Clinical features of infection may be absent despite bacteraemia. Prompt diagnosis and intervention may avoid chronic renal failure in a group that has a less favourable outcome with long-term dialysis.

Acute Disease↗
PubMed1993

Effect of peritoneal dialysis effluent on superoxide anion production by polymorphonuclear neutrophils.

Peritoneal dialysis effluent (PDE) contains at least 2 factors capable of affecting superoxide generation by polymorphonuclear neutrophils (PMN) in response to both particulate and soluble stimuli. A low molecular weight fraction (< 1.2 kD) enhanced the response to the chemotactic peptide fMLP and to preopsonised Staphylococcus epidermidis and Candida guilliermondii. A higher molecular weight fraction (> 1.2 kD) inhibited superoxide production in response to phorbol myristate acetate (PMA). The effects of PDE were dose dependent over the range of 10-70% (v/v) and simply augmented and reduced the dose-response curve to fMLP and PMA, respectively. There was no alteration in the concentration of stimulus required to give maximal superoxide production in either case. These data suggest that factors capable of affecting superoxide production by PMN accumulate in uraemia and are removed from the circulation into dialysis fluid.

Candida↗
PubMed1993

Clinical features of benign hypertensive nephrosclerosis at time of renal biopsy.

Although hypertension accounts for approximately 15-20% of end-stage renal disease and renal impairment occurs in 15% of patients with essential hypertension, there are few data available on the clinical features of patients with benign hypertensive nephrosclerosis, the histological consequence of hypertension on the kidney. To determine its prevalence on renal biopsy and its clinical features (including proteinuria and renal function), we used the U.K. MRC Glomerulonephritis Registry of 7339 biopsies from 20 centres to define all patients with benign hypertensive nephrosclerosis. In patients with no co-existing disease, 185 biopsies were classified solely as benign hypertensive nephrosclerosis (2.5%). Sixty-nine percent of patients were male and 72% aged over 50 years. Sixty-four percent had diastolic blood pressure above 90 mmHg and severe hypertension (diastolic > 120 mmHg) was present in 9%. Protein excretion of > 1.5 g/day was noted in 40%, with 22% excreting > 3 g/day. Eighteen percent had serum albumin values under 30 g/l. Eighty-one percent had serum creatinine > 120 mumol/l; in 51% this was > 250 mumol/l. There was significant correlation between serum creatinine and systolic blood pressure at time of biopsy (p = 0.01) and between serum creatinine and serum albumin (p = 0.001). Benign hypertensive nephrosclerosis accounts for 2.5% of all registered biopsies. Significant proteinuria is a common finding and proteinuria within the nephrotic range does occur. Systolic blood pressure appears to influence serum creatinine levels. Hypertensive nephropathy should be considered in all patients with heavy proteinuria and renal impairment.

Adult↗
PubMed1992

Abnormal cytoplasmic pH regulation during activation in uremic neutrophils.

Neutrophils isolated from ESRF patients demonstrated abnormal cytoplasmic pH changes after FMLP stimulation; the initial cytoplasmic acidification was absent (P less than 0.001 compared to controls) and the degree of alkalinization enhanced (P less than 0.05 compared to controls). This effect was not due to the absence of any of the factors associated with acidification in normal PMN since superoxide production was enhanced (P less than 0.05 compared to controls) and intracellular calcium release was normal. Our observations are not explicable by alterations in the function of the Na:H antiport since the kinetics of antiport activation by cytoplasmic pH were not different in uremic and control cells. Other factors must therefore be important in generating the abnormal pH response to chemotactic factors in uremic PMN. Cells from CAPD patients had some degree of initial acidification (P less than 0.001 compared to controls and P less than 0.05 compared to ESRF) and enhanced alkalinization (P less than 0.05 compared to controls). Preincubation of normal PMN in four-hour dwell PDE reproduced the responses of uremic PMN with absent acidification, enhanced alkalinization and enhanced superoxide generation after FMLP stimulation (P less than 0.05 compared to controls). Changes in the control of cytoplasmic pH in stimulated PMN may influence PMN function, and our observations may be relevant to the susceptibility of uremic patients to infection.

Adult↗
PubMed1992

Diabetic glomerulosclerosis without diabetes mellitus--two case reports and a review of the literature.

The duration of diabetes mellitus and presence of hyperglycaemia appear to be important in the development of diabetic nephropathy. The presence of nodular glomerulosclerosis is thought to be pathognomonic of the condition. We report two patients with histological features of diabetic glomerulosclerosis who did not have diabetes mellitus. The discussion reviews the literature and concludes that diabetic glomerulosclerosis with normal glucose tolerance is very rare and that most cases are due to overt diabetes mellitus or a degree of glucose intolerance. However, cases with only minimal glucose intolerance suggest that factor(s) other than hyperglycaemia are responsible for diabetic renal damage.

Aged↗
PubMed1992

Early deaths on renal replacement therapy: the need for early nephrological referral.

Forty-four patients who commenced renal replacement therapy between January 1983 and January 1988 died within 1 year of starting treatment. To examine the factors influencing early mortality of patients on renal replacement therapy these patients (group A) were compared with a group of 44 age- and sex-matched subjects who started dialysis over the same period and who survived more than 1 year (group B). The interval between first presentation and dialysis was significantly shorter in group A (median 36 days) than group B (median 30 months) patients. Plasma urea and creatinine were significantly greater in group A than group B at the time of first presentation to a nephrologist but not at first dialysis. Patients in group A were more often treated first by haemodialysis. Systemic disease as the cause of renal failure did not appear to influence early death. Early death on renal replacement therapy appears to be associated with late referral to a nephrologist. Early referral may be beneficial because it allows for planning of dialysis and treatment of the complications of progressive uraemia.

Adult↗
PubMed1991

Post-transplant erythrocytosis and immunosuppression with cyclosporin: a case-control study.

Review of 142 renal transplant recipients treated with cyclosporin and prednisolone revealed 23 patients with post-transplant erythrocytosis. The clinical characteristics of these patients were compared with 23 cyclosporin/prednisolone-treated control subjects matched for age, sex, and duration of transplant. Erythrocytosis developed between 6 weeks and 30 months (median 12 months) after transplant. It persisted in 16 patients and resolved spontaneously in five. In two patients the decrease in haematocrit was associated with acute leukaemia in one and sudden deterioration of renal function in the other. In the study group there were fewer HLA (A, B and DR) mismatches (P less than 0.05) and greater pretransplant haematocrit (P less than 0.01) than in the control group. Other clinical factors--previous allografts, panel reactive cytotoxic antibodies, duration and type of dialysis, transplant function, pre- and post-transplant blood pressure, number of rejection episodes, cyclosporin concentration and dose, smoking habits and use of diuretics--did not differ significantly between the two groups. In our experience, erythrocytosis in cyclosporin-treated patients is a relatively common phenomenon and does not, in general, resolve spontaneously. It is unrelated to transplant function or rejection episodes but affects patients with well-matched kidneys and elevated pretransplant haematocrit values.

Adult↗
PubMed1991

Peritonitis complicating continuous ambulatory peritoneal dialysis in Nottingham 1983-1988.

During the period 1983-1988 the incidence of peritonitis in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) in Nottingham fell from 2.0 to 1.2 episodes/patient/year. Cefuroxime, given intraperitoneally for 10 days, as recommended in published guidelines, failed to cure 35% of episodes of peritonitis, although only 7% of the pathogens responsible for these episodes were resistant in vitro. Cefuroxime is probably no longer appropriate as first line treatment of CAPD peritonitis.

Bacteria↗
PubMed1991

Treatment of acute myeloid leukaemia in a renal allograft recipient: implications of cyclosporin immunosuppressive treatment.

The clinical effects of cyclosporin were evaluated during cytotoxic treatment in a 61 year old man with acute myeloid leukaemia. He had required a renal transplant 18 months before presenting with acute myeloid leukaemia (FAB subtype M4). He had received cyclosporin 3.5-4.0 mg/kg daily to maintain a plasma cyclosporin concentration of 75-150 ng/ml. Cyclosporin was continued during induction chemotherapy with daunorubicin, cytarabine, and 6-thioguanine (DAT). He had fever and oropharyngeal candidiasis that was unresponsive to anti-bacterial drugs but responsive to systemic amphotericin. Bone marrow examination 14 days after chemotherapy showed complete haematological remission. Subsequently he tolerated consolidation treatment with DAT with no serious complications. Unfortunately he developed fatal septicaemia following a second consolidation with mitozantrone and cytarabine. Inhibition of P-glycoprotein activity by cyclosporin may not significantly increase the toxicity of aggressive chemotherapeutic regimens, and as benefit may be achieved by this approach further clinical evaluation is justified.

Antineoplastic Combined Chemotherapy Protocols↗