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Biomedical subjects

P McClelland

Publications and source records attributed to P McClelland.

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

Evidence of oxidant injury and tubular damage in early diabetic nephropathy.

Two groups of patients with insulin-dependent diabetes mellitus of > 10 years duration and either persistent normoalbuminuria (group 1, n = 49; albumin excretion < 30 mg/day) or microalbuminuria (group 2, n = 33; albumin excretion 30-300 mg/day) were investigated for evidence of free oxygen radical activity (erythrocytic superoxide dismutase and glutathione peroxidase) and oxidant injury (serum malondialdehyde). Glomerular proteinuria (albuminuria, transferrinuria), tubular proteinuria (retinol-binding protein) and tubular enzymuria (N-acetyl-glucosaminidase and leucine aminopeptidase) were also measured. Healthy controls (n = 38) were matched for age and sex. Groups 1 and 2 were similar in terms of age, sex, duration of diabetes and recent glycaemic control. Serum cholesterol and creatinine were similar in all three groups. Free-radical activity and oxidant injury were significantly higher in groups 1 and 2 than in controls (p < 0.001). Glomerular proteinuria, tubular proteinuria and enzymuria were significantly higher in group 2 than in group 1 and controls (p < 0.01). Group 1 had significantly higher transferrinuria, tubular enzymuria and tubular proteinuria than controls. However, groups 1 and 2 were similar in degree of free oxygen radical generation and oxidant injury. In diabetic nephropathy, oxidant injury and renal tubular damage accompany and may even precede microalbuminuria. The presence of these abnormalities in the absence of glomerular proteinuria favours the hypothesis that alterations first occur in the peritubular microcirculation, which by causing oxidant injury and tubular damage, may initiate diabetic nephropathy.

Adult↗
PubMed1994

Human urinary intestinal alkaline phosphatase as an indicator of S3-segment-specific alterations in incipient diabetic nephropathy.

Urinary enzymes were determined in a controlled study including 28 type I diabetes mellitus patients. Fifteen patients had persistent microalbuminuria and were compared to 13 normoalbuminuric patients with comparable age and sex distribution. All patients had normal renal function as measured by serum creatinine. Human intestinal alkaline phosphatase (hIAP), a specific marker of the proximal tubular S3 segment, was elevated in the urine of microalbuminuric patients while human tissue non-specific alkaline phosphatase (hTNAP), indicating effects mainly at the S1-S2 segments, was not. Urinary hIAP was correlated with serum glycated haemoglobin. These results suggest that tubular alterations are present at an early stage of diabetic nephropathy, especially at the S3 segment, and that hIAP may have promise as an early marker.

Acetylglucosaminidase↗
PubMed1993

Relationship between markers of endothelial dysfunction, oxidant injury and tubular damage in patients with insulin-dependent diabetes mellitus.

1. Diabetic nephropathy is a serious microvascular complication in patients with insulin-dependent diabetes mellitus, resulting in end-stage renal disease in 30-45% of such patients. Despite intensive investigation, the pathophysiology of diabetic renal disease has not been fully elucidated. However, several clinical and experimental studies have suggested that endothelial dysfunction and free-radical activity may be important factors. 2. Forty normotensive patients with insulin-dependent diabetes mellitus of between 10 and 20 years duration with persistent normoalbuminuria (albumin excretion < 30 mg/day) and normal renal function were investigated for markers of endothelial dysfunction (plasma von Willebrand factor, soluble thrombomodulin and angiotensin-converting enzyme activity), free oxygen radical generation (erythrocytic superoxide dismutase and glutathione peroxidase) and oxidant injury (serum malondialdehyde). Glomerular proteinuria (albuminuria, transferrinuria), tubular proteinuria (retinol-binding protein) and tubular enzymuria (N-acetyl glucosaminidase and leucine aminopeptidase) were also measured. 3. Patients were divided into two groups. Group 1 comprised 21 patients with elevated markers of endothelial dysfunction, and group 2 comprised 19 patients with normal levels of plasma von Willebrand factor, soluble thrombomodulin and angiotensin-converting enzyme activity. Thirty-eight healthy subjects matched for age and sex acted as controls. 4. Groups 1 and 2 were similar in age, sex, body weight, duration of diabetes mellitus and recent glycaemic control. Serum cholesterol, serum creatinine and glomerular proteinuria were similar in the three groups. Group 1 patients had significantly increased oxidant injury, tubular enzymuria and proteinuria compared with group 2 patients and control subjects (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Resistance to recombinant human erythropoietin due to aluminium overload and its reversal by low dose desferrioxamine therapy.

Seventeen severely anaemic and transfusion-dependent haemodialysis patients with a haemoglobin less than 7 g/dl were treated with recombinant human erythropoietin (r-Hu-EPO). Aluminium toxicity was diagnosed by a positive desferrioxamine (DFO) test and bone biopsy. Seven out of eight patients without aluminium toxicity responded to r-Hu-EPO therapy. Similarly all patients with aluminium toxicity (n = 4) but pre-treated with standard dose of DFO prior to r-Hu-EPO therapy responded but none of the patients with untreated aluminium toxicity (n = 5) responded to r-Hu-EPO therapy. In order to achieve adequate response in these patients, r-Hu-EPO and DFO had to be given in combination. The dose of desferrioxamine used to reverse r-Hu-EPO resistance was less and also used for a short time. We therefore confirm r-Hu-EPO resistance owing to aluminium overload and report its successful and safe reversal with low dose DFO therapy.

Aluminum↗
PubMed1992

Haemodialysis-related porphyria cutanea tarda and treatment by recombinant human erythropoietin.

Haemodialysis-related porphyria cutanea tarda is a rare, but serious and mutilating skin condition, resulting from extremely high plasma porphyrin levels because of their inadequate clearance by haemodialysis. The treatment is very difficult as chloroquine is ineffective and venesection, the conventional treatment of this disease, is not always an option because of anaemia of end-stage renal disease. We report a case of haemodialysis-related porphyria cutanea tarda and her successful management by recombinant human erythropoietin treatment.

Erythropoietin↗
PubMed1992

Urinary dopamine excretion in chronic renal disease.

We have measured unconjugated urinary dopamine and investigated its relationship to glomerular filtration rate in two groups of 22 patients with chronic renal failure matched for age and sex, one group with primary glomerular disease, the other with tubulo-interstitial disease. Urine dopamine excretion was similar in both glomerular and tubulo-interstitial disease groups, and correlated significantly with creatinine clearance. Although urinary protein excretion was significantly higher in glomerular disease, urinary sodium excretion, fractional sodium excretion, urine flow rate and free water clearance were similar in both groups and did not correlate with dopamine excretion. These results suggest that in patients with chronic renal disease, urinary dopamine excretion is mainly under the influence of the glomerular filtration rate, irrespective of the underlying pathology, and therefore interpretation of urinary dopamine excretion requires a knowledge of the patients' renal function.

Adult↗
PubMed1992

Prevention of bacterial infection and sepsis in acute severe pancreatitis.

Between 1984 and 1986 six patients with acute respiratory failure (requiring ventilation for at least 3 days) complicating acute pancreatitis were managed on the intensive care unit (median ventilation period 6 days; range 3-41 days). Between 1987 and 1989 nine similar patients were managed (median ventilation period 35 days, range 4-69 days), and a regimen of enteral tobramycin, polymyxin and amphotericin to selectively decontaminate the digestive tract (SDD) was introduced. Five of six patients treated before 1987 had serious infections (three Gram-negative, one fungal), compared with only one of nine patients treated with SDD (P < 0.05). Clinical signs of sepsis were evident for 62% of the pre-SDD period, compared with 39% of the period during SDD therapy (P < 0.001). Systemic antibiotic prescribing was reduced in the SDD group; however, mortality remained unaffected with only two patients surviving pre-SDD and three during SDD treatment. SDD reduces infection rates and sepsis in patients with acute pancreatitis and may help to improve the prognosis of this life-threatening condition.

Acute Disease↗
PubMed1991

The calpain-calpastatin system in vascular smooth muscle.

Vascular smooth muscle contains large amounts of the Ca(2+)-dependent protease calpain II. In this study, we compared bovine aortic muscle (muscle phenotype) to cultured bovine aortic cells of smooth muscle origin (modulated phenotype) with respect to major constituents of the calpain-calpastatin system. Bovine aortic muscle contained only calpain II by activity measurements, Western blot of tissue extracts and Northern blot of poly(A)+ RNA. On the other hand, using the same methodologies, both calpains I and II as well as the 110 kDa inhibitor protein, calpastatin, were identified in cultured bovine aortic cells of smooth muscle origin. We conclude that the phenotypic state of smooth muscle cells is associated with differential expression of major components of the calpain-calpastatin system. Moreover, bovine aortic muscle is the only tissue identified to date that contains calpain II exclusively.

Animals↗
PubMed1991

Necrotizing myopathy in critically-ill patients.

Skeletal muscle wasting is commonly observed in critically-ill patients and has been attributed to catabolic fibre atrophy and to neuropathy. This study describes the occurrence of a necrotizing myopathy in 15 out of 31 critically-ill patients who had percutaneous biopsies taken from the tibialis anterior muscles. While most cases showed necrosis of isolated fibres, 5 of the 12 patients who had serial biopsies showed progressive necrosis of up to 95 per cent of the fibres. One other case showed infarction and one case had staphylococcal vasculitis. Atrophy of type 1 and/or type 2 fibres was documented by morphometry in 12 cases. Myoglobin-containing casts were demonstrated immunohistochemically in renal tubules on either biopsy or necropsy material in 5 out of 7 cases. The presence of muscle necrosis was a clinically unexpected finding which may contribute to weakness, complicate the interpretation of tissue biochemistry and energy balance studies, and potentiate renal failure. The necrosis is probably multifactorial in origin, with ischaemia and sepsis contributing factors.

Acetaminophen↗
PubMed1991

Delayed recovery of renal function in patients with acute renal failure due to accelerated hypertension.

Five patients with acute renal failure due to accelerated hypertension required regular dialysis treatment for 2-12 months (mean 8.8), before recovering sufficient renal function for dialysis to be withdrawn. Two patients who had prior evidence of chronic renal impairment remained off dialysis for 20 and 27 months before decompensating again to require regular dialysis treatment. Two patients with no prior history of renal disease have remained independent of dialysis for 32 and 48 months. The fifth patient was lost to follow-up after a 7 month dialysis-free period. Delayed recovery of renal function following accelerated hypertension is a distinct possibility and should be considered in such patients before contemplating long term strategies such as renal transplantation.

Acute Kidney Injury↗
PubMed1990

Multiple organ failure--a role for plasma exchange?

Two patients with multiple organ failure, septicaemia and a deteriorating clinical course were treated by plasma exchange in addition to standard supportive measures. Dramatic improvements were seen in cardio-respiratory (patient 1), neurological and renal parameters (patient 2) which were attributable to the exchanges. Plasma exchange might be of value as adjunctive therapy where overwhelming septicaemia occurs with multiple organ failure.

Adult↗
PubMed1990

Reducing sepsis in severe combined acute renal and respiratory failure by selective decontamination of the digestive tract.

Fifteen patients with severe combined acute renal and respiratory failure (SCARRF), who required mechanical ventilation and renal replacement therapy for at least 5 days, were treated with a regimen to selectively decontaminate the digestive tract (SDD). In these patients the incidence of significant infection was compared with the infection rate in 12 similar patients with SCARRF who had not received SDD, treated over the preceding 12 months. Both groups were comparable for age, study period, sepsis score, and therapeutic intervention scoring system on admission, although the Acute Physiology and Chronic Health Evaluation score was higher (p less than .05) in the SDD-treated group. Ten (83%) of 12 control patients developed definable infections compared with five (33%) of 15 in the SDD group (p less than .05). Gram-negative bacteria and fungi were responsible for 14 of the 17 infections affecting ten control patients, compared with six of the seven infections in only four SDD patients (p less than .05). The most notable site to benefit was the respiratory tract, with only one patient in the SDD group developing a pulmonary infection compared with five in the control patients (p less than .05). Urine infections may have been reduced from six (50%) of the 12 control patients to two (13%) of the 15 SDD patients, but this difference was not significant. Although survival in the control and SDD group was comparable (42% vs. 40%), mortality overall seemed related to infection. Eleven (73%) of 15 patients with definite infection died, in contrast with five (42%) of 12 who had no infections, although this was not significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗
PubMed1989

Hyperthyrotrophinaemia during thyroxine replacement therapy.

During the follow-up of 224 cases of treated hypothyroidism, 14 clinically euthyroid patients were found to have elevated serum thyrotrophin and normal total thyroxine concentrations. Closer observation of these patients during the following 27 months resulted in the serum thyrotrophin levels returning to normal spontaneously in 8 patients (Group 1) whilst remaining elevated in 6 (Group 2), despite no significant differences in thyroid hormone levels between the two groups. Serum thyrotrophin in Group 2 patients remained high until an additional 50 micrograms/day thyroxine was prescribed although only 2 patients noted any benefit. Non-compliance or inadequate dosage of thyroxine are the probable causes of this sub-clinical hypothyroidism. Thyroid hormone estimations fail to differentiate the two conditions and we recommend a period of closer observation before making any thyroxine dosage adjustments in order to detect non-compliance.

Adult↗