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Biomedical subjects

E H Cooper

Publications and source records attributed to E H Cooper.

At least 37 records · Page 2Linked to original sources

Sodium dodecyl sulphate polyacrylamide gel electrophoresis patterns of proteinuria in various renal diseases of childhood.

This study examined the potential of an automated electrophoretic system (PHASTSYSTEM, Pharmacia. Uppsala, Sweden) to distinguish patterns of proteinuria in children with various renal diseases. It proved possible to produce ready-to-read sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS PAGE) separation of 1 microliter of unconcentrated urine in 2 h. Glomerular, tubular and mixed patterns of proteinuria were identified. Steroid-responsive nephrotic syndrome (SRNS) was readily identified by strong bands of albumin and transferrin during relapses. In contrast, steroid-resistant nephrotic syndrome was associated with two additional bands of haptoglobin and IgG. Albumin dimers (Mr 120 kDa) were found in the active phase of the disease in the urine of 90% of children with SRNS. Patterns of tubular proteinuria were found in children with proximal renal tubular abnormalities. The presence of mixed patterns of glomerular and tubular proteinuria strongly suggest renal insufficiency. SDS PAGE electrophoresis can readily be applied in clinical practice. It may prove helpful in the diagnosis and management of children with renal diseases enabling correlation to be made between proteinuria, renal pathology and prognosis.

Adolescent↗

Serum hyaluronate as a marker of hepatic derangement in acute liver damage.

Twenty patients with paracetamol(acetaminophen)-induced acute liver damage of varying severity were studied longitudinally with assessment of clinical state, standard liver function tests and radiometric hyaluronate (HYA) assay (Pharmacia). In patients (n = 6) who developed coma, HYA rose rapidly with clinical deterioration to reach a median value of 27,510 micrograms/l, 7 days post-ingestion, which was significantly higher (p less than 0.005) than in patients (n = 7) who exhibited only marked derangement of liver function tests without evidence of encephalopathy, HYA median value of 3240 micrograms/l. These peak values showed no correlation to the peak values of serum alanine aminotransferase (ALT). A third group of patients (n = 7) who were treated with N-acetyl cysteine, did not exhibit any evidence of liver failure and showed no significant rise in levels of HYA or ALT. The data demonstrate that HYA is a rapidly changing marker of liver derangement which appears to follow the clinical course of the patient. The increase to extremely high levels in patients with hepatic encephalopathy, suggests that there is a reversible defect in the hepatic endothelial cell HYA receptor, possibly due to endothelial cell damage or release of toxins from the necrotic liver.

Acetaminophen↗

Use of mucin like cancer associated antigen (MCA) in the management of breast cancer.

A study of the epithelial mucin marker MCA was made in 233 patients with breast cancer. Only 6% of 72 patients with Stage I-III disease had a raised MCA (greater than 15 U ml-1) when assessed following surgical treatment of the primary tumour. Raised levels of MCA occurred in one out of 20 (10%) patients with stable local recurrence, and six out of ten (60%) patients with progressive local recurrence. In 115 patients with metastases 89 (77%) had a raised MCA, tumour extent and disease activity both influenced the MCA level. The change of MCA level during the treatment of 11 cases of local recurrence and 55 cases of metastatic disease showed a 64 and 84% concordance respectively with the change in clinical status. Coincidental measurement of MCA and bone scans showed a raised MCA in one out of 63 (1.5%) patients with negative or equivocal scans, and 26 out of 35 (74%) with positive scans. MCA provides a useful marker for the monitoring of the treatment of local recurrence and metastatic disease, and an independent indicator of the effects of changes in treatment.

Antigens, Neoplasm↗

Occurrence of neuron specific enolase in tumour tissue and serum in small cell lung cancer.

An analysis has been made of the relationship between neuron specific enolase (NSE) in serum and immunohistochemically identified occurrence of NSE in the primary tumour in 56 patients with small cell lung cancer (SCLC). Patients were referred to the Finsen Institute for treatment during a period of 18 months. Forty-six tumours (82%) were NSE positive. To compare this staining with the occurrence of NSE in serum, a histological staining index (HSI) was established by semiquantitative gradation of the staining. No significant differences were found between distribution of serum NSE values in different HSI categories, and a high ranking in HSI was not associated with a high level of serum NSE. Both univariate and multivariate analysis selected serum NSE and not HSI as the most influential prognostic factor in SCLC.

Animals↗

Hyaluronic acid in end-stage renal failure treated by haemodialysis: clinical correlates and implications.

Serum hyaluronic acid was measured in 176 adults and 15 children receiving regular dialysis therapy. Hyaluronic acid was elevated to greater than 80 micrograms/l in more than 90%, with median value 182 micrograms/l (range 39-898 micrograms/l). Concentrations did not correlate with serum creatinine, but showed a significant correlation with duration of dialysis and serum beta 2-microglobulin. Values greater than 400 micrograms/l were frequent in patients whose clinical condition deteriorated, but in others, hyaluronic acid remained stable over 4-15 months. Serum hyaluronic acid is mainly in a high-molecular-weight form, which in the presence of normal hepatic function suggests that there is a metabolic disorder involving connective tissue and/or vascular endothelium that increases with progressive loss of renal function. Hyaluronic acid may also be a biochemical marker of patients whose condition deteriorates despite renal replacement therapy.

Adult↗

Renal tubular dysfunction in rheumatic diseases.

Evidence of renal tubular dysfunction as defined by abnormal urinary levels of alpha 1 and beta 2 microglobulin with or without microalbuminuria was found in 47 (16.5%) of 285 patients with a variety of rheumatic diseases, compared with a prevalence of less than 1% in 500 healthy adults. Previous work from this unit has shown a prevalence of tubular dysfunction of 24% in patients with severe rheumatic disease admitted to hospital, probably associated with severe rheumatoid arthritis. Although our study confirms a high prevalence of renal tubular dysfunction, we have shown that it is related to age and intercurrent illness, particularly urinary tract infection, rather than to rheumatic disease or drug therapy, although it is possible drug therapy could add to a compound insult on ageing or damaged kidney.

Aged↗

Prognostic indicators for the development of AIDS in HIV antibody positive haemophiliac patients: results of a three-year longitudinal study.

In February 1986, 40 out of 75 adult patients with haemophilia A attending St. James's University Hospital were human immunodeficiency virus (HIV) antibody positive. Over a three-year period these patients were prospectively studied with regard to possible prognostic indicators for the development of the acquired immune deficiency syndrome (AIDS). Using the Centres for Disease Control (CDC) classification of HIV infection, 17 patients (42.5%) developed group 4 disease during this time, giving an actuarial three-year progression rate of 44%, and 5 patients (12.5%) died. The following parameters measured at recruitment were found independently to predict progression to AIDS: a serum beta 2-m level of greater than 3.5 mg/l, (chi 2 = 15.95, P less than 0.001), a serum IgA level of greater than 4.5 milligram(s) (chi 2 = 6.08, P less than 0.02) and p24 antigenaemia (chi 2 = 5.7, P less than 0.05). The actuarial three-year progression rate in those patients abnormal by two or more of these parameters was 100% (n = 7), compared to only 7% in patients who were normal by all three values (n = 15). CD4+ lymphocyte counts and CD4+:CD8+ ratios were significantly lower in HIV positive compared with HIV negative patients (P less than 0.01), but did not predict the development of AIDS.

Acquired Immunodeficiency Syndrome↗

Tumour markers in prostatic cancer.

Prostate cancer is now the third commonest cancer in men. Extensive clinical trials comparing acid phosphatase, alkaline phosphatase (ALKP) and prostate specific antigen (PSA) have shown that PSA is the most sensitive and specific of the tumour markers available for prostate cancer. Caution is needed when comparing the results from different assay methods, there is no international standard for PSA. In the management of localised disease, radical treatment can reduce the PSA levels to less than 0.4 ng/ml, similar results can be obtained for a varying duration in patients sensitive to androgen withdrawal. Raised levels greater than 0.4 ng/ml after radical prostatectomy are indicative of residual disease. PSA is valuable in monitoring deferred treatment or the effects of hormone manipulation and give an indication of the prognosis and early warning of recurrence. In extensive metastatic disease the combination of PSA and ALP reflects the tumour activity. Less than 15 hot spots on the scintigram at presentation and a PSA less than 10 ng/ml 3 to 6 months after commencing treatment is associated with prolonged survival. The role of PSA in population screening for early prostatic cancer is uncertain; early results suggest it can be used in combination with digital rectal examination and ultrasonic examination of the prostate. The effect of a PSA decision level at 4 or 10 ng/ml has a considerable influence on the pick up rate.

Alkaline Phosphatase↗

Prostatic specific antigen and the prediction of prognosis in metastatic prostatic cancer.

Serum prostate-specific antigen (PSA) levels were studied in the EORTC trial of zoladex plus flutamide versus orchidectomy in metastatic prostatic cancer. Forty-four of 60 patients had a decrease of PSA to less than or equal to 10 ng/ml at 3 to 6 months after treatment. The combination of a PSA less than 10 ng/ml after 3 to 6 months treatment and less than 15 spots on the bone scintigram at entry gave the highest probability of not having progressed by 24 months. A rising PSA anticipated bone progression by 6 to 12 months in 13 of 28 patients (46%). The PSA at entry to the trial was related to survival; a discriminant of 300 ng/ml distinguished a poor and better risk group. The lowest level of PSA reached during the first 6 months of treatment was also a univariate survival factor.

Antigens, Neoplasm↗

Long-term prognostic value of serum beta 2 microglobulin in myelomatosis.

The prognostic value of serum beta 2 microglobulin (s beta 2m) measured at entry, at plateau and at 3-monthly follow-up times has been assessed for patients in the Medical Research Council's 4th and 5th Myelomatosis Trials. Analysis of 1014 patients confirmed the value of presentation s beta 2m of predicting survival in the short term but showed that predictive value was lost for subsequent survival in those patients who had survived for at least 2 years. However, measurements of s beta 2m taken during follow-up were predictive of subsequent survival. The predictive power of these follow-up measurements was very similar to that for the presenting measurement, and again they were only of value in predicting survival in the next 2 years.

Calcium↗

Clinical significance of the immunometric measurements of hyaluronic acid.

Hyaluronic acid (HA), an unbranched high molecular weight polysaccharide can now be measured by several immunometric assays. The connective tissues are the main source of HA and it is destroyed mainly in the liver. Very high levels of HA occur in mesothelioma. Wilms' tumour and acute liver failure, and moderate increases in rheumatoid diseases, renal failure and cirrhosis. Local increased production of HA is a feature of several forms of lung disease. HA is an indicator of connective tissue turnover, of the function of the receptor mechanisms for its capture and destruction by the liver, and of the removal of low molecular weight fragments by the kidney.

Arthritis, Rheumatoid↗