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Biomedical subjects

E H Cooper

Publications and source records attributed to E H Cooper.

At least 19 recordsLinked to original sources

Tumor markers in prostate cancer.

Prostatic specific antigen (PSA) is a tissue specific marker that is now the most widely used biochemical test for the assessment and follow-up of prostate cancer. The levels of PSA rise with tumor stage, but there is considerable overlap of their distribution between stages. PSA measurement now forms a part of the workup of a suspected carcinoma of the prostate, with a level of more than 4 ng/ml being an indication for further investigation. The sensitivity of PSA makes it an essential test for the postoperative assessment of radical prostatectomy and curative radiation therapy. The rates of change of PSA levels in locally advanced and metastatic disease treated by hormone manipulation can provide prognostic information. Low levels of PSA (less than 10 ng/ml) 6 months after treatment are a sign that the response will be prolonged. However, the sensitivity of PSA often results in a rising level preceding clinical evidence of progression by several months and is not necessarily an indication to change treatment. Alkaline phosphatase and prostatic acid phosphatase provide a less sensitive test for the bone response to skeletal metastases and tumor activity in advanced disease, respectively.

Acid Phosphatase

Serum bone alkaline phosphatase and CA 549 in breast cancer with bone metastases.

A monoclonal radioimmunometric assay for bone alkaline phosphatase (BAP) developed by Hybritech, USA, with an upper limit of normal of 40 U/l, was examined in 125 patients with breast cancer. Eleven patients who remained tumour free for 5-6 years had small intra-individual variations of BAP. The median value in 33 patients with multiple bone metastases of 60 U/l was elevated when compared with that in 40 patients with no evidence of metastases (22 U/l) and 34 U/l in 16 with limited bone disease (1-2 hot spots). By contrast, only 2 out of 25 patients with extensive local recurrence, lung, or hepatic metastases, without bone involvement showed an increase of BAP (< 200 U/l). The BAP levels were compared to total alkaline phosphatase (TAP), the breast cancer marker CA 549 (HybriBREScan). Longitudinal studies of 15 patients with bony metastases showed that TAP and BAP were well correlated only when the TAP was elevated; CA 549 and BAP could vary independently. The main use of BAP in patients with bone metastases appears to be an aid to the monitoring of treatment; however, it is not significantly raised in limited bone metastases.

Alkaline Phosphatase

Serum neuron specific enolase (NSE) is a determinant of response duration in small cell lung cancer (SCLC).

Seventy-two consecutive patients were eligible for a study of clinical determinants of response and response duration in small cell lung cancer (SCLC). Pretreatment values of routine laboratory parameters, and three tumour markers: neuron specific enolase (NSE), carcinoembryonic antigen (CEA), and acidic glycoprotein (AGP) were measured. Descriptive clinical variables as performance status (PS), extent of disease, age and sex were also included in the study. All variables were analysed for influence on the type and duration of response. The complete remission probability was only related to pretreatment extent of disease. In a multivariate analysis (Cox) of response duration, only NSE and type of response had significant influence. Consequently, measurements of NSE before therapy will be useful in future clinical trials on SCLC especially in situations, where responding patients are submitted to specific treatment strategies.

Adult

The prognostic value of the tumour markers CA 195 and CEA in patients with adenocarcinoma of the pancreas.

The serum levels of CA 195 were determined in 52 patients with histologically proven pancreatic carcinoma and compared with carcino-embryonic antigen (CEA), serum bilirubin and albumin. CA 195 levels were raised above the upper limit of 20 U/ml in 42 cases, giving a sensitivity of 80% for the detection of pancreatic carcinoma, whereas CEA was raised in only 55%. The levels of CA 195 and CEA were significantly higher in patients with metastatic disease, but potentially curable cases were not discriminated. Bilirubin and albumin levels were not significantly related to either the presence of metastases or the levels of the tumour markers. At the time of initial presentation, levels of both tumour markers correlated with the eventual duration of survival, but bilirubin and albumin did not. Significant increases in CEA and CA 195 were found in sequential blood samples, as the disease progressed. Neither CA 195 nor CEA was of sufficient sensitivity to be of value for screening, but both give an indication of the presence of metastases and of the subsequent duration of survival. CA 195 appeared to be more sensitive and might help to assess progress of the disease.

Adenocarcinoma

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