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Biomedical subjects

E H Cooper

Publications and source records attributed to E H Cooper.

At least 73 records · Page 4Linked to original sources

Analysis of proteinuria using a commercial system for automated electrophoresis and isoelectric focusing.

We describe an investigation of proteinuria using Pharmacia PhastSystemTM electrophoresis apparatus. The analysis of urinary proteins by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) of unconcentrated urine followed by silver staining took about 2 h and could clearly demonstrate tubular dysfunction or glomerular damage in urines with a negative or only trace-positive dip-stick test for protein. In addition, we show the identification of urinary proteins by immunoblotting from SDS-PAGE gels and the characterisation of Bence-Jones proteins by isoelectric focusing (IEF) and immunoblotting.

Autoanalysis↗

Serum low-molecular-weight proteins in haemodialysis patients: effect of residual renal function.

Serum low-molecular-weight proteins, beta-2-microglobulin and alpha-1-microglobulin, were measured in 34 patients undergoing maintenance haemodialysis. There was a strong positive correlation between beta 2M and alpha 1M and predialysis serum creatinine and strong negative correlations between these proteins and 24-h urine volume and creatinine clearance. Good correlation was also demonstrated with total duration of haemodialysis, which also correlated with residual renal function. It is suggested that the elevated beta 2M and alpha 1M in haemodialysis patients merely reflect the severity of renal failure and are not directly influenced by the duration of dialysis or type of dialysis membrane.

Adult↗

Acute phase reactant proteins as prognostic indicators in cancer.

Raised levels of APRPs in a patients with cancer at presentation are generally an unfavourable factor for the patient's survival. The APRPs can be prognostic indicators alone but are more effective when used in combination with powerful indices such as stage and clinical performance status. The pre-treatment APRPs tend to reflect shorter term survival risks up to 18 months and are often raised during the last 6 months of life in patients with disseminated cancer, as well as acute events such as sepsis.

Acute-Phase Proteins↗

Laboratory indices of prognosis in HIV infection.

The progression of a HIV seropositive patient from an asymptomatic infection or persistent generalised lymphadenopathy to AIDS is dependent on many factors. The most useful prognostic indicators appear to be CD4 + lymphocyte count, beta 2-microglobulin level, anti-p24 antibody titre and p24 antigenaemia. The use of a combination of prognostic indices can enhance the accuracy of the prediction.

Acquired Immunodeficiency Syndrome↗

An evaluation of serum CA 50 levels in cancer using a time-resolved fluoroimmunoassay.

The CA 50 levels in serum samples from 440 patients were estimated using a dissociated enhanced lanthanide immunofluorimetric assay. The distribution was similar to CA 50-RIA assays. Raised levels (greater than 14 U/ml) were present in 95% pancreatic cancer, 68% hepatoma, 54% advanced colorectal cancer, 58% advanced breast cancer and 48% lung cancer. High values were observed in adenocarcinoma of the lung, and were related to tumour mass in small cell lung cancer. CA 50 is independent of CEA. The marker is of considerable potential in pancreatic cancer where the majority of patients express the Can 50 Ag.

Antigens, Tumor-Associated, Carbohydrate↗

Separation and characterisation of glycoproteins from normal, pregnancy, and acute inflammatory sera.

A system of multiple chromatography combining anion-exchange, gel filtration, and affinity chromatography has been devised to separate several acute phase proteins from serum, including alpha 1 acid glycoprotein, transferrin, alpha 1-antichymotrypsin, alpha 1-antitrypsin and haemopexin. Only 5-15 ml of blood is required to provide milligram quantities of the purified proteins for further biochemical analysis. The system has been applied in a study of pregnancy and some diseases in order to investigate the changes in the serum protein profile and in individual proteins.

Acute-Phase Proteins↗

Neuron-specific enolase as a guide to the treatment of small cell lung cancer.

A retrospective evaluation of serial measurements of neuron-specific enolase (NSE) has been performed in 58 patients with small cell lung cancer (SCLC). All 58 patients received first-line chemotherapy and 11 patients received also second-line treatment after relapse. Samples were obtained every 3-4 weeks during treatment before each cycle of chemotherapy and every 6 or 12 weeks during follow-up. NSE values were depicted on semi-logarithmic paper. Fifty-one times a major response (complete or partial remission) was observed and 49 times the NSE level reached a plateau between 3.5-10 ng/ml. The NSE level did not discriminate between a complete or a partial remission. Seven times stable disease was obtained and the NSE level declined but remained above the normal plateau of 3.5-10 ng/ml. On 50 occasions progressive disease was found. In 3 cases progressive disease was due to a histologically-proven non-small cell lung cancer and NSE levels did not change. In only 5 out of the remaining 47 occasions NSE levels were normal at the time of relapse but rose later in 4. On 42 occasions of progressive SCLC an exponential rise of NSE was found, often within the range of 3.5-20 ng/ml. None of 6 patients, who are still incomplete remission for 1-5 years, showed a consistent rise of NSE. Serial measurements of serum NSE, can predict the occurrence of a major response, stable disease and progressive disease outside the brain with a very high accuracy and seem to be at least a useful addition to standard investigational methods to guide the treatment of SCLC.

Adult↗

Serum neuron-specific enolase in children's cancer.

To test its diagnostic potential and sensitivity in paediatric malignancy, serum NSE was measured at diagnosis in 191 children with solid tumours and 25 with acute leukaemia. In stages I + II, III + IV and IVs neuroblastoma median levels were 18.0, 91.0 and 24.0 ng ml-1 respectively. For Wilms' patients, median values for stages I, II, III and IV disease were 16.6, 18.0, 29.0 and 47.0 ng ml-1 respectively. High levels of NSE were also found in patients with other types of tumour. Children in clinical remission after treatment for neuroblastoma invariably had normal NSE levels (mean +/- s.d. = 9.2 +/- 3.0 ng ml-1) even though the majority had radiologically identifiable residual disease. The values rose when relapse was radiologically or clinically obvious. We conclude (a) that, though levels of greater than 100 ng ml-1 are highly suggestive of advanced neuroblastoma, caution should be exercised in using serum NSE as a diagnostic test in children with cancer and (b) that serum NSE levels are not a sensitive index of residual neuroblastoma in patients, with initially elevated levels, that are receiving treatment.

Child↗

Serum alpha-thiol protease inhibitor concentrations in health and disease.

Serum alpha-thiol protease inhibitor (alpha-TPI) concentration was assayed by radial immunodiffusion in normal subjects, pregnant women, and in a wide variety of diseases. The normal concentration (448 (SD 75) mg/l) increased significantly (p less than 0.001) in pregnancy to 575 (89) mg/l, and in prostatic cancer treated by oestrogens to 666 (87) mg/l. Inconsistent changes were observed in inflammatory and malignant disease and in liver disease. A temporary pronounced fall of alpha-TPI was seen after burn injury, and a sustained fall after bone marrow transplantation. Crossed immunoelectrophoresis showed that the serum alpha-TPI occurred in two forms, with alpha 2 and alpha 1 electrophoretic mobilities. A heavy demand on this antiprotease may result in suppression of the alpha 1 form.

Blood Proteins↗

Changes in plasma beta 2 microglobulin concentrations after allogeneic bone marrow transplantation.

Plasma concentrations of beta 2 microglobulin (B2M), the light chain of the class I major histocompatibility complex, were measured serially in 26 patients undergoing allogeneic bone marrow transplantation (BMT). The concentrations fell after conditioning treatment, and recovered when the marrow was transplanted. Bacterial infection did not influence B2M concentration, but nine of 22 episodes of acute graft versus host disease were associated with raised concentrations. Increased plasma B2M concentrations were also a feature of eight episodes of chronic graft versus host disease, and these fell after treatment. Reactivation of herpes simplex, varicella zoster, or cytomegalovirus infections were also accompanied by raised B2M concentrations. Three patients with cytomegalovirus pneumonitis had high concentrations of plasma B2M, the rise starting between five and 22 days before onset of symptoms. Although it is non-specific, serial measurement of plasma B2M in patients undergoing BMT may be clinically useful in monitoring chronic graft versus host disease.

Adolescent↗

Doubling time of neuron-specific enolase and survival in small cell lung cancer patients. Results of a preliminary analysis.

During a retrospective analysis of the value of neuron specific enolase (NSE) in patients with small cell lung cancer (SCLC) it became apparent that at progressive disease (PD) NSE rose exponentially with a doubling time (NSE-Td) varying from 10 - 94 days. In this study the influence of the NSE-Td on the survival of 29 SCLC-patients has been investigated. A significant correlation between survival from the start of rise of NSE at PD and NSE-Td was observed. By extrapolating the exponential rise of NSE to the start of treatment a theoretical logarithmic value of NSE, called Yr, could be calculated. When the patients were grouped according to the Yr value greater than -1, between -1 and -4 and less than or equal to -4 a highly significant correlation between the survival from the start of treatment and NSE-Td was found in all 3 groups. These preliminary data suggest that by means of NSE-Td and Yr value the survival of an SCLC-patient from the time of rise of NSE and from the start of treatment may be predicted within certain limits.

Carcinoma, Small Cell↗

Serum beta 2-microglobulin and human immunodeficiency virus infection.

Serum beta 2-microglobulin (beta 2-M) was measured in two prospectively evaluated groups of homosexual men in 1983 and 1985. Serum beta 2-M was raised in 64% of patients with HIV infection, but in only 6.7% of uninfected homosexuals. Depression of the total lymphocyte count was only clinically useful when it reached less than 1.0 X 10(9)/l. In further studies all patients with AIDS and AIDS-related complex (ARC) had raised levels of serum beta 2-M. Mean levels of beta 2-M did not differ between patients with persistent generalized lymphadenopathy (PGL) and asymptomatic HIV-infected patients. Raised serum levels of beta 2-M accompanied major immune dysfunction in HIV infection. Serum beta 2-M levels of greater than 3.0 mg/l in HIV-infected homosexual men were associated with progression to AIDS.

Acquired Immunodeficiency Syndrome↗

The role of a questionnaire and four biochemical markers to detect cancer risk in a symptomatic population.

The roles of a self-completed symptom questionnaire and four biochemical markers of disease were assessed to determine risk for gastric and colorectal cancer from within a hospital population and a random population. Eight-six patients with cancer, 168 subjects with benign conditions of the stomach and large bowel and 720 individuals from the community at large were investigated. Multivariate analyses of the questionnaire and biochemical data were performed individually and in combination using a data set comprising 54 cancer subjects, 80 patients with benign disease and 200 random individuals. The most favourable predictive equation derived was then applied to the remaining data set to determine its efficacy. In the primary analyses the questionnaire data identified 32 (60%) cancers successfully and using the biochemical markers alone 36 (67%) patients were also correctly classified as cancer bearing. However, the combination of the questionnaire and marker data improved the sensitivity for cancer to 50 cancers detected (92%) (P less than 0.02). Using the predictive equation from this combination of data to identify risk in the second data set 28/32 (88%) cancers were correctly identified with only an 11% false positive rate. An 18 month follow-up for the non-cancer group has to date revealed only one cancer (ca. pancreas). In this limited study, multivariate analysis of questionnaire and biochemical marker data does successfully identify individuals at "high risk' of harbouring gastric or colorectal cancer within a symptomatic population and may have a role in determining priority for investigation for a symptomatic individual.

Aged↗

Biochemical monitoring of carcinoma of prostate treated with an LH-RH analogue (Zoladex).

The levels of prostatic specific antigen (PSA) and prostatic acid phosphatase (PAP), both measured by radioimmunoassay, and two cancer indices given by the ratio of serum alpha-1 acid glycoprotein to prealbumin (AGP:Palb) and alpha-1 acid glycoprotein to alpha-2 HS globulin (AGP:HS) were evaluated as markers to assess the response of prostatic cancer to treatment with Zoladex, an LH-RH agonist. A rise in PSA and PAP occurred in 8/65 patients (12%) during the initial induction phase. In metastatic disease prior to treatment none of these indices was significantly different between patients who attained a sustained response and those whose response was nil or only transient. Responders and non-responders could, however, be distinguished by the levels of various analytes after treatment. At 6 months the median PSA in those who responded was 2.5 ng/ml compared with 51.5 ng/ml in the non-responders. At 12 months the figures were 3.0 and 155 ng/ml respectively. The corresponding median PAP levels were 1.4 and 19 ng/ml at 6 months and 1.3 and 18 ng/ml at 12 months. The AGP:Palb ratio was also significantly different in these two groups at 6 and 12 months. PSA appears to be the most sensitive indicator of the response to treatment. The likelihood of obtaining a prolonged clinical response can be assessed within 6 months of the start of treatment.

Acid Phosphatase↗

Isoelectric points of urinary light chains in myelomatosis: analysis in relation to nephrotoxicity.

Measurements of the isoelectric point (pI), sialic acid content, and polymerisation were made of 43 light chains isolated from the urine of patients with myelomatosis excreting large amounts of light chains. The pIs ranged from 3.5-9.5, and 23 were greater than 7.0. Sialylation was detected in 62% of light chains, and 69% showed microheterogeneity of charge. There was no clear association between the pI, sialylation, or polymerisation and the presence of renal failure, as assessed by serum creatinine concentrations. Light chains with pI spectrotype in the basic range, however, were found to produce more proximal tubular dysfunction than acidic light chains.

Acute Kidney Injury↗