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Biomedical subjects

R Fifield

Publications and source records attributed to R Fifield.

At least 37 records · Page 2Linked to original sources

Overestimation of immunoglobulins in the presence of rheumatoid factor by kinetic immunonephelometry and rapid immunoturbidimetry.

The United Kingdom External Quality Assessment Scheme for Specific Proteins has demonstrated that one method group, comprised of kinetic immunonephelometric assays, gives significantly higher results for immunoglobulins in certain pathological sera containing rheumatoid factor. Using IgM as a model, we have compared kinetic immunonephelometry and a rapid (5 min incubation) immunoturbidimetric assay with radial immunodiffusion (RID) on seven sera. Compared with RID significantly higher results were obtained by kinetic nephelometry on all five sera positive for rheumatoid factor, and by turbidimetry on three of the four of these studied. In a serum with IgM increased due to primary biliary cirrhosis lower results (P0.005) were obtained by nephelometry than by RID. The remaining serum was normal, and no significant intermethod differences were found. The possible causes for these discrepancies are discussed.

Humans↗

Use of immunoglobulin heavy- and light-chain measurements compared with existing techniques as a means of typing monoclonal immunoglobulins.

Using automated measurements of kappa and lambda light chains and IgG, IgA, and IgM, we assessed the utility of the kappa/lambda ratio and the heavy chain/light chain ratio in characterizing monoclonal immunoglobulins previously identified by sensitive electrophoresis on agarose gel and typed by immunofixation or immunoelectrophoresis. We examined 348 selected samples, of which 165 contained monoclonal components, finding that 93.4% were detected and 89% correctly typed by this approach. Eight samples were shown to contain monoclonal light chains that were not visible as bands on electrophoresis but demonstrated abnormalities of the kappa/lambda or heavy chain/light chain ratio.

Antibodies, Monoclonal↗

The plasma protein binding of metoclopramide in health and renal disease.

The plasma protein binding of metoclopramide was measured after addition of the drug (60 ng ml-1) to plasma from 18 patients with renal disease and 18 age and sex matched healthy individuals. The mean free fraction in renal disease (0.59 range 0.41-0.71) was not significantly different from controls (mean 0.6 range 0.56-0.69). In both groups the binding ratio of metoclopramide was significantly related to plasma alpha 1-acid glycoprotein (AAG) concentration but not to albumin or plasma non-esterified fatty acids concentration. Metoclopramide bound to human serum albumin (HSA) to a limited extent and to human AAG to a greater extent indicating that AAG is the major binding protein for the drug in plasma.

Blood Proteins↗

Cerebrospinal fluid C9 in demyelinating disease.

We measured CSF and plasma concentrations of C9, IgG, and albumin in 91 patients with demyelination and 73 controls with other neurologic diseases. The C9 index was reduced and IgG index increased in patients with multiple sclerosis and those with isolated demyelinating lesions, irrespective of disease activity; abnormalities were less marked in patients with isolated lesions than in those with MS. Humoral mechanisms may not be responsible for initiating demyelination, but activation of the complement system could amplify tissue damage and account for some symptomatic recovery.

Complement C9↗

Controlled trial of supplemented oral nutrition in Crohn's disease.

28 malnourished patients with Crohn's disease completed a controlled cross-over study to examine the effect of a low-residue liquid supplement on nutrition and disease activity. Patients spent two months on an ordinary diet (control period) and for two months took the nutritional supplement in addition (treatment period): the order of treatment and control periods was randomised. All anthropometric measurements, serum proteins, creatinine height index, and circulating T lymphocyte numbers increased significantly in the treatment period, while serum orosomucoid levels dropped significantly, suggesting that disease activity was reduced. The benefits were apparently due to the higher calorie intake with the enteral supplement. The results show that enteral supplementation can be managed successfully at home and may produce improvements in nutrition and disease activity.

Blood Proteins↗

Biochemical aids to the staging of breast cancer.

Up to fifteen plasma proteins were measured before treatment in 249 women presenting with lumps in the breast. Concentrations showed considerable overlap between the various clinical stages, and were often normal even in metastatic disease. A discriminant function is proposed, based on measurement of C-reactive protein, beta 2-microglobulin, carcinoembryonic antigen and ferritin and calculation of a score for each subject. High-risk scores resulted for all 18 patients with Stage 4 (i.e., metastatic) disease, and the number of Stage 1 patients attaining high scores was consistent with the reported incidence of development of metastases in such a group. Follow-up studies are in progress.

Blood Proteins↗

The investigation and treatment of germ cell tumours of the testis.

Fifty-five per cent of patients presenting with testicular tumours in 1973--78 had teratomata. A history of undescended testis was only found in patients with seminoma. The right testis was the more frequent site of the primary. Radiation doses of 3400 cGy (rad) in 20 fractions for seminoma and 4500 cGy in 25 fractions for teratoma were well tolerated and sterilised microscopic disease in the majority of patients. Forty-two of 44 seminoma patients are alive and free from disease at a median follow-up of three years. Only 15 of 22 Stage I teratoma patients remain disease free, however. A combination of vinblastine and bleomycin produced 12 complete remissions in 30 patients with metastatic teratoma. Survival was significantly longer for patients achieving complete remission. Although six of the complete responders remain alive, only three are in their initial complete remission. Alpha-foeto-protein and/or beta-subunit human chorionic gonadotrophin levels were elevated in almost all cases of advanced teratoma. The biological half-life of alpha-foeto-protein in the serum is less than six days. The value of these markers in predicting relapse was limited in this series. The doubling of complete response rate in metastatic teratomata that can be achieved by adding cis-platinum to the vinblastine/bleomycin combination, together with the propensity for extranodal metastasis shown by testicular teratomata, suggest that adjuvant chemotherapy should be explored in early disease.

Adult↗

Standardization of immunochemical determinations of serum albumin.

When we compared four commercially available preparations of human serum albumin with the human serum standard IFCC 74/1 by radial immunodiffusion, by immunoprecipitation turbidimetry, by laser nephelometry, and by "rocket" immunoelectrophoresis, three of the preparations gave almost "theoretical" results with the immunoprecipitation turbidimetric method. Results by the other three methods tended inconsistently to be low. Four pools of normal human serum were also analyzed for albumin by these four immunochemical methods, again with IFCC 74/1 as the reference standard. The results were virtually identical with those obtained by fractionation with 1.8 mol/L sodium sulfate and determination of protein nitrogen in the filtrate. We suggest that a combination of (a) fractionation of a pool of normal human serum in this way and (b) critical comparison with selected commercial preparations of human serum albumin will permit standardization of the serum albumin determination.

Humans↗

Clinical evaluation of a single antibody RIA assay for alpha-fetoprotein.

Open neural tube defects have been associated with elevated levels of alpha-fetoprotein in maternal serum and amniotic fluid. In the present study, specimens were collected during 14 to 20 weeks of gestation in five laboratories. Dates were confirmed by ultrasound. Among 1,049 subjects included in total serum alpha-fetoprotein determinations, 25 infants were born with neural tube defects, one patient had intrauterine fetal demise, and 1,023 delivered normal infants. The false-negative rate for serum alpha-fetoprotein was 0.38%, and the false-positive rate was 0.29%. For the total 1,211 amniotic fluid specimens, 23 infants were born with neural tube defects. The false-negative rate for amniotic fluid alpha-fetoprotein was 0.25%. All were closed lesions. There were no false-positive values. This study reaffirms the value of screening for neural tube defects by means of serum alpha-fetoprotein RIA. It also negates the argument that serum screening would promote excessive amniocentesis.

Amniotic Fluid↗

Atopic disease and dermatitis herpetiformis.

Patients with dermatitis herpetiformis were found to have an increased incidence of atopic disorders compared to an age and sex matched control group. The increase in incidence was statistically significant for atopic eczema and any atopic disorder. Serum immunoglobulins (including IgE) were estimated in forty-five dermatitis herpetiformis patients and no significant abnormalities were found.

Adolescent↗

Acute asthma compared with exacerbations of chronic bronchitis: changes in complement.

Complement levels were measured on admission and at 1 and 7 days following admission in twenty patients with acute severe asthma and ten patients with an acute exacerbation of chronic bronchitis. Although no evidence of hypocomplementaemia was found in any patient, there was a mean fall within the normal range of the individual complement components, C4, C3 and factor B in both groups. The mean fall occurred earlier in the bronchitics than in the asthmatics and this may be related to infection or the administration of corticosteroids. There was a significant fall in C3 (P greater than 0.05) in the bronchitics compared with the asthmatics at 24 hr. From our study, however, we could find no evidence of excessive utilization of complement in acute asthma.

Acute Disease↗

Lack of immunoglobulin E response to longstanding strongyloidiasis.

Patients harbouring worm infections usually have very marked elevations of serum immunoglobulin E (IgE) concentration. However, in a group of twenty ex-Far East prisoners of war with strongyloidiasis only two (10%) had raised levels due to the worm, and these were only moderately elevated. This poor IgE response may be related to the very longstanding nature of the infection (at least 30 years). The patients may have a form of immunological incompetence, or may have become immunologically tolerant to the parasite.

Chronic Disease↗

Method-specific variations in the calibration of a new immunoglobulin standard suitable for use in nephelometric techniques.

The putative International Federation of Clinical Chemistry immunoglobulin standard, IFCC 74/1, was calibrated against the World Health Organization (WHO) immunoglobulin standard 67/99 by three different methods: automated immunoprecipitation, Laurell rocket immunoelectrophoresis, and radial immunodiffusion. The same antisera were used in all the assays, which were performed in five expert laboratories. With the aid of linearizing transformations for the dilution curves of both materials and use of a carefully weighted statistical evaluation, values in International Units for IgG, IgA, and IgM were ascribed to IFCC 74/1. The values achieved by the three different methods were not statistically different, except in the case of IgA. IgM assays by automated immunoprecipitation were excluded owing to a high degree of imprecision.

Evaluation Studies as Topic↗

Serum beta2-microglobulin in controls and cancer patients.

Serum beta2-microglobulin levels have been measured in 210 cancer and control patients to assess the significance of this investigation in cancer patients. Subjects studied included patients with breast and gastrointestinal cancer, corresponding control patients in both categories, and healthy volunteers. The composition of these groups allowed an assessment of the relative importance of changes related to cancer, benign disease, age and sex. A significant rise in serum beta2-microglobulin levels with advancing age was demonstrated in the control subjects. Mean levels were also consistently higher in females than in males in each patient group. After statistical correction for these age and sex effects, mean values remained significantly higher in each of the various cancer groups than in their controls. Patients with more advanced breast cancer had higher levels than those with 'early' disease, as did patients with stomach cancer compared to those with colo-rectal cancer. One possible interpretation is that levels increase with increasing tumour bulk, and therefore the estimation of serum beta2-microglobulin may be useful as one of a battery of tests in the management of cancer patients.

Adult↗

Decomposition of supplementary vitamin C in diets compounded for laboratory animals.

Processing may result in losses approaching 20% of the added vitamin C. The extent of these losses depends upon the process and is apparently related to temperature and moisture. Storage losses are also related to processing conditions, and no more than 50% of the vitamin C present in the diet immediately after 6 weeks. These results indicate that the current practice of including 1000 mg/kg of vitamin C in pelleted guinea-pig diets should be satisfactory, provided such diets are used within 6 weeks of manufacture and are stored during this period in conditions conducive to stability, that is dry, not exposed to direct sunlight and, preferably, with an even cool temperature.

Animal Feed↗

Immunoglobulin E in rectal mucosa of patients with proctitis.

Rectal-biopsy specimens were obtained from a group of patients with proctitis in different stages of activity. Large numbers of brightly fluorescent IgE-producing cells were demonstrated in rectal-biopsy specimens taken from these patients during disease activity and clinical remission. An immediate hypersensitivity reaction is suggested as one of the mechanisms involved in the pathogenesis of proctitis.

Biopsy↗