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Biomedical subjects

M A Forbes

Publications and source records attributed to M A Forbes.

At least 37 records · Page 2Linked to original sources

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↗

An evaluation of mucin-like carcinoma associated antigen (MCA) in breast cancer.

Serum levels of mucin-like carcinoma associated antigen (MCA) were measured in 80 healthy women, 109 patients with breast cancer at presentation and in samples taken from 45 patients with active metastatic breast cancer. The MCA levels in controls had an upper limit of normal of 19.6 U ml-1 in post-menopausal and 16.4 U ml-1 in premenopausal women. The levels at presentation in stages I and II and III were not significantly different from the post-menopausal controls. Longitudinal studies over 5-9 years in 20 patients with stage I and II disease who had remained tumour-free showed a narrow MCA range for each individual patient, but the mean and range of a single measurement in a further 63 of these patients were similar to those of the normal controls. Rising MCA levels occurred in 12/14 patients who developed metastases in 2-8 years after surgery, but local recurrence was not associated with a rise of MCA. Eighty per cent of patients with active metastatic disease had MCA levels greater than 15 U ml-1. MCA levels fell during clinical responses to therapy in metastatic cancer. In the context of follow-up serum MCA levels appear to be a sensitive indicator of metastatic disease; caution is required in the interpretation of isolated measurements.

Antigens, Neoplasm↗

A method to detect the in vitro modification of serum beta-2-microglobulin in health and disease.

The electrophoretically fast moving form of beta-2-microglobulin (alpha-B2m) was shown by crossed immunoelectrophoresis to be produced in vitro after incubation at room temperature and was not present in freshly drawn sera. A radioisotopic assay was developed to measure this conversion to alpha-B2m in sera from 14 healthy individuals and from 208 patients with benign and malignant disease. The activity was present in all the sera tested and the levels were significantly higher in sera from patients with small cell lung cancer, prostate cancer and in childhood lymphomas when compared to the level in normal sera.

Carcinoma, Small Cell↗

Tubular dysfunction and microalbuminuria in insulin dependent diabetes.

The nature of microproteinuria in the early years of insulin-dependent diabetes was investigated in a cross sectional study of 80 children with insulin-dependent diabetes and 40 normal children. Urinary excretion of three low molecular weight proteins: alpha-1-microglobulin, beta-2-microglobulin and kappa light chains was used as an index of proximal renal tubular function. The first urine samples of the morning were collected and excretion of proteins measured was expressed as ratio of protein to creatinine. There was a strong correlation between excretion of alpha-1-microglobulin and chi light chains and their excretion was significantly higher in diabetic children indicating decreased proximal tubular reabsorbtion. The excretion of beta-2-microglobulin was found to be an unsatisfactory index of proximal tubular function. Urinary albumin excretion was not significantly raised in diabetic children and did not correlate with urinary alpha-1-microglobulin or chi light chain excretion. Glycaemic control might influence proximal tubular function as both urinary glucose concentration and glycosylated haemoglobin showed correlations with urinary alpha-1-microglobulin excretion and with urinary chi light chain excretion.

Adolescent↗

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↗

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↗

Serum beta 2-microglobulin and C reactive protein concentrations in viral infections.

Serum beta 2-microglobulin concentrations were assayed in a number of virus diseases. Infectious mononucleosis, cytomegalovirus, and influenza A were associated with pronounced increases in serum beta 2-microglobulin concentration. Smaller increases, with values generally less than 4 mg/l, were noted in other viral infections. Apart from in acute influenza A, the C reactive protein and beta 2-microglobulin responses were not associated.

Adolescent↗

Proximal renal tubular function in myelomatosis: observations in the fourth Medical Research Council trial.

Proximal renal tubular function was studied in 522 consecutive patients entered into the Medical Research Council's fourth myelomatosis trial. Assessment was made at presentation after a 48 h period of hydration but before administration of chemotherapy. The most common abnormalities in the urine other than light chain proteinuria were raised concentrations of the low molecular weight proteins alpha 1-microglobulin and alpha 1-acid glycoprotein. These were usually accompanied by increases in urinary beta-N-acetyl-D-glucosaminidase concentrations. The concentration of these substances in the urine directly correlated with urinary free light chain output. This tubular proteinuria was seen whether or not patients had impaired glomerular function, as assessed by a rise in serum creatinine concentration. Urinary concentrations of retinol binding protein, however, were generally increased only when serum creatinine concentrations were raised. This applied even when there were high concentrations of light chains, alpha 1-microglobulin, alpha 1-acid glycoprotein, and beta-N-acetyl-D-glucosaminidase in the urine. There is therefore a selective tubular proteinuria in myelomatosis which is seen in almost all patients with urinary light chain values greater than 1 u/l. This proteinuria is generally reversible, when light chains no longer appear in the urine. Patients whose serum creatinine was greater than 200 mumol/l, however, had increased urinary output of retinol binding protein in addition to increased excretion of alpha 1-microglobulin, alpha 1-acid glycoprotein, and beta-N-acetyl-D-glucosaminidase. Tubular proteinuria in many of these patients presenting in renal failure persisted even when light chain output was reduced after chemotherapy.

Acetylglucosaminidase↗

Plasma beta-2-microglobulin and fibronectin levels in beta-thalassaemia.

The plasma beta 2-microglobulin (beta 2-MG) levels in 118 children with thalassaemia were investigated. The mean level was higher than in healthy children. A significant increase of beta 2-MG was associated with hypersplenism (3.14 +/- 0.6 mg/l). The beta 2-MG levels appeared to reflect reticuloendothelial system activity but were not related to iron overload. Fibronectin levels were generally lower than in healthy adults; profound chronic fibronectin depletion was not accompanied by an increased liability to infection.

Adolescent↗

Alpha-1-microglobulin: an indicator protein for renal tubular function.

A comparison of urinary alpha 1-microglobulin concentrations to the behaviour of other indicators of renal tubular disorders, beta 2-microglobulin, retinol-binding protein and N-acetyl-beta-D-glucosaminidase (NAG) has been made. In acute tubular disorders the concentrations of urinary beta 2M and RBP are highly correlated (r = 0.89) but this is less marked for alpha 1M and beta 2M (r = 0.55) and alpha 1M and RBP r = 0.48. NAG tends to run a parallel course to alpha 1M concentrations but lags behind the recovery of low molecular weight protein reabsorption following injury of the tubular cells. The concentrations of alpha 1M, and in particular its stability at low pH suggest that this protein may be useful in screening for tubular abnormalities and detecting chronic asymptomatic renal tubular dysfunction. Urinary alpha 1M greater than 15 mg/g creatinine is strongly suspicious of a proximal tubular dysfunction. The distinction between pure tubular proteinuria and mixed glomerular and tubular proteinuria requires further analysis.

Adult↗

Serum beta-2-microglobulin in disorders of myeloid proliferation.

Serum beta-2-microglobulin (beta 2-m) was measured on 182 samples from 98 patients with diseases characterized by proliferation of predominantly non-lymphoid marrow elements. Raised levels were found in myeloproliferative disorders, chronic granulocytic leukaemia, acute myeloid leukaemia and in many patients with myelodysplastic syndromes. The most striking elevation was seen in acute and chronic myelomonocytic leukaemia. These raised serum levels are probably derived from increased cell turnover, and it is suggested that cells of monocyte-macrophage series are particularly high producers of beta 2-m.

Anemia, Aplastic↗