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Biomedical subjects

M C Browning

Publications and source records attributed to M C Browning.

At least 37 records · Page 2Linked to original sources
PubMed1989

Biologic variation of urinary albumin: consequences for analysis, specimen collection, interpretation of results, and screening programs.

Studies on the analytic and biologic variability of albumin concentration, albumin/creatinine ratio, and albumin excretion rate in first morning, random, and 24-hour urine specimens from healthy subjects suggest that (1) first morning specimens are preferred, (2) results should be expressed as albumin concentration, (3) assay of creatinine confers little advantage, (4) an analytical precision of coefficient of variation (CV) less than 18% is satisfactory, and (5) semiquantitative or qualitative analyses are suitable for screening programs. The intraindividual variation of albumin concentration in first morning specimens from diabetics is such that no threshold value gives the desired 100% nosological sensitivity. However, a threshold value of 30 mg/L confers 100% specificity, and a single abnormal result therefore requires initiation of therapy. Patients with negative results should continue to be monitored regularly.

Adolescent↗
PubMed1989

Clinical utility of assays of glycosylated haemoglobin and serum fructosamine compared: use of data on biological variation.

Assessment of the relative clinical usefulness of glycosylated haemoglobin (HbA1) and serum fructosamine is complicated by their markedly different half-lives. They have therefore been compared using a number of indices derived from data on biological variation, as applied in a study of blood glucose control in newly diagnosed diabetic patients. The within-subject (CVI) and between-subject (CVG) variation of fructosamine and HbA1 were assessed in 8 stable diabetic patients. A slightly smaller relative change, or critical difference, is required between serial HbA1 results than between fructosamine results before a significant change can be said to have occurred. The heterogeneity of within-subject variance is also less for HbA1, rendering the critical difference more generally applicable. HbA1 may therefore be more appropriate for long-term monitoring. Monitoring of blood glucose control of a group of 26 newly diagnosed diabetic patients before the commencement of therapy and 1, 2, and 3 months later by serum fructosamine or HbA1 provided very similar information. Fructosamine responds more rapidly with changes of blood glucose control. However, whether this confers any clinical advantage will depend upon the frequency of testing.

Aged↗
PubMed1989

Analytical goals for quantities used to assess thyrometabolic status.

Analytical goals for imprecision derived from data on intra-individual variation for total T4, free T4, total T3, free T3 and thyrotropin (TSH) are coefficients of variation (CV) less than or equal to 2.5, 4.7, 5.2, 3.9 and 8.1%, respectively. If total T4 is used to monitor replacement therapy with thyroxine, a more stringent goal of CV less than or equal to 1.4% is appropriate. For those analytes for which biological variation data are not available, analytical goals may be derived either from reference intervals or from the 'state of the art' as judged from the performance of a stated proportion of laboratories participating in an interlaboratory quality assessment scheme. Analytical goals for imprecision for reverse T3 and thyroxine-binding globulin derived from reference values are CV less than or equal to 10.7 and 7.2%, respectively. The goal for inaccuracy is that there should be none. Statements regarding the detection limit of an assay should be replaced with information about the range of concentrations over which specified goals for imprecision are met. If goals are not achieved at concentrations which are used for clinical decision making the 95% confidence limits of the extreme values of the 'working range' should be calculated using the relevant imprecision. Improved analytical performance will result in better between-laboratory comparability and eventually allow the use of universally applicable reference values.

Humans↗
PubMed1988

Intra-individual variation of thyroxin, triiodothyronine, and thyrotropin in treated hypothyroid patients: implications for monitoring replacement therapy.

We measured total thyroxin (TT4), free thyroxin (FT4), total triiodothyronine (TT3), free triiodothyronine (FT3), and thyrotropin (TSH) in serum sampled before and 1, 2, 4, 6, and 8 h after administration of prescribed doses of thyroxin to 12 patients with proven primary hypothyroidism. At 2, 4, and 6 h post-dose, the mean values for TT4 and FT4 and also that at 8 h for FT4 significantly (P less than 0.05) exceeded the corresponding pre-dose values. No significant changes were found for TT3, FT3, or TSH. The mean intra-individual CVs over the study period were TT4 4.9%, FT4 5.7%, TT3 8.7%, FT3 8.7%, and TSH 20.2%. Individual subjects showed small but predictable changes in TT4 and FT4. Changes in TT3 and FT3 were greater but random. Fluctuations in TSH were greatest, but in all subjects with detectable concentrations the variations were of similar magnitude. We conclude that strict adherence to timing of specimen collection in relation to dosage is probably unnecessary.

Adult↗
PubMed1988

Renal histopathology of the nail-patella syndrome in a two-year-old boy.

A two-year-old child with the clinical stigmata of nail-patella syndrome, congenital urinary tract anomalies and proteinuria underwent renal biopsy. Electron microscopy revealed characteristic electron lucent areas and collagen fibril-like deposits in the glomerular basement membrane. Of special interest, electron dense deposits were seen in subendothelial areas of the capillary loops and immunofluorescent staining was striking, particularly for IgM, in a peripheral capillary loop pattern.

Biopsy↗
PubMed1987

Hormone profiles and psychological symptoms in peri-menopausal women.

Hormone profiles for oestradiol, progesterone, follicle-stimulating hormone, luteinizing hormone, testosterone, androstenedione, prolactin, cortisol, thyroid-stimulating hormone (TSH) and triiodothyronine are presented for 85 peri-menopausal women. All subjects completed the 60-item General Health Questionnaire (GHQ) and 48 were interviewed using a standardized psychiatric interview. Some alterations in endocrine function were detected prior to the cessation of menstrual periods and there were changes in prolactin, cortisol, TSH and triiodothyronine in relation to menopausal status as well as in ovarian steroids and gonadotrophins. In comparison with other subjects, women with menorrhagia had higher circulating levels of oestradiol in the last week of the menstrual cycle and elevated prolactin levels. Women with high scores on the GHQ in the early post-menopausal years had significantly higher circulating levels of oestradiol than other subjects of the same menopausal status. No other significant difference in levels of reproductive hormones between high scorers and low scorers on the GHQ was detected. Women in the late pre-menopausal group who were clinically depressed had significantly higher levels of TSH and triiodothyronine than other subjects. These changes in thyroid function in the late pre-menopausal group may be related to the increase in psychiatric morbidity in the immediately pre-menopausal years reported in previous studies.

Adult↗
PubMed1987

The effective evaluation of thyroid status in patients on phenytoin, carbamazepine or sodium valproate attending an epilepsy clinic.

To assess the most efficient means of monitoring thyroid status in an epilepsy clinic, total thyroxine (T4), free thyroxine stimulating hormone (TSH) were measured in 71 adult patients treated long-term with either phenytoin (DPH), carbamazepine (CBZ) or sodium valproate (VAL). Twenty-seven patients with one or more abnormal thyroid hormone results were further investigated by a thyrotrophin releasing hormone (TRH) test and clinical assessment. T4 was found to be normal in 85% on VAL, 40% on CBZ and 39% on DPH. FT4 was normal in more patients, namely 95% on VAL, 70% on CBZ and 65% on DPH. The TRH tests indicated that FT4 was the most efficient screening test for hypothyroidism in this epileptic population. We estimate that the use of FT4 alone as a screening test would have reduced by 60% the number of TRH tests required.

Adult↗
PubMed1987

A method for simultaneously estimating plasma, erythrocyte, and leukocyte sodium, potassium, and magnesium: reference values and considerations from biological variation data.

We describe a method for measuring plasma, erythrocyte, and leukocyte sodium (Na+), potassium (K+), and magnesium (Mg2+) concentrations in 10-mL blood specimens. After separating cells with Ficoll-Hypaque and washing with isotonic choline chloride, erythrocytes and leukocytes are counted, so that results can be expressed as amount of substance per cell and also to monitor cell integrity and possible contamination. Plasma and cell lysates were analyzed (CV less than or equal to 7.0%) with flame photometry and atomic absorption spectrometry. Reference intervals for an elderly population with values for plasma electrolytes within reference intervals are similar to those for younger healthy subjects. From data on biological variation, reference values for erythrocyte cations are not of much use, and analytical goals for precision are not met, but the results might be useful for monitoring disease progression in individual patients. In contrast, reference values for leukocyte cations are theoretically of use and goals are achieved, but large changes are required before consecutive results can confidently be said to be significantly different.

Aged↗
PubMed1987

Deciding the optimum interval between specimen collections: theory and nomograms.

The time interval between collection of specimens from an individual patient is usually determined empirically. For analytes whose values decline according to first-order kinetics--for example, enzyme activities in serum after an acute myocardial infarction, tumor markers in serum after excision of the tumor, and drugs in serum after an overdose--the minimum time between collections (delta T) depends on the elimination half-life (t) and the analytical precision (CVA), according to the equation: delta T = (1/log2) X t X log (2.33 CVA/100 + 1). Nomograms showing this relationship graphically have been generated.

Antigens, Neoplasm↗
PubMed1987

Selecting the optimum specimen for assessing slight albuminuria, and a strategy for clinical investigation: novel uses of data on biological variation.

To investigate the optimum specimen for quantifying low, but abnormal, concentrations of albumin in urine, we assessed the analytical and biological components of variation in first morning, random untimed, and 24-h urine specimens from 11 apparently healthy individuals. The results were expressed in terms of albumin concentration, albumin/creatinine ratio, and albumin excretion rate. Analytical methods generally can meet the analytical goal of CV less than or equal to 18%. For reasons detailed herein, we prefer measurement of the albumin concentration in the first morning specimen. Expressing results as an albumin/creatinine ratio has little advantage. Albumin concentrations in first morning urines from 16 diabetic subjects showed larger intra-individual variation than for nondiabetic subjects but clearly fell into two groups: those with consistently normal albumin concentrations in urine and those with abnormal concentrations in some specimens. The intrinsic biological variation of the latter group means that the ideal 100% nosological specificity cannot be achieved with any cutoff point without inclusion of a large proportion of the former. Qualitative testing with a latex-agglutination technique also demonstrates this problem. Use of data on biological variation allows development of an appropriate clinical strategy to investigate diabetic patients.

Albuminuria↗
PubMed1987

Assay of serum fructosamine that minimizes standardization and matrix problems: use to assess components of biological variation.

Methodological problems with the assay of fructosamine in serum--standardization, matrix effects, and dependence on buffer pH--have been minimized with a method involving colorimetric assay of each specimen and subsequent re-assay after standard addition of 1-deoxy-1-morpholinofructose. Absorbance at optimum wavelength of 540 nm varies linearly with fructosamine concentration to at least 5.5 mmol/L, and between-run precision is about 6% for both patients' specimens and quality control materials. Correction of fructosamine to serum albumin of 40 g/L minimizes the effect of albumin while maintaining transferability of data and reference values. From data on biological variation, the analytical goal for precision (CV) is less than or equal to 2.6%. The square root of the ratio of intra- to interindividual variance is low, indicating that fructosamine concentrations have a high index of individuality; thus conventional population-based reference values are of limited use. Although this assay may be useful in monitoring disease, we doubt that it provides a valid screening test for diabetes.

Adult↗
PubMed1986

Vesicoureteral reflux, proteinuria and renal failure.

We report 3 cases of proteinuria, progressive renal insufficiency and vesicoureteral reflux with no history of urinary tract infection. Renal histology showed focal segmental glomerulosclerosis. These associations are unusual during childhood but they are common in adults. Generally, vesicoureteral reflux is discovered during radiological evaluation of children with recurrent urinary tract infections. Renal parenchymal damage in children typically results from recurrent infection or progressive hydronephrosis. Development of proteinuria with vesicoureteral reflux usually indicates an irreversible glomerular lesion. Antireflux surgery in patients with vesicoureteral reflux and decreased renal function may be beneficial if performed before the onset of proteinuria. We recommend antireflux surgery for children with persistent vesicoureteral reflux or decreased renal function.

Child↗
PubMed1986

Intra- and interindividual biological variation of five analytes used in assessing thyroid function: implications for necessary standards of performance and the interpretation of results.

Intra- and interindividual components of biological variation have been determined for total thyroxin (TT4), free thyroxin (FT4), total triiodothyronine (TT3), free triiodothyronine (FT3), and thyrotropin (TSH). Calculated analytical goals (CV, %) for the precision required for optimal patient care are: TT4 less than or equal to 2.5, FT4 less than or equal to 4.7, TT3 less than or equal to 5.2, FT3 less than or equal to 3.9, and TSH less than or equal to 8.1. The marked degree of individuality demonstrated for all hormones indicates that, if conventional population-based reference ranges are used uncritically, major changes in hormone concentration may not be correctly identified for some patients because observed values continue to lie within the reference range. At analyte concentrations approximating the mean values found in this study, and for analytical performance meeting the appropriate analytical goal, the differences required for consecutive results to be significantly different (p less than or equal to 0.5) have been calculated as: TT4, 14.7 nmol/L; FT4, 5.7 pmol/L; TT3, 0.6 nmol/L; FT3, 1.3 pmol/L, and TSH, 0.7 milli-int. unit/L.

Adult↗
PubMed1986

Artefactual increase in serum thyrotropin concentration caused by heterophilic antibodies with specificity for IgG of the family Bovidea.

A 19-year-old white woman presented with symptoms compatible with mild hyperthyroidism and biochemical evidence suggestive of autonomous thyrotropin (TSH) secretion. Intensive investigation of the pituitary-thyroid axis suggested that the basal concentrations of TSH were artefactually increased owing to heterophilic antibodies in the patient's serum with a broad specificity for immunoglobulin class G of the family Bovidea. These heterophilic antibodies complexed with the ovine antisera to human thyrotropin that are used in the RIA system, in particular blocking the binding of TSH but also partly blocking interaction with the second antibody. When TSH was measured immunometrically or by an RIA with TSH-specific antisera of rabbit origin, the concentrations measured were within the appropriate reference intervals. The blocking effect can be overcome by including large quantities of non-TSH-specific ovine IgG in assay incubation mixtures. Interference of this type is generally not appreciated and its incidence is poorly characterized, but it may have implications for any method in which antibodies are used as reagents.

Adult↗