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Biomedical subjects

G Mashiter

Publications and source records attributed to G Mashiter.

9 recordsLinked to original sources

Thyroid hormone concentrations in Nepal: a study of potential Gurkha army recruits. The effect of changes in diet.

A group of non goitrous, potential Gurkha army recruits were tested in Nepal for serum free triiodothyronine (fT3), free thyroxine (fT4) and thyrotropin (TSH) concentrations. Twenty-five percent of the men were recruited into the army and urine samples taken for analysis of iodine and creatinine. Twenty per cent of the recruits underwent thyrotropin releasing hormone (TRH) stimulation tests. After ten months basic training on a diet considered to be iodine sufficient, the tests were repeated on the same men. The results were also compared to army recruits in the UK. All the potential Gurkha recruits had higher serum levels of thyroid hormones than the UK recruits. Some regional differences were found with those men from the Western recruiting depot having lower fT4 and higher TSH concentrations. Urinary iodine and creatinine concentrations showed evidence of slight relative malnutrition and iodine deficiency which was more pronounced in the Western depot. TRH stimulation tests showed no evidence of thyroid dysfunction but highlighted the differences between the Eastern and Western groups. After ten months on an iodine sufficient diet the serum thyroid hormone concentrations became closer to those of the UK recruits, showing any differences to be reversible. The results from the two Gurkha groups became similar which was reflected in the urine analysis results.

Adolescent

Serum concentrations of alkaline phosphatase isoenzymes and osteocalcin in normal pregnancy.

We measured serum alkaline phosphatase isoenzymes and osteocalcin levels in 40 healthy women at 4-week intervals throughout uncomplicated pregnancies and 6 weeks after delivery in 17 women. Serum bone alkaline phosphatase was significantly higher in the third trimester than in early pregnancy (P less than 0.001), and this elevation was still apparent at the end of the puerperium, suggesting increased bone turnover. Serum osteocalcin was not detected (less than 0.2 micrograms/L) after the first trimester in the majority of women, and it reappeared within 48 h after delivery. The disappearance of osteocalcin after the first trimester and its rapid reappearance after delivery suggest placental clearance of this peptide. We conclude that serum osteocalcin measurements cannot be used as a marker of bone metabolism during pregnancy.

Adult

51Cr-EDTA/99Tcm-MDP ratio: a simple non-invasive method for assessing renal osteodystrophy.

We have used 99Tcm-MDP to develop a measure of overall skeletal activity for use in renal disease. The method utilizes the relative clearances of 99Tcm-MDP and 51Cr-EDTA from the blood after simultaneous injection. This is expressed as a ratio and the upper limit in normals is 1.4. This ratio has been evaluated in 42 patients with chronic renal failure and compared with appearances of left-hand radiographs. The ratio was elevated in these patients and the level corresponded to the degree of severity of the subperiosteal resorption. Similarly, there was a close correlation between the ratio values and the serum alkaline phosphatase measurements and parathyroid hormone values. Thirty-three patients had sequential studies performed at intervals of up to 2 years. Twenty-one patients showed no change on clinical, biochemical or bone scan evaluation. Of these, only one patient showed a change in ratio value of greater than 20%. Twelve patients showed evidence of change based either on clinical, biochemical or bone scan alteration and all 12 patients showed changes in ratio values greater than 20%. The 51Cr-EDTA/99Tcm-MDP ratio appears to offer not only a single plasma sample method for the detection and evaluation of renal bone disease, but our results also suggest that it may be valuable in the follow-up of these patients.

Chromium Radioisotopes

Osteocalcin: a potential marker of metastatic bone disease and response to treatment.

Serum osteocalcin (BGP) is an osteoblast product that probably reflects the rate of bone formation. It is a potential marker of skeletal metastases and, to investigate this, BGP was measured by radioimmunoassay in the serum of normal subjects and patients with breast or prostate cancer. Significantly higher levels were found in patients with metastatic bone disease in comparison to both normal subjects (P less than 0.001) and patients with non-metastatic cancer (P less than 0.05 for breast cancer and less than 0.001 for prostate cancer). The range of values was wide. Levels were higher in sclerotic than lytic bone metastases (P less than 0.01) and lower in patients with hypercalcaemia (P less than 0.001). Serial measurements of BGP were made in 53 patients with skeletal metastases from breast cancer receiving systemic therapy. At 1 month BGP rose by greater than 0.5 ng/ml in 15/16 responding patients compared with 7/23 patients with progressive disease (P less than 0.01). Responding patients also showed a rise in the bone isoenzyme of alkaline phosphatase and a paradoxical deterioration in the bone scan appearance, both reflecting a flare in osteoblast activity. The early increase in responding patients was followed by a gradual decrease over subsequent months as the osteoblast reaction induced by systemic therapy subsided. We conclude that BGP measurements reflect a wide variability of bone formation rates in metastatic bone disease. Bone formation was usually increased, particularly when metastases were sclerotic in appearance, but in patients with hypercalcaemia the low BGP levels suggest uncoupling of bone resorption and formation. Serial measurements of BGP may be useful in monitoring response to treatment.

Biomarkers, Tumor

Biochemical prediction of response of bone metastases to treatment.

Assessment of response of skeletal metastases to systemic therapy is currently dependent on radiological evidence of bone healing. We have performed a prospective study of additional response criteria in patients with progressive bone metastases from breast cancer. Changes in these potential markers of response were correlated with the radiological response and the time to treatment failure (TTF). Successful systemic therapy typically led to a transient increase in osteoblast activity ('flare'), a reduction in osteoclast activity and symptomatic improvement. After 1 month a greater than 10% rise in serum osteocalcin (BGP) and alkaline phosphatase bone isoenzyme (ALP-BI) and a greater than 10% fall in urinary calcium excretion were seen in 14/16 patients with radiographic evidence of bone healing (UICC partial responders). In comparison similar biochemical changes at 1 month were seen in only 4/20 patients with progressive disease (P less than 0.001). The predictive value and diagnostic efficiency (DE) of changes at 1 month in biochemical measurements and symptom score has been calculated. The combination of a greater than 10% rise in ALPBI and BGP and a greater than 10% fall in urinary calcium excretion had a DE of 89% for discriminating response from progression, 88% for response from non-response (progressing + no change patients), and 76% for TTF of greater than 6 months from TTF of less than 6 months. Serum calcium, tartrate resistant acid phosphatase (TRP), urinary hydroxyproline excretion and bone scan changes were unhelpful in discriminating between patient groups. Independent confirmation is needed, but our results suggest there are reliable alternatives to plain radiography in the early assessment of response of bone metastases to treatment.

Adult

Bone scan flare predicts successful systemic therapy for bone metastases.

Changes in osteoblast function, assessed by serial bone scans and serum alkaline phosphatase bone isoenzyme (ALP-Bl) and osteocalcin, have been studied in 53 patients receiving systemic therapy for bone metastases from advanced breast cancer. In 12/16 patients with healing of lytic disease on x-ray a paradoxical deterioration in the bone scan appearances after 3 mo treatment was seen. This was characterized by increased activity in baseline lesions and the appearance of new foci of tracer uptake; changes which are indistinguishable from progressive disease. After 6 mo successful treatment the bone scan improved with reduced tracer uptake and no new lesions since the 3-mo scan. New lesions appearing after 6 mo indicated progressive disease. These changes are attributed to a flare in osteoblast activity induced by successful systemic therapy and confirmed by a transient rise in osteocalcin and ALP-Bl. After 1 mo of treatment 15/16 responders showed a rise in both parameters compared with only 5/23 nonresponders (p = less than 0.001). The flare response is the rule rather than the exception after successful systemic therapy for bone metastases. The appearance of new lesions or increasing activity in known lesions during the first 3 mo is as likely to herald radiological response as disease progression.

Adult

Serum triiodothyronine: clinical experience with a new radioimmunoassay kit.

A new kit for measuring total serum triiodothyronine (T3) by radioimmunoassay ('T3 RIA'; Radiochemical Centre, Amersham) was evaluated using sera from 1114 patients and normal controls. The kit performed reliably with intraassay and interassay variability figures of 3.9% and 9.3%, respectively, at 'medium' concentrations of T3. A T3 measurement could be obtained conveniently within 18 h after overnight incubation at room temperature. There were no critical steps dependent on time or temperature. Serum T3 values showed no significant sex difference. There was no significant change in mean serum T3 between the ages of 15 and 69 years, but it fell by 0.15 nmol/l for every 5 years beyond the age of 70. Mean serum T3 (+/-SD) for 335 normal euthyroid subjects ages 15-69 years was 2.11+/-0.46 nmol/l (range: mean+/-2 SD = 1.19-3.03 nmol/l). 64% of pregnant euthyroid women and 12% of those taking oral contraceptives had elevated serum T3 levels, as did all hyperthyroid patients, apart from one with T4 toxicosis. Overlapping T3 values from hyperthyroid patients and euthyroid subjects with elevated concentrations of thyroid binding proteins could be separated completely by two correction techniques which related total serum T3 to the corresponding T3 resin uptake test, viz an 'augmented free T3 index', or a map plot of T3 vs T3 resin uptake. A 25% incidence of T3 toxicosis was observed. One hyperthyroid patient with T4 toxicosis, and seven euthyroid patients with 'biochemical T4 toxicosis' were investigated. 73% of moderately and 30% of severely hypothyroid patients had normal serum T3 levels. This overlap was not reduced by applying correction techniques. Our studies demonstrate the value of serum T3 measurements in screening for and diagnosing hyperthyroidism. As T3 measurements become more widely available, it would seem reasonable to subclassify hyperthyroid patients into three types: those with 'T3/4 toxicosis', 'T3 toxicosis' and 'T4 toxicosis'.

Adolescent

A rational approach to "in vitro" thyroid function testing.

A system of "in vitro" thyroid function testing is proposed whereby laboratory staff select the most appropriate screening test depending on the information supplied by the clinician. Total serum triiodothyronine (T3) or thyroxine (T4) are used for screening as appropriate. In borderline cases, secondary tests are performed automatically according to a flow chart. This system improves efficiency and is cost effective, saving approximately 1,800 pounds annually in a laboratory handling about 5,000 requests for thyroid function tests each year.

Aged