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Biomedical subjects

A W Hay

Publications and source records attributed to A W Hay.

At least 37 records · Page 2Linked to original sources

Short term effects of SHD 386L and levonorgestrel on bone and mineral metabolism in the postmenopause: a double-blind randomised placebo-controlled trial.

Forty-five healthy postmenopausal women participated in a study designed to examine the effects on bone and mineral metabolism of SHD 386L, a new hormone replacement therapy (HRT) regime. This oral preparation delivers 2 mg estradiol valerate daily and 75 micrograms of levonorgestrel from days 17-28 inclusive of a 28-day cycle. The study was double-blind, randomized and placebo controlled. Patients who received SHD 386L exhibited significant falls in plasma calcium, ionised calcium, phosphate and total alkaline phosphatase. No alteration, however, was observed in plasma osteocalcin. No significant changes in mineral metabolism were observed in a parallel group receiving levonorgestrel alone. The results indicate that SHD 386L is likely to be protective to the skeleton through inhibition of bone resorption and that such actions are attributable to the estrogen component. The preparation was well tolerated, compliance was satisfactory and serious adverse affects were not seen. The above biochemical evidence for skeletal protection will require to be supplemented by prospective biophysical evidence of the effect of SHD 386L on bone mineral density.

Alkaline Phosphatase↗

Plasma methadone measurements and their role in methadone detoxification programs.

We monitored eight patients who were receiving a decreasing dose of methadone for treatment for opioid addiction (detoxification). Patients with plasma concentrations of methadone less than 0.05 mg/L experienced withdrawal symptoms, relapsed, and re-abused illicit drugs. Four patients took extra methadone (illicitly obtained) during detoxification. None of the eight patients in our study were successfully weaned off methadone: all left the methadone detoxification program before the completion of treatment. Two patients subsequently returned to a fixed methadone program elsewhere, and four relapsed and returned to illicit drug misuse. Plasma measurements may help clinicians assess patients during methadone detoxification.

Adult↗

Methadone concentrations in plasma and their relationship to drug dosage.

We have developed a sensitive HPLC method for measuring methadone in plasma and have used it to establish that there is a linear relationship between plasma concentration and methadone dose over the range of 3-100 mg of methadone per day in a group of 31 addicts. We found a good correlation between dose and plasma concentration (r = 0.89), with the plasma methadone concentration increasing by 0.263 mg/L for every milligram of methadone consumed per kilogram of body weight. Five patients had unexpected high or low concentrations; this finding is discussed.

Chromatography, High Pressure Liquid↗

A rapid horizontal TLC method for detecting drugs of abuse.

We present a rapid, low-cost method for detecting opioids, cocaine and amphetamine in the urine of drug abusers. Rapid solid phase extraction of 2 mL of urine using octadecylsilane cartridges (Bond Elut C18) concentrates compounds of interest (including the polar metabolite of cocaine, benzoylecgonine), in a small volume of methanol, which is easily dried down. Four microlitres of aliquots of samples and standards are spotted on to 5 cm square polyester-backed silica gel plates, and developed (8-10 min) in a Desaga H-Chamber. Rf values of all relevant compounds are presented for two mobile phases using an iodoplatinate spray. The sensitivity of the method is not the same for all drugs but is always at least 1 microgram/mL urine. A number of investigations can be performed on a single extract from 2 mL of urine including confirmatory tests using different solvent systems or sprays.

Amphetamine↗

Screening for drugs of abuse: effect of heat-treating urine for safe handling of samples.

Heating urine samples from high-risk patients for 1 h at 56 degrees C is no longer believed to completely inactivate human immunodeficiency virus (HIV; AIDS virus). To protect staff who are handling infectious samples such as those from drug-addiction units, heating at a higher temperature may be necessary. We report the stability to heat treatment (at 60, 70, and 100 degrees C) at pH 5.1 and 7.6 of some commonly abused drugs, namely, methadone, pethidine, amphetamine, the cocaine metabolite, benzoylecgonine, and the dextropropoxyphene metabolite nordextropropoxyphene. Heat-treating urine at 60 degrees C for 1.5 h or 70 degrees C for 1 h did not significantly affect the measured concentrations of these drugs. However, heat treatment at 100 degrees C for 1 h reduced the recovery of all the drugs. Benzoylecgonine and amphetamine were most susceptible to the different forms of heat treatment.

Acquired Immunodeficiency Syndrome↗

The relationship between theophylline, caffeine and heart rate in neonates.

Plasma theophylline and caffeine levels were measured in neonates receiving aminophylline for apnoea. Significant levels of caffeine were present in neonates with high plasma theophylline levels and particularly in those children who had been on theophylline for 6 days, or more. Caffeine levels in plasma decreased slowly compared to theophylline. Tachycardia did not occur in any infants even at theophylline values greater than 20 mg/L. For theophylline concentrations above 10 mg/L there was no relationship between heart rate and drug level. Heart rate alone cannot be used to predict toxic drug levels, and high drug levels will not necessarily cause tachycardia.

Aminophylline↗

The relations between vitamin D2 and D3 in the diet and plasma 25OHD2 and 25OHD3 in elderly women in Great Britain.

Vitamin D2 and D3 intake and plasma 25OHD2 and 25OHD3 were measured in 70 elderly women; 13 living at home and 57 long-stay patients with no access to sunlight. Vitamin D2 intake and plasma 25OHD2 were correlated in the whole group (p less than .005) and vitamin D3 intake and plasma 25OHD3 and total D intake and total 25OHD were significantly correlated (p less than .005) in the patients. In the whole group the plasma 25OHD2 increased by 4.5 nmol/l for every 1 microgram increase in vitamin D2 intake. This was also the increase observed in a longitudinal study of vitamin D2 supplements in 11 patients. Vitamin D intake is a significant determinant of plasma 25OHD and the relation between them suggests that stores of vitamin D can be maintained at 20 nmol/l in the elderly by a daily intake of 4 micrograms of vitamin D, even in the absence of sunlight.

25-Hydroxyvitamin D 2↗

Tubular damage in patients with hypokalaemia.

Severe hypokalaemia is occasionally associated with gross changes in renal tubular function. We have looked for lesser degrees of renal tubular damage in unselected patients with hypokalemia by measuring the urine excretion of total protein, albumin, the low molecular mass protein beta 2-microglobulin (B2M) and two enzymes, N-acetyl-glucosaminidase (NAG) and alanine aminopeptidase (AAP). The frequency of abnormal values for these tests separately (compared with matched patients without hypokalaemia) was 39-56%. Many patients had an abnormal value for more than one of the tests, but this was at least partly due to chance association rather than to an underlying common mechanism for the several abnormalities. The frequency of abnormal values was greatest in the patients with the lowest plasma potassium concentrations, but not all of these patients had abnormal values for even one of the tests. Repeated measurements during treatment with potassium supplements showed that the tubular damage resolved in some patients but more slowly than the hypokalemia. These results demonstrate that renal tubular damage is common amongst patients with hypokalaemia and is probably a consequence of the hypokalaemia in most of them. The measurements allow detection of patients whose tissues (at least the kidney) are adversely affected by the hypokalaemia, but the clinical usefulness of this information is yet to be established.

Acetylglucosaminidase↗

The elution profile of vitamin D2 metabolites from sephadex LH20 columns.

A metabolite of vitamin D2 in the tissues of primates fed this vitamin co-migrates to a significant extent with 24,25-dihydroxyvitamin-D3 on columns of Sephadex LH20, with chloroform/n-hexane (60/40 by vol) as eluent. In individuals receiving vitamin D2 and in individuals with scant exposure to sunlight this metabolite, which we believe to be 25,26-dihydroxyvitamin-D2, may yield falsely higher concentrations of apparent 24,25-dihydroxyvitamin-D3 if separation on LH20 is used.

Animals↗

Binding properties of serum vitamin D transport proteins in vertebrates for 24R, 25-dihydroxycholecalciferol and 24S, 25-dihydroxycholecalciferol in vitro.

1. The affinities of the specific vitamin D plasma transport proteins for 25-hydroxycholecalciferol, 24R, 25-dihydroxycholecalciferol and 24S, 25-dihydroxycholecalciferol were studied in 34 vertebrate species. 2. Fish plasma proteins bound 25-hydroxycholecalciferol, 24R, 25-dihydroxycholecalciferol and 24S, 25-dihydroxycholecalciferol with equal efficiency. 3. Vitamin D transport proteins in birds and a monotreme bound 25-hydroxycholecalciferol more efficiently than 24R, 25-dihydroxycholecalciferol; in one bird the two seco-steroids were bound with equal efficiency. 4. Transport proteins from marsupial and placental mammals bound 24R, 25-dihydroxycholecalciferol more efficiently than 24S, 25-dihydroxycholecalciferol. 5. Twelve mammal transport proteins bound 25-hydroxycholecalciferol and 24R, 25-dihydroxycholecalciferol with equal efficiency, however, in six mammals 25-hydroxycholecalciferol was more efficiently bound.

24,25-Dihydroxyvitamin D 3↗

Vitamin D2 in vertebrate evolution.

1. The affinities of the specific vitamin D plasma transport proteins for 25-hydroxyergocalciferol and 25-hydroxycholecalciferol were studied in sixty three vertebrate species. 2. Fish, reptile, bird and monotreme plasma proteins bound 25-hydroxyergocalciferol considerably less efficiently than 25-hydroxycholecalciferol. 3. Vitamin D transport proteins from twenty-two placental mammals bound 25-hydroxyergocalciferol and 25-hydroxycholecalciferol with equal efficiency. 4. Proteins from nine mammals bound 25-hydroxycholecalciferol 10-30% more efficiently than 25-hydroxyergocalciferol.

Animals↗