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Biomedical subjects

A M Wallace

Publications and source records attributed to A M Wallace.

At least 91 records · Page 5Linked to original sources
PubMed1993

17-Hydroxyprogesterone rhythms and growth velocity in congenital adrenal hyperplasia.

Six patients on steroid replacement therapy for congenital adrenal hyperplasia provided capillary blood samples collected at 0800, 1200, 1700, and 2200 h, on to filter paper for 17-hydroxyprogesterone analysis. There was a strong correlation between 17-hydroxyprogesterone day profiles and height velocity over a 4 year period of study. Steroid over-replacement, identified by significantly decreased height velocity (Standard Deviation Score [SDS] 1.92), caused suppression of 17-hydroxyprogesterone concentrations to below 10 nmol/L throughout the day. Near average height velocity (Standard Deviation Score 0.245) was accompanied by suppression of 17-hydroxyprogesterone concentrations below 40 nmol/L but with significant diurnal variation. Under-replacement with rapid height velocity and bone maturation was accompanied by non-suppression of 17-hydroxyprogesterone concentrations (i.e. > 40 nmol/L). These results suggest that serial blood spot 17-hydroxyprogesterone measurements are a convenient and helpful supplement to measurements of height velocity and bone age maturation to monitor steroid replacement therapy in congenital adrenal hyperplasia. These measurements may be useful particularly in differentiating between over-replacement and appropriate replacement, and should allow adjustments in dose before abnormal growth patterns are established.

17-alpha-Hydroxyprogesterone↗
PubMed1992

Early diagnosis and management of 5 alpha-reductase deficiency.

Two siblings of Pakistani origin, karyotype 46 XY, were born with predominantly female external genitalia with minute phallus, bifid scrotum, urogenital sinus, and palpable gonads. The older sibling at the age of 8 days showed an adequate testosterone response to human chorionic gonadotrophin (hCG) stimulation. The diagnosis of 5 alpha-reductase deficiency was made at age 6 years when no 5 alpha-reduced glucocorticoid metabolites were detectable in urine even after tetracosactrin (Synacthen) stimulation. In the younger sibling the diagnosis of 5 alpha-reductase deficiency was provisionally made at the early age of 3 days on the basis of high urinary tetrahydrocortisol (THF)/allotetrahydrocortisol (5 alpha-THF) ratio and this ratio increased with age confirming the diagnosis. Plasma testosterone: dihydrotestosterone (DHT) ratio before and after hCG stimulation was within normal limits at age 3 days but was raised at age 9 months. Topical DHT cream application to the external genitalia promoted significant phallic growth in both siblings and in the older sibling corrective surgery was facilitated. In prepubertal male pseudohermaphrodites with normal or raised testosterone concentrations, phallic growth in response to DHT cream treatment could be an indirect confirmation of 5 alpha-reductase deficiency.

Administration, Topical↗
PubMed1991

Successful closure of intestinal fistulae in an infant using the somatostatin analogue SMS 201-995.

Enterocutaneous and other gastrointestinal fistulae create tough challenges with respect to wound care, nutrition, and strategy for closure. SMS 201-995 is a long-acting somatostatin analogue that has been effective in the treatment of adult enteric fistulae. The use of SMS 201-995 as an adjunct in the successful closure of intestinal fistulae in an infant is reported. This newborn infant developed a high-output enterocutaneous fistula and multiple enteroenteric fistulae after an intestinal resection for necrotizing enterocolitis. Copious fistulae output led to extensive wound breakdown, dehydration, and failure to thrive. Despite traditional management with bowel rest, total parenteral nutrition, antibiotics, and wound care, the high-output fistulae persisted unabated. On postoperative day 12, SMS 201-995 was started at 0.7 microgram/kg subcutaneously twice daily and gradually increased to 2.5 micrograms/kg. Within 2 days of SMS 201-995 therapy, the fistulae drainage had decreased from 62 mL/kg/d to 36 mL/kg/d, a 42% decrease from pretreatment levels. By day 8 of treatment, all fistulae had closed. After 14 days of treatment, the wound had healed and the infant was gaining weight. An upper gastrointestinal examination showed a patent ileostomy and no fistulae. Feeding was initiated, SMS 201-995 was discontinued without significant ileostomy output increase, and successful ileostomy closure took place 4 weeks posttreatment. Furthermore, the infant had no demonstrable side effects from the drug. Use of this drug should be considered in the treatment of other infants with complex, recalcitrant gastrointestinal fistulae.

Enterocolitis, Pseudomembranous↗
PubMed1991

Effect of surface characteristics and style of production on naming and verification of pictorial stimuli.

Theories of object recognition that are based purely on part decomposition do not take into account the role of textural, shading, and color information, nor do they differentiate between stylistic factors in the preparation of line-drawn pictorial stimuli. To investigate these factors, naming and verification experiments were performed using line drawings, monochrome photographs, and color photographs of common objects. For line drawings, it was shown that line width, exposure, and contrast affected naming latency, which increased for lines of narrow width and extremes of exposure. Naming latencies were compared for objects drawn by a professional artist, with varying degrees of surface detail, and objects produced by a computer-aided design (CAD) system, with no surface detail. The mean naming latencies for the artist set were faster than for the CAD set, though not significantly, with a significant degree of object correlation being observed. However, in certain cases there were significant differences between objects. These were investigated in a further experiment in which subsets with common properties of present or absent surface detail were selected from the artist-drawn stimuli. It was found that the presence of surface features resulted in lower response latencies even for those objects that intuitively could be recognized by parts alone. The time to name photographic and line-drawn stimuli was compared, and a progressive decrease in naming latency from line to monochrome to color stimuli was observed. In a verification task, no significant advantage for color or monochrome photographs over line drawings was found, either when comparing stimuli of equivalent or of different mode. However, there was a tendency for the comparison of different modes to take longer than the comparison of same modes. The results are discussed in terms of theories of human visual processing and cognitive and computational models of object recognition.

Adult↗
PubMed1990

Elevation of hormone-binding globulins in acute intermittent porphyria.

Sex hormone-binding globulin (SHBG), thyroxine-binding globulin (TBG) and cortisol-binding globulin (CBG) were measured in plasma of 26 patients with acute intermittent porphyria (AIP). Twelve patients had clinically manifest disease and all had elevated SHBG levels. All but one of 14 patients with latent porphyria had normal SHBG levels. TBG was elevated in 9 of the patients with clinically manifest porphyria and CBG elevated in three. Levels of TBG and CBG were either normal or only slightly elevated in those with latent porphyria. In a prospective study of 30 attacks of AIP in 7 patients, SHBG levels fell between admission and discharge, the fall being significant in the group of 21 attacks treated with haem arginate (p less than 0.001). Our findings suggest that a close correlation exists between elevated SHBG and clinical expression of AIP.

Adolescent↗
PubMed1990

Mineralocorticoid activity of carbenoxolone: contrasting effects of carbenoxolone and liquorice on 11 beta-hydroxysteroid dehydrogenase activity in man.

1. 11-beta-Hydroxysteroid dehydrogenase is an enzyme complex consisting of 11 beta-dehydrogenase and 11-oxoreductase responsible for the interconversion of cortisol to cortisone in man. Inhibition of 11 beta-dehydrogenase (e.g. after liquorice ingestion) results in cortisol acting as a potent mineralocorticoid. We have evaluated the effect of the synthetic liquorice derivative, carbenoxolone, on this enzyme complex. 2. Carbenoxolone given to six volunteers in metabolic balance produced sodium retention with suppression of the renin-angiotensin-aldosterone system. Plasma potassium fell, although there was no kaliuresis. This was associated with inhibition of 11 beta-dehydrogenase (as measured by a rise in the plasma half-life of [11 alpha-3H]cortisol). Unlike liquorice, however, carbenoxolone also inhibited 11-oxoreductase (as measured by the generation of cortisol after oral cortisone acetate). 3. The mineralocorticoid activity of carbenoxolone, like liquorice, is mediated via cortisol by inhibition of 11 beta-dehydrogenase. Carbenoxolone, however, also inhibits 11-oxoreductase activity and this may relate to its effect on renal potassium excretion.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1990

Hilus cell pathology and hirsutism.

Hilus cell abnormalities are uncommon causes of hirsutism with virilization. Although hilus cell tumours have been well described, hilus cell hyperplasia is rare and is poorly defined clinically. We describe three cases of hilus cell hyperplasia and compare them with a case of hilus cell tumour. Both pathologies were associated with increased testosterone and oestradiol secretion. Suppression of testosterone to the 'normal range' in response to exogenous oestrogen was seen only in the cases with hyperplasia; only partial responsiveness was seen in the case with hilus cell tumour. Bilateral oophorectomy offers the potential for cure for both hilus cell hyperplasia and tumour.

Aged↗
PubMed1990

Measuring free thyroxin by using magnetic antibody-containing microcapsules.

We describe a novel magnetic-separation microencapsulated antibody displacement assay for free thyroxin. The method is rapid (results available in just over an hour), with a detection limit of 3 pmol/L, and an interassay precision of less than 10% over the range 8-75 pmol/L. Results are not influenced by changes in the concentration of thyroxin-binding globulin or albumin, nor by the presence of circulating anti-thyroxin antibodies or physiological concentrations of nonesterified (free) fatty acids. A reference interval of 8.4-18.4 pmol/L was established for a large euthyroid adult population. Patients with various nonthyroidal illnesses exhibited a similar reference interval (6.2-17.4 pmol/L). Results from pregnant women, at all stages of gestation, were within the nonpregnant euthyroid reference interval. Complete discrimination was obtained between the euthyroid reference interval and values from patients with untreated thyrotoxicosis (24-75 pmol/L). Excellent, though incomplete, discrimination was obtained for patients with untreated hypothyroidism (less than 3.0-9.0 pmol/L). Results for a group of patients defined as having compensated euthyroidism (5.0-15 pmol/L) showed considerable overlap with the euthyroid reference interval. Patients taking thyroxin, who were clinically euthyroid and whose serum concentration of thyrotropin was within its euthyroid reference interval, had free thyroxin concentrations in the range 13.4-24.2 pmol/L. We discuss the validity of this assay in clinical practice.

Analysis of Variance↗
PubMed1990

LHRH analogue treatment for the prevention of premenstrual attacks of acute porphyria.

We have assessed the value of suppressing ovulation with the luteinizing hormone releasing hormone (LHRH) analogue buserelin in seven patients experiencing crises of acute intermittent porphyria related to the menstrual cycle. Clinical course, plasma oestradiol and progesterone levels, and urinary porphyrin and precursor excretion were monitored over a baseline period of approximately one year, and then for a similar period on buserelin treatment. There was a trend towards clinical improvement on buserelin therapy. The median number of attacks fell from seven during the baseline period to three on treatment (p = 0.06). The response to buserelin varied considerably, with those patients in whom the association between baseline attacks and the menstrual cycle was strongest gaining the most benefit. All patients became amenorrhoeic with suppression of plasma oestradiol and progesterone levels. Urinary delta-aminolaevulinic acid and total porphyrin excretion fluctuated widely both before and during treatment. Our experience indicates that ovulation suppression may be of value in the management of young women in whom recurrent attacks of porphyria are related to the menstrual cycle.

Acute Disease↗
PubMed1989

A bloodspot androstenedione assay suitable for home-monitoring of steroid replacement therapy in congenital adrenal hyperplasia.

A bloodspot assay has been developed using an antiserum raised against androstenedione-3-carboxymethyloxime-bovine serum albumin (AD-3CMO-BSA) conjugate and 125I-AD-3CMO-histamine tracer. The method has a detection limit of 0.6 nmol/L blood and a working range from 0.6 to 40 nmol/L blood. The between-batch precision ranged from 8.4% to 23.3%. Bloodspot androstenedione (AD) concentrations were measured in 50 neonates (26 male, 24 female) and in 95 children (54 male, 41 female) aged 6 months to 18 years. No sex difference in concentrations was found in neonates, in pre-pubertal children up to 8 years of age, in pubertal children (males 8-16 years, females 8-14 years) or post-puberty. Bloodspot AD concentrations ranged from less than 0.6 to 2.7 nmol/L in neonates, less than 0.6 nmol/L in pre-pubertal children, 0.6-2.1 nmol/L in pubertal children and less than 0.6-4.6 nmol/L post-puberty. Daytime bloodspot profiles in 10 children on replacement therapy for congenital adrenal hyperplasia generally showed good correlation between 17 alpha-hydroxyprogesterone and AD concentrations (r = 0.928, P less than 0.001). Bloodspot AD profiles have advantages over 17 alpha-hydroxyprogesterone profiles for the assessment of the adequacy of glucocorticoid replacement therapy.

17-alpha-Hydroxyprogesterone↗
PubMed1989

Hypokalaemia in alcoholics.

Hyponatraemia has been described in beer drinkers and hypokalaemia resulting from increased levels of aldosterone is well recognised in patients with cirrhosis and ascites. We have encountered episodes of hypokalaemia in alcoholics accompanied by normal or increased serum concentrations of sodium. Despite a resemblance to syndromes of mineralocorticoid excess, increased levels of aldosterone and other mineralocorticoids were not found.

Adrenal Cortex Hormones↗
PubMed1989

Role of low Km cyclic AMP phosphodiesterase inhibition in tracheal relaxation and bronchodilation in the guinea pig.

This study evaluated the relationship between inhibition of the rolipram-sensitive and the CI-930-sensitive low Km cyclic AMP-specific phosphodiesterase (PDE) isozymes (PDE IIIRO and PDE IIIc, respectively) and bronchomotor tone in the guinea pig. Rolipram and CI-930 exhibited biphasic concentration-response relationships for relaxation of carbachol-, histamine- and leukotriene D4-contracted trachea. However, each agent produced a monophasic (sigmoidal) concentration-response curve when tested in the presence of a fixed concentration (3 microM) of the other. The same relationships were observed for inhibition of tracheal peak III PDE isolated via diethylaminoethyl-cellulose chromatography. Whereas CI-930 was approximately equipotent inhibiting PDE IIIc and relaxing rolipram-pretreated trachea, rolipram was substantially more potent (EC50 = 0.02 microM) in relaxing CI-930-pretreated trachea than in inhibiting CI-930-pretreated PDE III (PDE IIIRO, IC50 = 2.6 microM). Among a series of PDE inhibitors, there was a highly significant correlation (r = 0.89, P less than .01) between PDE IIIc inhibition (i.e., PDE III in the presence of rolipram) and rolipram-pretreated tracheal relaxation, but not between PDE IIIRO inhibition and CI-930-pretreated tracheal relaxation (r = 0.23). Nine of the PDE inhibitors used in this study have been reported to displace rolipram from a high-affinity binding site in rat brain. A highly significant correlation between relaxation of CI-930-pretreated trachea and displacement of rolipram binding by these agents was observed (r = 0.97, P less than .0001).(ABSTRACT TRUNCATED AT 250 WORDS)

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1989

A 125I-radioimmunoassay for measuring androstenedione in serum and in blood-spot samples from neonates.

We developed a radioimmunoassay with a gamma-emitting radioligand to measure androstenedione in human serum and in dried blood-spot samples from newborns. Antisera were raised in rabbits against androstenedione linked to bovine serum albumin at positions 3, 6, or 11 on the steroid nucleus. Radioligands were prepared by linking [125I]iodohistamine at positions 3, 6, or 11. Linkages were through either carboxymethyloxime or hemisuccinate bridges. All label and antibody combinations were examined, and the most sensitive and specific combination (antiserum raised against androstenedione-3-carboxymethyloxime-bovine serum albumin with an androstenedione-carboxymethyloxime-[125I]iodohistamine label) was selected for full evaluation. We report the performance of these selected reagents in an immunoassay for androstenedione in both serum and dried blood-spot samples from neonates. We measured concentrations of androstenedione in serum under normal and pathological conditions such as congenital adrenal hyperplasia and polycystic ovarian disease. Diurnal variation in normal men was observed. Androstenedione was measured in blood spots from neonates born at term or prematurely, with respiratory distress syndrome, or with congenital adrenal hyperplasia.

Adrenal Hyperplasia, Congenital↗
PubMed1988

Aldosterone deficiency in infancy.

Two infants with a chronic salt wasting state secondary to a rare defect in mineralocorticoid synthesis are described. Management difficulties are illustrated highlighting the need for early definitive diagnosis based on measurement and correct interpretation of plasma renin, plasma aldosterone and urinary steroid metabolite concentrations.

Adrenal Cortex Hormones↗
PubMed1987

Mineralocorticoid activity of liquorice: 11-beta-hydroxysteroid dehydrogenase deficiency comes of age.

The sodium retention associated with liquorice ingestion has been thought to be due to a direct mineralocorticoid effect, despite the fact that it does not seem to occur in patients or animals with severe adrenal insufficiency. This study in seven normal subjects given liquorice showed that sodium retention is associated with a significant change in cortisol metabolism indicating inhibition of 11-beta-hydroxysteroid dehydrogenase (11 beta-OHSD). Congenital deficiency of this enzyme produces a syndrome of apparent mineralocorticoid excess. It is suggested that in both conditions there is a defect in the renal conversion of cortisol to cortisone by 11 beta-OHSD which results in high intrarenal cortisol levels, acting on type 1 mineralocorticoid receptors to cause sodium retention.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1987

Adrenal status during the first month of life in mature and premature human infants.

Measurements of 17-hydroxyprogesterone (17-OHP) in blood collected onto filter paper after heel puncture by lancet and steroid metabolites in random collections of urine, were made in human infants born from 25 weeks of gestation onwards. The concentration of 17-OHP in blood eluted from filter paper samples was inversely related to both gestational age and birth weight. In mature infants, 17-OHP concentrations fell rapidly soon after birth, whereas concentrations remained high over the first month of life in infants born earlier than 33 weeks of gestation. Sulphated urinary steroids were identified as having a 3 beta-hydroxy-5-ene structure and although the pattern of excretion was similar in mature and premature infants, significantly higher concentrations were found in the premature group. Steroid metabolites normally present when concentrations of circulating 17-OHP are increased due to 21-hydroxylase deficiency were not detectable in urine samples collected from infants born prematurely. Where direct comparison of 17-OHP in blood spots and urinary steroid metabolites was possible, the concentrations of 17-OHP in blood samples paralleled 3 beta-hydroxy-5-ene steroid metabolites in urine. The results suggest that a circulating cross-reacting 3 beta-hydroxy-5-ene steroid may be responsible for increased concentrations of 17-OHP in infants born prematurely. Increased concentrations of both 17-OHP in blood spots and steroid sulphates in urine were associated with stress in premature, but not in more mature, infants suggesting that in infants born prematurely postnatal stress may delay adrenal maturation.

17-alpha-Hydroxyprogesterone↗