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Biomedical subjects

A M Wallace

Publications and source records attributed to A M Wallace.

At least 73 records · Page 4Linked to original sources
PubMed1996

Relaxant effect of human brain natriuretic peptide on human artery and vein tissue.

Brain natriuretic peptide (BNP) is a cardiac-derived peptide hormone with cardiovascular and renal actions that is structurally and functionally related to atrial natriuretic peptide (ANP). Previous studies using rat vascular tissue have demonstrated a direct vasorelaxant effect of BNP. However, species-specific potency issues have precluded an accurate measurement of the effect of human BNP. This report demonstrates the vasorelaxant effects of human BNP on human vascular tissue prepared from internal mammary artery and saphenous vein samples. The vasorelaxant effect of human BNP is compared to the other members of the natriuretic peptide family, human ANP and C-type natriuretic peptide (CNP). With regard to potency and magnitude of effect, human BNP and human ANP were similar in relaxing arterial tissue preconstricted with endothelin-1 (BNP ED50 = 1.9 nmol/L and ANP ED50 = 1.8 nmol/L) or phenylephrine (BNP ED50 = 10 nmol/L and ANP ED50 = 19 nmol/L), while CNP was significantly less effective. All three natriuretic peptides exhibited weak venodilating action. These data demonstrate that human BNP is a potent inhibitor of the vasoconstrictive actions of endothelin-1 and the alpha-adrenergic agonist phenylephrine on isolated human artery tissue preparations.

Atrial Natriuretic Factor↗
PubMed1996

Unexpected vascular compromise in transverse rectus abdominis musculocutaneous (TRAM) flap reconstruction: a report of two patients.

Although the vascular anatomy of the transverse rectus abdominis musculocutaneous flap has been well described, poor flap perfusion can lead to partial or total flap ischemia. To minimize the potential for flap loss, criteria have been developed to identify those patients who are deemed to be high risk. Some of these high-risk patients include smokers and those with previous abdominal surgery, obesity, and/or poor medical health. Despite our diligence in patient and operative selection, 2 patients with no preexisting risk factors have recently had venous congestion of their transverse rectus abdominis musculocutaneous flap, necessitating a delayed procedure. The cases are presented here and the potential etiology for this venous congestion explored.

Breast↗
PubMed1996

Sodium status, corticosteroid metabolism and blood pressure in normal human subjects and in a patient with abnormal salt appetite.

1. A patient with severe hypertension was found to have mildly impaired 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) activity on the basis of urinary steroid metabolite ratios, low plasma aldosterone, angiotensin II and renin levels and marginally low levels of plasma potassium. 2. The patient also had a compulsively high salt intake. 3. We tested the hypothesis that high salt intake may affect 11 beta-HSD activity. 4. High salt intake in normal subjects did not significantly alter either blood pressure or 11 beta-HSD activity. 5. We suggest that the potentially small hypertensive effect of the partial enzyme deficiency in our patient, also reported in patients with essential hypertension, has been markedly amplified by the very high salt intake.

Adrenal Cortex Hormones↗
PubMed1996

Salivary cortisol and anxiety in recurrent aphthous stomatitis.

Anxiety and salivary cortisol were measured in two groups of patients with recurrent aphthous ulceration. One group of patients had persistent aphthae (Group 1) and the others had been relieved of their aphthae following correction of detected haematinic deficiency states (Group 2). Anxiety was measured using the Hospital Anxiety and Depression scale and radioimmunoassay of salivary cortisol. There was a statistically significant increased proportion of borderline or clinically anxious patients in Group 1 compared to Group 2 (P < 0.05). Median salivary cortisol levels also showed a statistically significant elevation in Group 1 (P < 0.01). It is concluded that stress may play a role in the aetiology of recurrent aphthous stomatitis, particularly in patients who have an underlying anxiety trait.

Adolescent↗
PubMed1996

Audit of height measurement at age 3 years: results of a survey of Scottish health boards.

Height measurement at about the age of 3 years is accepted as a routine practice by all 15 Scottish health boards and is a recommendation of the Hall report Health for all Children. As part of a Scotland-wide project to assess the feasibility of audit of preschool surveillance programmes using routinely collected data, all boards were asked for information about this procedure. The results show that, while all boards confirmed its usefulness as a screening measure, only one board was realistically able to audit height measurement at this age at all stages using routinely available data. The whole screening process, including programme management, equipment validation, staff training and referral criteria, was examined using the quality standards defined in the Hall report. Results showed a wide variation between boards. For example, fewer than half of the boards provided guidelines for height measurement at age 3 to all professionals involved. The availability of even basic outcome data, such as numbers of children measured at this age was patchy, although this will improve with the introduction of the national computerised preschool surveillance system. Two boards have no plans to record such data routinely. In conclusion, before outcome data can be used and relied on, health boards and trusts need to develop local guidelines including quality standards such as age limits for measurement, programme management, provision of equipment, and review and referral criteria for inclusion into contracts.

Age Factors↗
PubMed1996

Male pseudohermaphroditism secondary to panhypopituitarism.

An infant with a 46XY karyotype was born with ambiguous genitalia, including microphallus and perineal hypospadias. A female gender was assigned due to extreme failure of development of the external genitalia. Subsequent investigations demonstrated panhypopituitarism, and it is believed that severe gonadotrophin deficiency was responsible for the intersex state. This case illustrates the need to evaluate the hypothalamic-pituitary axis in selected cases of intersex, and also questions the prevailing assumption that testosterone secretion during embryogenesis is largely pituitary gonadotrophin independent, under the control of human chorionic gonadotrophin.

Disorders of Sex Development↗
PubMed1996

Comparison between testosterone enanthate-induced azoospermia and oligozoospermia in a male contraceptive study. III. Higher 5 alpha-reductase activity in oligozoospermic men administered supraphysiological doses of testosterone.

The administration of exogenous testosterone (T) to eugonadal men causes suppression of gonadotropin secretion and thus of spermatogenesis. This is currently being investigated as a possible method of hormonal male contraceptive, but complete suppression of spermatogenesis to azoospermia is induced in only 50-70% of Caucasian men; the remainder maintain a low rate of spermatogenesis. The basis for this polymorphism in response is unclear. The enzyme 5 alpha-reductase (5 alpha R) converts T to dihydrotestosterone (DHT) and is important in determining the magnitude of the androgen stimulus in some tissues. We investigated whether the maintenance of spermatogenesis in men remaining oligozoospermic while receiving suppressive doses of T is associated with evidence of increased 5 alpha R activity. Thirty-three normal men were given 200 mg T enanthate (TE), im, weekly in a clinical trial of hormonal male contraception. The MCR of T (MCRT) and the conversion ratio of T to DHT (CRT-DHT) were measured by infusion of [3H]T, plasma levels of DHT and androstanediol glucuronide (AdiolG) were measured by RIA, and 24-h urinary steroid metabolites were measured by capillary column gas chromatography. Sperm density decreased in all men; 18 achieved azoospermia by 20 weeks of treatment, and the remainder had a mean sperm density of 2.0 +/- 0.8 x 10(5)/mL at that time. This treatment caused increases in plasma T levels and MCRT, but with no differences between azoospermic and oligozoospermic responders. There were no differences in CRT-DHT plasma DHT, or AdiolG before treatment, but after 16 weeks, CRT-DHT had increased in the oligozoospermic responders, but not in the azoospermic responders. TE treatment increased plasma DHT and AdiolG levels in both groups, but the increases in both 5 alpha R metabolites were significantly greater in the oligozoospermic responders. Urinary excretion of etiocholanolone and androsterone was increased after 16 weeks of TE treatment, but did not differ between the two groups, andetiocholanolone/androsterone ratios did not differ greatly from unity. There was no change in urinary excretion of tetrahydrocortisol, allo-tetrahydrocortisol, or cortisone after 16 weeks of TE treatment in either group. These results suggest that after TE administration there is a selective increase in 5 alpha R activity in those men who remain oligozoospermic, but not in those becoming azoospermic. This difference in the androgenic milieu may underlie the incomplete suppression in the oligozoospermic responders, in whom a low rate of spermatogenesis is maintained despite the apparent absence of gonadotropins.

Adult↗
PubMed1996

Audit of the distraction test of hearing at about 8 months of age: results of a survey of Scottish health boards.

The distraction test of hearing at 8 months is offered in all Scottish health boards and is a recommendation of the Hall Report 'Health for all Children'. As part of a Scotland-wide project to assess the feasibility of an audit of pre-school surveillance programmes using routinely collected data, all boards were asked for information about this screening test. The results showed that all boards regarded it as a worthwhile screening test in the present circumstances for early detection of sensorineural hearing loss (SNHL). The limitations on the reliability of the test were recognized by many boards. The quality elements of the whole screening process were examined, including screening technique, recording of results, provision of equipment and suitable test conditions, and staff training. The results showed variations in the attention given to quality standards. The results also showed a number of gaps in availability of data on coverage, results, and outcomes. Only one board was realistically able to audit the distraction test at all stages using routinely collected data. Availability of data will improve with the introduction of the national computerized Pre-school Child Health Surveillance Programme (CHSP) into the majority of health boards. The reliability and validity of audit results whether at board level or Scotland-wide level will depend on maintenance and adherence to quality standards in performing the test, in recording of results and also in ensuring adequate coverage.

Health Promotion↗
PubMed1995

Women with steroid 5 alpha-reductase 2 deficiency have normal concentrations of plasma 5 alpha-dihydroprogesterone during the luteal phase.

Steroid 5 alpha-reductase 2 deficiency has been identified in two adult women from unrelated families, one a homozygote and the other a compound heterozygote. The homozygote carries the G183S mutation and is the sister of an affected male; the compound heterozygote (R246W/splice junction abnormality) is married to a heterozygote (splice junction abnormality) and is the mother of two compound heterozygotes and two homozygotes. The fact that these two women are the mothers of seven children and appear to be endocrinologically normal confirms the previous deduction that this disorder is not manifest in women. Concentrations of plasma 5 alpha-dihydroprogesterone were normal in these two women during the luteal phase; this finding implies that circulating 5 alpha-dihydroprogesterone in women is derived principally from the steroid 5 alpha-reductase 1 isoenzyme and leaves unresolved the question of whether 5 alpha-dihydroprogesterone plays a physiological role in women.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1994

Assessment of flosequinan's direct effect on human arterial, venous, and cardiac muscle: comparison with other classes of agents used to treat heart failure.

We wished to provide comparative information regarding the direct effects of flosequinan, a novel quinolone under development for treating heart failure, on isolated human arterial, venous, and cardiac muscle. A similar assessment was made for four other agents--milrinone, ouabain, captopril and diltiazem--that have been used to treat heart failure patients, as well as for flosequinoxan, which is the primary metabolite of flosequinan. Flosequinan produced a potent and balanced relaxant effect on norepinephrine (NE)-contracted human arterial and venous smooth muscle, with IC25 values of 0.32 and 0.50 microM, respectively. At higher concentrations, flosequinan also produced a positive inotropic effect on human cardiac muscle (EC25 = 32 microM). A similar pattern of responses was observed with flosequinoxan. The pharmacologic profile obtained for the other agents examined differed from that observed with flosequinan and flosequinoxan in the following ways: Milrinone produced both vascular relaxant and positive inotropic effects, but at comparable concentrations; ouabain produced both vasoconstrictor and positive inotropic effects; diltiazem exerted a vascular relaxant effect at low concentrations and a negative inotropic effect at higher concentrations; and captopril had slight arterial relaxant and negative inotropic effects. These results demonstrate that the pharmacologic profile of flosequinan and flosequinoxan is unique as compared with that of other agents that have been used to treat patients with heart failure.

Captopril↗
PubMed1994

Hazards of ketoconazole therapy in testotoxicosis.

An eight-year-old boy with Leydig cell hyperplasia (testotoxicosis) was admitted with a three-day history of rash, vomiting and diarrhoea, followed by acute onset of breathlessness and confusion. He was shocked, with liver cell and renal failure, erythematous rash and severe interstitial pneumonitis. He had been treated with ketoconazole for four years prior to admission, receiving 1200mg daily during the preceding year. Cessation of ketoconazole therapy was associated with full clinical recovery but relapse of testotoxicosis. Ketoconazole was reintroduced cautiously at a lower dose, with no ill-effect, and reasonable control of testotoxicosis. We conclude that this boy's illness, including the interstitial pneumonitis, represented a reaction to ketoconazole which was dose-related rather than idiosyncratic.

Child↗
PubMed1994

Mutation in 3 beta-hydroxysteroid dehydrogenase type II associated with pseudohermaphroditism in males and premature pubarche or cryptic expression in females.

A mutation (A82T) is described in the coding sequence of the gene for 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) type II that is associated with variable clinical consequences. Four homozygotes are described, all of which showed elevated levels of delta 5 steroids consistent with 3 beta-HSD deficiency. Two males from a consanguineous family were found to be homozygous for A82T and were affected with pseudohermaphroditism. They differed in their degree of mild salt loss. In the same family a female was found to be homozygous for A82T, but was clinically normal and had no history of premature pubarche or of abnormal menstrual cycles. However, in an apparently unrelated family, the A82T mutation was found in a female affected with premature pubarche. This is the first report of a proven mutation in 3 beta-HSD type II associated with premature pubarche.

3-Hydroxysteroid Dehydrogenases↗
PubMed1994

Mutation in the human gene for 3 beta-hydroxysteroid dehydrogenase type II leading to male pseudohermaphroditism without salt loss.

A 5-year-old XY pseudohermaphrodite was found to have a defect of steroid biosynthesis consistent with a partial deficiency of the enzyme 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD). Circulating concentrations of delta 5 steroids and delta 5 urinary steroid metabolites were elevated and remained elevated after orchidectomy. There was no evidence of salt loss, plasma renin being within normal limits, and no detectable glucocorticoid abnormality. The coding sequences of the genes for 3 beta-HSD types I and II were amplified by PCR and screened for mutations by denaturing gradient gel electrophoresis (DGGE) and manual and automatic DNA sequencing. A mutation in the gene for 3 beta-HSD type II was observed at codon 173 (CTA-->CGA), leading in the affected patient to a homozygous substitution in which the leucine at residue 173 was altered to an arginine (L173R). The propositus's 2-year-old XX sister was also homozygous for L173R and showed the biochemical characteristics of partial 3 beta-HSD deficiency without clinical symptoms or signs. The mutation segregated as an autosomal recessive. Three related heterozygous adult females showed evidence of a small over-production of delta 5 steroids and steroid metabolites and a variable reduction in ovarian function. Concentrations of delta 5 steroids and steroid metabolites in the heterozygous father of the propositus were within the normal range. These data are discussed in relation to the endocrine causes of pseudohermaphroditism and hirsutism. Evidence for tight linkage between the genes for 3 beta-HSD types I and II was obtained using a microsatellite polymorphism in the third intron of the gene for 3 beta-HSD type II and synonymous and non-synonymous mutations and polymorphisms in the gene for 3 beta-HSD type I. The latter polymorphisms were located 88 bp apart at the 3' end of the type I coding sequence and could be physically resolved as haplotypes using DGGE. The application of DGGE to the analysis of mutations in members of a multigene family is discussed.

3-Hydroxysteroid Dehydrogenases↗
PubMed1994

Association of severe haemophilia A with osteoporosis: a densitometric and biochemical study.

Following a femoral neck fracture and vertebral compression fractures in two patients with severe haemophilia A, bone density and turnover were measured in 19 males with severe haemophilia A (all HIV negative, 18/19 hepatitis C antibody positive) and in 19 age/sex matched controls. Bone density at the lumbar spine (L2-4), measured by dual energy X-ray absorptiometry, was significantly lower in the haemophiliac patients (HPs) at (mean +/- SEM) 1.109 +/- 0.042 g/cm2 vs. 1.234 +/- 0.027 in controls; p = 0.018. Femoral neck density was also lower at 0.877 +/- 0.034 g/cm2 (HPs) vs. 1.067 +/- 0.032; p < 0.0005. No significant differences were evident between the groups for serum calcium, parathyroid hormone, luteinizing hormone, follicle-stimulating hormone or 1,25 dihydroxyvitamin D3, nor for fasting urinary hydroxyproline, pyridinoline or deoxypyridinoline excretion. Serum total alkaline phosphatases was elevated in HPs at 200 +/- 10 U/l vs. 158 +/- 8; p = 0.004. Similarly, gamma-glutamyl transferase was elevated at 42 +/- 7 U/l (HPs) vs. 20 +/- 2; p = 0.007. Serum total testosterone and sex-hormone-binding globulin (SHBG) were higher in HPs at 26 +/- 2.5 nmol/l vs. 17.4 +/- 1.6 (p = 0.009) and 56 +/- 6 nmol/l vs. 27 +/- 3 (p = 0.0005), respectively. Free androgen index, however, was lower in HPs at 44 +/- 5 vs 69 +/- 7; p = 0.008. These results suggest significant osteopenia associated with haemophilia A. This may be partly due to liver dysfunction in HPs, but other factors, e.g. relative immobilization, may also be relevant.

Absorptiometry, Photon↗
PubMed1993

Relationship between inotropic activity and phosphodiesterase inhibition for flosequinan and milrinone.

The goal of this study was to assess the relationship between the positive inotropic response to high concentrations of the vasodilators flosequinan and BTS 53 554 (the sulfone metabolite of flosequinan) and the effect of both compounds on different forms of cyclic nucleotide phosphodiesterase. In addition, the relationship between inotropic activity and phosphodiesterase inhibition for the cardiotonic milrinone was also evaluated. All three agents exerted a positive inotropic effect on human cardiac muscle fibers. The concentration of milrinone required to increase cardiac contractility was comparable to the concentration required to inhibit the milrinone-sensitive subclass of cyclic AMP-specific phosphodiesterase (type III phosphodiesterase). However, no such relationship was observed for flosequinan and BTS 53 554. These results suggest that the cardiac response to high concentrations of flosequinan and BTS 53 554 is not mediated by inhibition of type III phosphodiesterase.

Humans↗
PubMed1993

Women's views of the Scottish Breast Screening Programme: a national consumer opinion survey.

A questionnaire survey of 3,000 women attending operative Scottish breast screening outlets was conducted to ascertain women's views of the Scottish Breast Screening Programme. The survey aimed to discover women's opinions of waiting areas, staff, changing facilities, screening procedure and intentions about returning for screening in the future. The response rate was 86%. Overall 84% found reception staff very helpful, 98% found undressing instructions clear, waiting areas comfortable and changing areas private enough; 77% thought the radiographers were very understanding; 97% received enough explanation about the mammogram and 96% felt able to ask questions; 89% said the entire screening process was as, or better than expected; 89% said they were very likely to come back in three years' time. At individual outlets up to 33% of women had insufficient information about breast screening prior to attending and up to 17% had to wait more than 20 minutes after their appointment times. Up to 21% felt moderate or severe pain on screening and up to 51% found pressure worse than expected. In conclusion, the Scottish Breast Screening Programme is very acceptable to women but at some outlets the appointments system, information giving and screening pressure needs to be reviewed.

Aged↗