PubMed Health⌕ Search

Biomedical subjects

M D Donaldson

Publications and source records attributed to M D Donaldson.

At least 55 records · Page 3Linked to original sources
PubMed1993

Plasma catecholamine levels in porcine Escherichia coli septicaemia and following treatment with buprenorphine or naloxone.

Changes in plasma catecholamine levels in response to the induction of shock and following treatment with buprenorphine or naloxone were determined in a porcine model of Escherichia coli septicaemia. Thirty animals were anaesthetised with alpha-chloralose and infused with live E. coli over 2 hr. One hour after starting the infusion, cardiac index, mean arterial pressure, and pH had decreased significantly (P < 0.001), and there was a significant increase in mixed venous blood lactate concentrations (P < 0.001). This was associated with significant increases in plasma concentrations of adrenaline and noradrenaline (P < 0.001). There was a strong correlation between the extent of the increase in circulating catecholamines and the severity of shock (as reflected by haemodynamic changes and lactic acidosis) as well as significantly higher peak plasma catecholamine concentrations (P < 0.01) and dramatic terminal increases in circulating catecholamines in nonsurviving animals. Animals were randomly divided into three groups and received either naloxone or buprenorphine or an equivalent volume of normal saline and were monitored for a further 3 hr. Both naloxone and buprenorphine produced significant improvements in cardiac index (P < 0.05) and limited the development of acidosis (P < 0.05). This was not associated with any further increase in plasma catecholamine concentrations; indeed, catecholamine levels tended to decrease in treated animals but continued to increase in controls. In summary, we have shown a correlation between the increase in plasma catecholamines and the severity of shock in this model. In addition, we observed that the beneficial effects of treatment with buprenorphine or naloxone were not accompanied by any further increase in plasma catecholamine concentrations.

Animals↗
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↗
PubMed1992

Endocrine deficit after fractionated total body irradiation.

Endocrine function was assessed in 31 children (17 boys) after fractionated total body irradiation used in the preparative regimen for bone marrow transplantation. Endocrine dysfunction was present in 25 children. Fifteen of 29 had growth hormone insufficiency 0.9-4.9 years after total body irradiation, yet only three of the 15 had received previous cranial irradiation. Five of 30 had thyroid dysfunction: two with a low thyroxine and raised thyroid stimulating hormone (TSH) concentration and three with a raised TSH and normal thyroxine concentration. Thus the incidence of thyroid dysfunction (16%) is much lower than that reported after single fraction total body irradiation (39-59%). In only two children were abnormalities of the hypothalamic-pituitary-adrenal axis demonstrated. The majority of pubertal children assessed (n = 15) showed evidence of gonadal damage. All the pubertal girls (n = 5) had ovarian failure, although there was evidence of recovery of ovarian function in one girl. All seven boys in late puberty showed evidence of damage to the germinal epithelium, and two of three in early puberty had raised follicle stimulating hormone concentrations. Despite the use of a fractionated total body irradiation regimen, endocrine morbidity is substantial and children undergoing such procedures will require long term endocrine review and management.

Adolescent↗
PubMed1991

Lack of effect of ACTH in porcine Escherichia coli septic shock.

The cardiovascular and metabolic responses to treatment with ACTH(1-24) were investigated in a porcine model of septicaemia. Sixteen anaesthetised, instrumented animals were infused with live Escherichia coli over 2 hr. During the first hour of the infusion, significant reductions in cardiac index, mean arterial pressure, and pH were observed together with a significant increase in mixed venous blood lactate concentrations and packed cell volumes. ACTH(1-24) 160 micrograms kg-1, given 1 hr after starting the E. coli infusion (n = 8), had no significant effect on these haemodynamic or metabolic measurements when compared with the control group (n = 8). These results do not support the suggestion that intravenous ACTH(1-24) reverses cardiovascular depression in septicaemic shock.

Adrenocorticotropic Hormone↗
PubMed1990

Alpha 1-microglobulin, beta 2-microglobulin and retinol binding protein in childhood febrile illness and renal disease.

Serum and urinary levels of alpha-1-microglobulin (A1M), beta-2-microglobulin (B2M) and retinol binding protein (RBP) were measured using a Mancini radial immunodiffusion technique in 52 children with renal disease, 36 with non-renal febrile illness and 29 controls. In controls the mean serum level for A1M was 25 +/- 4.6 (SD) mg/l for B2M 1.7 +/- 0.5 mg/l and for RBP 31 +/- 8 mg/l. A1M levels were not significantly altered by febrile illness while B2M was elevated and RBP markedly depressed. Serum A1M and B2M were elevated in the nephrotic syndrome, while serum B2M was also raised during infancy. Coefficients of log-transformed data with creatinine-derived glomerular filtration rate (GFR) were -0.87 for B2M, -0.71 for RBP, and -0.62 for A1M. In the urine A1M was always measurable in controls while B2M and RBP were undetectable in all but a small number. The urine levels of all three proteins increased in response to non-renal febrile illness, and rose invariably when GFR fell to below 40-50 ml/min per 1.73 m2. Of the three proteins A1M was most frequently elevated in the urine with febrile and renal illness. RBP was rarely detectable when the other two proteins were not. Urinary A1M was consistently elevated in the nephrotic syndrome in contrast to B2M, possibly as a reflection of the increased glomerular permeability. We conclude that serum B2M is superior to A1M and RBP as an index of glomerular filtration, although its levels should be interpreted with caution in febrile disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

Stability of alpha 1-microglobulin, beta 2-microglobulin and retinol binding protein in urine.

The stability of alpha 1-microglobulin (alpha 1M), beta 2-microglobulin (beta 2M) and retinol binding protein (RBP) in urine was determined in 135 random samples from children with renal disease, febrile illness, malignancy, and from controls. Immediately after voiding, samples were divided into two portions, one of which was alkalinized. After identical transit times and laboratory handling the pH and concentrations of the individual proteins in each pair were measured. beta 2M was unstable in urine of pH less than 7 and grossly so below pH 6. In some instances beta 2M was low or undetectable even in the alkalinized samples when alpha 1M and RBP levels were raised, suggesting that degradation of beta 2M may have occurred prior to voiding. Concentrations of alpha 1M and RBP were significantly lower in the non-alkalinized fractions at pH less than 7, although to lesser degree than for beta 2M. Contrary to previous reports, we conclude that the stability of all 3 proteins is affected by urinary pH and recommend that this be measured and alkalinisation performed at the time of voiding.

Alpha-Globulins↗
PubMed1988

Cardiovascular actions of trimetaphan nitroprusside. Comparison with sodium nitroprusside in greyhounds.

Trimetaphan nitroprusside (TNP) is a new potent hypotensive agent developed to induce and maintain decreases in arterial pressure unaccompanied by resistance. This study investigated its properties and compared them with those of sodium nitroprusside (SNP) in anaesthetized greyhounds. The mean dose response to TNP was obtained by measuring haemodynamic changes in five dogs. With increasing doses, stepwise decreases in mean arterial pressure and progressive increases in heart rate occurred: cardiac index did not change significantly. In a further six greyhounds, SNP and TNP were alternately infused to induce and maintain a 30% reduction in arterial pressure for 30 min. Both drugs were short-acting, decreased systemic vascular resistance and caused tachycardia. Infusion of TNP produced lower plasma and red cell cyanide concentrations; SNP maintained hypotension with significantly less tachycardia. We conclude that there was no outstanding advantage of TNP over SNP when given as a short-term infusion in greyhounds.

Anesthesia, General↗
PubMed1988

Beneficial effects of buprenorphine (a partial opiate agonist) in porcine Escherichia coli septicaemia: a comparison with naloxone.

The cardiovascular and metabolic responses to treatment with naloxone or buprenorphine (a partial opiate agonist) were investigated in a porcine model of septicaemia. Animals anaesthetised with alpha-chloralose were infused with live E. coli over two hours. They were then divided into three groups and received either naloxone (2 mg kg-1 + 1.5 mg kg-1 hr-1) or buprenorphine (0.3 mg kg-1) or an equivalent volume of normal saline. Treatment was started one hour after commencing the infusion, by which time a significant fall in cardiac index (CI), stroke index (SI), mean arterial pressure (MAP), and pH had occurred in all groups, together with a significant rise in mixed venous blood lactate and packed cell volume. Treatment with both naloxone and buprenorphine resulted in significant improvements in CI, pH, and base excess and in a fall in mixed venous lactate and packed cell volume. Although no significant effect on survival was seen at three hours after the start of treatment, buprenorphine may prove to be a suitable alternative to naloxone in the management of septic shock.

Animals↗
PubMed1987

Natural killer cells in viral arthritis.

Changes in natural killer (NK) cell activity were studied in patients with polyarthritis associated with rubella or Ross River virus infections. In 30 of 32 Ross River virus patients, peripheral NK cell activity was depressed at some stage of the disease but returned to normal levels as patients recovered from arthritic symptoms. Similar changes did not occur in rubella patients and no difference was found between changes in peripheral NK activity and serum interferon (IFN) levels in rubella patients with arthritis and those without. Neither the peak of NK cell activity in peripheral blood lymphocytes (PBL) recovered early in Ross River virus and rubella infections, nor the depression of NK cell activity late in Ross River virus infections could be correlated with changes in serum IFN levels. The decrease in PBL-NK cell activity in epidemic polyarthritis (EPA) patients could not be attributed solely to loss of NK cells from the peripheral circulation because limiting-cell-dilution (LCD) analyses indicated changes in peripheral NK cell activity were due to changes in both the number and lytic activity of NK cells. Despite the association between HLA-DR7 and EPA no differences were found in levels of peripheral NK cell activity in DR7+ and DR7- EPA patients. The demonstration that peripheral NK cells could kill autologous synovial cells suggested that NK cells in joints of EPA patients may contribute to the arthritis associated with Ross River virus infection.

Adult↗
PubMed1985

Isolation of Ross River virus from epidemic polyarthritis patients in Australia.

Ross River virus was isolated from two out of four seronegative serum samples obtained from epidemic polyarthritis patients in Australia. Virus isolated from each patient was found to be phenotypically diverse. These isolations suggest that previous failure to isolate virus from epidemic polyarthritis patients in this country may have been due to failure to obtain material (serum) from patients early enough in the course of the disease and to the use of relatively insensitive isolation techniques.

Alphavirus↗
PubMed1985

Familial juvenile nephronophthisis, Jeune's syndrome, and associated disorders.

Fourteen patients with familial juvenile nephronophthisis are described, eight of whom displayed one or more additional disorders. One boy with short limbed dwarfism and an abnormal chest was considered to have Jeune's syndrome; review of the published reports supports the view that nephronophthisis is the principal cause of renal failure in this disorder. Another patient with renal failure and retinitis pigmentosa at presentation developed progressive neurological and neuromuscular impairment leading to the discovery of ragged red fibre disease (mitochondrial cytopathy). Cardiomyopathy was present in this and one other patient. Tapeto-retinal degeneration, hepatic fibrosis, cerebellar ataxia, and oculomotor apraxia were among the other disorders encountered. Three patients presented in extremis with acute heart failure and irreversible oligo-anuria and this complication developed in another child who was already known to have nephronophthisis. Awareness of this disease and its associations is important for early diagnosis and appropriate management.

Adolescent↗
PubMed1984

Gonadotrophin responses to GnRH in precocious puberty treated with GnRH analogue.

The gonadotrophin releasing hormone analogue Buserelin was given by intranasal spray to 13 children with precocious puberty. The LH responses to GnRH reverted to prepubertal levels in the boys on 200-400 micrograms daily of the analogue while doses of 400-1200 micrograms daily were needed to suppress the girls. The significance of this apparent sex difference is uncertain.

Buserelin↗