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Biomedical subjects

B A Leatherdale

Publications and source records attributed to B A Leatherdale.

At least 19 recordsLinked to original sources
PubMed1998

Outpatient assessment of residual growth hormone secretion in treated acromegaly with overnight urinary growth hormone excretion, random serum growth hormone and insulin like growth factor-1.

OBJECTIVE: To assess the outpatient investigations, overnight urinary growth hormone (uGH) excretion, random serum GH and insulin like growth factor 1 (IGF-1), and GH indices from the oral glucose tolerance test (OGTT) (fasting, nadir and mean GH), as measures of mean GH secretion in treated acromegaly, in comparison with a GH day series, which served as a gold standard. DESIGN: Prospective cross-sectional study, with patients admitted to a metabolic ward for the following investigations: random GH, IGF-1, 6 point GH day series (day 1), 9 h timed overnight uGH excretion, OGTT with GH response (day 2). Agreements between the mean GH during the day series and the other outcome measures, and the diagnostic performance of the latter, for the presence or absence of active acromegaly (mean GH during day series > or = 5 or < 5 mU/l, respectively) were determined. PATIENTS: 26 patients with treated acromegaly (11 with inactive acromegaly off drug therapy). MEASUREMENTS: Serum GH and uGH were measured by immunoradiometric assays and IGF-1 by radioimmunoassay. RESULTS: Agreements with the mean GH during the day series were perfect for the nadir GH during the OGTT with a 2 mU/l cutoff (Cohen's kappa (kappa) = 1, P < 0.00001), almost perfect for the fasting and mean GH throughout the OGTT (both kappa = 0.92, P < 0.0001) and random GH (kappa = 0.85, P < 0.0001), and substantial for the nadir GH with a 5 mU/l cutoff (kappa = 0.77, P < 0.0001), IGF-1 (kappa = 0.62, P < 0.001) and overnight uGH excretion (kappa = 0.61, P = 0.002). Nadir GH with a 2 mU/l cutoff was completely accurate for diagnosing the presence or absence of active acromegaly (positive and negative predictive values (% +/- standard error percentage) 100 +/- 8% and 100 +/- 10%). None of the outpatient tests used alone was an adequate diagnostic test (positive and negative predictive values: overnight uGH excretion -86 +/- 10% and 75 +/- 13%; random GH -100 +/- 11% and 85 +/- 11%; IGF-1 -92 +/- 10% and 71 +/- 13%) and so combinations of tests were assessed. The best was overnight uGH excretion plus random GH (positive and negative predictive values 88 +/- 9% and 100 +/- 12%). Using all three outpatient investigations, the positive predictive value of three raised results was 100 +/- 13%. CONCLUSIONS: In treated acromegaly, residual GH secretion can be reliably assessed with the OGTT, using standard diagnostic criteria. It can also be assessed on an outpatient basis with overnight uGH excretion and random GH, as direct measures, and IGF-1. If these are all normal, active acromegaly is excluded. Three raised results denote active acromegaly, and one or two raised results would need further investigation with a GH day series.

Acromegaly↗
PubMed1997

Urinary growth hormone following exercise to assess growth hormone production in adults.

OBJECTIVE: The insulin stress test (IST) is the most commonly used test to assess the GH reserve in children and adults. It is a time-consuming, expensive and potentially dangerous test. We investigated whether measurement of urinary growth hormone excretion following exercise would prove on reliable method to diagnose adult GH deficiency. DESIGN: Healthy volunteers underwent a standard IST to confirm GH secretion. Using a standardized exercise protocol on a treadmill, the urinary excretion of GH was measured. Three patients confirmed as GH deficient by an IST were exercised during the same exercise protocol and their urinary excretion of GH was measured. PATIENTS: Ten healthy volunteers and three patients with hypopituitarism were evaluated. MEASUREMENTS: A standard IST was performed on both healthy volunteers and patients, with measurements of plasma GH and plasma cortisol. Urinary growth hormone and urinary GH/creatinine (GH/CR) ratios were measured before and after IST. On a separate visit, healthy volunteers and patients were exercised on the treadmill with measurements of plasma GH and cortisol. Urinary GH and GH/CR ratios were measured before and after exercise. RESULTS: There was at least a two-fold increase in urinary GH and GH/CR ratios following exercise in all healthy adults. By contrast, patients with GH deficiency showed no rise in urinary GH or urinary GH/CR ratios following exercise. CONCLUSIONS: Measurements of urinary GH following exercise can distinguish between GH-deficient adults and healthy volunteers. Urinary GH excretion can be measured over a timed interval following exercise or can be expressed as the GH/CR ratio. This can be measured on a single sample following exercise and can be used to diagnose GH deficiency. The exercise test employed for this study is arduous. We are therefore performing further studies with a less strenuous exercise protocol with a view to designing a 'patient-friendly' exercise test for GH deficiency in adults.

Adult↗
PubMed1997

RDCI, the vasoactive intestinal peptide receptor: a candidate gene for the features of Albright hereditary osteodystrophy associated with deletion of 2q37.

Albright hereditary osteodystrophy (AHO) is an autosomal dominant disorder characterised by the presence of brachymetaphalangism, short stature, obesity, and mental retardation. Variable biochemical changes many represent either pseudohypoparathyroidism (PHP) owing to resistance to parathormone (PTH) or pseudopseudohypoparathyroidism (PPHP) with no hormone resistance. In most cases of AHO, reduced levels of Gs alpha have been found and a number of deactivating mutations in the gene for Gs alpha located on chromosome 20q13 have been described. Recently a number of people with an AHO-like phenotype have been reported in whom a deletion of chromosomal region 2q37 has been found in the absence of biochemical abnormalities or a reduction in Gs alpha activity. We present a further female patient with a cytogenetically visible deletion of 2q37, an AHO-like phenotype, and unusual biochemistry suggesting moderate PTH resistance. The vasoactive intestinal peptide receptor (RDCI) has recently been mapped to 2q37 and we propose that this is a candidate gene, hemizygosity of which affects signal transduction and leads to the AHO-like phenotype found in patients with 2q37 deletions.

Adolescent↗
PubMed1993

Symmetry of cerebral blood flow and cognitive responses to hypoglycaemia in humans.

A low blood glucose level is associated with impairment of higher cerebral function and an increase in cerebral blood flow. This study examined whether there are differences in the physiological responses to hypoglycaemia between the cerebral hemispheres. Eight healthy men participated in two hyperinsulinaemic glucose clamp studies: after 60 min at 4.5 mmol/l, blood glucose was either lowered to 2.0 mmol/l and "clamped" there for 60 min (hypoglycaemia) or continuously maintained at 4.5 mmol/l (euglycaemia). Cardiac output, middle cerebral artery velocity (transcranial Doppler) and cerebral blood flow (133-xenon inhalation) were measured during the studies. Neuropsychological tests were used to determine whether hypoglycaemia caused differential impairment of hemispheric cognitive function. Hypoglycaemia was associated with symmetrical impairment of cognitive function in both cerebral hemispheres and a rise in cardiac output (from 5.5 [0.2] to 8.7 [0.2] l.min-1, p < 0.0001, mean [standard error]), middle cerebral artery velocity (from 55 [2.6] to 64 [2.8] cm.s-1, p < 0.002), and global cerebral blood flow (from 56 [2.6] to 69 [2.9] ml.100 g-1.min-1, p < 0.005 compared to pre-insulin values). There were no differences in the blood flow response during hypoglycaemia between hemispheres and the increase in blood flow did not correlate with either the change in cardiac output or rise in plasma catecholamine levels. After 120 min of hyperinsulinaemic, euglycaemia, global cerebral blood flow rose significantly above baseline (from 58 [2.4] to 63 [2.2] ml.100 g-1.min-1, p < 0.05). In conclusion, using the techniques described, the physiological and cognitive responses of each cerebral hemisphere to hypoglycaemia were symmetrical.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Importance of insulin in subjective, cognitive, and hormonal responses to hypoglycemia in patients with IDDM.

Not all episodes of hypoglycemia are recognized as such by diabetic patients, suggesting that it is possible for them to adapt to a low blood glucose level, although the mechanism involved is not known. The aim of this study was to examine whether insulin has an effect, independent of blood glucose, on the subjective, cognitive, and hormonal responses to hypoglycemia. Nine patients with insulin-dependent diabetes mellitus (IDDM) participated in three hyperinsulinemic glucose-clamp studies. After 60 min at 4.5 mM, blood glucose was randomized to be 1) maintained at 4.5 mM for 240 min, 2) lowered to 2.8 mM for 180 min followed by 60 min at 2 mM with an insulin infusion rate of 40 mU.m-2.m-1, and 3) fitted to the same protocol as 2 but with an infusion rate of 120 mU.m-2.min-1. Symptoms and awareness of hypoglycemia (100-mm visual analogue scales), cognitive function, and counterregulatory hormone levels were assessed every 30 min. There were no subjective or cognitive changes during the euglycemic study. Awareness and hypoglycemic symptoms (hunger, facial flushing, trembling, and sweating) were attenuated by the higher insulin infusion rate (P less than 0.05 and P less than 0.01, respectively). Cognition was significantly impaired after 60 min at 2.8 mM (P less than 0.001) and deteriorated further when the blood glucose level was lowered to 2 mM (P less than 0.01). Levels of cortisol (P less than 0.01) and growth hormone (P less than 0.05) but not epinephrine were suppressed by the higher insulin infusion rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Lactic acidosis due to metformin therapy in a low risk patient.

A 55 year old diabetic women treated with chlorpropamide and metformin for three years presented with acute oliguric renal failure and lactic acidosis from which she died. The plasma metformin level was very high suggesting that the lactic acidosis was caused by the drug. There were no contraindications to metformin therapy and renal function was normal three months previously. This case demonstrates that lactic acidosis can occur as a result of metformin therapy in the absence of pre-existing risk factors.

Acidosis, Lactic↗
PubMed1987

Diabetic impotence: risk factors in a clinic population.

Analysis of questionnaire replies from 292 diabetic men aged 20-59 revealed impotence in 23% (66), compared to 9% (7) of a sample of 81 non-diabetic outpatients. Further investigation of 45 impotent diabetic men and 45 matched non-impotent diabetic controls revealed greater psychological stress and poorer glycaemic control in the impotent group. There were no significant differences in the frequency of peripheral neuropathy, retinopathy, nephropathy or large vessel disease in the 2 groups. 20% (9) of the impotent diabetic group had definite autonomic neuropathy which was not present in any of the non-impotent group. The frequency of early autonomic damage was, however, similar in both groups. Impotence in diabetic men is associated with hyperglycaemia, stress and definite autonomic neuropathy. Our data suggest that men with early autonomic neuropathy are frequently potent.

Adult↗
PubMed1986

Specific thromboxane synthetase inhibition and retinopathy in insulin-dependent diabetics.

We have previously reported that specific thromboxane synthetase inhibition may be associated with a reduction in albumin excretion rate in insulin-dependent diabetics (IDD). We now report studies of retinal morphology assessed by serial fluorescein angiography in 25 insulin-dependent diabetics during a 16-week double-blind, randomized, placebo-controlled study of the specific thromboxane synthetase inhibitor UK-38,485. Assessment of angiograms was by, computerized image analysis indicating the percentage area of vascularization and, panel scoring by 4 ophthalmologists who scored the posterior pole in each of the 4 angiograms "blind" according to a prearranged system. There was no significant change in percentage area of vascularization in either placebo or "active" group during the study. Panel scoring, however, suggested that some patients deteriorated whilst others remained unchanged or improved. There was, however, no significant difference in these parameters between those subjects on UK-38,485 and those on placebo. We conclude that specific thromboxane synthetase inhibition is not associated with any significant change in diabetic retinopathy over a 4-month period of study.

Adult↗
PubMed1985

Cerasee, a traditional treatment for diabetes. Studies in normal and streptozotocin diabetic mice.

Cerasee, a wild variety of Momordica charantia is traditionally prepared as a tea for the treatment of diabetes mellitus in the West Indies and Central America. To investigate a possible hypoglycaemic effect, concentrated aqueous extracts of cerasee were administered to normal and streptozotocin diabetic mice. In normal mice, intraperitoneal administration of cerasee improved glucose tolerance after 8 hr, and in streptozotocin diabetic mice the level of hyperglycaemia was reduced by 50% after 5 hr. Chronic oral administration of cerasee to normal mice for 13 days improved glucose tolerance. The cerasee extracts did not significantly alter plasma insulin concentrations, suggesting that cerasee may exert an extrapancreatic effect to promote glucose disposal.

Administration, Oral↗
PubMed1985

Cigarette smoking, blood pressure and the control of blood glucose in the development of diabetic retinopathy.

We have investigated the relationship between diabetic retinopathy and cigarette smoking, blood pressure, control of blood glucose, duration of diabetes and insulin requirement in a cross sectional study of 193 adult patients attending 2 diabetic follow-up clinics. Multiple discriminate analysis demonstrated that the duration of diabetes was closely related to the development of retinopathy in both sexes. Cigarette smoking was related to retinopathy in men but not in women, although in that group the prevalence of smoking was low. The average blood glucose whilst attending the clinic was weakly related to retinopathy in men only whereas the presence of hypertension was weakly related in women only. Cigarette smoking in men at least may be an aggravating factor for diabetic retinopathy.

Age Factors↗
PubMed1984

Specific thromboxane synthetase inhibition and albumin excretion rate in insulin-dependent diabetes.

Albumin excretion rates (AER) were measured in 30 insulin-dependent diabetics during a 16-week double-blind, randomised, placebo-controlled study of the specific thromboxane synthetase inhibitor UK-38,485.6 of 15 subjects in the active group had microalbuminuria (defined as mean pretreatment AER 20-150 micrograms/min); in these patients AER fell from 32 +/- 3 micrograms/min to 11 +/- 1 micrograms/min at 8 weeks and 9 +/- 1 micrograms/min at 16 weeks. The AER rose again (to 29 +/- 8 micrograms/min) within 12 weeks of stopping the drug. There was no significant change in the 10 patients with microalbuminuria who received placebo. There was a strong correlation between change from baseline values and the baseline values themselves in the active, but not in the placebo group, and the change from baseline differed significantly between the two groups. There was no change in glycosylated haemoglobin or mean blood glucose levels during the study. In a separate study UK-38,485 caused significant suppression of thromboxane B2 synthesis in diabetic and non-diabetic subjects.

Adult↗