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Biomedical subjects

J M Kirk

Publications and source records attributed to J M Kirk.

At least 55 records · Page 3Linked to original sources
PubMed1992

Variation of sweat sodium and chloride with age in cystic fibrosis and normal populations: further investigations in equivocal cases.

Patients attending cystic fibrosis clinics had sweat sodium and chloride concentrations measured, were reassessed clinically and had DNA studies performed. Sweat test results were compared with a matched control population. In both populations sweat sodium increased with age up to 12 years, and did not change significantly thereafter. The age-related increase was significantly less in the cystic fibrosis group. Sweat chloride increased with age in normal, but not in cystic fibrosis children. After age 12 years there was no age-related change in the normal group, and a fall with age in the cystic fibrosis group. Sweat chloride provided the best discrimination between normal and cystic fibrosis populations and this was particularly important in older subjects. Combining sweat sodium and chloride results did not improve discrimination. Nine patients were identified with equivocal sweat chloride results. DNA studies showed six of these subjects were heterozygous for the delta F508 mutation in the cystic fibrosis gene. Clinical assessment did not always resolve cases with borderline sweat chloride results.

Adolescent↗
PubMed1992

Pyridostigmine partially reverses dexamethasone-induced inhibition of the growth hormone response to growth hormone-releasing hormone.

The GH response to insulin-induced hypoglycaemia and growth hormone-releasing hormone (GHRH) has been shown to be impaired in subjects with Cushing's syndrome and in healthy volunteers given oral glucocorticoids. Pyridostigmine is an anticholinesterase that stimulates GH secretion, probably by inhibition of hypothalamic somatostatin secretion. This work was designed to study the site of action of glucocorticoids in inhibiting the secretion of GH. Eight healthy male volunteers were studied on three occasions in random order. They took 2 mg oral dexamethasone or placebo at precisely 6-hourly intervals for 48 h before receiving 120 mg oral pyridostigmine or placebo, followed 60 min later by GHRH (100 micrograms) i.v. Samples for measuring GH were obtained at 15 min intervals for 2 h. The 'area under the curve' (AUC) for each of the treatments was significantly different: dexamethasone-pyridostigmine-GHRH (mean +/- S.E.M., 1938 +/- 631 mU/min per l), dexamethasone-placebo-GHRH (634 +/- 211) and placebo-placebo-GHRH (4267 +/- 1183) (P < 0.02, Wilcoxon test). In conclusion, dexamethasone given for 48 h significantly inhibited the AUC for GH following treatment with GHRH. However, pretreatment with pyridostigmine significantly reversed the inhibition although this was still partial. Our data suggested that this short-term suppressive effect of dexamethasone was independent of GHRH, and most probably relates to stimulation of the release of somatostatin.

Depression, Chemical↗
PubMed1991

Pyridostigmine fails to increase either spontaneous or GHRH-stimulated GH secretion during day or night in growth hormone-insufficient children.

OBJECTIVE The aim of the study was to investigate whether pyridostigmine, a cholinesterase inhibitor which is thought to act at the hypothalamus to inhibit somatostatin secretion, would augment spontaneous or GHRH-stimulated serum GH levels in patients with GH-insufficiency. DESIGN Oral pyridostigmine 60 mg or placebo was administered at the start of a 9-h subcutaneous infusion of either GHRH (1-29)NH2 10 micrograms/kg/h or saline control. Studies were performed during the daytime (0900-1800 h) in five patients, and the night-time (2100-0600 h) in a further five. PATIENTS Ten short, pre-pubertal children (aged 6-11 years; eight boys) with growth hormone insufficiency were studied. MEASURES Blood for serum GH was sampled every 20 min, and analysed using the PULSAR program. RESULTS The subcutaneous infusion of GHRH 10 micrograms/kg/h increased mean serum GH levels (+/- SEM): by day 17.7(+/- 6.8) vs placebo 2.2(+/- 0.4) mU/l (P less than 0.01), and by night 26.9(+/- 3.3) vs 5.5(+/- 1.3) mU/l (P less than 0.05). There was a significant rise in mean 'baseline' GH concentration: by day 5.5(+/- 1.7) vs 1.0(+/- 0.0) mU/l (P less than 0.05); and night 8.2(+/- 2.7) vs 1.3(+/- 0.3) mU/l (P less than 0.05). Pyridostigmine failed to produce a significant overall increase in either spontaneous or GHRH-stimulated GH secretion by day or night, although there was a significant rise in mean GH levels during the 3 h following pyridostigmine administration in the morning: 4.4(+/- 1.1) vs 2.4(+/- 0.5) mU/l (P less than 0.001). GHRH or pyridostigmine given singly or in combination had no significant effect on the number of pulses. Side-effects attributable to pyridostigmine occurred in seven children. CONCLUSIONS Pyridostigmine, either on its own or as an adjuvant therapy in combination with GHRH, acts for only a brief time and does not offer any potential benefit in the management of children with short stature.

Abdominal Pain↗
PubMed1991

The effects on anterior pituitary hormone secretion of salmon calcitonin in healthy volunteers.

The reports of the effect of calcitonin on pituitary function are confusing and often refer to uncontrolled studies. We have now carried out a double-blind placebo-controlled trial of intravenous and subcutaneous salmon calcitonin on anterior pituitary function in 17 healthy volunteers. Visual analogue scores for the nausea and vomiting seen after salmon calcitonin correlated with the rise in ACTH and, secondarily, cortisol. Calcitonin had no effect on growth hormone, prolactin, thyrotrophin, luteinizing hormone or follicle stimulating hormone. It is concluded that the stimulation of ACTH secretion following a single dose of salmon calcitonin is probably the result of the stress of nausea rather than a direct effect on the pituitary.

Adrenocorticotropic Hormone↗
PubMed1991

Outcome in tyrosinaemia type II.

Tyrosinaemia type II was diagnosed in a boy with failure to thrive and in his sister on neonatal screening. On diet the outcome, at 12 and 10 years respectively, has been excellent in respect of oculocutaneous sequelae, growth, and psychomotor development, contrasting with the generally unfavourable outcome in most reported cases.

Amino Acid Metabolism, Inborn Errors↗
PubMed1991

Dental health of young insulin dependent diabetic subjects in Northern Ireland.

The present study was undertaken to establish the dental disease and treatment levels in 101 young insulin dependent diabetic patients in Northern Ireland. There was a significantly greater proportion of children from the higher social classes in the diabetic group. Their dental caries experience was lower than that reported for the general population and the restorative indices were high. However, those whose diabetes was diagnosed at a late stage had a higher caries experience. There was significantly more gingivitis detected in older diabetic patients, but oral hygiene status did not significantly differ with age. There was a pattern of regular dental attendance in the majority of diabetic subjects.

Adolescent↗
PubMed1990

Subcutaneous growth hormone-releasing hormone augments pulsatile nocturnal GH release in GH-insufficient children, but may also raise basal GH secretion.

Growth hormone-releasing hormone (GHRH) when given s.c. to GH-insufficient children either as pulses, or once or twice daily, promotes linear growth. These treatment regimens, however, are not ideal as they require frequent drug administration and a significant proportion of patients do not show improved growth. We have now investigated the GH response to a nocturnal s.c. infusion of GHRH (1-29)NH2, at two dosages, 5 and 10 micrograms/kg/h, in a group of five GH-insufficient children. The s.c. infusion of GHRH between 2100 h and 0600 h augmented nocturnal pulsatile GH release in all five children. There was a dose-dependent response for the GH area under the curve (AUC), and mean total GH concentration. The AUC for GH was significantly greater after the 10 than 5 micrograms/kg/h GHRH which in turn was greater than that after placebo; mean (SD) AUC: 14816 (3978), 8125 (1931), 3032 (1582) mU min/l respectively (P less than 0.01 and P less than 0.05). There was no significant change in the number of GH pulses during the 9-h infusions when the subjects were infused with GHRH 10 or 5 micrograms/kg/h compared to placebo, and they occurred at similar times although the number of pulses tended to be greater after GHRH; the mean (SD) numbers of GH pulses were 5.0 (0.7), 3.8 (0.8), 3.2 (0.8), respectively. There was however a significant rise in the mean baseline GH concentration in all patients during the infusion of GHRH 10 micrograms/kg/h compared to placebo, but not with 5 micrograms/kg/h. Thus, GHRH(1-29)NH2 given s.c. augmented nocturnal pulsatile GH release in GH-insufficient children but it also increased baseline GH secretion. These results suggest that a sustained release preparation of GHRH could be a potential treatment for GH-insufficient children, and that a dose of 5 micrograms/kg/h would promote pulsatile GH release, but that at higher dosage it may also raise basal GH secretion.

Child↗
PubMed1990

Short stature, mental retardation, and hypoparathyroidism: a new syndrome.

Eight children (four boys and four girls) with extreme failure to thrive, dysmorphic features, developmental delay, hypoparathyroidism, and abnormal skeletal survey were studied. They were the products of seven consanguinous marriages, two of the patients being brothers. In the remaining six families, a further four children had affected siblings who had died in infancy. When assessed the children were aged 0.47-12.8 years; SD scores were less than -2 for height, weight, and head circumference in all patients. The children had identical facies with deep set eyes, depressed nasal bridge with beaked nose, long philtrum, thin upper lip, micrognathia, and large floppy earlobes. They were all developmentally retarded. The following abnormalities were found on investigation: hypocalcaemia in all (of whom six of seven had hypoparathyroidism), medullary stenosis and other skeletal survey defects in seven of the eight children, and reduced numbers of T cell subsets in four of four tested. We believe that these children represent a new, as yet undescribed genetically determined syndrome.

Child↗
PubMed1990

Female pseudohermaphroditism due to a maternal adrenocortical tumor.

A 15-yr-old, apparently male, patient presented with a 2-yr history of gynecomastia and poor genital development. A normally formed, but small, penis with a phallic urethra was present, and testes were impalpable. The karyotype was 46,XX, and at laparotomy a uterus, Fallopian tubes, and ovaries were found, but there was no testicular tissue. The mother had had regular periods ever since menarche at 14 yr. She had complained of hirsutism since the birth of the child, and on examination 15 yr later had marked clitoromegaly. Serum androgens were elevated: testosterone, 4.5 nmol/L (normal, 0.5-3); dehydroepiandrosterone sulfate, 18 mumol/L (normal, 3-12); and androstenedione, 35 nmol/L (normal, 3-8). All failed to suppress with dexamethasone. Abdominal computed tomographic scan revealed a 9 X 6-cm mass in the position of the left adrenal gland. This was removed at laparotomy and found to be an adrenocortical tumor. Postoperatively, the androgens returned to normal. Virilization of a female fetus due to androgens secreted by a maternal adrenal tumor has only been described three times previously, and the presentation has never been delayed so long.

17-alpha-Hydroxyprogesterone↗
PubMed1989

Difficulties in diagnosis of congenital H-type tracheo-oesophageal fistulae.

The case notes of 12 children with congenital H-type tracheo-oesophageal fistulae diagnosed at the Hospital for Sick Children, Great Ormond Street, who presented between 1980 and 1986 were reviewed. All patients presented early in the neonatal period with recurrent chest infections; abnormal chest radiographs were found in eight. Ten of a total of 19 contrast studies were negative. Tube oesophagograms were more likely to demonstrate a fistula than conventional contrast studies. Any delay in surgery was due to delay in diagnosis rather than to delay in presentation. The results suggest that tube oesophagograms should be performed early where there is clinical suspicion of an H-type fistula, and that other investigations (for example bronchoscopy) should be considered if the tube oesophagogram does not demonstrate a fistula.

Abnormalities, Multiple↗
PubMed1989

Serum type III procollagen peptide concentrations in systemic sclerosis and Raynaud's phenomenon: relationship to disease activity and duration.

Serum levels of the amino-terminal type III procollagen peptide (P-3-NP) have been used as an index of collagen synthesis. Systemic sclerosis (SS) is characterized by uncontrolled production of collagen of several types. This study aimed to explore the profile of P-3-NP in patients with SS and Raynaud's phenomenon, a common forerunner of the disease. Using a radioimmunoassay, the mean level for P-3-NP was found to be raised in SS compared with both the control (p less than 0.001) and Raynaud's groups (p less than 0.001). Analysis of serial samples from the patients with SS suggested that the P-3-NP level reflected changing clinical activity. Three groups emerged: a group with stable disease which showed a less than 20% change in P-3-NP level (mean 5.7%); a group with increasing activity which showed an increase of greater than 20% (mean 35.8%) and a group of decreasing activity which showed a decrease of greater than 20% (mean 33.6%). These data suggest that there is an increase in collagen metabolism in SS and that changes in P-3-NP levels may reflect the clinical course of the disease.

Adult↗
PubMed1989

Growth hormone response to overnight growth hormone-releasing hormone infusion and oral pyridostigmine in children with short stature.

The development of a long-acting or depot preparation of growth hormone-releasing hormone (GHRH) may have many advantages over conventional treatment (with GH) of GH-deficient children. Pyridostigmine, an acetylcholinesterase inhibitor, has been shown to augment basal GH secretion and the GH response to GHRH in short children. It may thus provide adjuvant therapy to depot GHRH. The GH response to a nocturnal subcutaneous infusion of GHRH (1-29)NH2 in doses of 5 and 10 micrograms/kg/hour was investigated in five short, slowly growing children. The effect of oral pyridostigmine 60 mg on nocturnal GH secretion and the GH response to a nocturnal infusion was also examined. The subcutaneous infusion of GHRH augmented pulsatile GH release in all five children. There was a dose-related response to subcutaneous GHRH for the GH area under the curve and mean GH pulse amplitude, but no change in the number of pulses. There was a significant rise in the mean baseline GH concentration during the GHRH infusion compared with placebo. Pyridostigmine had no effect on either basal or stimulated GH secretion.

Child↗
PubMed1989

Interpretation of sweat sodium results--the effect of patient age.

In a retrospective study of sweat tests performed on 650 patients, sweat sodium was shown to increase with age in children without cystic fibrosis. The clearest separation of children with and without cystic fibrosis was in the youngest infants, while the highest proportion of repeatedly equivocal results was in the older children. Applying age-related reference ranges did not resolve the equivocal cases without also missing some cases of cystic fibrosis.

Age Factors↗
PubMed1988

Somatostatin analogue in short term management of hyperinsulinism.

Five infants with hypoglycaemia due to hyperinsulinism were treated for between three and 11 days with a somatostatin analogue, which raised the mean blood glucose concentration and lowered the glucose requirements in all. Somatostatin analogue appears to be useful in the short term management of these patients.

Dose-Response Relationship, Drug↗