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Biomedical subjects

R Pelkonen

Publications and source records attributed to R Pelkonen.

At least 73 records · Page 4Linked to original sources

A crossover comparison of continuous insulin infusion and conventional injection treatment of type I diabetes.

We evaluated the feasibility and effectiveness of continuous subcutaneous insulin infusion therapy (CSII) as compared to conventional injection treatment (CIT) in an ordinary diabetic clinic in a one-year randomized crossover study of 65 type I diabetic patients. Home blood glucose levels were lower during CSII (8.6 +/- 0.2 mmol/l, mean +/- SEM) than during CIT (9.1 +/- 0.3 mmol/l, p less than 0.05). During the first six months, HbA1 fell on CSII therapy (from 10.6 +/- 0.4 to 9.7 +/- 0.3%, p less than 0.001), whereas no change occurred during CIT. After the crossover, HbA1 decreased again on CSII (p less than 0.05), but rose in patients shifted from CSII to CIT (p less than 0.05). The fall in glycosylated haemoglobin during CSII correlated with the initial HbA1 level (r = 0.54, p less than 0.001). Ketoacidosis was more common during CSII (16 vs. 2 verified episodes). Hypoglycaemia occurred infrequently, without difference between CSII and CIT. Fifty-six per cent of the patients preferred CSII after the study. In conclusion, while CSII slightly improves the metabolic control, the improvement in the unselected study population is less than previously reported among highly selected patients.

Adolescent↗

Sleep apnoea and daytime sleepiness in acromegaly: relationship to endocrinological factors.

Sleep history and pituitary function were studied and sleep polygraphy performed in 11 acromegalic patients before and after pituitary surgery. Excessive daytime sleepiness or habitual snoring or both together, as well as an elevated fasting level of serum GH occurred in all the patients. In five men but in none of the women an abnormal number of episodes of sleep apnoea were observed. Pituitary adenomectomy improved the apnoea frequency in one patient, whereas in the others the abnormality was still present 1 year later. After operation the fasting level of serum GH became normal in eight patients, two of them with persisting sleep apnoea. The sleep apnoea syndrome is common and clinically important in acromegaly. Its early diagnosis using polygraphic monitoring is emphasized, as it is a treatable disorder.

Acromegaly↗

Familial and sporadic medullary thyroid carcinoma: clinical and immunohistological findings.

We have studied the clinical and thyroid immunohistological features of 19 patients with sporadic medullary thyroid carcinoma and 16 patients with the hereditary syndrome multiple endocrine neoplasia 2a (MEN 2a). Both groups were identified by family screening using serum calcitonin determinations before and after pentagastrin stimulation. Pheochromocytoma and hyperparathyroidism were associated both with multiple endocrine neoplasia 2a and some cases of sporadic medullary thyroid carcinoma. Hereditary medullary thyroid carcinoma was invariably associated with C-cell hyperplasia, but C-cell hyperplasia was also associated with some sporadic tumours. All tumours were positive for calcitonin and carcinoembryonic antigen (by immunohistological staining) (CEA) and most tumours stained for somatostatin. C-cell hyperplasia also stained for calcitonin, CEA and somatostatin. We conclude that sporadic and familial medullary thyroid carcinoma cannot always be discriminated by clinical or immunohistological methods. Family screening is essential in the diagnosis of hereditary medullary thyroid carcinoma.

Adult↗

Acute ethanol intoxication does not influence gonadotropin secretion in postmenopausal women.

Acute effects of ethanol ingestion (1.0 g per kg body weight) on the serum levels of LH, FSH and prolactin were studied in 10 postmenopausal women. Ethanol was administered during the first 3 hr of the experiment and the hormone concentrations were monitored for 10 hr. Each subject served as her own control in an identical experiment without ethanol. Blood alcohol concentration reached its maximum 1.18 +/- 0.02 g/l (mean +/- S.E.M.) 3hr after the start of the drinking. No changes were found in the levels of LH and FSH during the experimental period. The increase of 80% in the mean concentration of prolactin at 4hr after the start of drinking was not statistically significant. On the basis of these and previous results we conclude that alcohol has no acute effects on the secretion of gonadotropins in women.

Aged↗

Effect of ethanol on serum concentrations of somatomedin C and the growth hormone (GH) secretion stimulated by the releasing hormone (GHRH).

To elucidate the site of the ethanol-induced inhibition of the secretion of the growth hormone (GH) we studied the effect of ethanol on the growth hormone releasing hormone- (GHRH) stimulated secretion of GH in 9 healthy men, aged 22 to 41 years. After fasting over night the subjects received ethanol (1.0 g/kg of body weight) during 1.5 hours in the morning. Thereafter 100 micrograms of GHRH were given intravenously and the blood or serum concentrations of ethanol, glucose, GH, sometomedin C, free fatty acids and acetate were monitored for 4 hours. Every subject served as his own control by participating in an identical session during which water was served instead of ethanol. In 6 out of 9 subjects ethanol augmented the response of GH secretion to GHRH. Interestingly, serum concentrations of somatomedin C were higher after ethanol intake than without ethanol. Ethanol had no effect on blood glucose but serum concentrations of free fatty acids were lower and those of acetate higher during the ethanol session than in the control experiment. The results favour the suggestion that ethanol does not inhibit the GH release at the hypohyseal level. In contrast, ethanol may enhance the effect of GHRH, possibly through its influence upon serum levels of free fatty acids.

Acetates↗

The effect of exogenous hyperinsulinemia on proinsulin secretion in normal man, obese subjects, and patients with insulinoma.

To examine possible feedback inhibition of insulin on proinsulin secretion, we measured serum proinsulin levels before and after 120 min of euglycemic hyperinsulinemia (90-100 mU/liter) in 11 normal and 7 obese hyperinsulinemic subjects and 6 patients with beta-cell adenoma (n = 4), carcinoma, or hyperplasia. Baseline proinsulin levels accounted for 19%, 14%, and 56% of the total immunoreactive insulin in the 3 groups, respectively. Compared to normal subjects, baseline proinsulin levels were elevated (P less than 0.02) by 4- and 6-fold in obese subjects and patients with autonomous insulin secretion, respectively, but there was an overlap between the groups. In both normal and obese subjects, hyperinsulinemia suppressed proinsulin secretion by 45-50% (P less than 0.02), whereas no response occurred in the patients. Thus, the 120 min values were clearly different in the patients and the normal or obese subjects. After removal of the adenoma in 4 patients, baseline proinsulin levels and the response to hyperinsulinemia were normalized, but they remained elevated after a partial pancreatectomy or tumor removal in the patients with beta-cell hyperplasia or carcinoma. Thus, proinsulin secretion is under negative feedback control of insulin in both normal man and hyperinsulinemic obese subjects. In patients with insulinoma or beta-cell hyperplasia, this control is lost.

Adenoma, Islet Cell↗

Patients with acromegaly come from tall families.

The heights of 59 patients with acromegaly and their first-degree relatives were studied. The mean height SD score (SDS) for the patients was 0.93 +/- 1.19 (equivalent to 5.6 cm above the population mean), and for their siblings (N = 166) 0.39 +/- 1.05 (2.3 cm above the population mean) (P less than 10-5 for difference from the general population). The height distribution of both groups was markedly positively skewed. Probably the parents were as tall (in relation to the population of their age) as the siblings. Growth data were available for 13 of the patients and showed that the height of the tall (SDS greater than 2.0) patients had increased by 2.5-10 (mean 5) cm after normal cessation of growth. This explains the extra height of the patients over their siblings. Only 2 of the 13 patients became oversized for their families during the normal growth period. We suggest that in a part of the population with acromegaly the disease is associated with primary genetic tallness.

Acromegaly↗

Pathogenesis and prevention of the dawn phenomenon in diabetic patients treated with CSII.

The mechanism of the dawn phenomenon was studied in 12 C-peptide-negative type I diabetic patients (age 30 +/- 2 yr) treated with continuous subcutaneous insulin infusion. During constant basal infusion, nocturnal glycemia remained constant until 4 a.m., but began to rise thereafter in 10/12 patients, with the mean rise from 4.6 +/- 0.4 mmol/L to 6.1 +/- 0.7 mmol/L (P less than 0.01) by 8 a.m. In these patients the rate of glucose production (Ra, 2.14 +/- 0.04 mg/kg/min, 3-H3-glucose infusion) exceeded the rate of utilization (Rd, 1.89 +/- 0.03 mg/kg/min, P less than 0.02). When the patients were restudied after the infusion rate was increased by 49 +/- 7%, Ra fell to 1.75 +/- 0.03 mg/kg/min (P less than 0.01) and the dawn phenomenon was abolished. However, both Ra and Rd remained higher in the diabetic subjects (P less than 0.05) than in eight healthy control subjects, in whom Ra (1.66 +/- 0.02 mg/kg/min) was equal to Rd with glycemia remaining unchanged. Peripheral free insulin levels in the diabetic patients were similar during constant (12.3 +/- 0.5 mU/L) and increased infusion rate (11.3 +/- 0.4 mU/L), and higher than those of the control subjects (5.2 +/- 0.2 mU/L, P less than 0.05). A diurnal rise in serum cortisol levels occurred 1 h earlier in the diabetic than in the control subjects, and Ra was directly proportional to serum cortisol concentration (r = 0.61, P less than 0.01). Serum growth hormone levels were also slightly higher in the diabetic than the control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Ketanserin without effects on basal anterior pituitary hormone secretion in healthy subjects.

The effect of ketanserin, a selective serotonin-2 (5-HT2) receptor blocking agent, on the secretion of anterior pituitary hormones was studied in 4 healthy volunteers. Ketanserin (10 mg) was administered as a slow iv injection and its effect was compared with that of saline. Ketanserin influenced neither the basal plasma levels of HGH, ACTH, TSH, LH or prolactin, nor the plasma levels of T4, T3, cortisol or glucose. Even if a single dose of ketanserin had no hormonal effects, this must also be studied after long term use.

Adrenocorticotropic Hormone↗

Transantral orbital decompression in the treatment of Graves' disease.

A series of twenty patients operated on for severe endocrine exophthalmos is presented. All the operations were performed by removing the orbital floor, making a total ethmoidectomy and removing part of the inferior orbital margin; in some cases, a section of the lateral orbital wall was also removed. No serious complications were detected. In all but one patient there was an immediate, marked decrease in exophthalmometry. A marked decrease of the inflammatory signs of the conjunctivae was also observed within a week following surgery.

Adult↗

Transient effect of the combination of insulin and sulfonylurea (glibenclamide) on glycemic control in non-insulin dependent diabetics poorly controlled with insulin alone.

In a double-blind cross-over study we compared the effects of insulin plus glibenclamide, 5 mg twice daily, with insulin plus placebo during 8-week periods on metabolic parameters in 13 non-insulin dependent diabetic (NIDDM) patients poorly controlled with insulin alone. The combination therapy improved diabetic control as assessed by fasting blood glucose (p less than 0.001), 24-hour urinary glucose (p less than 0.01) and glycohemoglobin (HbA1) concentrations (p less than 0.05 at week 12). The effect tended to cease with time. Significantly higher C-peptide values were found during combination treatment than during insulin-placebo (p less than 0.01) and the changes in fasting C-peptide concentrations correlated positively with the changes in HbA1 concentrations (r = 0.56, p less than 0.05). There was no difference in glucagon concentrations, insulin binding to erythrocytes or insulin sensitivity between the two study periods. Neither did the combination therapy influence blood lipids significantly. The present study shows that the combination of insulin and glibenclamide may be of limited value in the treatment of NIDDM patients poorly controlled with insulin alone. However, thus far the long-term results are uncertain. In the absence of significant effects on insulin binding and insulin sensitivity, the improved diabetic control seems to be explained, at least partly, by glibenclamide-induced stimulation of insulin secretion.

Blood Glucose↗

Haemostatic parameters in Cushing's syndrome.

We have studied haemostatic parameters in 12 patients with Cushing's syndrome. Three patients had prolonged bleeding times, and in all seven patients whose bleeding times were measured 3-6 months after surgical treatment the postoperative bleeding times were shorter (mean 7.5 min) than the pretreatment times (mean 12.3 min). In ADP- or adrenaline-induced aggregation the second wave was lacking in six and the degree of aggregation was borderline or subnormal in five patients. One patient had, in addition, a severe defect in collagen-induced aggregation. However, thromboxane B2 production of the platelets from both endogenous and exogenous arachidonic acid was unaffected. Factor VIII:C, RAg and Rcof activities were all elevated, and in patients with severe disease F VIIIR:Ag and F VIII:Rcof activities were markedly more elevated than F VIII:C activity. The changes in both primary haemostasis and in factor VIII activities correlated clearly with the clinical severity of the disease.

Adolescent↗

Failure to suppress C-peptide secretion by euglycaemic hyperinsulinaemia: a new diagnostic test for insulinoma?

In order to study the suppression of C-peptide secretion in 5 patients with insulin-producing tumours or beta cell hyperplasia, we raised and maintained plasma insulin at a high physiological level and kept plasma glucose unchanged for 2 h with combined infusions of glucose and insulin (insulin clamp technique). No suppression of C-peptide secretion was seen in any of the patients, in contrast with a 35-65% decline seen in each of 17 healthy control subjects. In 3 patients surgical removal of beta cell adenoma normalized the response, whereas it remained unchanged in a patient with beta cell hyperplasia after partial pancreatectomy and in another with inoperable carcinoma. These results indicate that insulin secretion by insulinomas is characterized by lack of suppression by insulin. Measurement of the insulin-insulin feedback loop by the clamp technique may provide a rapid test to reveal autonomous insulin secretion without the risk of hypoglycaemia.

Adenoma, Islet Cell↗

Computed tomography of the pituitary fossa in primary hypothyroidism. Effect of thyroxine treatment.

Computed tomography of the pituitary fossa was performed in 12 patients with primary hypothyroidism before and after thyroxine treatment. In three, herniation of the diaphragma sellae precluded accurate measurement of the density of the hypophysis. Eight of the remaining patients showed abnormally increased density of the pituitary gland after intravenous injection of contrast substance which was significantly correlated with the serum TSH-level (r = 0.913, P less than 0.001). After thyroxine treatment the intrasellar density decreased substantially in all but one. We suggest that the observed contrast enhancement reflects increased pituitary circulation associated with the augmented function of TSH-producing cells in response to thyroid hormone deficiency.

Adolescent↗

Glucocorticoid receptors and responsiveness of normal and neoplastic human adrenal cortex.

Glucocorticoids have been postulated to directly inhibit adrenocortical steroid production in laboratory animals. To investigate this in the human, we measured specific [3H]dexamethasone-binding sites in cytosol samples from normal and neoplastic human adrenal tissues. All nine normal adrenocortical samples, six adenomas (four cortisol-producing and two aldosterone-producing), and two hyperplastic adrenocortical samples studied were devoid of measurable specific glucocorticoid-binding activity. In contrast, steroid binding with characteristics of the glucocorticoid receptor (concentration of binding sites, 32-146 fmol/mg cytosol protein; Kd, 1.7-3.1 X 10(-9) M) was readily detectable in cytosol of all three adrenocortical carcinomas and all three pheochromocytomas examined. To elucidate the in vivo role of glucocorticoids as direct regulators of adrenocortical function, five patients with hypopituitarism receiving varying oral maintenance doses of dexamethasone were given ACTH iv. Increasing the orally administered dexamethasone dose from 1 to 8 mg/day did not alter the plasma cortisol response to a 4-h infusion of 250 micrograms synthetic ACTH in these patients. Collectively, these data cast doubt on the proposal that synthetic glucocorticoids directly suppress adrenocortical function in the human. Whether glucocorticoid receptors in tumor tissue could mediate the dexamethasone-induced suppression of hypercortisolism occasionally reported in patients with adrenocortical neoplasia remains to be investigated.

Adolescent↗