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Biomedical subjects

R Pelkonen

Publications and source records attributed to R Pelkonen.

At least 19 recordsLinked to original sources
PubMed1992

Cyclosporin reduces renal prostanoid excretion in type 1 diabetic patients.

Prostacyclin and thromboxane A2 are important regulators of kidney blood flow. To examine whether changes in their metabolism could be involved in the nephrotoxicity of cyclosporin, we determined urinary excretion of 6-keto PGF1a and dinor-6-keto PGF1a (prostacyclin metabolites) and dinor-TxB2 (thromboxane metabolite) in five newly diagnosed type 1 diabetic patients during and after stopping cyclosporin therapy. In the resting state, cyclosporin had no effect on prostanoid excretion. In response to exercise, urinary excretion of 6-keto PGF1a was reduced by 50% (P less than 0.02), dinor-6-keto PGF1a by 15% (P less than 0.05) and dinor-TxB2 by 45% (P less than 0.02), while albumin excretion increased 4.5-fold (P less than 0.05) during cyclosporin therapy. Simultaneously, there was a rise in serum creatinine concentration, and renal biopsy specimens obtained from three patients showed periglomerular and interstitial fibrosis and tubular atrophy. After the discontinuation of cyclosporin therapy, serum creatinine concentrations returned to normal, histological changes improved and there was an associated rise in urinary prostanoid excretion. These data suggest that a reduction in renal prostanoid synthesis by cyclosporin may diminish renal blood flow and function, and lead to histological changes in the kidney.

6-Ketoprostaglandin F1 alpha↗
PubMed1992

Normal renal sensitivity to atrial natriuretic peptide in Gordon's syndrome.

To test the hypothesis that renal sensitivity to atrial natriuretic peptide (ANP) is impaired in Gordon's syndrome (hypertension and hyperkalaemia with normal glomerular filtration rate) we infused alpha-hANP into two patients with this syndrome (a sister and a brother, 19 and 18 years of age). For comparison, 11 healthy volunteers were also examined. The infusion of alpha-hANP increased urinary volume and excretion of sodium similarly in the patients and controls. The excretion of potassium did not change in either the patients or the controls. The infusion of alpha-hANP had no effect on the serum potassium levels or the plasma CO2 content in the patients. The present results do not confirm the hypothesis of lack of sensitivity to ANP as a pathophysiological concept in Gordon's syndrome.

Adolescent↗
PubMed1992

Fuel and fluid homeostasis during long-term exercise in healthy subjects and type I diabetic patients.

OBJECTIVE: This study was designed to examine metabolic and hormonal effects of long-term exercise in healthy subjects and insulin-dependent (type I) diabetic patients. RESEARCH DESIGN AND METHODS: Two studies were performed. First, 16 healthy males (32 +/- 3 yr) were studied during a semitriathlon competition (2 km swimming, 90 km biking, and 21 km running). Second, 9 type I diabetic males (41 +/- 2 yr) and 17 healthy matched control subjects were studied during a 75 km cross-country skiing race. Blood samples were taken before and immediately after exercise, and also during the ski race. RESULTS: During the semitriathlon race, serum insulin, C-peptide, glucagon cortisol, growth hormone ACTH, prolactin, and plasma renin activity increased two- to ninefold, whereas serum testosterone fell. Apart from a fall in magnesium, serum electrolyte concentrations remained unchanged. Before long-term skiing, patients reduced their insulin dose by 30-40%. They were hyperglycemic during the initial part of the race, but near normoglycemic thereafter. There were large interindividual variations in the increments of counterregulatory hormones, whereas serum testosterone and luteinizing hormone fell quite uniformly. Plasma renin activity and aldosterone concentrations rose similarly in diabetic and healthy subjects, whereas the rise in antidiuretic hormone was slightly greater in diabetic patients. During the initial part of the race, serum atrial natriuretic peptide fell in both groups. CONCLUSIONS: Severalfold increments in hormone concentrations contribute to the maintenance of fuel and fluid homeostasis during long-term exercise. With an appropriate adjustment of insulin dose and diet, also type I diabetic patients can participate in competitive long-term exercise.

Adult↗
PubMed1991

Is the treatment of metastatic carcinoid tumor with interferon not as successful as suggested?

Eight patients with metastatic carcinoid tumor, seven of whom had symptoms of the carcinoid syndrome, were treated with either human leukocyte interferon (seven patients) or recombinant alpha-interferon (IFN alpha-2b) (one patient) at doses of 4.5 to 21 x 10(6) IU weekly for 1 to 21 (mean, 8.5) months. Tumor regression on computed tomography (CT) scan was found in one patient, the CT findings remained unchanged in three, and the tumor progressed in four patients. A clearcut and continuing decrease in urinary levels of 5-hydroxyindoleacetic acid (5-HIAA) was observed in one patient and a transient one in four patients. The symptoms improved in only two of seven patients. Four patients had leukopenia develop, which was circumvented by reducing the dose. The authors conclude that interferon therapy of the carcinoid tumor is not as successful as has been suggested in previous reports.

Adult↗
PubMed1991

Testosterone-secreting virilizing adrenal adenoma with human chorionic gonadotrophin receptors and 21-hydroxylase deficiency.

A 60-year-old woman was evaluated for persistently elevated serum testosterone concentrations after bilateral ovariectomy. Her serum cortisol, androstenedione, dehydroepiandrosterone sulphate and 17-hydroxyprogesterone levels were normal, and decreased after dexamethasone administration. Those of testosterone (17.8-18.4 nmol/l) were remarkably high (normal range 0.7-2.8 nmol/l), were not suppressed by dexamethasone, but clearly increased after hCG administration (up to 128 nmol/l). Computed tomography revealed an adenoma in the right adrenal gland and adrenal scintigraphy under dexamethasone suppression visualized this adenoma. A right adrenalectomy was performed. (1) The tumour was histologically and ultrastructurally adrenocortical adenoma of zona reticularis cell type. (2) The adenoma tissue contained hCG receptors (198 fmol/g). (3) During tissue culture both ACTH and hCG were capable of maintaining its testosterone production, which was attenuated with time without stimulation. (4) The adenoma tissue did not elaborate 21-hydroxylated steroids in contrast to normal adrenal tissue. Thus the aberrant endocrine behaviour of this gonadotrophin-responsive testosterone-secreting adenoma of adrenal zona reticularis cell origin can be explained by ectopic functional hCG receptors and the lack of 21-hydroxylase activity.

Adenoma↗
PubMed1991

Obstructive sleep apnoea syndrome in morbidly obese patients.

Twenty-seven morbidly obese patients (13 men and 14 women) with body mass index greater than or equal to 40 kg m-2 were examined. The mean age of the subjects was 36.9 +/- 8.2 years (range 23-51 years), and the mean BMI was 50.2 +/- 6.2 kg m-2 (range 40.0-62.9 kg m-2). A whole-night sleep recording was made for all patients with signs or symptoms indicative of possible obstructive sleep apnoea syndrome (OSAS). If the first nocturnal sleep recording was abnormal, it was controlled after 1 year. Eleven (10 men and one woman) of the 27 patients had an oxygen desaturation index (ODI) of 10 h-1. They were symptomatic with excessive daytime sleepiness or other daytime symptoms of OSAS. The occurrence of OSAS in men and women was 76.9 and 7.1%, respectively. Arterial hypertension was associated with OSAS, but not with smoking or the degree of obesity. Antihypertensive treatment was received by nine of the 27 patients; six of them had OSAS. Thus six of the 11 (54.5%) patients with OSAS and three of the 16 (18.8%) nonapnoeic patients were treated for arterial hypertension (Fisher exact test, P = 0.042). The odds ratio of OSAS for arterial hypertension is 5.2 (95% CI, 0.71-43.6). Vertical-banded gastroplasty was performed in 14 patients, three of whom had OSAS. The selection of patients for gastroplasty was made without taking into account the results of sleep recordings. In the three OSAS patients, a 30-38% reduction in BMI was achieved by surgery. Eight patients with OSAS were treated with an intensified dietary regimen, and the reduction in BMI ranged from -2.6 to 33%. OSAS was either cured or significantly improved in six (55%) patients, with a mean reduction in BMI of 27%, while in patients with persistent OSAS the mean reduction in BMI was only 7%.

Adult↗
PubMed1991

Hormonal changes in severely uncontrolled type 1 (insulin-dependent) diabetes mellitus.

To investigate endocrinological changes associated with severely uncontrolled type 1 (insulin-dependent) diabetes mellitus 27 patients (19 men, eight women) with ketoacidosis or severe ketonuria (= group 1) were examined on admission and after recovery. For comparison 13 non-ketotic patients (seven men, six women), admitted for adjustment of treatment because of poor diabetic control (= group 2), and 20 healthy controls were studied. On admission, the serum testosterone levels in men were lower in group 1 (15.1 +/- 2.0 nmol l-1) (mean +/- SEM) than in group 2 (27.2 +/- 2.8 nmol l-1) (p less than 0.01) and healthy controls (20.6 +/- 2.0 nmol l-1) (p less than 0.05). During treatment the testosterone levels in group 1 rapidly rose to the control level. The serum oestradiol levels in women were low in group 1 both on admission and discharge. The serum prolactin levels were low in female patients in group 1 (119 +/- 17 mIU l-1) compared with the women in group 2 (315 +/- 75 mIU l-1) (p less than 0.05). On admission the serum cortisol levels were higher and their response to 1 mg of dexamethasone was weaker in group 1 than in group 2 and healthy controls. After recovery the serum cortisol levels fell by 15% (p less than 0.01) and the response to 1 mg of dexamethasone returned to normal in group 1. In group 1 during treatment the serum free T4 and reverse T3 levels fell, and the T3 levels rose, whereas the thyroid stimulating hormone (TSH) levels and their responses to TRH remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Pituitary-gonadal hormones and adrenal androgens in non-cirrhotic female alcoholics after cessation of alcohol intake.

To investigate the sex-hormone profiles associated with chronic alcoholism in women we examined 16 non-cirrhotic alcohol abusers (aged 18-46 years). They were admitted for the treatment of alcoholism (duration of 2-16 yrs) to a social hospital for 6 weeks. Their mean daily alcohol consumption was 170 g. Blood samples for serum LH, FSH, prolactin (PRL), oestrone (E1), oestradiol (E2), progesterone (P), 17-alpha-hydroxyprogesterone (17-OHP), androstenedione (A) and dehydroepiandrosterone (DHEA) were drawn three times a week during the hospital stay. Similar blood samples were taken from 10 control women during one menstrual cycle. The cycles were anovulatory in two patients and in none of controls. Serum LH and FSH levels were similar in alcoholic and control women but serum concentrations of PRL were increased 2-4-fold in alcoholic women. In the patients serum, concentrations of E1 and E2 tended to be lower during the follicular and midcycle phases, as did those of P and 17-OHP during the luteal phase. Compared with the controls, serum levels of A were increased 2-3-fold in the patients. A parallel difference between the two groups was seen in serum DHEA concentrations. We conclude that until liver injury, even heavy alcohol drinking has only minor effects on the secretion of gonadotrophins and ovarian steroids. Hypersecretion of PRL and adrenal androgens may well be an initiating mechanism for sexual dysfunction of female alcoholics.

Adolescent↗
PubMed1990

Effects of orchiectomy and polyestradiol phosphate therapy on serum lipoprotein lipids and glucose tolerance in prostatic cancer patients.

In 17 prostatic cancer patients, changes in the plasma lipoprotein pattern, including high density lipoprotein (HDL) subfractions, and in glucose tolerance were compared after 6 months on parenteral polyestradiol phosphate (PEP; Estradurin, 80 or 160 mg/month) with the respective changes in orchiectomized patients. In the estrogen group there was no change in the total serum cholesterol level, whereas in the orchiectomy group an increase of 10% was observed. Estrogen therapy resulted in a significant increase of serum HDL (11%) and HDL2 cholesterol (26%) levels; in the orchiectomy group these fractions remained unchanged. Estrogen therapy induced a significant decrease in total serum triglycerides (24%) and in low density lipoprotein triglycerides (27%); in the orchiectomy group reverse changes were observed. PEP treatment caused changes in the serum lipoprotein pattern, which apparently decreases the risk of atherosclerosis.

Aged↗
PubMed1990

Why should we treat hyperglycaemia?

The life expectancy and quality of life of diabetic patients are largely determined by the long-term complications. Convincing evidence exists to show that the complications are secondary to the altered internal milieu caused by inappropriate insulin action--insulin deficiency in type 1 diabetes and insulin resistance in type 2 diabetes. Genetic factors play only a minor role in the process with the exception of diabetic nephropathy. Of the many metabolic disturbances present in diabetes hyperglycaemia seems to be the most important in this respect. Long-term it has a cumulative effect on the development of background retinopathy in the whole diabetic population and a similar effect on diabetic nephropathy in a genetically predisposed subset. The role of hyperglycaemia in the pathogenesis of macroangiopathy is less clear. Since diabetic microangiopathy is not related to diabetes itself but is secondary to its metabolic consequences, it is--at least in principle--preventable. That this is true has been shown in animal experiments but it has not been proved in human diabetes. There is, however, much evidence suggesting that the incidence of diabetic complications may be diminished when diabetes is well controlled. When the known facts about the rise and fall of the diabetic complications are taken into account the treatment of hyperglycaemia remains as one of the most essential aspects of managing diabetic patients.

Diabetes Complications↗
PubMed1989

A deficient response of atrial natriuretic peptide to volume overload in Gordon's syndrome.

Gordon's syndrome was diagnosed in a 19-year-old woman who had hypertension, hyperkalemia and hyperchloremic acidosis. In family screening, hyperkalemia and hyperchloremic acidosis were also found in the patient's mother and brother. The proband and her brother were studied and showed normal glomerular function with normal renal sodium conservation and urine acidification mechanisms. The levels of plasma aldosterone were normal in both subjects. The renin activity was low in the proband but normal in the brother. Both the basal and the volume-stimulated plasma concentration of atrial natriuretic peptide was low in the two patients. As compared with controls, the kaliuretic response to infusion of sodium chloride was not decreased in the patients. Hydrochlorothiazide promptly corrected the acidosis and the hyperkalemia as well as normalized the raised blood pressure of the proband. We suggest that a deficiency of atrial natriuretic peptide rather than an unusual avidity for sodium chloride reabsorption by the renal tubules plays a significant pathogenetic role in Gordon's syndrome.

Acid-Base Equilibrium↗
PubMed1989

Endocrine abnormalities in patients with adrenal tumours incidentally discovered on computed tomography.

To determine endocrine activity of adrenal tumours incidentally discovered on C.T., we examined 20 consecutive patients. They underwent thorough hormonal assessment and scintigraphic scanning with radioactive cholesterol under dexamethasone suppression (19 patients). Biochemical findings compatible with cortisol hypersecretion were detected in 5 patients. One patient had reduced reserves of cortisol secretion and one had hyporeninemic hypoaldosteronism. The scintigraphy showed no uptake in 10, unilateral uptake in 4, and bilateral uptake in 5 patients. In 3 patients the finding was unilateral on CT. but bilateral on scintigraphy. Signs of autonomous cortisol production were more common among patients who had uptake on scintigraphy. At the operation of 8 patients only benign lesions were found. During the follow-up (9 to 49 months) of the 12 unoperated patients, the tumour disappeared in one and remained unchanged in the others. No changes occurred in the biochemical findings except in one patient whose cortisol response to 1 mg of dexamethasone became abnormal. Since slight hypercortisolism or a bilateral disease often exists behind an incidentally discovered adrenal tumour, we emphasize the importance of careful assessment of cortisol metabolism and a scintigraphic scanning under dexamethasone suppression in the examination of these patients.

17-Ketosteroids↗
PubMed1989

Effect of interferon on glucose tolerance and insulin sensitivity.

Many viral infections induce interferon (IFN) production and cause insulin resistance. To examine the causal relationship between IFN and insulin resistance, we injected natural human leukocyte IFN-alpha (3 x 10(6) IU, i.m.) twice overnight in eight healthy subjects and determined oral (OGT) and intravenous (IVGT) glucose tolerance and sensitivity to insulin (287 nmol or 40 mU.m-2.min-1 euglycemic insulin clamp) the following morning. IFN caused mild influenzalike symptoms and induced a rise in circulating glucose, insulin, hydrocortisone (cortisol), growth hormone, and glucagon concentrations (P less than .05-.001). In the OGT test, the area under the glucose curve was 2.6-fold greater (P less than .02), and the disappearance rate of intravenously administered glucose was reduced by 28% (P less than .05) after IFN administration. The impairment in OGT and IVGT occurred despite augmented insulin response. Insulin-stimulated glucose disposal was reduced by 22% (P less than .005), and insulin clearance increased by 18% (P less than .02) after IFN administration. When the insulin-clamp study was repeated in patients with steady-state hyperinsulinemia that was 12% higher (P less than .005) after IFN, the glucose disposal rate was still reduced by 15% (P less than .01). These data indicate that IFN 1) stimulates counterregulatory hormone secretion, 2) impairs glucose tolerance and insulin sensitivity, and 3) stimulates insulin clearance. Thus, IFN may be involved in the development of insulin resistance during viral infections.

Adult↗
PubMed1989

Stimulation of prostacyclin synthesis by physical exercise in type I diabetes.

We examined the effect of short- and long-term exercise on prostacyclin (prostaglandin I2 [PGI2]) and thromboxane A2 (TXA2) synthesis in type I (insulin-dependent) diabetic patients and healthy control subjects. PGI2 synthesis was assessed by determining the urinary excretion of 6-keto-PGF1 alpha and 2,3-dinor-6-keto-PGF1 alpha and TX synthesis by measuring TXB2 in serum and urine. In the resting state, prostanoid excretion and concentrations were similar in diabetic and control subjects. During 40 min of ergometric cycling exercise, the urinary excretion of 6-keto-PGF1 alpha (a hydration product of vasodilatory PGI2) increased 5.8-fold more in the 12 control subjects than in the 15 diabetic patients (P less than .02). Serum TXB2 concentration rose similarly in diabetic patients and control subjects (P less than .05). During a 75-km competitive cross-country ski race (7 h, 30 min), urinary excretion of 6-keto-PGF1 alpha rose 1.9-fold in 7 diabetic (P less than .05) and 3.3-fold in 10 control (P less than .001) subjects, whereas urinary dinor excretion, reflecting vascular PGI2 synthesis more closely, increased only in the control subjects (P less than .01). Urinary TXB2 excretion remained unchanged in both groups during long-term exercise. These data suggest that diabetic patients have normal PGI2 and TXA2 synthesis in the resting state but diminished PGI2 response to both acute and prolonged exercise.

6-Ketoprostaglandin F1 alpha↗