Biomedical subjects

S L Karonen

Publications and source records attributed to S L Karonen.

At least 73 records · Page 4Linked to original sources

PubMed1988

Evaluation of salmon calcitonin treatment in bone metastases from breast cancer--a controlled trial.

Salmon calcitonin 100 MRCU/day or a saline placebo were given in daily injections for at least three months to 49 patients with bone metastases from breast cancer in a randomized double-blind trial. All patients were normocalcemic, and most patients had stable or regressing disease at start of trial. No improvement in general performance or bone pain was detected as measured by a visual analogue scale, the daily duration of pain or consumption of analgetic drugs. Calcitonin had no effect on disease progression as judged by bone scans and radiographs. Calcitonin therapy did not affect serum calcium, alkaline phosphatase, bone gla-protein, or the urinary excretion of calcium and hydroxyproline. Serum phosphate and magnesium decreased significantly during calcitonin treatment (p = 0.01, and 0.00005, respectively). It was concluded that salmon calcitonin in this dosage has no discernible effect on skeletal pain, general performance, bone metabolism or disease progression in patients with breast cancer metastatic to bone. A significant decrease in serum phosphate and magnesium probably indicated an effect of calcitonin on the renal excretion of these ions.

Bone Neoplasms↗

PubMed1988

Gastroscopic screening for gastric carcinoids and carcinoma in pernicious anemia.

Among 196 patients examined in 1972-1985 because of pernicious anemia (PA), 105 patients under the age of 76 years were invited for gastroscopic screening, and 71 patients (68%) participated. Gastroscopy revealed carcinoid tumor(s) in 5 patients (7%) but no case of carcinoma. In addition, one patient with gastric carcinoid, 5 patients with adenocarcinomas and one with a concomitant carcinoid and carcinoma had already been diagnosed earlier in the overall PA group on the basis of clinical symptoms. Thus, within a follow-up of 0-20 years (mean 7 years) the total frequency of gastric carcinoid tumors was 4% and that of carcinoma 3%. Patients with carcinoid tumors had a long duration of PA and young age of onset; these cases were not necessarily those with the highest serum gastrin levels. Even though most gastric carcinoids are small subclinical tumors of uncertain clinical significance, their unexpectedly high frequency, combined within the risk of carcinoma in PA, might indicate the need for gastroscopic follow-up, at least in cases of juvenile onset PA.

Adult↗

PubMed1988

Pharmacokinetics of contrast medium in experimental pancreatography.

The pharmacokinetics of a contrast medium in experimental pancreatography of 17 piglets were studied by repeated radiographs of the pancreas and by measuring the concentration of I125-labelled CM in the portal vein, inferior vena cava and in the thoracic duct. Intraduodenal and portal vein injections were performed for comparison. Contrast enhancement of the pancreas after pancreatography was measured by CT. High concentrations of CM were seen in the portal vein 40 seconds after pancreatography, demonstrating direct absorption into the local veins. The concentration of CM in lymph exceeded the systemic concentration 15 minutes after injection, suggesting absorption into lymphatic vessels from the pancreas. CT revealed parenchymal filling of the pancreas even though no acinar filling was seen in normal radiographs. This suggests "invisible" parenchymal filling during normal pancreatography.

Animals↗

PubMed1988

Insulin regulates the serum levels of low molecular weight insulin-like growth factor-binding protein.

The serum levels of 34K insulin-like growth factor (IGF)-binding protein were measured by RIA in 88 type 1 diabetic patients, 9 patients with type 2 diabetes, 7 patients with insulinoma, 19 normal subjects (all after an overnight fast), and 82 normal subjects after a breakfast meal. In addition, the effect of 2- to 3-h euglycemic steady state hyperinsulinemia on serum IGF-binding protein and IGF-1 levels was studied in some subjects in each of the fasted groups. Compared with normal subjects, the mean serum IGF-binding protein levels were 4-fold (P less than 0.001) higher in type I diabetic patients treated with conventional insulin injections, 2.5-fold (P less than 0.001) higher in those treated with continuous sc insulin infusion, and 2-fold (P less than 0.05) higher in patients with type 2 diabetes. In the patients with insulinoma, the mean IGF-binding protein level was 63% below normal (P less than 0.001), and it normalized after removal of the tumor. There was a slight negative correlation between the IGF-binding protein level and insulin dose in the diabetic patients (r = -0.22; P less than 0.05). In normal subjects, serum insulin concentrations were 2-fold higher (P less than 0.001) and the IGF-binding protein level was 29% lower after a meal (P less than 0.05) than in the fasting state. Serum IGF-I concentrations were virtually identical in the type 1 and 2 diabetic patients, insulinoma patients, and normal subjects. During steady state euglycemic hyperinsulinemia, the IGF-binding protein level fell by 40-70% in each group (P less than 0.001), whereas the IGF-I level declined (P less than 0.05) in the type 2 diabetic patients only. The decline of binding protein was closely related to the baseline level (r = 0.94; P less than 0.001). No correlation was found between serum IGF-I and binding protein levels in any group. In conclusion, 1) serum 34K IGF-binding protein levels are elevated in type 1 and 2 diabetic patients and decreased in patients with insulinoma; 2) the serum binding protein, but not IGF-I concentration is decreased by acute hyperinsulinemia; and 3) these data suggest that the serum insulin concentration plays a role in regulation of the serum 34K IGF-binding protein concentration.

Adult↗

PubMed1988

Localization of human malignant tumors with radioiodinated recombinant tissue plasminogen activator.

Human recombinant tissue plasminogen activator (tPA), labeled with 131I(1.1 to 6.2 mCi) by the iodogen method, was administered intravenously to 15 patients with various soft-tissue malignant tumors after blocking of thyroidal radioiodine uptake. Gamma camera imaging was performed 4 and 24 hr after injection; three patients were also imaged 5 days following injection. We observed accumulation of radioactivity in primary and secondary lesions in 11 patients. In this preliminary study we did not detect any definite association between the magnitude of uptake and type of tumor. Tumors were usually visualized already after 4 hr but the uptake was more intense at 24 hr. The target-to-nontarget ratios at 24 hr, determined by computer analysis of stored images, varied from less than 1.2 to 2.1. This is the first demonstration of accumulation of radiolabeled tPA in malignant tissue. We do not know the mechanism of the uptake but because tPA is known to be avidly bound to fibrin, a component of the stroma of many malignant tumors, it is possible that [131I]tPA is bound to fibrin rather than taken up by the malignant cell; various possible cell uptake mechanisms are discussed. Due to the relatively early maximal uptake of this radiopharmaceutical it will be possible to substitute 123I for 131I, a possibility suggesting a potential clinical use of radioiodinated tPA for the detection of malignant tumors of various origin.

Adult↗

PubMed1987

The response evaluation of bone metastases in mammary carcinoma. The value of radiology, scintigraphy, and biochemical markers of bone metabolism.

The correlation between response of metastatic bone lysis and bone pain, various biochemical markers of bone metabolism, and radiological and scintigraphic findings was investigated in 49 women with breast cancer included in a calcitonin supportive therapy trial. All patients had dominant skeletal disease and were on stable systemic treatment (cytotoxic or hormonal) for a least 6 months before the first response evaluation. Bone pain correlated poorly with treatment response. Changes in sclerotic metastases did not show any apparent relation to changes in lytic lesions. A correlation between bone scans and lytic activity on radiographs was found. The absolute level of biochemical bone markers did not correlate with treatment response, but seemed instead to reflect the rate of bone turnover. The relative level of bone markers with respect to baseline showed better correlation to treatment response. The best conventional marker of disease activity was urinary hydroxyproline/creatinine. Propeptide of Type III procollagen (PIIINP), a novel marker reflecting collagen turnover, promises to be at least as sensitive as hydroxyproline. Stable and regressing patients had the same prognosis and significantly longer survival than progressors.

Biomarkers, Tumor↗

PubMed1987

Role of lipase in the pathogenesis of experimental esophagitis in the rabbit.

The role of lipase in the pathogenesis of reflux esophagitis was investigated in an experimental model in which an in situ isolated segment of rabbit esophagus was perfused (at pH 7) with a solution containing lipase in concentrations of 2 and 10 mg/ml. The severity of mucosal damage was assessed using the following indicators of mucosal integrity: transmucosal potential difference, net flux of sodium, and mucosal permeability to erythritol labeled with carbon 14, a neutral molecule with a greatest molecular diameter of 8.2 nm. Furthermore, the morphologic characteristics of esophageal damage were studied by light and scanning electron microscopy. The results suggest that lipase significantly decreased transmucosal potential difference and increased mucosal permeability to sodium and erythritol labeled with carbon 14. Morphologically, lipase induced cytoplasmatic vesiculation and widening of intercellular spaces within the basal cell layer. The epithelial cell layers were also often seen to be sloughed off with consequent exposure of the subepithelial connective tissue at the mucosal surface. The findings suggest that lipase has an adverse effect on the esophageal mucosa that may have pathogenetic significance in clinical reflux esophagitis.

Animals↗

PubMed1987

Blood glucose and plasma insulin responses to fat free milk and low-lactose fat free milk in healthy human volunteers.

The blood glucose and plasma insulin responses to test milk samples were studied in healthy normal volunteers. After an overnight fast the subjects were given 500 ml of either regular fat free milk (approximately 25 g lactose) or 500 ml of a new low-lactose fat free milk (3.75 g lactose and 4.25 g fructose). Blood glucose levels were not significantly altered after either milk sample, but plasma insulin responses were significantly elevated after milk consumption. The response was slightly but not significantly higher after regular fat-free milk than after the low-lactose fat free milk. The results suggest that fat free milk does not exert a fast effect on blood glucose concentration and therefore fat free milk and especially low-lactose fat free milk may prove to be suitable for diabetic diets.

Animals↗

PubMed1987

Micronized oral progesterone increases the circulating level of endometrial secretory PP14/beta-lactoglobulin homologue.

The effect of luteal phase supplementation of micronized oral progesterone, 200 mg daily, on the serum levels of endometrial secretory placental protein 14 (PP14)/beta-lactoglobulin homologue was studied in a double blind/cross-over fashion on five infertile women with apparently normal ovulatory cycles. Blood samples were taken on cycle days 10-12, 20-22 and 24-27, and the serum progesterone and PP14 concentrations were measured by specific radioimmunoassays. In each progesterone cycle the serum progesterone levels were higher than in the corresponding placebo cycle. In each case, the serum concentration of endometrial PP14 was also higher during progesterone than placebo treatment, but this was seen in the late luteal phase only. In view of the previous demonstration of endometrial synthesis of PP14 and the immunological identity between PP14 and progestogen-dependent endometrial protein, these results indicate that endometrial protein secretion can be increased by micronized oral progesterone in infertile ovulatory women whose serum progesterone level is within the normal range.

Administration, Oral↗

PubMed1987

Serum group I pepsinogens during insulin and pentagastrin tests in unoperated and vagotomized duodenal ulcer patients.

The level of serum group I pepsinogens (PG I) has been studied during the conventional insulin-pentagastrin test in 29 duodenal ulcer (DU) patients before and 2 months after proximal selective vagotomy (PSV) and in 31 unoperated DU patients. The mean basal serum PG I level was 191.6 +/- 15.4 micrograms/l (mean +/- SEM) before and 143.7 +/- 24.0 micrograms/l after PSV. A significant increase in mean serum PG I above the initial value was found both in unoperated DU patients and in patients after PSV 1 h after insulin injection. In 29 PSV patients the mean serum PG I showed a paradoxical decrease during the 2nd h after insulin injection, and the mean postvagotomy serum PG I 2 h after insulin injection was significantly (p less than 0.01) lower than the respective preoperative value in the same patients, and the value was close to the basal serum PG I. The low level of serum PG I 2 h after insulin injection in vagotomized patients may reflect the deprivation of the reduced store of PG I in the absence of normal vagal tone. Both the basal serum PG I and serum PG I response during insulin-induced hypoglycaemia showed an overlap between unoperated and vagotomized DU patients. Therefore, serum PG I analyses during the insulin test cannot replace acid secretion tests in the assessment of the completeness of vagotomy.

Adult↗

PubMed1987

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↗

PubMed1986

No association between retinopathy and insulin resistance in type 1 diabetes.

Intact endothelial cell function has been suggested to be important for insulin action. An association between retinopathy and insulin resistance has been found in type 2 diabetes. To evaluate, whether insulin resistance is related to retinopathy in insulin dependent diabetes, we examined 36 type 1 diabetic patients with various degrees of retinopathy: 7 patients had proliferative, 15 had background and 14 patients had no retinopathy. The three groups were matched for age, sex, body weight and insulin dose. Compared with patients with no retinopathy, those with proliferative retinopathy had a longer (P less than 0.05) duration of diabetes (13 +/- 3 vs 22 +/- 3 years for no vs proliferative retinopathy), and higher (P less than 0.05) serum creatinine (74 +/- 4 vs 97 +/- 8 mumol/l), triglyceride (0.69 +/- 0.04 vs 1.02 +/- 0.17 mmol/l) and diastolic blood pressure (77 +/- 3 vs 90 +/- 10 mmHg) levels. The rate of insulin-mediated glucose metabolism (1 mU euglycaemic insulin clamp) was virtually identical in each diabetic group (4.80 +/- 0.42, 4.90 +/- 0.36 and 4.98 +/- 0.74 mg/kg/min) and 40% below that in 8 matched normal subjects (7.53 +/- 0.53 mg/kg/min, P less than 0.001). In conclusion, proliferative retinopathy is related to long duration of diabetes, incipient nephropathy and hypertension. Insulin resistance characterizes the majority of patients with type 1 diabetes but is unrelated to retinopathy.

Adult↗

PubMed1986

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↗

PubMed1986

Effects of dextran 70 versus crystalloids in the microcirculation of porcine hemorrhagic pancreatitis.

The cause of hemodynamic changes occurring during acute pancreatitis remains obscure. Using a pig model of acute hemorrhagic pancreatitis and the reference sample method with 113Tin and 46 Scandium labelled microspheres, blood flow to organs was determined before and five hours after the induction of pancreatitis. Blood pressure, pulse rate and cardiac output were measured hourly. There were two treatment groups. The first group received dextran 70 (5.7 milliliters per kilogram per hour) and saline solution (7.5 milliliters per kilogram per hour) in sufficient amounts to maintain cardiac output at the initial (prepancreatic) level. The second group received saline solution (26 milliliters per kilogram per hour) only and during the experiment the cardiac output was allowed to decrease to approximately one-half of the initial level. In the dextran 70 group, blood flow in various organs stayed at the initial level or was slightly increased. However, in the saline solution group there was a marked and significant decrease in the blood flow in all organs except the antral mucosa, gallbladder and adrenal glands. The changes in the pancreatic fraction of the cardiac output during the experiment were similar to those of other organs in respective treatment groups. In conclusion, adequate infusion of dextran maintains cardiac output and organ microcirculation at the initial level during the early phase of acute hemorrhagic pancreatitis. It is suggested that the hemodynamic changes which develop during acute pancreatitis are mainly secondary to the ensuing hypovolemia and not direct consequences of the pancreatic inflammatory process.

Animals↗

PubMed1985

Modification of dental pain and cutaneous thermal sensitivity by physical exercise in man.

The effect of physical exercise on dental pain thresholds, the release of pituitary stress hormones and thermal sensitivity of skin was tested in healthy human subjects. Different levels of exercise (100-300 W) at different pedal frequencies were produced by a cycle ergometer. Thermal limen (the interval between warm and cool thresholds) determined from glabrous hand, hairy forearm and leg was used as a parameter of thermal sensitivity. In all subjects the heart rate and blood pressure were increased with increasing work load. Dental pain thresholds were elevated at high work loads with a concomitant activation of pituitary stress hormone (especially growth hormone) release. Thermal limens at all 3 sites were increased work load, too, independent of the pedal frequency. The increase of thermal limen was most marked in the leg and least in the glabrous hand. The results indicate that physical exercise produces a non-segmental, load-dependent decrease of pain and thermal sensitivity with a concomitant activation of pituitary stress mechanisms. The magnitude of modification varies with skin region. Activation of inhibitory mechanisms at spinal levels via muscle and proprioceptive afferents, in a way suggested by the gate control theory of pain mechanisms, seems to have only a minor, if any, contribution to the present findings, since a higher pedal frequency did not produce a more marked decrease of sensitivity.

Adrenocorticotropic Hormone↗

PubMed1985

Cytochemical demonstration of estrogen binding sites in breast cancer by estradiol covalently linked to horseradish peroxidase.

17 beta-Estradiol-6-carboxymethyloxime was covalently linked to horseradish peroxidase for the cytochemical demonstration of estrogen binding sites in breast cancer tissue. The affinity of the 17 beta-estradiol-horseradish peroxidase (E2-HRP) conjugate for the estrogen receptor in a human myometrial cytosol preparation was reduced by a factor of about 16 relative to that of 17 beta-estradiol. The estradiol concentration of the E2-HRP conjugate used in the incubations was in the range 2 X 10(-9) -1 X 10(-7) mol/l which, when the reduced affinity of the conjugate is taken into account, corresponds to 1 X 10(-10) -7 X 10(-9) mol/l unbound estradiol. The cytochemical reaction was carried out on cytofuge preparations of cell suspensions of breast cancer tissue. The intensity of the cytochemical reaction was microscopically evaluated by scoring. The results were analyzed in a plot allowing the calculation of an apparent score-max and an apparent Kd value. The reaction intensity was reduced to 20-25% of the control level by a 20-fold excess of 17 beta-estradiol. The cytochemical results correlated positively with the content of estrogen receptors in the cytosol as measured by a validated radioligand method.

Breast Neoplasms↗

PubMed1985

Influence of body composition on insulin clearance.

The effect of body composition on clearance of infused insulin was studied in 21 young normal weight (relative body weight 107 +/- 2%, of ideal mean +/- SEM) healthy subjects. In each subject, the per cent of body weight made up of muscle and fat tissue (% muscle and % fat) were determined. Clearance of insulin was estimated during infusion of insulin at the rate of 40 mU/m2/min under maintenance of normoglycaemia using the euglycaemic clamp technique. Steady-state plasma insulin levels (92.6 +/- 3.2 mU/litre) correlated negatively with % muscle (r = -0.60, P less than 0.01), and positively with % fat (r = 0.55, P less than 0.01). Clearance of insulin was directly related to % muscle (r = 0.60, P less than 0.01), and inversely related to % fat (r = -0.48, P less than 0.01). Steady-state plasma insulin levels or insulin clearance did not correlate with relative body weight. Multiple linear regression analysis revealed a significant multivariate correlation between the rate of insulin clearance versus % muscle and % fat (r = 0.62, P less than 0.02). The changes in % muscle and % fat could predict 37% of the observed interindividual variance of insulin clearance. These results indicate that insulin clearance depends on body composition and is higher in muscular than in adipose subjects. This difference may reflect either a greater distribution space of insulin in muscular as compared to adipose subjects or an influence of body composition on insulin catabolism.

Adipose Tissue↗

PubMed1985

Relation between serum group II pepsinogen concentration and the degree of Brunner's gland hyperplasia in patients with chronic renal failure.

Serum concentrations of group I and II pepsinogens (PG I and PG II) were determined in 15 patients with chronic renal failure. Gastroduodenoscopy with biopsy and acid secretion tests were also performed. Five patients had histologically confirmed severe Brunner's gland hyperplasia manifesting as multiple polyps in the duodenal bulb. Five patients had a mild form of Brunner's gland hyperplasia which was evident only by histological analysis. Five had no signs of such alterations. The three groups of patients were comparable in age, sex, mean level of serum creatinine, mean duration of dialysis treatment, distribution of non-dialysed and dialysed patients, and gastric histology. In patients with severe Brunner's gland hyperplasia the mean serum PG II concentration was significantly higher than in the other patients. Both the serum PG I and the serum PG II concentrations decreased after receiving a well functioning renal transplant in the two patients who underwent transplantation.

Adult↗