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Biomedical subjects

M Frölich

Publications and source records attributed to M Frölich.

At least 163 records · Page 9Linked to original sources
PubMed1988

Insulin action is normalized in newly diagnosed type I diabetic patients after three months of insulin treatment.

We studied insulin action at submaximal and maximal insulin levels in seven newly diagnosed type I (insulin-dependent) diabetic patients after 2 weeks (t1/2) and after 3 months (t3) of insulin treatment, and in seven control subjects. Insulin action was determined with a sequential euglycemic (5.0 mmol/L) glucose clamp technique using insulin infusion rates of 0.5, 1.0, 2.0, and 5.0 mU.kg-1.min-1 in four periods of two hours each. The final 30 minutes of each infusion period (referred to as steady-state) were taken for the assessment of insulin action. Steady-state insulin levels were similar in the diabetic patients at t1/2 and t3, and in control subjects. During the first and second infusion periods, steady-state glucose infusion rates (SSGIR) were lower at t1/2 than at t3 (12.2 +/- 1.7 v 18.8 +/- 2.4, P less than .05, and 34.3 +/- 3.8 v 47.6 +/- 2.5 mumol.kg-1.min-1, P less than .02, respectively), and were lower at t1/2 compared to controls (12.2 +/- 1.7 v 22.4 +/- 2.3, P less than .01, and 34.3 +/- 3.8 v 47.3 +/- 2.8 mumol.kg-1.min-1, P less than .02). No differences were found during the third and fourth infusion periods between t1/2 and t3, or t1/2 and controls. When these data were used to construct dose-response curves, insulin action was decreased in the diabetic patients at t1/2 at submaximal insulin levels (shift to the right), while insulin responsiveness was unchanged. This finding may be regarded as a still-present manifestation of the metabolic derangement at the onset of the disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1988

Circulating 1,25-dihydroxycholecalciferol after intravenous injections of 1 alpha-hydroxycholecalciferol in patients on regular haemodialysis.

The formation of 1,25-dihydroxycholecalciferol (1,25-(OH)2D3) after single intravenous injections of 1 alpha-hydroxycholecalciferol (1 alpha-OHD3) was examined in four patients with chronic renal failure on regular haemodialysis. Following 1-3 micrograms 1 alpha-OHD3, administered at weekly intervals, 1,25-(OH)2D3 appeared in the circulation within 1 h, and peak concentrations were reached between 2 h and 5 h. By 8 h serum 1,25-(OH)2D3 concentrations had started declining and by 44 h they had returned to baseline after 1 microgram 1 alpha-OHD3, but they were still above basal after 2 and 3 micrograms by an average of 30 pmol/l. One week after injections, concentrations were back to basal in all patients studied. The serum 1,25-(OH)2D3 dose response to injected 1 alpha-OHD3 was linear, indicating ample capacity of the liver 25-hydroxylase to further hydroxylate 1 alpha-OHD3. However, examination of the individual responses revealed lower increments in serum 1,25-(OH)2D3 concentrations in the patients with the highest basal serum 25-hydroxyvitamin D concentrations. Intravenous 1 alpha-OHD3 may be useful in the further study of the interactions between 1,25-(OH)2D3, calcium and PTH in chronic renal failure, as well as of the hepatic metabolism of vitamin D.

Aged↗
PubMed1988

Quantitative assessment of long-term changes in insulin secretion after canine duct-obliterated pancreas transplantation.

In this study, we have quantitatively assessed the changes in insulin-secreting capacity after duct-obliterated segmental pancreatic autotransplantation in dogs. To this end, we have used a technique for the sampling of the complete and undiluted pancreatic venous blood with simultaneous flow measurement, by which means the actual insulin-secreting capacity was determined in a direct fashion. Histologic changes were analyzed in addition in order to address the underlying mechanisms of the changes in insulin-secreting capacity. Intraoperative glucose-stimulated insulin secretion of the left pancreatic lobe was measured before (group I, n = 8), at 6 weeks (group II, n = 5), and at 18-24 months (group III, n = 7) after duct-obliterated segmental pancreatic autotransplantation. At all 3 intervals, histologic analysis was performed. Since the experiments in groups I-III were performed under general anesthesia, a 4th group of dogs (group IV, n = 6) was studied in addition in order to determine the effect of general anesthesia on glucose metabolism. K-values appeared to be reduced to 1/5 and peripheral insulin response (AUC) to about 1/3 of the values obtained from fasting conscious dogs. Although all animals in groups I-III had normal fasting glucose levels and normal K-values at each test interval, a 75% reduction of insulin secretion after duct-obliterated transplantation was observed. Insulin secretion not only showed marked quantitative changes but significant qualitative alterations in glucose-stimulated insulin response were found. Disturbance of functional islet architecture appears to be the main causative factor in the decrease in insulin secretion. If applicable to man, our results indicate that especially the duct-obliterated graft, with its borderline endocrine capacity, is prone to loss of sufficient graft function by the damage induced by eventual rejection crises.

Animals↗
PubMed1988

The significance of the initial FT4-index for the management of single daily dose methimazole treatment of hyperthyroidism.

Since the effectiveness of 30 mg methimazole in a single daily dose in gaining initial control of hyperthyroidism may depend largely on patient characteristics, 52 patients (34 with diffuse and 18 with nodular goitre) were investigated in an attempt to determine the relative importance of a number of pretreatment variables. Return to normal thyroid hormone levels after 2 to 6 weeks of treatment appeared to be the rule, although eight of these patients formed notable exceptions (6-20 weeks). The individual duration of treatment until achievement of biochemical euthyroidism correlated with the initial free thyroxine index (r = 0.75, P less than 0.001) and the free triiodothyronine index (r = 0.70, P less than 0.001). For patients with a diffuse goitre it was also related to the thyroid volume estimated by ultrasound (r = 0.73, P less than 0.001). According to multiple linear regression analysis however these variables were found to have no independent prognostic value. The decrease in thyroid volume during initial therapy, the nature of the goitre, a medication compliance score and various other patient variables did not correlate with the effect of treatment. In 12 cases perchlorate discharge tests were performed. The results suggest continued hormone synthesis in patients with highly active iodine trapping as an important mechanism of the postponed attainment of euthyroidism.

Adult↗
PubMed1988

The effect of calcitonin on growth hormone secretion in man.

To determine whether human calcitonin inhibits GH secretion in man, as has been described for salmon calcitonin, the effect of an i.v. bolus of human calcitonin or saline on GH release after either insulin-induced hypoglycaemia or the administration of GH-releasing hormone (GHRH) or saline was studied. After the injection of calcitonin, no spontaneous GH surges were seen; the GH response to hypoglycaemia was diminished and the response to GHRH almost completely suppressed. Administration of calcitonin also caused a small and transient rise in plasma PRL and TSH but not LH levels, and no change in the integrated PRL or TSH response. Calcium and magnesium levels did not change. It is concluded that human calcitonin suppresses GH secretion in man, but not by suppressing GHRH and probably not by increasing somatostatin release. In addition, calcitonin has limited PRL and TSH-releasing activity.

Adult↗
PubMed1987

Thyroid function in leukaemia patients after allogeneic bone marrow transplantation.

The thyroid function of 29 patients who underwent allogeneic bone marrow transplantation preceded by total body irradiation was followed closely during four weeks after transplantation. Twenty patients showed a marked decrease of T3 and TSH levels, whereas T4 fluctuated. Long-term follow up from three to five years of the surviving 16 patients revealed a restoration of the T3 levels to normal, a slight increase in T4 levels and a doubling of the TSH levels. This indicates the necessity of a higher pituitary drive to maintain euthyroidism. One patient developed hypothyroidism.

Adolescent↗
PubMed1987

Interference by cyclosporine with the endocrine function of the canine pancreas.

This study addresses itself to the eventual interference of cyclosporine (CsA) with the function of pancreatic beta cells in vivo. We have used dogs that had at least six weeks previously been subjected to segmental pancreatic autotransplantation. This model has been well established to be associated with stable normoglycemia but with incomplete endocrine reserve capacity, which renders it suitable for detecting eventual toxic drug effects. CsA was administered for 6 weeks in an oral dose of either 30 mg/kg/day (first series of 4 dogs) or 40 mg/kg/day (second series of 7 dogs). CsA trough levels in blood were determined at least weekly, and the mean of the levels in each dog ranged from 218 to 1274 ng/ml, with one exception (2191 ng/ml). The endocrine function was tested not only before and after 6 weeks of CsA administration, but also at 4 weeks after cessation of CsA administration. The postprandial insulin output was reversibly reduced in the first series (P less than 0.05) and the i.v. glucose-stimulated insulin output was reversibly reduced in the second series (P less than 0.001). Other parameters, like postprandial peak and mean blood glucose levels and K-values, showed reversible changes that, although not always statistically significant, were compatible with a reversible suppressive effect by CsA in all instances. Finally, we found that the severity of suppression as expressed in individual reduction of i.v. glucose-stimulated insulin output correlated with the individual mean CsA trough level (r = 0.71, P less than 0.015). It is concluded that CsA exerts a detrimental effect on the function of canine beta cells in vivo, which effect is reversible and dependent upon the CsA blood level.

Animals↗
PubMed1987

Somatomedin-C levels in treated and untreated patients with acromegaly.

With the aid of a recently developed commercially available radioimmunoassay for Somatomedin-C (Sm-C) we measured the Sm-C levels in 38 controls, 24 untreated acromegalics, 45 inactive acromegalics and five pituitary dwarfs. With the exception of the dwarfs, the age and sex distributions for the various groups were similar. In inactive acromegalics the basal GH level (calculated as the mean of four blood samples taken during the day) was less than 5 mU/l; it was depressed to, or less than, 2.5 mU/l during the 100 g oral glucose tolerance test. The mean Sm-C level found for control subjects was 20.4 +/- 5.1 nmol/l and for untreated patients 85.6 +/- 25.7 nmol/l (mean +/- SD, P less than 0.001). The mean Sm-C level for inactive patients who had undergone surgery and invariably showed a normalized paradoxical reaction to TRH was 18.2 +/- 7.1 nmol/l (NS) vs 16.1 +/- 8.2 nmol/l (NS) for those who underwent surgery plus postoperative pituitary radiation therapy. Only one out of 45 inactive acromegalics exhibited an increased Sm-C level. The Sm-C levels correlated significantly not only with the log GH levels (r = 0.82) but also with the fasting insulin/glucose ratio the integrated incremental insulin levels, the maximal insulin increase and the integrated glucose levels during the oral glucose tolerance test as well as the 24-h urinary excretion of calcium and hydroxyproline.(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗
PubMed1986

Circadian rhythm of prolactin during the menstrual cycle.

Ten women with regular cycles volunteered in a study of the relationship between PRL diurnal rhythm and menstrual cycle. A PRL surge during the afternoon between 2:00 and 8:00 P.M. was observed in the luteal and periovulatory phases, but not in the early follicular phase. The authors advise PRL measurement in the morning between 10:00 A.M. and 12 noon for diagnosing hyperprolactinemia, because morning PRL levels seem to remain constantly low during the menstrual cycle.

Adult↗
PubMed1986

The interaction of growth hormone releasing hormone with other hypothalamic hormones on the release of anterior pituitary hormones.

To determine whether the 29 amino-acid fragment of growth hormone releasing hormone (GHRH) can be combined with other hypothalamic releasing hormones in a single test of anterior pituitary reserve, the responses of anterior pituitary hormones to combinations of an i.v. bolus of GHRH(1-29)NH2 or saline with an i.v. bolus of either LH releasing hormone (LHRH) plus TRH, ovine CRH(oCRH) or saline were studied. Each infusion of GHRH(1-29)NH2 resulted in a rapid increment of the plasma GH value. Infusion of GHRH(1-29)NH2 also caused a small and transient rise in plasma PRL, but no change in the integrated PRL response. The combination of GHRH(1-29)NH2 with LHRH plus TRH caused a larger increment of peak and integrated plasma TSH levels than LHRH plus TRH alone. GHRH(1-29)NH2 did not affect the release of other anterior pituitary hormones after infusion with oCRH or LHRH plus TRH. Because of the finding of potentiation of the TSH-releasing activity of LHRH plus TRH by GHRH(1-29)NH2, the study was extended to the investigation of TSH release after infusion of TRH in combination with either GHRH(1-29)NH2 or GHRH(1-40). In this study the combination of TRH with both GHRH preparations also caused a larger increment of the peak and integrated plasma TSH levels than TRH alone. It is concluded that GHRH(1-29)NH2 possesses moderate PRL-releasing activity apart from GH-releasing activity. In addition, GHRH potentiates the TSH-releasing activity of TRH.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Diurnal changes in serum triglycerides as related to changes in lipolytic enzymes, lipoproteins and hormones in patients with primary endogenous hypertriglyceridaemia on a carbohydrate-rich diet.

Parameters of diurnal triglyceride (TG) metabolism were investigated in 5 subjects with primary endogenous hypertriglyceridaemia and compared with those of normal subjects studied previously. The patients were in a steady state on a carbohydrate-rich diet (meals at 9.00, 13.00 and 17.00 h). Serum TG showed a wavelike pattern with a maximum at around 17.00 h. Post-heparin lipoprotein lipase (LPL) activity in the fasting state was not different from that in normals, but failed to show the normal increase in the fed state (16.30 h). This was due to the inability of patients to increase their adipose tissue (AT)-LPL activity in the course of the day. AT-LPL activity was throughout the day lower than in normal subjects. Skeletal muscle LPL activity was low and showed no diurnal change, equalling our findings in normal subjects. Low density lipoprotein cholesterol and high density lipoprotein (HDL) cholesterol concentrations showed no diurnal change. However, HDL phospholipids increased significantly in the course of the day.

Adipose Tissue↗
PubMed1985

Glucose tolerance and plasma immunoreactive insulin levels in acromegalics before and after selective transsphenoidal surgery.

The glucose and immunoreactive insulin (IRI) responses to a 100 g oral glucose tolerance test (oGTT) administered to 23 acromegalic patients before and after transsphenoidal adenomectomy and to a sex and age-matched control group were studied. The preoperative growth hormone levels, ranging from 11 to 360 mU/l, had normalized (i.e. less than or equal to 5 mU/l) after surgery in all cases. Before surgery paradoxical increases in the GH level, either after i.v. TRH injection or during the oGTT were seen in 14 patients. After surgery, the paradoxical reaction to the oGTT had normalized in all cases and the increase measured after the TRH injection normalized in nine out of 12 cases. The disturbed glucose tolerance (either impaired tolerance or frank diabetes) was cured by surgery. The plasma glucose levels determined 1 and 2 years after surgery did not differ from those found for the control group. Preoperative plasma IRI levels were significantly elevated, whereas after surgery the IRI levels had decreased. Fasting levels were normalized in all patients. Two years after surgery, eight patients still showed some abnormalities of the insulin secretion (as revealed by the integrated sum and the maximum increment in IRI levels during the oGTT) despite the presence of normal circulating GH levels and a normalized paradoxical reaction to TRH. The data show that after normalization of GH levels in acromegalics, increased insulin secretion may still occur after glucose ingestion in some patients. It is suggested that this abnormality could be the result of an increased pancreatic islet beta-cell mass, as a persisting abnormality of the acromegalic state, although peripheral insulin resistance cannot be excluded totally.

Acromegaly↗
PubMed1985

Long-term results of transsphenoidal pituitary microsurgery in 60 acromegalic patients.

Sixty patients with clinically and biochemically active acromegaly were treated by transsphenoidal surgery. All patients underwent a full assessment of pituitary function both preoperatively and postoperatively; these studies were repeated 6 months after surgery and every year, when possible. The mean follow-up period was 3.3 years (range 0.5-7 years). The GH level normalized in 62% of patients after surgery. A paradoxical reaction of GH to TRH was present in 35 patients before surgery and had normalized in 17 after surgery. Large tumours were associated with higher GH levels than smaller tumours. A prognostic factor in terms of normalization of both the GH level and an eventual paradoxical reaction to TRH or a glucose challenge was a low preoperative GH level. Three out of seven patients with either a positive postoperative TRH test but a normal GH level, or a slightly elevated GH level suffered a biochemical and clinical recurrence and two of them underwent reoperation. In contrast, when the TRH test had normalized (always in association with normal GH levels) no recurrence was found. The impact of surgery on the other pituitary functions was generally slight and the numbers of patients with preoperative and postoperative impairment were about equal. Postsurgical radiation therapy was administered to patients with an elevated GH level, a non-normalized TRH test irrespective of whether the GH level had normalized, or local invasion of the tumour. In 11 out of 17 patients with elevated GH levels after surgery, normalization was achieved by radiation therapy after a mean period of 2.7 years. The incidence of pituitary failure after irradiation appeared to be high; gonadal function in men and the GH reserve function were especially vulnerable. From this study we conclude that in many cases the adenoma can be removed effectively, without compromising the other pituitary functions. However, a substantial number of the patients require additional radiation therapy, leading to an inevitable loss of other pituitary functions.

Acromegaly↗
PubMed1985

Glucagon-stimulated plasma C-peptide and insulin levels in active and non-active acromegalics.

The glucagon-stimulated insulin and C-peptide release in patients with active acromegaly, cured acromegalic patients and healthy controls were studied. There was an elevation of the fasting insulin levels in active acromegalics and the fasting C-peptide levels in both patient groups. After i.v. injection of glucagon the insulin and C-peptide levels increased. The highest levels were recorded in active acromegalics, but cured patients also had higher levels than the control group. The insulin/C-peptide ratio was increased in active acromegalics in comparison with that found for inactive acromegalics and normal controls. In addition, the plasma half-lives (T1/2) of endogenous insulin and C-peptide were measured. It was found that the T1/2 for insulin was increased in active acromegalics only. From this study we conclude that even when the treatment of acromegaly is effective insulin and C-peptide secretion do not normalize due, probably, to increased synthesis and release upon stimulation of the pancreatic beta-cells. In active acromegaly the removal of insulin is probably also reduced.

Acromegaly↗
PubMed1985

The effects of duct obliteration and of autotransplantation on the endocrine function of canine pancreatic segments.

This study in dogs addresses itself to the endocrine function of the duct-obliterated left pancreatic lobe (body and tail), which is the portion of the pancreas used for segmental transplantation. The endocrine function was determined with intravenous (i.v.) glucose tolerance tests and expressed in K-values and insulin-response curves. Duct obliteration of the nontransplanted left lobe was associated with normal K-values in the presence of the unmodified right lobe, but with reduced K-values in its absence. Removal of the left lobe while leaving the right lobe untouched was not associated with reduced K-values, but duct obliteration of the whole pancreas was. When the duct-obliterated left lobe was transplanted onto the iliac vessels (segmental autografts), K-values were reduced when compared with the unmodified situation, but were significantly higher than with nontransplanted, duct-obliterated left lobes. Insulin-response curves of nontransplanted, duct-obliterated segments differed both qualitatively and quantitatively from the unmodified situation, but insulin-response curves of duct-obliterated segmental autografts showed only qualitative differences with the unmodified situation. It is concluded that duct obliteration rather than the absence of the right lobe is the predominant cause of reduced glucose tolerance with duct-obliterated left pancreatic lobes. It is suggested that duct obliteration affects the endocrine pancreas both in a qualitative and quantitative fashion. The qualitative effect is similarly demonstrable with segmental autografts and nontransplanted segments, but the quantitative effect is largely dissolved with autografting by virtue of caval as opposed to portal venous drainage.

Animals↗