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Biomedical subjects

M Frölich

Publications and source records attributed to M Frölich.

194 records · Page 11Linked to original sources

Normal prolactin response following thyrotrophin releasing hormone in patients with autonomously functioning euthyroid multinodular goitre.

Twelve female patients (mean age 60 years, range 41--74) with euthyroid multinodular goitre and a flat TRH test (median delta TSH 0.9 muIU/ml, range 0--3.5) had normal prolactin responses to TRH (median data prolactin 48 ng/ml, range 6--115). The results are comparable with those in euthyroid patients receiving full substitution doses of thyroid hormone without increasing T3 and/or T4 levels beyond the normal range.

Adult↗

Plasma levels of triamcinolone acetonide as determined by radioimmunoassay after topical application.

In this paper a method for the radioimmunological determination of triamcinolone acetonide (TAAc) in plasma is described. The antiserum used in the radioimmunological determinations showed high specifity for TAAc; the minimal detectable amount was 0.2 ng. The course of the plasma concentration-time curve of TAAc after intravenous injection into rats was analysed. The concentration of TAAc in the blood of the patients after topical application of the drug is very low. No detectable amount of TAAc was found in the blood of out-patients. Hospitalized patients treated with TAAc under plastic occlusion showed plasma levels ranging from 0.8 to 3.4 ng/ml. This level remained constant throughout the treatment.

Animals↗

The influence of combined cyproterone acetate-ethinyl oestradiol therapy on serum levels of dehydroepiandrosterone, androstenedione, and testosterone in hirsute women.

Serum levels of dehydroepiandrosterone, androstenedione, and testosterone in hirsute women suffering from either idiopathic hirsutism or the polycystic ovary syndrome were determined before and during treatment with cyproterone acetate combined with ethinyl oestradiol. During this treatment the hirsutism decreased markedly. In untreated hirsute women serum dehydroepiandrosterone levels do not differ from those in normal women and do not change during therapy; androstenedione levels are higher than normal and decrease markedly during treatment, and the testosterone levels are elevated compared to normals, with a considerable overlap, and show only a tendency to decrease. There is no correlation between dehydroepiandrosterone and androstenedione levels or between androstenedione and testosterone levels in the serum of untreated hirsute women. After 12-14 months of cyproterone acetate-ethinyl oestradiol therapy a linear correlation is found between dehydroepiandrosterone and androstenedione levels. This can be explained by the relatively higher contribution of the peripheral conversion of dehydroepiandrosterone to androstenedione to the occurrence of lower androstenedione levels. The linear correlation between androstenedione and testosterone after treatment, also found in normal women, indicates the restoration of the role of androstenedione as the major peripheral precursor of testosterone.

Adolescent↗

Growth hormone in blood sampled continuously during pentobarbitone-induced sleep in children.

Growth hormone has been estimated in blood sampled continuously in periods each lasting 30 min during the first 3-4 h of pentobarbitone-induced sleep in 69 children. With only two half-hour samples, almost the same information was obtained as with the estimation of growth hormone in all samples. In this way 95% of normally growing children showed growth hormone levels of 5 muU/ml of more. Children with growth retardation of unknown cause and overweight children showed on the average lower growth hormone levels, not rarely even below 5 muU/ml. Pituitary dwarfs all had maximum growth hormone levels of 3 muU/ml or less. Growth hormone levels during sleep may be normal in children who show negative results on provocation, while subnormal growth hormone levels during sleep have been encountered in some children with retarded growth who had a normal response upon provocation.

Body Height↗

Serum levels of unconjugated aetiocholanolone androstenedione, testosterone, dehydroepiandrosterone, aldosterone, progesterone and oestrogens during the normal menstrual cycle.

The results of daily determination of the levels of gonadotrophins, oestradiol, oestrone, progesterone, aldosterone, dehydroepiandrosterone, androstenedione, testosterone, and aetiocholanolone in the serum of 6 normal, ovulating women are reported and discussed. A pre-ovulatory aldosterone peak and rising values in the luteal phase of the cycle were found. Androstenedione, testosterone, and aetiocholanolone levels were significantly elevated from 3 days before until 3 days after ovulation. Since the mean androstenedione/aetiocholanolone ratio in the individual cycles in this period was similar to the ratio found during the rest of the cycle, we think it unlikely that aetiocholanolone is produced by the ovaries. No correlation was found between the aetiocholanolone patterns and the basal body temperature. In a case of conception followed for 20 days after ovulation, the steroid patterns remained unchanged until the presumed day of implantation, after which the aldosterone, androstenedione, testosterone, and aetiocholanolone levels started to rise. The mean androstenedione/aetiocholanolone ratio during the 10 days after implantation did not differ from the values obtained in the foregoing periods, so direct aetiocholanolone production by the ovaries after implantation seems unlikely.

Aldosterone↗

Assessment of islet isolation efficacy in dogs.

The outcome of islet isolation is considered uncertain because of the large variability of islet and insulin yield, but comparison of the isolated and native islet population has not been attempted. We therefore addressed the efficacy of collagenase digestion, and density gradient purification of islets from the splenic dog pancreas (n = 31) by morphometry of the islet volume and size distribution, and by extraction of insulin and amylase, in samples from the pancreas, the digest, and gradient fractions. In contrast to a approximately 90% recovery of pancreatic insulin and amylase after digestion, islet yield amounted to 50% of the islet content of the pancreas. After density separation, islets were mainly found in the purified fractions, while half of the recovered insulin was located in the acinar fraction of the gradients-indicating a substantial proportion of islets entrapped in acinar fragments. The islet and insulin content of the pancreas correlated well with islet and insulin yield after digestion (r = 0.7, p < .0001). The insulin content of digest suspensions did neither correlate with islet nor insulin recovery in the purified fraction of the gradients (r = 0.4) as opposed to the islet content of digest suspensions, which correlated with both (r = 0.7, p < .0001). After density separation near 100% purity was obtained, and no loss of insulin from isolated islets was demonstrated by extraction and microscopy. Size distributions of native and isolated islets demonstrated no fragmentation. We conclude that the variability of isolation outcome may be attributed to a large extent to the variability of the native endocrine pancreas. Isolation efficacy was best documented by morphometry, because insulin extraction did not discriminate between free and entrapped islets. However, assessment by both morphometry and extraction allowed the quantitation of entrapped islets, and demonstrated preservation of beta-cell granulation. Similar studies should facilitate the analysis of other factors affecting islet isolation in man.

Animals↗

Cell preservation in University of Wisconsin solution during isolation of canine islets of Langerhans.

Allogeneic islet transplantation in Type I diabetic patients is considerably hampered by the variable outcome of islet isolation and purification. After collagenase digestion of the pancreas, islet isolation is traditionally performed under hypothermic conditions in physiological solutions such as Hanks and RPMI. The University of Wisconsin solution (UWS) has been shown superior for hypothermic preservation of the pancreas. We, therefore, compared the UWS and RPMI for canine islet isolation and subsequent purification in either a conventional hyperosmotic density gradient of dextran in Hanks, or a novel normosmotic density gradient of Percoll in UWS. The isolation solution did not affect islet yield before purification (51% of the native islet mass). Loss of amylase (30%) and swelling of the acinar cells were observed in RPMI. In contrast, no loss of amylase and slight shrinkage of the acinar cells were observed in the UWS. Cell swelling affected the density separation and viability of the cells. Dextran density separation resulted in a 15% purity and 41% recovery of the islets isolated in RPMI, as compared to a 93% purity and 52% recovery of islets isolated in UWS. Percoll density separation improved the purity (99%) and recovery (74%) of islets isolated in UWS. Islets isolated in UWS demonstrated a superior basal and glucose stimulated insulin release during perifusion. Electron microscopy demonstrated a well-preserved islet ultrastructure after isolation in both solutions--except for slightly swollen mitochondria after isolation in RPMI. Autotransplantation of islets in pancreatectomised dogs was successful both after isolation in UWS and RPMI. We conclude that prevention of cell swelling during isolation and purification in the UWS resulted in an improved yield of viable and consistent virtually pure islets. Prevention of cell swelling during islet isolation should facilitate the analysis and control of other factors affecting outcome in man.

Animals↗

Glucoregulation after canine islet transplantation: contribution of insulin secretory capacity, insulin action, and the entero-insular axis.

The physiological glucoregulatory mechanisms after islet transplantation have been incompletely investigated. We studied the insulin secretory capacity (ISC) by intravenous arginine stimulation during 35-mM glucose clamps, insulin action during hyperinsulinemic euglycemic clamps, and mixed-meal stimulation at 6-9 mo after intrasplenic islet autotransplantation in 8 dogs, as compared with 30 controls. The enteroinsular axis in the recipients was examined by infusion of porcine glucose-dependent insulinotropic polypeptide (GIP) and human glucagon-like peptide-1 (GLP-1) (7-36 amide) under 8.5-mM glycemic clamp conditions in order to mimic the postprandial glycemia after transplantation. The grafts comprised 25% of the native islet mass, and the ISC likewise averaged 25% of the control value. The postprandial insulin response, in contrast, had increased to 140% after transplantation--albeit with a concomitant glucose excursion to approximately 8.5 mM. Insulin action declined on average by 45% posttransplant. The ISC correlated both with the postprandial glucose excursion and insulin action in the grafted dogs. Insulin action did not correlate with the postprandial glucose excursion. Infusion of GIP had no effect, but GLP-1 nearly doubled glucose-stimulated insulin. Thus, a hyperglycemia-enhanced insulinotropic effect of GLP-1, and perhaps other gut hormones, may account for the difference in the insulin response to the intravenous and oral challenges. Because the ISC reflects the engrafted islet mass and appears to be the primary determinant of glucose tolerance, transplantation of higher islet doses should allow prolonged near-normal glucoregulation--at least in the autotransplant setting.

Animals↗

Differential effects of counterregulatory stress hormones on serum albumin concentrations and protein catabolism in healthy volunteers.

Postoperative hypoalbuminemia occurs frequently; however, the cause of this disorder is not clear. In a double-blind, placebo-controlled study we investigated to what extent hypoalbuminemia and protein catabolism are caused by counterregulatory stress hormones, which play an important role in the metabolic changes that follow surgery. We simulated the postoperative endocrine response in healthy volunteers with a cocktail of the counterregulatory hormones epinephrine, glucagon, and hydrocortisone. Saline was infused as a control in a second experiment. Serum albumin and stress hormone concentrations and nitrogen balance were measured for 34 h and were compared with published values for patients after abdominal surgery. Triple-hormone infusion mimicked the endocrine response after abdominal surgery adequately. It caused a negative nitrogen balance comparable with that after moderately severe surgery but no hypoalbuminemia (serum albumin < 35 g/L), although serum albumin was slightly reduced relative to the control group. No net nitrogen loss or hypoalbuminemia occurred after saline infusion. In conclusion, counterregulatory stress hormones do not cause hypoalbuminemia in healthy volunteers, but do produce protein catabolism.

Diuresis↗