Biomedical subjects

B Glaser

Publications and source records attributed to B Glaser.

At least 91 records · Page 5Linked to original sources

PubMed1992

Growth-hormone-binding protein in patients with acromegaly.

The present study was undertaken to investigate the possible regulatory effect of chronic exposure to human growth hormone (hGH), in patients with acromegaly, on growth-hormone-binding protein (GH-BP). Nineteen patients with active acromegaly, before, during or after treatment, comprised the subjects of this study. Serum GH was measured by radioimmunoassay and GH-BP by a binding assay with dextran-coated charcoal separation. The specific binding of [125I]hGH (1 ng) obtained with 50 microliters serum was expressed as a percentage of total cpm. To evaluate the impact of the lower GH-BP on GH activity, we studied the effect of acromegalic serum on hGH displacement of [125I]hGH binding to GH receptors in rabbit liver membranes. Compared to normal controls (11.43 +/- 0.37%), the acromegalic patients had low serum levels of GH-BP (5.45 +/- 0.40%; p < 0.001), which correlated negatively with serum GH levels (p < 0.01). In 7 patients, GH-BP normalized within 2-3 months of successful therapy. The lower GH-BP was due to a reduction in binding capacity, whereas binding affinity remained unchanged. Acromegalic serum, with its low GH-BP, resulted in a shift to the left of the GH displacement curve when compared with normal human sera: IC50 values were 7.47 +/- 0.29 and 11.19 +/- 0.84 ng (p < 0.02) for acromegalic and normal human sera, respectively. We conclude that acromegaly is characterized by low levels of GH-BP due to a decrease in serum-binding capacity. The decrease in GH-BP may render the acromegalic serum GH relatively more active in the GH receptor assay.

Acromegaly↗

PubMed1992

Glycosylated serum protein levels assayed with highly sensitive immunoradiometric assay accurately reflect glycemic control of diabetic patients.

OBJECTIVE: To develop a sensitive and reliable immunoreadiometric assay to measure glycosylated lysine residues on serum proteins (GSP) and to evaluate its efficacy in monitoring glycemic control. RESEARCH DESIGN: The effect of acute and chronic in vitro and in vivo changes in glucose levels on GSP concentration was evaluated. GSP determinations from insulin-dependent diabetic (IDDM) patients, non-insulin-dependent diabetic (NIDDM) patients, and control subjects were correlated with other indices of glycemic control. RESULTS: The GSP levels were unaffected by acute glucose changes after food or intravenous glucose administration but increased during storage at -20 degrees C due to in vitro glycosylation by endogenous glucose. Immediate acidification of the serum prevented this, permitting long-term storage despite high ambient glucose levels. In randomly selected diabetic patients, 96% of GSP values were greater than the mean +3SD of nondiabetic control subjects. In diabetic patients, GSP levels correlated with mean plasma glucose concentrations (Kendall correlation statistics 0.47, P less than 0.001), fasting plasma glucose levels (Kendall statistics 0.42, P less than 0.001), and glycosylated hemoglobin (GHb, Kendall statistics 0.30, P less than 0.005). Induction of near-normal glycemia in poorly controlled NIDDM patients reduced GSP levels with a slope consistent with a half time of disappearance of 4.7 +/- 0.4 days. GSP levels remained elevated in 6 of 10 well-controlled NIDDM patients, despite normal GHb concentrations. Chronic hypoglycemic states, like pregnancy and hyperinsulinemic hypoglycemia, were associated with significantly low GSP levels. CONCLUSION: We describe a reproducible and sensitive immunoradiometric assay for GSP that closely reflects the degree of glycemic control in diabetic patients. Further studies are needed to determine whether this assay may be useful in screening for glucose intolerance or gestational diabetes.

Blood Glucose↗

PubMed1992

Acute and chronic effects of dexfenfluramine on glucose and insulin response to intravenous glucose in diabetic and non-diabetic obese subjects.

Fenfluramine improves glucose tolerance in obese subjects independently of its anorectic effect. Increased insulin action has been reported, but such an effect may be secondary to reduced hyperglycemia following augmented insulin secretion. For this reason, we investigated whether the dextro-enantiomer of fenfluramine (dexfenfluramine, dF) has a direct effect on insulin secretion using the glucose infusion test, a technique that can also be used to indirectly evaluate insulin action. Ten lean controls (BMI 21 +/- 0.4 kg/m2), 9 non-diabetic obese subjects (BMI 32.3 +/- 1.1) and 10 obese mild non-insulin dependent diabetics (BMI 36 +/- 2.6, fasting plasma glucose (FPG) 7.9 +/- 0.9 mmol/l) were studied with a random, double blind cross-over protocol. Each subject received 15 mg dF (or placebo) twice daily for 3 days prior to glucose infusion; 30 mg dF (or placebo) were given 90 min before the test. Obese control and diabetic subjects continued treatment with either dF or placebo for one month after which they were retested. There was no significant change in weight or fasting plasma glucose or insulin in any group. Biphasic insulin secretion was demonstrated in both non-diabetic groups, whereas a complete lack of first-phase and a delayed and reduced second phase insulin response was demonstrated in the diabetic subjects. There was no acute or chronic (obese subjects) effect of dF on insulin secretion in any group. In lean control subjects, plasma glucose curves during glucose infusion were unchanged by dF, whereas in non-diabetic obese subjects the glucose slope was improved after both acute and chronic dF, implying augmented glucose disposal. In diabetic patients, no significant acute or chronic effect of dF on glucose response was registered. When all obese subjects were re-grouped according to fasting plasma insulin levels (FPI) and not glucose tolerance, those with relative fasting hyperinsulinemia (> 100 pmol/l, mean +/- SE = 144 +/- 12 pmol/l) showed significant improvement of insulin action after dF, whereas those with low FPI (< 100 pmol/l, mean +/- SE = 65 +/- 7 pmol/l) did not. These findings, together with previously published results of improved insulin action in diabetics during hyperinsulinemic clamps, suggest that dF-mediated improvement in glucose clearance may require substantial plasma insulin concentrations.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

PubMed1992

Sigmoid volvulus presenting as chronic secretory diarrhea responsive to octreotide.

Secretory diarrhea can be seen in a variety of pathologic states; however, intermittent colonic obstruction usually is not considered as a possible cause. We report a 68-yr-old patient with chronic secretory diarrhea and hypokalemia due to intermittent sigmoid volvulus. Because the volvulus was not originally diagnosed, the patient was treated with the long-acting somatostatin analogue octreotide for 1 yr, with marked clinical improvement. Surgical resection of the redundant sigmoid responsible for the volvulus resulted in prompt and complete resolution of all signs and symptoms. Detailed macroscopic and microscopic examination of the resected specimen was normal. The patient continues to be asymptomatic 12 months after surgery. Increased colonic fluid and electrolyte secretion was caused by intermittent sigmoid volvulus and resulted in chronic secretory diarrhea.

Aged↗

PubMed1991

Effect of 6-month gliclazide treatment on insulin release and sensitivity to endogenous insulin in NIDDM: role of initial continuous subcutaneous insulin infusion-induced normoglycemia.

In 10 obese, new-onset non-insulin-dependent diabetes mellitus (NIDDM) patients (group A), continuous subcutaneous insulin infusion (CSII) was used to induce normoglycemia during 14 days. Fasting blood glucose was 4.6 +/- 0.2 mmol/L and mean daily blood glucose 5.8 +/- 0.2 mmol/L at the end of the CSII period. This excellent glycemic control was obtained with 35 +/- 4.8 U of insulin per day, corresponding to 0.47 +/- 0.06 U/kg/24 hours. Endogenous insulin production was markedly suppressed, since urinary C-peptide was reduced from 18.5 +/- 0.12 to 7.9 +/- 0.25 nmol/24 hours. Gliclazide was given to group A following CSII, and to five obese NIDDM patients (group B) in their habitual hyperglycemic state. Gliclazide maintained in group A, and induced in group B, excellent metabolic control. This was accompanied by the appearance of a small first-phase insulin response to intravenous glucose, and significant increases in the mean-daily-insulin to mean-daily-blood-glucose ratio, as well as in the 24-hour urinary C-peptide-to-glucose ratio. The gliclazide effects tended to be more pronounced in group A. No significant effect was seen on efficacy of endogenous insulin (slope of disappearance of blood glucose divided by insulin levels). During 6 months of gliclazide treatment, excellent glycemic control was maintained in all patients. This was paralleled by unchanged stimulation by gliclazide of first-phase insulin response to glucose, and augmented mean 48-hour insulin-to-glucose and urinary C-peptide-to-glucose ratios. No change in the ratio of glucose disposal to endogenous insulin was noted. We conclude that physiologic insulin replacement may induce normoglycemia in NIDDM, indicating that insulin resistance is not of clinical significance; gliclazide has a beta-cell-stimulating action that is maintained quantitatively unchanged for at least 6 months; the therapeutic effect of gliclazide in NIDDM seems to be mainly, if not exclusively, the result of its beta-cytotrophic action. Initial normoglycemia, induced here by CSII, may have a lasting enhancing effect on the gliclazide action.

Blood Glucose↗

PubMed1991

A new technique for explantation and in vitro cultivation of chicken embryos.

A technique is described for explanting and cultivating chicken embryos in plastic drinking cups which have been modified with plastic wrap to reproduce the geometry and dimensions of the egg shell. Successful explantation rates of 97% are possible with a double-window technique, and survivability in cups exceeds that achievable in other in vitro systems (i.e., petri dishes). Long-term survival to the 21st day of incubation is seen routinely. This system with cups is less expensive than that with petri dishes, and simpler than that with plastic wrap/tripods. Thus, this new method of in vitro cultivation of chicken embryos improves upon explantation rate, survivability and system design, and has a wide range of applications in developmental biology, angiogenesis, cancer, and pharmacology research.

Animals↗

PubMed1991

Effect of 6 months' gliclazide treatment on insulin release and sensitivity to endogenous insulin in NIDDM: role of initial CSII-induced normoglycemia.

In 10 obese, newly diagnosed non-insulin-dependent diabetes mellitus (NIDDM) patients (group A) continuous subcutaneous insulin infusion (CSII) was used to induce normoglycemia over a period of 14 days. Fasting blood glucose was 4.61 +/- 0.22 mmol/l and mean daily blood glucose 5.83 +/- 0.27 mmol/l at the end of the CSII period. This excellent glycemic control was obtained with 35 +/- 4.8 U insulin per day, corresponding to 0.47 +/- 0.06 U/kg/24 h. Endogenous insulin production was markedly suppressed, since urinary C-peptide was reduced from 56 +/- 0.35 to 24 +/- 0.76 micrograms/24 h. Thus, physiological insulin replacement induced normoglycemia in NIDDM, indicating that insulin resistance is not clinically important. Gliclazide was given to group A following CSII and to 5 obese NIDDM patients (group B) in their habitual hyperglycemic state. Gliclazide maintained in group A and induced in group B excellent metabolic control. This was accompanied by the appearance of a small first-phase insulin response to iv glucose and by significant increases in the mean daily insulin to mean daily blood glucose ratio and in the 24-h urinary C-peptide to glucose ratio. The gliclazide effects tended to be more pronounced in group A. No significant effect was seen on sensitivity to endogenous insulin (slope of disappearance of blood glucose as function of insulin response to glucose infusion). During the 6 months of gliclazide treatment, excellent glycemic control was obtained in all patients. This was paralleled by unchanged stimulation by gliclazide of first-phase insulin response to glucose as well as mean by 48-h insulin to glucose and urinary C-peptide to glucose ratios. Again, sensitivity to endogenous insulin was not augmented. We conclude that gliclazide has a beta-cell-stimulating action which is maintained quantitatively unchanged for at least 6 months. The therapeutic effect of gliclazide in NIDDM seems to be mainly, if not exclusively, the result of its beta-cytotrophic action. Initial normoglycemia, induced here by CSII, may have a lasting enhancing effect on gliclazide action.

Blood Glucose↗

PubMed1991

Unusual causes of I-131 metaiodobenzylguanidine uptake in non-neural crest tissue.

Three patients with clinical suspicion of pheochromocytoma were studied with metaiodobenzylguanidine (MIBG) labeled with I-123 or I-131. In these three patients, marked uptake of the radiopharmaceutical was demonstrated in tissues that were subsequently proven not to be of neural crest origin. Furthermore, extensive biochemical evaluations and long-term followup definitively excluded pheochromocytoma in all three. Therefore, these three cases represent unexpected "false-positive" MIBG uptake.

3-Iodobenzylguanidine↗

PubMed1991

Sebum measurements for rapid identification of hyperandrogenism due to an ovarian Leydig cell tumor.

Direct measurements of sebum with the Sebumeter were used in a patient with a benign androgen-producing tumor of the ovary. Androgen levels fell immediately after surgery, whereas the markedly elevated sebum levels found preoperatively dropped to normal after a delay of more than 2 weeks. Therefore, the Subumeter, due to its simplicity, may be useful for the preliminary screening and follow-up of patients with hyperandrogenic states.

Aged↗

PubMed1990

Persistent hyperinsulinemic hypoglycemia of infancy ("nesidioblastosis"): autosomal recessive inheritance in 7 pedigrees.

Persistent Hyperinsulinemic Hypoglycemia of Infancy (PHHI) is a rare disease characterized clinically by persistent hypoglycemia with inappropriately elevated circulating insulin concentrations. Here we report on 7 pedigrees including 21 cases. The pedigrees are derived from 3 distinct ethnic groups, and include a very large Bedouin family, and Arab family, and 5 smaller pedigrees of Jewish families all of Eastern European origin. Data obtained from these families and from other families reported in the literature strongly suggest that PHHI is inherited as an autosomal recessive disorder.

Female↗

PubMed1990

Regulation of insulin release in persistent hyperinsulinaemic hypoglycaemia of infancy studied in long-term culture of pancreatic tissue.

Pancreatic tissue was obtained during therapeutic subtotal pancreatectomy from five infants with persistent hyperinsulinaemic hypoglycaemia of infancy (so-called nesidioblastosis). Collagenase digests of the specimens were cultured in RPMI 1640 medium on extracellular matrix-coated plates. Acute insulin secretion showed minimal sensitivity to changes in glucose concentration. Sensitivity to other nutrient secretagogues such as glyceraldehyde, leucine, alpha-ketoisocaproic acid and arginine was variable, showing either diminished or absent response. On the other hand, stimulators of Beta cell cAMP and modulators of the phosphoinositide-protein kinase C pathway were effective inducers of insulin release. The response to cAMP stimulators was independent of the glucose concentration. Although insulin output was high in the absence of glucose, this was not due to passive leak of hormone, since both removal of calcium and addition of somatostatin and epinephrine inhibited the secretion. Beta cells were more sensitive to somatostatin than epinephrine; however, both agents failed to completely suppress the release even at suprapharmacological concentrations. Although it cannot be excluded that the culture conditions affected Beta cell function, the present findings may suggest that cultured Beta cells in persistent hyperinsulinaemic hypoglycaemia of infancy behave like fetal Beta cells at early developmental stages.

Cells, Cultured↗

PubMed1990

Long-term treatment with the somatostatin analogue SMS 201-995: alternative to pancreatectomy in persistent hyperinsulinaemic hypoglycaemia of infancy.

Nine patients with persistent hyperinsulinaemic hypoglycaemia of infancy (PHHI), aged 3 days to 11 months, received octreotide therapy at a dose of 5-10 micrograms s.c. every 4-8 h according to glucose response. The response to octreotide was variable and unpredictable. Two patients could not be weaned off intravenous glucose and 2 others could be weaned off but required continuous nasogastric feedings. In the remaining 5 patients relatively normal feeding schedules were instituted. Long-term ambulatory treatment is an attractive alternative to surgery in such patients if the family can cope with the injections and dietary regimens. Although octreotide suppresses growth hormone secretion, all patients continue to grow during octreotide treatment.

Birth Weight↗

PubMed1990

Binding of basic fibroblast growth factor to normal and neovascularized rabbit cornea.

The labeling pattern of frozen sections of rabbit cornea incubated with radioiodinated basic fibroblast growth factor (bFGF) was investigated in normal corneas and prostaglandin-induced neovascularized corneas by autoradiography followed by image analysis. 125I-bFGF binds to Bowman's, Descemet's, and vascular basement membranes in a dose-dependent manner. The specificity of the binding of bFGF to basement membrane was demonstrated by the following experiments: 1) an excess of unlabeled growth factor displaced the labeling; 2) histones did not modify the labeling; and 3) 2 M NaCl washing and enzymatic treatment with heparitinase prevented binding of labeled growth factor without apparent destruction of the overall structure of the basement membrane. Our results suggest that bFGF binds to the heparan sulfate proteoglycan of basement membranes. Both normal limbal vessels and the newly formed corneal vessels exhibited the same type of labeling but with different intensities, according to the degree of maturation of the new vessels. bFGF binding also is located clearly on the endothelial cells in both types of vessels. This second binding site could correspond to the high affinity receptors on the cell surface and suggests a direct interaction of bFGF with endothelial cells during new vessel formation.

Alprostadil↗

PubMed1990

Chronic treatment of a benign insulinoma using the long-acting somatostatin analogue SMS 201-995.

The newly developed long-acting somatostatin analogue SMS 201-995 was used to treat a patient with the presumptive diagnosis of benign insulinoma. Although intermittent injections with 50-100 micrograms s.c. every 8 h failed to produce any clinical improvement, continuous s.c. infusion with 150-300 micrograms/day prevented the hypoglycemic episodes absolutely, both during normal dietary intake and throughout 72 h of fasting. Chronic treatment (to date 30 months) has not been associated with any evidence of tachyphylaxis or rebound hypersecretion of insulin.

Adenoma, Islet Cell↗

PubMed1990

[Somatostatin analogue in the treatment of neuroendocrine gut tumors].

Somatostatin is a short-acting natural peptide secreted by specialized cells in the GI tract, the central and peripheral nervous systems, and a variety of other tissues. Its many actions include suppression of the secretion of GH, TSH, GI hormones, and inhibition of GI exocrine secretion. A long-acting analogue developed by Sandoz (Sandostatin, SMS 201-995) has been used to treat acromegaly and neuroendocrine tumors. We report our experience with it in carcinoid tumors (4 cases), glucagonomas (2), gastrinoma (1), VIPoma (1) and nonfunctioning islet cell tumor (1). It was given by continuous subcutaneous infusion, using a small portable pump, in doses ranging from 300 to 1500 mcg/day, without significant side-effects. 7 of the 9 patients had complete relief of symptoms, and tumoral hormone secretion decreased in 4 of the 5 in whom it was measurable, but there was no evidence of tumor regression. SMS 201-995 is useful for the symptomatic treatment of patients with neuroendocrine gut tumors.

Adenoma, Islet Cell↗

PubMed1989

Gastrin-producing ovarian cystadenocarcinoma: sensitivity to secretin and SMS 201-995.

We report a patient with severe peptic ulcer disease and a right ovarian mass that was found to be a gastrin-producing cystadenocarcinoma. Gastrin production by the tumor was stimulated by secretin and inhibited by the long-acting somatostatin analogue SMS 201-995. Following resection of the tumor, serum gastrin levels and the gastrin response to secretin returned to normal. Histologic examination, including Alcian blue staining for mucin and immunoperoxidase staining for gastrin, revealed gastrin at the base and mucin at the apex of the tumor cells. This report demonstrates secretin stimulation and somatostatin inhibition of gastrin secretion from a cell that is apparently not of endocrine origin.

Cystadenocarcinoma↗

PubMed1989

Persistent hyperinsulinaemic hypoglycaemia of infancy: long-term treatment with the somatostatin analogue Sandostatin.

Six infants with severe, persistent hyperinsulinaemic hypoglycaemia were treated with the long-acting somatostatin analogue SMS 201-995 (Sandostatin, Sandoz, Basle, Switzerland). Effective control of hypoglycaemia without the need for parenteral glucose was achieved in five of the six cases with doses ranging from 10 to 40 micrograms/kg day given either by four s.c. injections per day, or by continuous subcutaneous infusion (CSI). One has been well controlled on SMS 10 micrograms/kg day for 17 months as an out-patient without requiring surgery, while the five others underwent sub-total pancreatectomy after receiving short courses of the drug. In two patients where hypoglycaemia persisted after sub-total pancreatectomy SMS was effective in inhibiting insulin secretion and preventing hypoglycaemia. Plasma somatomedin concentrations and linear growth were not suppressed in any patient. It is concluded that Sandostatin is useful in the pre and post-operative management of most infants with this syndrome. In selected cases this analogue of somatostatin may also be a long-term treatment option in place of pancreatectomy.

Blood Glucose↗

PubMed1989

Lipid cell tumor of the ovary: steroid hormone secretory pattern and localization using 75Se-selenomethylcholesterol.

Ovarian lipid cell tumors are rare and can be difficult to localize by conventional means. We report a postmenopausal patient where rapid progression of symptoms and very high sebum levels suggested the presence of such a tumor which could not be visualized by computed tomography or ultrasound. Localization was accomplished noninvasively using 75Se-selenomethylcholesterol. Peripheral and ovarian vein steroid concentrations suggest that the tumor produced androgens preferentially by way of the delta 4 steroidogenesis pathway.

Adrenal Rest Tumor↗