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Biomedical subjects

T J Merimee

Publications and source records attributed to T J Merimee.

At least 37 records · Page 2Linked to original sources

Insulin-like growth factors in vitreous. Studies in control and diabetic subjects with neovascularization.

Vitreous and serum were obtained at the time of vitrectomy from 23 diabetic subjects with proliferative retinopathy and from 8 nondiabetic subjects. The mean concentration of IGF-I in vitreous from diabetic patients with neovascularization was 6.3 +/- 0.93 versus 2.7 +/- 0.96 ng/ml. Chi-square and rank analysis indicated that higher concentrations of IGF-I occurred in diabetic vitreous (P less than 0.01 by both analyses). IGF-II concentrations in vitreous of control and diabetic subjects were not significantly different. A positive correlation existed between the concentrations of IGF-I and IGF-II in vitreous and their concentrations in serum in diabetic subjects, but not in control subjects. When vitreous concentrations of IGF-I were calculated for diabetic subjects studied previously with rapid acceleration of retinal disease, these concentrations varied from 20 to 30 ng/ml. The concentrations of IGF-I in the vitreous of most diabetic subjects with severe neovascularization are thus in the range known to stimulate cellular differentiation and growth in several systems. Whether they do so in the eye, and thus contribute to the development of retinopathy, remains to be determined.

Adult↗

Effect of psychosocial factors on success in a program of self-glucose monitoring.

We examined prospectively the relationship of psychosocial factors to glycemic control in a program of self-glucose monitoring (SGM). Measured intelligence (IQ), educational level, and socioeconomic status (assessed by the Two-Factor Index of Social Position) were determined in 25 patients who were followed during 6 months of self-glucose monitoring. Personality categories, reflecting degrees of psychological disturbance, were assigned using the Minnesota Multiphasic Personality Inventory (MMPI). None of the measured psychosocial variables correlated significantly with initial Hgb A1 values. In contrast, after 6 months of SGM, Hgb A1 levels correlated significantly with both socioeconomic status (r = 0.42, p less than 0.05) and educational levels (r = -0.42, p less than 0.05). Hemoglobin A1 levels also correlated significantly with the recorded frequency of SGM (r = -0.65, p less than 0.01), a measure of patient compliance. No significant correlation between IQ and Hgb A1 levels was seen, either initially or during follow-up. High A1 values differed significantly among groups classified by MMPI testing. Patients with severe psychological abnormalities had higher (p less than 0.05) mean Hgb A1 levels. We conclude that psychosocial factors, but not measured intelligence, have an important bearing on patient success in a program of SGM.

Adult↗

Elevated L-xylulose concentrations in serum: a difference between type I and type II diabetes.

L-Xylulose, which can be derived from glucose directly or from mucopolysaccharide degradation, was measured in serum samples from 61 diabetics and 42 controls. All serum samples from the controls were negative for L-xylulose. Fifteen of 30 adult-onset diabetics, in contrast to only four of 31 juvenile-onset diabetics, had detectable L-xylulose levels. This difference between adult-onset and juvenile-onset diabetics was significant at the 0.001 level. Detectability of L-xylulose in serum did not appear to be influenced by the fasting mean or peak serum concentration of glucose. Mean serum concentrations of growth hormone did not correlate with L-xylulose levels. The reason for the variation of L-xylulose between type-I and type-II diabetic subjects could not be identified. We would postulate a variation in the degradation of glycosaminoglycan. These results support the view that type-I and type-II diabetes are different diseases.

Blood Glucose↗

Insulin-like growth factors in amniotic fluid.

The concentrations of insulin-like growth factors I and II (IGF-I and IGF-II) in amniotic fluid were determined by specific immunoassays in 58 women. IGF-I concentrations were constant throughout gestation at approximately 20 ng/ml; the mean IGF-II concentration was 114 +/- 13 (+/- SE) ng/ml at the earliest period of gestation studied and remained unchanged at 26 to 33 weeks despite a greater than 50% decrease in amniotic fluid total protein. A precipitous decrease in IGF-II concentration occurred at term which was not explainable by alterations in total amniotic fluid protein concentration. The concentrations of IGF-I and IGF-II in amniotic fluid did not correlate with concentrations of these factors in maternal serum (r = 0.08 and 0.09, respectively). [125I]IGF-I and [125I]IGF-II, after incubation with amniotic fluid, bound to a 40-45 K protein (or proteins). A carrier protein of greater mol wt, as in serum, was not detected. These findings indicate that there is dynamic control of IGF in amniotic fluid during normal pregnancy.

Amniotic Fluid↗

Von Willebrand factor (VIII R:Ag), fibronectin, and insulin-like growth factors I and II in diabetic retinopathy and nephropathy.

We have measured plasma von Willebrand factor (VWF) as the factor VIII-related antigen, plasma fibronectin, and two of the serum somatomedins, insulin-like growth factor I (IGF I) and IGF II, in 51 diabetic patients and 25 nondiabetic control subjects. VWF was significantly higher in the diabetic group than in the controls (173 +/- 9% SEM versus 101 +/- 9%, P less than 0.001), as has been reported by others. However, within the diabetic group there was no significant difference in VWF between those patients without retinopathy, those with background or proliferative retinopathy, or those with macular edema. There was also no difference in VWF between the diabetic subjects with and those without proteinuria. These results rule against a previously advanced hypothesis that the increase in VWF in patients with diabetes is secondary to microangiopathy. No significant difference was observed in fibronectin, IGF I, or IGF II between the diabetic and control groups, between the diabetic group without retinopathy and the retinopathic subgroups, and between the diabetic subjects with and without proteinuria. In the diabetic patients, there was no correlation between diabetic control as assessed by glycosylated hemoglobin and glycosylated serum protein, and the plasma levels of VWF, fibronectin, IGF I, or IGF II. The results of this study strongly suggest that neither plasma VWF, fibronectin, IGF I, nor IGF II plays an important primary role in the pathogenesis of diabetic microvascular disease, although one or more of these factors might play a permissive role.

Adult↗

Effect of glycemic control on serum insulin-like growth factors in diabetes mellitus.

We investigated the effect of improving glycemic control on serum concentrations of insulin-like growth factors I and II (IGF-I and IGF-II). In 22 adults followed during an intensive home glucose monitoring program for 6 mo, no effect of improving control was seen on either IGF-I or IGF-II. Similar results were obtained in young diabetic children less than 10 yr of age and in diabetic adolescents with detectable puberty before entering the study. In older diabetic children without evidence of puberty before treatment (Tanner prepubertal stage 1), initial IGF-I concentrations were low, but increased during establishment of glycemic control. Puberty developed during therapy in this latter group. Our data do not support a "global" effect of glycemic control on serum IGF-I in diabetic patients. Increases of IGF-I with better glycemic control appear most likely to occur when the metabolic consequences of diabetes have suppressed normal pubertal increases of IGF-I. IGF-II concentrations were unaffected by glycemic control in all subjects.

Adolescent↗

Insulin-like growth factors. Studies in diabetics with and without retinopathy.

To determine whether two insulin-like growth factors (IGF I and IGF II) influence the course of diabetic retinopathy, we measured the concentrations of these factors in 80 adult patients with diabetes and in 62 control subjects. In seven patients with Type I diabetes and rapidly deteriorating vision as a result of proliferative and exudative retinopathy, the serum concentration of IGF I was 722 +/- 41 ng per milliliter (mean +/- S.E.M.), as compared with 381 +/- 48 ng per milliliter in 26 patients who had Type I diabetes without retinopathy or with less severe forms of it, and 302 +/- 15 ng per milliliter in the controls (P less than 0.001 for both comparisons). Serum concentrations of IGF II were normal in subjects with Type I diabetes but were somewhat depressed in those with Type II disease. Whether elevated serum concentrations of IGF I cause the accelerated development of retinopathy in some patients remains to be determined. Such levels do appear to identify patients at high risk for rapid deterioration of vision, and hence may be useful in selecting patients for more intensive or alternative forms of therapy.

Adult↗

Resistance to subcutaneous and intramuscular insulin associated with deficiency of insulin-like growth factor (IGF) 2.

A diabetic patient is described whose serum was deficient in IGF 2. The patient responded appropriately to intravenous insulin but was resistant to subcutaneous and intramuscular insulin. His serum degraded insulin in vitro. This degradation was inhibited by IGF 2 and to a lesser extent by IGF 1 and insulin. We propose that this patient inactivated insulin at the injection site because of an insulin protease in his tissues that would normally be inhibited by serum IGF 2.

Adult↗

Insulin-like growth factor in pregnancy: studies in a growth hormone-deficient dwarf.

Serum concentrations of insulin-like growth factors I and II (IGF I and IGF II) were measured before, during and after pregnancy in a GH-deficient dwarf. At no time during these periods did the patient secrete GH in response to an arginine infusion or insulin tolerance test. IGF I and IGF II concentrations before pregnancy were low and similar to those of patients deficient only in GH. During the 35th week of gestation, IGF I and IGF II serum concentrations were within the normal range (165 and 127 ng/ml for IGF I and 740 and 860 ng/ml for IGF II). Abnormally low values of IGF I and IGF II were again recorded 36 h postpartum and 35 days later. These data indicate that some material, probably of placental origin, stimulates the secretion of not only IGF I, but IGF II as well. Alternatively, the human placenta may produce IGF. Such secretion can occur without the prior maternal secretion of pituitary GH.

Arginine↗

Insulin-like growth factors in the fed and fasted states.

The effect of GH administration (5 mg twice daily for 5 days) on the serum concentration of insulin-like growth factors I and II (IGF I and IGF II) was compared in GH-deficient subjects during a period of fasting and a period of normal food intake. Before treatment with GH, the mean concentration of IGF I was 35.2 +/- 7.5 ng/ml. After 5 days of GH treatment in the fed state, IGF I increased nearly 10-fold to 317.4 +/- 55.9 ng/ml (P less than 0.001 vs. pretreatment value). During fasting, identical treatment of the group resulted in only a modest increase of IGF I to 81 +/- 23 ng/ml (P less than 0.001 vs. fed state response). The serum concentration of IGF II before therapy was reduced to only 174 +/- 37 ng/ml. With GH given in the fed state, IGF II increased to 793 +/- 171 ng/ml. These data suggest that IGF II, like IGF I, is GH dependent and, hence, a somatomedin. GH therapy in the fasted state increased IGF II to 437 +/- 70 ng/ml (P = 0.05 vs. fed state response). In a second study, six normal subjects were fasted for 72 h. The integrated serum IGF I concentration (24 samples/subject) decreased 42% by the third day of fasting; IGF II decreased 27% during the same period. The data from both studies are consistent with the conclusion that the metabolic milieu of fasting inhibits IGF secretion in man. IGF I appears to be affected more than IGF II.

Adult↗

Dwarfism in the pygmy. An isolated deficiency of insulin-like growth factor I.

Insulin-like growth factors (IGFs) I and II, which are present in normal human beings, were measured in serum samples from 11 pygmies from the Central African Republic, 31 controls, and 12 patients with growth hormone deficiency. The mean serum concentration of IGF-I (+/- S.E.M.) was 68.6 +/- 8 ng per milliliter in pygmies, as compared with 193 +/- 10 ng per milliliter in controls (P less than 0.001) and 24 +/- 4 ng per milliliter in patients with growth hormone deficiency (P less than 0.05). Mean serum concentrations of IGF-II in controls, pygmies, and growth hormone-deficient patients were 647 +/- 22, 503 +/- 37, and 252 +/- 29 ng per milliliter, respectively. The serum IGF-I concentration was within the normal range in only one pygmy, whereas IGF-II values were within the normal range in 10 of 11. Pygmies appear to have a major defect in the production of IGF-I.

Adolescent↗

Non-enzymatically glycosylated serum protein in diabetes mellitus: an index of short-term glycaemia.

We measured non-enzymatically-glycosylated serum protein by a colorimetric assay in 107 diabetic and 82 control subjects. The mean level in diabetics was more than twice that in controls. Cross sectional and longitudinal studies in diabetic patients showed that glycosylated serum protein levels correlated with both fasting serum glucose and glycosylated haemoglobin levels. The correlation between glycosylated serum protein and fasting serum glucose was closer in Type 2 than in Type 1 diabetes. Treatment aimed at improving control in eight poorly controlled diabetic patients resulted in a 37% mean fall in glycosylated serum protein within one week, whereas glycosylated haemoglobin decreased only 8%. These studies confirm that non-enzymatic glycosylation of serum proteins is enhanced in diabetes. Measurement of glycosylated serum protein appears to provide an index of glycaemia over the preceding several days. It has the advantage of detecting improvements in glycaemic control much sooner than does glycosylated haemoglobin measurement.

Adult↗

Serum glycosidase activity in diabetes mellitus.

The activity of three glycosidic enzymes, B-glucuronidase, N-acetylglucosaminidase, and B-galactosidase were measured in plasma samples from 163 diabetic subjects and 72 normal controls. No age- or sex-based variation in concentration was noted in controls. Plasma activity of B-glucuronidase and N-acetylglucosaminidase in diabetics correlated directly with the overall level of glycemia as measured by HbA1c levels. B-galactosidase activity was consistently normal in diabetics. A significant age-based variation was noted in the diabetic group for B-glucuronidase and N-acetylglucosaminidase. Prior to age 12 B-glucuronidase and N-acetylglucosaminidase were normal in diabetics, but activity increased significantly after the age of 12, a change that appeared to coincide with the development of puberty.

Acetylglucosaminidase↗

Glycosylated serum protein and hemoglobin A1 levels to measure control of glycemia.

The value of glycosylated serum protein and glycosylated hemoglobin levels for estimating diabetic control was compared in 14 patients over 8 weeks during which glycemic control was improved. Glycosylated hemoglobin levels were not an effective indicator of improved glycemic control for the preceding 2 weeks; glycosylated serum protein values, however, accurately reflected alteration of mean glycemic levels 1 and 2 weeks after improvement of glycemic control. Both measurements were equally satisfactory after 8 weeks. In five patients glycosylated serum protein and glycosylated albumin values appeared equally effective in predicting glycemic control.

Blood Glucose↗

Human pancreatic polypeptide: studies in fasting and in the growth hormone deficient state.

Human pancreatic polypeptide (hPP) was measured in eight normal subjects and six growth hormone deficient dwarfs after insulin-induced hypoglycemia. hPP concentrations increased similarly in both groups with induction of hypoglycemia. In eight normal subjects fasted for 72 hours, no significant elevation of hPP occurred. This is contrary to a previous report indicating such a relationship. Despite the rationale that hPP might play a role in the metabolism of fasting and that its secretion might be altered by growth hormone, no evidence for these relationships could be documented in man.

Fasting↗