Teachers' mindsets in medical education: A pilot survey of clinical supervisors.

Purpose: Current medical education models maintain that competencies such as professionalism and communication can be taught; however, some argue that certain attributes that make up these competencies, such as empathy, are fixed. Teachers' implicit theories, or mindsets (beliefs about the fixed versus learnable nature of human attributes) have been shown to impact their teaching and assessment practices; but little work has explored mindsets in medical education. We examined clinical supervisors' mindsets of two cognitive attributes (intelligence and clinical reasoning) and two affective attributes (moral character and empathy).Methods: Clinical supervisors (n = 40) from three specialities completed a survey designed to measure mindsets using two existing instruments for intelligence and moral character and 18 new items for clinical reasoning and empathy. Participants completed the survey twice for test-retest reliability (n = 25).Results: New items had satisfactory psychometric properties. Clinical supervisors' mindsets were mixed. Only 8% of participants saw clinical reasoning as fixed while more saw empathy (45%), intelligence (53%), and moral character (53%) as fixed - running counter to current educational models that characterize these attributes as learnable.Conclusion: This study provides evidence supporting the use of these new tools to measure mindsets that may help to better understand the impact of mindsets on medical education.

Genetic analysis of familial isolated growth hormone deficiency type I.

Nuclear DNA from individuals belonging to nine different families in which two sibs were affected with isolated growth hormone deficiency type I were studied by restriction endonuclease analysis. By using 32P-labeled human growth hormone or the homologous human chorionic somatomammotropin complementary DNA (cDNA) sequences as a probe, the growth hormone genes of affected individuals from all families yielded normal restriction patterns. Polymorphic restriction endonuclease sites (HincII and MspI), which are closely linked to the structural gene for growth hormone on chromosome 17, were used as markers in linkage analysis of DNA of family members. Of the nine affected sib pairs two were concordant, three were possibly concordant, and four were discordant for both linked markers. Since only concordant sib pairs would have inherited the same growth hormone alleles, further studies to identify mutations of the growth hormone genes should be limited to this subgroup. It is unlikely that the discordance observed in four of the sib pairs is due to recombination, because the polymorphic HincII site is only 116 base-pairs from the -26 codon of the growth hormone gene. Thus, in at least four of the nine families, the mutation responsible for isolated growth hormone deficiency is not within or near the structural gene for growth hormone on chromosome 17.

Studies of insulin binding in children using human erythrocytes in small amounts of blood.

We have demonstrated specific insulin binding by the erythrocytes (RBCs) of children. Complete binding studies were done using as little as 5 ml of blood. The receptors exhibited competition-inhibition curves and nonlinear Scatchard plots similar to those reported for insulin target tissues, such as the hepatocyte and the adipocyte. Compared with those from adults, the RBCs from children had significantly greater numbers of insulin receptors per cell (P less than 0.05). The total insulin bound by the RBCs from both children and adults, however, was not different over the physiologic range of insulin concentrations. Cord blood RBCs showed greater numbers of receptors per cell than did those from either children or adults; however, the affinity for insulin was similar in both groups. The total amount of insulin bound by cord blood was significantly greater than that in either children (P less than 0.01) or adults (P less than 0.05) over the physiologic range of insulin concentrations. The method used to measure insulin binding by erythrocytes and relatively little intra- and interassay variability, and there was little diurnal variation in binding. Storage of heparinized blood at 4 degree C for 24--36 h had no effect on insulin binding by the RBCs. We conclude that the measurement of insulin binding by RBCs from small volumes of blood may be particularly useful in the study of infants and children with disorders of carbohydrate metabolism to elucidate the role, if any, of abnormal receptor function in their condition.

Chemical diabetes in childhood. Integrated concentrations of glucose, insulin, and growth hormone.

Children and adolescents with varying degrees of glucose intolerance were studied with constant, blood withdrawal methods, and concentrations of glucose, insulin, and growth hormone were evaluated during a normal twenty-four-hour routine. Integrated concentrations of glucose and insulin in children with chemical diabetes were normal despite abnormal oral glucose-tolerance tests. All but two insulin-dependent diabetics had elevated integrated concentrations of growth hormone, as did some but not all chemical diabetics. Three of four mildly ketoacidotic individuals with newly diagnosed diabetes, who were studied before insulin therapy, had normal growth hormone-integrated concentrations. These data differentiate pharmacologic and physiologic assessments of carbohydrate homeostasis, and they support the concept that elevated growth hormone concentrations may not be a direct result of poor diabetic control.

Increased integrated concentration of norepinephrine, epinephrine, aldosterone, and growth hormone in patients with uncontrolled juvenile diabetes mellitus.

The 24-h integrated plasma concentration of glucose (IC-glucose), norepinephrine (IC-NE), epinephrine (IC-E), cortisol (IC-F), growth hormone (IC-GH), aldosterone (IC-ALDO), and plasma renin activity (IC-PRA) were measured in 11 nonobese juvenile-onset nonketotic diabetic patients exhibiting hyperglycemia and glycosuria and 34 matched control subjects using a portable pump, drawing blood at a constant rate through a nonthrombogenic i.v. catheter. The diabetic patients had a noticeable rise of their IC-NE, IC-E, IC-GH, and IC-ALDO. There was no significant difference between the IC-F and IC-PRA of the patients and the control subjects.

Can caretakers of children with IDDM accurately measure small insulin doses and dose changes?

OBJECTIVE: To determine if caretakers of young children with IDDM could consistently reproduce small incremental measurements of insulin (U100). RESEARCH DESIGN AND METHODS: Fifteen caretakers of children with IDDM were asked to deliver repeated small doses of insulin, including doses separated by only 0.25 U of insulin. A sensitive gravimetric technique was used to determine the error in measurement of these low doses of insulin. Statistical analysis was used to evaluate accuracy and internal consistency of each caretaker at each dose. RESULTS: The means +/- SD at each dose level were as follows: 2.75 +/- 0.13 U at 2.5 U, 3.19 +/- 0.13 U at 3.0 U, 3.55 +/- 0.13 U at 3.25 U, and 3.70 +/- 0.11 U at 3.5 U. All doses were biased toward overadministration. There was as statistically significant difference in the dose delivered when the target doses were varied by only 0.25 U. The average differences and standard errors between 2.5 U and 3.0 U, 3.0 U and 3.25 U, and 3.25 U and 3.5 U were 0.44 +/- 0.20 U, 0.36 +/- 0.018 U, and 0.15 +/- 0.017 U, respectively. CONCLUSIONS: Participants were not accurate in measuring small insulin doses, consistently overdrawing insulin by an average of 0.22 U. Caretakers are reasonably internally consistent with a given dose, since participants were able to measure statistically significant differences in 0.25 U dose changes. The error in insulin measurement does not vary with the intended dose level. Caretakers in the same family deliver insulin doses as variable from each other as they are from the population as a whole; however, when two or more individuals are responsible for one insulin dose in a child with IDDM, they have a combined variability that is approximately 40% greater than a single individual's variability.

Autosomal dominant growth hormone (GH) deficiency type II: the Del32-71-GH deletion mutant suppresses secretion of wild-type GH.

Familial isolated GH deficiency type II is an autosomal dominant form of short stature, associated in some families with mutations that result in missplicing to produce del32-71-GH, a protein that cannot fold normally. The mechanism by which this mutant suppresses the secretion of wild-type GH encoded by the normal allele is not known. Coexpression of del32-71-GH with wild-type human GH in transient transfections of the neuroendocrine cell lines GH4C1 and AtT20 suppressed accumulation of wild-type GH. The suppression of wild-type GH accumulation by del32-71-GH was a posttranslational effect on wild-type GH caused by decreased stability, rather than decreased synthesis, of wild-type GH. Coexpression of del32-71-GH with human PRL did not suppress accumulation of PRL, indicating that there was not a general suppression of secretory pathway function. Accumulation of del32-71-GH protein was not necessary for the suppression of wild-type GH, because del32-71-GH did not accumulate in the neuroendocrine cell lines in which suppression of accumulation of wild-type GH was observed. Del32-71-GH did accumulate in transfected COS and CHO cells, but did not suppress the accumulation of wild-type GH in these cells. These studies suggest that del32-71-GH may cause GH deficiency in somatotropes of heterozygotes expressing both wild-type and del32-71-GH by decreasing the intracellular stability of wild-type GH.

Ontogeny of erythrocyte insulin binding in the sheep.

The ontogeny of insulin binding in the sheep was studied using the erythrocytes (RBCs) of 31 fetuses, 10 lambs, and 5 adult animals. Six fetuses were studied on three occasions over a 2-week period from 120--135 days of gestation to provide longitudinal data on changes in insulin binding. Maximal percent binding of [125I]iodoinsulin and receptor concentration decreased significantly as the age of the animal increased (r = 0.76, P less than 0.001 and r = --0.49, P less than 0.001, respectively). Total loss of insulin binding to RBCs was estimated to occur in the second postnatal month, and the RBCs from the adult sheep showed no specific insulin binding. The osmotic fragility of RBCs in each developmental group of animals was also studied to assess possible differences in RBC membrane properties. RBC osmotic fragility was significantly lower in fetuses than in adult sheep (osmotic fragility 50 = 0.55% phosphate-buffered saline vs. 0.76% phosphate-buffered saline, respectively; P less than 0.001). The data suggest that fetal RBCs of lower osmotic fragility and high insulin binding capacity are progressively replaced during late prenatal and early postnatal life by adult-type RBCs of increased osmotic fragility and lacking binding capacity for insulin. The timing of the disappearance of insulin binding to RBCs coincides with the final transition in the animals from a monogastric to a ruminant metabolic state, and may reflect a change in the need for insulin with age.

Erythrocyte insulin binding in obese children and adolescents.

Insulin binding studies in obese patients have been limited to adults due to the relative inaccessibility to tissues for study in the pediatric age group. Insulin binding to the erythrocytes (RBCs) of 9 obese pre-pubertal children, 8 obese adolescents, and 10 obese adults was studied. There was a mean decrease of 15% of insulin binding in the obese patients (P < 0.02 vs. controls). Calculation of receptor concentrations by means of Scatchard plots showed a mean 30% reduction in insulin receptors on the RBCs of obese patients as a group (P < 0.001 vs. controls). The binding of insulin and receptor concentration were inversely proportional to the fasting plasma insulin concentration (= -0.60 and -0.44, respectively). These correlations were significant (P < 0.001 and P < 0.05, respectively). The mean empty site receptor affinity (Ke) was significantly increased in obese patients, but only partially compensated for the loss of receptors with respect to total insulin bound over the physiological range of insulin concentrations. The results of binding studies in the obese adults were similar to those in the children and adolescents, and agreed with published reports of insulin binding in obese adults using adipocytes or monocytes as the source of insulin receptors. The observed decrease in insulin binding to the RBCs of obese children and adolescents correlated with fasting hyperinsulinemia and, therefore, may contribute to the etiology of the insulin resistance or glucose intolerance observed in these patients.

Integrated concentrations of luteinizing hormone and puberty.

Integrated serum concentrations of luteinizing hormone have been compared among 30-minute collections from 10 boys (6-18 years old) and 5 girls (5-11 years old). This study suggests that perpubertal as well as pubertal boys have greater mean integrated concentrations of LH during sleep than during waking. One of two pubertal girls had greater concentrations of LH during sleep, while three prepubertal girls did not.

Molecular scanning of beta-3-adrenergic receptor gene in total congenital lipoatrophic diabetes mellitus.

Total congenital lipoatrophic diabetes is characterized by absence of subcutaneous adipose tissue, hypertriglyceridemia, and insulin resistance. We hypothesized that mutations in the beta-3-adrenergic receptor (beta 3AR) gene might result in the lipoatrophic phenotype by preventing triglyceride storage in adipocytes; thereby, resulting in secondary insulin resistance. We screened the beta 3AR gene in 7 subjects with total congenital lipoatropic diabetes. We found a heterozygous substitution of a guanine to cytosine at position -153 (G-153C) in the 5'-untranslated region of 3 African-American lipoatrophic siblings and 1 sibling without lipoatrophy but with insulin resistance. To determine whether the base change was related to the lipoatrophic phenotype, we genotyped 69 African-Americans without lipoatrophy and found the G-153C substitution in 2 control subjects (allele frequency = 0.01). No other single-stranded polymorphism variants were found in any of the 7 lipoatrophic subjects. Direct sequencing of both alleles of 1 lipoatrophic subject demonstrated a thymidine insertion at position -300 in both alleles. All lipoatrophic subjects along with 20 African-American control subjects were homozygous for the base insertion, suggesting an error in the published sequence. In conclusion, mutations in the beta 3AR gene do not appear to be involved in the development of congenital total lipoatrophy.

Comparison of estimates of gonadotropin levels by isolated blood samples, integrated blood concentrations, and timed urinary fractions.

Gonadotropin levels in isolated blood samples, integrated plasma concentrations (IC), and timed urinary collections have been compared in 5 males with delayed puberty and 7 normal adult males. There was a significant correlation between urinary levels in 24-h collection and those in each of four shorter timed collections for both LH and FSH. Similarly, 24-h integrated plasma concentration and 4-h (0800--1200 h) integrated plasma concentration obtained on 10 additional subjects showed significant correlation. The 4-h integrated plasma concentrations correlated with single blood samples or the mean of three samples obtained at 0800, 1200, and 1600 h. These 4-h plasma samples also correlated significantly with all urine collections for FSH but only with the 2200--0800 h urine collection for LH. The study suggests that LH and FSH levels in urine samples collected over several hours correlate with 24-h urinary excretion and that levels in single blood samples estimate the 24-h plasma integrated concentration.

Comparison of physiological and pharmacological tests of growth hormone function in children with short stature.

We studied 30 short-statured children to investigate their 24-h integrated serum concentration of GH (ICGH) and its diurnal pattern and to compare this data with their responses to standard stimulation tests for GH release. Eight patients with normal stimulation tests had a mean (+/- SD) ICGH value of 8.0 +/- 3.8 ng/ml (range, 4.5--16.4), and all had several secretory peaks greater than 12 ng/ml. Nineteen patients with abnormal responses (peak, less than 10 ng/ml) had a mean ICGH value of 2.7 +/- 1.9 ng/ml (range, less than 0.8 to 7.0); this was significantly lower than that of control subjects and patients with normal stimulation tests. However, 5 of these patients had normal ICGH values. Three patients with borderline stimulation test responses (10--12 ng/ml) had normal ICGH values (3.2, 3.4, and 11.9 ng/ml). Of the 22 patients with either abnormal or borderline stimulation tests, 14 had an ICGH result below the range of normal. Of these 14, 11 had no secretory peaks greater than 10 ng/ml, whereas 3 had peaks between 10--12 ng/ml. The 8 other patients had ICGH results in the normal range. Despite significant correlation (r = 0.668), integrated GH values did not correlate with stimulation tests in a minority of the patients, the status of whom remains to be determined by long term response to exogenous GH therapy.

Integrated concentrations of follicle stimulating hormone and puberty.

Integrated serum concentrations of follicle stimulating hormone are compared from 25 males (aged 6-27 years) and 8 females (aged 5-16 years). Mean levels of FSH among prepubertal and early-to-mid pubertal individuals were significantly greater during sleep than while awake. Levels for late pubertal and postpubertal individuals do not differ between waking and sleeping periods.

Circadian variation of integrated concentration of growth hormone in children and adults.

A portable constant withdrawal pump was used to determine consecutive 30-min integrated concentrations of growth hormone (ICGH) for a 24-h period in 18 normal subjects, ages 5 to 28 yr. Seven prepubertal, 5 pubertal and 6 young adult subjects were studied under conditions of normal activity. Pubertal, prepubertal, and adult subjects had peaks during waking hours as well as during sleep, but peaks in the adults were usually lower than in the children. Using an analysis of variance, a significant (P smaller than 0.01) downward trend of ICGH was observed to occur during sleep. During waking hours a significant variation (P smaller than 0.01 by analysis of variance) was found with low levels in the first few hours after awakening and an upward trend as the evening approached. Food intake had no significant effect on ICGH nor did the introduction of the indwelling catheter. The mean apparent half-life values of growth hormone calculated on the basis of 87 episodes with 3 or more points on the downslope was 40.1 min. This is significantly higher than the known true half-life of the hormone, suggesting that complete secretory inactivity after a secretory episode is an infrequent event.

Three new mutations in the gene for the growth hormone (gh)-releasing hormone receptor in familial isolated gh deficiency type ib.

Isolated GH deficiency (IGHD) is familial in 5-30% of cases. The majority of patients have the type IB form, characterized by autosomal recessive transmission, low but measurable serum concentrations of GH, and responsiveness to exogenous GH therapy. Unique mutations in the gene encoding the GHRH receptor (GHRHR) have previously been described in 2 kindreds with IGHD IB. However, the prevalence of GHRHR mutations in patients with IGHD IB is unknown. We analyzed 30 families with IGHD IB in which more than 1 member was affected. Linkage analysis was performed in 28 of the families, and in 3 families sibling pair analysis indicated linkage to the GHRHR gene locus. These 3 families as well as 2 families in which linkage analysis was not performed were screened for mutations in the 13 coding exons, the intron-exon boundaries, and 327 bases of the promoter of the GHRHR gene. We identified novel GHRHR missense mutations in 2 of the 3 kindreds with informative linkage and in 1 family in which linkage had not been performed. In 1 family affected members were homozygous for a mutation in codon 144 that replaces leucine with histidine (L144H). Affected subjects in a second family were compound heterozygotes, carrying both the L144H mutation and a second mutation in codon 242 that replaces phenylalanine with cysteine. Affected subjects in a third family were homozygous for a mutation that replaces alanine at codon 222 with glutamic acid. All 3 mutations segregated with the IGHD phenotype. All 3 mutant receptors were expressed in CHO cells, and each failed to show a cAMP response after treatment of the cells with GHRH. These results demonstrate that missense mutations in the GHRHR gene are a cause of IGHD IB, and that defects in the GHRHR gene may be a more common cause of GH deficiency than previously suspected.

Short term improvement in glycemic control utilizing continuous subcutaneous insulin infusion: the effect on 24-hour integrated concentrations of counterregulatory hormones and plasma lipids in insulin-dependent diabetes mellitus.

Eight patients with established insulin-dependent diabetes mellitus were studied before and 2 weeks after the initiation of pumped continuous sc insulin infusion in order to investigate the effect of short term improvement of glycemic control on hormonal and lipid levels. Glycemic control was improved in all patients. Using a constant blood withdrawal pump, accurate 24-h average concentrations, denoted integrated concentrations, were obtained. The mean 24-h integrated concentrations of GH, cortisol, norepinephrine, and epinephrine did not change significantly. The mean fasting triglyceride concentration dropped from 119.1 to 83.4 mg/dl (P less than 0.05). The mean 24-h integrated concentration of plasma triglycerides fell from 132.1 to 101.5 mg/dl (P less than 0.02). Both mean fasting and mean 24-h integrated concentrations of plasma cholesterol were lower after improved control. Short term improvement in glycemic control was associated with a reduction in plasma lipid concentrations, but failed to alter mean 24-h integrated concentrations of the measured counterregulatory hormones.

Glucocorticoid and partial mineralocorticoid deficiency associated with achalasia.

A number of patients with ACTH unresponsiveness resulting in glucocorticoid deficiency with normal mineralocorticoid activity have been described. This could be due to an inherited defect within the adrenal gland causing primary unresponsiveness to ACTH or to an inherited progressive degenerative process. The association of achalasia, lack of lacrimation, and glucocorticoid deficiency in two pairs of siblings with normal mineralocorticoid activity has been recently reported. Our case describes an 8.8-yr-old female with glucocorticoid insufficiency, partial mineralocorticoid deficiency, achalasia, and evidence of decreased lacrimation. Sodium depletion produced hyponatremia, and she was unable to increase her plasma aldosterone levels sufficiently, although PRA was markedly elevated. Our case may be part of a progressive degenerative process, possibly affecting both the autonomic nerve structures and the adrenal gland, leading not only to glucocorticoid deficiency but also to abnormal mineralocorticoid secretion.

Long-term follow-up of hypopituitary patients treated with human growth hormone.

Thirty-six former human growth hormone (hGH) recipients underwent comprehensive physical, endocrine and lipoprotein evaluations as adults. Treatment was associated with a decrease in height standard deviation score (SDS) in males from 4.0 pretreatment to 2.1 as adults, and in females from 4.2 to 2.5. Males showed a better growth response to treatment than did females. Plasma somatomedin-C levels were subnormal in 30 patients, but were higher in isolated growth-hormone-deficient patients than in others. Three men and 1 woman showed evidence suggesting a disturbance in pulsatile gonadotropin release despite the previous documentation of normal serum gonadotropin levels. Hypertriglyceridemia was not observed, and the women's plasma cholesterol levels were unremarkable. Men, however, showed higher-than-expected total cholesterol, LDL-cholesterol, and HDL-cholesterol concentrations. The last finding may explain the lack of increased cardiovascular morbidity in this group.

Sustained effect of human growth hormone therapy on children with intrauterine growth retardation.

Previous studies have not clarified whether human growth hormone (HGH) therapy can significantly increase the height of patients with intrauterine growth retardation (IUGR). To determine whether the initial increase in growth rate is sustained through subsequent treatment, 19 prepubertal patients who had IUGR were treated with HGH. Ten of them received a second treatment course. Growth rates (in centimeters per year) were 4.8 +/- 1.4 (mean +/- SD) for the pretreatment period, 7.6 +/- 2.3 for the first treatment period, 4.2 +/- 2.5 for the interval between treatments, 5.9 +/- 1.4 for the second treatment period, and 4.3 +/- 2.6 for the posttreatment period. Growth rates for the two treatment periods were significantly greater than for the periods before, interval between, and posttreatment. Height expressed as the number of standard deviations below the mean for age increased significantly between the onset of treatment and the most recent measurement. These data indicate that HGH has a sustained positive effect on increasing growth rates in children with IUGR, although the magnitude of the effect may decrease with further treatment. Furthermore, we suggest that it is worthwhile to treat patients who have IUGR with HGH for prolonged periods of time, if supplies exceed those necessary to treat children with growth hormone deficiency.