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.

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.

Congenital micropenis: long-term medical, surgical and psychosexual follow-up of individuals raised male or female.

OBJECTIVES: To document long-term medical, surgical and psychosexual outcome of individuals with congenital micropenis (13 males, 5 females). METHODS: Physical measurements from childhood were collected retrospectively from medical records and at adulthood by physical examination. An adult psychosexual assessment was conducted with a written questionnaire and oral discussion. RESULTS: Adult penile length was below the normal mean in all men. Three women had vaginoplasty resulting in normal length. All men reported good or fair erections but 50% were dissatisfied with their genitalia. Dissatisfaction with body image resulted from having a small penis (66%), inadequate body hair (50%), gynecomastia (33%) and youthful appearance (33%). Ten men were heterosexual, 1 homosexual and 2 bisexual. Among women, 4 (80%) were dissatisfied with their genitalia. Three women reported average libido with orgasm and were also heterosexual. Two women had no sexual interest or experience. Finally, males were masculine and females feminine in their gender-role identity, and both groups were satisfied with their sex of rearing. CONCLUSIONS: Regarding choice of gender, male sex of rearing can result in satisfactory genito-sexual function. Female gender can also result in success, however it requires extensive feminizing surgery.

Combined inhaled anticholinergics and beta2-agonists for initial treatment of acute asthma in children.

BACKGROUND: Several randomized controlled trials have examined, with conflicting results, the efficacy of the addition of anticholinergics to beta2 agonists in acute pediatric asthma. The pooling for a larger number of randomized controlled trials may provide not only greater power for detecting group differences and also provide better insight into the influence of patients' characteristics and treatment modalities on efficacy. OBJECTIVES: The aims of this study were to estimate the therapeutic and adverse effects attributable to the addition of inhaled anticholinergics to beta2 agonists in acute pediatric asthma. SEARCH STRATEGY: We searched Medline (1966 to April 2000), Embase (1980 to April 2000), Cinahl (1982 to April 2000) and reference lists of studies. We also contacted drug manufacturers and trialists. SELECTION CRITERIA: Randomised trials comparing the combination of inhaled anticholinergics and beta2 agonists with beta2 agonists alone in children aged 18 months to 17 years with acute asthma. DATA COLLECTION AND ANALYSIS: Assessments of trial quality and data extraction were done by two reviewers independently. MAIN RESULTS: Of the 40 identified trials, 13 were relevant and eight of these were of high quality. The addition of a single dose of anticholinergic to beta2 agonists did not reduce hospital admission [RR=0.93 (95% CI: 0.65, 1.32)]. However, significant group differences in lung function supporting the combination of anticholinergics and beta2-agonists were observed 60 minutes [SMD=0.57 (95% CI:0.21, 0.93)] and 120 minutes [SMD=0.53 (95% CI: 0.17, 0.90)] after the dose of anticholinergic. In contrast, the addition of multiple doses of anticholinergics to beta2 agonists reduced the risk of hospital admission by 25% [RR=0.75 (95% CI: 0.62,0.89)] in children with predominantly moderate and severe exacerbations. Twelve (95% CI: 8, 32) children would need to be treated to avoid one admission. When restricting this strategy to children with severe exacerbations, seven (95% CI: 5, 20) children need to be treated to avoid an admission. At 60 minutes after the last anticholinergic inhalation, a weighted mean group difference of 9.68 in change in % predicted FEV1 [95% CI:5.70, 13.68] favored anticholinergic use. In the two studies where anticholinergics were systematically added to every beta2 agonist inhalation, irrespective of asthma severity, no group differences were observed for the few available outcomes. There was no increase in the amount of nausea, vomiting or tremor in patients treated with anticholinergics. REVIEWER'S CONCLUSIONS: A single dose of an anticholinergic agent is not effective for the treatment of mild and moderate exacerbations and is insufficient for the treatment of severe exacerbations. Adding multiple doses of anticholinergics to beta2 agonists appears safe, improves lung function and would avoid hospital admission in 1 of 12 such treated patients. Although multiple doses should be preferred to single doses of anticholinergics, the available evidence only supports their use in school-aged children with severe asthma exacerbation. There is no conclusive evidence for using multiple doses of anticholinergics in children with mild or moderate exacerbations.

Combined inhaled anticholinergic agents and beta-2-agonists for initial treatment of acute asthma in children.

BACKGROUND: Anti-cholinergic agents and beta2-agonist drugs are both bronchodilators used to reverse acute bronchospasm in children with asthma. These drugs have different modes of action, so may have complementary or additive effects. OBJECTIVES: The objective of this review was to assess the effects of adding inhaled anti-cholinergics to beta2-agonists in acute paediatric asthma. SEARCH STRATEGY: We searched Medline (1966 to 1996), Embase (1980 to 1995), Cinahl (1982 to 1995) and reference lists of studies. We also contacted drug manufacturers and researchers. SELECTION CRITERIA: Randomised trials comparing the combination of inhaled anti-cholinergics and beta2-agonists with beta2-agonists alone in children aged 18 months to 17 years with acute asthma. DATA COLLECTION AND ANALYSIS: Assessments of trial quality and data extraction were done by two reviewers independently. MAIN RESULTS: Ten trials involving a total of 836 children were included. Most trials were of high quality. When only one dose of anti-cholinergic inhalation was added to beta2-agonist therapy, there was an improvement in forced expiratory volume in one second after 60 minutes with combination therapy (weighted mean difference 16.1%, 95% confidence interval 5.5 to 26. 7% reduction). There was no reduction in hospital admission (odds ratio 0.80, 95% confidence interval 0.35 to 1.82, using a random effects model). For multiple doses in children with severe asthma, there was a reduction in forced expiratory volume in 1 second (weighted mean difference 9.8% predicted, 95% confidence interval 6. 5 to 13.1% predicted). There may also be a reduction in hospital admission (odds ratio 0.62, 95% confidence interval 0.38 to 0.99). Eleven children would need to be given multiple doses of anti-cholinergics in combination with beta2-agonists to avoid one hospital admission compared to children given beta2-agonists alone. REVIEWER'S CONCLUSIONS: In children with acute asthma, the addition of multiple doses of anti-cholinergics to inhaled beta2-agonists appears to improve lung function modestly and may decrease hospital admission. There is no associated increase in adverse effects. Single doses of anti-cholinergics may improve lung function in children with severe asthma, but do not appear to reduce hospital admissions.

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.

Should inhaled anticholinergics be added to beta2 agonists for treating acute childhood and adolescent asthma? A systematic review.

OBJECTIVES: To estimate the therapeutic and adverse effects of addition of inhaled anticholinergics to beta2 agonists in acute asthma in children and adolescents. DESIGN: Systematic review of randomised controlled trials of children and adolescents taking beta2 agonists for acute asthma with or without the addition of inhaled anticholinergics. MAIN OUTCOME MEASURES: Hospital admission, pulmonary function tests, number of nebulised treatments, relapse, and adverse effects. RESULTS: Of 37 identified trials, 10 were relevant and six of these were of high quality. The addition of a single dose of anticholinergic to beta2 agonist did not reduce hospital admission (relative risk 0.93, 95% confidence interval 0.65 to 1.32). However, significant group differences in lung function supporting the combination treatment were observed 60 minutes (standardised mean difference -0.57, -0.93 to -0.21) and 120 minutes (-0.53, -0.90 to -0.17) after the dose of anticholinergic. In contrast, the addition of multiple doses of anticholinergics to beta2 agonists, mainly in children and adolescents with severe exacerbations, reduced the risk of hospital admission by 30% (relative risk 0.72, 0.53 to 0.99). Eleven (95% confidence interval 5 to 250) children would need to be treated to avoid one admission. A parallel improvement in lung function (standardised mean difference -0.66, -0.95 to -0.37) was noted 60 minutes after the last combined inhalation. In the single study where anticholinergics were systematically added to every beta2 agonist inhalation, irrespective of asthma severity, no group differences were observed for the few available outcomes. There was no increase in the amount of nausea, vomiting, or tremor in patients treated with anticholinergics. CONCLUSIONS: Adding multiple doses of anticholinergics to beta2 agonists seems safe, improves lung function, and may avoid hospital admission in 1 of 11 such treated patients. Although multiple doses should be preferred to single doses of anticholinergics, the available evidence only supports their use in school aged children and adolescents with severe asthma exacerbation.

Effect of lipectomy on growth and development of hyperinsulinemia and hyperlipidemia in the Zucker rat.

The Zucker fat rat inherits obesity and hyperinsulinemia, exhibits insulin resistance, and is, therefore, a model of adult onset, or type II, diabetes. The purpose of this study was to determine if excision of fat depots from the infant Zucker (fa+/fa+) rat would affect growth, fat cell number, hyperinsulinism, and hyperlipidemia. In the experimental design, 10 percent of the total body weight (inguinal and interscapular depots) was excised at 6 weeks of age from 18 fat and 18 lean (fa+/fa-) litter mates, with 18 fat and 18 lean rats serving as nonoperated controls. At intervals, serum glucose, insulin, cholesterol, and triglycerides were measured. Initially, the operated fat group was significantly (p < 0.01) lighter than the nonoperated group. By 9 weeks postoperatively, the operated fat rat group had regained weight and continued to grow at the same rate as the nonoperated fat rats because of intra-abdominal fat depots. Lipectomy had no effect on growth rate of the lean rat group. Although lipectomy caused no consistent change in serum glucose or insulin levels, it caused a significant decrease in lipid levels. For example, the operated fat rats had a reduction in cholesterol from 876 to 171 mg/dl by 15 weeks postoperatively, and serum cholesterol persisted at about 50 percent of the nonoperated group throughout the rest of the study (38 weeks postoperatively). Even a greater reduction in triglyceride levels occurred, for example, from 7415 to 1082 mg/dl at 24 weeks postoperatively. Lipectomy did not cause a change in lipid levels in the lean group. It is concluded that the lipectomy in the Zucker fat group is an excellent model to evaluate the effects of changes in fat cell number on lipid metabolism.

Growth hormone treatment of girls with Turner syndrome: the National Cooperative Growth Study experience.

OBJECTIVE: To evaluate growth rate and adult height with recombinant growth hormone (GH) treatment in girls with Turner syndrome (TS) and predictors of their growth response. METHODS: Data on girls with TS who were treated with GH in the National Cooperative Growth Study (NCGS) were evaluated. As of January 1997, there were 2798 girls with TS in the NCGS database, 2652 of whom had not previously received GH. Follow-up data on growth were available for 2475 subjects, and data on adult height were available for 622. RESULTS: The average age of girls with TS at enrollment in the NCGS was 10.1 +/- 3.6 years. These patients had severely short stature compared with that of unaffected American girls (height, 118.5 +/- 16.5 cm; height standard deviation score [SDS], -3.1 +/- 0.9), but their heights were typical of those of American girls with TS (TS-specific height SDS, 0.01 +/- 0.9). Treatment with GH for an average duration of 3.2 +/- 2.0 years resulted in an increase in height SDS of 0.8 +/- 0.7 compared with unaffected girls and of 1.2 +/- 0.8 compared with TS standards. Growth rates increased from 4.0 +/- 2.3 cm/year before treatment to 7.5 +/- 2.0 cm/year after 1 year of treatment. Duration of treatment with GH was the strongest predictor of change in height SDS. After 6 to 7 years of treatment with GH, there was a cumulative change of 2.0 in mean height SDS. The 622 girls who reached adult height were older when they began taking GH. Their mean height gain over pre-GH projected height was 6.4 +/- 4.9 cm after 3.7 +/- 1.9 years of treatment. Their adult height was 148.3 +/- 5.6 cm. CONCLUSIONS: Although the response to treatment with GH varied, it was associated with highly significant gains in growth and adult height in girls with TS. Duration of treatment with GH was the most important variable predicting adult height.

Molecular investigation of two male subjects with short stature and a 45,X/46,X,ring(Y) karyotype.

We studied 2 subjects with a 45,X/46,X,ring(Y) karyotype. Both of them were evaluated because of short stature and a subnormal rate of linear growth. One patient had additional features of the Ullrich-Turner syndrome. Both subjects had normal male external genitalia. Two copies of the pseudoautosomal gene, MIC2, were present in DNA of each individual. All sequences examined on the Y-specific portion of the short arm, including those for the sex-determining region Y (SRY) gene, were present. By contrast, portions of the long arm of the Y chromosome were missing from DNA of both subjects. In subject 1, deletion intervals 6 and 7 were missing. In subject 2, deletion interval 5, distal to 5B, was missing in addition to intervals 6 and 7. The most likely explanation for the ring formation in these subjects is a chromosomal break in the long arm and in the pseudoautosomal region of the short arm distal to MIC2 with subsequent ligation of the remaining sequences on the long arm and short arm. However, a complex rearrangement cannot be excluded.

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.

Partial growth-hormone insensitivity: the role of growth-hormone receptor mutations in idiopathic short stature.

Mutations in the GHR locus may play a role in the cause of idiopathic short stature (ISS) by impairing growth-hormone (GH) receptor (GHR) function. At one extreme, mutations that nullify the function of the GH receptor are linked to complete GH insensitivity syndrome, or Laron syndrome, and we hypothesized that less-disruptive mutations could contribute to partial GH insensitivity syndrome. Low levels of GH binding protein may indicate mutations in the extracellular domain of the receptor, and by focusing on 14 children with ISS who had low GH binding protein and insulin-like growth factor I levels, we found three heterozygotes and one compound heterozygote for mutations in the extracellular domain of the receptor. We have since extended our study to a broader spectrum of patients, adding 76 patients with ISS who were treated with GH in a phase II study of the safety and efficacy of recombinant human GH in ISS and also adding 10 patients who were ascertained as having ISS by pediatric endocrinologists in private practice. The GHR gene has thus been analyzed in 100 patients with ISS, eight of whom were found to carry mutations: four in our original study and four with normal or elevated levels of GH binding protein. The latter group consists of three carriers of heterozygous extracellular domain mutations and one carrier of a heterozygous intracellular domain mutation. Family data suggest that the carriers of these mutations have a range of phenotypes, supporting our hypothesis that the expression of these heterozygous mutations as partial GH insensitivity syndrome depends on the genetic makeup of the person.

Diabetes as a complication of tacrolimus (FK506) in pediatric renal transplant patients.

Three cases of insulin-requiring diabetes mellitus associated with tacrolimus (FK506) therapy in pediatric renal transplant patients are presented. New-onset diabetes mellitus has been reported with tacrolimus therapy post liver and kidney transplants in up to 12% of adult patients, but is thought to be rare in pediatrics. Although insulin requirement with tacrolimus therapy has been occasionally reported in adolescent patients post liver transplant, only a single case in a pediatric kidney transplant recipient has been previously documented. These cases illustrate the significant diabetogenic effect of tacrolimus in pediatric renal transplant patients. As the use of tacrolimus becomes more prevalent in pediatric kidney transplantation, pediatric nephrologists should be aware of this potential complication.

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.

Abnormalities of thyroid function and glucose control in subjects with Rett syndrome.

We have identified subtle abnormalities of thyroid function and glucose control in patients with Rett syndrome. The mean serum total thyroxine (T4) concentration was significantly lower in a group of subjects with Rett syndrome (6.9 +/- 1.5 microgram/dl, n = 34; p < 0.001) than the adult reference range (8.5 +/- 1.75 microgram/dl, n = 200). This differences remained significant even for the 17 subjects not taking anticonvulsants (7.6 +/- 1.5 microgram/dl; p < 0.05 vs. adult reference). The difference was more marked when compared to age-adjusted normals, with 10 subjects having a serum total T4 concentration below normal for age including 3 of 17 of the subjects not taking anticonvulsants. This decrease in serum total T4 concentration was not due to changes in binding proteins as measured by 3,5,3'-triiodothyronine resin uptake, and was associated with a decreased concentration of thyroid-stimulating hormone (1.7 +/- 1.6 mU/l, n = 23 vs. 2.5 +/- 1.0 mU/l, n = 200; p < 0.01). Oral glucose tolerance tests were performed in 10 of the subjects with Rett syndrome. They had a delay in the peak glucose and insulin concentrations. Glucose levels were elevated at 1 and 2 hours (p < 0.05), and insulin levels were elevated at 1, 2, and 3 hours (p < 0.05). Two subjects fulfilled criteria for impaired glucose tolerance.

The effects of X monosomy on brain development: monozygotic twins discordant for Turner's syndrome.

Monosomy for the X chromosome is the most frequent cause of Turner's syndrome, a common clinical syndrome associated with particular physical and neurobehavioral features. The results from comprehensive assessment of prepubertal monozygotic female twins discordant for X monosomy are presented. Zygosity was established with DNA Fingerprinting and no evidence of chromosomal mosaicism was seen in either child. Physical features in the affected twin were relatively mild with respect to the full spectrum of physical malformations and disabilities associated with Turner's syndrome. The neurobehavioral phenotypes of the twins were compared. Although both sisters scored in the superior range of intelligence, the affected twin's Performance IQ was 18 points less than her sister, whereas Verbal IQ showed only a 3-point difference between the sisters. Other relative differences were noted within the executive, visuospatial, and visuomotor domains of function. Behavioral evaluation indicated greater problems with attention, hyperactivity, and anxiety in the affected twin. Quantitative analysis of brain anatomy revealed evidence of both general and regional effects of X monosomy on neurodevelopment. Cerebrospinal fluid volume was increased by 25% in the affected twin compared with her sister with a corresponding decrease in gray matter volume. The right frontal, right parietal-occipital, and left parietal-perisylvian regions showed the greatest discrepancy between the sisters with respect to increased cerebrospinal fluid and decreased gray matter volumes in twin with X monosomy. Differences in the posterior fossa were also noted with a 50% relative increase in the volumes of the fourth ventricle and cisterna magna and a 10 to 15% relative reduction in size of the cerebellar vermis, pons, and medulla in the affected twin. The association between the neurobehavioral and neuroanatomical findings in the affected twin is discussed. The unique nature of the naturally occurring genetic phenomenon seen in this twin pair provides an opportunity to more fully elucidate the neurobehavioral phenotype associated with X monosomy and Turner's syndrome.

Accuracy and precision of low-dose insulin administration.

OBJECTIVE: To determine the lowest dose of concentrated (U100) insulin that can be reproducibly delivered. METHODS: A telephone survey was used to determine current practices in major pediatric hospitals regarding the administration of low doses of concentrated insulin. A sensitive gravitometric technique was used to determine the error in measurement of low doses of U100 insulin by pediatric nurses and parents of diabetic children. RESULTS: A telephone survey revealed that doses as low as 0.5 or 1.0 U (5 to 10 microL) are routinely administered in pediatric hospitals. In our study of pediatric nurses, attempts to deliver 0.5, 1.0, and 2.0 U resulted in delivered doses of 0.975 +/- 0.315, 1.638 +/- 0.376, and 2.153 +/- 0.435 U (mean +/- standard deviation of the mean), respectively. The use of 0.3-mL syringes compared to 0.5-mL syringes did not improve accuracy or precision. Taken as a group, parents of children with diabetes were more accurate (mean delivered dose of 1.063 +/- 0.276 for the 1-U dose), but the individual means ranged from 0.641 to 1.300 and coefficients of variation ranged from 5% to 33%. Only three of the seven parents could deliver 1.0 U with acceptable precision and accuracy. CONCLUSIONS: When currently available syringes are used, insulin injections of less than 20 microL (2 U of U100) have an unacceptably large error. It is recommended that, in the inpatient setting, diluted insulin be used if the prescribed dose is less than 2.0 U.