Phenotypic characteristics of adolescents with concave and convex facial profiles - The National Health Examination Survey.

It has been suggested that facial traits are informative on the inherited susceptibility to tuberculosis and obesity, two current global health issues. Our aim was to compare the phenotypic characteristics of adolescents with dental markers for a concave (n=420), a convex (n=978), and a straight (n=3542) facial profile in a nationally representative sample of United States adolescents. The results show that adolescents with a concave facial profile, when compared to a straight facial profile, had an increased waist-to-height ratio (Δ, 1.1 [95% CI 0.5-1.7], p<0.003) and an increased acne prevalence (OR, 1.5 [95% CI 1.2-1.9], p<0.001). Adolescents with a convex facial profile, when compared to a straight facial profile, had an increased prevalence of tuberculosis (OR, 4.3 [95% CI 1.4-13.1], p<0.02), increased ectomorphy (Δ, 0.3 [95% CI 0.2-0.4], p<0.0001), increased left-handedness (OR, 1.4 [95% CI 1.1-1.7], p<0.007), increased color-blindness (OR, 1.7 [95% CI 1.3-2.3], p<0.004), and rhesus ee phenotype (OR, 1.3 [95% CI 1.1-1.5], p<0.008). Adolescents with a concave facial profile, when compared to a convex profile, had increased mesomorphy (Δ, 1.3 [95% CI 1.1-1.5], p<0.0001), increased endomorphy (Δ, 0.5 [95% CI 0.4-0.6], p<0.0001), lower ectomorphy (Δ, 0.5 [95% CI 0.4-0.6], p<0.0001), and lower vocabulary test scores (Δ, 2.3 [95% CI 0.8-3.8], p<0.008). It is concluded that population-based survey data confirm that distinct facial features are associated with distinct somatotypes and distinct disease susceptibilities.

Fixed ratio dosing of pramlintide with regular insulin before a standard meal in patients with type 1 diabetes.

Amylin is co-secreted with insulin and is therefore lacking in patients with type 1 diabetes. Replacement with fixed ratio co-administration of insulin and the amylin analogue pramlintide may be superior to separate dosing. This concept was evaluated in a ratio-finding study. Patients with type 1 diabetes were enrolled in a randomized, single-masked, standard breakfast crossover study using regular human insulin injected simultaneously with pramlintide 6, 9 or 12 mcg/unit insulin or placebo. Insulin dosage was reduced by 30% from patients' usual estimates. Plasma glucose, glucagon and pramlintide and adverse events were assessed. All ratios reduced 0-3-h glucose and glucagon increments by >50%. No hypoglycaemia occurred. Adverse events were infrequent and generally mild. All pramlintide/insulin ratios markedly and safely reduced glycaemic excursions and suppressed glucagon secretion in the immediate postprandial state. Further study using one of these ratios to explore the efficacy and safety of longer-term meal-time and basal hormone replacement is warranted.

Macimorelin (AEZS-130)-stimulated growth hormone (GH) test: validation of a novel oral stimulation test for the diagnosis of adult GH deficiency.

CONTEXT: In the absence of panhypopituitarism and low serum IGF-I levels, the diagnosis of adult GH deficiency (AGHD) requires confirmation with a GH stimulation test. Macimorelin is a novel, orally active ghrelin mimetic that stimulates GH secretion. OBJECTIVE: The objective of the study was to determine the diagnostic efficacy and safety of macimorelin in AGHD. DESIGN: This was a multicenter open-label study comparing the diagnostic accuracy of oral macimorelin with that of arginine+GHRH in AGHD patients and healthy, matched controls. After 43 AGHD patients and 10 controls were tested, the GHRH analog Geref Diagnostic [GHRH(1-29)NH2] became unavailable in the United States. The study was completed by testing 10 additional AGHD patients and 38 controls with macimorelin alone. MAIN OUTCOME MEASURE: Peak GH area under the receiver operating characteristic curve after macimorelin was measured. RESULTS: Fifty AGHD subjects and 48 controls were evaluated. Peak GH levels in AGHD patients and controls after macimorelin were 2.36 ± 5.69 and 17.71 ± 19.11 ng/mL, respectively (P < .0001). With macimorelin, the receiver operating characteristic analysis yielded an optimal GH cut point of 2.7 ng/mL, with 82% sensitivity, 92% specificity, and 13% misclassification rate. For subjects receiving both tests, macimorelin showed discrimination comparable with arginine+GHRH (area under the receiver operating characteristic curve 0.99 vs 0.94, respectively, P = .29). Obesity (body mass index > 30 kg/m(2)) was present in 58% of subjects, and peak GH levels were inversely associated with body mass index in controls (r = -0.37, P = .01). Using the separate cut points of 6.8 ng/mL for nonobese and 2.7 for obese subjects reduced the misclassification rate to 11%. Only 1 drug-related serious adverse event, an asymptomatic QT interval prolongation on the electrocardiogram, was reported. CONCLUSION: Oral macimorelin is safe, convenient, and effective in diagnosing AGHD with accuracy comparable with the arginine+GHRH test.

Influence of glucocorticoids and growth hormone on insulin sensitivity in humans.

The seminal concept proposed by Sir Harold Himsworth more than 75 years ago that a large number of patients with diabetes were 'insulin insensitive', now termed insulin resistance, has now expanded to include several endocrine syndromes, namely those of glucocorticoid excess, and growth hormone excess and deficiency. Synthetic glucocorticoids are increasingly used to treat a wide variety of chronic diseases, whereas the beneficial effects of recombinant growth hormone replacement therapy in children and adults with growth hormone deficiency have now been well-recognized for over 25 years. However, clinical and experimental studies have established that increased circulating levels of glucocorticoids and growth hormone can also lead to worsening of insulin resistance, glucose intolerance, overt diabetes mellitus and cardiovascular disease. Improved understanding of the physiological 24-h rhythmicity of glucocorticoid and growth hormone secretion and its influence on the dawn phenomenon and the Staub-Trauggot effect has therefore led to renewed interest in studies on the mechanisms of insulin resistance induced by exogenous administration of glucocorticoids and growth hormone in humans. In this review, we describe the physiological events that result from the presence of resistance to insulin action at the level of skeletal muscle, adipose tissue, and liver, describe the known mechanisms of glucocorticoid- and growth hormone-mediated insulin resistance, and provide an update of the contributions of glucocorticoids and growth hormone to understanding the pathophysiology of insulin resistance and its effects on several endocrine syndromes.

Therapeutic aspects of growth hormone and insulin-like growth factor-I treatment on visceral fat and insulin sensitivity in adults.

Growth hormone (GH) is generally considered to exert anti-insulin actions, whereas insulin-like growth factor I (IGF-I) has insulin-like properties. Paradoxically, GH deficient adults and those with acromegaly are both predisposed to insulin resistance, but one cannot extrapolate from these pathological conditions to determine the normal metabolic roles of GH and IGF-I on glucose homeostasis. High doses of GH treatment have major effects on lipolysis, which plays a crucial role in promoting its anti-insulin effects, whereas IGF-I acts as an insulin sensitizer that does not exert any direct effect on lipolysis or lipogenesis. Under physiological conditions, the insulin-sensitizing effect of IGF-I is only evident after feeding when the bioavailability of circulating IGF-I is increased. In contrast, many studies in GH deficient adults have consistently shown that GH replacement improves the body composition profile although these studies differ considerably in terms of age, the presence or absence of multiple pituitary hormone deficiency, and whether GH deficiency was childhood or adult-onset. However, the improvement in body composition does not necessarily translate into improvements in insulin sensitivity presumably due to the anti-insulin effects of high doses of GH therapy. More recently, we have found that a very low dose GH therapy (0.1 mg/day) improved insulin sensitivity without affecting body composition in GH-deficient adults and in subjects with metabolic syndrome, and we postulate that these effects are mediated by its ability to increase free 'bioavailable' IGF-I without the induction of lipolysis. These results raise the possibility that this low GH dose may play a role in preventing the decline of beta-cell function and the development of type 2 diabetes in these "high risk" subjects.

Audiometric configurations of hearing impaired children in Hong Kong: implications for amplification.

PURPOSE: Children with hearing loss who require special school placement may have a wide range of audiometric configurations. Since such children will vary in auditory status their amplification requirements may also be diverse. This study examined the audiological records of 231 children attending four schools for hearing impaired children in Hong Kong to gain an understanding of common audiometric patterns found in the school children and their auditory rehabilitation needs. METHOD: Data on the children's aetiology of hearing loss, hearing status, tympanometric findings and the electroacoustic characteristics of their hearing aids were obtained. For 424 children's ears considered having essentially sensorineural hearing loss, k-means cluster analysis methods were used to categorize audiometric configuration groups. RESULTS: Cluster analysis that indicated that five distinct audiometric configurations could be found among the school children. Different clusters contained children who had differing amplification needs. The study analysed a number of parameters to check fitting outcomes, including average prescribed gain, frequency-specific measured versus prescribed gain, prescribed frequency response, measured versus prescribed frequency response and the predicted aided thresholds for the children. CONCLUSION: The amplification needs associated with these five configurations, including recommended prescription gain, maximum power output and possible signal processing strategies, were considered. The clustering algorithm approach proved useful as a means of grouping distinctive audiometric profiles.

Diabetic neuropathic cachexia and acute bilateral cataract formation following rapid glycaemic control in a newly diagnosed type 1 diabetic patient.

In patients with Type 1 diabetes mellitus (DM), the development of complications within the first few years of diagnosis is very unusual and the development of complications within weeks of commencement of insulin therapy is exceptional. Diabetic neuropathic cachexia, unlike the other more common neuropathies associated with diabetes, is a rare form of peripheral neuropathy characterized by profound weight loss, painful dysaesthesias over the limbs and trunk with spontaneous resolution usually occurring within a year. The morphologically distinct diabetic or metabolic cataract in patients with newly diagnosed Type 1 DM is also a rare complication. We describe the first case of a young man with newly diagnosed Type 1 DM who developed these two rare complications within 3 months of diagnosis and insulin therapy commencement. Rapid development of complications in this patient raises two possibilities, i.e. a probable link between the pathophysiology of these two complications following rapid glycaemic control, and a subset of patients with unusual susceptibility to complications. We re-emphasize the need for vigilant monitoring of complications in young diabetic patients, even in the first few years of their disease. In particular, young patients with visual impairment should be evaluated carefully for evidence of treatable eye complications.

Screening for auditory neuropathy in a school for hearing impaired children.

OBJECTIVE: Hearing loss in children may be due to a wide variety of pathologies. Recently, use of otoacoustic emission technology has led to identification of auditory neuropathy as a distinct hearing disorder. Children with auditory neuropathy require audiological and educational management that may differ from that required by other hearing impaired students. For this reason, screening for auditory neuropathy may be appropriate for children attending schools for the hearing impaired. The study investigated the utility of using otoacoustic emission measures for school screening of hearing impaired children. METHODS: In this study, 81 children aged 6-12 years who attended one school for the deaf were screened for indications of auditory neuropathy. Children found to have consistent otoacoustic emissions were given a full diagnostic audiological test battery. RESULTS: Two children had transient otoacoustic emission results indicating normal outer hair cell function in one or both ears. A follow-up diagnostic assessment for the two positive cases was strongly suggestive of auditory neuropathy. CONCLUSIONS: There is a need for routine auditory neuropathy screening at schools for hearing impaired children.

Blindness following a diabetic foot infection: a variant to the 'eye-foot syndrome'?

AIMS: The 'eye-foot syndrome' was initially described by Walsh et al. to highlight the important association of foot lesions in patients with diabetic retinopathy. We present a case of a 58-year-old patient with Type 2 diabetes mellitus who developed blindness following endogenous staphylococcal endophthalmitis from an infected foot ulcer. RESULTS: Our case describes the link between the eye and the foot but is somewhat different to the association as described by Walsh et al. Endogenous endophthalmitis is rare with diabetic patients being especially at risk, and we report the first case of endogenous staphylococcal endophthalmitis related to a diabetic foot lesion. CONCLUSIONS: Our case illustrates several important issues in the management of diabetic patients admitted to hospital with infection; the need to thoroughly examine the feet to ascertain any foot lesions and any underlying peripheral vascular disease or peripheral neuropathy, to treat aggressively any infected foot lesions to prevent serious complications of septicaemia and to consider rare conditions like endogenous endophthalmitis in any diabetic patient presenting with acute visual impairment and septicaemia.

Percent body fat and bone mass in healthy Canadian females 10 to 19 years of age.

The primary aim of the investigation was to assess the relationship between whole-body fat expressed as a percentage of body weight with whole-body bone mineral content relative to age and anthropometry. Sixty females between 10 and 19 years of age were recruited to this cross-sectional study, which included measurements of weight and height and whole-body fat and bone mineral content using dual-energy X-ray absorptiometry. To assess bone mineral content, data were expressed as a weight or standard deviation scores using age and bone area. Relationships between outcome variables were determined using multiple correlation analysis followed by multiple linear regression with age, weight, height, and fat as predictor variables for outcomes of bone mineral content and density. Correlation analysis indicated that whole-body fat expressed as a percent was significantly related to weight (p < 0.01), but was not related to age or bone mineral content or density unless bone mineral content was corrected to age or bone area using standard deviation scores. In addition, body fat was associated with bone area for age and height (p < 0.01). However, multiple linear regression yielded opposite results. When included in regression, body fat had a negative impact on bone mineral content (p = 0.003), mineral content corrected to bone area (p = 0.02), and bone density (p = 0.003), while age, weight, and height had positive impacts on these outcome measurements. The data suggest that for younger children, the relative influence of percent body fat will be greater and could be linked with suboptimal attainment of peak bone mass. The females in this study appeared to be within reference limits for percent body fat. However, greater amounts of body fat relative to weight could be a marker for lifestyles that do not support attainment of optimal peak bone mass.

Fluorographic detection of [3H]thymidine-labeled deoxyribonucleic acid using agarose gels infused with 2,5-diphenyloxazole prior to electrophoresis.

A fluorographic procedure for the detection of [3H]thymidine-labeled deoxyribonucleic acids electrophoresed in agarose gels was developed. 2,5-Diphenyloxazole (PPO) was added to the agarose solution before pouring of the gel for electrophoresis. This procedure did not interfere with the electrophoretic mobility of the DNA molecules. The radioactive detection efficiency was found to be improved over an existing procedure whereby the agarose gel was infused with PPO after electrophoresis with the aid of acetic acid.

Efficient transfer of proteins from acetic acid-urea and isoelectric-focusing gels to nitrocellulose membrane filters with retention of protein antigenicity.

A method which facilitates the rapid and quantitative electrophoretic transfer of proteins from gels not containing sodium dodecyl sulfate (SDS) to nitrocellulose membranes is described. The equilibration of non-SDS-polyacrylamide gel electrophoretic gels in a buffer containing SDS confers a net negative charge to the proteins present, presumably as a result of the formation of SDS-protein complexes. Proteins from gels equilibrated in the SDS buffer and then electroblotted in a Tris-glycine buffer at pH 8.3 are transferred with much greater efficiency than are proteins from untreated gels. The method has been shown to significantly enhance the electrophoretic transfer of polyoma viral proteins resolved in either acetic acid-urea or isoelectric-focusing gels to nitrocellulose membranes, and it is suggested that the method should have universal applicability to all gel electrophoresis systems currently employed. The proteins from isoelectric-focusing gels treated with SDS and transferred to nitrocellulose membranes were found to retain antigenicity to antisera prepared against either denatured or native viral proteins.