An aetiological profile of short stature in the Indian subcontinent

To determine whether the genetic background of the insulin-producing beta cells of the pancreas contributes to autoimmune diabetes susceptibility, we have used a model of the disease based on transferring spleen cells from nonobese diabetic (NOD) <--> C57BL/6 (B6) embryo aggregation (EA) chimeras into B6 and NOD irradiated mice. Insulitis and diabetes could be induced into both B6 and NOD hosts, albeit with low incidence. Cyclophosphamide (CY) treatment, known to accelerate diabetes in prediabetic NOD mice, was found to increase diabetes incidence up to 50-60% in both B6 and NOD mice reconstituted with chimeric splenocytes, while diabetes did not occur in CY-treated B6 mice reconstituted with B6 splenocytes. We conclude that the genetic make-up of the target organ does not affect the final stage of the pathogenesis of insulin-dependent diabetes mellitus.     

Relation of weight to body image in pubertal girls and boys from two communities.

Community and gender differences in body image were examined in a randomly selected sample of 284 young adolescent boys and girls from 2 middle-class communities. Data gathered from interviews and questionnaires supported hypothesized Community?×?Sex interactions and sex differences. Specifically, girls' body image and weight satisfaction were higher in 1 community and lower in the other. Demonstrating no community differences, boys reported more positive body image and satisfaction with weight and perceived themselves to be more average in weight than did the girls. Community differences were found in girls' participation in school-related activities, satisfaction with athletic strength, and degree of perceived school cliquishness. When these variables were covaried in several analyses of covariance, community and sex differences in body and weight satisfaction were eliminated or reduced considerably. A series of regression analyses confirmed the importance of these variables to the body perceptions of these adolescents. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Acute effects of estradiol infusion and naloxone on luteinizing hormone secretion in pubertal boys

We have shown previously in pubertal boys that testosterone (T) suppresses the nocturnal augmentation of luteinizing hormone (LH) secretion principally by decreasing LH pulse frequency. As T can be aromatised to estradiol (E2), and E2 effects on LH secretory dynamics may be separate from those of T, we examined the effects of acute E2 infusion on LH secretion in pubertal boys. Opioid receptor blockade has been reported to increase LH secretion after estradiol suppression in adult men, so we also examined whether naloxone might augment LH secretion during E2 treatment in pubertal boys. Starting at 1000 h, eight pubertal boys were given a 33 h saline infusion, followed 1 week later by an E2 infusion at 4.6 nmol/m2/h. During both infusions, four iv boluses of saline were given hourly beginning at 1200 h on the first day, and four naloxone iv boluses, 0.1 mg/kg each, were given hourly beginning at 1200 h on the second day. Blood was obtained every 15 min for LH, and every 60 min for T and E2, from 1200 h until the end of the infusion. Pituitary responsiveness to gonadotropin-releasing hormone (GnRH) was assessed after both infusions by iv administration of 250 ng/kg synthetic GnRH. Estradiol infusion increased the mean plasma E2 concentration from 23 +/- 4 to 46 +/- 6 pmol/L (P < 0.01) and suppressed mean plasma T from 4.9 +/- 1.4 to 3.0 +/- 3.5 nmol/L (saline vs. E2 infusion, P < 0.05). The overall mean LH was suppressed by E2 infusion from 3.7 +/- 0.5 to 2.2 +/- 0.4 IU/L (saline vs. E2 infusion, P < 0.01). LH pulse frequency was suppressed by 50%, whereas mean LH pulse amplitude was not different between saline and E2 infusions. Administration of naloxone did not alter the mean LH, LH pulse frequency, or amplitude during either saline or E2 infusions. Pituitary responsiveness to exogenous GnRH was similar during both infusions. These studies indicate that E2 produces its negative feedback in pubertal boys principally by suppression of LH pulse frequency, and naloxone does not reverse these suppressive effects. Thus E2 suppression of LH secretion is mediated by a decrease of hypothalamic GnRH secretion that is independent of endogenous opioid pathways.     

GH and GnRH analog treatment in children who enter puberty at short stature

It is well known that height at the onset of puberty is closely related to final height. To improve final height of short children who enter puberty at short stature, twenty-one short boys and six short girls were treated with a combination of GH and GnRH analog. The boys started the combination treatment at a mean age of 12.0 years when their mean height was 128.5 cm (-2.74 SD) and the girls at a mean age of 10.68 years when their mean height was 126.4 cm (-2.23 SD). The boys discontinued GnRH at a mean age of 16.88 years after a mean treatment period of 4.89 years when their height was 153.7 cm (-2.75 SD), and the girls at a mean age of 13.89 years after a mean treatment period of 3.20 years when their height was 143.3 cm (-1.94 SD). Bone age maturation significantly decelerated during the combination treatment. Bone age rarely exceeded 14 years in boys and did not exceed 13 years in girls. Bone age maturation during combination treatment decelerated after bone age 12 years in boys and 10.5 years in girls. On average, bone age matured at a mean rate of 0.48 years a year in boys and 0.56 years a year in girls during the combination treatment. During the combination treatment, height velocity did not decelerate rapidly and remained at 3-5 cm/year for a longer duration because of the bone age deceleration, although a definite pubertal growth spurt was not observed. As a consequence, the mean projected height SDS for bone age increased 1.50 (+/- 0.76) SD in boys and 1.24 (+/- 0.49) SD during the combination treatment. Although most of the patients have not yet reached their final height, combined GnRH analog and GH treatment should increase the pubertal height gain and the adult height in short children who enter puberty early for height, when the post-GST growth is taken into account. The combination treatment seems more effective in boys than in girls. This improvement is attributed to the lengthening of the treatment period by slower bone maturation and maintained growth velocity.     

Serum growth hormone-binding protein is decreased in prepubertal children with idiopathic short stature

Every activity of a medical practitioner may be subjected to court control. This creates not only uncertainty gut also anger amongst most physicians. However, it is clear that no court judgement against a physician will be made without the competent support of independent medical experts. On the basis of the relevant legal literature and judgments, the present article is an attempt to consider medical errors in the administration of contrast media, to describe the required medical informed consent before such measures, and to discuss the ever increasing importance of adequate documentation in the light of malpractice proceedings. importance of adequate documentation in the light of malpractice proceedings. This is followed by a discussion of the very important medical necessity to inform the patient about recommended behaviour after injections of such contrast media, the responsibility question in both civil and criminal terms in case of an incident, and various tips for steps to be taken in the case of a liability action.     

Moral assessment of growth hormone therapy for children with idiopathic short stature

Subjects ranging in age from 50 to 89 years old, either with or without dementia were studied by both ELISA for anti-human T-cell lymphotropic virus type I (HTLV-I) gag 100-130 antibody and by cranial CT in order to clarify the relationship between HTLV-I infection and dementia. The frequency of anti-HTLV-I antibody was found to be significantly higher in the patients with dementia (24/130, 18.5%) than in those without dementia (11/139, 7.9%) (P=0.0169). Among the various types of dementia, HTLV-I seropositivity was found to be significantly associated with vascular dementia (11/48, 23%) (P=0.0087), but not with Alzheimer type dementia. In addition, HTLV-I seropositivity was also associated with Babinski sign, and the severity of cerebral infarction, ventricular dilatation and periventricular lucency on CT. The presence of HTLV-I therefore appears to be one of the risk factors for vascular dementia in HTLV-I endemic areas.     

Dental maturity in children of short stature, with or without growth hormone deficiency

Macrophages are important constituents of the immune system by exerting phagocytosis on invading pathogens as well as secreting various immunoregulatory factors. Generation of human macrophage hybridoma has not been possible so far due to the lack of an appropriate fusion partner cell line. In the present study, an 8'-azaguanine resistant cell line, termed HL-60R, was established by drug selection of the promyelocytic cell line HL-60. This novel cell line showed resistance to high concentrations of 8'-azaguanine and was sensitive to aminopterin. These characteristics make it suitable for serving as a potential fusion partner cell line in the development of macrophage hybridoma. Cell-surface analysis by FACS revealed that HL-60R cells per se do not express MHC-class II molecules or the macrophage marker, CD11b. PEG-mediated fusion of HL-60R was performed with PBMC-derived human macrophages. Fluorescence labelling of ex vivo isolated macrophages prior to fusion and subsequent FACS analysis showed that PEG-4000 is a more effective fusion agent than PEG-1500. The generation of this novel fusion partner cell line opens the possibility for development of human macrophage hybridoma or other cell lines from myelocytic origin. Such hybridoma clones will not only enable a more convenient study of these cell but will also provide an excellent host site for the proper production and expression of various recombinant proteins from myelocytic origin in vitro.     

Sensitive immunoassay and in vitro bioassay demonstrate constant bioactive/immunoreactive ratio of luteinizing hormone in healthy boys during the pubertal maturation

The quality of serum LH was assessed during pubertal maturation in boys by measuring immunoreactive (I) LH by a time-resolved immunofluorometric assay (IFMA, Delfia), and bioactive (B) LH by a sensitized in vitro bioassay. Seven samples were collected at 3-mo intervals from 14 healthy boys (median starting age 11.8 y) during pubertal maturation from Tanner stage I-III or II-IV (n = 7 for each). The mouse Leydig cell in vitro bioassay was sensitized 10-fold, to 0.05-0.1 IU/L, by including 1.5 mumol/L of forskolin in the incubation medium. The I- and B-LH levels showed good linear correlation throughout the concentration range analyzed. Mean I-LH increased between the pubertal stages I-IV from 0.42 to 2.24 IU/L and that of B-LH from 1.35 to 5.04 IU/L. No concomitant change occurred in the B-LH/I-LH (B/I) ratio, which was 2.84 +/- 0.54 in stage I and 2.58 +/- 0.48 in stage IV (mean +/- SEM, n = 7). Although the B/I ratios of LH varied from 0.59 to 5.85 in the samples analyzed, the intraindividual variation was small (mean coefficient of variance, 22%). In conclusion, IFMA and sensitized in vitro bioassay showed in healthy boys a similar 4-5-fold increase in the mean LH concentration during pubertal maturation, with no concomitant change in the B/I ratio. The sensitized in vitro bioassay of LH is useful for analysis of the low peripubertal LH levels. The good correlation between the I-LH and B-LH levels, and the lack of change in LH B/I ratio, indicate that IFMA correctly estimates the LH levels upon evaluation of pubertal maturation.     

The treatment with biosynthetic growth hormone (GH) of familial short stature

The effect of growth hormone (GH) treatment in non-GH deficient subjects has been amply studied over the past few years. Although the results of these studies are encouraging, there are still no definitive data since the findings are not comparable due to the different characteristics of the populations examined. In the present study the authors examined the following parameters: stature, height SDS, growth rate, bone age and final height prediction according to Tanner, pubertal stage, before and after treatment with biosynthetic GH at a dose of 1.4 IU/kg of bodyweight for 12 months. The population treated consisted of 10 subjects (5 males and 5 females) aged between 7.3 and 9.5 years old, all prepubertal, with "familial short stature", selected according to the following criteria: stature below the 3rd centile, normal growth rate, normal GH response to stimuli using clonidine and insulin, correlation with parental stature between 25th and 75th centile, bone age correlated to chronological age, absence of other pathologies. After 12 months height SDS moved from -2.75 +/- 0.26 to -2.23 +/- 0.25 (p < 0.5); the growth rate changed from 5.75 +/- 0.63 to 6.66 +/- 0.56 (p < 0.05). No abnormal acceleration of bone age as observed: it moved from 8.2 +/- 0.62 to 9.5 +/- 0.72; all subjects continued to be prepubertal. The expected final stature changed from 154 +/- 2.38 to 159 +/- 0.7 (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Development's tortoise and hare: Pubertal timing, pubertal tempo, and depressive symptoms in boys and girls.

Although the sequence of pubertal maturation remains consistent across most individuals, the timing and tempo of development fluctuate widely. While past research has largely focused on the sequelae of pubertal timing, a faster tempo of maturation might also present special challenges to children for acclimating to new biological and social milestones. Using latent growth curve modeling, the present study investigated how pubertal tempo and pubertal timing predicted depressive symptoms over a 4-year period in a sample of children recruited from New York City area public schools. Rate of intraindividual change in parent-reported Tanner stages was used as an index of pubertal tempo, and more advanced Tanner development at an earlier chronological age was used as an index of pubertal timing. For girls (N = 138, M = 8.86 years old at Time 1), pubertal timing emerged as the most salient factor, and the tempo at which girls progressed through puberty was not significant. In boys (N = 128, M = 9.61 years old at Time 1), both timing and tempo of development were significant; notably, however, the effects of pubertal tempo were stronger than those of timing. These findings highlight the need to consider multiple sources of individual variability in pubertal development and suggest different pubertal challenges for boys and girls. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Management of infections due to antibiotic-resistant Streptococcus pneumoniae

Antibiotic-resistant strains of Streptococcus pneumoniae are becoming more prevalent throughout the world; this has resulted in modifications of treatment approaches. Management of bacterial meningitis has the greatest consensus. Strategies for treating other systemic infections such as pneumonia, bacteremia, and musculoskeletal infections are evolving, in part related to the availability of new antibiotics which are active in vitro against isolates resistant to penicillin and the extended-spectrum cephalosporins. However, there are currently very limited data related to the clinical efficacy of these new agents. The studies upon which current recommendations are based are reviewed. Otitis media represents the single most common infection due to S. pneumoniae. Recommendations for treatment of acute otitis media due to drug-resistant strains and the rationale for these recommendations are discussed.     

Short-term effect of testosterone treatment on reduced bone density in boys with constitutional delay of puberty

We studied bone mineral content (BMC), bone mineral density (BMD), cortical thickness/total width (CT/TW) ratio and cortical area/total area (CA/TA) ratio in boys with constitutional delay of puberty and the effect of short-term testosterone treatment on bone mass. Seventeen boys (age 13.1-15.8 years) who met the family history and the clinical criteria of constitutional delay of puberty were selected and enrolled in the study. All subjects were eating a diet assuring an adequate intake of calories and calcium. A subset of 8 boys (group A) was treated with testosterone depot (100 mg/month x 6 months) while 9 boys (group B) were not. At inclusion, BMC and BMD were reduced in the patients according to their chronological age (BMC -4.04 +/- 1.34 standard deviation scores [SDS]; BMD -2.95 +/- 0.56 SDS), statural age (BMC -1.75 +/- 0.79 SDS; BMD -1.69 +/- 0.78 SDS), and bone age (BMC -1.80 +/- 0.65 SDS; BMD -1.86 +/- 0.68 SDS). No significant differences between the groups were found (group A: BMC 0.480 +/- 0.57 g/cm, BMD 0.488 +/- 0.037 g/cm2, CT/TW ratio 0.43 +/- 0.4, CA/TA ratio 0.68 +/- 0.04; group B: BMC 0.476 +/- 0.060, p = NS vs. group A; BMD 0.491 +/- 0.036 g/cm2, p = NS vs. group A). At 12 months of follow-up, BMC, BMD, CT/TW ratio, and CA/TA ratio significantly increased in group A (BMC 0.70 +/- 0.13 g/cm, delta +41.1 +/- 28.8%, p < 0.003 vs. 0 month; BMD 0.617 +/- 0.082 g/cm2, delta +26.2 +/- 13.6%, p < 0.005 vs. 0 month; CT/TW ratio 0.52 +/- 0.05, delta +20.59 +/- 10.65%, p < 0.001 vs. 0 month; CA/TA ratio 0.77 +/- 0.05 vs. 0 month; CT/TW ratio 13.60 +/- 6.65%, p < 0.004 vs 0 month), but not in group B (BMC: 0.48 +/- 0.05 g/cm; delta +5.1 7.8%, p = NS vs. 00 month; BMD: 0.492 +/- 0.037 g/cm2; delta +0.54 +/- 8.7%, p = NS vs. 0 month; CT/TW ratio 0.44 +/- 0.04, delta +4.04 +/- 6.75%, p = NS vs. 0 month; CA/TA ratio 0.68 +/- 0.05, delta +2.39 +/- 5.90%, p = NS vs. 0 month). We conclude that boys with constitutional delay of puberty have reduced BMC and BMD. The delay in statural and bone ages did not totally account for the decreased bone mass. Testosterone treatment for 6 months significantly increased BMC, BMD, CT/TW ratio, and CA/TA ratio in these patients, but definitive conclusions on the efficacy of the treatment in improving adult bone mass can be drawn only when our patients reach early childhood.     

Mental retardation, epilepsy, short stature, and skeletal dysplasia: confirmation of the Gurrieri syndrome

AIM: To study the relationship between the calcium and the release of platelet-activating factor (PAF) from rat peritoneal macrophages (PM?) stimulated by lipopolysaccharides (LPS). METHODS: The effects of tetrandrine (Tet), Fura 2-AM, and Bay k 8644 on the PAF release from rat PM? was investigated by the bio-assay of PAF. RESULTS: LPS stimulated PM? to release PAF, without increasing intracellular Ca2+ of PM?, Tet at 0.1, 1.0, 10, 100 mumol.L-1 and Fura 2-AM at 0.01, 0.1, 1.0, 10 mumol.L-1 could dose-dependently decrease the release of PAF (9.8 +/- 1.2, 6.5 +/- 1.6, 4.7 +/- 0.8, 3.4 +/- 0.4 microgram.L-1 and 9.2 +/- 1.7, 5.2 +/- 1.3, 3.7 +/- 0.4, 3.2 +/- 0.3 microgram.L-1, respectively, no drugs 11.8 +/- 1.2 micrograms.L-1), Bay k 8644 at 1.0, 5.0, 10 mumol.L-1 could dose-dependently increase the release of PAF (13.2 +/- 1.7, 16.2 +/- 1.4, 17.6 +/- 1.5 micrograms.L-1), and the effects of Tet and Fura 2-AM were completely or partly reversed by Bay k 8644 at 5.0 mumol.L-1. CONCLUSION: Although LPS did not increase intracellular Ca2+ of PM?, intracellular Ca2+ was necessary for PAF release from rat PM? stimulated by LPS.     

Insurance coverage, physician recommendations, and access to emerging treatments: growth hormone therapy for childhood short stature

CONTEXT: There is concern in both the medical community and the general public about mechanisms of medical decision making and the interplay of physician and insurer decisions in determining access to care. OBJECTIVE: To examine the medical process influencing access to growth hormone (GH) therapy for childhood short stature by comparing coverage policies of US insurers with the treatment recommendations of US physicians. DESIGN AND PARTICIPANTS: Independent national representative surveys were mailed to insurers (private, Blue Cross/Blue Shield, health maintenance organizations, programs for Children with Special Health Care Needs, and Medicaid programs, n=113), primary care physicians (n=1504), and pediatric endocrinologists (n=534) with response rates of 75%, 60%, and 81%, respectively. Each survey included identical case scenarios. Primary care physicians were asked decisions about referrals to pediatric endocrinologists. Endocrinologists were asked GH treatment recommendations. Insurers were asked coverage decisions for GH therapy. MAIN OUTCOME MEASURES: Insurer coverage decisions for GH in specific case scenarios were compared with the recommendations of primary care physicians and pediatric endocrinologists. RESULTS: Physician recommendations and insurance coverage decisions differed strikingly. For example, while 96% of pediatric endocrinologists recommended GH therapy for children with Turner syndrome, insurer policies covered GH therapy for only 52% of these children. Overall, referral and treatment decisions by physicians resulted in recommendations for GH therapy in 78% of children with GH deficiency, Turner syndrome, or renal failure; of those recommended for treatment, 28% were denied coverage by insurers. Similarly, GH therapy would be recommended by physicians for only 9% of children with idiopathic short stature, but insurers would not cover GH for the vast majority of these children. Furthermore, the data indicated considerable variation among insurers regarding coverage policies for GH (P<.01). CONCLUSIONS: Access to GH therapy differs depending on the type of insurance coverage. The deep discord between physician recommendations and insurance coverage decisions, exemplified by these findings, represents a major challenge to mechanisms of health care decision making, access, and costs.     

Apparently new syndrome of short stature, lumbar malsegmentation, and minor facial anomalies in two brothers

We describe a previously unrecognized syndrome in two brothers with short stature, webbed neck, unusual face, moderate malsegmentation of the lumbar spine, and unilateral Legg-Perthes-Calvé type "disease" of the hip. Autosomal recessive inheritance is proposed, although we cannot exclude the possibility of an X-linked recessive or an autosomal dominant condition with germinal mosaicism.     

Comparative study of bone mineralization in children and adolescents with familial short stature and a control group

Within the past year there has been a dramatic increase in the number of molecular epidemiologic studies reported in the literature, particularly those evaluating gene-gene and gene-environment interactions. Molecular epidemiologic studies have become more sophisticated owing to collaborations between laboratory scientists and epidemiologists, and because these studies are now conducted on well-characterized populations with appropriate study design. Although there continue to be inconsistencies across some studies, it is clear that the evaluation of gene-gene and gene-environment interactions can delineate portions of the population who are particularly sensitive to certain carcinogenic exposures, based on polymorphisms in genes involved in preventing and controlling carcinogenesis. Identification of these subsets of susceptible individuals can result in the design of preventive strategies targeting the most "at risk" populations.     

Short stature due to a partial idiopathic deficiency of the growth hormone. The role of the TW2 method in assessing treatment with r-hGH

The purposes of this study were: (1) to determine whether peripheral arterial occlusive disease (PAOD) patients who smoked had more severe claudication pain, reduced peripheral circulation, and poorer cardiopulmonary measurements at peak exercise than non-smoking patients, and (2) to determine whether the differences between the smoking and non-smoking patients persisted after controlling for the resting ankle/brachial systolic pressure index (ABI). Thirty-eight PAOD patients (ABI = 0.59 +/- 0.15, mean +/- SD) who smoked an average of 1.5 packs of cigarettes per day over 42 years and 100 PAOD patients (ABI = 0.74 +/- 26) who had quit smoking for an average of 7 years were recruited. Smokers refrained from smoking on the day of testing. Claudication pain times, oxygen uptake, ventilation, leg oximetry, and ankle systolic pressure responses to peak exercise were recorded. The smoking group had more severe claudication pain, as maximal pain occurred 1:37 min:s sooner during exercise (p < 0.05), and the pain took 2:21 min:s longer to subside (p < 0.01) compared to the non-smoking group. Additionally, at peak exercise the smoking group had a lower oxygen uptake (12.8 +/- 2.6 vs 13.9 +/- 2.4 ml/kg/min, p < 0.01), a higher ventilation (31.7 +/- 9.2 vs 27.9 +/- 7.1 liters/min, p < 0.05), and a higher oximeter electrode power (409 +/- 55 vs 385 +/- 37 mW, p < 0.01) than the non-smoking group. Differences between the groups persisted (p < 0.05) after adjusting for resting ABI. It is concluded that cigarette smokers with PAOD had more severe claudication pain, reduced peripheral circulation, and poorer cardiopulmonary measurements at peak exercise than non-smoking patients. These differences were independent of resting ABI. Thus, cigarette smoking reduces the exercise capacity of claudicants, placing patients who smoke at an even greater risk of living a functionally dependent lifestyle.