Growth monitoring: testing the new guidelines

OBJECTIVE: To assess the impact of recent guidelines from the UK joint working party of child health surveillance recommending that all children be measured at age 5 and again between 7 and 9 years of age to determine how many normal school age children are likely to be referred for specialist assessment. METHODS: The longitudinal data of 486 children measured by school nurses in a community setting were examined and compared with measurements made in a research setting by a single, skilled observer. MAIN OUTCOME MEASURES: Number of children identified as having abnormal stature (< 0.4th or > 99.6th centile) and abnormal growth rate height standard deviation score (HSDS) change > 0.67). RESULTS: The community survey identified seven (1.4%) children as having abnormal stature (four short, three tall), 11 (2.3%) were identified as "slow growing", and nine (1.9%) increased their HSDS by more than 0.67. These results were comparable to data collected in ideal research conditions. CONCLUSIONS: Following the recommendations would not result in an excess number of inappropriate referrals. However, this study highlights several unresolved issues such as interobserver variability and time interval between measurements. A large scale prospective study should be considered to establish realistic and cost-effective criteria before implementation of a national screening programme.     

Modulation of gastrointestinal function by MuDelta,a mixed μ opioid receptor agonist/ μ opioid receptor antagonist

BACKGROUND & PURPOSE

Loperamide is a selective µ opioid receptor agonist acting locally in the gastrointestinal (GI) tract as an effective anti-diarrhoeal but can cause constipation. We tested whether modulating µ opioid receptor agonism with δ opioid receptor antagonism, by combining reference compounds or using a novel compound (‘MuDelta’), could normalize GI motility without constipation.

EXPERIMENTAL APPROACH

MuDelta was characterized in vitro as a potent µ opioid receptor agonist and high-affinity δ opioid receptor antagonist. Reference compounds, MuDelta and loperamide were assessed in the following ex vivo and in vivo experiments: guinea pig intestinal smooth muscle contractility, mouse intestinal epithelial ion transport and upper GI tract transit, entire GI transit or faecal output in novel environment stressed mice, or four weeks after intracolonic mustard oil (post-inflammatory). Colonic δ opioid receptor immunoreactivity was quantified.

KEY RESULTS

δ Opioid receptor antagonism opposed µ opioid receptor agonist inhibition of intestinal contractility and motility. MuDelta reduced intestinal contractility and inhibited neurogenically-mediated secretion. Very low plasma levels of MuDelta were detected after oral administration. Stress up-regulated δ opioid receptor expression in colonic epithelial cells. In stressed mice, MuDelta normalized GI transit and faecal output to control levels over a wide dose range, whereas loperamide had a narrow dose range. MuDelta and loperamide reduced upper GI transit in the post-inflammatory model.

CONCLUSIONS AND IMPLICATIONS

MuDelta normalizes, but does not prevent, perturbed GI transit over a wide dose-range in mice. These data support the subsequent assessment of MuDelta in a clinical phase II trial in patients with diarrhoea-predominant irritable bowel syndrome.     

Spinocerebellar ataxia and hypergonadotropic hypogonadism associated with familial sensorineural hearing loss

Cerebellar ataxia has been described as being associated with hypogonadism for almost 100 years. In the majority of cases, hypogonadism is hypogonadotropic. The association of cerebellar ataxia with hypergonadotropic hypogonadism is a rare genetic disorder with a recessive mode of inheritance. Cerebellar ataxia and hypogonadism can also occur associated with a large spectrum of additional clinical manifestations, including mental retardation, sensorineural deafness, choroidal dystrophy, ectodermal dysplasia and short stature, and polyneuropathy. We report the case of a woman with early-onset spinocerebellar ataxia, primary amenorrhea due to hypergonadotropic hypogonadism, and late-onset sensorineural hearing loss. Additional family members from the father's side are affected with late-onset hearing loss, suggesting a dominant mode of inheritance.     

PAPULAR-PURPURIC GLOVES-AND-SOCKS SYNDROME

Background and Objective. Papular-purpuric gloves-and-socks syndrome (PPGSS) is a recently described dermatosis in which human parvovirus B19 (HPV B19) has been implicated as etiologic agent; however, it is suspected that PPGSS may be caused by various agents. This study was designed to survey the general characteristics of PPGSS and to determine the role of HPV B19 in its etiology. Methods. We analyzed data from 21 patients and examined serum samples from three new cases for various viruses. Results. The PPGSS displays a striking uniform clinical pattern. Histologic and immunofluorescence findings are nonspecific. Seroconversion of HPV B19 was reported in six cases and confirmed in two of our patients. In only one case was a possible causative role of Coxsackie virus B6 suggested consistently. Conclusions. The PPGSS represents a distinctive dermatosis and a manifestation of HPV B19 infection. Unlike erythema infectiosum, anti-HPV B19 antibodies seem to develop later after onset of the skin eruption and while viremia is still present.