Sotos syndrome with hypodontia

Sotos syndrome, or cerebral gigantism, is a rare genetic condition characterized by tall stature, gigantism, dolichocephaly, advanced bone age and learning disability. The purpose of this case report is to highlight the dental management of a 10-year-old boy with Sotos syndrome who presented with hypodontia and dental caries.     

Blocking airway mucous cell metaplasia by inhibiting EGFR antiapoptosis and IL-13 transdifferentiation signals

Epithelial hyperplasia and metaplasia are common features of inflammatory and neoplastic disease, but the basis for the altered epithelial phenotype is often uncertain. Here we show that long-term ciliated cell hyperplasia coincides with mucous (goblet) cell metaplasia after respiratory viral clearance in mouse airways. This chronic switch in epithelial behavior exhibits genetic susceptibility and depends on persistent activation of EGFR signaling to PI3K that prevents apoptosis of ciliated cells and on IL-13 signaling that promotes transdifferentiation of ciliated to goblet cells. Thus, EGFR blockade (using an irreversible EGFR kinase inhibitor designated EKB-569) prevents virus-induced increases in ciliated and goblet cells whereas IL-13 blockade (using s-IL-13Ralpha2-Fc) exacerbates ciliated cell hyperplasia but still inhibits goblet cell metaplasia. The distinct effects of EGFR and IL-13 inhibitors after viral reprogramming suggest that these combined therapeutic strategies may also correct epithelial architecture in the setting of airway inflammatory disorders characterized by a similar pattern of chronic EGFR activation, IL-13 expression, and ciliated-to-goblet cell metaplasia.     

Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock

OBJECTIVE: To determine the prevalence and impact on mortality of delays in initiation of effective antimicrobial therapy from initial onset of recurrent/persistent hypotension of septic shock. DESIGN: A retrospective cohort study performed between July 1989 and June 2004. SETTING: Fourteen intensive care units (four medical, four surgical, six mixed medical/surgical) and ten hospitals (four academic, six community) in Canada and the United States. PATIENTS: Medical records of 2,731 adult patients with septic shock. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The main outcome measure was survival to hospital discharge. Among the 2,154 septic shock patients (78.9% total) who received effective antimicrobial therapy only after the onset of recurrent or persistent hypotension, a strong relationship between the delay in effective antimicrobial initiation and in-hospital mortality was noted (adjusted odds ratio 1.119 [per hour delay], 95% confidence interval 1.103-1.136, p<.0001). Administration of an antimicrobial effective for isolated or suspected pathogens within the first hour of documented hypotension was associated with a survival rate of 79.9%. Each hour of delay in antimicrobial administration over the ensuing 6 hrs was associated with an average decrease in survival of 7.6%. By the second hour after onset of persistent/recurrent hypotension, in-hospital mortality rate was significantly increased relative to receiving therapy within the first hour (odds ratio 1.67; 95% confidence interval, 1.12-2.48). In multivariate analysis (including Acute Physiology and Chronic Health Evaluation II score and therapeutic variables), time to initiation of effective antimicrobial therapy was the single strongest predictor of outcome. Median time to effective antimicrobial therapy was 6 hrs (25-75th percentile, 2.0-15.0 hrs). CONCLUSIONS: Effective antimicrobial administration within the first hour of documented hypotension was associated with increased survival to hospital discharge in adult patients with septic shock. Despite a progressive increase in mortality rate with increasing delays, only 50% of septic shock patients received effective antimicrobial therapy within 6 hrs of documented hypotension.     

Childhood aplastic anaemia in Lucknow, India: incidence, organochlorines in the blood and review of case reports following exposure to pesticides

OBJECTIVES: A hospital-based case-control study, the first in India, was conducted to determine the incidence of childhood aplastic anaemia in and around Lucknow in the backdrop of organochlorine levels in the blood and review the database for any association between the disease and exposure to pesticides. DESIGN AND METHODS: A total of 25 cases of childhood aplastic anaemia were identified as per established criteria and enrolled over the study period of 1 year. Their blood organochlorine levels were determined using a gas-liquid chromatograph equipped with an electron capture detector. RESULTS: The annual incidence of childhood aplastic anaemia in and around Lucknow was found to be 6.8 cases per million which is higher than many countries (e.g., France, Brazil, UK, and United States) but lower than those reported in Sweden, China and an European-Israeli collaborative study. Blood levels of alpha-HCH, gamma-HCH, delta-HCH, total-HCH, and p, p'-DDE were higher in children with aplastic anaemia than in those of controls; only alpha-HCH differed significantly (P < 0.05). CONCLUSIONS: Although this pilot study, with limited statistical power, did not support any association between exposure to organochlorines and risk of childhood aplastic anaemia, a possible association between the two could not be ruled out in view of several cases identified following exposure to pesticides.     

Cervical inlet patch: case series and literature review

Heterotopic gastric mucosa patch (HGMP) has been reported to occur in various parts of the gastrointestinal system from mouth to anus. Extra-gastrointestinal locations have also been reported. Presence of ectopic gastric mucosa has been associated with complications such as ulceration, bleeding, perforations and malignant transformations. Most complications are probably related to acid production. Meckel diverticulum is the most commonly reported ectopic location. Similarly, esophageal HGMP, also known as cervical inlet patch (CIP), has been increasingly reported. Nonspecific oropharyngeal symptoms are common and thought to be due to laryngopharyngeal reflux. CIP is often missed due to its location in the esophagus, just distal to the upper esophageal sphincter, making endoscopic evaluation difficult. Hence the condition is most likely to be under-reported. This article presents a series of five cases of CIP and discusses the pathogenesis, clinical presentations and management of this interesting entity.     

Biomechanical measurement of post-stroke spasticity

BACKGROUND: spasticity following stroke is common, but clinical measurement is difficult and inaccurate. The most common measure is the modified Ashworth scale (MAS) which grades resistance to passive movement (RPM), but its validity is unclear. AIM: to assess the validity of the MAS. METHODS: spasticity was clinically graded using MAS and RPM measured biomechanically in the impaired arm of 111 patients following stroke. The biomechanical device measured RPM, applied force, angular displacement, mean velocity, passive range of movement (PROM) and time required. RESULTS: the median age was 72 years, and 66 subjects were male. The clinical grading by MAS was '0' in 15, '1' in 15, '1+' in 14, '2' in 13, '3' in 43 and '4' in 11. There was no difference in RPM among '0', '1', '1+' and '2' (P > 0.1). However, grade'4' was higher than '3' and below (P < 0.05). The force required increased with the increasing MAS while velocity and PROM decreased (P < 0.01). We regrouped the data using the algorithm: no stiffness = '0'; mild = '1' and '1+' and '2'; moderate = '3'; severe = '4'. There was no difference between 'no stiffness' and 'mild ' (P > 0.10), but 'mild' and moderate' as well as 'moderate' and 'severe' were different (P < 0.01). CONCLUSION: the MAS is not a valid ordinal level measure of RPM or spasticity. Objective measurement of RPM is possible in the clinical setting. However, additional measurements of muscle activity (electromyography) will be required to quantify spasticity.