Cellular localisation of HHV-8 in Castleman's disease: is there a link with lymph node vascularity?

AIMS: Human herpesvirus 8 (HHV-8) has been identified in multicentric Castleman's disease and in angioimmunoblastic lymphadenopathies. However, the presence of the virus does not necessarily indicate an aetiological role in these conditions. This study investigates the cell types infected by HHV-8 in Castleman's disease and examines the correlation between HHV-8 and Castleman's disease lymph node angiogenesis. METHODS: Sixteen formalin fixed, paraffin wax embedded samples from patients with Castleman's disease (six multicentric, 10 solitary) were examined for the presence of HHV-8 using the polymerase chain reaction (PCR), non-isotopic in situ hybridisation, PCR in situ hybridisation (PCR-ISH), and real time quantitative TaqMan PCR to HHV-8 open reading frame 26 (ORF-26), and viral (v)-cyclin encoding regions. Vascularity was assessed using CD34, CD31, and factor VIII immunocytochemistry, and lymph nodes were scored as "low" or "high". RESULTS: Five multicentric Castleman's disease and two solitary Castleman's disease biopsies were positive for HHV-8. HHV-8 was identified in approximately 10% of intranodal B lymphocytes, in endothelial cells, and in subcapsular spindle cell proliferations. The copy number of HHV-8 was low at 10-50 copies/1000 cells. The highest copy number was in subcapsular spindle cells. There was no correlation between vascularity score and HHV-8 status. CONCLUSION: The preferential localisation of HHV-8 in subcapsular spindle cell proliferations (where early intranodal Kaposi's sarcoma initiates) and endothelial cells in Castleman's disease might finally explain the link between intranodal Kaposi's sarcoma and Castleman's disease.     

Developmental evolutionary biology of the vertebrate ear: conserving mechanoelectric transduction and developmental pathways in diverging morphologies

This brief overview shows that a start has been made to molecularly dissect vertebrate ear development and its evolutionary conservation to the development of the insect hearing organ. However, neither the patterning process of the ear nor the patterning process of insect sensory organs is sufficiently known at the moment to provide more than a first glimpse. Moreover, hardly anything is known about otocyst development of the cephalopod molluscs, another triploblast lineage that evolved complex 'ears'. We hope that the apparent conserved functional and cellular components present in the ciliated sensory neurons/hair cells will also be found in the genes required for vertebrate ear and insect sensory organ morphogenesis (Fig. 3). Likewise, we expect that homologous pre-patterning genes will soon be identified for the non-sensory cell development, which is more than a blocking of neuronal development through the Delta/Notch signaling system. Generation of the apparently unique ear could thus represent a multiplication of non-sensory cells by asymmetric and symmetric divisions as well as modification of existing patterning process by implementing novel developmental modules. In the final analysis, the vertebrate ear may come about by increasing the level of gene interactions in an already existing and highly conserved interactive cascade of bHLH genes. Since this was apparently achieved in all three lineages of triploblasts independently (Fig. 3), we now need to understand how much of the morphogenetic cascades are equally conserved across phyla to generate complex ears. The existing mutations in humans and mice may be able to point the direction of future research to understand the development of specific cell types and morphologies in the formation of complex arthropod, cephalopod, and vertebrate 'ears'.     

Leptin and total cholesterol are predictors of weight gain in pre-pubertal children

OBJECTIVE: The aim of this study was to identify specifically which biochemical indices predict excessive weight gain over time in a cohort of pre-pubertal children. SUBJECTS: Fifty nine healthy pre-pubertal children (age: 6.3-9.8y). MEASUREMENTS: Children were defined anthropometrically and biochemically at baseline. Height and weight measurements were then repeated after six (n=52) and 12 months (n=37). RESULTS: Weight change after six months (defined by a change in body mass index (BMI) z-score from baseline) demonstrated no correlation with fasting plasma levels of leptin, insulin, insulin:glucose (IG) ratio, cholesterol, triglyceride or high density lipoprotein (HDL) cholesterol. However, after 12 months there was a significant negative correlation between BMI z-score change and initial plasma leptin (r=-0.35, P=0.048) and this relationship strengthened when adjusted for body fat (from bio-electrical impedance; r=-0.46, P=0.009). In addition, there was a significant positive relationship between plasma total cholesterol and BMI z score change (r=0.38, P=0.03) and this relationship remained unchanged when adjusted for body fat. No relationship was observed between weight change after 12 months and plasma levels of insulin, IG ratio, HDL cholesterol or triglyceride. CONCLUSION: Plasma leptin and total cholesterol were found to be predictive of weight gain over 12 months in a cohort of pre-pubertal children. These two potential predictors can be readily measured in clinical practice and these findings may represent a method of defining the 'at risk of obesity' state in childhood.     

Polyarteritis nodosa presenting with clinical and radiologic features suggestive of polymyositis

We report a patient who presented with clinical and MRI findings suggestive of polymyositis but, in whom, muscle biopsy disclosed a strikingly different diagnosis. A 65-year-old woman presented with 3-week history of bilateral proximal muscle pain and weakness. Laboratory investigations showed markedly elevated inflammatory markers and mildly elevated muscle enzymes. MRI scans of lower limbs showed features suggestive of polymyositis. However, muscle biopsy showed features of a polyarteritis-type vasculitis affecting an intramuscular blood vessel. Our reports highlight the critical role of muscle biopsy in establishing the correct diagnosis in patients with suspected myositis.     

A comparative study of psychosocial data on patients with maxillofacial injuries in an urban population--a preliminary study

A retrospective study of 75 patients who had sustained maxillofacial injuries was undertaken. These patients were assigned to one of three equal groups consisting of firstly, patients whose injuries had been inflicted by a person who had an established personal relationship to the victim, secondly, where the assailant was completely unknown to the victim, and thirdly, a group where inter-personal conflict was not involved. Psychological, social and clinical data was collected and analysed. A profile emerged of a patient who is 'at risk' from assault by a person well known to them. Two thirds of the victims were female; the victims were exclusively from social classes IV and V, and half of the victims had a previous record of assault against their person. Psychological indices of neuroticism were also higher in this group. This group of patients should be identified, and special consideration offered, including family support and referral to social workers, in addition to alerting their general medical practitioners.     

Uroplakin III is not a major candidate gene for primary vesicoureteral reflux

Vesicoureteral reflux (VUR) is the retrograde flow of urine from the bladder into the ureter and towards the kidneys. VUR is the most common cause of end stage renal failure in both children and adults and it is a major cause of severe hypertension in children. VUR is seen in approximately 1-2% of newborn Caucasians. Substantial evidence exists that VUR is a genetic disorder. Uroplakins are integral membrane proteins found in the bladder wall. Knockout studies in mice have suggested uroplakin III (UPK3) as a candidate gene for VUR. We have used parametric and nonparametric linkage analysis and tests for association, to investigate this possibility in a cohort of 126 sibling pairs affected with primary VUR. None of the analyses showed any substantial evidence for linkage or association of markers at the UPK3 locus to VUR. Our results do not support a role for UPK3 in primary VUR.     

<Emphasis Type="Italic">Mycoplasma pneumoniae</Emphasis> infection in primary care investigated by real-time PCR in England and Wales

Real-time PCR was employed to detect a conserved region of the P1 cytadhesin gene of Mycoplasma pneumoniae in combined nose and throat swabs collected from patients attending GP surgeries during 2005–2009 with symptoms of respiratory tract infection (RTI). Samples were collected as part of an annual winter epidemiological and virological linked study in England and Wales. A total of 3,987 samples were tested, 65 (1.7%, 95%CI 1.3–2.1) had detectable M. pneumoniae DNA. Positive patients were detected of both gender, aged from 9 months to 78 years, who had clinical signs of upper RTI, fever and/or myalgia, an influenza-like illness to lower RTI. Mixed infections were identified in four cases, two with influenza A H1, one with H3 and one with influenza B. Children aged 5–14 years were more likely to have detectable M. pneumoniae in samples than all other age groups (Fishers p = 0.03), attributed to the 2005–2006 season in which 6.0% (12/200, 95%CI 3.4–10.3) of 5–14 year olds had detectable M. pneumoniae in comparison to 2.2% in 2006–2007 (3/141 95%CI 0.5–6.4), 2.2% in 2007–2008 (2/89 95%CI 0.1–8.3) and 0% in 2008-2009 (0/151 95%CI 0–2.9).