Streptococcal necrotising fasciitis from diverse strains of Streptococcus pyogenes in tropical northern Australia: case series and comparison with the literature

BACKGROUND: Since the mid-1980's there has been a worldwide resurgence of severe disease from group A streptococcus (GAS), with clonal clusters implicated in Europe and the United States. However GAS associated sepsis and rheumatic fever have always remained at high levels in many less developed countries. In this context we aimed to study GAS necrotising fasciitis (NF) in a region where there are high background rates of GAS carriage and disease. METHODS: We describe the epidemiology, clinical and laboratory features of 14 consecutive cases of GAS NF treated over a seven year period from tropical northern Australia. RESULTS: Incidence rates of GAS NF in the Aboriginal population were up to five times those previously published from other countries. Clinical features were similar to those described elsewhere, with 7/14 (50%) bacteremic and 9/14 (64%) having associated streptococcal toxic shock syndrome. 11/14 (79%) had underlying chronic illnesses, including all four fatalities (29% mortality overall). Important laboratory differences from other series were that leukocytosis was absent in 9/14 (64%) but all had substantial lymphopenia. Sequence typing of the 14 NF-associated GAS isolates showed no clonality, with only one emm type 1 and two emm type 3 strains. CONCLUSIONS: While NF clusters can occur from a single emergent GAS clone, this was not evident in our tropical region, where high rates of NF parallel high overall rates of GAS infection from a wide diversity of strains. The specific virulence factors of GAS strains which do cause NF and the basis of the inadequate host response in those patients who develop NF on infection with these GAS require further elucidation

How effective is tetracaine 4% gel, before a venipuncture, in reducing procedural pain in infants: a randomized double-blind placebo controlled trial

BACKGROUND: Procedural pain relief is sub-optimal in neonates. Topical tetracaine provides pain relief in children. Evidence of its efficacy and safety in neonates is limited. The objective of this study was to assess the efficacy and safety of topical tetracaine on the pain response of neonates during a venipuncture. METHODS: Medically stable infants greater than or equal to 24 weeks gestation, requiring a venipuncture, were included. Following randomization and double blinding, 1.1 g of tetracaine or placebo was applied to the skin for 30 minutes. Participants received oral sucrose if they met local eligibility criteria. The venipuncture was performed according to a standard protocol. A medium effect size in the pain score (corresponding to about 2 point difference in the PIPP score) was considered clinically significant, leading to a sample size of 142 infants, with 80% statistical power. Local skin reactions and immediate adverse cardiorespiratory events were noted. The primary outcome, PIPP score at 1 minute, was analysed using an independent Student's t-test. RESULTS: One hundred and forty two infants were included, 33 +/- 4 weeks gestation, 2100 +/- 900 grams and 6 +/- 3 days of age. There was almost no difference in PIPP scores at 1 minute between groups (mean difference -0.09; 95% confidence interval [CI]: -1.68 to 1.50; P = . 91). Similarly, there were no differences in PIPP scores during the 2(nd), 3(rd )and 4th minute. Duration of cry did not differ between the groups (median difference, 0; 95% CI, -3 to 0; P = . 84). The majority of infants in both groups received sucrose 24%. Sucrose had a significant effect on the PIPP score, as assessed by an ANOVA model (p = 0.0026). Local skin erythema was observed transiently in 11 infants (7 in the tetracaine and 4 in the placebo group). No serious side effect was observed. CONCLUSION: Tetracaine did not significantly decrease procedural pain in infants undergoing a venipuncture, when used in combination with routine sucrose administration

How effective is tetracaine 4% gel, before a peripherally inserted central catheter, in reducing procedural pain in infants: a randomized double-blind placebo controlled trial [ISRCTN75884221]

BACKGROUND: Procedural pain relief is sub-optimal in infants, especially small and vulnerable ones. Tetracaine gel 4% (Ametop(®), Smith-Nephew) provides pain relief in children and larger infants, but its efficacy in smaller infants and for peripherally inserted central catheters (PICC) remains uncertain. The objective of this trial was to assess the safety and efficacy of tetracaine gel on the pain response of very low birth weight (VLBW) infants during insertion of a PICC. METHODS: Medically stable infants greater than or equal to 24 weeks gestation, requiring a non-urgent PICC, were included. Following randomization and double blinding, 1.1 g of tetracaine or placebo was applied to the skin for 30 minutes. The PICC was inserted according to a standard protocol. Pain was assessed using the Premature Infant Pain Profile (PIPP). A 3-point change in the pain score was considered clinically significant, leading to a sample size of 54 infants, with 90% statistical power. Local skin reactions and immediate adverse cardiorespiratory events were noted. The primary outcome, PIPP score at 1 minute, was analysed using an independent Student's t-test. RESULTS: Fifty-four infants were included, 27 +/- 2 weeks gestation, 916 +/- 292 grams and 6.5 +/- 3.2 days of age. Baseline characteristics were similar between groups. The mean PIPP score in the first minute was 10.88 in the treatment group as compared to 11.74 in the placebo group (difference 0.86, 95% CI -1.86, 3.58). Median duration of crying in non-intubated infants was 181 seconds in the tetracaine group compared to 68 seconds in the placebo group (difference -78, 95% CI -539, 117). Local skin erythema was observed transiently in 4 infants (3 in the treatment and 1 in the placebo group). No serious harms were observed. CONCLUSION: Tetracaine 4% when applied for 30 minutes was not beneficial in decreasing procedural pain associated with a PICC in very small infants

Maternal anthropometric characteristics in pregnancy and blood pressure among adolescents: 1993 live birth cohort, Pelotas, southern Brazil

<p>Abstract</p> <p>Background</p> <p>We investigated the association between maternal anthropometric measurements in prepregnancy and at the end of pregnancy and their children's systolic (SBP) and diastolic (DBP) blood pressure at 11 years of age, in a prospective cohort study.</p> <p>Methods</p> <p>All hospital births which took place in 1993 in the city of Pelotas - Brazil, were identified (5,249 live births). In 2004, the overall proportion of follow-up was 85% and we obtained arterial blood pressure measurements of 4,452 adolescents.</p> <p>Results</p> <p>Independent variables analyzed included maternal prepregnancy weight and body mass index (BMI) and maternal weight, and height at the end of pregnancy. Multiple linear regression analysis controlling for the following confounders were carried out: adolescent's skin color, family income at birth, smoking, alcohol intake during pregnancy, and gestational arterial hypertension. Mean SBP and DBP were 101.9 mmHg (SD 12.3) and 63.4 mmHg (SD 9.9), respectively. Maternal prepregnancy weight and BMI, and weight at the end of pregnancy were positively associated with both SBP and DBP in adolescent subjects of both sexes; maternal height was positively associated with SBP only among males.</p> <p>Conclusions</p> <p>Adequate evaluation of maternal anthropometric characteristics during pregnancy may prevent high levels of blood pressure among adolescent children.</p

Differentiating Embryonic Stem Cells Pass through ‘Temporal Windows’ That Mark Responsiveness to Exogenous and Paracrine Mesendoderm Inducing Signals

BACKGROUND: Mesendoderm induction during embryonic stem cell (ESC) differentiation in vitro is stimulated by the Transforming Growth Factor and Wingless (Wnt) families of growth factors. PRINCIPAL FINDINGS: We identified the periods during which Bone Morphogenetic Protein (BMP) 4, Wnt3a or Activin A were able to induce expression of the mesendoderm marker, Mixl1, in differentiating mouse ESCs. BMP4 and Wnt3a were required between differentiation day (d) 1.5 and 3 to most effectively induce Mixl1, whilst Activin A induced Mixl1 expression in ESC when added between d2 and d4, indicating a subtle difference in the requirement for Activin receptor signalling in this process. Stimulation of ESCs with these factors at earlier or later times resulted in little Mixl1 induction, suggesting that the differentiating ESCs passed through 'temporal windows' in which they sequentially gained and lost competence to respond to each growth factor. Inhibition of either Activin or Wnt signalling blocked Mixl1 induction by any of the three mesendoderm-inducing factors. Mixing experiments in which chimeric EBs were formed between growth factor-treated and untreated ESCs revealed that BMP, Activin and Wnt signalling all contributed to the propagation of paracrine mesendoderm inducing signals between adjacent cells. Finally, we demonstrated that the differentiating cells passed through 'exit gates' after which point they were no longer dependent on signalling from inducing molecules for Mixl1 expression. CONCLUSIONS: These studies suggest that differentiating ESCs are directed by an interconnected network of growth factors similar to those present in early embryos and that the timing of growth factor activity is critical for mesendoderm induction

Pleosporales

One hundred and five generic types of Pleosporales are described and illustrated. A brief introduction and detailed history with short notes on morphology, molecular phylogeny as well as a general conclusion of each genus are provided. For those genera where the type or a representative specimen is unavailable, a brief note is given. Altogether 174 genera of Pleosporales are treated. Phaeotrichaceae as well as Kriegeriella, Zeuctomorpha and Muroia are excluded from Pleosporales. Based on the multigene phylogenetic analysis, the suborder Massarineae is emended to accommodate five families, viz. Lentitheciaceae, Massarinaceae, Montagnulaceae, Morosphaeriaceae and Trematosphaeriaceae

A study of soft tissue sarcomas after childhood cancer in Britain

Among 16 541 3-year survivors of childhood cancer in Britain, 39 soft tissue sarcomas (STSs) occurred and 1.1 sarcomas were expected, yielding a standardised incidence ratio (SIR) of 16.1. When retinoblastomas were excluded from the cohort, the SIR for STSs was 15.9, and the cumulative risk of developing a soft tissue tumour after childhood cancer within 20 years of 3-year survival was 0.23%. In the case–control study, there was a significant excess of STSs in those patients exposed to both radiotherapy (RT) and chemotherapy, which was five times that observed among those not exposed (P=0.02). On the basis of individual radiation dosimetry, there was evidence of a strong dose–response effect with a significant increase in the risk of STS with increasing dose of RT (P<0.001). This effect remained significant in a multivariate model. The adjusted risk in patients exposed to RT doses of over 3000 cGy was over 50 times the risk in the unexposed. There was evidence of a dose–response effect with exposure to alkylating agents, the risk increasing substantially with increasing cumulative dose (P=0.05). This effect remained after adjusting for the effect of radiation exposure