Determining the best method of Nellcor pulse oximeter sensor application in neonates

Aim: To identify the optimal sensor application method that gave the quickest display of accurate heart rate (HR) data using the Nellcor OxiMax N‐600x pulse oximeter (PO). Methods: Stable infants who were monitored with an electrocardiograph were included. Three sensor application techniques were studied: (i) sensor connected to cable, then applied to infant; (ii) sensor connected to cable, applied to investigator’s finger, and then to infant; (iii) sensor applied to infant, then connected to cable. The order of techniques tested was randomized for each infant. Time taken to apply the PO sensor, to display data and to display accurate data (HR_PO = HR_ECG ± 3 bpm) were recorded using a stopwatch. Results: Forty infants were studied [mean (SD) birthweight, 1455 (872) g; gestational age, 31 (4) weeks; post‐menstrual age, 34 (4) weeks]. Method 3 acquired any data significantly faster than methods 1 (p = 0.013; CI, ?9.6 to ?3.0 sec) and 2 (p = 0.004; CI, ?5.9 to ?1.2 sec). Method 3 acquired accurate data significantly faster than method 1 (p = 0.016; CI, ?9.4 to ?1.0 sec), but not method 2 (p = 0.28). Conclusion: Applying the sensor to the infant before connecting it to the cable yields the fastest acquisition of accurate HR data from the Nellcor PO.     

Assessment of the steady-state pharmacokinetic interaction between etravirine administered as two different formulations and tenofovir disoproxil fumarate in healthy volunteers

Objective

Two open‐label, randomized, cross‐over trials in healthy volunteers were conducted to investigate the pharmacokinetic interaction between etravirine and tenofovir disoproxil fumarate.

Methods

Etravirine was administered as either 800 mg twice a day (bid) (phase II formulation in Study 1) or 200 mg bid (phase III formulation in Study 2) for 8 days followed by a 12 h pharmacokinetic evaluation. After a minimum of 14 days washout, tenofovir disoproxil fumarate 300 mg once a day was administered for 16 days. Volunteers were randomized to receive co‐administration of etravirine with tenofovir disoproxil fumarate on either days 1–8 or days 9–16 followed by a 12 h pharmacokinetic evaluation for etravirine on day 8 or 16, respectively. Plasma and urine tenofovir concentrations were determined on days 8 and 16 over 24 h.

Results

The least square mean (LSM) ratio [90% confidence interval (CI)] for the area under the plasma concentration–time curve from 0 to 12 h (AUC_{12 h}) for etravirine co‐administered with tenofovir disoproxil fumarate vs. etravirine alone was 0.69 (0.61–0.79) and 0.81 (0.75–0.88) in Studies 1 and 2, respectively. The LSM ratio (90% CI) for the effect of etravirine on tenofovir AUC_{24 h} was 1.16 (1.09–1.23) in Study 1 and 1.15 (1.09–1.21) in Study 2.

Conclusions

These alterations are not considered clinically relevant for either drug and no dose adjustment is necessary when etravirine and tenofovir disoproxil fumarate are co‐administered.     

Phenotype determining alleles in GM1 gangliosidosis patients bearing novel GLB1 mutations

Hofer D, Paul K, Fantur K, Beck M, Roubergue A, Vellodi A, Poorthuis BJ, Michelakakis H, Plecko B, Paschke E. Phenotype determining alleles in GM1 gangliosidosis patients bearing novel GLB1 mutations. GM1 gangliosidosis manifests with progressive psychomotor deterioration and dysostosis of infantile, juvenile, or adult onset, caused by alterations in the structural gene coding for lysosomal acid ß‐galactosidase (GLB1). In addition, allelic variants of this gene can result in Morquio B disease (MBD), a phenotype with dysostosis multiplex and entire lack of neurologic involvement. More than 100 sequence alterations in the GLB1 gene have been identified so far, but only few could be proven to be predictive for one of the GM1 gangliosidosis subtypes or MBD. We performed genotype analyses in 16 GM1 gangliosidosis patients of all phenotypes and detected 28 different genetic lesions. Among these, p.I55FfsX16, p.W65X, p.F107L, p.H112P, p.C127Y, p.W161X, p.I181K, p.C230R, p.W273X, p.R299VfsX5, p.A301V, p.F357L, p.K359KfsX23, p.L389P, p.D448V, p.D448GfsX8, and the intronic mutation IVS6‐8A>G have not been published so far. Due to their occurrence in homozygous patients, four mutations could be correlated to a distinct GM1 gangliosidosis phenotype. Furthermore, the missense mutations from heteroallelic patients and three artificial nonsense mutations were characterized by overexpression in COS‐1 cells, and the subcellular localization of the mutant proteins in fibroblasts was assessed. The phenotype specificity of 10 alleles can be proposed on the basis of our results and previous data.     

Evaluation of IL10, IL19 and IL20 gene polymorphisms and chronic hepatitis B infection outcome

Hepatitis B virus (HBV) infection remains a serious global health problem despite the availability of a highly effective vaccine. Approximately 5% of HBV-infected adults develop chronic hepatitis B, which may result in liver cirrhosis or hepatocellular carcinoma. Variants of interleukin-10 (IL10) have been previously associated with chronic hepatitis B infection and progression to hepatocellular carcinoma. Single nucleotide polymorphisms (SNP; n = 42) from the IL10, IL19 and IL20 gene regions were examined for an association with HBV infection outcome, either chronic or recovered, in a nested case-control study of African Americans and European Americans. Among African Americans, three nominally statistically significant SNP associations in IL10, two in IL20, and one haplotype association were observed with different HBV infection outcomes (P = 0.005-0.04). A SNP (rs1518108) in IL20 deviated significantly from Hardy-Weinberg equilibrium in African Americans, with a large excess of heterozygotes in chronic HBV-infected cases (P = 0.0006), which suggests a strong genetic effect. Among European Americans, a nominally statistically significant SNP association in IL20 and an IL20 haplotype were associated with HBV recovery (P = 0.01-0.04). These results suggest that IL10 and IL20 gene variants influence HBV infection outcome and encourage the pursuit of further studies of these cytokines in HBV pathogenesis.     

Increased severity of pentylenetetrazol induced seizures in leptin deficient ob/ob mice

Leptin modulates multiple ion channels making its net effect on brain excitability difficult to predict. One method of determining leptin's net effect on brain excitability is to examine brain excitability during chronic leptin deficiency. We compared the susceptibility of leptin deficient ob/ob and wild type mice to pentylenetetrazol (PTZ) induced seizures using continuous video electroencephalogram (EEG) recordings. We found that ob/ob mice were more likely to die and were more susceptible to generalized clonic and clonic-tonic seizures than wild type mice at submaximal PTZ doses. These findings suggest that chronic leptin deficiency in vivo increases seizure susceptibility.