Phosphatidylethanol (PEth) as a biomarker of alcohol consumption in HIV-positive patients in sub-Saharan Africa

Background: Alcohol is heavily consumed in sub‐Saharan Africa and affects HIV transmission and treatment and is difficult to measure. Our goal was to examine the test characteristics of a direct metabolite of alcohol consumption, phosphatidylethanol (PEth). Methods: Persons infected with HIV were recruited from a large HIV clinic in southwestern Uganda. We conducted surveys and breath alcohol concentration (BRAC) testing at 21 daily home or drinking establishment visits, and blood was collected on day 21 (n = 77). PEth in whole blood was compared with prior 7‐, 14‐, and 21‐day alcohol consumption. Results: (i) The receiver operator characteristic area under the curve (ROC‐AUC) was highest for PEth versus any consumption over the prior 21 days (0.92; 95% confidence interval [CI]: 0.86 to 0.97). The sensitivity for any detectable PEth was 88.0% (95% CI: 76.0 to 95.6) and the specificity was 88.5% (95% CI: 69.8 to 97.6). (ii) The ROC‐AUC of PEth versus any 21‐day alcohol consumption did not vary with age, body mass index, CD4 cell count, hepatitis B virus infection, and antiretroviral therapy status, but was higher for men compared with women (p = 0.03). (iii) PEth measurements were correlated with several measures of alcohol consumption, including number of drinking days in the prior 21 days (Spearman r = 0.74, p < 0.001) and BRAC (r = 0.75, p < 0.001). Conclusions: The data add support to the body of evidence for PEth as a useful marker of alcohol consumption with high ROC‐AUC, sensitivity, and specificity. Future studies should further address the period and level of alcohol consumption for which PEth is detectable.     

Frequent somatic mosaicism of NEMO in T cells of patients with X-linked anhidrotic ectodermal dysplasia with immunodeficiency

Somatic mosaicism has been described in several primary immunodeficiency diseases and causes modified phenotypes in affected patients. X-linked anhidrotic ectodermal dysplasia with immunodeficiency (XL-EDA-ID) is caused by hypomorphic mutations in the NF-κB essential modulator (NEMO) gene and manifests clinically in various ways. We have previously reported a case of XL-EDA-ID with somatic mosaicism caused by a duplication mutation of the NEMO gene, but the frequency of somatic mosaicism of NEMO and its clinical impact on XL-EDA-ID is not fully understood. In this study, somatic mosaicism of NEMO was evaluated in XL-EDA-ID patients in Japan. Cells expressing wild-type NEMO, most of which were derived from the T-cell lineage, were detected in 9 of 10 XL-EDA-ID patients. These data indicate that the frequency of somatic mosaicism of NEMO is high in XL-ED-ID patients and that the presence of somatic mosaicism of NEMO could have an impact on the diagnosis and treatment of XL-ED-ID patients.     

Hyperthyrotropinemia at 2 weeks of age indicates thyroid dysfunction and predicts the occurrence of delayed elevation of thyrotropin in very low birth weight infants

Background For preterm infants, transient hypothyroxinemia of prematurity and transient primary hypothyroidism, especially with delayed elevation of serum thyrotropin (TSH), are important. Methods To address the above two issues, we performed thyrotropin‐releasing hormone (TRH) stimulation tests at about 2 weeks of age for 31 preterm infants with a gestational age of 30 weeks or less. Results For basal TSH levels, 68% of infants (21 of 31) showed normal values (TSH < 10 mU/l) and 32% of infants (10 of 31) showed higher values (four infants: TSH 10–15 mU/l, six infants: TSH > 15 mU/l). Peak TSH values in response to TRH stimulation tests ranged from 9·76 to 114·8 mU/l. All infants showed a significant response to TRH stimulation tests. Only 9·5% of infants (two of 21) with normal basal TSH values showed a hyperresponse (peak TSH > 45 mU/l), whereas 80% of infants (eight of 10) who had higher basal TSH values showed a hyperresponse. All infants who showed mildly elevated basal TSH values (TSH 10–15 mU/l) and a hyperresponse to TRH stimulation tests showed delayed elevation of basal TSH values (TSH > 15 mU/l) later. Conclusions Thyrotropin‐releasing hormone stimulation tests at about 2 weeks of age suggested that the hypothalamic–pituitary–thyroid axis might be established even in extremely premature infants. Basal increased TSH levels (TSH > 10 mU/l) and a hyperresponse to TRH stimulation tests (peak TSH > 45 mU/l) suggested subclinical thyroid dysfunction. Serum TSH values at about 2 weeks of age could be useful for the prediction of delayed TSH elevation.     

Effect of platelet‐rich plasma on the biologic activity of the human rotator‐cuff fibroblasts: A controlled in vitro study

To assess the in vitro effect of platelet‐rich plasma (PRP) on biological activity of the human rotator cuff fibroblasts and to describe the optimal dose‐response to maximize cellular stimulation while reducing potential risk. Rotator cuff (RC) fibroblasts of n = 6 patients (mean age of 65.2 years) undergoing arthroscopic cuff tear reconstruction were cultured in vitro for 21 days and stimulated with PRP in three different concentrations (1‐, 5‐, and 10‐fold). Samples were obtained for DNA and GAG measurement at 1, 7, 14, and 21 days. The biological outcomes were regressed on the PRP concentration. The application of PRP significantly influenced the fibroblast proliferation and activity of the human rotator cuff with elevated glycosaminoglycan (GAG) and DNA levels. The dosage of PRP had the significantly highest impact on this proliferation using a onefold or fivefold application. PRP has a significant effect on fibroblast proliferation of the human rotator cuff in vitro with an optimal benefit using a onefold or fivefold PRP concentration. This study justifies further in vivo investigations using PRP at the human rotator cuff. © 2013 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 31:1249–1253, 2013