Can Birth Weight Influence the Development of Neonatal Abstinence Syndrome?

Background: Neonatal Abstinence Syndrome (NAS), a manifestation of the widespread opioid epidemic, has plagued our country, and particularly the region of Northeast Tennessee, for quite some time now. One question among many that seems to baffle almost everyone involved in research on the topic at hand is that why do only 35-40% of opioid exposed pregnancies result in NAS requiring medication while sparing the rest. Is there some discriminatory factor other than in utero opioid exposure involved? Thus, in light of this knowledge, we wanted to investigate whether birth weight at the time of delivery can influence the development of NAS; that is, are neonates of a low birth weight or high birth weight (with respect to gestational age thresholds) more likely to develop NAS. Methods: Therefore, we conducted a retrospective chart analysis of all deliveries within the Mountain States Health Alliance System over a 5 years period between July 1, 2011- June 30, 2016 at all 5 delivery sites in Northeast Tennessee and Southwest Virginia (N=18,728). Out of this sample size, we identified 2,392 at-term newborns as positive for prenatal opioid exposure, and then we stratified them into 2 categories: birth weight ≤3.5kg (proxy for low or average birth weight with respect to gestational age thresholds) and birth weight ≥3.5kg (proxy for high birth weight with respect to gestational age thresholds). Thereafter, we ran SPSS statistical analyses involving chi square, t tests, and logistic regression to assess whether one birth weight group was more likely to have a higher incidence rate of NAS compared to the other birth weight group. Results: We found that even after controlling for significant confounders such as marital status, race, and pregnancy smoking, benzodiazepine, and marijuana use, infants who were in the low to average birth weight group (≤3.5kg in this study) were almost twice as likely (statistically significant adjusted odds ratio of 1.95) to develop NAS compared to infants who were in the high birth weight group (≥3.5kg in this study). Our study helps shed some important light on the discriminatory factors for NAS development, with birth weight being a significantly associated clinical factor as we now know. Discussion & Implications: Unfortunately, the mechanism for the transport of opioids across the placenta is complicated, and poorly understood. There may be more ‘unbound or free opioids’ available in infants of low to average birth weight (with respect to gestational age thresholds) compared to infants of high birth weight (with respect to gestational age thresholds) resulting in a higher incidence of NAS in the former population. It is more of a speculation rather than a conclusion to explain the results of our study. However, being equipped with this knowledge that opioid exposed neonates of low to average birth weight (with respect to gestational age thresholds) have a higher risk of developing NAS will allow physicians to identify infants with a higher risk for NAS early, and this will subsequently lead to better outcomes and reduced severity in cases of NAS

Prolonged toxicity in a 2-year-old after accidental ingestion of aripiprazole.

Aripiprazole (Abilify), or 7-{4-[4-(2,3-dichlorophenyl)-1-piperazinyl]butyloxy}-3,4-dihydro-2(1H)-quinolone, is a novel atypical antipsychotic possessing a long half-life. Although not a Food and Drug Administration-approved indication, low-dose aripiprazole is used to treat pediatric psychiatric conditions. Data regarding toxicity of low-dose aripiprazole ingestions in children are limited. We report the case of an accidental ingestion of two 5-mg aripiprazole tablets by a 2-year-old girl with a measured drug level of 160 ng/mL approximately 34 hours after ingestion. She exhibited marked lethargy, tremor, and tachycardia persisting over 72 hours. Emergency physicians, pediatricians, and psychiatrists should be aware of the potential for significant and prolonged toxicity in children even with relatively small-dose aripiprazole exposures

Kratom-induced transaminitis with subsequent precipitated opioid withdrawal following naltrexone

Kratom is an herbal supplement that has gained popularity for recreational use within the United States. Kratom exerts opioid-like effects and, although not US FDA approved, is commonly used for self-treatment of pain, withdrawal management from opioids, and euphoria. Drug-related hepatic injury has been associated with kratom use. All of this raises concern for patient safety and monitoring. The potential for additive liver toxicity must be considered when kratom is used concurrently with hepatotoxic, over-the-counter, herbal, and prescription medications. This case report describes a case of kratom-induced liver inflammation complicated by opioid withdrawal that was precipitated by initiation of IM naltrexone. To our knowledge, there are no published case reports related to opioid withdrawal following naltrexone administration in patients using kratom (without other opioids). The purpose of this case report is to demonstrate potential complications that may arise with kratom use and considerations that should be taken prior to initiation of naltrexone in kratom users

Erythromycin lacks colon prokinetic effect in children with functional gastrointestinal disorders: a retrospective study

<p>Abstract</p> <p>Background</p> <p>Motilin, a peptide hormone has a direct excitatory effect on circular smooth muscle strips derived from the human colon. Reduced plasma motilin concentration has been reported in adults with chronic constipation. Erythromycin, a non-peptide motilin receptor agonist, induces phase 3 of the migrating motor complex (MMC) in the antro-duodenum and also reduces oro-cecal transit time. A pediatric study has reported an improvement in clinical symptoms of constipation following erythromycin administration, but the effect on colon motility in children has not been formally evaluated. We used colon manometry to study the effect of intravenous erythromycin lactobionate at 1 mg/kg on colon motiltiy in ten children.</p> <p>Methods</p> <p>We selected patients with normal antroduodenal and colon manometry studies that were performed simultaneously. All studies were performed for clinically indicated reasons. We quantified the effect of erythromycin on colon contraction by calculating the area under the curve (AUC).</p> <p>Results</p> <p>The mean (SE of mean) AUC in the colon during the fasting, post-erythromycin and postprandial phases of the study was 2.1 mmHg/sec (0.35), 0.99 mmHg/sec (0.17) and 3.05 mmHg/sec (0.70) respectively. The AUC following erythromycin was significantly less compared to the fasting phase of the study (p < 0.01).</p> <p>Conclusion</p> <p>Erythromycin lacks colon prokinetic effect in children with chronic constipation evaluated by colon manometry.</p

Study on the effects of nitrilotriproprionic acid and 4,5-dihydroxy-1,3-benzene disulphonate on the fractionation of beryllium in human serum using graphite furnace atomic absorption spectrometry

<p>Abstract</p> <p>Background</p> <p>Occupational exposure to beryllium may cause Chronic Beryllium Disease (CBD), a lung disorder initiated by an electrostatic interaction with the MHC class II human leukocyte antigen (HLA). Molecular studies have found a significant correlation between the electrostatic potential at the HLA-DP surface and disease susceptibility. CBD can therefore be treated by chelation therapy. In this work, we studied the effect of two complexing agents, nitrilotriproprionic acid (NTP) and 4,5-dihydroxy-1,3-benzene disulphonate (Tiron), on the fractionation of beryllium in human serum analysed by graphite furnace atomic absorption spectrometry (GFAAS).</p> <p>Results</p> <p>We found the average serum beryllium concentration of fourteen non-exposed individuals to be 0.53 (± 0.14) μg l^-1, with 21 (± 3)% of the beryllium mass bound to the low molecular weight fraction (LMW), and 79 (± 3)% bound to the high molecular weight fraction (HMW). The addition of Tiron increased the beryllium mass in the HMW fraction, while NTP was not seen to have any influence on the fractionation of beryllium between the two fractions. NTP was, however, shown to complex 94.5% of the Be mass in the LMW fraction. The beryllium GFAAS detection limit, calculated as three times the standard deviation of 10 replicates of the lowest standard (0.05 μg L^-1), was 6.0 (± 0.2) ng L^-1.</p> <p>Conclusion</p> <p>The concentration of beryllium or its fractionation in human serum was not affected by sex or smoking habit. On average, three quarters of the beryllium in serum were found in the HMW fraction. Of the two ligands tested, only Tiron was effective in mobilising beryllium under physiological conditions, thus increasing the Be content in the HMW fraction.</p

cDNA Sequence and Fab Crystal Structure of HL4E10, a Hamster IgG Lambda Light Chain Antibody Stimulatory for γδ T Cells

Hamsters are widely used to generate monoclonal antibodies against mouse, rat, and human antigens, but sequence and structural information for hamster immunoglobulins is sparse. To our knowledge, only three hamster IgG sequences have been published, all of which use kappa light chains, and no three-dimensional structure of a hamster antibody has been reported. We generated antibody HL4E10 as a probe to identify novel costimulatory molecules on the surface of γδ T cells which lack the traditional αβ T cell co-receptors CD4, CD8, and the costimulatory molecule CD28. HL4E10 binding to γδ T cell, surface-expressed, Junctional Adhesion Molecule-Like (JAML) protein leads to potent costimulation via activation of MAP kinase pathways and cytokine production, resulting in cell proliferation. The cDNA sequence of HL4E10 is the first example of a hamster lambda light chain and only the second known complete hamster heavy chain sequence. The crystal structure of the HL4E10 Fab at 2.95 Å resolution reveals a rigid combining site with pockets faceted by solvent-exposed tyrosine residues, which are structurally optimized for JAML binding. The characterization of HL4E10 thus comprises a valuable addition to the spartan database of hamster immunoglobulin genes and structures. As the HL4E10 antibody is uniquely costimulatory for γδ T cells, humanized versions thereof may be of clinical relevance in treating γδ T cell dysfunction-associated diseases, such as chronic non-healing wounds and cancer

A novel treatment of cystic fibrosis acting on-target:cysteamine plus epigallocatechin gallate for the autophagy-dependent rescue of class II-mutated CFTR

We previously reported that the combination of two safe proteostasis regulators, cysteamine and epigallocatechin gallate (EGCG), can be used to improve deficient expression of the cystic fibrosis transmembrane conductance regulator (CFTR) in patients homozygous for the CFTR Phe508del mutation. Here we provide the proof-of-concept that this combination treatment restored CFTR function and reduced lung inflammation (P<0.001) in Phe508del/Phe508del or Phe508del/null-Cftr (but not in Cftr-null mice), provided that such mice were autophagy-competent. Primary nasal cells from patients bearing different class II CFTR mutations, either in homozygous or compound heterozygous form, responded to the treatment in vitro. We assessed individual responses to cysteamine plus EGCG in a single-centre, open-label phase-2 trial. The combination treatment decreased sweat chloride from baseline, increased both CFTR protein and function in nasal cells, restored autophagy in such cells, decreased CXCL8 and TNF-α in the sputum, and tended to improve respiratory function. These positive effects were particularly strong in patients carrying Phe508del CFTR mutations in homozygosity or heterozygosity. However, a fraction of patients bearing other CFTR mutations failed to respond to therapy. Importantly, the same patients whose primary nasal brushed cells did not respond to cysteamine plus EGCG in vitro also exhibited deficient therapeutic responses in vivo. Altogether, these results suggest that the combination treatment of cysteamine plus EGCG acts ‘on-target' because it can only rescue CFTR function when autophagy is functional (in mice) and improves CFTR function when a rescuable protein is expressed (in mice and men). These results should spur the further clinical development of the combination treatment

Identification of the Feline Humoral Immune Response to Bartonella henselae Infection by Protein Microarray

Background: Bartonella henselae is the zoonotic agent of cat scratch disease and causes potentially fatal infections in immunocompromised patients. Understanding the complex interactions between the host’s immune system and bacterial pathogens is central to the field of infectious diseases and to the development of effective diagnostics and vaccines. Methodology: We report the development of a microarray comprised of proteins expressed from 96 % (1433/1493) of the predicted ORFs encoded by the genome of the zoonotic pathogen Bartonella henselae. The array was probed with a collection of 62 uninfected, 62 infected, and 8 ‘‘specific-pathogen free’ ’ naïve cat sera, to profile the antibody repertoire elicited during natural Bartonella henselae infection. Conclusions: We found that 7.3 % of the B. henselae proteins on the microarray were seroreactive and that seroreactivity was not evenly distributed between predicted protein function or subcellular localization. Membrane proteins were significantly most likely to be seroreactive, although only 23 % of the membrane proteins were reactive. Conversely, we found that proteins involved in amino acid transport and metabolism were significantly underrepresented and did not contain any seroreactive antigens. Of all seroreactive antigens, 52 were differentially reactive with sera from infected cats, and 53 were equally reactive with sera from infected and uninfected cats. Thirteen of the seroreactive antigens were found to be differentially seroreactive between B. henselae type I and type II. Based on these results, we developed a classifier algorith