Impact of opioid maintenance treatment during pregnancy on neonatal birth weight and head circumference.

BACKGROUND: Pregnant mothers with opioid dependency commonly receive maintenance treatment of opioid (OMT), either as buprenorphine (BMT) or methadone maintenance treatment (MMT). We investigated, whether OMT adversely affects standardized neonatal anthropometric outcomes and whether BMT is potentially safer than MMT in this regard. METHODS: Retrospective chart review of mother infant dyad, with and without OMT. Infant's absolute and standardized (z-score) anthropometric outcomes at birth were first compared, between OMT and control group (negative meconium drug screen), and then between BMT and MMT group. These outcomes were also compared between infants who did or did not require treatment after birth for neonatal abstinence syndrome (NAS). RESULT: A total of 1479 participants with MDS were included [Control = 1251; OMT = 228 (MMT = 181; BMT = 47)]. Both the z-scores of birth weight (BW) and head circumference (HC) was lower in OMT group (p < 0.001). Among the OMT group, GA at delivery was slightly higher in the BMT group (p = 0.05). There was an inverse correlation between maternal dose at the time of delivery and anthropometric z-scores in the BMT group, mainly in female infants (BW: p = 0.006; HC: p = 0.003). Furthermore, In BMT group, infants with lower HC were more likely to require treatment for NAS (p = 0.01). CONCLUSION: HC and BW when comparing Z-scores were not different between MMT and BMT. High maternal dosing of buprenorphine is associated with lower BW and HC Z-scores but dose effect is not seen with methadone. In addition, there seems to be an association between NAS severity and HC, especially in the BMT group.

Porphyromonas gingivalis Sphingolipid Synthesis Limits the Host Inflammatory Response.

Porphyromonas gingivalis, like other bacteria belonging to the phylum Bacteroidetes, synthesizes sphingolipids (SLs). However, their exact roles in microbial physiology and their potential role in mediating interactions with their eukaryotic host are unclear. Our working hypothesis for this study was that synthesis of SLs (host-like lipids) affords a mechanism that allows P. gingivalis to persist in homeostasis with its host. In a previous study, we deleted a gene (PG1780 in strain W83) predicted to encode a serine palmitoyl transferase (SPT)-the enzyme that catalyzes the first conserved step in the synthesis of SLs-and we determined that the mutant was unable to synthesize SLs. Here, we characterized the SPT enzyme encoded by PG1780, analyzed the impact of SPT deletion on P. gingivalis gene expression (RNA-Seq analysis), and began to define the impact of SL synthesis on its interactions with host cells. Enzymatic analysis verified that the protein encoded by PG1780 is indeed an SPT. RNA-Seq analysis determined that a lack of SL synthesis results in differential expression of extracytoplasmic function sigma factors, components of the type IX secretion system (T9SS), and CRISPR and cas genes. Our data demonstrate that when human THP1 macrophage-like cells were challenged with the wild type (W83) and the SL-null mutant (W83 ΔSPT), the SL-null strain elicited a robust inflammatory response (elevated IL-1ß, IL-6, IL-10, IL-8, RANTES, and TNFα) while the response to the parent strain W83 was negligible. Interestingly, we also discovered that SLs produced by P. gingivalis can be delivered to host cells independent of cell-to-cell contact. Overall, our results support our working hypothesis that synthesis of SLs by P. gingivalis is central to its ability to manipulate the host inflammatory response, and they demonstrate the integral importance of SLs in the physiology of P. gingivalis.

Hepatic arterial nodal metastases in pancreatic cancer: is this the node of importance?

BACKGROUND: The hepatic artery lymph node (HALN) is frequently sampled during pancreaticoduodenectomy (PD). Data suggest that survival in the setting of HALN metastases is similar to that of stage IV pancreatic ductal adenocarcinoma (PDAC). The objectives of this study were to describe the prognostic significance of HALN metastases and to assess the predictive performance of HALN compared to peripancreatic lymph node status. METHODS: Patients undergoing PD for PDAC from January 2000-October 2010 were identified from a prospectively maintained database. Patients were included if during PD the HALN was submitted for pathologic evaluation. Patients were excluded if margins were macroscopically positive, if pathology was found to be consistent with a diagnosis other than PDAC. Overall (OS) and disease-free survival (DFS) were estimated by Kaplan-Meier methods. RESULTS: Of the 671 patients who underwent PD for PDAC, HALN status was analyzed for 147 patients. HALN was positive in 23 patients (16 %), 38 were peripancreatic lymph node (PPLN) and HALN negative, and 86 were PPLN+/HALN-. Median follow-up for survivors was 10 months. In a multivariable model, lymph node status and tumor differentiation predicted OS and DFS. Hazard of death and relapse/death were highest among the HALN+ patients (hazard ratio [HR] 2.94; p = 0.017 and HR 2.66; p = 0.011, respectively). Kaplan-Meier analysis revealed significant differences in OS (p = 0.017) and DFS (p = 0.013) based on lymph node status. CONCLUSIONS: OS and DFS are significantly reduced in patients with a positive HALN. Differentiation and lymph node status were predictors of OS and DFS. In the multivariate models, differentiation and lymph node status remain independent predictors of OS and DFS.

Collagen XVIII/endostatin expression in experimental endotoxemic acute renal failure

Acute renal failure (ARF) is a frequent complication of Gram-negative sepsis, with a high risk of mortality. Lipopolysaccharide (LPS)-induced ARF is associated with hemodynamic changes that are strongly influenced by the overproduction of nitric oxide (NO) through the cytokine-mediated up-regulation of inducible NO synthase. LPS-induced reductions in systemic vascular resistance paradoxically culminate in renal vasoconstriction. Collagen XVIII is an important component of the extracellular matrix expressed in basement membranes. Its degradation by matrix metalloproteases, cathepsins and elastases results in the formation of endostatin, claimed to have antiangiogenic activity and to be a prominent vasorelaxing agent. We evaluated the expression of endostatin/collagen XVIII in an endotoxemic ARF model. ARF was induced in C57BL/6 mice by intraperitoneal injection of LPS (10 mg/kg) followed by sacrifice 4 and 12 h later. Kidney tissue was the source of RNA and protein and the subject of histological analysis. As early as 4 h after LPS administration, blood urea, creatinine and NO levels were significantly increased compared to control. Endostatin/collagen XVIII mRNA levels were 0.71 times lower than sham-inoculated mice 4 h after LPS inoculation, returning to normal levels 12 h after LPS inoculation. Immunohistological examination revealed that acute injury caused by LPS leads to an increase of endostatin basement membrane staining in association with the decrease of CD31 endothelial basement membrane staining. These results indicate that in the early phase of endotoxemic ARF the endostatin levels were not regulated by gene expression, but by the metabolism of collagen XVIII.

Collagen XVIII/endostatin expression in experimental endotoxemic acute renal failure.

Acute renal failure (ARF) is a frequent complication of Gram-negative sepsis, with a high risk of mortality. Lipopolysaccharide (LPS)-induced ARF is associated with hemodynamic changes that are strongly influenced by the overproduction of nitric oxide (NO) through the cytokine-mediated up-regulation of inducible NO synthase. LPS-induced reductions in systemic vascular resistance paradoxically culminate in renal vasoconstriction. Collagen XVIII is an important component of the extracellular matrix expressed in basement membranes. Its degradation by matrix metalloproteases, cathepsins and elastases results in the formation of endostatin, claimed to have antiangiogenic activity and to be a prominent vasorelaxing agent. We evaluated the expression of endostatin/collagen XVIII in an endotoxemic ARF model. ARF was induced in C57BL/6 mice by intraperitoneal injection of LPS (10 mg/kg) followed by sacrifice 4 and 12 h later. Kidney tissue was the source of RNA and protein and the subject of histological analysis. As early as 4 h after LPS administration, blood urea, creatinine and NO levels were significantly increased compared to control. Endostatin/collagen XVIII mRNA levels were 0.71 times lower than sham-inoculated mice 4 h after LPS inoculation, returning to normal levels 12 h after LPS inoculation. Immunohistological examination revealed that acute injury caused by LPS leads to an increase of endostatin basement membrane staining in association with the decrease of CD31 endothelial basement membrane staining. These results indicate that in the early phase of endotoxemic ARF the endostatin levels were not regulated by gene expression, but by the metabolism of collagen XVIII.

Dúvidas na indicaçäo cirúrgica da cerclagem do tronco pulmonar / Questions regarding surgical indications in pulmonary artery banding

No período de fevereiro de 1979 a março de 1986 foram submetidos a cerclagem do TP 40 pacientes portadores de cardiopatias congênitas com hiperfluxo pulmonar, insuficiência cardíaca e hipodesenvolvimento ponderal. Vinte e três pacientes eram do sexo masculino e 17 do feminino com idade média de 6 meses (20 dias a 17 meses). Foram as seguintes as malformaçöes: CIV (22 casos), AVC total (6), DSVD (2), TA (2), TGVB (3), AT (2), VU (1) e cardiopatia complexa (2 casos). A cerclagem foi relizada com controle de pressäo do TP de tal forma a reduzí-la de 50% nos acianóticos e de 40% nos cianóticos. Dois pacientes (5%) faleceram no pós-operatório imediato, sendo um em bloqueo A-V total (AVC, 1, 7 kg, 20 dias de idade) e outro em septicemia, 20 dias após a cirurgia (CIV). Um óbito tardio ocorreu por broncopneumonia. Os demais pacientes evoluíram satisfatoriamente, com resoluçäo da ICC e ganho de peso em média 400g por mês (peso pré: média 4 kg, peso pós: média 7,5 kg). Treze pacientes foram reestudados hemodinamicamente, em média 21 meses após a cerclagem. A relaçäo FP/FS reduziu de 2,7 para 0,92, ao mesmo tempo em que houve diminuiçäo também na relaçäo PSAP/PSAo de 0,73 para 0,28. Nestes pacientes houve uma melhora clínica observada pela diminuiçäo do déficit ponderal de 38 por cento, para 20 por cento. Treze pacientes, foram submetidos a correçäo total em média 21 meses após a cerclagem, com dois óbitos hospitalares, sendo um imediato e outro por intoxicaçäo digitálica, 1 mês após a cirurgia. Analisando-se, separadamente, os 6 casos de AVCT, em todos predominava o shunt e näo o refluxo valvar. Houve um óbito imediato e 5 pacientes foram reestudados hemodinamicamente. Observou-se reduçäo importante nas pressöes pulmonares e no fluxo arterial pulmonar. Estes pacientes foram reoperados para correçäo total, com boa evoluçäo