Routine cervical dilatation during elective cesarean section and its influence on maternal morbidity: a randomized controlled study

AIM: To determine the effect of routine intraoperative cervical dilatation during elective cesarean section on maternal morbidity. SUBJECTS AND METHODS: Patients with even numbers in the operative elective cesarean section list were included in the study. Of these, every second patient underwent intraoperative cervical dilatation. All participants in the two groups had otherwise similar preoperative care, operative procedures and subsequent clinical care. Blood loss was estimated and maternal infection status was assessed postoperatively by any rise of temperature or wound infection. RESULTS: Of the 131 patients included in the study, 67 underwent cervical dilation and 64 served as controls. There was no significant difference in postoperative hemoglobin, incidence of fever, or wound infection between the two groups. Only two of the cervical dilation group and one control patient developed postoperative fever. A hemoglobin drop of more than 0.5 g/dL was noted in 27 and 26 patients in the cervical dilation and the no dilation groups, respectively (NS). None of the study patients had signs of wound infection. CONCLUSION: Intraoperative cervical dilatation during elective cesarean section did not reduce the risk of postoperative maternal fever, wound infection or change in hemoglobin concentration.     

AAV-HDV: An Attractive Platform for the In Vivo Study of HDV Biology and the Mechanism of Disease Pathogenesis †

Hepatitis delta virus (HDV) infection causes the most severe form of viral hepatitis, but little is known about the molecular mechanisms involved. We have recently developed an HDV mouse model based on the delivery of HDV replication-competent genomes using adeno-associated vectors (AAV), which developed a liver pathology very similar to the human disease and allowed us to perform mechanistic studies. We have generated different AAV-HDV mutants to eliminate the expression of HDV antigens (HDAgs), and we have characterized them both in vitro and in vivo. We confirmed that S-HDAg is essential for HDV replication and cannot be replaced by L-HDAg or host cellular proteins, and that L-HDAg is essential to produce the HDV infectious particle and inhibits its replication. We have also found that lack of L-HDAg resulted in the increase of S-HDAg expression levels and the exacerbation of liver damage, which was associated with an increment in liver inflammation but did not require T cells. Interestingly, early expression of L-HDAg significantly ameliorated the liver damage induced by the mutant expressing only S-HDAg. In summary, the use of AAV-HDV represents a very attractive platform to interrogate in vivo the role of viral components in the HDV life cycle and to better understand the mechanism of HDV-induced liver pathology.     

Physiopathology of splanchnic vasodilation in portal hypertension

In liver cirrhosis, the circulatory hemodynamic alterations of portal hypertension significantly contribute to many of the clinical manifestations of the disease. In the physiopathology of this vascular alteration, mesenteric splanchnic vasodilation plays an essential role by initiating the hemodynamic process. Numerous studies performed in cirrhotic patients and animal models have shown that this splanchnic vasodilation is the result of an important increase in local and systemic vasodilators and the presence of a splanchnic vascular hyporesponsiveness to vasoconstrictors. Among the molecules and factors known to be potentially involved in this arterial vasodilation, nitric oxide seems to have a crucial role in the physiopathology of this vascular alteration. However, none of the wide variety of mediators can be described as solely responsible, since this phenomenon is multifactorial in origin. Moreover, angiogenesis and vascular remodeling processes also seem to play a role. Finally, the sympathetic nervous system is thought to be involved in the pathogenesis of the hyperdynamic circulation associated with portal hypertension, although the nature and extent of its role is not completely understood. In this review, we discuss the different mechanisms known to contribute to this complex phenomenon.     

Correlation of lipid profiles and anthropometric variables with serum lipoprotein(a) levels in childhood

The aim of the present study was to evaluate lipoprotein(a) distribution in children and to assess its association with lipid profile and anthropometric variables. We studied 98 children (44 girls and 54 boys) with ages ranging from 6 to 7 years, who were included in an epidemiological study on the prevalence of hypercholesterolemia in children in the province of Biscay. The following parameters were determined: weight and height, body mass index, lipoprotein(a), and lipid profile. Lipid profile included total cholesterol, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, triglycerides, apolipoprotein B, and apolipoprotein A1. The mean and median serum lipoprotein(a) levels were 13.07 and 5.56 mg/dl respectively and were 11.43 and 3.92 mg/dl for boys and 15.09 and 8.32 mg/dl for girls. Lipoprotein(a) concentrations > 30 mg/dl were found in 7.4% of the boys and in 11.4% of the girls. The mean values and prevalences of lipoprotein(a) > 30 mg/dl were lower in boys than in girls but these differences were not statistically significant. A positive correlation was found between lipid profile (LDL-cholesterol, apolipoprotein B and LDL-cholesterol/HDL-cholesterol index) and lipoprotein(a) levels. When evaluating anthropometric variables, we found a statistically significant inverse correlation between weight and lipoprotein(a). In view of the cumulative effect of cardiovascular risk factors and the results of this study, we believe that lipoprotein(a) determination should be considered in children with an unfavorable lipid profile.     

Clinical and angiographic expression of myocardial ischemia in stable angina as a function of its coronary reserve

We have studied the distribution of the coronary reserve, evaluated by serial effort tests, in patients with proved coronaropathy, determining the correlation between clinic (effort and mixed angina) and coronary reserve (fixed and variable), assessing angiographic findings in function to that reserve. We took 120 patients with stable angina to whom 2 effort tests were performed, basal and after vasodilator drugs. It was considered variable reserve if in the second test the S-T descend improved greater than or equal to 1 mm for a similar of greater double product and fixed when it didn't improve. In all patients coronarography was performed. Seventy two patients (60%) showed fixed reserve, 58 with effort angina (80%) and 14 (20%) with mixed. Forty eight showed variable reserve, 40 (80%) with mixed angina and 8 (17%) with effort. The group with fixed reserve had a greater S-T max. descent (2.9 +/- 0.9 vs 2.2 +/- 0.4) (p less than 0.001), a lower double product max. (221 +/- 44 vs 284 +/- 37) (p less than 0.001) and a lower maximal oxygen consumption (MVO2 7 +/- 2 vs 11 +/- 2) (p less than 0.001) than the variable reserve group. Considering the angiography, the fixed reserve group had more number of vessels affected (1.9 +/- 0.7 vs 1.4 +/- 0.5) (p less than 0.01), a higher angiographic score (4.88 +/- 2.4 vs 2.2 +/- 1.2) (p less than 0.001), a lower ejection fraction (59 +/- 8.5 vs 65 +/- 7.5) (p less than 0.001), more multivessel and descending anterior artery lesion than the variable reserve group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Selective impairment of spinal mu-opioid receptor mechanism by plasticity of serotonergic facilitation mediated by 5-HT2A and 5-HT2B receptors

Opioid analgesia is compromised by intracellular mediators such as protein kinase C (PKC). The phosphatidylinositol hydrolysis-coupled serotonin receptor 5-HT2 is ideally suited to promote PKC activation. We test the hypothesis that 5-HT2A and 5-HT2B receptors, which have been previously shown to become pro-excitatory after spinal nerve ligation (SNL), can negatively influence the ability of opioids to depress spinal excitation evoked by noxious input. Spinal superfusion with (100 nM) mu-opioid receptor (MOR)-agonist DAMGO significantly depressed C fiber-evoked spinal field potentials. Simultaneous administration of subclinical 5-HT2AR antagonist 4F 4PP (100 nM) or 5-HT2BR antagonist SB 204741 (100 nM) significantly reduced the IC50 value for DAMGO in nerve-ligated rats (97.56 nM ± 1.51 and 1.20 nM ± 1.28 respectively, relative to 104 nM ± 1.08 at the baseline condition), but not in sham-operated rats. Both antagonists failed to alter depression induced by delta-opioid receptor (DOR)-agonist D-ala2-deltorphin II after SNL as well as in the sham condition. Western blot analysis of dorsal horn homogenates revealed bilateral upregulation of 5-HT2AR and 5-HT2BR protein band densities after SNL. As assessed from double immunofluorescence labeling for confocal laser scanning microscopy, scarce dorsal horn cell processes showed co-localization color overlay for 5-HT2AR/MOR, 5-HT2BR/MOR, 5-HT2AR/DOR, or 5-HT2BR/DOR in sham-operated rats. Intensity correlation-based analyses showed significant increases in 5-HT2AR/MOR and 5-HT2BR/MOR co-localizations after SNL. These results indicate that plasticity of spinal serotonergic neurotransmission can selectively reduce spinal MOR mechanisms via 5-HT2A and 5-HT2B receptors, including upregulation of the latter and increased expression in dorsal horn neurons containing MOR.     

Atrophy of mesenteric sympathetic innervation may contribute to splanchnic vasodilation in rat portal hypertension

Background and aims: Portal hypertension is associated with downregulation of mRNA and proteins involved in adrenergic transmission in the superior mesenteric artery (SMA) in portal vein‐ligated (PVL) and cirrhotic rats. We aimed to investigate whether SMA adrenergic dysfunction was accompanied by sympathetic nerve structural changes and whether it was extensive to resistance mesenteric arteries. We also attempted to localize the origin of mRNA of specific adrenergic genes. Methods and results: In situ hybridization showed tyrosine hydroxylase (Th) mRNA expression in neuronal bodies of superior mesenteric ganglia and inside axonal fibres surrounding proximal SMA sections. Comparison of SMA by Th immunohistochemistry, both in PVL and bile duct‐ligated (BDL) rats, demonstrated a significant decrease in the number of nervous structures (69% PVL; 62% BDL), total nervous area (70% PVL; 52% BDL) and Th‐stained nervous area (89% PVL; 64% BDL) compared with sham rats. A strong correlation was detected between the Th‐stained nervous area and the haemodynamic parameters, mainly with SMA resistance (r=0.9, P<0.001 for PVL and r=0.75, P=0.018 for BDL). Western blot analysis of Th, dopamine β‐hydroxylase and synaptosome‐associated protein of 25 kDa indicated a significant inhibition in protein expression (35–58%) in mesenteric resistance arteries from both portal hypertension models compared with sham. By contrast, nervous structure analysis and protein expression in renal arteries showed no differences between sham and PVL rats. Conclusion: Portal hypertension is associated with sympathetic nerve atrophy/regression in the mesenteric arterial vasculature that could contribute to the splanchnic vasodilation associated with portal hypertension.