Profil épidémiologique des urgences chirurgicales viscérales pédiatriques au Centre Hospitalier Universitaire de Libreville / Epidemiological profile of pediatric visceral surgical emergencies at the Libreville University Hospital Center

Objectif : Etudier les urgences chirurgicales viscérales pédiatriques au Centre Hospitalier Universitaire de Libreville (CHUL).Patients et méthodes : Il s'agissait d'une étude prospective transversale monocentrique descriptive réalisée au CHUL du 1er janvier 2018 au 30 juin 2019. Les patients âgés de 0 à 15 ans ayant présenté une urgence chirurgicale viscérale dans les services des urgences, chirurgie viscérale et thoracique et de réanimation néonatale et néonatalogie ont été inclus.Résultats : Cette étude portait sur 156 patients. L'âge moyen était de 6,67 ans avec une prédominance du sexe masculin (107/49). Quarante-deux patients étaient référés d'autres structures sanitaires. La symptomatologie évoluait depuis plus de 3 jours chez 42,3% patients. Des explorations à visée diagnostique étaient réalisées dans 145 cas, dont 90 échographies, 51 radiographies de l'abdomen sans préparation et 4 TDM. Le délai de prise en charge était de plus de 6 heures dans 82,1% cas. La pathologie la plus rencontrée était l'appendicite aigue (53 cas). Nous avions répertorié 9 décès dont 7 en post-opératoire. La durée moyenne d'hospitalisation était de 7 jours avec des extrêmes de 3 et 54 jours.Conclusion : Les urgences chirurgicales viscérales occupent une place de choix dans la pathologie chirurgicale en général et chez l'enfant en particulier. La mortalité concerne majoritairement les nouveau-nés porteurs de malformations congénitales.

Objective: To study pediatric visceral surgical emergencies at the Center Hospitalier Universitaire de Libreville (CHUL).Patients and methods: This was a descriptive single-center cross-sectional prospective study carried out at the CHUL from January 1, 2018 to June 30, 2019. Patients aged 0 to 15 years having presented a visceral surgical emergency in the emergency departments, surgery visceral and thoracic and neonatal resuscitation and neonatology were included. Results: This study involved 156 patients. The average age is 6.67 years with a predominance of the male sex (107/49).Forty-two patients were referred from other health facilities. Symptoms have evolved for more than 3 days in 42.3% of patients. Diagnostic scans were performed in 145 cases, including 90 ultrasounds and 51 unprepared abdominal xrays and 4 CT scans. The time to treatment was more than 6 hours in 82.1% of cases. The most common pathology was acute appendicitis (53 cases). We have identified 9 deaths, including 7 postoperative. The average length of hospital stay was 7 days with extremes of 3 and 54 days. Conclusion: Visceral surgical emergencies occupy a prominent place in surgical pathology in general and in children in particular. Mortality mainly concerns newborns with congenital malformations.

Extracellular adenosine 5'-triphosphate concentrations changes in rat spinal cord associated with the activation of urinary bladder afferents. A microdialysis study. / Variação da concentração extracelular de 5'-trifosfato de adenosina na medula espinal de rata associadas a fibras aferentes vesicais. Um estudo com microdiálise

ABSTRACT Objective To determine adenosine 5’-triphosphate levels in the interstice of spinal cord L6-S1 segment, under basal conditions or during mechanical and chemical activation of urinary bladder afferents. Methods A microdialysis probe was transversally implanted in the dorsal half of spinal cord L6-S1 segment in female rats. Microdialysate was collected at 15 minutes intervals during 135 minutes, in anesthetized animals. Adenosine 5’-triphosphate concentrations were determined with a bioluminescent assay. In one group of animals (n=7) microdialysate samples were obtained with an empty bladder during a 10-minutes bladder distension to 20 or 40cmH2O with either saline, saline with acetic acid or saline with capsaicin. In another group of animals (n=6) bladder distention was performed and the microdialysis solution contained the ectonucleotidase inhibitor ARL 67156. Results Basal extracellular adenosine triphosphate levels were 110.9±35.34fmol/15 minutes, (mean±SEM, n=13), and bladder distention was associated with a significant increase in adenosine 5’-triphosphate levels which was not observed after bladder distention with saline solution containing capsaicin (10µM). Microdialysis with solution containing ARL 67156 (1mM) was associated with significantly higher extracellular adenosine 5’-triphosphate levels and no further increase in adenosine 5’-triphosphate was observed during bladder distension. Conclusion Adenosine 5’-triphosphate was present in the interstice of L6-S1 spinal cord segments, was degraded by ectonucleotidase, and its concentration increased following the activation of bladder mechanosensitive but not of the chemosensitive afferents fibers. Adenosine 5’-triphosphate may originate either from the central endings of bladder mechanosensitive primary afferent neurons, or most likely from intrinsic spinal neurons, or glial cells and its release appears to be modulated by capsaicin activated bladder primary afferent or by adenosine 5’-triphosphate itself.

RESUMO Objetivo Determinar as concentrações extracelulares do 5’-trifosfato de adenosina no interstício dos segmentos medulares L6-S1, em condições basais ou durante a ativação mecânica e química das fibras aferentes vesicais. Métodos Um cateter de microdiálise foi implantado no sentido transversal na parte dorsal da medula espinal, entre os segmentos L6-S1 de ratas. O microdialisado foi coletado em intervalos de 15 minutos, durante 135 minutos, com os animais anestesiados. A concentração de 5’-trifosfato de adenosina nas amostras foi determinada mediante ensaio de bioluminescência. Em um grupo de animais (n=7), as amostras de microdialisado foram obtidas com a bexiga vazia, com distensão da bexiga para volume de 20 ou 40cmH2O, com solução salina, solução salina com ácido acético, ou solução salina com capsaicina. Em outro grupo (n=6), foi realizada com a bexiga distendida, e a solução para microdiálise continha o inibidor de ectonucleotidase ARL 67156. Resultados Os níveis extracelulares de trifosfato de adenosina no início do estudo foram 110,9±35,36fmol/15 minutos (média±EPM, n=13), e a distensão da bexiga causou um aumento nos níveis de 5’-trifosfato de adenosina, o que não foi observado após a distensão da bexiga com solução salina contendo capsaicina (10µM). A microdiálise com solução contendo ARL 67156 (1mM) foi associada com significante aumento dos níveis de trifosfato de adenosina extracelular, e nenhum aumento do trifosfato de adenosina foi observado durante a distensão da bexiga. Conclusão O 5’-trifosfato de adenosina está presente no interstício do segmento L6-S1 da medula espinal, é degradado por ectonucleotidases, e sua concentração aumentou com a ativação das fibras aferentes mecanossensíveis da bexiga, mas não das quimiossensíveis. O 5’-trifosfato de adenosina pode ter sido liberado das terminações centrais dos neurônios aferentes primários mecanossensíveis ou, mais provavelmente, de neurônios espinais intrínsecos, ou ainda de células gliais. Sua liberação parece ser modulada por fibras aferentes primárias da bexiga ativadas pela capsaicina ou pelo próprio 5’-trifosfato de adenosina.

The central mechanisms underlying the phenomenon of acupoint sensitization evoked by visceral nociceptive afferent / 中国针灸

The physiological mechanism underlying the acupoint sensitization was evaluated systemically by using the method of electric physiology at spinal cord, medulla, and thalamus levels; the dynamic change of acupoint from the relative "silence" to the relative "activation" function was explained through the study on the dynamic process of acupoint sensitization; the biological process of the therapeutic effect of acupoint stimulation was illuminated through the research of the central mechanism underlining the dose effect relationship between the sensitive acupoint and the related brain area, thus scientific evidence for the functional link between the acupoint and internal organs as well as the nature of the acupoint were provided.

Mast Cell-dependent Mesenteric Afferent Activation by Mucosal Supernatant From Different Bowel Segments of Guinea Pigs With Post-infectious Irritable Bowel Syndrome

BACKGROUND/AIMS: Mesenteric afferent nerves (MANs) play a pivotal role in the visceral-nociceptive perception. Inappropriate activation of MANs may be involved in the pathogenesis of post-infectious irritable bowel syndrome (PI-IBS). However, the underlying mechanisms remain unclear. We assessed the effects of mucosal mediators from different bowel segments of guinea pigs with PI-IBS on MAN firing and the role of mast cells. METHODS: PI-IBS was induced in guinea pigs by Trichinella spiralis infection. Inflammation in terminal ileum, proximal and distal colon was scored with hematoxylin-eosin staining, and mast cell infiltration was assessed with immunofluorescence. We determined the effects of supernatant extracted from the mucosa of different bowel segments of PI-IBS on MANs activity, and assessed the role of mast cells in this process. RESULTS: Eight weeks after infection, intestinal inflammation resolved, whereas mast cell numbers increased significantly in terminal ileum and proximal colon (P < 0.05) compared with findings in controls. Mucosal supernatant from different bowel segments of PI-IBS models, but not from controls, significantly enhanced the frequency of MAN firing (terminal ileum 41.01 +/- 7.60 Hz vs. 26.55 +/- 0.67 Hz, P = 0.001; proximal colon 45.90 +/- 11.20 Hz vs. 30.88 +/- 6.92 Hz, P = 0.002; distal colon 48.25 +/- 9.70 Hz vs. 29.47 +/- 6.13 Hz, P < 0.001). In addition, the excitatory effects were inhibited by mast cell stabilizer Nasmil (terminal ileum, 32.71 +/- 2.52 Hz, P = 0.030; proximal colon, 30.94 +/- 4.44 Hz, P = 0.002; distal colon, 27.15 +/- 5.83 Hz, P < 0.001). CONCLUSIONS: Supernatant from the intestinal mucosa of different bowel segments of PI-IBS models markedly enhanced the MAN firing in a mast cell-dependent manner, indicating that mast cell-mediated MAN activation plays an important role in the pathogenesis of PI-IBS.

Ginger and Its Pungent Constituents Non-Competitively Inhibit Serotonin Currents on Visceral Afferent Neurons

Nausea and emesis are a major side effect and obstacle for chemotherapy in cancer patients. Employ of antiemetic drugs help to suppress chemotherapy-induced emesis in some patients but not all patients. Ginger, an herbal medicine, has been traditionally used to treat various kinds of diseases including gastrointestinal symptoms. Ginger is effective in alleviating nausea and emesis, particularly, for cytotoxic chemotherapy drug-induced emesis. Ginger-mediated antiemetic effect has been attributed to its pungent constituents-mediated inhibition of serotonin (5-HT) receptor activity but its cellular mechanism of action is still unclear. Emetogenic chemotherapy drugs increase 5-HT concentration and activate visceral vagal afferent nerve activity. Thus, 5-HT mediated vagal afferent activation is essential to provoke emesis during chemotherapy. In this experiment, water extract of ginger and its three major pungent constituent's effect on 5-HT-evoked responses were tested on acutely dispersed visceral afferent neurons with patch-clamp methods. The ginger extract has similar effects to antiemetic drug ondansetron by blocking 5-HT-evoked responses. Pungent constituents of the ginger, [6]-shogaol, [6]-gingerol, and zingerone inhibited 5-HT responses in a dose dependent manner. The order of inhibitory potency for these compounds were [6]-shogaol>[6]-gingerol>zingerone. Unlike well-known competitive 5-HT3 receptor antagonist ondansetron, all tested ginger constituents acted as non-competitive antagonist. Our results imply that ginger and its pungent constituents exert antiemetic effects by blocking 5-HT-induced emetic signal transmission in vagal afferent neurons.

Differentiation of autonomic reflex control begins with cellular mechanisms at the first synapse within the nucleus tractus solitarius

Visceral afferents send information via cranial nerves to the nucleus tractus solitarius (NTS). The NTS is the initial step of information processing that culminates in homeostatic reflex responses. Recent evidence suggests that strong afferent synaptic responses in the NTS are most often modulated by depression and this forms a basic principle of central integration of these autonomic pathways. The visceral afferent synapse is uncommonly powerful at the NTS with large unitary response amplitudes and depression rather than facilitation at moderate to high frequencies of activation. Substantial signal depression occurs through multiple mechanisms at this very first brainstem synapse onto second order NTS neurons. This review highlights new approaches to the study of these basic processes featuring patch clamp recordings in NTS brain slices and optical techniques with fluorescent tracers. The vanilloid receptor agonist, capsaicin, distinguishes two classes of second order neurons (capsaicin sensitive or capsaicin resistant) that appear to reflect unmyelinated and myelinated afferent pathways. The differences in cellular properties of these two classes of NTS neurons indicate clear functional differentiation at both the pre- and postsynaptic portions of these first synapses. By virtue of their position at the earliest stage of these pathways, such mechanistic differences probably impart important differentiation in the performance over the entire reflex pathways.

Hipersensibilidad visceral: un concepto a nuestro alcance / Visceral hypersensitivity: a concept within our reach

Despite significant advances in the recognition of etiological factors and pathological mechanisms, the pathophysiology of functional gastrointestinal disorders (FGD) is still not fully understood. Visceral hypersensitivity has been recognized as a characteristic of patients with FGD, especially in patients with irritable bowel syndrome (IBS). Visceral afferent input is modulated by a variety of mechanisms, operating between the gastrointestinal tract and the brain. Dysfunction of these regulatory mechanisms could distort gastrointestinal perceptions. Recent findings suggest that in the majority of cases of IBS the primary abnormality may be at the periphery with alterations of the motor and secretory sensory activity. Although imaging techniques indicate that there are also differences in cortical activation. Furthermore, selective serotonin reuptake inhibitors may benefit FGD. Recent pharmacological studies suggest that 5-HT3 antagonist such as alosetron and cilansetron, and 5-HT4 agonist such as tegaserod and prucalopride may also have a potential use in FGD

Intrarenal artery injection of capsaicin activates spontaneous activity of renal afferent nerve fibers / 生理学报

The effects of intrarenal artery injection of capsaicin on multi- and single-unit spontaneous discharges of renal afferent nerve fibers were investigated in anesthetized rabbits. The results obtained are as follows: (1) intrarenal artery injection of capsaicin (20, 40, and 60 nmol/kg) increased the renal afferent nerve activity (ARNA) in a dose-dependent manner with unchanged arterial pressure; (2) pretreatment with ruthenium red (40 mmol/kg), a capsaicin receptor antagonist, completely abolished the effect of capsaicin; and (3) pretreatment with a nitric oxide synthase inhibitor L-NAME (N(6)-nitro-L-arginine methylester, 0.1 mmol/kg), significantly enhanced the ARNA response to capsaicin. The results suggest that intrarenal artery injection of capsaicin can activate ARNA via capsaicin receptors in anesthetized rabbits and that nitric oxide may be involved in regulating the activity of renal sensory nerve fibers as an inhibitory neurotransmitter.

Change of Neuropeptides of Bladder Afferents after Intravesical Electrical Stimulation in Spinalized Rat / 대한비뇨기과학회지

PURPOSE: The clinical benefits of intravesical electrical stimulation (IVES), in patients with increased residual urine or reduced bladder capacity, have been reported. However, studies on the underlying mechanism of IVES have been limited to the Adelta afferent in healthy rats. This study investigated the changes in the calcitonin gene- related peptide (CGRP) and substance P (SP) expressions, in the lumbosacral dorsal root ganglia (DRG) and the bladder of spinalized rats, to determine the effect of IVES on the C fiber afferent nerve. MATERIALS AND METHODS: Forty Sprague-Dawley rats were divided into normal controls (n=10); IVES treated normal rats (n=10); spinalized rats (n=10) and IVES treated spinalized rats (n=10). The IVES was performed for 2 weeks (5 days a week), 3 weeks after the spinalization in the spinalized animals. All animals had their DRG removed at the lumbosacral (L5-S1) level. Changes in the CGRP and SP, at the DRG and bladder, were measured by western-blot analysis. RESULTS: The relative density of the CGRP and SP following spinalization was significantly higher than those in the controls in both the DRG and the bladder. However, IVES in the spinalized rat significantly decreased the relative density of the SP, in both the DRG and the bladder, compared to the rats with spinalization alone. IVES in the spinalized rats significantly decreased the relative density of the CGRP, in the DRG only, compared to the rats with spinalization. CONCLUSIONS: IVES significantly reduced the CGRP and SP levels in the DRG of spinalized rats, but only the SP levels in the bladder. CGRP and SP are the main factors contributing to the hyper-excitability of the micturition reflex following spinal cord injury. These results suggest that the bladder C fiber afferents are also involved in modulating the micturition reflex with IVES.

Membrane electrical properties of visceral nociceptive neurons in anterior cingulate gyrus of cat / 中国应用生理学杂志

<p><b>AIM</b>To explore the cerebral cortex mechanism of visceral nociceptive sensation and its characteristics on the cell level, we investigated the membrane electrical properties of 176 stimulus-relative neurons of greater splanchnic nerve (GSN) in anterior cingulate gyrus (ACG) of 20 adult healthy cats.</p><p><b>METHODS</b>We used intracellular recording techniques of glass microelectrode and injected polarizing current into the neurons in ACG.</p><p><b>RESULTS</b>Among 176 neurons, 148 were visceral nociceptive neurons (VNNs) and 28 non-visceral nociceptive neurons (NVNNs). The membrane resistance (Rm), time constant (tau), membrane capacity (Cm), and the I-V curve of both VNNs and NVNNs in ACG were significantly different. The discharge frequency and amplitude of both VNNs and NVNNs produced by injecting depolarized current were different, too.</p><p><b>CONCLUSION</b>The results suggest that structure of cell membrane, volume of the soma, and other aspects of morphology between VNNs and NVNNs in ACG may have significant differences. The results also might provide progressively experimental evidence for specific theory of pain sensation.</p>

Intrarenal artery injection of L-arginine inhibits spontaneous activity of renal afferent nerve fibers / 生理学报

The purpose of this study was to determine the effect of intrarenal artery injection of L-arginine on multi- and single-unit spontaneous discharges of renal afferent nerve fibers in anesthetized rabbits. The results obtained are as follows: (1) intrarenal artery injection of L-arginine (0.05, 0.24, and 0.48 mmol/kg) decreased the renal afferent nerve activity (ARNA) in a dose-dependent manner with arterial pressure unchanged; (2) pretreatment with a nitric oxide synthase inhibitor L-NAME (N6-nitro-L-arginine methylester, 0.11 mmol/kg), completely abolished the effect of L-arginine; and (3) intrarenal artery injection of a nitric oxide donor SIN-1 (3-morpholinosydnonimine, 3.75 micromol/kg) also resulted in an inhibition of ARNA. The results suggest that intrarenal artery injection of NO precursor (L-arginine) and donor (SIN-1) can inhibit ARNA in anesthetized rabbits.

Effects of intravesical capsaicin on the substance P- and CGRP-immunoreactive terminals of the rat spinal dorsal horn / 대한해부학회지

Visceral afferent nerve fibers containing substance P or calcitonin gene-related peptide (CGRP) are distributed in the bladder wall, and are known to be stimulated by and then desensitized by capsaicin. Recently, there have been some reports on the effectiveness of intravesical capsaicin administration for the treatment of hypersensitive lower urinary tract disorder or neurogenic bladder. In this study, the effects of intravesical capsaicin on the substance P or CGRP immunoreactivities in the spinal dorsal horn were investigated and the mechanism of capsaicin treatment for bladder disorders was revealed. After intravesical administration of capsaicin, the substance P and CGRP immunoreactive areas were measured at the dorsal horn of L4 and S1 spinal cord. Before capsaicin treatment, the substance P immuno- reactive area was 2.61+/-0.78 x 105 mm2 in L4 and 1.66+/-0.49 x 105 mm2 in S1. The substance P immunoreactivity was markedly reduced 1~2 weeks after capsaicin treatment in both L4 and S1 spinal cord. The CGRP immunoreactive area was 1.74+/-0.52 x 105 mm2 in L4 and 1.14+/-0.69 x 105 mm2 in S1, but was not reduced after capsaicin treatment. Therefore, capsaicin administered intravesically desensitizes nerve fibers containing substance P and consequently suppresses pain and voiding reflex.