Interest of submucosal dissection knife for endoscopic treatment of Zenker's diverticulum.

BACKGROUND: Dual-Knife(®) (Olympus) and Hydride-Knife(®) are new needle knives frequently used for submucosal dissection because of their safety and precision. In this study we aimed to evaluate the efficacy and safety of such devices in the diverticulopexy by flexible endoscopy. METHODS: From February 2009 to March 2013, 42 patients (25 men), mean age 74.5, with symptomatic Zenker's diverticulum, were included in a non-randomized prospective multicenter study. The symptoms described by all patients include dysphagia, regurgitation and/or swallowing disorders. The diverticulopexy was performed with the Dual-Knife(®) or Hydrid-Knife(®), after septum exposure with the diverticuloscope, and terminated with distal tip clips positioning. All complications were noted. Patients' symptoms were regularly assessed during follow-up visits or telephone interviews. RESULTS: The first endoscopy treatment was successful for all patients. Thirty-seven patients (88%) had symptoms improvement after the first treatment. The recurrence rate was 14% (6 patients); a second endoscopic treatment was required 12 months on average after the first treatment, with 100% efficiency. Mid-term (16 months) efficiency was 91.67% after 1 to 3 endoscopic treatments. A total of 55 procedures were performed without perforation or significant bleeding and 3 patients underwent surgery. In multivariate analysis, the diverticulum size and the type of dissection knife were not risks factors for recurrence. CONCLUSIONS: Endoscopic diverticuloscope-assisted diverticulotomy with submucosal dissection knives is a safe and effective alternative treatment for patients with a symptomatic Zenker's diverticulum measuring between 2 and 10 cm.

Intrinsic membrane properties of pre-oromotor neurons in the intermediate zone of the medullary reticular formation.

Neurons in the lower brainstem that control consummatory behavior are widely distributed in the reticular formation (RF) of the pons and medulla. The intrinsic membrane properties of neurons within this distributed system shape complex excitatory and inhibitory inputs from both orosensory and central structures implicated in homeostatic control to produce coordinated oromotor patterns. The current study explored the intrinsic membrane properties of neurons in the intermediate subdivision of the medullary reticular formation (IRt). Neurons in the IRt receive input from the overlying (gustatory) nucleus of the solitary tract and project to the oromotor nuclei. Recent behavioral pharmacology studies as well as computational modeling suggest that inhibition in the IRt plays an important role in the transition from a taste-initiated oromotor pattern of ingestion to one of rejection. The present study explored the impact of hyperpolarization on membrane properties. In response to depolarization, neurons responded with either a tonic discharge, an irregular/burst pattern or were spike-adaptive. A hyperpolarizing pre-pulse modulated the excitability of most (82%) IRt neurons to subsequent depolarization. Instances of both increased (30%) and decreased (52%) excitability were observed. Currents induced by the hyperpolarization included an outward 4-aminopyridine (4-AP) sensitive K+ current that suppressed excitability and an inward cation current that increased excitability. These currents are also present in other subpopulations of RF neurons that influence the oromotor nuclei and we discuss how these currents could alter firing characteristics to impact pattern generation.

Synaptic and morphological characteristics of temperature-sensitive and -insensitive rat hypothalamic neurones.

1. Intracellular recordings were made from neurones in rat hypothalamic tissue slices, primarily in the preoptic area and anterior hypothalamus, a thermoregulatory region that integrates central and peripheral thermal information. The present study compared morphologies and local synaptic inputs of warm-sensitive and temperature-insensitive neurones. 2. Warm-sensitive neurones oriented their dendrites perpendicular to the third ventricle, with medial dendrites directed toward the periventricular region and lateral dendrites directed toward the medial forebrain bundle. In contrast, temperature-insensitive neurones generally oriented their dendrites parallel to the third ventricle. 3. Both warm-sensitive and temperature-insensitive neurones displayed excitatory postsynaptic potentials (EPSPs) and inhibitory postsynaptic potentials (IPSPs). In most cases, EPSP and IPSP frequencies were not affected by temperature changes, suggesting that temperature-insensitive neurones are responsible for most local synapses within this hypothalamic network. 4. Two additional neuronal groups were identified: silent neurones having no spontaneous firing rates and EPSP-driven neurones having action potentials that are primarily dependent on excitatory synaptic input from nearby neurones. Silent neurones had the most extensive dendritic trees, and these branched in all directions. In contrast, EPSP-driven neurones had the fewest dendrites, and usually the dendrites were oriented in only one direction (either medially or laterally), suggesting that these neurones receive more selective synaptic input.

Temperature-sensitive properties of rat suprachiasmatic nucleus neurons.

The hypothalamic suprachiasmatic nucleus (SCN) contains a heterogeneous population of neurons, some of which are temperature sensitive in their firing rate activity. Neuronal thermosensitivity may provide cues that synchronize the circadian clock. In addition, through synaptic inhibition on nearby cells, thermosensitive neurons may provide temperature compensation to other SCN neurons, enabling postsynaptic neurons to maintain a constant firing rate despite changes in temperature. To identify mechanisms of neuronal thermosensitivity, whole cell patch recordings monitored resting and transient potentials of SCN neurons in rat hypothalamic tissue slices during changes in temperature. Firing rate temperature sensitivity is not due to thermally dependent changes in the resting membrane potential, action potential threshold, or amplitude of the fast afterhyperpolarizing potential (AHP). The primary mechanism of neuronal thermosensitivity resides in the depolarizing prepotential, which is the slow depolarization that occurs prior to the membrane potential reaching threshold. In thermosensitive neurons, warming increases the prepotential's rate of depolarization, such that threshold is reached sooner. This shortens the interspike interval and increases the firing rate. In some SCN neurons, the slow component of the AHP provides an additional mechanism for thermosensitivity. In these neurons, warming causes the slow AHP to begin at a more depolarized level, and this, in turn, shortens the interspike interval to increase firing rate.

Role of the preoptic-anterior hypothalamus in thermoregulation and fever.

Lesion and thermal stimulation studies suggest that temperature regulation is controlled by a hierarchy of neural structures. Effector areas for specific thermoregulatory responses are located throughout the brain stem and spinal cord. The preoptic region, in and near the rostral hypothalamus, acts as a coordinating center and strongly influences each of the lower effector areas. The preoptic area contains neurons that are sensitive to subtle changes in hypothalamic or core temperature. Preoptic thermosensitive neurons also receive a wealth of somatosensory input from skin and spinal thermoreceptors. In this way, preoptic neurons compare and integrate central and peripheral thermal information. As a result of this sensory integration and its control over lower effector areas, the preoptic region elicits the thermoregulatory responses that are the most appropriate for both internal and environmental thermal conditions. Thermosensitive preoptic neurons are also affected by endogenous substances, such as pyrogens. By reducing the activity of warm-sensitive neurons and increasing the activity of cold-sensitive neurons, pyrogens cause fever, a state in which all thermoregulatory responses have elevated set-point temperatures.

Synaptic inhibition: its role in suprachiasmatic nucleus neuronal thermosensitivity and temperature compensation in the rat.

1. Whole-cell patch clamp recordings of neurones in the suprachiasmatic nucleus (SCN) from rat brain slices were analysed for changes in spontaneous synaptic activity during changes in temperature. While recent studies have identified temperature-sensitive responses in some SCN neurones, it is not known whether or how thermal information can be communicated through SCN neural networks, particularly since biological clocks such as the SCN are assumed to be temperature compensated. 2. Synaptic activity was predominantly inhibitory and mediated through GABAA receptor activation. Spontaneous inhibitory postsynaptic potentials (IPSPs) and currents (IPSCs) were usually blocked with perifusion of 10-50 microM bicuculline methiodide (BMI). BMI was used to test hypotheses that inhibitory synapses are capable of either enhancing or suppressing the thermosensitivity of SCN neurones. 3. Temperature had opposite effects on the amplitude of IPSPs and IPSCs. Warming decreased IPSP amplitude but increased IPSC amplitude. This suggests that thermally induced changes in IPSP amplitude are primarily influenced by resistance changes in the postsynaptic membrane. The thermal effect on IPSP amplitude contributed to an enhancement of thermosensitivity in some neurones. 4. In many SCN neurones, temperature affected the frequency of IPSPs and IPSCs. An increase in IPSP frequency with warming and a decrease in frequency during cooling made several SCN neurones temperature insensitive, allowing these neurones to maintain a relatively constant firing rate during changes in temperature. This temperature-adjusted change in synaptic frequency provides a mechanism of temperature compensation in the rat SCN.

Hypothalamic neurons. Mechanisms of sensitivity to temperature.

Rostral hypothalamic neurons are influenced by endogenous factors that affect thermoregulation and fever. Intracellular recordings reveal the synaptic and intrinsic mechanisms responsible for neuronal thermosensitivity. Many temperature-sensitive and temperature-insensitive neurons display a depolarizing prepotential that precedes action potentials. Temperature has little effect on the prepotential of insensitive neurons; however, in warm-sensitive neurons, the prepotential's depolarization is elevated by warming, and this increases the firing rate. Intracellular cAMP can increase neuronal thermosensitivity by enhancing the thermal response of the prepotential, most likely by thermosensitive ionic conductances. Warm-sensitive neurons also receive inhibitory synaptic input (IPSPs) from temperature-insensitive neurons, enhancing the thermosensitivity of some neurons, because cooling increases IPSP amplitude and duration. Therefore, even though IPSP frequencies do not change, cooling can decrease firing rates by increasing IPSP amplitudes. Because endogenous factors change neuronal firing rate and thermosensitivity, these changes likely occur both post- and presynaptically as well as by ionic conductances that determine the time interval between action potentials.

Cholecystokinin in transient lower oesophageal sphincter relaxation due to gastric distension in humans.

BACKGROUND AND AIMS: Transient lower oesophageal sphincter relaxations (TLOSRs) has been found to be the main mechanism of gastro-oesophageal reflux. In dogs, cholecystokinin (CCK) is involved in their occurrence. The aim was to evaluate the role of endogenous and exogenous CCK in the occurrence of TLOSRs induced by gastric distension at constant pressure in humans. METHODS: Ten healthy volunteers were studied. Lower oesophageal sphincter pressure was monitored with a sleeve device and gastric distension was performed via an intragastric bag monitored by a barostat. During distensions, saline, CCK (30 ng/kg/h) or the CCK-A receptor antagonist loxiglumide (10 mg/kg/h) was perfused in a random double blind order. RESULTS: There was no significant difference between the number of TLOSRs during the different distensions with saline; CCK increased the number of TLOSRs at a mean rate of 13.1 compared with 9.1 with saline (p < 0.001). Loxiglumide significantly decreased the number of relaxations to 5.3 versus 8.3 under paired saline infusion (p < 0.001). CONCLUSIONS: In humans, CCK-A receptor subtype is involved in the occurrence of transient lower oesophageal sphincter relaxations induced by gastric distension.

[Peroperative manometric evaluation of posterior fundoplication by celioscopy]. / Evaluation manométrique peropératoire des fundoplicatures postérieures par coelioscopie.

The aim of this prospective study was to evaluate objectively the effects of a laparoscopic posterior fundoplication on the pressure and length of the lower oesophageal sphincter (LOS) and to compare these results to those of a group of patient who underwent the same technique through a laparotomy. Fourty six patients were included in the laparoscopic group and 48 in the open group. Intraoperative manometry was performed using the same material before and after the posterior fundoplication (after evacuating the pneumoperitoneum). Criteria of assessment were the increases in pressure and length of the LOS. The two groups were comparable regarding age, rate of hiatal hernia, and stage of the oesophagitis. In the laparoscopic group, the mean pressure of LOS (mmHg) increased from 10.1 +/- 3.8 to 35.2 +/- 12 after the fundoplication (that is 3.5 times) and the length of LOS (cm) increased from 3.4 +/- 0.8 to 4.8 +/- 0.8 (that is 1.4 times). In the open group the increase was for the pressure and length respectively 3.3 times and 1.5 times the initial values. Thus by performing the same procedure we obtained the same effects on the pressure and length of the LOS. The effectiveness of laparoscopic posterior fundoplication should be similar to that of the open procedure.

Laparoscopic myotomy for primary esophageal achalasia: prospective evaluation.

BACKGROUND/AIM: The feasibility and safety of the laparoscopic myotomy having been previously demonstrated, the purpose of this prospective study was to evaluate its effectiveness. MATERIALS AND METHODS: Eight patients with primary esophageal achalasia underwent a laparoscopic modified Heller's myotomy with a posterior fundoplication. Early post-operative course has been uneventful in all cases. Clinical, endoscopic, and manometric prospective evaluations were performed with a median follow-up of 21 months (range 4-40). RESULTS: Excellent or good clinical results were present in all cases. Endoscopic studies were normal in all cases and the post-operative esophageal manometry (n = 7) showed that the median pressure of the lower esophageal sphincter decreased to 8.5 mmHg (range 3-9) which was significant compared to the median pre-operative value of 35 mmHg (p < 0.01). CONCLUSION: Though this experience is limited, these mean-term results suggest that the laparoscopic myotomy is effective to treat achalasia. It combines the efficacy of surgery and the minimally invasive aspect of dilatations. Thus, a prospective controlled trial comparing laparoscopic myotomy and dilatations is needed.

Neuronal thermosensitivity and survival of rat hypothalamic slices in recording chambers.

Several studies have examined the activity of neurons in hypothalamic tissue slices. The present experiments studied relationships between neuronal activity (firing rate and thermosensitivity) and tissue survival as a function of time and slice thickness. Rat hypothalamic tissue slices were sectioned at different thicknesses (350, 450, and 600 microm) and maintained in an oxygenated interface chamber which was perfused with artificial cerebrospinal fluid (ACSF). Electron and light microscopy were used to examine tissue morphology at different depths from the slice surfaces, and extracellular recordings were used to measure each cell's spontaneous activity and response to changes in temperature. Tissue damage was most evident at tissue layers nearest the gas-exposed surface. At 9 h in the chamber, 350 microm thick slices showed subtle changes in morphology with little difference between the gas-exposed and ACSF-exposed surfaces. In the 450 and 600 microm thick slices, tissue degeneration became more evident with increased damage at the gas-exposed surface. This damage extended fully into the tissue of the 600 microm section. There were no differences in firing rate or thermosensitivity between 350 and 450 microm slices; but in 600 microm slices, there were fewer spontaneously active neurons, although these neurons had a higher mean thermosensitivity. Based on the incidence of spontaneous activity and morphological integrity, the results suggest that electrophysiological experiments using 350 microm slices are preferable to experiments using thicker slices.

Characterization of specific anti-Candida IgM, IgA and IgE: diagnostic value in deep-seated infections.

The proposed serological diagnosis of systemic Candida infections is based on a microplate immunocapture technique detecting IgM, IgA and IgE anti-Candida antibodies. Activity is revealed with a suspension of human erythrocytes sensitized with somatic antigen of Candida albicans, and is quantified on an automated plate reader. The sera were obtained from patients with deep-seated (n = 56) and superficial (n = 193) candidosis. We compared this immunological method with a combination of indirect immunofluorescence and co-immunoelectrodiffusion. The immunocapture method was more sensitive (80.4% vs. 48.2% with indirect immunofluorescence and 58.9% with co-immunoelectrodiffusion), and often provided the diagnosis at an earlier stage, with clear therapeutic advantages. The IgA isotype was a particularly valuable marker of deep-seated Candida infections.

Cellular mechanisms for neuronal thermosensitivity in the rat hypothalamus.

1. To study the basic mechanisms of neuronal thermosensitivity, rat hypothalamic tissue slices were used to record and compare intracellular activity of temperature-sensitive and -insensitive neurones. This study tested the hypothesis that different neuronal types have thermally dependent differences in the transient potentials that determine the interspike interval. 2. Most spontaneously firing neurones displayed depolarizing prepotentials that preceded each action potential. In warm-sensitive neurones, warming increased the rate of rise of the depolarizing prepotential which, in turn, decreased the interspike interval and increased the firing rate. In contrast, temperature had little or no effect on the rate of rise in prepotentials of temperature-insensitive neurones. 3. Prepotential depolarization can be due to increasing depolarizing conductances or decreasing hyperpolarizing conductances. These are differences in the ionic conductances responsible for prepotentials in temperature-sensitive and -insensitive neurones. In warm-sensitive neurones, the net ionic conductance decreased as the prepotential depolarized towards threshold, suggesting that the prepotential is primarily determined by a decrease in outward potassium conductances. In contrast, in low-slope temperature-insensitive neurones, the net conductance remained constant during the interspike interval, suggesting a more balanced combination of both depolarizing and hyperpolarizing conductances. 4. Transient outward potassium currents, including A-currents, are important determinants of neuronal firing rates. These currents were identified in all warm-sensitive neurones tested, as well as in many temperature-insensitive and silent neurones. Since warming increased the rates of inactivation of these currents, transient K+ currents may contribute to the temperature-dependent prepotentials of some hypothalamic neurones.

Fever's glass ceiling.

The importance of an upper limit of the febrile response has been recognized since the time of Hippocrates. Although the precise temperature defining this limit varies according to the site at which body temperature is measured, human core temperature is almost never permitted to rise above 41 degrees C-42 degrees C during fever. There are compelling physiological reasons for such an upper limit of regulated body temperature. The mechanisms by which the limit is maintained are most likely complex and involve special properties of thermoregulatory neurons themselves, circulating endogenous antipyretics (such as arginine vasopressin and alpha-melanocyte-stimulating hormone), and soluble receptors for the (pyrogenic) cytokine mediators of the febrile response.

Intraoperative esophageal manometry and fundoplications: prospective study.

The purpose of this study was to validate the use of intraoperative manometry for assessing fundoplication and to search for predictive manometric criteria. This prospective study concerned 48 patients operated for gastroesophageal reflux. The manometry was carried out pre- and intraoperatively for all patients and postoperatively as well for 30 patients. The operative procedures were total fundoplication (n = 25) and posterior (partial) fundoplication (n = 5). The lower esophageal sphincter (LES) pressures and lengths were similar in the preoperative and intraoperative measurements before any esophageal mobilization, whereas the intraoperative LES pressure was significantly higher after fundoplication. The mean postoperative LES pressure decreased by 50 +/- 19% compared with the intraoperative pressure after fundoplication. The final intraoperative pressures of two dysphagic patients were not the highest of the study. More importantly, their final intraoperative pressures were 7.5 and 8.2 times the initial pressure, respectively, which was significantly greater than the intraoperative pressure increase of the nondysphagic patients (4.6 +/- 2.0 times). The final intraoperative pressure of the only patient with recurrence (18.2 mmHg) was the lowest of the study. In conclusion, intraoperative manometry is an effective method for evaluating the LES, and it could have predictive value for the surgical management of gastroesophageal reflux disease.

Temperature effects on membrane potential and input resistance in rat hypothalamic neurones.

1. Whole-cell recordings were conducted in rat hypothalamic tissue slices to test the hypothesis that thermal changes in membrane potential contribute to neuronal thermosensitivity. Intracellular recordings of membrane potential and input resistance were made in eighty-two neurones, including twenty-four silent neurones and fifty-eight spontaneously firing neurones (22 warm-sensitive neurones and 36 temperature-insensitive neurones). Fifty-seven of the neurones were recorded in the preoptic and anterior hypothalamus. 2. Warm-sensitive neurones increased their firing rates during increases in temperature (1.07 +/- 0.06 impulses s-1 degree C-1), but their resting membrane potentials were not affected by temperature (0.06 +/- 0.06 mV degree C-1). Similarly, temperature did not affect the membrane potentials of temperature-insensitive neurones or silent neurones. 3. Silent neurones had significantly lower input resistances (256.9 +/- 20.0 M omega), compared with temperature-insensitive (362.6 +/- 57.2 M omega) and warm-sensitive neurones (392.2 +/- 50.0 M omega). Temperature had the same effect on all three types of neurones, such that resistance increased during cooling and decreased during warming. 4. If hyperpolarizing or depolarizing holding currents were applied to neurones, temperature caused changes in the membrane potentials. This spurious effect can be explained by thermally induced changes in the input resistance. 5. Measurements of electrode tip potentials indicated that artificial changes in membrane potential may also be recorded if grounding electrodes are not isolated from the changes in temperature. 6. These results suggest that physiological changes in resting membrane potentials do not determine neuronal warm sensitivity, and thermal changes in input resistance do not determine the primary differences between warm-sensitive and temperature-insensitive hypothalamic neurones.