The use of a novel synthetic resorbable scaffold (TIGR Matrix®) in a clinical quality improvement (CQI) effort for abdominal wall reconstruction (AWR).

PURPOSE: The use of hernia mesh is a common practice in abdominal wall reconstruction (AWR) operations. The high cost of biologic mesh has raised questions about the value of its use in AWR. Resorbable synthetic mesh may have the potential benefits of biologic mesh, minimizing the need for removal when infected, at a lower cost. METHODS: A hernia program has implemented the principles of clinical quality improvement (CQI) to improve patient outcomes. One process improvement attempt was implemented using a newly available resorbable synthetic scaffold. Long-term follow-up was obtained as a part of the CQI process. RESULTS: A total of 91 patients undergoing AWR were included between 8/11 and 9/15 (49 months). There were 58 female (64%) and 33 male (36%) patients. The average age was 57.2 years (28-80). The average BMI was 34.0 (17.6-53.4). There were 52 patients (57%) with recurrent hernias. Mean hernia defect size was 306.6 cm2 (24-720) and mean mesh size was 471.7 cm2 (112-600). Outcomes included a mean length of stay of 7.5 days (0-49), a recurrence rate of 12% (11/91) and a wound complication rate of 27% (25/91). The recurrence rate decreased to 4.5% (3/66) after several improvements, including adopting a transversus abdominus release (TAR) approach, were implemented. There were no mesh-related complications and no mesh removal (partial or total) was required. The mean follow-up length was 42.4 months (0-102). CONCLUSION: In this group of patients, an attempt at process improvement was implemented using a resorbable synthetic scaffold for AWR. With no mesh-related complications and no mesh removals required, there was an improvement in value due to the decrease in mesh cost and improved outcomes over time. Long-term follow-up demonstrated the durability of the repair.

Ion currents and spiking properties of identified subtypes of locust octopaminergic dorsal unpaired median neurons.

Efferent dorsal unpaired median (DUM) neurons are key elements of an insect neuromodulatory system. In locusts, subpopulations of DUM neurons mediate octopaminergic modulation at specific targets depending on their activity during different behaviours. This study investigates whether in addition to synaptic inputs, activity in DUM neurons depends on intrinsic membrane properties. Intracellular in situ recordings and whole-cell patch-clamp recordings from freshly isolated somata characterize somatic voltage signals and the underlying ion currents of individual subtypes of DUM neurons identified beforehand by a vital retrograde tracing technique. Na(+), Ca(2+), K(+) currents and a hyperpolarization-activated (I(h)) current are described in detail for their (in-)activation properties and subtype-specific current densities. In addition, a Ca(2+)-dependent K(+) current is demonstrated by its sensitivity to cadmium and charybdotoxin. This complex current composition determines somatic excitability similar in all subtypes of DUM neurons. Both Na(+) and Ca(2+) currents generate overshooting somatic action potentials. Repolarizing K(+) currents, in particular transient, subthreshold-activating A-currents, regulate the firing frequency and cause delayed excitation by shunting depolarizing input. An opposing hyperpolarization-activated (I(h)) current contributes to the resting membrane potential and induces rebound activity after prolonged inhibition phases. A quantitative analysis reveals subtype-specific differences in current densities with more inhibitory I(K) but less depolarizing I(Na) and I(h) - at least in DUM3 neurons promoting a reliable suppression of their activity as observed during behaviour. In contrast, DUM neurons that are easily activated during behaviour (DUM3,4,5 and DUMETi) express less I(K) and a pronounced depolarizing I(h) promoting excitability.

Neuromodulatory octopaminergic neurons and their functions during insect motor behaviour. The Ernst Florey memory lecture.

In this article we describe recent advances in functional studies on the role of octopamine released in the periphery by efferent dorsal or ventral unpaired median neurons. In addition to the previously described modulatory effects on the neuromuscular junction, we describe a metabolic regulatory role for these neurons. Due to their activity glycolytic rates in target tissues, such as muscles, are increased. In flight muscles that use carbohydrate catabolism only at take-off but have to switch to lipid oxidation during prolonged flight, these neurons are only active at rest but are inhibited as soon as flight motor patterns are selected.

Action of CCK and 5-HT on lateral hypothalamic neurons depends on early postnatal nutrition.

Wistar rats grown up during the early postnatal life (3-21 days after birth) in artificially built normal, small or large lifters developed a significantly different body weight. This difference persisted also during adulthood when they had free access to food and water. The influence of iontophoretically administered cholecystokinin (CCK8S), serotonin (5-HT) or co-ejection of both on firing of lateral hypothalamic neurons was investigated in adult, urethane anesthetized rats of the three groups. The responsiveness to CCK8S was significantly higher in large- and small-litter rats than in the normal control group. The differences were greater in males than in females. They resulted in the male large-litter group from an increase of excitatory responses, whereas in the male small-litter group the proportion of inhibitory responses was augmented. Co-administration of 5-HT generally reduced the neuronal responsiveness. Especially in the large-litter group excitatory responses were significantly reduced. It may be speculated that the availability of food in the early postnatal life influences the development of the hypothalamic regulatory network in such a way that it stabilizes the high or low food ingestion all the life. At least in males, a changed responsiveness and type of response to cholecystokinin of lateral hypothalamic neurons might be involved in this altered regulation.

Increased response to NPY of hypothalamic VMN neurons in postnatally overfed juvenile rats.

Rats postnatally overnourished due to a reduced litter size become persistently overweight. A presumed pathophysiological mechanism consists of a change in the activity and responsiveness to neuropeptides of the neuronal system regulating feeding behavior. This study aimed to find differences in the action of neuropeptide Y, orexin-A and cholecystokinin on single unit activity of the ventromedial hypothalamic nucleus in brain slices of normal and postnatally overfed juvenile rats. NPY inhibited significantly more neurons (15 of 23) of obese than of normal rats (6 of 27; p < 0.01, chi2). Orexin-A and CCK-8S mainly activated the neurons without significant differences between the groups. In conclusion, the stronger inhibition by NPY of VMN neurons which signal satiety might contribute to increased feeding behavior in postnatally overfed rats.

Action of cholecystokinin and serotonin on lateral hypothalamic neurons of rats.

Discharges of spontaneously active lateral hypothalamic neurons were extracellularly recorded during iontophoretic administration of cholecystokinin (CCK-8S) or/and serotonin (5-HT) in anesthetized rats. The main results are the following. (1) The proportion of neurons responsive to CCK-8S was 62% (61/99) and that responsive to 5-HT 42% (33/78). (2) Out of the neuronal sample, 36% were influenced by both transmitters, allowing an interaction between the two systems. (3) Co-ejection of CCK and 5-HT elicited a response in 40% of the tested neurons, which was a significantly smaller responsiveness than with separate ejection of CCK-8S. The effect resulted from a reduced number of excited neurons whereas the number of inhibitions did not change. The results show that effects of 5-HT and CCK can converge on the same neuron within the lateral hypothalamus. This might be of relevance in the regulation of feeding behavior.

Interactive effects of cholecystokinin-8S and serotonin on spontaneously active neurons in ventromedial hypothalamic slices.

The influence of cholecystokinin (CCK-8S) and serotonin (5-HT) on the discharge rate of spontaneously active ventromedial hypothalamic (VMH) neurons was investigated in brain slices. Drugs were drop-applied individually and concomitantly into the slice chamber. CCK-8S (0.1-2.5 microM) produced a dose-dependent increase in firing rate mainly mediated by the CCK(B) receptor subtype, because Suc-CCK-4 (a CCK(B) receptor agonist) acted like CCK-8S and A-71378 (a CCK(A) receptor agonist) rarely induced excitatory effects. The main response to serotonin application (2-20 microM) was an inhibition that could be mimicked by 8-OH-DPAT (a 5-HT1A receptor agonist). S-UH-301 (a 5-HT1A receptor antagonist) reversibly diminished or blocked this effect. Other 5-HT agonists like DOI and 2-Methyl-5-HT did not evoke relevant responses. Co-administration of CCK-8S and 5-HT induced counteracting effects at which CCK-8S significantly reduced the prevailing suppressive effect of serotonin. It is concluded that both substances, CCK and 5-HT, have a reciprocal influence on the regulation of neuronal activity within the VMH, a structure, which is involved in the mediation of signals for the state of satiety.