The trans-sphincteric posterior sagittal repair of recto-urinary and recto-vaginal fistulae using Surgisis™ mesh and fibrin sealant.

Recto-urinary, recto-vaginal and ileo-anal pouch-associated fistulae are rare yet a significant clinical problem due to their profound impact on patients' quality of life and are a challenge to repair. In this report, we describe repair of these complex fistulae using a modified trans-sphincteric posterior sagittal approach with Surgisis™ mesh and fibrin sealant and review our repair outcomes.

Regional differences in the sympathetic innervation of the guinea pig large intestine by neuropeptide Y- and tyrosine hydroxylase-immunoreactive nerves of divergent extrinsic origin.

Region-specific patterns of nerves with immunoreactivity to neuropeptide Y (NPY) have been described previously in the submucous plexus of guinea pig large intestine. Because these may have functional significance, the possibility of similar, characteristic variations of NPY-like immunoreactivity (NPY-ir) in the myenteric plexus was explored. Regional differences were found in the occurrence and pattern of distribution of NPY-ir in the myenteric plexus of the guinea pig large intestine. NPY-ir was present rarely within neuron somata in any region of the large intestine, and NPY-ir nerve fibers were present only within the distal large intestine, increasing progressively in density from the distal spiral to the rectum. Lesion of the colonic nerves, but not the hypogastric, intermesenteric, or lumbar splanchnic nerves, resulted in a loss of NPY-ir in the distal spiral and transverse colon but not in the descending colon or rectum. Ring myotomies in the descending colon resulted in a loss of NPY-ir proximal to the lesion. Dual-labeling immunohistochemical studies revealed that the NPY-ir nerve fibers rarely contained immunoreactivity for tyrosine hydroxylase (TH). Extrinsic nerve lesions resulted in an unequivocal reduction in NPY-ir in intraganglionic fibers of the submucosal plexuses of the transverse colon and a partial loss in the distal spiral and descending colon: the rectum was unaffected; in only a minority of guinea pigs, however, was any decrease in the NPY-ir innervation of submucosal blood vessels detected. The principal projections of NPY-ir nerves were from and through the inferior mesenteric ganglion; however, NPY-ir was not colocalized with TH-ir. It is proposed that nonnoradrenergic, NPY-containing neurons located in the inferior mesenteric ganglion project through the colonic nerves and that these proximally directed fibers innervate the transverse colon and the distal spiral. Nonnoradrenergic, NPY-ir neurons lying in the pelvic ganglia or sacral sympathetic chain may make an important contribution to the innervation of the myenteric plexus of the rectum and the descending colon.

Reappraisal of the innervation of rat intestine by vasoactive intestinal polypeptide and neuropeptide Y-immunoreactive neurons.

The occurrence and distribution of neurons and nerve fibres showing vasoactive intestinal polypeptide-like and neuropeptide Y-like immunoreactivity were re-examined in the enteric nervous system of the small and large intestine of the adult rat using dual-labelling indirect immunofluorescence histochemistry to detect the co-existence of these neuropeptides. In the myenteric plexus of both small and large intestine, a population of neuropeptide Y-immunoreactive neurons that did not contain vasoactive intestinal polypeptide was noted; it accounted for 29-53% of neuropeptide Y neurons. Such neurons were also found in the submucosa but there they constituted at most 2% of neuropeptide Y-immunoreactive neurons. In both myenteric and submucous plexuses, regional variations were observed in the number of immunoreactive neurons and in the proportion of dual-labelled neurons. In the myenteric plexus, for example, the density of neurons with immunoreactivity to these two neuropeptides was constant throughout the small intestine, whereas it progressively increased distally within the colon. In addition, a distinct but small subset of immunoreactive myenteric neurons was found to have a novel soma morphology, unclassifiable according to the criteria used for porcine or guinea-pig enteric neurons. Such neurons had one or more conspicuous processes, which were much longer than the short, lamellar somal processes of typical Dogiel Type 1 neurons; moreover, these protruded from an essentially smooth soma and terminated at distances of up to two cell diameters from their point of origin. Thus, our results suggest that the organization of the enteric nervous system of the rat differs from that of other species and indicate that investigation of the co-localizations of neuropeptides and biologically active mediators in the intestinal tract would be incomplete without reference to regional differences in the incidence and distribution of such neurochemicals.

Myenteric neurons of the rat descending colon: electrophysiological and correlated morphological properties.

Conventional intracellular electrophysiological recordings were made from 502 myenteric neurons of the rat descending colon. Myenteric neurons could be classified into three groups on the basis of distinct electrophysiological properties. The first group of neurons (51% of all neurons) fired tetrodotoxin-sensitive action potentials in response to direct somal depolarization and the majority (98%) of this group generated fast cholinergic excitatory synaptic potentials in response to focal stimulation and were therefore designated S/Type 1 neurons. The second group (40%) of neurons fired tetrodotoxin-insensitive action potentials which were followed by long-lasting membrane afterhyperpolarizations, hence were termed AH neurons. These neurons did not receive fast cholinergic synaptic inputs but ionophoretic application of acetylcholine induced rapid nicotinic cholinoceptor-mediated depolarizations. The final group of neurons (9%), named Type 3 neurons, received fast cholinergic synaptic inputs but could never be made to fire action potentials. Rundown in amplitude of successive fast excitatory synaptic potentials evoked by a short train of presynaptic nerve stimuli was observed in only a small proportion of neurons (8/37; 22%) with the majority of neurons (29/37; 78%) showing no such decrease in amplitude, even at frequencies of stimulation as high as 10 Hz. Superfusion of 5-hydroxytryptamine could induce both an inhibition and a facilitation of cholinergic fast synaptic transmission. Evidence was adduced that these presynaptic inhibitory and facilitatory actions appeared to be mediated via 5-hydroxytryptamine 1A and 5-hydroxytryptamine 4 receptors, respectively. Muscarinic slow excitatory synaptic potentials were not detected (9/9 neurons tested) and non-cholinergic slow excitatory synaptic potentials following repetitive focal presynaptic nerve stimulation were observed in only 39/502 (8%) of all neurons. In those neurons in which a demonstrable change in membrane input resistance was detectable, slow excitatory potentials were accompanied by an increased input resistance. In addition, in a small subset (4%) of S/Type 1 neurons, slow membrane hyperpolarizations accompanied by an increased membrane input resistance were observed following tetanic presynaptic nerve stimulation. Superfusion of 5-hydroxytryptamine induced both membrane depolarizations and hyperpolarizations. Membrane depolarizations were observed in 40% of all neuronal types (34% of S/Type 1 neurons, 58% of AH neurons and 11% of Type 3 neurons) and were accompanied by an increased membrane input resistance and occasionally, in S/Type 1 and AH neurons, by anodal break excitation or spontaneous action potential firing. Membrane hyperpolarizations were observed in S/Type 1 neurons (5%) only and were accompanied, unexpectedly, by an increased membrane input resistance. In those neurons that responded both to application of 5-hydroxytryptamine and tetanic presynaptic nerve stimulation, 5-hydroxytryptamine always mimicked the slow synaptic response indicating that 5-hydroxytryptamine may function as a slow synaptic mediator in some myenteric neurons. Myenteric neurons identified by intracellular injection of the neuronal marker Neurobiotin TM were found to conform to the morphological classification schemes proposed for myenteric neurons of the guinea-pig and porcine intestine, that is, Dogiel Types I and II and Stach Type IV neurons were present. Simultaneous electrophysiological recording and intracellular staining techniques revealed that a correlation existed between the electrophysiological and morphological properties of myenteric neurons of the rat colon, with electrophysiological classified S/Type 1 neurons having Dogiel Type I morphologies (95/108 neurons; 88%) and electrophysiological classified AH neurons having Dogiel Type II morphologies (87/94 neurons; 93%)...

Morphological studies of electrophysiologically-identified myenteric plexus neurons of the guinea-pig ileum.

The morphology of neurons in the myenteric plexus of the guinea-pig ileum has been studied by means of the intracellular application of Procion Yellow. Sixty-six electrophysiologically-unidentified cells showed a great variety of soma shapes and number of processes, the vast majority of the longer of which were circumferentially-orientated. The electrophysiological properties of an additional 47 neurons were ascertained; 29 were neurons with a slow after-hyperpolarization (AH-neurons), 14 showed fast excitatory synaptic potentials (S-neurons) and 4 were of neither category. Twenty-two of the AH-neurons had a smooth soma outline and, on average, each had 5 processes, of which the great majority of long processes were circumferentially-orientated and intraganglionic. The projection ratios of oral:circumferential:aboral processes were 6:61:9. Branching was a prominent feature of the processes. In contrast, a large soma with many broad, short processes was a feature of 8 of 14 S-neurons studied. The average number of processes was 8.6 per cell and relatively more of them were aborally-directed, giving projection ratios of 2:21:7. There was, however, such a variation and overlap in the morphology of AH- and S-neurons that it was not possible to achieve a simple, reliable classification. It is concluded that many neuronal processes may be intraganglionic and that longitudinal ones are mainly aboral. From the varied morphological characteristics of AH-neurons, it is unlikely that these neurons subserve a single function in the plexus. For the same reasons S-neurons may fulfil different physiological roles.

Slow intracellular potentials in AH-neurons of the myenteric plexus evoked by repetitive activation of synaptic inputs.

In after-hyperpolarization-neurons of guinea-pig myenteric plexus, several types of slow responses to repetitive activation of synaptic inputs were recorded. There were at least two types of slow excitatory depolarizing potential, both associated with an increased input resistance, but in one there was an abolition or marked attenuation of the amplitude of the slow after-hyperpolarization of the neuron, whereas in the other type the slow after-hyperpolarization was not significantly affected. Slow depolarizing and hyperpolarizing synaptic potentials associated with a decrease input resistance were also recorded in some neurons following transmural stimulation. The neural processes responsible for these slow potentials in after-hyperpolarization-neurons showed no preferential projection within the myenteric plexus.

Hyperpolarization of rabbit superior cervical ganglion cells due to activity of an electrogenic sodium pump.

1 The mechanisms underlying the hyperpolarization which follows depolarization of rabbit superior cervical ganglion cells by acetylcholine, have been investigated and compared with the mechanisms responsible for the hyperpolarizations induced by orthodromic stimulation of the ganglion.2 The amplitude of the drug-induced hyperpolarization (after-hyperpolarization) was diminished when [Na(+)](0) and the duration of the preceding depolarization were reduced.3 In K(+)-free solutions, the amplitude of the after-hyperpolarization was often diminished and its rate of development was reduced. In 12.5 mM K(+)-Krebs solutions, the amplitude and rate of development of the after-hyperpolarization were increased; the potential was still present when the resting potential was at or close to E(K).4 Ouabain (10 muM) prevented or greatly diminished the after-hyperpolarization. The rates of onset and decay of the after-hyperpolarization were reduced in glucose-free solutions.5 It is, therefore, concluded that the after-hypolarization is due to the activity of an electrogenic sodium pump.6 The positive after-potential associated with the ganglionic action potential was increased in K(+)-free solutions and diminished when the resting potential approached E(K), indicating that it is due to a period of increased K(+) conductance. In the presence of high concentrations of hexamethonium (276 muM), the P wave was not selectively depressed by ouabain and has been shown by other workers to be due to a mechanism not involving an increased potassium conductance. It is concluded, therefore, that the positive after-potential, the P wave and the after-hyperpolarization are due to different mechanisms.

Antibiotic-associated colitis: an in vitro investigation of the effects of antibiotics on intestinal motility.

1 Nine antibiotic compounds in common use were studied to determine their ability to affect intestinal motility in vitro, in the guinea-pig ileum and rabbit colon. 2 Ampicillin, doxycycline, mecillinam and metronidazole were without effect over a concentration range which included typical serum levels found when these drugs are used therapeutically. 3 Clindamycin, gentamicin, kanamycin, pivmecillinam and trimethoprim were all found to inhibit evoked and reflex responses of the guinea-pig ileum but only clindamycin and trimethoprim also affected evoked responses of the rabbit colon. 4 Kanamycin and gentamicin appeared to have a predominantly pre-junctional action, pivmecillinam and trimethoprim a predominantly post-junctional action. Clindamycin had a pre-junctional action at low concentrations and long exposure times, and a post-junctional action at high concentrations and short exposure times. 5 The concentration of each antibiotic required to inhibit the peristaltic reflex of the guinea-pig ileum was less than that required to inhibit its responses to electrical stimulation or exogenous acetylcholine or histamine but greater than the serum levels associated with their respective use in therapeutic doses. 6 A sequence of events whereby antibiotic-induced alterations in gastro-intestinal motility could lead to the development of pseudomembranous colitis is proposed.

Analysis of the mechanism of action of some ganglion-blocking drugs in the rabbit superior cervical ganglion.

1. Mechanisms of action of hexamethonium, mecamylamine and (+)-tubocurarine on the rabbit superior cervical ganglion were investigated by intracellular recording techniques.2. In concentrations up to 1 mM, none of these drugs affected the resting membrane potential nor altered the excitability of the postganglionic neurone to direct or antidromic stimulation.3. Post-tetanic potentiation of the excitatory postsynaptic potential (e.p.s.p.) was inhibited by mecamylamine (10-100 muM) but not affected by either hexamethonium (5-100 muM) or (+)-tubocurarine (10-50 muM).4. The decline in amplitude of successive e.p.s.ps in a train (40 Hz) was not influenced by hexamethonium or (+)-tubocurarine but was greatly exaggerated in the presence of mecamylamine; desensitization of the receptors for acetylcholine was excluded as a possible explanation for this latter finding.5. Mecamylamine depressed the quantal content of e.p.s.ps in a train, with the exception of the first e.p.s.p. which had an increased quantal content.6. Reduction in quantal content was attributed to a substantial fall in the size of the store of quanta of transmitter immediately available for release and to a reduction in the rate of mobilization of acetylcholine into that store; mecamylamine also caused a simultaneous increase in the fractional release.7. Hexamethonium and (+)-tubocurarine had no effect on transmitter release.8. The time-course of presynaptic effects of mecamylamine was similar to the duration of its postsynaptic blocking action.9. It is concluded that inhibition of ganglionic transmission by mecamylamine is due to both presynaptic and postsynaptic inhibitory actions; in contrast, hexamethonium and (+)-tubocurarine reduce transmission solely by their postsynaptic actions.

Investigation of occurrence of tolerance to bronchodilator drugs in chronically pretreated guinea-pigs.

1 The actions of sympathomimetic amines on isolated preparations of atria, trachea and ileum were studied in vitro in guinea-pigs, which had been pretreated for 5 or 12 days, by subcutaneous injection, with adrenaline (5 mug/kg), salbutamol (0.5 mug/kg), salbutamol (0.5 mug/kg), methoxamine (250 mug/kg) or saline (0.9% w/V NaCl solution). 2 In the trachea, a decrease in sensitivity (tolerance) to the relaxant effect of adrenaline was induced by pretreatment, for 12 but not for 5 days, with adrenaline. In these animals, cross-tolerance to isoprenaline or salbutamol was not observed. Tolerance to the relaxant actions of adrenaline isoprenaline or salbutamol was not observed after pretreatment with salbutamol. 3 In the trachea, pretreatment with methoxamine or adrenaline for 12 days did not change the sensitivity to the alpha-adrenoceptor-mediated contractor action of methoxamine. 4 In the atria from those guinea-pigs pretreated with adrenaline or salbutamol, there was no reduced sensitivity to the beta-adrenoceptor agonist actions of adrenaline, isoprenaline or salbutamol. In animals pretreated with methoxamine or adrenaline, there was no observable tolerance or cross tolerance to methoxamine with respect to its alpha-adrenoceptor-mediated positive inotropic action in the atria and no unequivocal evidence of a reduced sensitivity to that action of adrenaline. 5 It was confirmed that the twitch-like contractions of the longitudinal muscle of the electrically stimulated ileum were inhibited by sympatomimetic amines acting on alpha- and beta-adrenoceptors. There was no reduced sensitivity to the inhibitory actions of noradrenaline or isoprenaline on the twitch of ileum isolated from animals pretreated with adrenaline, salbutamol or methoxamine for 5 or 12 days. 6 From our results on these three preparations from the same animals, it is concluded that generalizations regarding changes in sensitivity to sympathomimetic amines following their prolonged administration should not be made in any one species.

Depressant effects of hypoxia and hypoglycaemia on neuro-effector transmission of guinea-pig intestine studied in vitro with a pharmacological model.

1. Since intermittent ischaemia may play an important role in the aetiology of Inflammatory Bowel Disease, particularly Crohn's Disease, a pharmacological model of neuronal ischaemia was applied to guinea-pig isolated intestinal preparations to mimic the acute effects of reduced blood flow on intestinal motility. 2. Neuro-effector transmission and smooth muscle performance were examined in myenteric plexus-longitudinal muscle preparations of guinea-pig ileum exposed to sodium cyanide (NaCN), in order to inhibit oxidative phosphorylation, or to iodoacetic acid (IAA), to block glycolysis. Comparisons were made with the effects due to simple deprivation of oxygen or glucose. 3. Depression of cholinergic neuro-effector transmission induced by hypoxia or NaCN (effective concentration range 0.1-3 mM), given as separate treatments, singly or repetitively over 60-90 min, were apparent within 30 s and were reversible. The maximum inhibition was 90% and the IC50 for NaCN was 0.3 mM. A conspicuous component of these inhibitions was prejunctional. 4. Non-cholinergic neuro-effector contractions were inhibited by up to 90% by anoxia or NaCN but recovery was incomplete and slower than with cholinergic contractions. 5. Glucose-free solutions also caused a reversible failure of cholinergic neuro-effector transmission but of slower onset. In contrast, IAA (0.06-1 mM) abolished contractions irreversibly, apparently by a direct depressant effect on smooth muscle contraction. Unlike NaCN, IAA caused an initial potentiation of electrically-induced contractions, partly by a prejunctional potentiation of cholinergic neuro-effector transmission. 6. It is concluded that a disruption of intestinal activity in pathological conditions associated with intestinal ischaemia may result from disturbances in the function of enteric neurones.

Y2-receptor-mediated selective inhibition of slow, inhibitory postsynaptic potential in submucous neurones of guinea-pig caecum.

1. The subtype of neuropeptide Y receptor mediating the selective inhibition of the slow inhibitory postsynaptic potential (i.p.s.p.) of submucous neurones in guinea-pig caecum was investigated by use of conventional intracellular electrophysiological recording techniques. 2. Neuropeptide Y (NPY) (1-300 nM) was found to depress or abolish reversibly the slow i.p.s.p. evoked by focal stimulation of internodal fibre tracts. At low concentrations (1-30 nM), a reduction in the duration of the slow i.p.s.p. was often apparent before any inhibition of the amplitude of this synaptic potential. 3. These inhibitory effects of NPY were mimicked by peptide YY (PYY; 0.3-100 nM), NPY13-36 (1-300 nM) and NPY22-36 (10-100 nM); [Leu31,Pro34]NPY ([Pro34]NPY) and bovine pancreatic polypeptide (bPP) were without pre- or postsynaptic effects at concentrations of up to 300 nM. The IC50 +/- s.e. mean values for PYY, NPY, and NPY13-36 were 2.7 +/- 0.3, 7.8 +/- 2.1 and 30 +/- 4.8 nM, respectively, and were significantly different from each other. Thus, the apparent rank order of potency was PYY > NPY > NPY13-36 >> [Pro34]NPY and bPP. 4. In concentrations of up to 300 nM, NPY and its analogues had no depressant effects on the active and passive properties of the impaled neurone and did not affect the amplitude or duration of either cholinergic fast synaptic potentials or non-cholinergic, slow excitatory postsynaptic potentials (e.p.s.ps). Furthermore, none of these peptides altered the amplitude or time-course of changes in membrane potential induced by focal application of acetylcholine or noradrenaline. 5. It is, therefore, concluded that the selective inhibition of the slow i.p.s.p. is mediated by Y2-receptors,located presynaptically on noradrenergic nerve terminals.

Effects of cannabinoid receptor ligands on electrophysiological properties of myenteric neurones of the guinea-pig ileum.

1. The effect of cannabinoid receptor agonists was studied in guinea-pig myenteric neurones in vitro by use of conventional intracellular recording techniques. 2. Exposure of myenteric neurones of the S-cell type to the cannabinoid receptor agonists WIN 55,212-2 (100 nM) and CP 55,940 (100 nM) reversibly and significantly depressed the amplitude of fast excitatory synaptic potentials (fast e.p.s.ps) by 46% and 37%, respectively. 3. The depressant effect of WIN 55,212-2 and CP 55,940 on fast e.p.s.p. amplitude (expressed as the area above the amplitude-time curve (mVs)) was significantly greater than that of the vehicle, Tween 80, which had no detectable effect. 4. The inhibitory effect of WIN 55,212-2 appeared to be concentration-dependent over the range 1-100 nM. WIN 55,212-3, its (-)-enantiomer (100 nM), was inactive. 5. The cannabinoid CB1 receptor antagonist, SR141716A (1 microM), reversed the inhibitory effects of WIN 55,212-2 on fast e.p.s.ps in 38% of neurones tested (3/8) and acetylcholine (ACh)-induced depolarizations in 42% of neurones tested (5/12). 6. When tested on its own, SR141716A (1 microM) caused a 40-50% reduction in the amplitude of fast e.p.s.ps (n = 9). 7. WIN 55,212-2 reversibly depressed the amplitude of the slow e.p.s.p. and, in 2 out of 7 neurones, this effect was reversed by SR141716A (1 microM). 8. It is concluded that cannabinoid-induced inhibition of fast cholinergic synaptic transmission occurred by reversible activation of both presynaptic and postsynaptic CB1 receptors and that slow excitatory synaptic transmission can also be reversibly depressed by cannabinoids. Furthermore, it would seem that subpopulations of myenteric S-neurones and their synapsing cholinergic and non-cholinergic, non-adrenergic terminals are not endowed with cannabinoid receptors.

Synaptic potentials recorded by the sucrose-gap method from the rabbit superior cervical ganglion.

1. Compound ganglionic potentials evoked by stimulation of the preganglionic nerves to the superior cervical ganglion of the rabbit were recorded by the sucrose-gap method.2. When the distal part of the ganglion was bathed in flowing isotonic sucrose solution or sodium-deficient solutions, ganglionic action potentials were no longer evoked, only large synaptic potentials.3. The compound synaptic potential, which remained unaltered for more than 1 h, originated in a population of cells at the interface between the Krebs and sucrose solutions. Hexamethonium reduced the size but did not alter the time course of the synaptic potential.4. It is suggested that a higher concentration of sodium ions is required for the generation of ganglionic action potentials than for either conduction in the postganglionic axons or production of synaptic potentials.5. When lithium replaced sodium in the solution bathing the distal part of the ganglion, the synaptic potential was greatly reduced in amplitude. Impulse propagation in the postganglionic axons was only slightly impaired when lithium replaced sodium in the solution bathing the axons.6. A quantitative assessment of the potency of the ganglion-blocking drugs nicotine, pentolinium, hexamethonium and pempidine was made by measuring the depression of the synaptic potentials produced by bathing the distal part of the ganglion in flowing isotonic sucrose solution. The concentrations which produced a 50% depression were 8.1 muM nicotine, 26.5 muM pentolinium, 111 muM hexamethonium and 22.2 muM pempidine.

Monochorionic diamniotic minimally conjoined twins: a case report.

We present the second case of monochorionic diamniotic (MC/DA) conjoined twins. There was minimal conjunction, which was predominantly extrafetal and confined to the periumbilical ventral region. The omphalopagus twins, attached to a single forked umbilical cord, were connected by a shared umbilical hernia containing the ileum of twin B. The only visceral conjunction, located just within the belly of twin A, was midileal with the 2 separate ileums converging toward a short segment of shared muscularis propria and of side-to-side fistulization. Gastrointestinal and musculoskeletal anomalies were present in both twins with severe amyoplasia and arthrogryposis multiplex in twin A. Possible mechanisms underlying this unusual form of MZ twinning are discussed.

Inhibitory effects of NPY on ganglionic transmission in myenteric neurones of the guinea-pig descending colon.

Intracellular recordings were made from myenteric neurones of the guinea-pig descending colon. Neuropeptide Y (NPY) and related pancreatic polypeptides were applied by superfusion and the effects upon the amplitude of fast excitatory synaptic potentials (ESPs) and the ratio of paired fast ESPs evoked by stimulation of internodal fibre tracts were noted. NPY produced a concentration-dependent inhibition in fast ESP amplitude in the majority of neurones (17/21) with a calculated IC50 value of 7 nM; in some neurones this inhibition was mediated via the local release of noradrenaline. Peptide YY (PYY) (eight out of 11 neurones; IC50 = 1 nM), NPY(3-36) (three out of three neurones) and [Leu31, Pro34]NPY (four out of five neurones) also decreased the amplitude of fast ESPs. The effects of two or more pancreatic polypeptides or analogues on fast synaptic transmission were compared directly in six neurones; the apparent relative potency of agonists suggested the involvement of Y2-receptors and at least one other Y-receptor type. In the absence of any direct postsynaptic effects of pancreatic polypeptides on the active or passive properties of myenteric neurones, or on their sensitivity to ionophoretically applied acetylcholine, inhibition of fast ganglionic transmission was presumed to be presynaptic in origin. It is concluded that, in addition to their previously described depressant actions on neuro-effector transmission to colonic smooth muscle, pancreatic polypeptides can exert powerful inhibitory effects on myenteric neurones of the descending colon.

Neuropeptide Y hyperpolarizes submucosal neurons of the guinea-pig descending colon.

Effects of neuropeptide Y (NPY) on submucosal neurons of the guinea-pig descending colon were investigated electrophysiologically by means of intracellular electrophysiological recordings. NPY (100 nM) induced a marked and prolonged hyperpolarization, accompanied by a decrease in input resistance in most (90%) neurons. This NPY-induced hyperpolarization was diminished and augmented by membrane hyperpolarization and depolarization, respectively. The NPY-hyperpolarization was not affected by exposure to either calcium-free solutions or the alpha2-adrenoceptor antagonist, idazoxan (1 microM). When more than one peptide was applied to a neuron, NPY, PYY and Pro34-NPY were equipotent, whilst NPY13-36 was less potent. It was concluded that NPY hyperpolarized submucosal neurons of the guinea-pig descending colon, possibly via a direct action on postsynaptic Y1-receptor and increasing potassium conductance.

Nutritional effects of surgical and medical treatment for short bowel syndrome.

BACKGROUND: The choice of treatment options in short bowel syndrome (SBS) is hampered by a lack of comparative studies. This study uses a previously validated juvenile pig model of SBS to compare nontreated controls (C), surgical treatment with either proximal colon interposition (CI) or bowel lengthening (BL), with medical treatment with codeine and cimetidine (M). METHODS: Treatment was initiated 6 weeks after resection of 75% of the small bowel, and animals were followed until sacrifice at week 16. Feed intake and weight gain were monitored throughout; in vivo nutrient absorption, in vitro nutrient transport, sodium-glucose cotransporter activity, and intestinal morphology (gross and microscopic) were examined at the end of treatment. RESULTS: BL and M treatments resulted in improved rates of weight gain; this improvement was associated with improved absorption of dietary fat. The treatments did not affect carbohydrate or protein absorption in vivo. In vitro fatty acid absorption was not increased in any group. Active uptake of glucose was increased in the colon interposition group, but phlorizin binding (reflecting sodium glucose cotransporter activity) did not differ between groups. Gross serosal and microscopic mucosal surface areas increased in all groups; however, there were no significant differences between the treatment groups. CONCLUSIONS: These results demonstrate that bowel lengthening and medical treatment improved the rate of weight gain in this model of SBS. This appeared to be due to improvement in the absorption of dietary fat, which was not caused by alterations in in vitro uptake or mucosal surface area, suggesting these treatments have their affects by altering motility or intraluminal digestion. These findings suggest that these treatments are worthy of further study in treating patients (primary pediatric) with SBS.

Esophagotomy for incarcerated esophageal foreign bodies.

Less than 1% of esophageal foreign bodies are irretrievable by endoscopic techniques. Incarcerated esophageal foreign bodies require esophagotomy for removal. A retrospective study was conducted to determine the incidence, predisposing factors, and optimal treatment of incarcerated esophageal foreign bodies. Four of 815 patients (0.5%) with esophageal foreign bodies required esophagotomy for foreign body removal. Two predisposing factors for incarceration were identified, and these factors were related to patient age. Two infants had neglected esophageal foreign bodies that partially migrated through the esophageal wall. In two adults, foreign body size and sharpness were responsible for incarceration. One cervical and three thoracic esophagotomies were done. One thoracic esophagotomy suture line dehiscence occurred. Occult foreign body pressure necrosis may be a factor in esophagotomy suture line leakage. Care is required in esophagotomy closure. Principles established for repair of esophageal perforations are also applicable to esophagotomy closure.

The efficacy of benzimidazole anthelmintics against late fourth stage larvae of Trichostrongylus colubriformis in gerbils and Nippostrongylus brasiliensis in rats.

The efficacy of eight benzimidazole anthelmintics has been examined against Trichostrongylus colubriformis in gerbils and Nippostrongylus brasiliensis in rats, when the parasites were entering into the fourth and final moult. The dose--response slopes obtained from the data for both host--parasite systems did not deviate significantly from a non-parallel model, and were used for relative potency determinations. The T. colubriformis assay ranked the benzimidazoles in order of potency as follows: albendazole, oxfendazole, fenbendazole, cambendazole, mebendazole, oxibendazole, parbendazole and thiabendazole. This compares favourably with the expected relative efficacies against trichostrongyles in sheep. N. brasiliensis was found to be far less useful in this respect. All compounds tested, with the exception of thiabendazole, were highly effective against both parasites. The T. colubriformis/gerbil assay could be a very useful tool for preliminary in vivo evaluation and possibly in the early selective optimisation of chemical series.