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Biomedical subjects

M Behan

Publications and source records attributed to M Behan.

At least 37 records · Page 2Linked to original sources

Effect of second vaginal delivery on anorectal physiology and faecal continence: a prospective study.

BACKGROUND: Because obstetric injury to the anal sphincters may be occult, and because the mechanism of injury differs between first and subsequent deliveries, we prospectively assessed the effects of first and second vaginal deliveries on anal physiology and continence. METHODS: We undertook a prospective observational study of 59 previously nulliparous women through two successive vaginal deliveries by means of a bowel-function questionnaire, and an anorectal-physiology assessment, both antepartum and 6-12 weeks post partum. FINDINGS: 13 (22%) women reported altered faecal continence after their first vaginal delivery: eight had persistent symptoms during their second pregnancy, of whom seven deteriorated after the second delivery; five regained continence before their second pregnancy, but two became incontinent again after the second delivery. Five women developed incontinence for the first time after their second vaginal delivery, of whom three had occult primiparous sphincter injury. 20 (34%) women, seven of whom had no symptoms, had anal-sphincter injury as a result of their first delivery, but only two new injuries occurred after the second vaginal delivery (p=0.013). Although pudendal neuropathy was no more common after the second than after the first vaginal delivery (15 vs 19%, p=0.8), pudendal-nerve latency was longer after the second delivery (p=0.02). INTERPRETATION: Primiparous women with persistent symptoms of altered faecal continence experience deterioration after a second vaginal delivery. Women with transient faecal incontinence or occult anal-sphincter injury after their first vaginal delivery are at high risk of faecal incontinence after a second vaginal delivery. The risk of mechanical anal sphincter injury is greatest after the first delivery.

Adult↗

Intrinsic and efferent connections of the endopiriform nucleus in rat.

The endopiriform nucleus is a large group of multipolar cells located deep to the piriform cortex. The function of this nucleus is unknown, but studies with animal models suggest that it plays an important role in temporal lobe epileptogenesis. To address questions concerning mechanisms of epileptogenesis and to gain insights into its normal function, efferent axons from the endopiriform nucleus were labeled by anterograde transport from small extracellular injections of Phaseolus vulgaris leucoagglutinin. Several principles of organization were derived: (1) heavy local and long intrinsic connections are present throughout the endopiriform nucleus; (2) endopiriform efferents target cortical rather than nuclear structures; (3) extensive projections from the endopiriform nucleus extend to most basal forebrain areas including the piriform cortex, entorhinal cortex, insular cortex, orbital cortex, and all cortical amygdaloid areas. The perirhinal cortex, olfactory tubercle, and most subdivisions of the hippocampal formation receive light projections; (4) projections are highly distributed spatially within all target areas; (5) efferent axons from the endopiriform nucleus are unmyelinated and give rise to boutons along their entire course rather than arborizing locally; and (6) the endopiriform nucleus and piriform cortex share target areas, but efferents from the endopiriform nucleus lack the precise laminar order of those from the piriform cortex, and provide a heavy caudal to rostral pathway that is lacking in the cortex. The significance of these findings for the triggering of generalized seizures from the deep piriform region are discussed. An hypothesis for a role of the endopiriform nucleus in memory storage is presented.

Amygdala↗

Age-related changes in serotonin in the hypoglossal nucleus of rat: implications for sleep-disordered breathing.

We are attempting to determine the neuronal factors that influence upper airway patency during sleep in the elderly. Serotonin has a facilitatory effect on hypoglossal motoneurons that innervate the tongue, and manipulations of the serotonergic system alter airway patency. We hypothesized that age-associated changes in serotonergic input to the hypoglossal nucleus might be a factor in the increased susceptibility to sleep-disordered breathing in the elderly. We used light microscopic immunocytochemistry to study the distribution of serotonin in the hypoglossal nucleus in young and old rats. Rats > 18 months had fewer serotonin immunoreactive axons and boutons in the hypoglossal nucleus than rats < 6 months. These data suggest that normal aging may result in a change in the availability of serotonin that results in decreased facilitation of hypoglossal motoneurons.

Aging↗

A prospective, randomized study comparing the effect of augmented biofeedback with sensory biofeedback alone on fecal incontinence after obstetric trauma.

PURPOSE: This study was designed to compare prospectively the effects of augmented biofeedback with those of sensory biofeedback alone on fecal incontinence and anorectal manometry after obstetric trauma. METHODS: A consecutive cohort of 40 females with impaired fecal continence after obstetric anal sphincter injury were recruited from a dedicated perineal clinic. Patients were randomly assigned to receive either augmented biofeedback or sensory biofeedback alone. All patients were assessed before and after twelve weeks of biofeedback training, using a fecal continence questionnaire and anorectal manometry. RESULTS: Thirty-nine of 40 females recruited completed the study. Continence scores improved in both treatment groups, but the results were better for those who received augmented biofeedback. Anorectal manometry was unchanged by sensory biofeedback, whereas anal resting and squeeze pressures increased with augmented biofeedback. No change in anal vector symmetry was observed in either group. CONCLUSION: Augmented biofeedback training is superior to sensory biofeedback alone in the treatment of impaired fecal continence after obstetric trauma.

Adult↗

The pretectum mediates rapid eye movement sleep regulation by light.

A variety of sensory stimuli (e.g., visual, auditory, and thermal) are known to induce rapid eye movement (REM) sleep in mammals. Studies have examined the induction of REM sleep in albino rats by light-to-dark transitions, a phenomenon referred to as REM sleep triggering. Recent research has demonstrated that aspiration lesions of the superior colliculus (SC) and pretectal area attenuated REM sleep triggering. To define more specifically the area or areas involved in mediating REM sleep responses to changes in illumination, fiber-sparing neurotoxic lesions were made to the pretectum (PT) or the SC. Lesions of the PT attenuated REM sleep triggering, whereas lesions of the SC did not. Thus, the role of the PT may be expanded to include the regulation of REM sleep in response to photic stimulation in albino rats. These findings provide a paradigm in which to study mechanisms of REM sleep generation and the effects of light on behavioral state.

Animals↗

The superior colliculus-pretectum mediates the direct effects of light on sleep.

Light and dark have immediate effects on sleep and wakefulness in mammals, but the neural mechanisms underlying these effects are poorly understood. Lesions of the visual cortex or the superior colliculus-pretectal area were performed in albino rats to determine retinorecipient areas that mediate the effects of light on behavior, including rapid eye movement sleep triggering by lights-off and redistribution of non-rapid eye movement sleep in short light-dark cycles. Acute responses to changes in light conditions were virtually eliminated by superior colliculus-pretectal area lesions but not by visual cortex lesions. Circadian entrainment was evident in both groups with lesions and in normal controls. Thus, acute light-dark effects on sleep and wakefulness appear to be mediated independently from cortical vision or circadian rhythms.

Animals↗

Absence of the beta subunit (cchb1) of the skeletal muscle dihydropyridine receptor alters expression of the alpha 1 subunit and eliminates excitation-contraction coupling.

The multisubunit (alpha 1s, alpha 2/delta, beta 1, and gamma) skeletal muscle dihydropyridine receptor transduces transverse tubule membrane depolarization into release of Ca2+ from the sarcoplasmic reticulum, and also acts as an L-type Ca2+ channel. The alpha 1s subunit contains the voltage sensor and channel pore, the kinetics of which are modified by the other subunits. To determine the role of the beta 1 subunit in channel activity and excitation-contraction coupling we have used gene targeting to inactivate the beta 1 gene. beta 1-null mice die at birth from asphyxia. Electrical stimulation of beta 1-null muscle fails to induce twitches, however, contractures are induced by caffeine. In isolated beta 1-null myotubes, action potentials are normal, but fail to elicit a Ca2+ transient. L-type Ca2+ current is decreased 10- to 20-fold in the beta 1-null cells compared with littermate controls. Immunohistochemistry of cultured myotubes shows that not only is the beta 1 subunit absent, but the amount of alpha 1s in the membrane also is undetectable. In contrast, the beta 1 subunit is localized appropriately in dysgenic, mdg/mdg, (alpha 1s-null) cells. Therefore, the beta 1 subunit may not only play an important role in the transport/insertion of the alpha 1s subunit into the membrane, but may be vital for the targeting of the muscle dihydropyridine receptor complex to the transverse tubule/sarcoplasmic reticulum junction.

Action Potentials↗

Endosonographic assessment of postpartum anal sphincter injury using a 120 degree sector scanner.

Obstetric injury is the principal cause of faecal incontinence in women. We describe use of a 120 degrees sector ultrasound probe to assess integrity of the anal sphincters in primigravid women. Eighty-eight women were successfully studied 6 weeks following vaginal delivery. Anal vector manometry and pudendal nerve studies were abnormal in 54 (61%), of whom 41 (71%) were symptomatic (urgency of defaecation, incontinence to flatus or faeces). The sonographic pattern of the anal sphincters described with a 360 degrees probe was reproduced. Forty-eight abnormal scans were reported by two radiologists with a kappa statistic of 0.65. Sphincter defects were found in 11 asymptomatic women. We conclude that anal endosonography has an important role screening for and diagnosis of postpartum anal sphincter defects. Use of a 120 degrees sector ultrasound probe may prove a cost-effective means of increasing the availability of this technique.

Adult↗

Spatial distribution of tectotectal connections in the cat.

In mammals, the paired superior colliculi of the midbrain play a significant role in the generation and guidance of eye movements that enable an animal to orient to novel visual stimuli. In several species including monkey, cat and hamster, the paired colliculi are connected by a commissure. In the cat, many commissural axons arise from tectotectal neurons located in the deep layers in the rostral two-thirds of the colliculus. The role of these tectotectal neurons is unclear, but it is likely that they play some role in eye movement control. In this study, the neuroanatomical tracer Biocytin was used to make small, localized injections into the deep layers of the cat superior colliculus at a variety of different locations in nine animals. The distribution of tectotectal synaptic terminals in the opposite colliculus was then plotted. Regardless of which layers were included the injection site, labelled boutons were most dense in the deep layers in the contralateral colliculus. There was a striking point-to-point organization in the tectotectal projection such that terminals were concentrated at an almost mirror-symmetrical region to the injection site in the rostrocaudal plane. In the majority of cases, however, the focus of terminal boutons was shifted medially by 1-2 mm. These results suggest that tectotectal connections may influence select populations of neurons in the contralateral colliculus. By coupling specific groups of neurons in the two colliculi, their effectiveness in sensory motor processing could be enhanced. At this time it is not clear whether specific commissural terminals contain excitatory or inhibitory neurotransmitters, and our ongoing studies are addressing this question.

Animals↗

Digital subtraction in contrast-enhanced MR imaging of the postoperative lumbar spine.

OBJECTIVE: The objective of this study was to evaluate the routine use of digital image subtraction as an adjunct to standard MR sequences in patients with failed lumbar spine surgery. MATERIALS AND METHODS: Unenhanced and contrast-enhanced T1-weighted MR images of 112 consecutive patients with failed back surgery were reviewed, and corresponding axial images at the level of previous surgery were digitally subtracted by using standard software. The technique was successful in 96 patients and was abandoned in 16 owing to patient motion. Two radiologists independently assessed the subtracted images for areas of enhancement not seen on T1-weighted images, and suggested a diagnosis based on a combination of the findings on standard and subtracted images. This diagnosis was compared with the original MR diagnosis, and surgical findings were sought in cases of conflict. RESULTS: Enhancement was best seen on the subtracted images in muscle fascial planes (100%), anterior epidural fibrosis (55%), spinal canal fat (31%), posterior epidural fibrosis (27%), types I and II marrow change (24%), and facet joints (17%). Subtraction improved the homogeneity of contrast enhancement, thereby improving the visualization of nerve roots lying in scar tissue (16%), and better defined the extent of epidural fibrosis, particularly when the fibrosis was contiguous with fat. The subtracted image increased diagnostic confidence in 25% of cases, but altered final diagnosis in only two patients. CONCLUSION: Although digital subtraction revealed areas of enhancement not seen on standard spin-echo MR images, it rarely altered final diagnosis and does not appear to be useful for routine imaging of patients with failed lumbar spine surgery. It might, however, be useful for increasing diagnostic confidence or as a problem-solving technique in selected patients.

Adult↗

Development of corticotectal synaptic terminals in the cat: a quantitative electron microscopic analysis.

We studied the development of corticotectal synaptic terminal boutons and synapses by making injections of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) into area 17 of visual cortex in kittens ranging from newborn to 12 weeks of age and in adults. The location and extent of the injection site, and labeled corticotectal axon terminals in the superficial layers of the superior colliculus were demonstrated histochemically with the cobalt-glucose oxidase diaminobenzidine reaction. During the first 2 weeks after birth, the majority of labeled profiles resembled axonal growth cones, or structures intermediate in morphology between growth cones and synaptic terminals, while very few corticotectal axon terminals forming well-defined synaptic contacts were observed. Labeled synaptic terminals in kittens at 1 and 2 weeks of age were small, contained very few synaptic vesicles, which were usually restricted to the contact zone, and exhibited few mitochondria. By 4 and 6 weeks after birth, a well-developed population of synaptic terminals was established; however, growth cones and intermediate profiles were still numerous. At 8 weeks of age synaptic terminals were morphologically mature, and growth cone-like profiles were no longer observed. To study quantitative changes in synapse development we used the disector method to obtain unbiased estimates of the density and number of corticotectal synaptic terminals and synapses; both the density and number of terminals and synapses increased steadily throughout postnatal development. These results suggest that the corticotectal projection develops by the progressive elaboration of synapses, as opposed to synapse overproduction and subsequent elimination.

Animals↗

Perfluorooctylbromide as a contrast agent for CT and sonography: preliminary clinical results.

OBJECTIVE: Perflubron emulsion is a bromine-based particulate contrast agent that is taken up selectively by the liver and spleen after IV injection. It does not leave the vascular space and also persists in the blood for a longer period than iodinated contrast agents do. We performed a preliminary study to determine the value of the IV perflubron emulsion as a contrast material for CT and sonography. SUBJECTS AND METHODS: To determine the safety and dose response of perflubron emulsion as an IV contrast agent for CT and sonography, 18 cancer patients, 14 of whom had hepatic metastases, were given 0.5-3.0 ml/kg of the emulsion. Sonography and CT of the liver and spleen were performed before and immediately after infusion and then again at 24 hr. RESULTS: A persistent increase in the density of blood, liver, and spleen was observed, where maximal enhancements of 55, 39, and 317 H, respectively, were achieved. Tumor conspicuity increased as metastases enhanced minimally (7 H or less). Peak enhancement of the liver and spleen was delayed to 24 hr with higher doses of perflubron; however, the immediate postinfusion scan allowed the distinction of vessels from hepatic lesions. Sonographically, an increase in tumor echogenicity relative to liver was observed in nine of the 14 subjects, allowing the detection of additional metastases in two. Splenic echogenicity in the near field increased relative to kidney; however, attenuation increased markedly at the time of peak concentration, limiting beam penetration. Similar but milder changes were observed in the liver. Adverse effects occurred in 14 of the subjects; these included lower back pain in six, delayed fever in eight, and malaise in three. CONCLUSION: Perflubron emulsion produced prolonged enhancement of blood, liver, and spleen and increased the conspicuity of liver metastases. However, the side effects encountered could limit its use to a selected population of patients.

Adult↗

Postnatal development of the corticotectal projection in cats.

Although numerous physiological studies have provided compelling evidence for the involvement of the corticotectal projection in the normal development of visual response properties of neurons in the superior colliculus, little information is available on the morphological development of corticotectal axons. Thus, our goal was to determine the postnatal changes characterizing the development of the topography and morphology of corticotectal axon arbors. Topographically restricted injections of Phaseolus vulgaris leucoagglutinin were made into striate cortex to label corticotectal axons and their terminal arbors. Following injections of similar size and location in kittens and adult cats, a similar, localized region of the superior colliculus was labeled at all ages. However, while present in the appropriate topographic location in colliculus, the corticotectal projection revealed a greater tangential distribution in kittens than adults. Corticotectal terminal zones underwent a twofold decrease in tangential area during the first 8 weeks after birth. From corticotectal terminal zones in kittens, extended many fine collaterals that ended as growth cones and radiated up to 1 mm from the focus of the terminal zone. By 8 weeks after birth, these immature collaterals were no longer observed, and the corticotectal terminal zone was indistinguishable from those in 12-week-old kittens and adult cats. Corticotectal axon arbors became more specialized in the first 8 weeks after birth; both en passant and terminal swellings increased in diameter, and terminal swellings increased in number, although the total number of swellings per unit length of axon remained relatively stable. The number of axonal branches increased threefold between 1 and 8 weeks after birth. Thus, as the corticotectal projection becomes spatially restricted during development, individual arbors become progressively more intricate with regard to focused collateral branching and the elaboration of complex axonal specializations.

Animals↗

Intrinsic circuitry in the cat superior colliculus: projections from the superficial layers.

The neuroanatomical tracer Phaseolus vulgaris leucoagglutinin (PHA-L) was used to label the local projections of neurons whose cell bodies are located in the superficial layers of the cat superior colliculus. Small, localized groups of neurons in the superficial layers project to all regions of the ipsilateral colliculus, including the deep layers. Comparable distributions of labeled terminals are seen throughout the colliculus when the PHA-L injection site is located in the rostral, middle, or caudal one-third of the colliculus. In addition, there is some evidence of a topographic projection from superficial to deep layers. These results suggest that a complex anatomical substrate exists for communication between the superficial and deep layers of the colliculus. Connections such as these may underlie the transfer of visual information from neurons in the superficial layers to populations of neurons in the deep layers that respond prior to saccadic eye movements.

Animals↗

Contrast variation studies of clathrin coated vesicles by small-angle neutron scattering.

Structural information on clathrin coated vesicles has been obtained by small angle neutron scattering using contrast variation. A characteristic peak in the neutron scattering profile, which is apparent in 75% D2O, as well as in H2O, disappears when contrast matching the protein component of the coated vesicles in 42% D2O. Neutron, as well as dynamic, light scattering give a coated vesicle size of about 900 A in H2O and D2O, but for neutron scattering the diameter decreases when matching out the protein coat of the clathrin coated vesicles. From the match point for the clathrin coated vesicles it is demonstrated that the clathrin cages do contain internal membrane. The mass of 34 MD and composition of 75% protein and 25% lipid found from the analysis of the small-angle scattering data are both in good agreement with the values reported in the literature. Electron microscopy gives an average outer diameter of 880 A for the coated vesicles and an average diameter of 460 A for the vesicle itself.

Biophysical Phenomena↗

Calcium binding protein (calbindin D28k) immunoreactivity in the hamster superior colliculus: ultrastructure and lack of co-localization with GABA.

The expression of specific calcium binding proteins is being used increasingly as a potential neuroanatomical marker for neurons with similar functions. In this study, the distribution of calbindin D28k in the superior colliculus (SC) of adult hamsters was examined by light and electron microscopy. Calbindin immunoreactivity was prominent in specific regions and laminae of the SC throughout its rostrocaudal extent, and was found to label horizontal, vertical and stellate cell types. In addition, calbindin label highlighted "bridges" of neuronal processes in the intermediate layers. The most frequent calbindin-immunoreactive profiles seen in the electron microscope were dendrites, some of which were post-synaptic to apparent retinal ganglion cell axon terminals. Labelled axons and axon terminals were less frequently encountered. There was considerable overlap between the size distribution of calbindin D28k-immunoreactive neurons and that of GABA-immunoreactive or Nissl stained neurons in the SC. However, using a double fluorescent labelling technique, and examination of the tissue with confocal laser microscopy, no neurons were observed in the hamster SC that showed immunoreactivity for both calbindin and GABA. In this regard, the SC is similar to the mammalian lateral geniculate nucleus and the pretectum, but differs from the neocortex, where calbindin and GABA are colocalized. The demonstration in the SC, as well as other parts of the nervous system, of sub-populations of neurons that contain distinct calcium-binding proteins suggests that these neurons have different functional properties. Correlative studies may clarify the relevance of these cytoplasmic components as cell markers, as well as their different patterns of association with neurotransmitters and peptides.

Animals↗