Does the guinea-pig ileum obey the 'law of the intestine'?
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1. We report the first simultaneous mechanical reflex responses of the longitudinal muscle (LM) and circular muscle (CM) layers of the guinea-pig ileum following mucosal stimulation and distension in vitro. 2. Dissection techniques were used to prevent mechanical interaction between the LM and CM layers both oral and anal to a stimulus site. 3. All graded stimuli produced graded contractions of both the LM and CM orally and anally to the stimulus. Contractions occurred synchronously in the LM and CM and under no circumstances were inhibitory responses recorded in either muscle layer, despite the presence of ongoing cholinergic tone in both the LM and CM. Contractions were abolished by tetrodotoxin (1.6 microM). 4. Local brush stroking of the mucosa evoked a peristaltic wave which readily conducted distally over 13 cm, without the presence of fluid in the lumen. No descending relaxation was observed. 5. Apamin (300 nM) disrupted evoked peristaltic waves and significantly increased the rate-of-rise of the LM and CM contractions anal to a stimulus, and the LM oral to a stimulus. 6. Nomega-nitro-L-arginine (100 microM), a nitric oxide synthesis inhibitor, had no overall significant effect on the characteristics of the LM and CM contractions, although on occasion an enhancement in their peak amplitude was noted. 7. It is suggested that the guinea-pig ileum does not conform to the 'law of the intestine' as postulated by Bayliss & Starling (1899). Rather, local physiological stimulation of the ileum elicits a contraction both orally and anally to a stimulus, which occurs synchronously in both the CM and LM layers. Apamin-sensitive inhibitory neurotransmission modulates the rate-of-rise of the anal contraction of the CM, possibly to generate distal propulsion. (+info)
Detection of human papillomavirus types 6 and 11 in pubic and perianal hair from patients with genital warts.
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Genital human papillomavirus (HPV) types 6 and 11 are of clinical importance due to their role in the development of anogenital warts. A pilot study was performed to investigate whether DNAs from HPV types 6 and 11 are present in hairs plucked from the pubic and perianal regions and eyebrows of patients with genital warts at present and patients with a recent history of genital warts. Genital HPV DNA was detected in 9 of 25 (36%) pubic hair samples and in 11 of 22 (50%) perianal hair samples by the CPI/CPIIg PCR. After sequencing of 17 of 20 samples, HPV type 6 or 11 was detected in 6 of 25 (24%) hair samples from the pubis and 8 of 22 (36%) hair samples from the perianal region. These types were not detected in plucked eyebrow hairs. In contrast, the HPV types associated with epidermodysplasia verruciformis were detected in similar proportions (62%) in both samples of pubic and eyebrow hairs. Moreover, HPV type 6 and 11 DNAs were detected in pubic hairs plucked from two patients who had been successfully treated and who did not show any lesion at the time of hair collection; this finding is an argument that HPV DNA may persist in this region. The presence of genital HPV types in plucked pubic and perianal hair suggests that there is an endogenous reservoir for HPV which may play a role in the recurrences of genital warts. (+info)
Laterality effects of human pudendal nerve stimulation on corticoanal pathways: evidence for functional asymmetry.
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BACKGROUND: Although motor and sensory pathways to the human external anal sphincter are bilateral, a unilateral pudendal neuropathy may still disrupt anal continence. Anal continence can, however, be preserved despite unilateral pudendal damage, and so to explain those differing observations, we postulated that pudendal innervation might be asymmetric. AIMS: To explore the individual effects of right and left pudendal nerve stimulation on the corticofugal pathways to the human external anal sphincter and thus assess evidence for functional asymmetric pelvic innervation. METHODS: In eight healthy subjects, anal sphincter electromyographic responses, evoked to transcranial magnetic stimulation of the motor cortex, were recorded 5-500 msec after digital transrectal electrical conditioning stimuli applied to each pudendal nerve. RESULTS: Right or left pudendal nerve stimulation evoked anal responses of similar latencies but asymmetric amplitudes in six subjects: dominant responses (>50% contralateral side) from the right pudendal in four subjects and from the left in two. Cortical stimulation also evoked anal responses with amplitude 448 (121) microV and latency 20.9 (1.1) msec. When cortical stimulation was preceded by pudendal nerve stimulation, the cortical responses were facilitated at interstimulus intervals of 5-20 msec. Dominant pudendal nerve stimulation induced greater facilitation of the cortically evoked responses than the non-dominant nerve. CONCLUSIONS: Cortical pathways to the external anal sphincter are facilitated by pudendal nerve conditioning, in an asymmetric manner. This functional asymmetry may explain the presence and absence of anal incontinence after unilateral pudendal nerve injury. (+info)
A comparison of injections of botulinum toxin and topical nitroglycerin ointment for the treatment of chronic anal fissure.
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BACKGROUND AND METHODS: Lateral internal sphincterotomy, the most common treatment for chronic anal fissure, may cause permanent injury to the anal sphincter, which can lead to fecal incontinence. We compared two nonsurgical treatments that avert the risk of fecal incontinence. We randomly assigned 50 adults with symptomatic chronic posterior anal fissures to receive treatment with either a total of 20 U of botulinum toxin injected into the internal anal sphincter on each side of the anterior midline or 0.2 percent nitroglycerin ointment applied twice daily for six weeks. RESULTS: After two months, the fissures were healed in 24 of the 25 patients (96 percent) in the botulinum-toxin group and in 15 of the 25 (60 percent) in the nitroglycerin group (P=0.005). No patient in either group had fecal incontinence. At some time during treatment, five patients in the nitroglycerin group had transient, moderate-to-severe headaches that were related to treatment. None of the patients in the botulinum-toxin group reported adverse effects. Ten patients who did not have a response to the assigned treatment - 1 in the botulinum-toxin group and 9 in the nitroglycerin group - crossed over to the other treatment; the fissures subsequently healed in all 10 patients. There were no relapses during an average of about 15 months of follow-up. CONCLUSIONS: Although treatment with either topical nitroglycerin or botulinum toxin is effective as an alternative to surgery for patients with chronic anal fissure, botulinum toxin is the more effective nonsurgical treatment. (+info)
Long-term results of artificial anal sphincter implantation for severe anal incontinence.
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OBJECTIVE: To evaluate the long-term results of implantation of an artificial anal sphincter (AAS) for severe anal incontinence. SUMMARY BACKGROUND DATA: Implantation of an AAS is one of the options for treatment of anal incontinence when standard operations have failed. It is the only surgical option for treatment of anal incontinence in patients with neurologic disease that affects the pelvic floor and the muscles of the lower limb. METHODS: Seventeen patients underwent implantation of an AAS before 1993. These patients have been followed and their continence status evaluated. RESULTS: Two patients died of unrelated causes within the first 3 years after surgery, and in three patients the AAS was explanted because of infection. During the follow-up period, four patients had the AAS removed because of malfunction, and eight patients had a functioning AAS > or =5 years after the primary implantation. Five of these patients had revisional procedures, mainly because of technical problems in the early part of the study, when a urinary sphincter or slightly modified urinary sphincter was used. Continence at follow-up was good in four patients and acceptable in three, whereas one patient still had occasional leakage of solid stool. One patient had rectal emptying problems, which she managed by enema. CONCLUSIONS: An AAS based on the same principles as the artificial urinary sphincter seems to be a valid alternative in selected patients when standard surgical procedures have failed or are unsuitable. Approximately half of the patients have an adequate long-term result. Infectious complications still present a problem, whereas mechanical problems are less frequent with the modification of the device now available. (+info)
Mechanism of action of cholera toxin on the opossum internal anal sphincter smooth muscle.
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Cholera toxin (CTX), an activator of G(s) protein, is an important pharmacological tool in G protein research. The effect and the mechanism of action of CTX in the gastrointestinal smooth muscle, including the internal anal sphincter (IAS), are not known. The present investigation was carried out to examine the effects of CTX on the signal transduction associated with the adenylate cyclase (AC) pathway on the basal tone of the IAS smooth muscle. CTX caused a prompt and dose-dependent fall in the basal tone of the IAS that was not affected by the neurotoxins TTX and omega-conotoxin or the nitric oxide synthase inhibitor N(G)-nitro-L-arginine. The cyclooxygenase inhibitor indomethacin, cAMP-dependent protein kinase inhibitor Rp-8-bromoadenosine 3',5' cyclic monophosphorothioate inhibited CTX-induced IAS smooth muscle relaxation. Furthermore, CTX caused a concentration-dependent relaxation of the isolated smooth muscle cells (SMC) of the IAS, which was blocked by G(s)alpha antibody (G(s)alpha-Ab). The IAS smooth muscle relaxation was accompanied with an increase in the GTPase activity that was also specifically blocked by G(s)alpha-Ab. We conclude that a major part of the inhibitory action of CTX in the IAS is via the direct response of the SMC that is linked with G(s) protein to the AC pathway. A part of the inhibitory action of CTX on the smooth muscle occurs via the activation of cyclooxygenase pathway. The relative contribution of such actions of CTX in the smooth muscle in the gastrointestinal motility disturbances following cholera infection remains to be determined. (+info)
Quantitative study of the effects of denervation and castration on the levator ani muscle of the rat.
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The levator ani muscle (LA) of the rat is highly androgen-sensitive and, like all skeletal muscles, deteriorates structurally and functionally when denervated. In order to elucidate the interplay of neural and endocrine influences, the separate and combined effects of denervation and castration on myofiber cross-sectional area and nuclear populations were quantitatively studied. In one group of 4-month-old male rats (A), the LA was denervated. Another group (B) was surgically castrated and a third group (C) was both denervated and castrated. The control rats (D) remained both gonad- and nerve-intact. After two months, the LA was obtained for myofiber and nuclear enumeration, cross-sectional area and satellite cell frequency determination. In the denervated muscle of gonad-intact rats (Group A), myofiber cross-sectional area was markedly diminished (265.84+/-11.38 microm2; compared with controls [Group D]: 1519.98+/-79.41 microm2; P < 0.05). Satellite cell nuclei, as a percentage of total sublaminar nuclei (i.e., satellite cell ratio), increased significantly (4.26%, from a control value of 1.91%). Castration alone (Group B) resulted in pronounced myofiber atrophy (mean cross-sectional area: 754.03+/-89.63 microm2) but had no significant effect on satellite cell ratio (2.36%). The combination of castration and denervation (Group C) elicited the same degree of myofiber atrophy as denervation alone (Group A) but had no significant impact on satellite cell ratio. Instead, the nuclear count per myofiber declined to about a third of the control level (300.5+/-38.49 compared with 861.7+/-24.8; P < 0.05). The results indicate that the atrophic effects of denervation and castration on the LA are non-synergistic and mechanistically similar. They also show that the inability of satellite cells to respond mitotically to the withdrawal of neural input under disandrogenized conditions is a factor in the myonuclear depletion of the denervated muscle of castrated rats. (+info)
Protracted elevation of neuronal nitric oxide synthase immunoreactivity in axotomised adult pudendal motor neurons.
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Neuronal nitric oxide synthase immunoreactivity (NOS1-ir) in sacral motor neurons of normal adult cats was compared with that in cats surviving 1-10 wk after unilateral transection and ligation of the pudendal nerve. Levels of immunostaining were measured by microdensitometry. In nonoperated cats 60% of motor neurons in the ventrolateral nucleus (VL) and Onuf's nucleus (ON) showed high levels of NOS1-ir with lower NOS1-ir in 40%. Following axotomy, motor neurons in ON on both sides of the cord showed an acute rise in mean level of NOS1-ir at 1 wk, with a further increase at 2 wk. Mean levels of NOS1-ir in the ipsilateral and contralateral ON remained elevated at 10 wk after axotomy. Elevation of NOS1-ir occurred in the VL with a similar time-course to that in ON, implying a wider response in motor nuclei synaptically coupled to ON. Measurements of neuronal size in ON and VL revealed an increase in neuronal size in ON but not VL, indicating increased NOSI-ir in ON was not an artifact of neuronal atrophy. The proportion of motor neurons in ON and VL possessing higher levels of NOS1-ir increased from 60% in controls to 100% at 2-3 wk postaxotomy. The proportion slightly declined by 8 wk due to re-emergence of motor neurons exhibiting low NOS1-ir, but remained greater than normal at 10 wk in both nuclei. Based on evidence from related analyses of synaptology, we argue that acute axotomy induced alterations in presynaptic complement which increased overall Ca2+ influx and thereby stimulated NOS1-ir. (+info)