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PubMed1998

Effect of mental stress and cisapride on autonomic nerve functions in functional dyspepsia.

BACKGROUND: Disordered autonomic nerve function is frequently present in patients with functional dyspepsia (FD). In this study we investigated whether the prokinetic cisapride, which acts via acetylcholine receptors, and stress may modulate these abnormalities. METHODS: Nineteen patients (6 men, 13 women) with FD and 10 healthy subjects (3 men, 7 women) were studied after 3 days' treatment with 10 mg cisapride three times daily and placebo in a crossover design. Mental stress was induced with a videogame. Sympathetic and vagal nerve functions were assessed noninvasively by skin conductance and respiratory sinus arrhythmia, respectively. RESULTS: Vagal tone was significantly lower in FD patients than in controls both before and after mental stress (P < 0.001). Sympathetic tone was higher in patients with FD than in controls (P < 0.03). Generally, stress scores were increased by mental stress in both groups (P < 0.001). In FD patients, but not in controls, cisapride significantly increased the sympathetic tone both before (P < 0.05) and after stress (P < 0.05). CONCLUSIONS: Patients with FD have lower vagal tone and higher sympathetic tone than healthy controls. Treatment with cisapride increased sympathetic tone in the patient group but had no effect on vagal tone.

Adult↗
PubMed2002

Possible pathways for cerebellar modulation of autonomic responses: micturition.

Experimental and clinical studies have shown that the cerebellum participates in the regulation of various visceral responses, including micturition. It is not yet clear through which parts of the central nervous system such cerebellar influences are mediated. However, a series of investigations have shown that the cerebellum is directly or indirectly connected to various centres that appear to be involved in autonomic control. These include parts of the cerebral cortex, the hypothalamus, the periaquaductal grey, nuclei in and around the pontine micturition centre, the dorsal vagal nucleus and nucleus of the solitary tract, and the medullary reticular formation. This article examines some of the circuits that may be involved in cerebellar modulation of visceral reflexes, especially the micturition reflex.

Animals↗
PubMedDate not supplied

Contribution of electron microscopy to understanding cellular differentiation in mesenchymal tumors of the gastrointestinal tract: a study of 82 tumors.

Eighty-two mesenchymal tumors of the gastrointestinal tract were examined by electron microscopy for the purposes of subtyping for diagnostic precision and of understanding cellular differentiation. Tumors were subclassified into leiomyoma/leiomyosarcoma, tumors of the interstitial cell of Cajal (equivalent to traditionally defined GISTs [Miettinen et al. Hum Pathol. 1999; 30:1213-1220; Mod Pathol. 2000; 13:1134-1142]), gastrointestinal autonomic nerve tumors (GANTs), and fibroblastic and myofibroblastic tumors, using criteria from the literature. Leiomyoma/leiomyosarcoma were diagnosed by myofilaments, attachment plaques, plasmalemmal caveolae, and lamina; GIST by processes or cell bodies full of intermediate filaments, solitary focal densities amid intermediate filaments, attachment plaques with incomplete lamina, scarce myofilaments, and smooth endoplasmic reticulum; GANTs by neuroendocrine granules, cell bodies/processes full of intermediate filaments (more rarely microtubules), and smooth endoplasmic reticulum; fibroblastic/myofibroblastic tumors by abundant rough endoplasmic reticulum, myofilaments, and fibronexuses. Seventy-three tumors (89%) were successfully subclassified, as 5 leiomyoma/leiomyosarcoma (6%), 36 GISTs (44%), 22 GANTs (27%), 10 fibroblastic and myofibroblastic tumors (12%). Results indicated overlap between poorly differentiated leiomyosarcoma and GIST, and between GIST and GANT. GANT is emphasized as a neuronal tumor identifiable by electron microscopy, and thereby distinguishable from GIST.

Aged↗
PubMed2004

Estrogen regulates vaginal sensory and autonomic nerve density in the rat.

Vaginal function is strongly influenced by reproductive hormone status. Vaginal dysfunction during menopause is generally assumed to occur because of diminished estrogen-mediated trophic support of vaginal target cells. However, peripheral neurons possess estrogen receptors and are potentially responsive to gonadal steroid hormones. In the present study, we investigated whether sensory and autonomic innervation of the vagina varies among rats during the estrus phase of the estrous cycle, following chronic ovariectomy, and after sustained estrogen replacement. Relative to rats in estrus, ovariectomized rats showed a 59% elevation in nerve density, as determined using the panneuronal marker PGP 9.5. This increase persisted even after correcting for differences in vaginal tissue size, indicating true axonal proliferation after ovariectomy rather than changes secondary to altered volume. Increased total innervation after ovariectomy was attributable to increased densities of sympathetic nerves immunostained for tyrosine hydroxylase (70%), cholinergic parasympathetic nerves immunoreactive for vesicular acetylcholine transporter (93%), and calcitonin gene-related peptide-immunoreactive sensory nociceptor nerves (84%). Myelinated primary sensory innervation revealed by RT-97 immunoreactivity did not appear to be affected. Sustained 17beta-estradiol administration reduced innervation density to an extent comparable to that of estrus, implying that estrogen is the hormone mediating vaginal neuroplasticity. These findings indicate that some aspects of vaginal dysfunction during menopause may be attributable to changes in innervation. Increased sympathetic innervation may augment vasoconstriction and promote vaginal dryness, while sensory nociceptor axon proliferation may contribute to symptoms of pain, burning, and itching associated with menopause and some forms of vulvodynia.

Animals↗
PubMed1996

Testis of prepubertal rhesus monkeys receives a dual catecholaminergic input provided by the extrinsic innervation and an intragonadal source of catecholamines.

The mammalian testis is innervated by extrinsic catecholaminergic nerves and responds to catecholamines with steroid secretion. Although the primate testis has also been shown to be innervated, potential differences in the density of this innervation between immature and sexually developed individuals have not been described. A recent study demonstrated that the primate ovary contains a network of neuron-like cells and that some of these cells are catecholaminergic. It is thus possible that the male gonad is also endowed with a similar intragonadal source of catecholamines. The present study addresses these two issues. Catecholaminergic nerves were identified as such by their content of immunoreactive tyrosine hydroxylase (TH; the rate-limiting step in catecholamine biosynthesis), and in some cases by glyoxylic acid histochemistry. Fibers containing TH were abundant in testes from juvenile animals (1-2 yr of postnatal life), but the density of this innervation was not maintained in adult animals, whose testis showed only a few TH-positive fibers scattered in the interstitial tissue. Testicular norepinephrine (NE) concentration was much lower in adult than in juvenile animals, suggesting that the marked increase in testicular weight that occurs with the attainment of sexual maturity is not accompanied by corresponding changes in NE content. At the ultrastructural level, testicular nerve fibers contained pleiomorphic, dense-core and clear vesicles, suggesting the presence of catecholamines and other neurotransmitters. In addition to this extrinsic catecholaminergic innervation, prepubertal testes, but not adult gonads, contained an intrinsic population of TH-immunopositive neuron-like elements, identified as cells by confocal scanning laser microscopy. To determine whether the prepubertal monkey testis indeed expresses the TH gene, testicular RNA was subjected to reverse transcriptase polymerase chain reaction to amplify the 5' end of TH mRNA, which encodes the regulatory domain of the enzyme. The cDNA that was obtained predicts an amino acid sequence similar, but not identical, to that encoded by the alternatively spliced type 1 TH mRNA form present in the adrenal gland. These results indicate 1) that the primate testis receives a dual catecholaminergic input, one provided by the extrinsic innervation and the other by neuron-like cells located within the gonad itself, and 2) that the influence exerted by both sources on testicular function may be more prominent during the prepubertal period than in adulthood. The presence in the testis of a TH mRNA variant encoding amino acid substitutions in its 5' end suggests that regulation of testicular TH enzyme activity may include a gonad-specific component.

Aging↗
PubMed2006

Cardiac autonomic modulation following high-intensity static muscle contractions.

BACKGROUND: The purpose of this investigation was to examine cardiac autonomic modulation, as measured by wavelet analysis of heart rate variability, following a series of high-intensity static muscle contractions. METHODS: After 10 minutes of rest, electrocardiograms (ECGs) were collected in 17 participants (age, 24.5 +/- 1 yr) 2.5 minutes before (REST) and 10 minutes after a series of static contractions of the knee extensors. Participants performed contractions with the nondominant leg (knee fixed at 90 degrees) at either 70% or 85% (randomized order) of their maximal voluntary contraction (MVC) on two separate visits. The postexercise ECGs were further divided into four consecutive 2.5-minute segments (POST 1-POST 4) to evaluate the time course of any possible autonomic changes after exercise. Each 2.5-minute segment was evaluated for the standard deviation of normal RR intervals (SDNN) and the percentage of successive RR intervals that differed by more than 50 ms (pNN50). Frequency-domain indices were obtained via wavelet transformation giving coefficients that reflected high- and low-frequency fluctuations in heart period (HFw and LFw). RESULTS: SDNN was elevated during POST-1 and pNN50 was reduced during POST-3 and POST-4 (P < 0.05) compared to REST for both intensities. Furthermore, HFw and LFw were increased during POST-1 and reduced during POST-3 and POST-4 compared to REST for both intensities (P < 0.05). CONCLUSION: These data suggest that complex alterations cardiac autonomic modulation exist for at least 10 minutes following a series of high-intensity static contractions performed at either 70% or 85% of MVC.

Adult↗
PubMed2002

Isoflurane depresses baroreflex control of heart rate in decerebrate rats.

BACKGROUND: Isoflurane inhibits baroreflex control of heart rate (HR) by poorly understood mechanisms. The authors examined whether suprapontine central nervous system cardiovascular regulatory sites are required for anesthetic depression. METHODS: The effects of isoflurane (1 and 2 rat minimum alveolar concentration [MAC]) on the baroreflex control of HR were determined in sham intact and midcollicular-transected decerebrate rats. Intravenous phenylephrine (0.2-12 microg/kg) and nitroprusside (1-60 microg/kg) were used to measure HR responses to peak changes in mean arterial pressure (MAP). Sigmoidal logistic curve fits to HR-MAP data assessed baroreflex sensitivity (HR/MAP), HR range, lower and upper HR plateau, and MAP at half the HR range (BP50). Four groups (two brain intact and two decerebrate) were studied before, during, and after isoflurane. To assess sympathetic and vagal contributions to HR baroreflex, beta-adrenoceptor (1 mg/kg atenolol) or muscarinic (0.5 mg/kg methyl atropine) antagonists were administered systemically. RESULTS: Decerebration did not alter resting MAP and HR or baroreflex parameters. Isoflurane depressed baroreflex slope and HR range in brain-intact and decerebrate rats. In both groups, 1 MAC reduced HR range by depressing peak reflex tachycardia. Maximal reflex bradycardia during increases in blood pressure was relatively preserved. Atenolol during 1 MAC did not alter maximum reflex tachycardia. In contrast, atropine during 1 MAC fully blocked reflex bradycardia. Therefore, 1 MAC predominantly depresses sympathetic components of HR baroreflex. Isoflurane at 2 MAC depressed both HR plateaus and decreased BP50 in both groups. CONCLUSIONS: Isoflurane depresses HR baroreflex control by actions that do not require suprapontine central nervous system sites. Isoflurane actions seem to inhibit HR baroreflex primarily by the sympathetic nervous system.

Adrenergic beta-Antagonists↗
PubMed1999

Role of nodal involvement and the periductal soft-tissue margin in middle and distal bile duct cancer.

OBJECTIVE: To determine the pattern of middle (Bm) and distal (Bi) bile duct cancers in an attempt to optimize surgical treatment. SUMMARY BACKGROUND DATA: Lymph node involvement and neural plexus invasion are the prognostic factors most amenable to surgery in Bm and Bi disease. However, a detailed analysis of these factors has not been conducted. METHODS: Fifty patients with Bm and Bi disease (Bm 14 patients, Bi 36 patients) were examined histopathologically. A precise determination was made of lymph node involvement and neural plexus invasion. Important prognostic factors were examined by clinicopathologic study to apply these findings to surgical management. RESULTS: Frequencies of nodal involvement for Bm and Bi disease were 57% and 71%, respectively. The inferior periductal and superior pancreaticoduodenal lymph nodes were most commonly involved. Neural plexus invasion occurred in 20% of patients, particularly involving the plexus in the hepatoduodenal ligament and pancreatic head. Tumor was present at the surgical margin in 50% and 14% of patients with Bm and Bi disease, respectively. Five-year survival rates were 65% in the absence of nodal metastasis and 21% with nodal metastasis. A significant correlation existed between absence of tumor at the surgical margin and survival. A Cox proportional hazard model projected absence of tumor at the surgical margin, followed by nodal involvement, as the strongest prognostic variables. CONCLUSIONS: Absence of tumor at the surgical margin and nodal involvement are important independent prognostic factors in Bm and Bi disease. Skeletonization of the hepatoduodenal ligament, including portal vein resection, is necessary for patients with Bm disease, and a wide nodal dissection is essential in all patients.

Adult↗
PubMed1994

Intraventricular application of BDNF and NT-3 failed to protect nucleus basalis magnocellularis cholinergic neurones.

Quantitative analysis of ChAT immunoreactive neurones was used to evaluate the protective potential of BDNF or NT-3 against retrograde changes in nucleus basalis magnocellularis (nbm) cholinergic neurones after unilateral partial devascularization of the rat neocortex. A daily intracerebroventricular dose of 12 micrograms, proven to be effective for NGF and aFGF in the same experimental paradigm, was administered by minipump infusion for a 1-week period. Thirty days after lesioning, neuronal shrinkage and loss of neuritic processes were not prevented by treatment. The results indicate that intracerebroventricularly delivered BDNF and NT-3 are not as effective as NGF and aFGF in protection of nbm cholinergic neurones against lesion-induced changes in adult rat brain.

Animals↗
PubMed1998

Comparison of 24-hour blood pressure, heart rate, and autonomic nerve activity in hypertensive patients treated with cilnidipine or nifedipine retard.

We compared the effects of cilnidipine and nifedipine retard on 24-h blood pressure (BP), heart rate (HR), and autonomic nerve activity in patients with essential hypertension. Cilnidipine is a novel and unique 1,4-dihydropyridine calcium antagonist that has the L-type and N-type voltage-dependent calcium channel-blocking action. Fourteen hypertensive outpatients (four men and 10 women; aged 64 +/- 2 years, mean +/- SEM) were enrolled in this study. Their ambulatory BP and electrocardiogram were monitored for 24 h at intervals of 30 min with a portable recorder after a 4-week drug-free period, after a 4-week treatment period with cilnidipine (5 or 10 mg once daily), and after a 4-week treatment period with nifedipine retard (10 or 20 mg twice daily). The order of the three periods was randomized. Autonomic nerve activity was evaluated by a power spectral analysis of HR variability, by using the high-frequency (HF) component as an index of parasympathetic nerve activity and the ratio of the low-frequency (LF) component to the HF component (LF/HF) as an index of sympathovagal balance. Cilnidipine and nifedipine retard significantly reduced the 24-h BP of these patients to similar extents (cilnidipine, -11 +/- 3/-6 +/- 1 mm Hg; nifedipine retard, -15 +/- 3/-6 +/- 2 mm Hg). Cilnidipine did not change the 24-h average HR, whereas nifedipine retard significantly increased it (+3.3 +/- 1.4 beats/min; p < 0.05). Nifedipine retard significantly increased the LF/HF ratio in the daytime and the nighttime. Such changes were limited to the daytime in the treatment period with cilnidipine. These results suggest that cilnidipine is effective as a once-daily antihypertensive agent and had less influence on autonomic nervous system and HR than did nifedipine retard.

Autonomic Pathways↗
PubMed2001

Calorie restriction reduced blood pressure in obesity hypertensives by improvement of autonomic nerve activity and insulin sensitivity.

Association between obesity and hypertension has been well recognized. A reduction in the body weight of over-weight hypertensive patients is a recommended lifestyle modification. The purpose of our study is to examine the relationship of insulin sensitivity and autonomic nervous activity with reduction of blood pressure by the calorie restriction. We evaluated the heart rate variability, nocturnal change of blood pressure and insulin resistance before and after a short-term low-calorie diet in 12 overweight essential hypertensives. After a week of standard diet (2000 kcal), 2 weeks of low-calorie diet (800 kcal) with normal sodium content induced a significant reduction in body mass index, triglyceride, fasting immunoreactive protein, homeostasis model assessment as an index of insulin resistance, and urinary excretion of sodium and potassium. Systolic blood pressure was significantly reduced both in daytime and night-time after the low-calorie diet (daytime, 134.5+/-6.0 to 122.0+/-4.1 mmHg; night-time, 126.8+/-5.2 to 113.4+/-7.2 mmHg). In daytime, diastolic blood pressure was also reduced (90.3+/-2.1 to 88.1+/-4.8 mmHg). Although heart rate was not significantly reduced, a rise of high frequency in night-time (346+/-82 to 572+/-108 ms2) and a fall of low frequency/high frequency in day-time (3.5+/-0.4 to 2.6+/-0.1) was significant after a low-calorie diet. In conclusion, weight loss by low-calorie diet with a constant intake of sodium, reduced blood pressure in obese hypertensives by improvement of vagal nervous activity and insulin resistance.

Adult↗
PubMed1997

Exercise effect on canine and miniswine cardiac catecholamines and enkephalins.

Chronic exercise changes cardiac function and responsiveness to autonomic control. Catecholamines and enkephalins are neuroendocrine transmitters involved in autonomic regulation and signaling. We hypothesized that intermittent increased sympathetic stimulation caused by exercise training would decrease cardiac catecholamine and enkephalin content. Dogs and miniswine were exercise trained and hearts extracted for catecholamine and enkephalin measurements. Atrial catecholamine content is greater than ventricular content in dog heart which is in keeping with the greater atrial neuronal density. In contrast, porcine epinephrine content was evenly distributed across heart sections and norepinephrine content was greater on the right side than the left. Changes in miniswine and dog heart catecholamine content after exercise training were different. Canine cardiac norepinephrine content decreased and porcine norepinephrine content increased. This indicates a difference in cardiac adrenergic control in miniswine versus canines. Methionine-enkephalin (met-enk) distribution across canine heart is uniform, unlike the miniswine, where the atria contain more than the ventricles. Proenkephalin processing produces four met-enk sequences and one met-enk-arg-phe; despite this, ventricles of both species contain more met-enk-arg-phe immunoreactivity than met-enk. Therefore, proenkephalin processing is incomplete in heart tissue. Exercise training in the dog resulted in decreased cardiac met-enk, decreased left atrial met-enk-arg-phe, and increased ventricular met-enk-arg-phe. Porcine cardiac enkephalin concentration was unchanged by training. The changes in the enkephalins may be explained by changes in proenkephalin processing and/or release. Met-enk-arg-phe is particularly good at modulating vagal stimulation of the canine heart. The changes in tissue content seen after exercise training may be a result of the exercise-induced change in autonomic tone to the heart. These data suggest species dependent changes in autonomic regulation.

Analysis of Variance↗
PubMedDate not supplied

Heart rate variability in adolescents and adults with type 1 diabetes.

BACKGROUND: Limited data are available regarding the onset or trajectory of cardiovascular autonomic deterioration in persons with type 1 diabetes. OBJECTIVE: To describe differences in heart rate variability among adolescents with type 1 diabetes, adults with type 1 diabetes who have coexisting renal failure, and adolescent and adult controls. RESEARCH DESIGN AND METHODS: A correlational design was used to compare the status of heart rate variability in adults with type 1 diabetes and renal failure (n = 62); healthy adult controls (n = 67); adolescents with type 1 diabetes (n = 55); and healthy adolescent controls (n = 28). Convenience samples of adult patients with diabetes awaiting kidney or pancreas and kidney transplantation, and adolescents with diabetes were recruited from local university-based clinics. Volunteers served as healthy controls. The short-term R-R variability measures included in this study were changes in heart rate with deep breathing and with the Valsalva maneuver. Twenty-four hour ambulatory heart rate monitoring with power spectral analysis was also obtained to assess longterm R-R variability. RESULTS: Adult patients with type 1 diabetes awaiting transplantation had significantly poorer heart rate variability measures than any of the other three populations studied (p < .0001). Adult control values also were significantly lower than either teenage controls or youths with diabetes (p < .05). Although most long-term R-R variability measures were lower in adolescents with diabetes versus controls, only one measure of parasympathetic modulation (i.e., pNN50) was significantly lower (p = .042). There were significant negative associations between HbA1c and sympathetic modulation (i.e., low hertz) in both the adult group (r= -.406, p = .029) and the adolescent group (r= -.324, p = .025) with diabetes. CONCLUSIONS: Type 1 diabetes is associated with decreased heart rate variability, with the extent of the decrease related to the age of the individual and the severity of the disease.

Adolescent↗
PubMed2001

Laparoscopic presacral neurectomy: a review.

Dysmenorrhea can be a severe and debilitating symptom in many women. Although most women may find adequate relief of symptoms from pharmacological approaches, there remain a few with resistant pain. Presacral neurectomy, although technically challenging, may be offered after other approaches are unsuccessful. The operation is now performed increasingly by the laparoscopic approach, which has revived this operation in some centers. The anatomy, technique, and indications as well as a review of the literature supporting this operation are reviewed. The potential complications of this operation are discussed also.

Autonomic Denervation↗
PubMed1994

Gustatory rhinorrhea--a complication of septoplasty.

A previously unreported complication of septoplasty, which is the profuse flow of thin clear nasal drainage on mastication, is described. Of a combined group of 1332 patients with septoplasty and septorhinoplasty, 6 females and 1 male presented with gustatory rhinorrhea after surgery. The average age of the patients who experienced this complication was 44.43 years. Three patients tested the efficacy of antihistamines, which proved helpful in reducing the severity of this condition. The cause of gustatory rhinorrhea is postulated as inadvertent injury to the nasopalatine nerve within the septal layers after removal of the deviated portion of the vomer and the perpendicular plate of the ethmoid bone during septoplasty. It is the authors' supposition that regenerating nerve sprouts are inappropriately directed toward nasal, rather than palatal, target receptors. Consequently, rhinorrhea results while eating. The pathophysiology of this new finding is not dissimilar to gustatory sweating after parotidectomy. Although this complication is not life-threatening, it is socially disturbing to patients. The authors believe that awareness of this sequela will lead to the discovery of a larger patient population and a potential treatment or prevention.

Adult↗
PubMed2003

Autonomic nerve changes in the mouse pancreas after pancreatic duct ligation.

INTRODUCTION: The mouse pancreas exhibits distinct atrophy of the exocrine tissue following pancreatic duct ligation. AIM: To investigate changes of innervation in the whole pancreas after pancreatic duct ligation. METHODOLOGY: The mouse pancreatic duct was ligated at 6 weeks of age. Pancreatic tissues were removed 7 days and 14 days after the ligation, fixed by perfusion and immersion with Zamboni solution, and embedded in gelatin. The whole organ was serially sectioned at a thickness of 100 microm, histochemically stained for cholinesterase, and observed by light microscopy. The number and volume of intrapancreatic ganglia, number of ganglion cells, and volume of each ganglion cell in the whole pancreas were quantitated. Some sections were analyzed using transmission electron microscopy after histochemically staining for cholinesterase. RESULTS: In the normal pancreas, ganglia were often situated on the outer surface of the islets of Langerhans. Thick nerve bundles ran along the arteries and emanated thin nerve fibers that surrounded the arterioles. In the atrophied pancreas following pancreatic duct ligation, ganglia remained on the islets of Langerhans as in normal mice, while the nerve fibers appeared dense, bending and curling in a more complex manner. The thin nerves also crossed each other in a complex network. Using morphometry in the pancreas following pancreatic duct ligation, the total ganglion cell number was found to decrease from normal levels. The mean ganglion cell volume in the ligated pancreas was significantly smaller than that in normal mice. As observed by transmission electron microscopy, some ganglion cells in the ligated pancreas were negative for cholinesterase activity but were surrounded by positive staining around the surface. CONCLUSIONS: These results suggest that the function of pancreatic ganglion cells changes with organ atrophy after pancreatic duct ligation.

Animals↗