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Residual urine volume after total mesorectal excision: an indicator of pelvic autonomic nerve preservation? Results of a case-control study.

OBJECTIVE: The rate of bladder dysfunctions after total mesorectal excision (TME) for rectal cancer can be decreased by bilateral pelvic autonomic nerve preservation (PANP). However, it is not clear yet, how often partial nerve impairment may lead to bladder dysfunction. It was the aim of a case-control study, to examine the residual urine volume in patients before and after TME with and without complete PANP, in order to clarify, whether this parameter allows conclusions on the quality of PANP. PATIENTS AND METHODS: Regarding bladder function, a case group (n = 26) without complete PANP was compared with a control group (n = 26) with complete identification and nerve preservation according to standadized intra-operative documentation. Twenty-six match pairs were established, identical regarding gender, wall infiltration depth, tumour site, operation procedure and operation extent. Rates of neoadjuvant therapy, R0-classification, anastomotic leakage, wound and urinary tract infection were equally distributed for both the case- and control group (P > 0.05). Residual urine volume was pre- and post-operatively determined by sonography. RESULTS: Pre-operatively, residual urine volumes differed neither between the pairs nor between both groups with and without nerve preservation. In the case group with incomplete PANP there was a difference between pre- and post-operative residual urine volume (median; quartil: 2.5 ml; 0.0-32.5 ml vs 130 ml; 0.0-317 ml; P = 0.001). In the control group there was no difference (median; quartile: 0.0 ml; 0.0-20 ml vs 15.5 ml; 0.0-62.0 ml; P = 0.07). The difference between the postoperatively measured volumes of the case and control group were significant (P = 0.001). With residual urine volume = 100 ml, the risk of incomplete PANP was 14 times higher (odds ratio). CONCLUSIONS: Residual urine volume is an indicator of the completeness of PANP during TME. It should be determined pre- and post-operatively, and besides the recording of the neurogenic bladder, serve as a quality control.

Adult↗

Development of nerves containing nitric oxide synthase in the human male urogenital organs.

OBJECTIVE: To determine the spatial and temporal distribution of nitric oxide synthase (NOS) in the urogenital organs of a series of human male fetuses, using an immunohistochemical technique. MATERIAL AND METHODS: Thirteen pre-natal specimens ranging in gestational age from 13 to 30 weeks were acquired following abortion or miscarriage. The distribution of NOS, which catalyses the production of nitric oxide (NO), was revealed using an indirect immunolabelling technique and compared with the overall innervation of each specimen visualized using the general nerve-marker protein gene product 9.5 (PGP). RESULTS: At 13 weeks of gestation the majority of nerves supplying the developing prostate gland expressed NOS while similar nerves formed a very minor proportion of the total innervation to the urinary bladder and intramural ureters. With increasing gestational age, NOS-containing nerves became more numerous in the lower urinary tract, the majority occurring at the bladder neck and around the prostatic urethra. In contrast, NOS-containing nerves were not detected in the muscle coat of the vas deferens and seminal vesicle until 23 weeks of gestation and at 30 weeks still only formed a small proportion of the intramuscular nerves. From 23 weeks onwards NOS-containing nerves were present occasionally in the dense subepithelial nerve plexuses which developed in the bladder, prostate, vas deferens and seminal vesicle. Also from 23 weeks onwards, many of the epithelial cells lining the vas deferens, seminal vesicle and ejaculatory ducts showed immunoreactivity to NOS but no immunoreactivity was observed in the epithelial lining of the urinary bladder and the intramural ureters. CONCLUSION: Based on the comparative density of NOS-containing nerves and the difference in their temporal development among the various urogenital organs it is apparent that NO plays an increasingly important role in the autonomic control of the lower urinary tract during fetal development but that its involvement in the functional control of the vas deferens and seminal vesicle is relatively minor before birth.

Autonomic Pathways↗

Prospective study of autonomic nerve function in type 1 and type 2 diabetic patients: 24 hour heart rate variation and plasma motilin levels disturbed in parasympathetic neuropathy.

To clarify the impact of autonomic neuropathy in diabetic patients, we have conducted a prospective study of 58 Type 1 and 51 Type 2 diabetic patients (investigated at baseline, after 4, and after 7 years). In Type 1 diabetic patients, the sympathetic nerve function (orthostatic acceleration and brake indices) and in Type 2 patients, parasympathetic nerve function (R-R interval variation; E/l ratio) deteriorated during 7 years of prospective observation. Symptoms of autonomic neuropathy were associated with signs of autonomic neuropathy (low brake indices) in Type 1 but not in Type 2 diabetic patients. In the latest assessment 24 h ECG recording was performed and blood samples assayed for neuropeptide Y (NPY) and motilin were obtained. Type 1 diabetic patients with parasympathetic neuropathy (abnormal E/l ratio) showed significantly lower SD value (less variation in the R-R intervals; 29 [17] vs 50 [16], [mean (interquartile range)]; p = 0.001) and higher postprandial plasma motilin values (70 [20] pmol l-1 vs 50 [15] pmol l-1; p < 0.01) than patients with normal parasympathetic nerve function. In Type 2 diabetic patients, sympathetic neuropathy (low brake indices) was associated with an increased frequency of ventricular extra systolic beats during 24 h ECG recording (rs = 0.65; p < 0.01). Postprandial plasma NPY levels were not associated with disturbed autonomic nerve function.

Adolescent↗

Two types of parasympathetic preganglionic neurones in the superior salivatory nucleus characterized electrophysiologically in slice preparations of neonatal rats.

1. The electrophysiological properties of parasympathetic preganglionic neurones in the superior salivatory nucleus were studied in thin- and thick-slice preparations of rats aged 1 and 2 weeks using the whole-cell patch-clamp technique. 2. The superior salivatory neurones were identified by a retrograde tracing method with dextran-tetramethylrhodamine-lysine. The injection of the tracer into the chorda-lingual nerve labelled the neurones innervating the submandibular ganglia and those innervating the intra-lingual ganglia, while the injection into the tip of the tongue labelled the latter group of neurones. 3. Firing characteristics were investigated mainly in the neurones of 6-8 days postnatal rats. In response to an injection of long depolarizing current pulses at hyperpolarized membrane potentials (< -80 mV) under a current clamp, the neurones labelled from the nerve displayed a train of action potentials with either a long silent period preceding the first spike (late spiking pattern) or a long silent period interposed between the first and second spikes (interrupted spiking pattern). The neurones labelled from the tongue invariably displayed the interrupted spiking pattern. 4. Under a voltage clamp, among the neurones from 6-8 days postnatal rats, those labelled from the nerve expressed either a fast or a slow transient outward current (A-current), while those labelled from the tongue invariably showed a slow transient outward current. Both the fast and slow A-currents were largely depressed by 1 mM 4-aminopyridine. 5. Similar fast and slow A-currents were observed in the neurones of rats aged 14-15 days. Both the time to peak and decay time constant of these A-currents were accelerated, suggesting a developmental trend of maturation in the activation and inactivation kinetics between 6 and 15 days postnatal. 6. Based on the differences in the firing pattern and outward current, the superior salivatory neurones can be separated into two distinct types. We discuss the functional aspects of these two types of neurones with reference to their target organs.

Algorithms↗

The transmitter released by stimulation of the bronchial sympathetic nerves of cats.

A study has been made of the transmitter released in a cat heart-lung preparation when the sympathetic chains were stimulated. The nervi accelerantes were always sectioned before stimulation. The transmitter appeared first in the pulmonary venous blood. In its actions on the heart-lung preparation, it resembled isoprenaline and not adrenaline. Chromatographic studies using three different solvents showed that 80 to 100% of this transmitter consisted of a catechol amine which had R(F) values which were identical with those of isoprenaline. Pharmacological studies failed to distinguish between the actions of this amine and those of isoprenaline, but clearly differentiated between those of the pulmonary amine, adrenaline, and noradrenaline.

Animals↗

Isolated rabbit atria with sympathetic nerve supply.

The atria of the rabbit heart have been isolated together with their sympathetic nerves, so that the latter could be stimulated and the effect on the rate and amplitude of beating could be measured. Cocaine and phenoxybenzamine increased the response to stimulation. When the preparation was from rabbits previously given reserpine, stimulation of the sympathetic nerves caused inhibition. This inhibition was increased by eserine and abolished by atropine.

Animals↗

The antagonism of cocaine to the action of choline 2,6-xylyl ether bromide at sympathetic nerve endings.

Choline 2,6-xylyl ether bromide (TM10) prevents contraction of the nictitating membrane and of the spleen in response to sympathetic nerve stimulation. It was confirmed that this effect was due to prevention of the release of noradrenaline ("sympathin") at the nerve endings. The intravenous injection of cocaine before choline xylyl ether blocked the action of the latter drug. However, when atropine was injected before the cocaine the effects of large doses of choline xylyl ether were not completely blocked. After block had been produced by choline xylyl ether the injection of cocaine partially restored both the secretion at the sympathetic nerve endings and the responses of the organs supplied by the nerves. Phenoxybenzamine did not restore the secretion at the nerve endings after it had been inhibited by choline xylyl ether, indicating that the latter did not cause an increased uptake of sympathin by the receptors.

Animals↗

The action of substances which block sympathetic postganglionic nervous transmission.

The substances which block sympathetic postganglionic transmission, xylocholine, bretylium and guanethidine, also block neuromuscular and sympathetic ganglionic transmission. To see if these last properties were related to the sympathetic blocking property, phenyltrimethylammonium, which blocks the neuromuscular junction (Riker, 1953), was used. It blocked the inhibition of the rabbit ileum produced by stimulating the periarterial nerves in the mesentery, though with higher concentrations the effect of stimulation was initially increased. The action was not modified by the presence of hyoscine. The blocking action was exerted on the response to stimulation of the highest frequency first, and on the response to stimulation of the lowest frequency last. This relation of block to stimulus frequency is similar to that at the neuromuscular junction when tubocurarine is used. Nine compounds have now been shown to block responses to sympathetic postganglionic stimulation, and seven of these are onium compounds. They are, however, mon-onium compounds, and not bis-onium compounds like hexamethonium and decamethonium, so that they can probably enter the postganglionic fibre, which bis-onium compounds (having a charged group at each end of the molecule) may not be able to do. Since these mon-onium compounds have some blocking action at neuromuscular junctions and at sympathetic ganglia, their block of postganglionic transmission may be essentially similar to that by hexamethonium at ganglia and to that by decamethonium at neuromuscular junctions. It is known that acetylcholine releases noradrenaline from sympathetic postganglionic terminations, and xylocholine and bretylium block this release in the vessels of the rabbit ear and in the rabbit isolated atria.

Acetylcholine↗

THE RELEASE OF ACETYLCHOLINE BY SYMPATHETIC NERVE STIMULATION AT DIFFERENT FREQUENCIES.

Supramaximal stimulation of the periarterial nerves in the mesentery to the rabbit isolated ileum causes inhibition which is increased when hyoscine is added to the bath. This increase is, however, usually seen only when the stimulus frequency is low, and the addition of hyoscine usually makes no difference when the frequency is 10 shocks/sec or more. The observations suggest that, at low frequency, stimulation releases both acetylcholine and noradrenaline, but that at higher frequencies only noradrenaline is released. Similar observations have been made for the nictitating membrane of the cat. When the postganglionic fibres from the superior cervical ganglion were stimulated supramaximally, the contractions of the membrane increased in size as the frequency rose. In the presence of hyoscine the contractions were smaller, the greatest difference being for the lowest stimulus frequency, the difference diminishing as the frequency rose. These observations are consistent with the view that sympathetic cholinergic fibres in many situations release acetylcholine to act directly only at low frequencies, and that at higher frequencies the acetylcholine is almost entirely used to release noradrenaline.

Acetylcholine↗

COMPARISON OF THE EFFECTS OF BRETYLIUM, GUANETHIDINE AND BETHANIDINE ON SMOOTH MUSCLE RESPONSES TO DIFFERENT RATES OF SYMPATHETIC NERVE STIMULATION.

The relative effects of bretylium, guanethidine and bethanidine on smooth muscle responses to different rates of sympathetic nerve stimulation have been compared. The responses studied were vasoconstriction in the femoral vascular bed and contraction of the spleen in anaesthetized cats, vasoconstriction in perfused ears of rabbits and inhibition of pendular movements in rabbit isolated ileum preparations. Except in the isolated ileum, the action of bretylium on curves relating the frequency of nerve stimulation and the effect on response was different from that of guanethidine. Whereas bretylium caused relatively greater inhibition of responses to high stimulus frequencies and depressed the slopes of the curves, guanethidine preferentially suppressed responses to low stimulus frequencies and caused roughly parallel shifts of the curves. In each situation tested bethanidine was the most potent of the three blocking agents and in general its effect on frequency/response curves was intermediate between those of bretylium and guanethidine.

Animals↗

EFFECTS OF AMPHETAMINE ON THE RESPONSES OF THE GUINEA-PIG ISOLATED VAS DEFERENS PREPARATION TO HYPOGASTRIC NERVE STIMULATION.

In concentrations from 1 to 100 mug/ml., amphetamine potentiated responses of the isolated vas deferens preparation of the guinea-pig stimulated via the hypogastric nerve at rates of from 5 to 40 shocks/sec. Potentiation was more pronounced with low than with high stimulus frequencies. A concentration of 500 mug/ml. of amphetamine had a blocking action which was more pronounced at high than at low stimulus frequencies. This effect contrasted with the ganglionic blocking action of hexamethonium which had a greater effect at low than at high stimulus frequencies.

Amphetamine↗

Effects of adrenomedullin and calcitonin gene-related peptide on airway and pulmonary vascular smooth muscle in guinea-pigs.

1. The airway and pulmonary vascular effects of adrenomedullin were studied in the guinea-pig isolated trachea, main bronchi and pulmonary artery in vitro and compared to the effects of calcitonin gene-related peptide (CGRP). 2. In tracheal rings, CGRP (1 nM to 1 microM) potentiated the cholinergic contractions induced by electrical field stimulation (EFS) at 5 Hz in a concentration-dependent manner. At a concentration of 1 microM, CGRP slightly decreased the responses to log EFS frequency, producing 50% of the maximum contraction from a control value of 0.77 +/- 0.10 Hz to 0.54 +/- 0.05 Hz without a significant effect on the concentration-response curves to acetylcholine (ACh). In contrast, adrenomedullin (1 nM to 1 microM) did not alter either EFS-induced cholinergic or ACh-induced contractions. 3. In bronchial strips, CGRP (1 nM to 1 microM) slightly reduced both the non-adrenergic non-cholinergic (NANC) contraction induced by EFS at 10 Hz and the substance P (1 microM)-induced contraction in a concentration-dependent manner, whereas adrenomedullin (1 nM to 1 microM) was without effect. 4. Neither CGRP (1 microM) nor adrenomedullin (1 microM) altered NANC relaxation induced by EFS at 5 Hz in tracheal rings precontracted with histamine (10 microM). 5. Adrenomedullin (1 nM to 1 microM) and CGRP (1 nM to 1 microM) induced a concentration-dependent relaxation of the histamine (10 microM)- and prostaglandin F2 alpha (10 microM)-precontracted pulmonary arterial rings with intact endothelium with a similar potency. 6. Neither removal of the endothelium nor NG-nitro-L-arginine methyl ester (100 microM) altered the vasorelaxant effects of adrenomedullin (1 nM to 1 microM) and CGRP (1 nM to 1 microM). 7. The putative CGRP receptor antagonist, CGRP8-37 (1 microM to 10 microM) concentration-dependently attenuated the CGRP (3 nM to 30 nM)-induced vasorelaxant actions, whereas it had no effect on the relaxation of vessel rings induced by adrenomedullin (3 nM to 30 nM). 8. These results suggest that adrenomedullin is a potent vasodilator of the pulmonary artery without any bronchomotor effect in the guinea-pig lung, and that the vasorelaxant actions of adrenomedullin are not mediated via the activation of CGRP1 receptors.

Adrenomedullin↗

Potential use of beta(3)-adrenoceptor antagonists in heart failure therapy.

Recently, a functional, negatively inotropic, beta(3)-adrenoceptor was characterized in the human heart. Several studies now suggest that this receptor might play an important role in the pathophysiology of heart failure, by counterbalancing the effects of a beta(1)- and beta(2)-stimulation. Therefore, this review summarizes the rationale and effects of beta-adrenergic blockade in chronic heart failure and specifically addresses the question of the potential use of beta(3)-adrenoceptor antagonists in the treatment of heart failure and other pathophysiological conditions associated with a decreased cardiac contractility.

Adrenergic beta-3 Receptor Antagonists↗

Pathogenesis of herpes simplex virus type 2 experimental genital infection in pregnant mice.

The progression of herpes simplex-2 genital infection in pregnant mice was studied by detection of viral antigens using immunoperoxidase in tissue sections, electron microscopy and virus isolation. The majority of mice (66.66%) died at 8-9 days post-inoculation. Abortions were observed in 69.23% of the infected mice along with impairment of labor and delivery. Herpes antigens were detected in most of the autonomic nerves of the uterus, including those surrounding small arterioles in the myometrium and the Auerbach and Meissner plexa of the large bowel, but not in the abortions or placentas. The infection of uterine autonomic fibers and myometrial cells could explain the delivery impairment and could have provoked a decrease in blood flow leading to abortions.

Abortion, Missed↗

Heart rate variability during high-intensity field exercise in female distance runners.

The purposes of this study were to demonstrate the transition of heart rate variability (HRV) during trials in the field and to examine the relationship between peak frequency of high-frequency band (HF) and stride frequency. Ten healthy long-distance college female runners (age 19-21 years) performed a 3000 m realistic time trial. The time-series power spectrum analysis by maximum entropy method was used to evaluate cardiac autonomic nervous activity during the race. Cross-correlation coefficients were calculated to estimate the degree of linear co-ordination between the central peak frequency of HF and stride frequency. Just after starting, the decrease in HF (0.15-1.00 Hz) and a transient increase of low-frequency band (LF)/HF were found. After that, the HF remained at a low level and LF/HF decreased sharply. These findings suggested that the parasympathetic activity was suppressed and sympathetic activity increased just after starting, and the sympathetic activity reached the saturated level according to continuation of high-intensity exercise. In spite of the significant decrease of HRV during trials, peak frequency of HF could be differentiated clearly. The cross-correlation coefficient of peak frequency of HF and stride frequency was from 0.703 to 0.868. This finding indicated that exercise rhythm reflected HRV during high-intensity running in the field.

Adolescent↗

The use of heart rate variability measures to assess autonomic control during exercise.

Heart rate variability (HRV) is a non-invasive indicator of cardiac autonomic modulation at rest. During rhythmic exercise, global HRV decreases as a function of exercise intensity. Measures reflecting sympathovagal interactions at rest do not behave as expected during exercise. This makes interpretation of HRV measures difficult, especially at higher exercise intensities. This problem is further confounded by the occurrence of non-neural oscillations in the high-frequency band due to increased respiratory effort. Alternative data treatments, such as coarse graining spectral analysis (CGSA), have demonstrated expected changes in autonomic function during exercise with some success. The separation of harmonic from fractal and/or chaotic components of HRV and study of the latter during exercise have provided further insight into cardioregulatory control. However, more research is needed. Some cross-sectional differences between HRV in athletes and controls during exercise are evident and data suggest longitudinal changes may be possible. Standard spectral HRV analysis should not be applied to exercise conditions. The use of CGSA and non-linear analyses show much promise in this area. Until further validation of these measures is carried out and clarification of the physiological meaning of such measures occurs, HRV data regarding altered autonomic control during exercise should be treated with caution.

Autonomic Pathways↗