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Bladder contractility is regulated by intrinsic myogenic mechanisms interacting with autonomic nerves. In this study, we have investigated the physiological role of spontaneous release of acetylcholine in guinea pig and rat bladders.Conventional isotonic or pressure transducers were used to record contractile activity of guinea pig and rat bladders.Hyoscine (3 micromol x L(-1)), but not tetrodotoxin (TTX, 1 micromol x L(-1)), reduced basal tension, distension-evoked contractile activity and physostigmine (1 micromol x L(-1))-evoked contractions of the whole guinea pig bladder and muscle strips in vitro. omega-Conotoxin GVIA (0.3 micromol x L(-1)) did not affect physostigmine-induced contractions when given either alone or in combination with omega-agatoxin IVA (0.1 micromol x L(-1)) and SNX 482 (0.3 micromol x L(-1)). After 5 days in organotypic culture, when extrinsic nerves had significantly degenerated, the ability of physostigmine to induce contractions was reduced in the dorso-medial strips, but not in lateral strips (which have around 15 times more intramural neurones). Most muscle strips from adult rats lacked intramural neurones. After 5 days in culture, physostigmine-induced or electrical field stimulation-induced contractions of the rat bladder strips were greatly reduced. In anaesthetized rats, topical application of physostigmine (5-500 nmol) on the bladder produced a TTX-resistant tonic contraction that was abolished by atropine (4.4 micromol x kg(-1) i.v.).The data indicate that there is spontaneous TTX-resistant release of acetylcholine from autonomic cholinergic extrinsic and intrinsic nerves, which significantly affects bladder contractility. This release is resistant to blockade of N, P/Q and R type Ca(2+) channels.

In the rat and guinea-pig isolated ureter electrical field stimulation of intrinsic nerves (10 Hz for 10 s) produced transient inhibition of evoked (20 mM KCl or 0.1–1 μM neurokinin A) rhtyhmic contractions by releasing transmitter(s) from peripheral endings of capsaicin-sensitive primary afferents. The C-terminal fragments of human calcitonin gene-related peptide (8–37) blocked the inhibitory effect of electrical field stimulation as well as that produced by exogenous calcitonin gene-related peptide, while leaving unaffected the inhibitory response to isoprenaline. Human calcitonin gene-related peptide (8–37) was devoid of any inhibitory activity of its own but enhanced the amplitude and frequency of KCl-evokded rhythmic contractions in the rat ureter, probably by antagonizing the inhibitory effect of endogenous calcitonin gene-related peptide released by KCl. Omega conotoxin fraction GVIA, a peptide which possesses a potent blocking activity of N-type voltage-sensitive calcium channels, prevented the inhibitory response to electrical stimulation in the guinea-pig ureter, while leaving the response unaffected in the rat ureter. Conotoxin had no effect toward the inhibition produced by exogenous calcitonin gene-related peptide indicating its prejunctional site of action, demonstrated previously in the guinea-pig ureter [Maggi et al. (1990) Neurosci. Lett.114, 203–206]. Dermorphin, an amphibian peptide with potent agonist activity on mu-type opioid receptors, inhibited the response to electrical stimulation in the guinea-pig ureter but had no effect in the rat ureter. Neuropeptide Y and galanin, at a concentration (0.1 μM) shown previously to inhibit sensory neuropeptide release in other guinea-pig tissue, had no effect in either the rat or guinea-pig ureter. These findings provide direct pharmacological evidence for a role of calcitonin gene-related peptide as an inhibitory transmitter in the ureter of both rats and guinea-pigs. A species difference emerges in the mechanisms of release of calcitonin gene-related peptide, conotoxin-sensitive calcium channels being important for electrically-evoked calcitonin gene-related peptide release in the guinea-pig but not in the rat ureter. Furthermore, organ-related differences in mechanisms of prejunctional modulation of sensory neuropeptide release may exist in guinea-pigs.

1. The effect of montelukast or MEN91507, selective leucotriene CysLT1 receptor antagonists, on antigen-induced airway inflammation and bronchoconstriction were compared in anaesthetized guinea-pigs. 2. In sensitized animals, ovalbumin (0.3 mg kg(-1), i.v.)-induced microvascular leakage in trachea, intrapulmonary airways, total lung (parenchyma and intrapulmonary airways) and urinary bladder was reduced by MEN91507 (0.01-1 micromol kg(-1), i.v.), whereas montelukast (0.01-1 micromol kg(-1), i.v.) antagonized the effect of the antigen only in the lung and urinary bladder. 3. Ovalbumin (1 mg kg(-1), i.v.)-induced bronchoconstriction was dose dependently antagonized by MEN91507 (10-30 micromol kg(-1), i.v.), whereas the effect of montelukast (0.1-30 micromol kg(-1), i.v.) was marginal (15-30% inhibition). Neither MEN91507 nor montelukast (30 micromol kg(-1), i.v.) affected the bronchoconstrictor response induced by acetylcholine (0.3 micromol kg(-1), i.v.) in sensitized animals. 4. It is concluded that montelukast and MEN91507 display a differential activity against the effect of endogenous leucotrienes, despite the fact that both compounds show a similar antagonist profile against exogenous leucotrienes acting through CysLT1 receptors.

The aim was to characterize the recently discovered non-peptide antagonist MEN16132 at the mouse B2 receptor, relative to other antagonists.[3H]-BK binding experiments used mouse lung and ileum tissue membranes and antagonist potency was measured in the isolated ileum contractility assay.Two BK binding sites resulted from saturation and homologous competition experiments. A role for the B1 receptor was excluded because of the poor affinity of B1 receptor ligands (pIC505). MEN16132, and the other reference antagonists, inhibited only one portion of BK specific binding, and the rank order of potency was (pIC50): Icatibant (lung 10.7; ileum 10.2)=MEN11270 (lung 10.4; ileum 9.9)=MEN16132 (lung 10.5; ileum 9.9).LF16-0687 (lung 8.9; ileum 8.8)FR173657 (lung 8.6; ileum 8.2). BK homologous curves performed with lung membranes after treatment with the antagonist MEN16132 or Icatibant (10 nM) displayed only the low affinity site. The functional antagonism by MEN16132 (pA2 9.4) and Icatibant (pA2 9.1), towards BK (control EC50 6.1 nM) induced ileum contractions, was concentration-dependent and surmountable, but the Schild plot slope was less than unity.In mouse tissue, radiolabelled BK recognizes two binding sites and B2 receptor antagonists can compete only for the higher affinity one. The pharmacological profile of the novel non-peptide antagonist MEN16132 indicates that it exhibits subnanomolar affinity and potency for the mouse B2 receptor and is suitable for further characterization in in vivo pathophysiological models.

A family with autosomal dominant inheritance of idiopathic strio-pallidodentate calcifications and late onset of extrapyramidal symptoms is reported. Clinical features consisted of parkinsonism in one member and postural tremor in two. Depression and dysarthria were present in all cases. All symptomatic members showed a peculiar biochemical abnormality consisting of reduced 25-OH vitamin D3 with normal levels of 1,25(OH)2 vitamin D3, suggesting an inborn error of Vitamin D metabolism. The biochemical, clinical, and genetic pattern of this family distinguishes this syndrome from the larger group of secondary familial basal ganglia calcifications.

Tachykinin NK2 receptor antagonists could reduce motility and symptoms during gastrointestinal diseases characterized by local inflammation such as diarrhea or colitis; however, how these conditions change pharmacodynamic and pharmacokinetic characteristics of NK2 receptor antagonists is unknown. We investigated the effect of the peptide NK2 receptor antagonist nepadutant on spontaneous intestinal motility or [betaAla8]NKA(4-10)-induced colonic and bladder contractions in rodent models of intestinal inflammation (enteritis induced by castor oil and rectocolitis induced by local instillation of acetic acid in rats, enteritis induced by bacterial toxins in mice). In the castor oil model, the oral/intraduodenal bioavailability of nepadutant was also determined. The intrarectal (i.r.) administration of nepadutant (100 nmol/kg) did not reduce [betaAla8]NKA(4-10) (10 nmol/kg i.v.)-induced colonic and bladder contractions in normal animals, but the same dose of nepadutant produced an inhibitory effect in the two organs following rectocolitis; in contrast, nepadutant is equieffective by the intravenous route in normal and colitic animals. In this model, nepadutant (100 nmol/kg i.r. or i.v.) decreased spontaneous colonic hypermotility, without affecting motility in controls. The intraduodenal administration of nepadutant (30 nmol/kg), which was ineffective on [betaAla8]NKA(4-10) (10 nmol/kg i.v.)-induced colonic and bladder contractions in control animals, abolished bladder contractions in castor oil-pretreated animals. In this latter group, the oral and intraduodenal bioavailability of nepadutant showed a 7- to 9-fold increase with respect to controls. Oral administration of nepadutant, in nanomolar or subnanomolar dosage, reduced diarrhea induced by bacterial toxins in mice. It is concluded that intestinal inflammation increases nepadutant absorption in the intestine, enhancing its activity. These results suggest that a drug with a limited oral bioavailability could be used for treating gastrointestinal diseases associated with a local inflammation.

In the gastrointestinal tract, tachykinin NK(2) receptors are localized both on smooth muscle and nerve fibres. NK(2) receptor antagonists reduce exaggerated intestinal motility in various diarrhoea models but the site of action contributing to this effect is unknown. In this study we investigated the effects of atropine (1.4 micromol kg(-1), i.v.), hexamethonium (13.5 micromol kg(-1), i.v.), and nepadutant (0.1 micromol kg(-1), i.v.), a selective tachykinin NK(2) receptor antagonist, on distension (0.5 and 1 ml)-, or irritation (acetic acid, 0.5 ml of 7.5% v v(-1))-induced motility in the rat distal colon in vivo. The effects of atropine, hexamethonium or N(omega)-nitro-L-argininemethylester (L-NAME, 1.85 micromol kg(-1), i.v.) on [betaAla(8)]NKA(4-10) (10 nmol kg(-1), i.v.)-induced colonic contractions were also investigated. When the colonic balloon was filled with a subthreshold volume (0.5 ml), the intraluminal instillation of acetic acid triggered a high-amplitude phasic colonic motility which was partially reduced by nepadutant and suppressed by either hexamethonium or atropine. Filling of the balloon with 1 ml evoked reflex (hexamethonium-sensitive), atropine-sensitive phasic colonic motility: nepadutant had no significant effect on the distension-evoked motility. Neither hexamethonium nor atropine significantly reduced [betaAla(8)]NKA(4-10)-induced colonic contractions, whereas nepadutant suppressed them. Following L-NAME pretreatment, [betaAla(8)]NKA(4-10)-induced colonic contractions were inhibited by both atropine and hexamethonium. In hexamethonium-pretreated animals, an atropine-sensitive component of [betaAla(8)]NKA(4-10)-induced colonic contractions was also evident. These results indicate that the application of irritants onto the colonic mucosa induces the release of endogenous tachykinins which enhance excitatory cholinergic mechanisms through the stimulation of NK(2) receptors.

To report our experience using the transbrachial approach, which is easily accepted by the patient, in the treatment of varicocele.Between January 1986 and December 1998, 1490 patients with clinical or subclinical varicocele, but with seminal fluid alterations, underwent spermatic phlebography using the transbrachial approach. Since 1991 the procedure has also been adopted at the Unit of Pediatric Surgery of our hospital, which proposes it as a first choice treatment in adolescents with varicocele. The procedure consists in accessing the basilic vein at the elbow level percutaneously and using a hydrophile guidewire and multipurpose angiographic catheter to reach and catheterise the spermatic vein responsible for the varicocele. During the first years, we used sclerotherapy alone; subsequently, if the varicocele recurred or if the reflux was refractory to sclerotherapy or if the veins were large we adopted vein embolisation. Follow-up was one year and consisted of testicular ultrasound, Doppler flowmetry and/or color Doppler ultrasound at one, six and twelve months after the procedure. Patients were considered restored if they were free of symptoms, showed no venous reflux and/or had normal seminal fluid parameters and improved if they were free of symptoms but still presented venous reflux. Varicocele was considered persistent if the procedure failed to produce any beneficial effects, and recurrent if, although absent at the first follow up, it reappeared after the fifth month.We found 1296 (86.9%) cases of left varicocele, 25 of right varicocele and 169 (11.3%) of bilateral varicocele. In all cases, the symptoms disappeared after the percutaneous procedure. Duration of radioscopy was reduced to 3.5'; the procedure lasted 90' for the monolateral varicoceles and 120' for the bilateral forms. 313 diagnostic procedures were performed (20.7%). The procedure could not be completed in 104 patients (6.8%) due to basilic vein spasms, difficulties encountered in catheterizing the spermatic vein and, particularly in pediatric patients, anatomic variations. A total of 1195 (79.2%) procedures were completed: sclerotherapy alone in 642 patients and sclerotherapy followed by scleroembolisation in 527. Sclerotherapy alone was sufficient to restore 524 patients (86.6%), while 384 (78.5%) required scleroembolization. A small number of patients underwent scleroembolization alone, which brings the success rate for the two procedures to 82% and 84%, respectively. No serious side-effects were noted.The transbrachial approach in spermatic phlebography has proved to be a safe and effective technique for the treatment of both monolateral and bilateral varicocele. Furthermore, the procedure is well accepted by patients and can be performed in a day-care setting. In some cases, we only obtained partial results because of the large caliber of the spermatic vein; in other cases, we were unable to complete the procedure due to anatomic variations or to the spasm of the basilic vein.The safety and effectiveness of this procedure make it a valid alternative to traditional surgery, that should be considered as a possible first-choice treatment for varicocele in adolescents.

Summary Purpose To evaluate ankle areflexia in Holmes-Adie syndrome (HAS). Patients and methods Hoffmann (H) and Tendon (T) soleus reflexes, tonic vibration reflex (TVR), and polysynaptic extension reflex of soleus muscle (PERS) were evaluated in eight patients with idiopathic HAS. Motor (MNCV) and sensory (SNCV) nerve conduction velocities, compound motor-action potential (CMAP), and sensory action potential (SAP) were also determined in upper and lower limbs. Results Soleus T reflex was obtained in one out of eight patients, and H-reflex was found in none of the patients. TVR was recorded in four out of eight patients, and PERS in all of the patients. MNCV, SNCV, CMAP and SAP showed normal values in all patients. In six out of the eight patients a late response following the tibial nerve stimulation showed constant latency, amplitude and morphology, with no recovery cycle or vibration inhibition. Conclusion In this study, the neurophysiological spinal reflex circuitry evaluations support the view that HAS ankles areflexia is due to a selective impairment of monosynaptic connections of la afferents. A normal nuclear excitability is suggested by polysynaptic activation of the soleus motor nucleus.

1. We have investigated the effect of nociceptin on the micturition reflex evoked by distension or topical application of capsaicin on the urinary bladder of urethane-anaesthetized rats. 2. Nociceptin produced a dose-dependent (3-100 nmol kg(-1) i.v.) transient suppression of the distension-evoked micturition reflex: its effect was not modified by guanethidine (68 micromol kg(-1) s.c.) nor by bilateral cervical vagotomy, alone or in combination, and by naloxone (1.2 micromol kg(-1) i.v.). 3. Nociceptin (100 nmol/kg i.v.) slightly (about 30%) inhibited the contractions of the rat bladder produced by pre- or postganglionic electrical stimulation of the pelvic nerve. 4. Nociceptin almost totally abolished the reflex component of the response to topical capsaicin (1 microg in 50 microl). 5. In the rat isolated bladder, submaximal contractions produced by electrical field stimulation were slightly reduced (25+/-4% inhibition) by 1 microM nociceptin. Nociceptin did not affect the contraction of the rat bladder induced by acetylcholine (10 microM) or ATP (1 mM). 6. These findings indicate that nociceptin exerts a naloxone-resistant suppression of the volume-evoked micturition reflex which involves inhibition of transmitter release from postganglionic bladder nerves. An inhibitory effect on bladder afferent nerves is also suggested.

1. The effects of the tachykinin NK2 receptor antagonist MEN 11420 (100 nmol kg(-1), i.v.) and isoprenaline (400 nmol kg(-1), i.v.) were compared in a model of distension-induced bladder activity in isovolumetric conditions. MEN 11420 induced a relaxation of the basal tone of the urinary bladder that was dependent on the volume of the viscus: the effect was absent at low volumes (0.2 and 0.5 ml) and it was maximal at high volumes of distension (1 and 2 ml), approaching about 60% of the isoprenaline-induced relaxation. The relaxant effect of isoprenaline was always evident at all volumes of distension. 2. Tetrodotoxin (1-100 microM, intravesically applied) abolished distension-evoked micturition contractions, but did not prevent the relaxant effect of MEN 11420- or isoprenaline on the bladder tone. 3. The cyclo-oxygenase inhibitor S-ketoprofen (0.5 micromol kg(-1), i.v.) produced a marked decrease of the bladder tone and a concomitant reduction of bladder motility at 1 ml volume of distension. At 2 ml of distension, S-ketoprofen still decreased the minimal pressure but had no significant effect on other parameters of vesical motility. In S-ketoprofen-pretreated rats, the relaxant effect of MEN 11420 was significant at 2 but not at 1 ml of distension, and that of isoprenaline was reduced by 50% at both 1 and 2 ml. 4. Ruthenium red (10 micromol kg(-1), i.v.) had no effect at a low volume of distension (0.2 ml) or at highest volume (2 ml) but decreased the basal tone and the frequency of bladder contractions at 1 ml of distension. In ruthenium red-pretreated rats, MEN 11420 failed to decrease bladder tone at 1 ml, whereas at 2 ml the effect of MEN 11420 was not different from that observed in controls (43 vs 60% of isoprenaline-induced relaxation, respectively). 5. At both 1 and 2 ml of distension, capsaicin pretreatment (164 micromol kg(-1), s.c. 5 days before) reduced the frequency of micturition contractions but had no effect on the bladder tone. Capsaicin pretreatment prevented the relaxant effect of MEN 11420 on the bladder tone both at 1 and at 2 ml of distension. 6. It is concluded that the release of tachykinins from capsaicin-sensitive afferent nerves induced by bladder distension is resistant to tetrodotoxin and to prostaglandin synthesis inhibition. Tachykinins modulate the vesical tone by acting through NK2 receptors.

1. The role of endogenous tachykinins on guinea-pig colonic propulsion was investigated by using potent and selective tachykinin NK1 and NK2 receptor antagonists. Colonic propulsion and contractions were determined by means of a balloon-catheter device, inserted into the rectum of guanethidine (68 micromol kg(-1), s.c., 18 and 2 h before)-pretreated, urethane-anaesthetized guinea-pigs. Propulsion of the device (dynamic model) was determined by measuring the length of the catheter expelled during 60 min filling of the balloon (flow rate 5 microl min(-1)). 2. In control conditions the tachykinin NK1 receptor antagonist SR 140333 (1 micromol kg(-1), i.v.) did not affect either colonic propulsion or the amplitude of contractions. The tachykinin NK2 receptor antagonists MEN 10627 and MEN 11420 (1 micromol kg(-1), i.v.) increased colonic propulsion at 10 min (+120% and 150%, respectively) but at 60 min the effect was significant only for MEN 10627 (+84%). SR 48968 (1 micromol kg(-1), i.v.) did not significantly enhance the colonic propulsion. None of these tachykinin NK2 receptor antagonists modified the amplitude of colonic contractions. In contrast, both atropine (6 micromol kg(-1), i.v., plus infusion of 1.8 micromol h(-1)) and hexamethonium (55 micromol kg(-1), i.v., plus infusion of 17 micromol h(-1)) abolished propulsion (81% and 87% inhibition, respectively) and decreased the amplitude of contractions (68% inhibition for either treatment). 3. In atropine-treated animals (6 micromol kg(-1), i.v., plus infusion of 1.8 micromol h(-1)), apamin (30 nmol kg(-1), i.v.) restored colonic propulsion (+416%) and increased the amplitude of contractions (+367% as compared to atropine alone). Hexamethonium (55 micromol kg(-1), i.v., plus infusion of 17 micromol h(-1)) abolished the apamin-induced, atropine-resistant colonic propulsion (97% inhibition) and reduced the amplitude of the atropine-resistant contractions (52% inhibition). 4. The apamin-induced, atropine-resistant colonic propulsion was inhibited by SR 140333 (-69% at 1 micromol kg(-1)), SR 48968 (-78% at 1 micromol kg(-1)), MEN 11420 (-59% at 1 micromol kg(-1)) and MEN 10627 (-50% at 1 micromol kg(-1)), although the latter effect was not statistically significant. The combined administration of SR 140,333 and MEN 10,627 (1 micromol kg(-1) for each antagonist) almost completely abolished colonic propulsion (90% inhibition). The amplitude of colonic contractions was also reduced by SR 140333 (-42%), SR 48968 (-29%), MEN 11420 (-45%) but not by MEN 10627 (-16%). The combined administration of SR 140333 and MEN 10,627 reduced the amplitude of contractions by 47%. SR 140603 (1 micromol kg(-1), i.v.), the less potent enantiomer of SR 140333, was inactive. 5. In control animals, apamin (30 nmol kg(-1), i.v.) enhanced colonic propulsion (+84%) and increased the amplitude of contractions (+68%), as compared to the vehicle. Hexamethonium (55 micromol kg(-1), i.v. plus infusion of 17 micromol h(-1)) inhibited propulsion (86% inhibition) and decreased the amplitude of contractions (49% inhibition). SR 140333, SR 48968, MEN 11420, MEN 10627, or the coadministration of SR 140333 and MEN 10627 had no effect. 6. In a separate series of experiments, the mean amplitude of colonic contractions was also recorded under isovolumetric conditions through the balloon-catheter device kept in place at 75 mm from the anal sphincter (static model). In control conditions, neither SR 140333 nor MEN 11420 modified the amplitude of contractions. In atropine-pretreated guinea-pigs, SR 140333 and MEN 11420 (0.1-1 micromol kg(-1)) dose-dependently decreased the amplitude of contractions. In apamin- and atropine-pretreated animals, only the highest (1 micromol kg(-1)) dose of SR 140333 or MEN 11420 significantly decreased the amplitude of contractions. The inhibitory potency of atropine (0.3-1 micromol kg(-1)) was similar in apamin-pretreated animals and in controls. 7. It was concluded that, in anaesthetized guinea-pigs, endogenous tachykinins, acting through both NK(1) and NK(2) receptors, act as non-cholinergic excitatory neurotransmitters in promoting an apamin-evoked reflex propulsive activity of the distal colon.

International audience; In this paper, modeling of MIMO nonlinear dynamic systems using a Takagi-Sugeno structure is discussed. A new formulation which leads to another interpretation of Takagi-Sugeno model and an improvement of the model parameter estimation is proposed. From inputs and outputs data, an identification algorithm of this model is presented. The parameter estimation is based on computation of sensitivity functions of the model with respect to parameters.

1. The aim of this study was a pharmacological characterization of the multiple NANC inhibitory transmission systems producing relaxation of the circular muscle of guinea-pig proximal colon. In the presence of atropine (1 microM), guanethidine (3 microM) and of the tachykinin NK1 and NK2 receptor antagonists, SR 140333 (0.3 microM) and MEN 10627 (1 microM), respectively, electrical field stimulation (EFS) produced a frequency-dependent (0.1-3 Hz) relaxation. During a cumulative frequency-response curve, the maximal relaxant effect was produced at 3 Hz and approached the maximal relaxation to 1 microM isoprenaline. In the presence of both apamin (0.3 microM) and L-nitroarginine (L-NOARG, 100 microM), EFS failed to evoke relaxation up to 1 Hz; at 1-10 Hz, a slowly developing relaxation ensured which approached 50% of the Emax to isoprenaline. The EFS-evoked NANC relaxation, either in the presence or absence of apamin and L-NOARG, was unaffected by in vitro capsaicin pretreatment (10 microM for 15 min). 2. Three protocols of EFS were developed for further pharmacological analysis: (a) EFS at 1 Hz for 5 s in the presence of L-NOARG, producing a transient fast apamin-sensitive relaxation; (b) EFS at 1 Hz for 5 s in the presence of apamin, producing a transient fast L-NOARG-sensitive relaxation; and (c) EFS at 10 Hz for 5 s in the presence of both apamin and L-NOARG, producing a transient but slowly developing and more sustained relaxation. 3. The neutral endopeptidase inhibitor, thiorphan (1-10 microM), enhanced and prolonged the apamin- and L-NOARG-resistant NANC relaxation produced by EFS at 10 Hz, without affecting that evoked at 1 Hz in the presence of apamin or L-NOARG. The angiotensin converting enzyme inhibitor, captopril (1-10 microM) was without effect. 4. The cAMP analogue inhibitor of protein kinase A, Rp-cAMPs (100-300 microM) significantly reduced and shortened the NANC relaxation produced by 10 Hz EFS in the presence of L-NOARG without affecting that produced by 1 Hz EFS in the presence of apamin or L-NOARG. 5. The inhibitor of sarcoplasmic reticulum Ca-ATPase, cyclopiazonic acid (CPA, 3-10 microM for 60 min) abolished the 1 Hz EFS-induced relaxation in the presence of L-NOARG, and greatly inhibited that produced by 10 Hz EFS in the presence of both apamin and L-NOARG. The relaxation produced by 1 Hz EFS in the presence of apamin was inhibited by about 32% at 10 microM only. 6. Nifedipine (1 microM) did not affect the EFS-induced NANC relaxations. In the presence of nifedipine, tetraethylammonium (TEA, 1 mM) enhanced the 1 Hz EFS-induced relaxation in the presence of L-NOARG (158% of control) and that produced by 10 Hz EFS in the presence of apamin and L-NOARG (215% of control) while that evoked by 1 Hz EFS in the presence of apamin was slightly affected (109% of control). 7. In the presence of atropine, guanethidine, SR 140333 and MEN 10627, bath application of human vasoactive intestinal polypeptide (VIP, 0.1 nM-10 nM) produced a concentration-dependent, slowly developing relaxation of colonic strips. The relaxation to VIP was unaffected by apamin (0.3 microM), L-NOARG (100 microM), nifedipine (1 microM) or nifedipine plus TEA (1 mM); it was inhibited by CPA (10 microM) and Rp-cAMPs (100 microM) and was potentiated by thiorphan (10 microM). 8. The putative VIP receptor antagonist, VIP(10-28) (10 microM) did not affect the VIP-induced relaxation nor the NANC relaxation to 10 Hz EFS in the presence of apamin and L-NOARG. 9. The present findings provide evidence that three distinct NANC inhibitory mechanisms mediate relaxation of the circular muscle of the guinea-pig proximal colon. The first system provides a fast relaxation in response to low frequency of stimulation and may involve the action of a transmitter(s) (possibly ATP) which mobilizes intracellular Ca2+ from sarcoplasmic reticulum leading to the activation of apamin-sensitive K+ channels. The second system likewise provides a fast relaxation of the colon in

We have determined the ability of the novel nonpeptide tachykinin (TK) NK3 receptor antagonist, SR 142801, [(S)-(N)-(1-(3-(1-benzoyl-3-(3,4-dichlorophenyl) piperidin-3-yl)propyl)-4-phenylpiperidin-4-yl)-N-methylaceta mide] in inhibiting the nitric oxide (NO)-independent prejunctional inhibition of cholinergic twitches and the NO-dependent relaxation produced by the NK3 receptor selective agonist, senktide, in the circular muscle of the guinea-pig proximal colon. Under moderate load (10 mN) and isometric recording of mechanical activity, single pulse electrical field stimulation (EFS) produced atropine- and tetrodotoxin-sensitive twitch contractions of mucosa-free circular muscle strips from the guinea-pig proximal colon. In the presence of NK1 and NK2 receptor antagonists (SR 140333 0.01 microM and GR 94800 0.1 microM, respectively) the NK3 receptor selective agonist, senktide (EC50 33 pM) and the NK3 receptor preferring natural TK, neurokinin B (NKB, EC50 13 pM) produced a concentration-dependent slowly developing inhibition of cholinergic twitches. Senktide (1 nM) did not affect the contractile response to acetylcholine (1 microM) indicating that depression of evoked twitches occurs prejunctionally. The inhibitory effect of senktide was unaffected when evoked in the presence of the cyclooxygenase inhibitor (S)-ketoprofen (10 microM), guanethidine (10 microM), naloxone (0.3 microM), the GABAB receptor antagonist 2-hydroxysaclofen (10 microM) or the combined application of the adenosine A1 and A2 receptor antagonists, 8-cyclopentyl-1,3-dipropylxanthine (10 microM) and 3,7-dimethyl-1-propargylxanthine (30 microM) respectively. In the presence of NK1 and NK2 receptor antagonists, the NO-synthase inhibitor L-nitroarginine (L-NOARG 30-100 microM) did not affect twitch inhibition induced by senktide (EC50 33 pM). The response to NKB (EC50 95 pM) was slightly reduced by L-NOARG, yet the bulk of the inhibitory effect of both agonists on cholinergic twitches was substantially independent of NO generation. SR 142801 (0.1-0.3 microM) produced a moderate rightward shift of the concentration-response curve to senktide without depression of the Emax to the agonist, yielding an apparent pKB value of 7.65. Under low resting tone (3 mN) and isotonic recording of mechanical activity, mucosa-free circular muscle strips from the guinea-pig proximal colon gained a high intrinsic tone suitable for testing the response to relaxant agents. In the presence of atropine (1 microM), guanethidine (3 microM), SR 140333 (0.01 microM) and GR 94800 (0.1 microM), senktide (EC50 50 pM) produced a concentration-dependent relaxation of the strips, which was blocked by L-NOARG. SR 142801 (0.01-0.1 microM) produced a large rightward shift of the L-NOARG-sensitive concentration-response curve to senktide yielding an apparent pKB value of 8.62. Under isometric recording condition, SR 142801 (0.1 microM) did not affect twitch inhibition produced by 3 nM clonidine. Under isotonic recording condition, SR 142801 did not affect the L-NOARG-sensitive relaxation produced by EFS. The present results indicate that NK3 receptor stimulation produces a NO-dependent relaxation of the guinea-pig colon and a substantially NO-independent prejunctional inhibition of cholinergic twitches. The variable affinities of SR 142801 in antagonizing various senktide-induced neuromodulatory effects in the guinea-pig intestine suggest a possible intraspecies heterogeneity of NK3 receptors in the enteric nervous system.

The tachykinin (NK2) receptor-mediating contraction of the human isolated bladder to NKA was investigated by studying the affinities of eight structurally different receptor-selective antagonists (linear peptides, cyclic peptides and pseudopeptides, nonpeptide NK2 receptor antagonists). The affinities of the antagonists were compared to those measured for the same ligands at the NK2 receptors previously characterized in the rabbit pulmonary artery and hamster trachea. In the presence of a cocktail of peptidase inhibitors (bestatin captopril and thiorphan, 1 microM each) no significant correlation was found between pA2 values measured in the human bladder vs. those measured in the other two NK2 receptor-bearing preparation. In the presence of the aminopeptidase inhibitor amastatin, however, pA2 values of linear antagonists bearing an N-terminal Asp residue MEN 10,207 and MEN 10,376 were significantly enhanced and these pA2 values were used for analysis; a significant correlation was found between pA2 values measured in the human urinary bladder and rabbit pulmonary artery. The pseudopeptide analog of NKA (4-10), MDL 28,564 which also bears a N-terminal Asp residue behaved as an agonist and its action was enhanced by amastatin. We conclude that the NK2 receptor-mediating contraction of the human urinary bladder smooth muscle is similar to that previously characterized in the rabbit pulmonary artery (NK2A receptor category); in the human bladder smooth muscle an amastatin-sensitive peptidase (possibly aminopeptidase A) limits biological activity of linear peptide derivatives of NKA bearing a N-terminal Asp residue.

Recently published literature on biliary extracorporeal shock wave lithotripsy (ESWL) has shown that high-energy ESWL utilizing high kV is more effective than the low-energy ESWL and low kV used previously. Prior studies have not reported injury to the gallbladder or adjacent liver following ESWL. Our study evaluated 29 patients that were treated with high kV ESWL. Magnetic resonance imaging (MRI) was used to study the gallbladder and adjacent liver for possible injury resulting from the high-energy treatment. The patients, selected using the Dornier MPL-9000 United States protocol, underwent ESWL using 18-24 kV (average 21 kV). MRI was done both pre and post-ESWL in all 29 patients. Ten patients had a second treatment to reduce fragment size and, subsequently, had an additional MRI examination. Spin echo MRI images were obtained at the level of the gallbladder fossa using a 0.5-Tesla ESATOM RM 5000 (ESAOTE Biomedica, Genva, Italy.) superconductive unit. Both T1- and T2-weighted images were obtained. In 26 patients the hepatic parenchyma was normal post-ESWL. Two patients had a hyperintense region on T1-weighted images post-ESWL that was felt to be related to pericholecystic fat. A third patient had an abnormality detected on T2-weighted images that was thought to be due to hepatic edema or microhemorrhage. No significant changes were shown by laboratory or concurrent ultrasound examinations. Repeat MRI examinations in these three patients were normal. High-energy ESWL appears as safe as low-energy ESWL in the treatment of patients with symptomatic gallstones.

Distension of a balloon placed in the proximal colon of anesthetized, guanethidine- and naloxone-pretreated guinea pigs elicited a series of long-lasting regular phasic pressure waves which were suppressed by hexamethonium. Activity evoked by a low degree of balloon distension was largely, but not completely, suppressed by atropine. Further balloon distension in atropine-treated animals enabled us to study the effect of tachykinin receptor antagonists on the atropine-resistant and hexamethonium-sensitive response to distension. The selective tachykinin receptor antagonists, (+/-)-CP 96,345 for the NK-1 receptor and L 659,877, MEN 10,376 and SR 48,968 for the NK-2 receptor, inhibited with varying potency the atropine-resistant response to distension. These antagonists also blocked the contraction of the guinea pig colon produced by the i.v. administration of selective NK-1 and NK-2 receptor agonists. In vitro experiments, using mucosa-free circular muscle strips from the guinea pig colon, proved the existence of functional NK-1 and NK-2 receptors in this tissue. We conclude that both NK-1 and NK-2 receptors participate in the atropine-resistant reflex contractions produced by localized balloon distension of the guinea pig colon in vivo.

This study investigates the role of peripheral tachykinin receptors in the initiation of reflex urinary bladder contractions in urethane-anesthetized rats. Intravenous administration of the selective tachykinin neurokinin (NK)-1 receptor agonist [Sar9]substance P (SP) sulfone (0.3-30 nmol/kg) or of the selective tachykinin NK-2 receptor agonist [beta Ala8]NK-A(4-10) (0.3-100 nmol/kg) produced dose-related bladder contractions. Among NK-3 receptor agonists, senktide (1-100 nmol/kg) was not effective; [MePhe7] NK-B (3-100 nmol/kg) induced bladder contraction, but the magnitude of the response was only 20 to 25% of that produced by NK-1 or NK-2 agonists. The NK-1 receptor antagonist GR 82,334 (0.1 mumol/kg i.v.) blocked the urinary bladder contraction induced by [Sar9]SP sulfone (1 nmol/kg i.v.), but not that induced by [beta Ala8]NK-A(4-10). On the contrary, the NK-2 receptor antagonist L 659,877 (0.1-1 mumol/kg i.v.) abolished the effect of [beta Ala8] NK-A(4-10) (1 nmol/kg i.v.), but failed to affect the response to [Sar9]SP sulfone. The combined administration of GR 82,334 (0.1 mumol/kg i.v.) and L 659,877 (1 mumol/kg i.v.) blocked the tonic bladder contraction induced by topical application of capsaicin in pelvic ganglionectomized rats (efferent response of sensory nerves), but did not affect the hexamethonium-sensitive phasic reflex bladder contractions evoked by capsaicin in sham-operated rats (chemonociceptive micturition reflex). GR 82,334 (0.1 mumol/kg i.v.) or L 659,877 (1 mumol/kg i.v.), alone or in combination, did not modify cystometric parameters of the volume-evoked micturition reflex.(ABSTRACT TRUNCATED AT 250 WORDS)

Thirty-six patients with a peripheral localized nerve lesion (18 of median nerve, 7 of ulnar nerve, 2 of radial nerve, 1 of lateral cutaneous brachii nerve, 1 of sciatic nerve, 5 of peroneal nerve and 2 of tibial nerve), were evaluated by Computed Tomography (CT). We used a high resolution scanner (Siemens Somatom CR) and we performed 2mm thickness slices. Sagittal and coronal reconstructed images were obtained too. Thirty-two out of 36 patients underwent surgery. CT scan was useful in all cases in defining the relationship between nerve lesions and surrounding tissues and in planning surgical procedures. The CT evaluation of tissues densities and characteristics allowed us to define the pathologic nature of the lesions in 10 cases.

Objective: Monitoring HIV infection in sentinel populations of sexually transmitted disease (STD) patients in several geographical areas. This paper describes the main characteristics of the study populations and compares HIV seropositivity rates within and between networks in different subgroups: homo-/bisexuals, intravenous drug users (IVDU) and non-IVDU heterosexuals. Design: HIV testing is performed with informed consent in most networks. It is mandatory for STD patients in Hungary, while the English and Welsh, Scottish and French networks use unlinked anonymous testing. Setting: Eighteen networks in 17 European countries are participating in the study. The networks usually consist of STD or dermato-venereology clinics. Patients: Patients presenting at any of the clinic sites with a new episode of one or more of a selected list of 12 STD were eligible for the study. This study recorded a total of 36827 STD episodes, registered between June 1990 and December 1991. HIV test results were known for 33004 (89.6%) of the patients. Results: HIV seropositivity rates were usually much higher for the homo-/bisexual and IVDU patients than for the non-IVDU heterosexuals. However, HIV-seropositive patients were found among non-IVDU heterosexuals in all but the Czech network. Conclusion: This Concerted Action has successfully launched an HIV sentinel surveillance programme among STD patients in 17 European countries using a standard methodology.

Results: Cartilage cultured in the presence of blood showed a decrease of proteoglycan synthesis rate of 70%, an increase of proteoglycan release of 100%, and a decrease of proteoglycan content of 15% after 16 days of culture (all p

The activity of short C-terminal fragments of human alpha calcitonin gene-related peptide (CGRP), CGRP(19-37), and CGRP(23-37), and of the N-terminally acetylated (Ac) derivative, AcCGRP(19-37), has been investigated in the guinea pig isolated left atria (electrically driven) for their ability to antagonize the positive inotropic effect of human alpha CGRP. All the peptides tested produced a rightward displacement of the curve to the agonist without depressing the maximal response: apparent pA2 values were 5.39 and 4.81 for CGRP(19-37) and CGRP(23-37), respectively, as compared to 6.81 for CGRP(8-37). AcCGRP(19-37) was a more potent antagonist than the parent peptide, with an apparent pA2 value of 6.03.

Intravenous administration of the selective 5-hydroxytryptamine (5-HT)1A receptor agonist 8-hydroxy-2-(di-N-propylaminotetralin (8-OH-DPAT) and of a low doses of buspirone elicited the supraspinal micturition reflex (SMR) in urethane-anesthetized rats when the urinary bladder was filled with just a subthreshold volume of saline (threshold conditions). The effect of i.v. 8-OH-DPAT was abolished by hexamethonium or spiroxatrine. When SMR was elicited by bladder distension (suprathreshold conditions), i.v. 8-OH-DPAT increased the frequency of bladder contractions. In threshold conditions, stimulation of SMR was also induced by i.c.v. or by i.t. administration of 8-OH-DPAT and 5-HT but not by topical application of 8-OH-DPAT onto the bladder. Guanethidine pretreatment, which produced detrusor hyperreflexia, antagonized the effect of both i.c.v. and i.t. 8-OH-DPAT. In rats treated with capsaicin as adults, the response to 8-OH-DPAT was unchanged. In rats treated with capsaicin as newborns, instead, the response to i.t. 8-OH-DPAT was abolished and that to i.c.v. 8-OH-DPAT was shifted to higher doses. Pretreatment with 5,7-dihyroxytryptamine did not affect the response to i.t. 8-OH-DPAT but shifted to higher doses the response to i.c.v. 8-OH-DPAT. Intravenous administration of spiroxatrine, methysergide, NAN-190 [1-(2-methoxyphenyl)-4-[4-(2-phtalimido)butyl] piperazine] or high doses of buspirone but not of 1-sulpiride inhibited SMR in suprathreshold conditions. The inhibitory effect of spiroxatrine, NAN-190 and buspirone was not reduced by guanethidine pretreatment. In chronically spinalized animals, i.v. 8-OH-DPAT increased the amplitude of the reflex bladder contractions induced by bladder distension.(ABSTRACT TRUNCATED AT 250 WORDS)

The accuracy of transrectal US (TRUS) and of MRI was evaluated in the preoperative staging and in local recurrences of rectal cancers. Fifty-four patients were examined: 45, with known rectal cancer, for preoperative staging, and 9 for the evaluation of local recurrences. Nineteen patients were examined with MRI in basal conditions, 21 after rectal air enema and 5 after paramagnetic contrast enema (Gd-DTPA). The following parameters were evaluated for preoperative staging: wall infiltration, invasion of perirectal fat and adjacent structures, lymph node involvement. Morphologic and signal intensity (on MRI) changes were evaluated for the diagnosis of local recurrences. TRUS provided 2 false positives. In the same patients, basal MRI results were poor, owing to difficult demonstration of the different wall layers, while in the patients studied after air enema, the lesion was hyperintense. In 20 patients with a fat-infiltrating tumor, TRUS provided 3 false negatives and 2 false positives; basal MRI yielded poor results, while air enema and paramagnetic contrast enema clearly demonstrated all fat-infiltrating lesions, with only one false positive.

The effect of intrathecal administration of the novel tachykinin NK-1 receptor antagonist GR 82,334 has been tested in three reflexes which excite urinary bladder motility. GR 82,334 at 1 but not at 0.1 nmol/rat blocked the chemonociceptive micturition reflex induced by the topical application of capsaicin (4 micrograms/50 microliters) onto the urinary bladder. At the same dose proven effective in the chemonociceptive reflex, GR 82,334 did not affect either micturition reflex induced by bladder filling or the urinary bladder contraction induced by perineal pinching. These results suggest that, in urethane-anesthetized rats, specific stimuli applied in the periphery activate NK-1 receptors at spinal cord level facilitating urinary bladder reflex contractions.

The effects of some newly developed tachykinin antagonists that are selective for the neurokinin (NK)-1 (L 668,169) or the NK-2 (MEN 10,207, L 659,877 and R 396) tachykinin receptor on the cholinergic and noncholinergic contraction and on the nonadrenergic noncholinergic relaxation produced by electrical field stimulation (50 Hz) were investigated in mucosa-free circular strips of the human ileum. The strips were contracted by substance P and neurokinin A as well as by selective NK-2-receptor ligands, [beta Ala8]neurokinin A(4-10), and MDL 28,564, the latter peptide being capable of discriminating between NK-2-receptor subtypes. The selectivity of the antagonists for NK-1 or NK-2 receptors was confirmed in pharmacological experiments using substance P, neurokinin A, and [beta Ala8]neurokinin A(4-10) as stimulants. Among the NK-2-selective antagonists, MEN 10,207 displayed the highest affinity, followed by L 659,877 and R 396. The antagonists MEN 10,207 and L 659,877 inhibited the noncholinergic contraction to electrical stimulation in a concentration-dependent manner; L 668,169 and R 396 were poorly effective. Thus the potency of antagonists toward the noncholinergic response closely paralleled their rank order of potency at NK-2 receptors. The cholinergic contraction and nonadrenergic noncholinergic relaxation were not inhibited by the antagonists. Both substance P- and neurokinin A-like immunoreactivities were detected in extracts of the human ileum, and the identity of the corresponding peptides was confirmed by reverse-phase high-performance liquid chromatography. It was concluded that in addition to NK-1 receptors, the circular muscle of the human ileum also contains NK-2 receptors. Activation of the latter is chiefly responsible for the noncholinergic contraction to nerve stimulation.

We have assessed the ability of compound 48/80, a mast cell degranulating agent, to activate the sensory and efferent function of capsaicin-sensitive primary afferents in the rat urinary bladder. Compound 48/80 produced a calcium-dependent release of calcitonin gene-related peptide-like immunoreactivity from the superfused rat urinary bladder. This effect was prevented by in vitro capsaicin desensitization, but was not affected by indomethacin, methysergide, ondansetron, chlorpheniramine or cimetidine, nor by systemic pretreatment with compound 48/80 at a dose regimen which prevented lethality produced by intravenous administration of it in anesthetized rats. Compound 48/80 also produced a contraction of the rat isolated bladder which was not reduced by methysergide, indomethacin or in vitro capsaicin desensitization. In vivo, topical application of compound 48/80 on the serosal surface of the rat urinary bladder activated a series of high amplitude rhythmic bladder contractions which were hexamethonium-sensitive (micturition reflex). This effect was prevented by systemic capsaicin desensitization while it was unchanged by chlorpheniramine, methysergide, indomethacin or ondansetron. Administered intravenously, compound 48/80 produced a plasma protein extravasation (Evans blue leakage technique) in the rat urinary bladder which was abolished by systemic capsaicin pretreatment or chlorpheniramine while it was unaffected by methysergide or indomethacin. The present findings provide direct neurochemical evidence that compound 48/80 activates the peripheral endings of capsaicin-sensitive primary afferent neurons, leading to a stimulation of their sensory and efferent functions in the rat urinary bladder. The possibility of a direct action of compound 48/80 in producing excitation of capsaicin-sensitive sensory nerves should be considered.

Magnetic resonance imaging during arterial portography (MRAP) was performed by the authors in a selected group of 12 patients with hepatic lesions. A low dose of gadopentetate dimeglumine (4 mL of a 0.5-mol/L solution, corresponding to a dose of 0.05-0.07 mmol/kg) was injected into the superior mesenteric artery during acquisition of breath-holding gradient-echo or rapid acquisition spin-echo images. Images were always acquired during the first passage of gadopentetate dimeglumine through the liver parenchyma. An increase in liver-to-lesion contrast was obtained with MRAP imaging (contrast-to-noise ratio = 8 +/- 1.8 vs 19 +/- 2.7). Signal intensity enhancement of the liver was high (signal-to-noise ratio = 9.48 +/- 2.42), while the lesion presented no significant enhancement (signal-to-noise ratio = 0.55 +/- 0.22). Lobar portal vein thrombosis was detected in one patient owing to lack of enhancement of the left lobe of the liver. No side effects related to administration of iodinated and paramagnetic contrast agents were observed. This new technique provides specific enhancement of liver parenchyma with improved liver-to-lesion contrast.

We have studied the effects of two newly developed tachykinin antagonists, MEN 10,207 and MEN 10,376, which are highly selective for NK-2 tachykinin receptors on tachykinin-induced contraction in the rat urinary bladder and guinea pig airways in vivo. MEN 10,207 exhibited antagonism only at doses which produced agonist effects. By contrast, MEN 10,376 was devoid of significant agonist activity at i.v. doses (1-3 mumol/kg) which selectively antagonized the effects of an NK-2 agonist [beta-Ala8]-neurokinin A(4-10) (bladder contraction in rats, bronchoconstriction in guinea pigs) without affecting the response to an NK-1 agonist [Sar9]-substance P sulfone (hypotension, salivation and bladder contraction in rats, bronchoconstriction in guinea pigs). At these NK-2-selective blocking doses, MEN 10,376: 1) did not affect urodynamic parameters at cystometry in normal rats but reduced amplitude of micturition contractions following induction of chemical (intravesical xylene) cystitis and 2) reduced by a maximum of 50% the noncholinergic bronchoconstrictor response to vagal nerve stimulation. These findings provide the first evidence for involvement of NK-2 receptors in physiological responses in the urinary and respiratory tracts.

Magnetic Resonance imaging of the upper abdomen was performed on more than 300 patients. The aim of the study was to determine the influence of spin-echo parameters on intrinsic image contrast. Different TR (ranging 260 to 2000 ms) and TE (ranging 20 to 120 ms) values were employed in two patients with a hepatic metastases and in a healthy volunteer with a hepatic cyst. The highest liver-to-lesion contrast was observed when the shortest TR and TE values (260 and 20 ms, respectively) were used, while the lesions appeared isointense with the surrounding parenchyma with TR 800 ms. In T2-weighted images TR 2000 ms allowed the complete recovery of longitudinal magnetization, giving a contrast relative only to the T2 of the lesion.

The case of a young woman suffering from a rare cerebrovascular disease associated with livedo reticularis (Sneddon syndrome) is reported. Hemicranic attacks were the first symptom detected. The patient had a progressive clinical course of neurologic symptoms. Cerebral CT scan, NMR and cerebral arteriography revealed a progressive cerebral multifarctual feature involving middle-size arteries.

Intravenous administration of cholecystokinin octapeptide (CCK-8) to urethane-anesthetized rats produced both inhibitory and excitatory effects on intestinal motility. The inhibitory effect, evident as a transient relaxation or inhibition of distension-induced reflex contractions, was abolished by adrenoreceptor blockade, guanethidine pretreatment or removal of the celiac ganglion complex, but was hexamethonium-and atropine-insensitive. The excitatory action of CCK-8 was atropine- and hexamethonium-sensitive, while being unaffected by guanethidine pretreatment. Ligation experiments indicated that the excitatory effect of CCK-8 originates from a stimulant action on structures in the upper duodenum/pyloric sphincter from which a propagated contraction travels to the distal duodenum. We conclude that i.v. CCK-8 inhibits small intestinal motility by directly activating sympathetic neurons in the celiac ganglion and initiates a propagated form of intestinal motility by stimulating neural elements in the upper part of the small intestine.

Twenty-five patients with bronchogenic carcinoma were prospectively studied by both CT and MR during 10 days preceding thoracotomy. MR scans included contiguous axial and coronal slices. Results of CT and MR studies were compared with the surgical and pathological findings. Although no significant difference was found between the two imaging methods for the evaluation of mediastinal nodes. MR appear to be superior to CT in the aortopulmonary and subcarinal node areas.