Prospective observational study on the clinical behaviour of dental implants in patients with haemophilia. Preliminary results.

Haemophilia is a recessive congenital hereditary haemorrhagic disorder characterised by the decrease in, or absence of, the functional activity of factor VIII (Haemophilia A) or factor IX (Haemophilia B). The haematological medical treatment for these patients is systemic replacement therapy with factor VIII or factor IX concentrates. Dental implants are considered the gold standard for the replacement of missing teeth. There is no evidence or safe protocol for their use in patients with haemophilia. The objective of this study was to evaluate the clinical osseointegration and the incidence of postoperative bleeding in patients with haemophilia. The patients included in this study were over 18 years old with a diagnosis of haemophilia. A surgical implant protocol was implemented, supported by systemic and local haemostatic measures. Age, type of haemophilia, pre- and post-factor levels, gingival index, surgical duration, oedema, and pain were recorded for each case. In the event of haemorrhage, the bleeding index was determined. At four months, the success of the implant was evaluated using the absence of pain, suppuration, and clinical mobility as parameters. Fifteen surgeries were performed and 21 implants were placed in 10 patients. All the implants were successful in terms of the evaluated parameters. Among the 15 surgeries performed, bleeding was detected in three. The preliminary results found in this study seem to establish that the proposed surgical implant and haemostatic protocol is a predictable treatment for the placement of dental implants in patients with haemophilia.

Anosmia in the first coronavirus disease 2019 outbreak in Europe: functional recovery after eight months.

BACKGROUND: Severe acute respiratory syndrome coronavirus-2 is a formidable virus, responsible for coronavirus disease 2019 and endowed with marked neurotropism. The damage it causes to the nervous system is manifold. The main neurological manifestation is anosmia. Olfactory damage is often transient, but there are no data reflecting an observational period of several months. OBJECTIVE: This study evaluated the trend of anosmia in patients affected by coronavirus disease 2019 in the eight months following diagnosis. METHODS: Fifty-five subjects who presented with symptoms suggestive of coronavirus disease 2019 and who developed anosmia, between the end of February and the beginning of March 2020, were investigated. The patients were interviewed after eight months to determine functional recovery and assess the degree of recovery. RESULTS: Ninety-one per cent of the population reported olfactory recovery and, of these, 53 per cent had total recovery after eight months. Females and younger age groups seem slightly advantaged in functional recovery. The elderly population appears to have excellent prospects for full functional recovery. CONCLUSION: Anosmia represents a frequent neurological manifestation during coronavirus disease 2019. Fortunately, it is transient in most cases, and only a small percentage of patients affected by it report long-term functional deficits.

Ultrasound-guided percutaneous irreversible electroporation of hepatic and abdominal tumors not eligible for surgery or thermal ablation: a western report on safety and efficacy.

PURPOSE: To report our first results on sixteen patients affected by liver and abdominal malignant tumors, unfit for surgery or thermal ablation, treated with US-guided percutaneous irreversible electroporation (IRE). METHODS: From June 2014 to December 2016, all patients meeting the inclusion criteria (malignant hepatic or abdominal tumors not eligible for resection or thermal ablation) and not meeting the exclusion criteria (heart arrhythmia, pro-hemorrhagic hematological alterations, tumor size > 8 cm, presence of a biliary metallic stent) referred to our institutions were prospectively enrolled to undergo percutaneous US-guided irreversible electroporation (IRE). Sixteen patients (age range 59-68 years, mean 63; 7 females) with 18 tumors (diameter range 1.3-7.5 cm) fulfilled the inclusion criteria and were included in the study. Data concerning efficacy (tested by a 1-week CEUS and a 4-week enhanced CT and/or enhanced MRI) and safety were recorded during a 18-month follow up. RESULTS: All patients completed a 35-50-min procedure without complications. One patient with 6 cm Klatskin tumor also underwent a second session for 1 month. A 1-week CEUS and a 4-week e-CT and/or e-MRI arterial phase contrast enhancement analysis showed an overall reduction of arterial flow with confirmation of unenhanced lesions for seven nodules. After 1-18 months of follow up, no major complications were recorded and no tumor-related death occurred. The lesions of two patients disappeared 3 and 6 months after their treatment, respectively. CONCLUSIONS: IRE is a promising ablation modality in the treatment of malignant hepatic and abdominal tumors unsuitable for resection or thermal ablation.

Ectopic teeth in the maxillary sinus: A case report and literature review.

Ectopic eruption of teeth is a rare phenomenon although there have been reports of teeth in the nasal septum, mandibular condyle, and maxillary sinus. This impaction can present itself in a variety of ways such as chronic or recurrent sinusitis, sepsis, and facial numbness and can also be asymptomatic. The aim of this study was to describe, by means of research literature and by a case report, the characteristics and occurrence of ectopic eruption in the maxillary sinus. We have analyzed and compared clinical cases of ectopic teeth in the maxillary sinus with a search on PubMed utilizing keywords such as "ectopic," "teeth," "sinus," "maxillary," and Boolean operators "or" and "and" up until 2016. Fifty-one cases were found, of which 53% were female. The age ranged between 3 and 72 years, with an average age of 28.36 years. The higher prevalence of ectopic teeth is the 3rd molars. Ten of these teeth are associated with a dentigerous cyst, 1 by an osteoma, and 2 by soft tissue. Standard treatment for an ectopic tooth is extraction, but for other patients, treatment of choice in asymptomatic ectopic tooth cases is continued observation. Ectopic teeth tend to form a cyst or tumor if not managed.

A different perspective on sofosbuvir-ledipasvir treatment of patients with HCV genotype 1b cirrhosis: The ital-c network study.

The effectiveness of a 12-week course of sofosbuvir-ledipasvir in treatment-experienced HCV genotype 1b-infected patients with cirrhosis is still under debate. Our primary endpoint was to compare the sustained virological response at post-treatment week 12 (SVR12) of sofosbuvir-ledipasvir in combination with ribavirin for 12 weeks, and sofosbuvir-ledipasvir alone for 24 weeks. This was a prospective observational study that enrolled 424 (195 naive, 229 experienced; 164 treated for 12 weeks with Ribavirin and 260 with sofosbuvir-ledipasvir alone for 24 weeks) consecutive HCV genotype 1b-infected patients with cirrhosis. The SVR12 rates were 93.9% and 99.2% in patients treated for 12 and 24 weeks, respectively (P = .002). The baseline characteristics of patients treated for 12 weeks were significantly different from those treated for 24 weeks as regards their younger age (P = .002), prevalence of Child-Pugh class A (P = .002), lower MELD scores (P = .001) and smaller number of nonresponders (P = .04). The shorter treatment was significantly associated with a lower SVR12 in univariate and multivariate analyses (P = .007 and P = .008, respectively). The SVR rate was unaffected by age, gender, BMI, Child-Pugh class, MELD score or previous antiviral treatment. Patients receiving ribavirin experienced more episodes of ascites and headache but less recurrence of hepatocellular carcinoma (HCC), and were prescribed more diuretics and cardiopulmonary drugs. No patient discontinued treatment. The therapeutic regimen of sofosbuvir-ledipasvir plus ribavirin administered for 12 weeks was less effective than sofosbuvir-ledipasvir alone given for 24 weeks. At odds with European guidelines, the recommended 12-week treatment with sofosbuvir-ledipasvir alone might be suboptimal for this setting of patients.

HCV genotype 1 subtypes (1a and 1b): similarities and differences in clinical features and therapeutic outcome.

AIM: To evaluate similarities and differences in HCV-1 subtypes 1a and 1b in the presenting clinical features and the response to peg-interferon and ribavirin (Peg/RIBA). PATIENTS AND METHODS: A total of 1,233 naïve patients with HCV genotype-1 infection, 159 (13%) with subtype 1a and 1,074 (87%) with subtype 1b were treated with Peg-IFN/RIBA at 12 Italian centers. Covariates included in the logistic model were age, gender, BMI, serum alanine aminotransferase, serum gamma-glutamiltranspeptidase (γGT), platelets counts, liver fibrosis, the occurrence of type 2 diabetes, baseline viremia, and IL28B genotype. RESULTS: At multivariate analysis, baseline characteristics differentiating patients with HCV-1a versus HCV-1b were young age, male gender, no F4 fibrosis, and no diabetes. SVR was achieved by 37% of patients with subtype 1b and 45% of those with subtype 1a, a nonsignificant difference of 8% (p = 0.069). In patients with subtype 1a, predictors of SVR were IL28B CC (OR 5.78, CI 1.98-16.83), RVR (OR 4.18, CI 1.66-10.55), female gender (OR 2.83, CI 1.83-6.78), and HCVRNA (OR 0.55, CI 0.32-0.96). In patients with subtype 1b, the ranking of predictors was levels RVR (OR 6.49, CI 4.32-9.73), IL28B CC (OR 3.32, CI 2.15-4.58), γGT (OR 1.59, CI 0.14-2.22), HCVRNA (OR 0.61, CI 0.47-0.79), and age (OR 0.01, CI 0.02-0.42). CONCLUSION: In Italy HCV-1 subtype 1a prevails in young male patients with less advanced liver damage, findings that imply a more recent spreading of the infection with this viral strain. The two HCV-1 subtypes appear equally responsive to Peg-IFN/RIBA, with IL28B genotyping and monitoring of RVR mostly influencing the therapeutic response.

Volatile compounds secreted by Brindley's glands of adult Triatoma infestans: identification and biological activity of previously unidentified compounds.

Volatile emissions of adult male Triatoma infestans were collected on non-polar SPME fibers and analyzed by gas chromatography linked to a mass spectrometer. A complex mixture of 16 short-chain esters and acids were identified. The composition of short-chain aliphatic acids (ethanoic to nonanoic acids) was similar to previously reported results. The most abundant aliphatic acid was 2-methylpropanoic acid, constituting 18% of the total volatile content. Also abundant were the esters 2- and 3-methylbutyl 2-methylpropanoate, which constituted 30% and 22%, respectively, of the total volatile content. A similar pattern of compounds was observed in the volatiles secreted by dissected male Brindley's glands; however, in this case, 2- and 3-methylbutan-1-ol were detected which were not found in live insect volatile emissions. Large variability in volatile composition was also observed among the glands excised from different insects. Electroantennographic (EAG) evaluation of the components of Brindley's gland showed significant responses for 2- and 3-methylbutyl 2-methylpropanoate compared to controls. The mixture of volatiles secreted by excised Brindley's glands and the isolated 2- and 3-methylbutyl 2-methylpropanoate had repellent effects on both male and female T. infestans, possibly associated with a defensive strategy.

Functional outcomes in patients reconstructed with flaps following surgery for hypopharyngeal cancer.

Following oncologic surgery for advanced cancer of the hypopharynx, primary closure of the defect of the upper aerodigestive tract is difficult to achieve. Usually locoregional or free flaps are used, the choice being determined by the extent of the surgical defect, the expertise of the surgeons and the general condition of the patient. Aim of the present study was to evaluate the functional recovery of patients who underwent surgical reconstruction, following hypopharyngeal cancer resection, with pedicled or free flaps. A retrospective analysis was conducted examining hospital records of the patients submitted to surgical treatment for hypopharyngeal cancer and reconstruction with pedicled or free flaps in the period between January 1995 and July 2004. Free flaps showed less severe complications, shorter hospital stay, less time to resume oral feeding compared with pedicled flaps. For this reason, we consider free flaps the gold standard for hypopharyngeal reconstruction, while pedicled flaps as the pectoralis major or other locoregional flaps should be used in those cases in which free flap reconstruction is not feasible or contraindicated.

[Decisional algorithm in extended neoplasms of the hypopharynx and the cervical esophagus]. / L'algoritmo decisionale nelle neoplasie estese dell'ipofaringe ed esofago cervicale.

Hypopharynx reconstruction must deal with restoration of not a simple tubed conduit but a complex arrangement of constrictive and propulsive forces with fine sensory circuits. The chosen surgical approach should guarantee both complete removal of tumor and re-establishement of the two primary functions of the district: first swallowing and then phonation. We retrospectively reviewed data of 67 patients who had undergone oncologic reconstruction of hypopharynx with either pedicled or free flaps at the ENT Department of IRCCS Policlinico S Matteo, University of Pavia, between November 1994 and July 2004. Type and extension of the defect following cancer removal guided the selection of reconstructive procedure. Partial defects, with more than 50% mucosa spared, in absence of chance of being closed primarly, were covered with radial forearm free flaps as first choice; pedicled flaps such as pectoralis major and SCM rotational flaps were used instead if free flaps contraindicated by general and/or local conditions. With circumferential defects reconstruction was accomplished by means of jejunum free flap, as first choice. Adverse local abdominal conditions mandated the alternative use of either tubulized or tunnelized fasciocutaneous free flaps, such as radial forearm and lateral thigh. When free flaps use contraindicated, or in case of salvage surgery after flap loss, pectoralis major and latissimus dorsi pedicled flap were chosen. Both reconstructions with free and pedicled flaps were successful in an high percentage of cases (>85%). Analysis of incidence and causes of flap failure are reported in this work. In the free flaps group of patients a lower rate of complications were registered, allowing a faster patient discharge from hospital (36% versus 81.3%). An oral swallowing function was gained in 92% of free flaps and 62.5% of pedicled flaps. Excellent and exclusive oral nutrition (free diet), was obtained in 54% of free flaps and 25% of pedicled flaps. None of patients undergone laryngectomy coupled in both groups with pharyngectomy achieved an intelligible esophageal speech. Only patients in the free flaps group benefitted from voice prosthesis implant: in fact this procedure was avoided in pedicled flaps due to the excessive tissue bulk. In conclusion, the data collected suggest that free flaps rapresent the first choice for both partial and total oncologic hypopharyngeal reconstruction, while pedicled flaps should be taken into account when free ones contraindicated by general or vascular conditions.

[Reconstruction options after extensive ablation of the mouth]. / Opzioni ricostruttive dopo ampie demolizioni del cavo orale.

Surgical treatment of the advanced tumors of the oral cavity determines challenging anatomical and functional defects of the involved districts. The aim of our study was to supply reconstructive guidelines for the surgical treatment of the tumors of the oral cavity. Indications and conclusions were drawn following a retrospective review of data of 76 patients undergone oral and oromandibular reconstruction with either pedicled (17) or free flaps (59). The analysis included for both groups the registration of type of selected flap, success rate, early and late complications rate, functional results at 6 months to 1 year, ie oral feeding recovery and quality of oral feeding. The results obtained point out that the anatomical and functional complexity of the oral cavity needs a wide armamentarium of surgical techniques and skills at prompt disposal of the reconstructive surgeon. Free flaps should be kept in mind as the first choice for middle-sized to wide defects. An extended range of options in this group are available, and the selection should be based on type and extent of the defect following surgical oncologic ablation, but also on the surgeon experience itself. Pedicled flaps should be alternatively selected on case of general, vascular or local contraindications to major free flaps surgery, for the higher complications rate and worse functional outcomes to be faced.

Serological study of a population of alpine chamois (Rupicapra r rupicapra) affected by an outbreak of respiratory disease.

A serological survey of respiratory virus infections was carried out from 1998 to 2001 in Lecco province, Italy, as part of a health monitoring programme in a population of alpine chamois, many of which died of pneumonia in autumn and winter 2000 to 2001; 194 carcases of all age classes were found over a short period and in a small area. Eighteen of them, which were examined postmortem, consistently showed signs of severe fibrinous lobar pneumonia or catarrhal bronchopneumonia. Samples of serum from 145 chamois collected from hunted animals and carcases were tested by a virus neutralisation test against bovine respiratory syncytial virus (BRSV), bovine viral diarrhoea virus, bovine herpesvirus type 1 and parainfluenzavirus type 3. Positive results were detected only for BRSV. The area was divided into two subunits on the basis of the distribution of deaths; in the areas where fatalities were observed there was a significant increase of BRSV titres at the beginning of the outbreak. Furthermore, during the 2000 and 2001 hunting seasons antibody titres to BRSV were significantly higher in the areas where mortality occurred. The roe deer living in the same area were not affected by pneumonia and had a low prevalence of titres to BRSV which did not vary during the period of the study.

Non-enveloped HCV core protein as constitutive antigen of cold-precipitable immune complexes in type II mixed cryoglobulinaemia.

Hepatitis C virus (HCV) infection has been detected in a large proportion of patients with mixed cryoglobulinaemia (MC). Circulating 'free' non-enveloped HCV core protein has been demonstrated in HCV-infected patients, and this suggests its possible involvement in the formation of cryoprecipitable immune complexes (ICs). Thirty-two anti-HCV, HCV RNA-positive patients with type II MC were evaluated. Non-enveloped HCV core protein, HCV RNA sequences, total IgM, rheumatoid factor (RF) activity, IgG and IgG subclasses, C3 and C4 fractions, C1q protein and C1q binding activity were assessed in both cryoprecipitates and supernatants. Non-enveloped HCV core protein was demonstrated in 30 of 32 (93.7%) type II MC patients. After separation of cold-precipitable material, the protein was removed completely from supernatant in 12 patients (40%), whereas it was enriched in the cryoprecipitates of the remaining 18. In addition, HCV RNA and IgM molecules with RF activity were concentrated selectively in the cryoprecipitates. Differential precipitation was found for both total IgG and IgG subclasses, as they were less represented in the cryoglobulins and no selective enrichment was noted. Immunological characterization of HCV core protein-containing cryoprecipitating ICs after chromatographic fractionation showed that the IgM monoclonal component had RF activity, whereas anti-HCV core reactivity was confined to the IgG fraction. C1q enrichment in addition to high avidity of ICs for C1q binding in the cryoprecipitates suggest that complement activation may occur through the C1q protein pathway. The present data demonstrate that non-enveloped HCV core protein is a constitutive component of cryoprecipitable ICs in type II MC patients.

Substance P-immunoreactive boutons closely appose inspiratory protruder hypoglossal motoneurons in the cat.

In anesthetized cats, we recorded intracellularly from 26 hypoglossal motoneurons which were antidromically activated following electrical stimulation of either the medial or lateral branches of the hypoglossal nerve. Twenty-one of these neurons were protruder motoneurons 6 of which had inspiratory activity. Three of the protruder motoneurons with inspiratory activity were filled with Neurobiotin and found to be closely apposed to substance P-like immunoreactive nerve terminals.

Characterization of reactive oxygen species induced effects on human spermatozoa movement and energy metabolism.

Reactive oxygen species (ROS) inhibit sperm movement and have been implicated in male infertility. In this study, we determined the effects of specific ROS produced by activated leukocytes on human spermatozoa and investigated their metabolic site of action. We used chemiluminescence and electron paramagnetic resonance (EPR) to characterize the ROS generated by both blood and seminal leukocytes. We also determined the effects of these ROS on sperm energy metabolism using biochemical analyses and flow cytometry. Both blood and seminal leukocytes produced the same characteristic ROS which were determined to be hydrogen peroxide (H2O2) and superoxide radicals (O2*-). EPR using the spin trapping technique indicated that superoxide radical-dependent hydroxyl radicals (HO.) were also generated. ROS generated by PMA-stimulated blood leukocytes (2-5 x 10(6)/ml) caused inhibition of sperm movement in 2 h (p < .01). Using the hypoxanthine/ xanthine oxidase (0.5 U/ml) system to generate ROS, we determined that spermatozoa ATP levels, after ROS treatment, were reduced approximately eight-fold in 30 min (0.10 x 10(10) moles/10(6) sperm cells) compared to control (0.84 X 10(-10) moles/10(6) sperm cells) (p < .01). Sperm ATP reduction paralleled the inhibition of sperm forward progression. Neither superoxide dismutase (100 U/ml) nor dimethyl sulfoxide (100 mM) reversed these effects; however, protection was observed with catalase (4 X 10(3) U/ml). Flow cytometric analyses of sperm treated with various doses of H2O2 (0.3 mM-20.0 mM) showed a dose-dependent decrease in sperm mitochondrial membrane potential (MMP); however, at low concentrations of H2O2, sperm MMP was not significantly inhibited. Also, sperm MMP uncoupling with CCClP had no effect on either sperm ATP levels or forward progression. These results indicate that H2O2 is the toxic ROS produced by activated leukocytes causing the inhibition of both sperm movement and ATP production. O2*- and HO. do not play a significant role in these processes. Low concentrations of H2O2 causing complete inhibition of sperm movement and ATP levels inhibit sperm energy metabolism at a site independent of mitochondrial oxidative phosphorylation.

Development and in vitro evaluation of buccoadhesive tablets using a new model substrate for bioadhesion measures: the eggshell membrane.

For oral delivery of antimicrobial and anti-inflammatory drug, mucoadhesive tablets based on gelatin/hydroxypropylcellulose (HPC), gelatin/hydroxypropylmethyl-cellulose (HPMC), and gelatin/sodium carboxymethylcellulose (NaCMC) at different ratios were prepared by direct compression of the mixed powders. Metronidazole and benzydamine were used as model drugs. The in vitro bioadhesive properties, evaluated by a commercial tensile tester, were significantly affected by the model substrate employed, that is, a polypropylene (PP) membrane or a biological membrane (eggshell membrane). The use of the biological substrate seemed to supply more reliable data. All studied formulations showed an erosion-diffusion mechanism of release, anomalous or non-Fickian release, in agreement with the behavior of the swellable systems.

Synthesis and NMR characterization of a novel class of thienomorphinans.

[formula: see text] Synthesis of four novel thieno derivatives 4-7 featuring the codeine skeletal backbone is reported. Characterization by 1H and 13C NMR is also discussed, along with binding profile for opioid receptors.

Control of negative inotropic vagal preganglionic neurons in the dog: synaptic interactions with substance P afferent terminals in the nucleus ambiguus?

Previous research from this laboratory has shown that substance P-immunoreactive (SP) terminals synapse upon negative chronotropic vagal preganglionic neurons (VPNs), but not upon negative dromotropic VPNs, of the ventrolateral nucleus ambiguus (NA-VL). Moreover, SP agonists injected into NA-VL cause bradycardia without decreasing AV conduction. In the current study, we have: (1) defined the electron microscopic characteristics of the SP neurons of NA-VL in dog; and (2) tested the hypothesis that SP nerve terminals synapse upon negative inotropic VPNs of NA-VL, retrogradely labeled from the cranial medial ventricular (CMV) ganglion. Numerous SP terminals and a few SP neurons were observed in the vicinity of retrogradely labeled neurons. SP terminals were observed forming synapses with unlabeled dendrites and with SP dendrites, but never with the retrogradely labeled neurons. Together, these results and earlier findings suggest that SP agonists may be able to induce bradycardia without decreasing AV conduction or ventricular contractility.

Hepatitis C virus infection involves CD34(+) hematopoietic progenitor cells in hepatitis C virus chronic carriers.

Although hepatitis C virus (HCV) mainly affects hepatocytes, infection is widespread and involves immunologically privileged sites. Whether lymphoid cells represent further targets of early HCV infection, or whether other cells in the hematopoietic microenvironment may serve as a potential virus reservoir, is still unclear. We studied whether pluripotent hematopoietic CD34(+) cells support productive HCV infection and can be used to establish an in vitro infection system for HCV. Six patients were selected as part of a cohort of HCV chronic carriers who developed a neoplastic disease. Reverse transcriptase-polymerase chain reaction (RT-PCR) and branched DNA signal amplification assays were used to detect and quantitate HCV RNA in extracted nucleic acids from purified bone marrow and peripheral blood CD34(+) cells. Direct in situ RT-PCR, flow cytometry analysis, and immunocytochemistry were applied to demonstrate specific viral genomic sequences and structural and nonstructural virus-related proteins in intact cells. Results indicated that both positive and negative HCV RNA strands and viral proteins were present in CD34(+) cells from all HCV-positive patients and in none of the controls. Additional experiments showed that a complete viral cycle took place in CD34(+) cells in vitro. Spontaneous increases in viral titers indicated that virions were produced by infected hematopoietic progenitor cells. To further define the cellular tropism, we attempted to infect CD34(+) cells in vitro. We were unable to demonstrate viral uptake by cells. These findings suggest that HCV replication can occur in the early differentiation stages of hematopoietic progenitor cells, and that they may be an important source of virus production.

Neural control of left ventricular contractility in the dog heart: synaptic interactions of negative inotropic vagal preganglionic neurons in the nucleus ambiguus with tyrosine hydroxylase immunoreactive terminals.

Recent physiological evidence indicates that vagal postganglionic control of left ventricular contractility is mediated by neurons found in a ventricular epicardial fat pad ganglion. In the dog this region has been referred to as the cranial medial ventricular (CMV) ganglion [J.L. Ardell, Structure and function of mammalian intrinsic cardiac neurons, in: J.A. Armour, J.L. Ardell (Eds.). Neurocardiology, Oxford Univ. Press, New York, 1994, pp. 95-114; B.X. Yuan, J.L. Ardell, D.A. Hopkins, A.M. Losier, J.A. Armour, Gross and microscopic anatomy of the canine intrinsic cardiac nervous system, Anat. Rec., 239 (1994) 75-87]. Since activation of the vagal neuronal input to the CMV ganglion reduces left ventricular contractility without influencing cardiac rate or AV conduction, this ganglion contains a functionally selective pool of negative inotropic parasympathetic postganglionic neurons. In the present report we have defined the light microscopic distribution of preganglionic negative inotropic neurons in the CNS which are retrogradely labeled from the CMV ganglion. Some tissues were also processed for the simultaneous immunocytochemical visualization of tyrosine hydroxylase (TH: a marker for catecholaminergic neurons) and examined with both light microscopic and electron microscopic methods. Histochemically visualized neurons were observed in a long slender column in the ventrolateral nucleus ambiguus (NA-VL). The greatest number of retrogradely labeled neurons were observed just rostral to the level of the area postrema. TH perikarya and dendrites were commonly observed interspersed with vagal motoneurons in the NA-VL. TH nerve terminals formed axo-dendritic synapses upon negative inotropic vagal motoneurons, however the origin of these terminals remains to be determined. We conclude that synaptic interactions exist which would permit the parasympathetic preganglionic vagal control of left ventricular contractility to be modulated monosynaptically by catecholaminergic afferents to the NA-VL.