[Unexpected pregnancy, experience of sexual violence and contraception among women who use cannabis or other illegal substance in the Great Paris Region: Data from the 2016 Health Barometer]. / Grossesses non prévues, violences sexuelles et contraception chez les femmes consommant du cannabis ou d'autres substances psychoactives illégales en Île-de-France : données du Baromètre Santé 2016.

BACKGROUND: Women who use psychoactive substances could have higher levels of unplanned pregnancy and of difficulties accessing long-term contraceptive methods than those who do not use these substances. General population data on this topic are rare, particularly in France. METHODS: This study is based on data from the French Health Survey 2016, collected from women aged 15 to 49 years and living in the Great Paris region (N=1626). Use of illegal psychoactive substances (cannabis, substances used via intranasal or intravenous administration) were evaluated over the lifecourse and, for cannabis, over the 12 months preceding the study. Unplanned pregnancies were ascertained over the preceding 5 years, emergency contraception, abortion, and the experience of sexual violence during the lifecourse. We also studied the number of sexual partners in the preceding 12 months, as well as current contraception. Data were analyzed using weighted logistic regression models, adjusted for participants' sociodemographic characteristics and tobacco use. RESULTS: Women who use illegal substances have a higher probability than non-users to experience an unplanned pregnancy in the preceding 5 years (OR associated with lifecourse cannabis use: 1.61, 95% CI 1.00-2.58), to have used emergency contraception (ORs between 2.20 to 2.90), to have had an abortion (OR associated with lifecourse cannabis use: 1.77, 95% CI 1.26-2.49), and to have experienced sexual violence (ORs between 1.87 to 3.14). They also had more sexual partners than non-users, but did not differ in terms of contraception. CONCLUSION: In the general population, there is a relationship between women's use of illegal substances and their probability of experiencing sexual violence. These results should be brought to the attention of health professionals in contact with women, to help identify those who have addictive behaviors and identify their sexual and reproductive health needs.

CYP21A2 genotypes do not predict the severity of hyperandrogenic manifestations in the nonclassical form of congenital adrenal hyperplasia.

There is a strong correlation between the severity of genotypes and 17OH-progesterone levels in patients with the nonclassical form of 21-hydroxylase deficiency (NC-CAH); however, there are few studies regarding the correlation with clinical signs. The aim of the study was to evaluate whether genotypes correlate with the severity of the hyperandrogenic phenotype. A cohort of 114 NC-CAH patients were diagnosed by stimulated-17OHP ≥10 ng/ml. CYP21A2 genotypes were divided into 2 groups according to the severity of enzymatic impairment; mild and severe. Clinical data and hormonal profiles were compared between the 2 groups. Age at onset of manifestations did not differ between children or adults carrying both mild and severe genotypes. Frequencies of precocious pubarche and hirsutism, with or without menstrual abnormalities, were similar between the 2 groups. There were no differences in basal testosterone levels of adult symptomatic females carrying both genotypes, but there were differences between adult females with (92.9±49.5 ng/dl) and without hirsutism (43.8±38 ng/dl) (p=0.0002). Similar frequencies of both genotypes were observed in asymptomatic females and in those with clitoromegaly. Nonclassical genotypes do not predict the severity of phenotype. Asymptomatic and virilized females carrying the same genotype suggest that there is a modulatory effect of genes involved in the androgen pathway on the phenotype.

Extensive Mycobacterium tuberculosis circulation in a highly endemic prison and the need for urgent environmental interventions.

Aimed at assessing the circulation of Mycobacterium tuberculosis in a highly endemic prison, this 13-month prospective study was performed on strains isolated from tuberculosis (TB) cases detected passively and actively. We used X-ray screening of newly admitted inmates and mass screening at the beginning of the study and again 1 year later. Of the 94 strains genotyped by restriction fragment-length polymorphism, 79 (84·0%) belonged to one of the 12 identified clusters (2-21 strains each), including two main clusters (18 and 21 cases, respectively). A history of TB treatment was reported in 22/79 (27·8%) clustered cases. Time-space distribution of clustered cases was predominantly consistent with transmission, in micro-epidemics. Given the dominant pattern of exogenous infection and the extensive strain circulation, effective TB control should emphasize reduction of overcrowding and improvement of environmental measures as a complement to detection and treatment of cases.

Ultrastructural evidence for selective GABAergic innervation of CNS vagal projections to the antrum of the rat.

We reported pharmacological data suggesting that stimulation of a vago-vagal reflex activates GABAergic neurons in the hindbrain that inhibit dorsal motor nucleus of the vagus (DMV) neurons projecting to the antrum, but not to the fundus (Ferreira et al., 2002). The purpose of this study was to use an ultrastructural approach to test the hypothesis that GABAergic terminals form synapses with DMV antrum-projecting neurons, but not with DMV fundus-projecting neurons. A retrograde tracer, CTB-HRP, was injected into the gastric smooth muscle of either the fundus or the antrum of anesthetized rats. Animals were re-anesthetized 48 h later and perfusion-fixed with acrolein and paraformaldehyde. Brainstems were processed histochemically for CTB-HRP, and immunocytochemically for glutamic acid decarboxylase isoenzyme 67 immunoreactivity (GAD67-IR) by dual-labeling electron microscopic methods. Most cell bodies and dendrites of neurons that were retrogradely labeled from the stomach occurred at the level of the area postrema. Examination of 214 synapses on 195 neurons that projected to the antrum revealed that 23.0+/-3.6% (n = 4) of synaptic contacts were with GAD67-IR terminals. The examination of 220 synapses on 203 fundus-projecting neurons revealed that only 7.9+/-3.1% (n = 4) of synaptic contacts were with GAD67-IR terminals. The difference between GAD67-IR synaptic contacts with antrum- and fundus-projecting neurons was statistically significant (p<0.05). These data suggest that brainstem circuitry controlling the antrum involves GABAergic transmission.

Screening for tuberculosis on admission to highly endemic prisons? The case of Rio de Janeiro State prisons.

SETTING: Rio de Janeiro (RJ) State prisons, where tuberculosis (TB) is highly endemic. OBJECTIVE: To measure TB prevalence, identify risk factors and ascertain the most appropriate screening method among inmates of the RJ prisons. DESIGN: Systematic chest X-rays (CXRs) were performed in 1696 male inmates of three RJ prisons. Inmates were selected for sputum examination and culture if their CXRs showed evidence of any pulmonary, pleural or mediastinal abnormality. TB diagnosis was based on bacteriological results or, if bacteriological results were negative, on response to TB treatment. RESULTS: TB prevalence was 2.7% (46/1696), and 32/46 cases (69%) were bacteriologically confirmed, including 19 smear-positive cases. CXR lesions were extensive in 43% of cases. In the logistic regression model, TB-associated variables were being illiterate (adjusted OR 2.10, 95%CI 1.02-4.34), cough >or=3 weeks (aOR 2.85, 95%CI 1.54-5.27), history of TB treatment (aOR 3.61, 95%CI 1.76-7.39), and living in Rio City suburbs (aOR 4.54, 95%CI 1.02-20.07) and in Rio City (aOR 5.48, 95%CI 1.29-23.33). A screening based on cough >or=3 weeks followed by sputum smear examination would have identified only 9 of the 46 cases. CONCLUSION: These results call for screening on admission to prison based, if feasible, on CXR, and demonstrate the urgent need to improve detention conditions and medical assistance in police remand cells.

Study of partner-related and situational risk factors for symptomatic male urethritis.

During the last decade, the incidence of male urethritis stopped declining in France. Risk factors associated with unprotected intercourse have been extensively studied in men who have sex with men, but not in men in general. The purpose of the study was to determine major risk factors for urethritis among men and to describe the sociodemographic and medical characteristics of this population in 2005. We conducted a prospective case-crossover study of sexual behaviors among men with acute urethritis attending at general practitioners or sexually transmitted infection (STI) clinics in France. Each patient filled out a selfcompleted questionnaire focusing on sociodemographic characteristics, and on sexual behaviors for the month before urethritis onset and for the preceding 3 months. The doctor reported medical information on a separate questionnaire. Between January and September 2005, 121 cases of male urethritis, defined as recent-onset pain on micturition and/or purulent or mucoid discharge, were included. Median age was 33 years, 22.3% were MSM, 55.1% were single, and 72.0% had at least high school education. Conditional logistic regression analysis showed that intercourse with only casual partners or with both casual and steady partners (OR = 2.6, CI 95%: 0.8-8.7, and OR = 8.7, CI 95%: 2.7-28.0), as well as inconsistent condom use (OR = 5.8, CI 95%: 1.7-19.2) significantly increased the risk of male urethritis. STI prevention campaigns should continue to focus on consistent condom use and should not neglect men over 30 years of age.

Ultrastructural evidence for selective noradrenergic innervation of CNS vagal projections to the fundus of the rat.

We reported pharmacological data suggesting that stimulation of the vago-vagal reflex activates noradrenergic neurons in the hindbrain that inhibit dorsal motor nucleus of the vagus (DMV) neurons projecting to the fundus, but not to the antrum [Ferreira Jr., M., Sahibzada, N., Shi, M., Panico, W., Neidringhaus, M., Wasserman, A., Kellar, K.J., Verbalis, J., Gillis, R.A., 2002. CNS site of action and brainstem circuitry responsible for the intravenous effects of nicotine on gastric tone. J. Neurosci. 22, 2764-2779.]. The purpose of this study was to use an ultrastructural approach to test the hypothesis that noradrenergic terminals form synapses with DMV fundus-projecting neurons, but not with DMV antrum-projecting neurons. A retrograde tracer, CTbeta-HRP, was injected into the gastric smooth muscle of either the fundus or the antrum of rats. Animals were re-anesthetized 48 h later and perfusion-fixed with acrolein and paraformaldehyde. Brainstems were processed histochemically for CTbeta-HRP, and immunocytochemically for either DbetaH or PNMT by dual-labeling electron microscopic methods. Most cell bodies and dendrites of neurons that were retrogradely labeled from the stomach occurred at the level of the area postrema. Examination of 482 synapses on 238 neurons that projected to the fundus revealed that 17.4+/-2.7% (n=4) of synaptic contacts were with DbetaH-IR terminals. Of 165 fundus-projecting neurons, 4.4+/-1.5% (n=4) formed synaptic contacts with PNMT-IR terminals. In contrast, the examination of 384 synapses on 223 antrum-projecting neurons revealed no synaptic contact with DbetaH-IR terminals. These data provide proof that norepinephrine containing nerve terminals synapse with DMV fundus-projecting neurons but not with DMV antrum-projecting neurons. These data also suggest that brainstem circuitry controlling the fundus differs from circuitry controlling the antrum.

Central control of atrio-ventricular conduction and left ventricular contractility in the cat heart: Synaptic interactions of vagal preganglionic neurons in the nucleus ambiguus with neuropeptide Y-immunoreactive nerve terminals.

In the cat, vagal postganglionic controls of heart rate, atrio-ventricular (AV) conduction and left ventricular contractility are mediated by three separate intrinsic cardiac ganglia, the sinoatrial (SA), AV and cranioventricular (CV) ganglia, respectively. The vagal preganglionic neurons (VPNs) that project to these ganglia are located in the ventrolateral nucleus ambiguus (NA-VL). We have previously shown that the VPNs projecting to the SA, AV and CV ganglia are distinct from one another. We have also demonstrated that neuropeptide Y-immunoreactive (NPY-IR) axon terminals synapse upon VPNs projecting to the SA ganglion. In the present study, we test the hypothesis that those VPNs projecting to the AV ganglion (negative dromotropic VPNs) and those projecting to the CV ganglion (negative inotropic VPNs) are innervated by NPY-IR terminals in NA-VL. A retrograde tracer was injected into the AV or CV ganglion of the cat, and the brains subsequently processed for visualization of tracer and the immunocytochemical visualization of NPY by dual labeling electron-microscopic methods. We observed that 11+/-5% of all axodendritic synapses and 8+/-6% of all axosomatic synapses upon negative inotropic VPNs were NPY-IR. Furthermore, 19+/-14% of all axodendritic synapses upon negative dromotropic VPNs were NPY-IR. A few NPY-IR axosomatic synapses upon negative dromotropic neurons were also observed. NPY-IR terminals in NA-VL occasionally formed axosomatic synapses with NPY-IR neurons and axoaxonic synapses with unlabeled terminals. These results suggest that central NPY afferents to the NA-VL modulate the vagal preganglionic control of AV conduction and left ventricular contractility.

Development and evaluation of tuberculosis screening scores in Brazilian prisons.

BACKGROUND: Tuberculosis (TB) is highly endemic in Rio de Janeiro State prisons. In addition to TB screening at entry and passive case detection, active case identification may be warranted. OBJECTIVES: To develop and evaluate performances of scores aimed at identifying "tuberculosis suspects" in order to target TB screening among inmates. METHODS: Systematic chest X-ray screening was carried out in two prisons (n=1910). TB was diagnosed among individuals with X-ray abnormalities by sputum microscopic examination and culture or, if bacteriological results were negative, by response to TB treatment. Using this strategy as a reference, the clinical score proposed in WHO guidelines "TB Control in Prisons" was evaluated. Using the same variables in a logistic regression comparing TB and non-TB cases, another score was developed and evaluated. Finally, a 'new score', based on socio-demographic and clinical variables was developed and evaluated. RESULTS: When applied to our study population (prevalence of active TB: 4.6%), these scores missed many TB cases (sensitivities: 56%, 72%, 74%, respectively). Among the "TB suspects", the probability of finding TB cases was low (positive predictive value: 10%). The scores had high negative predictive values (>97%); specificities (75%, 60%, 67%) were low. Performances were similarly poor for smear-negative and smear-positive cases. CONCLUSION: The scores investigated performed poorly and would be unhelpful to target TB screening. Therefore, systematic X-ray screening may be considered, at least during the initial stages of the reinforced TB programme, in order to reduce the impressive burden of TB.

Benefit of amoxicillin in differentiating between TB suspects whose initial AFB sputum smears are negative.

SETTING: Out-patient dispensary in Conakry, Guinea, West Africa. OBJECTIVE: To differentiate between pulmonary tuberculosis (PTB) and non-PTB diseases among 204 acid-fast bacilli (AFB) smear-negative adult TB suspects. DESIGN: We derived scores from clinical, serological and radiological findings among PTB suspects aged > or = 15 years who, after having had three AFB-negative smears, were treated for 10 days with amoxicillin (AMX, 1.5 g/day). RESULTS: At the selected cut-off score from model 1 (clinical), sensitivity for PTB was 95%, specificity 40%, negative predictive value (NPV) 84%, and positive predictive value (PPV) 69%. Comparable values from model 2 (clinical + serological + radiological) were: sensitivity 99%, specificity 45%, NPV 97%, and PPV 71%. Results from AMX were better: sensitivity 92%, specificity 93%, NPV 94%, and PPV 91%. Of the 117 suspects who failed to respond clinically and radiographically to AMX and remained AFB smear-negative, 110 (94%) had PTB, confirmed either by positive culture (73 patients) or response to anti-tuberculosis treatment (37 patients). CONCLUSION: The clinical and radiographic response to AMX is better than derived scores at differentiating between PTB and non-PTB in TB suspects presenting to a dispensary in Guinea, a low HIV-seroprevalence country.

Enkephalins and functionally specific vagal preganglionic neurons to the heart: ultrastructural studies in the cat.

In cat, distinct populations of vagal preganglionic and postganglionic neurons selectively modulate heart rate, atrioventricular conduction and left ventricular contractility, respectively. Vagal preganglionic neurons to the heart originate in the ventrolateral part of nucleus ambiguus and project to postganglionic neurons in intracardiac ganglia, including the sinoatrial (SA), atrioventricular (AV) and cranioventricular (CV) ganglia, which selectively modulate heart rate, AV conduction and left ventricular contractility, respectively. These ganglia receive projections from separate populations of vagal preganglionic neurons. The neurochemical anatomy and synaptic interactions of afferent neurons which mediate central control of these preganglionic neurons is incompletely understood. Enkephalins cause bradycardia when microinjected into nucleus ambiguus. It is not known if this effect is mediated by direct synapses of enkephalinergic terminals upon vagal preganglionic neurons to the heart. The effects of opioids in nucleus ambiguus upon AV conduction and cardiac contractility have also not been studied. We have tested the hypothesis that enkephalinergic nerve terminals synapse upon vagal preganglionic neurons projecting to the SA, AV and CV ganglia. Electron microscopy was used combining retrograde labeling from the SA, AV or CV ganglion with immunocytochemistry for enkephalins in ventrolateral nucleus ambiguus. Eight percent of axodendritic synapses upon negative chronotropic, and 12% of axodendritic synapses upon negative dromotropic vagal preganglionic neurons were enkephalinergic. Enkephalinergic axodendritic synapses were also present upon negative inotropic vagal preganglionic neurons. Thus enkephalinergic terminals in ventrolateral nucleus ambiguus can modulate not only heart rate but also atrioventricular conduction and left ventricular contractility by directly synapsing upon cardioinhibitory vagal preganglionic neurons.

Brain stem excitatory and inhibitory signaling pathways regulating bronchoconstrictive responses.

This review summarizes recent work on two basic processes of central nervous system (CNS) control of cholinergic outflow to the airways: 1) transmission of bronchoconstrictive signals from the airways to the airway-related vagal preganglionic neurons (AVPNs) and 2) regulation of AVPN responses to excitatory inputs by central GABAergic inhibitory pathways. In addition, the autocrine-paracrine modulation of AVPNs is briefly discussed. CNS influences on the tracheobronchopulmonary system are transmitted via AVPNs, whose discharge depends on the balance between excitatory and inhibitory impulses that they receive. Alterations in this equilibrium may lead to dramatic functional changes. Recent findings indicate that excitatory signals arising from bronchopulmonary afferents and/or the peripheral chemosensory system activate second-order neurons within the nucleus of the solitary tract (NTS), via a glutamate-AMPA signaling pathway. These neurons, using the same neurotransmitter-receptor unit, transmit information to the AVPNs, which in turn convey the central command to airway effector organs: smooth muscle, submucosal secretory glands, and the vasculature, through intramural ganglionic neurons. The strength and duration of reflex-induced bronchoconstriction is modulated by GABAergic-inhibitory inputs and autocrine-paracrine controlling mechanisms. Downregulation of GABAergic inhibitory influences may result in a shift from inhibitory to excitatory drive that may lead to increased excitability of AVPNs, heightened airway responsiveness, and sustained narrowing of the airways. Hence a better understanding of these normal and altered central neural circuits and mechanisms could potentially improve the design of therapeutic interventions and the treatment of airway obstructive diseases.

Parasympathetic control of the heart. I. An interventriculo-septal ganglion is the major source of the vagal intracardiac innervation of the ventricles.

The locations, projections, and functions of the intracardiac ganglia are incompletely understood. Immunocytochemical labeling with the general neuronal marker protein gene product 9.5 (PGP 9.5) was used to determine the distribution of intracardiac neurons throughout the cat atria and ventricles. Fluorescence microscopy was used to determine the number of neurons within these ganglia. There are eight regions of the cat heart that contain intracardiac ganglia. The numbers of neurons found within these intracardiac ganglia vary dramatically. The total number of neurons found in the heart (6,274 +/- 1,061) is almost evenly divided between the atria and the ventricles. The largest ganglion is found in the interventricular septum (IVS). Retrogradely labeled fluorescent tracer studies indicated that the vagal intracardiac innervation of the anterior surface of the right ventricle originates predominantly in the IVS ganglion. A cranioventricular (CV) ganglion was retrogradely labeled from the anterior surface of the left ventricle but not from the anterior surface of the right ventricle. These new neuroanatomic data support the prior physiological hypothesis that the CV ganglion in the cat exerts a negative inotropic effect on the left ventricle. A total of three separate intracardiac ganglia innervate the left ventricle, i.e., the CV, IVS, and a second left ventricular (LV2) ganglion. However, the IVS ganglion provides the major source of innervation to both the left and right ventricles. This dual innervation pattern may help to coordinate or segregate vagal effects on left and right ventricular performance.

Parasympathetic control of the heart. II. A novel interganglionic intrinsic cardiac circuit mediates neural control of heart rate.

Intracardiac pathways mediating the parasympathetic control of various cardiac functions are incompletely understood. Several intracardiac ganglia have been demonstrated to potently influence cardiac rate [the sinoatrial (SA) ganglion], atrioventricular (AV) conduction (the AV ganglion), or left ventricular contractility (the cranioventricular ganglion). However, there are numerous ganglia found throughout the heart whose functions are poorly characterized. One such ganglion, the posterior atrial (PA) ganglion, is found in a fat pad on the rostral dorsal surface of the right atrium. We have investigated the potential impact of this ganglion on cardiac rate and AV conduction. We report that microinjections of a ganglionic blocker into the PA ganglion significantly attenuates the negative chronotropic effects of vagal stimulation without significantly influencing negative dromotropic effects. Because prior evidence indicates that the PA ganglion does not project to the SA node, we neuroanatomically tested the hypothesis that the PA ganglion mediates its effect on cardiac rate through an interganglionic projection to the SA ganglion. Subsequent to microinjections of the retrograde tracer fast blue into the SA ganglion, >70% of the retrogradely labeled neurons found within five intracardiac ganglia throughout the heart were observed in the PA ganglion. The neuroanatomic data further indicate that intraganglionic neuronal circuits are found within the SA ganglion. The present data support the hypothesis that two interacting cardiac centers, i.e., the SA and PA ganglia, mediate the peripheral parasympathetic control of cardiac rate. These data further support the emerging concept of an intrinsic cardiac nervous system.

Parasympathetic control of the heart. III. Neuropeptide Y-immunoreactive nerve terminals synapse on three populations of negative chronotropic vagal preganglionic neurons.

The vagal postganglionic control of cardiac rate is mediated by two intracardiac ganglia, i.e., the sinoatrial (SA) and posterior atrial (PA) ganglia. Nothing is known about the vagal preganglionic neurons (VPNs) that innervate the PA ganglion or about the neurochemical anatomy of central afferents that innervate these VPNs. These issues were examined using light microscopic retrograde labeling methods and dual-labeling electron microscopic histochemical and immunocytochemical methods. VPNs projecting to the PA ganglion are found in a narrow column exclusively in the ventrolateral nucleus ambiguus (NA-VL). These neurons are relatively large (37.6 +/- 2.7 microm by 21.3 +/- 3.4 microm) with abundant cytoplasm and intracellular organelles, rare somatic and dendritic spines, round uninvaginated nuclei, and myelinated axons. Previous physiological data indicated that microinjections of neuropeptide Y (NPY) into the NA-VL cause negative chronotropic effects. The present morphological data demonstrate that NPY-immunoreactive nerve terminals formed 18 +/- 4% of the axodendritic or axosomatic synapses and close appositions on VPNs projecting to the PA ganglion. Three approximately equal populations of VPNs in the NA-VL were retrogradely labeled from the SA and PA ganglia. One population each projects to the SA ganglion, the PA ganglion, or to both the SA and PA ganglia. Therefore, there are both shared and independent pathways involved in the vagal preganglionic controls of cardiac rate. These data are consistent with the hypothesis that the central and peripheral parasympathetic controls of cardiac rate are coordinated by multiple potentially redundant and/or interacting pathways and mechanisms.

A GABAergic inhibitory microcircuit controlling cholinergic outflow to the airways.

GABA is the main inhibitory neurotransmitter that participates in the regulation of cholinergic outflow to the airways. We have tested the hypothesis that a monosynaptic GABAergic circuit modulates the output of airway-related vagal preganglionic neurons (AVPNs) in the rostral nucleus ambiguus by using a dual-labeling electron microscopic method combining immunocytochemistry for glutamic acid decarboxylase (GAD) with retrograde tracing from the trachea. We also determined the effects of blockade of GABAA receptors on airway smooth muscle tone. The results showed that retrogradely labeled AVPNs received a significant GAD-immunoreactive (GAD-IR) terminal input. Out of a pooled total of 3,161 synaptic contacts with retrogradely labeled somatic and dendritic profiles, 20.2% were GAD-IR. GAD-IR terminals formed significantly more axosomatic synapses than axodendritic synapses (P < 0.02). A dense population of GABAergic synaptic contacts on AVPNs provides a morphological basis for potent physiological effects of GABA on the excitability of AVPNs. GAD-IR terminals formed exclusively symmetric synaptic specializations. GAD-IR terminals were significantly larger (P < 0.05) in both length and width than unlabeled terminals synapsing on AVPNs. Therefore, the structural characteristics of certain nerve terminals may be closely correlated with their function. Pharmacological blockade of GABAA receptors within the rostral nucleus ambiguus increased activity of putative AVPNs and airway smooth muscle tone. We conclude that a tonically active monosynaptic GABAergic circuit utilizing symmetric synapses regulates the discharge of AVPNs.

Catecholaminergic microcircuitry controlling the output of airway-related vagal preganglionic neurons.

In this study, we have investigated the ultrastructure and function of the catecholaminergic circuitry modulating the output of airway-related vagal preganglionic neurons (AVPNs) in ferrets. Immunoelectron microscopy was employed to characterize the nature of catecholaminergic innervation of AVPN at the ultrastructural level. In addition, immunofluorescence was used to examine the expression of the alpha(2A)-adrenergic receptor (alpha(2A)-AR) on AVPNs, and norepinephrine release within the rostral nucleus ambiguous (rNA) was measured by using microdialysis. Physiological experiments were performed to determine the effects of stimulation of the noradrenergic locus coeruleus (LC) cell group on airway smooth muscle tone. The results showed that 1) catecholaminergic nerve endings terminate in the vicinity of identified AVPNs but very rarely form axosomatic or axodendritic synapses with the AVPNs that innervate the extrathoracic trachea; 2) AVPNs express the alpha(2A)-AR; 3) LC stimulation-induced norepinephrine release within the rNA region was associated with airway smooth muscle relaxation; and 4) blockade of alpha(2A)-AR on AVPNs diminished the inhibitory effects of LC stimulation on airway smooth muscle tone. It is concluded that a noradrenergic circuit originating within the LC is involved in the regulation of AVPN activity within the rNA, and stimulation of the LC dilates the airways by the release of norepinephrine and activation of alpha(2A)-AR expressed by AVPNs, mainly via volume transmission.

Useful clues to the presence of smear-negative pulmonary tuberculosis in a West African city.

OBJECTIVE: Tuberculosis suspects with negative sputum smears for acid-fast bacilli (AFB) may have either pulmonary tuberculosis (PTB) or some other pulmonary disease (non-PTB). The aim of this study was to improve the differentiation between PTB and non-PTB. DESIGN: We enrolled 396 tuberculosis suspects 15 years of age or older who had cough of 21 days or longer and three negative AFB smears. Non-PTB was diagnosed by clinical and radiographic responses to amoxicillin; smear-negative PTB was diagnosed by positive culture for Mycobacterium tuberculosis or response to antituberculosis chemotherapy. RESULTS: Multivariate analysis, without X-ray variables, of 79 patients with a final diagnosis of non-PTB and 110 patients with smear-negative PTB indicated that age less than 37 years, family contact with TB, never having been married, loss of weight, lack of expectoration, human immunodeficiency virus (HIV) seropositivity, and tuberculin reactivity were significantly associated with PTB. When the initial X-ray findings were included, age younger than 37 years, lack of expectoration, HIV seropositivity, and tuberculin reactivity remained in the model, and cavitation and patchy densities were significantly associated. CONCLUSION: The response to 10 days of amoxicillin and certain demographic, clinical and radiographic characteristics are useful in separating non-PTB from PTB in tuberculosis suspects with negative AFB smears.

Substance P afferent terminals innervate vagal preganglionic neurons projecting to the trachea of the ferret.

Airway disorders, such as asthma and chronic obstructive bronchitis, are, in part, due to abnormalities in the nervous control of the airways. However, the ultrastructural circuitry and neurochemical anatomy of afferents modulating the output of airway-related vagal preganglionic neurons (VPNs) in the nucleus ambiguus are poorly understood. We have examined the potential role of substance P (SP) immunoreactive afferents in the regulation of anatomically identified airway VPNs. Cholera toxin b-subunit conjugated to horseradish peroxidase was used as a retrograde cell body tracer to identify the central VPNs innervating the extra-thoracic trachea. Immunocytochemistry was employed to identify SP afferents. The external formation of the nucleus ambiguus was examined by electron microscopy using a simultaneous double labeling method. Cell bodies of tracheal VPNs were 31.7 +/- 1.18 x 23.0 +/- 1.3 microm (means +/- S.E.M.) in size, contained abundant endoplasmic reticulum, had a round nucleus with a prominent nucleolus, no satellite body and displayed somatic and dendritic spines. Somato-somatic appositions, somato-dendritic appositions without intervening glial processes and dendritic "bundling" commonly seen in esophageal motoneurons were not observed. The ultrastructural morphology of tracheal VPNs were also clearly distinguishable from pharyngeal and laryngeal motoneurons in other divisions of the nucleus ambiguus which lack somatic spines. These data are consistent with the hypothesis that differences in the ultrastructure and synaptology of the different divisions of the nucleus ambiguus may be associated with specific physiological functions. The mean size (+/- S.E.M.) of SP nerve terminals was 1.57 +/- 0.06 x 0.79 +/- 0.03 microm. SP terminals formed 17.5% of the axo-dendritic and 15.9% of the axo-somatic synapses which were observed upon retrogradely labeled tracheal VPNs. Synaptic contacts observed were both symmetric and asymmetric. These synaptic interactions define, in part, the neurochemical anatomy of neuronal circuits modulating vagal preganglionic control of tracheal functions.