Nomadic plastic surgery: from healthcare huts to war-zones. Our experience over 30 years.

We present 30 years' experience of "nomadic" plastic surgery missions carried out by a small non-governmental organization, specialized in reconstructive surgery in challenging conditions in developing countries. Here, we provide a record of missions carried out between 1993 and 2023. The study shows how surgical missions are conducted and the methodology used. We carried out 70 missions, with more than 8,000 consultations, and operated on 3,780 patients. A quarter of operations concerned clefts, a quarter tumors, a quarter burns and a quarter various diseases such as Noma and, recently, traumatic lesions secondary to armed conflict. We show some adaptations such as autonomy during missions, adjustment of indications to this new environment and the integration of local traditions in our therapeutic action. We offer practical ideas about surgery and some reflections on the social concerns.

Very Low Phytoplankton Diversity in a Tropical Saline-Alkaline Lake, with Co-dominance of Arthrospira fusiformis (Cyanobacteria) and Picocystis salinarum (Chlorophyta).

Lake Dziani Dzaha (Mayotte Island, Indian Ocean) is a tropical thalassohaline lake which geochemical and biological conditions make it a unique aquatic ecosystem considered as a modern analogue of Precambrian environments. In the present study, we focused on the diversity of phytoplanktonic communities, which produce very high and stable biomass (mean2014-2015 = 652 ± 179 µg chlorophyll a L-1). As predicted by classical community ecology paradigms, and as observed in similar environments, a single species is expected to dominate the phytoplanktonic communities. To test this hypothesis, we sampled water column in the deepest part of the lake (18 m) during rainy and dry seasons for two consecutive years. Phytoplanktonic communities were characterized using a combination of metagenomic, microscopy-based and flow cytometry approaches, and we used statistical modeling to identify the environmental factors determining the abundance of dominant organisms. As hypothesized, the overall diversity of the phytoplanktonic communities was very low (15 OTUs), but we observed a co-dominance of two, and not only one, OTUs, viz., Arthrospira fusiformis (Cyanobacteria) and Picocystis salinarum (Chlorophyta). We observed a decrease in the abundance of these co-dominant taxa along the depth profile and identified the adverse environmental factors driving this decline. The functional traits measured on isolated strains of these two taxa (i.e., size, pigment composition, and concentration) are then compared and discussed to explain their capacity to cope with the extreme environmental conditions encountered in the aphotic, anoxic, and sulfidic layers of the water column of Lake Dziani Dzaha.

Trajectories of river chemical quality issues over the Longue Durée: the Seine River (1900S-2010).

River quality trajectories are presented for (i) organic pollution, (ii) eutrophication, (iii) nitrate pollution, and (iv) metal contamination over the Longue Durée (130 to 70 years). They are defined by a quantified state indicator (S) specific to each issue, compared to drivers (D) or pressures (P) and to social responses (R) that reflect the complex interactions between society and river quality. The Lower Seine River, naturally sensitive to anthropogenic pressures, greatly impacted by Paris urban growth, industrialization, and intensive agriculture, and well documented by the PIREN-Seine 25-year research program, was chosen to illustrate these trajectories. State indicators, dissolved oxygen, algal pigments, nitrate, and heavy metals (Cd, Cr, Hg, Pb, Zn) in sediments have only been monitored by river basin authorities since 1971. Therefore, their past changes have been reconstructed using three approaches: (i) reassessment of historical sources, (ii) pressure-state models that reconstruct past water quality, and (iii) sedimentary archives of past persistent contamination from dated floodplain cores. The indicators were then transformed into river quality status using contemporary water quality criteria throughout these records. Each environmental issue shows specific trajectories because each has its own relationship between the issue evidence and the social response, but all are characterized by very poor quality in the past, largely ignored: the long-term summer hypoxia (<1880-1995), the summer eutrophication peak (1965-2005), the growing nitrate level since the 1950s, recently stabilized but still high, and the extreme metal contamination (>1935-2000) that peaked in the 1960s. The efficiency of social responses has been highly variable but more efficient in the last 15-25 years.

[Nomadic plastic surgery: 1 NGO, 10 years, 30 missions]. / Chirurgie plastique nomade: 1 ONG, 10 années, 30 missions.

This publication presents the results of 10 years of nomadic plastic surgery missions by a small French non-governmental organization: Interplast-France/surgery without borders (www.Interplast-France.net). This NGO is specialized in reconstructive surgery in challenging conditions and works in developing countries. We present a view of 10 years of missions carried out between 2003 and 2013. This experience covers a uniform period both by the objectives proposed and the regularity of missions observed. This work shows the way surgical missions take place and the methodology used. We carried out 30 missions. We made more than 4000 consultations and we operated 1500 patients. Interventions are divided into one quarter cleft, one quarter tumors, one quarter burn injuries and one quarter of various diseases such as noma and Buruli ulcer. We show some adaptations such as autonomy during missions, the adjustment guidance in relation to this new environment and the integration of local traditions in our therapeutic action. We offer practical notions on the surgical procedures and some reflections on the societal level. This work aims primarily to pay tribute to all the invisible actors in this long chain of humanity, and thanks to the simple intervention of men, a patient can have the same medical treatment whether he is in an industrial country or in some isolated place on this earth.

p16(INK4a) /Ki-67 dual labelling as a marker for the presence of high-grade cancer cells or disease progression in urinary cytopathology.

OBJECTIVE: Overexpression of p16(INK4a) independent of the presence of E6-E7 oncoproteins of high-risk papillomaviruses has been identified in bladder carcinoma in situ lesions with or without concurrent papillary or invasive high-grade (HG) urothelial carcinoma. As p16(INK4a) and Ki-67 co-expression clearly indicates deregulation of the cell cycle, the aim of this study was to investigate the frequency of p16(INK4a) /Ki-67 dual labelling in urinary cytology samples. METHODS: Immunolabelling was performed in demounted, destained Papanicolaou slides after ThinPrep(®) processing. A total of 84 urinary cytology samples (18 negative, 10 low grade, 19 atypical urothelial cells and 37 high grade) were analysed for p16(INK4a) /Ki-67 co-expression. We assessed underlying urothelial malignancy with cystoscopy, histopathology and follow-up data in every case. RESULTS: Compared with raw histopathological results, p16 (INK4a) /Ki-67 dual labelling was observed in 48 out of 55 (87.3%) HG lesions and in 11 out of 29 (37.9%) negative, papillary urothelial neoplasia of low malignant potential or low-grade carcinomas (P = 0.05). All cases with high-grade/malignant cytology were dual labelled. Sixteen out of 17 (94.1%) carcinoma in situ cases and eight out of 14 (57.1%) cases with atypical urothelial cells matching with HG lesions were dual labelled. Extended follow-up allowed three cases of progression to be diagnosed in dual-labelled cases with negative/low-grade cytology results after a 9- to 11-months delay. CONCLUSIONS: The data show that p16(INK4a) /Ki-67 co-expression allows most HG cancer cells to be detected initially and in the follow-up period. Additional studies are needed in order to determine whether dual labelling can be used as a triage tool for atypical urothelial cells in the urine.

Optimization of a photopolymerizable material based on a photocyclic initiating system using holographic recording.

A set of photoinitiating systems (PIS) for free radical photopolymerization was studied using time-resolved spectroscopic experiments, real-time FTIR and holographic recording. It is shown that the efficiency of the photoinitiating system can be drastically increased when a redox additive is added to the conventional dye/coinitiator system by virtue of photocyclic behaviour. The homogeneous photopolymerization process was found to reach a fast vitrification, limiting the conversion at about 55%. By contrast, holographic recording underlines the differences in photoinitiating system reactivity, allowing diffraction efficiencies close to unity for the most reactive PIS.

Efficacy of a home-based intervention programme on the physical activity level and functional ability of older people using domestic services: a randomised study.

OBJECTIVE: Our main objective was to assess whether a home-based program supervised by home helpers (HH) during their normal working hours can prevent excessive sedentariness (mainly maximum walking time and distance) and preserve functional status in elderly people at risk for frailty or disability and using domestic services. DESIGN: A four-month, open label, randomised trial with two groups called "prevention" and "control". SETTING: In the homes of study participants. PARTICIPANTS: The participants were all over 78 years old, lived independently at home, and received the visits of HHs at least once a week. INTERVENTION: The intervention combined a self-administered exercise program, with 10 g amino-acid supplementation under the supervision of HHs. MEASUREMENTS: Main outcome measures included physical activity (the PASE questionnaire), functional tests, nutritional and autonomy scores, and compliance (50% or more was considered satisfactory). Non-parametric methods were used for comparisons between the two groups. A linear regression model was fitted to assess the effect of the intervention on the relative variation of outcomes, adjusted for unbalanced baseline co-variables. RESULTS: One hundred and two persons (prevention n=53, control n=49) with a median age of 85 years were included. Their median Activities of Daily Living and Instrumental Activities of Daily Living (IADL) scores were 6 and 7 respectively. Twenty-three (44%) were good compliers for both interventions. The maximum walking time remained stable while decreasing by 25% in the control group (p=0.0015); and fewer participants had a worsened IADL score in the prevention group (p=0.05). The baseline IADL Score was significantly associated with good compliance to the prevention program (p=0.0011). In good compliers, maximum walking distance and maximum walking time increased by 29.15% (0.0 to 66.7) and 33.3% (-20.0 to 50.0) respectively. CONCLUSION: This study confirms the feasibility of a prevention program supervised by HHs, and some benefit from the intervention and identifies predictors for better compliance. It will help in the design of prevention trials for elderly people at risk for frailty.

Lack of involvement of type 7 phosphodiesterase in an experimental model of asthma.

Type 7 phosphodiesterases (PDE7) are responsible for the decrease of intracellular cyclic AMP (cAMP) in many cells involved in allergic asthma by suppressing their potential to respond to many activating stimuli. The elevation of intracellular cAMP has been associated with immunosuppressive and anti-inflammatory activities and represents a potential treatment of asthma. Our aim was to evaluate the impact of the deletion of the murine phosphodiesterase (PDE)7B gene and then to evaluate the efficacy of a newly described selective PDE7A and -B inhibitor on an ovalbumin (OVA)-induced airway inflammation and airway hyperreactivity (AHR) model in mice. Inflammation was determined 72 h after single OVA challenge or 24 h after multiple challenges by the relative cell influx and cytokine content in bronchoalveolar lavage fluid. AHR and immunoglobulin E levels in serum were determined after multiple challenges. For the first time, we have demonstrated that the deletion of the PDE7B gene or the pharmacological inhibition of PDE7A and -B had no effect on all the parameters looked at in this model. These results highlight the absence of any implication of the PDE7 enzyme in our model.

Comparison of the effects of two herbicides and an insecticide on tropical freshwater plankton in microcosms.

Natural plankton communities from a tropical freshwater reservoir (Combani Reservoir, Mayotte Island, Mozambique Channel) were exposed, in 20-l nutrient-enriched microcosms, to two nominal concentrations of three pesticides: the herbicides diuron (2.2 and 11 µg/l) and paraquat (10 and 40.5 µg/l) and the insecticide fenitrothion (10 and 100 µg/l), commonly used in the tropics for agriculture and disease vector control. Bacterioplankton, phytoplankton, and zooplankton communities were monitored for 5 days after exposure, and the concentrations of toxicant and major nutrients were measured. Bacterioplankton growth was noticeable in all systems and was slightly affected by pesticide at any concentration. A transitory increase in thymidine-based bacterial production was observed in diuron- and fenitrothion-treated microcosms, followed by a marked decrease in all microcosms after 5 days. The functional diversity of bacterioplankton, evaluated using BIOLOG ECO(®) microplates, was reduced by exposure to the highest pesticide concentrations. Phytoplankton was affected by pesticides in different ways. Chlorophyll biomass and biovolumes were increased by diuron addition and decreased by paraquat, whereas fenitrothion-treated microcosms remained unaffected relative to controls. Phytoplankton taxonomic diversity was decreased by paraquat and high doses of fenitrothion but was unaffected by addition of diuron. The decrease in diversity was due to a reduction in the number of species, whereas the density of small cells increased, especially after addition of paraquat. Heterotrophic flagellates were sensitive to paraquat and to the highest diuron concentration; a reduction in biomass of up to 90% was observed for 40.5 µg/l paraquat. Zooplankton, dominated by Thermocyclops decipiens and Diaphanosoma excisum, was slightly sensitive to diuron, and very sensitive to paraquat. High concentrations of the insecticide fenitrothion were effective only on young stages. The potential direct and indirect effects of pesticide contamination on such a simplified plankton food web, typical of newly constructed reservoirs, appear to differ significantly depending on the biological compartment considered. The overall sensitivity of tropical plankton is comparable to the sensitivity for temperate systems, and direct and indirect effects appeared rapidly, within 5 days of exposure.

Topical retinaldehyde with glycolic acid: study of tolerance and acceptability in association with anti-acne treatments in 1,709 patients.

BACKGROUND: Retinaldehyde (RAL), a key metabolite between vitamin A and retinoic acid, acts by modulating differentiation and proliferation of keratinocytes, which is of interest in acne lesions, mainly retentional lesions. Glycolic acid increases the exfoliation of corneocytes explaining its mild activity on retentional lesions. Thus, RAL and glycolic acid combined in the same product (Diacneal) have complementary activities which can be of interest for acne patients. The aim of this study was to evaluate the tolerance of Diacneal used by 1,709 acne patients in combination with their usual acne products except retinoids. RESULTS: This study demonstrated a very good tolerance of Diacneal when used with other acne treatments for 90 days. Complaints about side-effects were rare. Moreover, the significant decrease in both inflammatory and retentional lesions between day 0 and day 90 indicates that Diacneal could amplify the efficiency of other anti-acne products used at the same time by the patients. The subjective evaluation of the preparation's efficacy by investigators and patients was strongly favourable. CONCLUSION: These data show that a combination of RAL 0.1% and glycolic acid 6% may be used in association with other topical anti-acne treatments (benzoyl peroxide and topical antibiotics) with an excellent tolerance.

Solitary adult myofibroma of the mandible simulating an odontogenic cyst.

The solitary adult myofibroma is a rare lesion but has a predilection for the head and neck. Intraosseous lesions are common in childhood but uncommon in adults. The lesion is considered to be completely benign but there is the potential for it being confused with more aggressive spindle cell tumours. Histologically it is characterised by two cell types arranged in a biphasic pattern; namely centrally positioned small rounded cells with pale staining nuclei and eosinophilic cytoplasm and peripherally elongated spindle cells. A case is reported of a 34-year-old female patient who presented with a solitary myofibroma in the lower third molar region of the mandible which clinically and radiographically simulated an odontogenic cyst.

Origin of germ cells, sex determination, and sex inversion in medusae of the genus Clytia (Hydrozoa, leptomedusae): the influence of temperature.

In Cnidaria, a separation between soma and germline remains unclear. In this work, we studied the origin of germinal cells and determination of the sexual phenotype in Clytia hemisphaerica and Clytia sp. Colonies of C. Hemisphaerica were cultivated and the medusae liberated by each colony raised until maturity. Two hermaphrodite colonies were obtained, liberating male and female medusae. These two colonies and their medusae were raised at 15 degrees C, 21 degrees C, or 24 degrees C. The medusae budded and cultured at 24 degrees C were mainly female (80%). In contrast, if the medusae were released at 15 degrees C, at whatever temperature they were raised later, they were mainly male (85%). The same occurred if, after release at 24 degrees C but before the formation of the gametes, they were kept at 15 degrees C for at least 24 hr. We suggest that there are two subpopulations of germ cells. The female line will be dominant at 24 degrees C but temperature sensitive, with inhibition of this line by a temperature drop to 15 degrees C, this inverting the population sex-ratio. The irreversible action of a temperature drop to 15 degrees C supports the view that the germ cells are isolated very early. In C. hemisphaerica, hermaphrodite medusae were never observed. On the contrary, in Clytia sp., probably a new species, we have found male, female, but also hermaphrodite specimens. This is the second definite example of hermaphroditism described in any hydromedusan. The transformation of female into hermaphrodite then into male specimens occurs at 13 degrees C. These results demonstrate the unstable character of genetic sex determination in cnidarians, at least in certain species.

Activation of locomotor and grasping spine muscle fibres in chaetognaths: a curious paradox.

Chaetognath muscle fibres resemble vertebrate muscle fibres in having an abundant sarcoplasmic reticulum (SR) and analogues of the transverse (T) tubular system. but contraction is regulated differently. In intact chaetognaths electrically-evoked contractions of the striated locomotor muscles were largely or totally blocked by d-tubocurarine, by surgical removal of the ventral ganglion and by Co2 +. Contractions of single cells enzymatically dissociated from locomotor muscles were likewise blocked by Co2+, they twitched once only after calciseptine, showed neither contractures nor elevated intracellular Ca2+ with caffeine, and ryanodine did not block contractions. Whole cell voltage-clamped locomotor muscle cells displayed a typical inward rectified Ca2 + current that was sensitive to the Ca2+ channel blockers nifedipine and calciseptine and showed voltage-dependent activation with a threshold at approximately-25 mV and a peak inward current at approximately + 10 mV. In contrast, whole cell voltage-clamped cells from the muscles operating the grasping spines of the head showed an initial very rapid and rapidly-inactivating inward current abolished by tetrodotoxin (TTX), followed by a slower and slowly-inactivating inward current blocked by calciseptine. The relation between these observations and the unusual 'vertebrate-like' structure of the muscle cells is discussed.

Airway responsiveness to bradykinin is related to eosinophilic inflammation in asthma.

We investigated the relationship between airway inflammation and airway responsiveness, as assessed by PD15, to methacholine and to bradykinin in asthmatic patients. Bronchoalveolar lavage (BAL), bronchial biopsies, and methacholine and bradykinin challenges were performed in 18 nonsmoking subjects with mild or moderate perennial asthma. Bradykinin PD15 correlated negatively with eosinophil count in BAL (p < 0.05), in the epithelium (p < 0.05), in the lamina propria (p = 0.02) and in the total submucosa (p < 0.01). Conversely, no significant correlation existed between airway responsiveness to methacholine and eosinophil count in BAL or in airway mucosa. Airway responsiveness to either agonist did not correlate with the thickness of the basement membrane, the shedding of the airway epithelium, the count of lymphocytes in the airway mucosa, or the percentage of neutrophils, lymphocytes, and macrophage in BAL. The presence of degranulated eosinophils was associated with an increased number of eosinophils in the airway epithelium (p = 0.04), in the lamina propria (p = 0.03), in the total submucosa (p = 0.02), and with increased airway responsiveness to bradykinin (p < 0.02). We conclude that in asthmatic patients, airway responsiveness to bradykinin but not to methacholine is related to the magnitude of eosinophilic inflammation in the airway mucosa.

Effect of limonene and sobrerol on monocrotaline-induced lung alterations and pulmonary hypertension.

The effects of two monocyclic monoterpenes, limonene and sobrerol, known as inhibitors of farnesyltransferase activity, were studied on monocrotaline (MCT)-induced lung injury, pulmonary hypertension and right ventricular hypertrophy in male Wistar rats. After 14 days, pulmonary arterial pressure values and the right ventricle to left ventricle plus septum weight ratios, RV/(LV + S), were markedly increased in rats subcutaneously injected with MCT (60 mg/kg). Limonene and sobrerol, administered daily at the oral dose of 400 mg/rat, markedly decreased the MCT-induced alterations. After treatment for 21 days, limonene still prevented pulmonary hypertension and the increase in RV/(LV + S). Both monoterpenes also reduced the increase in pulmonary arterial media thickness, the development of interstitial fibrosis and the increase in the number of macrophages in intra-alveolar spaces and of lymphocytes around the pulmonary veins. The present data indicate that treatment of rats with inhibitors of farnesyltransferase, like limonene and sobrerol, regulate the development of pulmonary hypertension.

Inhibitory effect of cyclosporin A on eosinophil infiltration in the guinea-pig lung induced by antigen, platelet-activating factor and leukotriene B4.

The effect of the immunosuppressive compound, cyclosporin A, and the corticosteroid, betamethasone, was investigated on eosinophil accumulation in guinea-pig lung tissue induced by antigen, platelet-activating factor (PAF) and leukotriene B4 (LTB4). The accumulation of eosinophils in the peribronchial area was evaluated on histological preparations. The lung sections were stained with Luna's reagent specific for eosinophil granule content. Oral treatment of the guinea-pigs with cyclosporin, 10 mg.kg-1 three times a day for two days, and 10 mg.kg-1 1 h before antigen challenge, significantly reduced the accumulation of eosinophils observed at 4 and 24 h, in the peribronchial area of sensitized guinea-pig lung. Betamethasone (3 mg.kg-1), administered orally 24 h and 1 h before antigen challenge elicited a moderate but significant reduction of antigen-induced eosinophil accumulation. Pretreatment of the guinea-pigs with cyclosporin or betamethasone elicited a marked inhibition of the accumulation of eosinophils in the peribronchial area induced by aerosolized PAF (100 micrograms.ml-1) or LTB4 (5 micrograms.ml-1). Since cyclosporin and betamethasone significantly inhibit the antigen-induced eosinophil accumulation, these results suggest that antigen-induced lung eosinophilia is dependent of T-lymphocytes. However, cyclosporin and betamethasone may also reduce the chemotactic activity of PAF and LTB4 on guinea-pig eosinophils.

Effects of the platelet activating factor antagonists BN 52021 and BN 50730 on antigen-induced bronchial hyperresponsiveness and eosinophil infiltration in lung from sensitized guinea-pigs.

The involvement of platelet activating factor (PAF) in antigen-induced bronchial hyperresponsiveness was investigated by the use of the PAF antagonists BN 52021 and BN 50730, in a guinea-pig model where sensitization and challenge were performed by aerosol. Male Hartley guinea-pigs were sensitized by two aerosol exposures at 48 hr intervals to a 0.9% NaCl solution (saline) containing 2 mg/ml ovalbumin for 30 min. Fifteen to 20 days later, guinea-pigs were challenged by exposure to five successive aerosols of increasing concentrations of ovalbumin (OA) or respectively, 10 microg/ml, 100 microg/ml, 1 mg/ml, 5 mg/ml and 10 mg/ml for 15 min each, or saline alone. Three to four hr and 18-24 hr after the aerosol challenge the guinea-pigs were prepared for recording of bronchopulmonary response and aerosol administrations were then generated with an ultrasonic nebulizer. The bronchopulmonary responses induced by successive 1-min aerosol bursts of acetylcholine (ACh) was assessed. As compared with saline-challenged guinea-pigs, an enhanced bronchopulmonary response to aerosol administration of cumulative doses of ACh was observed, 3-4 hr and 18-24 hr post-ovalbumin challenge. When the sensitized guinea-pigs were pretreated 1 hr before ovalbumin exposure with BN 52021 or BN 50730 (25 mg/kg, per os), a significant inhibition of the increase in the bronchopulmonary response to ACh was observed, both at 3-4 hr and 18-24 hr. Furthermore, when guinea-pigs were treated 3-4 hr after the ovalbumin exposure with BN 52021 or BN 50730, a significant inhibition of the hyperresponsiveness to ACh was recorded at 18-24 hr. A marked accumulation of eosinophils in the peribronchial regions was observed on histological preparations of lung specimens collected 4 hr or 24 hr after ovalbumin exposure. Pretreatment of the guinea-pigs by BN 50730 or BN 52021 did not modify the eosinophil accumulation in the peribronchial area. No significant difference in the number of eosinophils collected in the bronchoalveolar lavage fluid is observed, 24 hr post-ovalbumin challenge, under the pretreatment with BN 52021 or BN 50730. Pretreatment of guinea-pigs by BN 50730 or BN 52021 significantly reduced the PAF-induced (100 microg/ml) increase in eosinophil number in the peribronchial area. By contrast, they did not inhibit the eosinophilia induced by aerosol administration of LTB4 (5 microg/ml). These results suggest that the bronchial hyperresponsiveness observed in this study is associated with eosinophil accumulation in the lung. The potent inhibition of the bronchial hyperresponsiveness by the two unrelated antagonists of PAF suggests that the lipid mediator is involved in its triggering and duration, but not in the eosinophil infiltration.

Computer-originated polarizing holographic optical element recorded in photopolymerizable layers.

The photosensitive system that is used in most cases to produce holographic optical holograms is dichromated gelatin. Other materials may be used, in particular, photopolymerizable layers. In the present investigation, we set out to use the polymer developed in the Laboratoire de Photochimie Générale in Mulhouse in order to duplicate a computer-generated hologram. Our technique is intended to generate polarizing properties. We took into account the fact that no wet chemistry processing is required; grating fringe spacings are not distorted through chemical development.

Bronchial responses to substance P after antigen challenge in the guinea-pig: in vivo and in vitro studies.

The effect of antigen challenge on the airway responses to substance P and on the epithelial neutral endopeptidase (NEP) activity was investigated in aerosol sensitized guinea-pigs. In vivo, bronchial responses to aerosolized substance P were similar to the responses observed in antigen-challenged guinea-pigs and in the control groups. In contrast, when the guinea-pigs were pretreated with the NEP inhibitor, phosphoramidon, a significant increase in the airway responses to substance P was observed after antigen challenge in vivo. However, in vitro, the contractile responses of the tracheal smooth muscle to substance P were similar between groups of guinea-pigs, in respect to the presence or absence of the epithelium and/or phosphoramidon. Histological studies showed an accumulation of eosinophils in the tracheal submucosa after antigen challenge and intact epithelial cells. These results show that in vivo bronchial hyperresponsiveness to substance P after antigen challenge in the guinea-pig is not associated with increased responses of the smooth muscle to exogenous SP in vitro. In addition, the results with phosphoramidon suggest that loss of NEP activity cannot account for the in vivo bronchial hyperresponsiveness to substance P presently observed.