Dissecting the phenotypic heterogeneity in sensory features in autism spectrum disorder: a factor mixture modelling approach.

BACKGROUND: Heterogeneity in the phenotypic presentation of autism spectrum disorder (ASD) is apparent in the profile and the severity of sensory features. Here, we applied factor mixture modelling (FMM) to test a multidimensional factor model of sensory processing in ASD. We aimed to identify homogeneous sensory subgroups in ASD that differ intrinsically in their severity along continuous factor scores. We also investigated sensory subgroups in relation to clinical variables: sex, age, IQ, social-communication symptoms, restricted and repetitive behaviours, adaptive functioning and symptoms of anxiety and attention-deficit/hyperactivity disorder. METHODS: Three hundred thirty-two children and adults with ASD between the ages of 6 and 30 years with IQs varying between 40 and 148 were included. First, three different confirmatory factor models were fit to the 38 items of the Short Sensory Profile (SSP). Then, latent class models (with two-to-six subgroups) were evaluated. The best performing factor model, the 7-factor structure, was subsequently used in two FMMs that varied in the number of subgroups: a two-subgroup, seven-factor model and a three-subgroup and seven-factor model. RESULTS: The 'three-subgroup/seven-factor' FMM was superior to all other models based on different fit criteria. Identified subgroups differed in sensory severity from severe, moderate to low. Accounting for the potential confounding effects of age and IQ, participants in these sensory subgroups had different levels of social-communicative symptoms, restricted and repetitive behaviours, adaptive functioning skills and symptoms of inattention and anxiety. LIMITATIONS: Results were derived using a single parent-report measure of sensory features, the SSP, which limits the generalisability of findings. CONCLUSION: Sensory features can be best described by three homogeneous sensory subgroups that differ in sensory severity gradients along seven continuous factor scores. Identified sensory subgroups were further differentiated by the severity of core and co-occurring symptoms, and level of adaptive functioning, providing novel evidence on the associated clinical correlates of sensory subgroups. These sensory subgroups provide a platform to further interrogate the neurobiological and genetic correlates of altered sensory processing in ASD.

Routine EGFR and KRAS Mutation analysis using COLD-PCR in non-small cell lung cancer.

Aims: Epidermal growth factor receptor (EGFR) antagonists are particularly active in non-small cell lung cancer (NSCLC) patients with tumours bearing mutations in the EFGR gene. EGFR mutation prevalence is very low in squamous histology. Response rates using these drugs in patients with KRAS mutations are low, so available KRAS mutation information may aid treatment selection in the second-line setting. Since 2009, patients presenting to this hospital with non-squamous histology have been routinely screened for mutations in both the EGFR and KRAS genes, with results used to inform treatment. We present an analysis of 215 consecutive patients for whom EGFR mutation analysis was informative. Methodology: EGFR and KRAS mutations were identified using a COLD-PCR technique confirmed with sequencing, which makes no prior assumption about location of specific mutations. Results were correlated with clinical and demographic data from hospital records, where available. Results: The prevalence of patients with EGFR mutations was 14% and for KRAS mutations it was 27%. Despite the conventional understanding that EGFR and KRAS mutations are mutually exclusive, we identified two dual mutations. Of 29 patients identified with mutated EGFR, there were 3/8/8/10 mutations in exons 18/19/20/21 respectively. Exon 20 mutations were identified in a proportion exceeding many other series because of the unbiased mutation analysis used, and clinical benefit was seen in some of these. Of 23 different EGFR mutations identified, 11 have not previously been described in the literature. Conclusions: The high prevalence of EGFR, KRAS or both mutations (40%) in this non-squamous population tested in clinical practice supports a policy of routine screening for these mutations in NSCLC.

Comparative analysis of recovery of cardiopulmonary bypass residual blood: cell saver vs. hemoconcentrator.

For surgical bleeding problems, the cell saver has been used to return shed blood; however, overuse can lead to a deficit in coagulation factors. Its usefulness has gained widespread use in many surgical settings. The hemoconcentrator can aid in raising the hematocrit level while reducing blood utilization where large blood volume and/or large amounts of irrigation are returned to the perfusion circuit. The hemoconcentrator returns red blood cells without removing coagulation factors, unlike the cell saver. In order to determine which method of returning residual blood from the cardiopulmonary bypass circuit is more desirable, blood samples were drawn both pre and post transfusion from 15 cell saver patients, and 14 hemoconcentrator patients. Twelve hour blood loss was recorded in 40 patients within each group. The fibrinogen, platelet count, total protein, albumin and white blood cell count were similar between the two groups, as was the blood loss. The only significant differences found were the post red blood cell count, post hemoglobin, and the delta hematocrit, all being higher in autotransfusion group. In conclusion, returning blood through the hemoconcentrator in the average adult perfusion circuit was not able to significantly raise certain coagulation parameters, nor reduce postoperative bleeding.

New perspectives in the pulmonary circulation and hypoxic pulmonary vasoconstriction.

In the past few years there has been a reawakening of interest in the systems that underly pulmonary vascular control and an increased awareness of the clinical potential of pharmacological manipulation of the pulmonary circulation. Nevertheless, although so much has been learned about the physiological role of the endothelium, vasoactive substances, and neural modulation of the pulmonary vasculature; how these disparate influences interact to control the matching of ventilation to perfusion remains uncertain. Consequently, even less is known of the way in which lung injury influences these regulatory processes. It is likely that the response to hypoxia may involve a system with many pathways and much redundancy, such that blockade of the production of a single agent has only a minor effect on HPV. We speculate that the products of arachidonic acid metabolism, PAF, adenosine and EDRF, may act in concert with neural pathways in a 'microenvironment' bounded by the alveolus and endothelium to modify pulmonary vascular tone during both normoxic and hypoxic conditions.

Sensory neuropeptides and hypoxic pulmonary vasoconstriction in the rat.

BACKGROUND: Endogenous vasodilators such as endothelially derived relaxant factor have been shown to modulate hypoxic pulmonary vasoconstriction. Sensory peptides such as substance P (SP) and calcitonin gene related peptide (CGRP) are also potent pulmonary vasodilators in both animals and humans. Their possible role in the modulation of the normal hypoxic pressor response has been examined in an isolated, ventilated, and blood perfused rat lung preparation. METHODS: Animals (n = 7) were pretreated with 50 mg/kg capsaicin administered subcutaneously to deplete nerve endings of sensory neuropeptides. A control group (n = 7) received a subcutaneous dose of capsaicin vehicle. One week later the rats were killed and the rise in pulmonary artery pressure was measured during four successive periods of hypoxic ventilation (FIO2 0.03), and after four injections of angiotensin II (1.0 microgram). RESULTS: A 60% depletion of SP levels was measured in the sciatic nerves of animals treated with capsaicin. The hypoxic pressor response was not significantly altered in capsaicin treated animals compared with controls, except during the fourth hypoxic episode when it was augmented. The angiotensin II pressor response was the same in both groups during each of the injections. CONCLUSION: The sensory neuropeptide SP (and possibly CGRP) does not have a major role in modulating the pulmonary vascular response to hypoxia.

Endothelium-derived relaxing factor activity in rat lung during hypoxic pulmonary vascular remodeling.

We have investigated the role of endothelium-derived relaxing factor in modulating hypoxic pulmonary vasoconstriction by inhibiting its synthesis with the false substrate NG-monomethyl-L-arginine (L-NMMA) in the isolated blood-perfused lungs of Wistar rats after chronic hypoxia (CH, fractional inspiratory O2 concentration 10%) for 15 h, 2 days, and 7 days. Lungs were perfused with blood of normal hematocrit at constant flow (18 ml/min) ventilated with 1) 95% air-5% CO2 (normoxia) and 2) 2% O2-5% CO2-93% N2 (hypoxia) and were studied in the absence and presence of L-NMMA (30 and 300 microM) or L-arginine (L-Arg, 1 and 6 mM) in separate groups. Pulmonary arterial pressure (Ppa) rose incrementally with hypoxic exposure (all P < 0.05 vs. normoxic control group). Hypoxic pulmonary vasoconstriction (HPV) was markedly reduced after 15 h and 2 days of CH: the mean increases in Ppa (delta Ppa) in hypoxia were 15.3, 3.5, 3.8, and 13.6 mmHg in control rats and rats exposed to 15 h (P < 0.05 vs. control and 7 days of CH), 2 days (P < 0.001 vs. control and 7 days of CH), and 7 days of CH, respectively. Ppa in control rats and rats exposed to 15 h, 2 days, and 7 days of CH were 137, 179, 184, and 166% of control, respectively, after 30 microM L-NMMA (all P < 0.05 when expressed as percent change vs. no L-NMMA). Similar augmentation in HPV was seen after 30 microM L-NMMA, with all hypoxic groups having a greater response than control groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of nitric oxide and guanosine 3',5'-cyclic monophosphate in mediating nonadrenergic, noncholinergic relaxation in guinea-pig pulmonary arteries.

1. Nonadrenergic, noncholinergic (NANC) nerves mediate vasodilatation in guinea-pig pulmonary artery (PA) by both endothelium-dependent and endothelium-independent mechanisms. The transmitter(s) involved in the endothelium-independent pathway have not yet been identified. We have therefore investigated the possibility that nitric oxide (NO) and guanosine 3',5'-cyclic monophosphate (cyclic GMP) may mediate this neural vasodilator response in guinea-pig branch PA rings denuded of endothelium. 2. Electric field stimulation (EFS, 50 V, 0.2 ms) induced a frequency-dependent (1-24 Hz), tetrodotoxin-sensitive relaxation of the U44069-precontracted PA rings in the presence of adrenergic and cholinergic blockade. 3. The NO synthase inhibitors NG-monomethyl L-arginine (L-NMMA, 100 microM) and NG-nitro L-arginine methyl ester (L-NAME, 30 microM), and the guanylyl cyclase inhibitor methylene blue (5 microM) inhibited the EFS (16 Hz)-induced relaxation by 53 +/- 5, 74 +/- 9 and 82 +/- 9% respectively (n = 5-7, P < 0.01, compared with control rings). 4. Excess concentrations of L-, but not D-arginine (300 microM) completely reversed the inhibitory effect of L-NMMA. 5. The EFS-elicited relaxation (4 Hz) was potentiated by 1 microM zaprinast, a type V phosphodiesterase inhibitor which inhibits guanosine 3':5'-cyclic monophosphate (cyclic GMP) degradation, but was unaffected by 0.1 microM zardaverine, a type III/IV phosphodiesterase inhibitor which inhibits cyclic AMP degradation. 6. EFS (50 V, 0.2 ms, 16 Hz) induced a 3 fold increase in tissue cyclic GMP content, an action which was inhibited by L-NMMA (100 microM). 7. Pyrogallol (100microM), a superoxide anion generator, also inhibited the EFS-induced relaxation by 53 +/- 9%, and this effect was prevented by superoxide dismutase.8. Chemical sympathetic denervation with 6-hydroxydopamine had no effect on the relaxant response to EFS in the endothelium-denuded PA rings.9. In endothelium-denuded branch PA rings at resting tone, L-NMMA (100 microM) significantly augmented the adrenergic contractile response, an effect which was completely reversed by L-arginine,but not by D-arginine. In the same groups of vessel rings, L-NMMA had no significant effect on the matched contractile response to exogenous noradrenaline.10. These results suggest that NO may be released from intramural nerve endings other than adrenergic nerves (probably NANC nerves), and this leads to vasodilatation via activation of guanylyl cyclase.

Chronic hypoxia impairs soluble guanylyl cyclase-mediated pulmonary arterial relaxation in the rat.

We have examined the effects of exposing rats to hypoxia (10% fractional inspired O2 concentration) for 2 and 7 days on endothelium-dependent and -independent vasodilation and also on the ability of guanosine 3',5'-cyclic monophosphate (cGMP) to activate cGMP-dependent protein kinase (G-kinase) in rat conduit pulmonary arteries (PA). The ability of acetylcholine (ACh) and sodium nitroprusside (SNP) to both relax PA rings and elevate tissue cGMP levels was significantly attenuated in PA from hypoxic animals. The ability of atrial natriuretic peptide to relax and generate cGMP in PA rings was unchanged by hypoxia. Relaxation and elevation of cGMP levels induced by SNP in aortic rings was unaltered by hypoxia. Similarly, hypoxia did not alter the concentration-dependent activation by exogenous cGMP of G-kinase. We conclude that chronic exposure of rats to hypoxia results in a selective impairment of soluble guanylyl cyclase in rat PA, leading to an attenuation of ACh- and SNP-induced cGMP accumulation and relaxation.

Bleomycin-induced acute lung injury in the rat does not influence pulmonary vascular responsiveness in vitro.

OBJECTIVE: To investigate the effects of the intratracheal and iv administration of bleomycin on the contraction and endothelially dependent vasodilation of rat pulmonary arteries in vitro. DESIGN: Prospective pharmacologic study. SETTING: National Heart and Lung Institute, London, UK. INTERVENTIONS: Intratracheal saline, intratracheal and iv bleomycin. MEASUREMENTS AND MAIN RESULTS: Rats treated with intratracheal bleomycin developed a significant increase in mean lung wet/dry weight ratio (5.6 +/- 0.4 [SEM] vs. 3.9 +/- 0.1, p less than .05) when compared with saline-treated control animals, confirming the development of pulmonary edema. However, these rats displayed normal relaxant responses to the endothelially dependent vasodilator acetylcholine and a normal contractile response to phenylephrine in vitro. Intravenous bleomycin had no effect on either wet/dry weight ratio or the response to either drug. CONCLUSIONS: Despite evidence for the loss of endothelial integrity that characterizes lung injury after intratracheal bleomycin, isolated pulmonary artery rings in vitro showed no loss of endothelial cell function. The role of the endothelium in modulating pulmonary ventilation/perfusion matching after lung injury is unclear.

Endothelin-3 is a potent pulmonary vasodilator in the rat.

The properties of endothelin-3 (ET-3) were investigated in isolated pulmonary artery rings and isolated blood-perfused lungs of the rat. ET-3 elicited a concentration-dependent relaxation of pulmonary artery rings, and effect inhibited by the nitric oxide synthesis inhibitor L-NG-monomethyl-L-arginine. At 0.1 microM, the response to ET-3 was biphasic, resulting in a sustained contraction. In the isolated lung, ET-3 caused a dose-dependent increase in pulmonary arterial pressure. In lungs ventilated with 3% oxygen, 10 nM ET-3 completely reversed the resultant hypoxic vasoconstriction (HPV) by 100 +/- 8%, an effect unchanged by either indomethacin (1 microM) or glibenclamide (10 microM). L-NG-monomethyl-L-arginine attenuated both the ET-3 dilation in prostaglandin F2 alpha-constricted lungs and the dose-dependent vasodilation of HPV by acetylcholine. ET-3 (10 nM) showed the response time to peak pulmonary arterial pressure generation by hypoxia, the size of the response being unchanged. These results demonstrate that ET-3 has both vasodilator and constrictor actions in the rat lung and that, like acetylcholine, the former is mediated in part via the release of nitric oxide. ET-3 also has the ability to modulate HPV.

Effect of tumor necrosis factor on hypoxic pulmonary vasoconstriction.

The effects of tumor necrosis factor (TNF) on hypoxic pulmonary vasoconstriction (HPV) and endothelium-dependent relaxation were examined in a blood-perfused rat lung preparation. Lungs from TNF-treated rats (0.26 mg/kg iv 12 h before experimentation) had a significantly greater HPV and a reduced vasorelaxant response to the endothelium-dependent vasodilator acetylcholine (ACh) but a similar vasorelaxant response to the endothelium-independent vasodilator nitroprusside compared with lungs from control rats (pretreated with 0.1 ml saline iv). Pentoxifylline (20 mg/kg iv and ip 20 min before administration of TNF) had no detectable effect on either HPV or ACh-induced relaxation but completely negated the augmentation on HPV and the inhibiting action on ACh-induced relaxation caused by TNF. The TNF effect on ACh relaxation was unaffected by pretreatment with L-arginine. These results indicate that TNF induces endothelial dysfunction and enhances HPV, effects that are inhibited by pentoxifylline.

Bleomycin-induced lung injury in rats selectively abolishes hypoxic pulmonary vasoconstriction: evidence against a role for platelet-activating factor.

1. The role of platelet-activating factor in the attenuated hypoxic pulmonary vasoconstriction associated with lung injury was evaluated using specific platelet-activating factor antagonists and an isolated perfused lung preparation. 2. Intratracheal bleomycin was administered to rats to produce acute lung injury. Animals received intratracheal saline (control), intratracheal bleomycin or the platelet-activating factor antagonists BN 52021, WEB 2170 or WEB 2086 before and after bleomycin treatment. Forty-eight hours after intratracheal administration of bleomycin or saline the animals were killed. 3. The increases in pulmonary artery pressure during two periods of hypoxic ventilation and in response to 0.2 microgram of angiotensin II were measured. Acetylcholine-induced vasodilatation after pre-constriction with prostaglandin F2 alpha was also measured. To quantify lung injury, the wet/dry ratio of lung weight was determined. 4. Bleomycin treatment attenuated the first and second hypoxic pressor responses by 93% and 77%, respectively, but not the pressor response to angiotensin II nor the vasodilator response to acetylcholine. BN 52021 plus bleomycin augmented the first hypoxic pressor response compared with bleomycin treatment alone, but the structurally unrelated platelet-activating factor antagonists WEB 2170 and WEB 2086 had no significant effect on the bleomycin-induced attenuation of hypoxic pulmonary vasoconstriction. None of the platelet-activating factor antagonists blocked the increase in the wet/dry lung weight ratio induced by bleomycin. 5. Bleomycin-induced lung injury selectively attenuates hypoxic pulmonary vasoconstriction, an effect that does not appear to be mediated by platelet-activating factor. The mechanism remains to be elucidated, but may involve destruction of the hypoxic 'sensor' within the respiratory tract.

Endothelium-dependent nonadrenergic, noncholinergic neural relaxation in guinea pig pulmonary artery.

The presence and the possible mechanism of action of the inhibitory nonadrenergic, noncholinergic nerve system (i-NANC) were investigated in guinea pig pulmonary artery (PA) precontracted with U44069 (a thromboxane analog). In the presence of alpha adrenergic blockage, electrical field stimulation induced a frequency-dependent, tetrodotoxin-sensitive relaxation. This relaxation was reduced by 9.1 +/- 1.9 and 19.4 +/- 2.8% by atropine (1 microM) and combined atropine and propranolol (both 1 microM), indicating that the main component is mediated by i-NANC neural mechanisms. In the branch PA rings, this i-NANC relaxation was unaffected by pretreatment with a cyclooxygenase inhibitor (indomethacin, 10 microM), 5-lipoxygenase inhibitor (A63162, 1 microM) or substance P desensitization, but was inhibited markedly by the P2y-purinoceptor antagonist reactive blue 2 (30 microM) and slightly potentiated by the peptidase alpha-chymotrypsin (2 U/ml). L-NG-monomethyl-arginine(L-NMMA), a nitric oxide synthesis inhibitor, caused a concentration-dependent inhibition of the i-NANC relaxation (53.9 +/- 4.1% at 100 microM), but had no effect on equivalent nitroprusside-induced relaxation. The inhibitory effect of L-NMMA was reversed completely by L-arginine (300 microM), but not by D-arginine (300 microM). Removal of vascular endothelium greatly reduced the i-NANC relaxation in the branch PA rings, but had no effect on i-NANC relaxation in main PA rings. Both in vivo capsaicinization and in vitro desensitization with capsaicin (1 microM) caused a significant reduction of the i-NANC relaxation in main PA, but had no significant effect in the branch PA.(ABSTRACT TRUNCATED AT 250 WORDS)

Endogenous nitric oxide modulates adrenergic neural vasoconstriction in guinea-pig pulmonary artery.

1. Electrical field stimulation (EFS) of guinea-pig isolated pulmonary artery induced a frequency-dependent contraction. This was abolished by tetrodotoxin (1 microM) and prevented by phentolamine and prazosin (both 1 microM), indicating a role for alpha 1-adrenoceptors activated by noradrenaline (NA) released from perivascular adrenergic nerves. 2. L-NG-monomethyl arginine (L-NMMA, 0.3-100 microM) caused a concentration-dependent enhancement of the EFS-induced contraction with a 3.4 +/- 0.5 fold increase at 100 microM n = 6). The augmenting effect of 30 microM L-NMMA on the contraction to EFS was completely reversed by 100-300 microM L-arginine, but not by an identical concentration of D-arginine. 3. The contractile response to exogenous NA was similarly enhanced by 30 microM L-NMMA (2.9 +/- 0.6 fold increase, n = 5). 4. The contractile responses to exogenous phenylephrine and prostaglandin F2 alpha while matched the contraction to EFS (4 Hz) were equally augmented by 30 microM L-NMMA. 5. In vessel rings submaximally contracted with the thromboxane analogue U44069 (2 microM), the selective alpha 2-adrenoceptor agonist UK14304 induced concentration-dependent relaxation, which was abolished by removal of endothelium. NA had little relaxant effect on these precontracted vessel rings unless in the presence of prazosin (1 microM). 6. Indomethacin had no significant effect on the contractile response to EFS or NA, indicating that vasodilator cyclo-oxygenase products such as prostacyclin are not involved in modulating these responses. 7. Our results suggest that endogenous nitric oxide inhibits the contractile response to adrenergic nerve stimulation in the guinea-pig pulmonary artery by a postjunctional mechanism, but release of prostacyclin does not modulate these responses. Basal release of nitric oxide from endothelial cells may account for this inhibition.

Endothelium-derived relaxing factor inhibits hypoxic pulmonary vasoconstriction in rats.

The hypothesis that endothelium-derived relaxing factor (EDRF) modulates hypoxic pulmonary vasoconstriction (HPV) was tested in isolated, blood-perfused rat lungs ventilated with gas mixtures of 21% O2-5% CO2-74% N2 (normoxia) or of 3% O2-5% CO2-92% N2 (hypoxia); 30 microM NG-monomethyl-L-arginine (L-NMMA), an inhibitor of EDRF production, caused a reduction in the endothelium-dependent relaxant response to acetylcholine (ACh) from 62 +/- 7, 88 +/- 4, and 100 +/- 4% to 26 +/- 8, 49 +/- 12, and 75 +/- 7% at ACh concentrations of 1, 10, and 100 microM, respectively (p less than 0.05 at all concentrations), indicating that L-NMMA acts via the inhibition of EDRF production. L-NMMA induced a concentration-related augmentation in HPV of 20 +/- 5, 32 +/- 8, and 34 +/- 8% at concentrations of 30, 300, and 1,000 microM (p less than 0.05, compared with a vehicle control group at all concentrations). The pressor response to a dose of angiotensin II (A-II), which produced the same increase in pulmonary artery pressure as that induced by hypoxia, was also significantly augmented (2 +/- 0.6%), but to a lesser extent. The augmentation of HPV by 30 microM L-NMMA was completely reversed by 1 mM L-arginine (a precursor of EDRF), but not by D-arginine (an isomer of L-arginine). One and 6 mM L-arginine, but not 6 mM D-arginine caused a significant inhibition of HPV by 20 +/- 2 and 47 +/- 12% (p less than 0.05, compared with the vehicle control group) and a small but not significant reduction in A-II-mediated contraction.(ABSTRACT TRUNCATED AT 250 WORDS)

Inhibitory role of endothelium-derived relaxing factor in rat and human pulmonary arteries.

1. The inhibitory role of endothelium-derived relaxing factor was studied in both rat and human pulmonary arteries in vitro by inhibiting its synthesis with the L-arginine analogue NG-monomethyl-L-arginine (L-NMMA). 2. In rat pulmonary arteries, L-NMMA pretreatment (10-300 microM) dose-dependently inhibited acetylcholine-induced relaxation (which is endothelium-dependent). NG-monomethyl-D-arginine (D-NMMA, 100 microM) was without effect. L-Arginine, but not D-arginine, dose-dependently reversed this inhibition. L-NMMA had no effect on relaxation induced by sodium nitroprusside. 3. In human small pulmonary arteries L-NMMA (100 microM) pretreatment similarly inhibited the acetylcholine-induced relaxation but had no effect on the sodium nitroprusside-induced relaxation. 4. In both rat and human pulmonary arteries, L-NMMA, but not D-NMMA, always caused contraction of preconstricted tissues whereas it had no effect on baseline tone. In the rat this contraction was completely prevented by prior treatment with L-arginine. 5. L-NMMA (100 microM) pretreatment mimicked the effect of endothelium removal on phenylephrine-induced vasoconstriction, both resulting in an increase in tension development at each concentration of phenylephrine. This enhancement was greatest at low concentrations of phenylephrine but was still present even at the highest concentrations. Pretreatment with L-NMMA (100 microM) also significantly increased the responses to single doses of phenylephrine. 6. These results suggest that endothelium-derived relaxing factor from endothelial cells both mediates the relaxation response to acetylcholine and also acts as a physiological brake against vasoconstriction in pulmonary vessels.

Enterocystoma of the head and neck.

Enterocystomas of the head and neck are exceedingly rare lesions; only 21 cases have been reported previously. We describe a case of a newborn infant with an enterocystoma of the anterior tongue. All of the previously reported cases and the three theories of embryogenesis are reviewed. Diagnostic evaluation includes computerized axial tomography and radioiodine thyroid scan, particularly if the tongue is involved. Complete surgical excision is the only appropriate therapy and is curative.