Human cytomegalovirus seropositivity is associated with reduced patient survival during sepsis.

BACKGROUND: Sepsis is one of the leading causes of death. Treatment attempts targeting the immune response regularly fail in clinical trials. As HCMV latency can modulate the immune response and changes the immune cell composition, we hypothesized that HCMV serostatus affects mortality in sepsis patients. METHODS: We determined the HCMV serostatus (i.e., latency) of 410 prospectively enrolled patients of the multicenter SepsisDataNet.NRW study. Patients were recruited according to the SEPSIS-3 criteria and clinical data were recorded in an observational approach. We quantified 13 cytokines at Days 1, 4, and 8 after enrollment. Proteomics data were analyzed from the plasma samples of 171 patients. RESULTS: The 30-day mortality was higher in HCMV-seropositive patients than in seronegative sepsis patients (38% vs. 25%, respectively; p = 0.008; HR, 1.656; 95% CI 1.135-2.417). This effect was observed independent of age (p = 0.010; HR, 1.673; 95% CI 1.131-2.477). The predictive value on the outcome of the increased concentrations of IL-6 was present only in the seropositive cohort (30-day mortality, 63% vs. 24%; HR 3.250; 95% CI 2.075-5.090; p < 0.001) with no significant differences in serum concentrations of IL-6 between the two groups. Procalcitonin and IL-10 exhibited the same behavior and were predictive of the outcome only in HCMV-seropositive patients. CONCLUSION: We suggest that the predictive value of inflammation-associated biomarkers should be re-evaluated with regard to the HCMV serostatus. Targeting HCMV latency might open a new approach to selecting suitable patients for individualized treatment in sepsis.

Tooth agenesis in German orthodontic patients with non-syndromic craniofacial disorder: a retrospective evaluation of panoramic radiographs.

OBJECTIVES: The study objective was to evaluate the tooth agenesis in German orthodontic patients with non-syndromic cleft lip and/or palate and Robin sequence compared to a control group without craniofacial disorder. MATERIALS/METHODS: A total of 108 panoramic radiographs were examined using the binary system of Tooth Agenesis Code (TAC) (excluding the third molar). Patients were divided into the craniofacial disorder group 1 (n = 43) and the healthy control group 2 (n = 65). Parameters such as skeletal class malformation, sex, localization of the cleft, craniofacial disorder, and interobserver reliability were assessed. RESULTS: Permanent tooth agenesis was observed in 44% of group 1 and 14% in group 2 with a statistically significant higher prevalence (p = 0.00162 (χ2)). Fourteen different TAC patterns were observed in group 1, ten of these occurring only once in separate patients. The distribution of the TAC codes in group 2 showed nine different possibilities of TAC code patterns; seven TACs were unique. In group 1, the most frequently absent teeth were the maxillary lateral incisor of the left side (30%); in group 2, the second premolar of the lower jaw on the right side (9%). Male patients with craniofacial disorder showed a higher percentage of tooth agenesis than female. CONCLUSION: The data presented here shows a statistically significant higher prevalence of tooth agenesis in German patients with non-syndromic craniofacial disorder. CLINICAL RELEVANCE: Radiographic evaluation enables the diagnosis of tooth agenesis. Recognizing early on the higher prevalence of tooth agenesis in patients exhibiting a craniofacial disorder is an important issue when developing long-term and comprehensive interdisciplinary treatment.

Technical note on introducing a digital workflow for newborns with craniofacial anomalies based on intraoral scans - part I: 3D printed and milled palatal stimulation plate for trisomy 21.

BACKGROUND: Advanced digital workflows in orthodontics and dentistry often require a combination of different software solutions to create patient appliances, which may be a complex and time-consuming process. The main objective of this technical note is to discuss treatment of craniofacial anomalies using digital technologies. We present a fully digital, linear workflow for manufacturing palatal plates for infants with craniofacial anomalies based on intraoral scanning. Switching to intraoral scanning in infant care is advantageous as taking conventional impressions carries the risk of impression material aspiration and/or infections caused by material remaining in the oronasal cavity. MATERIAL AND METHODS: The fully digital linear workflow presented in this technical note can be used to design and manufacture palatal plates for cleft palate patients as well as infants with functional disorders. We describe the workflow implemented in an infant with trisomy 21. The maxilla was registered using a digital scanner and a stimulation plate was created using dental CAD software and an individual impression tray module on a virtual model. Plates were manufactured using both additive and subtractive methods. Methacrylate based light curing resin and Poly-Ether-Ether-Ketone were the materials used. RESULTS: The palatal area was successfully scanned to create a virtual model. The plates fitted well onto the palatal area. Manual post-processing was necessary to optimize a functional ridge along the vestibular fold and remove support structures from the additively manufactured plate as well as the milled plate produced from a blank. The additively manufactured plate fitted better than the milled one. CONCLUSION: Implementing a fully digital linear workflow into clinical routine for treatment of neonates and infants with craniofacial disorders is feasible. The software solution presented here is suitable for this purpose and does not require additional software for the design. This is the key advantage of this workflow, which makes digital treatment accessible to all clinicians who want to deal with digital technology. Whether additive or subtractive manufacturing is preferred depends on the appliance material of choice and influences the fit of the appliance.

Technical note on introducing a digital workflow for newborns with craniofacial anomalies based on intraoral scans - part II: 3D printed Tübingen palatal plate prototype for newborns with Robin sequence.

BACKGROUND: Orthodontic treatment of newborns and infants with Robin-Sequence using the Tübingen Palatal Plate (TPP) is a complex procedure that could benefit from simplification through digitalization. The design of the velar extension (spur) and the palatal base determines the success of the treatment. Therefore, a prototype must be produced and inserted under endoscopic supervision in order to determine the appropriate shape, length and position of the spur. This technical note demonstrates a fully digital workflow for the design and manufacturing of a functional TPP prototype, based on an intraoral scan. This prototype can be altered and individualized digitally for each patient. After the shape and position of the spur have been optimized, the prototype is duplicated using a silicone mold. Then the definitive TPP is manufactured and inserted. We aim to present a workflow which facilitates the fitting procedure and does not require a conventional impression or a physical model to create the appliance. METHODS: As described in part I of this series, the intraoral scan is performed using the 3Shape TRIOS3 scanner and its corresponding acquisition software. The virtual model is rendered in the 3Shape ortho appliance designer and the base of the palatal plate is designed in the 3Shape dental designer. The palatal plate and the virtual model are then imported into Autodesk Meshmixer and a standardized spur is positioned and merged with the base. The TPP is exported in Standard Tessellation Language (STL) format and manufactured on a W2P Solflex 170 DLP printer using VOCO VPrint Splint material (MDR Class IIa). RESULTS: Based on an intraoral scan, the TPP prototype could be successfully manufactured and proved suitable for the patients' treatment. CONCLUSION: The new digital workflow for the design of the TPP can been successfully implemented into daily clinical routine in our facility. Patients could be alleviated from having to undergo conventional impression procedures and fitting of the TPP could be facilitated by producing multiple functional prototypes for endoscopic evaluation. Through rapid prototyping, the expenditure of the fitting process was reduced, which makes the TPP therapy more efficient and accessible to a wider range of clinicians.

Maxillary canine position of patients with non-syndromic craniofacial disorder: a retrospective evaluation of panoramic radiographs.

BACKGROUND: The study evaluates the position and displacement tendency of unerupted maxillary canines in orthodontic patients with non-syndromic craniofacial disorders (CD) compared to a control (C) group. METHODS: Canine position and displacement tendency were evaluated using panoramic radiographs (PAN) examined with parameters such as sector classification (sectors 1-5) and inclination angles (α and ß). The displacement tendency was defined as the positioning of the tip in sectors 1 or 2, as well as its combination with increased angles (α > 30° and ß > 39°). In addition, the correlation of the tooth position and agenesis, cleft side, and sex was assessed. RESULTS: A total of 116 pre-treatment PAN, divided into the CD group (n = 50; mean age 8.32 ± 2.27 years) and the C group (n = 66; mean age 10.80 ± 2.82 years), were evaluated in this study. The sector classification showed no displacement tendency in both groups. Inclination angles α/ß showed a statistically significant higher displacement tendency (p = 0.01) of the CD group (n = 5) on the right side, compared to healthy subjects (n = 1). Male CD patients had a statistically significant higher displacement tendency on the right side (p = 0.03). A statistically significant correlation between cleft and non-cleft-side (p = 0.03) was found. CONCLUSION: Patients with CD showed a statistically significant higher displacement tendency of the maxillary canine affected by the cleft side. The inclination angle was found to be the better predictor compared to the sector classification which should be considered in the orthodontic treatment planning.

Retrospective evaluation of the orthodontic treatment needs in primary school children with Robin sequence following Tübingen palatal plate therapy in infancy.

INTRODUCTION: The aim of this study was to investigate the orthodontic treatment needs (OTN) of children with RS treated with the TPP in infancy compared to age- and sex-matched controls. METHODS: The aim of this study was to investigate the orthodontic treatment needs (OTN) of children with RS treated with the TPP in infancy compared to age- and sex-matched controls. RESULTS: In 21 children with RS (n = 23; 19 non-syndromic, 4 syndromic; average age 9.9 years) showed high OTN, which was significantly higher than in controls (n = 21). The latter of 9 controls had minor OTN, followed by 8 participants with borderline OTN. Regarding the intraoral picture, patients with RS had an increased open bite tendency. Without considering the presence of a cleft palate, 16 children with RS had high or very high OTN, compared to 4 of controls. CONCLUSIONS: Patients with RS have significantly higher OTN than healthy controls, independent of cleft occurrence. RS is associated with dental anomalies and special skeletal growth patterns, both increasing malocclusion and negatively affecting dentoalveolar growth. This should raise awareness for identifying these needs and provide a comprehensive orthodontic treatment, where functional rehabilitation should be favored over aesthetic results.

Communication: Magnetic dipole transitions in the OH A 2Σ+ ← X 2Π system.

We report on the observation of magnetic dipole allowed transitions in the well-characterized A (2)Σ(+) - X (2)Π band system of the OH radical. A Stark decelerator in combination with microwave Rabi spectroscopy is used to control the populations in selected hyperfine levels of both Λ-doublet components of the X (2)Π(3/2), v = 0, J = 3/2 ground state. Theoretical calculations presented in this Communication predict that the magnetic dipole transitions in the A (2)Σ(+), v = 1 ← X (2)Π, v = 0 band are weaker than the electric dipole transitions by a factor of 2.58 × 10(3) only, i.e., much less than commonly believed. Our experimental data confirm this prediction.

Scattering resonances in slow NH3-He collisions.

We theoretically study slow collisions of NH(3) molecules with He atoms, where we focus in particular on the observation of scattering resonances. We calculate state-to-state integral and differential cross sections for collision energies ranging from 10(-4) cm(-1) to 130 cm(-1), using fully converged quantum close-coupling calculations. To describe the interaction between the NH(3) molecules and the He atoms, we present a four-dimensional potential energy surface, based on an accurate fit of 4180 ab initio points. Prior to collision, we consider the ammonia molecules to be in their antisymmetric umbrella state with angular momentum j = 1 and projection k = 1, which is a suitable state for Stark deceleration. We find pronounced shape and Feshbach resonances, especially for inelastic collisions into the symmetric umbrella state with j = k = 1. We analyze the observed resonant structures in detail by looking at scattering wavefunctions, phase shifts, and lifetimes. Finally, we discuss the prospects for observing the predicted scattering resonances in future crossed molecular beam experiments with a Stark-decelerated NH(3) beam.

Resonances in rotationally inelastic scattering of OH(X2Π) with helium and neon.

We present detailed calculations on resonances in rotationally and spin-orbit inelastic scattering of OH (X(2)Π, j = 3/2, F(1), f) radicals with He and Ne atoms. We calculate new ab initio potential energy surfaces for OH-He, and the cross sections derived from these surfaces compare well with the recent crossed beam scattering experiment of Kirste et al. [Phys. Rev. A 82, 042717 (2010)]. We identify both shape and Feshbach resonances in the integral and differential state-to-state scattering cross sections, and we discuss the prospects for experimentally observing scattering resonances using Stark decelerated beams of OH radicals.

Oral health-related quality of life in patients with cleft lip and/or palate or Robin sequence.

PURPOSE: To compare the oral health-related quality of life (OHRQoL) in patients with cleft lip and/or palate or Robin sequence versus a healthy control group using the Child Oral Health Impact Profile (COHIP-G19). Factors such as age, gender, and cleft type were considered. METHODS: Over an 8-month period, the OHRQoL was surveyed by using the COHIP-G19 questionnaire. Included were patients with a craniofacial disorder (n = 61; average age 11.24 years) and a healthy control group (n = 70, average age 12.63 years) for a total of 131 patients (average age 11.99 years) from the Department of Orthodontics University Hospital Tübingen, Germany. These were divided into two age groups (6-11 years; 12-18 years). RESULTS: Statistically, patients with a craniofacial disorder presented a significantly lower OHRQoL than the control group (p = 0.0055). In the craniofacial disorder group, older patients revealed a significantly (p = 0.005) lower OHRQoL than the younger patients. Female patients showed in nearly all groups a better OHRQoL than male patients, but this difference was not statistically significant (p > 0.05). Males with a craniofacial disorder scored significantly lower than males without (p = 0.016); females showed no differences between the groups. Visibility, location, and severity of the craniofacial malformation did not have a significant influence on the OHRQoL. CONCLUSION: The occurrence of a craniofacial malformation impacted the OHRQoL especially in older and male affected patients, unrelated to the expression level or localization. An early instruction about oral health, rehabilitation and functional training should be considered in therapy.

Characterization of [125I]ZM 241385 binding to adenosine A2A receptors in the pineal of sheep brain.

Adenosine is a ubiquitous neuromodulator and homeostatic regulator that exerts its physiologic actions through activation of A(1), A(2A), A(2B) and A(3) adenosine receptor subtypes. In the central nervous system, adenosine's action in neurons is manifested in its modulation of tonic inhibitory control. Adenosine released in the brain during hypoxia has critical depressant effects on breathing in fetal and newborn mammals, an action suggested to be mediated by A(2A) receptors in the posteromedial thalamus. In an effort to more accurately define the spatial distribution of adenosine A(2A) receptors in fetal sheep diencephalon, we have used a receptor autoradiographic technique utilizing an iodinated radioligand [(125)I]ZM 241385, which has greater sensitivity and resolution than the tritiated compound. The distribution of ligand binding sites in the fetal sheep diencephalon indicated that the highest levels of binding were in select thalamic nuclei, including those implicated in hypoxic depression of fetal breathing, and the pineal. Given the high density of labeled A(2A) receptors in the pineal, these sites were characterized more fully in homogenate radioligand binding assays. These data indicate that [(125)I]ZM 241385 binding sites display a pharmacological signature consistent with that of adenosine A(2A) receptors and are expressed at similar levels in fetal, lamb and adult ovine brain. The adenosine A(2A) receptor pharmacologic signature of the [(125)I]ZM 241385 binding site in pineal cell membranes generalized to the site characterized in membranes derived from other portions of the lamb thalamus, including the sector involved in hypoxic inhibition of fetal breathing. These results have important implications for the functional roles of adenosine A(2A) receptors in the thalamus and pineal of sheep brain.

Juvenile idiopathic arthritis and the temporomandibular joint: A comprehensive review.

Juvenile idiopathic arthritis is the most common inflammatory rheumatic disease of childhood and represents a series of chronic inflammatory arthritides of unknown cause. Involvement of the temporomandibular joint has been reported in up to 87% of children with juvenile idiopathic arthritis when based on magnetic tomography imaging; it can be asymptomatic and may lead to severe long term complications. In this review a summary of the contemporary literature of imaging of the temporomandibular joint in children with juvenile idiopathic arthritis will be provided, including ultrasound which is a valuable method for guided joint injections, but does not necessarily allow detection of acute inflammation, cone beam computed tomography, which has emerged as a feasible and accurate low-dose alternative as compared to conventional computed tomography to detect destructive change, and magnetic resonance imaging which is considered the method of choice for assessing acute, inflammatory change, although the lack of normative standards remains a challenge in children.

Pregnancy outcomes after the Fontan repair.

OBJECTIVES: This study sought to determine risks and outcome of pregnancy and delivery after the modified Fontan operation. BACKGROUND: Increasingly, female Fontan patients reaching child-bearing years are interested in having children. To date, the number of reported pregnancies is small, and pregnancy has therefore been discouraged. METHODS: One hundred ten of 126 female patients from the Fontan registries of the Mayo Clinic and University of California Los Angeles Medical Center responded to a mailed questionnaire. An additional six patients with a reported pregnancy from other centers were identified and reviewed to assess pregnancy outcomes. RESULTS: Among the participating centers, a total of 33 pregnancies after Fontan operation for various types of univentricular heart disease were reported. There were 15 (45%) live births from 14 mothers, with 13 spontaneous abortions and 5 elective terminations. In the 14 women with live births, the median number of years between operation and pregnancy was 4 (range 2 to 14). Reported prepregnancy problems in these gravidas included atrial flutter in one patient and ventricular dysfunction, aortic regurgitation and atrioventricular valve regurgitation in another. One patient developed supraventricular tachycardia during pregnancy and had conversion to sinus rhythm. No maternal cardiac complications were reported during labor, delivery or the immediate puerperium. There were six female and nine male infants (mean gestational age 36.5 weeks; median weight 2,344 g). One infant had an atrial septal defect. At follow-up, mothers and infants were alive and well. CONCLUSIONS: Pregnancy after the Fontan operation appears to have been well tolerated in 13 to 14 gravidas. There does appear to be an increased risk of miscarriage. The tendency to routinely discourage pregnancy may need to be reconsidered.

Placental calcification: a metastatic process?

Placental calcification commonly increases with gestational age. The mechanism of apatite mineralization probably involves one of three known mechanisms of tissue calcification: physiological (like bone), dystrophic (ischaemia-related) or metastatic (mineralization in a supersaturated environment). This study was designed to determine the mechanism of calcification by examining (1) the mineral content of placental calcifications in comparison to other physiological and pathological apatites, and (2) the expression of bone morphogenetic proteins (BMPs), which are important in physiological calcification, across gestational age. By energy-dispersive x-ray analysis (EDXA), the Ca/P weight ratio for apatitic mineral from mature calcifications was 2.00+/-0.05 (s.e.), which is similar to that for stones formed in a metastatic, supersaturated environment and lower than that observed in physiological calcification. Biologically active BMP, which was determined by bioassay, was demonstrated in mature and postmature placentae. The BMPs PLAB, PDF and related protein INSL-4 were identified by semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR), but their mRNA expression was independent of gestational age (7-41 weeks of gestation). We conclude that (1) the identified BMPs were not related directly to placental calcification, which argues against physiological calcification, and (2) the chemical composition of the apatitic mineral was suggestive of rapid formation in a supersaturated environment, which is consistent with a metastatic mechanism of calcification.

Fetal breathing, sleep state, and cardiovascular responses to adenosine in sheep.

The possibility that adenosine mediates hypoxic inhibition of fetal breathing and eye movements was tested in nine chronically catheterized fetal sheep (0.8 term). Intracarotid infusion of adenosine (0.25 +/- 0.03 mg.min-1.kg-1) for 1 h to the fetus increased heart rate and hemoglobin concentration but did not significantly affect mean arterial pressure or blood gases. As with hypoxia, adenosine decreased the incidence of rapid eye movements by 55% and the incidence of breathing by 77% without significantly affecting the incidence of low-voltage electrocortical activity. However, with longer (9 h) administration, the incidence of breathing and eye movements returned to normal during the adenosine infusion. Intravenous infusion of theophylline, an adenosine receptor antagonist, prevented most of the reduction in the incidence of breathing and eye movements normally seen during severe hypoxia (delta arterial PO2 = -10 Torr). It is concluded that 1) adenosine likely depresses fetal breathing and eye movements during hypoxia and 2) downregulation of adenosine receptors may contribute to the adaptation of breathing and eye movements during prolonged hypoxia.

Fetal breathing and sleep state responses to graded carboxyhemoglobinemia in sheep.

To investigate CO effects on brain oxygenation, graded carboxyhemoglobinemia (HbCO) was produced in nine unanesthetized fetal sheep by infusing CO-laden erythrocytes in exchange for fetal blood. For the 1st h after this procedure, the mean fetal carboxyhemoglobin levels were 16.5 +/- 0.4% [control (C) = 1.4 +/- 0.4%] for mild HbCO, 22.7 +/- 0.6% (C = 1.8 +/- 0.4%) for moderate HbCO, and 27.8 +/- 0.5% (C = 2.1 +/- 0.7%) for severe HbCO. This induction of HbCO significantly reduced mean preductal arterial PO2 values to 4.3 Torr below control for mild HbCO, 4.6 Torr below control for moderate HbCO, and 5.5 Torr below control for severe HbCO. The respective arterial O2 contents were decreased by 17, 21, and 29%. Mean arterial pH was lowered only during severe HbCO, and arterial PCO2 values were unchanged. HbCO produced a fetal tachycardia. Mean arterial blood pressure was only increased during severe HbCO. The incidences of rapid eye movements and breathing activity were decreased by HbCO in a dose-dependent manner. When related to calculated brain tissue PO2, these decreases were similar to those measured during hypoxic hypoxia and anemia, suggesting that carboxyhemoglobin effects result solely from diminished oxygenation. It is concluded that 1) the peripheral arterial chemoreceptors in the fetus apparently have little effect on hypoxic inhibition of breathing and 2) the carboxyhemoglobin concentrations required to inhibit fetal breathing are greater than those likely to be encountered clinically.

Fetal breathing, sleep state, and cardiovascular responses to graded hypoxia in sheep.

Graded isocapnic hypoxemia was produced in unanesthetized fetal sheep by varying the inspired O2 concentration (21, 12, 10.5, and 9%) of the ewe. This produced corresponding mean preductal arterial O2 tension (PaO2) values of 25.2 +/- 1.1 (control), 20.1 +/- 1.0 (mild hypoxia), 17.8 +/- 0.9 (moderate hypoxia), and 16.8 +/- 1.4 Torr (severe hypoxia). These were associated with mean arterial O2 contents (CaO2) of 7.18 +/- 0.44, 5.19 +/- 0.34, 4.24 +/- 0.33, and 3.27 +/- 0.20 ml/dl, respectively. The most severe hypoxia was associated with metabolic acidosis and fetal bradycardia. Hypoxia did not reduce significantly the incidence of low-voltage electrocortical activity. The incidence of breathing and rapid eye movements was not affected by mild hypoxia; however, the incidence of both was significantly reduced during moderate and severe hypoxia. It is concluded that 1) acute reductions in the mean PaO2 of 5.9 +/- 0.6 Torr and CaO2 of 2.00 +/- 0.23 ml/dl are critical in that greater reductions inhibit fetal eye and breathing activity and 2) hypoxia probably inhibits eye and breathing movements by altering sleep state.

Fetal breathing, sleep state, and cardiovascular responses to graded anemia in sheep.

Graded anemia was produced for 2 h in 10 unanesthetized fetal sheep by infusing plasma in exchange for fetal blood. This reduced the mean fetal hematocrits during the 1st h of anemia to 19.7 +/- 0.5% [control (C) = 28.2 +/- 1.1%] for mild anemia, 17.4 +/- 0.9% (C = 30.0 +/- 1.1%) for moderate anemia, and 15.1 +/- 1.0% (C = 29.2 +/- 1.3%) for severe anemia. The respective mean arterial O2 contents (CaO2) were 4.46 +/- 0.20, 3.89 +/- 0.24, and 3.22 +/- 0.19 ml/dl. Mean arterial PO2 was reduced significantly (by 2 Torr) only during moderate anemia, and mean arterial pH was decreased only during severe anemia. No significant changes occurred in arterial PCO2. Fetal tachycardia occurred during anemia. Mean arterial pressure was reduced by 2-3 mmHg during mild anemia; however, no significant blood pressure changes were observed for moderate or severe anemia. The incidence of rapid-eye movements and breathing activity was not affected by mild anemia, but the incidence of both was reduced significantly during moderate and severe anemia. It is concluded that 1) a reduction in CaO2 of greater than 2.48 +/- 0.22 ml/dl by hemodilution inhibits rapid-eye movements and breathing activity, and 2) the PO2 signal for inhibition does not come from arterial blood but from lower PO2 in tissue.

Adenosine stimulates breathing in fetal sheep with brain stem section.

Breathing responses to adenosine were determined in 12 chronically catheterized fetal sheep (greater than 0.8 term) in which hypoxic inhibition of breathing had been eliminated by brain stem section. The caudal extent of transection varied from the rostral midbrain to the pontomedullary junction. Isocapnic hypoxia [delta arterial PO2 (PaO2) of -12 Torr] doubled the incidence and depth of breathing activity and increased the incidence of eye movements. Intra-arterial infusion of adenosine (0.30 +/- 0.03 mg.min-1.kg fetal wt-1) increased the incidence and amplitude of breathing without affecting blood gases. Adenosine did not significantly alter the incidence of eye activity. Intra-arterial injection of oligomycin (120 +/- 26 micrograms/kg fetal wt), an inhibitor of mitochondrial oxidative phosphorylation, also stimulated breathing activity. In four fetuses with brain stem section, peripheral arterial chemodenervation blunted the stimulatory effects of hypoxia on breathing activity and abolished altogether the excitatory effects of adenosine. It is concluded that 1) hypoxia and adenosine likely inhibit breathing in normal fetuses by affecting similar areas of the brain stem and 2) in fetuses with brain section, hypoxic hyperpnea depends on peripheral and central mechanisms, whereas adenosine stimulates breathing via the peripheral arterial chemoreceptors.