The TPA score (total psoas muscle area) is the best marker for preoperative measurement of pre-sarcopenia in pancreatic surgery.

INTRODUCTION: Pre-sarcopenia, defined by the loss of muscle mass, is significantly associated with an increased risk of postoperative complications in digestive surgery, particularly pancreatic resection. The five predominant markers of sarcopenia are: psoas muscle area (TPA), intramuscular adipose tissue content (IMAC), Average Hounsfield Unit Calculation (HUAC), Skeletal Muscle Mass Index (MMI), and the ratio between visceral adipose tissue area and muscle surface area (VFA/TAMA). No standard reference marker has been determined. MATERIAL AND METHODS: This retrospective cohort included patients who underwent pancreatic resection at the University Hospital of Angers between January 2008 and June 2017. The goal was to determine the marker that was most significantly associated with morbidity and mortality in pancreatic surgery. The secondary objective was to determine the characteristics of pre-sarcopenic patients. RESULTS: The TPA score is the most sensitive marker for identifying patients at highest risk for immediate complications (P=0.008), proving far more sensitive than MMI (P=0.02), HUAC (P=0.34), IMAC (P=1), or VFA/TAMA (P=0.42). Postoperative mortality was 3.3% (n=5), morbidity was 63.8% (n=97). Pre-sarcopenic patients, as identified by the TPA index had significantly more immediate complications (71.2% versus 49.5%, P=0.008), in particular, more gastroparesis (P=0.02) and pancreatic fistula (P=0.03). CONCLUSION: In patients requiring pancreatic surgery, the prevalence of pre-sarcopenia is high and seems to be associated with a greater risk of immediate postoperative complications. The TPA score seems to be the most sensitive marker for detecting pre-sarcopenia. Evaluation of TPA preoperatively would make it possible to identify priority patients a priori who might benefit from pre-habilitation programs.

Comparison of neonatal outcomes of cesarean sections performed under primary or secondary general anesthesia: a retrospective study.

BACKGROUND: The conversion of neuraxial anesthesia (NA) to general anesthesia (GA) during a cesarean section (CS) may be associated with a higher risk of neonatal morbidity by adding the undesirable effects of both these anesthesia techniques. We aimed to compare the neonatal morbidity of non-elective CS performed after conversion from NA to GA (secondary GA) vs. that after GA from the outset (primary GA). METHODS: We performed a monocentric retrospective study at the Angers University Hospital (France). All non-elective CSs performed under GA between January 2015 and December 2019 were included. The CSs were classified using a three-color coding system (green for non-urgent delivery, orange for urgent CS, and red for very urgent CS). The primary neonatal outcome was a composite of umbilical artery pH <7.10 or 5-min Apgar score <7. The crude and adjusted odds ratios (OR) for the risk of neonatal morbidity associated with secondary GA were estimated. RESULTS: We included 247 patients, of whom 101 (41.3%) had a secondary GA and 146 (58.7%) had primary GA. In the secondary GA group, 86.1% (87/101) had epidural anesthesia and 13.9% (14/101) had spinal anesthesia. Multivariate analysis showed no difference in neonatal morbidity between the two groups (adjusted odds ratio 1.18, 95% CI 0.56 to 2.51). CONCLUSIONS: Our study found insufficient evidence to identify a difference in neonatal outcomes between secondary compared with primary GA for CS, regardless of the level of emergency. However, our study is underpowered and additional studies are needed to confirm these data.

Post-exercise ankle blood pressure and ankle to brachial index after heavy load bicycle exercise.

The American Heart Association (AHA) recommendations for diagnosing peripheral artery disease (PAD) after exercise are a decrease >20% of ankle brachial index (ABI) or >30 mm Hg of ankle systolic blood pressure (ASBP) from resting values. We evaluated ABI and ASBP values during incremental maximal exercise in physically active and asymptomatic patients. Patients (n = 726) underwent incremental bicycle tests with pre- and post-exercise recording of all four limbs arterial pressures simultaneously. Univariate and multivariate analyses were performed to define the correlation between post-exercise ABI with various clinical factors, including age. Thereafter, the population was divided into groups of age: less than 40 (G < 40), from 40 to 44 (G40/44) from 45 to 49 (G45/49), from 50 to 54 (G50/54), from 55 to 59 (G55/59), from 60 to 64 (G60/64), and 65 and above (G ≥ 65) years. Results are mean ± SD. * is two-tailed P < .05 for ANOVA with Dunnett's post-hoc test from G40. Changes from rest in ASBP were -3 ± 22 (G < 40), -2 ± 20 (G40/44), 4 ± 22* (G45/49), 10 ± 25* (G50/54), 18 ± 21* (G55/59), 23 ± 27* (G60/64), and 16 ± 22* (G ≥ 65) mm Hg. Decreases from rest in ABI were 32 ± 9 (G < 40), 33 ± 9 (G40/44), 29 ± 8 (G45/49), 27 ± 10* (G50/54), 24 ± 7* (G55/59), 22 ± 12* (G60/64), and 21 ± 12* (G ≥ 65) % of resting ABI. Maximal incremental exercise results in ABI and ASBP changes are mostly dependent on age. The AHA limits for post-exercise ABI are inadequate following maximal incremental bicycle testing. Future studies detecting PAD in active patients should account for the effect of age.

European and American suspected and confirmed pulmonary embolism populations: comparison and analysis.

BACKGROUND: If the prevalence of pulmonary embolism (PE) differs significantly between the US and Europe, this observation could reduce the generalizability of diagnostic protocols for PE derived in either location. OBJECTIVE: To determine possible causes and potential clinical consequences of these PE prevalence differences. METHODS: Secondary analysis of three prospectively collected multicenter samples (two French and one from the US) including 3174 European and 7940 American PE-suspected patients in Emergency departments (ED) (117 for Europe and 12 for US). Comparison of clinical features, resource use and outcomes of European- and US-suspected PE populations in ED. RESULTS: European patients evaluated for PE were significantly older and had a higher clinical pretest probability (CPP) for PE. The final PE prevalence was significantly higher in Europe, in the overall sample (26.5% vs. 7.6%) and in each level of CPP. Suspected European patients categorized as low CPP had a higher posttest probability than US low CPP patients. Suspected US patients categorized as high CPP had a much lower posttest probability of PE than in Europe. The mean number of tests performed for one PE diagnosis was lower in Europe (7.4 vs. 21.6). Among patients diagnosed with PE, European patients had a higher mean severity of illness score and a higher PE-mortality rate (3.4% vs. 0.7%). CONCLUSIONS: Among patients suspected of a PE and those ultimately diagnosed with a PE, European patients had higher acuity, a higher pretest probability and worse outcome than US patients. The present study underscores the importance of disease prevalence for pretest probability scoring approaches and for significance interpretation of imaging tests.

Exercise treadmill testing in patients with claudication, with and without diabetes.

AIM: To compare symptoms and walking capacities of patients with and without diabetes reporting vascular-type claudication. METHODS: We recorded self-reported maximal walking distance, maximal walking distance on treadmill test (3.2 km h(-1) , 10% slope), exercise transcutaneous oxygen pressure DROP index [limb transcutaneous oxygen pressure (TcpO2) changes from rest minus chest TcpO2 changes from rest] and symptoms on treadmill in 230 patients with diabetes and 982 patients without diabetes. Exercise-induced proximal and distal symptoms were analysed in the perspective of underlying proximal and distal ischaemia (DROP value < negative 15 mmHg). RESULTS: Self-reported maximal walking distance did not differ between groups, whereas maximal walking distance on treadmill test was lower in patients with diabetes vs. patients without diabetes (261 ± 257 and 339 ± 326 m, respectively; P < 0.05 when adjusted for potential confounders). In patients with ischaemia, the number of ischaemic areas (proximal and/or distal on right and/or left) was comparable between the two groups. Patients with diabetes had more distal ischaemia than patients without diabetes (38 vs. 29%, respectively; P < 0.01), whereas proximal ischaemia was similar between groups. The prevalence of lower-limb exercise-related symptoms without ischaemia was comparable between groups. There were more symptoms other than lower-limb pain in patients with diabetes than patients without diabetes (29.6 vs. 18.3%, respectively; P < 0.01). CONCLUSIONS: Patients with diabetes show more severe limitation on the treadmill and more non-limb symptoms than patients without diabetes, although self-reported walking capacity is comparable between the two groups. Using TcpO2, we confirm that patients with diabetes reporting claudication show more distal ischaemia than patients without diabetes, with no difference at the buttock level. Treadmill testing is of interest in patients with peripheral artery disease and diabetes.

Titrated mandibular advancement versus positive airway pressure for sleep apnoea.

The aim of this study was to compare mandibular advancement device (MAd) therapy and continuous positive airway pressure (CPAP) for obstructive sleep apnoea/hypopnoea syndrome (OSAHS) after one-night polysomnographic (PSG) titration of both treatments. 59 OSAHS patients (apnoea/hypopnoea index (AHI): 34+/-13 events x h(-1); Epworth scale: 10.6+/-4.5) were included in a crossover trial of 8 weeks of MAd and 8 weeks of CPAP after effective titration. Outcome measurements included home sleep study, sleepiness, health-related quality of life (HRQoL), cognitive tests, side-effects, compliance and preference. The median (interquartile range) AHI was 2 (1-8) events x h(-1) with CPAP and 6 (3-14) events x h(-1) with MAd (p<0.001). Positive and negative predictive values of MAd titration PSG for treatment success were 85% and 45%, respectively. Both treatments significantly improved subjective and objective sleepiness, cognitive tests and HRQoL. The reported compliance was higher for MAd (p<0.001) with >70% of patients preferring this treatment. These results support titrated MAd as an effective therapy in moderately sleepy and overweight OSAHS patients. Although less effective than CPAP, successfully titrated MAd was very effective at reducing the AHI and was associated with a higher reported compliance. Both treatments improved functional outcomes to a similar degree. One-night titration of MAd had a low negative predictive value for treatment success.

Relevance of Ki-67 and prognostic factors for recurrence/progression of gonadotropic adenomas after first surgery.

OBJECTIVE: Gonadotropin-secreting pituitary adenomas carry a high risk of local recurrence or progression (R/P) of remnant tumor after first surgery. The clinical characteristics and the long-term outcome of these silent adenomas, which show no signs of endocrine hyperfunction, differ from those of other types of pituitary adenomas. However, to date, no study has focused specifically on gonadotropic adenomas. MATERIALS AND METHODS: To identify prognostic factors of R/P of remnants, we studied the postoperative outcome of 32 gonadotropic pituitary adenomas, defined on immunohistochemical staining, according to their clinical and radiological characteristics as well as the Ki-67 labeling index (LI). RESULTS: The Ki-67 LI failed to provide independent information for the identification of patients at risk of progression of remnants or recurrence. Multivariate survival analysis (Cox regression) showed that neither invasiveness nor remnant tumors nor hyposomatotropism influenced tumor recurrence. The strongest predicting factors of R/P were the antero-posterior (AP) diameter in the sagittal plane (P = 0.014), and the age of the patient at surgery (P = 0.047), with younger patients being at greater risk. Hazard ratios were 2.11 for each 5 mm increase in AP diameter and 0.57 for every 10 years of age. CONCLUSION: The two simple clinical criteria revealed by our study, the AP diameter of the tumor and the age of the patient, should be helpful in planning clinical management and radiological monitoring after first surgery of gonadotropic adenomas, while awaiting the identification of other pathological parameters.

Fibromuscular dysplasia may herald symptomatic recurrence of cervical artery dissection.

BACKGROUND: The prevalence of fibromuscular dysplasia (FMD) in patients with cervical artery dissection (CAD) is unknown. Our objectives were to assess the risk of CAD recurring as a stroke or a transient ischemic attack and the association of these events with FMD. METHODS: We prospectively included and followed 103 consecutive patients who had been admitted for a CAD. The median follow-up was 4 years (range 4 months to 10 years). The main criteria for inclusion were a mural hematoma demonstrated by cervical magnetic resonance imaging and/or signs suggesting CAD on 2 other investigations. FMD was diagnosed on the so-called string of beads pattern by digital subtraction angiography. RESULTS: Five patients had CAD recurrence (60% occurred late). Four of these 5 patients had FMD. In 4 patients, CAD recurrence involved another cervical artery. CONCLUSION: The rate of symptomatic CAD recurrence was 1% per year and was often related to FMD.

Contribution of the study of acetabulum for the estimation of adult subjects.

INTRODUCTION: The study of the posterior part of the pelvis is of interest in forensic anthropology since it is an anatomical region that is very often preserved. The Lovejoy technique, using the auricular surface has brought about many studies and attracted many authors, among them Buckberry and Chamberlain utilized the criteria described by Lovejoy and developed new methods. By using this research as a starting point, we have described acetabular criteria. The goal of this study was to test these criteria and to link them to auricular surface reading criteria, as described by Buckberry and Chamberlain. METHOD: The study concerned 52 pelvises of known age and sex. We studied the age correlation of various criteria read at the acetabulum level and that of the auricular surface. We then went on to draw up scores and established a correlation of these scores with age. Intra- and inter-observer variability was also studied. We used the SPSS software package for statistical analyses. DISCUSSION: We were able to isolate four acetabular criteria and four auricular surface criteria which have a correlation with age. Establishing these scores (sum of criteria) allows a better age-based correlation to be obtained. Establishing an overall score, including acetabular criteria and auricular surface criteria, allows a good level of correlation to be obtained with age, with low intra- and inter-observer variability. CONCLUSION: The study of acetabulum is of interest for the age estimation of adult subjects. The joint study of the acetabulum and the auricular surface allows a higher correlation with actual age to be obtained. This study must be broadened to include a wider sample so as to allow fine-tuning of a method.

Immune restoration under HAART in patients chronically infected with HIV-1: diversity of T, B, and NK immune responses.

The aim of the study was to follow prospectively the humoral, cellular and innate immune responses under HAART and to verify if a functional restoration of the B lymphocytes could be evaluated by measuring the anti-HIV-1 IgG antibodies avidity index (AI). Eleven HIV-1 infected and immunosuppressed patients were included in the study. Viral load, naive and memory B-cells, CD4 and CD8 T-cells and NK-cells counts, and anti-HIV-1 IgG AI were determined during the follow-up (18 months). Ten patients were sustained responders under HAART and showed a quantitative restoration of the CD4 T-cell counts (+269 x 10(6)/L). The AI decreased for ten subjects (-11%, p = 0.006) but very slowly and continuously. A quantitative restoration of the humoral immune response began, mainly concerning the naive B-cells (+110 x 10(6)/L). Apart from one patient, the CD8 T-cell subset approached the reference values of healthy subjects either by decreasing or increasing their cell levels. No homogeneous evolution was described concerning the NK-cell subset, apart from trend towards increasing in patients with opportunistic infection (range, +58 to +291 x 10(6)/L). Our study, which evaluated simultaneously for the first time to our knowledge the cellular, humoral and innate immune responses showed that HAART induced a large diversity of immune restoration patterns in responder patients. However, the AI measure appears to be a weak marker to evaluate an immune restoration in chronic HIV-1 infected patients under HAART.

Transcutaneous oxygen pressure measurements (tcpO2) at ankle during exercise in arterial claudication.

AIM: Although a time consuming technique, tcpO2 provides complementary information as compared to other tests. Simultaneous recording of systemic and peripheral oxygen pressure changes with exercise could be interesting to confirm that local hypoxemia is of arterial origin, but accuracy versus gold standard arteriography and objectively determined cut-off points to be used in arterial claudication at the ankle are not reported. EXPERIMENTAL DESIGN: retrospective plus prospective study. SETTING: institutional practice, ambulatory care. PATIENTS: 100 patients suffering stage 2 claudication (group A) were retrospectively studied to objectively define cut-off points derived from tcpO2 recordings to be used in exercise testing. Then, applicability and reproducibility of these cut-off points were analysed prospectively in another 50 patients (group B). INTERVENTION: tcpO2 was measured on both calves and with a chest reference electrode. Arteriography on each side was quoted positive for a diameter stenosis superior to 75% or occlusion on the aorto-popliteal axis or of all-3-calf arteries. RESULTS: The best performance was obtained with tcpO2 changes from rest at the calf normalised to eventual chest changes (DROP) during or following the treadmill test. Optimal cut-off point determined through ROC curve analysis for DROP was -15 mmHg in group A. Applying this cut-off point in group B provided a 86/84% sensitivity/specificity and showed excellent reproducibility. CONCLUSIONS: TcpO2 measurement on the calf during exercise could be useful in a selected population of patients with claudication of questionable vascular origin and/or when other non-invasive investigations cannot be performed.

Mathematical analysis of Mayer waves.

The goal of this paper is to explore the low-frequency oscillations of arterial pressure in humans, also called Mayer waves. We carefully describe the cardiovascular control system in order to analyse how its different components may be involved in the occurrence of sustained oscillations. We carry out an analysis of stability leading to the definition of a stability index, which we use to study the influence of each control parameter on the stability of the cardiovascular system. We show that all major components of the control system are probably implicated in the appearance of Mayer waves, substantiating recent clinical results in human as well as experimental findings in rats.

Spectral and profile analysis of Doppler recording following below-knee arterial distal bypasses.

BACKGROUND: Arterial below knee distal bypasses are associated with a high risk of thrombosis as compared to proximal bypasses. We assumed that before the bypass occludes, in the early postsurgical period, measurable velocity changes, and/or the presence of high intensity transient signals (HITS) would occur. SETTINGS: institutional reference center, hospitalized patients. SUBJECTS: satisfactory Doppler recording was obtained in 51 among 61 consecutive patients (32 males, 19 females, height: 165+/-7 cm, weight: 68+/-12 kg) suffering lower extremity arterial disease, that underwent saphenous (n=33), prosthetic (n=4) or sequential (n=14) below knee bypasses. We performed a spectral and profile analysis of a single postsurgical 2 hour Doppler recording at the ankle level and analyzed Doppler derived indices and clinical risk factors in the evaluation of the risk of bypass occlusion within 7 days following surgery. RESULTS: Primary patency at day 7 was observed in 41 of the 51 operated patients. The presence of HITS was found in approximately 30% of the patients and provided no information on the risk of thrombosis. No clinical variable was significantly associated with an increased risk of thrombosis. Whatever the duration of recording, the presence of a diastolic forward flow and wide systolic velocity changes were poor indicators of bypass thrombosis risk. On 512 beat recordings, a mean systolic velocity below 1630 Hz and a standard deviation of the resistance index >0.095 were associated with a 6.74 [1.6-28.4] (p<0.01) and 14.5 [3.6-58.9] (p<0.001) times increases in the risk of bypass occlusion respectively, compared with subjects that do not fulfill each criteria. CONCLUSIONS: Periods of transient asymptomatic no-flow-reflow events may be observed before the bypass irreversibly occludes. Prolonged Doppler recording should be preferred to short term analyses, to allow for the detection of these transient events and may provide potential indices for future research.

Pressure measurements at rest and after heavy exercise to detect moderate arterial lesions in athletes.

PURPOSE: This study defined how ankle arterial blood pressure measurements should be analyzed for the detection of moderate arterial disease (asymptomatic while walking). We used external iliac artery endofibrosis as a unique model of an isolated moderate arterial lesion, the role of which in exercise-related pain can be surgically proven. METHODS: Patients who were ambulatory in our institutional referral center were studied. Brachial pressures, ankle pressures, and heart rate were measured simultaneously on all four limbs at rest and after maximal exercise in 108 healthy athletes and 78 patients (among 89 athletes referred for suspicion of endofibrosis) with confirmed or excluded external iliac endofibrosis. For these 78 patients, we calculated systolic ankle pressure change, ankle/brachial index, and deviation from the ankle/brachial index to heart rate regression line (DAHR) that was defined in the 108 healthy athletes. RESULTS: In patients with endofibrosis, ankle/brachial index and ankle pressure were normal at rest. One minute after exercise, areas (mean +/- SE of area) under the receiver operating characteristics curve for the diagnosis of endofibrosis were 0.91 +/- 0.02, 0.91 +/- 0.03, 0.95 +/- 0.02, and 0.96 +/- 0.02 for ankle pressure, pressure change, ankle/brachial index, and DAHR, respectively. For all criteria, area decreased with time in the recovery period. CONCLUSION: After heavy-load exercise, the ankle/brachial index at minute 1 should be used rather than the systolic ankle pressure value or ankle pressure change as a means of improving the efficacy of the detection of endofibrosis in athletes. A 0.66 value of the index at minute 1 after maximal exercise seems an optimal cutoff point for clinical use, providing a 90% sensitivity rate and 87% specificity rate in the diagnosis of moderate arterial lesions. At rest and after 1 minute of recovery, the ankle/brachial index to heart rate relationship should be considered to be an efficient tool for analyzing the results of pressures measurements and improving detection efficiency.

A new explicit stability criterion for human periodic breathing.

The aim of this paper is to carry out a stability analysis for periodic breathing in humans that incorporates the dynamic characteristics of ventilation control. A simple CO2 model that takes into account the main elements of the respiratory system, i.e. the lungs and the ventilatory controller with its dynamic properties, is presented. This model results in a three-dimensional non-linear delay differential system for which there exists a unique equilibrium point. Our stability analysis of this equilibrium point leads to the definition of a new explicit stability criterion and to the demonstration of the existence of a Hopf bifurcation. Numericall simulations illustrate the influence of physiological parameters on the stability of ventilation. and particularly the major role of the dynamic characteristics of the respiratory controller.

Thallium-201 right lung/heart ratio during exercise in patients with coronary artery disease: relation to thallium-201 myocardial single-photon emission tomography, rest and exercise left ventricular function and coronary angiography.

The aim of this study was to correlate lung thallium-201 uptake on exercise with 201Tl single-photon emission tomography (SPET) myocardial perfusion imaging, rest and exercise equilibrium radionuclide angiographic and coronary angiographic findings in patients with coronary artery disease (CAD) using a simple, reproducible lung/heart (L/H) ratio that would be easy to use in clinical practice. L/H ratio was defined on the anterior planar image obtained during exercise 201Tl SPET acquisition as the mean counts per pixel in an entire right lung field region of interest divided by the mean counts per pixel in the hottest myocardial wall region of interest. We studied 103 patients. Fifty-nine patients (group I) with <5% likelihood of CAD were used as a reference group. In 44 CAD patients (group II), L/H ratio was compared with 201Tl SPET, radionuclide angiographic and coronary angiographic variables. The group I L/H ratio of 0.35+/-0.05 (mean +/-1 SD) was significantly lower (P<0.001) than the group II L/H ratio of 0. 45+/-0.10. An L/H ratio >0.45 (mean + 2 SD in group I) was considered abnormal. In group II, L/H ratio showed a significant correlation with stress and rest 201Tl perfusion defect size (r = 0. 39 and r = 0.42, P<0.01, respectively), but not with extent of ischaemic myocardium. The mean L/H ratio was 0.41+/-0.10 in patients with one-vessel disease (n = 15), 0.46+/-0.08 in those with two-vessel disease (n = 17) and 0.47+/-0.12 in those with three-vessel disease (n = 12), but no significant difference was found between the three subgroups. L/H ratio showed a significant inverse relation with rest and exercise left ventricular ejection fraction (r = -0.37 and r = -0.50, P<0.05 and P<0.001, respectively). Using stepwise multiple regression analysis, exercise left ventricular ejection fraction and previous history of hypertension were the sole two variables independently predictive of the L/H ratio. In conclusion, although lung thallium uptake is usually found to correlate with extent and severity of CAD, increased L/H ratio should primarily be considered as a marker of exercise-induced left ventricular systolic and perhaps diastolic dysfunction, probably independent of the underlying cardiac disease.

mtDNA haplogroup J: a contributing factor of optic neuritis.

Optic neuritis frequently occurs in multiple sclerosis (MS), and shares several similarities with the optic neuritis of Leber's hereditary optic neuropathy (LHON), which is mainly due to maternally transmitted mitochondrial DNA (mtDNA) mutations. Our report shows for the first time that a mitochondrial DNA background could influence the clinical expression of MS. One European mtDNA haplogroup was found only in MS patients with optic neuritis but not in MS patients without visual symptoms. Therefore, we hypothesize that mtDNA haplogroup J might constitute a risk factor for optic neuritis occurrence when it is coincidentally associated with MS, but not be a risk factor for developing MS per se as suggested previously.

On the viability of a physiological system. Regulation of potassium by aldosterone.

Physiological systems maintain their variables within limits through regulatory processes. We have studied potassium regulation on the basis of the viability theory. The viability kernel is determined by taking into account the constraints of the variables of the dynamical system, i.e. the set of initial states for which there exists at least one viable trajectory. The set of regulations which maintain the viability of the physiological system is also determined. Finally, we investigate the influence of various strategies that allow the choice of one control among the viable regulations.

Delay equation analysis of human respiratory stability.

A mathematical analysis of the stability in human respiration, based on the tau-decomposition method, is conducted on a simple, but realistic CO2 model of the respiratory system. This model incorporates a two-compartment representation (lungs and tissues) for the plant and a very general class of controller. By deriving an explicit stability criterion, the stability domain of the respiratory system can be characterized. We quantify the influence of four major parameters of respiratory instability, i.e. transport delay, lung volume, and equilibrium values of lung CO2 partial pressure and controller gain. We demonstrate the existence of a bifurcation point and periodic solutions, giving some characteristics of solutions near the bifurcation point.