Lipid-lowering therapy of everolimus-related severe hypertriglyceridaemia in a pancreatic neuroendocrine tumour (pNET).

WHAT IS KNOWN AND OBJECTIVE: Hypertriglyceridaemia (HTG) is a potentially serious side effect of everolimus therapy. We here report a case of severe HTG in an everolimus-treated patient and provide recommendations for its management. CASE SUMMARY: The patient was a 70-year-old woman, being treated with everolimus for a pancreatic neuroendocrine tumour (pNET). She developed severe HTG to a maximum of 969 mg/dL after 22 months of therapy. Treatment with fenofibrate rapidly normalized triglyceride (TG) levels. WHAT IS NEW AND CONCLUSION: Severe HTG may occur in everolimus-treated patients. Prescription of the appropriate therapy can allow patients to continue this medication.

Preclinical and clinical evidence on the approach-avoidance conflict evaluation as an integrative tool for psychopathology.

The approach-avoidance conflict (AAC), i.e. the competing tendencies to undertake goal-directed actions or to withdraw from everyday life challenges, stands at the basis of humans' existence defining behavioural and personality domains. Gray's Reinforcement Sensitivity Theory posits that a stable bias toward approach or avoidance represents a psychopathological trait associated with excessive sensitivity to reward or punishment. Optogenetic studies in rodents and imaging studies in humans associated with cross-species AAC paradigms granted new emphasis to the hippocampus as a hub of behavioural inhibition. For instance, recent functional neuroimaging studies show that functional brain activity in the human hippocampus correlates with threat perception and seems to underlie passive avoidance. Therefore, our commentary aims to (i) discuss the inhibitory role of the hippocampus in approach-related behaviours and (ii) promote the integration of functional neuroimaging with cross-species AAC paradigms as a means of diagnostic, therapeutic, follow up and prognosis refinement in psychiatric populations.

LSD1 is an environmental stress-sensitive negative modulator of the glutamatergic synapse.

Along with neuronal mechanisms devoted to memory consolidation -including long term potentiation of synaptic strength as prominent electrophysiological correlate, and inherent dendritic spines stabilization as structural counterpart- negative control of memory formation and synaptic plasticity has been described at the molecular and behavioral level. Within this work, we report a role for the epigenetic corepressor Lysine Specific Demethylase 1 (LSD1) as a negative neuroplastic factor whose stress-enhanced activity may participate in coping with adverse experiences. Constitutively increasing LSD1 activity via knocking out its dominant negative splicing isoform neuroLSD1 (neuroLSD1KO mice), we observed extensive structural, functional and behavioral signs of excitatory decay, including disrupted memory consolidation. A similar LSD1 increase, obtained with acute antisense oligonucleotide-mediated neuroLSD1 splicing knock down in primary neuronal cultures, dampens spontaneous glutamatergic transmission, reducing mEPSCs. Remarkably, LSD1 physiological increase occurs in response to psychosocial stress-induced glutamatergic signaling. Since this mechanism entails neuroLSD1 splicing downregulation, we conclude that LSD1/neuroLSD1 ratio modulation in the hippocampus is instrumental to a negative homeostatic feedback, restraining glutamatergic neuroplasticity in response to glutamate. The active process of forgetting provides memories with salience. With our work, we propose that softening memory traces of adversities could further represent a stress-coping process in which LSD1/neuroLSD1 ratio modulation may help preserving healthy emotional references.

Three-dimensional longitudinal evaluation of facial mimicry in orthognathic class III surgery.

The effect of bimaxillary orthognathic surgery on facial mimicry was assessed longitudinally in 15 patients with dentoskeletal class III facial dysmorphism (seven men, eight women, mean age 28 years). The patients were analysed pre-surgery and at 6, 12, and 24 months post-surgery while performing verbal (five vowels) and non-verbal (open and closed mouth smile, lip purse) soft tissue facial movements. The three-dimensional motions of right and left nasogenian, crista philtri, cheilion, and lower lip landmarks were detected by an optoelectronic instrument, and a total mobility index was obtained. Differences between the sides were quantified by the symmetry index. Patient values were compared to those collected previously from healthy volunteers by computing z-scores. On average, no significant differences were found in the mobility of the buccal soft tissues at 24 months after surgery (ANOVA P-value, range 0.075-0.808), with positive median z-scores (pooled mean value close to 0.6). Symmetry indices ranged around the control reference values, showing no stage-related differences (Friedman test P-value, range 0.252-0.937), and exceeding 90% for all movements at 24 months after surgery. Bimaxillary osteotomy does not compromise facial mimicry in either verbal or non-verbal facial movements.

Maternal anxiety, depression and sleep disorders before and during pregnancy, and preschool ADHD symptoms in the NINFEA birth cohort study.

AIMS.: Maternal mental disorders have been associated with the risk of attention-deficit/hyperactivity disorder (ADHD) in children. Within the context of a mother-child cohort, we examined whether maternal anxiety, depression and sleep disorders are associated with pre-school ADHD symptoms. METHODS.: The study included 3634 singletons from the Italian NINFEA (Nascita e INFanzia: gli Effetti dell'Ambiente') cohort. Maternal doctor-diagnosed anxiety, depression and sleep disorders before and during pregnancy were assessed from the questionnaires completed during pregnancy and 6 months after delivery. Mothers rated child ADHD symptoms at 4 years of age, according to the Diagnostic and Statistical Manual of Mental Disorders. Hyperactive-impulsive (ADHD-H), inattentive (ADHD-I) and total ADHD scores were analysed in the models adjusted for child's gender, first-born status, maternal age, education, alcohol consumption and smoking during pregnancy. RESULTS.: The total ADHD score at age 4 was associated with maternal lifetime anxiety (17.1% percentage difference in score compared with never; 95% CI 7.3-27.9%), sleep disorders (35.7%; 95% CI 10.7-66.5%) and depression (17.5%; 95% CI 3.2-33.8%). Similar positive associations were observed also for ADHD-H and ADHD-I traits, with slightly attenuated associations between maternal sleep disorders and child ADHD-I score, and maternal depression and both ADHD scores. All the estimates were enhanced when the disorders were active during pregnancy and attenuated for disorders active only during the pre-pregnancy period. CONCLUSIONS.: Maternal anxiety, depression and sleep disorders are associated with a relative increase in the number of ADHD-H, ADHD-I and total ADHD symptoms in preschoolers.

Perinatal health services organization for preterm births: a multinational comparison.

OBJECTIVE: To explore population characteristics, organization of health services and comparability of available information for very low birth weight or very preterm neonates born before 32 weeks' gestation in 11 high-income countries contributing data to the International Network for Evaluating Outcomes of Neonates (iNeo). STUDY DESIGN: We obtained population characteristics from public domain sources, conducted a survey of organization of maternal and neonatal health services and evaluated the comparability of data contributed to the iNeo collaboration from Australia, Canada, Finland, Israel, Italy, Japan, New Zealand, Spain, Sweden, Switzerland and UK. RESULTS: All countries have nationally funded maternal/neonatal health care with >90% of women receiving prenatal care. Preterm birth rate, maternal age, and neonatal and infant mortality rates were relatively similar across countries. Most (50 to >95%) between-hospital transports of neonates born at non-tertiary units were conducted by designated transport teams; 72% (8/11 countries) had designated transfer and 63% (7/11 countries) mandate the presence of a physician. The capacity of 'step-down' units varied between countries, with capacity for respiratory care available in <10% to >75% of units. Heterogeneity in data collection processes for benchmarking and quality improvement activities were identified. CONCLUSIONS: Comparability of healthcare outcomes for very preterm low birth weight neonates between countries requires an evaluation of differences in population coverage, healthcare services and meta-data.

DOT1L-mediated H3K79me2 modification critically regulates gene expression during cardiomyocyte differentiation.

Epigenetic changes on DNA and chromatin are implicated in cell differentiation and organogenesis. For the heart, distinct histone methylation profiles were recently linked to stage-specific gene expression programs during cardiac differentiation in vitro. However, the enzymes catalyzing these modifications and the genes regulated by them remain poorly defined. We therefore decided to identify the epigenetic enzymes that are potentially involved in cardiomyogenesis by analyzing the expression profile of the 85 genes encoding the epigenetic-related proteins in mouse cardiomyocytes (CMs), and then study how they affect gene expression during differentiation and maturation of this cell type. We show here with gene expression screening of epigenetic enzymes that the highly expressed H3 methyltransferase disruptor of telomeric silencing 1-like (DOT1L) drives a transitional pattern of di-methylation on H3 lysine 79 (H3K79) in CMs at different stages of differentiation in vitro and in vivo. Through a genome-wide chromatin-immunoprecipitation DNA-sequencing approach, we found H3K79me2 enriched at genes expressed during cardiac differentiation. Moreover, knockdown of Dot1L affected the expression of H3K79me2-enriched genes. Our results demonstrate that histone methylation, and in particular DOT1L-mediated H3K79me2 modification, drives cardiomyogenesis through the definition of a specific transcriptional landscape.

Mould/dampness exposure at home is associated with respiratory disorders in Italian children and adolescents: the SIDRIA-2 Study.

AIMS: To report on the relation between home mould and/or dampness exposure and respiratory disorders in a large sample of children and adolescents in Italy, accounting for age at time of exposure. METHODS: 20,016 children (mean age 7 years) and 13,266 adolescents (mean age 13 years) completed questionnaires on indoor exposures and respiratory symptoms/diseases. Statistical analyses were adjusted for sex, age, questionnaire's compiler, area of residence, season of interview, parental educational status, family history of asthma, rhinitis, eczema, chronic obstructive pulmonary disease, presence of gas water heaters, passive smoking, pets, and active smoking (only for adolescents). Population attributable risk % (PAR) was also computed. RESULTS: Asthma was more strongly related to only early than to only current exposure, both in children (OR 1.80, 95% CI 1.41 to 2.30) and adolescents (OR 1.89, 95% CI 1.38 to 2.59). The same result was found for rhino-conjunctivitis (OR 1.46, 95% CI 1.17 to 1.82), in children, and for wheeze among adolescents (OR 1.56, 95% CI 1.15 to 2.11). In children, wheeze (OR 1.98, 95% CI 1.47 to 2.66) and eczema (OR 1.44, 95% CI 1.09 to 1.91) were more strongly related to mould/dampness when exposed both early and currently; the same occurred in adolescents for rhino-conjunctivitis (1.78, 95% CI 1.30 to 2.45). Although persistent cough/phlegm was significantly related to mould/dampness exposure in children, regardless of exposure timing, no significant association between mould/dampness exposure and eczema or cough/phlegm was found among adolescents. PAR estimates were higher for only early than only current exposures. Avoiding early only exposure would abate wheeze by 6%, asthma or cough/phlegm by 7%, rhino-conjunctivitis in children by 4%, and in adolescents, asthma by 6%, and wheeze by 4%. CONCLUSIONS: Respiratory disorders such as wheeze and asthma can often be explained by exposure to home mould/dampness, especially early in life. The association seems more evident in children than in adolescents. These findings may suggest the need for environmental prevention strategies.

Reference values for respiratory rate in the first 3 years of life.

BACKGROUND: Raised respiratory rate is a useful sign to diagnose lower respiratory infections in childhood. However, the normal range for respiratory rate has not been defined in a proper, large sample. OBJECTIVE: To assess the respiratory rate in a large number of infants and young children in order to construct percentile curves by age; to determine the repeatability to the assessment using a stethoscope and compare it with observation. METHODS: Respiratory rate was recorded for 1 minute with a stethoscope in 618 infants and children, aged 15 days to 3 years old, without respiratory infections or any other severe disease when awake and calm and when asleep. In 50 subjects we compared respiratory rate taken 30 to 60 minutes apart to assess repeatability, and in 50 others we compared simultaneous counts obtained by stethoscope versus observation. RESULTS: Repeatability was good as the standard deviation of differences was 2.5 breaths/minute in awake and 1.7 breaths/minute in asleep children. Respiratory rate obtained with a stethoscope was systematically higher than that obtained by observation (mean difference 2.6 breaths/minute in awake and 1.8 breaths/minute in asleep children; P = .015 and P < .001, respectively). A decrease in respiratory rate with age was seen for both states, and it was faster in the first few months of life when also a greater dispersion of values was observed. A second degree polynomial curve accurately fitted the data. Reference percentile values were developed from these data. CONCLUSIONS: The repeatability of respiratory rate measured with a stethoscope was good. Percentile curves would be particularly helpful in the first months of life when the decline in respiratory rate is very rapid and prevents to use cut off values for defining "normality."

Interleukin 6 activity in infants and children with bacterial meningitis. The Collaborative Study on Meningitis.

Concentrations of interleukin 6 (IL-6) in cerebrospinal fluid (CSF) and serum of infants and children with bacterial meningitis were determined and correlations were sought with other indices of inflammation and with outcome. Forty-two patients ages 1 month to 15 years (mean, 2.5 years) were studied. IL-6 activity was detectable (greater than 50 units/ml) in 30 of 36 CSF samples collected at admission from patients with meningitis and in 1 of 23 controls with fever and normal CSF findings. Mean values were 36,000 units/ml (range, 151-156,000). IL-6 activity in CSF persisted during the first 5 days of illness. IL-6 concentrations at admission were not associated with clinical findings, CSF leukocyte, protein and glucose concentrations, serum C-reactive protein concentration and neurologic complications or sequelae. IL-6 was also detected in the serum of 3 of 14 patients with meningitis and in 0 of 7 controls with no infectious disease. The presence of IL-6 was not associated with bacteremia or with duration of fever before admission. The presence of IL-6 in the CSF of pediatric patients with bacterial meningitis is in accordance with available data on other cytokines and suggests their role as mediators of meningeal inflammation.

Counterimmunoelectrophoresis and latex particle agglutination in the etiologic diagnosis of presumed bacterial pneumonia in pediatric patients.

A commercial latex agglutination (LA) kit (Wellcogen, Wellcome Diagnostics) used to detect bacterial polysaccharide antigens (Haemophilus influenzae type b and Streptococcus pneumoniae) was compared with a modified counterimmunoelectrophoresis technique and blood culture for etiologic diagnosis of presumptive bacterial pneumonia requiring hospitalization in 60 infants and children. Serum, urine and either sputum or nasopharyngeal secretions were collected during the first 5 days of therapy for antigen detection. Blood culture was positive in 6 of 52 (11.5%) of cases. Antigens were detected by counterimmunoelectrophoresis and/or LA in 13 of 60 (21.7%) serum samples, 2 of 16 (12.5%) unconcentrated urine samples, 19 of 42 (45.2%) urine samples concentrated 25-fold and 21 of 45 (46.7%) sputum or nasopharyngeal secretions. Antibiotic treatment for 5 days did not affect the antigen detection rate. Counter-immunoelectrophoresis was more sensitive than LA in serum and urine but not in sputum. However, because false positive reactions were frequently obtained with LA on nasopharyngeal secretions of an age-matched control group, this test appears unreliable.

Hering-Breuer reflex and respiratory rate: a biased association.

The Hering-Breuer reflex (HBR) plays an important role in the regulation of respiratory timing in infancy. Some investigators have noted that HBR is stronger when the respiratory rate (RR) is faster. However, this finding may be due to a spurious correlation, since one of the variables (expiratory time) used to calculate both HBR and RR is the same. We investigated this hypothesis with Monte Carlo (simulation) studies by using uncorrelated random numbers to calculate RR and HBR and found a strong spurious correlation (r = 0.7) between HBR and RR, i.e., subjects with higher RR had a stronger HBR. These results were confirmed algebraically, and the formula for the expected value of the correlation coefficient [E(r)] was derived. E(r) was always >0; it was 0.707 when no prolongation of inspiration occurred and was larger in the presence of a prolongation; when HBR strength was 100%, E(r) = 0.89, and when it was 200%, E(r) = 0.94. The expected value of the slope of the regression line of HBR on RR was found to be directly proportional to expiratory time during occlusion. As faster RRs produce stronger HBRs, any variable associated with RR, i.e., age, length, and weight, may influence HBR. This can lead to inconclusive or biased results in studies of the maturation of HBR with age and can confound comparisons across groups that do not have the same RR.

Changes in respiratory rate affect tidal expiratory flow indices in infants with airway obstruction.

Among the tidal expiratory flow measurements that have been suggested as surrogate tests for airway obstruction, a short time to reach peak tidal expiratory flow (t(pef)) is the most widely used. Time to peak expiratory flow is most often expressed as the ratio between t(pef) and total expiratory time (t(e)). As te strictly depends inversely on respiratory rate (RR), we studied the hypothesis that an increase in RR (and a fall in t(e)) with the development of airway obstruction during methacholine or histamine challenge in infants could mask a decrease of t(pef) when expressed as t(pef)/t(e). Thirty-three infants (ages 6.5-23 months) with recurrent wheeze were studied during sedated sleep. Runs of tidal breathing and maximal expiratory flow at FRC (V(maxFRC)) measured by the squeeze technique were obtained before and after the challenge. All infants responded to the challenge: the median fall in P(tCO2) was 25%, and it was 43% in V(maxFRC). RR increased from a median value of 31.1 to a median of 35.1 breaths/min. Both t(pef) and t(e) were significantly shorter after the challenge (P < 0.001 and 0.004, respectively); however, the decrease in t(pef)/t(e) was not significant (P=0.081). The change in t(pef)/t(e) was positively correlated with the change in RR (r = 0.51, P = 0.003). To analyze better the effect of changes in RR on various indices, we divided the patients into two groups: in 17 subjects with a small increase in RR (< 10%), t(e) did not change significantly, while t(pef) and t(pef)/t(e) did; in 16 subjects with a more marked increase in RR (> or = 10%), the shortening of te masked the simultaneous shortening of t(pef), so that t(pef)/t(e) did not change. These data demonstrate that t(pef)/t(e) cannot be reliably used to evaluate changes in airway obstruction when concomitant changes in RR occur.

Occlusion maneuver to detect the relative contribution of the rib cage and abdomen to tidal volume using respiratory inductive plethysmography in infants.

Respiratory inductive plethysmography (RIP) records movements of the rib cage (RC) and abdomen (AB). A calibration procedure is needed to determine their relative contribution to tidal volume. We evaluated the hypothesis that the relative contribution of the RC and AB could be defined from respiratory efforts made during a brief occlusion of the airways in 10 infants aged 6.5-19 months, who were studied in quiet sleep. Six occlusions were performed during tidal breathing, with and without a pneumotachograph (PNT) and face mask in place. We analyzed the periods of occluded respiratory effort when RC and AB were in opposite directions (paradoxical movements), plotting RC vs. AB and performing a least-squares linear regression to estimate the ratio of the coefficients of AB/RC. Multiple linear regression of AB and RC over tidal volume during about 100 seconds of tidal breathing provided a reference standard. A ratio of 1 means that AB and RC make equal contributions to tidal volume. The feasibility of the occlusion maneuver was poor; only 51% of occlusions with PNT and 54% without led to a paradoxical movement with a good fit (r > 0.9). The mean coefficient of variation (range) was 9.35% (3.9-15.3%) with PNT and 12.1% (2.5%-26.3%) without it. The accuracy was very poor, with the mean AB/RC value being 0.94 with occlusions and 2.39 with multiple linear regression. The mean difference was 1.45 (SD 0.80), yielding 95% confidence limits for the difference of 0.12-3.01. We concluded that, due to its very poor accuracy and feasibility, the occlusion technique is not a useful method to calibrate RIP in infancy.

Respiratory inductive plethysmography in the evaluation of lower airway obstruction during methacholine challenge in infants.

Respiratory inductive plethysmography (RIP) is a simple technique for an objective, noninvasive assessment of thoracoabdominal asynchrony, which in turn is an indirect measure of airway obstruction. We evaluated different indices of asynchrony obtained by RIP before and after methacholine-induced airway obstruction. Bronchial obstruction was elicited by progressive doubling concentrations of methacholine until a > 15% fall in the transcutaneous oxygen tension (PtcO2) had developed. Maximal expiratory flow rates at functional residual capacity (FRC) (VmaxFRC) was obtained by the squeeze technique before and after the challenge. Fifteen infants with a history of wheezing were studied after sedation. Thoracoabdominal movements were recorded with RIP bands placed around either the upper or the lower ribcage (RC) and around the abdomen (AB). An inspiratory asynchrony index (IAI) and an expiratory asynchrony index (EAI) were calculated as determined by the lag of RC relative to AB at start of inspiration and of expiration, respectively. The total time in asynchrony (TTA: the percentage of time in which the RC and the AB signals were in opposite direction) and phi (an angle derived from a Lissajous loop) were also calculated. All subjects responded to the challenge. The median fall in PtcO2 following methacholine challenge was 23.6% and in VmaxFRC was 43%. A large scatter of baseline values was found for all indices with the exception of TTA. There was no correlation between TTA and age, length, or VmaxFRC. The IAI and EAI with the RC band in the upper position were the most sensitive indices, both within subjects (65% of the subjects had a significant change in IAI and 80% in EAI) and for the group as a whole (median values increased for IAI, P = 0.007, and for EAI, P = 0.017). TTA and phi were less sensitive, and a great discrepancy was observed between the two measurements. Poor results were obtained with the RC band in the lower position. No correlations were found between the changes in IAI and EAI, with the RC band around the lower chest and VmaxFRC. We conclude that IAI and EAI, measured with the RC band in the upper position and another band around the abdomen, can detect changes in thoracoabdominal asynchrony in most infants. The usefulness of assessing IAI and EAI in infants with acute lower airway obstruction needs to be determined.

In-vitro susceptibility of Haemophilus influenzae to loracarbef (LY 163892) and other oral antibiotics. Collaborative Study Group on Pediatric Infectious Disease in Lombardy.

Data on susceptibility of Haemophilus influenzae are scanty in Italy. We compared the activity of loracarbef (Ly 163892), a new carbacephem, with that of 4 other agents against 265 strains of H. influenzae (46 type b, 219 nontypable) isolated from adults and children at Istituti Clinici di Perfezionamento of Milano, between 1/1/84 and 1/1/89, and also from 7 children at pediatric departments in Lombardy during 1988. In adults 72 strains were all isolated from sputum of patients with pneumonia or chronic bronchitis; in children 199 strains were isolated from conjunctiva (53% of the patients had also a concomitant respiratory infection), 24 from middle ear, 18 from sputum and 32 from blood or cerebrospinal fluid. Minimal inhibiting concentrations (MIC) were determined by the broth microdilution technique. The incidence of resistance of H. influenzae to ampicillin was 3.8%; the lowest percentage of resistance was found for loracarbef (0%) and the highest for erythromycin (94% for strains isolated from children and 97% for strains isolated from adults).

Gas exchange response to exercise in patients with chronic heart failure.

The objective of the study was investigate the pulmonary gas exchange response to exercise in 16 male patients with chronic heart failure (CHF) due to previous myocardial infarction and left ventricular dysfunction (ejection fraction < 45%). All patients underwent a symptom-limited exercise test during which cardiac frequency (fC), tidal volume (VT), respiratory frequency (fR), minute ventilation (V'E), oxygen consumption (V'O2) and carbon dioxide production (V'CO2) were measured on a breath-by-breath basis. Ventilatory equivalent for carbon dioxide (V'E/V'CO2) and lactate threshold (LT) were calculated. Arterial blood gas levels were measured at rest and at peak exercise. The dead space (VD) to tidal volume ratio (VD/VT) and alveolar-arterial oxygen gradient (PA-a,O2) were computed. Two subgroups of patients were identified according to peak V'O2 (V'O2,peak), group A (n = 7), V'O2,peak > 14 mL.kg-1.min-1 (17.2 +/- 2.5 SEM, range 14.5-20.8), and group B (n = 9), V'O2,peak < 14 mL.kg-1.min-1 (11.9 +/- 1.8, range 9.2-13.6). Arterial oxygen tension (Pa,O2) increased from rest to peak exercise in both groups (group A: 12.2 +/- 0.94 to 13.4 +/- 0.82 kPa (91.4 +/- 7.1 to 100.4 +/- 6.2 mmHg), p < 0.05; group B: 11.7 +/- 1.0 to 13.4 +/- 1.1 kPa (88.0 +/- 7.8 to 100.9 +/- 8.2 mmHg), p < 0.01), while a significant reduction in arterial carbon dioxide tension (Pa,CO2), from rest to peak exercise, was observed in group B only (4.64 +/- 0.39 to 4.08 +/- 0.36 kPa (34.9 +/- 2.8 to 30.7 +/- 2.7 mmHg), p < 0.005). Maximal V'E and maximal power (Powermax) were significantly lower in group B compared to group A (V'E 37.6 +/- 8.4 versus 52.1 +/- 13.8 L.min-1, p < 0.05; Powermax 64.4 +/- 12 versus 82.8 +/- 14.1 W, p < 0.01). fC was not significantly different at peak exercise, although the work load was significantly higher in group A. VD/VT failed to decrease significantly at maximal exercise in both groups. In group B, V'E/V'CO2 tended to be higher than in group A. In chronic heart failure patients, measurements of arterial blood gas levels during exercise might help to identify those subjects with a more pronounced depression of left ventricular function. At peak exercise, high ventilatory demand and respiratory alkalosis were observed in group B patients, suggesting an increased responsiveness of the respiratory centre that might be one major factor contributing to this excessive ventilatory response to exercise; vice versa, a combination of ventilation-perfusion mismatch, wasted ventilation and unpaired peripheral blood circulation seem to play only a minor role.