Effect of high-fat meals and fatty acid saturation on postprandial levels of the hormones ghrelin and leptin in healthy men.

OBJECTIVE: Ghrelin and leptin play a role in control of food intake and adiposity but mechanisms regulating these hormones in man are poorly defined and evidence that dietary fats may have adverse effects is inconclusive. We investigated whether high-fat meals, which differed in saturated fatty acid (SFA) content acutely modified these hormones. DESIGN: Randomised, double-blind, crossover trial. A high-fat (HF) test meal (59 +/- 4 g fat; 71% of energy as fat) was given for breakfast on two occasions. Meals comprised either high (approximately 70:30) or low (approximately 55:45) saturated:unsaturated fatty acid (SFA:USFA) ratio. Fasting and postprandial measurements of serum total ghrelin (RIA), leptin (enzyme-linked immunosorbent assay (ELISA)) and insulin (RIA) were made over 6 h. Postprandial measurements were also made at 10 and 24 h following a fat-exclusion lunch, snack and dinner. SUBJECTS: A total of 18 lean, healthy men. RESULTS: There was no significant effect of the fatty meal (time, P > 0.05), nor a differential effect of SFA:USFA ratio (treatment*time, P > 0.05) on ghrelin over 6h. Leptin decreased in response to both HF treatments (time, P < 0.001) but increased SFA content did not further inhibit hormone secretion (treatment*time, P > 0.05). There was no significant correlation between ghrelin or leptin and circulating insulin (P>0.05). CONCLUSION: We conclude that HF diets may adversely effect serum leptin, although the circadian decrease may account in part for this response. Increasing dietary SFAs had no deleterious effects on leptin or total ghrelin.

Quantitative noninvasive method to measure cerebral blood flow in newborn infants.

We measured cerebral blood flow (CBF) in 32 healthy neonates by venous occlusion plethysmography. Mean CBF was 63 ml/min/100 gm which compared favorably with invasive methods used in older children and adult subjects. We suggest that this is a useful method to quantify CBF in neonates. It may be valuable in assessing sequential changes occurring during asphyxia, intracranial hemorrhage, or during administration of various gas mixtures and drugs such as theophylline.

Arterial oxygen desaturation following salbutamol inhalation in acute asthma.

The practicality and accuracy of a new ear oximeter was evaluated. The SaO2 measured with this instrument correlated significantly with simultaneous SaO2 measurements with another ear oximeter in 12 children (age three months to 20 years) with chronic pulmonary or cardiac diseases (r = 0.93, p less than 0.001), and also correlated significantly (r = 0.96, p less than 0.001) with calculated SaO2 based on blood gas measurements of blood from the left side of the heart obtained during cardiac catheterization. The SaO2 was then measured continuously and readings were taken before and five, 15, and 30 minutes after salbutamol inhalation by face mask in 18 children. Following treatment, mean PEFR increased significantly, and mean SaO2 was significantly lower than preinhalation values at five and 15 minutes postinhalation. At 30 minutes, SaO2 had returned to control values. In nine of 18 subjects, SaO2 fell greater than or equal to 5 percent. This response was not predictable on the basis of different parameters (treatment, heart rate, PEFR). The findings suggest that supplemental O2 may be required during the first 30 minutes posttreatment.

The effect of 2% CO2, 100% O2, theophylline and 15% O2 on "inspiratory drive" and "effective" timing in preterm infants.

We studied 20 preterm infants (B.W. 1440 +/- 80 g (S.E.); G.A. 33 +/- 1 wk) to determine the effect of respiratory stimulants and depressants on respiratory output as measured by VE = VT . f, and VE = VT/Ti . Ti/Ttot. These 20 infants were divided in four groups of five infants. Each group received a respiratory stimulant (2% CO2, 100% O2 or theophylline) or'a respiratory depressant (15% O2). VT/Ti is mean inspiratory flow and represents a mechanic translation of neuronal output. Ti/Ttot is a dimensionless number and has been defined as effective timing. Each study consisted of 3-5 min while the infant breathed 21% O2, followed by 5 min breathing 2% CO2, 100% O2 or 15% O2. The effect of theophylline was assessed by 48-72 h after the initial dose. The respiratory stimulants caused an increase in VT with little or no change in f; 15% O2 produced a decrease in f primarily. According to the newer approach, 2% CO2, 100% O2 and theophylline produced an increase in "inspiratory drive" with little or no change in "effective" timing; 15% O2 decreased "effective" timing primarily via an increase in Te. These findings suggest that the paradoxical decrease in ventilation during hypoxia in preterm infants may not be solely dependent on the central depressant effects of O2. At least in part, the mechanism may be due to a direct action of low O2 on elements controlling expiratory time.

Ventilatory response to 100% and 15% O2 during wakefulness and sleep in preterm infants.

To examine the ventilatory response to 100% and 15% O2 during wakefulness and sleep, we studied eleven preterm infants birthweight 1770 +/- 102 g; gestational age 32 +/- 1 weeks; postnatal age 31 +/- 5 days) on two occasions each. Wakefulness (W) was present around feeding time and was defined by open eyes for more than 2 min plus presence of purposeful movements. Rapid eye movement (REM) and non-rapid eye movement (N-REM) sleep were defined using electroencephalogram (EEG), electrooculogram (EOG), electrocardiogram (ECG), and body movements. During 100% O2 breathing, immediate (30 s) decreases of 28, 39 and 37% followed by late (5 min) increases in ventilation (Ve) of 42, 49 and 27% were observed during W, REM and N-REM sleep (P greater than 0.05 between states). PaCO2 decreased significantly towards the end of 5 min of breathing 100% O2 in W, REM and N-REM sleep (P greater than 0.05). Average duration of apnea following sudden administration of 100% O2 was 8.5, 11.1 and 8.8 s during W, REM and N-REM sleep (P greater than 0.05 between states). During inhalation of 15% O2, there was a late decrease in ventilation of 19 and 23% during wakefulness and REM sleep, and a sustained increase in Ve of 17% during N-REM sleep (P less than 0.05). PaCO2 at the end of hypoxia (5 min) was significantly decreased in N-REM sleep only (P less than 0.05). We suggest that (i) peripheral chemoreceptor activity is qualitatively intact during W and sleep, as reflected by (a) the immediate changes in Ve during inhalation of high and low O2, and (b) apnea following administration of 100% O2. (ii) The late decrease in ventilation with hypoxia is absent in N-REM sleep.

Evaluating the cost-effectiveness of orthodontic provision.

The assessment of orthodontic provision is important to determine if treatment was necessary and undertaken appropriately. The ICON objectively quantifies orthodontic treatment need, complexity and outcome and is a valuable occlusal index in the assessment effectiveness of orthodontic care. It is possible to develop cost-effectiveness models by analysing the costs and effectiveness of orthodontic treatment. Several methods are illustrated to compare the orthodontic provision of specialist orthodontists.

Frequent feeding delays the gastric emptying of a subsequent meal.

To assess the suitability of the 13C-octanoic acid breath test for measuring gastric emptying in circumstances other than the post-absorptive state, a preliminary study was performed where 6 hourly spaced isoenergetic meals preceded the determination of gastric emptying of a subsequent 2 MJ meal. Emptying was measured in three individuals on four separate occasions, with a reproducibility of 8%. A crossover study was then conducted to test the hypothesis that meal frequency can modulate the gastric emptying of a subsequent meal, with the potential to influence appetite regulation. Sixteen subjects were fed to energy balance, receiving food either as 2 isoenergetic meals 3 h apart or 6 isoenergetic meals fed hourly. Gastric emptying of a subsequent 2 MJ meal was investigated. Visual analogue scales were used throughout to assess appetite. The maximum rate of gastric emptying was unchanged but the onset of emptying was delayed by the more frequent feeding pattern. There was no significant difference in subjective appetite before or after the test meal. In conclusion, short-term increases in feeding frequency delayed the gastric emptying of a subsequent meal, but significant effects on post-meal appetite could not be demonstrated.

Sarcoidosis of the larynx in a child.

Sarcoidosis is a multisystem disease of unknown etiology characterized by non-caseating granulomatous inflammation of various organs, but most frequently involving the lungs of young adults. Sarcoidosis is rare in the pediatric age group, however numerous extensive reviews have been published. The most commonly seen initial manifestations in childhood are non-specific constitutional symptoms such as lethargy, fatigue and malaise, followed by cough, dyspnea, fever, weight loss, and lymphadenopathy in order of decreasing frequency. The diagnosis is one of exclusion and is established when clinical and radiological findings are supported by histological evidence of widespread non-caseating epithelial cell granulomas in more than one organ, or a positive Kveim test. Laryngeal involvement is usually part of the systemic disease, but isolated laryngeal sarcoidosis has been reported in adults. We report here a case of isolated laryngeal sarcoidosis in a 13 year old girl. The differential diagnosis and management are discussed.

Cranial blood volume changes during mechanical ventilation and spontaneous breathing in newborn infants.

We derived a noninvasive method to compare changes in cranial blood volume during mechanical ventilation with changes occurring during spontaneous breathing in newborn infants. In ten infants receiving mechanical ventilation, cranial blood volume increased during inspiration by a mean of 8.3%. We found a consistent relationship between clinical estimation of lung compliance and the amount of cranial volume expansion. During spontaneous breathing in ten infants cranial blood volume decreased during inspiration by a mean of 5.8%. The findings indicate the need for careful monitoring during periods of rapid changes in lung compliance.

Effect of CO2 and 100% O2 on cerebral blood flow in preterm infants.

To determine 1) the effect of arterial CO2 change on the neonatal cerebral circulation and 2) whether 100% O2 would produce significant decrease in cerebral blood flow (CBF), we studied 24 preterm infants to explain the late (5 min) hyperventilation observed in them during hyperoxia. Of these, 12 were studied before and during inhalation of 2-3% CO2 and 12 before and during the inhalation of 100% O2. We measured CBF by a modification of the venous occlusion plethysmography technique and found that CBF increased 7.8% per Torr alveolar carbon dioxide pressure change and that it decreased 15% with 100% O2. These findings suggest that 1) CO2 is an important regulator of CBF in the perterm infant, 2) CBF-CO2 sensitivity in these infants may be greater than in adult subjects, 3) 100% O2 reduced CBF significantly, and 4) a decrease in CBF during administration of 100% O2 may be at least partially responsible for the increase in ventilation with hyperoxia.

Relationship between respiratory muscle strength, nutritional status, and lung volume in cystic fibrosis and asthma.

We measured static inspiratory and expiratory pressures (PImax and PEmax) in 29 patients with asthma for comparison with a previously reported group of 25 patients with cystic fibrosis (CF) and 80 normal control subjects. The purpose of the study was to assess the relationship between respiratory muscle strength, nutritional status, lung volumes, and training effect of the increased work of breathing in patients with chronic air-flow limitation. PEmax was similar in the asthma group, CF group, and normal control subjects despite a significant degree of malnutrition in the CF group (mean body mass percentile (BMP), 78 versus 107% in the asthma group, p less than 0.001). There was no correlation between BMP and PImax or PEmax in either study group. PImax, when corrected for lung volume, was greater than age- and sex-matched control values in 24% of the patients with CF and 48% of the patients with asthma. We conclude that respiratory muscle strength is not related to nutritional status (as measured by BMP) in patients with CF and asthma. Above-normal inspiratory muscle strength may result from a training effect of the increased work of breathing in both CF and asthma, regardless of nutritional status.

The effects of chronic hyperinflation, nutritional status, and posture on respiratory muscle strength in cystic fibrosis.

We measured maximal static inspiratory and expiratory pressures (PImax and PEmax) in 25 patients with cystic fibrosis (CF) and 80 normal control subjects to determine whether chronic hyperinflation and malnutrition reduce PImax and PImax/PEmax, respectively. In addition, we examined the effect of posture on pressures generated. We used a diminution in PEmax as an index of a malnutrition effect on pressures generated. The patients with CF, although significantly hyperinflated (ratio of residual volume to total lung capacity, 0.49), generated PImax values similar to those of the control subjects (p greater than 0.05). Despite evidence of malnutrition (mean body mass percentile, 78%) the PEmax values of patients with CF and those of control subjects were comparable (p greater than 0.05). There was no postural effect on pressures generated in the normal subjects or the CF group as a whole. We conclude that respiratory muscle strength is normal or supranormal in CF, despite chronic hyperinflation and malnutrition.

Spectral analysis of breath sounds in normal newborn infants.

To determine whether breath sounds in newborns are different from those described in older subjects, fast Fourier transform and power spectra analysis were performed on recorded breath sounds from 14 normal newborns. A respiration-triggered sampling technique was applied to compare early, middle, and late phases of inspiration and expiration, using a thoracic impedance signal. Peak frequencies were found in the range described for normal breath sounds in older subjects, and the frequency range of breath sounds was similar to that reported for older children and adults. The difference in breath sound quality of normal newborns appears to depend on the sound intensity during expiration. In contrast to older subjects, newborns showed only slightly less sound intensity during expiration; in the late phases of inspiration and expiration this intensity was almost equal.

Neonatal pulmonary infarction. A cause of 'cystlike' lucencies on the chest roentgenogram.

Perinatal pulmonary infarction is a difficult and infrequently made diagnosis. A male newborn had infarction of most of the right lung secondary to perinatal pulmonary thromboembolism (PTE). Serial chest roentgenograms initially showed opacity of most of the right lung, followed by the appearance of well-defined radiolucencies resembling pneumatoceles associated with mass effect. By the 25th day of life the localized "cystlike" lucencies were no longer evident and the right lung appeared predominantly hyperlucent. Although the presence of underlying disease makes the diagnosis of PTE in the infant and young child difficult, the clinical features and methods of diagnosis of PTE in this age group are similar to those for the adult. The diagnosis of PTE should be considered in the infant with respiratory distress and unusual findings on chest roentgenography.

Effect of feeding on the chemical control of breathing in the newborn infant.

To examine the influence of feeding on the chemical control of breathing in neonates, we studied the ventilatory response to 3% CO2 in air in nine bottle fed (BOT) and eight breast fed (BR) term infants during feeding while the infants were alert. Control responses were obtained either before or after feeding, VE, respiratory frequency, tidal volume, inspiratory time, expiratory time, and sum of inspiratory and expiratory time, VT/Ti/Ttot, PACO2 and slope (S) of CO2 response (liter/min/kg/mmHg) were determined. During 3% CO2 while resting BR had a lower VE, VT, VT/Ti than BOT and S in BR was 40% of BOT (P less than 0.05). During feeding and CO2 when compared to resting and CO2 there was no difference in either BR or BOT in VT/Ti but Ti/Ttot decreased in both groups. During feeding, S in BOT was reduced from 0.049 +/- 0.012 (mean +/- S.E.) to 0.013 +/- 0.002 (74% reduction) and in BR from 0.020 +/- 0.002 to 0.009 +/- 0.002 (55%). Thus, behavioral activity (either BR or BOT) markedly depresses the ventilatory response to chemical stimuli (CO2). This modification is primarily related to changes in "effective" respiratory timing (Ti/Ttot) rather than mean inspiratory flow (VT/Vi).

Effect of periodic or regular respiratory pattern on the ventilatory response to low inhaled CO2 in preterm infants during sleep.

We wanted to know whether the ventilatory response to low concentrations of CO2 is measurable in the absence of change in alveolar PCO2, is sleep state dependent, and is dictated by the resting respiratory pattern. Therefore, we gave 11 preterm infants (birth weight, 1,565 +/- 122 g; gestational age, 32 +/- 1 wk; postnatal age, 28 +/- 5 days) 0.5 to 1.5% CO2 after a control period of breathing 21% O2. They were studied on 2 or 3 occasions, the aim being to have 5 infants in each of 2 categories, periodic to regular breathing, and regular to regular breathing, after administration of CO2 in both sleep states (n = 20). In both sleep states, when low CO2 increased ventilation, alveolar PCO2 also increased. The increase in ventilation was primarily due to an increase in breathing frequency if breathing was periodic, and to an increase in tidal volume if breathing was regular. This response was not affected by sleep state. We conclude that changes in respiratory pattern with low inhaled CO2 are fundamentally dependent on whether the baseline respiration is periodic or regular.

Chemical control of respiratory frequency and tidal volume during sleep in preterm infants.

During a given sleep state, respiration changes from periodic to regular and vice-versa. Because such spontaneous changes occur without changes in electro-encephalogram (EEG), electro-oculogram (EOG), electro-cardiogram (ECG) or body movements, we hypothesized that they are induced by chemical stimuli such as CO2. To test this hypothesis we examined 12 preterm infants in whom spontaneous changes in respiratory pattern were allowed to occur within the same sleep state, and infants in whom such changes were induced by inhalation of 0.3% to 1.2% CO2. Using a nosepiece and a screen flowmeter we measured the respiratory pattern, VE, f, VT, TI, TE, Ttot, VT/TI, TI/Ttot and PACO2. In REM sleep, spontaneous changes from periodic to regular were associated with increase in VE from 0.466 (mean) to 0.530 L/min (P less than 0.5) and CO2 induced changes accompanied by an increase in VE from 0.416 to 0.571 L/min (P less than 0.05). Similarly in N-REM sleep, VE increased from 0.385 to 0.445 L/min (P less than 0.05) during CO2 induced changes, and from 0.420 to 0.454 L/min (P less than 0.05) during CO2 induced changes, and from 0.420 to 0.454 L/min (P less than 0.05) during CO2 induced changes. Increased VE produced both spontaneously or by CO2 administration was associated with decreased VT, decreased Ttot, decreased VT/TI and slight increase in PACO2. We suggest that changes in respiratory pattern occurring within the same sleep state are chemically mediated.