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Biomedical subjects

D Gozal

Publications and source records attributed to D Gozal.

At least 127 records · Page 7Linked to original sources

Maturation of kitten ventral medullary surface activity during pressor challenges.

We used large-array optical recording procedures to examine maturation of regional neural activity within the ventral medullary surface (VMS) of anesthetized kittens during pharmacologically induced blood pressure elevation. Under sodium pentobarbital anesthesia, the VMS was exposed in 10, 20 and 30- to 45-day-old kittens and in adult cats. Arterial pressure, costal diaphragmatic EMG, and ECG were continuously monitored. An imaging camera, composed of a charge-coupled device and a coherent bundle of optic fibers, was positioned over the VMS. Light at 660 nm illuminated the neural tissue, and was collected by the probe. Resulting light-scatter images were acquired at 2-second intervals during a baseline period, and following intravenous administration of phenylephrine at 10, 20 and 40 micrograms/kg. Sixty to seventy-five images within each epoch were averaged, and subtracted from baseline. Regional differences within the image were determined by ANOVA procedures (alpha = 0.05). Phenylephrine elicited dose-dependent elevations of blood pressure accompanied by decreased diaphragmatic EMG activity which were less profound in younger animals. With maturation, responsiveness of respiratory patterning to the pressor response increased. In contrast to adult cats, 10-day kittens increased VMS neural activity in a dose-dependent fashion with pressor stimulation. A progressive transition to adult response patterns was observed with increasing postnatal age, and was established in over half of the kittens by 30-45 days. We conclude that phenylephrine-induced baroreceptor stimulation elicits divergent VMS activity responses in developing and mature animals. Such a developmental pattern may reflect immature function of central and/or peripheral baroreflexes.

Aging↗

Peripheral chemoreceptor function in children with myelomeningocele and Arnold-Chiari malformation type 2.

Blunted rebreathing hyperoxic hypercapnic ventilatory and arousal responses are frequent in older children with myelomeningocele (MMC) and Arnold-Chiari malformation type 2 (ACM). In contrast, isocapnic hypoxic rebreathing ventilatory responses are only occasionally affected. Thus, regions mediating the hypoxic ventilatory response appear usually preserved in children with MMC and ACM. Peripheral chemoreceptor function (PCR), however, has not been critically assessed in these children. To study this, PCR was measured in ten children and adolescents with MMC and ACM with normal alveolar ventilation during wakefulness, and in ten sex- and age-matched controls by measuring the ventilatory responses induced by 100% O2 breathing, five tidal breaths of 100% N2, and vital capacity breaths of 15% CO2 in O2. In general, tidal breathing of 100% O2 resulted in smaller decreases in minute ventilation (VE) responses in patients with MMC, although absent VE responses to hyperoxia were found in four patients. Vital capacity breaths of 15% CO2 elicited similar increases in VE in five patients and in ten controls, but no changes in VE were found in the remaining five patients (p < 0.02). Acute hypoxia induced by N2 tidal breathing resulted in significant linear regression correlations between VE and SpO2 in five patients with MMC, while absent responses were measured in those same five patients with absent hypercapnic responses. We conclude that PCR, when assessed by acute hypoxia, hyperoxia, or hypercapnia is abnormal in some children with MMC and ACM, particularly in those demonstrating abnormal ventilation during sleep. We postulate that the large interindividual variability of PCR is dependent on the severity of brainstem involvement of PCR afferents or central respiratory integration sites.

Adolescent↗

Afferent contributions to intermediate area of the cat ventral medullary surface during mild hypoxia.

The intermediate area of the cat ventral medullary surface activates to mild hypoxia. Carotid body and vagal afferent contributions to this response were examined by recording activity levels, measured as changes in scattered 660 nm light, from the medullary surface in 7 anesthetized, spontaneously breathing cats following 12% O2 in N2 ventilatory challenge. A miniaturized video camera collected images synchronous with the peak of cardiac R wave at 1/s, from a 3.2 mm diameter area, before, and following bilateral carotid sinus denervation (CSD) and vagotomy. In intact animals, hypoxia increased activity; however, greater increases in activity levels followed CSD, while vagotomy elicited a marked reduction of the response. Thus, carotid body afferents exert inhibitory or disfacilitatory influences on intermediate area neurons, while the vagus appears to play an excitatory role.

Afferent Pathways↗

Dynamic magnetic resonance imaging of human Rolandic cortex.

Rolandic cortex was imaged with magnetic resonance (MR) in nine subjects while performing a motor activation task. Imaging was performed by a volumetric, T2-weighted pulse sequence in a conventional 1.5 Tesla scanner during both resting conditions and volitional toe flexion and extension of the dominant foot. Significant changes in MR signal intensity of 7.8 +/- 2.3% (mean +/- s.e.m.) were observed in the medial Rolandic cortex contralateral to the active foot. Changes were maximal in the vicinity of the central sulcus, but were also identified anteroposteriorly, across successive coronal planes. No significant changes were found in the ipsilateral Rolandic cortex or in other brain structures. Volumetric functional MRI strategies may provide an important non-invasive tool for assessment of cortical motor function.

Adolescent↗

Incidence of sudden infant death syndrome in infants with sickle cell trait.

The significantly higher incidence of both sickle cell trait (SCT) and sudden infant death syndrome (SIDS) in the black population suggests that SCT and SIDS may be epidemiologically related. To study this possibility, we identified, for the period of February 1990 to February 1992, all infants with SCT born in Los Angeles County whose disease was diagnosed through the California Newborn Screening Program. We matched these infants with all confirmed cases of SIDS in Los Angeles County from February 1990 to March 1993. Three cases of SCT among 589 infants confirmed to have had SIDS were identified. The incidence of SIDS was 1.25/1000 live births for the general population versus 0.58/1000 cases for the SCT group. This finding remained unchanged when rates were adjusted for ethnicity. We conclude that infants born with SCT are not at increased risk of dying of SIDS.

Black People↗

Bupivacaine wound infiltration in thyroid surgery reduces postoperative pain and opioid demand.

Control of postoperative pain is an important element in preventing the modification of the excitability of the dorsal horn neurons. We studied the efficacy of bupivacaine 0.5% wound infiltration for postoperative pain management following thyroid surgery. Forty consecutive ASA I-II patients, scheduled for thyroidectomy, were assigned randomly to two groups. Group I (n = 20) consisted of patients receiving bupivacaine 0.5% (10 ml) wound infiltration at the end of surgery and group II (n = 20 included patients without infiltration. The patients did not know whether the wound had been anaesthetized or not. All patients received balanced inhalational anaesthesia, including fentanyl (a total dose of up to 4 micrograms.kg-1). Postoperative pain medication included morphine IV or IM, as needed. Twenty-four hours after surgery the worst pain was recorded using a visual analogue scoring system, from 0 to 10. Twenty-four hour postoperative morphine requirement was recorded. Groups did not differ in demographic data. Pain scores significantly different in the two groups. In group I, the mean pain score was 3.7 +/- 1.6 compared with 6.9 +/- 1.7 in group II (P < 0.05). Only six patients (30%) in group I received opioids and only one of these (5%) had a pain score above 5. In comparison, 18 patients (90%) in group II received morphine during the first postoperative day. The local injection of bupivacaine corresponds to a block of the superficial branches of the cervical plexus. This study demonstrated a simple, efficient and safe way to reduce pain perception following a thyroidectomy.

Adolescent↗

Ventral medullary surface activity during sleep, waking, and anesthetic states in the goat.

We examined activity, measured as changes in reflected light, from the surface of a rostral ventral medullary area that is involved in cardiorespiratory control. We collected images during sleep and waking states and during halothane anesthesia in five adult unrestrained goats. During quiet sleep, overall activity increased and overall variability decreased compared with waking levels, whereas rapid eye movement sleep increased variability, and average activity decreased to near-waking levels. Distinct regions of activation and suppression appeared during sleep states. Deep anesthesia decreased activity and minimized variation. We speculate that alterations in rostral ventral medullary surface activity may play a role in state-dependent changes in cardiorespiratory control mechanisms.

Activity Cycles↗

Maturational differences in step vs. ramp hypoxic and hypercapnic ventilatory responses.

The influence of the speed of stimulus presentation on hypoxic and hypercapnic ventilatory responses (step vs. ramp) is not known. Furthermore, it is unclear whether children and adults respond similarly. We tested ramp ventilatory responses to hypercapnia and hypoxia with use of rebreathing in 8 prepubertal children and 11 adults. We tested step ventilatory responses to hypercapnia with single vital capacity breaths of 15% CO2 in O2 and to hypoxia with five tidal breaths of 100% N2. For children, slopes of step hypercapnic ventilatory responses were always greater than those of ramp responses (0.85 +/- 0.07 vs. 0.71 +/- 0.07 l.min-1.Torr end-tidal PCO2-1; P < 0.0005). Conversely, for adults, step responses were always less than ramp responses (0.88 +/- 0.19 vs. 2.10 +/- 0.29 l.min-1.Torr end-tidal PCO2-1; P < 0.0007). Similarly, for children, the slopes of step hypoxic ventilatory responses were always greater than those of ramp responses (-0.71 +/- 0.09 vs. -0.45 +/- 0.04 l.min-1.Torr O2 saturation-1; P < 0.02), and for adults, step responses were always less than ramp responses (-0.68 +/- 0.14 vs. -1.85 +/- 0.46 l.min-1.Torr O2 saturation-1; P < 0.04). We conclude that ventilatory responses vary depending on step vs. ramp presentation of hypercapnia or hypoxia and that the ratio of these responses is reversed in children compared with adults. We speculate that the responsiveness of peripheral chemoreceptors is increased in children compared with adults and that it may play a role in the mechanisms leading to increased ventilatory responses observed during childhood.

Adult↗

Localization of putative neural respiratory regions in the human by functional magnetic resonance imaging.

In humans, the location of brain regions responsible for mediating the ventilatory response to CO2 remains unknown. Most of the available knowledge has been derived from animal studies or from pathophysiological correlations in patients presenting altered control of breathing. Magnetic resonance imaging at a specific pulse sequence designed to assess changes in brain tissue microcirculation was performed in 11 healthy volunteers, during steady-state conditions, while breathing 100% O2 or 5% CO2-95% O2. In one subject, 10% CO2-90% O2 was employed to examine a dose-response effect. Significant changes in image signal intensity consistently occurred in ventral and dorsal regions of medullary structures as well as in the midline pons and ventral cerebellum. These responses appeared to be dose dependent and reproducible. Magnetic resonance imaging revealed patterns of activation in brain stem and cerebellar regions during hypercapnic ventilatory challenge. These areas may underlie mechanisms for mediating the response to chemoreceptor activation.

Adolescent↗

Hypoxic and hypercapnic ventilatory responses in Prader-Willi syndrome.

Abnormalities of ventilatory control may play a significant role in the pathophysiology of sleep-disordered breathing in patients with the Prader-Willi syndrome (PWS). We measured rebreathing hypercapnic and hypoxic ventilatory responses (HCVR and HPVR, respectively) during wakefulness in 8 nonobese PWS (NOB-PWS) and 9 obese PWS (OB-PWS) patients and compared their results with those from 24 healthy nonobese control (NOB-CON) and 10 obese control (OB-CON) subjects. The slope of HCVR was similar in NOB-PWS patients and NOB-CON subjects (NS). However, HCVR was significantly lower in OB-PWS patients than in OB-CON subjects (P < 0.02). In PWS patients, the mean point of origin of the positive slope of HCVR occurred at a significantly higher end-tidal PCO2 than in either control group. During isocapnic hypoxic challenges, six PWS patients had no significant HPVR. In the remainder, mean slopes of HPVR were -0.80 +/- 0.06 l.min-1.%arterial O2 saturation-1 in five NOB-PWS patients and -0.68 +/- 0.15 l.min-1.%arterial O2 saturation-1 in six OB-PWS patients. These responses were significantly decreased compared with those in the control groups (P < 0.006). We conclude that NOB-PWS patients have normal HCVR, which is blunted in OB-PWS patients. Furthermore, isocapnic HPVR is either absent or markedly reduced in PWS patients. The severity of abnormality of the HPVR is independent of the degree of obesity. We postulate that the primary abnormality of ventilatory control in PWS affects peripheral chemoreceptor pathways.

Adult↗

Absent peripheral chemosensitivity in Prader-Willi syndrome.

Abnormalities in ventilatory control during wakefulness and sleep have been observed in patients with Prader-Willi syndrome (PWS). The role of peripheral chemoreceptors in the pathophysiology of abnormal ventilatory responses in PWS is unknown. We studied peripheral chemoreceptor function during wakefulness in 17 genetically confirmed PWS patients [age 27.0 +/- 2.5 (SE) yr; 7 males, 10 females; body mass index 31.1 +/- 1.4 kg/m2] and compared their responses with 17 control subjects matched for age, sex, and body mass index. All PWS and control subjects had normal resting end-tidal PCO2 and arterial O2 saturation while awake. Peripheral chemoreceptor function was assessed by the ventilatory responses to 100% O2 breathing, five tidal breaths of 100% N2, and vital capacity breaths of 15% CO2 in O2. Control subjects decreased minute ventilation (VE) by 15.5 +/- 3.6% during hyperoxia. However, PWS patients increased VE by 17.6 +/- 3.3%, indicating a paradoxical response to hyperoxia (P < 0.00001). After CO2 vital capacity breaths, PWS patients showed no significant change and control subjects showed a marked increase (P < 0.0001) in VE. During N2 breathing, again PWS patients showed no change and control subjects exhibited a marked increase (P < 0.00005) in VE. We conclude that PWS patients have absent peripheral chemoreceptor ventilatory responses. We speculate that the lack of ventilatory responses is due to primary peripheral chemoreceptor dysfunction and/or defective afferent pathways to central controllers.

Adult↗

Ventilatory responses during wakefulness in children with obstructive sleep apnea.

The pathophysiology of the obstructive sleep apnea syndrome (OSAS) is not fully understood. In children, airway obstruction secondary to tonsilloadenoidal hypertrophy is the leading cause of OSAS. However, not all children with tonsilloadenoidal hypertrophy develop OSAS. Thus, other factors, including abnormalities in ventilatory control, may contribute to the etiology of OSAS. To test this, we performed polysomnography and hypercapnic and hypoxic ventilatory response testing in 20 children and adolescents with OSAS (mean age, 8 +/- 3 [SD] yr) and 19 control subjects. Only two children with OSAS were obese. Children with OSAS had an apnea index of 16 +/- 20, peak PETCO2 of 54 +/- 5 mm Hg, and SaO2 nadir of 84 +/- 13% during polysomnography. Ventilatory responses were performed by rebreathing techniques. The slope of the hypercapnic ventilatory responses, corrected for body surface area, was 1.74 +/- 0.79 L/min/m2/mm Hg PETCO2 in children with OSAS and 1.45 +/- 0.58 L/min/m2/mmHg PETCO2 in control subjects (NS). Hypoxic ventilatory responses, corrected for body surface area, were -0.94 +/- 0.49 L/min/m2/% SaO2 in children with OSAS and -0.95 +/- 0.45 L/min/m2/% SaO2 in control subjects (NS); however, the sample size was small. There was a weak inverse correlation between the slope of the hypercapnic ventilatory response and the duration of hypoventilation during polysomnography (r = -0.44, p < 0.05). We conclude that children with OSAS have normal ventilatory responses to hypercapnia, and they may have normal ventilatory responses to hypoxia. We speculate that abnormal central ventilatory drive plays little if any role in the pathogenesis of pediatric OSAS.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoids↗

Comparison of high frequency chest compression and conventional chest physiotherapy in hospitalized patients with cystic fibrosis.

Clearance of bronchial secretions is essential in the management of cystic fibrosis (CF) patients admitted for acute pulmonary exacerbation. Conventional physiotherapy (CPT) is labor-intensive, time-consuming, expensive, and may not be available as frequently as desired during hospitalization. High frequency chest compression (HFCC), which uses an inflatable vest linked to an air-pulse delivery system, may offer an attractive alternative. To study this, we prospectively studied 50 CF patients admitted for acute pulmonary exacerbation who were randomly allocated to receive either HFCC or CPT three times a day. On admission, clinical status and pulmonary function tests (PFT) in the HFCC group were not significantly different from those measured in the CPT group. Significant improvements in clinical status and PFT were observed after 7 and 14 d of treatment, and were similar in the two study groups, leading to patient discharge after similar periods of hospitalization. We conclude that HFCC and CPT are equally safe and effective when used during acute pulmonary exacerbations in CF patients. We speculate that HFCC may provide an adequate alternative in management of CF patients in a hospital setting.

Acute Disease↗

Genetic analysis of Hispanic individuals with cystic fibrosis.

We have performed molecular genetic analyses of Hispanic individuals with cystic fibrosis (CF) in the southwestern United States. Of 129 CF chromosomes analyzed, only 46% (59/129) carry delta F508. The G542X mutation was found on 5% (7/129) of CF chromosomes. The 3849 + 10kbC-->T mutation, detected primarily in Ashkenazi Jews, was present on 2% (3/129). R1162X and R334W, mutations identified in Spain and Italy, each occurred on 1.6% (2/129) of CF chromosomes. W1282X and R553X were each detected once. G551D and N1303K were not found. Overall, screening for 22 or more mutations resulted in detection of only 58% of CF transmembrane conductance regulator gene mutations among Hispanic individuals. Analysis of KM19/XV2c haplotypes revealed an unusual distribution. Although the majority of delta F508 mutations are on chromosomes of B haplotypes, the other CF mutations are on A and C haplotypes at higher-than-expected frequencies. These genetic analyses demonstrate significant differences between Hispanic individuals with CF and those of the general North American population. Assessment of carrier/affected risk in Hispanic CF individuals cannot, therefore, be based on the mutation frequencies found through studies of the general population but must be adjusted to better reflect the genetic makeup of this ethnic group. Further studies are necessary to identify the causative mutation(s) in this population and to better delineate genotype/phenotype correlations. These will enable counselors to provide more accurate genetic counseling.

Amino Acid Sequence↗

Sickle cell trait performance in a prolonged race at high altitude.

The limitation of aerobic exercise capacity of athletes with the sickle cell trait (SCT), under conditions of limited oxygen availability, is still controversial. To study this, we took advantage of an unique setting, the International Mount Cameroon Ascent Race, a 34.1-km race over difficult terrain, slopes ranging from 7 to 40%, and altitudes varying from 615 to 4095 m, combined with high prevalence rates of SCT among the African runners. Of 266 Cameroonian runners, SCT was detected in 33 athletes (12.4%), a prevalence similar to that of the ethnically corrected general population. However, in runners of the Bakoueri tribe whose performance is contingent with social stature, SCT was present in only 1 of 41 runners (2.4%), as compared with 15.6% in the general population of the Bakoueri tribe (P < 0.03). In general, performance times of SCT runners were not different from non-SCT runners, except during the portion of the race at altitudes ranging from 3800 to 4095 m, where significantly longer times were clocked by SCT subjects (P < 0.02). We conclude that prolonged aerobic efforts in hypobaric hypoxic conditions may be associated with a detrimental effect on performance in SCT carriers. If this is true, it might account for the reduced prevalence of SCT among those runners representing the Bakoueri tribe, provided an objective measure of performance at altitude was employed to select these representatives.

Altitude↗

Evolution of pulmonary function during an acute exacerbation in hospitalized patients with cystic fibrosis.

Few objective criteria have been validated for serial clinical monitoring in patients with cystic fibrosis (CF) during pulmonary exacerbations. While pulmonary function tests (PFT) are often used to monitor clinical improvement, it is not known which test correlates most closely with clinical improvement. To answer this, we measured routine PFT in 58 patients with CF before, during, and at discharge after 2-3 week hospital admission in 71 episodes of pulmonary exacerbation. Patients with CF were discharged based on clinical, radiological, and laboratory criteria. In general, all PFTs improved at midadmission and improved further by discharge, at which time forced expiratory volume in 1 second (FEV1), forced expiratory flow between 25% and 75% of forced vital capacity (FEF25-75), vital capacity (VC), maximal voluntary ventilation (MVV), and oxygen saturation by pulse oximetry (SPO2) increased. The residual volume to total capacity ratio (RV/TLC) and the slope of phase 3 in the single breath N2 washout curve (SP3 N2) decreased. The change in SP3 N2 was significantly greater than in any other PFT (P < 0.01 vs. VC and FEV1; P < 0.02 vs. RV and P < 0.001 vs. SPO2). A calculated optimal cut-off value for SP3 N2 improvement was significantly more sensitive in identifying patient improvement at discharge than any other pulmonary function test (P = 0.005). We speculate that clinical improvement in patients with CF is closely linked to improved distribution of ventilation.

Acute Disease↗