Biomedical subjects
Publications and source records attributed to D Gozal.
To determine how often inborn errors of metabolism may cause unexplained apnea or recurrent apparent life-threatening events in infants, we retrospectively reviewed the records of 166 infants who were referred for apnea evaluation. A metabolic disorder was identified in 7 infants (4.2%), all of whom had recurrent apparent life-threatening events.
Disorders of fatty acid beta-oxidation have been suggested as playing a significant role in the sudden infant death syndrome (SIDS). To elucidate the role of medium-chain acyl-coenzyme A dehydrogenase (MCAD) deficiency in SIDS, we identified all cases of SIDS occurring in Los Angeles County between January 1986 through December 1991. A total of 1304 SIDS deaths were identified; tissue samples were collected in 1236 cases (94.8%). Extraction of DNA was successful in 1224 tissue samples (93.9%), which were examined for the presence of the G985 mutation, identified as occurring in more than 88% of affected cases of MCAD deficiency. Three heterozygotes and no homozygotes were identified; this incidence does not differ from that reported in the general population. Review of the pathologic specimens from the identified heterozygotes and from 18 ethnic-, age-, and sex-matched control subjects revealed significant fatty infiltration of all organs examined in one of the three heterozygotes and in none of the control subjects. We conclude that MCAD deficiency does not play a significant role in the causation of SIDS.
We examined neuronal activation of the ventral medullary surface (VMS) during hypercapnic challenges using optical recording procedures. With a coherent imaging probe, we assessed reflected 700-nm light from 18 VMS sites in 11 spontaneously breathing adult cats and from the suprasylvian cortex in two cats. Video frames were acquired during a baseline period, hypercapnic (3, 5, and 10% CO2 in O2) exposure, and recovery. Hypercapnic exposure elicited overall reflectance changes in all VMS sites, but no changes in the suprasylvian cortex. Light reflectance changes, suggesting altered neuronal activity, were reproducible, occurred as early as 30 s after CO2 exposure, and were dose dependent. The changes persisted approximately 20-25 min beyond the stimulus, but respiratory responses consistently recovered within 2-3 min. Although more rostral VMS sites tended to be associated with decreased activity and caudal regions with increased excitation, no uniform topographical organization was apparent across animals. The variability in VMS optical reflectance patterns across animals during CO2 stimulation may reflect the heterogeneous topographical distribution of responsive neurons in the structure.
In children with the congenital central hypoventilation syndrome (CCHS), some patients require mechanical ventilation during sleep, whereas others need respiratory assistance even when awake. The cause of this disparity is unclear. We hypothesized that differences in peripheral chemoreceptor response (PCR) could provide an explanatory mechanism for this disparity in clinical manifestations. PCR was measured in five children with CCHS and five 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 5% and 15% CO2 in O2 and 5% CO2-95% N2. Tidal breathing of 100% O2 resulted in similar ventilatory responses in CCHS patients and controls with various changes dependent on the method of analysis of response used. Acute hypoxia by N2 tidal breathing resulted in a 39.2 +/- 22% increase in respiratory rate in CCHS patients and a 15.1 +/- 11.1% increase in controls (P < 0.05), with similar increases in minute ventilation (VE) of 124 +/- 69% and 85 +/- 11%, respectively. Vital capacity breaths of each of the CO2-containing gas mixtures induced similar increases in VE in CCHS patients and controls. The changes in VE obtained with 15% CO2-85% O2 and with 5% CO2-95% N2 were significantly greater than those with 5% CO2-95% O2, suggesting a dose-dependent response as well as additive effects of hypercapnic and hypoxic stimuli. We conclude that the PCR, when assessed by acute hypoxia, hyperoxia, or hypercapnia, is present and intact in CCHS children who are able to sustain adequate ventilation during wakefulness.(ABSTRACT TRUNCATED AT 250 WORDS)
Large-array optical recording procedures provide the potential to examine simultaneous activity of large numbers of neurons. We applied this technique to examine regional neuronal activation on the ventral medullary surface (VMS) of cats during hypoxic challenges. VMS was exposed through a ventral surgical approach in eight adult cats under pentobarbital sodium anesthesia. Arterial pressure, end-tidal CO2, costal diaphragmatic electromyograms, and electrocardiograms were continuously monitored. A coherent image conduit with 12-microns-fiber resolution was attached to a charge-coupled device camera and positioned over the VMS. Reflected 700-nm light was digitized continuously at 2- to 3-s intervals during baseline period, hypoxic (6, 9, and 12% O2 in N2) exposure, and recovery. Forty images within each epoch were averaged and subtracted from baseline. Regional differences within the image were determined by analysis of variance procedures (alpha = 0.05). In caudal VMS, hypoxic challenges with 12% O2 consistently induced a regional diminution in reflected light (increased neural activity) that was rapid in onset and persisted for approximately 20 min after termination of exposure, well beyond the duration of discernible ventilatory alterations. In contrast, the same challenge resulted in decreased neural activity of similar duration in rostral VMS areas. Challenges with lower inspired concentrations of O2 reversed the pattern of diminished neural activity in rostral regions and led to a dose-dependent increase in neural activity, a dependency also observed in caudal VMS. We conclude that caudal VMS neurons demonstrate a unidirectional dose-dependent response pattern to hypoxic stimuli, whereas rostral VMS regions exhibit a bidirectional response to increasing hypoxic stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)
Maximal transdiaphragmatic (Pdimax) and airway occlusion pressures (PaOmax) have been used to predict weaning from mechanical assisted ventilation in adults, but criteria for weaning are still based on trial and error in infants and young children. Because infants and young children cannot cooperate, crying Pdi and PaOmax against an occlusion have been used, but these may not yield maximal values. We hypothesized that breathing CO2 would achieve better Pdimax and PaOmax values by maximizing respiratory drive and help in establishing weaning criteria. To test this, we measured tidal breathing and occluded Pdi and PaOmax in 27 patients (mean age, 15.0 +/- 31.5 SD months) who required prolonged assisted mechanical ventilation and had failed previous weaning attempts. Measurements were performed while patients were breathing spontaneously 100% O2 and 5% and 7% CO2 in O2. The patients achieved higher Pdimax breathing 5% CO2 (73.2 +/- 24.4 cm H2O) than in O2 (61.6 +/- 24.4 cm H2O; p < 0.0001) or in 7% CO2 (69.1 +/- 23.4 cm H2O; p < 0.0001). They also achieved higher PaOmax in 5% CO2 (81.7 +/- 23.5 cm H2O) than with the other gases (69.9 +/- 25.5 in O2, and 77.5 +/- 24.1 in 7% CO2; p < 0.001); 19 patients (70%) were weaned from assisted ventilation within 3.2 +/- 1.9 wk. In 5% CO2, all patients who were weaned achieved Pdimax > 60 cm H2O and could sustain > 60% Pdimax for more than five successive occluded breaths (100% sensitivity; 100% specificity; p < 0.0005).(ABSTRACT TRUNCATED AT 250 WORDS)
STUDY OBJECTIVES: To compare the changes in resting energy expenditure (REE) to concomitant changes in clinical status and pulmonary function in cystic fibrosis (CF) patients during treatment for acute pulmonary exacerbation. To determine if weight loss during exacerbation in CF is related to decreased calorie intake or increased energy needs. DESIGN: Measurements of REE, pulmonary function tests, oxygen saturation, respiratory rate, maximal inspiratory pressure (MIP), white blood cell count, chest x-ray films and attribution of clinical score (ACS) on admission, mid-hospitalization, and discharge. Anthropometric measurements on admission, assessment of dietary intake and nitrogen balance upon admission and prior to discharge. SUBJECTS: Thirteen CF patients admitted for treatment of acute pulmonary exacerbation with a mean age of 11.0 +/- 7.9 (SD) years. RESULTS: From admission to discharge, REE decreased from 44.5 +/- 9.0 to 33.8 +/- 8.5 kilocalorie (kcal)/kg/d (p < 0.003). Similarly, the ACS improved from 7.5 +/- 2.0 to 4.0 +/- 2.2 (p < 0.0001); the absolute neutrophil count decreased from 10,685 +/- 6,226/microliters to 6,363 +/- 168/microliters (p < 0.005); respiratory rate decreased from 32.6 +/- 6.2 to 25.0 +/- 3.7 breaths per minute (p < 0.01); and MIP increased from 77.5 +/- 20.0 to 90.0 +/- 20.4 cm H2O (p < 0.01). In parallel, less significant improvements occurred in pulmonary function tests, oxygen saturation and chest x-ray film scores. Calorie intake was 1,893 +/- 635 and 2,054 +/- 707 kcal/d on admission and discharge, respectively (p = NS); during hospitalization, weight increased from 23.6 +/- 10.1 to 25.7 +/- 10.1 kg (p < 0.005). While carbohydrate and fat content of the diet remained essentially unchanged, a significant increase in protein intake (3.15 +/- 0.92 to 3.5 +/- 0.81 g/kg/d [p < 0.05]) and in nitrogen balance (1.8 +/- 2.5 to 5.6 +/- 2.9 g of nitrogen per day [p < 0.05]) were observed. CONCLUSIONS: In acute CF, pulmonary exacerbation, changes in REE parallel those of clinical improvements and are more sensitive than pulmonary function tests and chest x-ray films as an objective clinical correlate. Increased metabolic requirements but not decreased dietary intake are the cause of weight loss in CF patients.
We report the case of a tracheal stenosis in a young child as a result of prolonged intubation. The anesthetic management of the airway laser surgery is discussed. A multidisciplinary cooperation allowed good results.
Different recovery strategies from maximal exercise seem to induce different lactate utilization patterns without significantly affecting performance on one subsequent maximal exercise. It remains unclear however, how varying recovery modalities affects repeated maximal exercise. To study this, we examined in 16 subjects, the influence of passive (P), active leg (L) and active arm (A) twenty minutes recovery periods separating a series of four exhaustive exercises, up to two minutes duration. Significant decreases in performance between the first and fourth exercise were observed in all recovery series but a significant decrease in performance in the second exercise was observed during passive recovery alone (p < 0.01). When the different types of recovery are compared, a more pronounced decrement in performance was found during passive recovery when first and last exercises are compared (p < 0.04). Pedaling duration in each successive exercise was unaffected in A or L but was significantly shorter in P (p < 0.03). Highly significant differences in mean blood lactate kinetics were found for the three recovery patterns used, with more elevated peak and nadir levels in passive recovery, intermediate values in active arm and lowest concentrations in active leg recovery. However, no correlation was found between performance and lactate concentration at the onset of exercise (r = -0.15; p = NS). Mean heart rates were similar throughout the experimental protocol except for a lower cardiac frequency during the last 5 minutes of passive recovery (p < 0.01). Blood hematocrits showed higher hemoconcentrations in repeated exercise during passive recovery (p < 0.01) despite significantly lower total fluid losses in this group. A significant correlation between peak hematocrit and blood lactate was also found (r = 0.67; p < 0.001). We conclude that the type of recovery has a significant effect on blood lactate elimination kinetics, and active recovery is beneficial in the preservation of performance during repeated maximal exercise. Furthermore, plasma shifts across the extra and intravascular spaces are induced by maximal exercise, and appear to closely follow blood lactate kinetics.
Heart rate variability was assessed in 12 patients with congenital central hypoventilation syndrome (CCHS) and in age- and sex-matched controls using SD of time intervals between R waves (R-R intervals), R-R interval histograms, spectral analysis, and Poincaré plots of sequential R-R intervals over a 24-h period using ambulatory monitoring. Mean heart rates in patients with CCHS were 103.3 +/- 17.7 SD and in controls were 98.8 +/- 21.6 SD (p greater than 0.5, NS). SD analysis of R-R intervals showed similar results in both groups (CCHS 102.2 +/- 36.0 ms versus controls 126.1 +/- 43.3 ms; p greater than 0.1, NS). Spectral analysis revealed that, for similar epochs sampled during quiet sleep and wakefulness, the ratios of low-frequency band to high-frequency band spectral power were increased for 11 of 12 patients with CCHS during sleep, whereas a decrease in these ratios was consistently observed in all controls during comparable sleep states (chi 2 = 20.31; p less than 0.000007). During wakefulness, the ratios of low-frequency band to high-frequency band spectral power were similar in both patients with CCHS and controls. Poincaré plots displayed significantly reduced beat-to-beat changes at slower heart rates in the CCHS patients (chi 2 = 24.0; p less than 0.000001). The scatter of points in CCHS Poincaré plots was easily distinguished from controls. All CCHS patients showed disturbed variability with one or more measures. The changes in moment-to-moment heart rate variability suggest that, in addition to a loss of ventilatory control, CCHS patients exhibit a dysfunction in autonomic nervous system control of the heart.
The sickle cell trait (HbAS) does not seem to affect exercise performance. It remains unclear, however, whether the capability to sustain repeated brief maximal effort and recovery by HbAS subjects, is also preserved. To study this, nine HbAS and nine matched controls underwent on two different occasions, a series of four, approximately 2-min duration, maximal cycle exercise tests separated by 20-min recovery periods of either absolute rest (P) or light pedaling (A) as well as an incremental test to exhaustion. In all tests, work performed, heart rate, blood hematocrit, lactate, and serum creatine kinase (CK), lactate dehydrogenase (LDH), and aspartate aminotransferase (GOT) were measured. Performances were similar in HbAS and HbAA subjects in both the predominantly anaerobic and aerobic exercise series. There were no observable differences in work, power, or heart rate in the two groups both during peak exercise or recovery periods. A significant hemoconcentration was observed during P, with hematocrit increasing in HbAS from 46.4 +/- 0.7% to 48.3 +/- 0.4% at the end of the last recovery period. Similar changes were seen in HbAA. Significantly greater fluid losses were found during A (1.3 +/- 0.2 l in A and 0.6 +/- 0.1 l in P for HbAS; P < 0.001), but fluid losses were similar in each type of recovery in the two groups. Despite similar performance, significantly lower blood lactate concentrations were consistently found in HbAS in each of the three exercise series (P < 0.001). Lower lactate levels in HbAS were observed only at exercise loads above the lactate threshold during the incremental test (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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Severe hyponatremia may be associated with several complications leading sometimes to the death of the patient. We present the case of a healthy young pregnant woman who developed a severe acute iatrogenic hyponatremia (120 mEq.l-1). The treatment of the acute dehydration due to hyperemesis gravidarum led to a dilutional hyponatremia. The causes, complications and management of severe acute hyponatremia are discussed.
The incidence of clinical pulmonary manifestations during clinically mild Plasmodium falciparum malaria was studied in 50 patients. In nine patients (18%), respiratory symptoms developed and consisted of cough either productive (in 5) or dry and pleuritic (in 3), wheezing and dyspnea (in 2). Physical examination of these patients disclosed minimal decrease of breath sounds with diffuse moist rales over both lung bases. Chest X-rays showed small infiltrates and increased vascular markenings in most. Peak expiratory flow rates were measured in 38 of these patients and showed a mean decrease of 16.9% which reached its nadir on the third to fourth day of disease with return to normal values within 7.7 days. In patients with pulmonary symptoms a marked decrease in PEFR was observed (28.9%) and return to normal values was also longer (9.6 days). We conclude that mild, easily detectable and asymptomatic alterations of pulmonary function are observed in most patients with P. falciparum malaria and the incidence of respiratory manifestations in the uncomplicated forms of the disease is relatively high.
The predictive value of anthropometric measurements in the identification of infants at risk for early postnatal morbidity was assessed in a cohort of 490 neonates born in Yaoundé, Cameroon. Mid-arm circumference (MAC), head circumference, weight, and length were measured within 6 hours of birth, and the gestational age, individual MAC/head circumference ratio, and individual ponderal index were calculated. A detailed questionnaire on gestational medical history was also obtained from the mothers. All infants were then closely monitored during the first 72 hours after delivery for the appearance of symptoms requiring medical intervention and treated accordingly. Low birth weight (LBW) was observed in 37.75%, prematurity in 25.5%, and small size for gestational age in 14.1% of the neonates. Gestational medical problems were reported by 44.3% of the mothers; malaria was the most frequent. Early postnatal morbidity was observed in 26% of the infants; infection (53%), respiratory distress (26%), hypoglycemia (26%), and convulsions (11.7%) accounted for most of the problems. The MAC correlated best of all variables with birth weight (r = 0.91); a value of less than or equal to 9.5 cm had a 93% sensitivity and a 90.5% specificity in the prediction of LBW. An MAC cutoff value of less than or equal to 9.5 cm was also the best of all variables in the prediction of early postnatal morbidity, and 85.2% sensitivity and 74.3% specificity were achieved. We conclude that in developing countries, where scales are not always available and the overburdened maternity wards cannot allow for medical surveillance of every infant, the MAC can be used in the estimation of birth weight. Moreover, an appropriately calculated cutoff value of MAC may serve as a reliable indicator of LBW and of infants at risk for early postnatal morbidity.
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Cortical Infantile Hyperostosis (Caffey's disease) is a benign and self-limited disorder. Late recurrence or persistence of symptoms with deformity seems exceedingly rare. Its occurrence in isolated cases or in multiple members in families suggests the existence of two different forms, namely a sporadic form and a familial form. The tibia is the predominant bone known to be affected in the familial form, while the mandible is mostly affected in the sporadic form. The different pathological processes found in these two forms add further to the heterogeneity of this disorder. We describe an Arabic-Christian, non-consanguineous family with two affected sibs. In one, recurrent Caffey's disease was diagnosed at the age of 11 years.
One hundred thirty nonimmune subjects living in Yaoundé, Cameroon, completed an 18-month prospective study on the efficacy and safety of weekly chloroquine and daily proguanil (chloroguanide) (Ch-P) in malaria prevention. A total of 9 of 78 Ch-P-treated subjects and 26 of 52 subjects who received no prophylaxis contracted Plasmodium falciparum infection during this period (P less than 0.00005). These two groups were comparable for demographic parameters and degree of exposure. Clinical manifestations were of similar severities in the two groups, but parasite counts were significantly higher in the subjects who received no prophylaxis (P less than 0.00005). Side effects of prophylaxis were frequent (31%), minor, and related to chloroquine, and they usually resolved within 4 to 6 weeks. Prolonged administration of Ch-P is safe and effectively prevents P. falciparum malaria in an endemic area with a high prevalence of chloroquine resistance.