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Purpose: The changing expectations, therapies and outcomes for young people with cystic fibrosis (CF) necessitate a re-evaluation of the impact of this chronic illness on adolescent development. The aim of this study was to assess the psychological well-being and adjustment of contemporary adolescents with CF., Methods: Forty-nine adolescents with CF (24 males, 25 females) aged 14-18 years were enrolled from the Royal Children's Hospital CF Clinic, Melbourne, Australia. The Offer Self-Image Questionnaire was administered to participating subjects whose growth and pubertal developmental and pulmonary function was assessed., Results: The mean (SD) FEV1% was 82 (21), and mean (SD) National Institute of Health clinical score was 81 (12). There were no significant differences between males and females in pulmonary function or clinical scores, but growth and pubertal development were delayed in both sexes. Females, but not males, with CF were less well-adjusted than their healthy peers. Two-way analysis of variance was performed and showed significant sex differences in sub-scales of the Offer questionnaire numbers I, II, III, VI, VIII, IX, as well as in the total score. Age was significant only for scales II and VIII, and only scale II displayed an interaction between sex and age., Conclusions: This study suggests that adjustment and self-esteem are less than ideal in young people with CF, especially females.

Objectives: To determine asthma morbidity, use of medications and trigger factors for asthma attacks in an adult community sample., Methods: Follow-up questionnaires were sent to respondents indicating a history of asthma or any respiratory symptom on a screening questionnaire. A new scale to measure asthma severity was developed., Results: Questionnaires were returned by 74% (589/795). Respondents with diagnosed asthma had more frequent symptoms and more disruption to lifestyle than those with non-specific respiratory symptoms. Inhaled beta-agonist and oral theophylline preparations were used by 61% and 16% of asthmatics, respectively. Preventive medications such as inhaled corticosteroids and cromoglycate were used daily by only 15% and 4%, respectively. The most frequently reported trigger factors were viral upper respiratory tract infections, cigarette smoke, house dust, smog and other non-specific irritants. Twenty per cent of asthmatics reported occupational exacerbation of symptoms., Conclusions: There is substantial morbidity from asthma in Victorian adults, which could be reduced by greater use of preventive medications, avoidance of trigger factors, peak flow monitoring and action plans. The asthma severity scale proved to be reliable and valid.

Background: A number of chest radiographic scores have been developed to assess the severity of respiratory disease in cystic fibrosis but critical statistical evaluation has been limited. In particular, the chest radiograph component of the National Institutes of Health (NIH) clinical score has not previously been validated. Three different chest radiograph scores have been compared and the association between them and lung function tests investigated., Methods: The interobserver and intraobserver variation of the Brasfield, NIH chest radiograph, and the Royal Children's Hospital (RCH) chest radiograph score was assessed by three observers--a paediatric radiologist, a junior and a senior respiratory physician--who independently scored, on separate occasions, 62 chest radiographs randomly selected from three age strata of patients ranging from 7 to 18 years. Lung function tests were available for 61 patients obtained within three months of the chest radiograph. Two way analysis of variance was used to estimate components of variation in scores., Results: Results were similar for the Brasfield and NIH scores, both of which demonstrated greater precision than the RCH score, but the estimated repeatability of the Brasfield and NIH scores can be expected to differ by up to 20% of the maximum score. The reliabilities (intraclass correlation) are all reasonably high at 0.74, 0.73, and 0.61 for the Brasfield, NIH, and RCH scores, respectively. The estimated correlation between radiographic scores and lung function tests, adjusted for attenuation caused by measurement error, showed a similar correlation for all three scoring methods ranging from 0.55 to 0.78. Correlations were slightly greater with FEV1% than FVC%. These correlations are substantial but not high, indicating that a large proportion of the variability in radiographic scores cannot be explained by lung function measurements., Conclusions: The Brasfield and NIH chest radiograph scores have very similar statistical profiles and can be equally recommended if a chest radiograph score is to be used. The RCH radiographic score appears to be less reliable. The limitations of these scores need to be understood.

Objective: To determine which factors measured in childhood predict asthma in adult life., Design: Prospective study over 25 years of a birth cohort initially studied at the age of 7., Setting: Tasmania, Australia., Subjects: 1494 men and women surveyed in 1991-3 when aged 29 to 32 (75% of a random stratified sample from the 1968 Tasmanian asthma survey of children born in 1961 and at school in Tasmania)., Main Outcome Measures: Self reported asthma or wheezy breathing in the previous 12 months (current asthma)., Results: Of the subjects with asthma or wheezy breathing by the age of 7, as reported by their parents 25.6% (190/741) reported current asthma as an adult compared with 10.8% (81/753) of subjects without parent reported childhood asthma (P < 0.001). Factors measured at the age of 7 that independently predicted current asthma as an adult were being female (odds ratio 1.57; 95% confidence interval 1.19 to 2.08); having a history of eczema (1.45; 1.04 to 2.03); having a low mild forced expiratory flow rate (interquartile odds ratio 1.40; 1.15 to 1.71); having a mother or father with a history of asthma (1.74 (1.23 to 2.47) and 1.68 (1.18 to 2.38) respectively); and having childhood asthma (1.59; 1.10 to 2.29) and, if so, having the first attack after the age of 2 (1.66; 1.17 to 2.36) or having had more than 10 attacks (1.70; 1.17 to 2.48)., Conclusion: Children with asthma reported by their parents in 1968 were more likely than not to be free of symptoms as adults. The subjects who had more severe asthma (especially if it developed after the age of 2 and was associated with reduced expiratory flow), were female, or had parents who had asthma were at an increased risk of having asthma as an adult. These findings have implications for the treatment and prognosis of childhood asthma, targeting preventive and educational strategies and understanding the onset of asthma in adult life.

Ventilation is lower during sleep than wakefulness. An increase in airway resistance has been proposed as the critical factor. As the change in ventilation has been shown to occur abruptly at transitions between alpha and theta electroencephalogram activity, it was of interest to determine whether the increase in airway resistance between wakefulness and sleep also occurs at these transitions. Three young healthy male subjects were run for an average of 15 sleep onsets in each of three conditions. The three conditions were 1) an esophageal balloon was put in place to allow the measurement of airway resistance, 2) in addition to an esophageal balloon the nose was occluded, and 3) there was no esophageal balloon and the nose was not occluded. Ventilation and airway resistance were measured during sleep onset and analyzed as a function of arousal state. In those conditions of the experiment in which airway resistance was affected by state, the changes, like those in ventilation, occurred at transitions between alpha and theta electroencephalogram activity. However, in the three subjects studied, the magnitude of ventilatory changes at alpha-theta transitions and the extent to which changes in ventilation were associated with changes in airway resistance differed between subjects. It was concluded that although inspiratory airway resistance is a major component affecting the state-related changes in ventilation at sleep onset, the degree of its contribution may vary over individuals.

The aims of this study were (1) to quantify the prevalence of aeroallergen hypersensitivity in presentations for emergency treatment of asthma and (2) to determine the strength of association between viral upper respiratory tract infections (URTIs) and admission for treatment of asthma. A series of 209 asthmatic patients presenting to the Emergency Department (ED) of the Alfred Hospital over 6 months underwent skin prick testing and venipuncture for serum IgE and rye grass pollen (RGP) RAST. A case-control study of 38 asthmatic inpatients and 90 controls admitted for road trauma or endoscopy underwent nasopharyngeal aspiration for viral culture and immunofluorescence (IF). Eighty-four percent of ED asthmatic patients had one or more positive skin tests to common aeroallergens, 57% had a positive skin test, and 45% had a positive RAST to RGP. Viral cultures or IF studies were positive in 8 asthmatic patients and 2 controls. Asthmatic inpatients were 6 times more likely to have a viral URTI than were controls. It is concluded that aeroallergen hypersensitivity is present in most asthmatic patients presenting to the ED, and that there is a strong association between viral URTIs and admission for asthma.

A new pocket-sized ambulatory spirometer (meter) that measures FEV1 and PEFR was evaluated. The meter determines flow rate (V) from the differential pressure (P1-P2) across a sharp-edged orifice (V alpha square root of[P1-P2]). Ten meters were evaluated for accuracy using a computerized syringe to deliver the 24 ATS-recommended waveforms and nine scaled versions of a single waveform (PW#24). Within-meter reproducibility of FEV1 and PEFR was evaluated in two meters by passing five versions of waveform PW#24 through each meter 10 times. Reliability in the ambulatory setting was assessed in six meters on several occasions over a 10-week period using five versions of waveform PW#24. Results show that the 10 meters conform to the ATS accuracy specifications for PEFR with one or less errors and marginally outside these limits for FEV1 with four errors. For the nine versions of PW#24, the 95% confidence intervals indicate that the meter is accurate to within +/- 5.5% or +/- 15 L/min for PEFR and +/- 3.5% or +/- 0.12 L for FEV1. The mean within-meter coefficient of variation was 1.24% for FEV1 and 0.35% for PEFR. There was no significant change in meter accuracy or performance over the 10-wk reliability study. We conclude that the meter is suitable for use as an ambulatory spirometer for measuring FEV1 and PEFR.

Asthma mortality statistics issued by the Australian Bureau of Statistics (ABS) were compared with clinical data from a survey of asthma mortality. Deaths in Victoria from May 1986 to April 1987 containing 'asthma' in Parts 1 or 2 of the death certificate (N = 405) were reviewed. For each subject, the cause of death attributed by the Victorian Asthma Mortality Survey was compared with the ABS cause of death, by age and sex of the subject. Information on 393 of the 405 deaths investigated by the Victorian Asthma Mortality Survey was analysed. The ABS estimate of the total number of asthma deaths in Victoria was 47 per cent higher than the estimate of the Victorian Asthma Mortality Survey. In subjects under 50 years of age the two estimates were within 10 per cent. The difference between the estimates increased with age at death for persons over 50 years old and was equivalent for males and females. If the assessment by the Victorian Asthma Mortality Survey of the number of deaths due to asthma is accepted as accurate, then the ABS estimate of asthma deaths was reliable for those under 50 years of age. In those who died at an older age, the ABS significantly overestimated the number of deaths due to asthma in Victoria.

Mechanical ventilation causes significant morbidity and mortality in patients with severe asthma. Hypoventilation may reduce this morbidity and mortality, but indicators to guide the degree of hypoventilation are unclear. We used a measure of pulmonary hyperinflation to assess the degree of airflow obstruction and to guide the extent and duration of hypoventilation. Ten patients who required mechanical ventilation for acute severe asthma were studied. All were sedated, paralyzed, and given an initial minute ventilation (VE) of 200 ml/kg/min. End-inspiratory lung volume (VEI) above FRC was measured from the total exhaled gas volume during 40 to 60 s of apnea. VEI was used to regulate VE to a safe level (VEsafe), irrespective of PaCO2, by reducing the rate when VEI was > 20 ml/kg and increasing it when VEI was < 20 ml/kg. Each patient was weaned when VEsafe resulted in PaCO2 < or = 40 mm Hg (the weaning point). FRC was measured computer analysis of anterior and lateral chest radiographs taken at the end of apnea. Using the weaning point criterion, 2 patients (PaCO2 < 40 mm Hg) were weaned shortly after arrival. The remaining eight (initial PaCO2, 63 +/- 17 mm Hg) continued hypoventilation until the weaning point was reached (30 +/- 29 h). The weaning point was reached by the VE required for PaCO2 40 mm Hg decreasing concurrent with the VEsafe increasing. All but 1 patient were successfully weaned within 24 h of the weaning point.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute severe asthma is associated with significant morbidity and mortality. We retrospectively quantified hypotension, pulmonary barotrauma, and cardiac arrhythmias in all patients with severe asthma admitted to the intensive care unit (ICU) and prospectively evaluated the predictive value of a measurement of dynamic hyperinflation (DHI) in those patients who required mechanical ventilation. In the first study, 88 ICU admissions for severe asthma over 5 yr (73 patients, 40 +/- 18 yr, 36 men, 37 women) were evaluated. Fifty-one admissions were mechanically ventilated, 29 were not, and 8 previously ventilated patients remained briefly intubated but were not ventilated in the ICU. Hypotension (18/88, 20%), pulmonary barotrauma (12/88, 14%), and arrhythmias (9/88, 10%) were entirely confined to patients who had been mechanically ventilated. There were no significant differences in ventilatory parameters, airway pressures, or blood gases between mechanically ventilated patients with and without complications. Two patients with previous severe hypoxic cerebral damage died from this complication after ICU discharge. In the second study, the end-inspiratory lung volume (VEI) (1) was compared with standard ventilatory parameters in 22 patients. There were no ICU deaths, but high incidences of pulmonary barotrauma (27%) and hypotension (41%) were found. Both minute ventilation (VE and VEI) were significantly higher in patients who developed complications (VE 13.7 +/- 3.0 versus 11.2 +/- 2.5 L/min, VEI 26.1 +/- 4.7 versus 20.0 +/- 7.4 ml/kg, p less than 0.05) but only VEI had a threshold value significantly predictive of complications. For VEI less than 1.4 L, 0/5 (0%) patients had complications; for VEI greater than or equal to 1.4 L, 11/17 (65%) had complications (p = 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

To determine the prevalence of asthma in Victorian adults, we carried out a cross-sectional postal survey utilising a new screening questionnaire which gathered data on self reported respiratory symptoms, whether asthma had been diagnosed and, if so, how it had been treated. Questionnaires were returned by 2198 (72%) of 3095 adults selected randomly from the Victorian electoral roll, an adequate response rate. The reported prevalences of individual asthmatic symptoms in the last 12 months ranged from 8% for nocturnal wheeze to 22% for current wheeze. Thirteen per cent of respondents had ever had asthma, 7% had experienced an attack within the last 12 months and 6% were currently taking medication. The high prevalence of asthma revealed by our study has major implications for the planning of health services.

Myopathy complicating the therapy of severe asthma has been recently described in several case reports. Twenty-five consecutive patients admitted to the intensive care unit (ICU) at this hospital for mechanical ventilation for severe asthma were studied for the incidence of creatine kinase (CK) enzyme rise and for the development of clinical myopathy. Pharmacologic therapy was standardized, every patient receiving corticosteroids and aminophylline intravenously and salbutamol both nebulized and intravenously. Twenty-two patients received muscle relaxant therapy with vecuronium. In 19 of 25 (76%) of patients there was elevation of CK levels to a median of 1,575 U/L (range, 66 to 7,430) occurring 3.6 +/- 1.5 days after admission. In nine patients there was clinically detectable myopathy. The presence of either myopathy or CK enzyme rise was associated with a significant prolongation of ventilation time. Arterial blood gas measurements on admission to the ICU revealed a pH (mean +/- SD) of 7.07 +/- 0.21, a PaCO2 of 87.2 +/- 32.7, and a PaO2 (with a high FIO2) of 129 +/- 97 mm Hg; however, no correlation was found between the severity of initial metabolic disturbance and the subsequent development of myopathy. There was no association between the type of corticosteroid administered and the subsequent development of myopathy. Patients with myopathy had received a significantly higher total dose of vecuronium when compared with those who did not develop myopathy (p < 0.001, Kruskal Wallis test). We have therefore found a surprisingly high incidence of CK enzyme rise and myopathy in this group of mechanically ventilated patients with severe asthma.(ABSTRACT TRUNCATED AT 250 WORDS)

Previous reviews of pediatric asthma mortality have mostly been from hospital-based clinic populations and suggest that only those with severe asthma are most at risk. This report summarizes an investigation, by interviewer-administered questionnaire, into the circumstances surrounding the death in all patients aged 20 years or less who died from asthma in the State of Victoria over a 3 year period from May 1, 1986. During this period, 51 deaths due to asthma were reported. Thirty-three percent of these were judged to have a history of trivial or mild asthma, and 32% had no previous hospital admission for asthma. However, 36% were judged to have had severe asthma, 43% were taking regular inhaled beclomethasone or sodium cromoglycate, and 10% were taking regular oral steroids. Twenty-two percent had a previous admission to an ICU. Death occurred outside hospital in 40 (78%) subjects. In the final attack 63% had sudden onset and collapse within minutes, 12% were found dead, and 25% had acute progression of an established attack. The investigators assessed 39% of the deaths to have had potentially preventable elements. The preventable factors included: inadequate assessment or therapy of prior asthma (68%), poor compliance with therapy (53%), and delay in seeking help (47%). The majority of subjects in this survey could not be classified as "high risk." Therefore, clinicians should ensure that all young patients with asthma are aware of optimal maintenance management, can recognize deteriorating asthma, and follow a clear individualized crisis plan.

A two-phase study was undertaken designed to investigate the impact of computer-aided drug monitoring on tobramycin concentrations and clinical outcomes in adult patients with cystic fibrosis. In phase one, a baseline (historical control) study of drug use patterns was performed. During the second phase, patients admitted for intravenous treatment with tobramycin for acute exacerbations of pseudomonal pulmonary infections were randomly allocated to one of two schedules. Group A patients had tobramycin dosage regimens decided by clinicians based on pre-existing protocols using serum tobramycin assay data determined three times weekly. Group B patients had dosage regimens determined by a computerized pharmacokinetic predictive program using both population-based pharmacokinetic parameter estimation and fitting of serum concentration-time data using Bayesian regression. The agreed therapeutic target was a peak serum tobramycin concentration of 8-10 mg/L and a trough concentration of 1-2 mg/L. There was a major difference between the two groups comparing the number of paired trough and peak concentrations within the target concentration ranges (group A-14%; group B-34.7%, chi 2 test, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

A patient assessment with history, physical examination and simple tests of air flow limitation will usually allow the primary care physician to make the correct diagnosis and to commence treatment. Nevertheless, the diagnosis of asthma is not always easy and the author discusses approaches to adults if the diagnosis of asthma is uncertain.

The effect of hypoxia on plasma atrial natriuretic factor (ANF), plasma renin activity (PRA), and plasma aldosterone concentration (PAC) was evaluated during 2 h of treadmill exercise at 2 km/h, 0 grade at sea level. Six male subjects exercised on 2 separate days during normoxia (21% O2) and hypoxia (13.3 +/- 0.3% O2). No significant changes in ANF or PRA occurred during either normoxic or hypoxic exercise. However, PAC fell significantly during normoxic exercise (17.5 +/- 3.6 vs. 12.7 +/- 2.6 ng/dl, p less than 0.05) but not during hypoxic exercise. Serum potassium concentration fell during hypoxic exercise (5.0 +/- 0.1 vs. 4.4 +/- 0.1 mmol/l, p less than 0.05) along with bicarbonate (27.8 +/- 0.7 vs. 25.8 +/- 0.6 mmol/l, p less than 0.01). Between normoxic and hypoxic studies there was a significantly higher heart rate during hypoxic exercise (78 +/- 5 vs. 90 +/- 6 b/min, p less than 0.01). The major conclusion of this study is that hypoxia resulting in arterial oxygen saturations of 81 +/- 0.7% does not affect plasma atrial natriuretic factor levels during mild exercise in normal male subjects.

Udotea flabellum is a marine, macroscopic green alga with C4-like photosynthetic characteristics, including little O2 inhibition of photosynthesis, a low CO2 compensation point, and minimal photorespiration; but it lacks anatomical features analogous to the Kranz compartmentation of C4 plants, and phosphoenolpyruvate carboxylase [PEPC; orthophosphate:oxaloacetate carboxy-lyase (phosphorylating), EC 4.1.1.31] activity is negligible. Phosphoenolpyruvate carboxykinase (PEPCK) activity (carboxylating) in Udotea extracts was equivalent to that of ribulose-bisphosphate carboxylase [Rubisco; 3-phospho-D-glycerate carboxy-lyase (dimerizing), EC 4.1.1.39]. When PEPCK activity was inhibited in vivo with 3-mercaptopicolinic acid (MPA), thallus photosynthesis decreased by 70% and became sensitive to O2. Codium decorticatum, a related species that lacks C4-like photosynthetic features and PEPCK activity, showed no increase in O2 inhibition upon exposure to MPA. Rubisco and PEPC activities in Udotea were not inhibited by MPA. Labeling of the early photosynthetic products malate and aspartate was reduced 66% by MPA, while intermediates of the photorespiratory carbon oxidation cycle showed a 3-fold increase. Udotea evolved O2 in the light in the absence of inorganic carbon, suggesting it had an endogenous carbon source for photosynthesis. Exogenous malate stimulated this process, while MPA inhibited it. PEPCK was not involved in Crassulacean acid metabolism or dark CO2 fixation. These MPA studies establish a direct link between PEPCK activity and the low O2 inhibition of photosynthesis and low photorespiration in Udotea. The data are consistent with carboxylation by a cytosolic PEPCK providing a C4 acid, such as malate, to the chloroplast for decarboxylation to elevate the CO2 concentration at the Rubisco fixation site. Udotea is to date the most primitive plant with a C4-like form of photosynthesis.

Bronchodilator prescription and sales data for Australia from 1975 to 1986 were analysed. Inhaled beta-agonists were the most commonly prescribed antiasthmatic agents in 1986, followed by sustained-release theophylline and inhaled corticosteroids. Marked increases in prescription sales of these three drug groups over the period were noted. We estimate that non-prescription sales of salbutamol inhalers increased by 410% between 1980 and 1986 (P less than 0.01). Prescribing rates by general practitioners for beta-agonists, sustained-release theophylline and inhaled corticosteroids increased from 1979 to 1986. Prescribing rates of beta-agonists were highest for persons aged 1-11 years and 55 years and over, and increased markedly for children aged 1-11 years over the period. For sustained-release theophylline, prescribing rates were highest for persons 55 years and over. The difficulties in postulating possible relationships between prescribing trends and asthma mortality are discussed.

Pseudomonas aeruginosa is frequently grown from the sputum of adults with cystic fibrosis-related bronchiectasis. A rare case of pseudomonal empyema is reported in this clinical setting. Early diagnosis permitted successful treatment with closed needle aspiration and intravenous antibiotics.

The circumstances surrounding the death of all patients who died from asthma in the State of Victoria over a 12-month period from May 1, 1986 were investigated. Data were collected using an interviewer-administered questionnaire as soon as practicable after registration of the death. In 168 cases asthma was considered to be the cause of death and adequate data were obtained in 163; 75 of these were male (74 over 60 years of age). Thirteen per cent had a history of trivial or mild asthma, 22% of moderate and 65% of severe asthma. Thirty-four per cent had not been limited at all or only by active sport, while 39% had had no previous hospital admission for asthma. In only 18% had there been a previous admission to an intensive care unit. Forty-seven per cent were taking inhaled beclomethasone or sodium cromoglycate regularly and 27% were taking corticosteroids by mouth regularly. Death occurred outside hospital in 150 of 163 subjects. In the final attack 58% had a sudden onset and collapsed within minutes, 20% were found dead and 27% had an acute progression of an established attack. Twenty-nine per cent of the deaths were assessed as preventable: preventable factors included inadequate assessment or therapy of prior asthma (35%), poor compliance with therapy (33%) and delay in seeking help (43%). As a significant number of subjects in this survey could not be classified as "high risk", it is important that clinicians ensure that all patients are aware of optimal maintenance management and have a clear individualized plan of what to do in the event of deteriorating asthma.

We studied the effect of supplemental nocturnal oxygen on blood gases in 15 patients with severe but stable chronic obstructive lung disease (ratio of forced expired volume in one second to forced vital capacity, 37.2 +/- 1.8 [mean +/- S.E.] per cent of predicted; arterial oxygen tension, 50.7 +/- 1.4 mm Hg; and arterial carbon dioxide tension [PCO2], 53.1 +/- 1.5 mm Hg). Sleep variables and measures of gas exchange were determined on two consecutive nights; on the first night the subjects breathed supplemental oxygen, and on the second they breathed room air. Transcutaneous PCO2 was measured with an infrared sensor, and arterial oxygen saturation with an ear oximeter. Breathing of supplemental oxygen sufficient to keep oxygen saturation at or above 90 per cent was associated with only small increases (less than 6 mm Hg) in PCO2 throughout sleep, as compared with values while subjects were breathing room air. The increase in PCO2 occurred early in the night and was not progressive. Only three patients, who were found to have obstructive sleep apnea in addition to obstructive lung disease, had larger increases in PCO2 during sleep and reported morning headaches. We conclude that nocturnal oxygen does not induce clinically important increases in PCO2 during sleep in patients with stable obstructive lung disease and therefore can safely be used to prevent the dangerous consequences of hypoxia.

Soybean (Glycine max L. Merr. cv Bragg) was grown throughout its life cycle at 330, 450, and 800 microliters CO(2) per liter in outdoor controlled-environment chambers under solar irradiance. Leaf ribulose-1,5-bisphosphate carboxylase (RuBPCase) activities and ribulose-1,5-bisphosphate (RuBP) levels were measured at selected times after planting. Growth under the high CO(2) levels reduced the extractable RuBPCase activity by up to 22%, but increased the daytime RuBP levels by up to 20%.Diurnal measurements of RuBPCase (expressed in micromoles CO(2) per milligram chlorophyll per hour) showed that the enzyme values were low (230) when sampled before sunrise, even when activated in vitro with saturating HCO(3) (-) and Mg(2+), but increased to 590 during the day as the solar quantum irradiance (photosynthetically active radiation or PAR, in micromoles per square meter per second) rose to 600. The nonactivated RuBPCase values, which averaged 20% lower than the corresponding HCO(3) (-) and Mg(2+)-activated values, increased in a similar manner with increasing solar PAR. The per cent RuBPCase activation (the ratio of nonactivated to maximum-activated values) increased from 40% before dawn to 80% during the day. Leaf RuBP levels (expressed in nanomoles per milligram chlorophyll) were close to zero before sunrise but increased to a maximum of 220 as the solar PAR rose beyond 1200. In a chamber kept dark throughout the morning, leaf RuBPCase activities and RuBP levels remained at the predawn values. Upon removal of the cover at noon, the HCO(3) (-) and Mg(2+)-activated RuBPCase values and the RuBP levels rose to 465 and 122, respectively, after only 5 minutes of leaf exposure to solar PAR at 1500.These results indicate that, in soybean leaves, light may exert a regulatory effect on extractable RuBPCase in addition to the well-established activation by CO(2) and Mg(2+).

Water hyacinth (Eichhornia crassipes [Mart.] Solms) plants were grown in environmental chambers at ambient and enriched CO(2) levels (330 and 600 microliters CO(2) per liter). Daughter plants (ramets) produced in the enriched CO(2) gained 39% greater dry weight than those at ambient CO(2), but the original mother plants did not. The CO(2) enrichment increased the number of leaves per ramet and leaf area index, but did not significantly increase leaf size or the number of ramets formed. Flower production was increased 147%. The elevated CO(2) increased the net photosynthetic rate of the mother plants by 40%, but this was not maintained as the plants acclimated to the higher CO(2) level. After 14 days at the elevated CO(2), leaf resistance increased and transpiration decreased, especially from the adaxial leaf surface. After 4 weeks in elevated as compared to ambient CO(2), ribulose bisphosphate carboxylase activity was 40% less, soluble protein content 49% less, and chlorophyll content 26% less; whereas starch content was 40% greater. Although at a given CO(2) level the enriched CO(2) plants had only half the net photosynthetic rate of their counterparts grown at ambient CO(2), they showed similar internal CO(2) concentrations. This suggested that the decreased supply of CO(2) to the mesophyll, as a result of the increased stomatal resistance, was counterbalanced by a decreased utilization of CO(2). Photorespiration and dark respiration were lower, such that the CO(2) compensation point was not altered. The photosynthetic light and CO(2) saturation points were not greatly changed, nor was the O(2) inhibition of photosynthesis (measured at 330 microliters CO(2) per liter). It appears that with CO(2) enrichment the temporary increase in net photosynthesis produced larger ramets. After acclimation, the greater total ramet leaf area more than compensated for the lower net photosynthetic rate on a unit leaf area basis, and resulted in a sustained improvement in dry weight gain.

Soybean (Glycine max [L.] cv Bragg) was grown at 330 or 660 microliters CO(2) per liter in outdoor, controlled-environment chambers. When the plants were 50 days old, drought stress was imposed by gradually reducing irrigation each evening so that plants wilted earlier each succeeding day. On the ninth day, as the pots ran out of water CO(2) exchange rate (CER) decreased rapidly to near zero for the remainder of the day. Both CO(2)-enrichment and drought stress reduced the total (HCO(3) (-)/Mg(2+)-activated) extractable ribulose-1,5-bisphosphate carboxylase (RuBPCase) activity, as expressed on a chlorophyll basis. In addition, drought stress when canopy CER values and leaf water potentials were lowest, reduced the initial (nonactivated) RuBPCase activity by 50% compared to the corresponding unstressed treatments. This suggests that moderate to severe drought stress reduces the in vivo activation state of RuBPCase, as well as lowers the total activity. It is hypothesized that stromal acidification under drought stress causes the lowered initial RuBPCase activities. The K(m)(CO(2)) values of activated RuBPCase from stressed and unstressed plants were similar; 15.0 and 12.6 micromolar, respectively. RuBP levels were 10 to 30% lower in drought stressed as compared to unstressed treatments. However, RuBP levels increased from near zero at night to around 150 to 200 nanomoles per milligram chlorophyll during the day, even as water potentials and canopy CERs decreased. This suggests that the rapid decline in canopy CER cannot be attributed to drought stress induced limitations in the RuBP regeneration capability. Thus, in soybean leaves, a nonstomatal limitation of leaf photosynthesis under drought stress conditions appears due, in part, to a reduction of the in vivo activity of RuBPCase. Because initial RuBPCase activities were not reduced as much as canopy CER values, this enzymic effect does not explain entirely the response of soybean photosynthesis to drought stress.

Incubation of the submersed aquatic macrophyte, Hydrilla vertieillata Royle, for up to 4 weeks in growth chambers under winter-like or summer-like conditions produced high (130 to 150 μl CO2/l) and low (6 to 8 μl CO2/l) CO2 compensation points (Γ), respectively. The activities of both ribulose bisphosphate (RuBP) and phosphoenolpyruvate (PEP) carboxylases increased upon incubation but the major increase was in the activity of PEP carboxylase under the summer-like conditions. This reduced the ratio of RuBP/PEP carboxylases from 2.6 in high Γ plants to 0.2 in low Γ plants. These ratios resemble the values in terrestrial C3 and C4 species, respectively.Kinetic measurements of the PEP carboxylase activity in high and low Γ plants indicated the Vmax was up to 3-fold greater in the low Γ plants. The Km (HCO3 (-)) values were 0.33 and 0.22 mM for the high and low Γ plants, respectively. The Km (PEP) values for the high and low Γ plants were 0.23 and 0.40 mM, respectively; and PEP exhibited cooperative effects. Estimated Km (Mg(2+)) values were 0.10 and 0.22 mM for the high and low Γ plants, respectively.Malate inhibited both PEP carboxylase types similarly. The enzyme from low Γ plants was protected by malate from heat inactivation to a greater extent than the enzyme from high Γ plants. The results indicated that C4 acid inhibition and protection were not reliable methods to distinguish C3 and C4 PEP carboxylases. The PEP carboxylase from low Γ plants was inhibited more by NaCl than that from high Γ plants. These analyses indicated that Hydrilla PEP carboxylases had intermediate characteristics between those of terrestrial C3 and C4 species with the low Γ enzyme being different from the high Γ enzyme, and closer to a C4 type.

The use of nedocromil sodium 4 mg q.i.d. in asthmatics with mildly unstable asthma induced by a reduction of their inhaled beclomethasone dipropionate dose was investigated in a double-blind, parallel group, placebo-controlled study. Compared with placebo, nedocromil sodium improved night-time and daytime asthma score, night-time and daytime bronchodilator use, and evening PEFR at some stage during the 4-week treatment. It is concluded that nedocromil sodium exerts a beneficial effect in chronic asthma.

Light- and CO(2)-saturated photosynthetic rates of the submersed aquatic plants Hydrilla verticillata, Ceratophyllum demersum, and Myriophyllum spicatum were 50 to 60 mumol O(2)/mg Chl.hr at 30 C. At air levels of CO(2), the rates were less than 5% of those achieved by terrestrial C(3) plants. The low photosynthetic rates correlated with low activities of the carboxylation enzymes. In each species, ribulose 1,5-diphosphate carboxylase was the predominant carboxylation enzyme. The apparent K(m)(CO(2)) values for photosynthesis were 150 to 170 mum at pH 4, and 75 to 95 mum at pH 8. The K(m)(CO(2)) of Hydrilla ribulose 1,5-diphosphate carboxylase was 45 mum at pH 8. Optimum temperatures for the photosynthesis of Hydrilla, Myriophyllum, and Ceratophyllum were 36.5, 35.0, and 28.5 C, respectively. The apparent ability of each species to use HCO(3) (-) ions for photosynthesis was similar, but at saturating free CO(2) levels, there was no indication of HCO(3) (-) use. Increasing the pH from 3.1 to 9.2 affected the photosynthetic rate indirectly, by decreasing the free CO(2). With saturating free CO(2) (0.5 mm), the maximum photosynthetic rates were similar at pH 4 and 8. Carbonic anhydrase activity, although much lower than in terrestrial C(3) plants, was still in excess of that required to support HCO(3) (-) utilization.Hydrilla and Ceratophyllum had CO(2) compensation points of 44 and 41 mul/l, respectively, whereas the value for Myriophyllum was 19. Relatively high CO(2) compensation points under 1% O(2) indicated that some "dark" respiration occurred in the light. The inhibition of photosynthesis by O(2) was less than with terrestrial C(3) plants. Glycolate oxidase activity was 12.3 to 27.5 mumol O(2)/mg Chl.hr, as compared to 78.4 for spinach. Light saturation of photosynthesis occurred at 600 to 700 mueinsteins/m(2).sec in each species grown under full sunlight. Hydrilla had the lowest light compensation point, and required the least irradiance to achieve the half-maximal photosynthetic rate.Field measurements in a Hydrilla mat indicated that in the afternoon, free CO(2) dropped to zero, and O(2) rose to over 200% air saturation. Most photosynthetic activity occurred in the morning when the free CO(2) was highest and O(2) and solar radiation lowest. The low light requirement of Hydrilla probably provides a competitive advantage under these field conditions.

The development of the future air breathing respiratory system was investigated in eight carunclectomised fetal sheep and five control fetal animals over the last third of gestation (approximately day 100-day 145). Carunclectomy resulted in the test fetal animals being hypoxaemic, hypercapnic, hypoglycaemic and acidotic. All fetal animals were chronically instrumented with diaphragmatic electromyographic leads, fetal jugular vein and carotid artery catheters, an amniotic fluid catheter and small electrocardiographic leads placed on the chest wall. There was evidence of a significant, but small, reduced relative lung size in the carunclectomised animals by day 140 without corresponding relative changes in the weight of the brain, liver, or heart. Diaphragmatic electromyograph (EMG) was analysed in detail over the last third of gestation. In both groups of animals, the normal reduction in fetal 'breathing' rate, and the normal increase in fetal apnoea was noted with increasing periods of diaphragmatic silence as fetal apnoea was noted with increasing periods of diaphragmatic silence as gestation advanced. Linear regression analyses revealed that fetal breathing rate was significantly reduced over the last third of gestation, whilst fetal apnoea significantly increased in the carunclectomised animals. Average total integrated diaphragmatic activity was reduced prior to 120 days. This reduction was evident in the strength of each diaphragmatic contraction before 110 days. In three test and three control animals, histochemical analyses were undertaken to fibre type the muscles of the diaphragm. Fatigue resistant fibres were significantly reduced in the carunclectomised fetuses, and fibre diameters were diminished. Centroid analyses of the power spectrum of the diaphragmatic EMG did not however support the concept of increased muscle fatigue in the test animals.

Lung inflation is known to produce reflex relaxation of tracheal smooth muscle (TSM) and dilation of the upper airway, but the specific efferent pathway involved has not been established. Therefore we examined TSM tone in four trained awake dogs by measuring pressure changes in the water-filled cuff of an endotracheal tube that was inserted into the lower cervical trachea through a permanent tracheostomy. Under control conditions, sustained lung inflation with 1 liter of air produced apnea (Hering-Breuer inflation reflex) and a decrease in cuff pressure (Pcuff) of 37.4 +/- 12.0 (mean +/- SD) cmH2O. beta-Adrenergic blockade with propranolol had no effect on either the apneic or TSM responses to lung inflation. Efferent parasympathetic blockade with atropine sulfate (1.2-2.4 mg) abolished TSM tone, which was then restored to control levels by a continuous intravenous infusion of serotonin (14-28 micrograms X kg-1 X min-1). Under these conditions, lung inflation still induced reflex apnea but no longer relaxed TSM tone (mean decrease in Pcuff, 2.7 +/- 1.4 cmH2O, P less than 0.001). The findings indicate that reflex tracheal dilation in response to lung inflation is mediated by an efferent cholinergic (parasympathetic) pathway.

This report describes a patient with primary alveolar hypoventilation who, after 2 yr of successful treatment with nocturnal oxygen, developed severe hypoxemia and hypercapnia during sleep, morning headaches, and daytime fatigue. Sleep studies demonstrated prolonged periods of hypoventilation and apnea without evidence of upper airway occlusion. Therefore, a phrenic nerve stimulator was implanted to allow pacing of the diaphragm during sleep. However, diaphragm pacing was accompanied by paradoxical movement of the rib cage and upper airway occlusion during sleep, and was unsuccessful in maintaining adequate ventilation. Therefore, the patient underwent a tracheostomy after which diaphragm pacing maintained adequate nocturnal ventilation; however, paradoxical movement of the rib cage persisted. The induction of upper airway occlusion as a result of diaphragm pacing, in contrast to the absence of occlusion during spontaneous breathing, highlights the importance of the normal temporal coordination of inspiratory activation of the upper airway muscles and diaphragm. The findings have important implications for the pathogenesis of obstructive sleep apneas in general.

The submersed angiosperms Myriophyllum spicatum L. and Hydrilla verticillata (L.f.) Royal exhibited different photosynthetic pulse-chase labeling patterns. In Hydrilla, over 50% of the (14)C was initially in malate and aspartate, but the fate of the malate depended upon the photorespiratory state of the plant. In low photorespiration Hydrilla, malate label decreased rapidly during an unlabeled chase, whereas labeling of sucrose and starch increased. In contrast, for high photorespiration Hydrilla, malate labeling continued to increase during a 2-hour chase. Thus, malate formation occurs in both photorespiratory states, but reduced photorespiration results when this malate is utilized in the light. Unlike Hydrilla, in low photorespiration Myriophyllum, (14)C incorporation was via the Calvin cycle, and less than 10% was in C(4) acids.Ethoxyzolamide, a carbonic anhydrase inhibitor and a repressor of the low photorespiratory state, increased the label in glycolate, glycine, and serine of Myriophyllum. Isonicotinic acid hydrazide increased glycine labeling of low photorespiration Myriophyllum from 14 to 25%, and from 12 to 48% with high photorespiration plants. Similar trends were observed with Hydrilla. Increasing O(2) increased the per cent [(14)C]glycine and the O(2) inhibition of photosynthesis in Myriophyllum. In low photorespiration Myriophyllum, glycine labeling and O(2) inhibition of photosynthesis were independent of the CO(2) level, but in high photorespiration plants the O(2) inhibition was competitively decreased by CO(2). Thus, in low but not high photorespiration plants, glycine labeling and O(2) inhibition appeared to be uncoupled from the external [O(2)]/[CO(2)] ratio.These data indicate that the low photorespiratory states of Hydrilla and Myriophyllum are mediated by different mechanisms, the former being C(4)-like, while the latter resembles that of low CO(2)-grown algae. Both may require carbonic anhydrase to enhance the use of inorganic carbon for reducing photorespiration.

Interaction of the cardiovascular, homeothermic and behavioural systems has particular significance in early life as this period of development sees high cardiac output, limited circulatory reserves, a particular vulnerability to thermal stress, and long periods of rapid eye movement (REM) sleep during which thermal regulation may be suspended. In unstressed lambs, significant cardiovascular differences exist between behavioural states of sleep and wakefulness, with the REM sleep-state being outstanding. In REM sleep there is wide cardiac output variation, a low heart rate, and a high stroke volume. High levels of cardiac output occurring in combination with poorer oxygenation and respiration in REM may represent a risk to the newborn, as cardiac performance is already high and reserves are low in comparison with the adult. Lambs respond to cool stress with increases of cardiac output and oxygen consumption in wakefulness and quiet sleep, but not in REM sleep. Suspension of thermoregulatory processes in REM sleep also points to this as the more vulnerable state for the newborn. Arousal responses from quiet sleep or REM sleep to wakefulness occur if lambs are subjected to acute reductions of blood pressure. There is a delay before arousal which is longer in REM sleep than in quiet sleep. Animals fail to arouse in approximately 40% of hypotensive tests in both states. This shared feature of the sleep-states (failure to arouse) may be more important than the state-related difference (longer delay before arousal in REM) in understanding a cardiovascular mechanism of Sudden Infant Death Syndrome.