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Biomedical subjects

J Krieger

Publications and source records attributed to J Krieger.

At least 145 records · Page 8Linked to original sources

Long-term effects of treatment with nasal continuous positive airway pressure on daytime lung function and pulmonary hemodynamics in patients with obstructive sleep apnea.

Fifty-four patients with obstructive sleep apnea (OSA) syndrome received long-term treatment with nasal continuous positive airway pressure (CPAP). The effects on daytime lung function and pulmonary hemodynamics were prospectively evaluated by repeating pulmonary function tests, including right heart catheterization after a follow-up period of at least 1 yr (554 +/- 28 days, mean +/- SEM). PaO2 increased in the patient group as a whole from 69.9 +/- 1.4 to 72.8 +/- 1.4 mm Hg (p less than 0.02). The increase in PaO2 was greater (from 60.4 +/- 1.0 to 66.4 +/- 2.1, p less than 0.01) in those patients who were hypoxemic prior to treatment. PaCO2 decreased significantly only in the subgroup of patients with significant hypercapnia prior to treatment (n = 7), from 48.5 +/- 1.3 to 44.5 +/- 1.5 mm Hg (p less than 0.01). The improvement in daytime blood gases seemed to be related to an increase in the alveolar ventilation, from 5.2 +/- 0.2 to 5.9 +/- 0.3 L/min without a change in the alveolar-arterial PO2 difference, as calculated in 25 patients. Both the red blood cell count and the hematocrit decreased significantly, from 5,347 +/- 90 to 5,024 +/- 61 10(3)/mm3 and from 49.4 +/- 0.9 to 47.1 +/- 0.6%, p less than 0.001 and p less than 0.02, respectively. No change was observed in the resting pulmonary arterial pressure. We conclude that nasal CPAP is effective in improving daytime blood gases in patients with OSA.

Blood Pressure↗

Overnight decrease in hematocrit after nasal CPAP treatment in patients with OSA.

To clarify the paradox of a decrease in urine and sodium excretion occurring along with the elimination of peripheral edema when patients with obstructive sleep apnea (OSA) are treated with nasal continuous positive airway pressure (CPAP), we investigated the immediate effects of this treatment on the hematocrit and red blood cell count in eight patients with OSA. The hematocrit decreased in all patients, from a mean of 45.6 +/- 1.2 percent to 43.0 +/- 1.4 percent, with a parallel decrease in the red blood cell count from 4.777 +/- 0.168 millions/cu mm to 4.577 +/- 0.174 millions/cu mm (p less than 0.0005, one-tailed, in both cases). These results suggest that nasal CPAP treatment causes a hemodilution in patients with OSA, and are compatible with the hypothesis of an atrial natriuretic peptide-induced fluid shift from the intravascular to the extravascular volume in untreated patients with OSA. The reversal of these changes with CPAP treatment could explain the simultaneous decrease in sodium and urine excretion and the reduction of peripheral edema.

Darkness↗

Breathing during sleep in normal middle-aged subjects.

Although ventilation during sleep has been studied in normal young and elderly subjects, little data are available concerning possible quantitative changes in ventilatory parameters in normal middle-aged subjects. We studied the occurrence of respiratory events and the changes in minute ventilation, tidal volume, and respiratory rate during rapid-eye-movement (REM) and non-REM (NREM) sleep in 40 normal (20 men and 20 women) middle-aged subjects, using polysomnography with pneumotachography and oximetry. Apnea indices greater than 5, with apneas predominantly of the obstructive type, were found in 17.5% of the subjects (30% of the men and 5% of the women). These "apneic" subjects differed from the "nonapneic" subjects only in that they had a higher body mass index. Minute ventilation decreased from wakefulness to sleep by 14% to 19%, owing to a decrease in tidal volume without a significant change in respiratory rate. This decrease was not greater in slow wave (stage 3-4 NREM) or in REM sleep than in stage 2 NREM sleep, nor was it greater in men than in women. It correlated with the minute ventilation during wakefulness: the higher the minute ventilation during wakefulness, the greater the decrease during sleep. The occurrence of respiratory events was not related to the degree of the decrease in minute ventilation from wakefulness to apnea-free sleep.

Adult↗

Molecular cloning of an insect pheromone-binding protein.

Clones coding for the pheromone binding protein precursor have been selected from a cDNA library derived from antennae of the male moth, Antheraea polyphemus. The deduced protein sequence consists of a signal peptide of 20 amino acid residues and a mature binding protein of 142 amino acid residues. RNA blot hybridization indicated that the mRNA is selectively expressed in the antennae of the male moth.

Animals↗

[Renal function and sleep apnea syndromes].

Obstructive sleep apnea (OSA) patients have increased diuresis and natriuresis during sleep. In order to investigate the possible mechanisms of these changes in renal function, 35 consecutively diagnosed OSA patients were studied during sleep before and during nasal continuous positive airway pressure (CPAP) treatment, and were compared with 23 non-snoring controls. The excretion of urine and of electrolytes was increased before treatment and normalized with nasal CPAP treatment. The mechanism involved seems to be decreased sodium reabsorption at the level of the ascending limb of the loop of Henle. The observed increase in cyclic guanosine monophosphate excretion supports the hypothesis of increased atrial natriuretic peptide release during sleep in OSA patients.

Adult↗

Urinary excretion of guanosine 3':5'-cyclic monophosphate during sleep in obstructive sleep apnoea patients with and without nasal continuous positive airway pressure treatment.

1. It has recently been shown that obstructive sleep apnoea (OSA) patients have increased urinary water and salt excretion during sleep which tends to normalize with nasal continuous positive airway pressure (CPAP) treatment. 2. To investigate the mechanisms of these changes in renal function, nocturnal urinary excretion of catecholamines and guanosine 3':5'-cyclic monophosphate (cyclic GMP), which reflects atrial natriuretic factor (ANF) release, and next-morning plasma active renin concentrations were studied in 21 OSA patients on 2 consecutive nights, either untreated or treated with nasal CPAP. 3. In keeping with previous results, fractional urine flow and fractional Na+ and Cl- excretions were higher during untreated than during CPAP-treated nights. 4. No difference in plasma active renin concentration or in urinary excretion of noradrenaline, adrenaline, free dopamine and total dopamine could be demonstrated, but cyclic GMP excretion was significantly higher during untreated than during CPAP-treated nights. 5. The data are consistent with the hypothesis that the increased water and salt excretion in OSA patients is due to increased ANF release. 6. The proposed mechanism is an atrial distension due to increased (more negative) intrathoracic pressures during ineffective inspiratory efforts against the occluded upper airways which have been found in OSA.

Adult↗

Atrial natriuretic peptide release during sleep in patients with obstructive sleep apnoea before and during treatment with nasal continuous positive airway pressure.

1. Plasma levels of atrial natriuretic peptide (ANP) were measured in seven patients with obstructive sleep apnoea (OSA) while they were awake, during repetitive apnoea and during treatment with nasal continuous positive airway pressure (CPAP). 2. ANP levels in both pulmonary artery and peripheral venous samples were elevated during apnoeic sleep and reduced when apnoea was prevented by nasal CPAP. Mean values of pulmonary artery ANP were 116.3 +/- 17.9 pg/ml during apnoea and 64.8 +/- 15.2 pg/ml (P less than 0.05) on nasal CPAP. 3. It is concluded that there is increased ANP release during sleep in patients with OSA and that CPAP treatment normalizes ANP secretion. These findings may explain previously identified urinary abnormalities in OSA.

Atrial Natriuretic Factor↗

Pulmonary hypertension, hypoxemia, and hypercapnia in obstructive sleep apnea patients.

To define the parameters of respiratory insufficiency in OSA, 114 consecutive patients (108 men, six women) were prospectively studied. In addition to standard polysomnography, they underwent pulmonary function tests, right heart catheterization, and ventilatory response tests to hypercapnia. Nineteen patients (19 percent) had a resting PAP greater than or equal to 20 mm Hg. Multiple regression analysis showed that FEV1 and PaO2 (both with a negative coefficient) and PaCO2 (with a positive coefficient) significantly contributed to PAP. Thirteen patients (12 percent) had a PaCO2 greater than or equal to 45 mm Hg. A multiple regression analysis showed that FEV1 and the minute ventilation at PETCO2 = 60 mm Hg (both with a negative coefficient) and the cumulative apnea duration (with a positive coefficient) significantly contributed to PaCO2. Thirty-seven patients (33 percent) had a PaO2 less than or equal to 65 mm Hg. A multiple regression analysis showed that FEV1 (with a positive coefficient) and the hypopnea + apnea index (with a negative coefficient) significantly contributed to PaO2. These data confirm that impaired daytime pulmonary function (diffuse airway obstruction) contributes to the development of daytime pulmonary hypertension, hypoxemia, and hypercapnia in OSA patients. They show that the amount of sleep-related breathing disorders also plays a significant role.

Cardiac Catheterization↗

[Sleep apnea syndromes].

Sleep apnea syndromes have been identified only relatively recently. Their most frequent form is characterized by a sleep-related upper airway obstruction resulting in apneas which may repeat themselves up to several hundred times during a night's sleep. Their mean duration is about 30 to 40 seconds, but some apneas last over one minute. Breathing resumption requires an arousal, which may be clearly identified on the EEG but usually goes unnoticed by the patient. The most immediate consequence are hypoxemia and sleep fragmentation. There may be associated arrhythmias and hemodynamic changes, especially in the pulmonary circulation. The predominant clinical signs are snoring (during the breathing resumption between the apneas) and daytime somnolence due to sleep fragmentation. In addition to the risks of work and traffic accidents, these patients run a long-term risk of cardiovascular accidents. About 20% develop pulmonary hypertension, a contributing factor to right heart failure. About 50% are hypertensive, which combined with a frequently observed polycythemia, makes them vulnerable to ischemic accidents. The treatment is based upon the use of continuous positive airway pressure (CPAP) during sleep. In case of failure, surgical alternatives may be considered.

Electroencephalography↗

Studies on the capacity of intact cells and purified Ia from different B cell sources to function in antigen presentation to T cells.

In this study we have evaluated some of the potential mechanisms that may be responsible for the inefficiency with which resting B cells function as antigen-presenting cells (APC) and the mechanism by which that function is enhanced following treatment of B cells with neuraminidase. One mechanism that has been previously suggested is that glycosylation differences in Ia associated with different APC accounts for the different functional capacities of resting and activated B cells. It has been postulated that removal of sialic acid from resting B cell Ia results in a correction of its antigen-presenting defect. To study this possibility, we have used purified I-Ad from different B cell sources in a planar membrane system to present an immunogenic peptide of chicken ovalbumin (Ova) to an I-Ad-restricted Ova-specific T cell hybridoma. It was found that I-Ad isolated from resting B cells, B cell stimulatory factor 1 (BSF-1) or lipopolysaccharide and dextran sulfate-stimulated B cells, or A20 B lymphoma cells were all equivalent in their antigen-presenting capacity. Furthermore, removal of sialic acid from Ia did not enhance its capacity to serve as a restriction element. The mechanism by which neuraminidase treatment enhances B cell APC function was further investigated by studying the effect of sialic acid removal on a primary mixed leukocyte reaction (MLR). When allogeneic fixed B cells were used as stimulator cells it was found that neither resting nor BSF-1-stimulated B cells could induce a MLR. Following neuraminidase treatment, BSF-1-treated B cells, but not resting B cells, were capable of stimulating a MLR. However, a MLR was also stimulated by allogeneic BSF-1-treated B cells when the responder T cells, rather than the stimulator cells, were treated with neuraminidase. An enhancing effect similar to that obtained by neuraminidase treatment could be obtained by the addition of 2% polyethylene glycol to the MLR culture. These data suggest that the inability of BSF-1-stimulated cells to function efficiently as accessory cells in stimulating a primary MLR is due to their relative inability to interact physically with T cells, a deficiency that is overcome by neuraminidase treatment of either T or B cell populations or by the addition of polyethylene glycol to the culture. Although the reason for the failure of these same treatments to restore the accessory cell function of resting B cells is not known, some possible mechanisms are discussed.

Animals↗

Daytime pulmonary hypertension in patients with obstructive sleep apnea syndrome.

The frequency of daytime pulmonary hypertension (PH) in patients with obstructive sleep apnea syndrome (OSAS) has not been well established and its mechanisms are still under debate. We have thus performed right heart catheterization, in addition to standard spirography and arterial blood gas measurements, in a series of 46 consecutive patients in whom OSAS was firmly diagnosed by whole-night polysomnography. Only 9 of the 46 patients (20%) had PH defined by a mean resting pulmonary arterial pressure (Ppa) greater than or equal to 20 mm Hg. Among the patients without resting PH, 14 had exercising PH (defined by a Ppa greater than 30 mm Hg during 40-watt, steady-state exercise). Patients with resting PH differed from the others by a lower daytime PaO2 (60.8 +/- 7.6 versus 76.2 +/- 9.4 mm Hg; p less than 0.001), a higher daytime PaCO2 (44.6 +/- 4.2 versus 38.0 +/- 4.0 mm Hg; p less than 0.001), and lower VC and FEV1 (p less than 0.001). There was no difference between the 2 groups with regard to apnea index (62 +/- 34 versus 65 +/- 40) or the lowest sleep SaO2 (59 +/- 21 versus 66 +/- 18%) or the time spent in apnea. For the group as a whole, there was a good correlation between Ppa and daytime PaO2 (r = -0.61; p less than 0.001), PaCO2 (r = 0.55; p less than 0.001), and FEV1 (r = -0.52; p less than 0.001), but there was no significant correlation between Ppa and the apnea index, the lowest sleep SaO2, or the time spent in apnea.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗