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Biomedical subjects

J Krieger

Publications and source records attributed to J Krieger.

At least 19 recordsLinked to original sources

Expression of a pheromone-binding protein in insect cells using a baculovirus vector.

A cDNA encoding a pheromone-binding protein from the male silkmoth Antheraea pernyi has been integrated into the genome of the Autographa californica multiple nuclear polyhydrosis virus such that the transcription was under the control of the strong polyhedrin promoter. Recombinant pheromone-binding protein was expressed in a baculovirus-infected insect cell line (Sf9) and secreted from the cells into the culture medium. Using a two-step protocol, recombinant pheromone-binding protein has been isolated and purified to homogeneity. Pheromone binding of recombinant protein has been demonstrated using a tritiated analog of (E,Z)-6,11-hexadecadienyl acetate.

Affinity Labels

Daytime sleepiness after long-term continuous positive airway pressure (CPAP) treatment in obstructive sleep apnea syndrome.

A modified maintenance of wakefulness test was performed in 58 patients with obstructive sleep apnea (OSA) syndrome before treatment and after long-term (554 +/- 28 days) home therapy with nasal continuous positive airway pressure (CPAP). Before treatment the patients had a shorter mean sleep latency than controls (16 +/- 1 vs. 27 +/- 1 min, mean +/- SEM, P less than 0.001). After treatment, the mean sleep latency increased to 20 +/- 1 min (P less than 0.002 as compared to baseline), but was still shorter than in controls (P less than 0.001). The incomplete normalization of the mean latency contrasted with the patients' claim that they no longer felt sleepy. The improvement in daytime alertness was significantly correlated with the reduction in sleep fragmentation after CPAP treatment and with the baseline mean sleep latency. These results support the hypothesis that sleep disruption related to respiratory events plays a role in the pathogenesis of daytime sleepiness.

Electrocardiography

Long-term compliance with nasal continuous positive airway pressure (CPAP) in obstructive sleep apnea patients and nonapneic snorers.

In a prospective study aimed at evaluating objectively the compliance with nasal continuous positive airway pressure (CPAP) treatment, 233 obstructive sleep apnea (OSA) (apnea index, > 10 apneas/hour) patients and 36 nonapneic snorers were studied. The compliance to treatment was measured by the mean rate of use of the CPAP device, obtained from a built-in time counter. The follow-up period was 874 +/- 48 in OSA patients and 675 +/- 83 in snorers. CPAP was proposed to all OSA patients but only to those snorers who felt improved after an initial laboratory night on CPAP. Nineteen OSA patients refused CPAP. Of the 214 OSA patients who accepted CPAP, 181 are still on treatment, with a mean daily rate of use of 5.6 +/- 0.1 hours (mean +/- SEM); 22 patients stopped CPAP after a variable period of time; 10 patients died and one acromegalic patient was considered cured after hypophysectomy for a pituitary adenoma. Depending upon the definition of acceptable compliance, the compliance rate in this group was between 77% and 89%. The mean rate of use was correlated with indices of disease severity (apnea index, apnea+hypopnea index, minimal SaO2 during sleep, daytime PaO2, pulmonary artery pressure). Thirty-six nonapneic snorers accepted CPAP. In this group, 26 are still on CPAP, with a mean daily rate of use of 5.4 +/- 0.5 hours; one patient died; one underwent uvolopalatopharyngoplasty without follow-up; and eight stopped CPAP. The compliance rate in this group was between 58% and 78%. This study shows that CPAP is reasonably accepted by OSA patients as well as by nonapneic snorers.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Expression of odorant receptors in spatially restricted subsets of chemosensory neurones.

From a rat olfactory library a cDNA clone (OR37) which is supposed to encode an odorant receptor protein has been isolated and characterized. Specific antisense RNA and in situ hybridization techniques have been employed to monitor the olfactory epithelium for the distribution of olfactory neurones expressing the OR37-gene. The OR37-transcripts were detected only in a subset of receptor cells segregated in two restricted areas of the olfactory epithelium. The clusters of reactive cells appear symmetrically in both nasal cavities. Within a reactive region only a subset of the cells expressed the receptor. The segregation of neurones expressing a distinct receptor supports the notion that a spatial component may be involved in coding odour quality.

Amino Acid Sequence

[Pharyngeal obstruction and the functional adaptation of the natural posture of the head and the hyoid bone in sleep apnea syndrome].

Variations in natural head posture (NHP) and hyoid bone (HB) positioning impart changes in the size and shape of the pharyngeal airways. In SAS, which was shown to be correlated with detrimental craniofacial anatomical conditions, control of pharyngeal permeability is lost during sleep. The aim of this study was determine if functional adaptation of NHP and HB position to these detrimental conditions could be observed, using Bonferonni probabilities, in a cephalometric comparison of 38 SAS adults in the wakeful state and a control group of 38 healthy adults. Since HB relationships with craniofacial anatomical structures vary with the positioning of the head, the cephalograms were taken according to the preliminarily tested NHP, thus making the method reproducible. In SAS craniovertical angulation was unchanged, but the head was maintained in a forward position (increased cervico-vertical angulation, P < 0.001). Maintenance of an acceptable pharyngeal permeability was associated with a more distant positioning of HB from the cervical column (P < 0.01) and from craniofacial references (P < 0.001). In spite of these facts lower pharynx opening was still reduced (P < 0.05). Soft palate and facial divergence were expectedly increased in the apneic group. All the individuals but one control could be correctly reclassified with the help of soft palate length, facial divergence, and two HB related variables. Prevention of pharyngeal collapsibility in SAS seems to be commonly associated with functional adaptation of NHP and HP position. The precise control mechanisms of this adaptation remains to be elucidated. Skeletal predispositions to SAS do probably develop already during infancy.

Adaptation, Physiological

Chronic obstructive pulmonary disease and sleep apnea syndrome.

The term "overlap syndrome" was introduced by Flenley to describe the association of sleep apnea syndrome (SAS) with chronic obstructive pulmonary disease (COPD). Epidemiologic data on the prevalence of the overlap syndrome are not available, but the frequency of an associated COPD in SAS patients has been emphasized in almost all the studies analyzing the development of respiratory insufficiency in SAS patients. In a large series (n = 264) of unselected SAS patients who had undergone detailed pulmonary function tests, we observed an obstructive ventilatory defect (FEV1/VC < 60%) in 30 of 264 patients (11%). These patients had lower daytime PaO2 and higher PaCO2 than the other patients and they had higher resting and exercising pulmonary artery mean pressure (right heart catheterization was performed in 215 of 264 patients). We conclude that the risk of developing respiratory insufficiency and cor pulmonale is higher in overlap patients.

Adult

Decrease in haematocrit with continuous positive airway pressure treatment in obstructive sleep apnoea patients.

Previous preliminary results have shown an overnight decrease in haematocrit and red cell count after the first night of treatment with nasal continuous positive airway pressure (CPAP) in obstructive sleep apnoea (OSA) patients. The present study was designed to confirm these preliminary data, and to analyse the long-term effects of CPAP. The haematocrit and red cell count (RCC) were measured in 80 OSA patients on two consecutive mornings, after an untreated night and after a CPAP treatment night. The haematocrit and RCC significantly decreased with CPAP (from 44.0 +/- 0.5 to 42.4 +/- 0.4%, p less than 0.0001 and from 4.769 +/- 0.051 to 4.597 +/- 0.052 x 10(12) red cells.l-1, p less than 0.0001, respectively). Neither the decrease in haematocrit nor the decrease in RCC were correlated with the decrease in urine volume or flow which occurred with CPAP. Thirty five of these patients remained untreated for 45 +/- 4 days, before home treatment with CPAP was initiated. The haematocrit and RCC had returned to values close to those before initial treatment and decreased again after the first treatment night. Twenty one of the patients were re-evaluated after at least one year of home treatment with CPAP, again on two consecutive nights either with CPAP or untreated. The follow-up, post-CPAP haematocrit and RCC were slightly and nonsignificantly higher than after the baseline CPAP night, but still lower than after the baseline untreated night (p less than 0.02). After the untreated follow-up night, no significant change in haematocrit was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Erythrocyte Count

Cloning of genomic and complementary DNA encoding insect pheromone binding proteins: evidence for microdiversity.

Genomic DNA from the silk moth Antheraea pernyi bearing the gene of a pheromone binding protein has been isolated from a partial genomic library using specific cDNA probes. The DNA spans 3.5 kilobases, contains three exons and two intervening sequences that interrupt the protein coding region of the gene. A DNA fragment of a second gene was isolated and the complete primary structure of a corresponding cDNA clone was unravelled. The expression of two different genes, giving rise to different pheromone binding proteins, implies a more specific function of these proteins than was hitherto assumed.

Amino Acid Sequence

Effects of treatment with nasal continuous positive airway pressure on atrial natriuretic peptide and arginine vasopressin release during sleep in patients with obstructive sleep apnoea.

1. Patients with obstructive sleep apnoea have increased diuresis during sleep, which decreases with nasal continuous positive airway pressure treatment. These changes have been attributed to an increased release of atrial natriuretic peptide in obstructive sleep apnoea, and its decrease with continuous positive airway pressure treatment. 2. In order to clarify the change in plasma atrial natriuretic peptide level and to investigate the underlying mechanisms, blood samples were taken at 10 min intervals from nine patients with obstructive sleep apnoea during two nights when the patients were either untreated or treated with continuous positive airway pressure. Polysomnographic monitoring, including transcutaneous oximetry, and measurement of oesophageal pressure were performed simultaneously. Plasma arginine vasopressin was also measured. 3. The plasma level of arginine vasopressin did not change. The level of atrial natriuretic peptide was high and exhibited secretion bursts in six out of the nine patients; it drastically decreased with continuous positive airway pressure treatment. 4. Across the patients, the mean plasma levels of atrial natriuretic peptide was correlated with the degree of hypoxaemia and the degree of oesophageal pressure swings during the sleep apnoeas. 5. Within the patients, cross-correlation studies suggested that the atrial natriuretic peptide secretory bursts were related either to the oesophageal pressure swings or to the apnoea-related hypoxaemia. 6. We conclude that release of atrial natriuretic peptide decreases with continuous positive airway pressure treatment in those patients with obstructive sleep apnoea who have increased release of atrial natriuretic peptide before treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Urinary excretion of prostanoids during sleep in obstructive sleep apnoea patients.

1. Given the unexplained frequent association between systemic hypertension and obstructive sleep apnoea (OSA), the secretion of prostanoids during sleep was investigated (more specifically, the ratio of prostacyclin (PGI2) to thromboxane A2 (TxA2), since they have marked opposite effects on vascular tone). Prostacyclin has vasodilating effects, whereas thromboxane results in vasoconstriction. 2. In 11 OSA drug-free male patients (age 53 +/- 2 years, mean +/- s.e.m.; apnoea index 55 +/- 15 apnoeas/hour of sleep; body mass index 31 +/- 2 kg/m2), we measured the urinary excretion during sleep of 6-keto-PGF1-alpha and of thromboxane TxB2 (the stable metabolites of prostacyclin PGI2 and of thromboxane A2 respectively). This was done on two consecutive nights; one untreated, the other with nasal continuous positive airway pressure (CPAP) treatment. The results were compared with those of nine normal unobese male subjects. 3. The urinary ratio of 6-keto-PGF1-alpha to TxB2 was significantly (P less than 0.001) lower in the untreated OSA patients (1.7 +/- 0.2) than in the controls (3.1 +/- 0.3). It significantly increased with CPAP treatment to 2.3 +/- 0.2, P less than 0.02, which was no longer different from the controls. 4. These results suggest that OSA is associated with an abnormal release of prostanoids during sleep resulting in a decrease of the prostacyclin to thromboxane ratio which potentially has a vasoconstricting effect. The relationship between these changes and the systemic hypertension often observed in OSA patients remains to be established.

6-Ketoprostaglandin F1 alpha

Sleep and breathing abnormalities in a case of Prader-Willi syndrome. The effects of acute continuous positive airway pressure treatment.

This report describes the polysomnographic findings and the respiratory alterations during sleep in a 20-year-old patient with the Prader-Willi syndrome. Nocturnal recordings and a variant of the multiple sleep latency test showed excessive daytime sleepiness, sleep onset rapid eye movement episodes, snoring and sleep apnea. Treatment with nasal continuous positive airway pressure normalized the respiratory pattern and the sleep structure, except for rapid eye movement sleep onset. Whereas upper airway obstruction and obesity may explain the respiratory disorders, as shown by their resolution with continuous positive airway pressure treatment, hypothalamic dysfunction could play a role in the disruption of the normal nonrapid eye movement/rapid eye movement sleep periodicity.

Adult

Left ventricular ejection fraction in obstructive sleep apnea. Effects of long-term treatment with nasal continuous positive airway pressure.

The effects of treatment with nasal continuous positive airway pressure (CPAP) on left ventricular ejection fraction (LVEF) were assessed in 29 patients with obstructive sleep apnea (OSA) in a prospective study using multiple gated equilibrium radionuclide angiocardiography. All patients were evaluated before CPAP treatment was initiated and were reevaluated after one year (mean +/- SE, 415 +/- 6 days), of home treatment with nasal CPAP. The mean LVEF increased from 59 +/- 1 percent to 63 +/- 1 percent (p less than 0.005). The degree of improvement in LVEF was correlated with baseline LVEF (r = 0.54; p less than 0.003), meaning that the lower the baseline value, the greater the increase with treatment. The changes were not different when subgroups of medicated and unmedicated patients were considered separately. These results show that long-term nasal CPAP treatment results in improved left ventricular function in OSA.

Evaluation Studies as Topic

Obstructive sleep apnea treatment: peripheral and central effects on plasma renin activity and aldosterone.

To assess the effect of obstructive sleep apnea treatment on plasma renin activity (PRA) and plasma aldosterone seven male patients were studied under two conditions: untreated and treated with nasal continuous positive airways pressure (CPAP). PRA and plasma aldosterone were measured at 10-min intervals for both nights. CPAP treatment diminished the urinary and Na+ excretion, whereas plasma volume increased. The mean levels of PRA and aldosterone were significantly enhanced by the treatment, increasing respectively from 1.5 +/- 0.3 to 3.0 +/- 0.7 ngAI ml-1.hr-1 (p less than 0.05) and from 8.0 +/- 1.0 to 12.0 +/- 1.7 ng.100 ml-1 (p less than 0.05). PRA curves reflected the overall sleep structure as similarly described in normal subjects. The apnea-induced sleep disturbance led to flat PRA profiles and the restoration of a normal sleep pattern by treatment restored the PRA oscillations related to the sleep cycles and consequently restored aldosterone oscillations. The mean amplitude of these oscillations increased respectively from 1.0 +/- 0.1 to 1.8 +/- 0.4 ngAI ml-1.hr-1 and from 5.4 +/- 1.2 to 10.9 +/- 1.9 ng.100 ml-1. These results suggest that CPAP treatment modifies the nocturnal patterns of PRA and aldosterone by increasing their mean levels and their oscillation amplitude. This indicates increased secretion, which contributes to the normalization of urine and Na output.

Adult

Audit of ranitidine administration in parenteral nutrient solutions.

An audit of the use of ranitidine administered in parenteral nutrient (PN) solutions is reported. Pharmacists at a 747-bed teaching institution developed criteria addressing justification of the use of ranitidine in PN solutions, process indicators for monitoring, and outcome measures. All patients who received ranitidine in their PN solutions between October 29 and November 22, 1989, were included in the study. Data were collected on a standardized form. A total of 23 evaluable patients received ranitidine in PN solutions during the study period. No inappropriate uses of ranitidine were identified. Patients with renal impairment tended to be underdosed. There were no duplicate administrations of ranitidine by the i.v. minibag and PN solution routes. However, on four occasions the PN solution was interrupted for more than six hours; additional ranitidine by i.v. minibag was ordered for only one of these patients. Testing of nasogastric aspirates for pH was not performed in 17 of the 22 patients who needed this test. Gastrointestinal bleeding was observed in two patients, both of whom were not monitored for gastric pH and were underdosed. A program is being developed to promote the safe and effective use of ranitidine administered in PN solutions. An audit of the administration of ranitidine in PN solutions showed that the drug is usually used appropriately at the institution and that most of the patients had positive clinical outcomes.

Evaluation Studies as Topic

Frequency and mechanism of daytime pulmonary hypertension in patients with obstructive sleep apnoea syndrome.

In order to study the frequency and the mechanisms of daytime pulmonary hypertension (PH) in obstructive sleep apnoea syndrome (OSAS) lung function tests, blood gas analysis and right-heart catheterization were performed in 46 consecutive patients. OSAS was assessed by polysomnography. 9 patients only (20%) had PH (mean pulmonary artery pressure (Ppa) greater than or equal to 20 mmHg). Patients with PH had lower daytime PaO2 (60.8 +/- 7.6 vs. 76.2 +/- 9.4 mmHg; p less than 0.001), higher daytime PaCO2 (44.8 +/- 4.2 vs. 38.0 +/- 4.0 mmHg; p less than 0.001), lower forced vital capacity (FVC) and forced expiratory volume (FEV1) (p less than 0.001), but the severity of OSAS was not different whether PH was present or not (apnoea index: 62 +/- 34 hour in the PH group vs. 65 +/- 40 hour, apnoea + hypopnoea index 102 +/- 33 hour in the PH group vs. 86 +/- 36 hour, lowest sleep SaO2: 59 +/- 21% in the PH group vs. 66 +/- 18%). There were significant correlations between Ppa and: daytime PaO2 (r = -0.61; p less than 0.001), PaCO2 (r = 0.55; p less than 0.001), FEV1 (r = -0.52; p less than 0.001) but not between Ppa and apnoea index, apnoea + hypopnoea index, lowest sleep SaO2. PH and daytime hypoxaemia were associated either with chronic airway obstruction or with severe obesity.

Adult

[Role of sleep apnea in essential arterial hypertension].

Because sleep apnoea syndrome is often associated with arterial hypertension, it has been suggested that sleep apnoea might be responsible for hypertension. This hypothesis is mainly based on epidemiological studies showing a statistically significant association between snoring and arterial hypertension; this association remains true even after data correction to take into account the increased frequency of snoring with age and overweight. However, this statistical link is no evidence of a cause-effect relationship, and the mechanism through which sleep apnoea syndrome could produce arterial hypertension remains unknown. Yet treatment of sleep apnoea syndrome seems to improve arterial hypertension, and this alone would justify a search for sleep apnoea syndrome in all patients presenting with arterial hypertension.

Atrial Natriuretic Factor