Laser induced photoreceptor damage and recovery in the high numerical aperture eye of the garter snake.

The garter snake provides a unique model for in-vivo imaging of photoreceptor damage induced by laser retinal exposure. Laser thermal/mechanical retinal injury induced alterations in photoreceptor structure and leukocyte cellular behavior. Photoreceptors turned white, lost mode structure, and swelled; leukocyte activity was observed in the vicinity of photoreceptor cells. Non-thermal alterations were identified with a bio-tag for oxidative stress. Mechanisms of photoreceptor recovery and replacement were observed and evaluated for active cytoskeletal systems by using an anti-actin tag that could detect the presence of active cytoskeletal systems resident in photoreceptors as well as other retinal systems.

Adjustable maintenance dosing with budesonide/formoterol or budesonide: double-blind study.

Adjustable maintenance dosing with either budesonide/formoterol or budesonide was compared in asthma patients. This double-blind trial randomized 133 patients (mean forced expiratory volume in 1s 66% predicted) to receive 2 inhalations twice daily of budesonide/formoterol 160/4.5 microg (640/18 microg/day) or budesonide 320 microg (1280 microg/day) for 4 weeks. The study drug was adjusted in both groups according to symptoms to 2-4 inhalations daily during Weeks 5-8 and 1-4 inhalations daily during Weeks 9-20. Asthma was well controlled in both groups, with minimal levels of treatment failure (5 budesonide/formoterol vs. 2 budesonide patients; P=NS) and minimal use of reliever therapy. Clinically important improvements in health-related quality of life (HRQL) occurred in the physical functioning and emotional role functioning domains (both P<0.05) for the budesonide/formoterol group compared with budesonide. Physician and patient treatment satisfaction favored budesonide/formoterol (both P<0.05). Budesonide/formoterol patients used fewer daily inhalations of study drug (P=0.024). The median average daily inhaled corticosteroid dose during the study was 448 microg with budesonide/formoterol and 1152 microg with budesonide. Adjustable maintenance dosing with budesonide/formoterol and budesonide resulted in high levels of asthma control. Adjustable budesonide/formoterol treatment achieved greater HRQL benefits and patient satisfaction, with lower overall drug use.

No effect of naloxone on ventilatory response to progressive hypercapnia in IDDM patients.

The ventilatory response to hyperoxic progressive hypercapnia was examined by comparing 3 test groups: 7 diabetic patients with AN, 8 diabetic patients without AN, and 8 normal control subjects. In each group, a significant linear correlation was found between PaCO2 and VE. The slopes of the regression curves relating PaCO2 to VE were significantly steeper in the healthy control subjects and diabetic patients without AN than in those with AN (P < 0.01). We conclude that the ventilatory response to progressive hypercapnia is reduced in diabetic patients with AN. By analyzing the power spectrum and the amplitude behavior of the diaphragmatic EMG (calculated from the fc and RMS, respectively), we could exclude a disturbance of neural descending pathways and respiratory muscle dysfunction as possible causal mechanisms for the impaired ventilatory response to increasing CO2. By using lung function analysis, causal factors such as alterations in respiratory system mechanics also could be excluded. As diabetes is known to affect the endogenous opioid system, which, in turn, affects the ventilatory response to CO2, naloxone, as a specific opioid antagonist, was administered in all 3 test groups. Naloxone produced a significant increase of ventilatory response to hypercapnia in the healthy control subjects (P < 0.01), but produced no effect in either of the diabetic groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Systemic hypertension in snorers with and without sleep apnea.

To investigate the impact of sleep-disordered breathing events on daytime hypertension (HT) in patients with increased upper airway resistance during sleep, we studied 191 male snorers aged 49.9 +/- 0.8 years. In 116 of them, an apnea-hypopnea index (AHI) above 10--defined as the presence of obstructive sleep apnea (OSA)--was found; the other 75 subjects had an AHI lower than 10 and were classified as habitual snorers (HSN). Prevalence of HT was not different between OSA (56 of 116 = 48 percent) and HSN (33 of 75 = 44 percent) and there was also no difference in systolic, diastolic, and mean blood pressures between the two groups. Hypertensive OSA patients had higher body mass index (BMI) than normotensive OSA subjects (31.4 +/- 0.7 vs 29.4 +/- 0.6; p less than 0.05), but there was no difference in age, AHI, and nocturnal oxygenation parameters. The same was true for the HSN group, with hypertensive subjects being more obese than normotensive subjects (BMI: 30 +/- 0.8 vs 27.3 +/- 0.8; p less than 0.05), but no difference in age and polysomnographic features. Discriminant analysis with HT as the classification variable and age, BMI, AHI, mean, and lowest nocturnal oxyhemoglobin saturation as independent variables, revealed an independent influence on HT only for BMI (F-prob = 0.001). Thus, our results stand against the hypothesis of a causal relationship between sleep-disordered breathing events and daytime hypertension. We conclude that the high prevalence of HT in male snorers is more directly linked to obesity than to sleep apnea, but an independent effect of snoring per se cannot be excluded.

Nasal continuous positive airway pressure for nonapneic snoring?

The feasibility of nasal continuous positive airway pressure (CPAP) for heavy snoring associated with daytime sleepiness was studied in 118 consecutive patients with an apnea hypopnea index below 5. Fifty-nine of them reported daytime sleepiness in a questionnaire and were offered treatment with nasal CPAP. Whereas 48 patients refused it, the remaining 11 (19%) accepted nasal CPAP for home therapy. Acceptors and refusers did not differ in sleep structure, but acceptors had slightly more sleep-disordered breathing events per hour of sleep than refusers. The pressure needed to abolish snoring in these 11 patients was 7.3 +/- 1.6 cm H2O. Six months after prescription, the built-in time counters of the patients' devices were read. By dividing the hours of operation by the days since initiation of treatment, we found a mean daily use time of only 2.8 +/- 1.5 h. Nevertheless, eight patients (73%) reported that their sleepiness had improved with therapy. We conclude that only a minority of nonapneic snorers accept treatment with nasal CPAP on a long-term basis and that this subgroup is not predictable from polysomnography.

Breathing during sleep in patients treated for obstructive sleep apnea. Nasal CPAP for only part of the night.

To determine whether long-term NCPAP therapy influences severity of sleep disordered breathing during the second part of a night when NCPAP is applied for only the first four hours of sleep, we studied 21 patients with OSA receiving NCPAP therapy for 253 +/- 41.6 days. Results from polysomnography for the period after withdrawal from NCPAP (night B) were compared to the corresponding period of sleep prior to initiation of NCPAP therapy (night A). There was no significant change in RDI from night A (53.9 +/- 8.6) to night B (28.7 +/- 3.3), but maximal apnea length diminished from 55 +/- 2.9 s to 40 +/- 2.9 s (p less than 0.05). Whereas daytime Po2 and the amplitude of desaturations during sleep remained equal, overall oxygenation during sleep improved slightly (mean SaO2 night A = 90.6 +/- 0.9 percent; night B = 92.8 +/- 0.5 percent; p less than 0.05). Differences between nights A and B were more prominent the more severe sleep apnea had been prior to treatment and could not be explained by weight loss. There was strong correlation between improvements in oxygenation measurements and the daily time of NCPAP use. In conclusion, we found a subgroup of OSA patients receiving long-term NCPAP therapy with less disturbed ventilation during sleep following use of NCPAP for only the first part of the night, but in the majority of patients, sleep disordered breathing off NCPAP remained unchanged.

Acceptance of CPAP therapy for sleep apnea.

Although NCPAP is the most efficient nonsurgical treatment for patients with OSA, many patients do not accept sleeping with a nose mask. To determine the factors influencing acceptance, treatment with NCPAP was offered to 95 patients with an AHI greater than 15. After the first night on NCPAP, 47 of 65 patients decided to have NCPAP as a home therapy. Excessive daytime sleepiness was more frequently reported by acceptors than refusers. The frequency of complaints about psychomental symptoms such as poor mental performance and bad memory, was not different between the two groups. There was a close correlation between the rate of acceptance and the AHI as well as the number of positive answers to questions about symptoms of daytime sleepiness in a questionnaire, which correlated with the number and length of apneas. Acceptance of NCPAP was found to be dependent on the subjective feeling of impairment by hypersomnolence due to OSA.

Self-reported vs measured compliance with nasal CPAP for obstructive sleep apnea.

To estimate reliability of self-reported compliance with nasal continuous positive airway pressure (CPAP) therapy for obstructive sleep apnea (OSA), we studied 63 OSA patients aged 53.7 +/- 1.2 years (mean +/- SEM) with an apnea hypopnea index (AHI) of 50.8 +/- 2.9 and lowest sleep SaO2 of 65.6 +/- 2.3 percent receiving nasal CPAP for 539 +/- 44 days. During a follow-up polysomnography (PSG) on the pressure prescribed for home therapy (10.3 +/- 0.3 cm H2O), the hours of operation shown on the built-in time counter of the patients' devices were read to determine objective compliance by dividing the run time by the days since initiation of therapy. This parameter was compared with subjective compliance reported in a self-administered questionnaire. Mean measured use time was 4.9 +/- 0.3 h per night, whereas reported daily use time calculated from reported nights a week and hours a night was 6.1 +/- 0.3 h per night. As predominantly patients with poor compliance misestimated daily use time, we conclude that self-reports are unable to distinguish between compliant and noncompliant patients.

Nasal function and bronchial hyperresponsiveness to methacholine in children.

The objective of the present study was to investigate nasal function by active anterior rhinomanometry with respect to spirometric data and bronchial hyperresponsiveness to methacholine in 9-year-old children. The study population consisted of 300 children (ages 8 to 11 years; mean, 9.3 years; 161 male, 139 female), who underwent basal rhinomanometry followed by a decongestion test and a lung function test consisting of spirometry and a methacholine provocation test. The flow values of the basal rhinomanometry showed a significant correlation with height and bronchial hyperresponsiveness. The consecutive decongestion test showed a marked increase in flow rates at each level, which was found to be significantly higher in children with bronchial hyperresponsiveness (p < 0.01). The spirometric data showed no influence on rhinomanometric values. These results suggest that nasal dysfunction and reactivity in terms of the decongestion test may be associated with bronchial hyperresponsiveness in children.

Prediction of interstitial lung involvement in rheumatoid arthritis. The value of clinical data, chest roentgenogram, lung function, and serologic parameters.

We initiated the present study to predict interstitial lung involvement in rheumatoid arthritis (RA) by means of logistic regression analysis of clinical data, lung function, chest roentgenogram, and serologic parameters. Fifty-eight nonsmoking patients with RA were randomized from the rheumatologic unit and sent for investigation to the pulmonary department. Bronchoalveolar lavage (BAL) was performed in the middle lobe and the BAL fluid was considered abnormal in case of increased cell count per milliliter and/or lymphocytosis and/or neutrophil granulocytosis; these findings or combinations thereof were found in 42 (72.4 percent) of 58 cases. The patients' data that had an impact on the normality of BAL were the sex (p = 0.001), vital capacity (p = 0.028), peripheral blood T-helper cells (OKT4+) (p = 0.025), DR(+)-lymphocytes (p = 0.002), and antinuclear antibodies (p = 0.025). By means of the logistic regression analysis, it was possible to reach high significance in the prediction of interstitial lung involvement, with a sensitivity of 92.9 percent and a specificity of 75.0 percent (p less than 10(-6)). The efficiency of prediction was 87.9 percent. From these results, we conclude that interstitial lung involvement in RA is predictable from laboratory findings that have been yielded by noninvasive diagnostic techniques. These data should be used in clinical routine monitoring and they may help to facilitate the assessment of whether bronchoscopy is indicated.

2 Years' experience with inspiratory muscle training in patients with neuromuscular disorders.

PURPOSE: The aim of our study was to assess the long-term effects of specific inspiratory muscle training (IMT) in patients with neuromuscular disorders (NMDs) who have various degrees of respiratory impairment. PATIENTS AND METHODS: Twenty-seven patients with NMDs (Duchenne's muscular dystrophy, 18 patients; spinal muscular atrophy, 9 patients) underwent 24 months of IMT. Patients were divided into three groups according to their vital capacity (VC) values. VC was measured as the parameter for the respiratory system involvement of the disease. Maximal inspiratory pressure (PImax) was assessed as the parameter for respiratory muscle strength, and the results of the 12-s maximum voluntary ventilation test (12sMVV) were assessed as the parameter for respiratory muscle endurance. Pulmonary and inspiratory muscle function parameters were assessed 6 months before training, at the beginning of training, and then every 3 months. RESULTS: The PImax values improved in group A (VC, 27 to 50% predicted) from 51.45 to 87.00 cm H(2)O, in group B (VC, 51 to 70% predicted) from 59.38 to 94.4 cm H(2)O, and in group C (VC, 71 to 96% predicted) from 71.25 to 99.00 cm H(2)O. The 12sMVV values improved in group A from 52.69 to 69.50 L/min, in group B from 53.18 to 62.40 L/min, and in group C from 59.48 to 70.5 L/min. For all three groups, there was a significant improvement of PImax (p < 0.007) and 12sMVV (p < 0.015) until the 10th month when a plateau phase was reached with no decline in the following month until the end of training. CONCLUSION: With IMT, respiratory muscle function can be improved in the long term of up to 2 years.

Inspiratory muscle training in patients with Duchenne muscular dystrophy.

PURPOSE: The aim of this study was to assess the usefulness of a specific inspiratory muscle training in Duchenne muscular dystrophy (DMD). PATIENTS AND METHODS: Fifteen patients with DMD started 6 months of training the inspiratory muscles and 15 patients served as a control group. Pulmonary and inspiratory muscle function parameters were assessed 3 months before and at the beginning of training, in the first and third month of training, at the end, and 6 months after its cessation. Maximal sniff assessed esophageal and transdiaphragmatic pressure values served as indices for global inspiratory muscle strength and diaphragmatic strength, respectively. Inspiratory muscle endurance was assessed by the length of time a certain inspiratory task could be maintained. RESULTS: In 10 of the 15 patients, respiratory muscle function parameters improved significantly after 1 month of training. Further improvements were to be seen after 3 and after 6 months. Even 6 months after the end of training, those effects remained to a large extent. In the other five patients, there was no such improvement after 1 month of training, which was therefore discontinued. All these five patients had vital capacity values of less than 25 percent predicted and/or PaCO2 values of more than 45 mm Hg. The 15 control patients had no significant change in their respiratory muscle function parameters. CONCLUSION: We conclude that a specific inspiratory muscle training is useful in the early stage of DMD.

Neural drive to the diaphragm after lung volume reduction surgery.

STUDY OBJECTIVES: The aim of this study was to investigate prospectively the changes in neural drive to the diaphragm in the first year after lung volume reduction surgery (LVRS) in patients with COPD. PATIENTS AND METHODS: In 14 patients with severe emphysema (mean +/- SD; age, 53.7 +/- 8.3 years; FEV(1), 0.64 +/- 0. 18 L; residual volume [RV], 5.33 +/- 1.25 L; PaO(2), 62.3 +/- 9.0 mm Hg; PaCO(2), 39.0 +/- 6.0 mm Hg), we assessed lung function, arterial blood gases, maximal exercise capacity (Wmax), and oxygen uptake (f1.gif" BORDER="0">O(2)max); intrinsic positive end-expiratory pressure (PEEPi); diaphragmatic strength (transdiaphragmatic pressure, Pdisniff) and endurance capacity (tlim); central diaphragmatic drive assessed by root mean square analysis of the esophageal electromyogram (rmsdia); and isotime dyspnea during loaded breathing tests (BS). RESULTS: Despite a significant increase (expressed as a percentage of baseline) in FEV(1) (40.6%) and a decrease in RV (30.0%) and PEEPi (75.7%) 1 month after LVRS, the improvements in Wmax (31.2%) and f1.gif" BORDER="0">O(2)max (13.7%); Pdisniff (25.4%) and tlim (64.9%); rmsdia (34.6%); and BS (21.7%) did not reach statistical significance (p < 0.05) until 6 months after LVRS. Arterial blood gases did not change significantly. Significant correlations were found between decrease in rmsdia and changes in PEEPi (r = 0.69), Wmax (r = -0.56), Pdisniff (r = -0.65), tlim (r = -0.59), and BS (r = 0.71) 6 months after LVRS. CONCLUSIONS: Our results show that LVRS is able to increase the efficacy of the respiratory pump and by this way reduce ventilatory drive and respiratory effort sensation.

Defective endogenous opioid response to exercise in type I diabetic patients.

Plasma beta-endorphin (beta-E) concentration was determined before, during, and after a standardized incremental exercise test to maximal capacity in eight type I diabetic patients and eight normal control subjects. Diabetic patients were studied under normoglycemic and hyperglycemic conditions in a single-blind random fashion to differentiate between the effects of acute hyperglycemia and of diabetes per se on the beta-E response to exercise. The perceived magnitude of leg effort elicited by exercise was evaluated using a category scale. Whereas plasma beta-E concentrations increased in control subjects with increasing workload, causing significantly higher beta-E levels at the end of exercise than at the beginning (P < .001), no such increase could be observed in the diabetic patients under normoglycemic and hyperglycemic conditions. In addition, baseline plasma beta-E concentrations were significantly lower in normoglycemic (P < .01) and hyperglycemic (P < .001) diabetic patients than in control subjects. Even during the recovery period, patients' beta-E levels remained significantly lower than those of control subjects. At submaximal levels of power output, the perceived intensity of leg effort was significantly higher in normoglycemic and hyperglycemic diabetic patients than in control subjects. We conclude that in type I diabetic patients, the ability of the endogenous opioid system to respond to exercise-induced stress is impaired under hyperglycemic and even under normoglycemic conditions. Considering the effect of endogenous opioids on stress tolerance, such changes may compromise exercise performance in diabetic patients.

Common properties shared by growth-associated proteins of the regenerating optic nerve of goldfish (C. auratus).

Regenerating neurons synthesize new, rapidly transported, growth-associated proteins which are thought to mediate the regeneration process. We have studied these proteins in the regenerating optic nerves of goldfish by using two-dimensional polyacrylamide gel electrophoresis coupled with gel fluorography and computer analysis. The results indicate that goldfish retinal ganglion cells produce 3 polypeptides which qualify as growth-associated proteins. Properties shared by each of these 3 polypeptides suggest that they may originate from a common precursor.

On the use of schematic eye models to estimate retinal image quality.

The optical performance of the eyes of nine vertebrate species was evaluated using optical system design techniques and schematic eye models. Essential features of eyes, including the modulation transfer function (MTF) and the MTF cutoff frequency are related to the numerical aperture of the eyes. Superior resolution for in vivo imaging of photoreceptors may be achieved by dilating the iris pupil of an eye, minimizing coherence, and using short wavelength illumination. The difference of lateral and axial resolution between a small and a large eye for imaging photoreceptors in vivo.

Inspiratory muscle performance relative to the ventilatory threshold in healthy subjects.

Inspiratory muscle performance, ventilation, and gas exchange were studied during exercise in healthy subjects to look for typical changes of pattern of contraction at the ventilatory threshold (VT). The steepening of the slope of carbon dioxide output (VCO2) vs oxygen uptake (VO2) at the VT was accompanied by a nonlinear increase of the mean rate of esophageal pressure development (Pes/TI) vs the esophageal pressure time index (PTIes) reflecting both the relative force (Pbreath/Pesmax) and duration (TI/TTOT) required for inspiration. The esophageal pressure time integral within one breath (Pbreath.dTI) was one of the best single predictors of the ventilatory equivalent for oxygen (VE/VO2) at the VT. Moreover, we presented inspiratory muscle load indices as a mirror image of breathing pattern, with the obvious advantage that the ventilation component can be compared with better established methods of presenting ventilatory output. Inspiratory muscle performance during exercise should link the increased metabolic rate to ventilatory output. We conclude that 1) there exists an inspiratory muscle threshold that is well correlated to commonly used gas exchange thresholds, and 2) the efficiency of ventilation and gas exchange during exercise could be linked to pressure and timing of inspiratory muscle contraction.

Nucleolar silver staining patterns of lymphocytes in sarcoidosis.

Bronchoalveolar lavage lymphocytes from 15 patients with pulmonary sarcoidosis and 8 healthy controls were investigated for nucleolar silver staining patterns and lymphocyte subpopulations. Patients with sarcoidosis had increased numbers of silver stained dots versus controls (2.20 +/- 0.24 versus 1.78 +/- 0.07; p less than 0.001). The number of silver stained dots showed the strongest positive correlation to helper cells (OKT 4+) (r = 0.781; p less than 0.0001). These results may be interpreted as further evidence of lymphocytic activation, especially of helper cells (OKT 4+) in pulmonary sarcoidosis.

Kawan bronchial brush/cell block technique. Facilitation of the routine diagnosis of bronchial neoplasms.

OBJECTIVE: To evaluate cell block preparations as a tool for the diagnosis of pulmonary malignancy and to correlate the findings with those from brush cytology and histology from forceps biopsy. STUDY DESIGN: One hundred twenty consecutive samples from patients with primary or metastatic lung cancer were routinely processed and stained for cytologic and histologic examination. In addition to smears, a cell block was prepared from each brushing sample. Brush smears, cell blocks and biopsy specimens were compared and evaluated for their diagnostic accuracy. RESULTS: Brush cytology samples were interpreted as positive for malignancy in all 120 cases. In 42 cases immunohistochemistry performed on cell blocks led to the final precise type diagnosis. Owing to technical problems (stenosis, bleeding, peripheral location), forceps biopsy specimens were obtained from only 51 patients. CONCLUSION: In addition to lower patient risk, cell block preparation yields high diagnostic accuracy and may thus be considered an improvement in quality assurance.

Comparison of the properties and concentrations of the isoforms of retinol-binding protein in animals and human beings.

We used size-exclusion high-performance liquid chromatography (HPLC) to investigate the properties of the 2 isoforms of Vitamin A-containing (holo) retinol-binding protein (RBP) in animals: the form that is bound to transthyretin (holo-TTR-RBP), and the form that does not bind to TTR (holo-free RBP). We also used radial immunodiffusion to measure immunologically active RBP (apo + holo RBP). We compared the isoforms of RBP in animals with those of human beings to determine which animal is the best model of human RBP. Size-exclusion HPLC detected holo-free and holo-TTR-RBP in every animal species studied. Apparent concentration of holo-TTR-RBP varied among species: that of rabbits and dogs >> that of apes, sheep, goats, monkeys, rhinoceroses, felids, rats, human beings, and deer > that of pigs, zebra, and bison > that of penguins. Dogs have unusual RBP chromatograms; they have high concentration of RBP, but also appear to transport much of their vitamin A on protein other than RBP. Human RBP antibody preparations could detect apo + holo RBP immunologic activity only in apes, monkeys, and felids. Apes and monkeys appeared to have complete cross-reactivity to human RBP antibodies. Felids may have substantial, but partial, cross-reactivity. Apes and monkeys appear to be the most relevant animal models for study of human RBP transport. However, there is a need for less-expensive models. Further research is needed, but in the interim, rats or sheep may be satisfactory for some purposes.