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Abstract People with long COVID may suffer from a wide range of ongoing symptoms including fatigue, exertional dyspnea, reduced exercise performance, and others. In particular, impaired exercise performance is a condition that can be recovered in many people through an individualized physical exercise training program. However, clinical experience has shown that the presence of post-exertional malaise (PEM) is a significant barrier to physical exercise training in people with long COVID. Currently, there is no guideline or consensus available on how to apply exercise training in this cohort. Therefore, we conducted a literature review in the PubMed library using the following search terms: “COVID”, “post-COVID”, “long COVID” and “exercise” searching for studies from January 2020 to January 2024. Data from 46 trials were included. Exercise training regimes were very heterogeneous and none of these studies reported on the management of PEM in the context of an exercise training program. Based on the feedback from an additional survey that was answered by 14 international experts in the field of exercise training in long COVID, combined with the authors´ own extensive practical experience, a best practice proposal for exercise training recommendations has been developed. This proposal differentiates exercise procedures according to the presence of no, mild/moderate or severe PEM in people with long COVID. These recommendations may guide allied healthcare professionals worldwide in initiating and adjusting exercise training programs for people with long COVID, stratified according to the presence and severity of PEM.

Abstract Background Many animal models have been used to study the pathophysiology of hydrocephalus; most of these have been rodent models whose lissencephalic cerebral cortex may not respond to ventriculomegaly in the same way as gyrencephalic species and whose size is not amenable to evaluation of clinically relevant neurosurgical treatments. Fewer models of hydrocephalus in gyrencephalic species have been used; thus, we have expanded upon a porcine model of hydrocephalus in juvenile pigs and used it to explore surgical treatment methods. Methods Acquired hydrocephalus was induced in 33–41-day old pigs by percutaneous intracisternal injections of kaolin (n = 17). Controls consisted of sham saline-injected (n = 6) and intact (n = 4) animals. Magnetic resonance imaging (MRI) was employed to evaluate ventriculomegaly at 11–42 days post-kaolin and to plan the surgical implantation of ventriculoperitoneal shunts at 14–38-days post-kaolin. Behavioral and neurological status were assessed. Results Bilateral ventriculomegaly occurred post-induction in all regions of the cerebral ventricles, with prominent CSF flow voids in the third ventricle, foramina of Monro, and cerebral aqueduct. Kaolin deposits formed a solid cast in the basal cisterns but the cisterna magna was patent. In 17 untreated hydrocephalic animals. Mean total ventricular volume was 8898 ± 5917 SD mm3 at 11–43 days of age, which was significantly larger than the baseline values of 2251 ± 194 SD mm3 for 6 sham controls aged 45–55 days, (p

BACKGROUND: A test for diagnosis of active Tuberculosis (TB) from peripheral blood could tremendously improve clinical management of patients. METHODS: Of 178 prospectively enrolled patients with possible TB, 60 patients were diagnosed with pulmonary and 27 patients with extrapulmonary TB. The frequencies of Mycobacterium tuberculosis (MTB) specific CD4(+) T cells and CD8(+) T cells producing cytokines were assessed using overnight stimulation with purified protein derivate (PPD) or early secretory antigenic target (ESAT)-6, respectively. RESULTS: Among patients with active TB, an increased type 1 cytokine profile consisting of mainly CD4(+) T cell derived interferon (IFN)-γ was detectable. Despite contributing to the cytokine profile as a whole, the independent diagnostic performance of one cytokine producing T cells as well as polyfunctional T cells was poor. IFN-γ/Interleukin(IL)-2 cytokine ratios discriminated best between active TB and other diseases. CONCLUSION: T cells producing one cytokine and polyfunctional T cells have a limited role in diagnosis of active TB. The significant shift from a "memory type" to an "effector type" cytokine profile may be useful for further development of a rapid immune-diagnostic tool for active TB.

Importance: Overdose is the leading cause of death among people experiencing homelessness (PEH), but engagement in medication treatment is low in this population. Shelter-based buprenorphine may be a strategy for increasing initiation and retention on lifesaving medications., Objective: To estimate clinical outcomes and conduct an economic analysis of statewide shelter-based opioid treatment in Massachusetts., Design, Setting, and Participants: This economic evaluation study in Massachusetts used a cohort state-transition simulation model. Two cohorts were modeled starting in 2013, including (1) a closed cohort of a fixed population of PEH with history of high-risk opioid use over their lifetimes and (2) an open cohort in which membership could change over time, allowing assessment of population-level trends over a 10-year period. Data analysis occurred from January 2023 to April 2024., Exposures: Model exposures included (1) no shelter-based buprenorphine (status quo) and (2) offering buprenorphine in shelters statewide., Main Outcomes and Measures: Outcomes included overdose deaths, quality-adjusted life-years (QALYs) gained, and health care and modified societal perspective costs. Sensitivity analyses were conducted on key parameters., Results: In the closed cohort analysis of 13 800 PEH (mean [SD] age, 40.4 [13.1] years; 8749 male [63.4%]), shelter-based buprenorphine was associated with an additional 65.4 person-weeks taking buprenorphine over an individual's lifetime compared with status quo. Shelter-based buprenorphine was cost saving when compared with the status quo, with a discounted lifetime cost savings from the health sector perspective of $1300 per person, and 0.2 additional discounted QALYs per person and 0.9 additional life-years per person. In the population-level simulation, 254 overdose deaths were averted over the 10-year period with the shelter-based buprenorphine strategy compared with the status quo (a 9.2% reduction of overdose deaths among PEH in Massachusetts). Overdose-related and other health care utilization undiscounted costs decreased by $3.0 million and $66.4 million, respectively. Shelter-based opioid treatment generated $44.7 million in additional medication and clinical costs, but saved $69.4 million in overdose and other health costs., Conclusions and Relevance: In this economic evaluation of clinical and economic outcomes among PEH, shelter-based buprenorphine was associated with fewer overdose deaths and was cost saving. These findings suggest that broad rollout of shelter-based buprenorphine may be an important tool in addressing the overdose crisis.

Background: Community Health Workers (CHWs) provide vital services during disease outbreaks. Appropriate burials of those who died from an infectious disease outbreak is a critical CHW function to prevent infection and disease spread. During the 2018 Ebola Virus Disease (EVD) outbreak in Beni Town, North Kivu, Democratic Republic of the Congo, we sought to understand the levels of understanding, trust, and cooperation of the community in response to the outbreak, the barriers burial workers faced in their health work and its impact on local burial workers and other CHWs., Methods: 12 EVD burial CHWs in Beni Town completed an hour-long qualitative in-depth interview on their experiences. They were recruited from a local counseling center. Interviews were recorded, transcribed and translated into English. A team of 3 researchers identified structural and emergent themes using applied thematic analysis., Results: Workers reported major misconceptions in the community surrounding the initiation of the outbreak. Community misconceptions were based on widespread governmental mistrust as well as a belief system that intertwines traditional and scientific understandings of the world. EVD burial workers identified violence directed at them and community misinformation as the two largest barriers to effectively carrying out their work. They named several important support systems including family and friends, personal relaxation techniques, and a local counseling center., Conclusions: As with other disease outbreaks globally, we found that government mistrust and religious beliefs strongly impacted community perceptions of the EVD outbreak. Previous studies have demonstrated clinic-based medical personnel are often the targets of violence. Our research shows that burial workers were also targeted and exposed to extreme levels of violence in their work. Along with their ability to effectively respond to the outbreak, violence has a negative impact on their own mental wellbeing. Burial workers found group counseling sessions to be an effective tool for managing the stress associated with their work. Further developing and testing of group-based interventions for this group is a priority for future research., (© 2023. The Author(s).)

Objectives: Person-centred care (PCC) meets the needs of individuals by increasing convenience, providing supportive and culturally appropriate services to diverse populations, and engaging families, communities, and stakeholders in planning and provision of care. While the evidence demonstrates that PCC approaches can lead to clinical improvements across the HIV care continuum, it is not yet well defined in the context of HIV service delivery., Methods: A systematic review was conducted to define PCC practices for HIV treatment services in health facilities in sub-Saharan Africa. Data synthesis led to the development of a PCC framework including domain and sub-domain development. The study team used the Effective Public Health Project Practice tool for quantitative studies to assess the quality of the included studies., Results: Thirty-one studies from 12 countries met the inclusion criteria, including 56,586 study participants (females 42%-100% and males 0%-58%), resulting in three major domains and 11 sub-domains. These include staffing (sub-domains of composition, availability, and competency); service delivery standards (sub-domains of client feedback mechanisms; service efficiency and integration; convenience and access; and digital health worker support tools); and direct client support services (sub-domains of psychosocial services, logistics support, client-agency, and digital client support tools). Twenty-five of the person-centred interventions within these domains resulted in improvements in linkage to care, treatment retention, and/or viral suppression., Conclusions: The PCC framework can help to provide a more consistent classification of HIV treatment interventions and will support improved assessment of these interventions to ensure that people receive personalised care., (© 2022 The Authors Tropical Medicine & International Health Published by John Wiley & Sons Ltd.)

Objective: To assess the current state of asthma management in Austria and evaluate improvement of symptoms and quality of life (QoL) in asthma patients by adding the controller substance montelukast to existing therapy., Research Design and Methods: Office-based pneumologists across Austria were invited to participate in an open-label, multicenter observational study. Male and female patients aged from 12-50 years with mild or moderate persistent asthma according to GINA guidelines and FEV(1) > 70% predicted were included if they were on concurrent asthma treatment, but still had persistent symptoms and reduced quality of life. Asthma control was assessed at time of patient anamnesis and subsequent follow-up visits. In addition, a physical examination was performed, lung function (FEV(1)) was measured and two types of validated QoL questionnaires were used: the Juniper Asthma Control Questionnaire was evaluated and documented by the physicians at each study visit and the Asthma Quality of Life Questionnaire was completed by the patients following each visit., Results: A total of 851 patients (343 males, 508 females) were included and 328 patients were eligible for evaluation 3-5 months after completing at least two study visits. QoL rating by patients was available for 263 at baseline and for 216 patients after 3-5 months. The physicians' rating of asthma-related QoL showed improvements between 6.66 and 11.80% in the categories: nocturnal awakening, morning asthma symptoms, reduction of daily activities, wheezing and dyspnoea, but no reduction in the use of short acting ss(2)-agonists (SABA). The QoL judged by the patients by means of the QoL-Q showed statistically significant improvements in 13 of 15 parameters of QoL. The categories: response to cigarette smoke and response to air pollution showed positive trends (not significant) while the improvement of shortness of breath, response to dust, frustration, cough, anxiety, chest pressure, sleep quality, worries about asthma, wheezing, symptoms at heavy and moderate exercise and impairment of daily activities and activities at work reached statistical significance., Conclusion: This open-label, multicenter observational study shows significant improvement in six QoL parameters evaluated by the physicians and in 13 out of 15 QoL categories judged by the patients 3-5 months after adding montelukast to the ongoing asthma treatment in patients with mild or moderate persistent asthma. Limitations to these conclusions are the lack of a placebo control group (as this was an open-label study) and the continuing basal asthma therapy, which might contribute to improvement of asthma control.

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.

Objective: To determine whether methylprednisolone or indomethacin can enhance photoreceptor survival after laser retinal injury in an animal model., Design: Experimental study., Participants: Twenty rhesus monkeys., Methods: Twenty rhesus monkeys (Macaca mulatta) received a grid of argon green (514.5 nm, 10 ms) laser lesions in the macula of the right eye and a grid of neodymium:yttrium-aluminum-garnet (Nd:YAG; 1064 nm, 10 ns) lesions in the macula of the left eye, followed by randomization to 2 weeks of treatment in 1 of 4 treatment groups: high-dose methylprednisolone, moderate-dose methylprednisolone, indomethacin, or control. The lesions were assessed at day 1, day 14, 2 months, and 4 months. The authors were masked to the treatment group. This report discusses the histologic results of ocular tissue harvested at 4 months., Main Outcome Measure: The number of surviving photoreceptor cell nuclei within each lesion was compared with the number of photoreceptor nuclei in surrounding unaffected retina. The proportion of surviving photoreceptor nuclei was compared between each treatment group., Results: Argon retinal lesions in the high-dose steroid treatment group and the indomethacin treatment group demonstrated improved photoreceptor survival compared with the control group (P = 0.004). Hemorrhagic Nd:YAG lesions demonstrated improved survivability with indomethacin treatment compared with controls (P = 0.003). In nonhemorrhagic Nd:YAG laser retinal lesions, the lesions treated with moderate-dose steroids demonstrated improved photoreceptor survival compared with the control group (P = 0.004)., Conclusions: Based on histologic samples of retinal laser lesions 4 months after injury, treatment with indomethacin resulted in improved photoreceptor survival in argon laser lesions and hemorrhagic Nd:YAG laser lesions. Treatment with systemic methylprednisolone demonstrated improved photoreceptor survival in argon retinal lesions and in nonhemorrhagic Nd:YAG lesions.

Background: Gender-related differences in the symptom profile of patients with suspected sleep disordered breathing (SDB) may be one explanation of the clinical underrecognition of SDB in women., Study Objectives: The aim of this study was to prospectively assess gender-related differences in presenting symptoms in a clinical sample of patients with suspected sleep disordered breathing., Design: Administration of the Sleep Disorders Questionnaire prior to clinical and polysomnographic evaluation. Responses obtained from the questionnaire were used to construct 4 independent symptom scales: sleep apnea (SA), periodic limb movement syndrome (PLM), psychiatric sleep disorder (PSY), and narcolepsy (NAR). Analyses of variance were used to examine the effect of gender, AHI, and age on the symptom scales. Associations between gender and each diagnostic scale of the questionnaire were determined by multiple analyses of covariance., Setting: Tertiary pulmonary referral center., Participants: 2739 men and 782 women with suspected SDB. All patients who were referred to the sleep laboratory underwent full-night polysomnography, irrespective of the likelihood of SDB., Interventions: N/A., Measurements and Results: Overall, men scored significantly higher on items related to worsening of snoring/breathing with alcohol (P < 0.001) and smoking history (P < 0.01) than women. Complaints such as witnessed apneas (P < 0.001) and worsening of snoring in supine position (P < 0.05), however, were more frequently reported by men with an apnea-hypopnea index (AHI) < 5/hr, compared with AHI-matched women. There were no significant differences in these items in patients with an AHI > 15/hr. In contrast, women complained significantly more often of insomnia, restless legs, depression, nightmares, palpitations at night, and hallucinations than men. As a result, women had significantly higher scores on the PLM, PSY, and NAR scales of the Sleep Disorders Questionnaire (P < 0.001, for all). After adjustments for age, body mass index, AHI, arousal index, oxygen saturation data, and smoking history, by means of multiple analyses of covariances, gender differences remained significant (P < 0.001, for all scales)., Conclusions: We observed significant gender-related differences in presenting symptoms of patients with sleep disordered breathing at a tertiary level. These differences should be taken into consideration in clinical evaluation of women with suspected sleep disordered breathing.

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.

Background: There is no clear evidence whether inspiratory muscle strength (Pi(max)) is closely linked to inspiratory muscle endurance (T(lim)). Moreover, normal values of T(lim), measured by flow-resistive loads, have not been established., Objectives: We tried to find answers to the following questions: Is it possible to establish normative values of T(lim) when using flow-dependent, resistive loads? Are Pi(max) and Borg scale values predictors of T(lim)? Are anthropometric and spirometric data closely related to T(lim)? Is it really necessary to measure T(lim) in addition to Pi(max) when evaluating inspiratory muscle function?, Methods: Sixty-eight healthy Austrian volunteers between 17 and 75 years of age and with a sedentary lifestyle participated in our study. Pi(max) was defined as the maximal inspiratory mouth pressure, measured with a differential pressure transducer. T(lim) was determined as the time span until exhaustion, while breathing against a resistive loading device., Results: Pi(max) values showed a low intra- and high interindividual variability for both sexes and were significantly age, weight and height dependent. For male subjects, Pi(max) was also significantly related to spirometric parameters. T(lim) values showed a very high interindividual variability, but a low intraindividual variability. Interestingly, no correlation was found between T(lim) and Pi(max), nor lung function parameters and age., Conclusions: The results indicate that both Pi(max) and T(lim) have to be determined when inspiratory muscle function is measured. Normal values for T(lim), evaluated by flow-resistive loads, cannot be satisfactorily established due to the high interindividual variability.

Bilateral diaphragmatic paralysis (BDP) can occur in the course of motor neuron disease, myopathy, or from mechanical damage or the use of "ice slush" during cardiac surgery. BDP has been observed during and after infections, associated with systemic lupus erythematosus and mediastinal tumors, or may have idiopathic etiology. It is a serious and life-threatening condition. A 62-yr-old man presented with slowly progressive dyspnoea that worsened in the supine position and on bending forward. Chest X-rays, fluoroscopy, lung-function parameters and blood-gas analysis revealed respiratory failure. BDP was confirmed from a phrenic nerve stimulation test and measurement of transdiaphragmatic pressure (Pdi). Since there was no evidence of an obvious etiology, BDP was considered idiopathic. Other muscles were not involved. The pathological basis was probably focal demyelination in segments of the phrenic nerve. Because of increasing diaphragmatic muscle fatigue, the patient was treated with a nasal mask providing bi-level positive airway pressure (BiPAP) ventilation during the night. Clinical suspicion of BDP should always be raised in patients suffering slowly progressive dyspnoea without any obvious cardiac, metabolic or traumatic predisposing factors, and orthopnoea and dyspnoea on bending forward. Electromyographic tests and measurement of Pdi can reveal the correct diagnosis.

Purpose: To evaluate choroidal perfusion following creation of a laser-induced macular hole in a nonhuman primate model., Methods: Six rhesus monkeys underwent macular exposures delivered by a Q-switched Nd:YAG laser. The lesions were evaluated with fluorescein angiography and indocyanine green angiography using scanning laser ophthalmoscopy., Results: Each lesion produced vitreous hemorrhage and progressed to a full-thickness macular hole. Indocyanine green angiography revealed no perfusion of the choriocapillaris beneath the lesion centers. Fluorescein angiography demonstrated mild enlargement of the foveal avascular zone due to loss of perifoveal capillaries. Histopathologic evaluation showed replacement of the choriocapillaris with fibroblasts and connective tissue., Conclusions: Nd:YAG laser-induced macular holes result in long-term impairment of choroidal perfusion at the base of the hole due to choroidal scarring and obliteration of the choriocapillaris. Evaluation of choroidal perfusion may be useful in assessment of laser-injured patients. Impairment in choroidal perfusion may have functional implications for surviving photoreceptors.

During long-term viewing of a continuous light source, head and eye movements affect the distribution of energy deposited in the retina. Previous studies of eye movements during a fixation task provided data used for revising the safety limits for long-term viewing of such sources. These studies have been continued to determine the effect of source brightness on the nature of fixational eye movements. Volunteers fixated for 50 s on a HeNe laser (lambda = 632.8 nm) masked by a small aperture to produce a target subtending approximately 0.03 mrad in the visual field. The source was attenuated to yield corneal irradiance values in the range 0.6 pW cm(-2) to 6 microW cm(-2). Eye movements were recorded using a Dual Purkinje Image Eyetracker. The data were characterized by fixation ellipses that represent areas of the retina in which the image of the spot was located 68% of the time of each trial. Significant variation across subjects in the tightness of fixation was observed. Over the eight orders of magnitude of source brightness used in this experiment (10(-13) to 10(-6) W cm(-2)), no subject showed more than roughly a factor of two variation in the area of the fixation ellipse. No statistically significant trend in tightness of fixation as a function of source brightness was observed. There was no loss of ability to fixate, nor any drive to aversion, at the higher source intensities.

Tobacco smoking is the major cause of lung disease. This study aimed to determine: 1) the prevalence of tobacco smoking among office-based physicians; 2) their readiness to inquire about their patients' smoking habits and, if need be, to motivate them to stop smoking; 3) whether non-smoking doctors advise their patients more frequently to stop smoking than their smoker colleagues do. A self-designed questionnaire on a post card was sent to 7674 office-based general practitioners (GPs) and internists. 1395 (18.2%) questionnaires were returned. Independent telephone interviews with 91 doctors were also carried out to minimize the bias of self-presentation. Just under 11% of doctors were smokers. About 50% of all doctors who responded described themselves as ex-smokers. 38% of the smokers would accept outside help to stop smoking. About 50% of GPs and 90% of internists inquire about the smoking habits of their patients during history taking. Of these, 85% of GPs and 92% of internists recommend their patients to stop smoking. Doctors who themselves are smokers do so less than their non-smoker colleagues. For this reason, a further reduction in the smoking prevalence among doctors would be of special importance. Inquiry about smoking habits in the initial history taking should be stressed more to identify any smoker who can be subsequently encouraged to stop smoking.

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.

We studied the retinal effects of 1.25 GHz high peak power microwaves in Rhesus monkeys. Preexposure fundus photographs, retinal angiograms, and electroretinograms (ERG) were obtained to screen for normal ocular structure and function and, after exposure, as endpoints of the study. Histopathology of the retina was an additional endpoint. Seventeen monkeys were randomly assigned to receive sham exposure or pulsed microwave exposures. Microwaves were delivered anteriorly to the face at 0, 4.3, 8.4, or 20.2 W/kg spatially and temporally averaged retinal specific absorption rates (R-SAR). The pulse characteristics were 1.04 MW ( approximately 1.30 MW/kg temporal peak R-SAR), 5.59 micros pulse length at 0, 0.59, 1. 18, and 2.79 Hz pulse repetition rates. Exposure was 4 h per day and 3 days per week for 3 weeks, for a total of nine exposures. The preexposure and postexposure fundus pictures and angiograms were all within normal limits. The response of cone photoreceptors to light flash was enhanced in monkeys exposed at 8.4 or 20.2 W/kg R-SAR, but not in monkeys exposed at 4.3 W/kg R-SAR. Scotopic (rod) response, maximum (combined cone and rod) response, and Naka-Rushton R(max) and log K of scotopic b-waves were all within normal range. Retinal histopathology revealed the presence of enhanced glycogen storage in photoreceptors among sham (2/5), 8.4 W/kg (3/3), and 20.2 W/kg (2/5) exposed monkeys, while enhanced glycogen storage was not observed in the 4.3 W/kg (0/4) exposed group. Supranormal cone photoreceptor b-wave was R-SAR dependent and may be an early indicator of mild injury. However no evidence of degenerative changes and ERG depression was seen. We concluded that retinal injury is very unlikely at 4 W/kg. Functional changes that occur at higher R-SAR are probably reversible since we saw no evidence of histopathologic correlation with ERG changes. Bioelectromagnetics 21:439-454, 2000. Published 2000 Wiley-Liss, Inc.

The goal of this study was to show whether a correlation exists between the intensity of specific respiratory muscle training and the improvement of strength and endurance in inspiratory musculature in patients with neuromuscular disorders (NMD). Sixteen patients with NMD (13 with Duchenne muscular dystrophy and 3 with spinal muscular atrophy) performed inspiratory muscle training (IMT) at home with a special training apparatus for 9 months. Maximal inspiratory mouth pressure (PI(MAX)) and 12s-maximum voluntary ventilation (12s-MVV) test served as parameters for inspiratory muscle strength and endurance, respectively. In patients whose inspiratory vital capacity (VC(in)) declined by less than 10% during the year before training began (n = 10), a significant positive correlation was found between the number of successfully completed strength and endurance exercises and the improvement of PI(MAX) (P < 0.05) and 12s-MVV (P < 0.05). In patients whose VC(in)-decline exceeded 10% (n = 6), indicating more progressive respiratory system involvement of the disease, no significant correlation between the improvement of PI(MAX) and 12s-MVV and the intensity of training was found. In patients with NMD, the effects of IMT-runs are dose-dependent, provided that the respiratory system involvement of the disease is only slowly progressive., (Copyright 2000 John Wiley & Sons, Inc.)

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.

With the easy attainability of hand-held laser devices and the burgeoning light emitting diode (LED) technology, safety standards for long-term viewing of continuous light sources are being scrutinized. One concern is with quantifying the effect of head and eye movements on the distribution of energy over the retina. This experiment describes target motion over the retina as a result of head and eye movements during a deliberate fixation task. Volunteers deliberately fixated, with (fettered) and without (unfettered) head and chin rest support, on LEDs that subtended a 0.1 min of arc visual angle. A Dual Purkinje Image Eyetracker measured eye position during each 100-s fixation trial. The data showed an elliptical retinal energy distribution, oriented on the temporal/ nasal retinal axis, with a major axis 1.5 times greater than the minor. The average half-maximum diameter for the major axis was 40 microm for the fettered and 107 microm for the unfettered condition. The retinal area illuminated from head and eye movements showed a positive linear relationship with time. Peak retinal radiant exposure at 100 s was reduced by a factor of 10 as a result of eye movements and by a factor of 30 as a result of head and eye movements. Although the net result was a reduction in radiant exposure from a "no-movement" baseline, the distribution of energy over the retina was well within the 200 microm foveal boundary. The data suggest that the laser permissible exposure limits for long term viewing of a small continuous wave source include a factor that adjusts for this reduction in retinal radiant exposure with time.

Background: In recent studies, the efficacy of intermittent rest of the inspiratory muscles as an option of treating patients with severe chronic obstructive pulmonary disease (COPD) has become questionable., Objective: The aim of our study was to analyze the effects of feedback-controlled intermittent negative pressure ventilation (INPV) on stable, but severely hypercapnic COPD patients., Methods: 21 clinically stable, hypercapnic patients with severe COPD underwent INPV with chest shells for 3 weeks, 6 h a day. The INPV sessions were optimized by a visual biofeedback system, which enabled control over the decrease in diaphragmatic activity. Respiratory muscle (RM) function parameters, lung function parameters, blood gases and exercise capacity were analyzed., Results: In the end, 19 patients concluded INPV treatment. They had PaO(2) of 56.5 +/- 11.8 mm Hg, PaCO(2) of 50.2+/-2.7 mm Hg (mean +/- SD) and FEV(1) of 27.8 +/- 4.3% predicted before treatment. There was no statistically significant change in lung function parameters, RM function parameters, physical performance and level of dyspnea after 3 weeks of INPV., Conclusion: We conclude that intermittent RM rest induced by INPV can relax inspiratory muscles in most patients with stable severe COPD, but fails to improve RM function and exercise capacity., (Copyright 2000 S. Karger AG, Basel)

Recent investigation demonstrate that ocular motility in eyes with retinal pathology may show a lower propensity to visit such areas of the retina as compared to non-pathological retinal sites. While current ophthalmic instruments with the ability to image both the retina and visual function test target placement on the retina have provided this observation, the ability to quantify in real time these images as an eye movement measurement is presently lacking and the objective of this paper. A Rodenstock confocal scanning ophthalmoscope (CSLO) was used to image the retina during the performance of a visual fixation task. Direct observation of acuity target placement at the retina under continuous viewing conditions was possible with this apparatus. Target fixation eye movement images of the retina were rapidly digitized from video tape records and registered using a specialized rapid retinal image tracking algorithm. Fixational eye movement pattern densities at the retina were derived from these data. Preliminary data obtained demonstrate the utility of this technique in quantifying fixation eye movement patterns observed in three human patients with vocation-related laser retinal injury. In all patients, areas of severe retinal damage was generally avoided. The density of ocular eye movement tends to reflect regions of retinal normality and avoidance of retinal regions with severe pathology. Variation in eye movement density may exist where pathology is less severe.

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.

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.

Little is known about the effects of lung transplantation (LT) on the neural drive to the diaphragm and on the endurance of respiratory muscles in patients with severe chronic obstructive pulmonary disease (COPD). The aim of this study was to evaluate these effects of single-lung (SLT) and double-lung transplantation (DLT). The neural drive to the diaphragm was assessed during fatiguing inspiratory threshold loading manoeuvres in six SLT recipients, six DLT recipients and seven patients with severe COPD, by using diaphragmatic surface electromyograms. During threshold loading, the patients had to generate 80% of their maximal transdiaphragmatic pressure with each breath. The endurance of inspiratory muscles was defined as the time from the beginning of a resistive breathing trial until exhaustion (t lim). In DLT recipients and even in SLT recipients (on both sides), neural activation of the diaphragm was significantly lower than in COPD patients (p < 0.05). However, no statistically significant difference in t lim was seen between LT recipients and COPD patients. The data suggest that single-lung and double-lung transplantations cause a significant decrease of the neural drive to the diaphragm, while the endurance of inspiratory muscles is well-preserved in patients with advanced chronic obstructive pulmonary disease. This may contribute to reduced sensation of inspiratory effort during ventilatory stress, thus improving the quality of life.

The energy demand during physical exercise causes an increased oxygen uptake and supply to active tissues, which may increase the rate of free oxygen radical production and thereby affect the capacity of endogenous cellular defense systems. This could result in DNA base modifications, among which 8-hydroxydeoxyguanosine (8OHdG) is one of the most important and has widely been used as a biomarker of in vivo oxidative lesions. Therefore, we examined the effect of regular running exercise on the urinary levels of 8OHdG in 32 long-distance runners and in a group of untrained healthy subjects. The range of 8OHdG in urine was 0.12-6.45 mumol/mol creatinine in both groups, and no significant difference in the mean excretion levels between runners and control probands was observed. This gives no reason to believe that physical exercise in trained individuals may induce a disturbance of the oxidant-to-antioxidant balance.

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.

The sensitivity and specificity of Cyfra 21-1 as marker for lung cancer was evaluated in comparison with carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC) and neuron-specific enolase (NSE). Patients with histologically verified lung cancer and different groups without lung cancer were investigated. Sensitivity of Cyfra 21-1 (cut-off level 2.9 micrograms/l) was 40% for non-small cell lung cancer (NSCLC), 60% for rare histological types and 21% for small cell lung cancer (SCLC). In NSCLC sensitivity of Cyfra 21-1 was 35% for squamous cell carcinoma and 41% for adenomous carcinoma. The highest sensitivity for CEA was 45% in NSCLC, with 57% in the subtype of adenomous cell carcinoma; for SCC 30% was achieved in squamous cell carcinoma and for NSE 66% sensitivity was reached in SCLC. In our patients Cyfra 21-1 and CEA appeared equally useful for evaluating patients with NSCLC.

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.

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.

The impact of autonomic neuropathy (common in patients on haemodialysis) on ventilatory response to hypercapnia has been studied. We investigated cardiac reflex tests in 20 patients on chronic haemodialysis (8 patients were found with and 12 without neuropathy of the autonomic nervous system). Using the hyperoxic CO2-rebreathing method (according to Read), we tested the above-mentioned two groups of patients and compared them with 14 healthy control subjects. Accumulation of CO2 in blood with hyperoxic CO2 rebreathing stimulates central chemoreceptors, and therefore causes a progressive rise in minute ventilation. In patients with autonomic neuropathy (n = 8), ventilatory response to increasing pCO2 was significantly lower than that in the controls (1.7 +/- 0.3 versus 3.2 +/- 0.5 l/min/mmHg, P < 0.001). On the other hand ventilatory response in patients without autonomic damage (n = 12) showed no significant difference when compared to controls (3.1 +/- 0.8 l/min/mmHg). There were no differences in lung function, arterial blood gas analysis, blood chemistry, duration on dialysis, and demographic data when comparing the patients with and those without autonomic damage. Our analysis shows different patterns of ventilatory response to increasing pCO2 in patients on haemodialysis. Autonomic neuropathy has to be considered when rebreathing tests are interpreted. The clinical relevance of these findings needs further investigation.

Cycle ergometer training plays an important role in the rehabilitation of patients with chronic obstructive pulmonary disease (COPD), but the usefulness of specific inspiratory muscle training as part of pulmonary rehabilitation remains uncertain. To determine whether inspiratory muscle training could intensify the known beneficial effects of cycle ergometer training on exercise performance in these patients, we compared the effect of an 8 week inspiratory muscle training combined with cycle ergometer training with that of an 8 week cycle ergometer training alone on inspiratory muscle performance and general exercise capacity. Patients were randomly assigned to the two training groups; 21 patients received additional inspiratory muscle training (Group 1) and 21 did not (Group 2). Maximal sniff assessed oesophageal and transdiaphragmatic pressures served as parameters for global inspiratory muscle strength and diaphragmatic strength, respectively. The duration for which the patient could breathe against a constant inspiratory pressure load was used as an index of inspiratory muscle endurance. Exercise capacity was determined by an incremental symptom-limited cycle ergometer test. After the training period, inspiratory muscle performance improved significantly in the patients with inspiratory muscle training, but not in those without. Both training regimens increased maximal power output and oxygen uptake, but this improvement was significantly greater in the patients with inspiratory muscle training than in those without.(ABSTRACT TRUNCATED AT 250 WORDS)

The aim of our study was to evaluate the effect of aminophylline on the contractile function of the human diaphragm during varying muscle fiber length. Ten healthy subjects were studied during maximal sniff maneuvers and bilateral phrenic nerve twitch stimulations, with and without intravenous infusion of aminophylline in a randomized fashion. The transdiaphragmatic pressures generated at various baseline lung volumes, from residual volume to 90% of total lung capacity, were recorded before and after the induction of diaphragm exhaustion. At all levels of lung volume, aminophylline did not have an effect on the contractility of the fresh diaphragm. In the exhausted diaphragm, however, the pressure values, induced by sniffs and twitch stimulations, were significantly improved by aminophylline. This positive effect on diaphragm contractility was also impressive at 60, 75, and 90% of total lung capacity. This indicates that aminophylline significantly improves the contractile function of the exhausted human diaphragm, even if the muscle fibers are shorter than optimal. This effect occurs regardless of the neuronal firing rate, whether it is low (twitch stimulation) or high (sniff maneuver).

Background: To date there are no data on the effects of lung transplantation on diaphragmatic function in patients with end stage chronic obstructive pulmonary disease (COPD). It is not known whether the relation between the transdiaphragmatic pressure (PDI) and lung volume is altered in recipients after transplantation as a result of changes in diaphragmatic structure caused by chronic hyperinflation. The effect of lung transplantation on diaphragmatic strength was determined in patients with COPD and the relation between postoperative PDI and lung volume analysed., Methods: Diaphragmatic strength was assessed in eight double lung transplant recipients, six single lung transplant recipients, and in 14 patients with COPD whose lung function was similar to those of the transplant recipients preoperatively. PDI obtained during unilateral and bilateral phrenic nerve stimulation at 1 Hz (twitch PDI) at functional residual capacity (FRC) and during maximal sniff manoeuvres (sniff PDI) at various levels of inspiratory vital capacity (VCin) served as parameters for diaphragmatic strength. Sniff PDI assessed at the various VCin levels were used to analyse the PDI/lung volume relation., Results: Lung transplantation caused a reduction in lung volume, especially in the double lung transplant recipients. As a consequence sniff PDI was higher in the double lung transplant recipients than in the patients with COPD at all levels of VCin analysed. However, sniff PDI values analysed at comparable intrathoracic gas volumes were not reduced in the patients with COPD when compared with those who underwent lung transplantation. Bilateral twitch PDI values were similar in the patients with COPD and in the lung transplant recipients. In the single lung transplant recipients unilateral twitch PDI values were similar on the transplanted and the non-transplanted side. The relation between PDI and lung volume was similar in the patients with COPD and in the lung transplant recipients., Conclusions: In patients with COPD lung transplantation leads to an increase the maximal sniff induced PDI values by placing the diaphragm in a more favourable position for pressure generation. Since patients with COPD and postoperative lung transplant recipients showed similar PDI/lung volume relations, this suggests that chronic pulmonary hyperinflation does not cause major functional alterations of the diaphragm.

The purpose of the present study was to investigate the factors that may contribute to the sensitization to flour in baker's apprentices, and to predict this type of sensitization with a stepwise logistic regression model. Of the total of 258 baker's apprentices, 54 (20.9%) exhibited specific IgE development against flour allergens (wheat, rye, and/or barley). Allergologic variables, such as the total IgE level and IgE specific to grass pollen, tree pollen, weed pollen, molds, and animal dander, were found to correlate strongly with the sensitization to flour. However, the correlation between the presence of other manifest allergies and the sensitization to flour was weak. The presence of shadowing of the paranasal sinuses on the radiograph (mucosal thickening, opacity, air/fluid levels, and/or polypous shadowing) correlated with flour sensitization as well as with the leukocyte and lymphocyte counts in peripheral blood. Of the lung function data, only total lung capacity (in percentage of the predicted values) weakly correlated with the sensitization to flour. We were able to predict flour sensitization with a sensitivity of 63%, a specificity of 90%, and an efficiency of 84% by using the parameters that allow for the presence or absence of IgE specific to grass pollen and tree pollen, the presence or absence of radiographic shadowing, and total lung capacity in percentage of the predicted values.

Using a stepwise logistic regression analysis, we investigated clinical data, allergologic findings, spirometric data, and the cellular and humoral immune system in order to gain new insights into the role these parameters play in bronchial hyperresponsiveness to methacholine in children and to create a model for the prediction thereof. Bronchial hyperresponsiveness, which was found in 124 of 462 children (26.8%), was observed to have been influenced by an increased level of eosinophils, the positivity of the skin prick test for any of the allergens tested, a decreased baseline forced expiratory volume in 1 second (FEV1) (percent predicted), a decreased maximum expiratory flow at 50% expiration as a percent of forced vital capacity, and a decreased level of kappa-chain-assembled immunoglobulins. Logit analysis disclosed that the influence of all other parameters on the occurrence of bronchial hyperresponsiveness was of no further statistical significance. The degree of bronchial hyperresponsiveness (provocative dose causing a 20% fall in FEV1) showed a statistically significant correlation with the eosinophil count (Spearman's r = -0.198) and FEV1 (percent predicted) (Spearman's r= 0.203). Our findings suggest that allergic sensitization and eosinophilic reaction in children are major factors in contributing to the occurrence of bronchial hyperresponsiveness to methacholine.

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.

The present study examined possible short-term effects of the heat stress during sauna bathing on gas exchange, especially in correlation with changes in cardiac output. The results obtained are as follows: (1) The heat stress of sauna bathing caused a slight but not significant increase in diffusion capacity (p = 0.239) and no change in other pulmonary function parameters. (2) Cardiac output and cardiac index increased slightly but not significantly (p = 0.2455 and p = 0.2719). We conclude that heat stress in sauna neither influences gas exchange nor does it cause a significant increase in cardiac output.

We investigated 8 patients undergoing continuous ambulatory peritoneal dialysis (CAPD) for diaphragmatic strength and the neuromechanical efficiency of the diaphragm while the abdomen was filled with dialysate and while it was empty. Maximum transdiaphragmatic pressure (Pdimax) served as parameter for diaphragmatic strength; diaphragmatic efficiency was assessed by simultaneously monitoring transdiaphragmatic pressure (Pdi) and diaphragmatic electromyogram (EMGdi) during room-air breathing and hyperoxic CO2-rebreathing. After instilling dialysate, Pdimax increased from 76.7 +/- 12.1 cmH2O to 92.2 +/- 16.3 cmH2O (P < 0.05). While the slopes of the regression lines relating minute ventilation (VE) to arterial CO2 tension, and the change in VE for a given change in Pdi during hypercapnic rebreathing were similar in both states, the slope of EMGdi vs Pdi was significantly steeper when the abdomen was filled (P < 0.05). The increase in Pdimax observed in the filled state may suggest an adaptive rightward shift in the diaphragm's force-length relationship in CAPD patients, although this mechanism is insufficient to prevent a reduction of neuromechanical efficiency of the diaphragm.

The diagnostic value of chest X-ray following the ILO standards was compared with bronchoalveolar lavage (BAL) and the histology of transbronchial forceps biopsy in 83 patients with collagen vascular diseases. BAL in the middle lobe was considered abnormal in case of increased cell count per milliliter and/or lymphocytosis and/or neutrophil granulocytosis and this was found in 32 out of 42 cases (76.2%) with, and in 33 of out 41 cases (80.5%) without abnormal radiological finding. Pathological changes in the histology were found in 14 out of 20 cases (70.0%) with and in 40 out of 63 cases (63.5%) without abnormal chest X-ray in the upper lobe from which the transbronchial forceps biopsy specimens were obtained. In histological specimens obtained from transbronchial forceps biopsy, only fibrosis correlated with abnormal radiological findings in this region. Other inflammatory processes defied prediction by chest X-ray. This suggests that, regardless of chest X-ray findings, BAL should be performed together with transbronchial forceps biopsy for the histological examination of patients with collagen vascular diseases in which interstitial lung involvement is suspected.

To investigate the activity of the endogenous opioid system in patients with insulin-dependent diabetes mellitus during ventilatory stress situations, we measured plasma beta-endorphin levels in six male and five female diabetic patients breathing against fatiguing inspiratory resistive loads. The patients had to generate with each inspiration an esophageal pressure (Pes) 80% of maximum until they were exhausted and could no longer develop target Pes. The loaded breathing run was repeated three times with a 1-min interval between each run. Duty cycle, tidal volume, and breathing frequency were constant in all tasks. For each run plasma beta-endorphin levels were measured, inspiratory effort sensation assessed using a modified Borg scale, and inspiratory muscle endurance evaluated by the length of time the task could be maintained (Tlim). A group of 11 sex-, age-, height-, and weight-matched healthy individuals served as control subjects. Tlim was significantly lower in the diabetic patients. Evaluating respiratory effort during the three test runs in control subjects at a time corresponding to the break point of loaded breathing in patients showed significantly lower Borg ratings in the control group than in the patient group. Baseline plasma beta-endorphin was significantly lower in the diabetic patients (10.6 +/- 2.1 versus 27.0 +/- 4.2 pg/ml, p < 0.01). Additionally, whereas resistive loaded breathing caused a further increase in plasma beta-endorphin concentration in the control group (p < 0.005), absolutely no increase was found in the diabetic patients. We conclude that the endogenous opioid system in insulin-dependent diabetic patients does not respond to stress caused by breathing against fatiguing inspiratory resistive loads.

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.

Rehabilitation programmes in chronic obstructive pulmonary disease (COPD) require exercise training above the anaerobic threshold. However, not all COPD patients develop metabolic acidosis during exercise. The hypothesis of this study was that non-exercise variables, characterizing the mechanical load on the inspiratory muscles during breathing at rest, can be used to reliably predict which patients with COPD are not able to develop metabolic acidosis during exercise. Thirty participants with COPD performed a symptom-limited cycle ergometer test. The oesophageal pressure/time index (PTIoes: the product of pressure magnitude and duration), the mean rate of pressure development during inspiration (Poes/TI), and the mean airway resistance (Raw)/maximal oesophageal pressure (Poesmax) ratio served as indices for the mechanical load on the inspiratory muscles. The oxygen uptake (VO2) at which plasma standard bicarbonate was seen to decrease from its baseline value was taken as the anaerboic threshold (AT). Mean Raw was significantly higher in those patients in whom the AT could not be detected. No other lung function parameters measured at rest allowed the accurate selection of those patients who did or did not develop exercise metabolic acidosis. On the other hand, Raw/Poesmax, PTIoes and Poes/TI were significantly different in the two patient groups. Additionally, whereas in the patient group with identifiable AT exercise hyperpnoea produced a non-linear increase of Poes/TI with respect to PTIoes above the AT, in the patient group without identifiable AT there was a linear relationship between Poes/TI and PTIoes throughout exercise. We conclude that the determination of inspiratory muscle load indices at rest may be useful in pulmonary rehabilitation programmes, for identifying those patients with COPD who do not develop exercise induced metabolic acidosis.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

The effect of opioids on inspiratory muscle function under high mechanical load is still unknown. Even less clear is the extent to which opioids influence the shift of the electromyographic power spectrum of the inspiratory muscles to lower frequencies during ventilatory stress. We studied seven healthy subjects breathing against high inspiratory threshold loads until exhaustion while keeping the minute ventilation constantly high. We compared runs with and without administration of 0.2 mg kg-1 of morphine sulphate intramuscularly; two subjects were given 30 mg morphine sulphate so that we could study the effect of higher opioid concentration. The endurance time (Tlim), the diaphragmatic electromyogram (EMG), the transdiaphragmatic pressures (Pdi) and the ventilatory effort sensation were analysed. Morphine did not have any effect on Tlim or on the effort sensation elicited by the inspiratory resistance in both concentrations. Analysing the spectral shifts of the diaphragmatic EMG, we did not find any significant difference in the decrease of the centroid frequency between drug and control runs. Furthermore, the activation pattern of the diaphragm and the intercostal muscles, evaluated from the percentage contribution of oesophageal and gastric pressures on the transdiaphragmatic pressure swings, did not change following the administration of morphine. Our study shows that morphine does not change the function of the inspiratory muscles during high-resistive breathing. Morphine does not affect the electromyographic power spectrum of the diaphragm during those resistive breathing runs, either. This points out that during stressful ventilatory situations, the shift of the electromyographic power spectrum is attributed to a peripheral (muscular) event consequent to muscle fatigue and not to the elaboration of endogenous opioids.