Performance of a rapid human metapneumovirus antigen test during an outbreak in a long-term care facility.

Using a newly developed rapid test, an outbreak of human metapneumovirus (HMPV) infection in a long-term care facility was detected within only 2 days after the onset of symptoms in a putative index case. The outbreak was almost under control within 8 days mainly by zoning patients, with the exception of two cases of HMPV that were diagnosed 16 and 17 days after the onset of the outbreak. According to an immunological diagnosis as well as the rapid test, it was eventually proven that 18 patients had HMPV infections. We suspected that even asymptomatic residents, who had not been completely separated from the facility population, were a source of infection. That suggested that all asymptomatic residents should be tested and that the separation of the infected patients should be absolute, if an outbreak of HMPV infection is suspected in such a facility.

Effect of clinical signs, endocrinopathies, timing of surgery, hyperlipidemia, and hyperbilirubinemia on outcome in dogs with gallbladder mucocele.

Gallbladder mucocele (GBM) is a common extra-hepatic biliary syndrome in dogs with death rates ranging from 7 to 45%. Therefore, the aim of this study was to identify the association of survival with variables that could be utilized to improve clinical decisions. A total of 1194 dogs with a gross and histopathological diagnosis of GBM were included from 41 veterinary referral hospitals in this retrospective study. Dogs with GBM that demonstrated abnormal clinical signs had significantly greater odds of death than subclinical dogs in a univariable analysis (OR, 4.2; 95% CI, 2.14-8.23; P<0.001). The multivariable model indicated that categorical variables including owner recognition of jaundice (OR, 2.12; 95% CI, 1.19-3.77; P=0.011), concurrent hyperadrenocorticism (OR 1.94; 95% CI, 1.08-3.47; P=0.026), and Pomeranian breed (OR, 2.46; 95% CI 1.10-5.50; P=0.029) were associated with increased odds of death, and vomiting was associated with decreased odds of death (OR, 0.48; 95% CI, 0.30-0.72; P=0.001). Continuous variables in the multivariable model, total serum/plasma bilirubin concentration (OR, 1.03; 95% CI, 1.01-1.04; P<0.001) and age (OR, 1.17; 95% CI, 1.08-1.26; P<0.001), were associated with increased odds of death. The clinical utility of total serum/plasma bilirubin concentration as a biomarker to predict death was poor with a sensitivity of 0.61 (95% CI, 0.54-0.69) and a specificity of 0.63 (95% CI, 0.59-0.66). This study identified several prognostic variables in dogs with GBM including total serum/plasma bilirubin concentration, age, clinical signs, concurrent hyperadrenocorticism, and the Pomeranian breed. The presence of hypothyroidism or diabetes mellitus did not impact outcome in this study.

Association between neuroleptic drug-induced extrapyramidal symptoms and dopamine D2-receptor polymorphisms in Japanese schizophrenic patients.

The aim of the present study is to examine the relationship between dopamine D2-receptor gene (DRD2) polymorphisms (Taq1A, Taq1B, -141C Ins/Del) and the risk of extrapyramidal adverse effects (EPS), assessed according to the Drug-Induced Extra-Pyramidal Symptoms Scale (DIEPSS), or the maintenance dose of antipsychotics in schizophrenic patients. The DIEPSS score was significantly higher in patients bearing the -141C Del allele than in those without it. Taq1A and Taq1B restriction fragment length polymorphisms (RFLPs) did not significantly affect the DIEPSS score. On the other hand, maintenance doses of neuroleptics and antiparkinsonian drugs were significantly higher in patients with the B1 allele of Taq1B RFLP than in those without it, while the Taq1A RFLP and -141C Ins/Del polymorphisms were not significantly related to the maintenance doses. In conclusion, the risk of EPS may be increased in patients with the -141C Del allele of the DRD2 gene. In these patients, antipsychotics should be administered with caution.

Degradation of [125I]iodoglucagon by normal rat plasma in radioimmunoassay mixture containing aprotinin and its prevention by p-chloromercuriphenyl sulfonate and leupeptin.

Degradation of [125I]iodoglucagon during RIA of glucagon would result in erroneously high values for immunoreactive glucagon (IRG). Normal rat plasma was found to have high activity for glucagon degradation that was not suppressed by the aprotinin and EDTA routinely added to the RIA system. About 30% of the added radioactive glucagon was degraded during RIA in assay mixture at pH 7.4 containing 0.2 ml normal rat plasma, and the IRG value was calculated to be 150-180 pg/ml plasma. The degradation was completely inhibited by addition of 2 mM p-chloromercuriphenyl sulfonate (PCMS) plus 0.25 mM leupeptin as protease inhibitors, and in their presence the IRG value was about 80 pg/ml. The glucagon-degrading activity was about half as much in assay mixture at pH 8.8 as in that at pH 7.4, but the degradation still affected the accuracy of IRG values. When rat plasma was incubated with [125I]iodoglucagon in the assay conditions used for RIA and then subjected to Bio-Gel P-6 filtration, three new peaks of radioactivity were found in low mol wt fractions, with decrease in the peak corresponding to [125I]iodoglucagon, whereas on similar treatment in the presence of PCMS and leupeptin all the radioactivity was recovered in the glucagon fraction. The average recoveries of authentic glucagon as IRG in the absence and presence of the inhibitors were less than 60% and more than 90%, respectively. These findings indicate that determination of plasma IRG in rats by RIA with assay mixture containing aprotinin gives spuriously high values owing to degradation of the radiotracer, and that PCMS and leupeptin should be added to the sample and assay mixture to prevent this degradation.

Excitatory connections between upper cervical inspiratory neurons and phrenic motoneurons in cats.

This study aimed to determine whether upper cervical inspiratory neurons (UCINs), which are localized in the intermediolateral part of the gray matter of the upper cervical segments, have propriospinal connections to phrenic motoneurons of the ipsilateral lower cervical segment in anesthetized cats. Unit action potentials of UCINs were extracellularly recorded simultaneously with ipsilateral phrenic nerve activity. To eliminate the descending influences from medullary respiratory neurons to phrenic motoneurons, bulbospinal conduction paths were temporarily blocked by focal cooling applied to the ventral caudal medulla at the pyramidal decussation level by means of a cooling thermode (1 mm tip diam). By using a spike-triggered method, during cooling phrenic nerve activities were evoked by UCIN spikes that were elicited by microinjection of L-glutamate for 20 of the 55 (36%) UCIN units examined. The onset latencies of these phrenic motoneuron responses ranged from 1.5 to 7.1 ms (mean 3.6 ms), depending on synaptic transmission delays. These results clearly demonstrate that UCINs have, at least in part, excitatory mono- and paucisynaptic connections with ipsilateral phrenic motoneurons.

Coupling between respiratory and stepping rhythms during locomotion in decerebrate cats.

To determine whether and how the strength of coupling between respiratory and stepping rhythms varies depending on locomotor patterns, correlation analysis was done of diaphragmatic and gastrocnemius muscle activities. In spontaneously breathing cats decerebrated at the precollicular-post-mammillary level, tonic electrical stimulation was delivered to the mesencephalic locomotor region to induce locomotion on a treadmill. Electromyograms were recorded from the left hemidiaphragm and the bilateral gastrocnemius muscles. Various locomotor patterns were elicited by changes in the belt speed of the treadmill and in the intensity of stimulation of the mesencephalic locomotor region. Cross-correlograms between diaphragmatic and gastrocnemius activities showed that coupling was absent or weak when the cats walked slowly. The strength of locomotor-respiratory coupling tended to increase as the mean stepping interval shortened. When the animals were galloping, the respiratory rhythm was entrained 1:1 with the stepping rhythm. This study showed that the strength of coupling between respiratory and stepping rhythms varied depending on the locomotor patterns elicited, especially on whether the animals were running.

Depression of diaphragmatic and external intercostal muscle activities elicited by stimulation of midpontine dorsal tegmentum in decerebrate cats.

This paper describes the inhibitory influences on external intercostal muscle activity and diaphragmatic activity, evoked by stimulation of the dorsal tegmental field (DTF) of the pons in decerebrate cats. Stimulation of the DTF along the midline decreased both the diaphragmatic and the external intercostal activities. However, the inhibitory influences on the above two kinds of respiratory muscle activities were different in nature. Diaphragmatic activity, once suppressed by stimulation, recovered in spite of the continuation of stimulation. In contrast, DTF stimulation depressed tonic discharges of external intercostal muscle, and the depressed or abolished tonic discharges did not resume even after termination of stimulation. Rhythmic external intercostal muscle activity, synchronized with diaphragmatic activity, was also suppressed by DTF stimulation and the suppressed rhythmic activity seemed difficult to recover during stimulation, compared with the recovery process of the diaphragmatic activity.

Parallel suppression of extensor muscle tone and respiration by stimulation of pontine dorsal tegmentum in decerebrate cat.

This paper describes the pontine brainstem area responsible for the suppression of postural muscle tone as well as of respiration in acute precollicular-postmammillary decerebrate (mesencephalic) cats. Stimulation of the dorsal part of the pontine tegmentum (DTF) along the midline (P4-P7, H-5 to H-6) decreased the bilateral tone of the hindlimb extensor muscles and the diaphragmatic activity. Tonic discharges of the extensor muscles were suppressed by DTF stimulation and the suppression of muscle activity continued for more than 5 min after termination of the stimulation. In contrast, the suppression of the diaphragmatic activity, which resulted in apnea in some of the animals tested, resumed in spite of the continuation of the stimulation. However, the rebound augmentation of the diaphragmatic activity appeared immediately after the termination of the stimulation. The existence of such a rebound phenomenon suggested that the suppressive effects on the diaphragmatic activity persisted during the entire period of the stimulation. The recovery of respiratory movements during the stimulation led us to suggest that the strong respiratory drives emerge to overcome the exerted DTF-elicited suppressive effects on respiration. In the paralyzed and vagotomized animal, the DTF-elicited suppressive effects on phrenic neural discharges were minimal when the end-tidal pCO2 was set at a higher level than during spontaneous breathing.

Neuronal origin of parallel suppression of postural tone and respiration elicited by stimulation of midpontine dorsal tegmentum in the decerebrate cat.

This paper describes the possibility that rostal pontine neuronal structures cause the parallel suppression of postural tone and respiration evoked by stimulation of the dorsal tegmental field (DTF) of the pons in decerebrate cats. Stimulation of the DTF along the midline decreased both diaphragmatic activity and the bilateral tone of the hind-limb extensor muscles. Pontine neuronal structures located rostrally to the DTF, from which antidromically activated units could be recorded on stimulation of the DTF, were studied. Antidromic spikes were recorded in and near the nucleus reticularis pontis oralis. Tonic electrical stimulation of these sites caused parallel suppression of postural tone and respiration. These suppressive effects were almost similar to those elicited by the DTF stimulation.

Inhibitory influences on hypoglossal neural activity by stimulation of midpontine dorsal tegmentum in decerebrate cat.

In the spontaneously breathing decerebrate cat, the properties of the suppressive effects on hypoglossal nerve activity and on diaphragmatic activity elicited by stimulation of the midpontine dorsal tegmentum (DTF area) were analyzed. Stimulation simultaneously decreased the activities of the hypoglossal nerve as well as that of the diaphragm. However, the inhibitory influences on the above two kinds of activities were different in nature. Diaphragmatic activity, once suppressed by stimulation, recovered and gradually became greater in amplitude in spite of the continuation of stimulation. In contrast, DTF stimulation depressed tonic discharges of the hypoglossal nerve, and the decreased tonic nerve activity persisted after stimulation ended. Rhythmic hypoglossal activity, once suppressed by stimulation, reappeared during DTF stimulation. Such a rhythmic activity, however, vanished after the termination of stimulation, although the rhythmic diaphragmatic activity did not.

Coupling between respiratory and locomotor rhythms during fictive locomotion in decerebrate cats.

Fictive locomotion of the hindlimb was evoked by stimulation of the mesencephalic locomotor region (MLR) in immobilized, decerebrate cats. Fictive respiration can also be obtained in such a preparation after bilateral vagotomy. A cross-correlation technique was used to evaluate the strength of the coupling between the locomotor and respiratory rhythms. This study demonstrated that there was a locomotor-respiratory coupling of central origin and the strength of the coupling varied depending on the level of end-tidal pCO2, reflecting the arterial CO2 tension.

Effect of work rate on cardiorespiratory response to rhythmic-static exercise.

Influence of work rate (30 and 30 rpm) on exercise hyperpnoea, respiratory entrainment and cardiovascular system was studied in 9 healthy men performing rhythmic-static exercise (RSE). Respiratory frequency (f), tidal volume (VT), minute ventilation (VE), heart rate (HR), stroke volume (SV), and cardiac output (Q) were continuously measured. RSE was performed in upright position on a special motor-driven cycloergometer with an intensity of 40% VO2max for 5 min. The subjects opposed the flywheel movement by pressing the pedal alternately with left and right leg. It was found that in both work rates respiratory frequency followed the rhythm of exercise. The increases in f (28v35 breaths/min. p < 0.05) were associated with decreased VT (1.3v1.0L, p < 0.05) but they did not influence VE which was 33 and 36 1/min (NS). Accelerations of f and VE were faster for 30 than 60 rpm reaching respective values of 2.70v0.75 breaths/min/s (p < 0.05), and 0.59v0.31 1/min/s (p < 0.05). Cardiac response and its kinetics were found to be similar for both exercise rhythms. It is concluded that breathing entrainment does not affect either ventilation or the cardiac response during the RSE exercise. Since changes in acceleration of ventilation were not accompanied by appropriate changes in cardiac output acceleration the cardiodynamic hypothesis of exercise hyperpnoea does not seem to be valid for rhythmic-static exercise.

Effect of hypoxia and hyperoxia on cardiorespiratory responses during exercise in man.

To clarify the role of the carotid body in the mechanism governing exercise hyperpnea, the effect of hypoxia and hyperoxia on ventilation and cardiac output was studied in four healthy men. The VE increased 10.7% in hypoxia and decreased 10.1% in hyperoxia from normoxia as judged from the steady-state values during exercise. On the contrary, Q showed only a slight reduction of -3.2% in hyperoxia. The hypoxic hyperpnea and hyperoxic hypopnea led to a concomitant alteration in PETCO2. An overshoot following the onset of exercise was observed during the first 30s of VE response in hypoxia, which damped progressively in normoxia and hyperoxia. No remarkable difference was observed in the early transient responses of Q between hypoxia and hyperoxia. The discrepancy in the dynamics between VE and Q led to a phasic deviation in PETCO2; an isocapnic transition from the control to stimulus period in normoxia, hypocapnic in hypoxia and hypercapnic in hyperoxia. The time constant representing the kinetics of VE and that for VCO2 prolonged significantly in hyperoxia. These results support the cardiodynamic consequence of exercise hyperpnea, i.e., the carotid body is the first to respond to the increase in CO2 flow into the lungs.

Cardiorespiratory dynamics in men in response to passive work.

Dynamic characteristics of ventilation, cardiac output, and gas exchange in response to passive limb movements were studied in four healthy men in an upright position. Passive exercise was performed on a motor-driven bicycle ergometer, of which pedaling rate was varied from control (30 rpm) to stimulus (90 rpm) level in a stepwise fashion. Stroke volume (SV), heart rate (HR), and cardiac output (Q) were determined continuously during the exercise by using an automated impedance cardiograph. Minute ventilation (VE), respiratory frequency (f), tidal volume (VT), oxygen consumption (VO2), carbon dioxide output (VCO2), end-tidal pressure of oxygen and carbon dioxide (PETO2 and PETCO2), and the gas exchange ratio (R) were also determined at each breath. When the pedaling rate was increased, Q and VE rose in excess of metabolic need with a half response time of about 10 sec, and remained elevated for the duration of the stimulus. VO2 and VCO2 rose transiently, then recovered to the initial control level after a few min. PETCO2 remained at the control level for about one min, then decreased by 1 Torr. PETO2 and R rose transiently. These results suggest that hyperpnea during passive exercise is not induced by chemical stimuli to known chemoreceptors, but is due to reflexes mediated either by moving limbs or the right heart.

Neurogenic factors affecting ventilatory and circulatory responses to static and dynamic exercise in man.

The possible influence of neurogenic factors on respiratory and circulatory responses to continuous static (CSE), rhythmic static (RSE), and dynamic (DE) exercises was studied in 15 healthy young men. Ventilation (VE), oxygen uptake (VO2), cardiac output (Q), and blood pressure (BP) were measured during the steady-state of the exercise. For a given VO2, VE, and respiratory frequency (f) enhanced significantly with increasing frequency of RSE, and for the same frequency, the responses of these variables to RSE were significantly higher than those for DE. Although a similar trend was observed in heart rate (HR) and Q responses to exercises, it was not as strong as for ventilatory responses. These results lead to the conclusion that ventilation and circulation during exercise may be influenced by some neurogenic factors mediated either centrally or peripherally.

A new CO2 inhalation system for studying regulation of breathing.

This paper describes the development of a computer-controlled system that controls inspired CO2 or end-tidal PCO2 (PETCO2) to follow preprogrammed functions such as step, sinusoid, and pulse, under normoxic, hyperoxic, and hypoxic conditions. The system uses a proportional-integral (PI) controller that was optimized by adjusting the PI parameters so as to minimize the integral-time of absolute error (ITAE) performance parameter.

Cardiorespiratory dynamics during sinusoidal and impulse exercise in man.

Dynamic characteristics of ventilation, cardiac output, and gas exchange during sinusoidally varying work rates for the periods from 1 to 12 min and impulse work rate with a duration of 10 sec were studied on five healthy men in an upright position. Changes in work rate were given by controlling externally the electromagnetic braking system of a bicycle ergometer. Stroke volume, heart rate, and cardiac output during exercise were determined continuously by using an automated impedance cardiograph. Breath by breath determination in minute ventilation, respiratory frequency, tidal volume, oxygen consumption, carbon dioxide output, end-tidal pressures of oxygen and carbon dioxide, and gas exchange ratio were conducted. From these and steady-state response data amplitude and phase relations between each variable and the input work loads were obtained utilizing the frequency analysis techniques. The response characteristics to sinusoidal stimuli were well represented by first-order models with time constants for VE, VCO2, VO2, and Q averaging 75, 67, 52, and 36 sec, respectively. The kinetics of HR closely resembled that of Q. There was a close link between both the dynamics of VE and VCO2. On the other hand, the responses to impulse stimuli were better described by second-order models in which fast and slow response components were connected in parallel. However, the contribution of the fast component to total response was small. Although this response may support in its form the neuro-humoral concept to explain exercise hyperpnea, a tight linkage was observed between VE and VCO2 responses to impulse stimuli. Thus, hyperpnea during the unsteady-state of exercise may be explained by the cardiodynamic hypothesis.

Optical recording of spontaneous respiratory neuron activity in the rat brain stem.

We report on the optical imaging of spontaneous respiratory neuron bursts in the ventrolateral medulla (VLM) of medullary slices or brain stem-spinal cord preparations. A medullary slice with a thickness of 1.0-1.4 mm or brain stem-spinal cord from 0- to 4-d-old rats was stained with fluorescent voltage-sensitive dye, RH795. Optical signals were recorded as a fluorescence change by using an optical recording apparatus with a 128 x 128 photodiode array and a maximum time resolution of 0.6 ms. Motoneuronal activity was simultaneously recorded at the hypoglossal nerve roots or fourth cervical ventral roots. Fluorescence changes corresponding to the spontaneous inspiratory burst activity were detected in the hypoglossal nucleus and VLM in slice preparations, and in a limited area extending rostrocaudally in the VLM of the brain stem-spinal cord preparation. These measurements did not require signal averaging by multiple trials. Results suggest that inspiratory neurons are localized in more compact form at the level of the nucleus ambiguous than at the more rostral VLM, and that peak activity during the inspiratory phase propagates from the caudal to the rostral VLM. In 60% of brain stem-spinal cord preparations, weak and scattered fluorescence changes preceding the inspiratory burst activity were detected more predominantly in the rostral part of the VLM. The present findings show the feasibility of optical recordings for the in vitro analysis of spontaneous respiratory neuron activity in the medulla.

Distinguishing normal and abnormal tracheal breathing sounds by principal component analysis.

Expired and inspired tracheal breathing sounds (BS) were recorded from 10 normal subjects and 8 patients with respiratory diseases, including bronchial asthma, sarcoidosis, fibrosing lung disease, chronic bronchitis, and radiation pneumonitis. Frequency spectra were generated using Fast Fourier Transform (FFT), and we observed considerable differences between BS spectra of normal subjects and patients. The frequency of peak amplitude and mean frequency of the BS spectra of patients were significantly higher than those of normal subjects. Spectral features were extracted by dividing each spectra into equal frequency bands--each feature being the mean amplitude of each FFT element within a frequency band. We used Principal Component Analysis to compare spectral feature sets and found a clear separation between normal and abnormal tracheal BS for 10, 20, and 40 features/spectra. We conclude that Principal Component Analysis of BS could become a new method of diagnosing respiratory disease in an automated fashion.

A constant flux of carbon dioxide injected into the airways mimics metabolic carbon dioxide in exercise.

This paper reports the expired minute-ventilation (VE) responses of 5 subjects to three step levels in a) work rate on a bicycle ergometer (30, 50, and 70 W), b) inhaled constant fraction (CF) of CO2 (3, 5, and 7%), and c) inhaled constant flux (CFlux) of CO2 (0.3, 0.4, and 0.5 l/min (STPD) injected in the inspired air-stream). Both exercise (isocapnic with regulated PETCO2) and CFlux provoke larger and similar steady-state responses in VE, than CF. Both the CF and CFlux responses are hypercapnic, but the CFlux responses show evidence of "hypercapnic regulation." VE and total CO2 input into the alveoli (i.e., VCO2 plus inhaled CO2) are excellently correlated in both the CF and the CFlux cases. However, the CFlux delivery provokes a far greater VE for a given total input of CO2 than CF, and the CFlux response resembles the VE/VCO2 plot of exercise. We conclude that CFlux inhalation of CO2 simulates the metabolic CO2 production rate of exercise, and thus the humoral aspects of exercise hyperpnea in the steady state.