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.

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.

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.

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.

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.

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.

Differential projections to the raphe nuclei from the medial parabrachial-Kölliker-Fuse (NPBM-KF) nuclear complex and the retrofacial nucleus in cats: retrograde WGA-HRP tracing.

After injection of wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP, 2 x 30 nl) [corrected] into the nucleus raphe magnus (NRM) of 6 cats, a number of retrogradely labelled neurons were observed in the rostral pons, mainly in the pontine pneumotaxic area, i.e., the medial parabrachial and Kölliker-Fuse (NPBM-KF) nuclear complex, and the tegmental field. In addition, a cluster of labelled cells was observed in the retrofacial nucleus (RFN) and its adjacent areas in the medulla. Control injections of the same volume of WGA-HRP into the medullary magnocellular tegmental field (2 mm lateral to the NRM) resulted in a much lower number of labelled neurons in the areas described above, and the labelled cells in the tegmental fields were predominant ipsilateral to the injected side. Injections into the nucleus raphe pallidus caudal to the NRM resulted in a diffuse distribution of labelled neurons, mainly in the tegmental fields of the pons and medulla. This study demonstrates that the NRM receives specific convergent projections from the NPBM-KF complex and the RFN in the medulla. It is suggested that these pathways are involved in the control of respiration.

Effect of air flow and flow transducer on tracheal breath sounds.

Tracheal breath sounds (TBSs) were analysed in 12 normal adult subjects at the air flow levels of 1.6, 2.1 and 2.6 litres-1, using a low-resistance flow transducer, and at an estimated flow of 2.1 litres-1 without the flow transducer. The major findings were that the TBSs were significantly distorted by the flow transducer, but were independent of air flow. We therefore conclude that true TBSs can only really be recorded when an oral flow transducer is not used. The within-subject reproducibility of TBS was relatively good, while the cross-subject comparison of TBS showed that each subject produced their own unique spectral pattern, although the TBSs of normal subjects fall in a common frequency range. Also, inspiratory sounds were significantly lower in peak frequency than expiratory TBSs.

Kinetics of cardiorespiratory response to dynamic and rhythmic-static exercise in men.

Kinetics of cardiorespiratory response to dynamic (DE) and then to rhythmic-static exercise (RSE) was compared in nine male subjects exercising in an upright position on a cycle ergometer at an intensity of about 50% VO2max and a mean pedalling frequency of 60 rpm over 5 min. Respiratory frequency (fR), tidal volume (VT), minute ventilation (VE), heart rate (fc), stroke volume (SV), and cardiac output (Qt) were measured continuously. The RSE caused a greater increase in fR than DE, whereas VT increased more during DE. The effect of reciprocal changes in fR and VT was that VE and its kinetics, expressed as a time constant (tau), did not differ between experimental situations. The ventilatory equivalent for O2 (VE: VO2) was greater for RSE (31.3) than for DE (23.0, P less than 0.01). Elevation of fc was similar for both types of exercise. The SV increased suddenly at the beginning of DE from 54 ml to 74 ml and then decreased to the end of exercise. At the onset of RSE only a moderate increase in SV was observed, from 56 ml to 62 ml, and then SV remained stable. The DE caused a greater and faster increase in Qt (4.20 l.min-1, for tau equal to 16.1 s) than RSE (3.25 l.min-1, for tau equal to 57.0 s, P less than 0.05 and P less than 0.002, respectively). Total peripheral resistance was almost 40% greater for RSE than for DE. No relationship was found between Qt and VE at the first 15 s of both types of exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Modeling of alveolar carbon dioxide oscillations with or without exercise.

In five persons the transient ventilatory response was measured to three step levels of exercise, inhaled constant fraction of CO2, and inhaled constant flux of CO2. With constant CO2 fraction inhalation (3, 5, and 7%), the transient response of the minute-ventilation (VE) is associated with on- and off-time delays (Td). Our Td periods include equipment delay, and our bolus inhalations by constant flux provoke on- and off-Td's of 6-8 s, which approximate to the transport delay of blood passing from the alveoli to the peripheral chemosensitive areas. With exercise (30, 50, and 70 W) we found a fast rise in VE (i.e., mainly in respiratory frequency) within the first breath, but no detectable on- and off-Td. The ventilatory responses to exercise are equal to those of constant CO2 flux inhalation. We modeled PACO2 oscillations, which occur through a respiratory cycle, and show that the oscillations provoked by constant CO2 flux have modified timing, amplitude, and slope compared with those of constant CO2 fraction. The increase in ventilation is the same when the CO2 is achieved by constant flux inhalation at rest or by exercise.

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.

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.

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.

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.

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 response to absolute and relative work intensity in untrained men.

Twenty young, untrained men performed two tests on cycle ergometer in order to verify whether the kinetics of the cardiorespiratory reactions exhibit any relation to maximal oxygen uptake (VO2max) in the untrained state. On the 1st day, the subjects exercised at work intensities of 50 and 100 W, the increase as a step function, for periods of 10 min each. The next day, they performed exercise at a relative intensity of 50% VO2max for 10 min. Respiratory frequency, tidal volume, minute ventilation (VE), heart rate (HR), stroke volume (SV), and cardiac output (Q) were measured continuously. The SV was measured by impedance plethysmography. All the cardiorespiratory variables increased rapidly at the onset of both absolute and relative intensity of work, with a faster response for Q than for VE. The increase in absolute intensity of work from 50 to 100 W caused a significantly slower cardiorespiratory reaction than at the beginning of exercise. The SV increased by 20 ml during first 20 s of both absolute and relative intensities of work and then began to decrease after 6 and 4 min of the exercise, respectively. The decrease in SV was associated with an increase in HR and a stable value of Q. Acceleration at the beginning of, and deceleration during recovery from, the relative intensity of work for VE, HR, and Q were well correlated with individual levels of VO2max in the tested men. It is concluded that the kinetics of cardiorespiratory reaction to a constant, relative intensity of work is related to VO2max in untrained men, and that the kinetics probably constitute a physiological feature of an individual.