Search PubMed⌕ Search

Biomedical subjects

A Guz

Publications and source records attributed to A Guz.

At least 73 records · Page 4Linked to original sources

Changes in global cerebral blood flow in humans: effect on regional cerebral blood flow during a neural activation task.

1. The primary objective of this study was to examine in man, how induced changes in global cerebral blood flow (gCBF) affected a regional cerebral blood flow (rCBF) increase resulting from a neural activation task (opening of eyes). A secondary objective was to quantify how such induced changes in gCBF were distributed between representative regions of either predominantly grey matter or white matter. 2. Positron emission tomography with intravenous infusion of H2(15)O, was used to measure gCBF in six normal males. Concomitant measures of rCBF were obtained in three different regions of interest (ROI): a representative area of predominantly grey matter, a representative area of predominantly white matter and an area of visual cortex. 3. Cerebral blood flow was altered by establishing steady-state changes in PCO2 at a near constant ventilation of approximately 30 l min-1. The mean PET,CO2 (+/- S.D.) levels (mmHg) that resulted were: low, 21.8 +/- 1.8; normal, 39.8 +/- 1.0, and high, 54.8 +/- 1.2. The normal and high levels were obtained by adding appropriate amounts of CO2 to the inspirate. The corresponding mean gCBF levels across all six subjects with eyes closed were: low, 24.2 +/- 4.6; normal, 37.2 +/- 3.9 and high, 66.8 +/- 7.6 ml min-1 dl-1. 4. Blood flow in grey matter (insular cortex) and white matter (centrum semiovale) at normal levels of PCO2 averaged 56.8 +/- 10.1 and 20.3 +/- 3.4 ml min dl-1 respectively. As PCO2 rose, the increase in rCBF to grey matter was approximately three times greater than that to white matter. 5. An activation state of eyes open in a brightly lit room was compared to a baseline state of eyes closed in a darkened room at the three levels of PCO2 (and hence at three levels of gCBF). Over the whole gCBF range a significant (P = 0.028) effect of increasing rCBF in the visual cortex ROI was found in response to opening the eyes; the effect of this activation on rCBF was not significantly dependent (P = 0.34) on the PCO2 (and hence gCBF) level. The effect of the activation on the rCBF was apparently 'additive' to the rise of rCBF associated with PCO2-related gCBF increase. 6. The results confirm the need to normalize for changes in gCBF during studies of rCBF in response to an activation protocol. They also provide support for the use of an 'additive' model to achieve such normalization provided that other cortical areas behave in a similar manner to that of the visual cortex.

Adult↗

Effect of positive and negative step changes in intrathoracic pressure on left ventricular function in conscious man.

1. Breathing affects left ventricular stroke volume (LVSV) in normal subjects. The observed relationship may result from interaction between the effects of changing lung volume and intrathoracic pressure (IP). 2. To investigate the effect of IP on LVSV with minimal changes in lung volume, beat-by-beat LVSV (pulsed Doppler ultrasound) and systemic blood pressure (Finapres) were measured during obstructed inspiratory and expiratory efforts causing step changes in IP of +/- 15 cmH2O for 10 s, in seven subjects. Changes in mouth pressure (MP) during airway occlusion were used to indicate changes in IP. Group-averaged data for each second were compared to that in the second before the change in MP using Dunnet's multiple range test. 3. Step reductions in MP resulted in immediate and significant falls in LVSV (P < 0.05) and systolic blood pressure (P < 0.01) and increased heart rate, although this was not significant. These responses were transient, lasting only 3 s despite 10 s of reduced MP. 4. Step increases in MP caused biphasic cardiovascular responses. LVSV increased immediately, then fell significantly below control after 8 s (P < 0.01). Heart rate increased significantly between 5 and 9 s after the onset of the increase in MP (P < 0.05), suggesting activation of the baroreflexes by the accompanying progressive fall in systolic blood pressure. 5. The asymmetry in time course and magnitude between the responses to positive and negative pressure may reflect asymmetrical effects of MP on systemic venous return, right ventricular output, pulmonary venous return and left ventricular (LV) after-load, with the baroreceptors limiting changes in arterial pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Obliterative bronchiolitis with atypical features: CT scan and necropsy findings.

We describe the natural history of cryptogenic bronchiolitis obliterans in a patient followed for 24 yrs with serial pulmonary function tests and radiology. Severe, progressive airway obstruction developed, with overinflation but preservation of KCO. There was progressive hypoxaemia, which worsened on exertion; hypercapnoea was modest until late in the illness. Neither bronchodilators nor steroids were effective. The chest radiograph remained normal; CT showed irregular areas of low attenuation peripherally throughout the lungs, with Hounsfield numbers typical of emphysema, but no bullae. Postmortem studies included histology and quantitative studies of a corrosion cast of one lung. They showed marked airway narrowing at all levels, with pruning of peripheral branches, mucus plugging, and some emphysema. The case illustrates that cryptogenic bronchiolitis obliterans may be chronic and difficult to distinguish clinically or by investigation from other forms of chronic obstructive airways disease, particularly emphysema.

Adult↗

Personnalité ventilatoire--an overview.

An infinite number of possible combinations of tidal volume and breathing frequency, as well as pattern of airflow, can achieve the alveolar ventilation required for normal gas exchange. Individuals appear to select one particular pattern. This paper summarises our work relating to differences in the pattern of breathing between individuals when at rest and discusses the possible determinants of such individuality.

Adult↗

Central command influences cardiorespiratory response to dynamic exercise in humans with unilateral weakness.

1. Changes in ventilation and cardiovascular variables which occur during exercise may be partly due to 'radiation' of activity in central neurones innervating exercising muscles to the respiratory and cardiovascular control areas. To test this hypothesis, we compared ventilatory and cardiovascular responses to two levels of steady-state exercise with each leg separately, in subjects with painless unilateral leg weakness. We assumed that exercise with a weak leg would require more central neural drive than the same level of exercise with the normal leg. 2. Ventilation during exercise with the weak leg was greater than with the normal leg (P less than 0.02). This was a result of greater tidal volume (Vt; P less than 0.005). There was a greater increase in heart rate (P less than 0.005), and systolic (P = 0.001) and diastolic (P less than 0.02) blood pressures during exercise with the weak leg compared to exercise with the normal leg. The increases in stroke volume and cardiac output during exercise were not different with the two legs. 3. These results support the hypothesis that ventilation, blood pressure and heart rate are influenced by the central neural drive to exercise.

Adult↗

Lipopolysaccharide, tumor necrosis factor, and interleukin-1 interact to cause hypotension.

Lipopolysaccharide (LPS) causes the syndrome of septic shock by initiating the release of endogenous mediators such as tumor necrosis factor (TNF) and interleukin-1 (IL-1) from macrophages. Hypotension is one of the important clinical features of septic shock; however, TNF is only hypotensive in high doses. Therefore we have investigated the interactions of low, nonhypotensive doses of LPS, IL-1, and TNF in the restrained unanesthetized rabbit. Combinations of nonhypotensive doses of TNF, IL-1, and LPS produced significant (p less than 0.05) decreases in blood pressure as compared with doses of each of the substances alone. TNF bioactivity in animals that were made hypotensive with combinations of TNF, IL-1, and LPS was lower than in animals that were made hypotensive with TNF alone. This suggests that TNF release that is stimulated by LPS is not the sole cause of the hypotension that is seen in this model of endotoxic shock. In this model, interactions of LPS, IL-1, and TNF occur and may explain hypotension during some episodes of sepsis.

Animals↗

Isolation and characterization of sheep alpha 1-proteinase inhibitor.

Sheep plasma proteinase inhibitor, analogous to human alpha 1-proteinase inhibitor (alpha 1 PI), was isolated to homogeneity. Purification was achieved by using (NH4)2SO4 precipitation, concanavalin A-Sepharose chromatography, Mono Q ion-exchange chromatography and PAGE. Sheep alpha 1 PI had an Mr of 56,000, inhibited human leucocyte elastase, pig pancreatic elastase and bovine trypsin on a 1:1 molar basis and had a plasma concentration of 1.6 +/- 0.21 g/l (mean +/- S.D.). Amino acid/carbohydrate composition (15% glycosylated) was similar to that of human alpha 1 PI (16% glycosylated); N-terminal analysis to 31 residues revealed 48-52% identity between the human and sheep proteins. Sheep alpha 1 PI was susceptible to oxidative inactivation by chloramine-T. Re-activation with the use of methionine sulphoxide peptide reductase and dithiothreitol indicated the presence of a methionine residue at the active site. These results establish that sheep alpha 1 PI has functional and structural characteristics close to those of human alpha 1 PI.

Amino Acid Sequence↗

Urinary desmosine, elastolysis, and lung disease.

Desmosine is an amino acid specific to elastin. Animal studies suggest that urinary desmosine (UD) represents endogenous elastin degradation. Therefore, UD has previously been used to investigate endogenous elastolysis, but was not elevated in subjects with chronic obstructive airways disease (COAD), although accelerated pulmonary elastolysis is thought to contribute to COAD. We have investigated whether this reflects large day-to-day and between-subject variation in UD and whether, in man, dietary desmosine contributes significantly to that in urine. Mean 24-hour UD output (over 5 consecutive days) from 10 asymptomatic subjects (5 males) was higher in males than females (77.4 +/- 9.6 and 40.2 +/- 5.0 nmol/24 hours, respectively; mean +/- SD, P less than .001), but not significantly different when expressed in terms of creatinine (micrograms desmosine/100 mg creatinine: males, 2.5 +/- 0.4; females, 3.1 +/- 0.8; mean +/- SD). The lowest between-subject variation was observed when the mean of 5 days' 24-hour UD values was analyzed on the basis of gender (coefficient of variation [CV], 12.5%); when gender was not considered, the least between-subject variation was found for the mean of 5 days' desmosine/creatinine analysis (CV, 24.5%). Approximately 1% of dietary desmosine (ingested as [3H]elastin and [3H] desmosine) was excreted in the urine within 24 hours, contributing approximately 15% of UD while on a normal diet. Although ingestion of a low elastin diet (less than 1/10 desmosine/24 hours than a normal diet) resulted in lower within-subject variation in 24-hour UD excretion (mean CV decreased from 31.5% to 20.2%), the between-subject CV and UD levels did not alter.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Volume detection during voluntary and passive breathing.

The ability to detect small changes in tidal volume (VT) during either volitional or passive breathing was compared in seven normal subjects. Passive breathing was achieved with positive pressure applied at the mouth by a ventilator. Although baseline breathing pattern was similar for each subject during the two types of breathing, the ability of the subjects to detect changes in VT was at least as good, and in general better, during passive as compared to volitional breathing. This suggests that the generation of a motor cortical command to inspire and the resultant respiratory muscle contraction are not essential to the perception of a change in lung volume. An increase in information from receptors in the mouth, pharynx and extrathoracic airways sensitive to positive pressure may be responsible for the increased ability of most subjects to detect changes in VT during passive breathing.

Adult↗

Some factors affecting the maintenance of upper airway patency in man.

This paper describes some of the anatomical and physiological factors affecting the maintenance of upper airway patency in man. Such factors have particular relevance to the mechanisms responsible for maintaining upper airway patency during sleep, and the failure of these mechanisms in patients with the clinical syndrome of obstructive sleep apnoea: a condition in which repeated episodes of sleep-related inspiratory oropharyngeal collapse lead to recurrent hypoxaemia, disturbed sleep patterns and other clinical sequelae. The relationships between upper airway geometry, negative intrapharyngeal pressure, activation of upper airway dilator muscles, and sleep state are important factors affecting the maintenance of upper airway patency. The aim of this paper is not to consider such factors in isolation but to consider their interaction in affecting the adequacy of the upper airspace as a conduit for airflow.

Humans↗

Hypothermia and infection in elderly patients admitted to hospital.

Twenty-five consecutive elderly patients with hypothermia were studied. Data were gathered regarding their home conditions, the circumstances in which they had been found, and their recent medical history. Clinical and laboratory examinations were performed to establish accurate diagnoses of underlying illnesses present at the time of arrival in hospital. Patients were followed up until the completion of the study. Evidence of an underlying cause was found in all cases. Twenty-two patients had evidence of definite or probable infection at the time of admission. Drugs may have contributed in seven cases. There were multiple significant causes for hypothermia in nine cases. Only 12 patients survived the index admission, and six of these had previous or subsequent admissions with hypothermia.

Age Factors↗

The increase in body temperature of elderly patients in the first twenty-four hours following admission to hospital.

In 76 unselected patients aged 70 years or over, the mean increase in rectal temperature in the 24 hours following admission to hospital was 0.4 degrees C. In those who did not receive antibiotics on admission, the mean increase in rectal temperature was 0.6 degrees C, with increases of up to 2.3 degrees C recorded. There were no significant changes in C-reactive protein, white cell count or erythrocyte sedimentation rate over that period, suggesting that the changes were due to passive warming rather than to progression of the underlying disease. Infected patients may have low or normal body temperatures on admission. Within 24 hours, nearly all infected patients (excluding a few with low or normal temperatures on admission, who receive antibiotics) have a raised body temperature. The most sensitive test for a raised body temperature is the rectal temperature measured at least 24 hours after admission. A patient who has a low or normal body temperature on admission has a 61% chance of having a raised body temperature the next day. At least 55% of patients admitted with a febrile illness have low or normal body temperatures on admission.

Aged↗

Normal rectal, auditory canal, sublingual and axillary temperatures in elderly afebrile patients in a warm environment.

Fifty hospital inpatients were selected, who, on the basis of their history and on clinical and laboratory findings, were believed not to have a febrile illness. Body temperature was measured simultaneously at four sites, in order to compile a normal range of temperature at each site for patients under these conditions. The observed range of rectal temperature was 36.7-37.5 degrees C, auditory canal temperature 36.4-37.2 degrees C, sublingual temperature 36.2-37.0 degrees C, and axillary temperature 35.5-37.0 degrees C.

Aged↗

The febrile response to mild infections in elderly hospital inpatients.

We studied 74 patients whose temperature was normal according to nurses' temperature charts and who were not on antibiotic treatment. The subjects were inpatients whose condition had deteriorated on the ward, or patients admitted the previous day in whom no diagnosis had been established. One simultaneous set of measurements was made of sublingual, rectal, axillary and proximal auditory canal temperatures. A fever was recorded in 63 of 74 patients (85%); 54 febrile patients had a raised rectal temperature, and 54 had a raised proximal auditory canal temperature; 60 patients were febrile at one or both of these sites. A further three patients had raised sublingual temperatures alone. All patients who were regarded as being definitely or probably infected were febrile at one or more sites. Eighty-one per cent of those considered to be possibly infected, and 71% of those with no clinical evidence of infection were also febrile. Rectal and proximal auditory canal temperatures can each detect fever in approximately 86% of febrile patients, sublingual temperature in 66%, and axillary temperature in 32%. Rectal temperature is clinically the most useful temperature measurement in elderly patients. We conclude that significant infections in patients in a warm environment result in a fever which often remains undetected when only sublingual temperature is measured.

Age Factors↗

Evidence for reflex upper airway dilator muscle activation by sudden negative airway pressure in man.

1. To determine if negative upper airway pressure causes reflex pharyngeal dilator muscle activation, we used intra-oral bipolar surface electrodes to record genioglossus electromyogram (EMG) activity in response to 500 ms duration pressure stimuli of 0, -2.5, -5, -15, -25 and -35 cm H2O (0-90% rise time less than 30 ms) in ten normal, conscious, supine subjects. 2. With the subjects relaxed at end-expiration, stimuli were applied in each of three conditions: (i) glottis open (GO), (ii) glottis closed (GC) and (iii) controls with the mouth and nose closed. 3. Six rectified and integrated EMG responses were bin averaged for each pressure in each experimental condition. Response latency was defined as the time when the EMG activity significantly increased above pre-stimulus levels. Response magnitude was quantified as the ratio of the EMG activity for 80 ms post-stimulus to 80 ms prestimulus; data from after the subject's voluntary reaction time (for tongue protrusion) were not analysed. 4. Negative airway pressure activated the genioglossus. The median latency of activation (34 ms) was much faster than the time for voluntary activation (184 ms) indicating a reflex response. 5. Significant activation, compared to 0 cmH2O controls and controls with mouth and nose closed, occurred with pressures of at least -5 cm H2O (GC) and -15 cm H2O (GO). At -25 and -35 cm H2O, responses with GO were significantly greater than with GC. 6. The magnitude ('strength') of the responses differed between subjects; these differences were repeatable. 7. We conclude that negative airway pressure causes reflex pharyngeal dilator muscle activation in man. Responses with GC suggest that upper airway receptors can mediate the response but larger responses with GO indicate a contribution from subglottal receptors.

Adult↗

Afferent pathway(s) for pharyngeal dilator reflex to negative pressure in man: a study using upper airway anaesthesia.

1. To determine the afferent pathways mediating pharyngeal dilator muscle activation in response to negative airway pressure in man, we recorded genioglossus electromyogram (EMG) activity (via intra-oral bipolar surface electrodes) in response to 500 ms duration pressure stimuli of -15 and -25 cm H2O in normal, conscious, supine subjects relaxed at end-expiration; responses were compared before and after upper airway anaesthesia. 2. Six rectified and integrated EMG responses were bin averaged for pressure stimuli applied with the glottis open (GO) and closed (GC) and to the outside of the face only (controls). Response magnitude was quantified as the ratio of the EMG activity for an 80 ms post-stimulus period (before the subject's reaction time for tongue protrusion) to an 80 ms pre-stimulus period. 3. In eight subjects, upper airway anaesthesia reduced the EMG responses with GC to a level indistinguishable from controls. After anaesthesia, responses with GO remained higher than those with GC. 4. With GC, the mean EMG responses decreased by 43% after selective anaesthesia of the nasal mucosa (trigeminal nerves) in two subjects, 32% after selective anaesthesia of the laryngeal mucosa (superior laryngeal nerves) in six subjects and by 21% after selective anaesthesia of the oropharyngeal mucosa (glossopharyngeal and lingual nerves) in four subjects. 5. We conclude that upper airway afferents mediate pharyngeal dilator muscle activation in response to negative pressure with GC and that subglottal receptors caused the increased activation with GO. With GC, the trigeminal and superior laryngeal nerves mediate an important component of the responses with the glossopharyngeal nerves playing a less important role.

Adult↗

The influence of induced hypocapnia and sleep on the endogenous respiratory rhythm in humans.

1. Ventilation has been studied during hypocapnia produced by passive mechanical ventilation in ten normal human subjects. 2. During wakefulness, disconnection of the ventilator led to inconsistent apnoea of only brief duration. During sleep, at a similar degree of hypocapnia, disconnection of the ventilator led more consistently to apnoea which was also of much longer duration; the deeper the sleep stage, the longer the apnoea. 3. The resumption of breathing during sleep could precede or follow arousal or be unaccompanied by arousal; in the absence of prior arousal, the evidence suggests that a starting end-tidal CO2 pressure (PET, CO2) less than 41 mmHg could result in an apnoea during sleep stages I and II. 4. Subjects did not report any common sensation which led them to breathe following an apnoea whilst awake. 5. Prior hyperoxia in one subject prolonged the apnoea duration in both slow-wave sleep and rapid eye movement sleep. 6. The results are interpreted as showing that even during light sleep, the maintenance of the respiratory rhythm is critically dependent on the arterial CO2 and O2 tensions. During wakefulness, other behavioural drives, which may not reach consciousness, supervene.

Adult↗