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Biomedical subjects

G Jennings

Publications and source records attributed to G Jennings.

At least 73 records · Page 4Linked to original sources
PubMed1994

Persistent, recurring diarrhea in a colony of orangutans (Pongo pygmaeus) caused by multiple strains of Campylobacter spp.

A colony of 10 orangutans (Pongo pygmaeus) experienced persistent, recurring diarrhea caused by multiple infections with Campylobacter jejuni and C. coli. Infections appeared to have occurred through several mechanisms, including fecal-oral transmission between orangutans, and possibly transmission by houseflies contaminated with the organisms from nearby chicken feces. Among the 14 fecal and environmental C. jejuni isolates, 4 different antibiotic susceptibility profiles were detected; there were also 4 different profiles among the 8 isolates of C. coli. In 5 orangutans, there were back-to-back infections by different strains of C. jejuni, suggesting that a single C. jejuni infection may not confer protective immunity against heterologous strains circulating in the same vicinity. Transmission was effectively interrupted by environmental modifications and a 7-day course of oral erythromycin.

Animals↗
PubMed1994

Evidence for impaired endothelium dependent vasodilation in experimental left ventricular dysfunction.

1. The full range of vascular reactivity was investigated in the hindlimb circulation of conscious, autonomically blocked rabbits with experimental (adriamycin-induced) cardiomyopathy. 2. Adriamycin treatment caused a significant reduction in left ventricular systolic function, as assessed by echocardiography (left ventricular fractional shortening, controls vs adriamycin treatment; 36.7 +/- 1.7% vs 27.3 +/- 2.6%, P < 0.05). 3. Under pharmacological autonomic effector block, the range of the vasodilator response (resistance range, from resting to full vasodilatation) to acetylcholine was reduced by 41% (P < 0.05) and by 37% for adenosine (P < 0.05). Despite these changes the sensitivity (ED50) of the responses were unaltered. 4. The ED50 of constrictor responses to noradrenaline and angiotensin II were similarly unaltered, in conjunction with a non-significant attenuation of the constrictor-response range. 5. These results suggest that in this model of experimental left ventricular dysfunction, the capacity of the hindlimb circulation to respond to regionally infused endothelium dependent vasodilators is attenuated.

Acetylcholine↗
PubMed1994

Oral challenge with Aeromonas in protein-malnourished mice.

The lack of an animal model for Aeromonas-associated diarrhoea has hindered progress toward understanding the pathogenesis of this potentially important enteric infection. Protein-malnourished mice were challenged orally with Aeromonas strains to determine if diminished levels of resistance would allow the induction of a diarrhoeal response. The 15 Aeromonas spp. faecal isolates used for challenge included 7 A. caviae, 4 A. hydrophila, 1 A. sobria bv. sobria, and 1 A. sobria bv. veronii from patients with diarrhoea, and 2 A. caviae from healthy volunteers. All had at least 1 known virulence marker, with the exception of 1 strain. Mice on the protein deficient diet had lost an average of 23% of their initial body weight at the time of challenge. Although mice consumed 10(8) cfu per day for a minimum of 4 days, none became ill due to Aeromonas spp. ingestion. Aeromonas spp. were isolated from 75% of faecal cultures obtained 7 days after initial challenge, indicating bowel colonization had occurred.

Aeromonas↗
PubMed1993

Change in serum hyaluronan: a simple index of short-term drug-induced changes in hepatic sinusoidal perfusion.

BACKGROUND: Hyaluronan is an endogenous polysaccharide whose clearance from the plasma is predominantly by liver sinusoidal cells and is sinusoidal flow dependent. This study was designed to determine if a change in serum hyaluronan might reliably reflect short-term drug-induced changes in sinusoidal perfusion. METHODS: Hemodynamic changes following an oral dose of ketanserin were compared with changes in serum hyaluronan levels in 12 patients with alcoholic liver disease and portal hypertension. Indices determined comprised heart rate, mean arterial pressure (MAP), cardiac output (CO), systemic vascular resistance, hepatic venous pressure gradient (HVPG), indocyanine green (ICG) clearance and extraction, and total hepatic blood flow. Measurements were made in a basal state 1 hour after ketanserin ingestion and expressed as a ratio of values post- to pre-ketanserin administration. RESULTS: Ketanserin had variable effects comprising both increases and decreases in all indices. On univariate and multivariate analysis, changes in serum hyaluronan concentration (1.05 +/- 0.13, mean +/- SD) significantly correlated with only one index: changes in ICG clearance (0.93 +/- 0.17, r = -0.65, P = 0.02). CONCLUSIONS: Changes in serum hyaluronan levels reflect short-term drug-induced changes in sinusoidal perfusion in patients with alcoholic liver disease and portal hypertension. Serial measurement of serum hyaluronan levels may offer a simple method of screening vasoactive drugs for their short-term effects on sinusoidal perfusion.

Aged↗
PubMed1993

Impaired reactivity of the peripheral vasculature to pressor agents in alcoholic cirrhosis.

BACKGROUND: Studies of the in vivo vascular reactivity of the peripheral circulation to pressor agents in cirrhosis have produced conflicting results, possibly because of changes in mean arterial pressure that make it difficult to clearly separate peripheral and central effects. The aim of the present study was to assess the reactivity of the forearm circulation to pressor agents in vivo without activating central control systems. METHODS: Forearm blood flow was measured by venous occlusion strain gauge plethysmography in the basal state and during the infusion of subpressor doses of norepinephrine and angiotensin II into the brachial artery in 10 male patients with well-compensated alcoholic cirrhosis and 10 male age-matched controls. Plasma renin activity and aldosterone and angiotensin II concentrations were assayed. Forearm and systemic sympathetic nervous system activity was estimated using a norepinephrine spillover technique. RESULTS: Basal forearm blood flow, renin angiotensin aldosterone system activity, and forearm sympathetic nervous system activity were similar in both the control and cirrhotic groups. The cirrhotic patients showed an impaired response to both norepinephrine and angiotensin II. CONCLUSIONS: There is impaired reactivity of the peripheral vasculature to pressor agents in cirrhosis, indicating that the control of vascular tone is disturbed even in well-compensated cirrhosis.

Adult↗
PubMed1993

Aortic distensibility and left ventricular structure and function in isolated systolic hypertension.

Aortic mechanical properties were assessed in a group of elderly subjects with untreated isolated systolic hypertension using two-dimensional echocardiography. Echocardiographic (two-dimensional and Doppler) assessment of left ventricular structure and function was also made. Ten subjects (mean age 71.7 +/- 1.9 years, 20% male, mean clinic blood pressure 163.6/79.2 +/- 1.2/2.0 mmHg) were compared with 16 normotensive subjects of similar age (69.4 +/- 1.6 years, 38% male, mean clinic blood pressure 129.8/78.2 +/- 3.2/2.9 mmHg). Aortic distensibility at the level of the transverse aortic arch was significantly reduced among subjects with isolated systolic hypertension. The thickness of the interventricular septum was approximately 20% greater in the hypertensive subjects (P < 0.01) and the average wall thickness to radius ratio was increased by 30%. Patterns of transmitral diastolic flow were also different in subjects with isolated systolic hypertension. Deceleration time was significantly greater (P < 0.01) and the ratio of early to late transmitral diastolic peak flow velocities was significantly less in the hypertensive (P < 0.05) than in the normotensive group. Left ventricular systolic function was well preserved. These findings are consistent with the suggestion that isolated systolic hypertension represents a state of increased aortic stiffness which may contribute to the development of left ventricular hypertrophy. Whether this increase in aortic stiffness is the cause or effect of the elevated systolic blood pressure remains unresolved.

Aged↗
PubMed1993

Cyclosporine therapy after cardiac transplantation causes hypertension and renal vasoconstriction without sympathetic activation.

BACKGROUND: Hypertension frequently complicates the use of cyclosporine A (CyA) therapy, and it has been suggested that sympathoexcitation may be the underlying mechanism in this form of hypertension. METHODS AND RESULTS: To further investigate the possibility of a neurogenic mechanism for this hypertensive effect, we studied the effects of CyA on renal blood flow (n = 11), forearm blood flow (n = 8), and sympathetic nervous system activity, assessed by renal and whole-body radiolabeled norepinephrine plasma kinetics and muscle sympathetic nerve firing (using microneurography) in cardiac transplant recipients receiving CyA and a reference group of healthy age-matched control subjects (n = 17). In 11 cardiac transplant patients (2 hours after cyclosporine dose), renal blood flow was significantly lower than that in 8 control subjects (680 +/- 88 vs 1285 +/- 58 mL/min, P < .001). In 5 of these transplant patients, renal blood flow was measured before and for 2 hours after oral cyclosporine and fell progressively over this period, by 37% (P < .01). Total body and renal norepinephrine spillover rates in transplant patients were similar to those in control subjects (3070 +/- 538 vs 2618 +/- 313 pmol/min and 579 +/- 124 vs 573 +/- 95 pmol/min, respectively), and there was no progressive effect in the 2 hours after cyclosporine dosing. Forearm blood flow was increased 2 hours after CyA administration (1.74 +/- 0.31 to 3.12 +/- 0.50 mL x 100 mL-1 x min-1, P < .001), whereas mean arterial blood pressure and noninvasively determined cardiac output (indirect Fick method) were unchanged. Muscle sympathetic nerve discharge rates recorded in 6 of these transplant patients were not different from those in 9 healthy control subjects (37.9 +/- 10.1 vs 41.3 +/- 2.3 bursts per 100 beats per minute). During 90 to 120 minutes of recording after cyclosporine dosing, nerve firing rates remained unchanged. CONCLUSIONS: CyA therapy causes acute renal vasoconstriction without accompanying systemic hemodynamic effects. These renal effects are nonneural, not being attributable to sympathoexcitation.

Cyclosporine↗
PubMed1993

Functional and neurochemical evidence for partial cardiac sympathetic reinnervation after cardiac transplantation in humans.

BACKGROUND: The presence of cardiac reinnervation in humans after cardiac transplantation has been widely debated, based on the application of differing methods for the assessment of neuronal function. Some of these techniques have been rather indirect; consequently, the time course and extent of cardiac reinnervation remains uncertain. METHODS AND RESULTS: To test for the presence of cardiac reinnervation after transplantation, we examined neurochemical (radiolabeled norepinephrine [NE] kinetics) and functional markers (power spectral analysis, heart rate response to exercise) of cardiac sympathetic nerve integrity in 15 cardiac transplantation recipients and 25 healthy control subjects of similar age. Cardiac transplantation subjects were studied 9 weeks to 8 years after cardiac transplantation (10 "early" patients < 18 months and 5 "late" patients > 2 years after cardiac transplantation). At rest, cardiac NE spillover was markedly attenuated early after transplantation (11.2 +/- 18.3 pmol/min) compared with subjects late after transplantation (105 +/- 11 pmol/min, P < .01) or in healthy control subjects (103 +/- 15 pmol/min, P < .01). Heart rate variability (measured by total spectral power) was significantly reduced in cardiac transplantation recipients compared with control subjects (59.4 +/- 30 vs 1673 +/- 516 milliseconds squared; P < .05), with evidence of a trend toward increasing spectral power late after transplantation. During exercise, the cardiac NE spillover was significantly lower in early cardiac transplantation recipients when compared with control subjects (163 +/- 50 vs 1876 +/- 418 pmol/min, P < .01). Late cardiac transplantation subjects showed a response intermediate (1080 +/- 254 pmol/min) between that of the early cardiac transplantation and control groups. However, measurements of the neuronal reuptake process for NE (assessed by the fractional extraction of plasma labeled NE across the heart and tritiated dihydroxyphenylglycol release) were significantly depressed in both early and late cardiac transplantation subjects. CONCLUSIONS: The present study demonstrates a partial restoration of cardiac sympathetic nerve function in humans up to 8 years after heart transplantation.

Blood Pressure↗
PubMed1993

A rapid membrane based immunobinding assay for the detection of dengue virus in tissue culture.

A rapid, simple dot immunoassay (DOTIA) was developed and evaluated for the detection of dengue-1 viral antigen in infected Aedes albopictus C6/36 cells. Dengue virus infected cells were solubilize in sodium dodecyl sulfate (SDS) and the lysate was pressure filtered through a hydrophobic polyvinylidene difluoride (PVDF) membrane. Viral antigen retained in the membrane was detected by a dengue-1 type specific monoclonal antibody and a peroxidase-labeled second antibody. Addition of tetramethylbenzidene (TMB) substrate produced a blue-colored precipitate which allowed for quantitation of viral antigen using a portable white light reflectance densitometer. Estimate of viral infectivity in the cell lysates tested by the DOTIA was determined by standard plaque assays and the results indicated an excellent correlation between these two methods. The dot immunoassay detected dengue viral antigen in infected C6/36 cells between days three and eight post-inoculation, depending on the titer of the inoculum. An infectivity titer of at least 10(3) plaque forming units (PFU) per ml was required to detect antigen by the DOTIA. The DOTIA also detected viral antigen in cells inoculated with twelve acute sera from known dengue-1 virus infected patients, thus demonstrating that this technique is useful for the detection and identification of dengue-1 virus from clinical specimens.

Aedes↗
PubMed1992

Increased sympathetic nervous activity and the effects of its inhibition with clonidine in alcoholic cirrhosis.

OBJECTIVE: To study disturbances in sympathetic nervous system function in patients with alcoholic cirrhosis and the effect of clonidine on such disturbances. DESIGN: Cross-sectional physiologic and neurochemical evaluation of patients with cirrhosis and of healthy controls; an uncontrolled trial of intravenous clonidine in the cirrhotic patients. PATIENTS: Forty-four hospitalized patients with biopsy-proven alcoholic cirrhosis and 31 healthy controls. INTERVENTIONS: Intravenous clonidine. MAIN OUTCOME MEASURES: Radiotracer-derived measures of norepinephrine release to plasma, central hemodynamics, wedge hepatic vein pressure, and measures of renal function. MAIN RESULTS: In patients with cirrhosis, clonidine reduced previously elevated norepinephrine overflow rates for the whole body, kidneys, and hepatomesenteric circulation. This sympathetic inhibition was accompanied by the following potentially clinically beneficial effects: the lowering of renal vascular resistance (median reduction, 24%; 95% CI, 14% to 31%), the elevation of glomerular filtration rate (median increase, 27%; CI, 14% to 39%), and the reduction of portal venous pressure (median reduction, 25%; CI, 18% to 32%). The norepinephrine and hemodynamic responses to graded clonidine dosing (1, 2, and 3 micrograms/kg body weight intravenously) indicated that the sympathetic outflow to the hepatomesenteric circulation was more sensitive to pharmacologic suppression with clonidine than was the sympathetic outflow to the systemic circulation. CONCLUSIONS: The sympathetic nerves to the kidneys, heart, and hepatomesenteric circulation are stimulated in patients with cirrhosis. Clonidine inhibits these activated sympathetic outflows differentially, which could possibly provide a basis for the selective pharmacologic treatment of portal hypertension in patients with cirrhosis.

Adult↗
PubMed1992

The acute-phase response to turpentine-induced abscesses in malnourished rats at different environmental temperatures.

An assessment was made of the independent effect environmental temperature (13, 21, and 30 degrees C) and either protein deficiency or energy deficiency on the metabolic response of rats that had aseptic abscesses induced by subcutaneous injections of turpentine. Measurements of food intake, alpha 2-macroglobulin (alpha 2-M; a major acute-phase protein in the rat), albumin, and various circulating metabolites were made 48 hours after turpentine injection in animals acclimatized at 13, 21, and 30 degrees C and compared with pair-fed controls. Despite differences in basal circulating albumin concentrations between controls and protein deficient rats (P less than .001), turpentine produced a similar reduction in all groups of animals (approximately 10 g/L), independent of environmental temperature. The alpha 2-M response to turpentine was attenuated in all protein-deficient animals and also in the energy-restricted animals at 13 degrees C. The increase in circulating 3-hydroxybutyrate (BOH) and nonesterified fatty acid (NEFA) concentrations, which normally occur with reduced dietary intake, was reduced in the turpentine-injected animals to an extent that depended on prior dietary intake. It is concluded that the metabolic response, particularly the acute-phase protein response, to a standard form of "injury" is affected by protein deficiency and possibly by energy restriction under adverse environmental temperature.

Abscess↗
PubMed1992

Effect of aseptic abscesses in protein-deficient rats on the relationship between interleukin-6 and the acute-phase protein, alpha 2-macroglobulin.

1. Rats established on a normal (20% protein) diet or a protein-deficient (3% protein) diet were given either a subcutaneous injection of turpentine (5 ml/kg), which induces formation of aseptic abscesses, or saline. Plasma samples were obtained at timed intervals (0-14 days) after the injection for determination of albumin, total protein, alpha 2-macroglobulin (a major acute-phase protein in the rat) and interleukin-6 concentrations. The magnitude and pattern of the acute-phase protein response was then compared with the local inflammatory reaction, assessed histologically, and with changes in the circulating concentration of interleukin-6, which is an important mediator of the acute-phase protein response. 2. After turpentine injection there was an early fall in the plasma albumin and total protein concentrations in both normal and protein-deficient rats. After 12 h the total protein concentration increased in both groups of animals reaching a peak at about 48 h, whereas the plasma albumin concentration continued to fall reaching a minimum at 48 h. The main alpha 2-macroglobulin response was delayed and attenuated in the protein-deficient rats (onset 9 versus 24 h, peak concentration 8.95 +/- 0.5 versus 5.33 +/- 0.75 g/l, P < 0.01, and area under the concentration-time curve 18.43 +/- 2.13 versus 7.96 +/- 1.48 g/l-1 days, P < 0.01, in the normal group and protein-deficient group, respectively). 3. The circulating interleukin-6 concentration showed a transient early rise at 1 h, and was followed by a larger more sustained peak at 6-48 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Abscess↗
PubMed1992

The magnitude of the acute phase protein response is attenuated by protein deficiency in rats.

We assessed the growth rate and changes in plasma albumin, total protein and alpha 2-macroglobulin concentrations (a major acute phase protein in rats) before and after a subcutaneous injection of turpentine (0.5 mg/kg body wt) in groups of rats receiving one of a series of protein-deficient diets (protein concentrations of 0.5, 1.5, 3.0, 4.5 or 6.0 g/100 g) or a diet containing an adequate level of protein (20 g/100 g) for maximal growth. Increasing protein deficiency in the different groups of animals reduced the basal albumin and total protein concentrations and attenuated the total protein and alpha 2-macroglobulin responses to turpentine. Increasing protein deficiency delayed the time taken for alpha 2-macroglobulin to reach peak concentrations post-injection and its return to basal concentrations. The turpentine-induced hypoalbuminemia was similar in all groups of animals (approximately 10 g/L depression) but restoration to values that were present before turpentine injection was increasingly delayed with increasing protein deficiency. The magnitude of the acute phase response (peak alpha 2-macroglobulin concentration) was found to be directly related to growth rate (r = 0.70, P less than 0.001). We concluded that protein deficiency can alter the pattern and magnitude of the acute phase responses in circulating protein concentrations to an extent that is dependent on the severity of protein deficiency.

Acute-Phase Proteins↗
PubMed1992

Arterial elastic properties in man: a comparison of echo-Doppler indices of aortic stiffness.

Non-invasive assessment of mechanical properties of the aorta may prove useful in the early detection of atheroma. We have evaluated several of the available echocardiographic indices using ability to detect age-related changes in putatively disease-free vessels as a measure of sensitivity to changes in aortic mechanical properties. Suprasternal imaging was used in 49 healthy non-smoking volunteers to measure minimum and maximum aortic arch diameters. Maximal flow velocities, with corresponding acceleration times and heart periods, were determined in the descending aorta in 24 of these subjects. Blood pressure was recorded non-invasively immediately after the echocardiographic study. Doppler derived measurements of aortic flow acceleration did not relate to age (P greater than 0.05). Three different 2D echo assessments of aortic distensibility, however, all showed a close relationship to age. Ep elastic modulus and Beta index (derived from different stress-strain mechanical relationships) were significantly related to age with r = 0.69 and 0.65 respectively. There were no significant effects of gender or left ventricular systolic function on these relationships. There was a tendency for the relationship between these distensibility indices and age more closely to fit an exponential than a linear relationship. We conclude that 2D echocardiographic assessment of aortic distensibility is able to detect sensitively changes in aortic mechanical properties. Even in the absence of risk factors for cardiovascular disease there is a marked reduction in aortic distensibility with increasing age.

Adult↗
PubMed1992

Increases in plasma beta-endorphin concentrations during exercise do not contribute to increases in heart rate following autonomic blockade in man.

1. Intrinsic heart rate (IHR: heart rate following autonomic blockade with atropine and propranolol) increases with exercise. The opioid antagonist naloxone has been shown to decrease IHR at rest, raising the possibility that increases in IHR with exercise are beta-endorphin related, since beta-endorphin concentrations have also been shown to rise during exercise. 2. We examined the effects of naloxone (10 mg) on IHR and plasma beta-endorphin levels during aerobic exercise in eight healthy, male subjects in a single blind, crossover study. 3. IHR increased with 25 min bicycling from 97.1 +/- 1.4 to 129.7 +/- 1.2 beats min-1 (mean +/- s.e. mean). This rise was not affected by administration of naloxone. 4. Plasma beta-endorphin concentration rose from 31.1 +/- 3.8 to 94.9 +/- 23.9 pg ml-1 after 25 min exercise. This exercise-induced rise in beta-endorphin concentration was further increased (P less than 0.05) in the presence of naloxone. 5. Our results confirm a rise in IHR and beta-endorphin concentrations with acute exercise but indicate that the changes in IHR are not endorphin-related.

Adolescent↗
PubMed1992

Simultaneous measurements of cardiac noradrenaline spillover and sympathetic outflow to skeletal muscle in humans.

1. Muscle sympathetic nerve activity (MSA) was recorded in the peroneal nerve at the knee by microneurography in ten healthy subjects and determinations were made simultaneously of intra-arterial blood pressure, and whole-body and cardiac noradrenaline spillover to plasma. Measurements were made at rest, during isometric handgrip at 30% of maximum power and during stress induced by forced mental arithmetic. 2. At rest there were significant positive correlations between spontaneous MSA (expressed as number of sympathetic bursts min-1) and both spillover of noradrenaline from the heart and concentration of noradrenaline in coronary sinus venous plasma. 3. Both isometric handgrip and mental arithmetic led to sustained increases of blood pressure, heart rate and MSA. Plasma concentrations of noradrenaline and spillover of noradrenaline (total body and cardiac) increased. In general the effects were more pronounced during handgrip than during stress. 4. When comparing effects during handgrip and stress the ratio between the fractional increases of MSA and cardiac noradrenaline spillover were significantly greater during handgrip. 5. The data suggest (a) that there are proportional interindividual differences in the strength of resting sympathetic activity to heart and skeletal muscle which are determined by a common mechanism and (b) that handgrip and mental stress are associated with differences in balance between sympathetic outflows to heart and skeletal muscle.

Adult↗
PubMed1992

Pressor responsiveness in corticosteroid-induced hypertension in humans.

In previous studies short-term cortisol increased cold pressor responses and the rise in forearm vascular resistance accompanying intra-arterial norepinephrine without an increase in overall resting sympathetic nervous activity. The present study examined whether these alterations in pressor response are glucocorticoid or mineralocorticoid effects, or both. Normal male subjects (n = 12) received either fludrocortisone, 0.3 mg daily (n = 6), or dexamethasone, 3 mg daily (n = 6), for 7 days. Hemodynamic studies were performed before and on day 7 of treatment. Fludrocortisone increased body weight from 69.3 +/- 1.8 to 71.1 +/- 2 kg (p less than 0.001), cardiac output from 5.0 to 6.0 l/min (+/- 0.1, p less than 0.01), mean arterial pressure from 82 +/- 1 to 91 +/- 1 mm Hg (p less than 0.001), cold pressor responsiveness from 13.0 to 39.0 mm Hg/ml per 100 ml per minute (R units) (+/- 4.3, p less than 0.01), and forearm vascular response to intra-arterial norepinephrine (F = 59.4, p less than 0.01) and angiotensin II (F = 30.8, p less than 0.01) infusions. Total peripheral resistance fell from 22.0 to 20.1 mm Hg/l per minute (+/- 0.3, p less than 0.05). Dexamethasone did not increase cardiac output, 5.1 to 5.2 l/min (+/- 0.1), or body weight but did increase mean arterial pressure from 82 +/- 3 to 91 +/- 3 mm Hg (p less than 0.001), cold pressor responsiveness from 8.6 to 17.1 R units (+/- 2.8, p less than 0.05), and forearm vascular response to intra-arterial norepinephrine (F = 33.0, p less than 0.01) and angiotensin II (F = 54.9, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗