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Biomedical subjects

D Tighe

Publications and source records attributed to D Tighe.

At least 19 recordsLinked to original sources
PubMed2005

CT-angiography for the detection of a lower gastrointestinal bleeding source.

The evaluation of lower gastrointestinal bleeding (LGIB) often involves the collaborative efforts of the gastroenterologist, radiologist, and surgeon. Efforts to localize the acute LGIB have traditionally involved colonoscopy, technetium-labeled red blood cell (RBC) scintigraphy, angiography, or a combination of these modalities. The sensitivity of each method of diagnosis is limited, with the most common cause of a negative study the spontaneous cessation of hemorrhage. Other technical factors include vasospasm, lack of adequate contrast volume or exposure time, a venous bleeding source, and a large surface bleeding area. We report the use of multidetector computed tomography (MDCT), or CT-angiography (CT-A), in the initial evaluation of LGIB, and speculate on the incorporation of this technique into a diagnostic algorithm to treat LGIB. MDCT may offer a very sensitive means to evaluate the source of acute LGIB, while avoiding some of the morbidity and intense resource use of contrast angiography, and may provide unique morphologic information regarding the type of pathology. Screening with the more rapid and available MDCT, followed by either directed therapeutic angiography or surgical management, may represent a reasonable algorithm for the early evaluation and management of acute LGIB in which an active bleeding source is strongly suspected.

Adult↗
PubMed2000

Pathophysiology of septic encephalopathy: a review.

OBJECTIVES: Encephalopathy is a common complication of sepsis. This review describes the different pathologic mechanisms that may be involved in its etiology. DATA SOURCES: The studies described here were derived from the database PubMed (http:¿¿www.nlm.nih.gov) and from references identified in the bibliographies of pertinent articles and books. The citations are largely confined to English language articles between 1966 and 1998. Older publications were used if they were of historical significance. STUDY SELECTION: All investigations in which any aspect of septic encephalopathy was reported were included. This selection encompasses clinical, animal, and in vitro cell culture work. DATA EXTRACTION: The literature cited was published in peer-reviewed clinical or basic science journals or in books. DATA SYNTHESIS: Contradictions between the results of published studies are discussed. CONCLUSIONS: The most immediate and serious complication of septic encephalopathy is impaired consciousness, for which the patient may require ventilation. The etiology of septic encephalopathy involves reduced cerebral blood flow and oxygen extraction by the brain, cerebral edema, and disruption of the blood-brain barrier that may arise from the action of inflammatory mediators on the cerebrovascular endothelium, abnormal neurotransmitter composition of the reticular activating system, impaired astrocyte function, and neuronal degeneration. Currently, there is no treatment.

Brain Diseases↗
PubMed1999

Faecal peritonitis causes oedema and neuronal injury in pig cerebral cortex.

Encephalopathy is a common complication of sepsis. However, little is known about the morphological changes that occur in the brain during sepsis. Faecal peritonitis was induced in pigs that were killed 8 h later and frontal cortex samples were taken immediately after death. The tissue was investigated using light and electron microscopy and compared with frontal cortex samples taken from sham-operated controls. Septic pigs had 49.5% more perimicrovessel oedema than sham pigs. However, the tight junctions between cerebral microvessel endothelial cells appeared morphologically intact in both septic and sham pigs. Sepsis also resulted in neuronal injury, disruption of astrocytic end-feet and swollen, rounded erythrocytes. These morphological changes may be sufficient to underlie the clinical features seen in septic encephalopathy.

Animals↗
PubMed1998

Porcine hepatic response to sepsis and its amplification by an adrenergic receptor alpha1 agonist and a beta2 antagonist.

1. We investigated the effect of adrenergic receptor stimulation or inhibition on the hepatic ultrastructural changes in a porcine faecal peritonitis model of multi-organ failure. We infused either the alpha1 adrenergic receptor agonist methoxamine or the beta2 adrenergic receptor antagonist ICI 118551 during 8 h of the study.2. Anaesthetized pigs (25-30 kg) were divided into four non-septic groups (control, non-septic, non-septic methoxamine and non-septic ICI 118551) and three septic groups (septic, septic methoxamine and septic ICI 118551).3. Changes in hepatic ultrastructure were measured by morphometric analysis. The septic group was significantly worse than all the non-septic groups. Septic methoxamine and septic ICI 118551 were significantly worse than the septic group.4. Septic methoxamine and septic ICI 118551 had a significantly increased perisinusoidal space; septic methoxamine had significant hepatocyte vacuolation.5. Hepatic ultrastructural changes were independent of hepatic blood flow.6. Septic methoxamine had significant myocardial depression.7. The alpha1 adrenergic receptor agonist methoxamine or the beta2 antagonist ICI 118551 both amplified the hepatic injury normally found during sepsis in our porcine model.8. These findings suggest that during sepsis a protective endogenous beta2 adrenergic receptor-mediated anti-inflammatory response is activated via cell membrane transduction to stimulate the trimeric G-protein complex Gs and activate the second cell messenger cAMP.9. In addition, it is likely that alpha1 adrenergic receptor agonists amplify the inflammatory response by stimulating the cell-surface receptor-linked trimeric G-protein complex to activate Gq and the second cell messenger phospholipase C.

Adrenergic alpha-Agonists↗
PubMed1996

Cell surface adrenergic receptor stimulation modifies the endothelial response to SIRS. Systemic Inflammatory Response Syndrome.

The complex pathway seen in patients with the systemic inflammatory response syndrome (SIRS) does not readily respond to mediator blockade. All such trials conducted in SIRS patients have shown no benefit in reducing mortality. We have shown experimentally that in sepsis, the administration of beta 2-adrenoceptor agonists reduces hepatic cellular injury, whereas administration of an alpha 1-adrenoceptor agonist increases hepatic cellular injury. Inflammatory mediators can cause a dose-related reversible change in target endothelial cells (ECs). There is a substantial body of literature describing the anti-inflammatory effects of beta 2-adrenoceptor agonists. They reduce both the increased permeability and the production of inflammatory mediators from ECs. Cellular transduction processes are involved when adrenergic receptor agonists modify either the anti-inflammatory or proinflammatory response to sepsis in ECs. Inflammatory mediators and alpha 1-adrenoceptor agonists stimulate their trimeric G protein-linked receptors to produce diacylglycerol (DAG) and increase the intracellular concentration of calcium. DAG is involved in the production of both inflammatory proteins and lipids. In addition, mitogen-activated protein kinase (MAPK) is activated which is also involved in the production of inflammatory proteins and lipids. beta 2-adrenoceptor agonists activate their trimeric G protein-linked receptors to produce the stimulatory G protein (Gs). Gs stimulates adenyl cyclase to form cyclic adenosine monophosphate (cAMP) and activate protein kinase A (PKA). PKA is involved in activating gene transcription agents to produce anti-inflammatory proteins such as interleukin-10. PKA also inhibits phospholipase C and MAPK. Although promising, the use of beta-adrenoceptor agonists or agonists that increase cellular cAMP to activate the cells' endogenous anti-inflammatory pathway requires further study.

Adrenergic beta-Agonists↗
PubMed1995

Comparison of proximal isovelocity surface area method with pressure half-time and planimetry in evaluation of mitral stenosis.

OBJECTIVES: This study sought to 1) compare the accuracy of the proximal isovelocity surface area (PISA) and Doppler pressure half-time methods and planimetry for echocardiographic estimation of mitral valve area; 2) evaluate the effect of atrial fibrillation on the accuracy of the PISA method; and 3) assess factors used to correct PISA area estimates for leaflet angulation. BACKGROUND: Despite recognized limitations of traditional echocardiographic methods for estimating mitral valve area, there has been no systematic comparison with the PISA method in a single cohort. METHODS: Area estimates were obtained in patients with mitral stenosis by the Gorlin hydraulic formula, PISA and pressure half-time method in 48 patients and by planimetry in 36. Two different factors were used to correct PISA estimates for leaflet angle (theta): 1) plane-angle factor (theta/180 [theta in degrees]); and 2) solid-angle factor [1-cos(theta/2)]. RESULTS: After exclusion of patients with significant mitral regurgitation, the correlation between Gorlin and PISA areas (0.88) was significantly greater (p < 0.04) than that between Gorlin and pressure half-time (0.78) or Gorlin and planimetry (0.72). The correlation between Gorlin and PISA area estimates was lower in atrial fibrillation than sinus rhythm (0.69 vs. 0.93), but the standard error of the estimate was only slightly greater (0.24 vs. 0.19 cm2). The average ratio of the solid- to the plane-angle correction factors was approximately equal to previously reported values of the orifice contraction coefficient for tapering stenosis. CONCLUSIONS: 1) The accuracy of PISA area estimates in mitral stenosis is at least comparable to those of planimetry and pressure half-time. 2) Reasonable accuracy of the PISA method is possible in irregular rhythms. 3) A simple leaflet angle correction factor, theta/180 (theta in degrees), yields the physical orifice area because it overestimates the vena contracta area by a factor approximately equal to the contraction coefficient for a tapering stenosis.

Adult↗
PubMed1995

Goal-directed therapy with dopexamine, dobutamine, and volume expansion: effects of systemic oxygen transport on hepatic ultrastructure in porcine sepsis.

OBJECTIVES: Can the hepatic structural deterioration that occurs during peritonitis be attenuated by increasing cardiac output and oxygen consumption (VO2)? Do the agents used to achieve these increases have any characteristic affects on these hepatic structural changes? DESIGN: Randomized, prospective, observational animal study. SETTING: Research laboratory of a university medical school. SUBJECTS: Twenty-five Middle White adolescent pigs, weighing 25 to 30 kg, divided into five groups. INTERVENTIONS: A thermodilution flotation catheter was advanced into the pulmonary artery. Additional catheters were inserted into the jugular, portal, and hepatic veins, and into the femoral artery. Ultrasound flow probes were placed around the portal vein and the hepatic artery. A metabolic cart was attached to the ventilator. Baseline measurements were made and cardiac output was increased by > 25% by administering either dobutamine (10 micrograms/min), dopexamine (10 micrograms/kg/min), or colloid. A control group had its cardiac output maintained at its baseline value. Peritonitis was induced in the four groups by contamination with cecal content and maintained for 6 hrs. Hepatic tissue was then removed for ultrastructural analysis and the animals were killed. MEASUREMENTS AND MAIN RESULTS: Before infection, cardiac output, VO2, and hepatic blood flow were increased in the three treatment groups. In the dobutamine and dopexamine groups, oxygen delivery increased, but decreased in the volume group. Mean arterial pressure increased in the dobutamine and dopexamine groups, but in the volume group, mean arterial pressure was maintained. Six hours after infection, cardiac output and VO2 had further increased in the dobutamine and volume groups, but both variables had decreased in the dopexamine group. After infection in the control group, cardiac output had decreased, although oxygen delivery and VO2 increased. There were no significant differences between hepatic hemodynamic or oxygen transport variables in any of the groups during the infection period. Hepatic ultrastructure was well maintained in the dopexamine group, while considerable deterioration was seen in the volume and control groups. In the dobutamine group, hepatic deterioration was greater than in the other three groups. CONCLUSIONS: Increasing cardiac output and VO2 before and during infection was only protective when dopexamine was administered. Dobutamine infusion was associated with greater hepatic deterioration than that effect seen in either the control or volume groups.

Adrenergic beta-Agonists↗
PubMed1993

Dopexamine hydrochloride maintains portal blood flow and attenuates hepatic ultrastructural changes in a porcine peritonitis model of multiple system organ failure.

Fifteen anesthetised pigs (25-30 kg) were divided into three equal groups, sham, dopexamine (D) (10 micrograms/kg/min), and placebo (P). Sepsis was induced by fecal peritonitis in the D and P groups and colloid was infused to try to maintain mean arterial blood pressure (MABP) at a constant value and the hemodynamics measured at baseline and hourly for 8 hr. There was an initial increase in MABP and systemic vascular resistance (SVR) in the P group but not the dopexamine (D) group. Cardiac output (CO) in the P group showed a small decline but increased in the D group. The portal blood flow (PVF) in the P group fell with MABP but increased in the D group as MABP fell. The sham group showed normal ultrastructure and cellular integrity. Occlusion of the hepatic sinusoids was similar in the D and P groups. There was a greater area of Kupffer cells and endothelial cells in the P group, suggesting a greater inflammatory reaction than was found in the D group. Ultrastructure and mitochondrial integrity was better maintained in the D group. Dopexamine hydrochloride infusion maintained CO, increased PVF, and attenuated hepatic ultrastructural changes compared to placebo in a porcine fecal peritonitis model of multisystem organ failure.

Animals↗
PubMed1992

A narrow range, medium molecular weight pentastarch reduces structural organ damage in a hyperdynamic porcine model of sepsis.

OBJECTIVE: to compare diafiltered 6% pentastarch (Pentafraction--PDP, MWn 120,000 and MWw 280,000) and native pentastarch (Pentaspan--PSP, MWn 63,000 and MWw 264,000 dalton) in a porcine model of faecal peritonitis. DESIGN: Randomised prospective study in 12 adolescent pigs. INTERVENTIONS: Prior to infection the study solution was infused to increase Qt by 25%. Thereafter adjustments in infusion rate were made (up to 1 l/h) in an attempt to maintain Qt at 25% above baseline values. MEASUREMENTS AND RESULTS: Animals were sacrificed at 8 h. Tissue was excised from the right lobe of liver and from the right lung and fixed for later electron microscopy and digital morphometric analysis. Patent sinusoidal lumen was significantly greater in group PDP compared to PSP (11.3% +/- 2.3% of liver tissue versus 4.8% +/- 1.1%, p < 0.05) and this was accounted for by a significantly lower proportion of sinusoidal lumen occluded with white cells (2.1% +/- 0.6% versus 6.6% +/- 1.9%, p < 0.05). Similarly, patent capillary represented a significantly higher proportion of lung tissue for group PDP versus PSP (26.2% +/- 1.9% versus 18.5% +/- 2.7%, p < 0.05). The arithmetic mean alveolar capillary barrier thickness was significantly greater in group PSP than in group PDP (4.3 +/- 0.3 microns versus 2.5 +/- 0.3 microns, p < 0.01). CONCLUSIONS: The molecular weight profile of Pentafraction was associated with less structural organ damage including less tissue oedema and less white cell occlusion.

Biopsy↗
PubMed1992

Validation of bedside measurements of absolute human renal blood flow by a continuous thermodilution technique.

BACKGROUND AND METHODS: There is a clinical need for a system that would allow rapid assessment of renal blood flow in patients with oliguric circulatory shock. A local, continuous thermodilution technique for the measurement of renal venous blood flow, using readily available equipment, was developed. To test the hypothesis that this system would allow measurement of renal blood flow in clinical situations, we compared simultaneous measurements made by the continuous thermodilution technique with measurements of: a) absolute flow measured by volumetric collection in an in vitro flow model; b) renal arterial blood flow measured by electromagnetic flow probe under changing hemodynamic conditions in nine pigs; and c) calculated renal blood flow derived from a clearance technique in 16 patients after cardiac catheterization. The technique utilizes a short-duration, constant infusion of room temperature normal saline into the renal vein via a retrograde thermodilution catheter, with measurement of flow at a thermistor 1 cm back from the tip of the catheter. RESULTS: The method measured absolute blood flow in an in vitro model, with a correlation coefficient of .99 over blood flows ranging from 55 to 885 mL/min (r2 = .98). There was a .92 correlation coefficient with renal arterial blood flow measured by electromagnetic flow probe in a pig model (r2 = .85), and a .8 correlation with simultaneous measurement of renal blood flow by corrected iodohippurate clearance in humans (r2 = .64). Compared with electromagnetic flow probe measurements, a single measurement by the thermodilution technique would be accurate to within 80 mL/min in 95% of cases. Variability between individual measurements, expressed as the mean of the coefficient of variance for each patient, was 5.5 +/- 3.7%. CONCLUSIONS: This technique is simple to use, requires only venous cannulation and injection of normal saline, and allows rapidly repeatable, immediately available measurements of renal blood flow in a wide range of clinical circumstances, including severe renal impairment or anuria.

Animals↗
PubMed1992

Congestive heart failure in the elderly.

Congestive heart failure is in large part a disease of patients with advancing age. As our population ages, the incidence and prevalence of this disorder will continue to rise. The etiology of CHF in the elderly is multifactorial and one must take into account normal changes associated with aging, the heterogeneity of the elderly population, and possible noncardiac as well as cardiac disorders. Therapy must be aimed at the primary pathophysiologic process affecting the heart. Despite a number of therapeutic advances with medical therapy, CHF usually signals a generally irreversible process with a high mortality, especially in those patients with advanced disease. Therefore preventive measures should assume a paramount role in this disorder. Modification of risk factors such as diabetes, smoking, obesity, sedentary life style, and hypercholesterolemia should be aggressively stressed and pursued in patients of all ages. These preventive measures may have a substantial impact on the incidence of CHF in the elderly.

Aged↗
PubMed1991

The effects of dobutamine, dopexamine and fluid on hepatic histological responses to porcine faecal peritonitis.

We studied the effects of two catecholamines with differing receptor profiles on hepatic blood flow and hepatic structure in a porcine model of faecal peritonitis. We treated animals with dopexamine (group Dp) or dobutamine (group Db) and fluid, or fluid alone as a control, to achieve a 25% increase in Qt from baseline values. After the induction of faecal peritonitis the increased Qt was maintained throughout the 8 h study period by adjustment of the fluid infusion rate. The dose of catecholamines remained constant. Hepatic blood flow was correspondingly maintained at above baseline values throughout the study. Post-mortem liver biopsy specimens were analysed from experimental animals and 5 sham animals who had not been instrumented or infected. In experimental animals there was a reduction in sinusoidal patency between sham and group Dp (76% of total sinusoid vs 51%, p less than 0.05) and group Dp and control (51% vs 33%, p less than 0.05) or groups Dp and Db (51% vs 34%, p less than 0.05) animals. This was accounted for by an increase in sinusoidal leukocytes and endothelial swelling. In addition to the changes noted above there was marked hepatocellular destruction in group Db. We conclude that maintenance of organ blood flow does not guarantee structural integrity in the sepsis syndrome and hepatocellular damage was greater in group Db than group Dp or control.

Adrenergic Agonists↗
PubMed1991

Advantages of a narrow-range, medium molecular weight hydroxyethyl starch for volume maintenance in a porcine model of fecal peritonitis.

OBJECTIVE: To compare the effectiveness of two hydroxyethyl starch solutions of different molecular weight ranges for volume maintenance in a porcine model of fecal peritonitis. DESIGN: Randomized prospective trial. SETTING: Laboratory investigation. SUBJECTS: Adolescent female pigs weighing approximately 30 kg. INTERVENTIONS: We compared diafiltered 6% pentastarch with 6% high molecular weight hetastarch for volume maintenance in a porcine model of fecal peritonitis. The number average molecular weight of pentastarch is higher than hetastarch, although the weight average molecular weight is lower, i.e., a narrow range of medium weight molecules. The infusion rate of each agent was adjusted to maintain baseline arterial Hct for less than or equal to 7 hr after instrumentation and induction of fecal peritonitis. MAIN OUTCOME MEASUREMENTS: The volume of fluid required to maintain arterial Hct was compared along with comparisons of hemodynamic and histologic responses associated with the two agents. RESULTS: Significantly less pentastarch was required to prevent hemoconcentration than hetastarch (109 +/- 22.8 vs. 150 +/- 10.3 mL/kg; p less than .05) while hemodynamics, colloid osmotic pressure, and oxygen transport responses were similar. Capillary patency was greater (21.99 +/- 3.68 vs. 10.09 +/- 1.17%; p less than .05) and mean alveolar capillary barrier thickness was less (2.36 +/- 0.13 vs. 3.06 +/- 0.17 microns; p less than .05) with pentastarch than with hetastarch, as judged by electron microscopy. CONCLUSIONS: These data suggest that pentastarch is better retained in the circulation in capillary leak syndromes compared with hetastarch.

Animals↗
PubMed1991

Goal directed therapy with dobutamine in a porcine model of septic shock: effects on systemic and renal oxygen transport.

Systemic and renal haemodynamic and functional indices were measured in 15 anaesthetised pigs during systemic sepsis induced by faecal peritonitis. Five animals were assigned to maintenance of cardiac output (CO) at baseline, pre-infection values throughout the study (controls n = 5). In the remaining 10 animals, CO was increased by 25% prior to induction of sepsis and maintained at this level for the duration of the study using volume expansion with intravenous colloid and an infusion of either 20 micrograms/kg/min dobutamine (n = 5) or placebo (n = 5). Hourly measurements were made of CO, left renal blood flow, arterial and renal venous oxygen saturation, urine output, creatinine clearance and arterial partial pressure of oxygen until the animal died or until termination 8 h. Systemic indices of oxygen transport did not reflect the behaviour of the renal vascular bed during the management of sepsis. In the dobutamine group systemic oxygen uptake (VO2) increased from 173 +/- 30 to 277 +/- 73 ml/min (P less than 0.05), however this resulted in a decrease in renal DO2 (20 +/- 9 to 10 +/- 2 ml/min P less than 0.05) and there was no equivalent rise in renal VO2 (3.3 +/- 1.6 to 3.2 +/- 1.5 ml/min). There was however no significant difference in the effect on renal function of the three management protocols. Agents used to increase cardiac output during systemic sepsis may result in significantly different effects on the renal vascular bed which are not revealed by the measurement of systemic indices alone.

Animals↗
PubMed1990

Pretreatment with pentoxifylline improves the hemodynamic and histologic changes and decreases neutrophil adhesiveness in a pig fecal peritonitis model.

We investigated pentoxifylline (PTF) as a pretreatment of septic syndrome in pigs with fecal peritonitis. In the untreated group there was a progressive decrease in mean arterial pressure (MAP), cardiac output, mean pulmonary artery wedge pressure (WP), and a progressive rise in mean pulmonary artery pressure (MPAP), pulmonary vascular resistance (PVR), systemic vascular resistance (SVR), heart rate (HR), and core temperature (T). In those pigs given PTF there was a significantly smaller increase in SVR throughout and in PVR after 270 min. No significant differences were seen in MAP, MPAP, WP, HR, and T. Neutrophil adhesiveness did not change in the untreated group. However, it decreased markedly with PTF, both before and after peritonitis induction. Electron microscopy of the lungs, liver, and spleen in the test group showed severe damage, with endothelial disruption, capillary or sinusoidal occlusion, leukostasis, and neutrophil degranulation. Pretreatment with PTF attenuated these changes.

Animals↗