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Biomedical subjects

D Bennett

Publications and source records attributed to D Bennett.

At least 127 records · Page 7Linked to original sources

An epidemiological study of Candida species infection in cancer patients using genetic fingerprinting and morphotyping.

During a six-week period a cluster of four cases of Candida fungaemia occurred in a mixed haematology/oncology unit of a large Dublin teaching hospital. A study was conducted to determine whether the cluster of cases was caused by a particular strain. Nine patients were studied; five who were colonized with Candida spp. and four who developed Candida fungaemia. Twenty-two clinical isolates of Candida spp. were collected and identified. Three of the patients with fungaemia yielded Candida albicans from blood cultures and C. tropicalis was isolated from the fourth patient. C. albicans isolates were serotyped, morphotyped and analysed by DNA fingerprinting of total cellular DNA using the cloned C. albicans-specific, mid-repeat sequence element 27A as a molecular probe. All C. albicans isolates were of serotype A. Eight distinguishable types were identified by both morphotyping and DNA typing from 19 C. albicans isolates recovered from seven individual patients, although there were several discrepancies. Of three patients from whom two or more isolates of C. albicans were recovered on separate occasions, two yielded recurrent isolates with different morphotype codes. However, in both cases, the recurrent isolates from individual patients yielded indistinguishable, or closely related, DNA fingerprint profiles. Both morphotyping and DNA fingerprint analysis readily distinguished the three blood culture isolates of C. albicans. We conclude that the Candida spp. infections in the unit were not due to cross-infection and were probably related to the patients' indigenous flora.

Candida↗

Generation of multinucleated osteoclast-like cells from canine bone marrow: effects of canine distemper virus.

Recent evidence has implicated canine distemper virus (CDV) as a possible aetiologic agent in Paget's disease of bone and the canine bone disorder, metaphyseal osteopathy. We have therefore examined the effects of CDV on the formation of multinucleated osteoclast-like cells in cultures of canine bone marrow mononuclear cells. Marrow cells from a distemper-infected dog and from five uninfected dogs were cultured in the presence of 1 alpha, 25-(OH)2 vitamin D3 and the number of tartrate resistant acid phosphatase positive multinucleated cells (MNCs) was determined. The presence of calcitonin (CT) receptors was confirmed by autoradiography with 125I-labeled human CT. Cultures from the distemper-infected dog contained a higher level of MNCs than those from the normal dogs. The in vitro addition of CDV to the cultures from all the dogs produced a dose-dependent increase in the number of MNCs, and an increase in size of these cells in the cultures from the infected dog. Cells infected with CDV were hyperresponsive to 1 alpha,25-(OH)2 vitamin D3. The presence of the virus in the relevant samples was confirmed using molecular techniques. In situ hybridization studies also revealed a significant increase in the level of infection following in vitro addition of the virus to the culture from the distemper-infected dog, suggesting that further infection had taken place. Resorption pits were formed on bone slices, although the number of pits was not significantly altered by viral infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid Phosphatase↗

Canine bone marrow cell cultures infected with canine distemper virus: an in vitro model of Paget's disease.

We have previously shown that the canine paramyxovirus, canine distemper virus (CDV), is a possible aetiologic agent in Paget's disease of bone and in the canine bone disorder, metaphyseal osteopathy. More recently, we have examined the effects of CDV on the formation of multinucleated, tartrate resistant acid phosphatase positive, calcitonin receptor positive, osteoclast-like cells in cultures of canine bone marrow mononuclear cells, and shown that both in vitro and in vivo infection with CDV produced a dose dependent increase in the number and size of osteoclast-like cells. We have now extended these results to show that CDV infection induces interleukin-6 and c-Fos mRNA in these cells, similar to our recent findings in pagetic bone cells. These results further support the hypothesis that CDV might be involved in the aetiopathogenesis of Paget's disease and metaphyseal osteopathy and suggest that canine marrow culture systems will prove useful as an in vitro model to examine the disease processes in more detail.

Animals↗

Age-associated alterations in thirst and arginine vasopressin in response to a water or sodium load.

We have examined simultaneous changes in thirst, plasma osmolality and arginine vasopressin, after oral water loading or hypertonic saline infusion. The studies were carried out in the same subjects, comprising young controls aged 26.8 years (SD 4.8, n = 10) and health status-defined elderly people aged 72.1 years (SD 3.1, n = 10). Water loading caused significant falls in plasma osmolality (p < 0.001) and thirst (p < 0.001), but there was no variation with age. Infusion with 462 mmol/l of sodium chloride increased plasma osmolality significantly (p < 0.001), but there was no variation with age (p = 0.12). The perception of thirst during the osmotic loading experiment was recorded differently by the two age groups (p < 0.0001). However, linear regression analysis showed no age difference in the relationship between thirst and plasma osmolality during osmotic loading. During osmotic loading the relationship between the plasma concentration of arginine vasopressin in response to increasing plasma osmolality varied significantly (slope: p = 0.02; intercept: p = 0.02). Plasma arginine vasopressin rose more rapidly with increasing plasma osmolality in old subjects.

Adult↗

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↗

Rheumatoid factor, anti-heat shock protein (65 kDa) antibodies and anti-nuclear antibodies in equine joint diseases.

To consider the hypothesis that autoimmune mechanisms may contribute to the pathology of equine joint diseases, 3 autoimmune responses were assayed in sera and synovial fluids. IgM-rheumatoid factor and antibodies to heat shock protein 65 kDa were determined by ELISA; anti-nuclear antibodies were assayed by indirect immunofluorescence to whole cell nuclear components. All parameters showed only modest increases, if any and not in a pattern related to disease, although some statistically significant increases were detected. Group analysis showed significantly elevated synovial fluid IgM-rheumatoid factor (IgM-RF) in horses with OA (P < 0.01), traumatised joints (P < 0.01) and articular fractured bones (P < 0.001). There was no significantly increased IgM-RF in the sera of horses with joint disorders compared to control horses. Significantly raised anti-heat shock protein molecular weight 65 kDa (HSP65) antibodies were only found in the synovial fluids of the horses with traumatised joints (P < 0.001). No correlations were found between the synovial fluid and sera levels of IgM-RF or anti-HSP65 antibodies. Synovial fluid anti-HSP65 antibody and IgM-RF levels positively correlated in the OCD (P < 0.001), fracture (P < 0.01) and synovitis (P < 0.05) groups. As antibodies to HSP65 correlated with IgG concentrations in synovial fluids, it is not possible to draw conclusions on HSP roles in joint disease pathogenesis. No serum anti-nuclear antibodies (ANA) were detected by immunofluorescence using rat liver and a human epithelial cell line (HEp-2) as substrates.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Accuracy of in-line venous saturation and hematocrit monitors in pediatric perfusion.

Cardiopulmonary bypass (CPB) in neonates and infants routinely employs lower blood flow rates (BFR), temperatures, and hematocrits (Hct) than those typically observed in adult CPB. The purpose of this study was to evaluate the accuracy of three devices available for continuous in-line measurement of venous oxygen saturation (SvO2) and Hct during pediatric CPB. Venous blood samples were obtained over a range of BFR, temperatures, and Hct and analyzed on a Corning 2500 Co-Oximeter and HematoStat C-70 centrifuge. These values were then compared to those measured by the Bentley OxySat SM-0200, the Gish StatSat, and the 3M CDI 100 in-line monitors. Seventy samples were obtained and analyzed using linear regression, paired t-test and residual analysis to establish the reliability and accuracy of each device. The results demonstrate the CDI to be more statistically accurate (p > 0.05) than the Gish and Bentley devices for measuring SvO2 in nearly all circumstances, though all correlated well with the control (r > 0.70). When comparing spun Hct to the CDI and Gish values, the CDI in-line monitor demonstrated a greater reliability to predict actual patient Hct (r > 0.90) than the Gish StatSat (r > 0.60). Residual analysis revealed that even though the Gish StatSat had higher calculated p values (p > 0.05) than the CDI 100 for interpreting Hct, it was shown to display more inconsistent and sporadic values over the ranges of BFR and temperature studied. It is concluded that the CDI 100 proved to be more accurate, reliable, and consistent than the Gish StatSat and the Bentley Oxysat devices in determining SvO2 and Hct over all evaluated parameters in this study.

Adult↗

Type 1 prophospholipase A2 propeptide in acute lung injury.

Neutrophil sequestration and activation in the pulmonary vasculature and interstitium are important in acute lung injury. Phospholipase A2 plays an important part in the production of potent inflammatory mediators in this syndrome. We used our ELISA for type 1 prophospholipase A2 activation peptides, which have the aminoacid sequence Asp-Ser-Gly-Ile-Ser-Pro-Arg (DSGISPR), to show that DSGISPR concentrations in plasma and urine are a sensitive and specific marker of acute lung injury in patients admitted to intensive care. The detection of DSGISPR in the plasma of 11 of 50 unselected patients had a sensitivity of 100% and a specificity of 93% for the presence or future development of acute lung injury.

Amino Acid Sequence↗

Acute arthritis of cats associated with feline calicivirus infection.

Twelve specific pathogen-free cats were infected either by intra-articular inoculation or by contact exposure to one of two strains of feline calicivirus (FCV), either F65, a field strain originating from an outbreak of lameness in a group of cats, or a vaccine strain. Following either route of exposure, both strains induced signs typical of FCV infection including oral and nasal ulceration, conjunctivitis and ocular discharge. These signs were of equal severity for both virus strains, but overall, following either route of infection, F65 induced more severe disease than the vaccine strain, with marked pyrexia, lethargy and lameness. Vaccine virus only induced a relatively mild lameness following intra-articular inoculation. Gross pathological and histopathological lesions were seen in some of the joints, but again changes were more severe in the F65-exposed cats. Virus was isolated from both normal and affected joints from both groups of F65-exposed cats, and from a joint from each cat inoculated intra-articularly with vaccine virus. Mild transient lameness was also seen in one of two control cats inoculated intra-articularly, but no pathological changes were seen or virus isolated from joints. A cDNA probe used in RNA dot blot hybridisation experiments was found to be specific and more sensitive than virus isolation in detecting FCV in selected tissues. This may be useful in future studies on the pathogenesis of FCV disease and in studies on viral persistence in FCV carriers.

Acute Disease↗

Measurement of glycosaminoglycans and keratan sulphate in canine arthropathies.

Glycosaminoglycans (GAG) and keratan sulphate (KS) were measured in sera and synovial fluids from dogs with either osteoarthritis (OA) or rupture of the cranial cruciate ligament (CCL) and normal dogs. The dogs with OA had higher synovial fluid GAG levels (P < 0.002) and serum KS (P < 0.03) compared to the normal dogs. No significant differences in serum GAG were found in either group. In both OA and rupture of the CCL, GAG levels were increased in the synovial fluid from the affected joint compared with the clinically normal (inactive) contralateral joint. Neither GAG nor KS measurements correlated with serum and synovial fluid antibodies to collagen type II, synovial fluid white cell count or age of dog. It is unlikely that the measurement of these cartilage breakdown products is of value for diagnostic or prognostic use in canine arthropathies.

Analysis of Variance↗

Effects of 3,4-dichloroaniline on the growth of two freshwater macroinvertebrates in a stream mesocosm.

The growth of the freshwater macroinvertebrates Gammarus pulex (L.) and Chironomus riparius Meigen exposed to 3,4-dichloroaniline in chambers within stream mesocosms was determined. DCA significantly affected the growth of neonate G. pulex and third instar C. riparius over 25 and 12 days, respectively. The no-observed-effect concentrations (NOECs) obtained in the tests were 0.08 mg DCA liter-1 (G. pulex) and 0.76 mg DCA liter-1 (C. riparius) and these are compared to toxicity data from other investigations. Inclusion of single-species bioassays in mesocosm studies provides complementary information on toxicant effects and indicates the suitability of the results of such tests (which may be routinely performed under laboratory conditions) for protecting particular ecosystems.

Aniline Compounds↗

Hyaluronan in canine arthropathies.

Soluble hyaluronan (HA), which has been considered as a marker for joint disease in man, was measured in serum and synovial fluid (SF) from dogs with osteoarthritis (OA), rheumatoid arthritis (RA), and rupture of the cranial cruciate ligament (CCL) and from normal dogs (control). Dogs with OA and RA had significantly increased serum HA (P < 0.001) and decreased synovial fluid HA (P < 0.001), as did dogs with CCL rupture (serum, P < 0.05; synovial fluid, P < 0.005). In OA, HA was lower in the SF from the affected joint than in that from the clinically normal (inactive) contralateral joint; no such difference was seen in dogs with CCL rupture. Dogs with liver disease (portocaval shunts, viral infectious hepatitis, metastatic neoplasm and disease secondary to diabetes mellitus) had increased serum HA concentrations (P < 0.001). There was a significant overlap of HA values in the diseased and normal dogs. Therefore, it is unlikely that the measurement of this cartilage breakdown product would be of value for diagnosis or prognosis in canine arthropathies.

Animals↗

Psychosocial factors and chronic fatigue syndrome.

This study investigated the number and severity of life events, Type A behaviour, coping strategies and social support differences between chronic fatigue and irritable bowel syndrome patients prior to illness and between these groups and healthy controls. Although few differences were found between the groups for life events, a number of interesting results emerged with regard to different aspects of Type A behaviour, various coping strategies and social support. These findings are discussed with respect to existing research in the field.

Adaptation, Psychological↗

Recovery after oral surgery with halothane, enflurane, isoflurane or propofol anaesthesia.

We have compared the recovery characteristics of four different techniques for maintenance of anaesthesia in 99 day-case patients admitted for oral surgery. All patients received propofol for induction of anaesthesia followed by halothane, enflurane, isoflurane or propofol infusion for maintenance of anaesthesia. Each patient was subjected to a battery of psychometric tests which included Spielberger state, trait, mood stress and mood arousal questionnaires, Maddox-Wing test and five-choice serial reaction time. All tests were performed before operation and at 0.5, 1, 2, 4, 24 and 48 h after operation. Performance in the reaction time test decreased significantly in the immediate postoperative period, returning almost to preoperative values by 4 h. However, only those patients who received enflurane or propofol had returned to their performance level before surgery by 4 h, although all four groups had achieved this target by 24 h. There was a further improvement in performance at 48 h. Anxiety and stress were high before surgery and decreased rapidly in the postoperative period. The Maddox-Wing test demonstrated a significant impairment in performance in the first 1 h after surgery, which returned to normal by discharge at 4 h. There were no significant differences between the four groups in these latter tests.

Adult↗

Effects of a nitric oxide synthase inhibitor in humans with septic shock.

OBJECTIVE: Studies in animals have indicated that increased production of nitric oxide from an inducible isoform of nitric oxide synthase contributes to the pathophysiology of endotoxic and cytokine induced shock. The aim of this study was to determine the role of nitric oxide in septic shock in humans. METHODS: The study was a randomised, double blind, placebo controlled investigation of the effects of the nitric oxide synthase inhibitor NG monomethyl-L-arginine (L-NMMA) in 12 patients with severe sepsis associated with hypotension. Measurements of haemodynamic, haematological, and biochemical variables were made. RESULTS: L-NMMA (0.3 and 1 mg.kg-1) produced a dose dependent increase in mean arterial pressure, systemic vascular resistance, pulmonary vascular resistance, central venous pressure, and pulmonary artery occlusion pressure, and a decrease in cardiac output and heart rate. In response to the highest dose of L-NMMA systemic vascular resistance increased from 547(SEM 92) to 889(143) dyne.s.cm-5, mean arterial blood pressure increased from 80.9(2.9) to 100.5(6.1) mm Hg, and cardiac output decreased from 11.2(2.1) to 8.9(1.9) litres.min-1. Continuous infusion of L-NMMA (1 mg.kg-1 x h-1) produced sustained haemodynamic changes. Platelet numbers decreased during the course of the study in both the L-NMMA and the placebo group and did not differ significantly between the groups. CONCLUSIONS: Low doses of L-NMMA cause a widespread increase in vascular tone and raise blood pressure in patients with septic shock. Overproduction of nitric oxide appears to be an important mechanism in septic shock in patients, and inhibition of nitric oxide synthesis might provide a novel therapeutic approach to this condition. However, L-NMMA produced a fall in cardiac output and it is possible that this would worsen tissue perfusion. Larger studies examining the effects of L-NMMA on mortality and morbidity are now required.

Adult↗

Immune responses to canine distemper virus in joint diseases of dogs.

Measurement of immune complexes, antibodies against canine distemper virus (CDV) and anti-CDV antibodies in immune complexes were made in sera and SF from 'normal' dogs and from dogs with joint diseases. These data were compared with cytological analyses of SF samples. In dogs with canine rheumatoid-like arthritis (CRA) there were correlations between circulating anti-CDV antibody levels and circulating immune complex levels (P < 0.001) and between SF anti-CDV antibody levels and SF immune complex levels (P < 0.01). Furthermore, the SF PMN count in dogs with CRA correlated with both the SF anti-CDV antibody levels (P < 0.001) and the SF immune complex anti-CDV antibody levels (P < 0.001). The results demonstrated a relationship between CDV and ongoing synovial inflammation in dogs with CRA.

Animals↗

Cellular sources of proteolytic enzymes in equine joints.

Isolated equine blood and articular cells were investigated for proteolytic enzyme production by means of gel filtration and analysis on 14C-acetylated collagen and casein substrates. Significant amounts of collagenase and caseinase activity were produced by cultured synoviocytes stimulated with equine interleukin 1, although large amounts of collagenase also originated from neutrophils.

Animals↗