Search PubMed⌕ Search

Biomedical subjects

A O'Donnell

Publications and source records attributed to A O'Donnell.

At least 37 records · Page 2Linked to original sources
PubMed2001

The effects of fenoldopam on coronary conduit blood flow after coronary artery bypass graft surgery.

OBJECTIVE: To quantify the effects of fenoldopam, 0.1 microg/kg/min, on left internal mammary artery (LIMA) and saphenous vein blood flow after coronary anastomosis. DESIGN: Prospective, randomized, double-blind, placebo-controlled trial. SETTING: University teaching hospital, single institution. PARTICIPANTS: Thirty-one American Society of Anesthesiologists III patients undergoing elective coronary revascularization. INTERVENTIONS: A perivascular ultrasonic flow probe (Linton Instrumentation, Norfolk, UK) was placed around the LIMA and saphenous vein graft after coronary anastomosis. MEASUREMENTS AND MAIN RESULTS: Immediately before and at 5-minute intervals for 15 minutes after starting the infusion, blood flow was measured in the LIMA and one saphenous vein graft using a transit time ultrasonic flow probe. Heart rate, blood pressure, and central venous pressure were documented at these time points. Administration of fenoldopam, 0.1 microg/kg/min, did not alter heart rate or blood pressure. A small, nonsignificant increase in LIMA blood flow occurred during the 15-minute study period (30 +/- 12 to 35 +/- 10 mL/min) in patients who received fenoldopam. No significant changes occurred in the placebo group. CONCLUSIONS: The findings indicate that fenoldopam, 0.1 microg/kg/min, did not influence coronary conduit blood flow to a clinically significant extent. The small increase in LIMA blood flow may be of greater importance in high-risk patients or in the prevention of coronary arterial spasm.

Aged↗
PubMed2001

Impact of 2,4-diacetylphloroglucinol-producing biocontrol strain Pseudomonas fluorescens F113 on intraspecific diversity of resident culturable fluorescent pseudomonads associated with the roots of field-grown sugar beet seedlings.

The impact of the 2,4-diacetylphloroglucinol-producing biocontrol agent Pseudomonas fluorescens F113Rif on the diversity of the resident community of culturable fluorescent pseudomonads associated with the roots of field-grown sugar beet seedlings was evaluated. At 19 days after sowing, the seed inoculant F113Rif had replaced some of the resident culturable fluorescent pseudomonads at the rhizoplane but had no effect on the number of these bacteria in the rhizosphere. A total of 498 isolates of resident fluorescent pseudomonads were obtained and characterized by molecular means at the level of broad phylogenetic groups (by amplified ribosomal DNA restriction analysis) and at the strain level (with random amplified polymorphic DNA markers) as well as phenotypically (55 physiological tests). The introduced pseudomonad induced a major shift in the composition of the resident culturable fluorescent Pseudomonas community, as the percentage of rhizoplane isolates capable of growing on three carbon substrates (erythritol, adonitol, and L-tryptophan) not assimilated by the inoculant was increased from less than 10% to more than 40%. However, the pseudomonads selected did not display enhanced resistance to 2,4-diacetylphloroglucinol. The shift in the resident populations, which was spatially limited to the surface of the root (i.e., the rhizoplane), took place without affecting the relative proportions of phylogenetic groups or the high level of strain diversity of the resident culturable fluorescent Pseudomonas community. These results suggest that the root-associated Pseudomonas community of sugar beet seedlings is resilient to the perturbation that may be caused by a taxonomically related inoculant.

Chenopodiaceae↗
PubMed2001

The effects of venous cannulation technique and cardioplegia type on plasma potassium concentration and arterial blood pressure during cardiopulmonary bypass.

The cannulation method and cardioplegia solution used during cardiopulmonary bypass (CPB) may both influence plasma potassium concentrations ([K+]) and mean arterial blood pressure (MAP). Bi-caval or right atrial cannulation methods are routinely used in conjunction with crystalloid or blood cardioplegia. We investigated the influence of cannulation method and cardioplegia solutions on plasma [K+] and MAP during cardiopulmonary bypass. Sixty consecutive patients undergoing elective coronary artery bypass grafting (CABG) using CPB were studied. They were randomly divided into three groups of 20 patients. Patients in Group A underwent bi-caval venous cannulation and received crystalloid cardioplegia. Group B patients underwent right atrial cannulation and received crystalloid cardioplegia. Group C patients underwent right atrial cannulation and received blood cardioplegia. In each case. cardioplegia was administered antegrade via the aortic root. Plasma [K+], MAP. and hemoglobin concentration (Hb) were measured over an 8-min period following cardioplegia administration (pilot studies indicated pressure changes occuring post cardioplegia administration up to this time). The combination of bi-caval cannulation and crystalloid cardioplegia (Group A) was associated with the least increase in plasma [K+] and no decrease in MAP. The maximum [K+] for this Group was 4.2 mmol/L (4.6% increase). The minimum mean pressure was 57 mmHg (13.6% increase). Both right atrial cannulation groups (B and C) showed a large rise in plasma [K+] and a decrease in MAP. Group B maximum [K+] was 5.2 mmol/L (27.5% increase). Group C was also 5.2 mmol/L (26.0% increase). Group C showed the largest pressure decrease, the minimum mean pressure was 45 mmHg (21.3% decrease). The Group B minimum mean pressure was 45 mmHg (8.7% decrease). Our results show that patients undergoing CPB operations who are deemed to be at increased risk of suffering adverse effects from hypotensive episodes may benefit from bicaval cannulation and caval snaring, in preference to right atrial cannulation. Crystalloid cardioplegia may be preferable to blood cardioplegia in these cases to maintain the MAP.

Arteries↗
PubMed2000

Tobramycin solution for inhalation reduces sputum Pseudomonas aeruginosa density in bronchiectasis.

We conducted a placebo-controlled, double-blind, randomized study to evaluate the microbiological efficacy and safety of inhaled tobramycin for treatment of patients with bronchiectasis and Pseudomonas aeruginosa. Patients were randomly assigned to receive either tobramycin solution for inhalation (TSI) (n = 37) or placebo (n = 37), which was self-administered twice daily for 4 wk and followed by 2-wk off-drug. At Week 4, the TSI group had a mean decrease in P. aeruginosa density of 4.54 log(10) colony-forming units (cfu)/g sputum compared with no change in the placebo group (p < 0.01). At Week 6, P. aeruginosa was eradicated in 35% of TSI patients but was detected in all placebo patients. Investigators indicated that 62% of TSI patients showed an improved medical condition compared with 38% of placebo patients (odds ratio = 2.7, 95% confidence interval [CI] 1.1 to 6.9). Tobramycin-resistant P. aeruginosa strains developed in 11% of TSI patients and 3% of placebo patients (p = 0.36). The mean percent change in FEV(1) percent predicted from Week 0 to Week 4 was similar for the TSI and placebo groups (p = 0.41). More TSI-treated patients than placebo patients reported increased cough, dyspnea, wheezing, and noncardiac chest pain, but the symptoms did not limit therapy. Additional study is warranted to further evaluate TSI in bronchiectasis patients.

Administration, Inhalation↗
PubMed2000

Functional neuroimaging: enhanced understanding of migraine pathophysiology.

Research into migraine pathophysiology has been hampered by the episodic nature and unpredictable onset of migraine attacks. Recently, newer imaging techniques have been providing noninvasive methods of studying metabolism and hemodynamics in the brains of migraineurs during and between acute attacks. 133Xe blood flow techniques, transcranial Doppler, and SPECT have all been employed to investigate hemodynamic changes during migraine aura. PET has been useful in the study of migraine without aura, with findings of increased blood flow related to pain in cortical areas and in the medial brainstem. Currently, three functional MRI imaging techniques are being used in migraine research. Diffusion-weighted imaging has shown normal findings in measures of the ability of neurons to maintain osmotic gradients. Studies using perfusion-weighted imaging have shown alterations in relative cerebral blood flow (CBF), relative cerebral blood volume, and mean transit time during migraine visual aura. The blood oxygen level-dependent technique can supply information related to neuronal activation during acute migraine aura. MRS has been used with mixed success to look for evidence of abnormal energy metabolism in the brains of migraineurs. Magnetoencephalography studies support the presence of a spreading depression-like phenomenon in migraine with aura. Two groups have used transcranial magnetic stimulation to assess whether neurons in the occipital cortex are hyperexcitable, predisposing patients to develop aura symptoms. Despite conflicting findings, migraine with visual aura appears to be generally associated with transient decreases in regional CBF.

Brain↗
PubMed1999

Cytokine-induced prostaglandin E2 synthesis and cyclooxygenase-2 activity are regulated both by a nitric oxide-dependent and -independent mechanism in rat osteoblasts in vitro.

Osteoblasts respond to stimulation with interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma) by production of nitric oxide and prostaglandins (PGs). In this study the relationship between nitric oxide and PG synthesis was investigated after cytokine stimulation of cultured rat osteoblasts. IL-1, TNF-alpha, IFN-gamma, and exogenous sodium nitroprusside, a nitric oxide donor, all stimulated PGE2 production in a dose-dependent manner. PGE2 production was blocked by L-nitro-arginine methyl ester, an inhibitor of nitric oxide production, after IFN-gamma stimulation and was partially blocked after TNF-alpha stimulation. However, IL-1-induced PGE2 was unaffected. Similarly, expression of the cyclooxygenase-2 protein was stimulated by cytokines, and IFN-gamma-induced expression was again blocked by L-nitro-arginine methyl ester. In contrast, all cytokines induced the cyclooxygenase-2 mRNA expression independently of nitric oxide production, although exogenous sodium nitroprusside was able to induce the cyclooxygenase-2 mRNA in the absence of cytokines. The results show that nitric oxide can induce PG synthesis and cyclooxygenase-2 expression and may regulate cyclooxygenase-2 expression at both transcriptional and post-transcriptional levels. In addition, the data show the existence of both nitric oxide-dependent and -independent pathways of PG synthesis after cytokine stimulation of osteoblasts. The results suggest that nitric oxide may be an important mediator of PG production in inflammatory bone diseases.

Animals↗
PubMed1999

Hierarchical phosphorylation of recombinant tau by the paired-helical filament-associated protein kinase is dependent on cyclic AMP-dependent protein kinase.

Immunoaffinity-purified paired helical filaments (PHFs) from Alzheimer's disease (AD) brain homogenates contain an associated protein kinase activity that is able to induce the phosphorylation of PHF proteins on addition of exogenous MgCl2 and ATP. PHF kinase activity is shown to be present in immunoaffinity-purified PHFs from both sporadic and familial AD, Down's syndrome, and Pick's disease but not from normal brain homogenates. Although initial studies failed to show that the kinase was able to induce the phosphorylation of tau, additional studies presented in this article show that only cyclic AMP-dependent protein kinase-pretreated recombinant tau is a substrate for the PHF kinase activity. Deletional mutagenesis, phosphopeptide mapping, and site-directed mutagenesis have identified the PHF kinase phosphorylation sites as amino acids Thr361 and Ser412 in htau40. In addition, the cyclic AMP-dependent protein kinase phosphorylation sites that direct the PHF kinase have been mapped to amino acids Ser356 and Ser409 in htau40. Additional data demonstrate that these hierarchical phosphorylations in the extreme C terminus of tau allow for the incorporation of recombinant tau into exogenously added AD-derived PHFs, providing evidence that certain unique phosphorylations of tau may play a role in the pathogenesis of neurofibrillary pathology in AD.

Alzheimer Disease↗
PubMed1999

Recent advances in functional neuroimaging.

New functional imaging techniques, including positron emission tomography, transcranial magnetic stimulation and functional magnetic resonance imaging, promise to allow the noninvasive study of haemodynamic, metabolic and activation parameters during acute migraine attacks in humans. These techniques are currently being applied to the study of the transient neurologic symptoms of the aura, as well as the painful headache phase of migraine. This review summarizes the most recent of these studies and discusses how they relate to the prevailing theories of migraine pathophysiology.

Humans↗
PubMed1999

Prevention of cerebral malaria in children in Papua New Guinea by southeast Asian ovalocytosis band 3.

Southeast Asian ovalocytosis (SAO) occurs at high frequency in malarious regions of the western Pacific and may afford a survival advantage against malaria. It is caused by a deletion of the erythrocyte membrane band 3 gene and the band 3 protein mediates the cytoadherence of parasitized erythrocytes in vitro. The SAO band 3 variant may prevent cerebral malaria but it exacerbates malaria anemia and may also increase acidosis, a major determinant of mortality in malaria. We undertook a case-control study of children admitted to hospital in a malarious region of Papua New Guinea. The SAO band 3, detected by the polymerase chain reaction, was present in 0 of 68 children with cerebral malaria compared with six (8.8%) of 68 matched community controls (odds ratio = 0, 95% confidence interval = 0-0.85). Median hemoglobin levels were 1.2 g/dl lower in malaria cases with SAO than in controls (P = 0.035) but acidosis was not affected. The remarkable protection that SAO band 3 affords against cerebral malaria may offer a valuable approach to a better understanding of the mechanisms of adherence of parasitized erythrocytes to vascular endothelium, and thus of the pathogenesis of cerebral malaria.

Animals↗
PubMed1998

Red cell morphology and malaria anaemia in children with Southeast-Asian ovalocytosis band 3 in Papua New Guinea.

Southeast-Asian ovalocytosis (SAO) was diagnosed in children from Madang, Papua New Guinea, by detection of the SAO band 3 gene variant using the polymerase chain reaction. SAO band 3 was present in 16/241 (6.6%) children living in the community and 32/389 (8.2%) children with acute Plasmodium falciparum malaria (P=0.42). SAO band 3 was detected in 8.2% (23/281) of alpha+-thalassaemia homozygotes, 9.4% (20/214) of heterozygotes and 2.4% (2/85) of children with a normal alpha-globin genotype (P=0.12). The most consistent feature of SAO band 3 on microscopy of thin blood films was red cells with two or more linear or irregularly-shaped pale regions. In children living in the community, these were present in 15 with SAO band 3 (sensitivity 93.8%) and only two normals (specificity 99.1%). The presence of > or = 20% ovalocytosis was a poorer indicator of SAO band 3 (sensitivity 68.8% and specificity 100%). Haematological data were similar in SAO band 3 and normal children. However, in children with acute malaria, haemoglobin levels and red cell counts were significantly lower in SAO band 3 than normal children. The degree of ovalocytosis was lower in children with SAO band 3 during acute malaria, suggesting that a selective loss of ovalocytes may contribute to malaria anaemia in Southeast-Asian ovalocytosis.

Anemia↗
PubMed1998

Causes of preterm delivery and intrauterine growth retardation in a malaria endemic region of Papua New Guinea.

AIM: To identify causes of preterm delivery and intrauterine growth retardation (IUGR) in a malaria endemic region of Papua New Guinea. METHODS: Independent predictors of preterm delivery and birthweight in term infants were identified using multiple regression analysis in a prospective study of 987 singleton live births delivered in Madang Hospital. RESULTS: Overall, Plasmodium falciparum infection of the placenta was associated with a reduction in birthweight of 130 g. Malaria was significantly more common in primigravidae than multigravidae and probably contributed to both preterm delivery and IUGR. Maternal haemoglobin concentrations were significantly lower in malaria infected than noninfected women and reduced haemoglobin was the main determinant of preterm delivery. Poorer maternal nutritional status and smoking were associated with both prematurity and IUGR. Greater antenatal clinic attendance predicted increased birthweight in term infants. CONCLUSIONS: Protection against malaria during pregnancy, especially in primigravidae, improved nutrition in women and discouragement of smoking would probably reduce both preterm delivery and IUGR. Greater use of existing antenatal clinics might increase birthweight in term infants.

Adult↗
PubMed1998

Severe multi-system failure following delayed presentation with tiger snake envenomation.

A 68 year-old-man presented some twelve hours after a presumed Tiger Snake bite with coagulopathy, paralysis and muscle necrosis. He suffered multi-system failure requiring prolonged ventilation, haemodialysis and supportive care, to be discharged after 26 days. Delays to antivenom therapy after tiger snake envenomation can result in significant morbidity. Australian snakes are the most venomous in the world.

Aged↗
PubMed1997

alpha+-Thalassemia protects children against disease caused by other infections as well as malaria.

In the South West Pacific region, the striking geographical correlation between the frequency of alpha+-thalassemia and the endemicity of Plasmodium falciparum suggests that this hemoglobinopathy provides a selective advantage against malaria. In Vanuatu, paradoxically, alpha+-thalassemia increases the incidence of contracting mild malaria in the first 2 years of life, but severe disease was too uncommon to assess adequately. Therefore, we undertook a prospective case-control study of children with severe malaria on the north coast of Papua New Guinea, where malaria transmission is intense and alpha+-thalassemia affects more than 90% of the population. Compared with normal children, the risk of having severe malaria was 0.40 (95% confidence interval 0.22-0.74) in alpha+-thalassemia homozygotes and 0.66 (0.37-1.20) in heterozygotes. Unexpectedly, the risk of hospital admission with infections other than malaria also was reduced to a similar degree in homozygous (0. 36; 95% confidence interval 0.22-0.60) and heterozygous (0.63; 0. 38-1.07) children. This clinical study demonstrates that a malaria resistance gene protects against disease caused by infections other than malaria. The mechanism of the remarkable protective effect of alpha+-thalassemia against severe childhood disease remains unclear but must encompass the clear interaction between this hemoglobinopathy and both malarial and nonmalarial infections.

Child↗
PubMed1996

Severe malaria in children in Papua New Guinea.

The clinical features of severe falciparum malaria and risk factors for mortality were studied in 489 children admitted with malaria to Madang Hospital, Papua New Guinea. The most common severe manifestations of malaria were severe anaemia (22%) and coma (16%). Children with severe anaemia were younger than those with coma (median age 2.2 vs. 3.7 years) and had been ill for longer before admission (median 7 vs. 4 days, respectively). Although the clinical features of coma in Madang children with malaria resembled closely those reported in African children, mortality was lower (8% vs. 17-25%, respectively). Overall, 17 (3.5%) children died, most within 12 h of admission. A high level of plasma lactate (> or = 5 mmol/l) was common (20%) and was the major predictor of death in multiple regression analysis. Raised plasma creatinine and decreased plasma bicarbonate were also independent predictors of mortality. Coma was not predictive of death, although a high proportion of children with profound coma died. Investigation of the causes of acidosis in children with malaria is a high research priority. In view of the short time interval between admission and death in many children, emphasis must be placed on the prevention or early recognition and treatment of acidosis in the district health clinic as well as the central hospital.

Anemia↗
PubMed1992

Clinical significance of monoclonal proteins in chronic lymphocytic leukemia.

Serum monoclonal proteins were found in 36 of 111 (32%) chronic lymphocytic leukemia (CLL) patients studied using high-resolution agarose gel electrophoresis combined with immunofixation. In contrast, using immunoelectrophoresis (IEP) and serum protein electrophoresis (SPEP), monoclonal proteins were found in 20 and 4% of CLL patients, respectively. The presence of a monoclonal protein was associated with a median survival of 63 months compared to 103 months for individuals without a monoclonal spike (p < 0.012). This was independent of clinical stage. The data also suggests that the presence of a monoclonal protein may define a group of patients at greater risk for disease progression in the low and intermediate risk groups. (Rai stages, 0, I, II). Further follow-up will be required to determine if this is statistically significant.

Blood Proteins↗