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K Dowling

Publications and source records attributed to K Dowling.

At least 19 recordsLinked to original sources
PubMed2001

Activated clotting time as a screening test prior to catheter-based cardiovascular procedures.

The activated clotting time (ACT) was investigated as a rapid, inexpensive, point-of-service screening test for coagulation abnormalities prior to catheter-based procedures. A total of 963 patients were screened by obtaining a history, standard coagulation profile, and activated coagulation time. The prevalence of normal patients (normal ACT and coagulation profile) was 94% (sensitivity = 91%; specificity = 27%). A normal ACT had a positive predictive value of 95%. The ACT was an acceptable screening test due to its ability to predict positively a low rate of bleeding complication and normal coagulation studies. Patients with ACT > 150 sec should be further evaluated with a screening coagulation panel. Additionally, given its low specificity, coagulation studies should be obtained in high-risk patients since an abnormal ACT does not effectively correlate with abnormal coagulation studies.

Blood Coagulation Disorders↗
PubMed2001

Application of the stretched exponential function to fluorescence lifetime imaging.

Conventional analyses of fluorescence lifetime measurements resolve the fluorescence decay profile in terms of discrete exponential components with distinct lifetimes. In complex, heterogeneous biological samples such as tissue, multi-exponential decay functions can appear to provide a better fit to fluorescence decay data than the assumption of a mono-exponential decay, but the assumption of multiple discrete components is essentially arbitrary and is often erroneous. Moreover, interactions, both between fluorophores and with their environment, can result in complex fluorescence decay profiles that represent a continuous distribution of lifetimes. Such continuous distributions have been reported for tryptophan, which is one of the main fluorophores in tissue. This situation is better represented by the stretched-exponential function (StrEF). In this work, we have applied, for the first time to our knowledge, the StrEF to time-domain whole-field fluorescence lifetime imaging (FLIM), yielding both excellent tissue contrast and goodness of fit using data from rat tissue. We note that for many biological samples for which there is no a priori knowledge of multiple discrete exponential fluorescence decay profiles, the StrEF is likely to provide a truer representation of the underlying fluorescence dynamics. Furthermore, fitting to a StrEF significantly decreases the required processing time, compared with a multi-exponential component fit and typically provides improved contrast and signal/noise in the resulting FLIM images. In addition, the stretched-exponential decay model can provide a direct measure of the heterogeneity of the sample, and the resulting heterogeneity map can reveal subtle tissue differences that other models fail to show.

Animals↗
PubMed2001

Protein synthesis costs could account for the tissue-specific effects of sub-lethal copper on protein synthesis in rainbow trout (Oncorhynchus mykiss).

This study investigates protein synthesis, following exposure to sub-lethal Cu, in rainbow trout in vivo and in vitro. The investigation has two aims: to determine if perturbations in protein synthesis, compared with other physiological changes, are a biomarker of Cu pollution and to evaluate the most productive role of cellular models in ecotoxicology. Protein synthesis rates were measured by labelling with 3H-phenylalanine. In vivo this was applied by a single (i.p.) injection and in vitro by bathing the cells in 3H-phenylalanine labelled culture media. The effects in vivo were tissue specific. After 3 weeks' exposure to 0.7 microM Cu only skin protein synthesis was reduced. Gills and liver from the same fish were unaffected. This reduction in skin protein synthesis appears to be more sensitive than some other biomarkers reported in the literature. However, Cu concentrations greater by orders of magnitude were required to reproduce this reduction in protein synthesis in skin cell explants (200 and 400 microM). Hepatocyte protein synthesis was unaffected by 10, 20 and 40 microM Cu and a separate investigation has also shown that 25 and 75 microM Cu does not effect protein synthesis in cultured gill cells. Oxygen consumption rates were also measured in vitro by monitoring the decline in O2 partial pressure. The Cu concentrations given above resulted in a decline in O2 consumption rates in the respective cell types. By measuring protein synthesis and O2 consumption after treatment with a protein synthesis inhibitor (cycloheximide), the costs of protein synthesis were also determined. Synthesis costs in hepatocytes are close to the theoretical minimum and are only marginally affected by Cu. Gill cell synthesis costs are also minimal and are unaffected. In skin explants, the reduction in protein synthesis was accompanied by greatly increased synthesis costs. This in vitro result offers a hypothesis as to the tissue-specific effects in vivo; i.e. the energetic demand of protein synthesis may determine tissue sensitivity or susceptibility. Cell or tissue types with high protein synthesis rates are able to avoid detrimental increases in the synthesis cost when exposed to Cu. In tissues with a low protein synthesis rate any further reduction is more likely to incur a potentially damaging increase in protein synthesis costs. Thus, whilst in vitro models may have little practical use in environmental monitoring, they may be best used as a mechanistic tool in understanding susceptibility or tolerance to sub-lethal Cu.

Animals↗
PubMed2001

The further development of rainbow trout primary epithelial cell cultures as a diagnostic tool in ecotoxicology risk assessment.

The use of short-term cytotoxicity assays for the initial screening of chemicals not only aids in establishing priorities for the selection of chemicals that should be tested in vivo, but also decreases the time in which potential toxicants can be valued. Rainbow trout primary skin epithelial cell cultures are one such assay. Rainbow trout primary skin cell cultures contain two cell types, keratinocytes and goblet mucus cells. Two aquatic pollutants, copper and prochloraz were screened using this cell system. The influence of media composition on the effects of the aquatic pollutants was also studied by testing the chemicals in both serum-containing and serum-free medium and the morphological changes that occurred within the cell cultures recorded. The concentration of copper that causes a reduction of 90% in the residual of day 3 growth of the primary cell culture system was found to be approximately 10 fold more than that of prochloraz. Prochloraz was found to cause a greater reduction in growth area when added to the primary cell culture system in serum-free medium than in serum-containing medium. Copper, in contrast, was found to exert reduced toxicity when added to the test cultures in serum-free medium compared with addition in serum-containing medium. Prochloraz was found to kill the epithelial cells by a process of necrosis. Copper, was found to kill the epithelial cells by both necrosis and apoptosis in a ratio of 2:1. It was also observed that as the dose of both chemicals increased, the number of goblet cells contained in the cell cultures decreased. A PAS stain was carried out to determine if the goblet cells were exocytosing their contents onto the cell culture surface. It was found that as chemical exposure increased the number of cells expressing positivity for mucus also increased. The results of this study add further evidence to support that primary cell cultures are a very appropriate model for toxicity risk assessment.

Animals↗
PubMed2001

Time-domain whole-field fluorescence lifetime imaging with optical sectioning.

A whole-field time-domain fluorescence lifetime imaging (FLIM) microscope with the capability to perform optical sectioning is described. The excitation source is a mode-locked Ti:Sapphire laser that is regeneratively amplified and frequency doubled to 415 nm. Time-gated fluorescence intensity images at increasing delays after excitation are acquired using a gated microchannel plate image intensifier combined with an intensified CCD camera. By fitting a single or multiple exponential decay to each pixel in the field of view of the time-gated images, 2-D FLIM maps are obtained for each component of the fluorescence lifetime. This FLIM instrument was demonstrated to exhibit a temporal discrimination of better than 10 ps. It has been applied to chemically specific imaging, quantitative imaging of concentration ratios of mixed fluorophores and quantitative imaging of perturbations to fluorophore environment. Initially, standard fluorescent dyes were studied and then this FLIM microscope was applied to the imaging of biological tissue, successfully contrasting different tissues and different states of tissue using autofluorescence. To demonstrate the potential for real-world applications, the FLIM microscope has been configured using potentially compact, portable and low cost all-solid-state diode-pumped laser technology. Whole-field FLIM with optical sectioning (3D FLIM) has been realized using a structured illumination technique.

Animals↗
PubMed2001

Uterine artery embolization for the treatment of adenomyosis: clinical response and evaluation with MR imaging.

OBJECTIVE: This study was performed to evaluate the MR imaging appearance and clinical response of patients undergoing uterine artery embolization for the treatment of menorrhagia due to adenomyosis. MATERIALS AND METHODS: A retrospective review of 15 patients with adenomyosis and menorrhagia who underwent uterine artery embolization was performed. The diagnosis of adenomyosis was based on established MR imaging criteria. Clinical response was assessed at a minimum of 3 months after embolization. Follow-up MR imaging was performed 6 months after embolization. RESULTS: Of the 15 patients in this study, five had diffuse adenomyosis without evidence of uterine fibroids, one had focal adenomyosis without evidence of uterine fibroids, and the remaining nine had adenomyosis with one or more fibroids. At follow-up, 12 (92.3%) of the 13 patients reported significant improvement in presenting symptoms and quality of life. One patient continued experiencing menorrhagia, and one patient experienced amenorrhea during the 5 months of follow-up after embolization. MR imaging in nine patients, performed at a mean of 5.9 months after embolization, revealed significant reductions in median uterine volume (42%), median fibroid volume (71%), and mean-junctional-zone thickness (11 mm; 33%; p < 0.5). Six of the nine patients had subendometrial regions of decreased T2 signal intensity after embolization. CONCLUSION: Uterine artery embolization is a promising nonsurgical alternative for patients with menorrhagia and adenomyosis. Significant improvement in presenting symptoms and in quality of life is associated with decreases in uterine size and junctional zone thickness. Larger prospective studies are needed to establish the safety and efficacy of this procedure for patients with adenomyosis.

Arteries↗
PubMed2000

Outpatient uterine artery embolization for symptomatic uterine fibroids: experience in 49 patients.

PURPOSE: To assess the feasibility of performing uterine artery embolization as an outpatient treatment for symptomatic uterine fibroids. MATERIALS AND METHODS: Forty-nine consecutive patients (mean age, 44.5 years; range, 28-54 years) underwent uterine artery embolization during a 12-month period. Embolization was performed with 350-500 microm polyvinyl alcohol particles (44 of 49) or Gelfoam pledgets (five of 49). At discharge, patients were given instructions regarding the constitutional symptoms to expect after embolization. A specific medication regimen consisting of prochlorperazine, ketorolac, meperidine, and hydrocodone was prescribed for relief of these symptoms. All patients were telephoned within 24 hours of discharge. During long-term follow-up, a questionnaire was administered to all patients to evaluate the periprocedural experience. Three-month clinical follow-up was available in 26 patients and 6-month imaging follow-up was available in 16 patients. RESULTS: Fourteen patients presented with menorrhagia, six had bulk-related symptoms (abdominal distension, stress incontinence, pelvic pain), and 29 had both. Technical success for bilateral embolization was 98%. Forty-seven of 49 patients were discharged to home 6-8 hours after the procedure; two patients required overnight observation in an ambulatory unit (one because of postprocedure hypertension and one because of a late procedure completion time). At the first follow-up phone call, reported symptoms included pelvic pain/cramping in 83.7% (41 of 49), fatigue in 75.5% (37 of 49), nausea/vomiting in 46.9% (23 of 49), and a nonpurulent vaginal discharge in 18.4% (nine of 49). These symptoms were satisfactorily controlled with discharge medications in 48 of 49 patients. No patients returned to the hospital or visited an emergency room during the first 48 hours after discharge. Forty-six of 49 patients were satisfied with the decision for home discharge. The average uterine volume reduction in 16 patients with 6-month imaging follow-up was 47.5%; 88.5%, of patients (23 of 26) with 3-month clinical follow-up reported improvement or elimination of symptoms. CONCLUSION: With defined telephone follow-up, staff availability, and a protocol designed to alleviate the postprocedure constitutional symptoms, uterine artery embolization is both safe and effective when performed as an outpatient procedure.

Adult↗
PubMed1996

Interaction of the fibrinolytic receptor, annexin II, with the endothelial cell surface. Essential role of endonexin repeat 2.

Endothelial cells express a cell surface co-receptor for plasminogen and tissue plasminogen activator (t-PA) which we recently identified as annexin II (Hajjar, K. A., Jacovina, A. T., and Chacko, J. (1994) J. Biol. Chem. 269, 21191-21197). This protein enhances the catalytic efficiency of t-PA-dependent plasmin generation by 60-fold (Cesarman, G. M., Guevara, C. A., and Hajjar, K. A. (1994) J. Biol. Chem. 269, 21198-21203). Here, we demonstrate that annexin II is constitutively translocated to the endothelial cell surface within 16 h of biosynthesis, and that cell surface annexin II comprises 4.3 +/- 1.0% of the total cellular pool. Exogenous 125I-annexin II bound to EGTA-washed endothelial cells with high affinity (Kd 49 nM) and in a calcium-dependent (I50 = 3 microM), phospholipid-sensitive manner. Peptides KASMKGLGTDED and YDSMKGKGTRDK, mimicking the calcium-binding "endonexin" motif (KGXGT) of annexin II, blocked its interaction with endothelial cells. Recombinant annexin II, bearing the calcium-binding site substitution D161A of core repeat 2, failed to compete with binding of the wild type protein to the cell surface, while E246A and D321A mutants, corresponding to core repeats 3 and 4, behaved as effective competitors. These data suggest that translocated annexin II interacts with cell surface phospholipid via a high affinity calcium-dependent binding site that includes residues 118-122 (KGLGT) and the coordinating Asp161 of core repeat 2. Thus, calcium-regulated expression of annexin II on the endothelial cell surface may play a central role in control of plasmin-mediated processes.

Amino Acid Sequence↗
PubMed1992

Fish oil and oat bran in combination effectively lower plasma cholesterol in the rat.

Male rats were fed a semi-purified diet containing oat bran or wheat bran with or without a marine fish oil to investigate the effects of such combinations on lipid metabolism. Oat bran alone and wheat bran plus fish oil gave lower plasma cholesterol concentrations than wheat bran alone while oat bran plus fish oil gave the lowest. Oat bran increased plasma triacylglycerols compared with wheat bran but oat bran plus fish oil gave concentrations similar to those seen with wheat bran plus fish oil. Oat bran gave higher hepatic cholesterol synthesis rates and a higher activity of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase compared to wheat bran. The addition of fish oil to either bran diet decreased cholesterol synthesis but HMG CoA reductase activity was not reduced. Oat bran increased hepatic acyl coenzyme A:cholesterol acyl transferase (ACAT) activity and increased the ratio of esterified to unesterified cholesterol in hepatic microsomal membranes compared with wheat bran. Fish oil decreased hepatic LDL receptor activity and increased HDL binding activity when added to the wheat bran diet but these effects were not seen with oat bran. Oat bran also had no effect on hepatic lipoprotein receptor activity compared with wheat bran. These results show that fish oil and oat bran have complementary cholesterol lowering effects in the rat.

Animals↗
PubMed1991

Effects of solvent extraction on the hypocholesterolaemic action of oat bran in the rat.

In adult male rats fed on a cholesterol-free synthetic diet, plasma cholesterol concentrations were lowest with oat bran, intermediate with cellulose and highest with wheat bran. Plasma triacylglycerols (TAG) were similar with wheat bran and cellulose but higher with oat bran. The concentrations and pools of caecal volatile fatty acids (VFA) were lowest with cellulose and equally higher with oat bran and wheat bran. Plasma VFA concentrations in the hepatic portal vein reflected those in caecal digesta and were unrelated to plasma cholesterol. Feeding oat bran after extraction with n-pentane gave plasma cholesterol concentrations similar to that found with wheat bran. Reconstitution of oat bran with extracted lipids did not restore the cholesterol-lowering effect. Addition of the extracted material to a wheat-bran diet had no effect on plasma cholesterol. Plasma TAG were higher with the oat bran and reconstituted-oat-bran diets than with wheat-bran or cellulose diets. However, extracted oat bran + safflower oil gave similar TAG concentrations to that with wheat bran. These extractions and additions did not change caecal bile acid or neutral sterol concentrations. Effects of these diets on plasma cholesterol were unrelated to their tocotrienol or tocopherol content. Addition of n-pentane to oat bran followed by evaporation of solvent gave plasma cholesterol concentrations that were significantly higher than untreated oat bran but lower than similarly treated wheat bran. It is concluded that oat bran affects cholesterol metabolism through a pentane-soluble component as well as non-starch polysaccharides. It appears that the activity of this lipid is not transferable by simple addition of the solvent extract to the whole diet.

Animals↗
PubMed1990

The changing prevalence of cervical human papilloma virus infection.

In order to determine the change in frequency of human papillomavirus infection (HPV) over a 10-year period, cervical smears from 1978 were retrieved, cytologically reviewed and compared with cervical smears taken in 1988. In this way, the slides were reviewed using the same diagnostic criteria. The prevalence of HPV infection in the population assessed at Flinders Medical Centre, rose from 0.58% to 5.6% over this period.

Female↗
PubMed1988

Field measurement of plasma and erythrocyte cholinesterases.

We have optimized Ellman-type plasma and erythrocyte cholinesterase assays for the field determination of pesticide exposure. The assays employ stable, premixed, inexpensive colorimetric reagents and a simplified kinetic measurement procedure using a novel battery-operable light-emitting-diode-source colorimeter (LEDSC). These methods were compared to a field tintometric method for cholinesterase currently in widespread use, using samples from organophosphate-intoxicated hospitalized patients. In comparison to the colorimetric method, the tintometric method was less precise and consistently underestimated the extent of pesticide exposure. Methods for the effective field determination of pesticide exposure using cholinesterase assays are critically evaluated with regard to their practical, biochemical, and medical relevance.

Cholinesterases↗
PubMed1985

Management of nonfamilial adenomatous polyps and colon cancers.

There is evidence that patients with adenocarcinoma of the colon and synchronous adenomatous polyps are at an increased risk for developing metachronous colon cancer. A retrospective study was made of all patients with colon cancer at our institution and the associated Veterans Administration Hospital between 1974 and 1983 to help assess the need for more extensive colon resection in patients with colon cancer and synchronous adenomatous polyps. At our hospitals 470 new cases of colon cancer were identified. Nine percent (44/470) had colon cancer and concurrent adenomatous polyps. Seven (16%) of these 44 patients developed metachronous colon cancer, as compared with four of 426 patients without polyps at the initial surgery (p less than 0.001). Four patients without polyps at the initial surgery developed polyps at a later date; three of the four patients developed metachronous colon cancer. We believe that more extensive colon resection, such as total colectomy and ileoproctostomy, may play a role in preventing the occurrence of metachronous colon cancer in patients with colon cancer and synchronous adenomatous polyps. In addition, if adenomatous polyps develop after colon surgery, close endoscopic follow-up is required.

Adenocarcinoma↗