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Biomedical subjects

L Cole

Publications and source records attributed to L Cole.

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

Epidemiology, management, and outcome of severe acute renal failure of critical illness in Australia.

OBJECTIVE: To study the epidemiology, style of management, and outcome of intensive care patients with acute renal failure requiring replacement therapy in Australia. DESIGN: Prospective epidemiologic study. SETTING: Australian adult intensive care units providing acute renal replacement therapy. PATIENTS: Adult intensive care patients with acute renal failure treated with renal replacement therapy. INTERVENTIONS: Demographic and clinical data collection for 3 months. MEASUREMENTS AND MAIN RESULTS: A standardized data collection form for each case of severe acute renal failure was used to collect demographic, biochemical, clinical, and outcome data. Severe acute renal failure affected 299 patients (approximately eight cases per 100,000 adults per year). Among these patients, 99 (33.1%) had impaired baseline renal function, 238 (79.6%) needed mechanical ventilation, and 232 (77.6%) needed continuous vasoactive drug administration. Critical care physicians controlled patient care and renal replacement therapy in 289 cases (96.7%). Critical care nurses performed such therapy alone in 288 (96.3%) cases. Continuous renal replacement therapy was used in 292 (97.7%) patients. There was no nephrological input in 173 (57.8%) cases. Predicted mortality rates were 52.1% by Simplified Acute Physiology Score II, 49.5% by Acute Physiology and Chronic Health Evaluation II score, and 51.9% by an acute renal failure-specific score. Actual mortality rate was 46.8%. Only 25 (15.7%) patients were dialysis-dependent at hospital discharge. Of these patients, 20 (80%) had premorbid chronic impairment of renal function. CONCLUSION: In Australia, critical care physicians and nurses manage severe acute renal failure with limited consultative nephrological input. Renal replacement therapy is continuous and outcomes are satisfactory. Our findings support the view that this approach to management of severe acute renal failure is safe.

Acute Kidney Injury↗
PubMed2000

Brefeldin A affects growth, endoplasmic reticulum, Golgi bodies, tubular vacuole system, and secretory pathway in Pisolithus tinctorius.

Brefeldin A (BFA) reduced radial growth in Pisolithus tinctorius at a concentration as low as 2 microM. Use of endoplasmic reticulum (ER)-Tracker dye, unconjugated BFA, and fluorescent BFA (BODIPY-BFA) allowed comparison of the effects of BFA on the endomembrane system of P. tinctorius at the light and electron microscope levels. Both ER-Tracker dye and BODIPY-BFA have been shown previously to label the ER. Unconjugated BFA and BODIPY-BFA modified the ER network and disrupted the tubular vacuole system in the tip region. The ultrastructure in freeze-substituted hyphae showed that BFA treatment resulted in (i) disruption of the Spitzenkörper, (ii) reduction in number of apical vesicles, (iii) redistribution and mild dilation of ER, and (iv) persistence and increased size and complexity of Golgi bodies. The effects of BFA on the ER were only partially reversible in the time period examined. We conclude that in P. tinctorius, BFA as the free metabolite or BODIPY-BFA affects the tubular vacuole system as well as anterograde membrane flow between the ER and the Golgi bodies and post-Golgi transport.

Antifungal Agents↗
PubMed2000

Maternal urine beta-core hCG fragment level and small for gestational age neonates.

OBJECTIVE: To determine whether second-trimester urine beta-core fragments of hCG predict small for gestational age (SGA) neonates. METHODS: Spot urine beta-core levels were measured in 733 nonhypertensive women with singleton pregnancies who presented for amniocentesis and had karyotypically normal fetuses. The beta-core level was standardized to urine creatinine and expressed as multiples of the median. The area under a receiver operating characteristics curve was used to determine the screening efficiency of the urine analyte for prediction of small for gestational age (SGA) births. In a subgroup of cases, serum markers (alpha-fetoprotein [AFP], hCG, and unconjugated estriol) were compared using stepwise regression analysis to urine beta-core fragment for SGA prediction. RESULTS: There were 23 (3.0%) SGA neonates. The mean +/- standard deviation (SD) gestation at urine collection was 16.4 +/- 1.3 weeks and collection to delivery interval was 23.0 +/- 2.2 weeks. Mean beta-core (+/- SD) fragment levels were significantly higher in those who later had SGA infants compared with appropriately grown infants (2982.8 ng/mg creatinine versus 1447.4 ng/mg creatinine, P <.001). Stepwise logistic regression found that urine beta-core fragment and serum AFP were the only significant predictors of SGA, with statistically significant chi(2) values (P <.001 and P =.038, respectively). The urine analyte was significantly superior. Second-trimester urine beta-core fragment had a 78.3% sensitivity and 70% specificity for SGA prediction. Exclusion of preeclamptic cases resulted in a sensitivity of 84.2% and a specificity of 71.2%. CONCLUSION: Second-trimester elevated maternal urine beta-core fragment of hCG predicted SGA infants, and was superior to other serum analytes in that prediction.

Adult↗
PubMed2000

A long-term study of Rattus norvegicus in the London borough of Enfield using baiting returns as an indicator of sewer population levels.

This is a long-term study that investigates the dynamics of a population of Rattus norvegicus (Berk) inhabiting a sewerage system in London. Thirteen years (1986/7-1998/9) of data from sewer baiting records were analysed (a total of 35,478 records). Manholes were baited with the anticoagulant Brodifacoum (0.005%) on a pinhead oatmeal bait base. Time series analysis was conducted on the data set to determine the underlying trend of the data and the population fluctuations about this trend. An exponential curve was found to give an accurate and realistic fit to the data and indicated that the rat population had decreased over the study period. Decomposition analysis indicated a 5-year cycle best described fluctuations around this trend.

Animals↗
PubMed2000

ER-Tracker dye and BODIPY-brefeldin A differentiate the endoplasmic reticulum and golgi bodies from the tubular-vacuole system in living hyphae of Pisolithus tinctorius.

Two fluorochromes, ER-TrackerTM Blue-White DPX dye and the fluorescent brefeldin A (BFA) derivative, BODIPY-BFA, label the endoplasmic reticulum (ER) in hyphal tips of Pisolithus tinctorius and allow its differentiation from the tubular-vacuole system at the light microscope level in living cells. The ER-Tracker dye labels a reticulate network similar in distribution to ER as seen in electron micrographs of freeze-substituted hyphae. BODIPY-BFA stains a thicker axially aligned structure with an expanded region at the apex, which is similar to that seen when hyphae are stained with ER-Tracker dye in the presence of unconjugated BFA. This structure is considered to be ER modified by BFA, a view supported by ultrastructural observations of the effect of BFA on the fungal ER. Both fluorescent probes also stain punctate structures, which are most likely to be Golgi bodies. Neither probe labels the tubular-vacuole system.

Basidiomycota↗
PubMed2000

A prospective, multicenter study of the epidemiology, management, and outcome of severe acute renal failure in a "closed" ICU system.

The safety and effectiveness of "closed" intensive care units (ICUs) are highly controversial. The epidemiology and outcome of acute renal failure (ARF) requiring replacement therapy (severe ARF) within a "closed" ICU system are unknown. Accordingly, we performed a prospective 3-mo multicenter observational study of all Nephrology Units and ICUs in the State of Victoria (all "closed" ICUs), Australia, and focused on the epidemiology, treatment, and outcome of patients with severe ARF. We collected demographic, clinical, and outcome data using standardized case report forms. Nineteen ward patients and 116 adult ICU patients had severe ARF (13.4 cases/100, 000 adults/yr). Among the ICU patients with severe ARF, 37 had impaired baseline renal function, 91 needed ventilation, and 95 needed vasoactive drugs. Intensivists controlled patient care in all cases. Continuous renal replacement therapy (CRRT) was used in 111 of the ICU patients. Nephrological opinion was sought in only 30 cases. Predicted mortality was 59.6%. Actual mortality was 49.2%. Only 11 ICU survivors were dialysis dependent at hospital discharge. In the state of Victoria, Australia, intensivists manage severe ARF within a "closed" ICU system. Renal replacement is typically continuous and outcomes compare favorably with those predicted by illness severity scores. Our findings support the safety and efficacy of a "closed" ICU model of care.

Acute Kidney Injury↗
PubMed2000

The effect of pantethine and ultraviolet-B radiation on the development of lenticular opacity in the emory mouse.

PURPOSE: Few studies have examined the impact of long-term treatments or exposures on the development of cataract in maturity-onset animal models. We studied the effect of treatment with D-pantethine and exposure to ultraviolet-B (UVB) radiation on the development of lenticular opacity in the Emory mouse. METHODS: A total of 164 Emory mice were randomized by litter at weaning to exposure to UVB light at 12 mJ/cm(2) for 6 hr/day (UV) or usual room light (A), and within litter, were further randomized to bi-weekly intra-peritoneal injections of 0.8 g/kg pantethine (T) or no treatment (C). Retro illumination lens photos were taken at 2, 4, 6, 8, and 10 months after weaning, and graded in masked fashion. The animals were sacrificed at 10 months and the lenses analyzed for total pantethine and total cysteamine. RESULTS: Lens pantethine and cysteamine levels were significantly (P < 0.001) higher for the T as compared to C litters. Mean cataract grade increased monotonically over time for all four groups. Unadjusted mean grade for the AT group at 8 (1.32) and 10 (1.86) months appeared lower than for the other groups (AC: 2.17, 2.39; UVC: 1.77, 2.40; UVT: 1.88, 2.37). However, the mean grade for the pantethine-treated litters did not differ significantly from the untreated litters except at 2 months (when untreated litters had significantly lower grades), when adjusting for UV treatment, gender and litter effect. No significant difference in cataract score existed between UV-exposed and ambient litters. Mortality was higher among pantethine-treated (hazard ratio = 1.8, p = 0.05) and UV-exposed animals (hazard ratio = 1.8, p = 0. 03) than among the untreated and unexposed litters. CONCLUSION: Significantly increased lens levels of pantethine are achieved with long-term intra-peritoneal dosing. The impact of pantethine on the progression of lenticular opacity in the Emory mouse is less than has been reported in other models. This level of chronic UVB exposure appeared to have no effect on the development of cataract in this model.

Animals↗
PubMed2000

Urine hyperglycosylated hCG plus ultrasound biometry for detection of down syndrome in the second trimester in a high-risk population.

OBJECTIVE: To evaluate measurement of levels of urine hyperglycosylated hCG, a form of hCG with abnormally branched oligosaccharide side chains, in conjunction with ultrasound biometry for Down syndrome risk prediction in an at-risk group. METHOD: We prospectively measured urine hyperglycosylated hCG levels, humeral length, and nuchal thickness in women who had second-trimester amniocentesis. Urine hyperglycosylated hCG levels were measured by a two-step enzyme-immunometric assay using monoclonal antibody beta152. Humeral length, nuchal thickness, and hyperglycosylated hCG values were expressed as multiples of the median, and the Down syndrome screening efficiency of the three analytes plus age was determined. A receiver operating characteristic (ROC) curve was generated, and the area under the curve was used to assess the Down syndrome screening performance of the algorithm. RESULTS: There were 23 cases of Down syndrome among 1016 singleton pregnancies. Mean gestational age (+/- standard deviation) was 16.1 +/- 1.2 weeks at the time of amniocentesis. Mean maternal age was 37.1 +/- 3.2 years. Biometry and measurement of hyperglycosylated hCG levels had a 91.3% detection rate at a 3.2% false-positive rate and a 100% detection rate at a 10.7% false-positive rate. The area under the ROC curve was 0.986 (P <.001), and that for measurement of hyperglycosylated hCG levels plus age was 0.941 (P <.001). The area under the curve was significantly larger with combined biochemical and biometry markers compared with measurement of hyperglycosylated hCG levels plus age alone (P <.02), proving that the former was superior to the latter. CONCLUSION: A new Down syndrome biochemical marker combined with ultrasound biometry had a high screening efficiency in a high-risk group. All cases of Down syndrome in this study population would have been detected at an amniocentesis rate of less than 10.7%. Our results appear superior to those found with other second-trimester algorithms. The combination is promising as an alternative to "automatic" genetic amniocentesis in women of advanced maternal age and other high-risk groups.

Adult↗
PubMed1999

Microtubules, but not actin microfilaments, regulate vacuole motility and morphology in hyphae of Pisolithus tinctorius.

While it is now recognised that transport within the endomembrane system may occur via membranous tubules, spatial regulation of this process is poorly understood. We have investigated the role of the cytoskeleton in regulating the motility and morphology of the motile vacuole system in hyphae of the fungus Pisolithus tinctorius by studying (1) the effects of anti-microtubule (oryzalin, nocodazole) and anti-actin drugs (cytochalasins, latrunculin) on vacuolar activity, monitored by fluorescence microscopy of living cells; and (2) the ultrastructural relationship of microtubules, actin microfilaments, and vacuoles in hyphae prepared by rapid-freezing and freeze-substitution. Anti-microtubule drugs reduced the tubular component of the vacuole system in a dose-dependent and reversible manner, the extent of which correlated strongly with the degree of disruption of the microtubule network (monitored by immunofluorescence microscopy). The highest doses of anti-microtubule drugs completely eliminated tubular vacuoles, and only spherical vacuoles were observed. In contrast, anti-actin drugs did not reduce the frequency of tubular vacuoles or the motility of these vacuoles, even though immunofluorescence microscopy confirmed perturbation of microfilament organisation. Electron microscopy showed that vacuoles were always accompanied by microtubules. Bundles of microtubules were found running in parallel along the length of tubular vacuoles and individual microtubules were often within one microtubule diameter of a vacuole membrane. Our results strongly support a role for microtubules, but not actin microfilaments, in the spatial regulation of vacuole motility and morphology in fungal hyphae.

Actin Cytoskeleton↗
PubMed1999

Following metastatic placental site trophoblastic tumor with urine beta-core fragment.

OBJECTIVE: We document a case with metastatic placental site trophoblastic tumor in a 47-year-old postmenopausal women. METHODS: beta-core fragment was measured in urine using the Triton UGP kit. hCG was also measured using the Bayer Immuno-1hCG assay (at Memorial Sloan-Kettering Cancer Center). RESULTS: Over 2 years the patient underwent two courses of chemotherapy and two debulking operations. During this time, hCG levels decreased from 227 to 4.1 mIU/ml. hCG levels were close to the limit of detection (<3 mIU/ml), indicating complete or near-complete regression of disease. At this point urine beta-core fragment levels were determined. High levels were detected 7.9 fmol/ml, consistent with the continued existence of tumor (>1.9 fmol/ml). High-dose chemotherapy (CEM) was started with stem cell harvesting. In the following weeks hCG levels failed to identify the tumor (4.1 to <3 mIU/ml). In the first week (during therapy) beta-core fragment levels increased (12 fmol/ml), and in the following weeks (after therapy) levels regressed to 1.2 fmol/ml. CONCLUSION: Urine beta-core fragment may be a useful tumor maker when serum hCG levels are near to or below the limit of detection.

Biomarkers, Tumor↗
PubMed1999

A high-sensitivity alternative to "routine" genetic amniocentesis: multiple urinary analytes, nuchal thickness, and age.

OBJECTIVE: Our purpose was to evaluate the Down syndrome screening efficiency of a new algorithm consisting of multiple urinary biochemical and ultrasound markers for use in high-risk groups such as women of advanced maternal age. STUDY DESIGN: The urinary beta-core fragment of human chorionic gonadotropin (beta-core fragment) and total urinary estriol, along with fetal nuchal thickness, were measured prospectively in pregnant women who were undergoing genetic amniocentesis at midtrimester (15 to 24 weeks). The most common indication for amniocentesis was advanced maternal age (90.2%). An analyte ratio (beta-core fragment/total estriol ratio) was developed. The values were expressed as multiples of the normal median. An increase in the observed nuchal thickness (delta nuchal thickness) above that expected on the basis of the biparietal diameter was calculated. On the basis of the mean and standard deviations of the urinary analyte ratio in normal fetuses and also Down syndrome, we calculated individual Down syndrome likelihood ratios for each of the two parameters, using gaussian analysis. The product of the likelihood ratios, based on delta nuchal thickness and urinary beta-core fragment-total estriol values times the maternal age-related risk, gave the overall Down syndrome risk. The screening efficiency of our algorithm at various risk thresholds was determined. RESULTS: There were 13 (2.8%) cases of Down syndrome in a total study population of 457. At a risk threshold of >1 in 70, the sensitivity was 92.3% for a false-positive rate of 4.5%. Corresponding values at a risk threshold of >1 in 78 were a sensitivity of 100% with a false-positive rate of 5.2%. CONCLUSION: By combining urinary analyte, nuchal thickness, and maternal age data, we achieved a high Down syndrome detection rate with a low false-positive rate. This algorithm would be attractive as an alternative to "routine" amniocentesis based solely on advanced maternal age. The potential benefits of this protocol could include a significant reduction in the rate of amniocentesis, along with substantial savings in medical expenditures.

Adult↗
PubMed1999

Nuchal thickness, urine beta-core fragment level, and maternal age for down syndrome screening.

OBJECTIVE: Our purpose was to report the midtrimester Down syndrome screening efficiency of a 2-analyte algorithm, urine beta-core fragment (a metabolite of human chorionic gonadotropin) and nuchal thickness, along with maternal age in a high-risk population undergoing genetic amniocentesis. METHOD: Nuchal thickness, humerus length, and maternal urine beta-core fragment levels were measured prospectively before genetic amniocentesis in 1360 singleton pregnancies, 21 (1.5%) of which had fetal Down syndrome. All analyte levels were expressed as multiples of the normal medians based on biparietal diameter. Backward-stepwise logistic regression was used to determine whether the markers were significant independent predictors of fetal Down syndrome. Matrix analysis was used to calculate an adjusted Down syndrome likelihood ratio for each patient based on the significant screening markers. Multiplication by age-related midtrimester risk gave the adjusted Down syndrome risk. The sensitivity and false-positive rates at different Down syndrome screening thresholds were used to generate a receiver-operator characteristics curve. The area under the curve was used to assess the value of this screening test. RESULTS: On the basis of logistic regression, beta-core fragment level (P 1/60 the sensitivity and false-positive rate for Down syndrome were 85.7% and 4.9%, respectively, when beta-core fragment level, nuchal thickness, and maternal age were used. Correspondence screening values at a risk threshold > 1/150 were 95.2% and 10.8%, respectively. The area under the receiver-operator characteristics curve was 0.9357 (SE = 0. 0137), indicating that the algorithm is excellent for Down syndrome screening. CONCLUSION: In this study, a combination algorithm consisting of nuchal thickness, urine beta-core fragment level, and maternal age had a high screening efficiency for Down syndrome. This algorithm should be investigated as a new option for women at high risk of having a fetus with Down syndrome.

Adolescent↗
PubMed1999

Elevated maternal urine level of beta-core fragment of human chorionic gonadotropin versus serum triple test in the second-trimester detection of down syndrome.

OBJECTIVE: This study was undertaken to compare the Down syndrome screening efficiency of elevated maternal urine level of the beta-core fragment of human chorionic gonadotropin with that of the traditional serum triple test. STUDY DESIGN: Urinary beta-core fragment and serum analyte levels were measured prospectively in women with singleton pregnancies who were undergoing second-trimester genetic amniocentesis. Urinary analyte levels were measured within a week of specimen collection. In some cases only alpha-fetoprotein was measured initially and human chorionic gonadotropin and unconjugated estriol levels were subsequently determined from the stored serum specimens. The Down syndrome screening efficiency of urinary concentration of beta-core fragment plus maternal age was compared with that of the traditional triple test. Receiver operating characteristic curves were generated for each algorithm and the areas under the curves were compared to determine which algorithm was superior. RESULTS: There were a total of 926 study patients, of whom 21 (2.3%) carried fetuses with Down syndrome. The mean (+/-SD) gestations at amniocentesis were 16.6 +/- 1.5 weeks for the fetuses without Down syndrome and 17.7 +/- 2.3 for the fetuses with Down syndrome. A total of 539 women (4 of whom carried fetuses with Down syndrome) had serum alpha-fetoprotein alone measured initially. Urinary concentration of beta-core fragment had a 61.9% detection rate with a 4.9% false-positive rate for Down syndrome, whereas the values for the triple screen were 57. 1% and 11.2%, respectively. The areas under the receiver-operating characteristic curves were 0.8744 for elevated urinary beta-core fragment level and 0.7504 for the triple screen (P =.1116). When the false-positive rate was fixed at an ideal threshold value (</=5%) the urine test was superior (area under the curve, 0.0212 vs 0.0133, P <.05). Similarly, when we considered only cases in which the complete triple screen was performed prospectively (17 fetuses with Down syndrome and 431 fetuses without Down syndrome), the urine test was significantly better (area under the curve, 0.873 vs 0.624, P =.012). CONCLUSION: In this first reported direct comparison we consistently observed higher sensitivity values for screening with urinary levels of beta-core fragment than for serum triple screen, suggesting an equivalent or superior Down syndrome screening performance for the urinary analyte. It is important that freezing and prolonged urine storage before testing be avoided. The reduced cost (single- versus triple-analyte testing) and excellent screening performance support large-scale testing and evaluation of maternal urinary beta-core fragment measurement as an alternative to the traditional serum triple test.

Adult↗
PubMed1999

Development and characterization of antibodies to a nicked and hyperglycosylated form of hCG from a choriocarcinoma patient: generation of antibodies that differentiate between pregnancy hCG and choriocarcinoma hCG.

Human chorionic gonadotropin (hCG) exists in blood and urine as a variety of isoforms one of which contains peptide bond cleavages within its beta-subunit loop 2 and is referred to as nicked hCG (hCGn). This hCG isoform appears to be more prevalent in the urine of patients with certain malignancies and possibly in some disorders of pregnancy. Until now, only indirect immunoassays could be used to quantify hCGn. We report the development of two monoclonal antibodies (MAbs) to a form of hCGn isolated from a choriocarcinoma patient. This hCG isoform was not only 100% nicked, but also contained 100% tetrasaccharide-core O-linked carbohydrate moieties in its beta COOH-terminal region. Two-site immunometric assays have been developed using these new antibodies, B151 and B152. The former exhibits good specificity for hCGn independent of the source of the hCGn, the form excreted by choriocarcinoma patients or the form of hCGn from normal pregnancies. The latter antibody, B152, is sensitive to the carbohydrate moieties and possibly other differences in hCG isoforms, but is not for nicking of the beta-subunit. These two immunometric assays provide potential novel diagnostic tools for direct measurement of hCG isoforms which could not be accurately quantified earlier before development of the assays using these newly generated antibodies.

Animals↗
PubMed1999

Early enteral feeding after surgery.

The GI tract is an important line of defense in the body's immunologic system. Without the proper care and treatment, this defense fails, rapidly increasing critically ill patients' susceptibility to added infections and system failures. Through the initiation of enteral nutrition, the GI tract can be preserved, and thus possible avoidance of some of the complications of critical illness may occur. A review of the research has demonstrated that the initiation of enteral nutrition in critically ill or postoperative patients is feasible and cost-effective. As more research is completed, the role of the GI tract in critical illness and measures to maintain its integrity will be identified. In the meantime, the initiation of enteral nutrition is an important initiative.

Cost-Benefit Analysis↗
PubMed1998

Structure, function, and motility of vacuoles in filamentous fungi

Current information on the structure and function of motile tubular vacuoles in Pisolithus tinctorius and other fungi is reviewed. The use of fluorochromes to label the vacuole lumen is evaluated and observations on the structure and motility of vacuoles in P. tinctorius are differentiated from possible artifacts. The styryl dyes FM4-64 and MDY-64, used in yeast to demonstrate endocytosis, show little or no labeling of internal membranes in undamaged P. tinctorius cells. This agrees with our data showing that other probes for endocytosis such as Lucifer yellow CH are not taken up by hyphal tip cells. Overall, the observations do not support endocytosis in hyphal tips. It has been suggested that tubular vacuole systems carry out longitudinal transport, and evidence in favor of this hypothesis is evaluated. New data are presented to show that many of the large vacuoles in subapical cells are attached to the plasma membrane and are relatively immobile, while video sequences show movement of fluorochrome in pulses along a series of several large vacuoles, all interconnected via tubules. Tubular vacuoles from thick sections of hyphae processed under anhydrous conditions are shown by X-ray microanalysis to contain relatively high levels of P and K, as seen previously in the larger vacuoles. These results provide further evidence for a role of the tubular vacuoles in longitudinal transport of P. Copyright 1998 Academic Press.

Journal Article↗