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C Kelly

Publications and source records attributed to C Kelly.

At least 73 records · Page 4Linked to original sources
PubMed2000

Thermotolerance preserves endothelial vasomotor function during ischemia/reperfusion.

Ischemia/reperfusion (I/R) results in endothelial dysfunction, seen as loss of endothelium-dependent vasodilatation. In prolonged ischemia, this can result in marked vasospasm or no reflow in the microvasculature. Thermotolerance (T) attenuates I/R-induced microvascular injury. The aim of this study was to investigate the effect of thermotolerance on I/R-induced vasomotor changes and "no reflow." Sprague-Dawley rats were randomized into an ischemia/reperfusion group (I/R group) and a group in which thermotolerance (41 + 0.5 degrees C for 15 min 18 h prior to I/R) was induced (T + I/R group). IR injury was established by occlusion of the superior mesenteric and celiac vascular pedicle for 30 min, followed by 60 min of reperfusion. Vasomotor function [arteriolar constriction:dilatation (C:D) ratio] measured by response to acetylcholine (endothelium-dependent) and sodium nitroprusside (endothelium-independent) and "no-reflow" phenomenon were determined in mesenteric arterioles by intravital microscopy. Data are expressed as means +/- SEM and were analyzed using ANOVA and chi(2) test. I/R caused a significant decrease in endothelium-dependent vasodilatation (C:D = 1.37+/-0.31 in IR group vs. 2.06+/-0.20 in baseline, P<0.01) and no reflow in arterioles in 16 of 28 unheated rats. Endothelium-independent dilatation was not altered by I/R. Thermotolerance attenuated this impairment of endothelium-dependent dilatation (P<0.01 vs. IR; C:D = 1.95+/-0.19) and reduced no-reflow phenomenon to 4 of 16 rats (P<0.05 vs. IR). This study demonstrated that thermotolerance preserves endothelial vasomotor function and markedly reduces "no reflow" in arterioles.

Animals↗
PubMed2000

A combined subchronic (90-day) toxicity and neurotoxicity study of a single-cell source of docosahexaenoic acid triglyceride (DHASCO oil).

Docosahexaenoic acid (DHA), a 22-carbon long-chain polyunsaturated fatty acid of the omega-3 family, is a major structural component of neural membranes and is a particularly important nutrient during infant development. New safe and well-defined sources of DHA are required for infant formula fortification and dietary supplementation. DHASCO oil is an algal-derived triglyceride containing 40-50% DHA. Previous studies have shown that DHASCO oil is neither mutagenic nor toxic in acute or 28-day subchronic tests. To further establish the safety of this oil, a 90-day subchronic toxicity study in rats which included haematology, clinical chemistry, pathology and ophthalmologic, neurobehavioural and neuropathological assessments, using doses of 0.5 and 1.25g/kg body weight/day was performed. There were no treatment-related adverse effects in any of the parameters measured at either dose. Based on these results, the no-adverse-effect level (NOAEL) for DHASCO oil under the conditions of this study corresponds to the highest dose level. The DHA in the DHASCO oil was bioavailable, resulting in significant elevations in the levels of this fatty acid in liver, heart and brain after 90 days of administration. In conclusion, this 90-day subchronic toxicity study provides additional evidence that DHASCO oil is a safe and bioavailable source of dietary DHA.

Animals↗
PubMed2000

Biological effects of arginine metabolites.

Arginine and its metabolites exert physiological effects on the vasculature and on the kidney and also provide important influences on the regulation of cell proliferation. We summarize the known information regarding two major metabolites of arginine: (a) nitric oxide (NO) and (b) agmatine, decarboxylated arginine. Both agents appear to interact in producing vasodilation and increases in glomerular filtration rate (GFR) in the kidney. There is evidence for inter-regulation of arginine pathways in the sense that agmatine is capable of inhibiting inducible nitric oxide synthase (iNOS), the inflammatory NOS isoform. Both NO and agmatine influence cell proliferation via effects on polyamine synthesis. In addition, both NO and agmatine exert inhibitory effects on ornithine decarboxylase (ODC) and the putrescine transporter by significantly different mechanisms. Therefore, arginine and arginine metabolites exert both vascular regulatory functions and impact on the regulation of cell proliferation. Significant inter-regulation among arginine pathways occurs within the three metabolic major pathways within the cell: (1) nitric oxide synthase (2) arginase and ornithine decarboxylase, and (3) arginine decarboxylase.

Agmatine↗
PubMed2000

Trans-osseous passage of head and neck brachytherapy tubes.

Brachytherapy following surgical resection of head and neck malignancy is a useful adjunct if full dose external beam radiotherapy has been performed previously. Percutaneous tube placement has been described but accurate placement can be technically difficult in certain areas of the head and neck. A case report is presented of trans-osseous brachytherapy tube placement through the zygoma bone to allow for optimum surgical bed irradiation without kinking of the tubes. It is proposed that the trans-osseous placement is a useful technique when siting of the tubes is difficult.

Brachytherapy↗
PubMed2000

Streptococcus pneumoniae: bacteremia in an era of penicillin resistance.

BACKGROUND: The proportion of penicillin-resistant Streptococcus pneumoniae isolates and associated risk factors varies by geographic area in the United States. We conducted a retrospective study to determine the extent of penicillin-nonsusceptible S pneumoniae bacteremia and associated risk factors in a tertiary care medical center in San Diego. METHODS: Patients with S pneumoniae bacteremia at the University of California, San Diego Medical Center from September 15, 1991, through July 31, 1998, were identified by hospital-based computerized microbiology records. Hospital records included demographic information, patient data, and antibiotic prescription records for patients with bacteremia as a result of S pneumoniae. Univariate and multivariate analyses were used to determine risk factors for penicillin-nonsusceptible S pneumoniae bacteremia. RESULTS: Of 281 isolates of S pneumoniae identified, 192 (68%) were from hospitalized patients. After controlling for other factors, patients from 1 to 5 years of age (P = .01; odds ratio [OR] = 3.96; 95% CI, 1.50 to 10.44), 6 to 18 years of age (P =.04; OR = 6.42; 95% CI, 1.13 to 36.51), and HIV seropositive patients (P =.002; OR = 5.12; 95% CI, 1.83 to 14.32) were more likely to have penicillin-nonsusceptible S pneumoniae bacteremia. There was a significant increasing trend of penicillin-nonsusceptible S pneumoniae bacteremia from 14% in 1991 to 42% in 1998 (P = .001; OR = 1.42; 95% CI, 1.16 to 1.73); this included only 2 isolates that were highly resistant to penicillin. There was no increase in mortality in patients who had penicillin-nonsusceptible S pneumoniae bacteremia. CONCLUSION: With the increase in S pneumoniae resistance to penicillin, it is important to continue surveillance of infections caused by S pneumoniae. Hospital-based studies are useful for tracking epidemiologically important pathogens.

Adult↗
PubMed2000

A revisit on tests for homogeneity of the risk difference.

Lipsitz et al. (1998, Biometrics 54, 148-160) discussed testing the homogeneity of the risk difference for a series of 2 x 2 tables. They proposed and evaluated several weighted test statistics, including the commonly used weighted least squares test statistic. Here we suggest various important improvements on these test statistics. First, we propose using the one-sided analogues of the test procedures proposed by Lipsitz et al. because we should only reject the null hypothesis of homogeneity when the variation of the estimated risk differences between centers is large. Second, we generalize their study by redesigning the simulations to include the situations considered by Lipsitz et al. (1998) as special cases. Third, we consider a logarithmic transformation of the weighted least squares test statistic to improve the normal approximation of its sampling distribution. On the basis of Monte Carlo simulations, we note that, as long as the mean treatment group size per table is moderate or large (> or = 16), this simple test statistic, in conjunction with the commonly used adjustment procedure for sparse data, can be useful when the number of 2 x 2 tables is small or moderate (< or = 32). In these situations, in fact, we find that our proposed method generally outperforms all the statistics considered by Lipsitz et al. Finally, we include a general guideline about which test statistic should be used in a variety of situations.

Biometry↗
PubMed2000

Nithsdale Schizophrenia Surveys. 20. Cognitive function in a catchment-area-based population of patients with schizophrenia.

BACKGROUND: Cognitive deficits are a core aspect of schizophrenia but there has been no study of cognitive function in a catchment-area-based population of patients with schizophrenia. AIMS: To assess cognitive function in a population of patients with schizophrenia, and relate it to community functioning. METHOD: All patients with schizophrenia in Nithsdale, south-west Scotland, were identified (n = 182). Measures of assessment were: National Adult Reading Test (NART), Mini-Mental State Examination (MMSE), Rivermead Behavioural Memory Test (RBMT), Executive Interview (EXIT), FAS Verbal Fluency and Health of the Nation Outcome Scales (HoNOS). RESULTS: We assessed 138 patients, mean age 48 years (standard deviation (s.d.) 15). Only 14% were in-patients. The mean premorbid IQ as assessed by NART was 98 (s.d. 14); 15% of patients had significant global cognitive impairment (MMSE); 81% had impaired memory (RBMT); 25% had executive dyscontrol (EXIT); and 49% had impaired verbal fluency (FAS). Scores on the functional impairment sub-scale of HoNOS correlated with all measures of cognitive impairment. CONCLUSIONS: Cognitive dysfunction is pervasive in a community-based population of patients with schizophrenia.

Adult↗
PubMed2000

Maternally controlled (beta)-catenin-mediated signaling is required for organizer formation in the zebrafish.

We have identified and characterized a zebrafish recessive maternal effect mutant, ichabod, that results in severe anterior and dorsal defects during early development. The ichabod mutation is almost completely penetrant, but exhibits variable expressivity. All mutant embryos fail to form a normal embryonic shield; most fail to form a head and notochord and have excessive development of ventral tail fin tissue and blood. Abnormal dorsal patterning can first be observed at 3.5 hpf by the lack of nuclear accumulation of (beta)-catenin in the dorsal yolk syncytial layer, which also fails to express bozozok/dharma/nieuwkoid and znr2/ndr1/squint. At the onset of gastrulation, deficiencies in expression of dorsal markers and expansion of expression of markers of ventral tissues indicate a dramatic alteration of dorsoventral identity. Injection of (beta)-catenin RNA markedly dorsalized ichabod embryos and often completely rescued the phenotype, but no measurable dorsalization was obtained with RNAs encoding upstream Wnt pathway components. In contrast, dorsalization was obtained when RNAs encoding either Bozozok/Dharma/Nieuwkoid or Znr2/Ndr1/Squint were injected. Moreover, injection of (beta)-catenin RNA into ichabod embryos resulted in activation of expression of these two genes, which could also activate each other. RNA injection experiments strongly suggest that the component affected by the ichabod mutation acts on a step affecting (beta)-catenin nuclear localization that is independent of regulation of (beta)-catenin stability. This work demonstrates that a maternal gene controlling localization of (beta)-catenin in dorsal nuclei is necessary for dorsal yolk syncytial layer gene activity and formation of the organizer in the zebrafish.

Active Transport, Cell Nucleus↗
PubMed2000

Topley Online.

Explore the source record for details and available documents.

Humans↗
PubMed1999

NPY Y2 receptor agonist, N-acetyl [Leu28,Leu31]NPY24-36, reduces renal vasoconstrictor activity in anaesthetised dogs.

The actions of neuropeptide Y (NPY) at the autonomic neuroeffector junction have been attributed to two main receptor subtypes. At NPY Y1 receptors, located postsynaptically, NPY has been shown to produce vasoconstriction, or to potentiate the action of other vasoconstrictor agents. At NPY Y2 receptors, located presynaptically on nerve terminals, NPY inhibits the release of neurotransmitter from autonomic nerve terminals. In these experiments we have used the specific NPY Y2 receptor agonist, N-acetyl [Leu28,Leu31]NPY, which lacks local constrictor activity, and have demonstrated inhibition of nerve-evoked vasoconstriction in the renal circulation of anaesthetised dogs in a way that suggests an intra-renal regional specificity. Under control conditions stimulation of the renal sympathetic nerves over a range of frequencies (1-5 Hz) reduced renal vascular conductance and glomerular filtration rate (GFR). Following the injection of the selective NPY Y2 receptor agonist, N-acetyl [Leu28,Leu31]NPY24-36, nerve-evoked reductions in renal conductance were reduced by over 45%. At the lowest stimulation frequencies, reduced vasoconstrictor activity was associated with a marked increase in GFR in the presence N-acetyl [Leu28,Leu31]NPY24-36. At both higher levels of stimulation N-acetyl [Leu28,Leu31]NPY24-36 significantly inhibited vasoconstrictor activity and attenuated the nerve-evoked reductions in GFR. Full recovery of both variables was observed 20 min after N-acetyl [Leu28,Leu31]NPY24-36 injection. N-acetyl [Leu28,Leu31]NPY24-36 produced a similar inhibition of renal vasoconstrictor activity when the renal nerves were left intact and activated reflexly. These results suggest that NPY can act via NPY Y2 receptors to inhibit sympathetic vasoconstrictor activity in the renal circulation of dogs. On the basis of the demonstrated dissociation of effects on vascular conductance and GFR, we suggest that this might result from a preferential action of the NPY Y2 agonist on sympathetic nerves supplying the afferent arteriole of the kidney.

Anesthesia↗
PubMed1999

A note on interval estimation of kappa in a series of 2 x 2 tables.

When there are confounders in reliability studies, failing to stratify data to account for these confounding effects may produce a misleading estimate of the interrater agreement. In this paper, we focus discussion on interval estimation of kappa for measuring agreement between two raters with stratified data. Using Monte Carlo simulation, we compare four asymptotic interval estimators of kappa for stratified data: estimator (1), a weighted average of the stratum-specific kappa estimates with weights equal to the inverse of the estimated asymptotic variances of these estimates; the two estimators, (2) and (3), with use of the logarithmic and the square root transformations, respectively, and a principle similar as used in estimator (1); estimator (4), a weighted average of the stratum-specific kappa estimates with weights equal to stratum sizes. We find that while the coverage probability of the first three interval estimators (1)-(3) can often be less than the desired confidence level, the fourth interval estimator (4) consistently performs well in all the situations considered here. We further find that when the underlying kappa is moderate (0.30</=kappa</=0.50), we can substantially improve the performance of the first three estimators by using a point estimator recently proposed elsewhere for kappa in estimation of weights. Because interval estimator (4) outperforms the other three estimators in a variety of situations, we recommend this estimator for general use.

Computer Simulation↗
PubMed1999

Interleukin-4-dependent production of PPAR-gamma ligands in macrophages by 12/15-lipoxygenase.

The peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a ligand-dependent nuclear receptor that has been implicated in the modulation of critical aspects of development and homeostasis, including adipocyte differentiation, glucose metabolism and macrophage development and function. PPAR-gamma is activated by a range of synthetic and naturally occurring substances, including antidiabetic thiazolidinediones, polyunsaturated fatty acids, 15-deoxy-delta prostaglandin J2 and components of oxidized low-density lipoprotein, such as 13-hydroxyoctadecadienoic acid (13-HODE) and 15-hydroxyeicosatetraenoic acid (15-HETE). However, the identities of endogenous ligands for PPAR-gamma and their means of production in vivo have not been established. In monocytes and macrophages, 13-HODE and 15-HETE can be generated from linoleic and arachidonic acids, respectively, by a 12/15-lipoxygenase that is upregulated by the TH2-derived cytokine interleukin-4. Here we show that interleukin-4 also induces the expression of PPAR-gamma and provide evidence that the coordinate induction of PPAR-gamma and 12/15-lipoxygenase mediates interleukin-4-dependent transcription of the CD36 gene in macrophages. These findings reveal a physiological role of 12/15-lipoxygenase in the generation of endogenous ligands for PPAR-gamma, and suggest a paradigm for the regulation of nuclear receptor function by cytokines.

Animals↗
PubMed1999

Problem eating attitudes and behaviors in young children.

OBJECTIVE: The factor structure of the Children's Eating Attitudes Test (ChEAT) and the predictors of problem eating were examined in young boys and girls. METHODS: Two hundred and twenty eight children from Grades 2 and 4 completed questionnaires which examined problem eating attitudes and behaviors, body image, and self-concepts. RESULTS: Four factors were found for girls and boys. The girls' four factors, Dieting, Food Preoccupation, Social Pressure to Eat, and Restricting and Purging, corresponded closely to previous studies with older girls and women. Four different factors were found for the boys, Global Problems, Dieting versus Purging, Dieting and Food Preoccupation, and Emotional Eating. However, dieting behaviors in both girls and boys were predicted by poorer body image and in boys emotional concerns about eating were predicted by poorer body image and lower self-concepts. DISCUSSION: There is still relatively little research that has examined problem eating attitudes and behaviors of boys and men. As boys tend to report infrequent dieting, we may need to focus more on the emotional concerns about eating and becoming overweight as a potential indicator of eating problems in boys.

Attitude to Health↗
PubMed1999

Safe mobilization of normal progenitors in advanced chronic myeloid leukemia with intensive chemotherapy and granulocyte-colony stimulating factor.

Twenty-one patients with advanced chronic myeloid leukemia (late chronic phase (n = 8), accelerated phase (n = 11) and blast crisis (n = 2)) were treated with idarubicin, cytarabine, and etoposide followed by G-CSF and subsequent collection of peripheral blood progenitor cells in the early recovery phase. Treatment was reasonably well tolerated with no deaths or intensive care admissions. Despite the advanced phase of disease and heavy pretreatment with cytotoxics and interferon-alfa, 11 of 21 patients (52%) achieved a cytogenetic response. Of the nine major cytogenetic responses (complete (n = 3) and partial (n = 6)), seven achieved adequate progenitor collections for consideration for autologous transplantation. The only predictor of response was disease duration (P = 0.02). With a median follow-up of 1171 days from treatment it appears unlikely that G-CSF contributed to disease progression. Survival post-IcE was predicted by disease stage (P = 0.0001). Intensive chemotherapy followed by G-CSF allowed adequate yields of predominantly Philadelphia chromosome negative progenitor cells to be obtained from one-third of patients with advanced CML.

Adult↗
PubMed1999

Ethanol attenuates lactate production in hypoxic postnatal day 4 rat cerebella.

Ethanol consumption during pregnancy may lead to a low oxygen supply to the brain of the developing fetus. Such a reduction in the oxygen supply will result in changes in intra- and extracellular lactate production, which subsequently may lead to cytoplasmic acidosis, changes in cerebral metabolism, and eventually, cell death. We used a novel application of gas chromatography to measure lactate changes, on a global level, in the cerebellar tissue of postnatal day (PD) 4 and PD 10 rat pups following in vitro exposure of either hypoxia or hypoxia plus ethanol (hypoxia/ethanol). The results showed hypoxia-induced increases in lactate concentrations as a function of treatment time in both PD 4 and PD 10 cerebellar tissue. However, there was a differential response to the additional ethanol treatment between the two age groups assessed, with an attenuation of the time-dependent increase of lactate production following hypoxia treatment in PD 4 cerebellar tissue. The results also indicated that PD 4 cerebellar tissue had increased oxygen utilization when compared with PD 10 tissue exposed to the same conditions. The ethanol-induced reduction in lactate is hypothesized as being due to limitations in glucose transport and utilization under ethanol/hypoxia exposure. It is believed that such limitations in cellular function may initiate a sequence of events that produce at least some of the cerebellar neuronal loss reported in the fetal alcohol literature.

Age Factors↗
PubMed1999

The outcome of 26 patients with respiratory syncytial virus infection following allogeneic stem cell transplantation.

Respiratory syncytial virus (RSV) is known to cause acute lung injury in the immunocompromised host, especially recipients of bone marrow allografts. Specific prognostic factors for the development of severe life-threatening disease remain to be identified as does the optimum treatment of established disease. Over a 5-year period the incidence and outcome of RSV in BMT recipients was analysed retrospectively. Prognostic factors assessed included type of transplant, engraftment status at the time of infection, the presence of lower respiratory tract disease, viral genotype and treatment received. During the study period, 26 of 336 (6.3%) allogeneic stem-cell recipients were identified as having RSV. Five patients (19.2%) died as a direct result of RSV. One patient died secondary to an intracranial bleed with concomitant RSV. There were four patients with graft failure (two primary and two secondary) attributable to the presence of RSV, two of whom subsequently died of infections related to prolonged myelosuppression. The presence of lower respiratory tract infection and a poor overall outcome was the only statistically significant association. Unrelated donor transplants and AML as the underlying disease appeared to be associated with a poorer outcome. Engraftment status, viral genotype and RSV treatment received did not correlate with outcome. We conclude that future studies are required to identify early sensitive and reproducible prognostic factors of RSV in the immunocompromised host. The roles of intravenous and nebulised ribavirin need to be clarified by prospective controlled trials.

Adolescent↗