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T Donnelly

Publications and source records attributed to T Donnelly.

At least 19 recordsLinked to original sources
PubMed2004

Early-onset psychosis in youth with intellectual disability.

BACKGROUND: Accurate diagnosis of psychotic disorders may be very difficult in youth with intellectual disabilities. METHOD: The authors reviewed the assessment, treatment and follow-up of 21 youths with ID referred because of early onset of psychotic symptoms. RESULTS: Just over one half of the patients had a diagnosis of schizophrenia or schizoaffective disorder. One third of the sample carried the diagnosis of psychosis NOS (not otherwise specified). After careful review, five out of seven of these psychotic-like cases were assessed as non-psychotic. Patients with Psychosis NOS associated with moderate or severe ID had the worst outcome. CONCLUSION: This clinical review provides important information about the identification, diagnosis and outcome of psychotic symptoms in youth with low verbal abilities.

Adolescent↗
PubMed2003

Microbial mechanisms of carbon removal in subsurface flow wetlands.

The microbial mechanisms of carbon removal in subsurface flow wetlands were studied, in one wetland with plants and one without plants. Particular emphasis was given to the influence of plants in the treatment process. Wetlands without plants showed higher carbon removal than those with plants, 63% and 51%, respectively (p < 0.05). Molecular analysis of the bacterial diversity, growth rates and specific microbial activities showed that the two wetlands were different, especially towards the outlet of the two systems. Sulphate reducers and methanogens were found in both wetlands, and they are thought to be the main removers of soluble organic carbon in these two systems.

Biodegradation, Environmental↗
PubMed2001

Hydrogen isotope analysis of natural abundance and deuterium-enriched waters by reduction over chromium on-line to a dynamic dual inlet isotope-ratio mass spectrometer.

This paper describes the application of a simple chromium reduction furnace which can be interfaced with a dual inlet isotope-ratio mass spectrometer thus providing the capacity for cheap, fast, accurate and precise measurement of deltaD(V-SMOW) by dynamic mass spectrometry. Measurements are precise to the order of < or =0.5 per thousand. Mean 95% confidence intervals for the Vienna Standard Mean Ocean Water (V-SMOW) to Standard Light Antarctic Precipitation (SLAP) range are in the order of 2.5 per thousand and the system is linear over the range -428 to 23,000 per thousand. Memory effects do exist, but are small for natural abundance samples and can be minimised by careful planning of the analytical load.

Chromium↗
PubMed2001

Colour removal from a simulated dye wastewater using a two-phase anaerobic packed bed reactor.

In recent years, rapid technological advances in the textile and dyeing industry have yielded benefits to society but have also generated new and significant environmental problems. The treatment alternatives applicable for the removal of colour vary, depending upon the type of dye wastewater. A synthetic, simulated mixed dye waste (Basic Yellow 28, Basic Yellow 21, Basic Red 18.1, Basic Violet Red 16, Basic Red 46, Basic Blue 16, Basic Blue 41) representing a known waste from a fibre production factory, was investigated. The biological process of anaerobic digestion has been recognised as a simple and energy-efficient means of treating and stabilising a wide range of organic industrial wastewaters. This study sets out to demonstrate the effect of different loading rates, dye concentrations and hydraulic retention times (HRTs) on colour removal efficiency under mesophilic anaerobic conditions. The reactor was operated under mesophilic conditions at different organic loading rates (OLRs) and HRTs for nine months. The results of this study show that a 2-stage mesophilic anaerobic up-flow packed bed reactor can remove up to 90% of the colour from a mixed cationic dye containing 1000 mg/l of dye. Colour removal efficiency falls as the influent dye concentration increases, but rises with increased hydraulic retention time and increased organic loading. The primary colour removal mechanism was one of biosorption with subsequent biodegradation. Acetoclastic methanogens were moderately inhibited at low organic loading rates of 0.25 kg COD/m3 d, at which level, acidogenesis and acetogenesis appeared to be unaffected. Inhibition of acidogenesis became marked at higher OLRs (1 kg COD/m3 d) and when the HRT was reduced from 5 to 3 days.

Anaerobiosis↗
PubMed1999

Inhibition of advanced glycation endproduct formation by acetaldehyde: role in the cardioprotective effect of ethanol.

Epidemiological studies suggest that there is a beneficial effect of moderate ethanol consumption on the incidence of cardiovascular disease. Ethanol is metabolized to acetaldehyde, a two-carbon carbonyl compound that can react with nucleophiles to form covalent addition products. We have identified a biochemical modification produced by the reaction of acetaldehyde with protein-bound Amadori products. Amadori products typically arise from the nonenzymatic addition of reducing sugars (such as glucose) to protein amino groups and are the precursors to irreversibly bound, crosslinking moieties called advanced glycation endproducts, or AGEs. AGEs accumulate over time on plasma lipoproteins and vascular wall components and play an important role in the development of diabetes- and age-related cardiovascular disease. The attachment of acetaldehyde to a model Amadori product produces a chemically stabilized complex that cannot rearrange and progress to AGE formation. We tested the role of this reaction in preventing AGE formation in vivo by administering ethanol to diabetic rats, which normally exhibit increased AGE formation and high circulating levels of the hemoglobin Amadori product, HbA1c, and the hemoglobin AGE product, Hb-AGE. In this model study, diabetic rats fed an ethanol diet for 4 weeks showed a 52% decrease in Hb-AGE when compared with diabetic controls (P < 0.001). Circulating levels of HbA1c were unaffected by ethanol, pointing to the specificity of the acetaldehyde reaction for the post-Amadori, advanced glycation process. These data suggest a possible mechanism for the so-called "French paradox," (the cardioprotection conferred by moderate ethanol ingestion) and may offer new strategies for inhibiting advanced glycation.

Acetaldehyde↗
PubMed1999

Effect of repaglinide addition to metformin monotherapy on glycemic control in patients with type 2 diabetes.

OBJECTIVE: To compare the effect of repaglinide in combination with metformin with monotherapy of each drug on glycemic control in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 83 patients with type 2 diabetes who had inadequate glycemic control (HbA1c > 7.1%) when receiving the antidiabetic agent metformin were enrolled in this multicenter, double-blind trial. Subjects were randomized to continue with their prestudy dose of metformin (n = 27), to continue with their prestudy dose of metformin with the addition of repaglinide (n = 27), or to receive repaglinide alone (n = 29). For patients receiving repaglinide, the optimal dose was determined during a 4- to 8-week titration and continued for a 3-month maintenance period. RESULTS: In subjects receiving combined therapy, HbA1c was reduced by 1.4 +/- 0.2%, from 8.3 to 6.9% (P = 0.0016) and fasting plasma glucose by 2.2 mmol/l (P = 0.0003). No significant changes were observed in subjects treated with either repaglinide or metformin monotherapy in HbA1c (0.4 and 0.3% decrease, respectively) or fasting plasma glucose (0.5 mmol/l increase and 0.3 mmol/l decrease respectively). Subjects receiving repaglinide either alone or in combination with metformin, had an increase in fasting levels of insulin between baseline and the end of the trial of 4.04 +/- 1.56 and 4.23 +/- 1.50 mU/l, respectively (P < 0.02). Gastrointestinal adverse events were common in the metformin group. An increase in body weight occurred in the repaglinide and combined therapy groups (2.4 +/- 0.5 and 3.0 +/- 0.5 kg, respectively; P < 0.05). CONCLUSIONS: Combined metformin and repaglinide therapy resulted in superior glycemic control compared with repaglinide or metformin monotherapy in patients with type 2 diabetes whose glycemia had not been well controlled on metformin alone. Repaglinide monotherapy was as effective as metformin monotherapy.

Australia↗
PubMed1998

Meningitis following spinal anaesthesia - a coincidental infection?

We report a case of meningitis developing a number of days after a subarachnoid block for caesarean section. No organisms were grown but the clinical picture was suggestive of bacterial meningitis, the clinical course of which had been modified by the administration of antibiotics for presumed wound infection. The possible aetiology is discussed.

Journal Article↗
PubMed1998

Skin2--an in vitro human skin model: the correlation between in vivo and in vitro testing of surfactants.

The availability of an in vitro test system to replace animal testing of potential irritants is becoming more and more urgent especially in Europe as a consequence of the European Community Cosmetics Directive. To evaluate the ability of Advanced Tissue Sciences' (ATS) ZK1301 skin model to predict the skin irritation potential of surfactants, we performed a pilot validation study utilizing four different laboratories. The in vitro protocol was designed as a quantitative pre-screen for the clinical patch studies. Sixteen substances, representing various surfactant categories and ranges of irritation potential, were tested. The 3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay was used to quantitate viability in vitro. We documented the viability of tissues exposed to unknown substances for specific periods. The in vitro results were calculated as percent distilled water controls (DWC). The time required to reduce the viability of each tissue to 50% of the distilled water controls (T50) was compared to mean erythema and edema scores from the clinical studies by Pearson's correlation. The individual laboratories demonstrated coefficients of 0.72. The results indicated that the 30 min percent untreated control values best predicted the 24 h clinical patch scores. No statistically significant interlab variability was found. Only one false negative was seen when non/mild and moderate/severe irritant categories were assigned according to the in vitro scores. These results demonstrate that the skin2 in vitro test system may serve as a good screening method prior to clinical patch studies.

Adolescent↗
PubMed1998

MIF expression in the rat brain: implications for neuronal function.

BACKGROUND: The mediator known historically as macrophage migration inhibitory factor (MIF) has been identified recently as being released into the circulation by the anterior pituitary gland as a consequence of stress or during a systemic inflammatory response. Macrophages and T cells also secrete MIF, both in response to proinflammatory factors or upon stimulation with glucocorticoids. Once released, MIF "overrides" or counterregulates the immunosuppressive effects of steroids on cytokine production and immune cellular activation. To further investigate the biology of MIF and its role in the neuroendocrine system, we have studied the regional and cellular expression of MIF in brain tissue obtained from normal rats and rats administered LPS intracisternally. MATERIALS AND METHODS: Rat brain sections were analyzed by immunohistochemistry utilizing an affinity-purified, anti-MIF antibody raised to recombinant MIF, and by in situ hybridization using a digoxigenin-labeled, antisense MIF cRNA probe. The kinetics of MIF mRNA expression in brain were compared with that of IL-1, IL-6, and TNF-alpha by RT-PCR of total brain RNA. The cerebrospinal fluid content of MIF and TNF-alpha proteins was analyzed by Western blotting and ELISA. RESULTS: A strong baseline expression pattern for MIF was observed in neurons of the cortex, hypothalamus, hippocampus, cerebellum, and pons. By in situ hybridization, MIF mRNA was found predominantly in cell bodies whereas MIF protein was detected mostly within the terminal fields associated with neurons. There was a marked pattern of MIF immunoreactivity within the mossy fibers of the dentate gyrus and dendrites of the hippocampal CA3 field. These structures have been shown previously to be involved in glucocorticoid-induced tissue damage within the hippocampus, suggesting an association between MIF and targets of glucocorticoid action. The intracisternal injection of LPS increased MIF mRNA and protein expression in brain and MIF immunoreactivity was due in part to infiltrating monocytes/macrophages. MIF protein also was found to be rapidly released into the cerebrospinal fluid. This response corresponded with that of LPS-induced cytokine release and MIF mRNA expression increased in a distribution that colocalized in large part with that of TNF-alpha, IL-1 beta, and IL-6. CONCLUSION: The significant levels of baseline and inducible MIF expression in the brain and its regional association with glucocorticoid action underscore the importance of this mediator as a physiological regulator of the inflammatory stress response and further define its role within the neuroendocrine system.

Animals↗
PubMed1997

Migration inhibitory factor expression in experimentally induced endotoxemia.

Macrophage migration inhibitory factor (MIF) is an important constituent of the host response to stress and infection and is the first mediator that has been identified to be released from immune cells upon stimulation with glucocorticoids. MIF also has been shown to be secreted from the anterior pituitary gland, monocytes/macrophages, and T cells activated by various proinflammatory stimuli. Once released, MIF acts to counter-regulate the inhibitory effect of glucocorticoids on inflammatory cytokine production. To characterize more precisely the role of MIF in the host response to infection, we undertook a systematic analysis of MIF expression in various organs of the rat after endotoxin (lipopolysaccharide) administration. MIF protein and mRNA were analyzed by immunohistochemistry and in situ hybridization, respectively. MIF was found to be expressed constitutively in organs such as the lung, liver, kidney, spleen, adrenal gland, and skin. Significant quantities of MIF protein were detected preformed in various cell types and appeared to be released as a consequence of endotoxemia. In virtually all tissues examined, the loss of MIF protein 6 hours after lipopolysaccharide administration was accompanied by the induction of MIF mRNA and, at 24 hours, by the restoration of immunoreactive, intracellular MIF. The constitutive production of MIF by several cell and tissue types together with its rapid release from intracellular pools distinguishes MIF from other cytokines or hormonal mediators and significantly expands the physiological role of this unique counter-regulator of glucocorticoid action.

Adrenal Glands↗
PubMed1997

Immunocytochemical localization of macrophage migration inhibitory factor in human hypophysis and pituitary adenomas.

OBJECTIVE: To establish the presence of macrophage migration inhibitory factor (MIF) in human nontumorous and adenomatous pituitaries. DESIGN, SETTING, AND PATIENTS: Macrophage migration inhibitory factor was demonstrated by immunocytochemistry on paraffin sections with a polyclonal antirecombinant murine MIF using the streptavidin-biotin-peroxidase complex method. Nontumorous hypophyses (14 cases) obtained from autopsy and 54 surgically removed pituitary adenomas were studied. In nontumorous pituitaries, serial sections were immunostained for both pituitary hormones and MIF. RESULTS: Macrophage migration inhibitory factor was localized in all corticotrophs, including basophils extending into the posterior lobe, Crooke's cells, and a few thyrotrophs. The posterior lobe was immunonegative for MIF. Densely (five cases) and sparsely (six cases) granulated somatotroph and lactotroph (six cases) adenomas lacked MIF immunostaining. Macrophage migration inhibitory factor was found in 3 of 4 thyrotroph adenomas, 3 of 6 gonadotroph adenomas, 10 of 11 functioning corticotroph and 8 of 10 silent corticotroph adenomas, 3 of 3 null cell adenomas, and 3 of 3 oncocytic adenomas. The immunopositivity was diffuse or focal, and the intensity was variable. CONCLUSIONS: This study is the first to demonstrate the presence of MIF in human nontumorous and adenomatous pituitaries using an immunocytochemical staining technique.

Adenoma↗
PubMed1996

An essential regulatory role for macrophage migration inhibitory factor in T-cell activation.

The protein known as macrophage migration inhibitory factor (MIF) was one of the first cytokines to be discovered and was described 30 years ago to be a T-cell-derived factor that inhibited the random migration of macrophages in vitro. A much broader role for MIF has emerged recently as a result of studies that have demonstrated it to be released from the anterior pituitary gland in vivo. MIF also is the first protein that has been identified to be secreted from monocytes/macrophages upon glucocorticoid stimulation. Once released, MIF acts to "override" or counter-regulate the suppressive effects of glucocorticoids on macrophage cytokine production. We report herein that MIF plays an important regulatory role in the activation of T cells induced by mitogenic or antigenic stimuli. Activated T cells produce MIF and neutralizing anti-MIF antibodies inhibit T-cell proliferation and interleukin 2 production in vitro, and suppress antigen-driven T-cell activation and antibody production in vivo. T cells also release MIF in response to glucocorticoid stimulation and MIF acts to override glucocorticoid inhibition of T-cell proliferation and interleukin 2 and interferon gamma production. These studies indicate that MIF acts in concert with glucocorticoids to control T-cell activation and assign a previously unsuspected but critical role for MIF in antigen-specific immune responses.

Animals↗
PubMed1996

Prevention of cardiovascular and renal pathology of aging by the advanced glycation inhibitor aminoguanidine.

Human aging is impacted severely by cardiovascular disease and significantly but less overtly by renal dysfunction. Advanced glycation endproducts (AGEs) have been linked to tissue damage in diabetes and aging, and the AGE inhibitor aminoguanidine (AG) has been shown to inhibit renal and vascular pathology in diabetic animals. In the present study, the effects of AG on aging-related renal and vascular changes and AGE accumulation were studied in nondiabetic female Sprague-Dawley (S-D) and Fischer 344 (F344) rats treated with AG (0.1% in drinking water) for 18 mo. Significant increases in the AGE content in aged cardiac (P < 0.05), aortic (P < 0.005), and renal (P < 0.05) tissues were prevented by AG treatment (P < 0.05 for each tissue). A marked age-linked vasodilatory impairment in response to acetylcholine and nitroglycerine was prevented by AG treatment (P < 0.005), as was an age-related cardiac hypertrophy evident in both strains (P < 0.05). While creatinine clearance was unaffected by aging in these studies, the AGE/ creatinine clearance ratio declined 3-fold in old rats vs. young rats (S-D, P < 0.05; F344, P < 0.01), while it declined significantly less in AG-treated old rats (P < 0.05). In S-D but not in F344 rats, a significant (P < 0.05) age-linked 24% nephron loss was completely prevented by AG treatment, and glomerular sclerosis was markedly suppressed (P < 0.01). Age-related albuminuria and proteinuria were markedly inhibited by AG in both strains (S-D, P < 0.01; F344, P < 0.01). These data suggest that early interference with AGE accumulation by AG treatment may impart significant protection against the progressive cardiovascular and renal decline afflicting the last decades of life.

Acetylcholine↗
PubMed1996

An essential role for macrophage migration inhibitory factor in the tuberculin delayed-type hypersensitivity reaction.

30 years ago, investigations into the molecular basis of the delayed-type hypersensitivity reaction (DTH) provided evidence for the first lymphokine activity: a lymphocyte-derived mediator called macrophage migration inhibitory factor (MIF), which inhibited the random migration of peritoneal macrophages. Despite the long-standing association of MIF with the DTH reaction and the cloning of a human protein with macrophage migration inhibitory activity, the precise role of MIF in this classic cell-mediated immune response has remained undefined. This situation has been further complicated by the fact that two other cytokines, interferon gamma and IL-4, similarly inhibit macrophage migration and by the identification of mitogenic contaminants in some preparations of cloned human MIF. Using recently developed molecular probes for mouse MIF, we have examined the role of this protein in a classical model of DTH, the tuberculin reaction in mice. Both MIF messenger RNA and protein were expressed prominently in DTH lesions, as assessed by reverse transcription polymerase chain reaction, in situ hybridization, and immunostaining with anti-MIF antibody. The predominant cellular origin of MIF appeared to be the monocyte/macrophage, a cell type identified recently to be a major source of MIF release in vivo. The administration of neutralizing anti-MIF antibodies to mice inhibited significantly the development of DTH, thus affirming the central role of MIF in this classic immunological response.

Animals↗