Adding risperidone to selective serotonin reuptake inhibitor improves chronic depression.
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Adult↗
Biomedical subjects
M O'Connor
Publications and source records attributed to M O'Connor.
Nasolacrimal intubation in adults.
BACKGROUND/AIMS: Silicone intubation has been shown to be successful in the management of epiphora in children. The effectiveness of this procedure was assessed in adults. METHODS: 70 eyes from 53 patients underwent nasolacrimal intubation. Mean age at intubation was 54.7 years. Mean follow up period was 15 months. The results were based on improvement of symptoms. RESULTS: Complete resolution of symptoms was reported in 54.3%. A partial improvement was reported in 14.3%, a transient improvement in 10%, and no improvement in 21.4%. A better outcome was associated with canalicular than with nasolacrimal obstructions (complete resolution of symptoms in 75.9% versus 25%). Only 17.1% have subsequently required dacryocystorhinostomies. CONCLUSION: Silicone intubation of the nasolacrimal system is a successful procedure in the management of adult epiphora.
Adolescent↗
Effects of low-dose morphine on gastric emptying in healthy volunteers.
Appropriate preoperative pain therapy for patients undergoing surgery may be withheld due to the fear that opioids will inhibit gastric emptying and increase the risk of aspiration. Previously, doses of 5 to 10 mg of morphine have been shown to delay gastric emptying time. However, the effect of lower doses of morphine on gastric emptying in humans has not been reported. In this study, the effects of intravenous morphine 0.05 mg/kg-3.5 mg for 70-kg body weight, a dose that can cause analgesia--on gastric emptying were evaluated in a double-blind, randomized, placebo-controlled study in 15 healthy human volunteers using the acetaminophen test. Our data indicated that this low dose of morphine significantly prolonged the gastric emptying time. Thus, even small doses of morphine inhibit gastric emptying. This effect may be important in patients undergoing surgery, in patients receiving other oral medications after surgery in ambulatory settings, and in instances of patient-controlled analgesia.
Acetaminophen↗
Technological medicine and the elderly.
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Aged↗
Genetic selection of rRNA mutations.
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Mutation↗
Do doctors benefit from their profession?--A survey of medical practitioners' health promotion and health safety practices.
Three hundred Irish Medical Organisation members were surveyed on health promotion and health and safety issues. 64.7% responded (65.3 males; 33.7% < thirty-five years). Over half (54.9%) were aware of the safety legislation and very few reported available occupational health services. A majority wanted more such services. Nearly all believed health promotion was important yet only 35.2% always availed of opportunities to give such advice. 36.3% were often stressed, particularly at work. Alcohol was sometimes or frequently used to cope by around half of respondents. Although less than half (47.7%) used whole milk, one third usually or always added salt to their food. 15.5% took no weekly aerobic exercise but 42.0% claimed to do so three times weekly. 11.4 were current smokers. A third of women had never had a cervical smear. We conclude doctors require adequate occupational health services.
Adult↗
MMPI/MMPI-2: comparisons of amnesic patients.
The amnesic population provides a unique opportunity to examine the reliability of clinical tests because amnesics do not consciously recollect initial testing sessions. In this study, amnesic subjects were studied to examine the reliability between the Minnesota Multiphasic Personality Inventory (MMPI) and the MMPI-2. Findings indicated that there were no statistical differences between versions of the MMPI and further revealed that many of the scales were significantly correlated. Amnesic patients produced elevated scores on subscales two (depression) and eight (schizophrenia), not unlike various other groups of neurologically impaired individuals. This indicates that MMPI and MMPI-2 scores in these patient populations may reflect the medical and psychosocial effects of brain damage rather than premorbid personality dysfunction. A close evaluation of amnesics' performance, in conjunction with the critical items they endorsed, offers insight into the personality traits of the amnesic patient population. The relative stability of performance across personality tests administered over several weeks is relevant to the formation and stability of the amnesic's concept of self.
Journal Article↗
Endothelial dysfunction in a rat model of endotoxic shock. Importance of the activation of poly (ADP-ribose) synthetase by peroxynitrite.
DNA single strand breakage and activation of the nuclear enzyme poly (ADP-ribose) synthetase (PARS) contribute to peroxynitrite-induced cellular injury. We investigated the role of PARS activation in the pathogenesis of endothelial dysfunction. In human umbilical vein endothelial cells (HUVEC), DNA strand breakage (alkaline unwinding assay), PARS activation (incorporation or radiolabeled NAD+ into proteins), mitochondrial respiration [conversion of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide to formazan] and apoptotic index (cytoplasmatic release of histones) were measured. Endotoxin shock was induced in rats by bacterial lipopolysaccharide. Vascular reactivity of thoracic aortic rings were measured in organ chambers. In HUVEC, peroxynitrite caused a dose-dependent suppression of mitochondrial respiration, induced DNA strand breakage and caused an activation of PARS. Pharmacological inhibition of PARS reduced the acute and delayed suppression of mitochondrial respiration when cells were exposed to intermediate, but not high doses of peroxynitrite. Similarly, protection against the intermediate, but not high doses of peroxynitrite was seen in fibroblasts from the PARS-/- mice, when compared to wild-type controls. These data suggest that PARS plays a role in peroxynitrite-induced cytotoxicity, but at very high levels of oxidant exposure, PARS-independent cytotoxic mechanisms become predominant. Peroxynitrite-induced apoptosis was not affected by PARS inhibition. Vascular rings exposed to peroxynitrite and rings taken from rats subjected to endotoxic shock exhibited reduced endothelium-dependent relaxant responses in response to acetylcholine. The development of this endothelial dysfunction was ameliorated by the PARS inhibitor 3-aminobenzamide. Activation of PARS by peroxynitrite, therefore, may be involved in the development of endothelial dysfunction in endotoxemia.
Animals↗
Endogenously produced peroxynitrite induces the oxidation of mitochondrial and nuclear proteins in immunostimulated macrophages.
Here we investigated the role of endogenous nitric oxide (NO) and peroxynitrite in the process of protein oxidation (as measured by the detection of 2,4-dinitrophenylhydrazine-reactive carbonyls) in immunostimulated macrophages. Immunostimulation of the macrophages by bacterial lipopolysaccharide and gamma-interferon (LPS/IFNgamma) resulted in a marked increase in the oxidation of a large number of mitochondrial and nuclear proteins. The inhibitor of NO synthase, N(G)-methyl-L-arginine (3 mM), and the cell-permeable superoxide dismutase mimetic Mn(III)tetrakis(4-benzoic acid)porphyrin (300 microM) both reduced the extent of protein oxidation in response to LPS/IFNgamma. These results support the view that endogenously produced peroxynitrite induces protein oxidation in the mitochondria and nucleus of immunostimulated macrophages.
Adjuvants, Immunologic↗
Decoding fidelity at the ribosomal A and P sites: influence of mutations in three different regions of the decoding domain in 16S rRNA.
The involvement of defined regions of Escherichia coli 16S rRNA in the fidelity of decoding has been examined by analyzing the effects of rRNA mutations on misreading errors at the ribosomal A and P sites. Mutations in the 1400-1500 region, the 530 loop and in the 1050/1200 region (helix 34) all caused readthrough of stop codons and frameshifting during elongation and stimulated initiation from non-AUG codons at the initiation of protein synthesis. These results indicate the involvement of all three regions of 16S rRNA in decoding functions at both the A and P sites. The functional similarity of all three mutant classes are consistent with close physical proximity of the 1400- 1500 region, the 530 loop and helix 34 and suggest that all three regions of rRNA comprise a decoding domain in the ribosome.
Amino Acid Sequence↗
Confabulation, memory deficits, and frontal dysfunction.
This paper explores potential cognitive deficits underlying confabulation of patient, G.S., following an anterior communication artery aneurysm. G.S.'s performance on tasks assessing memory for temporal duration, temporal order, and speaker identification is examined as is his recollection of autobiographical events. We compare G.S. with three nonconfabulating patients matched with him for age, education, and neuropsychological measures of memory and frontal deficits and with three age- and education-matched control subjects. Like frontal control patients, G.S. underestimated temporal durations and showed poor source monitoring (speaker identification). In addition, G.S. showed an even more pronounced deficit in recall of autobiographical memories and relatively more detailed reports of laboratory-induced memories for imagined events. We suggest that this configuration of deficits rather than any single factor accounts for G.S.'s tendency to confabulate.
Amnesia↗
Accelerated forgetting in association with temporal lobe epilepsy and paraneoplastic encephalitis.
The association between epilepsy and amnesia is studied in patient J.T. who presented with a very unusual pattern of memory loss with retention of information for hours to days but rapid forgetting of information that exceeded this time frame. J.T.'s unusual memory profile was studied with several tests administered over week-long intervals of time. There was evidence that his retention decreased in conjunction with increased seizures. During a trial of paraldehyde, a decrease in seizure frequency was associated with enhanced memory. J.T.'s memory problem was unlike that described in prototypical cases of amnesia. His day-long retention of new information alongside his absolute loss of that information days later is consistent with the idea that consolidation is a process that occurs over lengthy periods of time.
Adult↗
The role of the vasculature in regulating venous return and cardiac output: historical and graphical approach.
PURPOSE: To review the physiology of cardiac output regulation by the peripheral vasculature. This will enable the clinician to understand and manage the complex circulatory changes in various forms of shock, and in other common altered circulatory states encountered in anaesthetic practice. SOURCE: Articles were obtained from a Medline review (1966 to present; search terms: shock, venous return, cardiac output) and a hand search (Index Medicus). Other sources include review articles, personal files, and textbooks. PRINCIPAL FINDINGS: At steady state, cardiac output is equal to venous return (VR). Venous return depends on mean systemic pressure (PMS), which is the pressure in the peripheral vasculature driving blood flow to the heart, right atrial pressure (PRA), and the resistance to venous return (RV). When considering VR, PRA is the downstream pressure to VR, and not simply an indirect measure of the volume status. The pressure gradient for VR is, therefore, PMS-PRA, and in a system obeying Ohm's Law, [formula: see text] Shock and other altered circulatory states cause changes in both VR and cardiac function. The circulation can be conveniently described by a venous return and a cardiac output curve. By drawing these curves for each clinical situation, a clear understanding of the altered circulatory state is obtained, and treatment options can be clearly defined. CONCLUSION: The peripheral circulation controls cardiac output in many clinical conditions. Manipulation of the peripheral circulation is as important to the successful treatment of shock and other altered circulatory states, as is the manipulation of cardiac output.
Animals↗
The inhibitory effects of mercaptoalkylguanidines on cyclo-oxygenase activity.
1. It has been proposed that in inflammatory conditions, in which both the inducible isoforms of nitric oxide synthase (iNOS) and cyclo-oxygenase (COX-2) are induced, inhibition of NOS also results in inhibition of arachidonic acid metabolism. In the present study we have investigated whether mercaptoalkylguanidines, a novel class of selective iNOS inhibitors, may also influence the activity of cyclo-oxygenase (COX). Therefore, the effect of mercaptoethylguanidine (MEG) and related compounds on the activity of the constitutive (COX-1) and the inducible COX (COX-2) was investigated in cells and in purified enzymes. Aminoguanidine, NG-methyl-L-arginine (L-NMA) and NG-nitro-L-arginine methyl ester (L-NAME) were also studied for comparative purposes. 2. Western blot analysis demonstrated a significant COX-1 activity in unstimulated J774 macrophages and in unstimulated human umbilical vein endothelial cells (HUVEC). Immunostimulation of the J774 macrophages by endotoxin (lipopolysaccharide of E. coli, LPS 10 micrograms ml-1) and interferon gamma (IFN gamma, 100 u ml-1) for 6 h resulted in a significant induction of COX-2, and a down-regulation of COX-1. No COX-2 immunoreactivity was detected in unstimulated HUVEC or unstimulated J774 cells. Therefore, in subsequent studies, the effect of mercaptoalkylguanidines on COX-1 activity was studied in HUVEC stimulated with arachidonic acid for 6 h, and in J774 cells stimulated with arachidonic acid for 30 min. The effect of mercaptoalkylguanidines on COX-2 activity was studied in immunostimulated J774 macrophages, both on prostaglandin production by endogenous sources, and on prostaglandin production in response to exogenous arachidonic acid stimulation. In addition, the effect of mercaptoalkylguanidines on purified COX-1 and COX-2 activities was also studied. 3. In experiments designed to measure COX-1 activity in HUVEC, the cells were stimulated by arachidonic acid (15 microM) for 6 h. This treatment induced a significant production of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha, the stable metabolite of prostacyclin), while nitrite production was undetectable by the Griess reaction. MEG (1 microM to 3 mM) caused a dose-dependent inhibition of the accumulation of 6-keto-PGF1 alpha, with an IC50 of 20 microM. However, aminoguanidine, L-NAME or L-NMA (up to 3 mM) did not affect the production of 6-keto-PGF1 alpha in this experimental system. In experiments designed to measure COX-1 activity in J774.2 macrophages, the cells were stimulated by arachidonic acid (15 microM) for 30 min; this also induced a significant production of 6-keto-PGF1 alpha and MEG (1 microM to 3 mM), aminoguanidine (at 1 and 3 mM), but neither L-NAME nor L-NMA inhibited the production of prostaglandins. 4. In experiments designed to measure prostaglandin production by COX-2 with endogenous arachidonic acid, J774.2 cells were immunostimulated for 6 h in the absence or presence of various inhibitors. In experiments designed to measure prostaglandin production by COX-2 with exogenous arachidonic acid, J774.2 cells were immunostimulated for 6 h, followed by a replacement of the culture medium with fresh medium containing arachidonic acid and various inhibitors. Both of these treatments induced a significant production of 6-keto-PGF1 alpha. Nitrite production, an indicator of NOS activity, was moderately increased after immunostimulation. MEG (1 microM to 3 mM) caused a dose-dependent inhibition of the accumulation of COX metabolites. Similar inhibition of LPS-stimulated 6-keto PGF1 alpha production was shown by other mercaptoalkylguanidines (such as N-methyl-mercaptoethylguanidine, N,N'-dimethyl-mercaptoethylguanidine, S-methyl-mercaptoethylguanidine and guanidino-ethyldisulphide), with IC50 values ranging between 34-55 microM. However, aminoguanidine, L-NAME and L-NMA (up to 3 mM) did not affect the production of prostaglandins.5. In comparative experiments indomethacin, a non selective COX inhibitor, and NS-398, a selective COX-2 inhibitor, reduced (LPS) stimulated 6-keto-PGF1alpha production in J774 macrophages in a dose-dependent manner without affecting nitrite release. Indomethacin, but not NS-398, inhibited 6-keto-PGF1alpha production in the HUVECs. 6.The inhibitory effect of MEG was due to direct inhibition of the catalytic activity of COX as indicated in experiments with purified COX-1 and COX-2. MEG dose-dependently inhibited the purified COX-1 and COX-2 activity with IC50 values of 33microM and 36microM, respectively. Aminoguanidine (at the highest concentrations) inhibited the formation of COX-1 metabolites, without affecting COX-2 activity. High doses of L-NAME (3mM) decreased COX-1 activity only, while L-NMA (up to 3mM) had no effect on the activity of either enzyme. 7.These results suggest that MEG and related compounds are direct inhibitors of the constitutive and the inducible cyclo-oxygenases, in addition to their effects on the inducible NOS. The additional effect of mercaptoalkylguanidines on COX activity may contribute to the beneficial effects of these agents in inflammatory conditions where both iNOS and COX-2 are expressed.
6-Ketoprostaglandin F1 alpha↗
Role of peroxynitrite and activation of poly (ADP-ribose) synthase in the vascular failure induced by zymosan-activated plasma.
1. Zymosan is a wall component of the yeast Saccharomyces Cerevisiae. Injection of zymosan into experimental animals is known to produce an intense inflammatory response. Recent studies demonstrated that the zymosan-induced inflammatory response in vivo can be ameliorated by inhibitors of nitric oxide (NO) biosynthesis. The cytotoxic effects of NO are, in part, mediated by the oxidant preoxynitrite and subsequent activation of the nuclear enzyme poly (ADP-ribose) synthetase (PARS). In the present in vitro study, we have investigated the cellular mechanisms of vascular failure elicited by zymosan-activated plasma and the contribution of peroxynitrite production and activation of PARS to the changes. 2. Incubation of rat aortic smooth muscle cells with zymosan-activated plasma (ZAP) induced the production of nitrite, the breakdown product of NO, due to the expression of the inducible isoform of NO synthase (iNOS) over 6 24 h. In addition, ZAP triggered the production of peroxynitrite in these cells, as measured by the oxidation of the fluorescent dye dihydrorhodamine 123 and by nitrotyrosine Western blotting. 3. Incubation of the smooth muscle cells with ZAP induced DNA single strand breakage and PARS activation. These effects were reduced by inhibition of NOS with NG-methyl-L-arginine (L-NMA, 3 mM), and by glutathione (3 mM), a scavenger of peroxynitrite. The PARS inhibitor 3-aminobenzamide (1 mM) inhibited the ZAP-induced activation of PARS. 4. Incubation of thoracic aortae with ZAP in vitro caused a reduction of the contractions of the blood vessels to noradrenaline (vascular hyporeactivity) and elicited a reduced responsiveness to the endothelium-dependent vasodilator acetylcholine (endothelial dysfunction). 5. Preincubation of the thoracic aortae with L-NMA (1 mM), glutathione (3 mM) or by the PARS inhibitor 3-aminobenzamide (1 mM) prevented the development of vascular hyporeactivity in response to ZAP. Moreover, glutathione and 3-aminobenzamide treatment protected against the ZAP-induced development of endothelial dysfunction. The PARS-related loss of the vascular contractility was evident at 30 min after incubation in endothelium-intact, but not in endothelium-denuded vessels and also manifested at 6 h after incubation with ZAP in endothelium-denuded rings. The acute response is probably related, therefore, to peroxynitrite formation (involving the endothelial NO synthase), whereas the delayed response may be related to the expression of iNOS in the smooth muscle. 6. The data obtained suggest that zymosan-activated plasma causes vascular dysfunction by inducing the simultaneous formation of superoxide and NO. These radicals combine to form peroxynitrite, which, in turn causes DNA injury and PARS activation. The protective effect of 3-aminobenzamide demonstrates that PARS activation contributes both to the development of vascular hyporeactivity and endothelial dysfunction during the vascular failure induced by ZAP.
Animals↗
Analgesic effect of intra-articular bupivacaine or diamorphine after arthroscopic surgery of the knee joint in day-case patients.
A prospective, randomized, double-blind, controlled study was conducted to assess the efficacy of intra-articular bupivacaine and diamorphine. Ninety-six day-case patients were allocated randomly to receive intra-articular injections of either 20 mL 0.9% saline (control, n = 35), 20 mL 0.5% plain bupivacaine (n = 31), or 20 mL 0.9% saline with 5 mg diamorphine (n = 30) prior to tourniquet release. Visual analogue scales (VAS) were completed at 1 h, 3 h (discharge) and 24 h, and supplementary analgesia noted. Intra-articular analgesics conferred a noticeable improvement in patient comfort. First, the quantity of supplementary analgesia required prior to discharge was significantly reduced (P = 0.016); second, patients reported a less disturbed night's sleep (P = 0.034).
Adolescent↗
Ten-year survival of Down syndrome births.
OBJECTIVE: To determine the survival status of children with Down syndrome (DS), and to document factors influencing survival. DESIGN: Follow-up study of cases identified from the Dublin European Register of Congenital Anomalies and Twins (EUROCAT) Register. Follow-up was attempted for each case until death or 1992 or until the date last known to be alive. SETTING: Eastern Health Board, Dublin. SUBJECTS: In all, 389 DS children, born between 1 January 1980 and 31 December 1989 were followed up. RESULTS: Survival rates of 88% at one year and 82% at 10 years were found. There was a non-significant improvement in survival between the cohort born in 1980-1984 and that born in 1985-1989. Congenital heart defects reduced survival to 72% and complete atrio-ventricular canal defects (CAVD) had the poorest prognosis (58% survival at 10 years). Cases with CAVD showed a trend towards improved survival when surgically treated. Maternal age mother's county of residence, sex of infant, season of birth and presence of additional non-cardiac congenital anomalies had no impact on survival. CONCLUSIONS: Four out of five DS children now survive at least 10 years. Adequate educational and health service provision needs to be made for them, especially those with congenital heart defects. The need for studies which compare survival and quality of life in DS children with CAVD who undergo cardiac surgery versus those who do not, taking account of various selection factors, is identified.
Child↗
Pharmacokinetics and pharmacodynamics of propofol in a new solvent.
UNLABELLED: Pain on injection is the most commonly reported adverse event after propofol injection. In a randomized, cross-over study in two groups of 12 healthy male volunteers (24-42 yr), we compared the pharmacokinetics and pharmacodynamics of two new propofol formulations (1% and 2% concentrations) in a fat emulsion consisting of medium- and long-chain triglycerides with the standard propofol formulation. After a single intravenous bolus injection of 2 mg/kg, propofol blood levels were measured for 24 h and evaluated according to an open three-compartment model. The derived pharmacokinetic variables were not different among formulations. Additionally, electroencephalographic recordings of the onset and duration of hypnotic action were comparable with all formulations. After propofol 1% in the new formulation, fewer volunteers reported severe or moderate pain on injection (9%) than after the standard formulation (59%) (P < 0.05). We attribute this result to a lower concentration of free propofol in the aqueous phase of the new formulation. IMPLICATIONS: Changing the composition of the carrier fat emulsion for propofol does not have an impact on the pharmacokinetics and efficacy of propofol, but it promises to provide better patient acceptance by lowering the incidence of moderate and severe pain on injection.
Adult↗