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Biomedical subjects

M O'Connor

Publications and source records attributed to M O'Connor.

At least 127 records · Page 7Linked to original sources
PubMed1996

A comparison of retrospective versus contemporaneous nausea scores with patient-controlled analgesia.

In the search for an effective method of reducing the incidence of postoperative nausea, a standardised system of patient assessment is required. We examined 76 patients who had undergone elective total abdominal hysterectomy and were receiving patient-controlled analgesia with morphine. Nausea scores were obtained using an 11-point rating score. Repeated contemporaneous assessments were compared with a single retrospective score made 5 days after surgery. Retrospective nausea scores were higher than those recorded contemporaneously. Maximum contemporaneous score showed greater agreement with the retrospective score than did the median, mean, or minimum contemporaneous score. Collectively, these results suggest that patients tend to remember their episodes of nausea vividly, even if these episodes were punctuated by relatively nausea-free periods. The variability between the two sets of results suggests that contemporaneous and retrospective nausea scores should not be used interchangeably.

Adult↗
PubMed1996

Antiemetic efficacy of ondansetron with patient-controlled analgesia.

A double-blind, randomised, placebo-controlled study was performed to assess the antiemetic efficacy of ondansetron in women receiving morphine from a patient-controlled analgesia system after total abdominal hysterectomy. Sixty-six ASA grade 1 or 2 patients scheduled for total abdominal hysterectomy were randomly allocated into one of two groups. All patients received a standardised anaesthetic and postoperative patient-controlled analgesia regimen. Group 1 received ondansetron 4 mg at induction of anaesthesia, repeated 8 h later. Group 2 received saline as a placebo at the same times. Pain scores, nausea scores, episodes of vomiting, use of rescue antiemetics and recollection of nausea and vomiting were not different between the groups. Only 15% of patients who received ondansetron and 30% of patients who received the placebo recorded no nausea or vomiting in the first 24 h. We conclude that ondansetron, in the dose studied, does not reduce nausea and vomiting in women receiving morphine from a patient-controlled analgesia system after total abdominal hysterectomy.

Adult↗
PubMed1996

Spontaneous rearrangement of aminoalkylisothioureas into mercaptoalkylguanidines, a novel class of nitric oxide synthase inhibitors with selectivity towards the inducible isoform.

1. The generation of nitric oxide (NO) from L-arginine by NO synthases (NOS) can be inhibited by guanidines, amidines and S-alkylisothioureas. Unlike most L-arginine based inhibitors, however, some guanidines and S-alkylisothioureas, in particular aminoethylisothiourea (AETU), show selectivity towards the inducible isoform (iNOS) over the constitutive isoforms (endothelial, ecNOS and brain isoform, bNOS) and so may be of therapeutic benefit. In the present study we have investigated the effects of AETU and other aminoalkylisothioureas on the activities of iNOS, ecNOS and bNOS. 2. AETU, aminopropylisothiourea (APTU) and their derivatives containing alkyl substituents on one of the amidino nitrogens, potently inhibit nitrite formation by immunostimulated J774 macrophages (a model of iNOS activity) with EC50 values ranging from 6-30 microM (EC50 values for NG-methyl-L-arginine (L-NMA) and NG-nitro-L-arginine were 159 and > 1000 microM, respectively). The inhibitory effects of these aminoalkylisothioureas (AATUs) were attentuated by L-arginine in the incubation medium, indicating that these agents may complete with L-arginine for its binding site on NOS. 3. The above AATUs undergo chemical conversion in neutral or basic solution (pH 7 or above) as indicated by (1) the disappearance of AATUs from solution as measured by h.p.l.c., (2) the generation of free thiols not previously present and (3) the isolation of species (as picrate and flavianate salts) from neutral or basic solutions of AATUs that are different from those obtained from acid solutions. 4. Mercaptoalkylguanidines (MAGs) were prepared and shown to be potent inhibitors of iNOS activity with EC50s comparable to those of their isomeric AATUs. 5. These findings suggest that certain AATUs exert their potent inhibitory effects through intramolecular rearrangement to mercaptoalkylguanidines (MAGs) at physiological pH. Those AATUs not capable of such rearrangement do not exhibit the same degree of inhibition of iNOS. 6. In contrast to their potent effects on iNOS, some AATUs and MAGs were 20-100 times weaker than NG-methyl-L-arginine and NG-nitro-L-arginine as inhibitors of ecNOS as assessed by their effects on the conversion of L-arginine to L-citrulline in homogenates of bovine endothelial cells and by their pressor effects in anaesthetized rats. Thus mercaptoalkylguanidines represent a new class of NOS inhibitors with preference towards iNOS. 7. AETU and mercaptoethylguanidine (MEG), when given as infusions, gave slight decreases in MAP in control rats. However, infusions of AETU or MEG to endotoxin-treated rats caused an increase in MAP and restored 80% of the endotoxin-induced fall in MAP. 8. High doses of MEG (30-60 mg kg-1) caused a decrease in MAP of normal rats. This depressor effect may be a consequence of the in vivo oxidation of MEG to the disulphide, guanidinoethyldisulphide (GED), which caused pronounced, transient hypotensive responses in anaesthetized rats and caused endothelium-independent vasodilator responses in precontracted rat aortic rings in vitro. 9. In some cases, slight differences were observed in the activities of AATUs and the corresponding MAGs. These may be explained by the formation of other species from AATUs in physiological media. For example, AETU can give rise to small amounts of the potent ecNOS inhibitor, 2-aminothiazoline, in addition to MEG. This may account for the differences in the in vitro and in vivo effects of AETU and MEG. 10. In conclusion, the in vitro and in vivo effects of AETU and related aminoalkylisothioureas can be explained in terms of their intramolecular rearrangement to generate mercaptoalkylguanidines, a novel class of selective inhibitors of iNOS.

Animals↗
PubMed1996

Infection of primary human microglia and monocyte-derived macrophages with human immunodeficiency virus type 1 isolates: evidence of differential tropism.

To ascertain whether viruses present at the time of primary viremia can infect the central nervous system and to determine if microglial tropism is distinct from tropism for monocyte-derived macrophages (MDM), 27 human immunodeficiency virus type 1 (HIV-1) isolates obtained from acutely infected individuals, as well as laboratory strains, were assayed for their ability to replicate in primary adult microglial cultures and in MDM. Most of the isolates replicated equally well in both microglia and MDM, but several isolates replicated preferentially in one of the two cell types, differing by as much as 40-fold in p24gag production. This indicated that while MDM and microglial tropism overlap, a subset of isolates is particularly tropic for one of the two cell types. One isolate was further adapted to microglia by 15 sequential passages, raising the peak p24 concentration produced by 1,000-fold. In addition, the passaged virus induced marked cytopathologic changes (vacuolization and syncytium formation) in infected microglial cultures. Sequence comparison of the V3 loop of unpassaged and multiply passaged virus revealed amino acid changes shown to be associated with isolates from patients with HIV dementia. Our data support the hypothesis that HIV-1 infection can be established in the central nervous system by viruses present early in HIV infection, that some of these viruses are particularly tropic for microglia, and that adaptation in this cell type can result in the selection of a pool of predominantly microglia-tropic (neurotropic) viruses.

Adult↗
PubMed1996

Induction and activity of nitric oxide synthase in cultured human intestinal epithelial monolayers.

We have examined the induction and activity of inducible nitric oxide (NO) synthase (iNOS) in monolayers of DLD-1 cells, an epithelial cell line derived from a human intestinal adenocarcinoma. Induction of iNOS transcription?by a combination of the cytokines interferon-gamma and IL-1 beta was inhibited by genistein, pyrrolidine dithiocarbamate, or dexamethasone and unaffected by pretreatment with ethylene glycol-bis(beta-aminoethyl ether)-N, N,N',N'-tetraacetic acid, basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), or the isoflavone daidzein. iNOS activity and NO synthesis were inhibited by nitro-L-arginine methyl ester, NG-monomethyl-L-arginine, S-methyl-isothiourea sulfate, or aminoethyl-isothiourea, but not by dexamethasone. NO synthesis was potently inhibited by N-alpha-p-tosyl-lysine chloromethyl ketone and hypoxia. In the absence of cytokines no iNOS induction was observed with oxidant stress (H2O2), growth factors (bFGF, EGF), hypoxia or hypoxia reoxygenation. We conclude that in this model of the human intestinal epithelium 1) cytokine-mediated induction of iNOS is Ca2+ independent, weakly steroid sensitive, and may involve the activation of nuclear factor-kappa B and a tyrosine kinase, and 2) iNOS activity is Ca2+ -independent and inhibited by hypoxia, NG-substituted L-arginine analogues, and isothioureas.

Enzyme Induction↗
PubMed1996

Noninvasive perfusion MRI in Alzheimer's disease: a preliminary report.

We performed functional MRI using the echo-planar imaging and signal targeting with alternating radio frequency (EPISTAR) technique in 11 patients with Alzheimer's disease (AD) and 8 age-matched control subjects. Seven of the AD patients had qualitatively apparent focal areas of hypoperfusion in the posterior temporoparietal-occipital regions. At the earliest inversion time producing cortical enhancement, the ratios of parieto-occipital and temporo-occipital to whole slice signal intensity were significantly lower in the AD patients than in the controls. Parieto-occipital hypoperfusion correlated with dementia severity as measured by the Blessed Dementia Scale. EPISTAR may prove to be a rapid, noninvasive alternative to other functional neuroimaging modalities in the evaluation of patients with dementia.

Aged↗
PubMed1996

The latex dilemma: an actual case.

Health care institutions across the country are dealing with a relatively new phenomenon: staff sensitivity to latex. This article presents the issues involved through an actual case and the response of one institution.

Adult↗
PubMed1996

Influence of teaching on the triage of multiple injury patients.

Attempts to improve the standard of early trauma management through the training and instruction of medical personnel have had variable results. Knowledge of trauma care is inadequate among all grades of medical and paramedical staff, and not much improvement has been made by the availability of instruction courses in trauma management. Staff most likely to attend such courses are seemingly already more proficient than staff who choose not to. To achieve maximum benefit from future courses, therefore, we believe attendance should be compulsory for all personnel involved in acute trauma care.

Case-Control Studies↗
PubMed1995

The involvement of two distinct regions of 23 S ribosomal RNA in tRNA selection.

The role of ribosomal RNA in maintaining the accuracy of translation has been investigated genetically by selecting for rRNA mutations that promoted frameshifting at a specific site in a reporter gene in Escherichia coli. Mutations were recovered in two different regions of 23 S rRNA and each promoted readthrough of stop codons as well as increasing the levels of frameshifting. The first group of mutations was in a small stem loop (the 1916 loop) in domain IV of 23 S rRNA. This stem-loop has been mapped to the subunit interface of the ribosome, close to the decoding center on the 30 S subunit. The second group of mutations was in helix 89, one of the helices emerging from the central loop of domain V. Helix 89 has been implicated in subunit-subunit interactions and peptidyltransferase activity, and it is proposed that mutations in helix 89 influence the accuracy of decoding by affecting the interaction of the CCA end of the tRNA with the peptidyltransferase center.

Base Sequence↗
PubMed1995

Oct-1 activates the epithelial-specific enhancer of human papillomavirus type 16 via a synergistic interaction with NFI at a conserved composite regulatory element.

A highly conserved composite regulatory element in the epithelial-specific enhancer of human papillomaviruses (HPVs) consists of an octamer motif separated by exactly 2 bp from a nonpalindromic NFI site. Point mutations within this composite element, created to prevent the binding of Oct-1 or NFI, result in up to 10- to 12-fold decrease in enhancer activity. A mutation preventing the binding of both proteins does not, however, result in any further decrease in activity suggesting a cooperative interaction between these two factors. Electrophoretic mobility shift assays provide evidence that the simultaneous binding of both factors to the composite element is indeed required for efficient activation. Furthermore, evidence demonstrating the inability of Oct-1 by itself to elicit a transcriptional response from this enhancer position suggests that Oct-1 does not activate transcription directly, but rather may play a crucial role in the viral enhancer by tethering NF1 to the composite element. This finding represents both a potentially important mechanism by which HPV gene expression can be regulated and an interesting model for the study of transcriptional cooperativity.

Base Sequence↗
PubMed1995

In vitro evidence for a dual role of tumor necrosis factor-alpha in human immunodeficiency virus type 1 encephalopathy.

Microglial cell activation, myelin alteration, and abundant tumor necrosis factor (TNF)-alpha message have been observed in the brains of some human immunodeficiency virus type 1 (HIV-1)-infected and demented patients. We therefore used cultures of purified human microglia and oligodendrocytes derived from adult human brain to examine the role of TNF-alpha in HIV-1 encephalopathy. Human microglia synthesize TNF-alpha message and protein in vitro. When these cells were infected with HIV-1 JrFL and maintained in the presence of TNF-alpha antibodies, soluble TNF-alpha receptors, or the TNF-alpha inhibitor pentoxifylline, viral replication was delayed or strongly inhibited. Both human microglia and oligodendrocytes express the two TNF receptors, TNF-R1, which has been implicated in cytotoxicity, and TNF-R2. While TNF-alpha may enhance HIV-1 replication in an autocrine manner, it is not toxic for microglia. In contrast, recombinant human TNF-alpha causes oligodendrocyte death in a dose-dependent manner. In situ detection of DNA fragmentation in some cells indicated that oligodendrocyte death may occur by apoptosis. Addition of live microglia or medium conditioned by these cells also resulted in 30 to 40% oligodendrocyte death, which was largely prevented by TNF-alpha inhibitors. We propose that TNF-alpha plays a dual role in HIV-1 encephalopathy, enhancing viral replication by activated microglia and damaging oligodendrocytes. Thus, TNF-alpha inhibitors may alleviate some of the neurological manifestations of acquired immunodeficiency syndrome.

AIDS Dementia Complex↗
PubMed1995

Is follow-up of lung cancer patients after resection medically indicated and cost-effective?

BACKGROUND: There are no guidelines for the appropriate follow-up of patients after pulmonary resection for lung cancer. METHODS: Three-hundred fifty-eight consecutive patients who had undergone complete resections of non-small cell lung cancer between 1987 and 1991 were evaluated for tumor recurrence and development of second primary tumors. Recurrences were categorized by site (local or distant), mode of presentation (symptomatic or asymptomatic), treatment given (curative intent or palliative), and duration of overall survival. RESULTS: Recurrences developed in 135 patients (local only, 32; local and distant, 13; and distant only, 90). Of these, 102 were symptomatic and 33 were asymptomatic (most diagnosed by screening chest roentgenogram). Forty patients received treatment with curative intent (operation or radiation therapy > 50 Gy) and 95 were treated palliatively. The median survival duration from time of recurrence was 8.0 months for symptomatic patients and 16.6 months for asymptomatic patients (p = 0.008). Multivariate analysis shows that disease-free interval (greater than 12 months or less than or equal to 12 months) was the most important variable in predicting survival after recurrence and that mode of presentation, site of recurrence, initial stage, and histologic type did not significantly affect survival. New primary tumors developed in 35 patients. CONCLUSIONS: Although detection of asymptomatic recurrences gives a lead time bias of 8 to 10 months, mode of treatment and overall survival duration are not greatly affected by this earlier detection. Disease-free interval appears to be the most important determinant of survival. Screening for asymptomatic recurrences in patients who have had lung cancer is unlikely to be cost-effective. Frequent follow-up and extensive radiologic evaluation of patients after operation for lung cancer are probably unnecessary.

Adult↗
PubMed1995

The perceived relationship between neck symptoms and precedent injury.

A questionnaire survey of 328 hospital employees was used to establish the general prevalence of neck symptoms related to everyday activities in a representative population of working society. The response rate was 92 per cent. Of the study population of 302, 54 had suffered neck injury, and of this group, 43 (80 per cent) had some neck discomfort during or after performing normal everyday tasks. Of the symptomatic cases, only seven (16 per cent) admitted that they had suffered from some neck symptoms before the injury, whilst 36 (84 per cent) attributed all of their neck symptoms to the injury sustained. Of the total population, 248 had not suffered a neck injury and of this group 84 (34 per cent) suffered some neck discomfort during or after performing normal everyday tasks. The chi 2 test was used to test the null hypothesis that the sub-group attributing their symptoms to injury, in whom only 16 per cent acknowledged pre-existent neck symptoms, was derived from the same population as the group who had not suffered any definite neck injury, and yet were still troubled with some neck symptoms in 34 per cent of cases. This hypothesis was rejected (P < 0.01), indicating that there was a significant difference between these two groups. We conclude that some individuals who suffer a neck injury do not recall that they suffered some minor neck symptoms before injury. The statistical analysis and alternative possible explanations are discussed. Our conclusions may be of medico-legal importance in cases where compensation is being sought.

Accidents, Occupational↗
PubMed1995

Delayed-type hypersensitivity to human gonadotropin: case report.

OBJECTIVE: To investigate adverse reactions to hMG preparations in two women in IVF programs. DESIGN: Two case reports with skin tests for delayed hypersensitivity (DH) to hMG and a biopsy of one delayed reaction. SETTING: Allergy and infertility clinics in university medical center. PATIENTS: Two affected patents with a history of local reactions to the injected hMG, one of whom also had fever, and nine control subjects. INTERVENTIONS: Skin tests and biopsy. MAIN OUTCOME MEASURES: Delayed hypersensitivity skin response to hMG in affected patients indicated by timing and biopsy results. Negative skin test with the purified hFSH, which was also used in treatment with no adverse effects. CONCLUSION: Use of the purified preparation avoids DH reaction.

Adult↗
PubMed1995

Lidocaine and the inhibition of postoperative pain in coronary artery bypass patients.

OBJECTIVE: This study was designed to evaluate whether a continuous low-dose lidocaine infusion reduces postoperative pain and anxiety in patients undergoing coronary artery bypass grafting (CABG) and to retrospectively examine time to extubation, intensive care unit stay (ICU), and hospital length of stay. DESIGN: A double-blinded, randomized, and prospective approach. SETTING: Hospital patients undergoing first-time CABG. PARTICIPANTS: After informed consent, 100 patients were enrolled in this study. INTERVENTIONS: Lidocaine infusion or placebo substitute was begun after induction of anesthesia. The fentanyl/midazolam infusion was discontinued on ICU admission; lidocaine or placebo continued until ICU discharge. Supplemental fentanyl, midazolam, or propranolol was administered for pain, anxiety, or hemodynamic stress. MEASUREMENTS AND MAIN RESULTS: Drug dosages were compared between groups. Postoperative assessment included visual analog pain score, hemodynamics, sedation score, and nursing assessment. Mean total dosages of fentanyl, midazolam, and propranolol between the lidocaine and placebo groups were 620.40 +/- 815.74 microgram versus 689.16 +/- 692.99 microgram, p = 0.244; 0.54 +/- 1.13 mg versus 1.20 +/- 2.44 mg p = 0.465; 0.11 +/- 0.75 mg versus 3.56 +/- 17.2 mg, p = 0.564, respectively. Times to extubation, ICU length of stay, and hospital stay did not achieve statistical significance. CONCLUSIONS: Continuous infusion of low-dose lidocaine did not significantly decrease supplemental fentanyl, midazolam, or propranolol requirement postoperatively. Similarly, a lidocaine infusion does not result in reduced time to extubation. ICU stay, or hospital length of stay.

Aged↗
PubMed1995

Greater severity of clinical features in older patients with Duane's retraction syndrome.

Duane's retraction syndrome (DRS) is a well-described entity. However, the possibility of this condition having progressive features has not been previously documented. We studied 21 consecutive patients with this disorder and found that the incidence of severe retraction on adduction, the occurrence of enophthalmos in the primary position and the presence of upshoots and downshoots were significantly higher in adults with type I DRS than in children. Awareness that the clinical features may increase in severity is important as parental counselling, coupled with effective communication to general practitioners, can prompt re-referral should such problems arise. Surgical intervention as a consequence, becomes an available option to correct disease progression.

Adolescent↗
PubMed1995

Adenosine-sensitive atrial tachycardia.

Limited data suggest that adenosine termination of atrial tachycardia is uncommon. To investigate further the effect of adenosine on atrial tachycardia, adenosine (6-12 mg) was administered during sustained atrial tachycardia in 17 patients. All patients underwent electrophysiological study to exclude other mechanisms of supraventricular tachycardia. Mean patient age was 51 +/- 20 years (range 18-82 years). Seven patients had no structural heart disease. The mean atrial tachycardia cycle length was 390 +/- 80 msecs (range 260-580). Sustained atrial tachycardia was induced with atrial extrastimuli in 8 patients, and was either incessant at baseline or developed spontaneously during isoproterenol infusion in 9 patients. Adenosine terminated atrial tachycardia in 3 patients (18%), transiently suppressed atrial tachycardia in 4 patients (23%), and produced AV block without affecting tachycardia cycle length in the remaining 10 patients. Adenosine sensitivity was observed in 3 of 8 patients with tachycardias initiated and terminated by atrial extrastimuli, and in 4 of 9 patients with spontaneous, but not inducible tachycardias including 3 of 4 patients with isoproterenol facilitated tachycardias. Of multiple clinical and electrophysiological variables examined as potential predictors of adenosine sensitivity, only isoproterenol facilitation of spontaneous or inducible sustained tachycardia predicted adenosine sensitivity (P = 0.02). These observations suggest that adenosine-sensitive atrial tachycardia may be more common than previously recognized. Adenosine sensitivity does not appear to be specific for tachycardia mechanism and cannot be predicted by response to pacing. Atrial tachycardias dependent on beta-adrenergic stimulation are most likely to be terminated by adenosine.

Adenosine↗