Referral for abortion.
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Abortion, Legal↗
Biomedical subjects
P O'Neill
Publications and source records attributed to P O'Neill.
Postal questionnaire study of disability in the community associated with psoriasis.
OBJECTIVE: To study the disability caused by psoriasis in patients recorded as having psoriasis by their general practitioner. DESIGN: Postal questionnaire survey using the psoriasis disability index and SF-36. SETTING: Five general practices in Cleveland. SUBJECTS: Of 767 patients identified, 546 completed the questionnaire and 435 were eligible and gave informed consent. MAIN OUTCOME MEASURES: Scores on SF-36 and psoriasis disability index. RESULTS: The psoriasis disability index score was highly negatively correlated with all eight of the SF-36 health measures (P < 0.0001 for each), and the manual social classes scored higher than the non-manual social classes (P < 0.0001). The manual social class group scored significantly lower scores than the controls on all the SF-36 scales, and the non-manual group scored significantly lower for physical and mental role limitation (P < 0.0004 and P = 0.026), mental health (P < 0.0001), energy and vitality (P < 0.0004), and health perception (P < 0.0001). Also, the manual group had poorer health perception on five of the SF-36 variables when compared with the non-manual group. CONCLUSIONS: Patients with psoriasis have an overall lower perception of their quality of life than healthy controls, and those in the lower social classes suffer a greater degree of disability from their disease than the higher social classes.
Attitude to Health↗
An outbreak of Salmonella typhimurium DT104 food poisoning associated with eating beef.
An outbreak of Salmonella typhimurium DT104 infection in Shropshire in May 1995 was identified when four isolates were noted to be from members or supporters of a local football team that had held several social functions in the same week. The subsequent investigation identified 16 people with gastrointestinal symptoms and 12 with microbiologically confirmed infection. The outbreak was complex, associated with several social functions on different days, but infection was associated with eating beef at a public house. A number of errors were detected in the cooking, storage, and handling of the implicated food. The investigation identified beef as the vehicle of infection in this outbreak but was unable to show whether it was the original source of infection or whether cross or manual contamination occurred in the kitchen.
Animals↗
Identification of the residues responsible for the alkaline inhibition of Cu,Zn superoxide dismutase: a site-directed mutagenesis approach.
The catalytic rate of wild type, two single (Lys 120-->Leu, Lys 134-->Thr), and one double (Lys 120-->Leu-Lys 134-->Thr) mutants of Xenopus laevis B Cu,Zn superoxide dismutase has been studied by pulse radiolysis as a function of pH. The pH dependence curve of the wild-type enzyme can be deconvoluted by two deprotonation equilibria, at pH 9.3 (pK1) and at pH 11.3 (pK2). Catalytic rate measurements on single and double mutants indicate that pK1 is mainly due to the deprotonation of Lys 120 and Lys 134, with only a minor contribution from other surface basic residues, whereas pK2 is due to titration of the invariant Arg 141, likely coupled to deprotonation of the copper-bound water molecule. Accordingly, Brownian dynamics simulations carried out as a function of pH reproduce well the pH dependence of the catalytic rate, when the experimentally determined pKs are assigned to Lys 120, Lys 134, and Arg 141.
Animals↗
Absence of correlation between chemo- and radioresistance in a range of human tumour cell lines.
The correlation between cellular resistance to radiation and to chemotherapeutic drugs has been investigated in a number of solid tumour cell lines, and preliminary results indicate no direct relationship. The acquisition of a multidrug resistance (MDR) profile by adriamycin-selected variants of a human squamous lung carcinoma, an ovarian carcinoma, a cervical carcinoma and by a colchicine-selected variant of a Chinese hamster ovarian carcinoma resulted in alterations to their radiosensitivity. However, the degree of change in the radiosensitivity of the MDR cell lines could not be predicted from their level of resistance to adriamycin. Clonal populations derived from DLKP-A, an adriamycin-selected MDR variant of the human lung carcinoma cell line DLKP, exhibited individual radiosensitivity profiles, which did not correlate with their chemoresistance. Exposure of DLKP to consecutive increasing doses of radiation did not confer cross-resistance to chemotherapeutic drugs.
Animals↗
Are residents' work schedules related to their in-training examination scores?
OBJECTIVE: To study the relationship between residents' pre-test available study time and subsequent examination performance. METHODS: We compiled rotation schedules and in-training examination performances for all residents enrolled in the two University of Texas Medical School-Houston obstetrics and gynecology residencies between 1993 and 1995. Services on which the residents had rotated were ranked by surveying all enrolled residents as to their perceived available study time while on those services. A mean available study time rating was computed for each service, which was used to describe each resident's schedule. Pearson correlations between available preparation-time preceding the in-training examination and examination performance were calculated. "Tough" and "easy" rotation subgroups were defined; two-tailed t tests were performed to compare the in-training examination performance of these subgroups. RESULTS: No significant correlation was found between available study time and subsequent examination scores beyond that which could be accounted for by year of training. Scores of residents in the "tough" subgroup were not significantly different from those in the "easy" subgroup on any examination performance measure. For correlations at the one-tailed .05 level, statistical power to detect relationships predicting 16% of variance ranges from approximately 85% for samples of 42 to 68% for samples of 27. CONCLUSION: Residents' in-training examination performance was not significantly affected by their service obligations. Altering resident monthly schedules is not likely to improve in-training examination performance.
Educational Measurement↗
Prospective survey of the incidence, risk factors and outcome of hospital-acquired infections in the elderly.
Four hundred and thirty-six patient admissions to either an acute assessment or a rehabilitation ward for the care of the elderly were studied. A total of 113 episodes fitting the definition of a hospital-acquired infection (HAI) occurred in 81 (18.5%) of admissions. The global infection rate was 10.8 per 1000 patient bed days and did not differ between the wards. The chest and urinary tract were the commonest sites of infection, and 26 patients appeared to be infected at more than one site. The majority of first infections occurred within 14 days of admission. Median length of stay for patients with one or more infective episodes was significantly longer than for those who did not develop an HAI. The presence of an HAI, multiple-site infections and chest infections were significantly associated with fatal outcome. HAI occurs commonly in elderly patients and is associated with prolonged hospital stay and increased mortality.
Adult↗
The use of an information leaflet for patients undergoing wisdom tooth removal.
Attempts to inform the patient about surgical procedures have increased for the purposes of ensuring informed consent and improving satisfaction with the service provided. Leaflets are being used as an additional aid in general practice and in hospital units. However, such written information is seldom evaluated. This study was conducted to assess the influence of using an information leaflet for patients attending oral surgery clinics at a local dental hospital. Sixty-six patients were included in the study and invited to complete a questionnaire to assess knowledge of wisdom tooth removal at the time of examination and just prior to surgery. The validity of the knowledge measure had been previously tested. At 1 month follow-up a patient satisfaction questionnaire was completed by the sample. Patients were randomised at the examination appointment into four groups. The first group was provided with the leaflet and prompted to read it by the dentist (WTL + Prompt). The second group was given the leaflet but not prompted (WTL only). The two other groups acted as controls. The third group was provided with a dental health education leaflet with no prompting (Control 1). The fourth and final group was given no additional written material (Control 2) but provided with verbal information and routine warnings in a similar way to all other groups participating in the study. The WTL + Prompt Group showed increased knowledge on retest (P < 0.001). The WTL Group showed a trend to greater knowledge (P < 0.06) however the control groups showed no improvement (P > 0.5). Patient satisfaction, although greatest in the group given a leaflet without prompting, was not simply related to leaflet provision.
Analysis of Variance↗
Internal carotid artery gunshot wounds.
OBJECTIVE: To review a series of patients who sustained internal carotid artery (ICA) gunshot wounds. DESIGN, MATERIALS, AND METHODS: We retrospectively studied the demographics and clinical presentation, angiographic findings, methods of treatment, and outcome of 38 consecutive patients who had ICA injury identified by angiography. RESULTS: Thirty-four of 38 patients were symptomatic with neck hematomas (32 patients), active hemorrhage (12 patients), and/or neurologic deficit (10 patients). Angiography showed active bleeding in 22 patients and occlusion in 16 patients. Twelve patients were treated operatively by ligation (seven patients), repair (four patients), or intracranial/extracranial bypass (one patient). Twenty-six patients were managed nonoperatively either by angioplasty (one patient), embolotherapy (17 patients), or observation alone (eight patients). Percutaneous balloon catheters were also used in three patients for vascular control of the ICA before operative repair or as a method of assessing intracranial collateral circulation. The mortality of 18.4% was largely related to strokes. CONCLUSIONS: Penetration of the ICA is a very severe injury with a high mortality. The major cause of death in this series was related to neurologic damage associated with carotid injury and shock. However, neurologic deficit among the survivors was uncommon and often resulted from emboli. Interventional radiology can play an important role in the management of these wounds and often obviates the need for operative exploration.
Adolescent↗
Rejoining of gamma-radiation-induced single-strand breaks in plasmid DNA by human cell extracts: dependence on the concentration of the hydroxyl radical scavenger, Tris.
The rejoining of single-strand breaks induced by gamma irradiation in plasmid DNA under different scavenging conditions is described using human cell extracts. As the scavenging capacity of the irradiated solution increases from 1.5 x 10(7) to 3 x 10(8) s-1 using Tris-HCl as a scavenger, the ratio of single- to double-strand breaks is reduced from approximately 70:1 to 40:1. After irradiation, a proportion of DNA molecules have no initial strand breaks but contain damage that is converted to strand breaks when incubated either at 37 degrees C or in the presence of cellular extract. Repair of damage by the extracts is dependent upon the scavenging capacity of the irradiated solution. Optimal rejoining is observed when the scavenging capacity is < 1.5 x 10(7) s-1, and results in the repair of some initial strand breaks. As the scavenging capacity increases to 3 x 10(8) s-1 the proportion of breaks repaired is significantly reduced. The relative increase in the yield of double-strand breaks and reduced repairability of single-strand breaks at a scavenging capacity of 3 x 10(8) s-1 is consistent with the concept that the severity of damage increases upon increasing the scavenger concentration.
Cell Line↗
Identification of the residues responsible for the alkaline inhibition of the activity of Cu,Zn superoxide dismutase: a study of native and chemically modified enzymes.
The pH dependence of the activity of Cu,Zn superoxide dismutases from bovine erythrocytes and shark liver was studied by pulse radiolysis in both the native enzymes and those chemically modified at lysine side chains. The study was aimed at identifying the residues responsible for the activity decrease at pH > 9, observed in all native Cu,Zn superoxide dismutases, and is based on the Lys-->Arg substitution present in the shark protein at position 134, which has been established to be critical for the catalytic efficiency of the enzyme. Both native enzymes display a pH dependence that can be deconvoluted by three deprotonation equilibria, at pH 9-9.5 (pK1), at pH 10.2 (pK2), and at pH 11.5 (pK3). pK1 is lacking in both the modified enzymes and thus can be assigned to activity-linked lysine residues. pK2 is clearly dominated by Arg134 in the modified shark enzyme and can be assigned to surface arginine residues. pK3 is shared by all four enzyme forms and is likely to be due to the invariant Arg141.
Amino Acid Sequence↗
Modulation of the catalytic rate of Cu,Zn superoxide dismutase in single and double mutants of conserved positively and negatively charged residues.
The catalytic rate of four single and three double mutants of Xenopus laevis Cu,Zn superoxide dismutase B, neutralized at Lys120, Asp130, Glu131, and Lys134, has been determined by pulse radiolysis as a function of ionic strength. Neutralization of Glu131 increases the catalytic rate by 80% at low ionic strength, but the effect is reduced to 50% at physiological ionic strength. The rate is unperturbed upon neutralization of Asp130, while neutralization of either of the two lysines drastically decreases the enzyme activity. The Lys120Leu-Lys134Thr and Lys134Thr-Asp130Gln double mutations have an additive and a compensative effect, respectively, on the activity values, while neutralization of the Glu131-Lys134 pair, which also has a compensative effect, gives rise to a faster enzyme at any ionic strength value. The effects observed in the single Asp130Gln and Lys120Leu mutants differ from those reported on human or bovine enzymes [Getzoff et al. (1992) Nature (London) 358, 347-351; Sines et al. (1990) Biochemistry 29, 9403-9412], indicating that some residues occupying the same position in the linear sequence of different Cu,Zn superoxide dismutases have a different functional weight. Our results also suggest that the strategy of multiple charge mutation may be a promising approach in order to increase the catalytic rate of Cu,Zn SODs independently of ionic strength.
Animals↗
New technique for lesser saphenous vein harvesting.
A new technique using the Thompson self-retaining retractor system (Thompson Surgical Instruments, Inc, Traverse City, MI) to harvest lesser saphenous veins is presented. This modification, used in 10 patients undergoing redo myocardial revascularization, provided a rapid, comfortable, and convenient method for harvesting lesser saphenous veins.
Coronary Artery Bypass↗
193 nm light induces single strand breakage of DNA predominantly at guanine.
Irradiation of DNA with 193 nm light results in monophotonic photoionization, with the formation of a base radical cation and a hydrated electron (phi PI = 0.048-0.065). Although > 50% of the photoionization events initially occur at guanine in DNA, migration of the "hole" from the other bases to guanine occurs to yield predominantly its radical cation or its deprotonated form. From sequence analysis, the data reveal that 193 nm light induces single strand breaks (ssb) in double-stranded DNA preferential 3' to a guanine residue. However, it has previously been reported that 193 nm light yields very low yields of ssb (< 2% of the yield of e-aq). The distribution of these ssb at guanine is nonrandom, showing a dependence on the neighboring base moiety. The efficiency of ssb formation at nonguanine sites is estimated to be at least one order of magnitude lower. The preferred cleavage at guanine is consistent with migration and localization of the electron loss center at guanine. It is argued that singlet oxygen and the photoionized phosphate group of the sugar moiety are not major precursors to ssb. At present, the mechanisms of strand breakage are not known although a guanine radical or one of its products remain potential precursors.
Base Sequence↗
The effect of dimethyl sulfoxide on the induction of DNA double-strand breaks in V79-4 mammalian cells by alpha particles.
The present study was undertaken to assess the protective effect of dimethyl sulfoxide (DMSO) against the induction and rejoining of DNA double-strand breaks (DSBs) and inactivation of V79-4 Chinese hamster cells by both high- and low-linear energy transfer (LET) radiations. The cells were exposed under aerobic conditions as monolayers to either low-LET photons (60Co gamma rays) or high-LET alpha particles (238Pu) at 277 K. The initial yield of DSBs, determined by elution under nondenaturing conditions, is linearly dependent on dose. When the irradiation was carried out in the presence of DMSO (0-0.6 mol dm-3), the initial yields of DSBs induced by both gamma and alpha-particle irradiation decrease. With gamma irradiation at [DMSO] > 0.6 mol dm-3, a further decrease in the yield of DSBs occurs. DMSO (0.5 mol dm-3) reduces the initial yield of DSBs by 50 +/- 5% and 32 +/- 4% for photons and alpha particles, respectively. DMSO protects more effectively against cellular inactivation and DSB induction at low LET compared with alpha-particle irradiation with protection factors of 1.7 and 1.4, respectively, for survival and 2.0 and 1.5, respectively, for DSBs. After incubation of the irradiated cells for 3 h at 310 K after high-LET irradiation, the residual yield of DSBs is reduced by < 13% when the irradiations were carried out in the presence of 0.5 mol dm-3 DMSO. With gamma irradiation in the presence of 0.5 mol dm-3 DMSO, 90% of the DSBs are rejoined by 3 h incubation at 310 K. Therefore, the nonscavengeable DSBs induced by alpha particles are not significantly rejoined within 3 h, in contrast to rejoining of the majority of the nonscavengeable DSBs induced by gamma irradiation. From comparison of the data on DSBs and survival for alpha-particle irradiation, it is inferred that the severity of damage is reduced by DMSO through minimizing the formation of OH-induced sugar/base modifications in the vicinity of nonscavengeable DSBs.
Alpha Particles↗
Mutation of Lys-120 and Lys-134 drastically reduces the catalytic rate of Cu,Zn superoxide dismutase.
Lys-120 and Lys-134, located at the edge of the active site channel in most Cu,Zn superoxide dismutases, have been suggested to play a major role in steering the anionic substrate towards the catalytic copper ion. In this study, mutants of Xenopus laevis Cu,Zn superoxide dismutase have been engineered, with Lys-120 and Lys-134 changed into leucine and threonine, respectively, and their catalytic properties have been investigated by pulse radiolysis. Results obtained demonstrate that both residues decrease the catalytic rate by about 40%, in partial disagreement with previous brownian dynamics calculations, carried out on bovine Cu,Zn superoxide dismutase.
Animals↗
Radiolytic and photochemical reduction of the hypoxic cytotoxin 1,2-dihydro-8-(4-methylpiperazinyl)-4-phenylimidazo [1,2-a] pyrido [3,2-e] pyrazine 5-oxide (RB90740) and a potential mechanism for hypoxia-selective toxicity.
PURPOSE: To study the reduction of RB90740 (1), a fused pyrazine mono-N-oxide that has an oxic:hypoxic cytotoxicity ratio of > 10 in a range of murine and human tumor cells in vitro. METHODS AND MATERIALS: Reduction of 1 has been initiated radiolytically and photochemically in aqueous solution and the products isolated and characterized by high performance liquid chromatography (HPLC). RESULTS: Radiolytic reduction of 1 leads to the formation of the 2-electron reduced product, 2. The stoichiometry of the reduction is pH dependent, increasing from 1 to 2 with increasing pH, but independent of the presence of formate or 2-methyl 2-propanol in the reduction mixture. A dimerization product, 3, is also found, which is produced in greater yields at lower pH (< 6). Photochemical reduction of 1 to 2 was also found to be facile. Photolysis of 1 also leads to a deoxyribonucleic acid cleavage reaction. CONCLUSION: Since 2 is not cytotoxic towards hypoxic cells at concentrations at which 1 is toxic, a probable candidate as the cytotoxic species under hypoxic conditions is the 1-electron reduced intermediate species.
Animals↗
Molecular modeling and electrostatic potential calculations on chemically modified Cu,Zn superoxide dismutases from Bos taurus and shark Prionace glauca: role of Lys134 in electrostatically steering the substrate to the active site.
The three-dimensional structure of Cu,Zn superoxide dismutase (SOD) from the shark Prionace glauca was homology modeled on the structure of the bovine enzyme used as a template. Shark SOD displays the conservative substitution of one of the residues involved in the electrostatic guidance of superoxide toward the active site of the enzyme, i.e., Lys134, which is replaced by arginine. The association rate, calculated by brownian dynamics simulations incorporating electrostatic terms, and the enzyme reaction rate, measured by the pulse radiolysis method, were found to be identical for both bovine and shark SODs. In order to quantify the role of Lys134 in electrostatically steering the superoxide to the active site, chemical modification of the lysine residues by carbamoylation was carried out on both bovine and shark SODs. Experimental determination of the enzymatic reaction rate indicated that the charge located on the residue 134 gives 19% contribution to the guidance of superoxide anion at low ionic strength. This value matches the association rates predicted by brownian dynamics.
Amino Acid Sequence↗