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M O'Rourke

Publications and source records attributed to M O'Rourke.

At least 55 records · Page 3Linked to original sources
PubMed1995

Opa-typing: a high-resolution tool for studying the epidemiology of gonorrhoea.

A single gonococcus possesses a family of 11 distinct and highly variable opa genes. The extensive variation and rapid evolution of the opa gene repertoire has been exploited to provide a high-resolution typing method for studies of the short-term transmission of gonorrhoea. The 11 opa genes are amplified with a single pair of primers by the polymerase chain reaction, digested with frequently-cutting restriction enzymes, and the fragments are fractionated on polyacrylamide to provide an opa-type. The method appeared to be highly discriminatory as the opa-types of gonococci, isolated world-wide over the last 30 years, were all different. Opa-typing discriminated between isolates of the same auxotype/serovar class. Similarly, there were 41 opa-types among 43 consecutive isolates from a sexually transmitted disease (STD) clinic. The two pairs of isolates from this clinic that gave the same opa-types were identical by other criteria and may have been from unsuspected sexual contacts. With one minor exception, identical opa-types were obtained from gonococci recovered from known sexual contacts. These results suggest that variation in the family of 11 opa genes evolves so rapidly that the opa-types of gonococci are distinguishable, unless the isolates are from sexual contacts or a short chain of disease transmission. The identification of gonococci with identical opa-types is therefore believed to be a good indicator that the individuals from which they were recovered were sexual partners, or part of a short chain of disease transmission.

Antigens, Bacterial↗
PubMed1995

Interspecies recombination in nature: a meningococcus that has acquired a gonococcal PIB porin.

A vaginal isolate of Neisseria has been reported to resemble Neisseria meningitidis in biochemical characteristics but to react with serological reagents that are specific to the PI porin from Neisseria gonorrhoeae. We have confirmed that this isolate has the biochemical attributes of a meningococcus and have shown that it clusters among meningococcal isolates on a dendrogram based on isoenzyme variation within housekeeping enzymes from populations of N. meningitidis and N. gonorrhoeae. Furthermore, the sequences of the fbp and adk genes were typical of those of N. meningitidis and were distinct from those of N. gonorrhoeae. However, the porB gene was very similar to the por genes of N. gonorrhoeae isolates that express the PIB class of outer-membrane porin (differing from one gonococcal por allele at only a single nucleotide site), and was clearly distinct from the porB genes of N. meningitidis. The isolate therefore appears to be a typical meningococcus, except that its porB gene has been replaced with the por gene from a gonococcus.

Adenylate Kinase↗
PubMed1995

Investigation of the actions of chloroethylclonidine in rat aorta.

1. The interaction between chloroethylclonidine (CEC) and noradrenaline (NA) has been examined at alpha-adrenoceptors mediating contractions of rat aorta. 2. In rat aorta, the competitive antagonist prazosin, over the concentration-range 0.01-10 microM, produced concentration-dependent shifts in the contractile potency of NA, so that there was no component of the NA contraction resistant to prazosin. 3. The irreversible alpha 1-adrenoceptor antagonists, phenoxybenzamine (PBZ) (1-10 microM) and benextramine (10 microM) produced shifts in potency of NA and reduced the maximum response in a concentration-dependent manner. 4. The irreversible alpha 1-adrenoceptor antagonist, CEC (100 microM), produced a non-parallel shift in the NA concentration-response curve so that low concentrations of NA produced relatively small contractions but relatively high concentrations produced further contractions, so that the maximum response was not significantly reduced. 5. The combination of CEC pretreatment and subsequent prazosin (0.1 microM) produced a parallel shift in the potency of NA. However, prazosin (10 microM) failed to produce any further effect on the response to high concentrations of NA following CEC pretreatment. Hence, a component of the contraction to NA in the presence of CEC was resistant to subsequent prazosin. Likewise, this component was resistant to a combination of prazosin (10 microM) and yohimbine (10 microM). 6. Receptor protection experiments were carried out in which tissues were exposed to NA (100 microM), yohimbine (10 microM) or prazosin (0.1 microM) prior to and during exposure to CEC. Receptor protection with NA, yohimbine or prazosin (0.1 microM), followed by washout prevented the shift in potency of NA produced by CEC. 7. Further experiments examined the effects of prazosin (10 microM) on responses to NA following receptor protection with NA (100 microM), yohimbine (10 microM), prazosin (10 microM), or xylazine (100 microM). In receptor protection studies with NA, subsequent prazosin (10 microM) produced a shift in response to NA following CEC which was not signficantly different from the shift produced by prazosin alone in the absence of receptor protection. In receptor protection studies with prazosin, yohimbine or xylazine, subsequent prazosin (10 microM) produced shifts in the response to NA following CEC which were significantly less than the shift produced by prazosin alone in the absence of receptor protection.8. It is concluded that CEC has two actions in the rat aorta. Firstly, it behaves as an irreversible a,-adrenoceptor antagonist, reducing the response to low concentrations of NA (up to 10 microM). However,after exposure to CEC, concentrations of NA of 10 microM and above produced contractions resistant toprazosin. This resistant component was still present following receptor protection with alpha1,- or alpha2-adrenoceptor antagonists, but absent following receptor protection with NA. Hence, the latter response may represent an irreversible agonist interaction between CEC, NA and alpha-adrenoceptors which cannot be affected by subsequent competitive antagonism, but which can be prevented by receptor protection with the agonist NA prior to CEC.

Adrenergic alpha-Antagonists↗
PubMed1995

Randomized comparison of vinorelbine and melphalan in anthracycline-refractory advanced breast cancer.

PURPOSE: This prospective multicenter randomized trial was performed to compare the effectiveness and safety of intravenous (i.v.) vinorelbine tartrate (Navelbine [NVB]; Burroughs Wellcome Co, Research Triangle Park, NC) with i.v. melphalan (Alkeran [ALK]; Burroughs Wellcome Co) in a heavily pretreated population of patients with anthracycline-refractory advanced breast cancer (ABC). Efficacy end points included time to disease progression (TDP), time to treatment failure (TTF), survival, tumor response rates, and quality of life (QL) and relief of cancer-related symptoms. PATIENTS AND METHODS: Between August 24, 1990, and December 1, 1992, 183 patients were randomized (2:1) to treatment with NVB (30 mg/m2 weekly) or ALK (25 mg/m2 every 4 weeks) i.v. Patients were stratified by measurable or nonmeasurable-assessable disease and by treatment center. RESULTS: Time to disease progression was significantly longer with NVB than with ALK, with a median 12 weeks versus 8 weeks, respectively (P < .001). NVB patients also had significantly longer time to treatment failure than ALK patients, with a median 12 weeks versus 8 weeks, respectively (P < .001). The effect of NVB on survival was also statistically significant (P = .034): 1-year survival rates were 35.7% with NVB and 21.7% with ALK and the median survival rate was 35 weeks and 31 weeks, respectively. In total, 46.5% of NVB patients and 28.2% of ALK patients achieved an objective response or stabilization of disease (P = .06). No intergroup differences were noted in patient-assessed QL and cancer-related symptoms. The most common toxicities were hematologic, including granulocytopenia with NVB and thrombocytopenia and granulocytopenia with ALK. Both drugs were generally well tolerated, and no septic deaths were reported. CONCLUSION: This randomized trial demonstrates a survival benefit in anthracycline-refractory ABC. NVB was well tolerated and demonstrated activity superior to ALK in anthracycline-refractory ABC, without compromising QL. Based on activity of single-agent NVB in this difficult-to-treat patient population, investigations of NVB in combination with other anticancer drugs are warranted.

Adult↗
PubMed1994

Computer image analysis in the diagnosis of melanoma.

BACKGROUND: It is often difficult to differentiate early melanoma from benign pigmented lesions of similar clinical appearance. OBJECTIVE: Our purpose was to develop a computer image analysis system that has the potential for use as an adjunct to the clinical distinction of melanoma from less serious pigmented lesions. METHODS: The system, consisting of a hand-held device incorporating a color video camera and color frame grabber mounted in a microcomputer, was used in a pigmented lesion clinic. Analysis software extracted features relevant to the size, color, shape, and boundary of each lesion, and these features were correlated with clinical and histologic characteristics on which standard diagnoses of skin tumors are based. For discriminant analysis based on image analysis measurements, equal prior probabilities were assigned to two specified diagnostic groups, namely melanoma and "other pigmented lesions," most of which were melanocytic nevi. RESULTS: In a 20-month period, video images of 164 unselected pigmented lesions for which complete diagnostic data were available were successfully captured using the camera. Sixteen of 18 melanomas, and 89% of pigmented lesions overall, were correctly classified by the image analysis system, compared with 83% based on clinical gradings of lesion characteristics. CONCLUSION: Computer image analysis has the potential to provide a valuable diagnostic aid that could enable clinicians to make highly sensitive and specific diagnoses of early, curable melanoma.

Adolescent↗
PubMed1994

Further evidence for the non-clonal population structure of Neisseria gonorrhoeae: extensive genetic diversity within isolates of the same electrophoretic type.

Analysis of data from multilocus enzyme electrophoresis has revealed that Neisseria gonorrhoeae populations are non-clonal. Fifteen percent of 227 isolates of N. gonorrhoeae had an identical multilocus genotype (ET1) and were recovered world-wide over a 26 year period. The recovery of isolates of identical multilocus genotype from geographically and temporally unassociated hosts is a common criterion of a clonal population structure. However, in a recombining (non-clonal) population, isolates with the same multilocus genotype can arise by the random association of the most common alleles in the population. Analysis of the variation in two further enzymes, in the restriction patterns obtained from the glutamine synthetase gene, and in the DNA fragments obtained using an arbitrarily primed polymerase chain reaction, was used to show that members of ET1 were almost as variable as randomly selected N. gonorrhoeae isolates. Unlike the situation in a strongly clonal species, the 26 ET1 isolates examined were increasingly sub-divided to give 19 distinguishable groups as variation at further loci was examined, and 24 distinguishable groups when auxotypes were also considered. We conclude that, as expected of a non-clonal population, the most commonly encountered N. gonorrhoeae multilocus genotype does not define a clone.

Bacterial Proteins↗
PubMed1994

Daily low-dose cisplatin plus concurrent high-dose thoracic irradiation in locally advanced unresectable non-small-cell lung cancer: results of a phase II Southwest Oncology Group study.

PURPOSE: This single-arm phase II trial was designed to evaluate the efficacy and toxicity of continuous-course, high-dose thoracic irradiation (RT) combined with concurrent daily low-dose cisplatin followed by high-dose cisplatin consolidation in patients with locally advanced unresectable non-small-cell lung cancer (NSCLC). The daily chemotherapy regimen was designed to optimize the radiosensitizing properties of cisplatin. PATIENTS AND METHODS: Sixty-five patients from 21 participating institutions were entered onto the study between April 1989 and May 1991. Protocol therapy consisted of daily intravenous (i.v.) cisplatin (5 mg/m2) plus concurrent continuous-course RT (61 Gy over 6 1/2 weeks) both delivered Monday through Friday each week. After a 3- to 4-week rest period, this was followed by three 28-day cycles of cisplatin at 100 mg/m2 or subsequently 50 mg/m2 administered i.v. on days 1 and 8 of each cycle. RESULTS: Sixty-four patients were eligible; the majority had unresectable stage IIIa (36%) or IIIb (55%) NSCLC. The remaining 9% had recurrent disease confined to the chest (five patients) or stage II disease (one patient). The feasibility of this regimen is demonstrated by the fact that only five patients (8%) were unable to complete daily cisplatin and RT because of toxicity. Esophagitis (16%), leukopenia (14%), nausea (8%), and vomiting (6%) were the most common severe (grade 3) toxicities. There was only one life-threatening toxicity (grade 4 nausea) and no treatment-related deaths. The objective response rate was 39%, and six patients (9%) achieved a radiographic complete response (CR). The median survival duration for all patients was 14 months, and the 1- and 2-year actuarial survival rates were 56% and 24%, respectively. For stage IIIa patients, the median survival duration and 2-year survival rate were 17 months and 38%, as compared with 10 months and 14% for stage IIIb patients, respectively. CONCLUSION: Daily low-dose cisplatin plus concurrent high-dose continuous-course RT is a well-tolerated out-patient regimen. The survival results are encouraging and appear to be equivalent to more toxic combined approaches. These results warrant further testing of combined daily platinum analogs with RT.

Adult↗
PubMed1994

Arterial haemodynamics and ventricular-vascular interaction in hypertension.

Comprehensive studies of arterial pressure require understanding of the whole pressure waveform, not just the extremes of pressure (systolic and diastolic) in a peripheral artery. Such studies have been conducted in Sydney from the early 1960s and have been based on the concepts of steady state analysis, of vascular impedance, and of transfer function for pressure and flow in the frequency domain. These studies have emphasised the importance of wave reflection and have identified the cause of wave reflection, and shown how wave reflection can be modified. In the elderly and hypertensive, wave reflection returns early from peripheral sites, as a consequence of arterial stiffening, and boosts systolic pressure in the ascending aorta; this is responsible for "isolated systolic hypertension". Wave reflection in the upper limb causes the ill effects of arterial stiffening and the beneficial effects of vasodilator drugs to be underestimated. A new process, which combines the old technique of sphygmography with conventional sphygmomanometry, enables more precise evaluation of hypertensive subjects. Abnormal (early) wave reflection is a particular disadvantage in the presence of myocardial hypertrophy and impairment, and can explain development of cardiac failure. These concepts explain the favorable therapeutic effects of vasodilator drugs as being a consequence of reduction in wave reflection, as well as resulting from reduced peripheral resistance.

Animals↗
PubMed1994

Arterial stiffening and vascular/ventricular interaction.

Arterial stiffness is the major determinant of systolic pressure and increases with age and hypertension, especially in the thoracic aorta and major central elastic arteries. The effects of arterial stiffening on aortic and left ventricular systolic pressure are underestimated when taken from conventional recordings of systolic pressure in the brachial artery or in other arteries of the upper limb, as a consequence of pressure wave transmission in the upper limb. A method has been devised to synthesise the ascending aortic pressure wave from the radial or brachial artery pressure wave, as measured invasively by arterial cannula or noninvasively by applanation tonometry. Results obtained in this way are similar to, but more consistent than, those obtained through measurement of carotid artery pressure waves by applanation tonometry. The ability to synthesise the ascending aortic waveform enables one to measure augmentation of late systolic pressure caused by arterial stiffening as well as the effects of antihypertensive drug therapies on systolic pressure augmentation. Results have shown that drugs which dilate small peripheral arteries and thereby reduce wave reflection (nitrates, ACE inhibitors, calcium antagonists) reduce ascending aortic pressure augmentation during systole, often without corresponding reduction in brachial or radial artery systolic pressure. These agents are more appropriate therapy for isolated systolic hypertension than beta-blockers and diuretics.

Aorta↗
PubMed1993

Ecological separation and genetic isolation of Neisseria gonorrhoeae and Neisseria meningitidis.

BACKGROUND: Classifying bacteria into species is problematic. Most microbiologists consider species to be groups of isolates that share some arbitrary degree of relatedness of biochemical or molecular (such as DNA sequence) features and that, ideally, are clearly delineated from all other groups of isolates. The main problem in applying to bacteria a biological concept of species based on the ability or inability of their genes to recombine, is that recombination appears to be rare in bacteria in nature, as indicated by the strong linkage disequilibrium between alleles found in most bacterial populations. However, there are some naturally transformable bacteria in which assortative recombination appears to be so frequent that alleles are in, or close to, linkage equilibrium. For these recombining populations a biological concept of species might be applicable. RESULTS: Populations of Neisseria gonorrhoeae and Neisseria meningitidis from Spain were analysed by multilocus enzyme electrophoresis. The data indicate that assortative recombination occurs frequently within populations, but not between populations. Similarly, the sequences of two house-keeping genes show no evidence of intragenic recombination between N. gonorrhoeae and N. meningitidis. CONCLUSIONS: N. gonorrhoeae and N. meningitidis represent extremely closely related 'sexual' populations that appear to be genetically isolated in nature, and thus conform to the biological concept of species. The extreme uniformity of N. gonorrhoeae house-keeping genes suggests that this species may have arisen recently as a clone of N. meningitidis that could colonize the genital tract. Ecological isolation - of populations that can colonize the genital tract from those that can colonize the nasopharynx - may have been an important component in speciation, leading to a lower frequency of recombination between species than within species.

Journal Article↗
PubMed1993

How clonal are bacteria?

Data from multilocus enzyme electrophoresis of bacterial populations were analyzed using a statistical test designed to detect associations between genes at different loci. Some species (e.g., Salmonella) were found to be clonal at all levels of analysis. At the other extreme, Neisseria gonorrhoeae is panmictic, with random association between loci. Two intermediate types of population structure were also found. Neisseria meningitidis displays what we have called an "epidemic" structure. There is significant association between loci, but this arises only because of the recent, explosive, increase in particular electrophoretic types; when this effect is eliminated the population is found to be effectively panmictic. In contrast, linkage disequilibrium in a population of Rhizobium meliloti exists because the sample consisted of two genetically isolated divisions, often fixed for different alleles: within each division association between loci was almost random. The method of analysis is appropriate whenever there is doubt about the extent of genetic recombination between members of a population. To illustrate this we analyzed data on protozoan parasites and again found panmictic, epidemic, and clonal population structures.

Animals↗
PubMed1993

Genetic structure of Neisseria gonorrhoeae populations: a non-clonal pathogen.

Reproduction by binary fission generates a clonal genetic structure in bacterial populations in the absence of a high rate of recombination. The extent of recombination in natural populations of Neisseria gonorrhoeae was determined from an analysis of electrophoretically demonstrable allelic variation at structural genes encoding nine enzyme loci in 227 worldwide isolates. No significant linkage disequilibrium was evident in the population, indicating that recombination must be frequent, relative to binary fission. The genetic structure of N. gonorrhoeae was compared with that of Bacillus subtilis from an earlier study. Linkage disequilibrium was less extreme in the N. gonorrhoeae population than in the local population of B. subtilis, in which only modest clonal structure was evident. Thus, N. gonorrhoeae, unlike pathogens so far examined, has a non-clonal population structure. As expected in a freely recombining population, no correlation was found between electrophoretic genotype and serovar or auxotype.

Genetic Linkage↗
PubMed1993

Early thrombolytic treatment in acute coronary thrombosis.

It is now accepted that the earliest event in acute myocardial infarction is coronary occlusion caused by fissuring of an atherosclerotic plaque, with resultant platelet deposition on the mural flaw and build up of thrombus within the lumen. The symptoms generated are caused by myocardial ischaemia, as first described by Herrick and Levine some 80 years ago. If occlusion is not relieved, irreversible damage (infarction) begins in the ischaemic region within 30 minutes, is half completed by 2.5 hours, and is virtually completed by six hours. Thrombolysis is now accepted therapy for acute evolving myocardial infarction, but in most cases such therapy is not commenced for four hours after symptom onset, when most of the irreparable damage has already been done and when the potential for benefit has fallen substantially. The average time to thrombolysis in GUSTO worldwide, however, was two hours and, in Australia, 2.8 hours. Only patients who could be submitted to thrombolysis within six hours of the onset of pain were included. The results of thrombolytic therapy in acute thrombosis are likely to be improved if delays are minimised. This requires education of the public in the symptoms of this condition, and on the actions to take if such symptoms arise. It also requires expeditious transfer to hospital (or appropriate treatment outside) and above all it requires expeditious assessment and treatment when patients arrive in hospital. Use of the diagnosis 'myocardial infarction' for such patients implies that irreversible damage has already occurred and serves as a disincentive for the speedy, aggressive management that is logical and appropriate for dissolution of the offending coronary thrombus.

Acute Disease↗
PubMed1993

Marginal seal of cervical tooth-coloured restorations. A laboratory investigation of placement techniques.

Incremental placement of composite resin has been suggested as a means of overcoming the contraction that occurs during polymerization of the composite material and as a consequence should allow an improved gingival dentine seal. Numerous incremental placement techniques for composite resin restorations have been documented in the literature. This study examined four different methods of placing Silux in class V cavities, located in the region of the cemento-enamel junction, and lined with Vitrabond. None of the placement methods used completely sealed either the enamel or dentine margins. Of the four techniques employed, the one which involved incremental placement of the gingival component first showed the least amount of leakage at the dentine margin. This result, however, was only significantly different from that of the bulk placement method. In the majority of cases where leakage did occur at the dentine margin, it progressed no further than the Vitrabond lining. It appeared that the high initial adherence to dentine of the light cured glass-ionomer cement prevented deeper penetration of the dye.

Bisphenol A-Glycidyl Methacrylate↗