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Biomedical subjects

A O'Brien

Publications and source records attributed to A O'Brien.

At least 37 records · Page 2Linked to original sources

5-Alkyltryptamine derivatives as highly selective and potent 5-HT1D receptor agonists.

A series of 5-alkyltryptamines (6) and the corresponding conformationally constrained analogues (8) have been synthesized. The structure activity relationships (SAR) at the 5-position of the indole skeleton and the ethylamine side chain have been studied. Functional activities were assessed using isolated rabbit saphenous vein. Potent, selective ligands were found (6e, Ki 2.5 nM, 5-HT1B/5-HT1D 125-fold) that have potential for treating acute migraine.

Animals↗

Pulmonary hypertension update.

Research into the causes and treatment of primary pulmonary hypertension (PPH) has provided new hope for this disease. This article reviews recent developments in its pathogenesis, classification, and treatment. An approach to diagnosing the patient with pulmonary hypertension also is outlined.

Humans↗

The effect of accuracy of perceptions of dietary-fat intake on perceived risk and intentions to change.

Consumption of excess fat increases risk for many health problems and diseases. In the present study, 188 undergraduate students were studied to understand self-perceptions of dietary-fat intake and the impact of those perceptions. Findings indicated that the majority of participants had inaccurate perceptions about the amount of fat in their diets. Further, compared to people who overestimated dietary-fat intake, people who underestimated fat intake had lower perceived risk of cancer, had lower intentions to change, and demonstrated less knowledge about the dietary-fat content of many foods. Findings suggest that this unrealistic underestimation of fat intake is a cognitive barrier to dietary change and people who underestimate dietary fat intake may require more intensive intervention to change their diets.

Adolescent↗

An outbreak of multiply resistant Serratia marcescens: the importance of persistent carriage.

An outbreak of multi-resistant Serratia marcescens involving 24 patients occurred in a bone marrow transplant and oncology unit, from September 1998 to June 1999, of whom 14 developed serious infection. This is the first such outbreak described in a BMT unit. All isolates demonstrated the same antimicrobial susceptibility pattern and were the same unusual serotype O21:K14. The antimicrobial susceptibility profile showed reduced susceptibility to ciprofloxacin, gentamicin and piperacillin-tazobactam. As the latter two antimicrobials are part of our empiric therapy for febrile neutropenia, they were substituted with meropenem and amikacin during the outbreak. Investigation revealed breaches in infection control practices. Subsequently, the outbreak was contained following implementation of strict infection control measures. A prominent feature of the outbreak was prolonged carriage in some patients. These patients may have acted as reservoirs for cross-infection. This report also indicates that patients who become colonised with Serratia marcescens may subsequently develop invasive infection during neutropenic periods.

Adult↗

Caring attributes, professional self concept and technological influences in a sample of Registered Nurses in eleven countries.

Caring, the theoretical foundation of nursing, is identified as one of the core values by Hospital Authorities world-wide to be actualised in clinical practice. Exactly how caring attributes relate to nurses' professional self image and quality nursing service in the context of a contemporary technological environment have yet to be operationalised. In total, 1957 Registered Nurses from 11 different countries were involved in the study which aimed to: develop an understanding of and compare the responses to items relating to caring, professional self concept and technological influences. To collect data an instrument containing 104 Likert items was administered to RNs working in general hospitals. The instrument contained sections which examined professional self concept, technological influences and caring attributes. Descriptive and inferential statistics revealed that many of the Asian nurses in the sample were younger, had less experience yet were more qualified than their 'western' colleagues. The mean scores for the caring attributes for nurses from the Philippines, Sweden and South Africa were significantly higher than those from China (Beijing), Korea, China (Hong Kong) and Scotland. The Korean sample demonstrated the lowest mean score for professional self concept while the New Zealand sample the highest. The Australian, Canadian, NZ, Scotland and Swedish samples were strongly of the opinion that the increase in technology has not brought about the any more spare time in nursing and generally had a more negative opinion about the influence of technology when compared to those from China (Beijing), Philippines, China (Hong Kong) and Singapore. The results are discussed in the light of the cultural differences in the sample and recommendations for future research are considered.

Adult↗

Effect of current level on electrode discrimination in electrical stimulation.

The effect of the stimulation intensity (current amplitude) on the ability to discriminate electrodes was tested in an experiment with four adult users of the Nucleus-22 cochlear implant. A total of 12 adjacent pairs of electrodes were used in the four-interval forced-choice discrimination task with random current variation. Tests were carried out at three average stimulation levels: 40 and 70% of the dynamic range and close to maximum comfortable loudness. Analysis of variance revealed a significant (P<0.0001) deterioration in electrode discrimination with a decreasing level. However, the overall effect was very small, representing a deterioration in the discrimination score of only 18% correct from the highest to lowest levels tested. The reason for the small deterioration in discriminability with a decreasing level is difficult to determine from this experiment, however, the results are consistent with the hypothesis that changes in the 'peak' or 'edge' of the excitation pattern are more important for discrimination tasks than the relative amount of non-overlap of the excitation areas from the two electrodes.

Analysis of Variance↗

To determine whether the temperature of 2% lignocaine gel affects the initial discomfort which may be associated with its instillation into the male urethra.

OBJECTIVE: To determine whether the temperature of 2% lignocaine hydrochloride gel affects the initial discomfort during instillation into the male urethra. PATIENTS AND METHODS: Sixty consenting men were randomized to receive 11 mL of 2% lignocaine hydrochloride gel (Instillagel, Farco-Pharma GmbH, Cologne, Germany) at 4 degrees C, 22 degrees C or 40 degrees C. The three groups were well matched for age and numbers of previous flexible cystoscopies. The gel was instilled by one operator and the patients were then immediately asked to score the pain on instillation using a 100-mm nongraphical visual analogue scale. RESULTS: Compared with the control group (at 22 degrees C), there was a statistically significant reduction in pain score in the group receiving cold gel (Student's t-test, P<0.05). CONCLUSION: The cooling of 2% lignocaine gel significantly reduced the initial discomfort associated with its delivery into the male urethra before any form of urethral instrumentation.

Administration, Topical↗

Polymer additive migration to foods--a direct comparison of experimental data and values calculated from migration models for high density polyethylene (HDPE).

To reduce the amount of compliance testing for food contact polymers the use of migration modelling has been proposed. This study was conducted to provide valid data for the independent evaluation of two such diffusion-based models using a range of different high density polyethylene (HDPE) polymers and plastics additives. Seventy-two experimental migration data have been obtained in triplicate and used to evaluate two Fickian-based migration models in the prediction of specific migration of four HDPE additives into olive oil. All tests were conducted using olive oil, representing the most severe case for fatty foods with test conditions of 2 h at 70 degrees C, 6 h at 70 degrees C, 10 days at 40 degrees C representing short term exposures at high temperatures and room temperature storage. Predicted migration values were calculated by inserting the measured initial concentration of additive in the polymers (Cp,0) into the equations together with known variables such as additive molecular weight, temperature and exposure time. The results indicate that both models predict migration values into olive oil close to, or in excess of, the experimental results. The Piringer migration model, using the 'exact' calculations of the Migratest Lite program, gave an overestimation for 83% of the migration values generated in this study. The highest overestimation was 3.7 times the measured value. For all measurements, the predicted migration from the Migratest Lite program was greater than 50% of the observed value. The FDA model was found more accurately to predict migration in most situations but underestimated migration more frequently. Differences in the polymer specification had little effect on specific migration of the additives investigated.

Chemical Phenomena↗

[Prevalence of the 185Ag deletion of the BRCA1 gene in Chilean women with breast neoplasm].

BACKGROUND: The most important identified pathogenic factor for breast cancer is the presence of mutations in BRCA1 gene. These are associated with familial breast cancer in up to 80% of cases. The most frequent mutation of BRCA1 gene in Caucasian populations is the exon 2 185AG deletion. AIM: To study the presence of 185AG deletion in Chilean women with sporadic or familial breast cancer. PATIENTS AND METHODS: We studied 15 women with familial breast cancer, in whom at least one close relative was affected, and 40 women with sporadic breast cancer. In genomic DNA obtained from a blood sample, an allele specific polymerase chain reaction was done. This reaction allows the identification of 185AG deletion and uses two pairs of primers. One for the native form that renders a 118 base pairs product and one for the deletion that renders a 170 base pairs product, both with a respective 280 base pairs internal control. RESULTS: The diagnosis of breast cancer was done at 40 +/- 5 and 65 +/- 10 years old in women with familial and sporadic breast cancer, respectively. In none of the samples, the amplification of the 170 base pairs band that corresponds to 185AG deletion, was obtained. In both groups, the product of the amplification was the 118 base pairs band, that corresponds to the native form of BRCA1 gene. The polymerase chain reaction was optimized for a duration of 90 minutes. CONCLUSIONS: 185AG deletion of BRCA1 gene was not detected in this group of Chilean women with sporadic or familial breast cancer.

Adult↗

[Aldose reductase gene polymorphism and rate of appearance of retinopathy in non insulin dependent diabetics].

BACKGROUND: Recent studies suggest that polymorphisms associated to the aldose reductase gene could be related to early retinopathy in noninsulin dependent diabetics (NIDDM). There is also new interest on the genetic modulation of coagulation factors in relation to this complication. AIM: To look for a possible relationship between the rate of appearance of retinopathy and the genotype of (AC)n polymorphic marker associated to aldose reductase gene. PATIENTS AND METHODS: A random sample of 27 NIDDM, aged 68.1 +/- 10.6 years, with a mean diabetes duration of 20.7 +/- 4.8 years and a mean glycosilated hemoglobin of 10.6 +/- 1.6%, was studied. The genotype of the (AC)n, polymorphic marker associated to the 5' end of the aldose reductase (ALR2) gene was determined by 32P-PCR plus sequenciation. Mutations of the factor XIII-A gene were studied by single stranded conformational polymorphism, sequenciation and restriction fragment length polymorphism. RESULTS: Four patients lacked the (AC)24 and had a higher rate of appearance of retinopathy than patients with the (AC)24 allele (0.0167 and 0.0907 score points per year respectively, p = 0.047). Both groups had similar glycosilated hemoglobin (11.7 +/- 0.2 and 10.5 +/- 1.6% respectively). Factor XIII gene mutations were not related to the rate of appearance of retinopathy. CONCLUSIONS: Our data suggest that the absence of the (AC)24 allele of the (AC)n polymorphic marker associated to the 5' end of the aldose reductase gene, is associated to a five fold reduction of retinopathy appearance rate.

Age of Onset↗

Evaluation of a type definition for representing nursing activities within a concept-based terminologic system.

A terminology model is a conceptual representation that is optimized for the management of terminologic definitions. The purpose of this study was to evaluate one component of a terminology model, a type definition for nursing activity concepts. Two research questions were examined: 1) What percentage of nursing activity terms includes the three essential properties of the type definition (Delivery Mode, Activity Focus, and Recipient)? and 2) Can the nursing activity terms be reliably decomposed into the three elements of the type definition? The sample comprised 1039 non-redundant nursing activity terms collected from the health records of patients hospitalized for an AIDS-related condition. Each nursing activity term was decomposed into the three elements of the type definition by three raters. Percent agreement among the raters ranged from 91.5% to 96.2%. All terms included either an Explicit (82.0%) or Implicit (18.0%) Delivery Mode. Activity Focus was present in 95.1% of the terms in the sample. Recipient was coded as Explicit in 19.2%, Implicit in 75.9%, and Ambiguous in 4.8% of the nursing activity terms in the data set. Mapping among nursing terminologies and convergence of nursing terms within large concept-based health care terminologies has been hindered by the lack of a robust concept representation. A type definition is an essential component of such a representation. Further research is needed to refine the type definition and to incorporate it within a terminology model for nursing concepts.

Humans↗

Specific migration testing with alternative fatty food simulants.

Many additives used in plastics materials and articles intended for food contact are expected to be assigned specific migration limits (SMLs) in a future amendment to EC Directive 90/128/EEC. In order to demonstrate compliance with these restrictions, specific migration tests will need to be performed on the finished plastics packaging using foods or the appropriate EC food simulants. Owing to the involatile and lipophilic nature of many of these additives, their analysis in the conventional fatty food simulant, olive oil, presents technical difficulties. One way of overcoming these difficulties would be to use a simple solvent alternative to olive oil as has been proposed for overall migration testing. The objective of this work is to compare specific migration data obtained using olive oil with alternative fat simulants iso-octane and 95% ethanol, to find out if similar results are obtained and identify the most appropriate alternative simulant to use for future testing. Good agreement with the olive oil migration data was obtained using 95% ethanol (equivalent exposure conditions) for both of the additives studied in polyolefins. For the polystyrene materials studied it is unlikely that the SMLs for the two additives would be exceeded, and in these cases iso-octane (1.5 h at 60 degrees C) could be used as a rapid 'alternative test'.

Adipates↗

An evaluation of pharmacokinetics and pharmacodynamics of leuprorelin acetate 3M-depot in patients with advanced and metastatic carcinoma of the prostate.

OBJECTIVES: The investigational objectives of this open, noncomparative phase I study were to determine the pharmacokinetic profile of a single dose of 11.25 mg leuprorelin acetate, the effective duration of the chemical castration (serum testosterone < or = 1.73 nmol/l) and safety in patients with locally advanced and/or metastatic carcinoma of the prostate foreseen for chemical castration, in the hope that such a dose of leuprorelin acetate may be suitable as a depot formulation to be administered 3-monthly to these patients. METHODS: A total of 24 males up to 85 years old with histologically proven advanced carcinoma of the prostate were enrolled in the study to obtain 18 eligible patients. Each patient was given 11.25 mg of leuprorelin acetate in a depot formulation subcutaneously after reconstitution in 2 ml of a special suspension vehicle. The study period lasted 24 weeks. Patients whose serum testosterone levels reincreased prior to the end of the observation period of 24 weeks were withdrawn from the study and received the monthly depot formulation of 3.75 mg of leuprorelin acetate. RESULTS: The 3M-depot formulation of leuprorelin acetate ensured continuous and constant drug release and effective suppression of testosterone serum levels to castration range for at least 13 weeks. After an initial rise, 5 alpha-dihydrotestosterone as well as the gonadotropin serum levels of luteinizing hormone and follicular stimulating hormone reflected the testosterone serum pattern. CONCLUSION: The results of this study show that the 3M-depot preparation of leuprorelin acetate is effective in suppressing the serum testosterone levels to the castration range for a targeted period of at least 13 weeks.

Adult↗

A case of respiratory muscle weakness due to cytochrome c oxidase enzyme deficiency.

Mitochondrial myopathy is a rare cause of dyspnoea and respiratory failure, usually presenting in infancy. We describe a 27 yr old woman with a partial cytochrome c oxidase enzyme deficiency causing respiratory muscle weakness and respiratory failure. The onset was acute, with no preceding respiratory symptoms. The patient was successfully treated with bilevel positive airway pressure therapy.

Adult↗

Glucose turnover and gluconeogenesis in human pregnancy.

The rate of appearance (Ra) of glucose in plasma and the contribution of gluconeogenesis were quantified in normal pregnant women early ( approximately 10 wk) and late ( approximately 34 wk) in gestation. Their data were compared with those of normal nonpregnant women. Glucose Ra was measured using the [U-13C]glucose tracer dilution method. Gluconeogenesis was quantified by the appearance of 2H on carbon 5 and 6 of glucose after deuterium labeling of body water pool. Weight-specific glucose Ra was unchanged during pregnancy (nonpregnant, 1.89+/-0.24; first trimester, 2.05+/-0.21; and third trimester 2.17+/-0.28 mg/kg.min, mean+/-SD), while total glucose Ra was significantly increased (early, 133.5+/-7.2; late, 162.6+/-16.4 mg/min; P = 0.005). The fractional contribution of gluconeogenesis via pyruvate measured by 2H enrichment on C-6 of glucose (45-61%), and of total gluconeogenesis quantified from 2H enrichment on C-5 of glucose (i.e. , including glycerol [68-85%]) was not significantly different between pregnant and nonpregnant women. Inasmuch as total glucose Ra was significantly increased, total gluconeogenesis was also increased in pregnancy (early pregnancy, 94.7+/-15.9 mg/min; late pregnancy, 122.7+/-9.3 mg/min; P = 0.003). These data demonstrate the ability of the mother to adapt to the increasing fetal demands for glucose with advancing gestation. The mechanism for this unique quantitative adjustment to the fetal demands remains undefined.

3-Hydroxybutyric Acid↗