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Biomedical subjects

M Young

Publications and source records attributed to M Young.

At least 91 records · Page 5Linked to original sources

A circumcision service for religious reasons.

OBJECTIVE: To review the results of a pioneering service introduced under National Health Service (NHS) cover, providing circumcision on religious grounds. SUBJECTS AND METHODS: The service was offered to all male babies aged 6-14 weeks. Circumcision was carried out using the Plastibell technique under 1% lignocaine ring block/penile block anaesthesia. Between July 1996 and August 1998, 168 circumcisions were performed and assessed postoperatively by telephone enquiry, visiting at home by the nurse and review at the hospital if and when required. RESULTS: Of the 168 babies, 31 required some follow-up care. In six babies the separated ring tracked back onto the shaft of the penis and had to be removed using a ring-cutter. Ten babies were referred for incomplete separation of the Plastibell ring; only two required removal, the rest of the rings detaching spontaneously within a few days. Two babies were reviewed for early separation of the ring and seven were reviewed for bleeding within 24 h of the operation. Two of these were immediately after circumcision, when the bleeding was seen to be from the torn frenulum. They were converted to a more formal circumcision without the Plastibell under the same anaesthesia. Surveillance with no intervention was required in the others, except one who needed a compression dressing. One baby had apyrexia, requiring antibiotics. Four babies had suspected wound infection but none was clinically significant. One parent remained dissatisfied and complained about the inadequate removal of the foreskin. CONCLUSION: The aim of the service was to provide safe circumcision requested on religious grounds. The technique was simple and easily learned by nurses. Parents have generally been very satisfied and the complication rate was acceptable, with most problems occurring early in the series, suggesting an improvement with experience.

Child Health Services↗

Pituitary hyperplasia resulting from primary hypothyroidism mimicking macroadenomas.

Three patients presented with clinical and imaging features suggestive of a primary functional pituitary adenoma. Surprisingly, thyroid function testing revealed co-existing primary hypothyroidism. The pituitary tumours represented hyperplasia of anterior pituitary thyrotrophs secondary to hypothyroidism. Complete regression was achieved with thyroxine replacement therapy. Careful attention should be paid to differentiating this condition from prolactinoma or the rare TSH producing adenoma.

Adenoma↗

The Transtheoretical Model and cervical screening: its application among culturally diverse communities in Queensland, Australia.

OBJECTIVES: To apply the Transtheoretical Model of Behaviour Change (TTM) to cervical cancer screening to determine and report on the level of support required by different language and cultural groups in Queensland to enhance participation. The model consists of six stages: Pre-contemplation (no intention to be screened, no past action), Contemplation (intention to be screened, no past action), Action (intention to be screened, initial screening), Maintenance (intention to be screened, regular screening), Relapse (no intention to be screened, initial screening) and Relapse Risk (no intention to be screened, regular screening). DESIGN: Focus groups and structured interviews were used to classify women in terms of the model and collect information regarding knowledge, health service contact barriers and enhancing factors and sources of information in relation to cervical cancer screening. The sample was recruited by bi-cultural workers for each community using snowball techniques. RESULTS: The interview sample consisted of Australian South Sea Islanders, Chinese, German, Greek and Moslem women. There was no evidence of significant differences in TTM stage according to ethnicity. Women who intended to be screened in the future were more likely to have positive decisional balance scores and higher knowledge scores than women who did not. Women who had had Pap tests were significantly more likely to have received information from their general practitioner (GP) than women who had not had Pap tests. Women in Action and Maintenance were also more likely to have had their last Pap test by a female GP compared to women in relapse categories. Women in Pre-contemplation were more likely than women who had Pap tests to agree that they would travel a long way to see a practitioner who spoke their own language. CONCLUSION: Classification based on the model was supported both by the decisional balance scale and measures of knowledge. Women in earlier stages of the model were more likely to express preferences for the provision of services in their own language and by a female. Cervical cancer screening among women in Action and Maintenance appeared to be better supported by GPs. Cervical cancer screening promotion for women of diverse cultures and ethnicities has tended to focus on Pre-contemplation and Contemplation stages, however, as most women in this sample were in Action or Maintenance, as are most Australian-born women, structuring cervical cancer screening promotion in terms of the TTM may significantly improve the effectiveness of interventions for women of diverse cultures and ethnicities.

Adult↗

Partners in care: a model of collaboration.

It is estimated that 3 million persons in the United States have congestive heart failure. This diagnosis accounts for more than 5% of total health expenditures. A method to decrease the costs of health care was initiated through the partners-in-care model of collaborative practice. A research study exploring the use of nurse case managers in collaboration with cardiologists and primary care physicians is being conducted with persons older than 65 years. This care encompasses both inpatient and outpatient care. The intervention comprises nurse visits in the hospital and in the home as well as telephone support for 6 months after the index hospitalization. The outcomes of quality of life, functional status, mortality, morbidity, and costs are being examined. Collaborative health care partnerships may be an effective strategy to decrease health care costs and improve quality of life and functional status of older persons with congestive heart failure.

Aged↗

Predicting conformational switches in proteins.

We describe a new computational technique to predict conformationally switching elements in proteins from their amino acid sequences. The method, called ASP (Ambivalent Structure Predictor), analyzes results from a secondary structure prediction algorithm to identify regions of conformational ambivalence. ASP identifies ambivalent regions in 16 test protein sequences for which function involves substantial backbone rearrangements. In the test set, all sites previously described as conformational switches are correctly predicted to be structurally ambivalent regions. No such regions are predicted in three negative control protein sequences. ASP may be useful as a guide for experimental studies on protein function and motion in the absence of detailed three-dimensional structural data.

Adenylyl Cyclases↗

Predicting allosteric switches in myosins.

The sequences of several members of the myosin family of molecular motors are evaluated using ASP (Ambivalent Structure Predictor), a new computational method. ASP predicts structurally ambivalent sequence elements by analyzing the output from a secondary structure prediction algorithm. These ambivalent sequence elements form secondary structures that are hypothesized to function as switches by undergoing conformational rearrangement. For chicken skeletal muscle myosin, 13 discrete structurally ambivalent sequence elements are identified. All 13 are located in the heavy chain motor domain. When these sequence elements are mapped into the myosin tertiary structure, they form two compact regions that connect the actin binding site to the adenosine 5'-triphosphate (ATP) site, and the ATP site to the fulcrum site for the force-producing bending of the motor domain. These regions, predicted by the new algorithm to undergo conformational rearrangements, include the published known and putative switches of the myosin motor domain, and they form plausible allosteric connections between the three main functional sites of myosin. The sequences of several other members of the myosin I and II families are also analyzed.

Allosteric Regulation↗

Clinical pharmacokinetics of troglitazone.

Troglitazone is a new thiazolidinedione oral antidiabetic agent approved for use to improve glycaemic control in patients with type 2 diabetes. It is rapidly absorbed with an absolute bioavailability of between 40 and 50%. Food increases the absorption by 30 to 80%. The pharmacokinetics of troglitazone are linear over the clinical dosage range of 200 to 600 mg once daily. The mean elimination half-life ranges from 7.6 to 24 hours, which facilitates a once daily administration regimen. The pharmacokinetics of troglitazone are similar between patients with type 2 diabetes and healthy individuals. In humans, troglitazone undergoes metabolism by sulfation, glucuronidation and oxidation to form a sulfate conjugate (M1), glucuronide conjugate (M2) and quinone metabolite (M3), respectively. M1 and M3 are the major metabolites in plasma, and M2 is a minor metabolite. Age, gender, type 2 diabetes, renal impairment, smoking and race do not appear to influence the pharmacokinetics of troglitazone and its 2 major metabolites. In patients with hepatic impairment the plasma concentrations of troglitazone, M1 and M3 increase by 30%, 4-fold, and 2-fold, respectively. Cholestyramine decreases the absorption of troglitazone by 70%. Troglitazone may enhance the activities of cytochrome P450 (CYP) 3A and/or transporter(s) thereby reducing the plasma concentrations of terfenadine, cyclosporin, atorvastatin and fexofenadine. It also reduces the plasma concentrations of the oral contraceptive hormones ethinylestradiol, norethindrone and levonorgestrel. Troglitazone does not alter the pharmacokinetics of digoxin, glibenclamide (glyburide) or paracetamol (acetaminophen). There is no pharmacodynamic interaction between troglitazone and warfarin or alcohol (ethanol). Pharmacodynamic modelling showed that improvement in fasting glucose and triglyceride levels increased with dose from 200 to 600 mg. Knowledge of systemic troglitazone exposure within a dose group does not improve the prediction of glucose lowering response or adverse effects beyond those based on the administered dose.

Biological Availability↗

Modified stages of acquisition of gateway drug use: a primary prevention application of the stages of change model.

The purpose of the study was to identify the stages of acquisition of gateway drugs in fourth, fifth, and sixth graders. The Stages of Acquisition model is a primary prevention application of the Stages of Change model. The subjects in the study were 811 students from seventeen elementary schools in Arkansas and Missouri. The instrument elicited information regarding the stages of acquisition and individual self-reported drug use. The data were analyzed using frequency, distribution, discriminant analysis, and correlation analyses. Stage placement was confirmed using a series of drug use measures. Results confirmed the existence of discrete stages of acquisition. Results supported the concept of gateway drugs in that subjects indicated they had progressed further through the stages of acquisition of alcohol use than through the stages of acquisition of cigarettes use, smokeless tobacco use, or marijuana use.

Arkansas↗

Prognostic markers in clinically localised prostate cancer.

The prognostic value of immunohistochemical staining of P53, BCL-2, p27kip1, PSA, AR and MIB-1 was compared with that of established prognostic variables (Gleason score, surgical margins, tumour volume) following radical prostatectomy. Five groups were selected: negative margins with stable serum PSA (n=11), negative margins with rising serum PSA (n=7), positive margins with stable serum PSA (n=7), positive margins with rising serum PSA (6) and patients with micrometastatic disease diagnosed in lymph nodes removed during radical prostatectomy (n=8). Gleason score and tumour volume were of prognostic significance and immunohistochemical staining for MIB-1 and BCL-2 showed added independent prognostic significance in multivariate analysis.

Antigens, Nuclear↗

The application of a selenium fertiliser for the correction of marginal deficiencies in grazing sheep.

A commercial fertiliser, consisting of a poorly soluble barium selenate core with a coating of highly soluble sodium selenite, was evaluated in 2 trials for the provision of selenium (Se) to grazing sheep. The fertiliser was administered at a level of 1 kg per hectare to 3 of 6 kikuyu paddocks during 1995 and 1996 in Trial 1, while the other paddocks were left untreated. The Se status of SA mutton merino ram lambs, as reflected by whole blood, liver and kidney Se concentrations, was elevated (P < 0.01) for at least 5 months after application of the fertiliser. Whole blood and liver Se concentrations of animals grazing unfertilised control paddocks were indicative of a subclinical Se deficiency at times (<100 ng Se/ml whole blood and <300 microg Se/kg liver dry matter). In Trial 2, 4 of 7 paddocks on which an oat fodder crop was established were treated with the Se fertiliser during 1995 and 1997. The remaining 3 paddocks were left unfertilised as controls. Groups of 10-15 pregnant SA mutton merino ewes were introduced to these paddocks within 2 weeks of parturition. These ewes and their progeny utilised these paddocks for a mean (+/- SD) period of 41 +/- 8 days after parturition. The whole blood Se concentrations of these ewes and their offspring were elevated (P < 0.01) relative to their contemporaries utilising control paddocks. No suggestion of a subclinical Se deficiency was discernible in animals grazing control paddocks, although whole blood Se levels approached 100 ng Se/ml during 1997. The application of Se fertiliser did not result in improvements in ewe reproduction or lamb growth. There was a suggestion of an improvement (P = 0.21) in mean (+/- SE) lamb survival on paddocks receiving Se fertiliser compared to control paddocks (71.5 +/- 4.6% vs 62.2 +/- 5.3% respectively).

Animal Husbandry↗

Efficacy of computerized decision support for mechanical ventilation: results of a prospective multi-center randomized trial.

200 adult respiratory distress syndrome patients were included in a prospective multicenter randomized trial to determine the efficacy of computerized decision support. The study was done in 10 medical centers across the United States. There was no significant difference in survival between the two treatment groups (mean 2 = 0.49 p = 0.49) or in ICU length of stay between the two treatment groups when controlling for survival (F(1df) = 0.88, p = 0.37.) There was a significant reduction in morbidity as measured by multi-organ dysfunction score in the protocol group (F(1df) = 4.1, p = 0.04) as well as significantly lower incidence and severity of overdistension lung injury (F(1df) = 45.2, p < 0.001). We rejected the null hypothesis. Efficacy was best for the protocol group. Protocols were used for 32,055 hours (15 staff person years, 3.7 patient years or 1335 patient days). Protocols were active 96% of the time. 38,546 instructions were generated. 94% were followed. This study indicates that care using a computerized decision support system for ventilator management can be effectively transferred to many different clinical settings and significantly improve patient morbidity.

Adult↗

Role of REM sleep and dream affect in overnight mood regulation: a study of normal volunteers.

To test that REM sleep and/or dreaming aid in the overnight regulation of negative mood, 60 student subjects, selected to have no current or past episodes of depression, were tested with the Profile of Mood States (POMS) before and after two nights of laboratory sleep. There was a significant overnight effect of sleep on the Depression scale (Dep) both on a sleep-through night and a night of REM awakenings for dream recall. Pre-sleep Dep was significantly correlated with the affect in the first REM report. Although Dep scores were truncated due to the screening criteria, a subgroup of the 10 highest scorers differed from the 50 low scorers in the distribution of dream affect categories across the night. Low scorers displayed a flat distribution of positive and negative affect in dreams, while those with some pre-sleep depressed mood showed a pattern of decreasing negative and increasing positive affect in dreams reported from successive REM periods. This suggests that dreaming may actively moderate mood overnight in normal subjects.

Adult↗

Immunohistochemical expression of BRCA2 protein and allelic loss at the BRCA2 locus in prostate cancer. CRC/BPG UK Familial Prostate Cancer Study Collaborators.

Many epidemiological studies have reported an association between breast and prostate cancer. BRCA2 functions as a tumour-suppressor gene in about 35% of large familial breast-cancer clusters; its role in the pathogenesis of sporadic breast cancer is less clear. We have evaluated immunohistochemical expression of BRCA2 protein and allelic loss of markers at the BRCA2 locus in tissue derived both from sporadic and from familial cases of prostate cancer. Immunohistochemical analysis was performed in 167 paraffin-embedded archival specimens. Normal prostate and 75% (120/160) of prostate-cancer tissue did not express BRCA2 protein. However, 25% (40/160) of cancer cases did express patchy staining; of these, 17% (2711 60) expressed positive nuclear staining in normal glandular tissue adjacent to tumour (either in addition to, or, independent of tumour). Allelic loss is the hallmark of a tumour-suppressor gene. Markers flanking (D13S267, D13S260) and within (D13S171) the BRCA2 gene indicated allelic loss in at least one locus in 23% (17/73) of tumours analyzed. There was no difference in the rates of allelic loss between sporadic and familial tumours, nor was there any association between immunohistochemical staining and allelic loss. Although immunohistochemical staining provided no useful prognostic information, allelic loss at BRCA2 was shown in univariate analysis to be associated with poorer survival (log-rank test, p = 0.046).

BRCA2 Protein↗

A bacterial cytokine.

Viable cells of Micrococcus luteus secrete a factor, which promotes the resuscitation and growth of dormant, nongrowing cells of the same organism. The resuscitation-promoting factor (Rpf) is a protein, which has been purified to homogeneity. In picomolar concentrations, it increases the viable cell count of dormant M. luteus cultures at least 100-fold and can also stimulate the growth of viable cells. Rpf also stimulates the growth of several other high G+C Gram-positive organisms, including Mycobacterium avium, Mycobacterium bovis (BCG), Mycobacterium kansasii, Mycobacterium smegmatis, and Mycobacterium tuberculosis. Similar genes are widely distributed among high G+C Gram-positive bacteria; genome sequencing has uncovered examples in Mycobacterium leprae and Mb. tuberculosis and others have been detected by hybridization in Mb. smegmatis, Corynebacterium glutamicum, and Streptomyces spp. The mycobacterial gene products may provide different targets for the detection and control of these important pathogens. This report is thus a description of a proteinaceous autocrine or paracrine bacterial growth factor or cytokine.

Amino Acid Sequence↗

Principles for Sustainable Governance of the Oceans

Pressures being exerted on the ocean ecosystems through overfishing, pollution, and environmental and climate change are increasing. Six core principles are proposed to guide governance and use of ocean resources and to promote sustainability. Examples of governance structures that embody these principles are given.

Journal Article↗

Prognostic value of bone sialoprotein expression in clinically localized human prostate cancer.

BACKGROUND: Bone sialoprotein (BSP), a bone matrix protein, was recently found to be expressed ectopically in breast cancer and to have a statistically significant association with poor prognosis and the development of bone metastases in that disease. These data prompted us to investigate whether BSP might also be expressed in human prostate cancer, which often metastasizes to bone, and be predictive for progression risk. METHODS: Tissue sections from 180 patients who had undergone a radical prostatectomy for localized prostate cancer were analyzed immunohistochemically for BSP expression. Biochemical progression was defined as an increasing serum prostate-specific antigen level of 0.5 ng/mL or more. Statistical analysis was used to assess associations between pathologic findings and level of BSP expression, and a Cox proportional hazards model was used to determine which clinical and histologic parameters, including stage, Gleason score, and BSP expression (immunostaining intensity and extent), were independently associated with biochemical progression. All P values were two-sided. RESULTS: Most of the prostate cancer lesions examined (78.9%) expressed detectable levels of BSP, compared with no or low expression in the adjacent normal glandular tissue. A statistically significant association was found between BSP expression and biochemical progression in both univariate and multivariate analyses. After a follow-up interval of 3 years, the biochemical relapse rate was 36.7% (95% confidence interval [CI] = 23.4%-47.7%) in patients whose tumors expressed high levels of BSP compared with 12.1% (95% CI = 2.3%-20.8%) in patients whose tumors expressed no or a low detectable level of the protein (logrank test, P = .0014). BSP expression status could identify those patients at higher risk of biochemical progression (logrank test, P<.05) among patients with moderately differentiated tumors or with pathologically confined tumors. CONCLUSIONS: To our knowledge, this study is the first to demonstrate BSP expression in human prostate cancer and to highlight the protein's statistically significant prognostic value in patients with clinically confined prostate adenocarcinomas.

Adenocarcinoma↗