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Biomedical subjects

D Newby

Publications and source records attributed to D Newby.

At least 19 recordsLinked to original sources

Effect of cryopreservation on human cytotrophoblast cells in culture: hCG and PALP production.

Term villous cytotrophoblasts differentiate into syncytiotrophoblast during culture exhibiting characteristic changes in cellular morphology and protein expression profiles. Measurement of human chorionic gonadotropin (hCG) and placental alkaline phospatase (PALP) is often used to assess viability and syncytialisation of cultured cells. The objective of this study was to assess the effect of cryopreservation of isolated cytotrophoblasts on the expression hCG and PALP by cells during subsequent culture. Villous cytotrophoblasts isolated from term placentae from uncomplicated pregnancies were either cultured immediately after isolation or were cryopreserved (liquid nitrogen) prior to culture. Cells were cultured in identical conditions (5% CO(2) in air) for 96 h. Protein and DNA content of cells and HCG and PALP levels in culture medium were measured at 24 h intervals. Cryopreservation had no significant effect on the protein or DNA content of cultured cells but hCG levels in culture medium were significantly reduced after 72 h (P=0.025) compared to cultures of fresh cells. PALP levels were unchanged. Cryopreservation of cytotrophoblast cells prior to culture resulted in a decrease in basal secretion of hCG possibly caused by a failure or delay in the morphological and functional differentiation of cells.

Alkaline Phosphatase↗

Manufacture and acoustical characterisation of a high-frequency contrast agent for targeting applications.

The aim of this study was to develop and acoustically to optimise an ultrasonic contrast agent for research imaging applications at 40 MHz. A range of liposomal dispersions were manufactured and the mean backscatter power was measured using a Boston Scientific ClearView Ultra intravascular scanner with a 40 MHz, 2.5 Fr Atlantis SR Plus catheter. The scanner had been modified to allow access to the unprocessed ultrasound data, which were digitised, and the mean backscatter power was calculated over a region-of-interest centred at 2 mm from the transducer. Mean backscatter power was normalised to the data collected from a water-air interface. The effects of sonication and rapid shaking on six liposomal samples were also studied and this indicated that both techniques significantly reduced the size of the liposomes within the dispersions. Maximum mean backscatter power was measured for sonicated liposomal dispersions with 60% by weight of phosphatidylethanolamine. Moreover, this dispersion had greater mean backscatter power than sheep blood at 40 MHz.

Contrast Media↗

Giving and receiving of gifts between pharmaceutical companies and medical specialists in Australia.

BACKGROUND: This study investigated the 'gift-relationship' between pharmaceutical companies and doctors. METHODS: The study was based on a survey questionnaire of 823 medical specialists from across Australia. The aim of this study was to investigate gifts offered to medical specialists in Australia by pharmaceutical companies, financial support actively sought by medical specialists for activities other than research and to consider what is ethically appropriate. RESULTS: A high percentage of specialists received offers of food (96%), items for the office (94%), personal gifts (51%) and journals or textbooks (50%). Most specialists were invited to product launches, symposia or educational events (75-84%) and 52% received offers of travel to conferences. A high proportion of offers were accepted (66-79%) except invitations to product launches (49%), sponsored symposia (53%) and offers of travel that included partners (27%). Fifteen per cent of specialists requested financial support from pharmaceutical companies for activities and items, including conferences, travel, educational activities, salaries and donations to specific funds. The study outlined guidelines on gifts from pharmaceutical companies and differing standards applying to gifts and grants for travel. We found that, although most gifts and requests for support complied with professional and pharmaceutical industry guidelines, some--including personal gifts, tickets to sporting events, entertainment and travel expenses for specialists' partners--did not. CONCLUSION: To ensure that physicians' judgements are free from real or perceived influence from industry and to maintain public trust, we support a shift towards more conservative standards on gifts and support for travel evident in recent guidelines.

Adult↗

Dissolved oxygen concentration in culture medium: assumptions and pitfalls.

Oxygen is a key factor in the regulation of cytotrophoblast differentiation, proliferation and invasion in early pregnancy. Abnormalities in oxygen concentration have also been linked to a number of pregnancy disorders. Cell culture models have been used to study the effect of oxygen on cytotrophoblast behaviour in vitro, however, there is often little or no validation of oxygen levels in these cell culture systems. In this study, dissolved oxygen levels in culture medium maintained in standard culture conditions (18% O(2)) measured 18%. On transfer to a low oxygen environment (2% O(2)), oxygen levels decreased to 6-8% after 4h and reached 2% only after 24h in culture. Culture medium pre-gassed with nitrogen to remove dissolved oxygen quickly absorbed oxygen when exposed to ambient air during dispensing and required further incubation in a 2% oxygen environment before dissolved oxygen levels equilibrated to 2%. Thus, cultured cells placed in a low oxygen environment would be exposed to varying levels of oxygen before the desired level of oxygen exposure is reached. This study highlights the importance of validation of oxygen levels and potential problems associated with in vitro studies on the regulatory effects of oxygen.

Absorption↗

Cooperative partnerships or conflict-of-interest? A national survey of interaction between the pharmaceutical industry and medical organizations.

BACKGROUND: There is extensive and varied interaction between the pharmaceutical industry and the medical profession. Most empirical research concerns contact between individual physicians and industry, and reflects North American experience. We sought to clarify the extent and nature of relationships between the pharmaceutical industry and Australian medical organizations. METHODS: We administered questionnaires to 63 medical organizations concerned with clinical practice, continuing medical education or professional accreditation, or the political representation of medical professionals. RESULTS: Survey instruments were received from 29 organizations, giving a response rate of 46%. Seventeen of these organizations (59%) had received support from one or more pharmaceutical company in the past financial year. Support was predominantly for annual conferences, with some support for continuing medical education, research, travel and library purchases. The majority of organizations had an academic journal or newsletter, and 10 (34%) accepted revenue from pharmaceutical advertising. Twenty organizations (72%) had policies or guidelines covering their relationship with industry. Few organizations indicated that they would be unable to continue their activities without pharmaceutical industry support. CONCLUSION: These data indicate a high level of inter-action between the pharmaceutical industry and medical organizations in Australia. While most organizations have policies for guiding their relationship with industry, it is unclear whether these are effective in preventing conflicts of interest and maintaining public trust.

Australia↗

The SoS trial.

Explore the source record for details and available documents.

Coronary Artery Bypass↗

Use of pharmacoeconomics in prescribing research. Part 2: cost-minimization analysis--when are two therapies equal?

UNLABELLED: This is the second paper in a series looking at pharmacoeconomic methods. The first paper discussed how costs are identified for pharmacoeconomic studies. This article will examine one of the four main evaluation methods in health economics, cost-minimization analysis (CMA). The remaining three methods (cost-effectiveness, cost-utility and cost-benefit analysis) will be discussed in later papers. KEY MESSAGES: Cost-minimization is the appropriate form of economic analysis to carry out whenever two drugs have the same clinical effect. True equivalence studies are uncommon; a more useful approach is to assess the size of the confidence interval around the difference between treatments and determine whether it excludes clinically relevant effects. The critical issue for cost-minimization analyses is determining equi-effective doses.

Costs and Cost Analysis↗

Effects of recombinant ovine leptin on in vitro lipolysis and lipogenesis in subcutaneous adipose tissue from lactating and nonlactating sheep.

Direct effects of recombinant ovine leptin on adipose metabolism in sheep were investigated. Lipolytic and lipogenic rates were assessed following preincubation of subcutaneous adipose tissue explants with recombinant ovine leptin. Leptin had no consistent effect on the basal (unstimulated) lipolytic rate in adipose tissue from wethers. Lipolytic rate measured in the presence of combinations of adenosine deaminase, isoprenaline, and N6-phenylisopropyl adenosine was unaffected by pretreatment with leptin. In lactating ewes, there was no relationship between increasing concentrations of leptin and basal lipolytic rate. Leptin had no effect on basal (unstimulated) lipogenesis, or on insulin-stimulation or growth hormone inhibition of lipogenesis in adipose tissue from wethers. Lipogenesis in adipose tissue from lactating ewes was also unaffected by preincubation with leptin; however, at supraphysiological concentrations of leptin, there was a small reduction in the rate of insulin-stimulated lipogenesis. Leptin failed to induce phosphorylation of the signal transducers and activators of transcription, STAT 3 and STAT 5, in sheep adipocytes. These results suggest that leptin does not have a direct physiological effect on subcutaneous adipose tissue metabolism in sheep.

Adenosine Deaminase↗

Evaluation of signals activating ubiquitin-proteasome proteolysis in a model of muscle wasting.

The ubiquitin-proteasome proteolytic system is stimulated in conditions causing muscle atrophy. Signals initiating this response in these conditions are unknown, although glucocorticoids are required but insufficient to stimulate muscle proteolysis in starvation, acidosis, and sepsis. To identify signals that activate this system, we studied acutely diabetic rats that had metabolic acidosis and increased corticosterone production. Protein degradation was increased 52% (P < 0.05), and mRNA levels encoding ubiquitin-proteasome system components, including the ubiquitin-conjugating enzyme E214k, were higher (transcription of the ubiquitin and proteasome subunit C3 genes in muscle was increased by nuclear run-off assay). In diabetic rats, prevention of acidemia by oral NaHCO3 did not eliminate muscle proteolysis. Adrenalectomy blocked accelerated proteolysis and the rise in pathway mRNAs; both responses were restored by administration of a physiological dose of glucocorticoids to adrenalectomized, diabetic rats. Finally, treating diabetic rats with insulin for >/=24 h reversed muscle proteolysis and returned pathway mRNAs to control levels. Thus acidification is not necessary for these responses, but glucocorticoids and a low insulin level in tandem activate the ubiquitin-proteasome proteolytic system.

Acidosis↗

'Cloze' procedure refined and modified. 'Modified Cloze', 'reverse Cloze' and the use of predictability as a measure of communication problems in psychosis.

BACKGROUND: 'Cloze' procedure assesses the predictability of text by deleting words at set intervals and having a panel of raters fill the blanks. Two refinements to the procedure are described: 'modified Cloze' and 'reverse Cloze', the latter examining the subject's ability to interpret a partial transcript. METHOD: Samples of speech were obtained from patients with schizophrenia, manic-depression and orthopaedic disorders using a standard prompt, and the output analysed using modified Cloze. In addition, subjects completed a reverse Cloze passage. RESULTS: Both modified Cloze and reverse Cloze discriminated the performance of patient groups, with patients with schizophrenia performing worst. CONCLUSIONS: These techniques extend earlier findings suggesting reduced predictability in psychotic speech, particularly for patients with schizophrenia. The reverse Cloze procedure suggests a 'mirror-image' deficit and is a potential objective index of psychopathology that is much simpler to apply than traditional Cloze.

Adult↗

Biochemical markers of trisomy 21 and the pathophysiology of Down's syndrome pregnancies.

Using biochemical and immunocytochemical methods, we have investigated endogenous levels of various markers in tissues obtained from 67 Down's syndrome pregnancies after therapeutic abortion in the second trimester and in corresponding tissues from unaffected abortuses. Alpha-fetoprotein (AFP), intact and free beta human chorionic gonadotrophin (hCG), pregnancy-specific beta-1 glycoprotein (SP-1), placental alkaline phosphatase (PALP), pregnancy-associated plasma protein A (PAPP-A), and gamma glutamyl transferase (GGT) were investigated in placental tissue; AFP and GGT in fetal liver; and GGT in fetal intestine. The results indicate that maternal serum levels of placental products reflect those found in the placenta: intact hCG, free beta hCG, and SP-1 levels were elevated in Down's syndrome pregnancies, while PAPP-A and PALP levels were little changed. This suggests that membrane passage of these markers is not affected but there is altered synthesis of hCG and SP-1. AFP levels were strikingly elevated in placental homogenates and unchanged in liver homogenates from Down's syndrome pregnancies, while the levels in maternal serum were reduced, pointing to a possible transport defect specific to AFP. GGT levels were high in placenta and liver from Down's syndrome pregnancies but low in fetal intestine.

Biomarkers↗

Syntactic processing and written language output in first onset psychosis.

Written language samples from 45 schizophrenic patients were compared with those from 15 manics and 18 non-psychiatrically ill control subjects. We used the Hunt test to generate written language samples. This consists of 32 simple propositions describing the manufacture of Aluminum. Subjects are asked to rewrite the propositions in a more concise style. Analysis of the subjects' responses yields measures of syntactic complexity as well as syntactic and semantic errors. Schizophrenics performed as well as the other groups as far as complexity was concerned. This was quite unexpected, given the substantial evidence from speech studies that schizophrenic utterance is characterized by low syntactic complexity. Both patient groups also made more errors and had difficulty in integrating information successfully, compared with controls. Some of these differences were related to educational differences between the groups, as well as impairments in attention and working memory. A possible mechanism for these relationships is outlined. The results suggest that although working memory and attention have an important bearing on linguistic performance, there is in addition, a specific failure of language processing.

Adolescent↗

Expressed emotion and schizophrenia: the ontogeny of EE during an 18-month follow-up.

Key relatives of 30 first or early admission psychotic patients (mainly with a diagnosis of schizophrenia) were interviewed (for a second time) 18 months after participating in an initial assessment of expressed emotion (EE). The patients were followed up throughout the interim period, during which time 17 experienced a psychotic relapse. Although there continued to be a negligible association between initial EE rating (established during the index admission) and relapse, a significant association between EE rating at 18 months and psychiatric status of the patient during the follow-up period emerged. Results are discussed in the context of recent interactional theories of the relationship between household EE and psychiatric morbidity.

Adult↗

Expressed emotion and early onset schizophrenia: a one year follow-up.

Key relatives of 33 first or early admission psychotic patients (mainly schizophrenics) were interviewed to determine household levels of expressed emotion (EE). The patients were followed up for 12 months from index admission, during which time 13 (39%) experienced psychotic relapse. There was no association between relapse rate and household EE, but correlations between individual components of EE and pre-morbid measures suggest that level of criticism may be related to less acute onset of index episode, greater elapsed time since first signs of illness, and poor adjustment in the realm of work/study. The results are discussed in the context of continuing uncertainties about the precise nature of the relationship between EE and relapse.

Adult↗

Gender differences in the incidence of definite schizophrenia and atypical psychosis--focus on negative symptoms of schizophrenia.

In a catchment area study of 101 first inceptions of schizophrenia, mania and atypical psychoses, women were significantly more likely to have atypical psychosis and men were more likely to have definite schizophrenia. Negative symptoms such as affective flattening and poverty of speech were already present in many cases, and were significantly increased in patients with definite schizophrenia (geometric mean 5.6) compared with those with atypical psychosis (geometric mean 3.2) and mania (geometric mean 1.5). Negative symptoms were also twice as severe in men (geometric mean 5.5) than women (geometric mean 2.6). There was a significant increase in negative symptom severity with longer illness and greater depression, but the diagnosis and the sex effects were not caused by these factors. We suggest that our findings are further support for the hypothesis that men have a greater biological vulnerability to negative symptoms and consequent social disability in the face of psychosis, particularly a schizophrenic psychosis, and that this may be one explanation for the apparently greater risk of definite schizophrenia and its poorer prognosis in men.

Adult↗