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Biomedical subjects

A Potter

Publications and source records attributed to A Potter.

At least 37 records · Page 2Linked to original sources

Midwives in Victoria, Australia: a survey of current issues and job satisfaction.

OBJECTIVE: To describe demographic and work profiles of registered practising midwives, to assess their job satisfaction and their knowledge of and attitudes to the 1990 Victorian Birthing Services review. DESIGN: A questionnaire posted in 1995 to a population-based random sample of registered midwives. PARTICIPANTS: Two hundred and forty midwives currently using their midwifery skills in their work. SETTING: One thousand names and addresses were randomly selected from a database of midwives registered to practise in Victoria, Australia in 1993. FINDINGS: There was a 72% response rate to the postal questionnaire. Two hundred and forty practising midwives returned completed questionnaires. Seventy-three per cent were in full time employment, 49% lived in rural Victoria, 80% were born in Australia, more than half were aged 40 or more years and 72% had at least one child. Twenty-six per cent worked in postnatal wards, 9% in each the labour ward and the neonatal nursery, 2% in birthing centres and 12% in out of hospital settings. Eighty per cent were satisfied with their work and interactions with women were the most important aspect. Satisfaction was associated with working in a labour ward, feeling adequately prepared by midwifery education and training, nursing for more than 15 years and having continuing education. Neonatal and rotating positions were significantly associated with dissatisfaction. Less than one-half of the midwives had read some of the Birthing Services Review, and of these only one-half had changed their attitudes or practice. One-third knew little of the imminent changes to the Midwifery Regulations. CONCLUSION: Although most midwives enjoyed their work there was little evidence of increasing autonomy or involvement in change.

Adult↗

Is baby too warm? The use of infant clothing, bedding and home heating in Victoria, Australia.

Overheating of infants has been associated with a raised risk for sudden infant death syndrome (SIDS). Data on the use of heating, bedding and clothing and other measures affecting the thermal environment of 4 week old infants were collected at a home interview for infants of women born in Australia (Anglo-Celtic background), in Southern Europe, in Asia and of women who had a planned out-of-hospital birth. These groups have different risks of SIDS not explained by the classic social and perinatal risk factors nor associated with the currently promoted 'new' risk factors. Thermal insulation of the infant's bedding and clothing and excess thermal insulation (for any observed room temperature) were calculated. Bed sharing differed significantly between the groups as did the use of a sheepskin, tucking in firmly, the closing of doors and windows and the use of heating in the infant's room. After stratifying by bed sharing practice and season of interview, it was found that bed sharing infants had more thermal insulation than those sleeping alone irrespective of season of interview. Infants sleeping alone in the Asian-born and Southern European-born groups were kept warmer than infants in the other two groups. Cultural factors appear to affect the thermal environment in which infants are raised. Some bed sharing infants in all four groups were inappropriately warm, particularly in colder weather, but this was more likely in the Asian-born (low risk) group than in the home birth (high risk) group. These results do not explain the differences in SIDS incidence between the groups.

Adult↗

Development of walking, swimming and neuronal connections after complete spinal cord transection in the neonatal opossum, Monodelphis domestica.

Development of coordinated movements was quantitatively assessed in adult opossums (Monodelphis domestica) with thoracic spinal cords transected by (1) crushing 7-8 d after birth [postnatal days 7-8 (P7-P8)]; at 2-3 years of age, systematic behavioral tests (e.g., climbing, footprint analysis, and swimming) showed only minor differences between control (n = 5) and operated (n = 10) animals; and (2) cutting on P4-P6; at 1 month these opossums exhibited coordinated walking movements but were unable to right themselves from a supine position, unlike controls (n = 6). When tested at 2 or 6 months, they could right themselves and showed remarkable coordination, albeit with more differences from controls than after a crush. No animals with spinal cords that were crushed at P14-18 survived because of cannibalism by the mother. Morphological studies (n = 10) 3 months-3 years after crush at 1 week showed restoration of structural continuity and normal appearance at the lesion site. Animals with cut rather than crushed cords showed continuity but greater morphological deficits. That lesions were complete was demonstrated by examining morphology and nerve impulse conduction immediately after crushing or cutting the spinal cord in controls. After lumbar spinal cord injection of 10 kDa dextran amine, retrogradely labeled cells were found rostral to the lesion in hindbrain and midbrain nuclei. Conduction was restored across the site of the lesion. Thus complete spinal cord transection in neonatal Monodelphis was followed by development of coordinated movements and repair of the spinal cord, a process that included development of functional connections by axons that crossed the lesion.

Animals↗

Advantages of impact testing over hardness testing in determining physical integrity of tablets.

An investigation of four different tablet strength tests was carried out on four different placebo formulations (differing in Avicel: Pharmatose ratios). The results analysis compared fatigue failure, work of failure, and impact failure to diametrical compression measurements (hardness). The impact results clearly show how different formulations can have the same hardness, yet their impact resistance can vary by as much as 200%. The impact test used in this work and other tests described are useful in tablet development to understand, compare, and mitigate tablet breakage during subsequent unit operations.

Cellulose↗

TGF-beta receptor type II and fetuin in the developing sheep neocortex.

Fetuin shows a characteristic pattern of distribution in the developing neocortex in many mammalian species. Its expression is confined to early-appearing cortical-plate and later subplate neurons. A short 19 amino-acid sequence of fetuin shows a degree of homology to an 18 amino-acid sequence of the TGF-beta type II receptor (TbetaR-II) and in vitro fetuin binds to members of the TGF-beta family of cytokines. It has been suggested that fetuin is the biologically significant antagonist of these cytokines. We have compared, using immunocytochemistry, the distribution pattern of TbetaR-II and fetuin in the developing neocortex of foetal sheep. TbetaR-II immunoreactivity first appears at around 40 days of gestation in the fetal sheep (E40, term in sheep is 150 days from conception), localised in two discreet bands: one just outside the cortical plate in the inner part of the marginal zone and one deep in the cortical plate in what becomes the transient subplate zone. By E70-E80, TbetaR-II is prominent in a population of subplate cells, whereas, by E120 only small patches of TbetaR-II-positive cells are visible, principally in pyramidal cells in layer VI. The developmental sequence of the staining pattern for TbetaR-II in the neocortex is complementary to that for fetuin, rather than overlapping with it. Double-labelling of fetuin and TbetaR-II shows some cellular co-localisation, especially at E60, but most fetuin-positive cells are not immunoreactive for TbetaR-II. Thus, fetuin's proposed role as an antagonist of TGF-beta cytokines and mimic of TbetaR-II is not consistent with the observed distribution of these two molecules in the developing neocortex of the foetal sheep.

Animals↗

Cytogenetic abnormalities and their prognostic significance in idiopathic myelofibrosis: a study of 106 cases.

The prognostic significance of cytogenetic abnormalities was determined in 106 patients with well-characterized idiopathic myelofibrosis who were successfully karyotyped at diagnosis. 35% of the cases exhibited a clonal abnormality (37/106), whereas 65% (69/106) had a normal karyotype. Three characteristic defects, namely del(13q) (nine cases), del(20q) (eight cases) and partial trisomy 1q (seven cases), were present in 64.8% (24/37) of patients with clonal abnormalities. Kaplan-Meier plots and log rank analysis demonstrated an abnormal karyotype to be an adverse prognostic variable (P<0.001). Of the eight additional clinical and haematological parameters recorded at diagnosis, age (P<0.01), anaemia (haemoglobin < or = 10 g/dl: P<0.001), platelet (< or = 100 x 10(9)/l, P<0.0001) and leucocyte count (> 10.3 x 10(9)/l; P=0.06) were also associated with a shorter survival. In contrast, sex, spleen and liver size, and percentage blast cells were not found to be significant. Multivariate analysis, using Cox's regression, revealed karyotype, haemoglobin concentration, platelet and leucocyte counts to retain their unfavourable prognostic significance. A simple and useful schema for predicting survival in idiopathic myelofibrosis has been produced by combining age, haemoglobin concentration and karyotype with median survival times varying from 180 months (good-risk group) to 16 months (poor-risk group).

Adult↗

Genomic variation and gene conversion in spinal muscular atrophy: implications for disease process and clinical phenotype.

Autosomal recessive spinal muscular atrophy (SMA) is classified, on the basis of age at onset and severity, into three types: type I, severe; type II, intermediate; and type III, mild. The critical region in 5q13 contains an inverted repeat harboring several genes, including the survival motor neuron (SMN) gene, the neuronal apoptosis inhibitory protein (NAIP) gene, and the p44 gene, which encodes a transcription-factor subunit. Deletion of NAIP and p44 is observed more often in severe SMA, but there is no evidence that these genes play a role in the pathology of the disease. In > 90% of all SMA patients, exons 7 and 8 of the telomeric SMN gene (SMNtel) are not detectable, and this is also observed in some normal siblings and parents. Point mutations and gene conversions in SMNtel suggest that it plays a major role in the disease. To define a correlation between genotype and phenotype, we mapped deletions, using pulsed-field gel electrophoresis. Surprisingly, our data show that mutations in SMA types II and III, previously classed as deletions, are in fact due to gene-conversion events in which SMNtel is replaced by its centromeric counterpart, SMNcen. This results in a greater number of SMNcen copies in type II and type III patients compared with type I patients and enables a genotype/phenotype correlation to be made. We also demonstrate individual DNA-content variations of several hundred kilobases, even in a relatively isolated population from Finland. This explains why no consensus map of this region has been produced. This DNA variation may be due to a midisatellite repeat array, which would promote the observed high deletion and gene-conversion rate.

Centromere↗

Anaemia of chronic disease in rheumatoid arthritis: in vivo effects of tumour necrosis factor alpha blockade.

Anaemia of chronic disease (ACD) is a common feature of active rheumatoid arthritis (RA). Inflammatory cytokines, particularly tumour necrosis factor alpha (TNF-alpha), interleukin-1 (IL-1) and interleukin-6 (IL-6), are thought to contribute to the pathogenesis of ACD, possibly by inhibiting erythropoietin (EPO) production. In this study, we examined the in vivo effects of TNF-alpha blockade with a chimeric monoclonal antibody, cA2, on erythropoiesis in RA patients with ACD. Administration of cA2 led to a dose-dependent increase in haemoglobin levels compared to placebo and these changes were accompanied by a reduction in both EPO and IL-6 levels. The data support the notion that TNF-alpha is important in the causation of ACD, but suggest a mechanism independent of EPO suppression. Instead, TNF-alpha may act directly on bone marrow red cell precursors.

Anemia↗

A national survey to define a new core curriculum to prepare physicians for managed care practice.

All levels of medical education will require modification to address the challenges in health care practice brought about by managed care. Because preparation for practice in a managed care environment has received insufficient attention, and because the need for change is so great, in 1995 the authors sought information from a variety of sources to serve as a basis for identifying the core curricular components and the staging of these components in the medical education process. This research effort consisted of a survey of 125 U.S. medical school curriculum deans (or equivalent school representatives); four focus groups of managed care practitioners, administrators, educators, and residents; and a survey of a national sample of physicians and medical directors. Findings indicate that almost all the 91 responding school representatives recognized the importance of revising their curricula to meet the managed care challenge and that the majority either had or were developing programs to train students for practice in managed care environments. The focus groups identified a core set of competencies for managed care practice, although numbers differed on whether the classroom or a managed care setting was the best place to teach the components of a new curriculum. Although medical directors and staff physicians differed with respect to the relative levels of importance of these competencies, the findings suggest that before medical school, training should focus on communication and interpersonal skills, information systems, and customer relations; during medical school, on clinical epidemiology, quality assurance, risk management, and decision analysis; during residency, on utilization management, managed care essentials, and multidisciplinary team building; and after residency, on a review of customer relations, communication skills, and utilization management. The authors conclude that a core curriculum and its sequencing can be identified, that the majority of curricular components exist but in s some cases needed to be modified to more clearly relate to managed care practice, and that their findings may provide a useful starting point for making decisions about curricular reform.

Curriculum↗

Nicotinic system involvement in Alzheimer's and Parkinson's diseases. Implications for therapeutics.

Advances in our understanding of the structure, function and distribution of nicotinic acetylcholine receptors in the CNS have provided the impetus for new studies examining the role(s) that these receptors and associated processes may play in CNS functions. Further motivation has come from the realisation that such receptors must be involved in the maintenance of cigarette smoking, and from clues provided by studies of degenerative neurological diseases such as Alzheimer's disease and Parkinson's disease, in which the loss of nicotinic receptors has been described. Ongoing investigations of the molecular substructure of central nicotinic receptors and their pharmacology have begun to open up new possibilities for novel CNS therapeutics with nicotinic agents. Exploiting these possibilities will require understanding of the role(s) that these receptor systems play in human cognitive, behavioural, motor and sensory functioning. Clues from careful studies of human cognition are beginning to emerge and will provide direction for studies of potentially therapeutic novel nicotinic agents. Despite the promising results of acute studies, few long term studies with nicotine or nicotinic drugs have been performed in dementing disorders. Thus there is uncertainty as to whether long term nicotinic treatment will provide sustained cognitive benefit. It is even more uncertain whether such cognitive benefit will have a significant clinical impact on patients and their families. To maximise the potential benefit of long term treatment with nicotinic agonists (or other cholinergic drugs), we suggest that drug treatment should be combined with cognitive rehabilitation strategies. This will enable patients and/or their families to focus on the particular cognitive domains that may be improved.

Alzheimer Disease↗

The 'new' risk factors for SIDS: is there an association with the ethnic and place of birth differences in incidence in Victoria, Australia?

Home interviews and assessments of infant development were carried out in a project examining the family environments of four groups of women and their infants with different risks of sudden infant death syndrome (SIDS): a reference group of 200 Australian-born (Anglo-Celtic) women (SIDS incidence, 2.04/1000), 101 women born in Asia (0.97/1000) and 56 women born in Southern Europe (0.58/1000) whose infants have a very low risk of SIDS and 102 women who chose to give birth at home whose infants have a high risk of SIDS (8.9/1000). As these differences are not explained by the classic social and perinatal risk factors, it was possible that they might be attributable to the 'new' risk factors: prone sleeping position, not fully breast feeding, exposure to cigarette smoke and bed sharing. Analysis of the data did not show this expected association: there were no significant differences between the groups in the use of the prone position; although only two Asian-born women smoked, infant exposure to cigarette smoke was similar in the other three groups; choice of infant feeding method did not fit the expected pattern--homebirth infants were fully breast fed almost exclusively while this was so for only about 50% of infants in both low risk groups; more than 50% of homebirth families slept with their infants, but bed sharing was also significantly more common in the Asian-born group than in the reference group.

Asia↗

Molecular characterization of the 7q deletion in myeloid disorders.

Deletion of the long arm of chromosome 7 is a common karyotypic finding in myeloid disorders and in particular is found in association with secondary leukaemias. We have used restriction fragment length polymorphisms and gene dosage experiments to assess the loss or retention of sequences localized to chromosome 7q in five patients with clonal myeloid disorders and a 7q deletion. The deletion was interstitial in all cases with retention of the anonymous marker pS194 located at 7q36-qter. Three out of five cases also retained the more proximal gene T-cell receptor beta (TCR beta) located at 7q35. The proximal breakpoints of all five cases were localized to 7q22 by cytogenetic analysis. In two cases the proximal breakpoint lay between the genes for elastin (ELN) and collagen type 1 alpha (COL1A2) and in three cases distal to this region between the genes for erythropoietin (EPO) and acetylcholinesterase (ACHE). The genes of ACHE, plasminogen activator inhibitor 1 (PLANH1), CCAAT displacement protein (CUTL1) and Met proto-oncogene (MET) were deleted in all cases. Molecular analysis of the 7q deletion in myeloid leukaemias demonstrates heterogeneity of the breakpoints, supporting a recessive mechanism of tumourigenesis.

Adult↗

Age-related effects of the nicotinic antagonist mecamylamine on cognition and behavior.

Studies of the neurochemical pathology of Alzheimer's disease and Parkinson's disease reveal a severe and specific loss of central nicotinic cholinergic receptors. We have investigated the functional significance of this finding for cognitive functioning by studying the effects of the centrally active nicotinic antagonist mecamylamine. Single oral doses of mecamylamine were administered to 12 healthy young males and 15 healthy elderly subjects in doses of 5, 10, and 20 mg in a placebo-controlled, double-blind study. In both groups, the 20-mg dose caused a significant increase in errors in the learning condition of the Repeated Acquisition Task, producing a slower acquisition curve. There was no effect of drug on the performance component (retrieval of previously learned information). However, elderly subjects showed enhanced sensitivity to mecamylamine, with 10-mg dose producing significant impairment of learning not seen in the young normals. On a recognition memory task, there was an age-associated shift in response bias, with the elderly subjects becoming more liberal with increasing dose. Reaction-time measures suggested a dose-related slowing of reaction time on several tasks. Behavioral effects were minimal and physiologic effects were consistent with dose-related ganglionic blockade. These results indicate that acute blockade of nicotinic receptor function can produce measurable and significant cognitive impairment similar to some deficits seen in dementing illnesses, and that there is an age-related increase in sensitivity to nicotinic blockade.

Adult↗

Karyotypic and ras gene mutational analysis in idiopathic myelofibrosis.

Karyotypic analysis was performed in a total of 69 patients with well-characterized idiopathic myelofibrosis. Karyotypic abnormalities were detected in 46% of cases examined during the chronic phase (29/63); with three abnormalities, del(13q), del(20q) and partial trisomy 1q, accounting for 75% of all abnormalities at diagnosis. The absence of del(5q), trisomy 8 and 21, as well as the rarity of monosomy 7, contrasts with pooled published data and may reflect our exclusion of closely related disorders, in particular MDS with fibrosis. Chromosomal aberrations increased to approximately 90% (8/9) in patients analysed during acute transformation. Mutational activation of codons 12, 13 and 61 of N-, Ha- and Ki-ras genes were assessed by polymerase chain reaction and hybridization with synthetic non-radioactive digoxigenin-labelled probes. Three mutations were detected in samples of peripheral blood DNA taken from 50 patients during the chronic phase of their disease: one N12 Asp (GGT-->GAT) and two N12 Ser (GGT-->AGT) mutations. The results from this study indicate that karyotypic abnormalities are present in at least 29% of cases at diagnosis and that del(13q), del(20q) and partial trisomy 1q are the most frequent findings. Ras mutations were relatively infrequent (6%) and appeared restricted to the N-ras gene. Karyotypic analysis at diagnosis was found to be of prognostic significance.

Adult↗

Effect of indomethacin on cerebral oxidized cytochrome oxidase in preterm infants.

To determine the effect of i.v. indomethacin on cerebral intracellular oxygenation, as judged by changes in the concentration of oxidized cytochrome oxidase, studies were performed using near-infrared spectroscopy on 15 infants of 23 to 29 wk gestation, aged 8 to 30 d, who required the drug for closure of a patent ductus arteriosus. Indomethacin caused significant (p < 0.01) falls in cerebral blood flow, oxygen delivery, and blood volume and its reactivity to changes in arterial carbon dioxide tension, as previously reported. In 11 of the 15 infants, significant (p < 0.01) falls of 0.18 to 0.92 mumol.L-1 in the concentration of oxidized cytochrome oxidase were observed. Parallel experiments on synaptosomes derived from rat brain showed that indomethacin was most unlikely to have had a direct effect on mitochondrial respiration. These results are consistent with the hypothesis that the observed falls in the concentration of oxidized cytochrome oxidase resulted from hemodynamic perturbations that reduced cerebral intracellular oxygenation.

Animals↗

Acute nicotinic blockade produces cognitive impairment in normal humans.

Single oral doses of the central and peripheral nicotinic antagonist mecamylamine were administered to healthy young normal males in doses of 5, 10, and 20 mg in a placebo-controlled, double-blind study. The 20 mg dose caused a significant increase in errors in the learning condition of the Repeated Acquisition task, producing a slower acquisition curve. The lower doses produced less errors, but more than in the placebo condition. There was no effect of drug on the performance component (retrieval of previously learned information). On the recognition memory task, dose-related increases in false-alarms during the delay period were seen, with little effect on misses or hits. Reaction time measures suggested a dose-related slowing of RT on several tasks. Behavioral effects were minimal and physiologic measures were consistent with dose-related ganglionic blockade. We interpret these results to indicate that acute blockade of nicotinic receptor function can produce measurable and significant cognitive impairment, even in non-smoking normals.

Adult↗