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Biomedical subjects

A Curtis

Publications and source records attributed to A Curtis.

At least 37 records · Page 2Linked to original sources

Computer modelling of the adsorption of proteins on solid surfaces under the influence of double layer and van der Waals energy.

The study of protein interactions with surfaces is important in many branches of biomedical engineering. A computer model has been set up in order to aid the understanding and prediction of the likelihood of protein adsorption at a surface and of coagulation between two proteins. In this model, a protein is represented as a hard sphere, neglecting conformation changes which may occur during the adsorption process. The sphere is assumed to be in a medium whose properties are described by the ionic strength, the pH and the dielectric permittivity. It is considered to interact both with an infinite plane, representing the surface, and with another sphere, representing another protein. The model focuses on the total interaction energy between a protein and a surface and between two proteins. The energy is expressed according to the DLVO theory of colloidal stability, which assumes that the adsorption behaviour of proteins at a surface depends, first, on the van der Waals interactions energy and, second, on the electrostatic double layer interaction energy. The conditions under which adhesion is prevented correspond to the presence of local extremes of the energy function, whereas the conditions under which adhesion is likely to take place correspond to absence of local extremes.

Adsorption↗

Delayed engraftment and mixed chimerism after HLA-identical sibling donor BMT in Fanconi anaemia.

A 12-year-old girl with Fanconi anaemia (FA) received a bone marrow transplant from her HLA-identical brother following conditioning with cyclophosphamide (20 mg/kg), thoraco-abdominal radiation (TAI) (4 Gy) and equine anti-thymocyte globulin (ATG) (90 mg/kg). Engraftment was delayed and initially tenuous, and was followed by mixed chimerism (MC) over a follow-up period of 2 years. DNA analysis of engraftment was performed on whole peripheral blood and on separated granulocytes, B and T lymphocytes using PCR detection of CA tandem repeat polymorphisms. At 10 weeks post BMT, granulocytes were predominantly donor, but B and T lymphocytes recipient, in origin. Over the subsequent 90 weeks, granulocytes and B lymphocytes were donor-derived, whilst T cells showed persistent MC but with an increasing donor component. Marrow haemopoietic function (Hb, ANC and platelet count) improved gradually in parallel with a rise in the proportion of donor lymphocyte engraftment. We postulate that a population of recipient lymphocytes survived conditioning and in turn delayed the development of full donor chimerism. Although transient MC has been described after allogeneic BMT in FA, its association with delayed engraftment, and persistence for more than 1 year post BMT, has not been documented clearly.

Bone Marrow Transplantation↗

New depths in cell behaviour: reactions of cells to nanotopography.

The physical and molecular biological bases of the reactions of cells to features of the topography of the substratum or environment on which and in which cells live, both in culture and in the embryo, are discussed. The fact that most, if not all, cells react to micrometric and nanometric topography is stressed. Some cell types will react to steps as shallow as 11 nm. Methods of fabricating such topographies in a variety of materials are outlined. Types of topography and the reactions of cells to these are described. It is emphasized that different cell types are sensitive to fairly specific ranges of size of topography. Reactions to topography include cell orientation, changes in cell motility, cell adhesion and cell shape. The term 'contact guidance' has been used in this field, but the term 'topographic reaction' is more appropriate, since it covers the wide range of reactions that are reported. In addition, the reactions involve activation of tyrosine kinases, cytoskeletal condensation and further downstream activation and inactivation of gene expression. The reactions to topography are probably due to stretch reactions of the cells to the substratum and not to chemical details of the substratum. The reasons for this are that a given cell type reacts in much the same way to the same topography made with different materials and that, when both chemical patterns and topographic ones are offered to cells, topography tends to have a greater effect than chemical patterns.

Animals↗

Evaluation of the implant master cast by means of the Periotest method.

Accurate master casts are essential for the construction of implant-supported prostheses with a precision of fit. The stability of the abutment replicas in the master cast is critical in the accurate reproduction of the patient's oral presentation. The Periotest method is an objective method of quantifying mobility in a tooth and implant. Eighteen gypsum implant master casts containing two brass abutment replicas per cast were evaluated. The abutment replicas were measured three times each for a total of 108 measurements. The mean periotest values and standard deviations were calculated for the master casts and the abutment replicas. The abutment replicas displayed mean periotest values that ranged from +1.3 to -8.0. The study shows that there are significant differences between stable and unstable implant master casts (P = 0.0001, ANOVA-Fisher's protected least significant difference) and abutment replicas (P = 0.0001, Contrast test). The Periotest method will quantify differences in gypsum stone implant master casts as well as the prosthesis supporting brass abutment replicas that are an integral part of the master cast.

Analysis of Variance↗

'Practice professional development plans': general practitioners' perspectives on proposed changes in general practice education.

BACKGROUND: The Chief Medical Officer has presented a report proposing a change in general practitioners' education towards a 'Practice Professional Development Plan', which, in principle, is based around formal needs assessment, practice-based learning in areas identified by those involved, and with the potential for multi-professional learning. This aims to replace the present system of a financial allowance earned by attending a certain amount of educational activity. AIM: To study the opinions of a group of general practitioners attending a course that included workshops that introduced and considered this educational initiative. METHOD: Semi-structured interviews four weeks after the course. RESULTS: Educational benefits were clearly seen, while issues such as funding and time will present difficulties in implementation. CONCLUSIONS: This proposal was seen as an improvement to the existing postgraduate educational allowance system. To maintain enthusiasm, successful introduction will depend on the issues of support and resources.

Adult↗

Familial adenomatous polyposis associated with multiple adrenal adenomas in a patient with a rare 3' APC mutation.

Familial adenomatous polyposis (FAP) is characterised by hundreds of colorectal adenomas. Endocrine neoplasms have occasionally been reported, as have gastric polyps, which are usually hamartomatous in the fundus of the stomach and adenomatous in the antrum. A 57 year old man with colorectal, gastric, and periampullary adenomatous polyposis, in association with three bilateral adrenocortical adenomas, is presented. Mutation screening showed a 5960delA germline mutation in the adenomatous polyposis coli (APC) gene predicted to lead to a premature stop codon. This mutation was found in three of the four children of the patient. Western blot analysis of a lymphoblastoid cell line derived from the patient failed to detect any truncated APC polypeptide. This rare 3' mutation is responsible for an unusually complex and late onset phenotype of FAP.

Adenomatous Polyposis Coli↗

Mutation screening in exons 3 and 4 of alpha-synuclein in sporadic Parkinson's and sporadic and familial dementia with Lewy bodies cases.

Recently it has been reported that a missense G(88)C mutation within exon 3 and a missense G(209)A mutation within exon 4 of the alpha-synuclein gene were linked to familial Parkinson's Disease (PD). We decided to investigate if these and any other mutations in exons 3 and 4 of the alpha-synuclein gene could be detected in sixty two sporadic PD and dementia with Lewy bodies (DLB) patients. Four cases of familial DLB were also studied, two of which were from the same family. Single stranded conformational polymorphism, DNA sequencing analyses and PCR-RFLP of exons 3 and 4 failed to reveal any nucleotide changes. However, three nucleotide differences occurred in the intron 4 sequence compared to the published sequence. This study adds further support to the idea that these particular mutation in the alpha-synuclein gene are a rare case of PD and now, as we have shown here, also of DLB.

Dementia↗

Novel insertion in the KSP region of the neurofilament heavy gene in amyotrophic lateral sclerosis (ALS).

The abnormal assembly and accumulation of neurofilaments (NF) in the perikarya and proximal axons of motor neurones is a characteristic of ALS. Deletions in the KSP repeat region of the NF-H gene have previously been reported in seven patients with sporadic ALS. Here we report the identification of a novel 84 bp insertion in the NF-H gene. This leads to an extra four KSP repeat elements in a highly conserved repetitive region of the gene. Although neurofilament mutations are only associated with a very small proportion of ALS cases, this insertion provides further support of a role for neurofilaments in the pathogenesis of ALS.

Aged↗

Agency-Community Partnership in Landcare: Lessons for State-Sponsored Citizen Resource Management

/ With over 2500 Australian Landcare groups, 65,000 volunteer members, and considerable evidence of program impact, Landcare is an important example of state-sponsored rural development in a developed nation. The agency-community partnership is a fundamental element of Landcare and getting the partnership right is vital to long-term program success. After reviewing the emergence of Landcare in the state of Victoria, the author reports research from a 1995 survey of Victorian Landcare groups. Survey information highlighted the extent of agency-group contact, the important roles agency staff played in many Landcare groups, and the positive impact of agency contact and government funding upon group activity. Large majorities of groups reported they were satisfied with their relationship with agency staff. However, a majority of groups reported money or materials provided to manage land and water degradation was inadequate. Recently proposed changes to the Landcare program will provide government funding of work on private property and may address this concern. A majority of groups also reported support for leadership and management training was inadequate and respondents emphasized the need to revise program guidelines that limit funding for group coordinators. This information highlighted the importance of articulating a practical model of community participation in Australia and adopting a systematic approach to providing agency support for Landcare groups. Reflecting upon the Landcare experience, the author suggests some of the key elements of a practical model of state-sponsored citizen resource management contributing to rural development.KEY WORDS: Landcare; Australia; Community participation; Rural development; Citizen resource management; Sustainable agriculture

Journal Article↗

Sensitive determination of erythromycin in human plasma by LC-MS/MS.

A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the analysis of erythromycin in human plasma (EDTA as anticoagulant) was developed and validated. The concentration ranges were 0.5-50 and 50-5000 ng ml-1. The procedure involved alkalization of 0.5 ml of plasma, one step liquid-liquid extraction, dryness of the extract and reconstitution in 80:20 water:acetonitrile. An Inertsil ODS-2 5 microns, 3.0 x 50 mm column (Metachem) with a C8 guard column and isocratic mobile phase were used for liquid chromatography. The mobile phase consisted of 1:1 acetonitrile:water with 2 mM NH4OAc and 0.1% HOAc. A flow rate of 0.7 ml min-1 was used. The analysis time on LC-MS/MS for one sample was approximately 2 min. A Turbo-Ionspray source was interfaced between the HPLC and triple quadrupole mass spectrometer (Sciex API III Plus). MS/MS analysis used Multi-Reaction Monitoring (MRM) mode. The lowest limit of quantitation (LOQ) was 0.5 ng ml-1 with all Quality Control (QC) sample recoveries varying between 88 and 105%. Nine intraday and interday calibration curves were generated yielding correlation coefficients ranging from 0.995 to 1.000. Average recovery for erythromycin at 1 ng ml-1 was 105% (+/- 4.5%). Average recovery for the internal standard was 83-103%. Short-term and long-term stability in the freezer (-20 degrees C), bench stability, and stability after 3 freeze/thaw cycles at -20 and -80 degrees C were conducted. The samples were found to be stable under all conditions. The method developed and validated proved useful for clinical pharmacokinetic study sample analysis with high throughput due to its high sensitivity and very short analysis time.

Anti-Bacterial Agents↗

Kennedy's disease: unusual molecular pathologic and clinical features.

Two patients with the Kennedy's disease (KD) mutation have been identified in the Newcastle Brain Tissue Bank. One of these patients had presenile dementia as a prominent clinical feature, previously undescribed in KD. The pathologic substrate underlying the cognitive changes in this patient included neuronal depletion and gliosis in the hippocampus and subcortical gliosis in the prefrontal region. Immunostaining for macrophage markers showed evidence for subtle corticospinal tract pathology in both cases. In contrast to the molecular pathologic features found in ALS, surviving motor neurons in the two KD cases showed no evidence of ubiquitinated inclusions or alterations in neurofilament phosphorylation.

Astrocytes↗

CNS tissue Cu/Zn superoxide dismutase (SOD1) mutations in motor neurone disease (MND).

DNA extracted from CNS tissue of 79 cases of motor neurone disease (MND) was screened by single strand conformation analysis (SSCA) and heteroduplex analysis (HA) for mutations in the Cu/Zn superoxide dismutase (SOD1) gene. The aims were to determine whether somatic mutations of SOD1 may underlie some cases of MND and to characterize the genetic abnormalities by sequencing, for subsequent correlation with the molecular pathological phenotype. In 3 cases a point mutation was found in exon 4: E100G in one familial case, and I113T in two cases (one familial, one sporadic). Two cases had previously undescribed mutations in the 3' untranslated region (3'UTR) of SOD1 and one case had a single base substitution in the intronic sequence upstream from exon 2. None of these patients had a positive family history. Non-CNS tissue was available for 3 out of the 6 cases in whom changes were found. In all 3 the same changes were consistently found in both CNS and non-CNS tissue, excluding the presence of somatic mutations in SOD1. We investigated many MND blood samples and normal controls for the presence of the 3'UTR deletions. We found the 4 bp deletion in 1/90 sporadic MND patients and 1/209 non-MND controls. If the 3'UTR deletions are pathogenic, they would have to operate via a loss of the function mechanism, and further work is necessary to define their significance.

Adult↗

Topographical control of cells.

We review the literature on the reaction of cells to their surrounding topography. The topography may be that of surrounding cells, intercellular materials or biomaterials. The reactions include cell orientation, rates of movement, and activations of the cells. We concentrate on those papers where quantitative measurements of the reactions have been made and largely ignore those on subjective impressions. A wide range of topographies are considered but special attention is given to results on groove-ridge topographies. The question of whether the cells are reacting to the topography directly or to patterned substratum chemistry formed on the topography is discussed. The review ends with a summary of the types of prosthesis where advantage has been taken of the ability to fabricate topography.

Animals↗

Acromion-splitting approach through an os acromiale for repair of a massive rotator cuff tear.

Os acromiale, failure of fusion of the secondary centers of ossification of the acromion process, has been noted as a contributing factor in shoulder impingement syndrome and rotator cuff tears. Treatments for symptomatic os acromiale with or without rotator cuff tears have been reported in the literature and range from excision of small fragments to fusion of larger, fragments with internal fixation and bone grafting. Generally, rotator cuff repairs have been performed when possible. We report an acromion splitting approach through an existing os acromiale to gain exposure for the repair of a massive rotator cuff tear. Subsequent to this repair, the acromion was repaired with internal fixation. Good functional use of the patient's upper extremity was obtained and the patient expressed satisfaction with the surgical outcome. The acromion splitting approach is a viable approach in patients with an os acromiale and a coexistent rotator cuff tear.

Acromion↗

Impaired recognition of disgust in Huntington's disease gene carriers.

Face processing and facial expression recognition were investigated in the earliest stages of Huntington's disease, by studying 40 people who presented for genetic testing. Twenty-three of these 'at risk' individuals turned out not to carry the gene for Huntington's disease (the AR- group). Seventeen were found to be gene carriers (the AR+ group); 15 from genetic testing, and two who showed signs of early stages of Huntington's disease. A number of standard tasks were used to provide background information, including recognition memory for words, picture naming, verbal fluency, and figure copying; none revealed significant differences between the AR+ and AR- groups. Face processing abilities were investigated using tests of identification of familiar (famous) faces, unfamiliar face matching, recognition memory for faces, and recognition of facial expressions of emotion. No statistically significant differences between the AR+ and AR- groups were found for any of these tests, but the AR+ group showed a borderline overall impairment in recognizing facial expressions of emotion (0.05 < P < 0.1). When recognition of each of the six basic emotions used was examined separately, only disgust was found to be significantly impaired. This highly selective deficit in the recognition of disgust was confirmed in the subgroup of 15 individuals shown by genetic testing to be Huntington's gene carriers; it was therefore found in people who were free from clinical symptoms and did not perform significantly more poorly than non-carriers on any of the background tests, on any of the other face processing tasks, and even for recognition of any other basic emotion. This points strongly to the importance of the basal ganglia in the emotion of disgust.

Adult↗

Hernia of the lung: a case report and review of literature.

Lung hernia is a protrusion of pulmonary tissue through an abnormal defect in the wall of the thoracic cavity. Though the hernias may be congenital, they are usually acquired following a penetrating injury and surgical intervention. Symptoms are usually vague and infrequent. Pain and discomfort may be present at the site of a chest swelling that increases with forced expiration and valsalva and is readily reducible. Diagnosis may be confirmed radiologically by an oblique chest roentgenogram or a computed tomographic scan. Lung hernias only occasionally require surgical repair. We report the case of a 38-year-old man with acquired lung hernia, through a thoracotomy scar, and presenting as chest pain. A review of the literature is presented.

Adult↗