Biomedical subjects

C Harper

Publications and source records attributed to C Harper.

At least 19 recordsLinked to original sources

PubMed2006

Brain donation for research: who donates and why?

Understanding what influences people to donate or not donate body organs is critical for the future of transplant surgery and medical research. Are people involved with a brain donor program for research influenced by the same factors, and are they also donors for organ transplantation? Using web-based technology, people involved in an Australian brain donation program (for research) were asked to complete a questionnaire designed to elicit demographic information, motivational factors and information about involvement in organ transplantation programs. The response rate was 82%. The majority of people involved in the program are young, well-educated Australian females. Seventy-eight percent are involved in other organ and tissue donation programs. People involved in the 'Using our Brains' program are the same group as those who are organ and tissue donors. An improvement in the overall donation rate might be possible if the resources of the research and transplant organisations were combined.

Adolescent↗

PubMed2006

Differential protein expression in the prefrontal white matter of human alcoholics: a proteomics study.

Neuroimaging and post-mortem studies indicate that chronic alcohol use induces global changes in brain morphology, such as cortical and subcortical atrophy. Recent studies have shown that frontal lobe structures are specifically susceptible to alcohol-related brain damage and shrinkage in this area is largely due to a loss of white matter. This may explain the high incidence of cognitive dysfunction observed in alcoholics. Using a proteomics-based approach, changes in protein expression in the dorsolateral prefrontal region (BA9) white matter were identified in human alcoholic brains. Protein extracts from the BA9 white matter of 25 human brains (10 controls; eight uncomplicated alcoholics; six alcoholics complicated with hepatic cirrhosis; one reformed alcoholic) were separated using two-dimensional gel electrophoresis. Overall, changes in the relative expression of 60 proteins were identified (P<0.05, ANOVA) in the alcoholic BA9 white matter. In total, 18 protein spots have been identified using MALDI-TOF; including hNP22, alpha-internexin, transketolase, creatine kinase chain B, ubiquitin carboxy-terminal hydrolase L1 and glyceraldehyde-3-phosphate dehydrogenase. Several of these proteins have been previously implicated in alcohol-related disorders and brain damage. By identifying changes in protein expression in this region from alcoholics, hypotheses may draw upon more mechanistic explanations as to how chronic ethanol consumption causes white matter damage.

Adult↗

PubMed2006

Development of a clinical chart audit programme.

Radiation oncology charts containing medical information and treatment details are the major methods of communication between the various personnel involved in delivering radiation therapy to the patient. It is paramount to good patient care for this communication to be clear, precise and accurate in detail. A regular chart audit should be a part of the quality assurance programme of every radiation oncology department. The primary aim of this study was to develop and assess an objective and quantitative programme for reviewing radiation oncology charts, thereby improving the quality of communication and hence patient management. A secondary aim was to compare the charts of radically treated patients with those treated palliatively. A pilot study using a new chart review tool, developed at the Perth Radiation Oncology Centre, was carried out over an 8-month period. A sample of charts, representing 25% of our treatment group, were assessed using the tool on a monthly basis. A total of 156 charts were reviewed during this time period. Fifty-six per cent were radical treatments and 44% were palliative. The overall mean chart scores significantly improved over the time of this study (P < 0.001). The individual radiation oncologists' scores were also seen to improve during the study period. The alpha coefficients for intra-rater and inter-rater reliability were 0.99 and 0.88, respectively. The chart review programme was found to be an easy-to-use and a reliable tool by both medical and non-medical reviewers. It appeared to have a positive influence on the standard of radiation oncology charts in our department.

Analysis of Variance↗

PubMed2006

Thiamine (vitamin B1) deficiency and associated brain damage is still common throughout the world and prevention is simple and safe!

Many different population groups throughout the world have thiamine deficiency and are at risk of developing severe neurological and cardiac disorders. Alcoholics are most at risk but other important clinical groups should be monitored carefully. The most severe, potentially fatal disease caused by thiamine deficiency is the neurological disorder Wernicke-Korsakoff syndrome. This can be difficult to diagnose and many cases remain undiagnosed. Treatment with thiamine generally results in a dramatic clinical improvement. Thiamine supplementation of stable food products like flour is an effective, simple and safe public health measure that can improve the thiamine status of all population groups.

Brain Damage, Chronic↗

PubMed2003

Comparison of daily urine, sweat, and skin swabs among cocaine users.

This study (1) compares urine, skin swabs, and PharmChek sweat patches for monitoring drug use; (2) measures possible environmental contamination in recent cocaine (COC) users; and (3) evaluates various immunoassays (IA) for screening COC in diverse matrices. Unique aspects include daily urine monitoring of 10 participants for 4 weeks, multiple monitoring methods, analysis for all specimens by IA and gas chromatography (GC)/mass spectrometry (MS), and the potential for continued illicit drug use by participants. Urine served as the "gold standard" specimen for determining drug use. Only cocaine and related substances were detected. Trace amounts of drugs were found on the skin (<50 ng per swab) of urine-negative participants' hands or forehead. In contrast, larger quantities of COC were found on the skin of individuals with BE-positive urines or individuals living with drug users (up to 20 microg per swab). Patch COC amounts among the three regular users (250-9000, 0-240, 160-22,000 ng per patch) exceeded BE (50-950, none, 30-2200 ng per patch). Pre-swabs, valuable for interpreting the source or time frame of positive patch results, contained substantial COC (38-1160, 0-152, 34-762 ng per swab) prior to patch application; therefore, patch results may represent current use, prior use, contamination, or a combination. In three individuals with no indication of cocaine use, false positives (defined as sweat patch positive when urine specimens were <300ng BE/ml) occurred at a 7% rate. Proposed cut-off concentrations of 75 ng cocaine per patch and 300 ng BE/ml urine curtail the incidence of false positives in this limited population. Three immunoassays were compared to screen specimens for cocaine: a modified, manual Microgenics CEDIA; a Cozart ELISA; and an OraSure ELISA. CEDIA's limit of detection (LOD) was 81ng/ml, compared with LODs of 4 ng/ml for the Cozart ELISA and 1.5 ng/ml for the OraSure ELISA. Cozart correlated with OraSure results for COC concentrations <2000 ng per swab (n=117), r(2)=0.79.

Adult↗

PubMed2002

Consensus neuropathological diagnosis of common dementia syndromes: testing and standardising the use of multiple diagnostic criteria.

The aim of this study was to assess the variation between neuropathologists in the diagnosis of common dementia syndromes when multiple published protocols are applied. Fourteen out of 18 Australian neuropathologists participated in diagnosing 20 cases (16 cases of dementia, 4 age-matched controls) using consensus diagnostic methods. Diagnostic criteria, clinical synopses and slides from multiple brain regions were sent to participants who were asked for case diagnoses. Diagnostic sensitivity, specificity, predictive value, accuracy and variability were determined using percentage agreement and kappa statistics. Using CERAD criteria, there was a high inter-rater agreement for cases with probable and definite Alzheimer's disease but low agreement for cases with possible Alzheimer's disease. Braak staging and the application of criteria for dementia with Lewy bodies also resulted in high inter-rater agreement. There was poor agreement for the diagnosis of frontotemporal dementia and for identifying small vessel disease. Participants rarely diagnosed more than one disease in any case. To improve efficiency when applying multiple diagnostic criteria, several simplifications were proposed and tested on 5 of the original 20 cases. Inter-rater reliability for the diagnosis of Alzheimer's disease and dementia with Lewy bodies significantly improved. Further development of simple and accurate methods to identify small vessel lesions and diagnose frontotemporal dementia is warranted.

Alzheimer Disease↗

PubMed2002

Variation at the APOE -491 promoter locus is associated with altered brain levels of apolipoprotein E.

The apolipoprotein E (APOE, gene; apoE, protein) type 4 isoform is a well-established risk factor for late-onset Alzheimer's disease (AD), and new data suggest that APOE promoter polymorphisms might also modulate AD risk, perhaps by altering transcription of the APOE gene. The current study was undertaken to determine whether the presence of the APOE promoter -491AA genotype (that appears to increase the risk for AD) is associated with an increase in the levels of apoE in brain tissue. Among 40 control and 20 autopsy-confirmed AD brain samples, levels of apoE were increased in the frontal cortex of AD cases (P < 0.001), consistent with the well-recognized up-regulation of APOE expression in reactive astrocytes. Among controls, the -491A allele appeared to impart a gene dose-dependent effect on the levels of apoE in frontal cortex. The levels of apoE in the brains of AD patients with the -491AA genotype were increased as compared to control subjects with the same genotype (P< 0.001). These data support the notion that the -491AA APOE promoter genotype is associated with elevated brain apolipoprotein E levels, suggesting that the risk for AD may be modulated by the apoE protein level as well as by the apoE protein isoform.

Age of Onset↗

PubMed2002

Conditional reasoning and the Tower of Hanoi: the role of spatial and verbal working memory.

This paper reports a study that investigated the relationships between verbal and spatial measures of working memory capacity and performance on the Tower of Hanoi and a conditional reasoning task. Four working memory measures were included, a simple word span, a simple spatial span, a complex verbal span and a complex spatial span. The participants were 70 undergraduate students. Solution time on the Tower of Hanoi task correlated highly with both measures of spatial memory capacity, but not with the verbal working memory spans. In contrast, logical performance on the conditional reasoning task correlated highly with the complex verbal working memory span, but not with the spatial spans. A confirmatory factor analysis of the data elicited a best-fit model comprising a correlated spatial and verbal factor. The results are interpreted in the context of recent work that suggests a dissociation between spatial and verbal resources at the level of the central executive.

Cognition↗

PubMed2001

Cervical neoplasia risk in women provided hormonal contraception without a Pap smear.

The study was conducted to determine whether women using a demonstration program providing hormonal birth control without concurrent pelvic examination (First Stop) are at higher risk of cervical neoplasia compared to women using traditional family planning clinics. Using retrospective ion of medical charts, we compared risk factors for cervical neoplasia among 400 First Stop clients and 400 traditional site clients matched on age, race, and contraceptive method. We determined prevalence of these factors: previous abnormal cervical smear, <16 years at first intercourse, multiple sexual partners, high parity, history of sexually transmitted infections, and current cigarette smoking. First Stop clients were not at greater likelihood of having any risk factor for cervical neoplasia except high parity. First Stop clients who failed to follow through on a referral to a traditional clinic were not more likely to be of higher risk than those who did follow through. Of 13 First Stop clients with the highest risk profiles (previous abnormal cervical smear plus one other risk factor), one did not follow through with referral. First Stop clients choosing hormonal contraception without a pelvic examination do not appear to be at substantially higher risk of cervical neoplasia. Future research should quantify more precisely the risks and benefits of the general application of this strategy on a population level.

Adolescent↗

PubMed2001

Comparing the effects of stimulation and propofol infusion rate on implicit and explicit memory formation.

Doubt remains about the conditions under which learning persists despite anaesthesia. This study investigated the relative importance of dose of anaesthetic and stimulation for learning during propofol infusion before surgery. Thirty-six patients were randomly assigned to three groups. Group 1 received two word lists (category examples and nonsense words) during infusion of propofol to a target concentration of 2 microg ml(-1). Groups 2 and 3 received the word lists during infusion of propofol 5 microg ml(-1). Group 2 received nonsense words before tracheal intubation and category examples during intubation; Group 3 heard category examples before and nonsense words during intubation. Bispectral index was recorded as a measure of depth of sedation/anaesthesia. We assessed explicit memory on recovery using a structured interview and a recognition test. We assessed implicit memory using a category generation test and a preference rating task. To establish baseline, a control group of 12 patients completed the category generation test without receiving the category examples during anaesthesia. Overall, there was no evidence for learning during propofol infusion, though the category generation task showed a trend towards more implicit memory for words presented during intubation than during anaesthesia. We conclude that learning does not occur during anaesthesia without surgery.

Anesthetics, Intravenous↗

PubMed2001

Neuroimaging in alcoholism: ethanol and brain damage.

This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The co-chairs were Karl Mann and Ingrid Agartz. The presentations were (1) Neuropathological changes in alcohol-related brain damage, by Clive Harper; (2) Regional brain volumes including the hippocampus and monoamine metabolites in alcohol dependence, by Ingrid Agartz, Susan Shoaf, Robert R, Rawlings, Reza Momenan, and Daniel W Hommer; (3) Diffusion tensor abnormalities in imaging of white matter alcoholism, by Adolf Pfefferbaum and Edith V. Sullivan; (4) Use of functional MRI to evaluate brain activity during alcohol cue exposure in alcoholics: Relationship to craving, by Raymond F. Anton, David J. Drobes, and Mark S. George; and (5) mu-Opiate receptor availability in alcoholism: First results from a positron emission tomography study, by Karl Mann, Roland Bares, Hans-Juergen Machulla, Goetz Mundle, Matthias Reimold, and Andreas Heinz.

Alcoholism↗

PubMed2001

Paraneoplastic brain stem encephalitis in a woman with anti-Ma2 antibody.

A woman developed brain stem encephalopathy in association with serum anti-Ma2 antibodies and left upper lobe lung mass. T2 weighted MRI of the brain showed abnormalities involving the pons, left middle and superior cerebellar peduncles, and bilateral basal ganglia. Immunohistochemical analysis for serum antineuronal antibodies was confounded by the presence of a non-neuronal specific antinuclear antibody. Immunoblot studies showed the presence of anti-Ma2 antibodies. A premortem tissue diagnosis of the lung mass could not be established despite two CT guided needle biopsies, and the patient died as a result of rapid neurological deterioration. The necropsy showed that the lung lesion was an adenocarcinoma which expressed Ma2 immunoreactive protein. Neuropathological findings included prominent perivascular inflammatory infiltrates, glial nodules, and neuronophagia involving the brain stem, basal ganglia, hippocampus and the dentate nucleus of the cerebellum. Ma2 is an autoantigen previously identified in patients with germ cell tumours of the testis and paraneoplastic brain stem and limbic encephalitis. Our patient's clinical and immunopathological findings indicate that this disorder can affect women with lung adenocarcinoma, and that the encephalitic changes predominate in those regions of the brain known to express high concentrations of Ma proteins.

Aged↗

PubMed2001

Permacol: clinical experience with a new biomaterial.

Permacol (Tissue Science Laboratories plc, Aldershot, Hants) is a new biomaterial which combines the strength and permanence of synthetic surgical repair materials with the biocompatibility of natural materials. This article examines the clinical application of Permacol in a range of different surgical procedures.

Adolescent↗

PubMed2000

Novel prion protein gene mutation in an octogenarian with Creutzfeldt-Jakob disease.

BACKGROUND: The transmissible spongiform encephalopathies constitute a fascinating and biologically unique group of invariably fatal neurodegenerative disorders that affect both animals and humans. Creutzfeldt-Jakob disease (CJD), Gerstmann-Straussler-Scheinker syndrome, and fatal familial insomnia represent the more common human phenotypes. Excluding the small number of iatrogenically transmitted cases, approximately 85% to 90% of patients develop CJD without identifiable explanation, with an increasing number of different mutations in the prion protein gene (PRNP) recognized as probably causative in the remainder. OBJECTIVE: To report on an 82-year-old woman with pathologically confirmed CJD found unexpectedly to harbor a novel mutation in PRNP. METHODS: Routine clinical investigations were undertaken to elucidate the cause of the rapidly progressive dementia and neurological decline manifested by the patient, including magnetic resonance imaging of the brain, electroencephalography, and cerebrospinal fluid analysis for the 14-3-3 beta protein. Standard postmortem neuropathological examination of the brain was performed, including immunocytochemistry of representative sections to detect the prion protein. Posthumous genetic analysis of the open reading frame of PRNP was performed on frozen brain tissue using polymerase chain reaction and direct sequencing. RESULTS: Concomitant with the exclusion of alternative diagnoses, the presence of characteristic periodic sharp-wave complexes on the electroencephalogram in combination with a positive result for 14-3-3 beta protein in the cerebrospinal fluid led to a confident clinical diagnosis of CJD, confirmed at autopsy. There was no family history of dementia or similar neurological illness, but patrilineal medical information was incomplete. Unexpectedly, full sequencing of the PRNP open reading frame revealed a single novel mutation consisting of an adenine-to-guanine substitution at nucleotide 611, causing alanine to replace threonine at codon 188. CONCLUSIONS: In addition to expanding the range of PRNP mutations associated with human prion diseases, we believe this case is important for the following reasons. First, from an epidemiological perspective, the avoidance of occasional incorrect classification of patients manifesting neurodegenerative disorders that may have a genetic basis requires systematic genotyping, particularly when there are uncertainties regarding the family history. Second, the incidence of spongiform encephalopathy in elderly patients beyond the typical age range may be underestimated and does not preclude a genetic basis. Finally, as a corollary, this case highlights problematic issues in human transmissible spongiform encephalopathies, as illustrated by disease penetrance and age of onset in genotype-phenotype correlations.

14-3-3 Proteins↗

PubMed2000

Emergency contraception: advance provision in a young, high-risk clinic population.

OBJECTIVE: To assess whether advance provision of emergency contraception increases its use and whether it has secondary effects on regular contraceptive use. METHODS: We conducted a controlled trial of female clients, aged 16-24 years, who attended a publicly funded family planning clinic. Women were systematically assigned to receive an advance provision of emergency contraception and education (treatment) or education only (control). Among 263 participants enrolled (133 treatment, 130 control), follow-up was completed in 213 (111 treatment, 102 control). The main outcome measures were emergency contraception knowledge and use, frequency of unprotected sex, and pattern of contraceptive use in the past 4 months. RESULTS: Participants were aware of emergency contraception at follow-up, but the treatment group was three times as likely to use it (P =.006). Although the treatment group did not report higher frequencies of unprotected sex than the control group, women in the treatment group (28%) were more likely than those in the control group (17%) to report using less effective contraception at follow-up compared with enrollment (P =.05). The proportion of women in both groups who reported consistent pill use increased from enrollment to follow-up (34% versus 45%); however, the control group (58%) was more likely than the treatment group (32%) to report consistent pill use at follow-up (P =.03). CONCLUSION: Use of emergency contraception was increased by providing it in advance, but not by education alone. Changes to less effective contraceptive methods and patterns of pill use were potentially negative effects that need to be explored in relation to observed benefits.

Adolescent↗

PubMed2000

Treatment of choroidal melanoma by stereotactic radiosurgery.

The case of a 49-year-old woman with an intermediate-sized choroidal melanoma who was treated with stereotactic radiosurgery with good tumour resolution is presented. Sight and globe preservation were achieved. The treatment technique is discussed.

Choroid Neoplasms↗

PubMed2000

Iodine-I25 episcleral plaque therapy in uveal melanoma.

PURPOSE: To assess the efficacy of iodine-125 (I-125) episcleral plaque therapy in the management of uveal melanoma with regard to local control, survival, globe preservation and visual outcome. METHODS: Between January 1985 and January 1997, 50 patients with the diagnosis of uveal melanoma were treated with I-125 episcleral plaques. The mean initial tumour height was 5.5 mm (range, 2.0-9.5 mm) and basal diameter 9.5 mm (range, 4.0-14.5 mm). I-125 seeds with a mean activity of 1259.1 MBq were used. The mean apical dose was 80.5 Gy (range, 68.0-95.0 Gy). Scleral dose ranged from 225.0 to 940.0 Gy. Pretreatment visual acuity was 6/60 or better in 43 patients. RESULTS: One patient was lost to follow up and excluded from analysis. The remaining 49 patients had a mean follow up of 39.5 months. There were seven local failures, with a mean duration to tumour progression of 16.7 months. All seven patients were successfully managed with enucleation. Five other enucleations were performed for treatment-related complications. At the time of analysis, 10 patients have died, five of metastatic melanoma. Of the patients with preserved globes, corrected visual acuity was 6/60 or better in 31 patients. CONCLUSIONS: Good local tumour control and survival can be achieved with episcleral plaque therapy. Globe preservation with useful vision was possible in the majority of cases. Our findings are in keeping with other reported series.

Adult↗

PubMed2000

WESTCOP: a disease management approach to coronary artery disease.

Disease management is a systematic approach to improving care of populations of patients with specific clinical conditions. Critical to success are the formation of collaborative teams of health care stakeholders, development and promulgation of clinical practice guidelines, and performance measurement and feedback to providers as a process of continuous practice improvement. This article describes a disease management program for patients with coronary artery disease in a provincial health district with a population of 180,000. It discusses the rationale and methods behind the operationalisation of the main program elements, benefits achieved to date and challenges confronted.

Acute Disease↗