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Biomedical subjects

P Harris

Publications and source records attributed to P Harris.

At least 55 records · Page 3Linked to original sources
PubMed2000

Statins and cardiovascular diseases: the multiple effects of lipid-lowering therapy by statins.

Cholesterol lowering involving different therapies improves the clinical outcome of patients. To define the underlying pathomechanism, we studied whether treatment with statins was associated with changes in blood thrombogenicity, endothelial dysfunction and soluble adhesion molecule levels. Fifty hypercholesterolemic patients were treated with pravastatin (40 mg/day, n=24) or simvastatin (20 mg/day, n=26). Lipid profile and blood thrombogenicity were assessed in all patients before and after 3 months of cholesterol reducing therapy. Blood thrombogenicity was assessed as thrombus formation, perfusing non-anticoagulated blood directly from the patients' vein through the Badimon perfusion chamber (shear rate 1690/s). Endothelial-dependent vasomotor response was tested by laser-Doppler flowmeter. Soluble adhesion molecule level were measured by ELISA. Total and LDL cholesterol were reduced in the two treatment groups by statin therapy. Statin therapy was associated with a significant reduction in blood thrombogenicity and endothelium-dependent vasoresponse. No differences were observed between simvastatin or pravastatin treatment. Lipid lowering by statins had no effect on plasma levels of fibrinogen, sL-selectin, sP-selectin and sICAM-1 antigen. Cholesterol lowering by both statins reduced the increased blood reactivity and endothelial dysfunction present under hypercholesterolemia. The multiple effects of lipid lowering therapy by statins may explain the benefits observed in recent epidemiological trials.

Anticholesteremic Agents↗
PubMed2000

Childhood tumors.

Pediatric solid tumors represent a distinct set of malignancies of embryonal origin whose incidence peaks in the first years of life. Specific genetic anomalies with pathogenic significance, which have helped to define the diagnosis better and to improve the prognosis of children with these tumors, recently have been discovered. Survival of children with solid tumors also has improved significantly because of effective multidisciplinary care, which, in this case, always involves chemotherapy and surgery. These favorable results require that children with these diseases are referred and treated at institutions that have multidisciplinary teams and the infrastructure and expertise for caring for these children. Diagnostic and therapeutic principles for the most common childhood solid tumors are discussed in this article, with an emphasis on surgical procedures.

Adolescent↗
PubMed2000

Steady-state visually evoked potential topography during the continuous performance task in normal controls and schizophrenia.

OBJECTIVES: To examine the latency topography of the steady-state visually evoked potential (SSVEP) in patients diagnosed with schizophrenia and normal controls while undertaking a visual vigilance task. METHODS: Twenty patients diagnosed with schizophrenia and 18 normal controls performed the A-X version of the continuous performance task (CPT A-X) where subjects are required to press a micro-switch on the unpredictable appearance of an 'X' that had been preceded by an 'A.' Brain electrical activity was recorded from 64 scalp sites and a 13 Hz spatially uniform visual flicker presented with the task was used to elicit a steady-state visually evoked potential (SSVEP). RESULTS: Following the appearance of the 'A' and 'X,' the control group demonstrated a transient SSVEP latency reduction at parietal and prefrontal sites. By contrast, the patients group showed no such SSVEP latency reduction. The prefrontal SSVEP latency changes in the 500 ms interval following the appearance of the 'X' were correlated with mean individual reaction time in both populations. CONCLUSIONS: We suggest that the SSVEP latency reduction may index excitatory processes and that the absence of prefrontal SSVEP latency reduction in schizophrenic patients may be a manifestation of reduced prefrontal activity or 'hypofrontality' observed with other neuroimaging modalities.

Adult↗
PubMed2000

Teaching on the run: teaching skills for surgical trainees.

BACKGROUND: Increasing recognition of the need for training in teaching skills for clinical teachers has coincided with data that registrars and residents conduct much 'on the job' teaching as part of their routine work. While attention has been devoted to training consultants, support for the teaching role of the junior staff has been relatively neglected. The aim of the present report is to describe the teaching experiences of surgical registrars and the impact of a registrar teaching workshop. METHOD: A half-day programme combining presentation and discussion of surgical teaching with practical skills sessions was designed for surgical registrars at Prince of Wales Hospital. The programme included observation and feedback of brief teaching simulations at the bedside of volunteer patients to newly commenced clinical students, and small group sessions on clinic and operating theatre teaching. A pre-workshop questionnaire sought information about the registrars' own teaching, and a survey 3 months after the workshop determined if any changes to teaching practice had occurred. RESULTS: The registrars were generally moderately to very confident with their teaching ability but more than 75% felt that they were more confident after the workshop. Only three of 39 registrars had received any instruction aimed at improving their teaching skills, yet 34/39 had taught either on the ward, in the clinics or in the operating room. Follow-up after 3 months revealed that most registrars were enjoying their teaching tasks more, and half had increased their teaching since the workshop and began discussing teaching with their surgical colleagues. CONCLUSIONS: The present project demonstrates that relatively brief interventions focused on skill development may enhance the confidence and enjoyment of junior clinical teachers and increase the frequency of 'teaching on the run'.

Attitude of Health Personnel↗
PubMed2000

The prevalence of complementary and alternative medicine use among the general population: a systematic review of the literature.

OBJECTIVE: To conduct a systematic review of published research investigating the prevalence of complementary and alternative medicine (CAM) use in the general population. DESIGN: A protocol was developed for a systematic review of survey literature identified using two bibliographic databases and citation tracking. The protocol specified criteria for: 1) database searches; 2) selection of studies for review; and 3) description of methodological and substantive aspects of the studies. RESULTS: Twelve studies were reviewed. These estimated the prevalence of CAM use in Australia, Canada, Finland, Israel, the UK, and the USA. The most rigorous studies, conducted in Australia and the USA, showed that a high proportion of the population was using CAM. There was evidence from the USA that CAM use increased significantly among the general population during the 1990s. CONCLUSION: CAM is used by substantial proportions of the general population of a number of countries, but differences in study design and methodological limitations make it difficult to compare prevalence estimates both within and between countries.

Australia↗
PubMed2000

[Spanish verbal fluency. Normative data in Argentina].

Letter and category fluency tasks are used to assess semantic knowledge, retrieval ability, and executive functioning. The original normative data have been obtained mainly from English speaking populations; there are few papers on norms in other languages. The purpose of this study was to collect normative scores in Argentina and to evaluate the effects of sex, age, education and cognitive status on the letter and category fluency tasks, in 266 healthy Spanish-speaking participants (16 to 86 years). Mean education span was 12.8 +/- 4 years. In each subject a neuropsychological battery (Minimental State Exam, Signoret Memory Battery, Boston Naming Test and Trail Making Test) was carried out as well as category fluency (naming animals in one minute) and letter fluency (words beginning with letter "p" in one minute). The sample was arranged into a group of subjects with less than 45 years and further groups up to 10 more years, until 75 years (or more) with three different levels of education. Significant effects were found for age, education, and Minimental State Exam on performance of both fluencies. Mean performance scores are presented for each group to be used in Argentina.

Adolescent↗
PubMed1999

The Ovarian Tumor Index predicts risk for malignancy.

BACKGROUND: Prediction of ovarian malignancy by ultrasonographic findings and patient age in the scenario of clinically suspected adnexal masses is a desirable goal. METHODS: Prospective evaluation of clinically suspected adnexal masses was performed with transvaginal ultrasound using real-time, Doppler velocimetry, and color-flow mapping. Continuous ultrasound variables included ovarian volume, the Sassone morphology scale, and Doppler determination of angle-corrected systole, diastole, and time-averaged velocity, in addition to patient age. The Doppler pulsatility index (PI), vessel location, presence of a diastolic notch, and echogenic predominance of the lesion, suggestive of dermoid, also were assessed. RESULTS: Of 244 women with follow-up, 214 had nonmalignant findings (85 of which were benign neoplasms), and 30 had malignant neoplasms. Age and all ultrasound continuous variables except systole were found to be statistically significant (P < 0.05) between patients with both malignant (N = 30) and nonmalignant masses (N = 214), as well as those with benign (N = 85) and malignant (N = 30) neoplasms. By adding the continuous measures (age [in years], ovarian volume [mL], and Sassone morphology scale [1-15]) and weighting other variables ([-10] x PI, central or septal location [+10], peripheral location [-10], and echogenic [-10]), a receiver operating characteristic curve was generated (area under the curve = 0.91), which was found to be discriminating, predictive, and able to replicate the more complex logistic regression model. Prediction of malignancy was generated from the population-based data of the current study. CONCLUSIONS: The Ovarian Tumor Index, which combines patient age with specific ultrasonographic markers, is an accurate method for predicting ovarian malignancy in the clinical scenario of suspected adnexal masses.

Adolescent↗
PubMed1999

TCR repertoire of suppressor CD8+CD28- T cell populations.

The cellular basis of graft rejection and the development of strategies for specific suppression of T cell responses against allogeneic and xenogeneic transplants represents an area of active investigation. Recently, a population of MHC-class I restricted CD8+CD28- T suppressor cells (Ts) which are able to inhibit specifically the proliferative response of allospecific, xenospecific and nominal-antigen specific CD4+ T helper cells (Th) has been identified. We have studied the TCR V beta gene repertoire expressed by CD8+CD28- Ts isolated from allospecific, xenospecific, and nominal antigen-specific T cell lines (TCL). A limited V beta repertoire has been found in all TCLs studied. The most restricted TCR V beta usage was observed within the population of Ts from xenospecific TCLs. The TCR V beta usage within the Ts subset of TCL differs from the TCR repertoire expressed by the CD4+ Th subset of the same TCL. This is consistent with the fact that Ts and Th cells recognize distinct MHC/ antigen complexes. The finding that the TCR repertoire used by Ts is limited opens new avenues for studying the mechanisms of transplant rejection.

Animals↗
PubMed1999

Development of autologous human dermal-epidermal composites based on sterilized human allodermis for clinical use.

The aim of this study was to identify a sterilization technique for the preparation of human allodermis which could be used as a dermal component in wound healing and as the dermal base for production of dermal-epidermal composites for one-stage grafting in patients. We report that it is possible to produce dermal-epidermal composites which perform well in vitro and in vivo using a standard ethylene oxide sterilization methodology. Prevention of ethylene oxide-induced damage to the dermis was achieved using gentle dehydration of the skin prior to ethylene oxide sterilization. The issue of whether viable fibroblasts are required for composite production was examined in comparative studies using glycerol vs. ethylene oxide sterilized dermis. Where good collagen IV retention was achieved following preparation of acellular de-epidermized dermis there was no advantage to having fibroblasts present in vitro or in vivo; however, where collagen IV retention was poor or where keratinocytes were initially expanded in culture then there was a significant advantage to introducing fibroblasts to the composites during their preparative 10-day period in vitro. The requirement for fibroblasts became less evident when composites were grafted on to nude mice. In conclusion, we report a protocol for the successful sterilization of human allodermis to achieve an acellular dermis with good retention of collagen IV. This acellular dermis would be appropriate for clinical use as a dermal replacement material. It can also be used for the production of dermal-epidermal composites using autologous keratinocytes (with or without fibroblasts).

Adult↗
PubMed1999

Genetic studies of a family with hereditary hyperparathyroidism-jaw tumour syndrome.

BACKGROUND AND OBJECTIVES: Familial hyperparathyroidism may occur as familial isolated hyperparathyroidism (FIHP) or as part of an inherited syndrome, in particular multiple endocrine neoplasia types 1 and 2A (MEN1, MEN2A) and hyperparathyroidism-jaw tumour (HPT-JT) syndrome. The localization of the genes responsible for these syndromes has enabled genetic screening of families with primary hyperparathyroidism (PHPT) to be carried out. This has important clinical implications in terms of individual follow-up and management. We previously reported a large FIHP family with an increased risk of parathyroid cancer and excluded its linkage to MEN1, MEN2 and PTH genes. Here we re-analysed this family and performed genetic linkage to the HPT-JT locus in chromosome 1q21-q32. Loss of heterozygosity studies of 1q21-q32, 11q13 and X chromosome were also performed. PATIENTS AND DESIGN: We studied 19 family members, aged 6-63 years. High molecular weight DNA was isolated from peripheral blood samples from 17 family members. For the two deceased individuals, DNA was extracted from normal paraffin embedded tissues. MEASUREMENTS: All individuals (except two deceased patients) had serum corrected calcium, inorganic phosphate, intact PTH, prolactin and various pancreatic hormones, measured on fasting blood samples. Twenty microsatellite markers were examined for the 1q21-q32 region, the locus for the HPT-JT gene. Genetic polymorphisms were determined by polymerase chain reaction amplification of genomic DNA and genetic linkage analysis was performed. Loss of heterozygosity studies were performed using paraffin-embedded parathyroid tissues from four affected members. RESULTS: Seven of the eight affected family members included in this study had biochemical evidence of PHPT and surgically proven parathyroid tumours. Indication of linkage of the disease to the HPT-JT locus was demonstrated with a maximum lod score of 2.32 by two-points linkage analysis. Linkage data were supported by multi-point analysis which gave a maximum lod score of 2.7. Meiotic recombinations detected in one affected individual narrowed the region to 26 cM. As a result of the genetic findings, we re-screened the living family members by orthopantomograph and renal ultrasound, and identified two jaw lesions in two gene carriers. One affected family member demonstrated polycystic kidney disease, thus establishing the association between the two conditions. A reduced penetrance of HPT in females was evident, in agreement with our previous study. No allelic deletion was detected in any tumour at 1q21-q32, 11q13 or X chromosome. CONCLUSIONS: This study illustrates the usefulness and importance of genetic studies in familial isolated hyperparathyroidism families. Our clinical and genetic findings indicate that this previously reported familial isolated hyperparathyroidism family has hyperparathyroidism-jaw tumour syndrome.

Adolescent↗
PubMed1999

Rat renomedullary interstitial cells possess bradykinin B2 receptors in vivo and in vitro.

1. Renomedullary interstitial cells (RMIC), abundant throughout the medulla of the kidney, have been demonstrated to have binding sites for many vasoactive peptides, including atrial natriuretic peptide, endothelin, angiotensin II and bradykinin (BK). These observations would support the hypothesis that interactions between RMIC and vasoactive peptides are important in the regulation of renal function. 2. We aimed to localize the BK B2 receptor binding site to RMIC in vivo and to also demonstrate that these receptors are biologically active in vitro. 3. The present study demonstrates BK B2 binding sites on RMIC of the inner stripe of the outer medulla and the inner medulla of the rat kidney in vivo. 4. We further demonstrate that the BK B2 radioligand [125I]-HPP-Hoe140 specifically bound to rat RMIC in vitro. In addition, reverse transcription-polymerase chain reaction detected the mRNA for the BK B2 receptor subtype in cell extracts. 5. For RMIC in vitro, cAMP levels were increased at 1 min and cGMP levels were increased at 2 min after treatment with 10(-10) and 10(-7) mol/L BK, respectively. Inositol 1,4,5-trisphosphate was increased at 10 s treatment with both 10(-6) and 10(-7) mol/L BK. 6. For RMIC in vitro, BK induced an increase in cell proliferation ([3H]-thymidine incorporation) and an increase in extracellular matrix synthesis (ECM; trans-[35S] incorporation), both effects mediated by BK B2 receptors. 7. We conclude that BK B2 receptors are present on RMIC both in vivo and in vitro. These receptors are coupled to intracellular second messenger systems and, in vitro, their stimulation results in cellular proliferation and synthesis of ECM.

Animals↗
PubMed1999

Seven novel mutations of the PKD2 gene in families with autosomal dominant polycystic kidney disease.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is genetically heterogeneous, with at least three chromosomal loci accounting for the disease. Mutations in the PKD2 gene on the long arm of chromosome 4 are expected to be responsible for approximately 15% of cases of ADPKD. METHODS: We report a systematic screening for mutations covering the 15 exons of the PKD2 gene in eight unrelated families with ADPKD type 2, using the heteroduplex technique. RESULTS: Seven novel mutations were identified and characterized that, together with the previously described changes, amount to a detection rate of 85% in the population studied. The newly described mutations are two nonsense mutations, a 1 bp deletion, a 1 bp insertion, a mutation that involves both a substitution and a deletion (2511AG-->C), a complex mutation in exon 6 consisting of a simultaneous 7 bp inversion and a 4 bp deletion, and the last one is a G-->C transversion that may be a missense mutation. Most of these mutations are expected to lead to the formation of shorter truncated proteins lacking the carboxyl terminus of PKD2. We have also characterized a frequent polymorphism, Arg-Pro, at codon 28 in this gene. The clinical features of these PKD2 patients are similar to the previously described, with the mean age of end-stage renal disease being 75.5 years (SE +/- 3.8 years). CONCLUSIONS: Our results confirm that many different mutations are likely to be responsible for the disease and that most pathogenic defects probably are point or small changes in the coding region of the gene.

Amino Acid Sequence↗
PubMed1999

Implementation of nationally developed guidelines in cardiology: a survey of NSW cardiologists and cardiothoracic surgeons.

BACKGROUND: In July 1996, the National Health and Medical Research Council (NHMRC) published clinical practice guidelines for 'The Procedural and Surgical Management of Coronary Heart Disease'. Despite increasing interest in dissemination and implementation of guidelines, initial reactions to these specific Guidelines and factors critical to their successful implementation had not been determined until our study. AIMS: To determine views of New South Wales (NSW) clinicians towards these NHMRC Guidelines; to identify perceptions about local relevance, usefulness and likely impact and to elicit preferred implementation strategies. METHODS: A postal survey in November 1997 of all cardiologists and cardiothoracic surgeons in NSW. RESULTS: One hundred and ten of 174 clinicians returned the questionnaire (63% response rate). Forty-eight per cent indicated that they were aware of the Guidelines before receiving a copy with the questionnaire while 26% had commented on the draft version of the Guidelines when distributed in November 1995. More than half of respondents 'agreed' or 'strongly agreed' with six of nine statements about potential strengths of the Guidelines. While at least 25% 'disagreed' or 'strongly disagreed' on 11 out of the 13 statements about potential criticisms of the Guidelines, more than half agreed or 'strongly' agreed that the Guidelines did not tell them 'anything they didn't already know'. Fifty-two per cent 'agreed' or 'strongly agreed' that guidelines will be misinterpreted by lawyers. At least 30% rated nine out of 11 implementation strategies as important. Local audits of care and regular feedback, reports from colleagues at conferences and hospital workshops outranked other implementation strategies in encouraging uptake of the Guidelines. CONCLUSIONS: Clinicians in NSW have generally positive views about the Guidelines, however, medicolegal concerns are apparent. To strengthen evidence-based decision-making as exemplified by the Guidelines, audits, presentations by opinion leaders and hospital-based workshops are recommended.

Attitude of Health Personnel↗
PubMed1999

A comparison of grain, oil and beet pulp as energy sources for the exercised horse.

High-grain diets for the exercising horse were compared with diets which provided 15% of the total caloric intake from either vegetable oil or a highly fermentable fibre source (beet pulp). Six Thoroughbreds age 3 years were fed one of 3 diets or 5 weeks in a replicated 3 x 3 Latin square. The CONTROL diet was 3.65 kg of sweet feed (SF), 0.9 kg of a protein/vitamin/mineral pellet and 5.45 kg of hay cubes. The FAT diet replaced 1.15 kg of SF with 0.45 kg of soybean oil and the FIBRE diet replaced 1.15 kg of SF with 1.36 kg of beet pulp. Horses were exercised 3 times per week on a high-speed treadmill. During the last week of each period, the horses performed a standardised exercise test (SET). A series of blood samples was drawn immediately before feeding and every 0.5 h for 3 h after feeding, throughout the exercise bout and 30 min post exercise. Plasma was analysed for lactate, glucose, cortisol, insulin, packed cell volume, total protein and triglycerides. Water intake was measured at regular intervals during SET day. Blood glucose was lower (P < 0.05) in the FAT-fed horses during the 3 h post feeding as compared to either CONTROL or FIBRE-fed horses. Insulin was lower (P < 0.05) in the FAT-fed both post feeding and throughout exercise. Cortisol was lower (P < 0.05) in the FAT than the CONTROL-fed during exercise. Following exercise, the FAT-fed drank more water (P < 0.01) than either CONTROL or FIBRE-fed. Substituting 15% of DE as vegetable oil had a greater effect on metabolic response to exercise than a 15% substitution of beet pulp.

Animal Feed↗
PubMed1999

A large pelvic arteriovenous malformation in an adult patient with cystic fibrosis.

We present a prepubertal male cystic fibrosis patient with high circulating oestrogen levels (as a consequence of sever cystic-fibrosis-related hepatobiliary disease) who subsequently developed a large pelvic arteriovenous malformation. This has not previously been described in patients with cystic fibrosis, despite the association between high oestrogen levels and arteriovenous malformations. The aetiology and treatment options of arteriovenous malformations are discussed.

Adolescent↗
PubMed1999

Longitudinal aneurysm shrinkage following endovascular aortic aneurysm repair: a source of intermediate and late complications.

PURPOSE: To report the incidence of delayed complications following endovascular abdominal aortic aneurysm (AAA) repair and the relationship of these sequelae to morphological changes in the sac and endograft. METHODS: Twenty-six AAA patients treated with Vanguard endografts had completed > or = 1-year follow-up. Postoperative angiograms and spiral computed tomographic (CT) scans with 3-dimensional reconstruction were compared to the 1-year images to determine morphological changes in the aneurysm sac and the endograft. These changes were then related to complications occurring between 1 and 12 months postoperatively in the study group. RESULTS: Comparison of angiograms uncovered endograft buckling in 18 (69%) patients and acutely angled or kinked endografts in 10 (38%). Measurements from the CT scans found that undistorted endografts had a mean change in sac length of +6.6 mm. Mean sac length change in buckled endografts was -3.1 mm, while kinked endografts displayed a mean change of -6.2 mm (p < 0.002, Student's t-test). Five (19%) patients, all with distorted endografts, demonstrated late (1 to 12 months) complications (4 endoleaks and 1 graft limb thrombosis) owing to component separation, distal stent migration, and acute angulation. No movement in the proximal stent was observed. Elongation of the endograft (flow line measurement) was observed in one tube graft only. CONCLUSIONS: In this study, longitudinal shrinkage of the sac following endovascular aortic aneurysm repair led to buckling or kinking of the endograft within 1 year in 69% of patients. This appears to be an important source of delayed complications.

Aged↗