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Biomedical subjects

J Ross

Publications and source records attributed to J Ross.

At least 19 recordsLinked to original sources
PubMed2006

Nanointerrogation of ultrasonic contrast agent microbubbles using atomic force microscopy.

Predicting the acoustic response of an encapsulated microbubble to ultrasound requires an accurate assessment of the mechanical properties of the microbubble shell. Atomic force microscopy (AFM) provides an unprecedented spatial and force resolution of the order of Angstroms and subnanonewtons, respectively. It is introduced here as a means to interrogate microbubbles manufactured for ultrasonic imaging. The advantage of AFM over scanning electron microscopy (SEM) is that the microbubbles need not be subjected to a low temperature or low-pressure environment. The microbubbles were interrogated in a liquid environment, which could potentially be a simulated physiological environment. AFM was used in tapping mode imaging to reveal topographical detail of biSphere microbubbles. Because microbubbles are large objects compared with the overall size of usual AFM tips, a convolution between the AFM tip and the microbubble was typical of the acquired topographies. However, a part of the top half of the bubble was imaged with nanometer resolution, and roughness measurements are reported. Force-distance curves were captured using contact mode AFM. The range of stiffness or effective spring constant of biSphere was found to be between 1 and 6 N m(-1). In conclusion, the AFM is proposed here for the first time as a tool to image the surface of bubbles at the nanometer range in liquid and to perform reproducible measurements on the mechanical properties of individual microbubbles.

Biomechanical Phenomena↗
PubMed2005

Comparative performance evaluation of the HIV-1 LiPA protease and reverse transcriptase resistance assay on clinical isolates.

BACKGROUND: Assays that provide information regarding HIV-1 resistance to antiretroviral drugs are widely used to help manage antiretroviral treatment. The most commonly used HIV genotypic resistance assays are based on DNA sequencing (TRUGENE, ViroSeq, and home-brew) or reverse hybridization (LiPA). OBJECTIVES: This study compares the results from clinical specimens using two assay methods: the LiPA HIV-1 protease (PR) and reverse transcriptase (RT) resistance assay and DNA sequencing. STUDY DESIGN: Operators at each of three sites tested 10-20 randomly selected clinical specimens using LiPA (three strips total with probes for PR codons 30, 46, 48, 50, 54, 82, 84, and 90, and RT codons 41, 69, 70, 74, 75, 103, 106, 151, 181, 184, and 215) and DNA sequencing (TRUGENE) HIV-1 Genotyping Assay or home-brew methodology). Results from the two methods were categorized for each codon as follows: (i) concordant (LiPA and sequencing having the same result for wild-type (WT), mutant, and mixture); (ii) partially concordant (mixture by one method and not by the other); (iii) indeterminate (no result by LiPA); and (iv) discordant (LiPA and sequencing detecting different amino acids). RESULTS: A total of 50 clinical specimens were tested using the LiPA PR strip; 40 of these were also tested using the LiPA RT strip. For PR, 91.3% of the codon results were concordant, 3.0% were partially concordant, 4.5% were indeterminate by LiPA, and 1.3% were discordant. For RT, 88.0% of the codon results were concordant, 5.9% were partially concordant, 5.2% were indeterminate, and 0.9% were discordant. LiPA detected 3.0% (PR) and 6.4% (RT) WT/mutant mixtures, compared to 0.5% (PR) and 3.2% (RT) mixtures by sequencing. CONCLUSIONS: More WT/mutant mixtures were detected using LiPA, possibly indicating increased sensitivity. Relatively high concordance and low discordance rates were observed between LiPA and DNA sequencing. The indeterminate rate for LiPA was moderately high and may limit the clinical utility of this assay.

Codon↗
PubMed2004

Gene expression profiles predict complete pathologic response to neoadjuvant paclitaxel and fluorouracil, doxorubicin, and cyclophosphamide chemotherapy in breast cancer.

PURPOSE: The goal of this study was to examine the feasibility of developing a multigene predictor of pathologic complete response (pCR) to sequential weekly paclitaxel and fluorouracil + doxorubicin + cyclophosphamide (T/FAC) neoadjuvant chemotherapy regimen for breast cancer. PATIENTS AND METHODS: All patients underwent one-time pretreatment fine-needle aspiration to obtain RNA from the cancer for transcriptional profiling using cDNA arrays containing 30721 human sequence clones. Analysis was performed after profiling, and 42 patients' clinical results were available, 24 of which were used for predictive marker discovery; 18 patients' results were used as an independent validation set. RESULTS: Thirty-one percent of patients had pCR (six discovery and seven validation), defined as disappearance of all invasive cancer in the breast after completion of chemotherapy. We could identify no single marker that was sufficiently associated with pCR to be used as an individual predictor. A multigene model with 74 markers (P <or=.09) was built using data from the discovery samples and tested on the validation samples. Overall, a 78% (14 of 18) predictive accuracy was observed, with a 100% (three of three) positive predictive value for pCR, a 73% (11 of 15) negative predictive value, a sensitivity of 43% (three of seven), and a specificity of 100% (11 of 11). The expected response rate to T/FAC neoadjuvant therapy in unselected patients is 28%. CONCLUSION: Our results suggest that transcriptional profiling has the potential to identify a gene expression pattern in breast cancer that may lead to clinically useful predictors of pCR to T/FAC neoadjuvant therapy.

Adult↗
PubMed2004

The chlamydia screening studies: rationale and design.

BACKGROUND: Screening has been recommended to reduce the prevalence and morbidity associated with genital chlamydia infection in the United Kingdom. METHODS: We describe the rationale and study design of the Chlamydia Screening Studies (ClaSS), a collaborative project designed to evaluate screening outside genitourinary medicine clinics. A non-selective, active screening approach in 16-39 year olds randomly sampled from 27 general practice lists in the Bristol and Birmingham areas formed the basis of interlinked studies: a case-control study was used to investigate factors to improve the targeting of screening; participants with chlamydia were invited to enroll in a randomised controlled trial to evaluate partner notification conducted in primary care; and laboratory based studies were used to assess the best specimens and tests. We also explored psychosocial effects of screening and partner notification and modelled the cost effectiveness of the programme. CONCLUSION: Results from four pilot practices show that mailing of specimens for chlamydia testing is feasible but that it is difficult to achieve high response rates with postal screening. The high prevalence of asymptomatic infection in men suggests that efforts to screen men for chlamydia should be strengthened.

Adolescent↗
PubMed2003

'Advanced' generation lentiviruses as efficient vectors for cardiomyocyte gene transduction in vitro and in vivo.

Efficient gene transduction in cardiomyocytes is a task that can be accomplished only by viral vectors. Up to now, the most commonly used vectors for this purpose have been adenoviral-derived ones. Recently, it has been demonstrated that lentiviral vectors can transduce growth-arrested cells, such as hematopoietic stem cells. Moreover, a modified form of lentiviral vector (the 'advanced' generation), containing an mRNA-stabilizer sequence and a nuclear import sequence, has been shown to significantly improve gene transduction in growth-arrested cells as compared to the third-generation vector. Therefore, we tested whether the 'advanced' generation lentivirus is capable of infecting and transducing cardiomyocytes both in vitro and in vivo, comparing efficacy in vitro against the third-generation of the same vector. Here we report that 'advanced' generation lentiviral vectors infected most (>80%) cardiomyocytes in culture, as demonstrated by immunofluorescence and FACS analyses: in contrast the percentage of cardiomyocytes infected by third-generation lentivirus was three- to four-fold lower. Moreover, 'advanced' generation lentivirus was also capable of infecting and inducing stable gene expression in adult myocardium in vivo. Thus, 'advanced' generation lentiviral vectors can be used for both in vitro and in vivo gene expression studies in the cardiomyocyte.

Animals↗
PubMed2003

In vivo high-efficiency transcoronary gene delivery and Cre-LoxP gene switching in the adult mouse heart.

High-efficiency somatic gene transfer in adult mouse heart has not yet been achieved in vivo. Here, we demonstrate high-efficiency in vivo transcoronary gene delivery to the adult murine myocardium using a catheter-based technique with recombinant adenovirus (AdV) and adeno-associated virus (AAV) vectors in normal and genetically engineered mice. The method involves immersion hypothermia followed by transient aortic and pulmonary artery occlusion with proximal intra-aortic segmental injection of cardioplegic solution containing substance P and viral vectors. Gene expression measured using a LacZ marker gene was observed throughout both ventricles. The expression efficiency of a cytoplasmic LacZ marker gene in the left ventricular myocardium was 56.4+/-14.5% (mean+/-s.d.) at 4 days with an AdV vector, and with an AAV vector it was 81.0+/-5.9% at 4 weeks. Following AAV gene transfer, no gene expression was found in kidney, brain, lung, and spleen, but there was slight expression in liver. In addition, we demonstrate temporally controlled genetic manipulation in the heart with an efficiency of 54.6+/-5.2%, by transferring an AdV vector carrying Cre recombinase in ROSA26 flox-LacZ reporter mice. Procedure-related mortality was 16% for AdV and zero for AAV transfer. Thus, this method provides efficient, relatively homogeneous gene expression in both ventricles of the adult mouse heart, and offers a novel approach for conditional gene rescue or ablation in genetically engineered mouse models.

Adenoviridae↗
PubMed2003

Removal of the tracheostomy tube in the aspirating spinal cord-injured patient.

STUDY DESIGN: Four related case reports, occurring within a 10-month time frame during 2001. OBJECTIVES: Aspiration is commonly reported in the literature as a contraindication to decannulation. We report four examples of successful removal of the tracheostomy tube in the presence of aspiration by an experienced team, utilising a risk management approach. SETTING: Victorian Spinal Cord Service (VSCS), Austin Hospital, Melbourne, Australia. METHODS: Four individuals in our unit with traumatic spinal cord injury, three quadriplegic and one paraplegic, presented with aspiration identified by a positive modified Evan's blue dye test or constant coughing, gagging and oxygen desaturation during cuff deflation trials. In three of the four cases, the tracheostomy tube had been in situ for a prolonged period and the patients had failed to progress towards decannulation. A decision was made to decannulate these four patients in spite of the presence of traditionally held contraindications for decannulation. The multidisciplinary team carefully compared the inherent risks of premature decannulation against those of prolonged tracheostomisation. Given the risk associated with this procedure, a closely monitored decannulation protocol was instituted. RESULTS: All four patients were successfully decannulated with improved quality of life, eating between 1 and 4 days and communicating immediately after decannulation. None experienced respiratory deterioration. CONCLUSION: It is possible to safely decannulate aspirating spinal cord injured individuals in some instances, using a risk management approach.

Adult↗
PubMed2003

Acute respiratory distress syndrome: an audit of incidence and outcome in Scottish intensive care units.

This prospective audit of incidence and outcome of the acute respiratory distress syndrome was conducted as part of the national audit of intensive care practice in Scotland. All patients with acute respiratory distress syndrome in 23 adult intensive care units were identified using the diagnostic criteria defined by the American-European Consensus Conference. Daily data collection was continued until death or intensive care unit discharge. Three hundred and sixty-nine patients were diagnosed with acute respiratory distress syndrome over the 8-month study period. The frequency of acute respiratory distress syndrome in the intensive care unit population was 8.1%; the incidence in the Scottish population was estimated at 16.0 cases.100,000(-1).year(-1). Intensive care unit mortality for acute respiratory distress syndrome was 53.1%, with a hospital mortality of 60.9%. In our national unselected population of critically ill patients, the overall outcome is comparable with published series (Acute Physiology and Chronic Health Evaluation II standardised mortality ratio = 0.99). However, mortality from acute respiratory distress syndrome in Scotland is substantially higher than in recent other series suggesting an improvement in outcome in this condition.

Adult↗
PubMed2003

Central pontine myelinolysis complicating treatment of multicentric Castleman's disease and Kaposi's sarcoma in a patient with AIDS.

An HIV positive black African woman presented with widespread lymphadenopathy and pancytopenia that had been ascribed to tuberculosis. Lymph node biopsy showed both Kaposi's sarcoma and multicentric Castleman's disease. Despite antiretroviral therapy and chemotherapy the patient deteriorated, developing confusion and dysphasia. A cranial magnetic resonance scan showed central pontine myelinolysis. Despite supportive therapy the patient died.

AIDS-Related Complex↗
PubMed2002

Impact of early endovascular aneurysmal occlusion on outcome of patients in poor grade after subarachnoid haemorrhage: a prospective, consecutive study.

Patients in poor grade (WFNS IV and V) after aneurysmal subarachnoid hemorrhage (SAH) often have a bad outcome. To evaluate early GDC embolisation on such patients a prospective observational study, with comparison to a historical cohort was performed. From January 1996 to December 1998 113 patients were admitted to the Department of Clinical Neurosciences in poor grade after SAH (45 WFNS IV and 68 WFNS V). Eighty-one patients were managed actively with endovascular occlusion of the aneurysm (n = 42) where possible and delayed clipping (n = 16) where not. On an intention to treat basis, 46% had a favourable outcome (Glasgow Outcome Score IV or V) and 48% had died by 3 months. Compared to an historical cohort managed in the same unit between 1992 and 1995 (n = 62, 52% favourable outcome) these results suggest that early GDC aneurysmal occlusion has had a minimal impact on overall outcome.

Adult↗
PubMed2002

Early cervical cancer rescreening.

INTRODUCTION: The extent of early cervical rescreening, defined as rescreening earlier than the recommended interval for a given initial test result, is difficult to determine mainly because the testing history of women is incomplete, especially with newer population based screening registers. METHODS: Estimation of early rescreening is based on analysis of a 1 month cohort of women (February 1997) recorded on the New South Wales Pap Test Register (PTR) who initially tested negative and who had no recorded history of a positive test result. For the purposes of estimating early rescreening rates and sources of multiple screening occurring within the recommended 2 yearly screening interval for New South Wales, the cohort excluded the estimated proportion of women with an unrecorded history of a positive result. Approaches to exclusion were different for women with a history of a high grade result (CIN2 or higher) or a low grade result (CIN1 or lower). RESULTS: Characteristic rescreening peaks occurred at 6, 12, 18, 24 and 27 months according to negative result category. The rescreening peak at 27 months illustrates the effect of the PTR late reminder system. After adjusting the cohort for estimated proportions of women with a history of a lesion, the number of women estimated to have rescreened early was approximately 156 000 over 1997-8, and the early rescreening rate was estimated as 15.3% of women who have a Pap test. A feasible target for reducing rescreening through service provider interventions was estimated to be a reduction of 7.4%, based on reducing the overscreening proportion from 15.3% to 7.9% through truncating characteristic rescreening peaks to background levels of rescreening. This represents just under 200 000 screens that could be performed over 2 years on New South Wales women who are underscreened or unscreened without incurring additional costs due to screening. CONCLUSIONS: Reasonable estimates of early cervical rescreening can be derived but some assumptions in estimating the proportion of women with a positive test result history may be needed particularly if a screening programme is new and universal recording of screening data is only recent. Characteristic peaks, as departures from a background of random noise in time plots of rescreening indicate that a component of early rescreening is systemic and the chief source of such variation in screening behaviour would be service providers.

Adult↗
PubMed2001

A defect in the Kv channel-interacting protein 2 (KChIP2) gene leads to a complete loss of I(to) and confers susceptibility to ventricular tachycardia.

KChIP2, a gene encoding three auxiliary subunits of Kv4.2 and Kv4.3, is preferentially expressed in the adult heart, and its expression is downregulated in cardiac hypertrophy. Mice deficient for KChIP2 exhibit normal cardiac structure and function but display a prolonged elevation in the ST segment on the electrocardiogram. The KChIP2(-/-) mice are highly susceptible to the induction of cardiac arrhythmias. Single-cell analysis revealed a substrate for arrhythmogenesis, including a complete absence of transient outward potassium current, I(to), and a marked increase in action potential duration. These studies demonstrate that a defect in KChIP2 is sufficient to confer a marked genetic susceptibility to arrhythmias, establishing a novel genetic pathway for ventricular tachycardia via a loss of the transmural gradient of I(to).

Action Potentials↗
PubMed2001

Levels of physical activity of a sample of 10-13 year old New Zealand children.

AIMS: To determine what proportion of a sample of 10 to 13 year old New Zealand children attained the Ministry of Health's physical activity guidelines. These guidelines recommend that children accumulate a minimum of 30 minutes of moderate intensity physical activity on most, preferably all, days of the week. METHODS: The heart rates of sixty 10-13 year olds were monitored at one minute intervals, for twelve hours on three week days and one weekend day. For each day, the number of minutes when the subject's heart rate exceeded 139 beats per minutes (bpm) was determined. The proportion of subjects who accumulated at least 30 minutes of heart rates > 139 bpm on three of the four recording days was determined. These subjects were deemed to have met the physical activity guidelines. RESULTS: 53% of subjects met the minimum physical acivity guidelines. Boys spent significantly more of their time with their heart rates elevated above 139 bpm than girls. There was no significant difference between the number of children achieving the recommended guidelines and their school's decile ranking. CONCLUSION: There are indications that children's lives are becoming more sedentary due in part to the popularity of passive forms of leisure and the reduced incidence of active forms of transportation like walking or cycling to school. The low proportion of New Zealand children meeting the minimum physical activity guidelines is a cause for great concern.

Adolescent↗
PubMed2001

Overexpression of an mRNA-binding protein in human colorectal cancer.

A Coding Region instability Determinant-Binding Protein (CRD-BP) binds in vitro to c-myc mRNA and appears to stabilize the mRNA. The CRD-BP gene is amplified in one-third of human breast cancer cases, and the CRD-BP appears to be an oncofetal protein. To analyse CRD-BP expression in human cancer tissue, paired extracts of cancer and normal colon specimens from 21 patients were analysed by immunoblotting and/or reverse transcriptase-polymerase chain reaction. Seventeen cancer specimens out of 21 (81%) were positive for CRD-BP expression by one or both assays. With one exception, normal colon specimens were negative for CRD-BP expression; specimens of inflammatory bowel and a villous adenoma also had no detectable CRD-BP. The lack of CRD-BP expression in normal colon did not result from indiscriminate protein or RNA degradation. c-myc mRNA levels appeared to be elevated in tumor specimens. We conclude that the CRD-BP is scarce or absent from normal colon but is overexpressed in colorectal cancer. The CRD-BP might be a novel human tumor marker.

Adult↗