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John Anderson

Publications and source records attributed to John Anderson.

At least 19 recordsLinked to original sources
PubMed2026

Large-scale multiethnic electronic health record resource for diabetes complications research: the North West London Diabetes Cohort (NWLDC) - cohort profile.

PURPOSE: The North West London Diabetes Cohort is established to provide systematic characterisation of a large diabetes population as a foundation for complications research and prognostic modelling. Many predictive modelling studies neglect the essential descriptive characterisation of underlying cohorts, focusing narrowly on model accuracy. This cohort profile addresses this gap by comprehensively describing the demographic composition, clinical characteristics and complication incidence patterns. The notably diverse, multiethnic population enables examination of ethnic disparities and supports future development of reliable prognostic models and evidence-based prevention strategies for diabetes complications. PARTICIPANTS: At baseline, 337 271 patients with diabetes were identified. It includes 279 067 patients with type 2 diabetes, 17 638 with type 1 diabetes, 33 590 with gestational diabetes and 6916 with unspecified diabetes. The earliest diabetes diagnosis dates to January 1932, with data updated to 27 May 2025. FINDINGS TO DATE: This cohort profile describes baseline characteristics of patients with comprehensive data collected on demographics (age, sex, Deprivation Index, ethnicity), clinical measures (glycated haemoglobin, body mass index, blood pressure, lipids and estimated glomerular filtration rate) and 14 major diabetes complications tracked longitudinally. Key findings for patients with type 2 diabetes reveal diabetic retinopathy as the most common complication (74.6 per 1000 person-years), followed by hypertension (51.0) and kidney disease (31.4). Cumulative incidence analyses using the Aalen-Johansen estimator, which accounts for mortality as a competing risk, demonstrated significant ethnic disparities, with black, Asian, mixed and other ethnic groups showing elevated risk compared with white patients. Time-varying Cox models identified strong clustering between cardiovascular and renal complications, confirming a cardiometabolic-renal syndrome. Mental health conditions (depression and anxiety) were prevalent throughout the disease timeline, occurring both before and after diabetes diagnosis. FUTURE PLANS: This cohort will be used as a platform for developing and validating prognostic models for diabetes complications, enabling risk stratification and targeted interventions. Future work will incorporate medication data to refine diabetes type classification, examine the effectiveness of antidiabetic medications in preventing different complications and address demographic differences in prognostic model performance and prediction accuracy. To better characterise lifestyle, further interrogation of electronic health record data will examine recording of advice given, including dietary advice, referral to weight management schemes and presence of alcohol consumption codes.

Humans↗
PubMed2006

Evaluation of three 3ABC ELISAs for foot-and-mouth disease non-structural antibodies using latent class analysis.

BACKGROUND: Foot-and-mouth disease (FMD) is a highly contagious viral disease of even-toed ungulates. Serological diagnosis/surveillance of FMD presents several problems as there are seven serotypes worldwide and in the event of vaccination it may be necessary to be able to identify FMD infected/exposed animals irrespective of their vaccination status. The recent development of non-structural 3ABC protein (NSP) ELISA tests has greatly advanced sero-diagnosis/surveillance as these tests detect exposure to live virus for any of the seven serotypes of FMD, even in vaccinated populations. This paper analyses the performance of three NSP tests using a Bayesian formulation of the Hui-Walter latent class model to estimate test sensitivity and specificity in the absence of a "gold-standard" test, using sera from a well described cattle population in Cameroon with endemic FMD. RESULTS: The analysis found a high sensitivity and specificity for both the Danish C-ELISA and the World Organisation for Animal Health (O.I.E.) recommended South American I-ELISA. However, the commercial CHEKIT kit, though having high specificity, has very low sensitivity. The results of the study suggests that for NSP ELISAs, latent class models are a useful alternative to the traditional approach of evaluating diagnostic tests against a known "gold-standard" test as imperfections in the "gold-standard" may give biased test characteristics. CONCLUSION: This study demonstrates that when applied to naturally infected zebu cattle managed under extensive rangeland conditions, the FMD ELISAs may not give the same parameter estimates as those generated from experimental studies. The Bayesian approach allows for full posterior probabilities and capture of the uncertainty in the estimates. The implications of an imperfect specificity are important for the design and interpretation of sero-surveillance data and may result in excessive numbers of false positives in low prevalence situations unless a follow-up confirmatory test such as the enzyme linked immunoelectrotransfer blot (EITB) is used.

Aging↗
PubMed2006

Usefulness of body surface maps to demonstrate ventricular activation patterns during left ventricular pacing and reentrant activation during ventricular tachycardia in men with coronary heart disease and left ventricular dysfunction.

Epicardial electrical events were reconstructed using an inverse model for left ventricular (LV) pacing and during ventricular tachycardia (VT) induced during implantation of a biventricular pacemaker and/or internal defibrillator. The electrocardiographic position of the pacing lead, determined from the region of most negative potential 30 ms after the pacing spike, was compared with the radiographic position. Activation characterized by isochronal maps was correlated with the echocardiographic/myocardial scintigraphic data. Reconstructed epicardial isopotential/isochronal maps during VT were used to determine the presence of reentry. In 7 patients during LV pacing, epicardial isopotential maps located the maximum negative potentials anterolaterally (n = 3), posterolaterally (n = 2), and posteriorly (n = 2). Isochronal maps demonstrated activation patterns including regions of delayed activation that, in 5 patients, correlated with areas of akinesia/hypokinesia or fixed defects on echocardiography/myocardial scintigraphy. The mean difference between the radiographically measured right ventricular to LV pacing lead distance and calculated electrocardiographic right ventricular to LV pacing site distance was 1.7 cm. During VT, induced in 5 patients, single-loop reentry was observed in 3 and figure-of-8 reentry in 2. Exit site and regions of fast/slow conduction and conduction block that correlated with anatomic areas of infarction defined by echocardiography/myocardial scintigraphy were demonstrated. In conclusion, epicardial maps reconstructed from the body surface map can identify LV pacing sites and demonstrate reentry during VT. The body surface map could thus identify optimal pacing sites for LV pacing and targets for VT ablation.

Aged↗
PubMed2006

Tolerability, efficacy and pharmacokinetics of bicalutamide 300 mg, 450 mg or 600 mg as monotherapy for patients with locally advanced or metastatic prostate cancer, compared with castration.

OBJECTIVE: To evaluate the pharmacokinetics, tolerability and effect on endocrinology of bicalutamide given as once-daily monotherapy at doses of >150 mg to patients with locally advanced (M0) or metastatic (M1) prostate cancer, with efficacy as a secondary endpoint. PATIENTS AND METHODS: Patients were initially enrolled to receive bicalutamide 300 mg in a non-randomized phase, after which further patients were randomized to higher bicalutamide doses (in 150 mg increments) or castration. Overall, 248 patients received bicalutamide at 300 mg (21), 450 mg (95) or 600 mg (42), or castration (90). RESULTS: Systemic exposure to bicalutamide stabilised at a dose of approximately 300 mg, as determined by pharmacokinetic analysis. The tolerability of high doses of bicalutamide was similar to that of the 150 mg dose, with no increase in the incidence of adverse events. Patients receiving bicalutamide had early increases in the mean levels of oestradiol, testosterone and luteinizing hormone, which were maintained throughout the study. Levels of these hormones rapidly decreased in the castration group and remained low. From baseline (first day of treatment) to 12 weeks there was an equivalent reduction in prostate-specific antigen (PSA) levels across all four groups. At a median follow-up of 5 years, there was no significant survival difference between patients who received bicalutamide and those who received castration, either in M0 or M1 disease. CONCLUSION: The low median PSA level (180 ng/mL) of patients with M1 disease might account for the lack of survival difference between the treatment groups. Further studies are needed to assess whether high-dose bicalutamide monotherapy can provide equivalent efficacy to castration in patients with M1 prostate cancer.

Aged↗
PubMed2006

Rapid and accurate determination of MYCN copy number and 1p deletion in neuroblastoma by quantitative PCR.

MYCN amplification and 1p36 deletion are adverse prognostic factors in neuroblastoma, and rapid accurate determination of MYCN amplification is essential for risk stratification. MYCN copy number and 1p36 deletion status were determined by fluorescence in situ hybridization (FISH) and real time PCR in a diagnostic pathology laboratory setting on 35 consecutive patients with neuroblastoma. The PCR technique was technically successful in all cases and results were generally available within 24 hr of biopsy. There was no discordance between FISH and PCR results. Real time PCR is a reliable, accurate, and simple technique that can be applied to small neuroblastoma biopsies allowing rapid diagnosis.

Child, Preschool↗
PubMed2006

The MET receptor tyrosine kinase contributes to invasive tumour growth in rhabdomyosarcomas.

The receptor tyrosine kinase MET and its ligand hepatocyte growth factor (HGF), have been implicated in the genesis of the paediatric tumour rhabdomyosarcoma (RMS). Addition of exogenous HGF to RH30 RMS cells enhanced non-chemotactic migration. Stable transfection of dominant negative MET into RH30 cells attenuated Matrigel invasion and in vivo tumour growth. To assess the role of a putative HGF-MET pathway in human RMS, we measured their expression in a panel of 68 human primary tumours. All tumours expressed MET but with a three orders of magnitude variation of expression and 62% of tumours co-expressed HGF. In contrast with other tumour types, neither high-MET expression nor HGF/MET coexpression correlated with metastatic disease. In a microarray screen, we identified CCN1 as being 7.8-fold up regulated following addition of HGF to RH30 cells and in RMS tumours, CCN1 expression correlated with HGF expression. Surprisingly, we identified MET as a consistent feature of embryonal and not alveolar RMS.

Animals↗
PubMed2006

Drug-eluting and bare nitinol stents for the treatment of atherosclerotic lesions in the superficial femoral artery: long-term results from the SIROCCO trial.

PURPOSE: To review clinical outcomes of patients with chronic limb ischemia and TASC type C lesions treated with sirolimus-eluting versus bare SMART nitinol self-expanding stents. METHODS: Data were obtained from a randomized, multicenter, double-blinded study conducted in 2 phases. All 93 patients had chronic limb ischemia and superficial femoral artery (SFA) occlusions or stenoses (average lesion length 8.3 cm). In total, 47 patients (31 men; mean age 66.3+/-9.1 years, range 50-84) received the sirolimus-eluting SMART stent and 46 patients (36 men; mean age 65.9 +/-10.8 years, range 38-83) received a bare SMART nitinol stent. Both groups were followed for a mean 24 months. RESULTS: Both the sirolimus-eluting and the bare SMART stents were effective in revascularizing the diseased SFA and in sustaining freedom from restenosis. For both types of stents, improvements in ankle-brachial indices (ABI) and symptoms of claudication were maintained over 24 months (median 24-month ABI 0.96 for the sirolimus group versus 0.87 for the bare stent group, p>0.05). At 24 months, the restenosis rate in the sirolimus group was 22.9% versus 21.1% in the bare stent group (p>0.05). The cumulative in-stent restenosis rates according to duplex ultrasound were 4.7%, 9.0%, 15.6%, and 21.9%, respectively, at 6, 9, 18, and 24 months; the rates did not differ significantly between the treatment groups. The TLR rate for the sirolimus group was 6% and for the bare stent group 13%; the TVR rates were somewhat higher: 13% and 22%, respectively. Mortality rates did not differ significantly between the groups. CONCLUSION: These data demonstrate that the sirolimus-eluting and the bare SMART stent are effective, safe, and free from restenosis in a majority of patients for up to 24 months. Because the restenosis rate in the bare stent group is unexpectedly low, no significant difference could be found between the sirolimus-eluting and the bare SMART stents.

Adult↗
PubMed2006

MYCN deregulation as a potential target for novel therapies in rhabdomyosarcoma.

Rhabdomyosarcoma is the most common soft-tissue sarcoma of childhood. Treatment requires a multimodality approach combining chemotherapy with surgery and radiotherapy. Although overall outcomes have improved considerably, the outlook for patients with high-risk disease, particularly the alveolar subtype, remains bleak and there is a clear need for new chemotherapeutic strategies. This review focuses on the possibilities for interventions targeting myc myelocytomatosis viral related oncogene, neuroblastoma derived (MYCN). The importance of aberrant expression of this oncogene is well established in neuroblastoma and recent data indicate that MYCN deregulation also occurs in up to a quarter of alveolar subtype cases. A range of possible approaches to target MYCN is discussed, including nucleic acid-based and immunotherapy strategies.

Antineoplastic Agents↗
PubMed2006

Autologous platelet gel: an in vitro analysis of platelet-rich plasma using multiple cycles.

Autologous platelet gel (APG) has become an expanding field for perfusionists. By mixing platelet-rich plasma (PRP) with thrombin and calcium, platelet gel is prepared and used in many surgical settings. There are many devices used to produce PRP. This study evaluates the Medtronic Magellan Autologous Platelet Separator. The purpose of this study was to show that processing two cycles of the same syringe could reduce the amount of blood required to produce a specific volume of PRP. Three 60-mL syringes of whole blood with anticoagulant were removed from 15 elective coronary artery bypass patients. Each syringe produced 9 mL of PRP and 1 mL was sent to the laboratory for analysis. The remaining whole blood in each syringe was processed a second time with a yield of 5 mL of PRP with 1 mL sent to the laboratory. With this data, the Magellan was assessed in three phases. The first phase focused on the consistency of the Magellan. Laboratory values of hematocrit, platelet count, white blood cell count, and fibrinogen were compared between each syringe processed by the device. The second phase dealt with the percentage of platelets in the PRP that the Magellan was able to capture. Finally, results of both cycles were combined and compared against baseline values. Most of the hematological factors evaluated between each syringe were consistent in both cycles. The Magellan was able to capture nearly 70% of all platelets in the PRP of the first cycle and 18.5% in the second cycle. By mathematically combining both cycles, platelet counts averaged 2.8 times baseline with a 3.3 times baseline increase when the volume of the two cycles was weighted. This weighted average was done to reflect a higher concentration of Cycle 1 platelets than Cycle 2 in each sample. This study proved that processing each syringe of whole blood twice could reduce blood requirements while maintaining an effective platelet yield and volume. It also showed that the Magellan does conform to benchmark testing done at Medtronic.

Blood Platelets↗
PubMed2005

Coordinated oncogenic transformation and inhibition of host immune responses by the PAX3-FKHR fusion oncoprotein.

Tumors have evolved elaborate mechanisms for evading immune detection, such as production of immunoinhibitory cytokines and down-regulation of major histocompatibility complex (MHC) expression. We have studied PAX3-FKHR as an example of an oncogenic fusion protein associated with an aggressive metastatic cancer. We show that PAX3-FKHR alters expression of genes that are normally regulated by Janus kinase/signal transducer and activator of transcription (STAT) signaling pathways. This occurs as a result of a specific interaction between PAX3-FKHR and the STAT3 transcription factor, which results in a dramatic reduction in tumor MHC expression, and an alteration in local cytokine concentrations to inhibit surrounding inflammatory cells and immune detection. Collectively, these data show that an oncogenic transcription factor can promote tumor growth and tissue invasion while inhibiting local inflammatory and immune responses. This is the first time that an immunomodulatory role has been described for an oncogenic fusion protein.

Animals↗
PubMed2005

Secretory IgA as an indicator of oro-pharyngeal foot-and-mouth disease virus replication and as a tool for post vaccination surveillance.

A serotype-specific ELISA was developed to detect foot-and-mouth disease virus (FMDV) specific IgA antibody in the saliva of cattle, and the method was evaluated for its feasibility in detecting serotype O FMDV carrier animals, particularly amongst vaccinated cattle that had subsequently become sub-clinically infected. For this purpose, saliva samples were collected from naïve cattle (n = 173), FMDV challenged cattle (n = 10), FMDV vaccinated cattle (n = 40) and FMDV vaccinated-and-challenged cattle (n = 40). A subset of 29 cattle was sampled for 105-168 days after challenge. The FMDV infection status of each of the cattle was determined by virus isolation and RT-PCR tests on oesophago-pharyngeal fluids and the ability of the IgA test to detect viral infection and persistence was compared to an ELISA for the detection of serum antibodies against the 3ABC non-structural proteins of FMDV. Eleven out of twelve vaccinated cattle that were shown to be persistently infected with FMDV up to or beyond 28 days post challenge, were also detected by the IgA test on saliva. With some modification and further validation, this test could be useful in post-vaccination surveillance to help confirm the absence of sub-clinical infection in order to regain the FMD-free status of a region or country.

Animals↗
PubMed2005

A molecular map of mesenchymal tumors.

BACKGROUND: Bone and soft tissue tumors represent a diverse group of neoplasms thought to derive from cells of the mesenchyme or neural crest. Histological diagnosis is challenging due to the poor or heterogenous differentiation of many tumors, resulting in uncertainty over prognosis and appropriate therapy. RESULTS: We have undertaken a broad and comprehensive study of the gene expression profile of 96 tumors with representatives of all mesenchymal tissues, including several problem diagnostic groups. Using machine learning methods adapted to this problem we identify molecular fingerprints for most tumors, which are pathognomonic (decisive) and biologically revealing. CONCLUSION: We demonstrate the utility of gene expression profiles and machine learning for a complex clinical problem, and identify putative origins for certain mesenchymal tumors.

Gene Expression Profiling↗
PubMed2005

Relationship between MYCN copy number and expression in rhabdomyosarcomas and correlation with adverse prognosis in the alveolar subtype.

PURPOSE: Amplification of the transcription factor MYCN is an important molecular diagnostic tool in stratifying treatment for neuroblastoma. Increased copy number and overexpression of MYCN in the pediatric cancer rhabdomyosarcoma has been described in a number of small studies with conflicting conclusions about its association with clinicopathologic characteristics. We aimed to study the phenomenon in the largest series to date. PATIENTS AND METHODS: Using quantitative polymerase chain reaction, we measured MYCN copy number and expression levels in rhabdomyosarcoma samples from 113 and 92 individuals with a confirmed diagnosis of rhabdomyosarcoma, respectively. RESULTS: Increased copy number of MYCN was found to be a feature of both the embryonal and alveolar subtypes. The copy number and expression levels were significantly greater in the alveolar subtype, although the range of expression in both subtypes spanned several orders of magnitude. MYCN copy number showed a significant correlation with expression in the alveolar subtype; this relationship between copy number and expression could be modeled as a logarithmic function. It is notable that relatively high expression frequently occurred in embryonal rhabdomyosarcoma without high copy number and that low expression was found in some cases with high copy number. In patients with alveolar rhabdomyosarcoma, overexpression (greater than median) or gain of genomic copies of MYCN were significantly associated with adverse outcome. CONCLUSION: MYCN deregulation is a feature of rhabdomyosarcoma tumorigenesis, defines groups of patients with a poor prognosis, and is a potential target for novel therapies.

Child↗
PubMed2005

Clinical and pathologic evidence of corticobasal degeneration and progressive supranuclear palsy in familial tauopathy.

BACKGROUND: Corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP) are neurodegenerative tauopathies. Sporadic and familial cases of PSP and CBD have been noted, but both have not been reported in a single family. OBJECTIVE: To describe the clinical, oculomotor, balance, functional imaging, histopathologic, and genetic studies in a family with CBD and PSP. DESIGN: A report of the clinical and pathological features in a familial tauopathy. SETTING: University of Minnesota. Patients We evaluated 2 siblings and clinically assessed 20 additional family members. MAIN OUTCOME MEASURES: Demonstration of salient features in deceased and living family members. RESULTS: Histopathologically confirmed CBD in one sibling and PSP in another deceased sibling were demonstrated; both had clinical features of corticobasal syndrome. In addition, 3 siblings had probable PSP by clinical criteria. Genetic studies of 4 affected family members demonstrated the H1/H1 haplotype but did not reveal pathogenic tau mutations. The family history revealed consanguinity. CONCLUSIONS: This is the first report, to our knowledge, of CBD and PSP in 2 individuals in a single family who presented with corticobasal syndrome and had other affected siblings with clinical PSP. Despite clinical and pathologic heterogeneity, a unifying genetic etiology appears likely in this familial tauopathy.

Basal Ganglia Diseases↗
PubMed2005

Late fatigue fracture of a modern cemented [corrected] cobalt chrome stem for total hip arthroplasty: a report of 10 cases.

We report 10 fatigue fractures of a modern, cemented, cobalt chromium alloy stem (Osteonics Omnifit) for total hip arthroplasty occurring between 1995 and 2004. The primary total hip arthroplasties had been performed between 1989 and 1996. The average age at the time of surgery was 54 years (range, 34-70 years), and the average body mass index was 29 (range, 20-38). The time in situ of the prosthesis at the time of fracture averaged 8 years (range, 4-12 years). Intermediate follow-up radiographs before the fracture were available in 7 cases, all of which demonstrated loss of calcar support. Scanning electron microscopy of the fracture surfaces in 3 of the components showed porosity near the initiation site. Metallography of polished and etched cross sections near the fracture surface revealed large grain size. In the presence of a spontaneous onset of thigh pain at intermediate follow-up in patients with this stem, particularly if associated with loss of calcar support, a fatigue fracture should be considered.

Adult↗
PubMed2005

Sirolimus-eluting versus bare nitinol stent for obstructive superficial femoral artery disease: the SIROCCO II trial.

PURPOSE: To investigate further the safety and efficacy of the sirolimus-eluting S. M.A.R.T. Nitinol Self-expanding Stent by comparison with a bare stent in superficial femoral artery (SFA) obstructions. MATERIALS AND METHODS: This randomized, double-blind study involved 57 patients (29 in the sirolimus-eluting stent group and 28 in the bare stent group) with chronic limb ischemia and SFA occlusions (66.7%) or stenoses (average lesion length, 81.5 mm +/- 41.2). Stent implantation followed standard interventional techniques and a maximum of two stents could be implanted. The primary endpoint was the in-stent mean lumen diameter at 6 months as determined by quantitative angiography. RESULTS: Both stent types were effective in revascularizing the diseased SFA and allowing sustained patency for at least 6 months. There was no statistically significant difference between treatment groups in the in-stent mean lumen diameter at 6 months (4.94 mm +/- 0.69 and 4.76 mm +/- 0.54 mm for sirolimus-eluting and bare stent groups, respectively; P = .31). Although the diameter of the target lesion tended to be larger and percent stenosis tended to be lower with the sirolimus-eluting stent, there were no statistically significant differences between treatments in terms of any of the variables. The mean late loss values were 0.38 mm +/- 0.64 and 0.68 mm +/- 0.97 for the sirolimus-eluting stent group and the bare stent group, respectively (P = .20). The binary restenosis rates, with a cutoff of 50% at 6 months, were zero in the sirolimus-eluting stent group and 7.7% in the bare stent group (P = .49). Clinical outcomes matched angiographic outcomes with improvements in ankle-brachial index and symptoms of claudication. There was no significant difference between treatments in terms of adverse events. CONCLUSION: Although there is a trend for greater efficacy in the sirolimus-eluting stent group, there were no statistically significant differences in any of the variables.

Aged↗