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Biomedical subjects

M Taylor

Publications and source records attributed to M Taylor.

At least 145 records · Page 8Linked to original sources
PubMed2001

Plasminogen activator inhibitor-1 as a measure of vascular remodelling in breast cancer.

The generation of urokinase plasminogen activator (uPA) by tumours is an important pathway for neoplastic cell invasion and metastasis. Indeed in several tumour types, elevated levels of uPA, its receptor (uPAR) or its inhibitor plasminogen activator inhibitor-1 (PAI-1) is associated with a poorer prognosis. Since endothelial cells also use this proteolytic system to remodel the extracellular matrix during angiogenesis and since angiogenesis, as assessed by microvessel density, is also a predictor of patient survival, this study was designed to investigate the relationship between angiogenesis and the urokinase system in breast tumours. The aims were to assess whether the uPA, uPAR and/or PAI-1 correlates with angiogenic activity and could therefore be a useful objective clinical measure of tumour neovascularization; and to clarify whether the poor outcome associated with high levels of the urokinase system is due to its association with angiogenesis. The study also sought to examine the relationship between the uPA system and vessel remodelling using loss of a basement membrane epitope (LH39) normally associated with established capillaries. The cytosolic levels of uPA, PAI-1 and uPAR were therefore measured by enzyme linked immunoabsorbent assay, together with tumour vascularity, in 136 well-characterized invasive breast carcinomas. There were significant relationships between uPA and uPAR (Spearman r=0.37, p<0.0001), uPA and PAI-1 (Spearman r=0.19, p=0.03) and between uPAR and PAI-1 (Spearman r=0.23 p=0.01). A significant correlation was also observed between PAI-1 and vessel remodelling (Spearman r=0.34, p=0.04), patient age (p=0.01), nodal status (p=0.047) and tumour grade (p=0.04), but no association between tumour vascularity and PAI (p=0.96), uPA (p=0.69) or uPAR (p=0.81) was present. No significant association was seen between any of the urokinase variables and expression of the angiogenic factor thymidine phosphorylase. Furthermore, no significant associations were found between any of the studied parameters and overall survival in a univariate analysis of the cancer patients. A multivariate Cox proportional hazard model of overall survival showed that uPA (p=0.15), but not uPAR (p=0.52) or PAI-1 (p=0.61), gave no additional prognostic information. These findings show that uPA may work via an independent pathway to angiogenesis and therefore combined blockade of uPA and angiogenesis may have additional therapeutic benefits. It also shows, as recently demonstrated in animal models, that PAI-1 may be a key regulator of vascular remodelling in human cancer.

Adult↗
PubMed2001

Prenatal diagnosis of succinic semialdehyde dehydrogenase deficiency: increased accuracy employing DNA, enzyme, and metabolite analyses.

Inherited succinic semialdehyde dehydrogenase (SSADH; EC1.2.1.24; McKusick 271980) deficiency is a defect of GABA degradation which leads to accumulation of 4-hydroxybutyric acid (gamma-hydroxybutyric acid; GHB) in physiologic fluids of patients. Prenatal diagnosis (PND) was performed in three at-risk pregnancies employing combinations of: (1) reverse-transcription-polymerase chain reaction (RT-PCR) and genomic DNA amplification followed by sequencing using isolated leukocytes or cultured human lymphoblasts; (2) GHB quantitation in amniotic fluid; or (3) SSADH enzyme assay in chorionic villus (CV) and/or amniocytes. In two pregnancies, all analyses were concordant for prediction of disease status in the fetus. In the third case, enzyme activity in CV (deficient) and metabolite analysis in amniotic fluid (normal) were discordant. For clarification, mutation analysis was undertaken in CV, confirming heterozygosity for the mutation previously identified in the proband. We hypothesize that delayed transit time for shipment of CV between Greece and the United States (8 days) led to enhanced degradation of heterozygous SSADH enzyme activity. Our data demonstrate the importance of combined metabolite, enzyme, and DNA analysis for increased accuracy in the PND of SSADH deficiency.

Aldehyde Oxidoreductases↗
PubMed2001

An exception to the rule: ectopic ACTH production from functional neuroendocrine tissue in an ovarian dermoid cyst.

Ectopic ACTH production accounts for 15% of Cushing's syndrome presentations and is characterized by the presence of an excess of ACTH precursors. However in the case presented here ectopic ACTH production was from functional pituitary tissue within an ovarian dermoid cyst. Endocrine investigations showed that the problem behaved more like pituitary-dependent Cushing's disease and this is discussed. Furthermore, this case is one of familial dermoid cysts, another unusual phenomenon.

ACTH Syndrome, Ectopic↗
PubMed2001

Extracorporeal membrane oxygenation in children after repair of congenital cardiac lesions.

BACKGROUND: The purpose of this study was to review our experience in the early application of extracorporeal membrane oxygenation (ECMO) in patients requiring mechanical assistance after cardiac surgical procedures. METHODS: The hospital records of all children requiring ECMO after cardiac operation were retrospectively reviewed, and an analysis of variables affecting survival was performed. RESULTS: Fifty pediatric patients between May 1997 and October 2000 required ECMO for cardiopulmonary support after cardiac operation. Patients ranged in age from 1 day to 11 years (median age, 40 days). Forty-eight patients underwent repair of congenital cardiac lesions and 2 were included after receiving a heart transplant. Twenty-two children could not be weaned from cardiopulmonary bypass and were placed on ECMO in the operating room for circulatory support. Of the 28 children who required ECMO in the intensive care unit, 10 had ECMO instituted after cardiopulmonary arrest (mean cardiopulmonary resuscitation time 42 minutes; range, 5 to 110 minutes). In infants with single-ventricle physiology, survival to discharge was 61% (11 of 18 patients) as compared with 43% (14 of 32 patients) in those with biventricular physiology. Thirty of the 50 patients (60%) were successfully weaned from ECMO, of which 25 (83%) were discharged home. Overall survival to discharge in the entire cohort was 50%. Extracorporeal membrane oxygenation support greater than 72 hours was a grave prognostic indicator. Overall survival in this group was 36% (9 of 25 patients) compared with 56% (14 of 25 patients) in those with ECMO support less than 72 hours (p < 0.05). Univariate analysis revealed the presence of renal failure, extended periods of circulatory support, and a prolonged period of cardiopulmonary resuscitation as risk factors for mortality. The presence of shunt-dependent flow, operative procedure, and institution of ECMO in the intensive care unit did not alter survival. CONCLUSIONS: Extracorporeal membrane oxygenation provides effective support for postoperative cardiac and pulmonary failure refractory to medical management. Early institution of ECMO may decrease the incidence of cardiac arrest and end-organ damage, thus increasing survival in these critically ill patients.

Child↗
PubMed2001

Hyaluronate receptors mediating glioma cell migration and proliferation.

The extracellular matrix (ECM) of the central nervous system (CNS) is enriched in hyaluronate (HA). Ubiquitous receptors for HA are CD44 and the Receptor for HA-Mediated Motility known as RHAMM. In the present study, we have investigated the potential role of CD44 and RHAMM in the migration and proliferation of human astrocytoma cells. HA-receptor expression in brain tumor cell lines and surgical specimens was determined by immunocytochemistry and western blot analyses. The ability of RHAMM to bind ligand was determined through cetylpyridinium chloride (CPC) precipitations of brain tumor lysates in HA-binding assays. The effects of HA, CD44 blocking antibodies, and RHAMM soluble peptide on astrocytoma cell growth and migration was determined using MTT and migration assays. Our results show that the expression of the HA-receptors, CD44, and RHAMM, is virtually ubiquitous amongst glioma cell lines, and glioma tumor specimens. There was a gradient of expression amongst gliomas with high grade gliomas expressing more RHAMM and CD44 than did lower grade lesions or did normal human astrocytes or non-neoplastic specimens of human brain. Specific RHAMM variants of 85- and 58-kDa size were shown to bind avidly to HA following CPC precipitations. RHAMM soluble peptide inhibited glioma cell line proliferation in a dose-dependent fashion. Finally, while anti-CD44 antibodies did not inhibit the migration of human glioma cells, soluble peptides directed at the HA-binding domain of RHAMM inhibited glioma migration both on and off an HA-based ECM. These data support the notion that HA-receptors contribute to brain tumor adhesion, proliferation, and migration, biological features which must be better understood before more effective treatment strategies for these tumors can be found.

Antibodies, Monoclonal↗
PubMed2001

Pharmacologic rescue of lethal seizures in mice deficient in succinate semialdehyde dehydrogenase.

Succinate semialdehyde dehydrogenase (ALDH5A1, encoding SSADH deficiency is a defect of 4-aminobutyric acid (GABA) degradation that manifests in humans as 4-hydroxybutyric (gamma-hydroxybutyric, GHB) aciduria. It is characterized by a non-specific neurological disorder including psychomotor retardation, language delay, seizures, hypotonia and ataxia. The current therapy, vigabatrin (VGB), is not uniformly successful. Here we report the development of Aldh5a1-deficient mice. At postnatal day 16-22 Aldh5a1-/- mice display ataxia and develop generalized seizures leading to rapid death. We observed increased amounts of GHB and total GABA in urine, brain and liver homogenates and detected significant gliosis in the hippocampus of Aldh5a1-/- mice. We found therapeutic intervention with phenobarbital or phenytoin ineffective, whereas intervention with vigabatrin or the GABAB receptor antagonist CGP 35348 (ref. 2) prevented tonic-clonic convulsions and significantly enhanced survival of the mutant mice. Because neurologic deterioration coincided with weaning, we hypothesized the presence of a protective compound in breast milk. Indeed, treatment of mutant mice with the amino acid taurine rescued Aldh5a1-/- mice. These findings provide insight into pathomechanisms and may have therapeutic relevance for the human SSADH deficiency disease and GHB overdose and toxicity.

Aldehyde Oxidoreductases↗
PubMed2001

Approaches to vaccines for Psoroptes ovis (sheep scab).

A brief outline of the history of sheep scab in the UK is presented together with the current chemical methods used for its control and problems associated with these. Possible alternative approaches to control are discussed, as are selected aspects of the physiology of Psoroptes ovis and the pathogenesis of the scab lesion from the perspective of control through immunisation. Evidence is provided that immunity to the disease can indeed be acquired, both naturally after a previous infection and following inoculation of mite proteins in adjuvant. These results support the view that control by vaccination may be possible, although little is known to date about the antigens involved or the mechanism of protection.

Animal Feed↗
PubMed2001

Molecular cytogenetic analysis of glial tumors using spectral karyotyping and comparative genomic hybridization.

BACKGROUND: Glial tumors are the most common tumors of the central nervous system, affecting individuals of all ages. Conventional cytogenetics have been unable to identify a consistent chromosomal translocation or rearrangement in this group of tumors; thus, more advanced molecular cytogenetic approaches are required. METHODS AND RESULTS: In this study, 16 glial tumors, including two recurrences and six glioma cell lines, were analyzed by spectral karyotyping (SKY) and comparative genomic hybridization (CGH). From 169 rearrangements detected by SKY, chromosomes 1 and 10 were the most frequently affected by translocation (18 of 169 and 16 of 169 rearrangements, respectively). Other frequently altered chromosomes included chromosomes 3 (13 of 169 rearrangements), 5 (ten of 169 rearrangements), 7 (ten of 169 rearrangements ), and 11 (ten of 169 rearrangements). A clustering of centromeric breakpoints was detected in chromosomes 3, 5, 10, 11, 16, 17, and 20. CGH analysis identified consistent gain of part or all of chromosome 7 among the 10 astrocytic tumors (five of ten specimens) in the study group. Analysis of the three gangliogliomas and one ependymoma identified a much simpler pattern of primarily numerical change. CONCLUSION: Application of improved cytogenetic methods can increase our abilities to progress toward effective strategies of molecular diagnosis and classification of glial tumors.

Adult↗
PubMed2001

The effect of sequential use of vacuum and forceps for assisted vaginal delivery on neonatal and maternal outcomes.

OBJECTIVE: To determine the risk of neonatal and maternal disease associated with the sequential use of vacuum and forceps compared with spontaneous vaginal delivery. STUDY DESIGN: Using Washington state birth certificate data linked to hospital discharge records, we compared 3741 vaginal deliveries by both vacuum and forceps, 3741 vacuum deliveries, and 3741 forceps deliveries to 11,223 spontaneous vaginal deliveries. RESULTS: Compared with spontaneous vaginal deliveries, deliveries by sequential use of vacuum and forceps had significantly higher rates of intracranial hemorrhage (relative risk [RR], 3.9; 95% confidence interval [CI], 1.5 to 10.1), brachial plexus (RR, 3.2; 95% CI, 1.6 to 6.4), facial nerve injury (RR, 13.3; 95% CI, 4.7 to 37.7), seizure (RR, 13.7; 95% CI, 2.1 to 88.0), depressed 5-minute Apgar score (RR, 3.0; 95% CI, 2.2 to 4.0), assisted ventilation (RR, 4.8; 95% CI, 2.1 to 11.0), fourth-degree (RR, 11.4; 95% CI, 6.4 to 20.1 among multiparous women) and other lacerations, hematoma (RR, 6.2; 95% CI, 2.1 to 18.1 among multiparous women), and postpartum hemorrhage (RR, 1.6; 95% CI, 1.3 to 2.0). The relative risk of sequential vacuum and forceps use was greater than the sum of the individual relative risks of each instrument for intracranial hemorrhage, facial nerve injury, seizure, hematoma, and perineal and vaginal lacerations. CONCLUSION: Sequential use of vacuum and forceps is associated with increased risk of both neonatal and maternal injury.

Adult↗
PubMed2001

Epidemiology of helminth infections: implications for parasite control programmes, a South African perspective.

OBJECTIVES: To determine the epidemiology of helminthic infections and the efficacy of parasite treatment among rural South African primary school children in the province of KwaZulu-Natal. To assess the South African government's parasite control policy. METHODS: The study recruited 268 school children, aged 8 to 10, and randomly allocated them into treatment and placebo groups (treatment consisted of a single dose of albendazole (400 mg) and praziquantel (40 mg/kg)). Anthropometric measurements and the prevalence and intensity of helminth infections were taken at baseline (prior to treatment) and 16 weeks post treatment. Two weeks after treatment prevalence and intensity were again measured for an approximate 50% sub-sample of the children to investigate efficacy of treatment. An analysis of the South African government's policies concerning parasite control is assessed in the light of these epidemiological findings. RESULTS: Low levels of both stunting and wasting were observed throughout the study (approximately 10% and 1%, respectively), but did not vary significantly across either treatment group or time period (P >0.50). At baseline the observed prevalences for the three main helminths found in this study among the treated children were Ascaris lumbricoides 29.5%, Trichuris trichiura 51.9% and Schistosoma haematobium 22.3%. These prevalences declined significantly to 4.7% (P <0.0005), 38.0% (P < 0.03), and 3.3% (P < 0.0002), respectively, 16 weeks post treatment. The majority of infections observed at baseline were of light intensity, namely A. lumbricoides (50%), T. trichiura (80%) and S. haematobium (100%), and following treatment these levels were reduced significantly (P <0.0001, P< 0.05 and P < 0.005, respectively). The levels of both prevalence and intensity in the untreated group remained constant. The cure rates over the first two weeks of the study were found to be 94.4% for A. lumbricoides, 40% for T. trichiura and 72.2% for S. haematobium. CONCLUSION: The benefits of targeted, school-based treatment in reducing the prevalence and intensity of infection supports the South African government's focus of using school-based interventions as part of an integrated parasite control programme. These strategies and programmes are consistent with recommendations of the World Health Organization (WHO) and The United Nations Children's Fund (UNICEF).

Albendazole↗
PubMed2001

A randomized controlled trial of the effect of antihelminthic treatment and micronutrient fortification on health status and school performance of rural primary school children.

Single interventions for helminthic infections and micronutrient deficiencies are effective, but it is not clear whether combined interventions will provide equal, additive or synergistic effects to improve children's health. The study objective was to determine the impact of single and combined interventions on nutritional status and scholastic and cognitive performance of school children. A double-blind, randomized, placebo-controlled trial in 11 rural South African primary school randomly allocated 579 children aged between 8 and 10 years into six study groups, half of whom received antihelminthic treatment at baseline. The de-wormed and non-de-wormed arms were further divided into three groups and given biscuits, either unfortified or fortified with vitamin A and iron or with vitamin A only, given daily for 16 weeks. The outcome measures were anthropometric, micronutrient and parasite status, and scholastic and cognitive test scores. There was a significant treatment effect of vitamin A on serum retinol (p < 0.01), and the suggestion of an additive effect between vitamin A fortification and de-worming. Fortified biscuits improved micronutrient status in rural primary school children; vitamin A with de-worming had a greater impact on micronutrient status than vitamin A fortification alone and antihelminthic treatment significantly reduced the overall prevalence of parasite infection. The burden of micronutrient deficiency (anaemia, iron and vitamin A) and stunting in this study population was low and, coupled with the restricted duration of the intervention (16 weeks), might have limited the impact of the interventions.

Analysis of Variance↗
PubMed2001

Child seduction and self-representation on the Internet.

This paper presents a case study of a man charged with the offense of downloading child pornography from the Internet. He had used the Internet to traffic child pornography, and, in addition, to locate children to abuse, to engage in inappropriate sexual communication with children, and to communicate with other pedophiles. Such offenses were facilitated by self-representing in Chat rooms as both a child and an adult. The case study illustrates how such offenders move through a repertoire of offending behavior and discusses the role that the Internet can play in supporting inappropriate and disinhibited sexual behavior that victimizes children through the trading of child pornography and possible child seduction. The Internet is seen to play a unique role in allowing individuals to self-represent aspects that might otherwise remain hidden or dormant.

Adult↗
PubMed2001

Thymidylate synthase expression in stage II and III colon cancer: a retrospective review.

This study is a retrospective analysis of thymidylate synthase (TS) levels in patients with stage II (T3 or T4) and III colon cancer. Two groups of patients were identified: one undergoing surgery alone (98 patients) and the second receiving adjuvant 5-fluorouracil chemotherapy (112 patients). TS analyses were carried out using the 106 monoclonal antibody and a published grading system dividing staining into high and low intensity. The distribution of patients with low versus high TS levels was similar in the two groups. There was no association between TS staining intensity and grade, stage or location of primary. Seventy-nine patients have relapsed: 46 (48%) in the surgery only group, 33 (30%) in the adjuvant therapy group (median follow-up: 51 and 61 months). Similar proportions relapsed when analyzed according to TS: in the surgery only group, 41% of patients with low TS, 48% with high TS; in the adjuvant group, 31% with low TS, 30% with high TS. In the surgery only group, a trend toward improved disease-free survival (DFS) was seen in the low TS group (84 versus 63% at 2 years, p = 0.08). No difference was seen in overall survival. There were no differences in DFS or overall survival in patients receiving adjuvant therapy according to TS intensity. The trend for worse outcome in patients with high TS is consistent with previous reports. The lack of difference in outcome for patients with low and high TS receiving chemotherapy suggests that high TS levels may predict greater benefit from adjuvant treatment.

Aged↗
PubMed2001

Renal cell carcinoma.

Several renal cell carcinoma (RCC) prognostic factors show promise, including K1-67, p53/mdm-2, and vascular endothelial growth factor. The combination of increased incidence of RCC and diagnosis during earlier stages has generated interest in local therapeutic options. Nephron-sparing surgery and laparoscopic nephrectomy continue to gain support and may become the standard of care in select patients. Standard therapy for metastatic disease continues to be cytokine-based therapy with little benefit gained from adding granulocyte-macrophage-colony-stimulating factor, retinoic acid, or adoptive immunotherapy. The addition of chemotherapy, such as capecitabine, floxuridine, and vinblastine, may increase the effectiveness of immunotherapy; nonmyeloablative stem cell transplantation has shown early promise in metastatic disease.

Carcinoma, Renal Cell↗
PubMed2001

Development of a universal connectivity and data management system.

Point-of-care testing (POCT) is an increasingly popular method of delivering laboratory testing. Management of POCT is challenging given the variety of devices, locations, and staff that need to be coordinated to ensure quality results and meet regulatory guidelines. Electronic capture and transfer of data are preferred for managing POCT, but there is currently no standard method of connecting different devices. Johns Hopkins Medical Institutions (JHMI) developed a common data management system with interfaces to all of its POCT devices. All POCT data are collected in one database and analyzed in a similar fashion. Where data were once collected by carrying laptops to each nursing unit, the POCT devices can now connect directly to the database over the Internet. Algorithms have been created to automate the data analysis and review process. Over the several years that this software has been used, JHMI has experienced improved quality, accuracy, and management of its POCT program. The labor saved by increased automation of data review is refocused on enhancing the performance and scope of the program. Current connectivity and analysis algorithms have future application to remote consultation, management of home self-monitoring patients, and examination of real-time data.

Academic Medical Centers↗