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Biomedical subjects

A Moore

Publications and source records attributed to A Moore.

At least 163 records · Page 9Linked to original sources

Outcomes from adult implantation, the first 100 patients.

We present the outcome of implantation in the first 100 adult patients treated under the Midland Cochlear Implant Programme. All patients were post-lingually deaf with profound or total hearing loss. Performance was tested in lip-reading, implant only and combined lip-reading and implant modes using BKB sentences, connected discourse tracking (CDT) and environmental sound recognition. Assessments were made at nine and 18 months post-implant. The dominant aetiologies were idiopathic and meningitis. Meningitis was associated with the greatest numbers of ossified cochleas. Forty-three per cent of cases of partial ossification were identified only at surgery. Four per cent of patients became non-users of their devices, however the majority used their implants for more than 12 hours each day. The mean scores at nine months post-implant, in the implant only mode, were for environmental sound recognition 56.7 per cent, for BKB sentences 46.6 per cent (80 per cent of patients scored above 0 per cent) and for CDT 31.2 words per minute (w.p.m.) (62 per cent scored above zero per cent). In the combined lip reading and implant mode the mean scores, at nine months, were for BKB sentences 81.5 per cent and for CDT 65.8 w.p.m. All results were sustained at 18 months. Patients reported that implantation significantly reduced their hearing handicap. Pre-operative measures of depression were also significantly reduced at nine months post-implant. Results were sustained at 18 months. Post-operative audiological outcomes in the electrical stimulation only mode correlated significantly with length of profound deafness. Results suggest that performance outcome is also related to the number of active electrodes.

Aged↗

Measuring transferrin receptor gene expression by NMR imaging.

The human transferrin receptor (hTfR) has been used as a model molecular target to direct therapeutic agents to tumor cells and to shuttle drugs across the blood-brain-barrier. We show in the current study that receptor expression and regulation can be visualized by NMR imaging, when the receptor is probed with a sterically protected iron containing magnetic hTfR probe. We were able to demonstrate that the novel receptor probe was an iron source that could enter the cells via the hTfR but did not play an immediate role in iron downregulation of hTfR within incubation times tested. Using genetically engineered rat 9L gliosarcoma cell lines with three different forms of the hTfR, we also demonstrated that receptor expression and regulation can be visualized by NMR imaging using the probe. This research provides proof of the principle that it is possible to image receptor gene expression and regulation and it demonstrates that it may be possible to image gene transfer in vivo.

Animals↗

Azimilide dihydrochloride, a novel antiarrhythmic agent.

Azimilide, a novel class III antiarrhythmic agent, blocks both the slowly activating (IKs) and rapidly activating (IKr) components of the delayed rectifier potassium current, which distinguishes it from conventional potassium channel blockers such as sotalol and dofetilide, which block only IKr. Azimilide is being developed to prolong the time to recurrence of atrial fibrillation, atrial flutter, and paroxysmal supraventricular tachycardia in patients with and without structural heart disease. Azimilide is also being studied for its role in prevention of sudden cardiac death in high-risk patients after myocardial infarction (MI). Preclinical and clinical studies indicate that azimilide prolongs cardiac refractory period in a dose-dependent manner, as manifested by increases in action potential duration, QTc interval, and effective refractory period. Azimilide does not affect PR or QRS interval and minimally affects hemodynamic properties such as blood pressure and heart rate. Its in vivo effects appear to be rate-independent and are maintained under ischemic or hypoxic conditions, properties of potential clinical significance. Azimilide has shown excellent efficacy (>85%) in suppressing supraventricular arrhythmias in a variety of dog models. It also suppressed complex ventricular arrhythmias in infarcted dogs and, in a sudden death cardiac model, decreased mortality. Azimilide pharmacokinetics are very predictable. The drug is completely absorbed, and the extent of absorption is not affected by food. It can be administered once daily. Clinical data suggest that dose adjustments of azimilide are not required for age, gender, hepatic or renal function, or concomitant use of digoxin or warfarin. Azimilide has a good safety profile in open-label safety studies in >800 supraventricular arrhythmia patients, most with structural heart disease. The incidence of serious adverse events, including torsade de pointes, is low. The rate of patient withdrawal from long-term studies is also encouragingly low. Unlike amiodarone, azimilide has shown no evidence of pulmonary or ocular toxicity. Azimilide is expected to provide a unique new therapy for the prevention of supraventricular arrhythmias and sudden cardiac death when Phase III clinical trials are complete and safety and efficacy are confirmed.

Animals↗

Health warning.

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Hospitals, Public↗

Novel gliosarcoma cell line expressing green fluorescent protein: A model for quantitative assessment of angiogenesis.

Angiogenesis is essential for tumor proliferation and metastasis. The extent of angiogenesis is measured by microvessel density (MVD) which has been identified as an independent prognostic factor for relapse-free survival in cancer patients. Existing methods of MVD assessment measure the microvessel count in the most active area of neovascularization ("hot spots") using antibodies against vascular endothelial antigens. This may produce unreliable results because of tissue volume loss and misshapening during the fixation and dehydration procedures. We report here a genetically engineered 9L cell line constitutively expressing green fluorescent protein that can be visualized using fluorescence microscopy without additional histological staining. The model developed in this study allows for the performance of simple and easy MVD counting, assuming that nonfluorescent "black spots" visible by fluorescence microscopy within the borders of the tumor tissue represent blood vessels. This assumption was confirmed by a comparative study utilizing conventional histological methods, anti-CD31 immunohistology, and Hoechst 33258 dye exclusion. This model is also useful for delineation of the true borders between tumor and normal brain tissue, including microscopic tumor extensions, without multiple histological staining. The suggested model allows quantification of tumor angiogenesis in tissue specimens, thus providing independent prognostic information about tumor growth and regression. It is expected to be most valuable in evaluating the efficacy of anti-angiogenic therapy.

Animals↗

The role of peritoneal drains in treatment of perforated necrotizing enterocolitis: recommendations from recent experience.

BACKGROUND/PURPOSE: Intraperitoneal drains have been used in the treatment of perforated necrotizing enterocolitis (NEC), especially in infants less than 1,000 g, yet their role is still debated. The authors wished to examine their more recent experience in the treatment of NEC to make recommendations for operative management. METHODS: The authors reviewed the records of all infants seen between 1989 and 1995 who had clinical and radiological evidence of NEC at the Hospital for Sick Children, Toronto, Ontario. One hundred sixty-seven infants were treated for NEC and 73 (44%) infants required surgical intervention. RESULTS: Forty-five patients had perforated NEC; 23 were treated initially by peritoneal drainage and 22 by primary laparotomy. The 23 newborns who had peritoneal drainage were of significantly lower birth weight, and 19 (83%) of these infants required subsequent laparotomy for worsening disease. The overall mortality rate for perforated NEC was 36%. CONCLUSION: Insertion of a peritoneal drain is still useful in resuscitating small critically ill infants with NEC; however, the majority of these infants will also require laparotomy.

Drainage↗

Effect of prednisone on prostate-specific antigen in patients with hormone-refractory prostate cancer.

OBJECTIVES: To evaluate the effects of prednisone on prostate-specific antigen (PSA) in a cohort of patients with "hormone-refractory" prostate cancer. METHODS: Data were collected from 29 consecutive patients with hormone-refractory progressive prostate cancer who were treated with 10 mg of prednisone orally two times a day. Patients were included in this analysis only if other factors known to influence PSA levels (antiandrogen withdrawal, radiation, and/or other concomitant anticancer therapies) were definitively excluded as potentially confounding variables. RESULTS: The mean and median PSA decline after initiating prednisone was 33% (95% confidence interval [CI] 20% to 46%) and 24% (range 0% to 99%), respectively. Ten patients (34%) had a PSA decline of more than 50% and 4 patients (14%) had PSA declines of more than 75%. The average and median time for progression-free survivals were 2.8 (95% CI 1.7 to 3.8) and 2.0 (range 0 to 11) months. Four (14%) patients had PSA declines lasting 6 months or more. Median survival was 12.8 months. Additional analyses indicated that a PSA decline of more than 50%, compared with less than 50%, was associated with a longer survival. Toxicities included steroid myopathy (n = 4), new-onset diabetes (n = 1), and dyspnea (n = 1). CONCLUSIONS: Prednisone (10 mg orally two times a day) can decrease PSA by more than 50% in approximately one third of patients with hormone-refractory progressive prostate cancer. On the basis of comparisons with other data sets, we hypothesize a dose-response relationship between glucocorticoid dose and PSA decline.

Aged↗

Simultaneous measurement of cell cycle and apoptotic cell death.

Understanding the dynamics of cell death in conjunction with those of cell cycle can be illuminating in the investigation of various cellular behaviors. Robust assays for measuring such parameters are invaluable. Many assays of apoptosis and/or cell cycle use flow cytometry. This chapter describes two different assays to measure apoptosis and cell cycle simultaneously using flow cytometry. The first involves the use of terminal transferase (the "TUNEL" assay) together with propidium iodide for identification of cell cycle. The second uses fluorescently labeled annexin V, together with propidium iodide as an indicator of cell membrane integrity; and additionally Hoechst 33342 for determination of cell cycle. Each assay has positive and negative attributes. The terminal transferase assay is performed using fixed cells and is therefore useful in the analysis of samples collected over time. The annexin V assay is performed using unfixed cells, and thus provides information regarding membrane integrity. Other practical aspects of both assays are discussed.

Animals↗

Anterior polar cataract: clinical spectrum and genetic linkage in a single family.

Anterior polar cataract can occur as a sporadic finding, in association with other ocular abnormalities or as an inherited, autosomal dominant disorder. We have demonstrated linkage in a family with autosomal dominant anterior polar cataract to the short arm of chromosome 17, locating the gene to the region 17p12-13. All affected members of this large family had an opacity at the anterior pole of the lens that varied only in size and the effect on visual acuity. Anterior polar cataract is thought to have a minimal effect on visual acuity although in the affected members of this family there was a high incidence of unilateral amblyopia.

Cataract↗

Approaches to new vaccines.

The explosive technological advances in the fields of immunology and molecular biology in the last 5 years had an enormous impact on the identification of candidate vaccines against diseases, which until a few years ago seemed uncontrollable. Increased knowledge of the immune system has helped to define the mechanisms that underlie successful immunization and is now being exploited to develop improved versions of existing vaccines and new vaccines against emerging pathogens, tumors, or autoimmune diseases. An understanding of the mechanisms of action of novel adjuvants and the development of new vector and delivery systems will have a major impact on vaccine strategies. The use of DNA encoding antigens from pathogenic viruses, bacteria, and parasites as vaccines is a new approach that is receiving considerable attention. This and other innovative approaches, including vaccine production in plants, are appraised in this review. The successful eradication of smallpox and the imminent eradication of poliomyelitis by worldwide immunization campaigns provide positive examples of how the vaccine-mediated approach can lead to disease elimination; with the advent of new vaccines and improved delivery systems, there is no scientific reason why these successes cannot be repeated.

Adjuvants, Immunologic↗

A missense mutation in the human connexin50 gene (GJA8) underlies autosomal dominant "zonular pulverulent" cataract, on chromosome 1q.

CZP1, a locus for autosomal dominant "zonular pulverulent" cataract, previously had been linked with the Duffy blood-group-antigen locus on chromosome 1q. Here we report genetic refinement of the CZP1 locus and show that the underlying mutation is present in GJA8, the gene for connexin50. To map the CZP1 locus we performed linkage analysis using microsatellite markers on two distantly related branches of the original Ev. pedigree, which now spans eight generations. Significantly positive two-point LOD score (Z) values were obtained for markers D1S2669 (maximum Z [Zmax] = 4.52; maximum recombination frequency [thetamax] = 0) and D1S514 (Zmax = 4.48; thetamax = 0). Multipoint analysis gave Zmax = 5.22 (thetamax = 0) at marker D1S2669. Haplotyping indicated that CZP1 probably lies in the genetic interval D1S2746-(20.6 cM)-D1S2771. Sequence analysis of the entire protein-coding region of the GJA8 gene from the pedigree detected a C-->T transition in codon 88, which introduced a novel MnlI restriction-enzyme site that also cosegregated with the cataract. This missense mutation is predicted to result in the nonconservative substitution of serine for a phylogenetically conserved proline (P88S). These studies provide the first direct evidence that GJA8 plays a vital role in the maintenance of human lens transparency and identify the genetic defect believed to underlie the first inherited disease to be linked to a human autosome.

Cataract↗