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Biomedical subjects

C Cole

Publications and source records attributed to C Cole.

At least 19 recordsLinked to original sources
PubMed2006

Mouse bone marrow and peripheral blood erythroid cell counts are regulated by different autosomal genetic loci.

Erythropoiesis is under fine control and genetic loci that affect it are likely to be important in a range of conditions. To assess the relative contributions of different genetic loci to parameters of erythropoiesis, we have measured RBC counts in the peripheral circulation and committed erythroid cells (RBC and small normoblasts) in the bone marrow in a cohort of (CBA/H x C57BL/6) F2 mice to map quantitative trait loci (QTL). Candidate genes were assessed using bioinformatics and DNA sequencing. Different autosomal loci affect bone marrow (chromosomes 5, 11 and 19) and peripheral blood (chromosome 4) erythroid cell counts but there may be a common chromosome X locus. Spleen weight QTL were found on chromosomes 3, 15 and 17. Surprisingly, erythropoietin (Epo) is the best candidate quantitative trait gene (QTG) in the chromosome 5 locus that affects bone marrow but not peripheral blood erythroid cell counts. Epo gene expression is known to be genetically regulated in mice, but our data suggest a tissue-specific role for epo in mouse erythropoiesis that is also genetically determined. The identity of the other QTG will be important both to further knowledge of the control of erythropoiesis and as potential modifier genes for haematological disorders.

Animals↗
PubMed2006

Masked orbital abscess in Wegener's granulomatosis.

Two patients with chronic Wegener's granulomatosis presented with worsening proptosis and visual acuity. Both patients had been maintained on long-term corticosteroids, which led to masking of the signs of orbital sepsis with potentially life-threatening implications.

Abscess↗
PubMed2005

Operative treatment for hip subluxation in spinal muscular atrophy.

Subluxation of the hip is common in patients with intermediate spinal muscular atrophy. This retrospective study aimed to investigate the influence of surgery on pain and function, as well as the natural history of subluxed hips which were treated conservatively. Thirty patients were assessed clinically and radiologically. Of the nine who underwent surgery only one reported satisfaction and four had recurrent subluxation. Of the 21 patients who had no surgery, 18 had subluxation at the latest follow-up, but only one reported pain in the hip. We conclude that surgery for subluxation of the hip in these patients is not justified.

Adolescent↗
PubMed2004

Phase I/II study of DHA-paclitaxel in combination with carboplatin in patients with advanced malignant solid tumours.

DHA-paclitaxel is a conjugate of paclitaxel and the fatty acid, docosahexaenoic acid. Preclinical studies have demonstrated increased activity, relative to paclitaxel, with the potential for an improved therapeutic ratio. We conducted a phase I study to determine the maximum tolerated doses of DHA-paclitaxel and carboplatin when administered in combination. Two cohorts of patients were treated: carboplatin AUC 5 with DHA-paclitaxel 660 mg m(-2) and carboplatin AUC 5 with DHA-paclitaxel 880 mg m(-2). Both drugs were given on day 1 every 21 days. A total of 15 patients were enrolled with a median age of 59 years (range 33-71). All patients had advanced cancer refractory to standard treatment, performance status 0-2 and were without major organ dysfunction. A total of 54 cycles of treatment were delivered. No dose-limiting toxicity (DLT) was seen in the first cohort of three patients. In an expanded second cohort, neutropenia was the main DLT, occurring in the first cycle of treatment in five of 12 patients: three of these patients and one additional patient also experienced dose-limiting grade 3 transient rises in liver transaminases. No alopecia was seen and one patient developed clinically significant neuropathy. One partial response was seen in a patient with advanced adenocarcinoma of the oesophago-gastric junction and 12 patients had stable disease with a median time to progression of 184 days (range 60-506 days). The recommended phase II dose in pretreated patients is Carboplatin AUC 5 and DHA-paclitaxel 660 mg m(-2) given every 21 days. Further studies with Carboplatin AUC 5 and DHA-paclitaxel 880 mg m(-2), given every 28 days, are warranted in chemo-naive patients.

Adult↗
PubMed2004

A phase II feasibility study of carboplatin followed by sequential weekly paclitaxel and gemcitabine as first-line treatment for ovarian cancer.

A total of 53 women with chemotherapy-naïve stage Ic-IV ovarian cancer were treated with four cycles of carboplatin area under the curve 7 every 3 weeks, followed by four cycles of paclitaxel 70 mg m(-2) (days 1, 8, and 15) and gemcitabine 1000 mg m(-2) (days 1 and 8) every 3 weeks. In all, 37 (70%) had stage III/IV disease, with 22 (42%) having tumour >2 cm; 38 patients (72%) completed all planned treatment; 27 of the 32 (84%) patients with radiologically evaluable disease had partial or complete responses; and 30 of the 39 patients (77%) with elevated cancer antigen (CA) 125 had a greater than 75% fall in this value. At a median follow-up of 28 months, 31 patients had relapsed with a median progression-free survival of 19.5 months. In total, 79% of patients were alive at 2 years. Common Toxicity Criteria grade 3/4 haematological toxicity, predominantly neutropenia, was seen in 57% of the patients. A certain degree of pulmonary toxicity was observed; eight patients had symptomatic breathlessness, +/- decreased diffusing capacity of the lung for carbon monoxide, and interstitial chest X-ray changes during the weekly phase. In all cases, this toxicity was reversible. No significant neurotoxicity was seen. This regimen is generally well tolerated with encouraging efficacy. However, the observation of pulmonary toxicity, potentially a feature of the weekly taxane-gemcitabine regimen, was of some concern. Alternative schedules, including 3-weekly taxanes, are currently being evaluated.

Adult↗
PubMed2002

Allogeneic bone marrow transplant improves outcome for juvenile myelomonocytic leukaemia.

OBJECTIVE: To correlate clinical presentation and therapeutic outcomes in children with a diagnosis of juvenile myelomonocytic leukaemia. METHODS: The medical records of 14 children who fulfilled the International Juvenile Myelomonocytic Leukaemia Working Group Criteria for a diagnosis of juvenile myelomonocytic leukaemia (JMML) presenting to a single institution were reviewed, and their clinical status at September 2000 was documented. RESULTS: The most common presenting features were hepatosplenomegaly and lymphadenopathy. Fifty per cent of cases presented in the first year of life. Nine of 14 patients initially received chemotherapy otherwise used in the treatment of acute myeloid or lymphoblastic leukaemia with no apparent benefit. All six patients who received conditioning therapy with chemotherapy alone, followed by allogeneic bone marrow transplant (BMT), are in complete remission at a median follow-up duration of 12 months (range 5-91 months). Five of six patients surviving post-allogeneic BMT received marrow from an unrelated donor. Only one of seven patients who did not receive BMT survived long-term. CONCLUSION: Children with a diagnosis of JMML should be treated with allogeneic BMT as soon as a suitable donor is found. The role of anti-leukaemic therapy in this disease, prior to BMT, requires further investigation in the context of a multicentre clinical trial.

Antineoplastic Agents↗
PubMed2001

Electrochemiluminescence of copper(I) bis(2,9-dimethyl-1,10- phenanthroline).

The electrochemical and electrochemiluminescence (ECL) properties of Cu[dmp]2+ (dmp = 2,9-dimethyl-1,10-phenanthroline) have been investigated. ECL has been observed for Cu(dmp)2+ in aqueous, nonaqueous, and mixed solvent solutions using tri-n-propylamine as an oxidative-reductive coreactant. The ECL intensity peaks at potential corresponding to oxidation of both the coreactant and Cu(dmp)2+. The peak potential corresponding to maximum ECL emission is approximately 500 mV more anodic than corresponding oxidative peak potentials, indicating that the ECL emission may be due to the formation of either the *Cu(dmp)2+ metal-to-ligand charge-transfer excited state or an excited-state product of Cu(dmp)2+ oxidation. ECL efficiencies (phiecl = photons generated per redox event) are solvent-dependent (phiecl (CH3CN) > phiecl (50:50 (v/v) CH3CN:H20) > phiecl (H2O)) and correspond fairly well with photoluminescence efficiencies. Increased ECL efficiencies (> or = 50-fold) are observed in the presence of the nonionic surfactant Triton X-100.

Copper↗
PubMed2001

Retrograde amnesia after hippocampal damage: recent vs. remote memories in two tasks.

We review evidence from experiments conducted in our laboratory on retrograde amnesia in rats with damage to the hippocampal formation. In a new experiment reported here, we show that N-methyl-D-aspartate (NMDA)-induced hippocampal damage produced retrograde amnesia for both hidden platform and two-choice visible platform discriminations in the Morris water task. For both problems there was a significant trend for longer training-surgery intervals to be associated with worse retention performance. Little support is offered by our work for the concept that there is a process involving hippocampal-dependent consolidation of memories in extrahippocampal permanent storage sites. Long-term memory consolidation may take place within the hippocampus. The hippocampus may be involved permanently in storage and/or retrieval of a variety of relational and nonrelational memories if it was intact at the time of learning, even involving information which is definitely not affected in anterograde amnesia after hippocampal damage.

Amnesia, Retrograde↗
PubMed2001

Effect of dorzolamide timolol combination versus timolol 0.5% on ocular bloodflow in patients with primary open-angle glaucoma.

PURPOSE: Addition of dorzolamide to timolol in primary open-angle glaucoma shows augmented reduction of intraocular pressure. It is unknown as yet if addition of dorzolamide will alter hemodynamics. METHODS: Fifteen patients with primary open-angle glaucoma were placed on a medication-dependent 1-week to 4-week washout that included maintenance on timolol. After washout, baseline measurements were taken (timolol). They were studied after a month on timolol or dorzolamide-timolol (Cosopt; Merck, Inc, Whitehouse Station, New Jersey), with the second drug preceded by another month of timolol maintenance and second baseline measurements. At each visit, visual function, intraocular pressure, and ocular hemodynamics were monitored, including indocyanine green and fluorescein angiography and color Doppler imaging. RESULTS: Cosopt significantly reduced intraocular pressure (14.7 to 13.4 mm Hg, P <.05) and increased arteriovenous passage time (superior temporal artery) of fluorescein dye (2.13 to 1.76 seconds, P =.01) but had no effect on visual function. CONCLUSIONS: When compared with timolol in primary open-angle glaucoma, Cosopt augments ocular tension reduction and reduces the amount of time required for blood to pass through the superior retinal vasculature.

Adrenergic beta-Antagonists↗
PubMed2001

Sunscreen protection in the ultraviolet A region: how to measure the effectiveness.

Products containing ultraviolet (UV) radiation absorbing or scattering ingredients provide varying degrees of protection from sunlight (or other UV sources), thus minimizing the deleterious effects on the skin. The "sun protection factor" (SPF) of sunscreen products has become a well recognized indicator of protection against sunburn induced predominantly by ultraviolet B radiation (UVB: 290-320 nm). A similar system of denoting sunscreen protection from ultraviolet A (UVA: 320-400 nm) radiation has not been universally recognized. A variety of test methods have been proposed, both in vitro and in vivo, each with specific virtues and shortcomings. Regulatory agencies and industry have been reviewing the available methods over the past decade in an effort to develop consumer meaningful claims and appropriate substantiation methods. This article reviews these test methodologies, in vitro and in vivo, as well as the biological background that establishes the need for UVA protection, and the UVA content of solar radiation and its variability.

Animals↗
PubMed2000

Effect of iron salts, haemosiderins, and chelating agents on the lymphocytes of a thalassaemia patient without chelation therapy as measured in the comet assay.

Impairment of haemoglobin synthesis occurs in the genetic diseases known as thalassaemia. The consequent chronic anaemia leads to increased dietary iron absorption which results in iron overload. Treatment through regular blood transfusions increases oxygen capacity, but also adds iron from haemoglobin. An essential treatment, in parallel with transfusions, is the use of chelating agents to remove the excess iron. Thalassaemia patients are particularly at risk of free radical damage. Human lymphocytes from normal individuals can be investigated in vitro as a model system in the presence of free radicals in the Comet assay. This assay measures DNA damage, particularly DNA strand breakage. We examined cells from an Australian thalassaemic patient (sickle/beta thal double heterozygote-sickle phenotype) who had not yet received chelation therapy to determine if the cells were more sensitive to simulated iron overload and to haemosiderins. Lymphocytes from the patient were received as frozen samples after 28 h on dry ice and then placed in liquid nitrogen. Normal lymphocytes frozen under the same conditions and normal nonfrozen lymphocytes were compared. The lymphocytes from a normal female did not respond in vitro to ferric chloride (FeCl(3)) or haemosiderin but did to ferrous chloride (FeCl(2)) and ferrous sulphate (FeSO(4)). Deferoxamine appeared to reduce the response to FeCl(2) and FeSO(4) but deferiprone did not. When the lymphocytes from the nonchelated patient were treated with FeSO(4) and hydrogen peroxide, deferoxamine and deferiprone both reduced the response. Over the same dose range of iron salt (FeSO(4)), the lymphocytes from the thalassaemic patient were more sensitive, with much higher background levels of damage and induced damage. When deferiprone and deferoxamine were compared over a nontoxic range, deferiprone appeared to produce a greater reduction of damage in lymphocytes of the thalassaemia patient. Ferritin iron appears to be more available than haemosiderin iron in reactions leading to DNA damage. Haemosiderin containing higher amounts of the goethite-like (alpha-FeOOH) iron oxide phase leads to lower levels of DNA damage.

Australia↗
PubMed2000

Common object request broker architecture (CORBA)-based security services for the virtual radiology environment.

The US Army Great Plains Regional Medical Command (GPRMC) has a requirement to conform to Department of Defense (DoD) and Army security policies for the Virtual Radiology Environment (VRE) Project. Within the DoD, security policy is defined as the set of laws, rules, and practices that regulate how an organization manages, protects, and distributes sensitive information. Security policy in the DoD is described by the Trusted Computer System Evaluation Criteria (TCSEC), Army Regulation (AR) 380-19, Defense Information Infrastructure Common Operating Environment (DII COE), Military Health Services System Automated Information Systems Security Policy Manual, and National Computer Security Center-TG-005, "Trusted Network Interpretation." These documents were used to develop a security policy that defines information protection requirements that are made with respect to those laws, rules, and practices that are required to protect the information stored and processed in the VRE Project. The goal of the security policy is to provide for a C2-level of information protection while also satisfying the functional needs of the GPRMC's user community. This report summarizes the security policy for the VRE and defines the CORBA security services that satisfy the policy. In the VRE, the information to be protected is embedded into three major information components: (1) Patient information consists of Digital Imaging and Communications in Medicine (DICOM)-formatted fields. The patient information resides in the digital imaging network picture archiving and communication system (DIN-PACS) networks in the database archive systems and includes (a) patient demographics; (b) patient images from x-ray, computed tomography (CT), magnetic resonance imaging (MRI), and ultrasound (US); and (c) prior patient images and related patient history. (2) Meta-Manager information to be protected consists of several data objects. This information is distributed to the Meta-Manager nodes and includes (a) radiologist schedules; (b) modality worklists; (c) routed case information; (d) DIN-PACS and Composite Health Care system (CHCS) messages, and Meta-Manager administrative and security information; and (e) patient case information. (3) Access control and communications security is required in the VRE to control who uses the VRE and Meta-Manager facilities and to secure the messages between VRE components. The CORBA Security Service Specification version 1.5 is designed to allow up to TCSEC's B2-level security for distributed objects. The CORBA Security Service Specification defines the functionality of several security features: identification and authentication, authorization and access control, security auditing, communication security, nonrepudiation, and security administration. This report describes the enhanced security features for the VRE and their implementation using commercial CORBA Security Service software products.

Artificial Intelligence↗
PubMed2000

Is altered nutritional status the root cause of your clients' negative outcomes?

The impact of altered nutritional status is costly. Surgical patients have 2-3 times the risk of complications, length of stay is extended by 90%, and charges are 35-75% higher. Risk factors are numerous; therefore, collaboration among all members of the health care team is required to impact patient outcomes positively. The purpose of this article is to review the significance of alteration in nutrition and its impact on patient outcomes. The article demonstrates two approaches to improve the quality of care given to clients with an identified alteration in nutritional status: a clinical research project and a quality improvement project.

Deglutition Disorders↗