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Robert Duncan

Publications and source records attributed to Robert Duncan.

At least 37 records · Page 2Linked to original sources
PubMed2004

Tenofovir therapy for lamivudine resistance following liver transplantation.

BACKGROUND: Resistant hepatitis B virus (HBV) strains develop in 30% of liver transplant recipients treated with lamivudine within 2 years from the time of transplantation. OBJECTIVE: To assess safety and outcomes of tenofovir salvage therapy for patients with lamivudine resistance in a retrospective cohort of liver-transplanted patients. METHODS: Medical records were retrospectively evaluated for patients who received tenofovir. Data collected included demographics, HBV serologic information prior to and during tenofovir therapy, drug-related complications, and creatinine clearance. Criteria for lamivudine resistance included elevation of liver chemistries along with reappearance of hepatitis B surface antigen, hepatitis Be antigen, and/or HBV DNA. RESULTS: Sixteen patients showed resistance to lamivudine at 10-85 months (median 26) following liver transplantation. Tenofovir 300 mg/day orally was added in 8 patients 1-66 months after the development of viral lamivudine resistance and continued for 14-26 months (median 19.3). All 8 patients experienced HBV DNA viral suppression, with 7 currently nondetectable. No adverse events were reported, and creatinine clearance was not impaired. CONCLUSIONS: Our results suggest that tenofovir safely and markedly decreases replication of lamivudine-resistant HBV variants after liver transplantation and is another potential option for the treatment of HBV lamivudine resistance.

Adenine↗
PubMed2004

Comparison of the prognostic potential of hyaluronic acid, hyaluronidase (HYAL-1), CD44v6 and microvessel density for prostate cancer.

Despite the development of nomograms designed to evaluate a prostate cancer (PCa) patient's prognosis, the information has been limited to PSA, clinical stage, Gleason score and tumor volume estimates. We compared the prognostic potential of 4 histologic markers, hyaluronic acid (HA), HYAL-1-type hyaluronidase (HAase), CD44v6 and microvessel density (MVD) using immunohistochemistry. HA is a glycosaminoglycan that promotes tumor metastasis. CD44 glycoproteins serve as cell surface receptors for HA, and the CD44v6 isoform is associated with tumor metastasis. HYAL-1-type HAase is expressed in tumor cells and, like other HAases, degrades HA into angiogenic fragments. Archival PCa specimens (n=66) were obtained from patients who underwent radical prostatectomy for clinically localized PCa and had a minimum follow-up of 72 months (range 72-131 months, mean 103 months). For HA, HYAL-1 and CD44v6 staining and MVD determination, a biotinylated HA-binding protein, an anti-HYAL-1 IgG, an anti-CD44v6 IgG and an anti-CD34 IgG were used, respectively. HA and HYAL-1 staining was classified as either low- or high-grade. CD44v6 staining and MVD were evaluated quantitatively and then grouped as either low- or high-grade. Using 72 months as the cut-off limit for evaluating biochemical recurrence, HA, HYAL-1, combined HA-HYAL-1, CD44v6 and MVD staining predicted progression with 96%, 84%, 84%, 68% and 76% sensitivity, respectively. Specificity was, 61% (HA), 80.5% (HYAL-1), 87.8% (HA-HYAL-1), 56.1% (CD44v6) and 61% (MVD). Sensitivity and specificity values for each marker did not change significantly in a subset of 45 patients for whom follow-up of longer than 112 months was available. In univariate analysis using the Cox proportional hazards model, preoperative PSA, Gleason sum, margin status, seminal vesicle, extraprostatic extension (EPE), HA, HYAL-1, HA-HYAL-1 and MVD, but not CD44v6, age and clinical stage, were significant in predicting biochemical recurrence (p < 0.05). In multivariate analysis using stepwise selection, only preoperative PSA (hazard ratio/unit PSA change=1.086, p < 0.0001), EPE (hazard ratio=6.22, p=0.0016) and HYAL-1 (hazard ratio=8.196, p=0.0009)/HA-HYAL-1 (hazard ratio=5.191, p=0.0021) were independent predictors of biochemical recurrence. HA was an independent predictor of prognosis if HYAL-1 staining inference was not included in the multivariate model. In our retrospective study with 72- to 131-month follow-up, EPE, preoperative PSA and HYAL-1 either alone or together with HA (i.e., combined HA-HYAL-1) were independent prognostic indicators for PCa.

Biomarkers, Tumor↗
PubMed2004

Elevated expression of IFN-gamma in the HIV-1 infected brain.

We determined the extent of expression of three cytokines (IFN-gamma, IL-4, and TNF-alpha ) in brain tissue infected with human immunodeficiency virus-1 (HIV-1). The selections were IFN-gamma as a Th1 cytokine, IL- 4 as a Th2 cytokine, and TNF-alpha as a pro-inflammatory cytokine (and because of its prior implication in brain tissue damage due to HIV-1 infection). Based on current models for pathogenesis of HIV-1-associated dementia (HAD), in the periphery, Th1 cytokines are considered to be salutary, whereas Th2 cytokines are regarded as deleterious. However, we hypothesized that in the CNS these roles are reversed. Post-mortem temporal lobe tissue specimens from 16 HIV-1-seropositive patients and 11 HIV-1-seronegative controls were stained for IFN-gamma, IL-4, and TNF-alpha utilizing immunohistochemistry and alkaline phosphatase. HIV-1 infection causes alterations of brain cytokine expression that include increased IFN-gamma expression for HIV-1-seropositive vs. HIV-1-seronegative individuals. There was increased expression of IFN-gamma for HIV-1-seropositive individuals with or without HAD, with or without the broader category of neuropsychiatric impairment (NPI), and with or without opportunistic infections (OIs) compared to HIV-1-seronegatives. A significant inverse correlation between IFN-gamma vs. IL-4 in HIV-1-seropositives with HAD and in seronegative individuals was observed. There was an inverse correlation in seropositives between IFN-gamma vs. TNF-alpha, a positive trend with HAD, significant without HAD, significant with NPI and significant without OIs. Between IL-4 vs. TNF-alpha there was a correlation (trend) in seropositives, a trend with NPI, significant without NPI, and a trend without OI. Due to HIV-1 infection of the brain and neurological disease there is a prominent increased expression of IFN-gamma, an inverse expression of IFN-gamma vs. TNF-alpha, and TNF-alpha vs. IL-4. The inverse correlation between increased IFN-gamma and decreased IL-4 expression is consistent with the stimulation of activated macrophages, and T cells, greater toxicity in the HIV-1-infected brain, and is supportive of the significance of IFN-gamma in HIV-1-infected patients.

Adolescent↗
PubMed2004

Centrin gene disruption impairs stage-specific basal body duplication and cell cycle progression in Leishmania.

Centrin is a calcium-binding cytoskeletal protein involved in the duplication of centrosomes in higher eukaryotes. To explore the role of centrin in the protozoan parasite Leishmania, we created Leishmania deficient in the centrin gene (LdCEN). Remarkably, centrin null mutants (LdCEN(-/-)) showed selective growth arrest as axenic amastigotes but not as promastigotes. Flow cytometry analysis confirmed that the mutant axenic amastigotes have a cell cycle arrest at the G(2)/M stage. The axenic amastigotes also showed failure of basal body duplication and failure of cytokinesis resulting in multinucleated "large" cells. Increased terminal deoxy uridine triphosphate nick end labeling positivity was observed in centrin mutant axenic amastigotes compared with wild type cells, suggesting the activation of a programmed cell death pathway. Growth of LdCEN(-/-) amastigotes in infected macrophages in vitro was inhibited and also resulted in large multinucleated parasites. Normal basal body duplication and cell division in the LdCEN knockout promastigote is unique and surprising. Further, this is the first report where disruption of a centrin gene displays stage-specific/cell type-specific failure in cell division in a eukaryote. The centrin null mutant defective in amastigote growth could be useful as a vaccine candidate against leishmaniasis.

Animals↗
PubMed2004

Outcome of motorcycle riders at one year post-injury.

OBJECTIVE: There is little information about the long-term effects of injury on victims of motorcycle crashes. Following the repeal of the mandatory helmet law in Florida, we studied the impact of crashes on riders and their outcomes one year post-injury. SUBJECTS: All patients involved in a motorcycle crash over a six-month time period were assessed at one year post-injury. Demographic information, health status, motorcycle and helmet usage, and employability were surveyed. RESULTS: There were 94 patients evaluated at our center for the first six-month period following the repeal of the helmet law, where 50 (56%) were wearing a helmet at the time of injury. Of the 94, we were able to contact 45 (48%) at one-year follow up. Fourteen (31%) of those contacted were not wearing a helmet at the time of their crash. At one year post-injury, 23 (51%) reported physical deficits, while 39 (86%) were working. Only 12 (27%) were riding a motorcycle again, and 11 (92%) were wearing a helmet. CONCLUSIONS: Motorcycle riders at one year post-injury continue to experience physical deficits related to their accidents. There is a small percentage of riders that resume riding a motorcycle after injury. Being involved in a motorcycle accident has deterred the injured rider from riding a motorcycle again at one year post-injury.

Accidents, Traffic↗
PubMed2004

Pediatric pedestrian trauma study: a pilot project.

OBJECTIVE: To evaluate the implementation of the WalkSafe Program, a school based educational injury prevention program for children grades Kindergarten through 5. METHODS: A randomized comparative design was used for this study. The study was conducted in two high-risk urban school districts, which were chosen based on the geographic areas with the highest pedestrian injury and fatality rates. Four elementary schools (two in each district) were identified as potential study sites. Two intervention schools, one in each school district, were randomly chosen to receive the WalkSafe program; the other two schools served as controls, and received no intervention. The data was collected within the classroom setting for both the intervention and control schools. All elementary school children were administered the same pedestrian safety questionnaire as a pre-test, post-test and at three months following the intervention. RESULTS: A total of 2300 children participated in the WalkSafe program. The intervention (I) schools showed significant improvement in post-test scores then the control (C) schools (p = 0.012), and the (I) schools were able to maintain their test scores as reflected in a three-month follow-up evaluation (p = 0.47). Grades 3-5 of the (I) schools showed significant improvement in their test scores over grades K-2 (p < 0.0001). CONCLUSION: The WalkSafe program was shown to improve the pedestrian safety knowledge of elementary school children. Future research will include implementing the WalkSafe program at each elementary school within a single high-risk district.

Accidents, Traffic↗
PubMed2004

WalkSafe: a school-based pedestrian safety intervention program.

OBJECTIVE: To evaluate the effectiveness of the WalkSafe program, an elementary school-based pedestrian safety program in a single high-risk district in Miami-Dade County. METHODS: Sixteen elementary schools were identified in a single high-risk district and enrolled in a one-year study. All schools implemented the WalkSafe program on the last week of January 2003. A pre, post, and three-month post testing of pedestrian safety knowledge was conducted. An observational component was also implemented at four schools that were randomly chosen. Engineering recommendations and law enforcement initiatives were also performed. RESULTS: A total of 6467 children from K-5th grade from 16 elementary schools participated in the program. Of these 5762 tests were collected over three different testing times. A significant difference (p-value < 0.001) was found between the pre and post testing conditions across all grade levels. There was no significant difference found between the post and three-month post testing conditions across all grade levels (p-value > 0.05). The observational data collected at four schools across the different testing times demonstrated a significant difference found between pre and post testing conditions for Group A (stop at the curb and look left, right, left) and also for Group B (midstreet crossing and darting out) (p-value < 0.05). There was no difference found between comparing the pre-test or post-test condition with the three-month post-test time. There were many environmental modifications that were recommended and actually performed. CONCLUSION: The WalkSafe program implemented in a single high-risk district was shown to improve the pedestrian safety knowledge of elementary school children. The observational data demonstrated improved crossing behaviors from pre-test to post-testing conditions. Future research will focus on sustaining the program in this district and expanding the program throughout our county.

Accidents, Traffic↗
PubMed2004

DNA polymorphism assay distinguishes isolates of Leishmania donovani that cause kala-azar from those that cause post-kala-azar dermal Leishmaniasis in humans.

Leishmania donovani in India causes visceral infection (kala-azar) and dermal infection (post-kala-azar dermal leishmaniasis). We report here the identification of polymorphism in a well-defined genetic locus among the Leishmania parasites causing the visceral and dermal manifestations, in a comparison of 15 post-kala-azar dermal leishmaniasis and 12 kala-azar patient isolates.

Animals↗
PubMed2004

Placental teratocarcinoma in a mare with possible metastasis to the foal.

A teratocarcinoma was diagnosed in the amnion of a 5-year-old Arabian mare that delivered a healthy, full-term foal. The foal died at 2.5 months of age as a result of metastasis of an undifferentiated component of the mass. This case is unique because it is the first reported case of placental teratocarcinoma in animals and the malignant component apparently metastasized to the foal resulting in its death.

Animals↗
PubMed2003

An in vitro system for developmental and genetic studies of Leishmania donovani phosphoglycans.

Glycoconjugates have been shown to play important roles in Leishmania development. However, the ability to study these molecules and other processes would benefit greatly from improved methods for genetic manipulation and analysis of the amastigote stage. This is especially challenging for L. donovani, the agent of the most severe form of leishmaniasis, which can rapidly lose virulence during in vitro culture. Here we report on a clonal subline of an L. donovani 1S2D (LdBob or LdB), which differentiates readily from promastigotes to amastigotes in axenic culture, and maintains this ability during extended parasite cultivation in vitro. This derivative can be plated and transfected efficiently while grown as promastigotes or amastigotes. Importantly, LdB maintains the ability to differentiate while undergoing genetic alterations required for creation of gene knockouts and complemented lines. Like virulent L. donovani, LdB exhibits down-regulation of lipophosphoglycan (LPG) synthesis and up-regulation of A2 protein synthesis in amastigotes. We showed that knockouts of LPG2, encoding a Golgi GDP-mannose transporter, eliminated phosphoglycan synthesis in LdB axenic amastigotes. These and other data suggest that LdB axenic amastigotes will be generally useful as a differentiation model in studies of gene expression, virulence, glycoconjugate function and drug susceptibility in L. donovani.

Animals↗
PubMed2003

Programmed cell death in trypanosomatids and other unicellular organisms.

In multicellular organisms, cellular growth and development can be controlled by programmed cell death (PCD), which is defined by a sequence of regulated events. However, PCD is thought to have evolved not only to regulate growth and development in multicellular organisms but also to have a functional role in the biology of unicellular organisms. In protozoan parasites and in other unicellular organisms, features of PCD similar to those in multicellular organisms have been reported, suggesting some commonality in the PCD pathway between unicellular and multicellular organisms. However, more extensive studies are needed to fully characterise the PCD pathway and to define the factors that control PCD in the unicellular organisms. The understanding of the PCD pathway in unicellular organisms could delineate the evolutionary origin of this pathway. Further characterisation of the PCD pathway in the unicellular parasites could provide information regarding their pathogenesis, which could be exploited to target new drugs to limit their growth and treat the disease they cause.

Amphotericin B↗
PubMed2003

A double-blinded, randomized, placebo-controlled pilot study of the safety and efficacy of Myobloc (botulinum toxin type B)-purified neurotoxin complex for the treatment of crow's feet: a double-blinded, placebo-controlled trial.

Crow's feet develop with age and are one of the earliest signs of the normal aging process. Botulinum toxin type A, approved by the Food and Drug Administration for the treatment of glabellar wrinkles in April 2002, has been used off-label to treat facial wrinkles since 1981. Botulinum toxin type B (BTX-B, Myobloc) was Food and Drug Administration-approved for use in cervical dystonia in the United States in December 2000 and has subsequently been used in an off-label indication to treat facial wrinkles. There are sparse data in the literature evaluating the safety and efficacy of BTX-B for the treatment of facial wrinkles. In this pilot study, participants with moderate or severe crow's feet wrinkles were treated with Myobloc versus placebo. The duration of correction and side effect profile are reported.

Adult↗
PubMed2003

Neuronal ceroid-lipofuscinosis in a Labrador Retriever.

An 8-year-old Labrador Retriever with an 11-month history of progressive partial seizures and necropsy examination findings characteristic of the lamellar form of canine neuronal ceroid-lipofuscinosis (NCL) is presented. The clinical, light microscopic, and ultrastructural features of this case most closely resemble human adult-onset NCL (Kufs disease). This is the first report of NCL occurring in the Labrador Retriever breed.

Animals↗
PubMed2003

Cancer pain management in Lanarkshire: a community-based audit.

BACKGROUND: A prospective, longitudinal audit of pain management in patients with cancer was conducted in an unselected community population in Lanarkshire, Scotland. METHODS: Using a modified Delphi technique, a recording form was developed and a dedicated project manager was appointed to oversee the development and implementation of the audit. Community staff recorded pain level and analgesic prescribing on consecutive home visits to patients with cancer-related pain. Areas of good and poor prescribing were assessed using standards previously developed for the Scottish Cancer Pain Audit. These results were fed back to prescribers in a variety of ways and used as a focus for a programme of primary care-based education. RESULTS: Five hundred and forty-one patients have been entered in the audit between May 1999 and end October 2002. A total of 3259 visits have been recorded and 88% of general practices in Lanarkshire submitted forms during this period. Pain scores were recorded in 90% of visits. Specific gaps in prescribing practice were identified. CONCLUSION: The audit demonstrated that it is possible to engage primary care teams in a continuing audit of cancer pain management, which is achievable within the context of normal care. It provided a means to collect and analyse serial data on pain level and pain management and to identify areas of prescribing in need of improvement. Concerted efforts to establish the legitimacy and relevance of the project in the eyes of key stakeholders proved fundamental to encouraging longer-term behavioural change in the management of cancer pain.

Analgesics↗
PubMed2002

Mice lacking the gene for inducible or endothelial nitric oxide are resistant to sporocyst induced Sarcocystis neurona infections.

Equine protozoal myeloencephalitis (EPM) is a neurologic syndrome in horses from the Americas and is usually caused by infection with the apicomplexan parasite, Sarcocystis neurona. Little is known about the role of immunobiological mediators to this parasite. Nitric oxide (NO) is important in resistance to many intracellular parasites. We, therefore, investigated the role of inducible and endothelial NO in resistance to clinical disease caused by S. neurona in mice. Groups of interferon-gamma gene knockout (IFN-gamma-KO) mice, inducible nitric oxide synthase gene knockout (iNOS-KO) mice, endothelial nitric oxide synthase gene knockout (eNOS-KO) and appropriate genetic background mice (BALB/c or C57BL/6) were orally fed sporocysts or Hanks balanced salt solution. Mice were observed for signs of clinical disease and examined at necropsy. Clinical disease and deaths occurred only in the IFN-gamma-KO mice. Microscopic lesions were seen only in the brains of IFN-gamma-KO mice. Results of this study indicate that iNOS and eNOS are not major mediators of resistance to S. neurona infections. Results of this study suggest that IFN-gamma mediated immunity to S. neurona may be mediated by non-NO-dependent mechanisms.

Animals↗
PubMed2002

Acupuncture therapy for the symptoms of Parkinson's disease.

Interest in alternative medical treatments, including acupuncture, is increasing. Alternative treatments must be subjected to the same objective standards as all medical treatments. A non-blinded pilot study of the safety, tolerability, and efficacy of acupuncture (ACUPX) for the symptoms of (PD) was performed. Twenty PD patients (mean age, 68 years; disease duration, 8.5 years; Hoehn and Yahr [H&Y] stage, 2.2; Unified Parkinson's Disease Rating Scale score [UPDRS], 38.7) each received acupuncture treatments by a licensed acupuncturist. All patients were treated with two acupuncture treatment sessions per week. The first seven patients received 10 treatments and the last 13 patients 16 treatments. Patients were evaluated before and after ACUPX with the Sickness Impact Profile (SIP); UPDRS; H & Y; Schwab and England (S & E); Beck Anxiety Inventory (BAI); Beck Depression Inventory (BDI); quantitative motor tests, including timed evaluations of arm pronation supination movements, finger dexterity, finger movements between two fixed measured points, and the stand-walk-sit test; and a patient questionnaire designed for the study. Following ACUPX, there were no significant changes in the UPDRS, H&Y, S&E, BAI, BDI, quantitative motor tests, total SIP or the two SIP Dimension scores. Analysis of the 12 SIP categories not corrected for multiple comparisons revealed a post-ACUPX improvement in the sleep and rest category only (P = 0.03). On the patient questionnaire, 85% of patients reported subjective improvement of individual symptoms including tremor, walking, handwriting, slowness, pain, sleep, depression, and anxiety. There were no adverse effects. ACUPX therapy is safe and well tolerated in PD patients. A range of PD and behavioral scales failed to show improvement following ACUPX other than sleep benefit, although patients reported other discrete symptomatic improvements. A broad battery of tests in PD patients suggested that ACUPX resulted in improvement of sleep and rest only. This finding needs to be verified using more in-depth and controlled evaluation of ACUPX for PD-related sleep disturbance.

Activities of Daily Living↗
PubMed2002

Assessment of the impact of pain and impairments associated with spinal cord injuries.

OBJECTIVES: To determine the adequacy of the Multidimensional Pain Inventory (MPI) for assessing pain impact after spinal cord injury (SCI) and to determine whether the impact of pain can be separated from other consequences of SCI. DESIGN: Postal survey. SETTING: General community. PARTICIPANTS: Of the 159 subjects contacted who experienced chronic pain, 120 (75.5%) participated. INTERVENTIONS: Subjects were mailed the original MPI and a set of additional items specific to SCI. MAIN OUTCOME MEASURE: The MPI. RESULTS: Confirmatory (CFA) and exploratory factor analyses were performed for each section of the MPI. Elimination of several items, including those related to work in section 1 (pain impact), improved the goodness-of-fit index (GFI). A CFA for section 2 (response of significant other) resulted in acceptable GFI after 2 items were deleted. Decrease in activity levels (section 3) because of other consequences of injury was significantly greater after tetraplegia than after paraplegia. In contrast, pain-related reduction in activities was not associated with injury level. Although other consequences of SCI may have greater impact on activities than pain, severe pain is likely to affect activity levels significantly. CONCLUSION: The MPI appears to be appropriate for use in a SCI population when modified to eliminate questions related to work and to supplement the activity scale with items addressing decreased activity levels due to pain.

Adult↗