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Biomedical subjects

Scott Campbell

Publications and source records attributed to Scott Campbell.

18 recordsLinked to original sources

12-month safety and efficacy of everolimus with reduced exposure cyclosporine in de novo renal transplant recipients.

The proliferation signal inhibitor everolimus (Certican), has demonstrated efficacy with full-dose cyclosporine (CsA) (Neoral). Two multicenter randomized controlled studies were performed to compare 12-month efficacy and safety of everolimus 1.5 and 3.0 mg/day with reduced-dose CsA. Study 1 enrolled 237 de novo renal allograft recipients, randomizing 222 nonblack patients to either everolimus 1.5 or 3.0 mg/day, with the Neoral) dose guided by C(2) (monitoring of CsA concentration 2 h after dosing). Study 2 had a similar protocol, with basiliximab included, enrolling 256 recipients and randomizing 243 nonblack patients. In Study 1, there was a lower incidence of acute rejection in nonblack patients on 3 mg/day (16.4%) compared with 1.5 mg/day (25.9%), P = 0.08. In Study 2, the inclusion of basiliximab lowered the overall incidence of acute rejection; 14.3% of nonblack patients (3 mg/day) and 13.6% of nonblack patients (1.5 mg/day) had acute rejection by 12 months (P =0.891). Renal function was preserved throughout the study, with no differences observed between groups within studies. Everolimus was well tolerated with no significant differences between doses. Everolimus, in combination with reduced-dose Neoral), demonstrated efficacy and was well tolerated. Basiliximab allows for utilization of lower doses of everolimus with reduced dosing of Neoral).

Adult↗

Warm-up or stretch as preparation for sprint performance?

Warm-up and stretching are widely used as techniques in preparation for intense physical activity, yet there is little information available to compare their effectiveness in relation to athletic performance. Fourteen elite Under-19 year old rugby league footballers undertook each of four preparation protocols (no preparation, stretching only, warm-up only, warm-up and stretching) in four successive testing sessions. Protocols were randomly allocated to players in a counterbalanced design so that each type of preparation occurred equally on each day of testing. During each session, athletes performed three solo sprint trials at maximum speed. Sprints were of 40-m distance and were electronically timed with wind speed and direction recorded. Preparation involving warm-up resulted in significantly faster sprint times compared to preparations having no warm-up, with a diminishing effect over the three trials. On the first trial, warm-up resulted in a mean advantage of 0.97 m over 40 m. Stretching resulted in a mean disadvantage of 0.18 m on the first trial, and no significant effect overall despite significant wind assistance. Warm-up was effective at improving immediate sprint performance, whereas an equivalent duration of lower limb stretching had no effect.

Adolescent↗

Parental concerns and medical-seeking behavior after immunization.

OBJECTIVE: To examine demographics and immunization attitudes, beliefs, and behaviors of parents who sought medical attention for a child due to an adverse event following immunization (AEFI). METHODS: A sample of households that participated in the National Immunization Survey was re-contacted during 2001. This analysis was conducted in 2004 and 2005. RESULTS: Of 2286 respondents, 223 (6.9%, weighted) sought medical attention for a child due to an AEFI. Compared with parents reporting no adverse event, parents who sought medical attention were less likely to be African American (adjusted odds ratio [AOR]=0.34, 95% confidence interval [CI]=0.16-0.75) or Hispanic (AOR=0.16, 95% CI=0.07-0.39) versus white, aged 35 years or older versus 25 to 34 (AOR=0.35, 95% CI=0.17-0.72), more likely to believe that immunizations cause minor side effects (AOR=5.74, 95% CI=2.99-11.00), report unwanted yet required childhood immunizations (AOR=3.54, 95% CI=1.45-8.66), not want a new baby to be fully immunized (AOR=3.48, 95% CI=1.25-9.67), report concern about immunization safety (AOR=2.08, 95% CI=1.07-4.05), believe that immunizations are dangerous (AOR=3.56, 95% CI=1.14-11.13), and have a child missing two or more doses of three immunizations (measles-containing vaccine, DTaP/DTP, or hepatitis B) (AOR=2.30, 95% CI=1.17-4.55). CONCLUSIONS: This study suggests that research is needed to determine whether negative parental attitudes associated with a child's AEFI might be lessened by improving vaccine safety communication between physician and parent.

Adult↗

Effects of eutrophication on vitellogenin gene expression in male fathead minnows (Pimephales promelas) exposed to 17alpha-ethynylestradiol in field mesocosms.

This study evaluated the effect of aquatic secondary nutrient supply levels (nitrogen and phosphorus) on the subcellular response of adult male fathead minnows (Pimephales promelas) exposed to a single nominal concentration of 17alpha-ethynylestradiol (EE2), a potent synthetic estrogen, under quasi-natural field conditions. Outdoor mesocosms were maintained under low, medium, and high nutrient supply conditions as categorized by total phosphorus (TP) level (nominal 0.012, 0.025, and 0.045 mg TP/L, respectively), and treated with EE2 with and without a carrier solvent. Using reverse transcription-polymerase chain reaction methods, vitellogenin gene (Vg) expression was determined in the fish collected at 0 h, 8 h, 24 h, 4 d, 7 d, and 14 d post-exposure. Induction of Vg was detected as early as 8h post-exposure, with and without the carrier solvent, and persisted through Day 14. Results showed Vg to be significantly greater at low nutrient levels (p<0.05), suggesting that EE2 bioavailability to the fish was likely greater under less-turbid water conditions.

Animals↗

Metabolism and transporter-mediated drug-drug interactions of the endothelin-A receptor antagonist CI-1034.

CI-1034, an endothelin-A receptor antagonist was being developed for pulmonary hypertension. Drug-drug interaction studies using human hepatic microsomes were conducted to assess CYP1A2, CYP2C9, CYP2C19, CYP3A4 and CYP2D6 inhibition potential; CYP3A4 induction potential was evaluated using primary human hepatocytes. CI-1034 moderately inhibited CYP2C9 (IC(50) 39.6 microM) and CYP3A4 activity (IC(50) 21.6 microM); CYP3A4 inhibition was metabolism-dependent. In human hepatocytes, no increase in CYP3A4 activity was observed in vitro, while mRNA was induced 15-fold, similar to rifampin, indicating that CI-1034 is both an inhibitor and inducer of CYP3A4. A 2-week clinical study was conducted to assess pharmacokinetics, pharmacodynamics and safety. No significant changes were observed in [formula: see text] between days 1 and 14. However, reversible elevations of serum liver enzymes were observed with a 50mg BID dose and the program was terminated. To further understand the interactions of CI-1034 in the liver and possible mechanisms of the observed hepatotoxicity, we evaluated the effect of CI-1034 on bile acid transport and previously reported that CI-1034 inhibited biliary efflux of taurocholate by 60%, in vitro. This indicated that inhibition of major hepatic transporters could be involved in the observed hepatotoxicity. We next evaluated the in vitro inhibition potential of CI-1034 with the major hepatic transporters OATP1B1, OATP1B3, OATP2B1, MDR1, MRP2 and OCT. CI-1034 inhibited OATP1B1 (K(i) 2 microM), OATP1B3 (K(i) 1.8 microM) and OATP2B1 activity (K(i) 3.3 microM) but not OCT, MDR1 or MRP2 mediated transport. Our data indicates that CI-1034 is an inhibitor of major hepatic transporters and inhibition of bile efflux may have contributed to the observed clinical hepatotoxicity. We recommend that in vitro drug-drug interaction panels include inhibition and induction studies with transporters and drug metabolizing enzymes, to more completely assess potential in vivo interactions or toxicity.

Blotting, Western↗

Active telephone surveillance to evaluate adverse events among civilian smallpox vaccine recipients.

OBJECTIVE: Better characterize and monitor adverse events following Dryvax vaccinia vaccination in civilian health care workers and other first responders. DESIGN: Telephone interviews to ascertain adverse events experienced. RESULTS: Eight hundred twenty-five vaccinees, including 44 in the comparison group, were interviewed. At 10 days, 71.4% reported blisters, 35.1% reported bumps at the vaccination site, 48.5% swelling, 47.3% scab, tiredness/lethargy/fatigue (43.6%), headache (34.2%), lymph node swelling/tenderness (28.5%), muscle pain (23.1%), chills (14.4%), joint pain 11.8%, and fever >100 degrees F (12.5%). The 12.5% reported missing work because of vaccine adverse events. Most adverse events were anticipated and of short duration.

Adverse Drug Reaction Reporting Systems↗

Responses of molecular indicators of exposure in mesocosms: common carp (Cyprinus carpio) exposed to the herbicides alachlor and atrazine.

Common carp (Cyprinus carpio) were treated in aquatic mesocosms with a single pulse of the herbicides atrazine or alachlor to study the bioavailability and biological activity of these herbicides using molecular indicators: Liver vitellogenin gene expression in male fish for estrogenic activity, liver cytochrome P4501A1 gene expression, and DNA damage in blood cells using the single-cell gel electrophoresis method. Both alachlor and atrazine showed dose-related increases in DNA strand breaks at environmentally relevant concentrations (<100 ppb). Gene expression indicators showed that neither herbicide had estrogenic activity in the carp, whereas atrazine at concentrations as low as 7 ppb induced cytochrome P4501A1. These results support the study of molecular indicators for exposure in surrogate ecosystems to gauge relevant environmental changes following herbicide treatments.

Acetamides↗

Assays to detect West Nile virus in dead birds.

Using oral swab samples to detect West Nile virus in dead birds, we compared the Rapid Analyte Measurement Platform (RAMP) assay with VecTest and real-time reverse-transcriptase-polymerase chain reaction. The sensitivities of RAMP and VecTest for testing corvid species were 91.0% and 82.1%, respectively.

Animals↗

Postlicensure safety surveillance for 7-valent pneumococcal conjugate vaccine.

CONTEXT: Clinical trials evaluate a vaccine's safety before approval, but some risks may escape detection or adequate characterization until larger population exposures occur after licensure. OBJECTIVE: To summarize reports of events occurring after vaccination with 7-valent pneumococcal conjugate vaccine (PCV), including those that may warrant further investigation to assess possible causation by PCV. DESIGN: Descriptive epidemiology of reports submitted to the Vaccine Adverse Event Reporting System (VAERS), a national passive surveillance database. SETTING AND PATIENTS: United States during first 2 years after licensure of PCV (February 2000 through February 2002). Reports studied were for children younger than 18 years and vaccinated with PCV. MAIN OUTCOME MEASURES: Numbers and proportional distributions of reports. RESULTS: A total of 4154 reports of events following PCV were submitted to VAERS, for a rate of 13.2 reports per 100,000 doses distributed. Multiple vaccines were given in 74.3% of reports. The most frequently reported symptoms and signs included fever, injection site reactions, fussiness, rashes, and urticaria. Serious events were described in 14.6% of reports. There were 117 deaths, 23 reports of positive rechallenges, and 34 cases of invasive pneumococcal infections possibly representing vaccine failure. Immune-mediated events occurred in 31.3% of reports. All 14 patients with anaphylactic or anaphylactoid reactions survived. Thrombocytopenia developed in 14 patients and serum sickness in 6 others. Neurologic symptoms occurred in 38% of reports. Seizures described in 393 reports included 94 febrile seizures. CONCLUSIONS: The majority of reports to VAERS in the first 2 years after licensure of PCV described generally minor adverse events previously identified in clinical trials. The proportion of reports portraying serious events was similar to that for other vaccines. Although there are important limitations in passive surveillance data, and caution in their interpretation is necessary, symptoms experienced by a few children more than once after successive PCV doses, including allergic reactions, prolonged or abnormal crying, fussiness, dyspnea, and gastrointestinal distress, warrant continued surveillance, as do reports of rare but potentially serious events, such as seizures, anaphylactic or anaphylactoid reactions, serum sickness, and thrombocytopenia.

Adolescent↗

Separation of craniopagus twins: the Brisbane experience.

INTRODUCTION: There are many problems facing the neurosurgeon when separating craniopagus twins. The condition is rare, with an incidence of 1 in 2.5 million births. As such there is a paucity of information in the literature regarding strategies for separation. SURVIVAL RATES: Over the last 20 years, there has been a gradual improvement in survival rates due to a combination of improved imaging, surgical/anaesthetic techniques and postoperative care. Currently, survival rates following surgery are at 50-60%. More information regarding this condition is needed to make surgical separation a safer event. AIM: The aim of this article is to discuss the preoperative work-up, technical details of surgery, postoperative care and lessons learned with respect to the separation of craniopagus twins.

Australia↗

Psychological determinants of willingness to taste and purchase genetically modified food.

Decreasing acceptance of biotechnologies over time has been reported in Europe. Studies claim that attitudes are negative, even hostile, and that people are very worried about genetic engineering in food and medicine. However, such studies are mostly based on surveys and these have significant methodological problems, such as low response rates, which may indicate that only those with strong views respond, thus biasing the sample. Here an alternative method, involving "topic-blind" recruitment of participants and a behavioral measure (food tasting), was used. We show that in a topic-blind sample of 100 individuals, 93% willingly tasted and ate what they believed to be genetically modified (GM) food in an experimental setting, and 48% said they would buy GM food in the future, results that are surprising in the context of other reports about attitudes and intentions toward GM food. Purchasers and nonpurchasers differed in their attitudes toward GM food on key risk-related scales (particularly on a dread-not dread scale--a measure of integral affect--and an ethical-unethical scale). Despite these differences, however, and despite their negative attitude, most nonpurchasers (85.7%) still tasted the GM apple. Incidental affect (state stress and trait worry) was not found to influence risk-related judgments about GM food. Integral affect (dread of GM plants and animals used for food) and concerns about the future risks of GM animals in food were found to be key predictors of willingness to purchase GM food.

Adolescent↗

Everolimus with optimized cyclosporine dosing in renal transplant recipients: 6-month safety and efficacy results of two randomized studies.

Two prospective, randomized studies evaluated everolimus 1.5 vs. 3 mg/day with steroids and low-exposure cyclosporine (CsA) (C2 monitoring) in de novo renal transplant patients. Everolimus dosing was adjusted to maintain a minimum trough level of 3 ng/mL. Study 1 (A2306; n=237) had no induction therapy; in Study 2 (A2307; n=256) basiliximab was administered (Days 0 and 4). The primary endpoint was renal function at 6 months. CsA C2 target levels, initially 1200 ng/mL in Study 1 and 600 ng/mL in Study 2, were tapered over time post-transplant. Median creatinine levels in Study 1 were 133 and 132 micromol/L at 6 months in the 1.5 and 3 mg/day groups, respectively, and 130 micromol/L in both groups in Study 2. Biopsy-proven acute rejection (BPAR) occurred in 25.0% and 15.2% of patients in the 1.5 and 3 mg/day groups in Study 1, and 13.7% and 15.1% in Study 2. Incidence of BPAR was significantly higher in patients with an everolimus trough <3 ng/mL. There were no significant between-group differences in the composite endpoint of BPAR, graft loss or death, nor any significant between-group differences in adverse events in either study. Concentration-controlled everolimus with low-exposure CsA provided effective protection against rejection with good renal function.

Adult↗

Request for applications: islet cell replacement in type 1 diabetes.

The American Diabetes Association announces funding for clinical and basic science studies in three major areas of research that focus on cell-based insulin replacement in type 1 diabetes: 1. Genetic engineering of nonpancreatic cells into glucose-sensitive insulin-producing cells; 2. Transforming stem cells, pancreatic ductal cells, or pancreatic endocrine cell lines into glucose-sensitive insulin-producing cells; and 3. Xenografts of nonhuman islet cells.

Animals↗

Craniopagus: second Brisbane case. Case report.

Craniopagus is a rare and intriguing condition with an incidence of one in 2.5 million births. The chance of a neurosurgeon seeing a case in a working lifetime is unlikely. The chances of two cases from the same community within 12 months are remote in the extreme. The authors present a second case of craniopagus born and separated in Brisbane, Australia, in 2001 and discuss the intricacies of surgical separation and the lessons learned.

Australia↗

A comprehensive approach to percutaneous injury prevention during phlebotomy: results of a multicenter study, 1993-1995.

OBJECTIVE: To examine a comprehensive approach for preventing percutaneous injuries associated with phlebotomy procedures. DESIGN AND SETTING: From 1993 through 1995, personnel at 10 university-affiliated hospitals enhanced surveillance and assessed underreporting of percutaneous injuries; selected, implemented, and evaluated the efficacy of phlebotomy devices with safety features (ie, engineered sharps injury prevention devices [ESIPDs]); and assessed healthcare worker satisfaction with ESIPDs. Investigators also evaluated the preventability of a subset of percutaneous injuries and conducted an audit of sharps disposal containers to quantify activation rates for devices with safety features. RESULTS: The three selected phlebotomy devices with safety features reduced percutaneous injury rates compared with conventional devices. Activation rates varied according to ease of use, healthcare worker preference for ESIPDs, perceived "patient adverse events," and device-specific training. CONCLUSIONS: Device-specific features and healthcare worker training and involvement in the selection of ESIPDs affect the activation rates for ESIPDs and therefore their efficacy. The implementation of ESIPDs is a useful measure in a comprehensive program to reduce percutaneous injuries associated with phlebotomy procedures.

Attitude of Health Personnel↗

Separation of craniopagus joined at the occiput. Case report.

Siamese or conjoined twins have intrigued both the physician and layperson for centuries. The craniopagus type (joined at the head) is exceedingly rare, with an incidence of one in 2.5 million births. Most clinicians never see a case of craniopagus, and those who do rarely see more than one. The authors present a case of the craniopagus type of conjoined twins born and recently separated in Brisbane, Australia. The prenatal diagnosis, subsequent investigations, separation, and outcome are presented.

Brain↗

New Explanation for Ligand Bending in Transition Metal Tris(dithiolate) Complexes.

The results of Fenske-Hall molecular orbital calculations are reported for the trigonal prismatic complexes Mo(S(2)C(2)H(2))(3) and Mo(S(2)C(6)H(4))(3). Both complexes exhibit a bend of the S-C-C-S ligand plane away from the S-Mo-S plane. A series of calculations which systematically follow the changes in electronic structure as the bend angle alpha is varied between 0 and 30 degrees indicates that the bend can be attributed to a second order Jahn-Teller distortion. The driving force for this distortion, which allows mixing between a set of ligand pi orbitals and the metal d(z)()()2 orbital, should be greatest for d(0) systems. In these systems the bent geometry leads to the stabilization of the doubly occupied HOMO. The driving force for ligand bending should be lower in systems having more or fewer electrons (e.g. Re(S(2)C(2)Ph(2))(3) or V(S(2)C(2)Ph(2))(3), respectively). While the steric bulk of the dithiolate ligands in the latter complexes may also influence the degree of ligand bending, this is probably a secondary effect.

Journal Article↗