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Biomedical subjects

L Chandler

Publications and source records attributed to L Chandler.

At least 19 recordsLinked to original sources
PubMed2006

Chick embryo lethal orphan virus can be polymer-coated and retargeted to infect mammalian cells.

Non-human adenovirus vectors have attractive immunological properties for gene therapy but are frequently restricted by inefficient transduction of human target cells. Using chicken embryo lethal orphan (CELO) virus, we employed a nongenetic mechanism of polymer coating and retargeting with basic fibroblast growth factor (bFGF-pc-CELOluc), a strategy that permits efficient tropism modification of human adenovirus. bFGF-pc-CELOluc showed efficient uptake and transgene expression in chick embryo fibroblasts (CEF), and increased levels of binding and internalization in a variety of human cell lines. Transgene expression was also greater than unmodified CELOluc in PC-3 human prostate cells, although the specific activity (RLU per internalized viral genome) was decreased. In CEF, the specific activity of bFGF-pc-CELOluc was considerably higher than in the human prostate cell line PC-3. Retargeted virus was fully resistant to inhibition by human serum with known adenovirus-neutralizing activity in vitro, while in mice CELOluc was cleared less rapidly from the blood than Adluc following i.v. administration in the presence of adenovirus neutralizing serum. Polymer coating and retargeting with bFGF further reduced rates of clearance for both viruses, suggesting protection against both neutralizing and opsonizing factors. The data indicate that CELO virus may be retargeted to infect human cells via alternative, potentially disease-specific, receptors and resist the effects of pre-existing humoral immunity.

ATPases Associated with Diverse Cellular Activitie↗
PubMed2001

Reliability and validity of a structured interview guide for the Hamilton Anxiety Rating Scale (SIGH-A).

The Hamilton Anxiety Rating Scale, a widely used clinical interview assessment tool, lacks instructions for administration and clear anchor points for the assignment of severity ratings. We developed a Structured Interview Guide for the Hamilton Anxiety Scale (SIGH-A) and report on a study comparing this version to the traditional form of this scale. Experienced interviewers from three Anxiety Disorders research sites conducted videotaped interviews using both traditional and structured instruments in 89 participants. A subset of the tapes was co-rated by all raters. Participants completed self-report symptom questionnaires. We observed high inter-rater and test-retest reliability using both formats. The structured format produced similar but consistently higher (+ 4.2) scores. Correlation with a self-report measure of overall anxiety was also high and virtually identical for the two versions. We conclude that in settings where extensive training is not practical, the structured scale is an acceptable alternative to the traditional Hamilton Anxiety instrument.

Anxiety Disorders↗
PubMed2000

In vitro bleeding time test can diagnose thrombotic thrombocytopenia purpura and can possibly monitor therapeutic plasma apheresis.

Thrombotic thrombocytopenia purpura (TTP) is perplexing, mainly because of its difficult diagnosis and dramatic clinical presentations, high mortality rates, and the effectiveness of empirical plasma infusions and plasma exchanges. Scientific evidence supports the hypothesis that TTP results from platelet hyperagglutination. To support this, a new in vitro bleeding time (Platelet-Stattrade mark) test was used. Eleven patients had a mean in vitro bleeding time of 7.3 +/- 2.1 seconds prior to plasma exchange and eight patients had a mean of 13.6 +/- 4.7 seconds after the plasma exchange procedure. Normal controls were 14 +/- 2 seconds. The test was used to monitor plasma exchanges in two patients. At the time the platelet count and LDH returned to normal, the Platelet-Stattrade mark remained shortened. The two patients relapsed and required continued plasma exchanges until Platelet-Stattrade mark corrected to normal. These results suggest that plasma exchanges may be effectively monitored by Platelet-Stattrade mark rather than the traditional parameters, i.e., LDH. Therefore, the Platelet-Stattrade mark test may be a useful test to diagnose TTP and monitor therapy in this disease.

Bleeding Time↗
PubMed2000

Complications of plasma exchange in 71 consecutive patients treated for clinically suspected thrombotic thrombocytopenic purpura-hemolytic-uremic syndrome.

BACKGROUND: With the increased frequency of diagnosis and improved survival of thrombotic thrombocytopenic purpura-hemolytic-uremic syndrome (TTP-HUS), the morbidity of plasma exchange (PE) treatment has become more important. STUDY DESIGN AND METHODS: Data were prospectively collected on 71 consecutive patients referred to the Oklahoma Blood Institute (OBI) for PE treatment for clinically suspected TTP-HUS from mid-1996 to mid-1999. Complications were defined as major or minor, and distinguished between those related to central venous catheter access or to the plasma. RESULTS: Twenty-one patients (30%) had 27 major complications, which caused two deaths. The major complications included 2 episodes of hemorrhage after subclavian line insertion (1 death), 1 pneumothorax requiring a chest tube, 12 systemic infections (1 death), 7 episodes of catheter thrombosis requiring removal of the central venous catheter, 2 episodes of venous thrombosis requiring anticoagulant treatment, 2 episodes of hypoxemia and hypotension, and 1 episode of serum sickness. Minor complications occurred in 22 additional patients (31%). Twenty-eight patients (39%) had no complications. CONCLUSIONS: The morbidity and mortality of catheter placement and PE are important considerations when PE treatment for clinically suspected TTP-HUS is anticipated.

Bacteremia↗
PubMed1999

Genetic variation in geographical populations of western and Mexican corn rootworm.

Genetic variation in the nuclear rDNA ITS1 region of western corn rootworm, Diabrotica virgifera virgifera (WCR), and Mexican corn rootworm, D. v. zeae (MCR) was studied. Two sites were detected which differentiated WCR and MCR in the 642-base sequence. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis of the first internal transcribed spacer region (ITS1) sequence revealed no variation within or among the twelve WCR and two MCR populations. PCR-RFLP of 75% of the mitochondrial DNA genome detected one significant polymorphic site out of the approximately 190 restriction sizes observed in WCR. The polymorphism did not differentiate geographical populations of WCR and is not diagnostic for the subspecies. The low levels of variation observed in WCR suggests either high levels of gene flow or a recent geographical expansion from a relatively small base. Gene flow would facilitate the rapid spread of traits that could compromise control programmes, such as insecticide resistance or behavioural modifications. The minimal genetic differentiation between WCR and MCR raises questions about the evolutionary history of these subspecies and how the distinct phenotypes are maintained.

Animals↗
PubMed1999

The Harvard Group Scale of Hypnotic Susceptibility and related instruments: individual and group administrations.

The Harvard Group Scale of Hypnotic Susceptibility, Form A (HGSHS:A), Tellegen's Absorption Scale (TAS); Dissociative Experiences Scale (DES); and Phenomenology of Consciousness Inventory (PCI) were administered either individually or in groups. Eighty students from undergraduate Introduction to Psychology classes were randomly assigned to 1 of the 2 administration conditions with 40 students each. Although there was a general trend of differential item difficulty levels across the 2 administration conditions, a variety of results (descriptive characteristics, reliability, and validity) point to the similarity of behavioral and subjective responses to hypnosis in the 2 conditions. The TAS, DES, and PCI also produced similar results across both conditions of administration.

Adult↗
PubMed1999

Chizé virus, a new phlebovirus isolated in France from Ixodes (Trichotoixodes) frontalis.

A new phlebovirus (Bunyaviridae family, Phlebovirus genus), provisionally designed Chizé virus, was isolated from a nymph of Ixodes (Trichotoixodes) frontalis collected on a wren (Troglodytes troglodytes) found dead in the Chizé forest, western France. Chizé virus produced a lethal encephalitis in one-day-old mice and cytopathic effect (CPE) in Vero cells. Extracellular particles with a mean diameter of 105 nm with surface spikes characteristic of Uukuniemi (UUK) serogroup viruses were observed in Vero cells. Chizé virus reacted in complement-fixation test with several UUK serogroup viruses but was readily distinguished from all registered viruses in the serogroup. I. frontalis is highly specific for birds and unlikely to transmit Chizé virus to humans or domestic animals; the pathogenicity of the new virus to wild birds remains to be clarified.

Animals↗
PubMed1998

Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome: diagnosis and management.

Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS) is a clinical syndrome defined by the presence of thrombocytopenia and microangiopathic hemolytic anemia without a clinically apparent etiology. Patients may also have multiple other symptoms and signs including neurologic and renal abnormalities and fever. In the era prior to effective therapy with plasma exchange, most patients developed multisystem abnormalities and the syndrome was more easily recognized. Now, since there is urgency to begin treatment, sufficient diagnostic criteria for TTP-HUS are only thrombocytopenia and microangiopathic hemolytic anemia without a clinically apparent cause; patients may have no neurologic symptoms, renal abnormalities, or fever. This has lead to an apparent increased incidence because of both the increased importance of early recognition and the decreased specificity of the diagnostic criteria. Effective treatment has also revealed new aspects of the clinical course of TTP-HUS following the initial response to plasma exchange treatment: prompt exacerbations, which are common when plasma exchange is diminished in frequency or discontinued, and later relapses, which may occur many years after the initial episode. This review describes the evolution of the syndrome of TTP-HUS in the current era of effective treatment, and describes the management and clinical outcomes among patients treated by the Oklahoma Blood Institute.

Hemolytic-Uremic Syndrome↗
PubMed1998

Anti-interleukin 8 antibody abolishes effects of lipoid nephrosis cytokine.

Supernatant factor from peripheral blood mononuclear cell (PBMC) cultures of idiopathic minimal lesion nephrotic syndrome (IMLNS) patients in relapse induces in vivo albuminuria and increases 35sulfate uptake by glomerular basement membrane (GBM) in rats. The purpose of this study was to evaluate the effect of anti-interleukin 8 (IL8) neutralizing antibody on the effects induced by the supernatant factor. Supernatant factor collected from six cultures of PBMC from IMLNS patients in relapse were combined and aliquotted into two samples. Anti-IL8 neutralizing antibody (750 ng) was added to one. Supernatant factor or supernatant factor and anti-IL8 antibody were infused for 5 days into the left renal artery of Wistar rats using an osmotic pump. On the last day of infusion, rats were injected with 35sulfate (1.0 mCi/200 g) intraperitoneally and killed after 8 h. Glomeruli were isolated and GBM obtained. There was a significant increase in 35sulfate uptake of the infused kidney (169 +/- 52 cpm/mg dry glomerular weight, mean +/- SEM) compared with the uptake seen in the contralateral kidney (116 +/- 41, P < 0.05) when the supernatant factor was infused alone. No significant differences in 35sulfate incorporation were seen between infused kidney (173 +/- 5) and contralateral kidney (190 +/- 49) when supernatant factor and anti-IL8 antibody were administered. A significant increase in albuminuria was seen on the last day of infusion (0.43 +/- 0.11 albumin/ creatinine ratio, mean +/- SEM) compared with the ratio prior to infusion of the supernatant factor alone (0.18 +/- 0.03, P <0.05). No significant differences in urinary albumin/creatinine ratios prior to and on the 5th day of infusion were seen when the supernatant factor was administered with anti-IL8 antibody. Supernatant factor effects were abolished by the addition of anti-IL8 neutralizing antibody, suggesting that the described effects are mediated by IL8.

Adolescent↗
PubMed1998

Conversion from Sandimmune to Neoral in organ transplant recipients.

The pharmacokinetic profiles of Sandimmune and Neoral vary considerably among transplant recipients. Cyclosporine exposure is far more consistent with Neoral than it is with Sandimmune. Because intrapatient variability of drug exposure has been demonstrated to be a risk factor for chronic rejection, this difference becomes important. Neoral also has a linear dose response and a stronger correlation between trough level and drug exposure. Dose linearity greatly facilitates accurate dose titration. Results of controlled studies in which kidney, liver, and heart transplant recipients were converted from Sandimmune to Neoral have shown that conversion on a 1:1 mg basis results in more predictable bioavailability and often in reductions in cyclosporine dose. Carefully monitored conversion has not been associated with increased side effects, and any side effects that do emerge can usually be managed by taking Neoral with food, changing the dose from every 12 hours to every 8 hours, or through dose reduction.

Cyclosporine↗
PubMed1997

Ultraviolet light in the orthopaedic operating theatre.

This article looks at the physical aspects of Ultraviolet C light and the practical aspects encountered when setting up a UVC system in Winford Orthopaedic Hospital, Bristol for the purposes of a clinical trial to study the effect of UVC on bacterial load in the theatre air and in the wounds of patients undergoing total joint replacement. The results of that clinical trial will then be described followed by an outline of the problems encountered with using UVC.

Air Microbiology↗
PubMed1992

Hyperlipidemia after heart transplantation: report of a 6-year experience, with treatment recommendations.

Mean plasma lipid values in 100 patients who survived greater than 3 months after heart transplantation increased significantly at 3 months over pretransplantation values: total cholesterol from 168 +/- 7 to 234 +/- 7 mg/dl, low density lipoprotein (LDL) cholesterol from 111 +/- 6 to 148 +/- 6 mg/dl, high density lipoprotein (HDL) cholesterol from 34 +/- 1 to 47 +/- 1 mg/dl and triglycerides from 107 +/- 6 to 195 +/- 10 mg/dl. There were no significant increases after this time. The LDL cholesterol values reamined greater than or equal to 130 mg/dl in 64% of patients and triglyceride values remained greater than or equal to 200 mg/dl in 41% of patients 6 months after postoperative dietary instructions. Beginning in 1985, select patients whose total cholesterol values remained greater than 300 mg/dl despite 6 months of dietary intervention were treated with lovastatin given alone in a high dose (40 to 80 mg/day) or in combination with another hypolipidemic agent. Four of the five patients so treated developed rhabdomyolysis; two of the four had acute renal failure. Beginning in 1988, a second protocol--lovastatin at 20 mg/day as monotherapy--was used in patients who despite dietary intervention had total cholesterol greater than 240 mg/dl (mean follow-up 13 months). In the 15 patients so treated, mean total cholesterol decreased from 299 +/- 10 mg/dl before treatment with lovastatin to 235 +/- 9 mg/dl during treatment (21% reduction, p less than 0.001) and mean LDL cholesterol was reduced from a baseline value of 190 +/- 10 to 132 +/- 12 mg/dl during treatment (31% reduction, p less than 0.001). In this study, lovastatin at a dose of less than or equal to 20 mg/day as monotherapy was a well tolerated, effective treatment for hyperlipidemia after heart transplantation. It did not result in rhabdomyolysis and required no alteration in immunosuppressive therapy. However, the dose should not exceed 20 mg/day and combination therapy with either gemfibrozil or nicotinic acid should be avoided, even if the target LDL cholesterol value is not reached.

Analysis of Variance↗
PubMed1985

Perturbation of egg phosphatidylcholine and dipalmitoylphosphatidylcholine multilamellar vesicles by n-alkanols. A fluorescent probe study.

The perturbing effects of n-alkanols (pentanol, decanol and tetradecanol) in egg phosphatidylcholine and dipalmitoylphosphatidylcholine multilamellar vesicles were studied with five fluorescent probes, 1-(4'-trimethylaminophenyl)-6-phenylhexa-1,3,5-triene (TMA-DPH), 1,6-diphenyl-1,3,5-hexatriene, and 2-, 7-, and 12-(9-anthroxyloxy)stearic acid (2-, 7-, and 12-AS). These probes localize at various depths in the membrane, enabling study of the membrane-order gradient. Phase-modulation fluorescence spectroscopy was used to measure steady-state anisotropies, excited-state lifetimes and differential polarized lifetimes from which the limiting hindered anisotropies (r infinity) and the logarithm of the rotational rate (log R) were calculated. The probes that localize at about the same depth in the membrane (TMA-DPH and 2-AS, diphenylhexatriene and 12-AS) generally, but not always, showed similar changes in r infinity and log R with added alkanols. However, the absolute values of r infinity and log R were usually different. The inconsistencies are attributed to differences in the probes' sizes, structures, photophysical properties and perturbing abilities. The perturbation of membranes by alkanols is chain-length-dependent. Pentanol disorders the membrane at all depths but is more effective in the membrane center than nearer to the polar headgroups of the phospholipids, tetradecanol can be accommodated into the membrane without effect or with increased order and the effects of decanol are intermediate between pentanol and tetradecanol. Our results with alkanols indicate that: a single perturber can have different effects on membrane order at different depths in the bilayer; the perturbation is observed at and distant from the perturbers' location in the membrane, and the bilayer center is more susceptible to perturbation by alkanols than the region of the bilayer near the phospholipid headgroups.

Fatty Alcohols↗
PubMed1985

Legionella infections in cyclosporine-immunosuppressed cardiac transplants.

Pulmonary infections from bacterial or viral agents, as well as rare infectious agents, such as Toxoplasma gondii, Aspergillus, and Pneumocystis carinii, have been a bane to the clinician in charge of the care of transplant patients. One such opportunistic Organism, Legionella pneumophila, was responsible for four episodes of infection in three of our patients who survived due to better management of immunosuppression, together with aggressive therapy and early diagnosis of the infectious complications.

Journal Article↗
PubMed1977

Behavioral and neurological comparisons of neonates born to mothers of differing social environments.

Sixty newborn infants, 30 born to parents of middle to upper-middle socioeconomic status and 30 born to parents of limited personal-social resources, were assessed on the Neonatal Behavioral Assessment Scale. Although no difference between groups was found in motor and neurological status, data from this study did indicate that the prenatal factors, having no obvious physiological base, associated with the parental social environment, may affect the newborn's behavioral outcome.

Child Behavior↗