Role of radionuclide imaging in trials of antiangiogenic therapy.
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Angiogenesis Inhibitors↗
Biomedical subjects
C Anderson
Publications and source records attributed to C Anderson.
Microdialysis technique as a method to study the percutaneous penetration of methyl nicotinate through excised human skin, reconstructed epidermis, and human skin in vivo.
PURPOSE: The aim was to assess the feasibility of cutaneous microdialysis as a method to study percutaneous penetration of methyl nicotinate through human skin in vitro and in vivo. METHODS: Microdialysis was applied in vitro in excised human skin, in isolated dermis, in reconstructed human epidermis and in vivo in the volar forearm skin of volunteers using methyl nicotinate (MN) as a model compound. After topical application of MN, aliquots of the perfusate were collected and analyzed for the presence of MN spectrophotometrically and by HPLC. In vivo, visual scoring and laser Doppler perfusion imaging (LDPI) were used to monitor the effects on skin blood flow. RESULTS: In vitro, MN was detected in the dialysate after a 1 min exposure of excised skin to concentrations as low as 25 mM. Higher concentrations up to 500 mM showed increased levels. Prolongation of the application time to 60 min resulted in increased levels of MN in the perfusate as the duration of application increased. Reconstructed epidermis and isolated dermis showed an almost 2- and 20-fold higher penetration compared to excised skin, respectively. In vivo, LDPI measurements showed a rapid increase in skin blood flow after application of 25 to 100 mM MN for 1 min. MN was only detectable in the microdialysate after application of 100 mM for 10 min (two of three subjects). CONCLUSIONS: Cutaneous microdialysis may be a tool for comparative studies linking responses in human skin in vivo to in vitro data using the same technique and endpoint.
Administration, Cutaneous↗
The spectrum of inflammatory cell response to dimethyl sulfoxide.
Dimethyl sulfoxide (DMSO), depending upon the concentration and mode of application to the skin, can induce either a non-immunological immediate contact urticaria or an irritant reaction. The dermal cellular infiltrate after open application of varying concentrations of DMSO has been studied in an experimental guinea pig model. The composition of the dermal cellular infiltrate showed a spectrum dependent on the concentration and number of applications of DMSO. The immediate reaction infiltrate 3 h after application of 100% DMSO consisted of 50% granulocytes, basophils being predominant. On the other hand, 12% DMSO applied 3 x daily for 3 days (cumulative insult) caused histologically a cellular reaction in which 80% of the infiltrate consisted of mononuclear cells. The present findings are compared to the microscopic findings in 3 other cutaneous reactions previously studied in this animal model, namely, the Type I immediate hypersensitivity reaction, the Type IV delayed hypersensitivity reaction, and the irritant reaction. Differing cellular infiltrate patterns are discernible at the same time points. The study illustrates the spectrum of inflammatory reactions seen in the skin and provides background information for future clinical studies, for instance, on the role of the basophil granulocyte in immediate contact reactions.
Administration, Topical↗
Regulation of TNFalpha production and release in human and mouse keratinocytes and mouse skin after UV-B irradiation.
TNFalpha is a primary cytokine responsible for inflammatory and immunosuppressive responses in skin. After UV-B irradiation of cultured human keratinocytes, we found that TNFalpha was released into the media, as monitored by ELISA, and was bound to cells, as observed by immunofluorescence microscopy. The release of TNFalpha into cell culture supernatant during the 24 h after UV-B irradiation was augmented by the addition of IL-1alpha to the cells. Further, we found this secretion was unaffected by rapamycin, and therefore independent of FRAP DNA-protein kinase mediated signal transduction. However, UV-B also induced expression of membrane-bound TNFalpha, and this was dependent on FRAP signaling. In wild type mice, TNFalpha bound to skin increased immediately after irradiation, declined at 6 h, and then rose again at 12 h before falling by 24 h. This pattern of induction was confirmed by RT-PCR of TNFalpha mRNA message in cultured epidermal cells. Induction of membrane-bound TNFalpha was also found in c-fos gene knockout mice deficient in the AP-1 transcription factor, suggesting that, although AP-1 containing c-fos signaling is required for some UV responses, AP-1 containing c-fos is not required for this TNFalpha activation. However, in homozygous p53 knockout mice the basal level of TNFalpha bound to the epidermis was greatly elevated without UV irradiation. This level declined and remained constant following irradiation. This implies that p53 directly or indirectly represses TNFalpha gene expression and that modification of p53 mRNA stability or phosphorylation of p53 protein after UV may be responsible for TNFalpha induction in the membrane. Overexpression of the immunosuppressive cytokine TNFalpha in this locale may contribute to the carcinogen-susceptibility of p53 knockout mice.
Animals↗
Termination of spiral waves with biphasic shocks: role of virtual electrode polarization.
INTRODUCTION: This simulation study seeks to extend the virtual electrode polarization (VEP) theory for defibrillation to explain the success and failure of biphasic shocks. The goals of the study are to (1) provide insight into why optimal biphasic shocks have a lower voltage defibrillation threshold than monophasic shocks, (2) examine the mechanisms of biphasic shock failure and to determine whether they differ from those of monophasic shocks, and (3) study how the timing of biphasic shock delivery to a spiral wave affects voltage defibrillation threshold. METHODS AND RESULTS: A spiral wave is initiated in a bidomain representation of a 2-cm x 2-cm sheet of ventricular myocardium. The model incorporates nonuniform fiber curvature, membrane kinetics suitable for high-strength shocks, and electroporation. A spatially uniform extracellular field is delivered by line electrodes. The shock establishes VEP that dictates the postshock activity in the tissue. Our results demonstrate that the second phase of biphasic shocks leaves the tissue with substantially smaller postshock excitable gap, thus eliminating the majority of the substrate for reinitiation of reentrant activity. Further, the occurrence of break excitations for weaker biphasic shocks indicates that the mechanisms for biphasic shock failure are more complex than for monophasic shocks. Biphasic voltage defibrillation thresholds range from 8 to 16 V/cm, depending on the position of the spiral wave. An increase in the amount of preshock excitable gap leads to an increase in voltage defibrillation threshold. CONCLUSION: This study demonstrates the importance of VEP and its interaction with preshock activity in the success and failure of biphasic defibrillation shocks.
Computer Simulation↗
The quantitation of 2-oxo-3-hydroxy lysergic acid diethylamide (O-H-LSD) in human urine specimens, a metabolite of LSD: comparative analysis using liquid chromatography-selected ion monitoring mass spectrometry and liquid chromatography-ion trap mass spectrometry.
This paper compares the potential forensic application of two sensitive and rapid procedures (liquid chromatography-mass spectrometry and liquid chromatography-ion trap mass spectrometry) for the detection and quantitation of 2-oxo-3-hydroxy lysergic acid diethylamide (O-H-LSD) a major LSD metabolite. O-H-LSD calibration curves for both procedures were linear over the concentration range 0-8,000 pg/mL with correlation coefficients (r2) greater than 0.99. The observed limit of detection (LOD) and limit of quantitation (LOQ) for O-H-LSD in both procedures was 400 pg/mL. Sixty-eight human urine specimens that had previously been found to contain LSD by gas chromatography-mass spectrometry were reanalyzed by both procedures for LSD and O-H-LSD. These specimens contained a mean concentration of O-H-LSD approximately 16 times higher than the LSD concentration. Because both LC methods produce similar results, either procedure can be readily adapted to O-H-LSD analysis for use in high-volume drug-testing laboratories. In addition, the possibility of significantly increasing the LSD detection time window by targeting this major LSD metabolite for analysis may influence other drug-free workplace programs to test for LSD.
Chromatography, High Pressure Liquid↗
Patterns of adolescent smoking initiation rates by ethnicity and sex.
OBJECTIVE: To define US national sex specific rates of smoking initiation among Hispanic, non-Hispanic white, and African American adolescents aged 12-17 years for each calendar year from 1940 through 1992. METHODS: Adult survey data from the tobacco use supplement of the Current Population Survey in 1992-93 and 1995-96 were used to reconstruct the age at which individuals began to smoke and the calendar year in which they were that age. From these data, the number of individuals who began a calendar year as never smokers and who were aged 12-17 years during that year could be estimated and formed the denominator of the initiation rate. The number of these individuals who reported taking up smoking during that year formed the numerator of the initiation rate. RESULTS: Initiation rates among male adolescents in each of the three racial/ethnic groups have declined since 1945. However, since 1983, initiation rates among male adolescents overall have increased. Non-Hispanic white male adolescents generally initiated cigarette smoking at higher rates than Hispanic or African American male adolescents. Initiation rates among Hispanic male adolescents have not been statistically different from initiation rates among African American male adolescents. From 1978 to 1982, initiation rates among Hispanic and African American male adolescents experienced a sharp decline, and the rate of decline was steeper than that experienced by non-Hispanic white male adolescents. Initiation rates among female adolescents have increased since 1940, catching up to male adolescent initiation rates by the mid 1970s. Initiation rates among female adolescents appeared to level off or increased slightly again from the mid 1980s to 1990. Non-Hispanic white female adolescents generally initiate cigarette smoking at higher rates than Hispanic or African American female adolescents. Initiation rates among non-Hispanic white and African American female adolescents equalled the initiation rates of their male counterparts by the mid 1970s, but initiation rates among Hispanic female adolescents did not overlap with initiation rates of Hispanic male adolescents until 1990. From 1975 to 1980, initiation rates among African American female adolescents decreased sharply, but, unlike initiation rates among the two other ethnic groups, rates continued to decline from 1984 to 1990. CONCLUSIONS: Different patterns of increasing and decreasing smoking initiation among sex and ethnic adolescent groups suggest the effect of varying social and cultural influences. These findings support the importance of including ethnic factors in studies of smoking behaviour.
Adolescent↗
Home or hospital for stroke rehabilitation? results of a randomized controlled trial : I: health outcomes at 6 months.
BACKGROUND AND PURPOSE: We wished to examine the effectiveness of an early hospital discharge and home-based rehabilitation scheme for patients with acute stroke. METHODS: This was a randomized, controlled trial comparing early hospital discharge and home-based rehabilitation with usual inpatient rehabilitation and follow-up care. The trial was carried out in 2 affiliated teaching hospitals in Adelaide, South Australia. Participants were 86 patients with acute stroke (mean age, 75 years) who were admitted to hospital and required rehabilitation. Forty-two patients received early hospital discharge and home-based rehabilitation (median duration, 5 weeks), and 44 patients continued with conventional rehabilitation care after randomization. The primary end point was self-reported general health status (SF-36) at 6 months after randomization. A variety of secondary outcome measures were also assessed. RESULTS: Overall, clinical outcomes for patients did not differ significantly between the groups at 6 months after randomization, but the total duration of hospital stay in the experimental group was significantly reduced (15 versus 30 days; P<0.001). Caregivers among the home-based rehabilitation group had significantly lower mental health SF-36 scores (mean difference, 7 points). CONCLUSIONS: A policy of early hospital discharge and home-based rehabilitation for patients with stroke can reduce the use of hospital rehabilitation beds without compromising clinical patient outcomes. However, there is a potential risk of poorer mental health on the part of caregivers. The choice of this management strategy may therefore depend on convenience and costs but also on further evaluations of the impact of stroke on caregivers.
Aged↗
Home or hospital for stroke Rehabilitation? Results of a randomized controlled trial : II: cost minimization analysis at 6 months.
BACKGROUND AND PURPOSE: The goal of the present study was to examine the resource and economic implications of an early hospital discharge and home-based rehabilitation scheme for patients with acute stroke. METHODS: A cost minimization analysis in conjunction with a randomized controlled trial was carried out at 2 affiliated teaching hospitals in the southern metropolitan region of Adelaide, South Australia, between 1997 and 1998. Eighty-six hospitalized patients with acute stroke who required rehabilitation were randomized to receive both early hospital discharge and home-based rehabilitation, or conventional in-hospital rehabilitation and community care. Direct and indirect costs related to stroke rehabilitation were calculated, including hospital bed days, home-based intervention program, community services, and personal expenses during the 6 months after randomization. RESULTS: The mean cost per patient was lower for patients randomized to the early hospital discharge and home-based rehabilitation ($8040) compared with those who received conventional care ($10 054). This cost saving was not statistically significant (P=0.14). However, sensitivity analyses indicated that the cost of home-based rehabilitation was consistently lower than that of conventional care except when hospital costs were assumed to be 50% less than those used in the main analysis. Multiple regression analysis demonstrated that the cost of the home-based program was significantly related to a patient's level of disability after adjustment for age, comorbidity, and the presence or absence of a caregiver. CONCLUSIONS: The early hospital discharge and home-based rehabilitation scheme was less costly than conventional hospital care for patients with stroke. Limitation of the provision of such services to patients with mild disability is likely to be most cost effective.
Cost Savings↗
Neurotoxicity and dysfunction of dopaminergic systems associated with AIDS dementia.
Infection with the human immunodeficiency virus (HIV) selectively targets the basal ganglia resulting in loss of dopaminergic neurons. Although frequently asymptomatic, some patients may develop signs of dopamine deficiency de novo. Accordingly, they are highly susceptible to drugs that act on dopaminergic systems. Both neuroleptics and psychostimulants may exacerbate these symptoms. Experimental evidence suggests that viral proteins such as gp120 and Tat can cause toxicity to dopaminergic neurons, and this toxicity is synergistic with compounds such as methamphetamine and cocaine that also act on the dopaminergic system. In addition, other neurotransmitters that modulate dopaminergic function, such as glutamate and opioids, may also modify the susceptibility of the dopamine system to HIV. Therefore, a thorough understanding of the mechanisms that lead to this selective neurotoxicity of dopaminergic neurons would also likely lead to the development of therapeutic modalities for patients with HIV dementia.
AIDS Dementia Complex↗
Enteral feeding: a change in practice.
There is an unacceptably high incidence of malnutrition in PICU. The delivery of nutritional support requires a structured approach. Early enteral feeding has been shown to reduce the stress response. Implementing a change in practice involves identification of resources, objectives and motivation for change. A randomised retrospective audit of the change in practice did demonstrate the value of earlier commencement of enteral feeding. Informal interviews with practitioners suggested improved practice and knowledge.
Algorithms↗
Hypochondriacal concerns, somatosensory amplification, and primary and secondary cognitive appraisals.
This paper uses data from four studies (N = 150, 150, 154 and 79) to examine the associations between hypochondriacal concerns (HCs) and stress appraisals (primary and secondary). A search activity account of HCs suggests that increased levels of HCs should be associated with positive appraisals of a stressful situation (i.e., increased levels of perceived challenge and perceived control). However, the results indicated that in terms of primary appraisals, increased perceptions of threat and not challenge were consistently associated with increased levels of HCs. Further, the results indicated that the association between threat and HCs is mediated by somatosensory amplification. Consistent with the search activity account it is shown that increased levels of perceived control (secondary appraisals) are associated with increased levels of HCs. The association for perceived control remains once variance due to somatosensory amplification is partialled and generalizes to a sample of patients with a sexually transmitted infection. The results are interpreted in relation to the transactional model of the stress process.
Adult↗
Exploring the factors influencing relapse and recovery among drug and alcohol addicted women.
1. Both women who were in treatment for relapse to and in sustained recovery from drugs and alcohol had multiple co-occurring addictions such as relationship, spending, food, and shopping that complicated the recovery process. 2. Depression is a major trigger for relapse in women with alcohol and drug problems. Recognition and treatment of depression is critical to achieve successful outcomes of treatment for these women, and teaching them to monitor their mood changes and seek help will improve the chances of preventing relapse. 3. Subjects in neither the relapse nor recovery sample recognized the significant influence of current violent partnerships or the ending of a violent relationship on their relapse or recovery.
Adult↗
Synergistic neurotoxicity by human immunodeficiency virus proteins Tat and gp120: protection by memantine.
Human immunodeficiency virus type 1 (HIV-1) proteins Tat and gp120 have been implicated in the pathogenesis of dementia associated with HIV infection. Recently, we showed the presence of Tat protein in brains of patients with HIV-1 encephalitis as well as macaques with encephalitis caused by a chimeric strain of HIV and simian immunodeficiency virus, and that even transient exposure of cells to Tat leads to release of cytopathic cytokines. Now, we report the first demonstration of gp120 protein in brain of patients with HIV encephalitis. We tested the hypothesis that Tat and gp120 would act synergistically to potentiate each protein's neurotoxic effects and determined the extent to which pharmacological antagonists against processes implicated in HIV-1 neuropathogenesis could block HIV-1 protein-induced neurotoxicity. Subtoxic concentrations of Tat and gp120, when incubated together, caused neuronal cell death and prolonged increases in levels of intracellular calcium. A transient exposure of neurons to Tat and gp120 for seconds initiated neuronal cell death, but maximal levels of neuronal cell death were observed with exposures lasting 30 minutes. The neurotoxicity caused by Tat and gp120 applied in combination was blocked completely by memantine, partially by amiloride, and not at all by dipyridamole or vigabatrin.
AIDS Dementia Complex↗
The psychosocial aspects of osteoporosis in women.
Osteoporosis has been documented to be a physiologically and psychologically debilitating disease. Health perceptions can be improved through both psychosocial support and specific intervention programs. These programs can improve independence and the quality of life of many people afflicted with this disease.
Exercise↗
Can tissue drug concentrations be monitored by microdialysis during or after isolated limb perfusion for melanoma treatment?
Isolated limb perfusion (ILP) with melphalan is used to treat recurrent melanoma. This study aimed to develop a microdialysis technique for melphalan tissue concentration measurement during ILP. The effects of melphalan concentration (50-600 microg/ml), microdIalysis flow rate (0.55-17.5 microl/min), probe length (5-50 mm) and temperature (25-41.5 degrees C) on in vitro recovery were studied. In addition, in vivo recovery was measured in rat hindlimbs perfused with melphalan using 50 mm microdialysis probes implanted subcutaneously and into muscle. Both dialysate and tissue sample melphalan concentrations were determined by high performance liquid chromatography. The in vitro recovery of melphalan was not affected by melphalan concentration or temperature, but increased with probe length and decreased with flow rate. The melphalan concentrations in subcutaneous and muscle dialysates were not significantly different. A linear relationship was found between tissue dialysate concentrations and actual tissue concentrations of melphalan (r2 = 0.97). Microdialysis is a potential method for tissue drug monitoring which may assist in the efficacious use of cytotoxics in human ILP.
Animals↗
Developing a model law restricting the transporting of passengers in the cargo areas of pickup trucks.
Pickup trucks have become increasingly popular in the United States, accounting for about one in five vehicles involved in fatal motor-vehicle crashes. A critical factor in these deaths is the practice of carrying passengers in truck cargo areas, which are not designed for this purpose. Each year approximately 200 deaths occur to occupants riding in the back of pickup trucks. Over half the states have laws dealing with preventable injury problem, but these laws vary widely and most are too limited to be effective. We have reviewed existing laws, as well as crash injury data, and we have developed and recommend a model bill. The bill focuses on intended use, restricting passengers to only those portions of a vehicle designed for human transport. We have also conducted and report on a survey of legislative sponsors of pickup truck legislation.
Accidents, Traffic↗
[Depression after cerebrovascular accident (CVA)].
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Cerebrovascular Disorders↗