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Biomedical subjects

J Anderson

Publications and source records attributed to J Anderson.

At least 307 records · Page 17Linked to original sources

Hypericin: a new laser phototargeting agent for human cancer cells.

Laser activation of anthracycline-related drugs combines chemotherapy with photoablation for improved treatment. Hypericin, a structurally related anthraquinone, was tested for laser activation and cytotoxicity in human cancer cells. Viability of P3 squamous cell carcinoma cells incubated with 1 to 20 microgram/mL hypericin was reduced by more than 95% after 1 minute exposure at 4 degrees C to an argon laser (514 nm, 5 W), a KTP-532 laser (532 nm, 5 W), or a 20-A xenon lamp. Viability was reduced over 90% in six human carcinoma, sarcoma, and melanoma cell lines by this combined treatment, but only trace toxicity was seen after separate exposure to hypericin or light alone. These results show that hypericin is a sensitive agent for phototherapy of human cancer cells in vitro and indicate that this drug may be useful for tumor targeting via minimally invasive imaging-guided laser fiber optics.

Anthracenes↗

Regional cerebral blood flow changes after light therapy in seasonal affective disorder.

There is considerable evidence to indicate that depressive disorders may be associated with changes in regional cerebral blood flow (rCBF), and that successful treatment may reverse these changes. We studied patients with seasonal affective disorder (SAD) using 99Tcm-hexamethylpropylene amine oxime (99TCm-HMPAO) single photon emission tomography (SPET) to examine the effect of light therapy on rCBF. Ten depressed patients (8 females, 2 males) with a mean (+/- S.D.) age of 33.5 +/- 11.3 years underwent 99TCm-HMPAO SPET studies before and after light therapy. The treatment response was evaluated using the Structured Interview Guide for the Hamilton Depression Rating Scale-Seasonal Affective Disorders Version (SIGH-SAD). A patient was considered responsive to light therapy if the post-treatment SIGH-SAD score was reduced by 60% or more in comparison to the pre-treatment score (responders, n = 5; non-responders, n = 5). Pre- and post-treatment SIGH-SAD scores and SPET data were compared in each patient. An improvement in depressive symptoms after light therapy was associated with an increase in rCBF in the frontal and cingulate regions as well as the thalamus. Such changes were not seen in non-responsive subjects.

Adult↗

International comparison of baccalaureate nursing degrees: collaboration in qualitative analysis.

This paper describes a study which investigated the perceived similarities and differences of a selection of baccalaureate nursing degrees from different continents. An international research team was formed, and by using a modified version of the Delphi process and nominal group techniques the group undertook a qualitative analysis of curriculum documents. The major areas analysis were: aims, content, methods and assessment. Under these headings the group produced a list of key issues supported by a number of indicative statements by collating the independent analyses undertaken by each of the team members. Examples of findings are that critical thinking and personal development are most obvious in aims but that the progression of curricula may not achieve this, there are differences in 'western' and 'asian' orientations to the concept of personal autonomy. Sciences are valued more than arts or humanities. The lecture method as well as practice placement dominate the teaching methods. Transcultural nursing is not significant except where there are two therapeutic ideologies in existence. Assessment methods are largely summative. The findings have application in the development of credit transfer and international exchange schemes. The conclusions highlight areas of special considerations when designing such schemes.

China↗

Reciprocal inhibition of nitric oxide and prostacyclin synthesis in human saphenous vein.

1. Angiotensin II (AII) causes contraction of isolated rings of human saphenous vein, responses that are attenuated by the presence of functional endothelium. In this study, we have investigated the mechanisms controlling the release by AII of two endothelial-derived vasorelaxants, prostacyclin (PGI2) and nitric oxide (NO). 2. Myotropic and biochemical changes were measured in response to AII. The biochemical responses measured were the output of PGI2 (as 6-oxo-PGF1 alpha) and of NO (as cyclic GMP). Inhibitors of cyclo-oxygenase (COX; piroxicam) or NO synthase (NOS; L-NAME), were added to the system to determine the influence of endogenous prostaglandins and NO on both myotropic and biochemical responses. Furthermore, to mimic the effects of endogenous, PGI2 or NO, exogenous forms of these relaxants were added, during inhibition of their endogenous release. 3. Contractions of the rings of saphenous vein in response to AII (1-100 nM) were unaffected by treatment with either piroxicam (5 microM) or L-NAME (200 microM) individually. However, when these two inhibitors were used together, there was an increase in the contractions in response to AII. 4. Biochemical analyses revealed that during stimulation by AII, levels of PGI2 and NO were enhanced when synthesis of the other vasodilator was inhibited, suggesting that endogenous NO inhibits PGI2 synthesis and endogenous, PGI2 or another vasorelaxant PG can inhibit NO synthesis. 5. Exogenous PGI2 (as iloprost) or NO (from glyceryl trinitrate) inhibited the increased output of endogenous NO or PGI2 respectively. 6. These results demonstrate the presence, in human saphenous vein, of a mechanism which ensures that levels of vasodilatation are maintained through a compensatory increase in one relaxant agonist when output of the other is decreased. If present in vivo such a mechanism would be important in maintaining saphenous vein graft patency as both PGI2 and NO are not only vasodilators, but inhibit platelet aggregation and myoinitimal hyperplasia, processes implicated in degeneration of graft function.

Angiotensin II↗

First trimester aneuploidy screening using nuchal translucency, free beta human chorionic gonadotrophin and maternal age.

Screening for aneuploidy using maternal age has a low detection rate and high false positive rate. Second trimester maternal serum screening increases trisomy 21 detection and decreases the false positive rate. First trimester screening would enable definitive diagnosis with chorionic villus sampling, and simple surgical termination of affected pregnancies would still be an option. Nuchal translucency (NT), free beta human chorionic gonadotrophin (f beta HCG) and maternal age were assessed in 302 patients before chorionic villus sampling. NT positively and f beta HCG negatively correlated with gestation, but neither correlated with maternal age nor with each other. Both NT and f beta HCG were increased in trisomy 21. NT was increased and f beta HCG was decreased in trisomy 18. Multivariate discriminant analysis enabled 87.5% detection of trisomy 21 in this high-risk population, for a 14% false positive rate. In a simulated normal population, using a risk cut-off of 1 in 250, 71% detection was achieved for a 7% false positive rate. The combination of NT, f beta HCG and maternal age is a simple, readily available and viable first trimester screening strategy.

Adult↗

Management of ventricular fibrillation with transvenous defibrillators without baseline electrophysiologic testing or antiarrhythmic drugs.

INTRODUCTION: Baseline electrophysiologic study (EPS) is routinely performed in patients resuscitated from ventricular fibrillation (VF) to risk stratify and select patients for chronic antiarrhythmic drug therapy. The role of EP testing prior to insertion of a multiprogrammable implantable cardioverter defibrillator (ICD), however, is unclear. METHODS AND RESULTS: This study was a retrospective review of outcome in 66 survivors of an initial episode of out-of-hospital VF not associated with a Q wave myocardial infarction or reversible causes, treated with transvenous ICDs as first-line therapy. Patients were excluded from the study if they had a previous history of monomorphic ventricular tachycardia (VT), a clinical history suggestive of supraventricular tachycardia, or had undergone preoperative EP testing. Fifty-two of the patients (79%) were male with an average age of 58 +/- 11 years. Coronary artery disease was present in 43 patients (66%), cardiomyopathy in 15 patients (23%), and valvular heart disease in 1 patient (1.5%). Seven patients (11%) had no detectable structural heart disease. The mean left ventricular ejection fraction was 0.40 +/- 0.16. With an average follow-up of 25 +/- 12 months, survival free of death from any cause was 100%. Twenty-three patients (35%) experienced 48 episodes of recurrent rapid VT or VF (average cycle length: 236 +/- 47 msec) treated by their device. The mean time to first therapy was 223 +/- 200 days. Only one of these patients also received antitachycardia pacing for two episodes of VT. One patient (1.5%) temporarily received amiodarone after removal of an infected device that was subsequently replaced. No other patient received antiarrhythmic drug therapy. CONCLUSION: After a cardiac arrest due to primary VF, select patients treated with multiprogrammable ICDs can be managed successfully without baseline EPS or antiarrhythmic drug therapy.

Aged↗

Lipid screening in an elderly population: difficulty in interpretation and in detection of occult metabolic disease.

AIMS: To determine lipid profiles and associations with other metabolic disease in a representative British elderly population. METHODS: Part of a prevalence survey of dementia in all 75+ year olds conducted from the large general practice serving the town and surrounding area of Melton Mowbray, Leicestershire (the M-old study). Patients (n = 224) aged from 75 to 98 years, and representative of the overall population, also provided pre-prandial blood samples on which various age and nutrition related analytes were determined. These included documented medical history, thyroid stimulating hormone (TSH), glucose, immunoglobulins, and lipid profile in plasma. RESULTS: Cholesterol and lipid variables showed wide scatter, with some negative trends but no significant associations with age for total cholesterol, high density lipoprotein (HDL) cholesterol, the ratio of total to HDL cholesterol or triglycerides. Women had significantly higher concentrations of total and HDL cholesterol at all ages. Serum TSH was above 6.0 mU/1 in 10/205 patients, random glucose was above 11.2 mmol/l in nine of 207 patients, borderline dysglobulinaemia was present in four of 210 patients, all without correlation with cholesterol concentrations. CONCLUSION: This British data is consistent with an inverse correlation between survival and cholesterol, but wide scatter restricts reliance on single result lipid data in individual patient management. Random lipid screening is also unhelpful, inefficient and without added value in revealing other age related and unrecognised occult metabolic disease.

Aged↗

Uveitis associated with rifabutin and macrolide therapy for Mycobacterium avium intracellulare infection in AIDS patients.

OBJECTIVE: Uveitis has been increasingly recognised as a side effect of rifabutin regimens in the prophylaxis and treatment of Mycobacterium avium intracellulare (MAI) infection. This study describes the clinical features and analyses the factors associated with rifabutin induced uveitis. DESIGN: Retrospective observational study. SETTING: Tertiary care institution, The Royal Hospitals NHS Trust, London. PATIENTS: 68 HIV seropositive individuals receiving rifabutin for prophylaxis or treatment of MAI infection. RESULTS: 11 episodes of uveitis occurred in 10 different individuals at a median of 62 days. The disease was bilateral in four and unilateral in the remainder. All subjects experienced ocular pain and photophobia and 9 individuals had a significant reduction in visual acuity. Uveitis was treated with mydriatics and topical steroids and resolved in all cases when rifabutin was stopped. The risk of uveitis was significantly increased with concurrent clarithromycin therapy, Odds Ratio 13.08, 95% Confidence Interval 1.98 to 83.12. CONCLUSION: Rifabutin can cause a reversible uveitis. This risk is increased with concurrent clarithromycin therapy. Adverse drug interactions can be an important cause of morbidity in patients with advanced HIV disease.

AIDS-Related Opportunistic Infections↗

Malignant intracranial teratoma in a juvenile Wistar rat.

An intracranial malignant teratoma was identified in a 91-day-old male Wistar rat manifesting central nervous system-related clinical signs. This tumor occupied the right midbrain and portions of the right caudal cerebrum and cranioventral cerebellum. Microscopically, the tumor contained intermingled cartilage, bone (with medullary hematopoietic tissue), fibrous connective tissue, skeletal muscle, fat, pseudostratified ciliated epithelium, stratified squamous epithelium, serous and mucoserous glands, and neural tissue with ependymal and choroid plexus epithelia. Poorly differentiated cells with primitive cartilaginous matrix were present throughout the lining of lateral ventricles, in the aqueduct of Sylvius, and in meninges overlying normal cerebellar tissue indicating tumor metastasis occurred via cerebrospinal fluid. This neoplasm was not identified in extracranial sites and hence was considered a primary intracranial malignant teratoma with metastases via cerebrospinal fluid.

Animals↗

Phase I trial of dose escalation with growth factor support in patients with previously untreated diffuse aggressive lymphomas: determination of the maximum-tolerated dose of ProMACE-CytaBOM.

PURPOSE: The aim of this study was to determine the maximum-tolerated dose (MTD) of cyclophosphamide, doxorubicin, etoposide, prednisone, bleomycin, cytarabine, methotrexate, and leucovorin (ProMACE-CytaBOM) when the myelotoxic drugs cyclophosphamide, doxorubicin, etoposide, and cytarabine are escalated. PATIENTS AND METHODS: Thirty-eight eligible patients with diffuse aggressive non-Hodgkin's lymphoma were treated on a phase I trial of dose escalation using the ProMACE-CytaBOM regimen and granulocyte-macrophage colony-stimulating factor (GM-CSF; Schering, Kenilworth, NJ). Patients were treated with recombinant (r)GM-CSF 10 microg/kg/d subcutaneously from day 9 to 19. Twenty-seven patients had stage IV disease, four had stage III, and seven had bulky stage II. Half of the patients had bone marrow involvement. The median age was 45 years. RESULTS: We found that the MTD was 200% for the escalated drugs in this regimen (although we never escalated above the MTD or defined by dose-limiting toxicity) and that the normalized dose-intensity (NDI; defined as the ratio of the received dose-intensity to the 100% dose-intensity of ProcMACE-CytaBOM) decreased with each cycle and was lower for the day-8 drug (cytarabine) than for the day-1 drugs. The complete response (CR) rate was 66%, and 92% of patients who achieved CR are alive without disease with a median follow-up time for survival of 3.6 years. CONCLUSION: The MTD of cyclophosphamide, doxorubicin, etoposide, and cytarabine in the ProMACE-CytaBOM regimen given with growth factor support is 200%, and this dose should be tested in larger phase II trials.

Adult↗

Neuropsychological assessment in a case of pseudoneurologic symptamology.

A 35-year-old woman undergoing an evaluation for possible multiple sclerosis had deficits in motor coordination, information processing speed, memory, verbal fluency and executive functions on neuropsychological testing Although presenting symptoms and cognitive impairments suggested multiple sclerosis, clinical history, personality features and neurologic workup were more consistent with a somatoform disorder This case illustrates the importance of interpreting neuropsychological deficits within a broad clinical context.

Journal Article↗

Pet ownership may be a factor in improved health of the elderly.

The familiar adage "pets are good for your health" is an interesting but largely untested theory. A new model was developed, based on pet ownership leads to better self care, to show possible associations between pet ownership with eating, exercise, nutritional status, and specific cardiovascular risk factors. Seniors aged sixty and above were solicited mainly at senior congregate meals program sites in north-central Colorado (n = 127) to participate in this cross-sectional, observational study. Statistical analyses of questionnaire, anthropometric, physiological, and biochemical data were performed. Dog owners walked significantly longer than non-owners (p < 0.05), and pet owners had significantly lower serum triglycerides than non-owners (p < 0.01). Results suggest that pets may be good for your health.

Aged↗

Otoacoustic emission amplification after inner hair cell damage.

Otoacoustic emissions (OAEs) are considered to originate from active cochlear processes involving the outer hair cells (OHC). These emissions are suppressed by activity in the efferent olivocochlear bundle (OCB) and following OHC damage caused by noise exposure or ototoxic drugs. Temporary enhancement of OAEs may occur following noise exposure, and permanent enhancement of emissions has been associated with primary afferent dysfunction in the auditory system. This suggests that there are active adaptation processes in the cochlea exist that could potentially compensate for loss of afferent input. We have used the anti-cancer drug carboplatin to induce selective inner hair cell (IHC) lesions in the cochleae of chinchilla and measured the elevation of auditory thresholds that occurred using brainstem responses (ABR). Following carboplatin treatment click evoked otoacoustic emissions (CEOAEs) were amplified from cochlear frequency regions, which demonstrated extensive IHC damage but apparently normal OHCs. These results support the theory that OHCs cells are involved in the production of these cochlear emissions but also provides further evidence that active adaptation processes exist in the cochlea. It is postulated that loss of afferent input reduces the activity in the medial efferent OCB resulting in de-suppression of OHC contractility. Enhanced OHC contractility could then produce amplification of CEOAEs.

Acoustic Stimulation↗

Sleeping with the past: the ethics of post-termination patient-therapist sexual contact.

OBJECTIVE: The aim of the paper is to devise an ethical argument to support the contention that post-termination patient-therapist sexual contact (PTSC) is always unethical. METHOD: Arguments both defending and condemning post-termination PTSC are reviewed and their strengths and weaknesses explored. RESULTS: Analysis of these arguments reveals a strong case for the universal condemnation of post-termination PTSC. CONCLUSIONS: Ethical codes, including that of the Royal Australian and New Zealand College of Psychiatrists, should be amended to explicitly prohibit post-termination PTSC.

Australia↗

The white-coat response in ambulatory blood pressure monitoring: elimination and attenuation.

BACKGROUND: The white-coat response can be identifiede on ambulatory blood pressure (ABP) monitoring (ABPM) and it is seen for around 2 h if the ABPM period is started in the hospital. The white-coat response to ABPM can be calculated by subtracting the 25th h ABP from the 1st h ABP; this eliminates any effect of the 24 h variation in blood pressure. METHODS: In this report we have examined whether the white-coat response is due to the environment alone or partly due to the ABPM machine (study 1). We also examined whether the white-coat response found with ABPM attenuates on repeated visits (study 2). In study 1 we started ABPM at the subject's home 3 h after an initial explanation and measurement of blood pressure in the hospital (hospital blood pressure) and examined the white-coat response (measured as the 1st h - 25th h ABP). In study 2 we performed ABPM on three occasions starting ABPM in the hospital and examined the magnitude of the white-coat response at each visit. RESULTS: In study 1 the hospital blood pressure was significantly higher than the hourly mean blood pressure at the same time of day on the following day. There was no significant difference between the 1st and 25th hourly means or the 2nd and 26th hourly means after the monitoring had been restarted at home. In study 2, the 1st and 25th mean hourly ambulatory blood pressures showed a significant reduction in the 1st h blood pressure over the three visits whereas the 25th h blood pressure was similar. The 1st h - 25 h systolic ambulatory blood pressure was significantly reduced ( P = 0.025) whereas the reduction in diastolic ambulatory blood pressure did not attain statistical significance (P = 0.182). CONCLUSION: The ABPM device itself does not cause the white-coat response seen on ABPM. This response appears to be related to the environment in which ABPM is commenced and can be eliminated by calculating the ABP beginning 3 h after the subject has left the hospital environment. Attenuation of this response is seen on repeated ABPM.

Journal Article↗

Effects of irradiation of CBA/CA mice on hematopoietic stem cells and stromal cells in long-term bone marrow cultures.

Following 200 cGy total body irradiation, 20-25% of CBA/Ca mice and their CBA/B and CBA/H sublines develop myeloid leukemia. To determine whether hematologic changes in vitro were detectable, long-term marrow cultures (LTBMCs) were established from the right and left hind limbs of 11 individual control and 11 CBA/B mice 100-114 days after 200 cGy total body irradiation. Individual cultures were studied weekly for cumulative production of nonadherent cells and colony-forming, hematopoietic progenitor cells. Control cultures produced significantly more nonadherent cells over 25 weeks in long-term marrow culture compared to those from irradiated (treated) mice. Permanent stromal cell lines were established from control and irradiated CBA/B mouse LTBMCs and clonal sublines were established. The stromal cell lines from LTBMCs of in vivo irradiated CBA/B mice had uniformly lower plating efficiencies, and only one formed a permanent clonal subline at 100-fold lower frequency compared to stromal cell lines from control mouse LTBMCs. The irradiation sensitivity of both uncloned and clonal sublines was similar by single-hit, multi-hit or by linear quadratic formula. Cocultivation of an IL-3 dependent hematopoietic progenitor cell line established from a control CBA/B, LTBMC with control of irradiated stromal cell lines derived from either a control (CC3) or the one successfully cloned in vivo irradiated (CT4) LTBMC, produced few cobblestone islands in the presence of IL-3. In contrast, formation of cobblestone islands in the presence of L cell-condition medium as a source of M-CSF was significantly greater, and these persisted for 21 days on both CC3 and CT4 stromal lines. The data provide evidence for irradiation induced changes in the bone marrow stromal cell compartment of CBA/B mice which persist and are detectable in vitro 6 months after explant of the cells to culture. These marrow stromal cell lines may provide valuable resources for analyzing the molecular biologic changes in the hematopoietic microenvironment during irradiation leukemogenesis.

Animals↗