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Biomedical subjects

L Olson

Publications and source records attributed to L Olson.

520 records · Page 29Linked to original sources
PubMedDate not supplied

Low-level cadmium exposure of lactating rats causes alterations in brain serotonin levels in the offspring.

Effects on monoaminergic and cholinergic transmitter systems as well as neurotrophins were characterized in developing Sprague-Dawley rats directly exposed to 5 ppm cadmium in the drinking water or indirectly via exposed dams. Cadmium was given to dams during the lactation period, from parturition to postnatal day 17, and/or to the offspring until postnatal day 42. Cresyl violet staining and glial fibrillary acidic protein immunohistochemistry did not reveal any obvious neuropathology after cadmium exposure. Following high-power microwave fixation, concentrations of acetylcholine (ACh) and monoamines were determined in cerebral cortex, striatum, and hippocampus using HPLC with electro-chemical detection. ACh, dopamine, and noradrenaline levels were not significantly affected after the different cadmium exposures. Cortical levels of serotonin were significantly reduced in rats exposed to cadmium during lactation as well as in rats exposed to cadmium during both lactation and postweaning. A major decrease in 5-hydroxyindoleacetic acid was found in cortex and hippocampus in rats exposed to cadmium during lactation. The regional characteristics of cadmium toxicity as reflected in changes of neurotrophins were studied using in situ hybridization histochemistry with oligonucleotide probes and phosphoimaging evaluation. No significant changes in the mRNA expression of brain-derived neurotrophic factor (BDNF), neurotrophin-3, and the high-affinity tyrosine kinase receptor of BDNF, trkB, were detected. The present results demonstrate that exposure to levels of cadmium as low as 5 ppm in the drinking water leads to neurochemical disturbances of the serotonergic system in the offspring during the lactational period.

Acetylcholine↗
PubMedDate not supplied

Minor immunoreactivity in GDNF-, BDNF-, or NT-3-treated substantia nigra allografts.

Glial-cell-line-derived neurotrophic factor (GDNF) stimulates the survival of dopaminergic neurons. Little is known, however, about the possible immune sequelae of GDNF exposure or of exposure to other putative trophic factors. To address these questions, pieces of mesencephalic tissue, substantia nigra, from 15-day-old donor embryos were transplanted into the anterior chamber of the eye of adult male Sprague-Dawley recipient rats. At 5-day intervals, an aliquot (0.5 microgram) of GDNF, brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), or cytochrome-C (CC) was injected into the anterior chamber of the eye of the recipients, and the sizes of the transplants were measured. GDNF increased transplant survival and growth. On day 42, all rats were sacrificed, and the grafts were evaluated by cresyl-violet staining and by immunohistochemistry using antibodies raised against neurofilament (NF), tyrosine hydroxylase, or glial fibrillary acidic protein (GFAP), as well as the following monoclonal antibodies: OX-38 anti-CD4, OX-8 anti-CD8, OX-18 anti-MHC class I, OX-6 anti-MHC class II, OX-42 anti-CD11b, R-73 anti-alpha and anti-beta T-cell receptor, and ED1 raised against monocytes/macrophages. BDNF-treated grafts showed only weak immunoreactivity, and even weaker reactions were seen in grafts treated with NT-3, GDNF, or CC. No single immune system marker was significantly elevated in grafts from any treatment group. We used OX-42 and ED1 to study possible alterations of microglial components. Ramified microglial cells were found in GDNF-treated grafts and to a lesser extent in NT-3 and BDNF-treated grafts. ED1-labeled reactive microglial components were found in NT-3- and BDNF-treated grafts. Additionally, large and rounded OX-42-positive phagocytic cells were found in NT-3-treated grafts. Together with our previous finding that GDNF treatment of spinal cord transplants activates immune responses and leads to microglial activation, our data demonstrate that although treatment with GDNF and to some degree with BDNF can enhance immune responses to immunogenic grafts, such as fetal spinal cord grafts, but the trophic factors per se do not elicit any marked response in non-immunogenic grafts like substantia nigra.

Animals↗
PubMedDate not supplied

Intracerebroventricular infusion of nerve growth factor in three patients with Alzheimer's disease.

Nerve growth factor (NGF) is important for the survival and maintenance of central cholinergic neurons, a signalling system impaired in Alzheimer's disease. We have treated 3 patients with Alzheimer's disease with a total of 6.6 mg NGF administered continuously into the lateral cerebral ventricle for 3 months in the first 2 patients and a total of 0.55 mg for 3 shorter periods in the third patient. The patients were extensively evaluated with clinical, neuropsychological, neurophysiological and neuroradiological techniques. Three months after the NGF treatment ended, a significant increase in nicotine binding was found in several brain areas in the first 2 patients and in the hippocampus in the third patient as studied by positron emission tomography. A clear cognitive amelioration could not be demonstrated, although a few neuropsychology tests showed slight improvements. The amount of slow-wave cortical activity as studied by electroencephalography was reduced in the first 2 patients. Two negative side effects occurred with NGF treatment: first, a dull, constant back pain was observed in all 3 patients, which in 1 patient was aggravated by axial loading resulting in sharp, shooting pain of short duration. When stopping the NGF infusion, the pain disappeared within a couple of days. Reducing the dose of NGF lessened the pain. Secondly, a marked weight reduction during the infusion with a clear weight gain after ending the infusion was seen in the first 2 patients. We conclude from this limited trial that, while long-term intracerebroventricular NGF administration may cause certain potentially beneficial effects, the intraventricular route of administration is also associated with negative side effects that appear to outweigh the positive effects of the present protocol. Alternative routes of administration, and/or lower doses of NGF, perhaps combined with low doses of other neurotrophic factors, may shift this balance in favor of positive effects.

Aged↗
PubMedDate not supplied

Human fetal cortical tissue fragments survive grafting following one week storage at +4 degrees C.

Grafting of human fetal tissue fragments has been used successfully in experimental and clinical trials. The development of techniques to store human fetal tissue fragments for longer time periods would allow to establish temporary tissue banks. We dissected several human cortical tissue fragments from one fetus and tested different storage conditions (cooling, freezing, culturing). After storage, the tissue fragments were transplanted into cavities in the cortex of host rats and the volume of the surviving grafts calculated. We report that human cortical tissue fragments grafted immediately after dissection (control group) or grafted after storage for 3 h in cryopreservation medium at room temperature survived grafting and resulted in graft sizes of 102 +/- 26 mm3 and 242 +/- 210 mm3, respectively, however, statistically not different. When the human cortical tissue fragments were slowly frozen and stored for 1 wk and/or when the fragments were cultured for 1 week in culture medium using a roller tube technique, grafts did not survive under our conditions. However, when the human cortical tissue fragments were stored for 1 week at +4 degrees C in cryopreservation medium, the graft size (48 +/- 24 mm3) was reduced but statistically not different from the control group. We conclude that human cortical tissue fragments can be stored at +4 degrees C for at least 1 wk without major loss of ability to survive grafting.

Abortion, Induced↗
PubMedDate not supplied

Characterization of a fibrin glue-GDNF slow-release preparation.

One novel method to deliver trophic factor locally in the CNS is to mix it into fibrin glue. In the present studies, [125I]-labeled GDNF-containing fibrin glue balls were used to determine binding and spread of the trophic factor. First, the binding of different concentrations of [125I]-labeled GDNF in fibrin glue was determined in vitro. Within the six concentrations used (from 200 nM to 0.004 nM, 0 M as control), there was a strong linear correlation between the [125I]-GDNF concentration and the recovered radioactivity (r = 0.992). The mean bound radioactivity in 16 samples with 4 nM [125I]-GDNF was 71262 +/- 2710 CPM, and accounted for 89.8% of the mean initial count of free [125I]-GDNF (79369 +/- 3499 CPM). Second, [125I]-GDNF-containing glue balls were implanted into the anterior chamber of adult rats. The implanted fibrin glue balls decreased in size with time, but could still be identified on the irises 2 wk after implantation. Radioactivity was concentrated at the implantation sites in the early stages with a distribution in the surrounding iris tissue, which became separated into focal radioactive spots at the third week. Counts of radioactivity were significantly higher in the [125I]-GDNF glue ball-implanted irises than controls until 14 days after implantation. A study of the [125I] decay over time using least-squares linear regression demonstrated first-order kinetics (r = -0.98, p <0.02) with k = 0.0091 and T 1/2 = 76 h. Finally, [125I]-GDNF-containing glue balls were implanted in the spinal cord of adult rats. Radioactivity was concentrated at the implantation sites in the early stages and was later distributed more widely in the surrounding thoracic cord. The [125I]-GDNF-containing glue degraded over time and became a porous meshwork with decreasing radioactivity at the later time points. Radioactivity in the spinal cords subjected to implantation of [125I]-GDNF-containing glue balls was higher than in controls for 14 days. Study of the [125I] decay by time with least-squares linear regression demonstrated first-order kinetics (r = -0.97, p = 0.001) with T 1/2 = 75.6 h. We conclude that the trophic factor GDNF becomes bound in the fibrin glue matrix from which it is gradually released. Our results suggest that fibrin glue is an effective substrate for keeping a trophic factor localized in situ for a finite period, protected from the circulation, surrounding aqueous humor or CSF.

Animals↗
PubMedDate not supplied

The doctor-physiotherapist relationship: the physiotherapists' perspective.

A study of the professional relationship between physicians and physiotherapists, as perceived by physiotherapists, was undertaken. An analysis of the replies of a sample of physiotherapists to 20 closed-ended questions is presented in the context of the controversy about the proper relationship between medicine and physiotherapy. The data reveal that physiotherapists wish to strengthen their bond with physicians, but are not satisfied with the performance of doctors as team leaders, consultants, and resource personnel. It is possible, the data suggest, that the physician may not be the best qualified to act as team leader in every situation, for every aspect of medical treatment, for the care of every patient.

Allied Health Personnel↗
PubMedDate not supplied

Priorities for maternal and child health services: the consumer's perspective.

A convenience sample of 206 inner city department of public health patients were asked to rank the importance of health care services relative to other problems they face. Respondents spontaneously ranked money, unemployment, and housing as their most pressing concerns. When presented with a list of potential problems, housing, crime, and rent were most frequently cited. Health of children and own health were priorities for 15 and 21 respondents respectively. Pregnancy prevention and having a good pregnancy were important for seven individuals. The priorities attached by these medically and socially high risk people for maternal and child health services are placed in the context of published data on expert opinion on need for maternal and child health services and the availability of these services. The results of this survey suggest that public health administrators define realistic, specific goals for preventive maternal and child health services. Aggressive consumer education programs aimed at providing information on the importance of these services to maintaining well-being are also in order.

Adult↗
PubMedDate not supplied

Comparison of benefits provided by different hearing aid technologies.

The performance of 40 hearing-impaired adults with the GN ReSound digital BZ5 hearing instrument was compared with performance with linear hearing aids with input compression limiting (AGC-I) or two-channel analog wide dynamic range compression (WDRC) instruments. The BZ5 was evaluated with an omnidirectional microphone, dual-microphone directionality, and a noise reduction circuit in combination with dual-microphone directionality. Participants were experienced hearing aid users who were wearing linear AGC-I or analog WDRC instruments at the time of enrolment. Performance was assessed using the Connected Speech Test (CST) presented at several presentation levels and under various conditions of signal degradation and by the Profile of Hearing Aid Benefit (PHAB). Subjective ratings of speech understanding, listening comfort, and sound quality/naturalness were also obtained using 11-point interval scales. Small performance advantages were observed for WDRC over linear AGC-I, although WDRC did not have to be implemented digitally for these performance advantages to be realized. Substantial performance advantages for the dual microphones over the omnidirectional microphone were observed in the CST results in noise, but participants generally did not perceive these large advantages in everyday listening. The noise reduction circuit provided improved listening comfort but little change in speech understanding.

Aged↗
PubMedDate not supplied

The Medicaid program and consumer needs: a survey among residents of a poor Chicago neighborhood.

A convenience sample of 200 inner-city residents were interviewed about their knowledge of benefits available under the Illinois Medicaid fee-for-service and prepaid programs; a second sample of 200 residents from the same community were interviewed about their health care information needs. All respondents were recruited from a Chicago neighborhood with one of the nation's highest rates of poverty, infant mortality, and births of low birth weight infants. The neighborhood also has been targeted as a demonstration site for an Illinois Department of Public Aid's prepaid Medicaid program. Responses to the first interview indicated that neighborhood residents did not understand the operational features of Medicaid prepaid plans or the programmatic mission of these plans, and they did not want to enroll in existing prepaid plans. As determined in the second interview, residents desired information on the scope of Medicaid services, ways to assess quality of health care received, and options for maintaining their freedom to choose hospitals and physicians or clinics. The survey findings are compared with what is known about the reasons middle class employed families enroll in and disenroll from prepaid plans and the position of poor families in a cost-conscious health care system.

Aid to Families with Dependent Children↗
PubMedDate not supplied

Effects of nefiracetam (DM-9384), a pyrrolidone derivative, on brain monoamine systems.

The pyrrolidone cyclic gamma-aminobutyric acid (GABA) derivative nefiracetam [DM-9384; N-(2,6-dimethylphenyl)-2-(2-oxo-1-pyrrolidinyl)acetamide] has been shown to enhance acquisition and ameliorate amnesia in different learning tasks in rodents. In the present study, the effects of nefiracetam on the brain monoamine systems were studied. Male, adult Sprague-Dawley rats were treated with nefiracetam in single doses (0, 1, 3, 10, 30 or 100 mg/kg, p.o.) and analyzed after 1 and 4 hr, or treated by daily doses (0, 1, 3, 10 or 30 mg/kg, p.o.) for 2 weeks. In general, no or only weak effects were observed on tissue monoamine levels, either following acute or 14 days treatment with nefiracetam. Acute administration of intermediate doses of nefiracetam induced minor increases in dopamine (DA) and homovanillic acid (HVA) tissue levels in the striatum, while hypothalamic 3,4-dihydroxyphenylacetic acid (DOPAC) decreased at 1 hr. Noradrenaline (NA) and serotonin (5-HT) levels increased in some regions after higher doses of nefiracetam. Increases in 5-hydroxyindoleacetic acid (5-HIAA) were also seen at 4 hr, but only after the 3 mg/kg dose. Minor decreases of HVA and DOPAC levels were seen in some regions after treatment with various doses of nefiracetam for 14 days, while an increase in 5-HT levels was observed occasionally. Using in vivo microdialysis in freely moving animals, no significant effects on extracellular levels of HVA, DOPAC and 5-HIAA in the striatum or of HVA, DOPAC and NA levels in the dorsal hippocampus were seen after acute administration of nefiracetam. On the other hand, extracellular hippocampal 5-HIAA levels decreased by 20% after the 1 and 3 mg/kg doses. Nefiracetam, in a concentration range of 1 nM to 10 microM, did not affect the in vitro synaptosomal uptake of [3H]NA and [3H]5-HT in the cortex or of [3H]DA in the striatum. Taken together, nefiracetam appears to exert minor, regionally restricted and not dose-dependent effects on the monoamine systems following either acute or repeated administrations in normal rats. A direct or indirect, possible GABA-mediated, influence of nefiracetam may underlie the modest changes seen on monoamines. The cognitive-enhancing action of nefiracetam does not seem to be related to effects on presynaptic monoamine functions.

3,4-Dihydroxyphenylacetic Acid↗
PubMedDate not supplied

Ethical climate in health care organizations.

An organization's policies, procedures and practices on ethical issues can influence the amount of risk nurses will take in voicing their opinions about patient care issues. While the concepts of organizational climate and culture are frequently referred to, the concept of ethical climate is relatively new.

Decision Making, Organizational↗