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Biomedical subjects

L Olson

Publications and source records attributed to L Olson.

At least 73 records · Page 4Linked to original sources
PubMed1999

Microangiopathy in kidney and simultaneous pancreas/kidney recipients treated with tacrolimus: evidence of endothelin and cytokine involvement.

BACKGROUND: In the past 3 years, three transplant recipients [one kidney, two simultaneous pancreas/kidney (SPK)] developed a thrombotic thrombocytopenic purpura-like clinical syndrome. This was characterized by an abrupt fall in the hematocrit and platelet count with evidence of hemolysis (fragmented red blood cells and schistocytes) and transplant kidney dysfunction during the first 2 weeks after transplantation. This was also associated with pancreatic dysfunction in the two SPK recipients. In all three patients, elevated tacrolimus levels (>24 ng/ml) occurred. METHODS: Serum cytokine and endothelin levels were determined retrospectively from stored (-70 degrees C) sera. RESULTS: In each case tacrolimus was discontinued, and treatment with plasmapheresis, fresh frozen plasma, steroids, and OKT3 was begun. The clinical courses varied from mild (one patient), to moderate (one patient), to severe (one patient), complicated with seizures and coma. Each patient responded clinically and ultimately was converted to cyclosporine A, and/or mycophenolate mofetil. These clinical events were associated with a rise in serum levels of endothelin and several cytokines. Levels of endothelin were elevated at 209+/-137 pg/ml, particularly in the severe episode where peak levels reached 480 pg/ml (normal 0-20 pg/ml). Peak levels of IL-8 (104+/-36 pg/ml), interleukin- (IL) 10 (238+/-105 pg/ml), and/or IL-12 (306+/-119 pg(ml) mean+/-SE, occurred during or before the clinical event. Serum levels of tumor necrosis factor-a and interferon-gamma were elevated in 2 patients while levels of IL-2, IL-4, and IL-6 were not elevated during the acute phase. CONCLUSIONS: These data are consistent with a mechanism of microangiopathy involving endothelial cell injury (associated with tacrolimus treatment), and accompanied by cytokines (IL-10, IL-12, tumor necrosis factor-a, interferon-gamma) that affect expression of adhesion molecules, chemokines (IL-8) that direct the influx of white blood cells and endothelins that may exacerbate underlying hypertension and increase shear force-related red blood cell destruction.

Adult↗
PubMed1999

Addiction-prone Lewis but not Fischer rats develop compulsive running that coincides with downregulation of nerve growth factor inducible-B and neuron-derived orphan receptor 1.

We have examined the effects of chronic voluntary running for 30 d on the levels of nerve growth factor inducilble-B (NGFI-B) and neuron-derived orphan receptor 1 (NOR1) mRNAs in Fischer and Lewis rats. The aim was to compare the addiction-prone Lewis rat strain to the Fischer strain in a plausible model for natural reward. The Lewis strain ran markedly more than the Fischer strain, as indicated by the length of running per day when given free access to running wheels. Both strains progressively increased their amount of daily running. By day 14, Lewis rats had reached a maximal level corresponding to 10 km/d, which slowly decreased to approximately 8 km/d. Fischer rats ran considerably less, averaging approximately 1. 5 km/d by day 30. After 30 d of running, levels of mRNA encoding NGFI-B and Nor1 were decreased in cerebral cortex in Lewis but not Fischer rats. The downregulation of NGFI-B mRNA in Lewis rats could not be attenuated by the opioid receptor antagonist naloxone. Instead, naloxone by itself downregulated NGFI-B in striatum and cerebral cortex in both strains. In contrast, naloxone had no effect on Nor1 mRNA levels, although the running-induced downregulation of Nor1 was, in most cases, attenuated by naloxone. Data from the present study suggest that the same genetic factors contributing to the drug addiction-prone behavior of Lewis rats also control the excessive running behavior and that this coincides with downregulation of transcription factors of the NGFI-B family.

Animals↗
PubMed1999

Health indicators and intimate partner violence among women who are members of a managed care organization.

BACKGROUND: There have been no population-based studies estimating the prevalence of intimate partner violence (IPV) in an insured population. There is also little information on how well routinely collected health status information predicts IPV risk. Many women now obtain health care from providers who are members of a managed care organization (MCO). To justify efforts to routinely screen for IPV, it is essential to know the prevalence of IPV in this growing population and to identify correlates of IPV among female MCO members. METHODS: A telephone survey with questions on health status, behavioral risk factors, preventive services use, and the Conflict Tactics Scale was completed by 2,415 female members of a New Mexico MCO. RESULTS: Overall, 13.5% of respondents reported experiencing major verbal aggression and 6.7% reported experiencing physical aggression. Younger age, degree of sadness, and inability to handle stress, and a perception of a poorer general health status were significantly associated with major verbal aggression. Race/ethnicity, degree of sadness, and average number of drinks consumed at one sitting were significantly associated with physical aggression. CONCLUSIONS: There is a low but important annual prevalence of IPV among female members of a MCO that occurs across all variables studied. This information is needed to develop appropriate screening protocols and interventions in this population.

Adult↗
PubMed1999

Transplantation of islets of Langerhans in patients with insulin-requiring diabetes mellitus undergoing orthotopic liver transplantation--the Miami experience.

Most patients with cirrhosis of the liver have detectable insulin resistance. In 60-80% of patients with cirrhosis, impaired glucose tolerance can be uncovered; approximately 20% of these patients eventually develop overt diabetes. Theoretically, insulin resistance and glucose intolerance could be improved or reversed by orthotopic liver transplantation alone or in association with a simultaneous transplant of pancreatic islet cells from the same donor. To investigate these possibilities we initiated a pilot study of simultaneous liver and pancreatic islet cell transplantation in seven patients with diabetes and liver cirrhosis. Donor bone marrow cells were also infused to enhance the acceptance of the grafts. Seven patients who received only orthotopic liver transplantation and donor bone marrow cells were used as historical controls. The preliminary results of this pilot trial suggest that islet cell transplantation in conjunction with orthotopic liver transplantation improves glucose metabolism in patients with liver cirrhosis in association with reduced insulin requirements and HbA1c levels. These results were evident in spite of pre- and post-transplant basal C-peptide levels that were unchanged. Further evaluation of the effects of orthotopic liver transplantation with or without islet cell transplantation will require a randomized prospective trial including accurate metabolic evaluation with the euglycemic insulin clamp technique.

Adolescent↗
PubMed1999

Deprived of habitual running, rats downregulate BDNF and TrkB messages in the brain.

To study possible effects of physical training on the expression of neurotrophic factors and their receptors in the brain, we used a rat strain (spontaneously hypertensive rat, SHR), known to spontaneously run up to 20 km/night. We show that such long-distance running affects the brain-derived neurotrophic factor (BDNF) and TrkB system in hippocampus, and in particular that abrupt deprivation of habitual running leads to long-lasting decreases of BDNF/TrkB expression in hippocampus. Quantitative in situ hybridization demonstrates that running increases the expression of mRNA coding for BDNF and its high affinity receptor TrkB in hippocampus in a running length dependent manner. In addition, we show that an abrupt interruption of prolonged spontaneous exercise decrease expression of mRNA encoding BDNF and TrkB in certain hippocampal areas and that this decrease lasts at least 10 days. This down-regulation was most prominent in medial cornu ammonis 3 (CA3M). Several other trophic factors and receptors were investigated, including NGF, NT3, GDNF, trkC and p75. For these other probes investigated, no robust changes in mRNA expression were noted. Areas examined included sensorimotor cortex and hippocampus. For RET, p75, NT3, TrkB and BDNF we also examined the spinal cord without detecting any robust changes. We conclude that spontaneous running as well as its abrupt termination, leads to area-specific and trophic factor-specific changes in hippocampus.

Animals↗
PubMed1999

Guns, alcohol, and intimate partner violence: the epidemiology of female suicide in New Mexico.

Suicide is among the leading causes of death in the United States, and in women the second leading cause of injury death overall. Previous studies have suggested links between intimate partner violence and suicide in women. We examined female suicide deaths to identify and describe associated risk factors. We reviewed all reports from the New Mexico Office of the Medical Investigator for female suicide deaths occurring in New Mexico from 1990 to 1994. Information abstracted included demographics, mechanism of death, presence of alcohol/drugs, clinical depression, intimate partner violence, health problems, and other variables. Annual rates were calculated based on the 1990 census. The New Mexico female suicide death rate was 8.2/100,000 persons per year (n = 313), nearly twice the U.S. rate of 4.5/100,000. Non-Hispanic whites were overrepresented compared to Hispanics and American Indians. Decedents ranged in age from 14 to 93 years (median = 43 years). Firearms accounted for 45.7% of the suicide deaths, followed by ingested poisons (29.1%), hanging (10.5%), other (7.7%), and inhaled poisons (7.0%). Intimate partner violence was documented in 5.1% of female suicide deaths; in an additional 22.1% of cases, a male intimate partner fought with or separated from the decedent immediately preceding the suicide. Nearly two-thirds (65.5%) of the decedents had alcohol or drugs present in their blood at autopsy. Among decedents who had alcohol present (34.5%), blood alcohol levels were far higher among American Indians compared to Hispanics and non-Hispanic Whites (p = .01). Interpersonal conflict was documented in over 25% of cases, indicating that studies of the mortality of intimate partner violence should include victims of both suicide and homicide deaths to fully characterize the mortality patterns of intimate partner violence.

Adolescent↗
PubMed1999

Role of retinoids in the CNS: differential expression of retinoid binding proteins and receptors and evidence for presence of retinoic acid.

Retinoic acid (RA), a retinoid metabolite, acts as a gene regulator via ligand-activated transcription factors, known as retinoic acid receptors (RARs) and retinoid X receptors (RXRs), both existing in three different subtypes, alpha, beta and gamma. In the intracellular regulation of retinoids, four binding proteins have been implicated: cellular retinol binding protein (CRBP) types I and II and cellular retinoic acid binding protein (CRABP) types I and II. We have used in situ hybridization to localize mRNA species encoding CRBP- and CRABP I and II as well as all the different nuclear receptors in the developing and adult rat and mouse central nervous system (CNS), an assay to investigate the possible presence of RA, and immunohistochemistry to also analyse CRBP I- and CRABP immunoreactivity (IR). RXRbeta is found in most areas while RARalpha and -beta and RXRalpha and -gamma show much more restricted patterns of expression. RARalpha is found in cortex and hippocampus and RARbeta and RXRgamma are both highly expressed in the dopamine-innervated areas caudate/putamen, nucleus accumbens and olfactory tubercle. RARgamma could not be detected in any part of the CNS. Using an in vitro reporter assay, we found high levels of RA in the developing striatum. The caudate/putamen of the developing brain showed strong CRBP I-IR in a compartmentalized manner, while at the same time containing many evenly distributed CRABP I-IR neurons. The CRBP I- and CRABP I-IR patterns were closely paralleled by the presence of the corresponding transcripts. The specific expression pattern of retinoid-binding proteins and nuclear retinoid receptors as well as the presence of RA in striatum suggests that retinoids are important in many brain structures and emphasizes a role for retinoids in gene regulatory events in postnatal and adult striatum.

Animals↗
PubMed1999

Early outpatient preoperative anesthesia assessment: does it help to reduce operating room cancellations?

UNLABELLED: Increased understanding of the high cost associated with operating room (OR) cancellations has led to efforts by healthcare providers to decrease case cancellations on the day of surgery. To investigate whether preoperative evaluations within 24 h of surgery were associated with more frequent OR cancellations than those completed 2-30 days before surgery, we prospectively studied OR cancellations for 3 mo. Of the 529 patients in the study, 166 were seen within 24 h of surgery (standard group), and the remaining 363 patients were seen 2-30 days before surgery (early group). There were 70 OR cancellations on the day of surgery, and the largest single group of cancellations was related to administrative problems. The standard group and the early group were similar in terms of gender, age, ASA physical status, and percentage of patients undergoing major surgery. The OR cancellation rates were also comparable between groups: 13.3% for the standard group and 13.2% for the early group. These data suggest that patients can be evaluated in an outpatient preoperative evaluation clinic in a timeframe that is convenient for the patient without adversely affecting the cancellation rate on the day of surgery. IMPLICATIONS: The operating room cancellation rate for outpatients evaluated 2-30 days before surgery was compared with the cancellation rate for outpatients who received their anesthesia evaluation within 24 h of surgery. Because both groups had similar rates, outpatients may be seen at a convenient time without adversely affecting operating room cancellations.

Ambulatory Surgical Procedures↗
PubMed1999

Evidence that tacrolimus augments the bioavailability of mycophenolate mofetil through the inhibition of mycophenolic acid glucuronidation.

We previously reported an unexpected augmentation of mycophenolic acid (MPA) levels (trough and AUC0-12) in patients receiving mycophenolate mofetil (MMF) in combination with tacrolimus versus patients receiving the same dose of MMF in combination with cyclosporin A (CsA). This finding was accompanied by a corresponding reduction of the inactive glucuronide metabolite of MPA (MPAG) in patients, suggesting that tacrolimus may effect the conversion of MPA to MPAG by the enzyme UDP-glucuronosyltransferase (UDPGT). To investigate this possibility directly, UDPGT was extracted from human liver and kidney tissue and its activity was characterized using MPA as a substrate in vitro, assessing the conversion of MPA to MPAG using analysis by high-performance liquid chromatography. With crude microsomal preparations, amounts of UDPGT at least 100 times higher in specific activity (i.e., units to milligrams of protein) could be extracted per gram of tissue from kidney as opposed to liver. This result did not appear to be related to the coextraction of a liver-specific UDPGT inhibitor because initial enzyme kinetic values (Vmax and km) were identical for kidney and liver extracts, and further purification of the liver enzyme did not enhance activity (as is seen when inhibitors are removed during purification). With further UDPGT purification (approximately 200-fold) from kidney extracts using a combination of ammonium sulfate precipitation, followed by anion exchange, hydroxyapatite, and size exclusion chromatography, the enzyme was more than 80% pure when assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Initial enzyme kinetic analysis of this purified product showed a km value for MPA of 35.4+/-5.7 microg/mL and a Vmax of 2.87+/-0.31 MPAG produced per hour (n = 7). The addition of clinically relevant concentrations of CsA (200-1,000 ng/mL) or tacrolimus (10-25 ng/mL) resulted in a dose-dependent inhibition of the UDPGT enzyme by both agents with tacrolimus, which was approximately 60-fold more efficient as an inhibitor. The calculated inhibition constants (KI) of tacrolimus and CsA for the purified UDPGT were 27.3+/-5.6 ng/ml and 2,518+/-1473 ng/ml. respectively. Both agents displayed an inhibition profile characteristic of a competitive inhibitor (substrate) that could be demonstrated in a reciprocal experiment with CsA as a substrate, but not with tacrolimus. This finding suggested that the significantly more efficient inhibition of UDPGT by tacrolimus may occur by a more complicated mechanism that is yet to be determined.

Biological Availability↗
PubMed1999

A comparison of OPO pulsatile machine preservation practices and results.

CONTEXT: Kidney preservation has been performed by either ice (static) or machine pulsatile perfusion. Ice storage is simple, with only 1 methodology. Machine perfusion, on the other hand, is accomplished using multiple methodologies. This article delineates the different methodologies of pumping centers throughout the country. OBJECTIVE: Pulsatile machine perfusion is again being viewed as the preservation method of choice for kidneys from non-heart-beating cadaver donors and cadaver kidneys from marginal donors. To develop indices to predict the viability of cadaver kidneys for transplant, a review of the organ procurement organizations, specific perfusion techniques, and a comparison of the delayed graft function and graft survival rates were considered. METHODS: A survey, asking for specifics on perfusion parameters, pulsatile machine perfusion experience, and criteria for perfusion implementation and graft survival results, was mailed to all organ procurement organizations in the United States. RESULTS: Of the 44 centers that responded to the survey, 12 used pulsatile machine perfusion (11 used the Waters perfusion machine), 6 pumped marginal cadaver kidneys, and the remaining 6 pumped all cadaver kidneys. Minimum perfusion criteria, pulse rates, perfusate composition, pressures, renal resistance, and renal pressure and flow were considered. Vasodilators and other machine additives were used to improve flow. The variance in each center's number of cadaver kidneys pumped each year, as well as the differences in pump times, was noted. CONCLUSION: Twelve centers use pulsatile machine perfusion. A variety of techniques are used to perform pulsatile machine perfusion, but 11 of 12 have less delayed graft function than those programs employing ice storage preservation.

Cryopreservation↗
PubMed1999

A 15-week experimental exposure of pigs to airborne dust with added endotoxin in a continuous flow exposure chamber.

The purpose of this study was to evaluate the effect of longterm exposure to airborne dust and endotoxin on the respiratory system of pigs. A continuous flow exposure chamber was built for the purpose of exposing pigs to selected airborne contaminants. Pigs (n = 6) were exposed to a combination of a very fine corn/soybean meal (40.6 mg/m3) with added lipopolysaccharide (LPS; 12.4 microg/m3) for 8 h/d over 5 d for 15 wk (75 d of exposure). Control pigs (n = 6) were housed in a room with minimal contamination of these airborne contaminants. Surprisingly, dust in the exposure chamber and the control room was highly contaminated with peptidoglycan. Changes in the lung were monitored by collecting bronchoalveolar lavage (BAL) fluid for cytology at 5 different time points throughout the exposure period. Blood samples were collected at the same time for hematology. A non-specific respiratory inflammatory response was found in exposed and control pigs, as suggested by the increased neutrophils in BAL fluid and the small inflammatory areas in the lung tissue. No macroscopic lung lesions were observed in control or exposed pigs. The findings in the control pigs imply that even low dust concentrations and possibly peptidoglycan contamination can induce cellular changes in the BAL fluid and that a true control pig does not exist. In addition, the exposed pigs developed a mild eosinophilia, indicating an allergic response to the airborne contaminants.

Air Pollutants↗
PubMed1999

Assessment of the malignant potential of mitogen stimulated human Schwann cells.

Human Schwann cells (SCs) can be isolated and expanded with mitogens using cell culture techniques. These cells have been demonstrated to promote axonal regrowth in both the central and peripheral nervous system. Primary rat SCs can be immortalized with long-term exposure to mitogens. Transplantation of these cells into an autogenic host sciatic nerve results in the formation of tumors. Human cells are, in general, relatively more resistant to malignant transformation, but any potential risk for inducing tumor after transplantation of SCs in humans must be excluded. In this study, the malignant potential of mitogen expanded human SCs injected into the sciatic nerve of immunodeficient mice was investigated. Human SCs were isolated from human peripheral nerves and placed in cell culture, expanded with mitogens (heregulin and forskolin) for many passages (0-6 times), and then injected within the sciatic nerve of Severe Combined Immunodeficient (SCID) rat or mice. As a positive control for tumor formation in this xenograft model, human glioma cells were also injected. The proliferation index (PI) of the human SCs gradually decreased with each passage in cell culture. SC purity remained stable until the 6th passage, and then decreased significantly for older passages, so that the cultures were over-grown with fibroblasts. The incidence for rat or human glioma cells to induce tumors was 100% and 92%, respectively. In contrast, there was no tumor induced by human primary or mitogen expanded SCs. Demyelination, remyelination and formation of connective sheath at the injection site were observed in some cases after injection of the human SCs. Thus, mitogen-expanded human SCs do not produce tumors when transplanted in vivo, which suggests that these cells are safe, and deserve further study towards their use in clinical transplantation.

Animals↗
PubMed1999

Kidney transplantation at the University of Miami.

Of the 1,679 renal allografts performed at the University of Miami between January 1, 1979 and October 31, 1999, 1,154 were from cadaver donors (CAD), 515 were from living-related donors (LRD), and 10 were from living-unrelated donors. The 3 ethnic groups: Black Caribbean-African-American, Hispanic, and others were almost equally represented among recipients. Recipient ages ranged between 1-83 years. In the CAD group, HLA matching was emphasized so that no patient received a kidney with less than one DR match, and for the entire series a mean of 2.59 of 6 HLA antigens were matched between donors and recipients. Overall actuarial 20-year patient and graft survival rates were 65.3% and 30.7%, respectively, with 69.2% patient and 38.5% graft survival rates for LRD, and 65.6% patient and 29.0% graft survival rates for CAD recipients. Several factors adversely affected long-term graft outcome. African-Americans had an overall 20-year graft survival rate of 13.6% compared with 34% for non African-Americans (p < 0.001) (not dependent on patient survival). Diabetic patients had an overall 20-year graft survival rate of 13.5% versus 34.2% for non-diabetics (primarily dependent on patient survival). In the category of non African-American, non-diabetic patients under age 36 (n = 412), the 20-year patient survival rates in the LRD and CAD groups were 85.0% and 79.3%, respectively, and the graft survival rates were 55.7% and 46.5%, respectively. This differed markedly from the results for the entire series.

Adolescent↗
PubMed1998

Retinoid-X receptor signalling in the developing spinal cord.

Retinoids regulate gene expression through the action of retinoic acid receptors (RARs) and retinoid-X receptors (RXRs), which both belong to the family of nuclear hormone receptors. Retinoids are of fundamental importance during development, but it has been difficult to assess the distribution of ligand-activated receptors in vivo. This is particularly the case for RXR, which is a critical unliganded auxiliary protein for several nuclear receptors, including RAR, but its ligand-activated role in vivo remains uncertain. Here we describe an assay in transgenic mice, based on the expression of an effector fusion protein linking the ligand-binding domain of either RXR or RAR to the yeast Gal4 DNA-binding domain, and the in situ detection of ligand-activated effector proteins by using an inducible transgenic lacZ reporter gene. We detect receptor activation in the spinal cord in a pattern that indicates that the receptor functions in the maturation of limb-innervating motor neurons. Our results reveal a specific activation pattern of Gal4-RXR which indicates that RXR is a critical bona fide receptor in the developing spinal cord.

Animals↗
PubMed1998

TrkB and neurotrophin-4 are important for development and maintenance of sympathetic preganglionic neurons innervating the adrenal medulla.

The adrenal medulla receives its major presynaptic input from sympathetic preganglionic neurons that are located in the intermediolateral (IML) column of the thoracic spinal cord. The neurotrophic factor concept would predict that these IML neurons receive trophic support from chromaffin cells in the adrenal medulla. We show here that adrenal chromaffin cells in the adult rat store neurotrophin (NT)-4, but do not synthesize or store detectable levels of BDNF or NT-3, respectively. Preganglionic neurons to the adrenal medulla identified by retrograde tracing with fast blue or Fluoro-Gold (FG) express TrkB mRNA. After unilateral destruction of the adrenal medulla, 24% of IML neurons, i.e., all neurons that are preganglionic to the adrenal medulla in spinal cord segments T7-T10, disappear. Administration of NT-4 in gelfoams (6 microgram) implanted into the medullectomized adrenal gland rescued all preganglionic neurons as evidenced by their presence after 4 weeks. NT-3 and cytochrome C were not effective. The action of NT-4 is accompanied by massive sprouting of axons in the vicinity of the NT-4 source as monitored by staining for acetylcholinesterase and synaptophysin immunoreactivity, suggesting that NT-4 may enlarge the terminal field of preganglionic nerves and enhance their access to trophic factors. Analysis of TrkB-deficient mice revealed degenerative changes in axon terminals on chromaffin cells. Furthermore, numbers of FG-labeled IML neurons in spinal cord segments T7-T10 of NT-4-deficient adult mice were significantly reduced. These data are consistent with the notion that NT-4 from chromaffin cells operates through TrkB receptors to regulate development and maintenance of the preganglionic innervation of the adrenal medulla.

Adrenal Medulla↗
PubMed1998

Neurotoxic effects of fractionated diesel exhausts following microinjections in rat hippocampus and striatum.

Exhaust emissions from a heavy-duty diesel vehicle, separated into particulate and semivolatile phases and thereafter fractionated according to polarity, were studied in the adult rat brain after intracranial microinjections using cresyl violet staining and immunohistochemistry. Intrastriatal as well as intrahippocampal injections of particulate fractions III [containing mononitro-polycyclic aromatic hydrocarbon (PAH)], IV (dinitro-PAH and quinones) and V (polar material) and of semivolatile fractions IV and V, in amounts corresponding to a driven length of 19.5 m, caused major lesions with tissue loss and disappearance of immunoreactivity for glial fibrillary acidic protein, tyrosine hydroxylase, and acetylcholine esterase. Particulate fractions I ("light" aliphatic hydrocarbons) and II ("heavy" aliphatic hydrocarbons and PAH) and semivolatile fraction III produced smaller lesions; semivolatile fractions I and II led to lesions equivalent to those of the vehicle dimethyl sulfoxide alone. Microinjected doses of particulate fractions III or IV corresponding to driven lengths of 2.0 and 9.8 m produced a variable lesion. Thus, fractions containing nitro-derivatives of PAH, quinones, and polar material caused the greatest damage after intracranial injections. It is concluded that intracerebral microinjections of fractionated motor vehicle exhausts provide a method for systematic testing of direct neurotoxicity.

Animals↗