A Medical School Prematriculation Program for Rural Students: Staying Connected With Place, Cultivating a Special Connection With People.

PROBLEM: Rural medical students who attend urban medical schools experience urban disruption that may make it less likely that they will return to rural practice. Most prematriculation programs focus on academic preparation and are in urban areas, potentially adding to urban disruption. Most initial learning experiences concerning communication with patients are also in urban areas. INTERVENTION: Fifty-nine rural preclinical students completed a 3-week summer rural prematriculation program from 2009 to 2014. The focus was on learning a holistic approach to interviewing patients and experiential learning based in a rural practice. Group reflection sessions focused on understanding health beliefs, psychosocial details of the patient's life, and the importance of the sense of place. Measures included student reports, program evaluations, and a pre- and post- 10-item opinion survey focused on the students' perceived importance of traditional biomedical and psychosocial knowledge. CONTEXT: The program was based at the Trover Campus, a regional clinical campus of the University of Louisville School of Medicine, in a town of 20,000 in the western Kentucky coalfields that is 150 miles from the main urban campus. Practice site assignments were in surrounding medically underserved towns in family medicine practices. OUTCOME: After the 3-week experience, students became comfortable with interviews concerning health habits using the Prochaska model of lifestyle modification and expressed an increased importance of some psychosocial factors and a corresponding decrease in importance of traditional biomedical factors in choosing treatment for an individual patient (significant results by Mann-Whitney, two-tailed, ranged U = 1136.0, p = .001 to U = 1377.5, p ≤ .05). Student reports showed that the students gained a new detailed understanding of rural practice. Students also expressed an appreciation for having developed a support network of fellow rural students with whom they would begin medical school on the urban campus. LESSONS LEARNED: These results support the value of a summer prematriculation program for rural students based in a rural area. New appreciation for psychosocial patient factors, new skills in communication with patients, new understanding of the details of rural practice, and new relationships with other rural classmates were perceived as positive aspects of the program. Longer term measures of whether the program decreased urban disruption significantly will require continued tracking of the students until they make a practice choice 7 to 9 years later. Wider collaboration with other medical school rural programs is necessary to determine which aspects of rural-focused training are most effective.

Humoral response to 2 inactivated bluetongue virus serotype-8 vaccines in South American camelids.

BACKGROUND: Bluetongue virus serotype 8 (BTV-8) has caused disease in domestic ruminants in several countries of northern Europe since 2006. In 2008 a mass-vaccination program was launched in most affected countries using whole virus inactivated vaccines. OBJECTIVE: To evaluate 2 inactivated vaccines (Bovilis BTV 8; BTVPUR AlSap8) for immunogenicity and safety against BTV-8 in South American camelids (SAC) in a field trial. ANIMALS: Forty-two SAC (25 Alpacas, 17 Llamas) aged between 1 and 16 years. METHODS: The animals were vaccinated twice at intervals of 21 days. They were observed clinically for adverse local, systemic, or both reactions throughout the trial. Blood samples collected on days 0, 14, 21, 43, and 156 after vaccination were tested for the presence of BTV-8 virus by real time-polymerase chain reaction and of specific antibodies by competitive ELISA and a serum neutralization test. RESULTS: All vaccinated animals developed antibodies to BTV-8 after the 2nd administration of the vaccine. No adverse effects were observed except for moderate local swellings at the injection site, which disappeared within 21 days. Slightly increased body temperatures were only observed in the first 2 days after vaccination. The BTV was not detected in any of the samples analyzed. CONCLUSIONS AND CLINICAL IMPORTANCE: The administration of the 2 inactivated commercial vaccines was safe and induced seroconversion against BTV-8 in all vaccinated animals. The results of this study suggest that 2 doses injected 3 weeks apart is a suitable vaccination regimen for SAC.

[Vaccination against bluetongue: safety and immune response in the field]. / Impfung gegen die Blauzungenkrankheit: Verträglichkeit und Immunantwort in der Praxis.

Bluetongue, caused by the bluetongue virus serotype 8 has rapidly spread through Europe since 2006. The first cases in Switzerland were detected in October 2007. The European Union and Switzerland launched a vaccination campaign in June 2008. This study aims to demonstrate the safety and the immune response of the three vaccines used in Switzerland under practical conditions in the field. The trial was carried out in cattle, sheep and goats. Based on the results of this study recommendations for the 2009 campaign are presented.

Outcomes and cost savings of free clinic care.

Healthcare costs and client health status were measured in a 10-month period before and after an index free clinic visit for 26 poor, working, uninsured patients. A significant number of patients reported overall improvement in their health. During the period of free clinic management, the equivalent of dollar 6500 of care was provided. Compared to utilization before the free clinic period, a savings of dollar 33,145 was realized, largely due to decreased emergency department care and hospitalization.

[Single Subcutaneous Palmar Injection vs. 2 Dorsal Injections for Finger Anaesthesia in Hand Surgery - Randomised Prospective Comparison of Application Pain and Efficacy]. / Vergleich zweier Fingerleitungsanästhesie-Techniken - randomisierte, prospektive Studie bezüglich Applikationsschmerz und Wirksamkeit zwischen dem singulären subkutanen Digitalblock und der Oberst-Leitungsanästhesie.

PURPOSE: This randomised prospective study compared pain during application and efficacy of the palmar subcutaneous single injection block (PSSIB) and the traditional dorsal 2 injection block (DTIB). METHODS: During a 2 year period, a total of 190 patients with an average age of 43 years (18-82) and an isolated finger injury were included in the study. The injection was applied by residents (n=29) of the emergency department. 96 patients received PSSIB (72 men, 24 women) and 94 DTIB (55 men, 39 women) with 3 ml of Mepicavain(®) 1%. Randomisation was performed by even/odd hospital admission number. EXCLUSION CRITERIA: Thumb injury, progressive infection with visible redness at injection point. Application pain was recorded immediately after injection and registered on a VAS (0-10). Efficacy was checked 5 min after application. The patients quoted the efficacy as complete pain-free, almost pain-free and inadequate anesthesia (second injection was necessary). Statistical analysis was performed using the chi-quadrat and the t test; the level of significance was set at p<0.05. RESULTS: There was no significant difference in terms of analgesic efficacy (p=0,096), while the PSSIB required fewer second injections. Application pain was rated as being significantly (p=0.002) less painful for PSSIB (3.2) than for DTIB (4,0). CONCLUSIONS: This study shows that PSSIB gives reliable analgesia and the application pain is significant less than during DTIB.

[Postoperative Osteomyelitis of a Distal Phalanx Caused by Raoultella ornithinolytica]. / Postoperative Osteomyelitis einer Endphalanx am Finger durch Raoultella ornithinolytica.

We report on a case of osteomyelitis of a distal phalanx of the right ring finger of a 62-year-old patient, which occurred 11 months after transosseous-transungual refixation of a closed flexor digitorum profundus tendon avulsion caused by Raoultella ornithinolytica. R. ornithinolytica is an encapsulated Gram-negative aerobic bacillus. In the literature only 13 cases of human infection by R. ornithinolytica are mentioned. To the best of our knowledge, this is the first case of an osteomyelitis caused by R. ornithinolytica.

Increasing the Rural Physician Workforce: A Potential Role for Small Rural Medical School Campuses.

PURPOSE: To address the issue of physician maldistribution, some medical schools have rural-focused efforts, and many more are in the planning or early implementation stage. The best duration and structure of the rural immersion experience are unclear, and the relative effects of rural upbringing and rural training on subsequent rural practice choice are often difficult to determine. METHODS: To determine the effect of adding a rural clinical campus to our school, we analyzed the variables of rural upbringing, demographics, family medicine residency choice, and campus participation using a multivariate model for association with rural practice choice. We included graduates from the classes of 2001-2008 from both campuses (urban and rural) in the analysis. FINDINGS: We found similar associations to those reported previously of rural upbringing (OR = 2.67 [1.58-4.52]) and family medicine residency (OR = 5.08 [2.88-8.98]) with rural practice choice. Even controlling for these 2 variables, participation in the full 2 years at the rural clinical campus showed the strongest association (OR = 5.46 [2.61-11.42]). All 3 associations were significant at P < .001, and no other variables were significant. CONCLUSIONS: We conclude that the investment of resources in our rural campus may add an increment to rural practice choice beyond the established associations with rural upbringing and family medicine residency. The decision of practice site choice is complex, and collaborative studies that include data from several schools with differently structured rural exposures, including those with rural clinical campuses, are needed.

Site-specific migration and neuronal differentiation of human neural progenitor cells after transplantation in the adult rat brain.

Neural progenitor cells obtained from the embryonic human forebrain were expanded up to 10(7)-fold in culture in the presence of epidermal growth factor, basic fibroblast growth factor, and leukemia inhibitory growth factor. When transplanted into neurogenic regions in the adult rat brain, the subventricular zone, and hippocampus, the in vitro propagated cells migrated specifically along the routes normally taken by the endogenous neuronal precursors: along the rostral migratory stream to the olfactory bulb and within the subgranular zone in the dentate gyrus, and exhibited site-specific neuronal differentiation in the granular and periglomerular layers of the bulb and in the dentate granular cell layer. The cells exhibited substantial migration also within the non-neurogenic region, the striatum, in a seemingly nondirected manner up to approximately 1-1.5 mm from the graft core, and showed differentiation into both neuronal and glial phenotypes. Only cells with glial-like features migrated over longer distances within the mature striatum, whereas the cells expressing neuronal phenotypes remained close to the implantation site. The ability of the human neural progenitors to respond in vivo to guidance cues and signals that can direct their differentiation along multiple phenotypic pathways suggests that they can provide a powerful and virtually unlimited source of cells for experimental and clinical transplantation.

The 6-OHDA mouse model of Parkinson's disease - Terminal striatal lesions provide a superior measure of neuronal loss and replacement than median forebrain bundle lesions.

Unilateral 6-hydroxydopamine (6-OHDA) lesions of the nigrostriatal pathway produce side-biased motor impairments that reflect the motor deficits seen in Parkinson's disease (PD). This toxin-induced model in the rat has been used widely, to evaluate possible therapeutic strategies, but has not been well established in mice. With the advancements in mouse stem cell research we believe the requirement for a mouse model is essential for the therapeutic potential of these and other mouse-derived cells to be efficiently assessed. This aim of this study focused on developing a mouse model of PD using the 129 P2/OLA Hsd mouse strain as this is widely used in the generation of mouse embryonic stem cells. Both unilateral 6-OHDA medial forebrain bundle (MFB) and striatal lesion protocols were compared, with mice analysed for appropriate drug-induced rotational bias. Results demonstrated that lesioned mice responded to d-amphetamine with peak rotation dose at 5mg/kg and 10mg/kg for MFB and striatal lesions respectively. Apomorphine stimulation produced no significant rotational responses, at any dose, in either the MFB or striatal 6-OHDA lesioned mice. Analysis of dopamine neuron loss revealed that the MFB lesion was unreliable with little correlation between dopamine neuron loss and rotational asymmetry. Striatal lesions however were more reliable, with a strong correlation between dopamine neuron loss and rotational asymmetry. Functional recovery of d-amphetamine-induced rotational bias was shown following transplantation of E13 mouse VM tissue into the lesioned striatum; confirming the validity of this mouse model.

Grafts of EGF-responsive neural stem cells derived from GFAP-hNGF transgenic mice: trophic and tropic effects in a rodent model of Huntington's disease.

The present study examined whether implants of epidermal growth factor (EGF)-responsive stems cells derived from transgenic mice in which the glial fibrillary acid protein (GFAP) promoter directs the expression of human nerve growth factor (hNGF) could prevent the degeneration of striatal neurons in a rodent model of Huntington's disease (HD). Rats received intrastriatal transplants of GFAP-hNGF stem cells or control stem cells followed 9 days later by an intrastriatal injection of quinolinic acid (QA). Nissl stains revealed large striatal lesions in rats receiving control grafts, which, on average, encompassed 12.78 mm3. The size of the lesion was significantly reduced (1.92 mm3) in rats receiving lesions and GFAP-hNGF transplants. Rats receiving QA lesions and GFAP-hNGF-secreting grafts stem cell grafts displayed a sparing of striatal neurons immunoreactive (ir) for glutamic acid decarboxylase, choline acetyltransferase, and neurons histochemically positive for nicotinamide adenosine diphosphate. Intrastriatal GFAP-hNGF-secreting implants also induced a robust sprouting of cholinergic fibers from subjacent basal forebrain neurons. The lesioned striatum in control-grafted animals displayed numerous p75 neurotrophin-ir (p75NTR) astrocytes, which enveloped host vasculature. In rats receiving GFAP-hNGF-secreting stem cell grafts, the astroglial staining pattern was absent. By using a mouse-specific probe, stem cells were identified in all animals. These data indicate that cellular delivery of hNGF by genetic modification of stem cells can prevent the degeneration of vulnerable striatal neural populations, including those destined to die in a rodent model of HD, and supports the emerging concept that this technology may be a valuable therapeutic strategy for patients suffering from this disease.

Functional and morphological outcome of knee joint transplantation in dogs depends on control of rejection.

BACKGROUND: The reconstruction of massive osteochondral defects extending to weight-bearing joints remains a surgical challenge. Total knee joint transplantation has been performed experimentally, but these studies lacked prospective evaluation of functional outcome, graft vascularization, and graft viability. METHODS: Replantation and transplantation of vascularized knee joints was performed in dogs (n=4 per group), comparing functional and morphological results during a 6-month follow-up. RESULTS: All replant recipients and three transplant recipients survived the 6-month follow-up period. At this time, duplex sonography and angiography revealed patent anastomoses in all animals. Increases in volumetric flow rates and vascular collateralization were observed in allografts, as compared with replanted joints (100+/-16 ml/min vs. 31+/-15 ml/min at 6 months after transplantation). Bone fusion at the graft-host interface was verified by fluorography in all animals at 3 months after transplantation. Six months after transplantation, microradiographies and computerized tomographies revealed spongialization of the cortical bone and filling of the medullary space by trabecular bone in transplanted joints. Such alterations were not detectable in replanted joints. Chondrocyte viability exceeded 80% in all but one transplanted joint. Lymphocyte infiltration of synovia and arterial walls was detected in all transplanted joints, suggesting the presence of chronic rejection. Weight-bearing capacity recovered in all replanted animals (weight-bearing index before transplantation: 0.499+/-0.080; 6 months after transplantation: 0.38+/-0.16) but only in two of four transplanted animals (weight-bearing index 6 months after transplantation: 0.37, 0.28, and 0.00). CONCLUSIONS: These data demonstrate the potential of joint grafting and the critical dependence of allotransplantation on the control of rejection.

The effects of donor stage on the survival and function of embryonic striatal grafts in the adult rat brain. I. Morphological characteristics.

The effects of the stage of donor embryos on the survival of grafts from different neuronal cell types have been well documented. Indeed, this parameter has been shown to be highly important in the survival and function of transplants of various tissues of the CNS. However this question has not been addressed in grafts of embryonic striatal tissue transplanted into animal models of Huntington's disease. In this study, rats which had received a unilateral ibotenic acid lesion in the dorsal striatum received grafts from a standard dissection of embryonic striatal primordium taken from donors of embryonic stage either E14, E16, E17 or E19 days. Three months after transplantation six rats from each group were killed for analysis of graft survival and morphology. The remaining animals in each group were killed between 10 and 14 months after grafting. Graft morphology was detected using a range of markers including: acetylcholinesterase and Cresyl Violet, the 32,000 mol. wt dopamine- and cyclic AMP-regulated phosphoprotein (DARPP-32), tyrosine hydroxylase and striatally-enriched phosphatase. All the grafts from different donor stages survived well at both time-points and Cresyl Violet staining indicated neuronal cell types spread throughout the grafts. The transplants were seen to have a characteristic "patchy" appearance with areas of dense AChE activity and DARPP-32 immunopositivity interspersed with areas of much lighter expression. These areas also co-localized consistently with striatally-enriched phosphatase and tyrosine hydroxylase expression, indicating that they comprised the striatal-like compartment of the graft (the so called P zones, containing cells of the mature striatum), and receiving specific afferent input from the host dopaminergic system. There was no significant difference in total graft volume, when comparing individual groups at both time-points from grafting. However, when comparing the volume of the P zones, the striatal primordium from the youngest donor stages (E14 and E16) produced grafts with a significantly higher proportion of striatal-like tissue. Therefore, in order to increase the proportion of striatal tissue within these grafts, tissue from younger embryonic donors should be used. This has important implications in the application of this model towards clinical trials in Huntington's disease.

The effects of donor stage on the survival and function of embryonic striatal grafts in the adult rat brain. II. Correlation between positron emission tomography and reaching behaviour.

Grafts of embryonic striatal primordia are able to elicit behavioural recovery in rats which have received an excitotoxic lesion to the striatum, and it is believed that the P zones or striatal-like tissue within the transplants play a crucial role in these functional effects. We performed this study to compare the effects of different donor stage of embryonic tissue on both the morphology (see accompanying paper) and function of striatal transplants. Both the medial and lateral ganglionic eminence was dissected from rat embryos of either 10 mm, 15 mm, 19 mm, or 23 mm crown-rump length, and implanted as a cell suspension into adult rats which had received an ibotenic acid lesion 10 days prior to transplantation. After four months the animals were tested on the "staircase task" of skilled forelimb use. At 10-14 months rats from the groups which had received grafts from 10 mm or 15 mm donor embryos were taken for positron emission tomography scanning in a small diameter positron emission tomography scanner, using ligands to the dopamine D1 and D2 receptors, [11C]SCH 23390 and [11C]raclopride, respectively. A lesion-alone group was also scanned with the same ligands for comparison. Animals which had received transplants from the 10 mm donors showed a significant recovery with their contralateral paw on the "staircase test". No other groups showed recovery on this task. Similarly, the animals with grafts from the youngest donors showed a significant increase in D1 and D2 receptor binding when compared to the lesion-alone group. No increase in signal was observed with either ligand in the group which had received grafts from 15 mm donors. Success in paw reaching showed a strong correlation to both the positron emission tomography signal obtained and the P zone volume of the grafts. These results suggest that striatal grafts from younger donors (10 mm CRL) give greater behavioural recovery than grafts prepared from older embryos. This recovery is due to both the increased proportion of striatal-like tissue within the grafts and an increase in functional D1 and D2 dopamine receptors measured by positron emission tomography, i.e. a more extensive integration of the graft with the host brain.

The nursing home at night: effects of an intervention on noise, light, and sleep.

OBJECTIVES: The sleep of nursing home residents is fragmented by frequent awakening episodes associated, at least in part, with environmental variables, including noise and light changes. The purpose of this study was to improve sleep by reducing the frequency of nighttime noise and light changes. PARTICIPANTS AND SETTING: Two hundred sixty-seven incontinent nursing home residents in eight nursing homes. DESIGN: A randomized control group design with a delayed intervention for the control group. MEASUREMENTS: Bedside noise and light monitors recorded the number of 2-minute intervals at night with peak sounds recorded above 50 dBs and the number of light changes of at least 10 lux between adjacent 2-minute intervals. Daytime behavioral observations measured sleep and in-bed time during the day, and wrist activity was used to estimate sleep at night. Awakening events associated with the environmental variables were derived from the wrist activity data. INTERVENTION: A behavioral intervention implemented between 7:00 p.m. and 6:00 a.m. that involved feedback to nursing home staff about noise levels and implementation by research staff of procedures to both abate noise (e.g., turn off unwatched television sets) and to individualize nighttime incontinence care routines to be less disruptive to sleep. RESULTS: Noise was reduced significantly, from an average of 83 intervals per night with peak noises recorded above 50 dBs to an average of 58 intervals per night in the group that received the initial intervention, whereas noise in the control group showed no change (MANOVA group x time P < .001). All 10-dB categories of noise from 50 to 90+ dBs were reduced, and light changes were reduced from an average of four per night per resident to two per night (P < .001). Despite these significant changes in the environmental variables, there was a significant differential improvement in the intervention group on only two night sleep measures: awakening associated with a combination of noise plus light (P < .001) and awakening associated with light (P < .001). However, there was a significant correlation between change in noise and change in percent sleep from baseline to intervention (r = -.29, P < .05), suggesting that the intervention did not reduce noise to low enough levels to produce a significant improvement in sleep. The intervention effects on all environmental variables were replicated in the delayed intervention group, who again showed significant improvement on the same sleep measures. Observations of day sleep and in-bed time did not change over the phases of the trial for either group. CONCLUSION: The significant reductions in noise and light events resulting from the intervention did not lead to significant improvements in the day sleep and most night sleep measures. An intervention that combines both behavioral and environmental strategies and that addresses daytime behavioral factors associated with poor sleep (e.g., excessive time in bed) would potentially be more effective in improving the night sleep and quality of life of nursing home residents.

The localization of an antibody to STEP in embryonic striatal tissue grafts.

We used immunohistochemical staining with antibodies against the novel protein striatal enriched phosphatase (STEP) to investigate the internal organization of grafts of embryonic striatal tissues implanted in the ibotenic acid-lesioned neostriatum of adult rats. STEP immunoreactivity was found in discrete patches within the grafts, which colocalized with areas designated as 'patch' zones when stained for the enzyme acetylcholinesterase and with antibodies against tyrosine hydroxylase and DARPP-32. As previously hypothesized, the pattern of STEP immuno-reactivity in embryonic striatal tissue grafts provides further indication that the patch zones are indeed comprised of striatal like cell populations. The novel protein STEP provides a sensitive and precise marker for this compartment within the grafts.

Assessment of striatal graft viability in the rat in vivo using a small diameter PET scanner.

A small diameter positron emission tomography (PET) scanner has been used to monitor [11C]raclopride (D2 receptor) binding in vivo in either intact striatum, denervated striatum following an excitotoxic lesion with ibotenic acid, or lesioned and grafted striatum following implantation of cortical or striatal tissue grafts in rats. Binding of [11C]raclopride was localized in the intact striatum within 20 min of injection of the radioligand, and was much reduced within the lesioned striatum. Cortical grafts exhibited a similar low level of binding to the lesioned striatum, whereas striatal grafts showed specific binding at an intermediate level. The [11C]raclopride binding signal in vivo correlated well with the extent of surviving or grafted striatal tissue observed post morten by Nissl staining and acetylcholinesterase histochemistry. Thus, the distribution of dopamine receptors as seen in the PET scanner are consistent with post mortem anatomical observations of striatal, lesion and graft sizes, and suggest that PET can provide a useful tool for monitoring the viability of implanted striatal graft tissues in vivo.

A comparative study of preparation techniques for improving the viability of nigral grafts using vital stains, in vitro cultures, and in vivo grafts.

The intracerebral transplantation of embryonic dopaminergic nigral neurons, although relatively successful, leads to a fairly low yield of surviving cells. Many factors may influence the viability of dopaminergic grafts and one of these is the preparation of the tissue prior to transplantation. We have investigated the effects of different steps during the preparation and storage of embryonic rat nigral cell suspensions on their subsequent survival at a variety of different time points using a combination of techniques and studies. For studies concerned with the first 24 h we employed vital stains, in the period covering the next 7 days we used in vitro cultures, and in the long term experiment we used in vivo grafts. The results suggest that nigral cell suspensions may remain sufficiently viable for grafting for much longer periods than previously reported. In addition a number of parameters which affect cell survival have been characterised, including the age of the embryonic donor tissue, the use of proteolytic enzymes and the trituration procedure used during the preparation of the suspension. The optimal preparation technique, therefore, uses E13-E14 embryos with the dissected ventral mesencephalon being incubated in purified 0.1% trypsin solutions for 60 min and triturated using a flame polished Pasteur pipette. This may have important implications in improving intracerebral transplantation for Parkinson's disease.

A comparative study of preparation techniques for improving the viability of striatal grafts using vital stains, in vitro cultures, and in vivo grafts.

Cell suspension grafts from embryonic striatal primordia placed into the adult rat striatum survive well and are able to alleviate a number of behavioral deficits caused by excitotoxic lesions to this structure. However, neither the anatomical connectivity between the graft and host nor the functional recovery elicited by the grafts is completely restored. One way in which the survival and function of embryonic striatal grafts may be enhanced is by the improvement of techniques for the preparation of the cell suspension prior to implantation, an issue that has been addressed only to a limited extent. We have evaluated a number of parameters during the preparation procedure, looking at the effects on cell survival over the first 24 h from preparation using vital dyes and the numbers of surviving neurons in vitro, after 4 days in culture, in addition to graft survival and function in vivo. Factors influencing cell survival include the type of trypsinization procedure and the age of donor tissues used for suspension preparation. The presence of DNase has no effect on cell viability but aids the dissociation of the tissue to form single cells. These results have important implications for the use of embryonic striatal grafts in animal models of Huntington's disease, and in any future clinical application of this research.

The potential of high-resolution positron emission tomography to monitor striatal dopaminergic function in rat models of disease.

The use of a recently commissioned small-diameter, high-resolution positron emission tomography (PET) to obtain a measure of specific binding of 3 carbon-11 labelled ligands in rat striatum is described. Using cerebellum as a reference tissue, compartmental modelling was used to obtain individual estimates of striatal binding potential (defined as the ratio of rate constants to and from the specifically bound compartment) for [11C]raclopride (D2 receptors), [11C]SCH 23390 (D1 receptors) and [11C]RTI-121 (dopamine transporter). The coefficients of variation in control, anaesthetized rats were of the order of 10%. Using two models of human disease, namely striatal injection of ibotenic acid to produce postsynaptic cell loss as in Huntington's disease, and 6-hydroxydopamine injection into substantia nigra pars compacta to mimic dopaminergic terminal loss in Parkinson's disease, marked reductions in binding potential were observed for the corresponding pre- or postsynaptic markers. When the regions of interest are so small as to be of the order of the spatial resolution of the system, factor such as spill over and partial volume negate absolute quantification of tissue radioactivity. Nevertheless, the use of PET to monitor relative changes in dopaminergic integrity should be considered as a viable complement to established in vivo microdialysis and post mortem techniques.

The placement of a striatal ibotenic acid lesion affects skilled forelimb use and the direction of drug-induced rotation.

The motor consequences of excitotoxic striatal damage have been evaluated extensively in the rat, using tests of whole body motor asymmetry and of deficits in skilled paw and limb movements. However conflicting results of both the type and extent of behavioural deficits have been reported, particularly in the direction of rotation observed in response to the dopamine receptor agonist, apomorphine. The present study investigated the effect of unilateral ibotenic acid lesions in the dorsal striatum of the adult rat, placed at either anterior, posterior, medial, or lateral loci, on rotation in response to both amphetamine and apomorphine, and in the "staircase test" of skilled forelimb use. In a 2 x 2 matrix design experiment, adult female albino rats received a double unilateral lesion of 0.5 microliter 0.06 M ibotenic acid injected at each of two sites either anterior (medial and lateral), posterior (medial and lateral), medial (anterior and posterior), or lateral (anterior and posterior). Rats that received posterior lesions showed a marked ipsilateral rotation in response to both amphetamine and apomorphine, while animals receiving anterior lesions showed little ipsilateral or a slight contralateral bias. Rats receiving lateral lesions showed a marked impairment of contralateral paw use on the "staircase test," while animals with medial lesions showed no significant difference to control unoperated animals. These results confirm the somatotopic organisation of the dorsal striatum in its control of motor functions, and indicate the need to take into account the locus of an excitotoxic lesion in the design of lesion and transplantation studies if we are to achieve reliable tests of the behavioural deficits and recovery.