Clinical indications for carbon-ion radiotherapy in the UK: A critical review.

INTRODUCTION: Carbon-ion radiotherapy (CIRT) has unique radiobiological properties that cause increased radiobiological effect and tumour control, especially with hypoxic tissues. This critical review aimed to evaluate clinical response to CIRT across all published tumour sites to establish if there is a clinical need for a CIRT centre in the UK. METHODS: A critical review was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Literature searching was undertaken in November 2022 within the PubMed, Science Direct, SCOPUS and Web of Science databases using the term 'carbon ion radiotherapy' in the title, abstract or author keywords. RESULTS: After critical appraisal, data was extracted from 78 primary study papers. Strong evidence supported use of CIRT for chondrosarcoma, chordoma, nasopharyngeal, non-small cell lung cancer (NSCLC), oral cavity, prostate, rectal and salivary gland tumours. Further research is needed to strengthen the evidence base for some other tumour types. CONCLUSION: The UK's incidence and mortality rates suggest a clinical need for CIRT for chondrosarcoma, chordoma, NSCLC, oral cavity, prostate, and rectal tumours. There is a need to improve survivorship amongst pancreatic, liver, and oesophageal cancer patients. Data published relating to CIRT for these tumours is promising but of lower quality and more research is needed in these areas. IMPLICATIONS FOR PRACTICE: The clinical response to CIRT for certain tumours suggests the need for a carbon-ion centre in the UK. Demand for further research [phase III trials] has been identified, giving the UK opportunity to establish a research centre, with opportunity to treat, contributing to world-renowned research whilst improving patient outcomes.

Evaluating the impact of training on therapeutic radiographer awareness of the signs and symptoms of neutropenic sepsis in patients undergoing concurrent chemoradiotherapy.

INTRODUCTION: Neutropenic sepsis is a life-threatening combination of neutropenia and infection. Patients undergoing concurrent chemoradiotherapy are at a high risk of neutropenic sepsis and thus are likely to present in a clinical setting. This study aimed to evaluate levels of Therapeutic Radiographers' understanding of sepsis signs and response pathways along with the impact of a training session on this. METHODS: A teaching session at the trust was conducted by the Sepsis Lead Nurse and utilised a range of active learning techniques including scenario-based questions and a sepsis game. Pre and post-training questionnaires were completed by participants which comprised of multiple-choice questions related to sepsis identification and response. Respondents were asked to rate their confidence in each answer. This enabled scoring to award penalties for higher levels of confidence in incorrect answers and reward high confidence in correct answers. Lower levels of confidence attracted or lost smaller marks. RESULTS: There was a statistically significant (p < 0.0002) improvement in questionnaire scores after the training session from 42% to 66%. Lower scores on the pre-test responses mainly related to incorrect selection of responses to scenario questions. CONCLUSION: This service evaluation has highlighted a lack of sepsis awareness amongst Therapeutic Radiographers. It also demonstrates that an active learning based training session can significantly improve understanding of sepsis. IMPLICATIONS FOR PRACTICE: Sepsis training utilising scenario and response questions should be provided to Therapeutic Radiographers more frequently who are likely to work with patients undergoing concurrent chemoradiotherapy.

Post COVID-19 trends in simulation use within diagnostic radiography and radiation therapy education.

PURPOSE: Simulation is used within medical radiation science training. Recent global events and simulation resource uptake has led to significant changes. The aim of this study was to capture post COVID-19 trends and activity of simulation-based education (SBE) in diagnostic radiography and radiation therapy. METHODS: An online survey was designed to investigate the role of simulation within diagnostic radiography and radiation therapy education. Survey design was based on literature and experience within the research team. Questions were based around access and use of simulation, future trends and the effects of COVID-19. Participants were diagnostic radiography and/or radiation therapy educators. Data captured in this study was undertaken in March 2022 and compared with previous data from Bridge and colleagues (2021). RESULTS: Sixty-seven responses were received across five continents (two from North/South America), Europe was the most widely represented (n = 58, 87%). Fifty-three (79%) of participants reported that they use simulation as part of their teaching and learning. Twenty-seven (51%) respondents reported that they had increased their use of simulation because of COVID-19. Sixteen (30%) respondents stated that they were now able to enrol more students because of the pandemic. Fixed models and immersive environments were the two most common simulation activities. Participants reported, to different degrees, that simulation was used across all parts of the curriculum. CONCLUSIONS: Simulation is deeply embedded into diagnostic radiography and radiation therapy education. Evidence suggests that the growth of simulation may be slowing. Opportunities exist for the development of guidance, training and best practice resources around simulation. IMPLICATIONS FOR PRACTICE: Simulation is a key pedagogical approach for diagnostic radiography and radiation therapy education. Key stakeholders now need to work collaboratively to define standards and best practices.

Candida keroseneae sp. nov., a novel contaminant of aviation kerosene.

AIMS: To characterize and identify a novel contaminant of aviation fuel. METHODS AND RESULTS: Micro-organisms (yeasts and bacteria) were isolated from samples of aviation fuel. A yeast that proved to have been unrecorded previously was isolated from more than one fuel sample. This novel yeast proved to be a new species of Candida and is described here. Ribosomal RNA gene sequence analyses of internal transcribed spacer (ITS) regions (including 5·8S subunit) plus the 26S D1/D2 domains showed the strains to cluster within the Candida membranifaciens clade nearest to, but distinct from, Candida tumulicola. Phenotypic tests were identical for both isolates. Physiological and biochemical tests supported their position as a separate taxon. The yeast was assessed for its effect on the main constituent hydrocarbons of aviation fuel. CONCLUSIONS: Two strains (IMI 395605(T) and IMI 395606) belonging to the novel yeast species, Candida keroseneae, were isolated from samples of aircraft fuel (kerosene), characterized and described herein with reference to their potential as contaminants of aviation fuel. SIGNIFICANCE AND IMPACT OF THE STUDY: As a result of isolating a novel yeast from aviation fuel, the implications for microbial contamination of such fuel should be considered more widely than previously thought.

Late effects arising from volumetric modulated arc therapy to the breast: A systematic review.

INTRODUCTION: Volumetric modulated arc therapy (VMAT) to the breast offers the potential for excellent dose conformity with the possibility of integrating a simultaneous boost within the treatment plan. This technique, however, also delivers a low dose to a large amount of healthy tissue. This systematic review aimed to determine if VMAT offers a clinically significant difference in late effects compared with conformal radiotherapy techniques for breast radiotherapy. METHODS: A systematic review and quality appraisal of primary studies evaluating VMAT to the breast was performed, adopting the PRISMA checklist. RESULTS: A total of 8 studies were included in the review. These demonstrated variation in prescription, outcome measures and cohort characteristics. Findings supported the value of VMAT for reducing organ at risk (OAR) doses but also confirmed the potential secondary cancer risk arising from the low dose bath. Hybrid techniques combining VMAT with tangential intensity modulated or standard radiotherapy showed promise when tangential plans failed to meet objectives. CONCLUSION: VMAT alone does not offer any significant benefit to late effects over conventional for breast radiotherapy due to the creation of a low dose bath, despite improving OAR doses. More research into hybrid techniques is warranted to identify the most appropriate treatment for different patient subgroups and tumour locations. IMPLICATIONS FOR PRACTICE: VMAT may not be the optimal technique for breast radiotherapy; hybrid plans combining tangential IMRT with VMAT are recommended.

Radiotherapy-specific interprofessional learning through simulation.

INTRODUCTION: Interprofessional learning (IPL) is a vital aspect of training in radiation oncology professions, yet is rarely delivered to those professionals who work most closely together in clinical practice. Scenario-based learning using simulation facilities provides a unique opportunity to facilitate this learning and this project aimed to determine the impact and value of this initiative. METHODS: Small groups comprising post-graduate diploma pre-registration therapeutic radiographers, medical physics trainees and radiation oncology registrars were challenged with 4 plausible and challenging radiotherapy scenarios within an academic simulation centre. Pre- and post-event completion of the "Readiness for Interprofessional Learning Scale" measured impact and a Likert-style survey gathered feedback from participants. RESULTS: The session increased participants' teamwork and collaboration skills as well as strengthening professional identities. Participants reported high levels of enjoyment related to collaborative working, communication and observing other professionals deploying their technical skills and specialist knowledge. CONCLUSION: Although beneficial, simulated scenarios offering equal opportunities for engagement across the professions are challenging to plan and timetabling issues between the 3 groups present significant difficulties. The safe environment and unique opportunity for these groups to learn together was particularly well received and future oncology-specific simulated scenario sessions are planned with larger cohorts. IMPLICATIONS FOR PRACTICE: Simulated scenario training can be used to improve team working across the radiotherapy interprofessional team and may have wider use in other specialist interdisciplinary team development.

International audit of simulation use in pre-registration medical radiation science training.

INTRODUCTION: Simulation-based education (SBE) can replicate the challenging aspects of real-world clinical environments, while providing a safe and less intimidating setting. Literature supports its use within medical radiation science (MRS) training for safe practice of psychomotor skills, development of problem solving, team working, interpersonal and decision-making skills and embedding awareness of patient safety. This project aimed to quantify usage of SBE resources and activities internationally and to evaluate how this changed during COVID-19 restrictions. METHODS: An anonymous online survey tool gathered data relating to programme demographics, simulation resources, simulation activities and future plans. A link to the survey was distributed to programme leads via social media, professional bodies and national networks. RESULTS: A total of 72 responses were received from a range of countries and representing a range of programme structures. Most respondents reported up to 100 h of SBE per student per year with low fidelity resources and image viewing software featuring most prominently. There was low reported engagement of service users within simulation activities. Respondents also indicated that COVID-19 had been a trigger for rapid uptake of simulation resources. CONCLUSION: SBE forms an important aspect of MRS training internationally with low-fidelity resources being widely deployed. Where available, high fidelity virtual reality and specialised profession-specific resources were used heavily. There was a low level of reported engagement with service users or expert patients in simulation activities. Future research will identify whether the rapid uptake of SBE during COVID-19 continues and clarify the role of service users in SBE provision. IMPLICATIONS FOR PRACTICE: Increased collaboration between MRS education providers may help to improve parity of SBE provision and identify additional opportunities to engage service users within SBE.

Evaluating the perceptions of the transgender and non-binary communities of pelvic radiotherapy side effect information booklets.

INTRODUCTION: Patients undergoing radiotherapy for pelvic cancers will often experience acute and late toxicity which can result in symptoms which have a significant impact on psychosocial functioning and quality of life. Having written information regarding these symptoms enables informed decision-making and ongoing support. Transgender and non-binary communities are a marginalised but steadily growing subsection of the radiotherapy patient population yet their needs differ from those of the general population. This study aimed to evaluate the relevance of the pelvic radiotherapy patient information booklets with regard to this communities. METHODS: An online survey was distributed via social media to evaluate the perceptions of these communities of four commonly distributed pelvic radiotherapy information booklets. RESULTS: There were 19 full responses and most participants expressed discomfort regarding being provided with (11/19) or picking up (10/19) the booklets. Although most (11/19) agreed that the material in the booklets was relevant, the same number felt that the wording was not. Some of the language and assumptions made regarding the transgender and non-binary communities were incorrect and had the potential to cause distress. CONCLUSION: The importance of providing guidance and support to these communities was identified. IMPLICATIONS FOR PRACTICE: Further research is required to establish how best to provide inclusive patient information for transgender and non-binary individuals.

Simulated versus traditional therapeutic radiography placements: A randomised controlled trial.

INTRODUCTION: Clinical placements provide rich learning environments for health professional pre-registration education but add significant workload pressure to clinical departments. Advances in simulation approaches mean that many aspects of students' clinical learning can be undertaken in the academic environment. There is, however, little data identifying specific pedagogical gains afforded by simulation compared to clinical placement. This study measured the impact of a comprehensive integrated simulation placement on student clinical skill acquisition. METHODS: A virtual department was developed using a range of simulation equipment and software, with actors and service users providing a range of patients for students to engage with. A cohort of 29 first-year undergraduate therapeutic radiography students were randomly assigned to either simulated or conventional clinical placement. Clinical skills assessment scores provided by a blinded assessor were then compared. RESULTS: Mean overall assessment scores for each cohort were within 3% of each other. The simulation cohort had over 10% higher "communication" scores than the traditional group (p = 0.028). The ability to gain both technical and interpersonal skills simultaneously improved learning compared to clinical placement. Students valued the structured approach of the simulated placement and the opportunity to practice techniques in a safe unpressured environment. CONCLUSION: An integrated simulated placement can help students to achieve clinical learning outcomes and lead to improved interpersonal skills. IMPLICATIONS FOR PRACTICE: Use of blended simulation resources can enable students to acquire technical, procedural and interpersonal skills which in turn may enable reduction of overall clinical placement time and departmental training burden.

Lung function measurement in prematurely born preschool children with and without chronic lung disease.

OBJECTIVE: Prematurely born infants often have recurrent wheeze and long-term respiratory morbidity at follow-up. Assessment of airways obstruction in preschool children is feasible using the interrupter resistance (Rint) but has rarely been examined in preterm children with and without chronic lung disease (CLD). The objective of this study was to determine lung function measured by the interrupter technique, its feasibility in the ambulatory setting and respiratory health in prematurely born preschool children with and without CLD. STUDY DESIGN: Preterm children of 2 to 4 years with severe CLD (>30% oxygen at 36 weeks and discharged home receiving supplemental oxygen) (n=43, median gestational age 27 weeks and median birth weight 995 g) and without CLD (n=33, median gestational age 29 weeks and median birth weight 1366 g) attempting lung function test for the first time were enrolled. Respiratory symptoms score was calculated using a questionnaire. A single set of 10 consecutive Rint measurements was obtained using a portable device (MicroRint). Median of at least five occlusions with consistent shape of mouth pressure-time curves was taken to be a Rint measurement. To assess feasibility the children were categorized as 'satisfactory', 'failure' and 'rejected' depending on the outcome of the test. Outcome variables were respiratory symptoms score and Rint. RESULT: Satisfactory Rint measurement was obtained in 46 (61%) children, 9 (36%) 2-year olds, 17 (65%) 3-year olds and 20 (80%) 4-year olds. As compared with the preterm control children (n=18), CLD children (n=28) had significantly higher respiratory symptoms score (18.5 vs 6, P<0.01) and Rint expressed as absolute values (kPa l(-1)) and z-scores (1.33 vs 1.16 and 1.42 vs 1.0, P<0.01), respectively. CONCLUSION: Rint measurement is feasible in prematurely born children of preschool age in the ambulatory setup. Preschool children with severe CLD may be identified from preterm children without CLD by increased Rint that may be used as a screening tool and as an outcome measure for interventions.

An association between the Antarctic mite Alaskozetes antarcticus and an entomophthoralean fungus of the genus Neozygites.

A fungal pathogen provisionally identified as Neozygites cf. acaridis has recently been isolated from the Antarctic oribatid mite Alaskozetes antarcticus. The identification of the fungus is discussed with reference to recent changes in the taxonomy of Neozygites. The potential role of the fungus in the Antarctic mite populations is considered in relation to the known mite life cycles, and the particular environmental conditions in the Antarctic.

How should we estimate driving pressure to measure interrupter resistance in children?

Interrupter resistance (R(int)) is a widely used measure of airway caliber, but concerns remain about repeatability and sensitivity. Some R(int) variability may derive from the linear back-extrapolation algorithm (LBE 30/70) usually used to estimate driving pressure. To investigate whether other methods of estimating driving pressure could improve repeatability and sensitivity, we studied 39 children with asthma. Two measurements of R(int)-each the median of 10 interruptions-were made 5 min apart, and 14 children had a third measurement after bronchodilator (R(int)BD). Mouth pressure transients were analyzed using several algorithms, to compare the magnitude, repeatability, and sensitivity to bronchodilator change of R(int) values yielded. Algorithms taking driving pressure from later in the transient, predictably, yielded higher values of R(int) than those which back-extrapolated to time of valve closure. Algorithms which did not rely on back-extrapolation, including mean oscillation pressure (MOP) and mean plateau pressure (MP 30/70) had better repeatability. Sensitivity to detect change, calculated as ratio of bronchodilator response to repeatability coefficient (DeltaR(int)/CR), was also better for non-extrapolating algorithms: MP 30/70 1.67, LBE 30/70 1.28 (P = 0.0004). Measuring R(int) using techniques other than conventional back-extrapolation may give more consistent and clinically useful results, and these approaches merit further exploration.

Mutation of DNAJC19, a human homologue of yeast inner mitochondrial membrane co-chaperones, causes DCMA syndrome, a novel autosomal recessive Barth syndrome-like condition.

BACKGROUND: A novel autosomal recessive condition, dilated cardiomyopathy with ataxia (DCMA) syndrome, has been identified in the Canadian Dariusleut Hutterite population, characterised by early onset dilated cardiomyopathy with conduction defects, non-progressive cerebellar ataxia, testicular dysgenesis, growth failure, and 3-methylglutaconic aciduria. OBJECTIVE: To map DCMA syndrome and identify the mutation underlying this condition. METHODS: A genome wide scan was undertaken on consanguineous Hutterite families using a homozygosity mapping approach in order to identify the DCMA associated chromosomal region. Mutation analysis was carried out on positional candidate genes in this region by sequencing. Reverse transcriptase polymerase chain reaction and bioinformatics analyses were then used to characterise the mutation and determine its effect on the protein product. RESULTS: The association of DCMA syndrome with a 2.2 Mb region of chromosome 3q26.33 was found. A disease associated mutation was identified: IVS3-1 G-->C in the DNAJC19 gene, encoding a DNAJ domain containing protein of previously unknown function (Entrez Gene ID 131118). CONCLUSIONS: The DNAJC19 protein was previously localised to the mitochondria in cardiac myocytes, and shares sequence and organisational similarity with proteins from several species including two yeast mitochondrial inner membrane proteins, Mdj2p and Tim14. Tim14 is a component of the yeast inner mitochondrial membrane presequence translocase, suggesting that the unique phenotype of DCMA may be the result of defective mitochondrial protein import. It is only the second human disorder caused by defects in this pathway that has been identified.

The secretin G-protein-coupled receptor family: teleost receptors.

Twenty-one members of the secretin family (family 2) of G-protein-coupled receptors (GPCRs) were identified via directed cloning and data-mining of the Fugu Genome Consortium database, representing the most comprehensive description of secretin GPCRs in a teleost fish to date. Duplicated genes were identified for many of the family members, namely the receptors for pituitary adenylate cyclase-activating polypeptide (PACAP)/vasoactive intestinal peptide (VIP), calcitonin, calcitonin gene-related peptide (CGRP), growth hormone releasing hormone (GHRH), glucagon receptor/glucagon-like peptide (GLP) and parathyroid hormone-related peptide (PTHrP)/PTH. Mining of other teleost genomes (zebrafish and Tetraodon) revealed that the duplicated genes identified in the Takifugu genome were also present in these fish. Additional database searching of the Escherichia coli, yeast, Drosophila, Caenorhabditis elegans and Ciona genomes revealed that the family 2 of GPCRs were only present in the multicellular organisms. Orthologues of all the human secretin receptors were identified with the exception of secretin itself. Additional database searches in the Fugu Genome Consortium database also failed to reveal a secretin ligand and so it is hypothesised that both the receptor and the ligand evolved after the divergence of teleost/tetrapod lineages. Phylogenetic analysis at both the protein and the DNA level provided strong support for each of the individual receptor family groupings, but weak support between groups, making evolutionary inferences difficult. A more critical analysis of the PACAP/VIP receptor family confirmed previous hypotheses that the vasoactive intestinal peptide receptor (VPAC(1)R) gene is the ancestral form of the receptor.

Skin-prick testing as a diagnostic aid for childhood asthma.

Diagnosing asthma is problematic when based solely on reported symptoms. The purpose of this study was to evaluate skin-prick testing as a diagnostic aid for asthma in children. Skin-prick testing (SPT) was undertaken in children aged 2-10 years with either no history of wheeze (n = 149) or recent doctor-observed wheeze which responded to treatment with a bronchodilator, the "gold standard" (n = 164). Children with moderate or severe asthma were excluded. SPT positivity increased sharply at age 5 years in wheezers. Data were therefore divided into two age groups: 2- < 5 years (57 controls, 97 wheezers) and 5-10 years (92 controls, 67 wheezers). The sensitivity, specificity, and likelihood ratios of SPT positivity for wheeze were 32%, 89%, and 2.9, respectively, in the younger children, and 82%, 85%, and 5.5, respectively, in the older children. For a prevalence of 30% for asthma, the positive predictive values of a positive SPT were 55% and 70% for the younger and older age groups, respectively. The test characteristics of SPT for helping diagnose asthma in schoolchildren are good. The prevalence of wheeze in preschool children is high, and so SPT should be helpful even in this group. We suggest that clinicians consider skin-prick testing as a diagnostic aid for asthma.

Magnetic resonance imaging evidence of "silent" cerebrovascular toxicity in cocaine dependence.

BACKGROUND: Cocaine and its metabolites can produce vasospasm. Cocaine-dependent (CD) patients are at increased risk for stroke, and a high frequency of brain perfusion defects has been observed in clinically asymptomatic CD subjects. This is the first controlled magnetic resonance imaging (MRI) study of clinically asymptomatic CD subjects. METHODS: Two age-matched groups of male subjects (61 CD and 57 control) participated in the study. Subjects with a history of neurologic symptoms or major medical or neurologic illness, such as hypertension, diabetes, or significant head trauma, were excluded. The severity of hyperintense lesions observed on T2-weighted MRI images were rated on a 0-3-point scale by an experienced radiologist who was blind to all clinical data. Ratings of 3 were felt to be significant indicators of a possible disease process and were used in the data analysis. Three regions were separately rated: the cerebral white matter, subinsular white matter, and subcortical gray matter (basal ganglia and thalamus region). RESULTS: Despite the exclusion criteria minimizing risk factors for cerebrovascular events, 17 of the 61 (27.9%) CD subjects and 4 of 57 (7%) of the control subjects had severe hyperintense lesions suggestive of subclinical or "silent" anoxic vascular events. Significant group differences were observed in the two white matter regions but not in the subcortical gray matter region. The risk of severe white matter lesions in the CD group increased with age, reaching 50% in the oldest age quartile (46-58 years), and this increase was not related to the number of years cocaine was used. CONCLUSIONS: The data suggest that asymptomatic CD patients are a heterogeneous population with a significantly increased age-related risk of white matter neurovascular toxicity. Premature neurovascular damage may impact treatment outcomes and, as the CD population ages, may manifest as an increased incidence of cognitive deficits.

The effects of NMDA receptor antagonists and nitric oxide synthase inhibitors on opioid tolerance and withdrawal. Medication development issues for opiate addiction.

This article is an exploration of the National Institute on Drug Abuse (NIDA) Technical Review on the role of glutamatergic systems in the development of opiate addiction. The effects of "glutamate antagonist" medications on opioid tolerance and withdrawal are examined. In rodents, mu opioid tolerance can be inhibited by noncompetitive N-methyl D-aspartate (NMDA) receptor antagonists [MK801, dextromethorphan (DM), ketamine, phencyclidine (PCP)], competitive NMDA receptor antagonists (LY274614, NPC17742, LY235959), partial glycine agonists (ACPC), glycine antagonists (ACEA-1328), and nitric oxide synthase (NOS) inhibitors [L-NNA, L-NMMA, methylene blue (MB)]. Similarly, some of the symptoms of opioid withdrawal observed in opioid-dependent rodents also can be inhibited by noncompetitive NMDA receptor antagonists (MK801, DM, ketamine), competitive NMDA receptor antagonists (LY274614), glycine antagonists (felbamate), and NOS inhibitors (L-NNA, L-NMMA, L-NAME, L-NIO, 7-NI, MB). There are some serious toxicological effects associated with the administration of some of the noncompetitive NMDA receptor antagonists in rodent but not in squirrel monkey brain, and some medications induce PCP-like behavioral effects. The medications with the most immediate clinical appeal are those that could be coadministered with methadone to decrease mu opioid tolerance and dependence; they include DM, MB, 7-NI, ACPC, and ACEA-1328.

Increased CSF volumes are associated with diminished subjective responses to cocaine infusion.

We evaluated the hypothesis that ventricular and cortical CSF volume increases are associated with reductions in the magnitude of euphoric effects produced by intravenous IV cocaine infusion in cocaine dependent (CD) individuals. Eleven CD patients participating in a cocaine-infusion study and eleven control subjects underwent magnetic resonance imaging (MRI). Two CSF regions of interest (lateral ventricles and frontal cortex CSF) and two comparison regions (third ventricle and posterior cortex CSF) were measured. Self-reported ratings of the intensity of euphoric response ("high") were obtained from the CD subjects at 3, 10, and 30 minutes after IV administration of cocaine. A significant negative correlation was observed between the volume of the lateral ventricles and subjective ratings of the "high" experienced at 3 minutes, but not at 10 and 30 minutes after cocaine infusion. In contrast, a significant negative correlation between frontal cortex CSF volume and the intensity of euphoric response was observed at 30 minutes after IV cocaine. No significant associations were observed between the volumes of the two comparison regions and any subjective ratings of "high." No significant volume differences were observed between the CD and control groups in any region. The results suggest larger lateral ventricular volumes are associated with a decrease in immediate euphoria while larger frontal cortex CSF volumes are associated with a decrease in the duration of the euphoria induced by cocaine infusion. The age-related brain volume reductions underlying the volume increase in these two CSF spaces may be the neurobiological basis of the age-related reduction in the rates of addiction.

Peptide T and glucose metabolism in AIDS dementia complex.

AIDS dementia complex (ADC) is the most common presenting neurologic manifestation of human immunodeficiency virus (HIV)-1 infection. We report FDG-PET studies in a 39-year-old man who had ADC and completed a 12-wk treatment protocol with 1.2 mg/day of intranasal peptide T, one before and one after 12 wk of treatment with peptide T. Peptide T is an octapeptide under investigation for treatment of ADC patients. Values of rCMRglc were converted to Z scores using the mean and standard deviation of values of rCMRglc in three HIV-seronegative matched controls, each of which was studied twice, at the beginning and end of a 12-wk interval. Thirty-five of 60 regions assayed showed Z scores with absolute values > or = 3 (considered abnormal) in the baseline study. Regions with high absolute values of Z scores were located in subcortical areas and in the limbic system, and to a lesser degree in the frontal, temporal and parietal lobes. Thirty-four of these 35 regions showed remission (decrease in the absolute values of Z scores) after treatment. Only one region showed no improvement in the second study. Three regions with absolute values of Z scores < 3 in the baseline study manifested Z scores with magnitudes > or = 3 in the second study. These preliminary observations suggest that functional neuroimaging techniques provide a useful tool in the evaluation of the response to treatment in ADC patients.

Effect of heterozygosity for the methionine synthase 2756 A-->G mutation on the risk for recurrent cardiovascular events.

Increased dietary intake of folate has been shown to significantly reduce the risk for fatal myocardial infarction, possibly by lowering homocysteine levels. We therefore investigated the association between recurrent cardiovascular events and a mutation in methionine synthase (2756 A-->G)--an enzyme directly involved in folate and homocysteine metabolism. This mutation significantly reduced the risk for recurrent cardiovascular events and elevated red blood cell folate levels.