The differences in short- and long-term varicella-zoster virus (VZV) immunoglobulin G levels following varicella vaccination of healthcare workers measured by VZV fluorescent-antibody-to-membrane-antigen assay (FAMA), VZV time-resolved fluorescence immunoassay and a VZV purified glycoprotein enzyme immunoassay.

Healthcare workers (HCWs) reporting no history of varicella frequently receive varicella vaccination (vOka) if they test varicella-zoster virus (VZV) immunoglobulin G (IgG) negative. In this study, the utilities of VZV-IgG time-resolved fluorescence immunoassay (VZV-TRFIA) and a commercial VZV-IgG purified glycoprotein enzyme immunoassay (gpEIA) currently used in England for confirming VZV immunity have been compared to the fluorescent-antibody-to-membrane-antigen assay (FAMA). A total of 110 HCWs received two doses of vOka vaccine spaced 6 weeks apart and sera collected pre-vaccination (n = 100), at 6 weeks post-completion of vaccination (n = 86) and at 12-18 months follow-up (n = 73) were analysed. Pre-vaccination, by FAMA, 61·0% sera were VZV IgG negative, and compared to FAMA the sensitivities of VZV-TRFIA and gpEIA were 74·4% [95% confidence interval (CI) 57·9-87·0] and 46·2% (95% CI 30·1-62·8), respectively. Post-completion of vaccination the seroconversion rate by FAMA was 93·7% compared to rates of 95·8% and 70·8% determined by VZV-TRFIA and gpEIA, respectively. At 12-18 months follow-up seropositivity rates by FAMA, VZV-TRFIA and gpEIA were 78·1%, 74·0% and 47·9%, respectively. Compared to FAMA the sensitivities of VZV-TRFIA and gpEIA for measuring VZV IgG following vaccination were 96·4% (95% CI 91·7-98·8) and 74·6% (95% CI 66·5-81·6), respectively. Using both FAMA and VZV-TRFIA to identify healthy adult VZV susceptibles and measure seroconversion showed that vOka vaccination of HCWs is highly immunogenic.

Radiosynthesis, In Vivo Biological Evaluation, and Imaging of Brain Lesions with [123I]-CLINME, a New SPECT Tracer for the Translocator Protein.

The high affinity translocator protein (TSPO) ligand 6-chloro-2-(4'-iodophenyl)-3-(N,N-methylethyl)imidazo[1,2-a]pyridine-3-acetamide (CLINME) was radiolabelled with iodine-123 and assessed for its sensitivity for the TSPO in rodents. Moreover neuroinflammatory changes on a unilateral excitotoxic lesion rat model were detected using SPECT imaging. [(123)I]-CLINME was prepared in 70-80% radiochemical yield. The uptake of [(123)I]-CLINME was evaluated in rats by biodistribution, competition, and metabolite studies. The unilateral excitotoxic lesion was performed by injection of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid unilaterally into the striatum. The striatum lesion was confirmed and correlated with TSPO expression in astrocytes and activated microglia by immunohistochemistry and autoradiography. In vivo studies with [(123)I]-CLINME indicated a biodistribution pattern consistent with TPSO distribution and the competition studies with PK11195 and Ro 5-4864 showed that [(123)I]-CLINME is selective for this site. The metabolite study showed that the extractable radioactivity was unchanged [(123)I]-CLINME in organs which expresses TSPO. SPECT/CT imaging on the unilateral excitotoxic lesion indicated that the mean ratio uptake in striatum (lesion:nonlesion) was 2.2. Moreover, TSPO changes observed by SPECT imaging were confirmed by immunofluorescence, immunochemistry, and autoradiography. These results indicated that [(123)I]-CLINME is a promising candidate for the quantification and visualization of TPSO expression in activated astroglia using SPECT.

Subclinical VZV reactivation in immunocompetent children hospitalized in the ICU associated with prolonged fever duration.

A prospective observational study was conducted to examine whether asymptomatic VZV reactivation occurs in immunocompetent children hospitalized in an ICU and its impact on clinical outcome. A secondary aim was to test the hypothesis that vaccinated children have a lower risk of reactivation than naturally infected children. Forty immunocompetent paediatric ICU patients and healthy controls were enrolled. Patients were prospectively followed for 28 days. Clinical data were collected and varicella exposure was recorded. Admission serum levels of TNF-a, cortisol and VZV-IgG were measured. Blood and saliva samples were collected for VZV-DNA detection via real-time PCR. As a comparison, the detection of HSV-DNA was also examined. Healthy children matched for age and varicella exposure type (infection or vaccination) were also included. VZV reactivation was observed in 17% (7/39) of children. Children with VZV reactivation had extended duration of fever (OR = 1.17; 95% CI, 1.02-1.34). None of the varicella-vaccinated children or healthy controls had detectable VZV-DNA in any blood or saliva samples examined. HSV-DNA was detected in saliva from 33% of ICU children and 2.6% of healthy controls. Among children with viral reactivation, typing revealed wild-type VZV and HSV-1. In conclusion, VZV reactivation occurs in immunocompetent children under severe stress and is associated with prolonged duration of fever.

Second-line pemetrexed versus docetaxel in Chinese patients with locally advanced or metastatic non-small cell lung cancer: a randomized, open-label study.

INTRODUCTION: This randomized, open-label study compared pemetrexed versus docetaxel as second-line therapy for Chinese patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). The primary endpoint tested non-inferiority of overall survival (OS) on the combined data from these patients and those in the global registration trial. Data from patients in the current study only (Chinese patients) were the basis for the study's secondary objectives. METHODS: Patients with stage IIIB/IV disease were randomized (1:1) to receive pemetrexed (500 mg/m(2); 107 randomized; 106 treated) or docetaxel (75 mg/m(2); 104 randomized; 102 treated) on Day 1 of each 21-day cycle. Treatment continued until progressive disease, unacceptable toxicity or patient/investigator decision. All efficacy and safety data were analyzed at the pre-specified study completion; supplementary OS analyses were performed later, after additional events had been recorded. RESULTS: The primary endpoint of OS noninferiority of pemetrexed to docetaxel was not met, the lower CL was <50% and P>0.025 (efficacy retained=97.9% [95% CLs: 47.1, 141.9]; P=0.0276), in the combined population (pemetrexed: n=390, docetaxel: n=392). Supplementary values were 101.3% (95% CLs: 57.9, 148.8), P=0.0186. For the secondary objectives, assessed in the population from the current study (pemetrexed: n=107, docetaxel: n=104), median OS was 11.7 and 12.2 months for the pemetrexed and docetaxel arms, respectively (HR [95% CLs]: 1.14 [0.78, 1.68], P=0.492). Supplementary values were 11.4 and 11.5 months, respectively (HR [95% CLs]: 1.02 [0.74, 1.40], P=0.926). Median PFS values were 2.8 and 3.1 months (HR [95% CLs]: 1.05 [0.75, 1.46], P=0.770) and ORR values were 9.6% and 4.1% (odds ratio [95% CLs]: 2.50 [0.76, 8.25], P=0.133) for pemetrexed and docetaxel, respectively. Pemetrexed-treated patients had significantly fewer drug-related grade 3-4 adverse events (pemetrexed: 20.8%, docetaxel: 40.2%; P=0.003). Few drug-related serious adverse events were reported (pemetrexed: 5 patients, docetaxel: 8 patients). CONCLUSION: The comparable efficacy and superior tolerability of pemetrexed compared with docetaxel in this study supports the use of single-agent, second-line pemetrexed for advanced non-squamous NSCLC in Chinese patients. ClinicalTrials.gov: NCT00391274.

Efficacy in high burden locally advanced cervical cancer with concurrent gemcitabine and cisplatin chemoradiotherapy plus adjuvant gemcitabine and cisplatin: prognostic and predictive factors and the impact of disease stage on outcomes from a prospective randomized phase III trial.

OBJECTIVE: We recently published results of a phase III trial demonstrating superior outcomes in patients with locally advanced cervical cancer (LACC) when concurrent cisplatin chemoradiotherapy is supplemented with concurrent gemcitabine and adjuvant gemcitabine/cisplatin. We present prognostic and predictive factors identified in that study, along with analyses of the effect of disease stage and post-study therapy. PATIENTS AND METHODS: In that trial, 515 patients with stage IIB-IVA LACC were administered concurrent cisplatin chemoradiotherapy with or without gemcitabine and adjuvant gemcitabine/cisplatin. Cox models were used to identify prognostic and predictive factors. Survival was estimated using the Kaplan-Meier method. RESULTS: Advanced (stage III-IVA) disease, squamous histology, low hemoglobin, the presence of ≥1 enlarged para-aortic lymph nodes, and large tumor size, were associated with poorer prognosis, regardless of treatment assigned. Tumor size and histology were predictive of treatment efficacy. Chemoradiotherapy supplemented with gemcitabine produced relatively greater benefit in patients with stage III/IVA disease. Post-study therapy did not appear to affect the overall survival outcome. CONCLUSION: Prognostic factors identified in this study are consistent with other reports. The finding of relatively greater benefit in advanced-stage patients makes for an important factor in consideration of treatment for these patients and the design of future studies.

Comparison of a commercial Varicella Zoster glycoprotein IgG enzyme immunoassay with a reference time resolved fluorescence immunoassay (VZV TRFIA) for measuring VZV IgG in sera from pregnant women, sera sent for confirmatory testing and pre and post vOka vaccination sera from healthcare workers.

BACKGROUND: Recently, a commercial, standardised VZV IgG glycoprotein EIA, Binding Site VaccZyme™VZV glycoprotein IgG low level EIA (VaccZyme™EIA) has become available. The VaccZyme™EIA is more robust and user friendly than the reference VZV time-resolved fluorescence immunoassay (VZV TRFIA). OBJECTIVES: To assess the usefulness of the VaccZyme™EIA in the diagnostic laboratory by comparing VZV IgG levels generated by both assays on serum panels representing, non-vaccinated, and vOka vaccinated populations. STUDY DESIGN: Sera from non-vaccinated individuals were tested; 248 from pregnant women, 117 from various patient groups referred to the Virus Reference Department for confirmatory VZV IgG testing and 102 from healthcare workers enrolled in a study (ROVE) of antibody/IgG response to vOka. From the ROVE study, 282 post vaccination sera were tested; 108 and 101 collected at six weeks post first and second doses of vOka, respectively, and 73 collected at 18 month follow-up. RESULTS: Sensitivities and specificities (equivocals treated as negatives) of the VaccZyme™EIA for sera from pregnant women were 97.8% (95% CI: [94.6%, 99.4%]) and 96.8% (95% CI: [89.0%, 99.6%]), respectively, and for sera referred for confirmatory testing were 81.2% (95% CI: [71.2%, 88.8%]) and 96.9% (95% CI: [83.8%, 99.9%]), respectively, and for ROVE baseline sera were 54.2% (95% CI: [32.8%, 74.4%]) and 100% (95% CI: [95.4%, 100.0%]), respectively. For the post vOka serum panels sensitivities of the VaccZyme™EIA ranged from 65.3% (95% CI: [50.4%, 78.3%]) to 80.4% (95% CI: [71.1%, 87.8%]). Specificities were all 100%. Correlation with VZV TRFIA was high and agreement varied between the serum panels tested. CONCLUSIONS: VaccZyme™EIA is recommended for detecting VZV IgG in sera from non-vaccinated populations; however, caution is advised when measuring post vOka VZV IgG levels.

The molecular epidemiology of equine influenza in Ireland from 2007-2010 and its international significance.

REASONS FOR PERFORMING THE STUDY: Antigenic and genetic drift of equine influenza (EI) virus is monitored annually by the Expert Surveillance Panel (ESP), which make recommendations on the need to update vaccines. Surveillance programmes are essential for this process to operate effectively and to decrease the risk of disease spread through the international movement of subclinically infected vaccinated horses. Not only is surveillance necessary to inform vaccine companies which strains are in circulation, but it serves as an early warning system for horse owners, trainers and veterinary clinicians, facilitating the implementation of appropriate prophylactic and control measures. OBJECTIVE: To summarise the genetic analysis of EI viruses detected in Ireland from June 2007 to January 2010. METHODS: The HA1 gene of 18 viruses was sequenced and phylogenetic analysis undertaken. RESULTS: All viruses belonged to the Florida sublineage of the American lineage. Clade 2 viruses predominated up to 2009. The viruses identified on 4 premises in 2007 displayed 100% nucleotide identity to A/eq/Richmond/1/07, the current clade 2 prototype. The first clade 1 virus was identified in November 2009 and, thereafter, clade 1 viruses were responsible for all the outbreaks identified. The Irish clade 1 viruses differ from the clade 1 virus responsible for the EI outbreaks in Japan and Australia in 2007. No virus of the Eurasian lineage was isolated during this surveillance period. CONCLUSIONS: In 2010 the ESP recommended that the vaccines should not include a H7N7 virus or a H3N8 virus of the Eurasian lineage but that they should contain both a clade 1 and clade 2 virus of the Florida sublineage. The surveillance data presented here support these recommendations and indicate that they are epidemiologically relevant. POTENTIAL RELEVANCE: These data also serve as a scientific basis for investigating the source of epizootics and outbreaks both nationally and internationally.

Population diversity in batches of the varicella Oka vaccine.

The Oka vaccine is a live attenuated vaccine for the prevention of varicella. Although the vaccine differs from the progenitor virus by over 40 mutations, only three of these are fixed, the rest being a mixture of the wildtype and the vaccine allele. To examine the extent of this variability between two of the three commercially available vaccine preparations, we analysed the vaccine/wildtype allele frequencies present at fifteen vaccine loci in five preparations each from two different manufacturers of the vOka vaccine. Our results suggest that differences in manufacturing processes between the two companies have resulted in significant variation in the frequencies of the vaccine/wildtype alleles in their vaccines. Yet despite these differences, the allele frequencies in the vaccines from the two companies are strongly correlated. We discuss the significance of these findings and the role of evolutionary processes that influence the production of this live attenuated vaccine.

Persistence of varicella-zoster virus viraemia in patients with herpes zoster.

BACKGROUND: Herpes zoster is caused by the reactivation of varicella-zoster virus from sensory neurons. The commonest complication following zoster is chronic pain termed post herpetic neuralgia. OBJECTIVES: To investigate the dynamics of VZV viraemia and viral load following the resolution of zoster and its relationship to PHN development. STUDY DESIGN: Blood samples were collected at baseline, 1 month, 3 months and 6 month from a prospective study of 63 patients with active zoster. Quantification of VZV DNA in whole blood was performed using a real-time PCR assay. RESULTS: During acute zoster, all patients had detectable VZV DNA in their blood. VZV DNA remained detectable in the blood of 91% of patients at 6 months although levels declined significantly (p<0.0001). A history of prodromal symptoms (p=0.005) and severity of pain at baseline (p=0.038) as well as taking antivirals (p=0.046) and being immunocompromised (p=0.043) were associated, with longer time to recovery from PHN. Viral DNA loads were consistently higher in patients with risk factors for PHN and higher viral DNA loads over time were associated with longer time to recovery (p=0.058 overall and 0.038 in immunocompetent). CONCLUSIONS: Based on these observations we hypothesise that VZV replication persists following acute shingles and that higher viral DNA loads contribute to the risk factors for PHN.

Real-time RT-PCR for the detection and quantitative analysis of equine rhinitis viruses.

REASONS FOR PERFORMING STUDY: Equine rhinitis viruses (ERV) cause respiratory disease and loss of performance in horses. It has been suggested that the economic significance of these viruses may have been underestimated due to insensitive methods of detection. OBJECTIVES: To develop a sensitive, rapid, real-time RT-PCR (rRT-PCR) assay suitable for the routine diagnosis and epidemiological surveillance of the A and B variants of ERV. METHODS: TaqMan primer probe sets for ERAV and ERBV were designed from conserved regions of the 5' UTR of the ERV genome. Over 400 samples from both clinically affected and asymptomatic horses were employed for validation of the assays. ERAV samples positive by rRT-PCR were verified by virus isolation and ERBV positive samples were verified by rRT-PCR using a different set of primers. RESULTS: The detection limit of the rRT-PCR for both viruses was 10-100 genome copies. Of 250 archival nasal swabs submitted for diagnostic testing over a 7 year period, 29 were ERAV positive and 3 were ERBV positive with an average incidence rate per year of 10 and 1.5%, respectively. There was evidence of co-circulation of ERAV and ERBV with equine influenza virus (EIV). Of 100 post race urine samples tested, 29 were ERAV positive by rRT-PCR. Partial sequencing of 2 ERBV positive samples demonstrated that one was 100% identical to ERBV1 from a 270 bp sequence and the other was more closely related to ERBV2 than ERBV1 (95% compared to 90% nucleotide identity in 178 bp). CONCLUSIONS: The rRT-PCR assays described here are specific and more sensitive than virus isolation. They have good reproducibility and are suitable for the routine diagnosis of ERAV and ERBV. POTENTIAL RELEVANCE: These assays should be useful for investigating the temporal association between clinical signs and rhinitis virus shedding.

Influenza A viruses with truncated NS1 as modified live virus vaccines: pilot studies of safety and efficacy in horses.

REASONS FOR PERFORMING STUDY: Three previously described NS1 mutant equine influenza viruses encoding carboxy-terminally truncated NS1 proteins are impaired in their ability to inhibit type I IFN production in vitro and are replication attenuated, and thus are candidates for use as a modified live influenza virus vaccine in the horse. HYPOTHESIS: One or more of these mutant viruses is safe when administered to horses, and recipient horses when challenged with wild-type influenza have reduced physiological and virological correlates of disease. METHODS: Vaccination and challenge studies were done in horses, with measurement of pyrexia, clinical signs, virus shedding and systemic proinflammatory cytokines. RESULTS: Aerosol or intranasal inoculation of horses with the viruses produced no adverse effects. Seronegative horses inoculated with the NS1-73 and NS1-126 viruses, but not the NS1-99 virus, shed detectable virus and generated significant levels of antibodies. Following challenge with wild-type influenza, horses vaccinated with NS1-126 virus did not develop fever (>38.5 degrees C), had significantly fewer clinical signs of illness and significantly reduced quantities of virus excreted for a shorter duration post challenge compared to unvaccinated controls. Mean levels of proinflammatory cytokines IL-1beta and IL-6 were significantly higher in control animals, and were positively correlated with peak viral shedding and pyrexia on Day +2 post challenge. CONCLUSION AND CLINICAL RELEVANCE: These data suggest that the recombinant NS1 viruses are safe and effective as modified live virus vaccines against equine influenza. This type of reverse genetics-based vaccine can be easily updated by exchanging viral surface antigens to combat the problem of antigenic drift in influenza viruses.

A case of varicella caused by co-infection with two different genotypes of varicella-zoster virus.

We describe for the first time a case of varicella caused by co-infection with 2 genotypes of Varicella-zoster virus in a 19 month old child 3 days post-immunization with the varicella live vaccine. The presence of 2 different wild-type viruses in vesicular fluid was confirmed by amplification from single virus genomes and genotyping of single nucleotide polymorphisms (SNPs) known to distinguish the 5 different genotypes of VZV. The finding has important implications for recombination of wild type VZV.

Diagnosis of equine infectious anaemia during the 2006 outbreak in Ireland.

In 2006 there was an outbreak of equine infectious anaemia (EIA) in Ireland. This paper describes the use of the diagnosis of clinical and subclinical cases of the disease. In acute cases the ELISAs and the immunoblot were more sensitive than the AGID. In one mare, fluctuating antibody levels were observed in all the serological assays before it seroconverted by AGID. Viral RNA and DNA were detected by RT-PCR and PCR in all the tissues from the infected animals examined postmortem. The PCR detected viral DNA in plasma regardless of the stage of the disease. In contrast, the RT-PCR detected RNA in only 52 per cent of the seropositive animals tested and appeared to be most sensitive for the detection of virus early in infection. Both PCR and RT-PCR demonstrated potential to detect acutely infected horses earlier than some of the official tests. The serological data suggest that the usual incubation/seroconversion period for this strain of the virus was approximately 37 days but may be more than 60 days in a few cases.

Varicella-zoster-virus genotypes in East London: a prospective study in patients with herpes zoster.

A total of 298 patients with herpes zoster were recruited as part of 2 community-based studies in East London between 1998 and 2003. Single nucleotide-polymorphism analysis of 4 regions (genes 1, 21, 37, and 60) found that most genotypes were European strains C and B, representing 58% and 21% of all samples collected. No change in the proportion of these European clades has occurred during the past 80 years, strongly supporting the hypothesis that these strains are indigenous to the United Kingdom. White patients almost exclusively had reactivation of genotypes C (66%) and B (21%), whereas patients from Africa, Asia, or the Caribbean mainly had reactivation of genotypes A and J. An increase in BglI-positive A and J genotypes in UK cases of zoster is only partly explained by immigration from endemic regions. The data presented provide a baseline against which to evaluate changes in the molecular epidemiology of varicella-zoster virus and the effect of immunization with the Japanese Oka vaccine strain.

Effect of viral load on the outcome of herpes zoster.

Varicella-zoster virus (VZV) is a member of the Herpesviridae family, primary infection with which causes varicella, more commonly known as chicken pox. Characteristic of members of the alphaherpesvirus subfamily, VZV is neurotropic and establishes latency in sensory neurons. Reactivation of VZV causes herpes zoster, also known as shingles. The most frequent complication following zoster is chronic and often debilitating pain called postherpetic neuralgia (PHN), which can last for months after the disappearance of a rash. During episodes of acute zoster, VZV viremia occurs in some, but not all, patients; however, the effect of the viral load on the disease outcome is not known. Here we describe the development of a highly specific, sensitive, and reproducible real-time PCR assay to investigate the factors that may contribute to the presence and levels of baseline viremia in patients with zoster and to determine the relationship between viremia and the development and persistence of PHN. VZV DNA was detected in the peripheral blood mononuclear cells (PBMCs) of 78% of patients with acute zoster and in 9% of healthy asymptomatic blood donors. The presence of VZV in the PBMCs of patients with acute zoster was independently associated with age and being on antivirals but not with gender, immune status, extent of rash, the age of the rash at the time of blood sampling, having a history of prodromal pain, or the extent of acute pain. Prodromal pain was significantly associated with higher baseline viral loads. Viral load levels were not associated with the development or persistence of PHN at 6, 12, or 26 weeks.

Real-time quantitative RT-PCR and PCR assays for a novel European field isolate of equine infectious anaemia virus based on sequence determination of the gag gene.

In 2006, an outbreak of equine infectious anaemia (EIA) occurred in Ireland. The initial source of the outbreak is believed to have been contaminated plasma imported from Italy. This paper presents the nucleotide sequence of the gag gene of the virus identified in Ireland (EIAV(Ire)), the first for a European strain of EIAV. Comparison of the gag gene with North American and Asian strains of the virus showed that the gag gene is less well conserved than previously believed, and that EIAV strains can have similar phenotypes despite considerable variations in genotype. On the basis of the deduced sequence of the EIAV(Ire) gag gene, highly sensitive, specific and quantitative RT-PCR and PCR assays were developed, and used to quantify the EIAV nucleic acid in postmortem tissues, plasma and secretions of infected horses. This is the first report of the detection and quantification of EIAV in nasal, buccal and genital swabs by RT-PCR.

Genotyping of varicella-zoster virus and the discrimination of Oka vaccine strains by TaqMan real-time PCR.

Single nucleotide polymorphisms (SNPs) in five genes have been used to identify four major subtypes of wild-type varicella-zoster virus (VZV) A, B, C, and J. Additional SNPs, located in the IE62 major transactivating gene can be used to differentiate the Oka vaccine strain (vOka) from wild-type VZV. Primer-probe sets for the detection of the five polymorphic loci were designed by Applied Biosystems for the ABI 7900HT platform. Probes for each allele were labeled with VIC or 6-carboxyfluorescein fluorogenic markers. Each primer-probe set was validated to establish assay sensitivity and specificity using VZV DNA of predetermined copy number and genotype. Further evaluation was carried out using DNA samples from the vesicle fluid or skin swab of the rash of adult patients with herpes zoster or rashes due to vOka. Assay sensitivity ranged from 10 and 10(8) copies/ml of VZV DNA (equivalent to 2 to 20 copies per reaction). Statistical analyses showed that for each genotype, a set of two probes clearly differentiated the nucleotide present (allele) at that locus (P < 0.0001). It was possible to determine the genotype of wild-type VZV using one of four SNP assays and also to differentiate wild type from vOka using a single SNP assay. The assay can be used for diagnostic and epidemiological studies of VZV, including the differentiation of vOka from wild-type strains, investigation of breakthrough infections, and varicella outbreaks following immunization.

Reactivation of 2 genetically distinct varicella-zoster viruses in the same individual.

Varicella-zoster viruses recovered from 2 episodes of herpes zoster in an immunocompetent man were found to be different genotypes. The fact that the 2 isolates came from the same individual was confirmed by DNA fingerprinting. Immunity following chickenpox may not always protect against systemic reinfection. This finding raises questions about varicella-zoster virus pathogenesis and may have an impact on public health policy.

Behavioural effects of parafascicular thalamic lesions in an animal model of parkinsonism.

We recently reported that the centromedian-parafascicular thalamic complex (CM-Pf) degenerates in Parkinson's disease and progressive supranuclear palsy. The contribution of such thalamic pathology to disease symptoms has not yet been established. The present study therefore investigated the behavioural impact of lesioning the corresponding thalamic region (termed Pf) on a range of behaviours present in rodents. There were four surgical groups: (1) sham medial forebrain bundle (mfb)+sham Pf, (2) 6-OHDA mfb lesion+sham Pf, (3) sham mfb+NMDA Pf lesion, (4) 6-OHDA+NMDA Pf lesions. Posture, sensory functions and apomorphine-induced rotational asymmetry were assessed before and after each surgery. Other assessments performed including a timed motivational task, grooming behaviours and piloerection. 6-OHDA lesions induced postural (ipsilateral curling and head position biases), sensorimotor (increased latency to respond to tactile stimulation of the contralateral side when eating or grooming) and rotational abnormalities (contralateral circling after apomorphine). The main effects of combined 6-OHDA+Pf lesions were improved performance in a motivational task (decreased latency to retrieve reward) but worsened piloerection, relative to animals with either 6-OHDA or Pf lesions alone. The thalamic zone common to all lesioned animals involved the posterior Pf. Our data suggests that the posterior CM-Pf may be involved in motivational responses and autonomic dysfunction in parkinsonian disorders.

The relationship of the Allen Cognitive Level Test to demographics, diagnosis, and disposition among psychiatric inpatients.

OBJECTIVE: This study examined the relationship of the Allen Cognitive Level Test (ACL) to demographics, diagnosis, and disposition after hospitalization among persons with psychiatric disorders. METHOD: Data were retrospectively collected from medical records, including initial occupational therapy evaluation notes, on 62 female and 38 male patients consecutively admitted to an urban, acute psychiatric inpatient unit. Collected was information on demographics, diagnosis, mental and physical health history, initial ACL scores, role involvement, and discharge living situation (DLS). RESULTS: Patients with higher initial ACL scores were more likely to be younger, to have lived independently before admission, to have been given nonpsychotic diagnoses, and to have been suicidal before admission. Although DLS was most strongly correlated with living situation before admission, ACL scores showed the second strongest correlation to DLS. Patients with higher ACL scores were significantly more likely to be discharged to independent living than were patients with lower ACL scores. CONCLUSIONS: These results provide evidence that patients' cognitive level, as measured by the ACL, may be a useful predictor of community functioning. However, further research is needed to validate the Cognitive Disabilities Model.