Patient-reported outcome measurements in facial skin surgery and a comparison between Mohs micrographic surgery and conventional excisions.

BACKGROUND: Knowledge of the psychosocial impact of facial skin surgery on patients can help improve counselling strategies. OBJECTIVES: The objective was to measure the psychological impact of facial skin cancer surgery on patients over a 1-year period. Secondary objective was to measure the difference between Mohs micrographic surgery (MMS) and conventional excision (CE) on these parameters. METHODS: This observational survey study was conducted between March 2019 and July 2020. Patients who had facial skin surgery using MMS or CE were selected. Five surveys were conducted on four timepoints (preoperative, 1 week, 3 months and 1 year post-operative) measuring the quality of life, perceived stigmatization, body image, satisfaction with facial appearance and psychosocial distress. RESULTS: A total of 228 patients (MMS 154 patients, CE 74 patients) were included for the analysis. Scores for quality of life did not significantly change, in the year after surgery (PCS-12 mean 50.5, SD 9.3 and MCS-12 50.6, SD 9.4); however, stigmatization (F (3, 235,39) 7,26, p < 0.01, d = -0.07), body image concerns (F (3, 198,28) = 3.75, p < 0.01, d = -0.14), satisfaction with facial appearance (F (3, 205,18) = 10.74, p < 0.01, d = 0.43) and psychosocial distress (F (3, 208,69) = 9.26, p < 0.01, d = -0.15) did change over time. The use of MMS or CE did not significantly affect outcome scores after 1 year. CONCLUSION: Patients receiving facial skin cancer surgery exhibited low scores for perceived stigmatization and body image concerns. Their quality of life was not statistically influenced by facial surgery, and their satisfaction with their facial appearance and psychosocial distress even improved after 1 year. The results suggest that the surgical treatment type (MMS or CE) does not influence the outcome. The overall results can help in counselling strategies to improve expectations for patients receiving facial surgery.

Validity of a two-antibody testing algorithm for mismatch repair deficiency testing in cancer; a systematic literature review and meta-analysis.

Reflex mismatch repair immunohistochemistry (MMR IHC) testing for MLH1, PMS2, MSH2 and MSH6 is used to screen for Lynch syndrome. Recently MMR-deficiency (MMRd) has been approved as a pan-cancer predictive biomarker for checkpoint inhibitor therapy, leading to a vast increase in the use of MMR IHC in clinical practice. We explored whether immunohistochemical staining with PMS2 and MSH6 can be used as a reliable substitute. This two-antibody testing algorithm has the benefit of saving tissue, cutting costs and saving time. PubMed, Embase and Cochrane library were systematically searched for articles reporting on MMR IHC. The weighed percentage of cases with isolated MLH1 or MSH2 loss or combined MLH1/MSH2 loss alone was analyzed using a random effects model meta-analysis in R. The search yielded 1704 unique citations, of which 131 studies were included, describing 9014 patients. A weighed percentage of 1.1% (95% CI 0.53-18.87, I = 87%) of cases with isolated MLH1 or MSH2 loss or combined MLH1/MSH2 loss alone was observed. In the six articles with the main aim of investigating the two-antibody testing algorithm all MMRd cases were detected with the two-antibody testing algorithm, there were no cases with isolated MLH1 or MSH2 loss or combined MLH1/MSH2 loss alone. This high detection rate of MMRd of the two-antibody testing algorithm supports its use in clinical practice by specialized pathologists. Staining of all four antibodies should remain the standard in cases with equivocal results of the two-antibody testing algorithm. Finally, educational sessions in which staining pattern pitfalls are discussed will continue to be important.

Predictive Parameters in Patients Undergoing Percutaneous Hepatic Perfusion with Melphalan for Unresectable Liver Metastases from Uveal Melanoma: A Retrospective Pooled Analysis.

PURPOSE: The aim of this study was to identify positive predictors for survival in uveal melanoma (UM) patients treated with percutaneous hepatic perfusion with melphalan (M-PHP), by retrospectively pooling data from three centers. MATERIALS AND METHODS: Retrospective analysis including patients ([Formula: see text] 18 years) treated with M-PHP between February 2014 and December 2019 for unresectable liver-dominant or liver-only metastases from UM. Predictors for OS were assessed using uni- and multivariate analyses. Other study outcome measures were response rate, progression-free survival (PFS), liver progression-free survival (LPFS), overall survival (OS) and complications according to CTCAEv5.0. RESULTS: In total, 101 patients (47.5% males; median age 59.0 years) completed a minimum of one M-PHP. At a median follow-up time of 15.0 months, complete response (CR), partial response (PR), stable disease (SD) and progressive disease were seen in five (5.0%), 55 (54.5%), 30 (29.7%) and 11 (10.9%) patients, respectively, leading to a 89.1% disease control rate. Median PFS, LPFS and OS were 9.0, 11.0 and 20.0 months, respectively. Survival analyses stratified for radiological response demonstrated significant improved survival in patients with CR or PR and SD category. Treatment of the primary tumor with radiotherapy, ≥ 2 M-PHP and lactate dehydrogenase (LDH) < 248 U/L were correlated with improved OS. Thirty-day mortality was 1.1% (n = 2). Most common complication was hematological toxicity (self-limiting in most cases). CONCLUSION: M-PHP is safe and effective in patients with UM liver metastases. Achieving CR, PR or SD is associated with improved survival. Primary tumor treatment with radiotherapy, normal baseline LDH and > 1 M-PHP cycles are associated with improved OS.

Risk factors for incomplete excision of cutaneous squamous cell carcinoma: a large cohort study.

BACKGROUND: The standard treatment for cutaneous squamous cell carcinoma (cSCC) is surgical excision. Failure to radically remove a cSCC is a risk for recurrence, progression and metastasis. OBJECTIVES: This study investigates several risk factors for incomplete excision of cSCC. METHODS: All consecutive patients in a single institution treated with wide local excision for primary cSCC over a 10-year period were included in this study. Risk factors such as: gender, age, immunosuppression, tumour size, location, differentiation grade, tumour depth, perineural and lymphovascular invasion (PNI and LVI) were extracted from the database. Univariable and (if applicable) multivariable logistic regression analysis were used to identify risk factors (P < 0.05). Generalized estimating equations (GEEs) were used for multiple tumours within the same patients. RESULTS: A total of 566 patients with 1159 cSCC were identified. Univariable and multivariable logistic regression analysis showed that depth beyond the dermis (OR: 5.7 95% CI: 3.1-10.5) was the only risk factor for incomplete excision of cSCC. Immunosuppression was only a risk factor in the deep plane (OR: 2.5, 95% CI: 1.3-4.6). CONCLUSION: Tumour depth beyond the dermis is the most important risk factor for incomplete excision of cSCC. Immunosuppression is a risk factor in the deep plane but its relevance is uncertain. Immunosuppression is not consistently included in the current cSCC staging systems, but care should be taken when treating these patients.

HPV type-specific distribution among family members and linen in households of cutaneous wart patients.

BACKGROUND: Common and plantar warts are caused by human papillomaviruses (HPV). Mode of transmission of wart HPVs within families is largely unknown. OBJECTIVE: To demonstrate similarity of HPV type(s) among wart cases, family members and household linen. METHODS: In a cross-sectional study, swabs taken from 123 warts and foreheads of 62 index patients and 157 family members and from 58 kitchen towels and 59 bathroom mats were tested for DNA of 23 cutaneous wart-associated HPV types. Generalized estimating equations (GEE) were used to estimate the chance of detecting the same HPV type as was found in the index patients on the family contacts and on the kitchen towels and bathroom mats. RESULTS: HPV1, HPV2, HPV27 and HPV57 were the most prevalent types in the warts of the index patients. Altogether, 60 (42.3%) of the 142 family members without warts had HPV DNA on their foreheads. When HPV1 and HPV2 were found in the warts, these types were also frequently (>50%) found on the foreheads of index patients and their family members, as well as on the kitchen towels and the bathroom mats. HPV27 and HPV57 were less frequently found (<25%) on foreheads and linen. No associations were found for age, sex and site of HPV DNA presence. CONCLUSION: Dissemination of skin wart-causing HPV types, from wart cases to household contacts and linen, such as kitchen towels and bathroom mats, is more likely for HPV1 and HPV2 than for HPV27 and HPV57. The role of towels and bathroom mats in HPV transmission deserves further investigation.

Dynamics of the bacterial gut microbiota during controlled human infection with Necator americanus larvae.

Hookworms are soil-transmitted helminths that use immune-evasive strategies to persist in the human duodenum where they are responsible for anemia and protein loss. Given their location and immune regulatory effects, hookworms likely impact the bacterial microbiota. However, microbiota studies struggle to deconvolute the effect of hookworms from confounders such as coinfections and malnutrition. We thus used an experimental human hookworm infection model to explore temporal changes in the gut microbiota before and during hookworm infection. Volunteers were dermally exposed to cumulative dosages of 50, 100 or 150 L3 Necator americanus larvae. Fecal samples were collected for microbiota profiling through 16S rRNA gene amplicon sequencing at weeks zero, four, eight, fourteen and twenty. During the acute infection phase (trial week zero to eight) no changes in bacterial diversity were detected. During the established infection phase (trial week eight to twenty), bacterial richness (Chao1, p = .0174) increased significantly over all volunteers. No relation was found between larval dosage and diversity, stability or relative abundance of individual bacterial taxa. GI symptoms were associated with an unstable microbiota during the first eight weeks and rapid recovery at week twenty. Barnesiella, amongst other taxa, was more abundant in volunteers with more GI symptoms throughout the study. In conclusion, this study showed that clinical GI symptoms following N. americanus infection are associated with temporary microbiota instability and relative abundance of specific bacterial taxa. These results suggest a possible role of hookworm-induced enteritis on microbiota stability.

Microarray Gene Expression Analysis to Evaluate Cell Type Specific Expression of Targets Relevant for Immunotherapy of Hematological Malignancies.

Cellular immunotherapy has proven to be effective in the treatment of hematological cancers by donor lymphocyte infusion after allogeneic hematopoietic stem cell transplantation and more recently by targeted therapy with chimeric antigen or T-cell receptor-engineered T cells. However, dependent on the tissue distribution of the antigens that are targeted, anti-tumor responses can be accompanied by undesired side effects. Therefore, detailed tissue distribution analysis is essential to estimate potential efficacy and toxicity of candidate targets for immunotherapy of hematological malignancies. We performed microarray gene expression analysis of hematological malignancies of different origins, healthy hematopoietic cells and various non-hematopoietic cell types from organs that are often targeted in detrimental immune responses after allogeneic stem cell transplantation leading to graft-versus-host disease. Non-hematopoietic cells were also cultured in the presence of IFN-γ to analyze gene expression under inflammatory circumstances. Gene expression was investigated by Illumina HT12.0 microarrays and quality control analysis was performed to confirm the cell-type origin and exclude contamination of non-hematopoietic cell samples with peripheral blood cells. Microarray data were validated by quantitative RT-PCR showing strong correlations between both platforms. Detailed gene expression profiles were generated for various minor histocompatibility antigens and B-cell surface antigens to illustrate the value of the microarray dataset to estimate efficacy and toxicity of candidate targets for immunotherapy. In conclusion, our microarray database provides a relevant platform to analyze and select candidate antigens with hematopoietic (lineage)-restricted expression as potential targets for immunotherapy of hematological cancers.

Identification of biomarkers for tuberculosis disease using a novel dual-color RT-MLPA assay.

Owing to our lack of understanding of the factors that constitute protective immunity during natural infection with Mycobacterium tuberculosis (Mtb), there is an urgent need to identify host biomarkers that predict long-term outcome of infection in the absence of therapy. Moreover, the identification of host biomarkers that predict (in)adequate response to tuberculosis (TB) treatment would similarly be a major step forward. To identify/monitor multi-component host biomarker signatures at the transcriptomic level in large human cohort studies, we have developed and validated a dual-color reverse-transcriptase multiplex ligation-dependent probe amplification (dcRT-MLPA) method, permitting rapid and accurate expression profiling of as many as 60-80 transcripts in a single reaction. dcRT-MLPA is sensitive, highly reproducible, high-throughput, has an extensive dynamic range and is as quantitative as QPCR. We have used dcRT-MLPA to characterize the human immune response to Mtb in several cohort studies in two genetically and geographically diverse populations. A biomarker signature was identified that is strongly associated with active TB disease, and was profoundly distinct from that associated with treated TB disease, latent infection or uninfected controls, demonstrating the discriminating power of our biomarker signature. Identified biomarkers included apoptosis-related genes and T-cell/B-cell markers, suggesting important contributions of adaptive immunity to TB pathogenesis.

Inhibition of Gsk3ß in cartilage induces osteoarthritic features through activation of the canonical Wnt signaling pathway.

OBJECTIVE: In the past years, the canonical Wnt/ß-catenin signaling pathway has emerged as a critical regulator of cartilage development and homeostasis. In this pathway, glycogen synthase kinase-3ß (GSK3ß) down-regulates transduction of the canonical Wnt signal by promoting degradation of ß-catenin. In this study we wanted to further investigate the role of Gsk3ß in cartilage maintenance. DESIGN: Therefore, we have treated chondrocytes ex vivo and in vivo with GIN, a selective GSK3ß inhibitor. RESULTS: In E17.5 fetal mouse metatarsals, GIN treatment resulted in loss of expression of cartilage markers and decreased chondrocyte proliferation from day 1 onward. Late (3 days) effects of GIN included cartilage matrix degradation and increased apoptosis. Prolonged (7 days) GIN treatment resulted in resorption of the metatarsal. These changes were confirmed by microarray analysis showing a decrease in expression of typical chondrocyte markers and induction of expression of proteinases involved in cartilage matrix degradation. An intra-articular injection of GIN in rat knee joints induced nuclear accumulation of ß-catenin in chondrocytes 72 h later. Three intra-articular GIN injections with a 2 days interval were associated with surface fibrillation, a decrease in glycosaminoglycan expression and chondrocyte hypocellularity 6 weeks later. CONCLUSIONS: These results suggest that, by down-regulating ß-catenin, Gsk3ß preserves the chondrocytic phenotype, and is involved in maintenance of the cartilage extracellular matrix. Short term ß-catenin up-regulation in cartilage secondary to Gsk3ß inhibition may be sufficient to induce osteoarthritis-like features in vivo.

Prevalence and incidence of dementia among 75-80-year-old community-dwelling elderly in different districts of Antwerp, Belgium: the Antwerp Cognition (ANCOG) Study.

OBJECTIVE: To analyse the prevalence and incidence of dementia in a population of community-dwelling elderly (aged 75-80), living in socio-economically differing districts of Antwerp (Belgium), taking into account possible gender and educational differences. METHODS: A longitudinal cohort study (N=825) with a 3-year follow-up period (N=363). The Mini Mental State Examination (MMSE) was used as a primary screen of cognitive functioning. Scoring 21 or below led to a second phase examination by a neurologist, including the CAMDEX-R-N and a neurological examination, to provide a tentative aetiological diagnosis of dementia. These procedures were conducted annually during a 3-year follow-up period. RESULTS: In accordance with international literature, the overall prevalence rate of dementia was 8.7%. The cumulative incidence rate (IR) of dementia was 36.60 per 1000Py with annual IRs ranging from 34.39 over 35.16 to 49.04 per 1000Py. Dementia of the Alzheimer type (DAT) was the most occurring prevalent and incident cause. Women appeared to be at higher risk and the occurrence of cognitive deterioration was more prominent in districts with lower socio-economic status, possibly related to a lower education level. CONCLUSION: We demonstrate dementia is a considerable health problem in an urban Belgian population of community-dwelling elderly aged between 75 and 80 years old. In order to prepare health care and social security systems for the future management of dementia, proper epidemiological insight into the current and future magnitude of the burden of dementia, taking into account socio-economic differences, to which this study contributes, are required.

Synthesis, radiosynthesis and in vivo evaluation of [I]-4-(2-(bis(4-fluorophenyl)methoxy)ethyl)-1-(4-iodobenzyl)piperidine as a selective tracer for imaging the dopamine transporter.

Dopamine transporter (DAT) neuroimaging is a useful tool in Parkinson's disease diagnosis, staging and follow-up providing information on the integrity of the dopaminergic neurotransmitter system in vivo. 4-(2-(Bis(4-fluorophenyl)-methoxy)ethyl)-1-(4-iodobenzyl)piperidine (7) has nanomolar affinity for DAT and better selectivity over the other monoamine transporters compared with the existing SPECT radioligands for DAT. The aim of this study was to synthesize and evaluate [(123)I]-7 as an in vivo tracer for DAT.The tributylstannyl precursor was synthesized with an overall yield of 25%. [(123)I]-7 was synthesized by electrophilic destannylation with a yield of 40±10%. Radiochemical purity appeared to be >98%, whereas specific activity was at least 667 GBq/µmol. Biodistribution studies in mice showed brain uptake of 0.96±0.53%ID/g at 30 s post injection (p.i.) and 0.26±0.02%ID/g at 3 h p.i. High blood activity was observed at all time points. Pretreatment with Cyclosporin A raised brain uptake indicating that [(123)I]-7 is transported by P-glycoprotein (P-gp) pumps. In rats, regional brain distribution of [(123)I]-7 was not in agreement with DAT distribution. These results indicate that [(123)I]-7 is not suitable for mapping DAT in vivo but could be a useful tracer for the P-gp transporter.

Prospective Belgian study of neurodegenerative and vascular dementia: APOE genotype effects.

OBJECTIVE: The authors conducted a prospective study of neurodegenerative and vascular dementia in Belgium. Strict diagnostic inclusion criteria were used to include well defined patients and controls. The results of apolipoprotein E (APOE) genotype effect on risk and clinical characteristics are presented. METHODS: APOE genotyping was performed in patients with probable Alzheimer's disease (AD) (n=504), frontotemporal dementia (FTD) (n=47), vascular dementia (VaD) (n=152), mixed dementia (n=132), mild cognitive impairment (MCI) (n=44), Parkinson's disease (PD) (n=30), dementia with Lewy bodies (DLB) (n=17), and multisystem atrophy (MSA)/progressive supranuclear palsy (PSP) (n=12). RESULTS: The APOE allele frequencies of this Belgian control population (epsilon 2: 6.9%; epsilon 3: 76.2%; epsilon 4: 16.9%) did not differ from those reported for other white populations. AD, MCI, and mixed dementia patients had higher APOE epsilon 4 (32.9%, 38.6%, and 28.4% respectively) and lower APOE epsilon 3 (62.2%, 53.4%, and 66.3%) frequencies compared with controls, whereas only AD and mixed dementia patients had lower APOE epsilon 2 frequencies (4.9% and 5.3%). Apart from a borderline significant different distribution of APOE allele frequencies in VaD patients compared with controls, no other differences were detected. The influence of APOE epsilon 4 on clinical features of dementia was limited to lower age at onset in AD patients and a less pronounced negative correlation between age at onset and number of epsilon 4 alleles in MCI and mixed dementia patients. CONCLUSIONS: This study confirmed the risk association between APOE epsilon 4 and AD. The observation that APOE epsilon 4 is associated with mixed dementia reflected the role of AD in the aetiopathogenesis of this condition. Although MCI is an aetiologically heterogeneous syndrome, the increased APOE epsilon 4 frequencies indicated that a large proportion of the MCI patients included in the study might be predisposed to develop AD.

Alkyl-lysophospholipid 1-O-octadecyl-2-O-methyl- glycerophosphocholine induces invasion through episialin-mediated neutralization of E-cadherin in human mammary MCF-7 cells in vitro.

1-O-octadecyl-2-O-methyl-glycerophosphocholine (ET-18-OMe) is an analogue of the naturally occurring 2-lysophosphatidylcholine belonging to the class of antitumor lipids. Previously, we demonstrated that ET-18-OMe modulates cell-cell adhesion of human breast cancer MCF-7 cells. In the present study, we tested the effect of ET-18-OMe on adhesion, invasion and localisation of episialin and E-cadherin in MCF-7/AZ cells expressing a functional E-cadherin/catenin complex. The MCF-7/6 human breast cancer cells were used as negative control since their E-cadherin/catenin complex is functional in cells grown on solid substrate but not in suspension. The function of E-cadherin, a calcium-dependent transmembrane cell-cell adhesion and signal-transducing molecule, is disturbed in invasive cancers by mutation, loss of mRNA stability, proteolytic degradation, tyrosine phosphorylation of associated proteins and large cell-associated proteoglycans or mucin-like molecules such as episialin. Episialin, also called MUC1, is an anti-adhesion molecule that by its large number of glycosylated tandem repeats can sterically hinder the adhesive properties of other glycoproteins. ET-18-OMe inhibited the E-cadherin functions of MCF-7/AZ cells as measured by inhibition of fast and slow aggregation and by the induction of collagen invasion. These effects were enhanced by MB2, an antibody against E-cadherin and blocked by monoclonal antibodies (MAbs) 214D4 or M8 against episialin. ET-18-OMe had no influence on tyrosine phosphorylation of beta-catenin and the E-cadherin/catenin complex remained intact. Transcription, translation, protein turnover and cell surface localisation of episialin were not altered. ET-18-OMe induced finger-like extensions with clustering of episialin together with E-cadherin and carcinoembryonic antigen but not with occludin. In cells in suspension, ET-18-OMe caused a shift in the flow-cytometric profile of episialin toward a lower intensity for MCF-7/AZ cells. In contrast with MCF-7/AZ cells, the adhesion-deficient and noninvasive MCF-7/6 cells showed neither morphotypic changes nor induction of aggregation nor invasion in collagen I upon treatment with ET-18-OMe. Co-localisation of episialin with E-cadherin was rarely observed. We conclude that in the human breast cancer cells MCF-7/AZ, E-cadherin and episialin are key molecular players in the regulation of promotion and suppression of cell-cell adhesion and invasion.

Sudan-ß-d-glucuronides and their use for the histochemical localization of ß-glucuronidase activity in transgenic plants.

Synthesis of five different Sudan-ß-D-glucuronides (I, II, III, IV, and RedB) was performed by condensation of a set of red Sudan diazo dyes with methyl (1-deoxy-2,3,4-tri-O-acetyl-1-trichloroacetimidoyl-α-D-glucopyran)uronate. After the acid and alcohol groups had been deprotected, the resulting compounds were used for histochemical localization of ß-glucuronidase (GUS) activity in transgenic plants (Petunia hybrida, Arabidopsis thaliana, and Nicotiana tabacum) that contained the GUS reporter system. Because the cleavage of the ß-glucuronide results in the liberation of an insoluble Sudan dye, Sudan substrates gave no diffusion artifacts as described for the commonly used 5-bromo-4-chloro-3-indolyl-ß-D-glucuronide (X-gluc). A comparison of assays with different Sudan glucuronides and X-gluc demonstrated that the SudanIV variant is a valuable glucuronide substrate for the precise histochemical localization of GUS activity in transgenic plants.

From neuronal and vascular impairment to dementia.

This paper reviews aspects of existing knowledge and recent concepts related to the development of vascular dementia which, after Alzheimer's disease, is the most frequent type of dementia. The disorder may result from cerebrovascular disorders, including multi-infarct dementia due to thromboembolic disease, other less common vasculopathies and ischemic brain damage secondary to systemic hypotension. Characteristic clinical features are stepwise cognitive deterioration resulting from repeated strokes and the presence of focal signs and symptoms. The clinical distinction between Alzheimer's disease and vascular dementia may be difficult and strict criteria (NINDS/ AIREN) have recently been adopted as standard guidelines for research studies. Vascular dementia and Alzheimer's disease can co-exist, so-called "mixed dementia", and the presence of cerebrovascular disease may worsen Alzheimer dementia. Indeed, there is often a vascular component in the pathogenesis of dementia. The pathogenesis of vascular dementia is complex. Post-stroke patients are at increased risk; some predisposing or risk factors are the volume, number and site (whether strategic or not) of cerebral injuries, distal field vascular injury with reduced cerebral blood flow, white matter ischemia due to small vessel disease, the co-existence of vascular disease and Alzheimer's dementia, and the presence of cognitive decline prior to stroke. There is increasing evidence of a complex relationship between vascular dementia and Alzheimer's disease. When post-stroke dementia is progressive this may reflect associated Alzheimer's disease either unrecognized or asymptomatic prior to the stroke. The apolipoprotein E4 genotype is a risk factor for ischemic stroke, vascular dementia and Alzheimer dementia. Although dementia is usually irreversible, it is now accepted that cognitive impairment may be delayed, stabilized or sometimes reversed. The treatment of vascular dementia consists of two approaches: preventive measures, including attempts to control risk factors for stroke and the use of antiplatelet agents and/or surgery, and the treatment of cognitive symptoms. Nootropic and vasodilator agents have been reported to improve cognitive impairment from various causes. Ongoing research is attempting to show their specific benefit in vascular dementia.

Superoxide dismutase activity in cerebrospinal fluid of patients with dementia and some other neurological disorders.

Data on superoxide dismutase (SOD) activity in the cerebrospinal fluid (CSF) of patients suffering from dementia (n=32) as compared with a control group (n=58), a Parkinson disease (PD) patient group (n=12), and a group of individuals suffering from epilepsy (n=13) are presented. SOD activity was determined by electron spin resonance spectrometry using the spin trap method. No significant correlation was found between CSF SOD activity and age in the control group. In addition, CSF SOD activity was not gender dependent. One-way analysis of variance showed a highly significant between-groups effect for the CSF SOD activity and specific CSF SOD activity of the four major groups (p=0.0008). Post hoc comparison (Fisher PLSD test) revealed significant differences between the control group and the total dementia group (p < 0.001), between the dementia group and the epilepsy group (p < 0.01), and between the dementia group and the PD group (p < 0.05). The CSF of patients with PD or epilepsy showed a similar SOD activity as the CSF of control patients. In addition, CSF SOD activity levels were significantly lower in the total dementia group (p=0.002) and in the group with dementia of the Alzheimer type (DAT) (p=0.001) than in the dementia age-matched control group. No significant difference was found for CSF SOD activity levels between the control group and the non-DAT dementia group. This result corresponded with a reduction of CSF SOD activity in the total dementia group, DAT subgroup, and non-DAT subgroup of 37, 43, and 22%, respectively. No significant correlation between the Mini-Mental State Examination score and CSF SOD activity was found in DAT. The lowered CSF SOD activity in Alzheimer disease, as demonstrated here, may reflect impaired radical defense mechanisms and may have possible pathophysiological significance.

Discriminative use of SPECT in frontal lobe-type dementia versus (senile) dementia of the Alzheimer's type.

UNLABELLED: Dementia of the Alzheimer's type [(S)DAT] and dementia with frontal features (FLD) are nosological entities with different prognoses and presumed pathophysiology. There is a need for noninvasive differential diagnostic tools. To evaluate whether SPECT perfusion imaging could discriminate between these neurodegenerative disorders, we performed a comparative study. METHODS: SPECT scans using 99mTc-hexamethylpropylene amine oxime (99mTc-HMPAO) of 21 patients with FLD were compared with those obtained in a group of 19 age- and severity-matched patients suffering from (S)DAT. Brain SPECT perfusion deficits were scored by visual qualitative analysis with respect to location, lateralization and severity. A total severity score of cerebral hypoperfusion (maximal value = 18) was calculated by adding all severity scores (scored between 0 and 3; 0 = no perfusion deficit; 1 = 13%-30% hypoperfusion; 2 = 30%-50%, hypoperfusion and 3 = > 50% hypoperfusion including breaching of the cortex) for right and left frontal, parietal and temporal lobes. Moreover, bifrontal hypoperfusion (Fa) was scored, yielding a value between 0 and 6 by adding the two frontal severity scores. RESULTS: No significant correlation was found between MMSE scores and total severity scores on SPECT. A statistically significant correlation was found between the Middelheim frontality score and frontal severity score. Statistically more significant bilateral hypoperfusion of the parietal lobes was found in the (S)DAT group. Conversely, bifrontal hypoperfusion was found more in the FLD group. Stepwise logistic regression analysis identified the severity of bifrontal hypoperfusion as the most significant contributing parameter to correctly classifying (S)DAT versus FLD on SPECT. The probability of predicting (S)DAT based on the SPECT scan is calculated with the following formula: [equation: see text] Using this equation, a value above 0.5 was predictive for (S)DAT and a calculated value under 0.5 was predictive for FLD. Using this model, 81% of the FLD group and 74% of the (S)DAT were correctly classified. CONCLUSION: Technetium-99m-HMPAO SPECT may help in discriminating FLD from (S)DAT. Bifrontal hypoperfusion was found to be the most powerful predictor of clinical classification. Further validation of the presented logistic regression model is warranted.

Dementia paralytica in a fifteen-year-old boy.

A 15-year-old boy, whose history revealed an unremarkable pregnancy, birth and neonatal period and who had shown a normal motor and mental development, presented at the hospital with deterioration of cognitive functions since the age of 7. He was bedridden with manifest ataxia involving all limbs, anisocoria and a sluggish to absent pupil reaction to light. Syphilis serology was positive with a Venereal Disease Research Laboratory (VDRL) titer of 1:256 and a Treponema pallidum Haemagglutination Assay (TPHA) titer of 1:163840. Cerebrospinal fluid (CSF) protein concentration was 55 mg/dl and CSF-leucocyte count was 14/mm3 (85% mononuclear cells). CSF-VDRL-titer was 1:16. A diagnosis of congenitally acquired dementia paralytica was made, since the boy's parents' clinical exam and serology results were suggestive for latent syphilis. Although cognition was still very much deteriorated five months following penicillin treatment, clinical examination revealed partial recuperation. Screening for syphilis should be part of routine testing in every subject presenting with cognitive deterioration, regardless of age.

Immunization with recombinant p17/p24:Ty virus-like particles in human immunodeficiency virus-infected persons.

In studies of the natural history of human immunodeficiency virus type 1 (HIV-1) infection, it has been repeatedly shown that higher-titer antibody responses to the HIV gag p24 protein correlate with less rapid disease progression. In HIV-negative persons, immunization with HIV-1 p17/p24:Ty virus-like particles (p24-VLP) induced humoral and cellular immune responses to p24. This construct was therefore studied as a potential immunotherapeutic agent with the objective of augmenting the immune response to p24 in a double-blind placebo-controlled trial involving 74 p24 antibody-positive, asymptomatic HIV-1-infected subjects with CD4 cell counts > 350/mm3. Immunization with p24-VLP was generally well tolerated. Immunization with p24-VLP did not increase p24 antibody levels and had no effect on CD4 cell counts or virus load. The failure to increase p24 antibody titers cannot entirely be explained by the subjects' immunodeficiency because most generated an antibody response to Ty, a yeast component of the immunogen.

Similar serological response to conventional therapy for syphilis among HIV-positive and HIV-negative women.

OBJECTIVES: To compare characteristics of syphilis serological reactivity in HIV positive (+) and HIV negative (-) female sex workers, as well as the serological response to therapy after treatment with intramuscular benzathine penicillin, 2.4 million U weekly, for three consecutive weeks. METHODS: Rapid plasma reagin (RPR) and Treponema pallidum haemagglutination assay (TPHA) results of 72 HIV-positive and 121 HIV-negative women reactive in both tests were assessed. The response to therapy was prospectively monitored with quantitative RPR serology in 47 HIV-positive and 73 HIV-negative patients. Cumulative probabilities of becoming nonreactive by RPR were compared at six months, one and two years after therapy. RESULTS: At enrolment, the geometric mean titres of RPR and TPHA were lower in HIV-positive patients (RPR, 1:2.6) than in HIV-negative patients (RPR, 1:3.8; p < 0.01). The evolution over time of RPR titres was similar among HIV-positive patients as compared to HIV-negative patients. Among patients with an initial RPR titre of < 1:8, 53% of HIV-positive and 44% of HIV-negative patients became RPR negative two years after therapy. Among patients with an RPR titre of 1:8 or greater at enrolment, 83% of HIV-positive and 90% of HIV-negative patients had reached at least a fourfold decline of RPR titres two years after therapy. CONCLUSIONS: Syphilis serology findings (both RPR and TPHA) may be altered in the presence of HIV infection, but the serological response to therapy was similar in HIV-positive and HIV-negative patients.