Efficacy of a web-based cognitive rehabilitation intervention for adult cancer survivors: A pilot study.

The purpose of this study was to evaluate the efficacy of a web-based cognitive rehabilitation intervention in survivors of adult-onset cancer and a sample of non-cancer community dwelling adults. Fifty-one participants were recruited and allocated to a cancer intervention group, a non-cancer intervention group, or a non-cancer waitlist group. Intervention groups completed a 4-week online program and all participants were assessed at baseline, post-intervention and 3-month follow-up. The primary outcome measure was subjective cognitive functioning. Secondary outcome measures included objective cognitive functioning, distress, quality of life (QoL), illness perception and program satisfaction. Results from the study found significant improvements on self-report measures of cognitive functioning in both treatment groups, as well as improvements on objective measures assessing attention and executive functioning. No intervention effects were observed for distress, QoL or illness perception. High participant satisfaction was observed with 75% of participants in the cancer group reporting being either "satisfied" or "very satisfied" with the program compared to 87% in the non-cancer treatment group. Initial evaluation of the program suggests that the web-based cognitive rehabilitation intervention shows potential for improving subjective and objective cognitive functioning in cancer survivors and community dwelling adults.

Psycho-oncology assessment in Chinese populations: a systematic review of quality of life and psychosocial measures.

This systematic review describes psychosocial and quality of life (QOL) measures used in psycho-oncology research with cancer patients and caregivers in China. Medline and PsycINFO databases were searched (1980-2014). Studies reviewed met the following criteria: English language; peer-reviewed; sampled Chinese cancer patients/caregivers; developed, validated or assessed psychometric properties of psychosocial or QOL outcome measures; and reported validation data. The review examined characteristics of measures and participants, translation and cultural adaptation processes and psychometric properties of the measures. Ninety five studies met review criteria. Common characteristics of studies reviewed were they: assessed primarily QOL measures, sampled patients with breast, colorectal, or head and neck cancer, and validated existing measures (>80%) originating in North America or Europe. Few studies reported difficulties translating measures. Regarding psychometric properties of the measures >50% of studies reported subscale reliabilities <α = 0.70, <50% reported test-retest reliability, and <30% reported divergent validity. Few reported sensitivity, specificity or responsiveness. Improved accuracy and transparency of reporting for translation, cultural adaptation and psychometric testing of psychosocial measures is needed. Developing support structures for translating and validating psychosocial measures would enable this and ensure Chinese psycho-oncology clinical practice and research keeps pace with international focus on patient reported outcome measures and data management.

Does Playing Mahjong Benefit Older Individuals? A Scoping Review.

Playing mahjong is a popular intellectual and social leisure activity in Asian countries. It is culturally believed that this activity is beneficial to cognitive and psychological functioning in older adults. However, empirical evidence of the benefits of playing mahjong is scant and scattered across the Western and Asian literature. This scoping review comprehensively examined previous studies of the relationships between playing mahjong and cognitive, psychological, and functional abilities in older adults, highlighted gaps in the literature, and identified directions for future research. A systematic search of the literature was conducted across thirteen Western and Asian databases. Fifty-three studies, including forty-seven observational and six intervention studies, were identified. Overall, the results of the observational studies suggested that more mahjong-playing experience was associated with better cognitive, psychological, and functional abilities. As an intervention, playing mahjong was found to enhance general cognitive abilities and short-term memory and relieve depressive symptoms. However, because most of the reviewed studies adopted a correlational methodology, the neural mechanism underlying the benefits of playing mahjong awaits further elucidation. The findings of this review suggest that more randomized controlled trials should be conducted to explore the effects of playing mahjong on higher-level cognitive functioning in older populations.

Patients with bipolar disorders share similar but attenuated prospective memory impairments with patients with schizophrenia.

BACKGROUND: Prospective memory (PM) refers to the ability to remember to carry out an intended action in the future. PM is consistently found to be impaired in individuals with schizophrenia. Bipolar disorder and schizophrenia may represent conditions along a continuum, and share similar neurocognitive and genetic architecture. This study aimed to compare the nature and extent of PM impairment in individuals with schizophrenia and bipolar disorder. METHOD: Participants were 38 out-patients with schizophrenia and 40 out-patients with bipolar disorder in an early psychosis intervention programme, and 37 healthy controls. Time-, event- and activity-based PMs were assessed using a dual-task laboratory paradigm. Self-reported PM performance was gauged using the Prospective and Retrospective Memory Questionnaire. Analysis of covariance (ANCOVA), with intelligence quotient (IQ) and education included as covariates, was used to examine group difference on various types of PM. Repeated measures of ANCOVA were used to examine the group × PM type interaction effect. Correspondence between laboratory and self-reported PM measures was examined using correlational analysis. RESULTS: The group × PM type interaction effect was not significant, but the main effect of group was significant. Patients with schizophrenia and patients with bipolar disorder both performed more poorly than healthy participants in PM. The two clinical groups did not significantly differ in PM. Laboratory and self-reported PM measures did not correlate significantly with each other. CONCLUSIONS: Patients with bipolar disorder shared a similar PM impairment with those with schizophrenia. Findings of this study extended the similarity in neurocognitive impairments between the two psychiatric disorders to PM.

BDNF and TNF-α polymorphisms in memory.

Here, we investigate the genetic basis of human memory in healthy individuals and the potential role of two polymorphisms, previously implicated in memory function. We have explored aspects of retrospective and prospective memory including semantic, short term, working and long-term memory in conjunction with brain derived neurotrophic factor (BDNF) and tumor necrosis factor-alpha (TNF-α). The memory scores for healthy individuals in the population were obtained for each memory type and the population was genotyped via restriction fragment length polymorphism for the BDNF rs6265 (Val66Met) SNP and via pyrosequencing for the TNF-α rs113325588 SNP. Using univariate ANOVA, a significant association of the BDNF polymorphism with visual and spatial memory retention and a significant association of the TNF-α polymorphism was observed with spatial memory retention. In addition, a significant interactive effect between BDNF and TNF-α polymorphisms was observed in spatial memory retention. In practice visual memory involves spatial information and the two memory systems work together, however our data demonstrate that individuals with the Val/Val BDNF genotype have poorer visual memory but higher spatial memory retention, indicating a level of interaction between TNF-α and BDNF in spatial memory retention. This is the first study to use genetic analysis to determine the interaction between BDNF and TNF-α in relation to memory in normal adults and provides important information regarding the effect of genetic determinants and gene interactions on human memory.

A systematic review of psycho-oncology research in Chinese populations: emerging trends.

The burden of cancer in China is increasing with future psycho-oncological interventions crucial. A systematic review of psycho-oncology research in China was undertaken to assess quantity, design and target trends over time. Medline, PsycINFO, CINAHL, ProQuest, Web of Science (1999-November Week 4, 2012) were searched. Inclusion criteria were: included cancer patients and/or partners or caregivers from resident Chinese populations (either at least 80% of participants are from China, Hong Kong or Taiwan); assessed psychological adjustment relating to cancer and published in English after 1 January 1999 and prior to 30 November 2012. In all, 208 articles met inclusion criteria. Of these: 52 were cross-sectional descriptive quantitative; 30 were cross-sectional descriptive qualitative; 27 were prospective descriptive quantitative; 2 were prospective descriptive qualitative; 18 assessed interventions; 79 presented instrument validation. Publications increased eightfold from 1999 to 2012. Most studies included patients (n = 195) with 11 articles focusing on caregivers and two on patient-caregiver dyads. The most common cancer studied was breast cancer. The psycho-oncology research effort in China is dramatically increasing. A focus on culturally relevant approaches to underpin the evaluation of empirically derived interventions is warranted; as is direction of efforts to other cancers such as lung and prostate.

Neural stem cells harvested from live brains by antibody-conjugated magnetic nanoparticles.

It stems from the magnetism: The extraction of stem/progenitor cells from the brain of live animals is possible using antibodies conjugated to magnetic nanoparticles (Ab-MNPs). The Ab-MNPs are introduced to a rat's brain with a superfine micro-syringe. The stem cells attach to the Ab-MNPs and are magnetically isolated and removed. They can develop into neurospheres and differentiate into different types of cells outside the subject body. The rat remains alive and healthy.

Cool and hot executive functions in medication-naive attention deficit hyperactivity disorder children.

BACKGROUND: This study aimed to compare 'cool' [working memory (WM) and response inhibition] and 'hot' (delay aversion) executive functions (EFs) in children with and without attention deficit hyperactivity disorder (ADHD). METHOD: A total of 100 ADHD children (45 with family history of ADHD and 55 with no family history) and 100 healthy controls, all medication free, were tested on tasks related to the 'hot' (i.e. two choice-delay tasks) and 'cool' domains of EF (i.e. Digits backward, Corsi Block Task backward, Go/No-Go Task, Stop-Signal Task, and the Stroop). RESULTS: Compared with the controls, children with ADHD were found to perform significantly worse on one or more measures of response inhibition, WM, and delay aversion after controlling for co-morbidities and estimated IQ. In addition, comparisons between ADHD children with family history of ADHD and those with no family history found significant differences on measures of response inhibition and WM but not delay aversion. These results are largely supported by results of two logistic regressions. CONCLUSIONS: ADHD was found to be associated with deficits on both cool and hot EFs. There is also evidence to suggest that cool EFs impairment is related to a family history of ADHD. Findings of this study have helped to elucidate the nature and extent of EF deficits in children with ADHD.

Health, pre-disease and critical transition to disease in the psycho-immune-neuroendocrine network: Are there distinct states in the progression from health to major depressive disorder?

The psycho-immune-neuroendocrine (PINE) network is a regulatory network of interrelated physiological pathways that have been implicated in major depressive disorder (MDD). A model of disease progression for MDD is presented where the stable, healthy state of the PINE network (PINE physiome) undergoes progressive pathophysiological changes to an unstable but reversible pre-disease state (PINE pre-diseasome) with chronic stress. The PINE network may then undergo critical transition to a stable, possibly irreversible disease state of MDD (PINE pathome). Critical transition to disease is heralded by early warning signs which are detectible by biomarkers specific to the PINE network and may be used as a screening test for MDD. Critical transition to MDD may be different for each individual, as it is reliant on diathesis, which comprises genetic predisposition, intrauterine and developmental factors. Finally, we propose the PINE pre-disease state may form a "universal pre-disease state" for several non-communicable diseases (NCDs), and critical transition of the PINE network may lead to one of several frequently associated disease states (influenced by diathesis), supporting the existence of a common Chronic Illness Risk Network (CIRN). This may provide insight into both the puzzle of multifinality and the growing clinical challenge of multimorbidity.

Conduction Mechanisms on High Retention Annealed MgO-based Resistive Switching Memory Devices.

We report on the conduction mechanisms of novel Ru/MgO/Cu and Ru/MgO/Ta resistive switching memory (RSM) devices. Current-voltage (I-V) measurements revealed Schottky emission (SE) as the dominant conduction mechanism in the high resistance state (HRS), which was validated by varying temperatures and transmission electron microscopy (TEM) results. Retention of more than 10 years at 85 °C was obtained for both Ru/MgO/Ta and Ru/MgO/Cu RSM devices. In addition, annealing processes greatly improved the consistency of HRS and LRS switching paths from cycle to cycle, exhibiting an average ON/OFF ratio of 102. Further TEM studies also highlighted the difference in crystallinity between different materials in Ru/MgO/Cu RSM devices, confirming Cu filament identification which was found to be 10 nm in width.

From feedback loop transitions to biomarkers in the psycho-immune-neuroendocrine network: Detecting the critical transition from health to major depression.

BACKGROUND: Biological pathways underlying major depressive disorder (MDD) can be viewed as systems biology networks. The psycho-immune-neuroendocrine (PINE) network comprises central nervous, immune, endocrine and autonomic systems, integrating biological mechanisms of MDD. Such networks exhibit recurrent motifs with specific functions, including positive and negative feedback loops, and are subject to critical transitions, influenced by feedback loop transitions (FLTs). AIMS: We aim to identify critical feedback loops and their FLTs, as well sentinel network nodes (SNNs), key network nodes that drive FLTs, within the PINE network. Examples of biomarkers are provided which may reflect early warning signs of impending critical transition to MDD. RESULTS: Disruption of homeostatic feedback loops reflects the physiological transition to MDD. Putative FLTs are identified within hypothalamic-pituitary-adrenal (HPA) and sympathetic-parasympathetic axes, the kynurenine pathway, gut function and dysbiosis. CONCLUSIONS: Progression from health to disease is driven by FLTs in the PINE network, which is likely to undergo changes characteristic of system instability. Biomarkers of system instability may effectively predict the critical transition to MDD.

Tyrosine kinase receptor immunoreactivity in trigeminal mesencephalic and motor neurons following transection of masseteric nerve of the rat.

Neurotrophins are known to promote survival after neural injury. To determine the relative importance of tyrosine kinase receptors on the survival of axotomized trigeminal nuclear neurons, we examined the temporal expression profile of tyrosine kinase A, tyrosine kinase B and tyrosine kinase C receptors in the mesencephalic trigeminal nucleus and the motor trigeminal nucleus following transection of the masseteric nerve in rats. Axotomized neurons in these nuclei were retrogradely identified with FluoroGold. We found increase in tyrosine kinase A-immunoreactive mesencephalic trigeminal nucleus neurons in the second week after axotomy but no change in the number of tyrosine kinase A-immunoreactive motor trigeminal nucleus neurons. There was no change in the number of tyrosine kinase B-immunoreactive mesencephalic trigeminal nucleus neurons but the significant increase of tyrosine kinase B-immunoreactive motor trigeminal nucleus neurons throughout the period of observation (3 weeks) peaked at approximately 1 week after axotomy. There was no alteration in the number of tyrosine kinase C-immunoreactive mesencephalic trigeminal nucleus neurons but significant increase in tyrosine kinase C-immunoreactive motor trigeminal nucleus neurons observable by 4 days post-axotomy was followed by decline to levels lower than the control in 2 weeks. Temporal changes in the expression of individual tyrosine kinase receptors in mesencephalic trigeminal nucleus and motor trigeminal nucleus neurons following transection of the masseteric nerve suggest differential contribution of tyrosine kinase-specific neurotrophins to the survival of these neurons after axotomy.

Differential expression of NMDA and AMPA/KA receptor subunits in the inferior olive of postnatal rats.

We have employed immunohistochemistry to determine the expression patterns of receptor subunits of N-methyl-d-aspartate (NMDA-NR1 and NR2A/B) and alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid/kainic acid (AMPA/KA-GluR1, GluR2, GluR2/3, GluR4, and GluR5/6/7) in the inferior olive of postnatal rats up to adulthood. Immunoreactivity for distinct receptor subunits was predominantly localized in the soma and dendrites of neurons. Semi-quantification showed that the overall immunoreactivity in the inferior olive of adults was intense for GluR1, moderate for NR1 and NR2A/B, and low for GluR2, GluR2/3, GluR4, and GluR5/6/7. At P7, GluR1 was restricted to the dorsomedial cell column, subnucleus beta, principal nucleus and ventrolateral protrusion while the other subunits were found in all subnuclei of the inferior olive. The immunoreactivities for all glutamate receptor subunits ranged from low to moderate. As the rats matured, the immunoreactivity of GluR4 decreased after the second postnatal week, while those of the other subunits showed a general trend of increase, reaching adult level during the third postnatal week. Double immunofluorescence revealed that all NR1-containing neurons exhibited NR2A/B immunoreactivity, indicating that native NMDA receptors comprise of hetero-oligomeric combinations of NR1 and NR2A/B. Furthermore, co-localization of NMDA and AMPA/KA receptor subunits was demonstrated in individual neurons of the inferior olive. All NR1-containing neurons exhibited GluR1 immunoreactivity, and all NR2A/B-containing neurons showed GluR5/6/7 immunoreactivity. Our data suggest that NMDA and AMPA/KA receptors are involved in glutamate-mediated neurotransmission, contributing to synaptic plasticity and reorganization of circuitry in the inferior olive during postnatal development.

Chondroitinase ABC enhances axonal regrowth through Schwann cell-seeded guidance channels after spinal cord injury.

Grafting of Schwann cell-seeded channels into hemisected adult rat thoracic spinal cords has been tested as a strategy to bridge the injured cord. Despite success in guiding axonal growth into the graft, regeneration across the distal graft-host interface into the host spinal cord was limited. We hypothesized that chondroitin sulfate (CS) glycoforms deposited at the gliotic front of the interface constitute a molecular barrier to axonal growth into the host cord. Because CS glycoforms deposited by purified astrocytes in vitro were removable by digestion with chondroitinase ABC, we attempted to achieve likewise by infusion of the enzyme to the host side of the interface. By 1 month post-treatment, significant numbers of regenerating axons crossed an interface that was subdued in macrophage/microglia reaction and decreased in CS-immunopositivity. The axons extended as far into the caudal cord as 5 mm, in contrast to nil in vehicle-infused controls. Fascicular organizations of axon-Schwann cell units within the regenerated tissue cable were better-preserved in enzyme-treated cords than in vehicle-infused controls. We conclude that CS glycoforms deposited during gliosis at the distal graft-host interface could be cleared by the in vivo action of chondroitinase ABC to improve prospects of axonal regeneration into the host spinal cord.

Expression of Trk receptors in otolith-related neurons in the vestibular nucleus of rats.

The expression of the three Trk receptors (TrkA, TrkB, and TrkC) in otolith-related neurons within the vestibular nuclei of adult Sprague-Dawley rats was examined immunohistochemically. Conscious animals were subjected to sinusoidal linear acceleration along either the anterior-posterior (AP) or interaural (IA) axis on the horizontal plane. Neuronal activation was defined by Fos expression in cell nuclei. Control animals, viz labyrinthectomized rats subjected to stimulation and normal rats that remained stationary, showed only a few sporadically scattered Fos-labeled neurons. Among experimental rats, the number of Fos-labeled neurons and their distribution pattern in each vestibular subnucleus in animals stimulated along the antero-posterior axis were similar to those along the interaural axis. No apparent topography was observed among neurons activated along these two directions. Only about one-third of the Trk-immunoreactive neurons in the vestibular nucleus expressed Fos. Double-labeled Fos/TrkA, Fos/TrkB and Fos/TrkC neurons constituted 85-98% of the total number of Fos-labeled neurons in vestibular nuclear complex and its subgroups x and y. Our findings suggest that Trk receptors and their cognate neurotrophins in central otolith neurons may contribute to the modulation of gravity-related spatial information during horizontal head movements.

Expression of chondroitin sulfate proteoglycans in the chiasm of mouse embryos.

Chondroitin sulfate (CS) proteoglycans have been implicated as molecules that are involved in axon guidance in the developing neural pathways. The spatiotemporal expression of CS was investigated in the developing retinofugal pathway in mouse embryos by using the CS-56 antibody. Immunoreactive CS was detected in inner regions of the retina as early as embryonic day 11 (E11). Its expression in subsequent stages of development followed a centrifugal, receding gradient that appeared to correlate with the sequence of axogenesis in the retina. In the chiasm, immunoreactive CS was expressed at E12, before the arrival of retinal axons. When the retinal axons navigated in the chiasm at E13-E14, immunoreactive CS remained at a low level in the optic fiber layer of the chiasm but was observed prominently in the caudal parts of the ventral diencephalon. This pattern followed closely the array of stage-specific-embryonic-antigen-1-positive neurons in the ventral diencephalon, with a V-shaped configuration that bordered the posterior boundary of the retinal axons, and a rostral raphe extension that ran across the decussating axons in the chiasm. Thus, the CS epitope is implicated in patterning the course of early retinal axons and in regulating axon divergence in the chiasm. At the lateral region of the chiasm, where the retinal axons cross the midline and approach the optic tract, a CS-immunopositive region coincided with the region in which active sorting of dorsal retinal axons from ventral retinal axons occurs. Moreover, at the threshold of the optic tract, the immunoreactive CS was restricted only to the deep part of the optic fiber layer, suggesting an inhibitory role of the CS epitope in repelling newly arrived axons to superficial regions of the optic tract during the development of chronotopic order at this part of the retinofugal pathway.

Neuronal response sensitivity to bidirectional off-vertical axis rotations: a dimension of imbalance in the bilateral vestibular nuclei of cats after unilateral labyrinthectomy.

In decerebrate cats after acute hemilabyrinthectomy, the response sensitivity of extracellularly recorded vestibular nuclear neurons on the lesioned and labyrinth-intact sides were examined quantitatively during constant velocity off-vertical axis rotations with an aim to elucidate the functional contribution of otolithic inputs to the ipsilateral and contralateral vestibular nuclei. The bidirectional response sensitivity, delta, was determined as the ratio of the gain during clockwise to that during counterclockwise rotations. A continuum of response sensitivity was identified: one-dimensional neurons showed symmetrically bidirectional response patterns, while two-dimensional neurons showed asymmetrically bidirectional patterns that in some cases approached unidirectional patterns with change in velocity. The proportion of two-dimensional neurons was significantly increased after acute hemilabyrinthectomy. Two-dimensional neurons that responded only to one direction of rotation in at least one of the velocities tested were described as unidirectional neurons. This unidirectional response pattern was observed in one-third of the entire neuronal population studied, but not in cats with both labyrinths intact, thus suggesting that such prominent broadly tuned responses are normally masked by converging otolithic inputs from the contralateral side. These neurons were found in higher proportion on the lesioned side than on the labyrinth-intact side. Among the 70% of unidirectional neurons that exhibited bidirectional response at some velocities and unidirectional response at others, prominent shifts in delta values (i.e. between 0/infinity and finite values) with velocity can be computed for each neuron. The shifts in delta values correlated with large shifts in the response dynamics and spatial orientation as the response pattern changed with velocity. The response orientations of the unidirectional neurons pointed in all directions on the horizontal plane. When all the two-dimensional neurons (i.e. both the unidirectionally and bidirectionally responsive ones) were pooled, imbalances in the distribution of the response orientations and in response gain were found between the ipsilateral-side-down/head-down half-circle and the contralateral-side-down/head-up half-circle on the labyrinth-intact side, but not on the lesioned side. These results, derived from spatiotemporal processing of gravitational signals, reveal a novel dimension of imbalance between neuronal populations in the two vestibular nuclear complexes after acute lesion of one labyrinth. This feature would provide, on the one hand, deranged cues of spatial orientation and direction during slow head excursions and, on the other, a framework for the dynamic behavioral deficits associated with hemilabyrinthectomy.

Adhesion molecule expression in a rat model of Staphylococcus aureus endophthalmitis.

PURPOSE: To determine whether Staphylococcus aureus and its components induce expression of E-selectin and intercellular adhesion molecule (ICAM)-1 in rat ocular tissues and on human endothelial cells in culture. METHODS: Experimental and control rat eyes were injected with 80 colony-forming units of viable S. aureus and lipopolysaccharide-free sterile saline (NS), respectively. Eyes were enucleated and immediately frozen. E-selectin and ICAM-1 expression were evaluated on frozen sections by using standard immunohistochemical techniques. Using an enzyme-linked immunoassay, in vitro expression of E-selectin and ICAM-1 was evaluated on macrovascular endothelial cells after stimulation with S. aureus and selected purified components. RESULTS: In S. aureus-injected eyes, E-selectin and ICAM-1 expression peaked at six to 24 hours, decreased slightly at 24 and 48 hours, and further declined by 72 hours. However, in NS-injected eyes, peak levels of E-selectin and ICAM-1 were seen at 6 hours, after which expression declined in the areas in which an increase was previously observed. In in vitro assays, peptidoglycan (0.01 microg/ml) induced a fourfold increase in E-selectin (P < 0.0001) and a twofold increase in ICAM-1 (P < 0.002) expression. Ribitol teichoic acid (RTA) (1 microg/ml) induced a twofold increase in E-selectin (P < 0.0001) and a threefold increase in ICAM-1 (P < 0.0001) expression. CONCLUSIONS: Eyes injected with S. aureus demonstrated a more intense and prolonged expression of both E-selectin and ICAM-1 than did eyes injected with NS. In addition, S. aureus components induced the in vitro expression of these adhesion molecules on macrovascular endothelial cells. The relevance of these findings to microvascular endothelial cells is yet to be determined.

Paraganglioma of the urinary bladder: immunohistochemical, ultrastructural, and DNA flow cytometric studies.

Primary paraganglioma arises infrequently in the urinary bladder. We present the clinicopathologic, immunohistochemical, ultrastructural, and DNA flow cytometric findings in three cases (one man and two women). Ages at diagnosis were 19, 35, and 45 years. One female presented with paroxysmal headaches and hypertension that followed urination; the remaining two patients presented with hematuria. Immunohistochemical studies revealed positive reactivity for chromogranin (three patients), met-enkephalin (three), leu-enkephalin (three), vasoactive intestinal polypeptide (two), serotonin (one), and S-100 protein (one; sustentacular cells only). Neurosecretory granules were identified in all cases; in the patient with hypertension, the granules were small with eccentric cores similar to those of adrenal pheochromocytomas. A nondiploid DNA flow cytometric pattern was present in all three patients, an aneuploid pattern was present in two, and a tetraploid pattern was present in one. After diagnosis, one patient was alive without progression at 7 years, one died of an uncertain cause at 5 years, and one suffered multiple recurrences over a 24-year period before developing metastatic disease. While the presence of aneuploidy has been shown to be a predictor of malignant behavior in adrenal pheochromocytomas, our study illustrates that DNA ploidy cannot be used as a diagnostic criterion for malignancy in urinary bladder paraganglioma.

Proliferating cell nuclear antigen (PCNA); prognostic value in the clinical recurrence of primary basal cell carcinoma.

Proliferating cell nuclear antigen (PCNA) is a nuclear protein which is correlated with the S-phase of the cell cycle and has been utilized by many investigators as a marker of cell proliferation. A previous immunohistochemical study revealed increased PCNA staining in clinically and histologically aggressive basal cell carcinoma and the present study evaluated the prognostic value of PCNA in clinical recurrence of primary basal cell carcinoma. Thirty patients with primary basal cell carcinoma (BCC) treated with shave biopsy followed by electrodesiccation in 1989 and have been regularly followed up for local recurrence were selected for this study. The histology of their primary BCC's was reviewed and the presence of PCNA in the tumor cells was studied immunohistochemically. Ninety-six percent of the non-recurrent BCC's had < 10% of tumor cells showing a positive staining for PCNA whereas 100% of the BCC's that recurred showed more than 30% of tumor cells staining positive for PCNA. In comparison, 88.9% of the non-recurring group showed non-aggressive histological features and only 66.7% of the recurring group was aggressive by microscopic appearance. In summary, the PCNA staining appeared to be superior to traditional histologic features in predicting clinical recurrence in primary BCC's and further prospective studies in a larger patient group are warranted.