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1.  Gastrointestinal lymphomas: Morphology, immunophenotype and molecular features 
Primary gastrointestinal lymphoma comprises 10-15% of all non-Hodgkin lymphomas and encompasses 30-40% of the total extranodal lymphomas. Approximately 60-75% of cases occur in the stomach, and then the small bowel, ileum, cecum, colon and rectum. Lymphoid neoplasms may consist of mature B, T and less commonly extranodal NK/T cells. Of these, the two most frequently encountered histologic subtypes are extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma), where Helicobacter pylori infection is implicated in a number of cases, and diffuse large B cell lymphoma. Several B cell lymphomas are associated with chromosomal aberrations. Enteropathy-associated T cell lymphoma, type I in particular, usually arises in a background of celiac disease. T cell gene rearrangement confirms clonality. NK/T cell neoplasms are invariably associated with Epstein-Barr virus infection and are often aggressive; thus, differentiation from a benign NK-cell enteropathy is paramount. Although incidence of other hematopoietic malignancies in the gastrointestinal tract such as plasma cell myeloma associated with amyloidosis, plasmablastic lymphoma, Hodgkin disease, histiocytic sarcoma and mast cell sarcoma is extremely rare, these entities have been documented, with the latter two demonstrating aggressive clinical behavior. Endoscopic ultrasonography is an important adjunct in disease staging and follow-up. Conservative antibiotic treatment of stage I MALT lymphomas with associated Helicobacter pylori infection achieves good clinical outcome with high remission rate. Chemotherapy, radiation and rarely surgery are reserved for advanced diseases or cases resistant to conservative therapy and those not associated with Helicobacter pylori infection.
PMCID: PMC3418529  PMID: 22943012
Gastrointestinal lymphomas; MALT lymphoma; NK/T-cell enteropathy
2.  Alteration of Methamphetamine-Induced Stereotypic Behaviour in Transgenic Mice Expressing HIV-1 Envelope Protein gp120 
Journal of neuroscience methods  2009;186(2):222-225.
The use of drugs for recreational purposes, in particular Methamphetamine, is associated with an increased risk of infection with human immunodeficiency virus (HIV)-1. HIV-1 infection in turn can lead to HIV-associated neurological disorders (HAND) that range from mild cognitive and motor impairment to HIV-associated dementia (HAD). Interestingly, post mortem brain specimens from HAD patients and transgenic (tg) mice expressing the viral envelope protein gp120 in the central nervous system display similar neuropathological signs. In HIV patients, the use of Methamphetamine appears to aggravate neurocognitive alterations. In the present study, we injected HIV/gp120tg mice and non-transgenic littermate control animals with Methamphetamine dissolved in Saline or Saline vehicle and assessed locomotion and stereotyped behaviour. We found that HIVgp120-transgenic mice differ significantly from non-transgenic controls in certain domains of their behavioural response to Methamphetamine. Thus this experimental model system may be useful to further study the mechanistic interaction of both the viral envelope protein and the psychostimulant drug in behavioural alterations and neurodegenerative disease.
PMCID: PMC3432271  PMID: 19917310
Methamphetamine; HIV; envelope protein; behaviour; stereotypy; neurodegeneration; drug abuse
3.  Are Time- and Event-based Prospective Memory Comparably Affected in HIV Infection?† 
According to the multi-process theory of prospective memory (ProM), time-based tasks rely more heavily on strategic processes dependent on prefrontal systems than do event-based tasks. Given the prominent frontostriatal pathophysiology of HIV infection, one would expect HIV-infected individuals to demonstrate greater deficits in time-based versus event-based ProM. However, the two prior studies examining this question have produced variable results. We evaluated this hypothesis in 143 individuals with HIV infection and 43 demographically similar seronegative adults (HIV−) who completed the research version of the Memory for Intentions Screening Test, which yields parallel subscales of time- and event-based ProM. Results showed main effects of HIV serostatus and cue type, but no interaction between serostatus and cue. Planned pair-wise comparisons showed a significant effect of HIV on time-based ProM and a trend-level effect on event-based ProM that was driven primarily by the subset of participants with HIV-associated neurocognitive disorders. Nevertheless, time-based ProM was more strongly correlated with measures of executive functions, attention/working memory, and verbal fluency in HIV-infected persons. Although HIV-associated deficits in time- and event-based ProM appear to be of comparable severity, the cognitive architecture of time-based ProM may be more strongly influenced by strategic monitoring and retrieval processes.
PMCID: PMC3081684  PMID: 21459901
AIDS dementia complex; Episodic memory; Executive functions; Neuropsychological assessment
4.  Incidence and Nature of Cognitive Decline Over One Year Among HIV-infected Former Plasma Donors in China 
AIDS (London, England)  2010;24(7):983-990.
To quantify and characterize the nature of cognitive change over one year in a cohort of HIV+ former plasma donors in rural China.
Observational cohort study
192 HIV+ and 101 demographically comparable HIV− individuals, all former plasma donors, who lived in a rural part of China, received comprehensive medical and neuropsychological (NP) examinations. At study entry 56% of HIV+ group was on combination antiretroviral treatment (cART) and 60.9% at followup. Multiple regression change score approach was used with the HIV− sample to develop norms for change that would be then applied to the HIV+ participants. Followup test scores adjusted for the control group practice effect.
53 HIV+ individuals (27%) developed significant cognitive decline as compared to five (5%) of HIV− individuals. Cognitive decline was predicted at baseline by AIDS status, lower nadir CD4, and worse processing speed; at follow-up, it was associated with lower current CD4 and failure of viral suppression on cART. NP decline also was associated with decreased independence in activities of daily living. Using NP-impairment scores that were corrected for “practice” on repeated testing, we found that among the decliners, 41.5% (N=22) had incident impairment, while 38% (N=20) declined within the impaired range and another 20.7% (N=11) declined within the normal range.
This study demonstrates that despite ongoing cART, cognitive decline in HIV+ people is common over a one year follow-up. Regression-based norms for change on Western NP tests can be used to detect disease-related cognitive decline in a developing country.
PMCID: PMC2898923  PMID: 20299964
HIV/AIDS; Neurocognitive Disorders; Incidence Studies; China; Longitudinal Studies; Neuropsychological Tests; Antiretroviral Therapy; Highly Active
5.  Neurobehavioral effects of HIV infection among former plasma donors in rural China 
Journal of neurovirology  2008;14(6):536-549.
The HIV epidemic in China has expanded rapidly in recent years, but little is known about the prevalence and features of HIV Associated Neurocognitive Disorders (HANDs) in this part of the world. We administered a comprehensive Western neuropsychological (NP) test battery to 203 HIV+ and 198 HIV-former plasma donors in the rural area of Anhui province. We found that 26% in the HIV- sample, and 46% in the HIV+ sample were infected with HCV, which can also have CNS effects. To classify NP impairment, we developed demographically corrected test norms based upon individuals free of both infections (N=141). Using a global summary score, NP impairment was found in 34.2% of the HIV mono-infected group and 39.7% of the co-infected group, as compared to 12.7% of the uninfected controls (p<.001). HIV+ participants with AIDS were more likely to be impaired (43%) than non-AIDS individuals (29%, p<.05). Lastly, when all infection groups were combined, participants with NP impairment reported more cognitive complaints (p<.01) and increased dependence in everyday functioning (p=.01). In sum, NP impairment in this large rural Chinese sample was associated with both HIV and HCV infections, and the impairment's prevalence, severity, and pattern were similar to those reported by Western studies. Clinical significance of NP impairment in this population is suggested by the participants’ reports of reduced everyday functioning. These findings indicate that HAND is likely to be an important feature of HIV infection in developing countries, underscoring the need for international efforts to develop CNS relevant treatments.
PMCID: PMC2889205  PMID: 18991068
HIV; HCV; neurocognitive disorders; China
6.  Neurobehavioral effects of HIV-1 infection in China and the United States: A pilot study 
The HIV epidemic in China has been increasing exponentially, yet there have been no studies of the neurobehavioral effects of HIV infection in that country. Most neuroAIDS research has been conducted in Western countries using Western neuropsychological (NP) methods, and it is unclear whether these testing methods are appropriate for use in China. Twenty-eight HIV seropositive (HIV+) and twenty-three HIV seronegative (HIV−) individuals with comparable gender, age, and education distributions were recruited in Beijing and the rural Anhui province in China. Thirty-nine HIV+ and thirty-one HIV− individuals were selected from a larger U.S. cohort recruited at the HIV Neurobehavioral Research Center, in San Diego, to be matched to the Chinese sample for age, disease status, and treatment variables. The NP test battery used with the U.S. and China cohorts included instruments widely used to study HIV infection in the United States. It consisted of 14 individual test measures, each assigned to one of seven ability areas thought to be especially vulnerable to effects of HIV on the brain (i.e., verbal fluency, abstraction/executive function, speed of information processing, working memory, learning, delayed recall, and motor function). To explore the cross-cultural equivalence and validity of the NP measures, we compared our Chinese and U.S. samples on the individual tests, as well as mean scaled scores for the total battery and seven ability domains. On each NP test measure, the mean of the Chinese HIV+ group was worse than that of the HIV−group. A series of 2 × 2 analyses of variance involving HIV+ and HIV− groups from both countries revealed highly significant HIV effects on the Global and all Domain mean scaled scores. Country effects appeared on two of the individual ability areas, at least partly due to education differences between the two countries. Importantly, the absence of HIV-by-Country interactions suggests that the NP effects of HIV are similar in the two countries. The NP test battery that was chosen and adapted for use in this study of HIV in China appears to have good cross-cultural equivalence, but appropriate Chinese norms will be needed to identify disease-related impairment in individual Chinese people. To inform the development of such norms, a much larger study of demographic effects will be needed, especially considering the wide range of education in that country.
PMCID: PMC2857379  PMID: 17697409
HIV/AIDS; Neuropsychological functioning; Cognition; China; Cross-cultural assessment; Everyday functioning
7.  HIV Protease Inhibitors and Risk of Peripheral Neuropathy 
Annals of neurology  2008;64(5):566-572.
Two recent analyses found that exposure to protease inhibitors (PIs) in the context of antiretroviral therapy (ART) increased the risk of distal sensory polyneuropathy (DSPN) in patients with HIV infection. These findings were supported by an in vitro model in which PI exposure produced neurite retraction and process loss in DRG sensory neurons. Confirmation of peripheral nerve toxicity with PIs could substantially limit their long-term use in HAART.
We evaluated current and past exposure to PIs as a risk factor for DSPN in 1159 HIV-infected individuals enrolled in a large, prospective, observational, multicenter study. Signs of DSPN were ascertained by neurological examination. Subjects were grouped into categories according to past and current exposure to any ARV and to PIs. We included disease indicators such as nadir CD4, plasma viral load, and duration of HIV infection, as well as advancing age and exposure to dideoxynucleoside ARVs in multivariate models.
In univariate analyses, both past and current PI exposure significantly increased the risk of DSPN. However, after adjusting for previously validated concomitant risk factors in multivariate models, none of the PI exposure groups was more likely to have DSPN than ARV naïve subjects. A secondary evaluation of duration of PI use and exposure to individual PI drugs was similarly non-significant in multivariate models, except for small effects of amprenavir and lopinavir.
Evaluation of concomitant risks for HIV DSPN suggests that the independent risk attributable to PIs, if any, is small. This risk must be weighed against the important role of PIs in modern ART regimens.
PMCID: PMC2605176  PMID: 19067367

Results 1-7 (7)