Gregory Taylor

Epstein-Barr virus-targeted therapy for AIDS-related primary lymphoma of the central nervous system

Epstein-Barr virus (EBV) targeted therapeutic strategies for viral associated malignant diseases have received only perfunctory consideration, first, because latent herpesviruses have been intractable to antiviral chemotherapy and, second, because the role EBV has in maintenance of the malignant cell phenotype has been uncertain. Two patients with EBV related primary central nervous system lymphoma (PCNSL) in the setting of advanced AIDS, were treated with low dose hydroxyurea based on in vitro anti-EBV activity. The responses obtained here suggest the promise of antiviral approaches in select cancers.

Prospective CT Screening for Lung Cancer in a High-Risk Population: HIV-Positive Smokers

Background: Epidemiological evidence suggests that HIV-infected individuals are at increased risk of lung cancer, but no data exist because large computed tomography (CT) screening trials routinely exclude HIV-infected participants. Methods: From 2006 to 2013, we conducted the worlds first lung cancer screening trial of 224 HIV-infected current/former smokers to assess the CT detection rates of lung cancer. We also used 130 HIV-infected patients with known lung cancer to determine radiographic markers of lung cancer risk using multivariate analysis. Results: Median age was 48 years with 34 pack-years smoked. During 678 person-years, one lung cancer was found on incident screening. Besides this lung cancer case, 18 deaths (8%) occurred, but none were cancer related. There were no interim diagnoses of lung or extrapulmonary cancers. None of the pulmonary nodules detected in 48 participants at baseline were diagnosed as cancer by study end. The heterogeneity of emphysema across the entire lung as measured by CT densitometry was significantly higher in HIV-infected subjects with lung cancer compared with the heterogeneity of emphysema in those without HIV (p ⩽ 0.01). On multivariate regression analysis, increased age, higher smoking pack-years, low CD4 nadir, and increased heterogeneity of emphysema on quantitative CT imaging were all significantly associated with lung cancer. Conclusions: Despite a high rate of active smoking among HIV-infected participants, only one lung cancer was detected in 678 patient-years. This was probably because of the young age of participants suggesting that CT screening of high-risk populations should strongly consider advanced age as a critical inclusion criterion. Future screening trials in urban American must also incorporate robust measures to ensure HIV patient compliance, adherence, and smoking cessation.

Renal Involvement of Human Parvovirus B19 in an Immunocompetent Host

Human parvovirus B19, which is most commonly known to cause erythema infectiosum in children, is also known to cause infection in adults, with complications ranging from a self-limited polyarthropathy in immunocompetent patients to hydrops fetalis in pregnant women, transient aplastic crises in patients with chronic hemolytic anemias, and chronic aplastic anemia in immunocompromised hosts. We describe a previously healthy immunocompetent woman who presented with manifestations of acute parvovirus B19 infection.

Cryptococcal Meningitis in an HIV-Positive Pregnant Woman:

Cryptococcal meningitis is uncommon in pregnant HIV-infected women. The clinical care of an HIV-1 positive pregnant woman with cryptococcal meningitis whose pathology has been previously reported is reviewed to highlight the treatment of the disease and some of the challenges associated with antifungal therapy during pregnancy, including the teratogenicity of antifungal agents, their variable pharmacokinetics in pregnancy, the lack of well-defined treatment duration for such infections, and host factors including compliance. This patient’s disease relapsed due to nonadherence after an initial course of intravenous amphotericin. Subsequently, she was successfully treated, with a favorable fetal outcome, with another 2 weeks of amphotericin B, followed by consolidation and maintenance with fluconazole and antiretroviral treatment. This case highlights and reviews the complexities of the management of cryptococcal meningitis in HIV-infected pregnant women.

Placental Cryptococcus neoformans infection without neonatal disease: case report and review of the literature.

We report placental cryptococcosis in a woman with multi-drug resistant human immunodeficiency virus (HIV) infection. She received antifungal therapy for cryptococcal meningitis prior to delivery. Cesarean section was performed with delivery of a single full-term male infant. There was no evidence of HIV or cryptococcal infection in the infant. The placenta grossly showed multiple white nodules. Microscopically, numerous encapsulated budding yeasts, morphologically consistent with cryptococci, were identified in the intervillous space and, to a lesser extent, in the chorionic villi. Cryptococcal infections are not uncommon, but only 2 cases of placental cryptococcosis have been reported. Our case is the 1st account documenting cryptococcal organisms within the chorionic villi, and yet there was no evidence of infection in the infant. Mother-to-fetal transmission of cryptococcal infection is not well defined. We review the literature and discuss its possible mechanisms.

Anal Cancer Screening in an Urban HIV Clinic: Provider Perceptions and Practice.

In this article, we sought to understand the perceptions and practice of providers on anal cancer screening in HIV-infected patients. Providers in an academic outpatient HIV practice were surveyed. Data were analyzed to determine the acceptability and perceptions of providers on anal Papanicolaou tests. Survey response rate was 55.3% (60.7% among male and 47.4% among female providers). One-third of the providers had received screening requests from patients. Female providers had higher self-rated comfort with anal Papanicolaou tests, with a mean score of 7.1 (95% confidence interval [CI] 4.7-9.5) compared to 3.6 (95% CI 1.5-5.7) for male providers, P = .02. Sixty-seven percent of male providers and 37.5% of female providers would like to refer their patients for screening rather than perform the test themselves. Only 54.2% of our providers have ever performed anal cytology examination. Our survey revealed that not all providers were comfortable performing anal cancer screening for their patients.

The Genome of the Northern Sea Otter (Enhydra lutris kenyoni)

The northern sea otter inhabits coastal waters of the northern Pacific Ocean and is the largest member of the Mustelidae family. DNA sequencing methods that utilize microfluidic partitioned and non-partitioned library construction were used to establish the sea otter genome. The final assembly provided 2.426 Gbp of highly contiguous assembled genomic sequences with a scaffold N50 length of over 38 Mbp. We generated transcriptome data derived from a lymphoma to aid in the determination of functional elements. The assembled genome sequence and underlying sequence data are available at the National Center for Biotechnology Information (NCBI) under the BioProject accession number PRJNA388419.

The Genome of the Beluga Whale (Delphinapterus leucas)

The beluga whale is a cetacean that inhabits arctic and subarctic regions, and is the only living member of the genus Delphinapterus. The genome of the beluga whale was determined using DNA sequencing approaches that employed both microfluidic partitioning library and non-partitioned library construction. The former allowed for the construction of a highly contiguous assembly with a scaffold N50 length of over 19 Mbp and total reconstruction of 2.32 Gbp. To aid our understanding of the functional elements, transcriptome data was also derived from brain, duodenum, heart, lung, spleen, and liver tissue. Assembled sequence and all of the underlying sequence data are available at the National Center for Biotechnology Information (NCBI) under the Bioproject accession number PRJNA360851A.

Highly active antiretroviral therapy reduces pulmonary IL-8 in HIV-positive women smokers.

Increased levels of the proinflammatory cytokine IL-8 are detected in the sputum of patients with chronic obstructive pulmonary disease (COPD) and during the pathological pulmonary manifestations of HIV infection : To explore a potential interrelationship between smoking, highly active antiretroviral therapy (HAART) and HIV immune status, we collected sputum samples, along with complete pulmonary function tests from groups of HIV-infected women smokers who were either on or off HAART. Analysis of the patients sputum for cell count along with quantitative measures of IL-8 was performed and correlated with concurrent assessment of pulmonary function test (PFT). We found that HIV-positive smokers had decreased measurements on PFT of the diffusing capacity of the lung for carbon monoxide (D(LCO)) compared to standard reference values that did not differ with HAART usage. HAART, when controlled for CD4, showed a suppressive effect on the levels of pro inflammatory cytokine IL-8 in sputum. We conclude that in the era of HAART, HIV along with concurrent tobacco smoking is associated with declines in PFT in HIV-infected women. The use of HAART in patients appears to mitigate the increases in IL-8 levels in relation to immune status based on CD4 count.