High-Grade Atypical Teratoid/Rhabdoid Tumor in the Pituitary Region.

Atypical teratoid/rhabdoid tumors (AT/RTs) are embryological tumors of the central nervous system (CNS). They are typically found in children, with rare presentations in adults. We describe the presentation of an AT/RT in the pituitary region of a 37-year-old female. The patient presented with a two-week history of intractable cephalgia with sudden onset of monocular diplopia and left-sided cranial nerve VI palsy. The patient underwent transsphenoidal resection of their mass, which revealed the diagnosis. She then underwent systemic therapy with chemotherapy as well as radiation. She ultimately died 14 months after treatment completion due to unrelated events. The case highlights the rarity of AT/RT in adults, emphasizing the challenge of establishing standardized treatment protocols due to its rarity in adult presentations.

Biliotórax: una entidad rara para un diagnóstico frecuente. Un reporte de caso / Bilothorax: a Rare Entity for a Frequent Diagnosis. A Case Report

Introducción: El biliotórax es una condición infrecuente definida por la presencia de bilis en el espacio pleural. Actualmente, hay alrededor de 70 casos descritos en la litera-tura. Sigue siendo relativamente desconocido, por lo tanto, poco sospechado. Esta entidad suele ser el resultado de una lesión iatrogénica, a menudo secundaria a cirugías o traumatismos del tracto biliar, que conduce a la formación de una fístula pleurobiliar.

Introduction: Bilothorax is a rare condition defined by the presence of bile in the pleural space. Currently, there are around 70 cases described in the literature. It remains relatively unknown and, therefore, little suspected. This entity is usually the result of an iatrogenic injury, often secondary to surgery or trauma to the biliary tract, leading to the formation of a pleurobiliary fistula

Risk transfer from a megacity to a peri-urban agricultural community: wastewater reuse and effects on groundwater quality.

Urban wastewater is a resource that can be reused, but its management must be carefully executed, considering its potential impact on public and environmental health. Unfortunately, marked differences in the quality of treatment, management, collection, and the monitoring of wastewater exist among low-, middle-, and high-income countries. This is the case of the Mezquital Valley, a semi-rural area that is composed of agricultural and industrial communities on the outskirts of Mexico City. For over 100 years, wastewater from Mexico City and its areas of conurbation has been sent to the Mezquital Valley, with few studies having been conducted to assess the existence and severity of bacterial and pathogen infiltration into the local aquifer. In this research, we present an assessment of wastewater infiltration transported from Mexico City, used for irrigation, with potential infiltration into the Mezquital Valley aquifer. We utilized stable isotope analysis of deuterium and oxygen-18 to determine whether a mixture of untreated wastewater from the Mexico City Metropolitan Area (MCMA) flows into the Mezquital aquifer. Also, tests for adenovirus, rotavirus, fecal coliform, fecal enterococci, Giardia lamblia, and Cryptosporidium parvum were employed to determine the presence of fecal indicators and pathogens in different water sources in the study area. The results show the presence of indicators and pathogens in local wells used as water supply in Mezquital Valley. The presence of such indicators suggests that pathogens can reach the water consumed by the inhabitants, posing a hazard to persons exposed to these waters during their normal daily-life activities.

Frequency and Risk Factors for Spontaneous Pneumomediastinum in COVID-19 Patients.

Background: Spontaneous pneumomediastinum (SPM) is an uncommon condition in COVID-19 patients. No information about outcome or risk factors is available at the time. The aim of this research is to report on the frequency and risk factors of spontaneous pneumomediastinum in COVID-19 patients. Materials and Methods: An unmatched case-control study was carried out in a tertiary health-care facility for patients with COVID-19. Electronic files were reviewed to identify patients with confirmed COVID-19 infection by RT-PCR. Univariate analysis was used to describe demographic data. Mean differences were calculated using the Mann-Whitney test. Frequency and odds ratios were calculated by standard operations. Results: A total of 271 patients were included in the study. Nine patients showed spontaneous pneumomediastinum and four of them presented associated spontaneous pneumothorax. The most common risk factors associated with poor outcomes in COVID-19 patients were not considered as risk factors for spontaneous pneumomediastinum development. Conclusion: Spontaneous pneumomediastinum is an uncommon clinical feature in COVID-19 patients. More research is necessary to formulate statements regarding prevalence, risk factors, and outcome.

Evaluation of cranial base repair techniques utilizing a novel cadaveric CPAP model.

BACKGROUND: Although recent guidelines for obstructive sleep apnea recommend early postoperative use of continuous positive airway pressure (CPAP) after endonasal skull base surgery, the time of initiation of CPAP is unclear. In this study we used a novel, previously validated cadaveric model to analyze the pressures delivered to the cranial base and evaluate the effectiveness of various repair techniques to withstand positive pressure. METHODS: Skull base defects were surgically created in 3 fresh human cadaver heads and repaired using 3 commonly used repair techniques: (1) Surgicel™ onlay; (2) dural substitute underlay with dural sealant onlay; and (3) dural substitute underlay with nasoseptal flap onlay with dural sealant. Pressure microsensors were placed in the sphenoid sinus and sella, both proximal and distal to the repair, respectively. The effectiveness of each repair technique against various CPAP pressure settings (5-20 cm H2 O) was analyzed. RESULTS: Approximately 79%-95% of positive pressure administered reached the sphenoid sinus. Sellar pressure levels varied significantly across the 3 repair techniques and were lowest after the third technique. "Breach" points (CPAP settings at which sellar repair was violated) were lowest for the first group. All 3 specimens showed a breach after the first repair technique. For the second repair technique, only a single breach was created in 1 specimen at 20 cm H2 O. No breaches were created in the third group. CONCLUSION: Different skull base repair techniques have varying ability to withstand CPAP. Both second and third repair techniques performed in a nearly similar fashion with regard to their ability to withstand positive pressure ventilation.

A cadaveric model for measuring sinonasal continuous positive airway pressure-a proof-of-concept study.

BACKGROUND: Obstructive sleep apnea is a common respiratory disorder that can have negative effects on health and quality of life. Positive pressure therapy (CPAP) is the primary treatment. There is a lack of consensus on the risk of postoperative CPAP after endoscopic sinus or skull base surgery. We present a proof-of-concept cadaver model for measuring sinonasal pressure delivered by CPAP. METHODS: Three fresh cadaver heads were prepared by removing the calvaria and brain. Sphenoidotomies were made and sellar bone was removed. Pressure sensors were placed in the midnasal cavity, sphenoid sinus, and sella. CPAP was applied and the delivered pressure was recorded at increasing levels of positive pressure. Paired t tests and intraclass correlation coefficients were used to analyze results. RESULTS: Increases in positive pressure led to increased pressure recordings for all locations. Nasal cavity pressure was, on average, 81% of delivered CPAP. Pressure was highest in the sphenoid sinus. The effect of middle turbinate medialization on intrasphenoid pressure was not statistically significant in 2 heads. Intrasellar pressure was 80% of delivered CPAP with lateralized turbinates and 84% with medialized turbinates. Pressure recordings demonstrated excellent reliability for all locations. All heads developed non-sellar-based cranial base leaks at higher pressures. Cribriform region leaks were successfully sealed with DuraSeal®. CONCLUSION: Our proof-of-concept cadaver model represents a novel approach to measure pressures delivered to the nasal cavity and anterior skull base by CPAP. With further study, it may have broader clinical application to guide the safe postoperative use of CPAP in this population.

The Role of Free Tissue Transfer in the Management of Chronic Frontal Sinus Osteomyelitis.

OBJECTIVES/HYPOTHESIS: Chronic frontal sinus infection is managed with a combination of medical and surgical interventions. Frontal bone osteomyelitis due to recurrent infection following trauma or prior open surgery may require more significant debridement. Free tissue transfer may allow for extensive debridement with replacement of tissue, and definitive eradication of osteomyelitis. STUDY DESIGN: Retrospective chart review. METHODS: Patients undergoing free flap obliteration of the frontal sinus for frontal bone osteomyelitis at a single institution were included in the study. Clinical, radiologic, and surgical data were collected. Surgeries before and after free flap obliteration were compared by Wilcoxon signed rank test. RESULTS: Fifteen patients were identified; however, one patient had less than 6 months of follow-up and was excluded from analysis. Of the remaining 14 patients, mean follow-up duration was 26 months (range, 6-120 months). Mean number of surgeries prior to free flap was 3.7 (range, 1-8 surgeries). Free flap obliteration resolved chronic frontal sinusitis in all patients. Two patients experienced postoperative infection, and the overall complication rate was 29%. Eight patients underwent cranioplasty (six immediate, two delayed) without complication. All patients received planned courses of postoperative antibiotics. A statistically significant decrease in the number of surgeries after free flap obliteration was observed P ≤ .01). CONCLUSIONS: Extensive debridement followed by free tissue transfer and antibiotics offers a definitive treatment for complicated, recurrent frontal osteomyelitis. Simultaneous cranioplasty provides immediate protective and aesthetic benefit without complication. Consideration should be given for free tissue transfer and cranioplasty earlier in the algorithm for treatment of refractory frontal sinus osteomyelitis. LEVEL OF EVIDENCE: 4 Laryngoscope, 129:1497-1504, 2019.

Minimizing Septectomy for Endoscopic Transsphenoidal Approaches to the Sellar and Suprasellar Regions: A Cadaveric Morphometric Study.

The purpose of this study was to evaluate the effect of posterior septectomy size on surgical exposure and surgical freedom during the endoscopic transsphenoidal approach to the sella and parasellar region. Dissections were performed on 10 embalmed cadaver heads. Dissections started with wide bilateral sphenoidotomies, lateralization of middle turbinates, and a 5-mm posterior septectomy. The posterior septectomy was increased in 5-mm increments to a maximum of 35 mm, followed by bilateral middle turbinectomies. Surgical exposure was defined as the distance between the ipsilateral and contralateral limit of exposure as allowed by the posterior septum along a midsphenoid horizontal meridian. Surgical freedom was defined as the angle between the ipsilateral and contralateral limit. The mean baseline width of the posterior sphenoid sinus was 29.4 ± 3.7 mm. With a 5-mm septectomy, the mean width of surgical exposure was 21.1 ± 2.8 mm. The surgical exposure increased significantly with progressively larger posterior septectomy until a 20-mm posterior septectomy, after which no further increase in surgical exposure or freedom was obtained. Bilateral lateral opticocarotid recesses were accessible with a 15-mm posterior septectomy. The addition of bilateral middle turbinectomies did not significantly increase lateral exposure within the sphenoid sinus compared with middle turbinate lateralization.

Perforation of a nasoseptal flap does not increase the rate of postoperative cerebrospinal fluid leak.

BACKGROUND: The nasoseptal flap (NSF) has been shown to be a valuable addition to the reconstructive armamentarium of the endoscopic skull-base surgeon. We aimed to evaluate the rate of postoperative cerebrospinal fluid (CSF) leak after use of a NSF that had a small tear during harvest. METHODS: After Institutional Review Board (IRB) approval, we analyzed our database of patients undergoing skull-base resection. We included all patients who had a NSF reconstruction, septoplasty, and/or spur on preoperative computed tomography (CT) imaging. We then evaluated video of each procedure to determine if a tear occurred in the NSF during harvest. Patient records were reviewed to determine if a postoperative CSF leak occurred. RESULTS: We evaluated video of 21 patients who underwent a skull-base resection, were reconstructed with a NSF, and had either a septoplasty or evidence of a septal spur on CT imaging. Of these 21 cases, 11 small tears occurred during harvest of the NSF flap and none of the patients with a torn NSF had a postoperative CSF leak. CONCLUSION: Our series shows a 0% postoperative CSF leak rate in patients undergoing skull-base reconstruction with a NSF that was torn during harvest. Small tears in the NSF do not seem to affect postoperative CSF leak rates.

Complications after mesial temporal lobe surgery via inferiortemporal gyrus approach.

OBJECT: The purpose of this study was to identify the complications associated with the inferior temporal gyrus approach to anterior mesial temporal lobe resection for temporal lobe epilepsy. METHODS: This retrospective study examined complications experienced by 483 patients during the 3 months after surgery. All surgeries were performed during 1998-2012 by the senior author (F.L.V.). RESULTS: A total of 13 complications (2.7%) were reported. Complications were 8 delayed subdural hematomas (1.6%), 2 superficial wound infections (0.4%), 1 delayed intracranial hemorrhage (0.2%), 1 small lacunar stroke (0.2%), and 1 transient frontalis nerve palsy (0.2%). Three patients with subdural hematoma (0.6%) required readmission and surgical intervention. One patient (0.2%) with delayed intracranial hemorrhage required readmission to the neuroscience intensive care unit for observation. No deaths or severe neurological impairments were reported. Among the 8 patients with subdural hematoma, 7 were older than 40 years (87.5%); however, this finding was not statistically significant (p = 0.198). CONCLUSIONS: The inferior temporal gyrus approach to mesial temporal lobe resection is a safe and effective method for treating temporal lobe epilepsy. Morbidity and mortality rates associated with this procedure are lower than those associated with other neurosurgical procedures. The finding that surgical complications seem to be more common among older patients emphasizes the need for early surgical referral of patients with medically refractory epilepsy.

HIV and syphilis infection among men attending a [corrected] sexually transmitted infection clinic in Puerto Rico.

OBJECTIVE: This study aimed to assess the demographic, behavioral, and clinical factors associated with HIV and syphilis infection among a sample of men attending a sexually transmitted infection clinic during 2009 to 2010 in San Juan, Puerto Rico (PR). METHODS: A sample of 350 clinical records from men visiting the clinic for the first time during 2009 to 2010 was reviewed. Descriptive statistics were used to describe the study sample, and bivariate analyses were performed separately for HIV and syphilis to identify factors associated with these infectious diseases. Variables that were significantly associated (p < 0.05) with HIV and syphilis in the bivariate analysis were considered for inclusion in the logistic regression models. RESULTS: Overall, 11.2% and 14.1% of the men were infected with HIV and syphilis, respectively, and 5.1% were coinfected with HIV and syphilis. In multivariate logistic regression models, ever injecting drugs (POR = 8.1; 95% CI 3.0, 21.8) and being a man who has sex with men (MSM) (POR = 5.3; 95% CI 2.3, 11.9) were positively associated with HIV infection. Being a man older than 45 years (POR = 4.0; 95% CI: 1.9, 8.9) and being an MSM (POR = 2.5; 95% CI: 1.3, 4.9) were both significantly associated with syphilis infection. CONCLUSION: These findings reinforce the need for greater education and prevention efforts for HIV and other STIs among men in PR, particularly those who are MSM. However, there is a need to make an a priori assessment of the level of health literacy in the members of this group so that a culturally sensitive intervention can be provided to the men who attend this STI clinic.

Awareness and knowledge of human papillomavirus (HPV) infection among high-risk men of Hispanic origin attending a sexually transmitted infection (STI) clinic.

BACKGROUND: Genital human papillomavirus (HPV) is one of the most commonly diagnosed sexually transmitted infection (STIs) in men and women. Knowledge about HPV infection among men is limited. This study aims to determine correlates of adequate knowledge of HPV infection among men who attend an STI clinic in Puerto Rico. METHODS: A cross-sectional study of 206 men was conducted at an STI clinic in San Juan, PR. Adequate knowledge was defined as a score of at least 70% of correct responses among those men who reported having ever heard of HPV. Variables that achieved statistical significance in the bivariate analysis (p<0.05) were included in the multivariate logistic regression model. RESULTS: Although 52.5% of men reported having heard of HPV infection before the survey, only 29.3% of this sub-group had an adequate knowledge of HPV. Most men did not know that HPV is a risk factor for anal (38.7%), penile (50.0%) and oral (72.6%) cancer. Factors associated with adequate knowledge of HPV in age-adjusted models were being men who have sex with men (MSM) (OR=2.6;95%CI=1.1-6.1), self-report of genital warts (OR=3.2;95%CI=1.3-7.9) and herpes (OR=7.4;95% CI=2.2-25.1). MSM was marginally associated with adequate knowledge (OR=2.3;95% CI=0.9-5.9) and self-report of herpes remained significantly associated (OR=5.0;95%CI=1.3-18.4) in multivariate logistic regression analysis. CONCLUSIONS: Awareness and knowledge of HPV was very low in this group of men. Interventions to increase knowledge and awareness in this group are necessary to promote preventive practices for HPV-related cancers in high-risk groups.

A preliminary profile of HIV risk in a clinic-based sample of MSM in Puerto Rico: implications for sexual health promotion interventions.

OBJECTIVE: Puerto Rico has one of the fastest growing HIV epidemics in the United States and--consistent with patterns observed in the Caribbean region as a whole--data on new infections shows the increased influence of sexual transmission in the local epidemic. Historically, both epidemiology and prevention activities have focused primarily on the islands' large heroin injector population. Although the available surveillance data indicate high rates of STIs and HIV among men who have sex with men (MSM), there has been little social and behavioral research among MSM and hence little empirical information to inform intervention development and planning. METHODS: Given the absence of data on MSM and their importance in the emerging epidemic on the island, this paper describes a sample of MSM patients in an STI/HIV treatment center in the San Juan metropolitan area between October 2009 and June 2011 (n = 120). Assessment of sexual risk includes measures of onset of oral, vaginal, and anal sex, as well as current sexual practices and partner characteristics. Self-reported history of STI diagnoses and current HIV status are described. RESULTS: Overall, MSM evidenced relatively large numbers of multiple, concurrent sexual partners, substantial age-discordance among partners, and limited condom use. Relative to HIV-negative MSM, HIV-positive MSM have had more cumulative male sexual partners in anal intercourse (p = 0.005). HIV-negative MSM were more likely to have had sex without a condom at last receptive anal intercourse (p = 0.012) as well as at last insertive anal sex intercourse (p = 0.001). CONCLUSION: Priorities for advancing HIV interventions for MSM are delineated, including the need for targeted sexual health interventions, mental health services, and improved strategies for engaging and retaining MSM in health services.

More than foreskin: circumcision status, history of HIV/STI, and sexual risk in a clinic-based sample of men in Puerto Rico.

INTRODUCTION: Circumcision among adult men has been widely promoted as a strategy to reduce human immunodeficiency virus (HIV) transmission risk. However, much of the available data derive from studies conducted in Africa, and there is as yet little research in the Caribbean region where sexual transmission is also a primary contributor to rapidly escalating HIV incidence. AIM: In an effort to fill the void of data from the Caribbean, the objective of this article is to compare history of sexually transmitted infections (STI) and HIV diagnosis in relation to circumcision status in a clinic-based sample of men in Puerto Rico. METHODS: Data derive from an ongoing epidemiological study being conducted in a large STI/HIV prevention and treatment center in San Juan in which 660 men were randomly selected from the clinic's waiting room. MAIN OUTCOME MEASURES: We assessed the association between circumcision status and self-reported history of STI/HIV infection using logistic regressions to explore whether circumcision conferred protective benefit. RESULTS: Almost a third (32.4%) of the men were circumcised (CM). Compared with uncircumcised (UC) men, CM have accumulated larger numbers of STI in their lifetime (CM = 73.4% vs. UC = 65.7%; P = 0.048), have higher rates of previous diagnosis of warts (CM = 18.8% vs. UC = 12.2%; P = 0.024), and were more likely to have HIV infection (CM = 43.0% vs. UC = 33.9%; P = 0.023). Results indicate that being CM predicted the likelihood of HIV infection (P value = 0.027). CONCLUSIONS: These analyses represent the first assessment of the association between circumcision and STI/HIV among men in the Caribbean. While preliminary, the data indicate that in and of itself, circumcision did not confer significant protective benefit against STI/HIV infection. Findings suggest the need to apply caution in the use of circumcision as an HIV prevention strategy, particularly in settings where more effective combinations of interventions have yet to be fully implemented.

A double-blind, randomized clinical trial comparing soybean oil-based versus olive oil-based lipid emulsions in adult medical-surgical intensive care unit patients requiring parenteral nutrition.

OBJECTIVE: Parenteral nutrition has been associated with metabolic and infectious complications in intensive care unit patients. The underlying mechanism for the high risk of complications is not known but may relate to the proinflammatory effects of soybean oil-based lipid emulsions, the only Food and Drug Administration-approved lipid formulation for clinical use. DESIGN: Prospective, double-blind, randomized, controlled trial. SETTING: Medical-surgical intensive care units from a major urban teaching hospital and a tertiary referral university hospital. PATIENTS: Adult medical-surgical intensive care unit patients. INTERVENTION: Parenteral nutrition containing soybean oil-based (Intralipid) or olive oil-based (ClinOleic) lipid emulsions. MEASUREMENTS: Differences in hospital clinical outcomes (nosocomial infections and noninfectious complications), hospital length of stay, glycemic control, inflammatory and oxidative stress markers, and granulocyte and monocyte functions between study groups. RESULTS: A total of 100 patients were randomized to either soybean oil-based parenteral nutrition or olive oil-based parenteral nutrition for up to 28 days. A total of 49 patients received soybean oil-based parenteral nutrition (age 51 ± 15 yrs, body mass index 27 ± 6 kg/m2, and Acute Physiology and Chronic Health Evaluation II score 15.5 ± 7 [±SD]), and a total of 51 patients received olive oil-based lipid emulsion in parenteral nutrition (age 46 ± 19 yrs, body mass index 27 ± 8 kg/m2, and Acute Physiology and Chronic Health Evaluation II score 15.1 ± 6 [±SD]) for a mean duration of 12.9 ± 8 days. The mean hospital blood glucose concentration during parenteral nutrition was 129 ± 14 mg/dL, without differences between groups. Patients treated with soybean oil-based and olive oil-based parenteral nutrition had a similar length of stay (47 ± 47 days and 41 ± 36 days, p = .49), mortality (16.3% and 9.8%, p = .38), nosocomial infections (43% vs. 57%, p = .16), and acute renal failure (26% vs. 18%, p = .34). In addition, there were no differences in inflammatory and oxidative stress markers or in granulocyte and monocyte functions between groups. CONCLUSION: The administration of parenteral nutrition containing soybean oil-based and olive oil-based lipid emulsion resulted in similar rates of infectious and noninfectious complications and no differences in glycemic control, inflammatory and oxidative stress markers, and immune function in critically ill adults.

Sexually transmitted infections clinics as strategic venues for targeting high risk populations for HIV research and sexual health interventions.

Puerto Rico has one of the highest incidence rates of HIV in the U.S. Concurrent with increases in sexually transmitted infections (STI), an increasing share of the new infections in PR are associated with sexual transmission. Much of the available research on sexual risk in PR derives from STI/HIV surveillance data. There is limited social and epidemiological research on sexual risk in PR, particularly in hidden and often hard-to-reach populations at high risk. Despite the absence of substantial resources that most epidemiological studies require, a research collaboration was initiated in 2007 between researchers in the School of Public Health at the University of Puerto Rico and the Centro Latinoamericano de Enfermedades de Transmisión Sexual (CLETS), one of the largest publicly funded centers for STI/HIV screening and treatment in the San Juan metropolitan area. Structured as a case study in the development of community-based research collaborations, this paper describes the early history and development of the project, including formative research, recruitment and training of students, and evolution in the study design that contributed to the current configuration of the ongoing "Core" study. Preliminary data are presented, highlighting data from a number of subpopulations that may contribute to our understanding of the role of behavioral risk in the STI/HIV epidemics in PR. More generally, the paper may guide the development of similar collaboration elsewhere in the Caribbean where HIV risk is increasing but where resources for research in high risk settings and groups are scarce.

Preliminary Evidence of Significant Gaps in Continuity of HIV Care among Excarcerated Populations in Puerto Rico.

OBJECTIVE: Puerto Rico has high HIV prevalence and incidence rates, including a large prison population living with HIV. While HIV treatment is available within the prisons, there are no linkages to care or treatment preparedness interventions following release. METHODS: In an effort to assess the risk of treatment discontinuity in this group, we examined data from an ongoing epidemiological study in the largest, publicly funded HIV/sexually transmitted infection (STI) treatment center in the San Juan area. RESULTS: Among the newly enrolled, HIV-positive patients with a history of incarceration, there was an average 4-year gap in reengagement in treatment. Drug and sexual risk behaviors were prevalent, as was evidence of significant immune impairment (including high viral load and low CD4 count). CONCLUSIONS: Treatment discontinuity may contribute to poor health outcomes in this group and also fuel new infections. There is an urgent need for interventions to retain HIV-positive inmates in community HIV care following release.

Prevalence of human immunodeficiency virus-associated cognitive impairment in a group of Hispanic women at risk for neurological impairment.

Human immunodeficiency virus (HIV)-associated cognitive impairment, a significant cause of morbidity, affects up to 30% of HIV-infected people. Its prevalence doubled as patients began to live longer after the introduction of highly active retroviral therapy. Women are now one of the fastest growing groups with acquired immunodeficiency syndrome (AIDS) in the United States and Puerto Rico, but relatively little is known about the prevalence and characteristics of cognitive dysfunction in HIV-infected women. In this study the authors investigated its prevalence in a group of HIV-1-seropositive Hispanic women in Puerto Rico. Forty-nine women with a nadir CD4 cell count of < or = 500 cells/mm3 were enrolled. Cognitive impairment was defined according to the American Academy of Neurology criteria for HIV dementia as modified to identify an "asymptomatic cognitively impaired" group. Observed prevalence was compared with prevalence in other populations in United States, Europe, and Australia. Differences in clinical markers and neuropsychological test performance among the cohort stratified by cognitive impairment were tested. Cognitive impairment was observed in 77.6% (38/49) of cases; asymptomatic cognitive impairment in 32.7% (16/49); minor cognitive motor disorders in 16.3% (8/49); and HIV-associated dementia (HAD) in 28.6% (14/49). Cognitive impairment did not correlate with age, CD4 cell count, viral load, or treatment modality. The cross-sectional prevalence of HIV-associated cognitive impairment was 77.6% (28.6% for HAD). These findings should enhance awareness of the prevalence of HIV-associated cognitive impairment, both clinically apparent and "asymptomatic," in Hispanic women and lead to improvements in areas such as education and compliance and to reevaluation of treatment interventions.

An inhibitor of DNA recombination blocks memory consolidation, but not reconsolidation, in context fear conditioning.

Genomic recombination requires cutting, processing, and rejoining of DNA by endonucleases, polymerases, and ligases, among other factors. We have proposed that DNA recombination mechanisms may contribute to long-term memory (LTM) formation in the brain. Our previous studies with the nucleoside analog 1-beta-D-arabinofuranosylcytosine triphosphate (ara-CTP), a known inhibitor of DNA ligases and polymerases, showed that this agent blocked consolidation of conditioned taste aversion without interfering with short-term memory (STM). However, because polymerases and ligases are also essential for DNA replication, it remained unclear whether the effects of this drug on consolidation were attributable to interference with DNA recombination or neurogenesis. Here we show, using C57BL/6 mice, that ara-CTP specifically blocks consolidation but not STM of context fear conditioning, a task previously shown not to require neurogenesis. The effects of a single systemic dose of cytosine arabinoside (ara-C) on LTM were evident as early as 6 h after training. In addition, although ara-C impaired LTM, it did not impair general locomotor activity nor induce brain neurotoxicity. Importantly, hippocampal, but not insular cortex, infusions of ara-C also blocked consolidation of context fear conditioning. Separate studies revealed that context fear conditioning training significantly induced nonhomologous DNA end joining activity indicative of DNA ligase-dependent recombination in hippocampal, but not cortex, protein extracts. Finally, unlike inhibition of protein synthesis, systemic ara-C did not block reconsolidation of context fear conditioning. Our results support the idea that DNA recombination is a process specific to consolidation that is not involved in the postreactivation editing of memories.

Lack of evidence for in vivo transformation of zidovudine triphosphate to stavudine triphosphate in human immunodeficiency virus-infected patients.

The in vivo and in vitro determination of significant intracellular stavudine (d4T) triphosphate (d4TTP) concentrations in human immunodeficiency virus (HIV)-infected subjects and NS-1 cells treated with zidovudine (ZDV) has recently been reported. This study was conducted to corroborate these findings with in vivo samples from HIV-infected subjects taking ZDV and in vitro CEM(SS) cells incubated with different ZDV concentrations. Previously, we have reported on our validated high-performance liquid chromatography coupled with tandem mass spectrometry methodology for the simultaneous determination of d4TTP, lamivudine triphosphate, and ZDV triphosphate (ZDVTP) concentrations. Using this methodology, we monitored the d4TTP concentration in more than 100 samples from HIV-infected subjects treated with d4T. In addition, we simultaneously monitored the concentrations of d4TTP and ZDVTP in more than 500 samples from HIV-infected individuals who were taking ZDV. Finally, we performed in vitro studies by incubating CEM(SS) cells with 10 microM, 50 microM, and 100 microM ZDV and monitored the formation of d4TTP at 24 and 48 h. We could measure d4TTP concentrations from HIV-infected individuals with a limit of quantitation (LOQ) of 2.7 fmol/10(6) cells (total injection, 54 fmol). In the in vivo studies, we measured the d4TTP concentrations among patients receiving d4T treatment, but the samples from patients taking ZDV did not provide d4TTP concentrations above the LOQ. Furthermore, in vitro samples did not produce any signal for d4TTP, despite the detection of substantial ZDVTP concentrations in CEM(SS) cells. Thus, contrary to the previous report, we found no evidence for the in vivo or in vitro transformation of ZDVTP to d4TTP in HIV-infected subjects or CEM(SS) cells.