Clinical spectrum of peripheral facial paralysis in HIV-infected patients according to HIV status.

Although peripheral facial palsy is the most common cranial neuropathy in HIV-infected patients, no series have been reported recently in the literature. In this study we reviewed the clinical records of HIV-infected patients with a diagnosis of peripheral facial palsy between 2000 and 2011 attending the Hospital Marqués de Valdecilla (Infectious Diseases Unit), a 900-bed university hospital in northern Spain. We identified eight patients (4 men, 4 women): median CD4 count and viral load were 232 cells per µL and 130,000 RNA copies per mL, respectively. Most of them presented co-morbidities, including hepatitis C virus in 75%, hepatitis B virus in 15% and tuberculosis in 15%. Aetiologies of palsy were varied: idiopathic Bell's palsy predominated at early stages of the disease, whereas secondary causes, such as lymphoma and infections were frequently the cause of paralysis in advanced HIV/AIDS. At early stages of HIV infection, facial palsy is similar, both in aetiology and prognosis, to cases in the general population. However, in advanced stages the palsy is frequently secondary to underlying complications. Clinicians should be aware of these differences to tailor the diagnostic work-up.

Long-term benefits of nevirapine-containing regimens: multicenter study with 506 patients, followed-up a median of 9 years.

OBJECTIVE: To evaluate long-term outcomes in patients maintaining a nevirapine (NVP)-based regimen. METHODS: Retrospective, multicenter, cohort study including patients currently receiving an NVP regimen that had been started at least 5 years previously. Demographic, clinical, and analytical variables were recorded. RESULTS: Median follow-up was 8.9 (5.7-11.3) years. Baseline characteristics: 74% men, 47 years old, 36% drug users, 40% AIDS, 40% HCV+, 51.4% detectable HIV-1 viral load, CD4 count 395 (4-1,421)/µL, 19% CD4 < 200/µL, 27% ALT grade 1-2, 36% AST grade 1-2. Thirty percent ART-naive, 83%received NVP associated with 2 nucleoside analogues during the study period, and 17% a protease inhibitor. A significant improvement was observed in general health status markers, including hemoglobin, platelets, and albumin, regardless of HCV coinfection. CD4 cell gain was +218 and +322/µL after 6 and 9 years, respectively (+321 and +391 in naive patients). Triglycerides significantly decreased in pretreated patients, whereas the percentage of patients with HDLc < 1.03 mmol/L and LDL-c > 3.37 mmol/L significantly decreased in a subsample with available values. A significant decrease in transaminases, alkaline phosphatase, and Fib4 score was observed, mainly in HCV+ and ARV-naive patients. CONCLUSIONS: In patients who tolerate NVP therapy, (even those with HCV coinfection), long term benefits may be significant in terms of a progressive improvement in general health status markers and CD4 response, a favorable lipid profile, and good liver tolerability.

Delayed ischemic preconditioning protects against liver ischemia-reperfusion injury in vivo.

OBJECTIVES: Ischemic preconditioning (IP) affords resistance to liver ischemia-reperfusion (IR) injury, providing an early phase of protection. Development of delayed IP against IR injury was assessed using partial IR in rat liver. METHODS: The IP manuver (10 minutes of ischemia and up to 72 hours of reperfusion) was induced before 1 hour of ischemia and 20 hours of reperfusion. At the end of the reperfusion period, blood and liver samples were analyzed for serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), haptoglobin and tumor necrosis factor-alpha (TNF-alpha) levels, hepatic histology, protein carbonyl and glutathione (GSH) contents as well as nuclear factor-kappaB (NF-kappaB), and activating protein-1 (AP-1) DNA binding. RESULTS: The IP manuver significantly increased protein carbonyl/GSH ratios (275%), serum ALT (42%), and AST (58%); these changes normalized after 12 hours. Serum AST, ALT, and LDH levels were significantly increased by IR (4-, 5.6-, and 7.0-fold, respectively), with significant changes in liver histology, protein carbonyl/GSH ratio (481% enhancement), and serum TNF-alpha (6.1-fold increase). Delayed IP in IR animals reduced serum AST (66%), ALT (57%), and LDH (90%) and liver GSH depletion (89%), with normalization of protein carbonyl content, serum TNF-alpha levels, and liver histology. Enhanced AP-1/NF-kappaB DNA binding ratios and diminished haptoglobin expression induced by IR were normalized by IP. CONCLUSION: These data support that delayed IP suppresses IR-induced liver injury, oxidative stress, and TNF-alpha response, which coincide with recovery of IR-altered signaling functions represented by normal AP-1/NF-kappaB DNA binding ratios and acute phase responses.

Effect of simplification from protease inhibitors to boosted atazanavir-based regimens in real-life conditions.

BACKGROUND: Atazanavir (ATV) boosted with ritonavir (ATV/r) is a potent, well-tolerated, once-daily protease inhibitor (PI). Few data are available on this agent as a treatment simplification option for patients taking other PIs. OBJECTIVE: The aim of the study was to determine the effectiveness and safety of ATV-containing regimens in patients who have simplified their antiretroviral treatment. METHODS: SIMPATAZ was a multicentre, prospective, noninterventional study in patients who had undetectable HIV RNA on their current PI-containing therapy and who were switched to an ATV/r-based regimen. Patients underwent a routine physical examination, and data were collected on HIV RNA levels, CD4 cell counts, liver function, lipid parameters, adverse reactions, adherence to treatment and patient satisfaction. RESULTS: A total of 183 patients were enrolled in the study and included in the analysis (80% were male, 29% had AIDS, and 52% were coinfected with HIV and hepatitis B virus or hepatitis C virus). The median baseline CD4 count was 514 cells/µL. Median exposure to previous HIV therapy was 8 years, and 32% of patients had a history of PI failures. Lopinavir boosted with ritonavir was the most frequent PI replaced (62%) and tenofovir+lamivudine /emtricitabine the backbone most used during the study (29%). The study drug was discontinued early by 25 patients (14%), two of whom discontinued as a result of adverse events (Hodgkin lymphoma and vomiting). Two patients died (lung cancer and myocardial infarction). At month 12, 93% of the study population had an undetectable HIV RNA viral load. Hyperbilirubinaemia >3 mg/dL and increased alanine aminotransferase levels>200 IU/L were observed in 38.5% and 4.4% of patients, respectively. Median changes from baseline to month 12 in total cholesterol, triglycerides and low-density lipoprotein cholesterol were -13 mg/dL (-7%; P<0.0001), -19 mg/dL (-13%; P<0.0001) and -7 mg/dL (-6%; P=0.021), respectively. CONCLUSIONS: In a real-world setting, switching from other PIs to ATV/r is a well-tolerated and safe option for improving the lipid profile and for retaining virological response in controlled pretreated patients.

Critical role of ribavirin for the achievement of early virological response to HCV therapy in HCV/HIV-coinfected patients.

The response to hepatitis C virus (HCV) therapy seems to be lower in HCV/HIV-coinfected patients than in HCV-monoinfected individuals. Given that most pivotal trials conducted in coinfected patients have used the combination of pegylated interferon (pegIFN) along with fixed low doses (800 mg/day) of ribavirin (RBV), it is unclear whether HIV itself and/or suboptimal RBV exposure could explain this poorer outcome. Two well-defined end points of early virological response were evaluated in Peginterferon Ribavirina España Coinfección (PRESCO), a multicentre trial in which the combination of pegIFN plus RBV (1000 mg if body weight <75 kg and 1200 mg if >75 kg) was prescribed to coinfected patients. For comparisons, we used unpublished data from early kinetics in two other large trials, one performed in HIV-negative patients [Pegasys International Study Group (PISG)] in which RBV 1000-1200 mg/day was used and another [AIDS Pegasys Ribavirin Coinfection Trial (APRICOT)] in which HIV-positive patients received fixed low RBV doses (800 mg/day). A total of 348 HCV/HIV-coinfected patients from the PRESCO trial were analysed as well as all patients treated with pegIFN plus RBV, who completed 12 weeks of therapy in the comparative studies (435 in PISG and 268 in APRICOT). Negative serum HCV-RNA at week 4 (which has the highest positive predictive value of sustained virological response, SVR) was attained in 33.3%, 31.2% and 13% of treated patients with HCV genotype 1, respectively, in PRESCO, PISG and APRICOT. For HCV genotypes 2/3, responses were 83.7%, 84.2% and 37%, respectively. A decline lower than 2 log(10) at week 12 (which has the highest negative predictive value of SVR) was seen in 25.5%, 19.5% and 37% of HCV genotype-1-infected patients, and in 2.1%, 2.9% and 12% of genotypes-2/3-infected patients, respectively. Prescription of high RBV doses enhances the early virological response to HCV therapy in HCV/HIV-coinfected patients, with results approaching those seen in HCV-monoinfected patients.

Prenatal care utilization among non-Hispanic Whites, African Americans, and Mexican Americans.

OBJECTIVES: The general objective of this study is to explain differentials in prenatal care (PNC) utilization in a nationally representative sample of non-Hispanic White (Anglo), African American, and Mexican American women. METHOD: The analysis is based on the National Maternal and Infant Health Survey. Multivariate, multinomial logistic regression models were employed to adjust for demographic, socioeconomic, medical risk, and program participation factors, as well as for perceived barriers. Both race/ethnic-specific models and models with race/ethnicity as a covariate were estimated. RESULTS: Inadequate PNC use was much less common among Anglos (10.4%) as compared to African Americans and Mexican Americans (22.1% and 25.0%, respectively). In fully adjusted models, the odds ratio (OR) of African Americans receiving inadequate PNC was 1.46, while the risk for Mexican Americans was greater (OR = 1.93). Perception of obstacles to PNC access doubled the odds of receiving inadequate care, but this psychosocial variable had little impact on race/ethnic differentials. Race/ethnic-specific models uncovered potentially important racial/ethnic variations associated with perception of barriers, marital status, and program participation. CONCLUSIONS: Although the same risk factors sometimes have different effects across race/ethnic groups, and while certain findings indicate a beneficial impact of health outreach efforts and program participation, our findings support the conclusion that PNC utilization continues to be stratified along race/ethnic lines.

Limited immune reconstitution at intermediate stages of HIV-1 infection during one year of highly active antiretroviral therapy in antiretroviral-naive versus non-naive adults.

Although several reports have attributed the clinical benefits of highly active antiretroviral therapy (HAART) to a possible immune restoration, long-term data are still scarce and most derive from patients with either advanced or very early stages of HIV infection. In the present study, changes in lymphocyte subsets, activation markers, and adhesion molecules in CD4+ and CD8+ lymphocytes were carefully monitored over a 1-year period in 27 HIV-infected adults at an intermediate stage of HIV infection. Cytokine-producing patterns were also studied. In these patients the HIV viral load disappeared by month 4 of HAART. Only limited immunological changes were observed: an incomplete recovery of naive CD4+ T cells, a less activated state of CD8+ T cells, and a repopulation of IL-2- and IFN-gamma-producing CD4+ T cells. These changes were observed principally in patients with more advanced disease. Furthermore, HIV-infected subjects who had received HAART previously showed less marked immunological changes than antiretroviral-naive individuals. In conclusion, the sustained viral suppression during 1 year of HAART was accompanied by limited immunological recovery at intermediate stages of HIV infection. This finding indicates a need for longer HIV suppression in order to achieve effective recovery of the immune system.

[BICAP tumor probe in the palliative treatment of malignant esophageal stenosis]. / BICAP tumor probe en el tratamiento paliativo de la estenosis esofágicas malignas.

BACKGROUND: BICAP tumor probe is a device that consists in an energy source and olives that deliver bipolar electricity. It can be used for the fulguration of esophageal tumors after endoscopic dilatation. AIM: To report the experience in the treatment of malignant esophageal stenoses using the BICAP tumor probe. PATIENTS AND METHODS: Patients with advanced esophageal tumors in aphagia, that were not candidates for palliative surgery were included in this study. After endoscopic dilatation, the tumor was fulgurated with the BICAP tumor probe. RESULTS: Twenty one patients (nine male, aged 43 to 91 years old) were treated with the device. A mean of 1.3 sessions with BICAP were necessary to obtain tumor permeabilization, which was obtained in all patients. One patient died of pneumonia 15 days after the procedure. All other patients were ingesting liquid or semisolid diets after two months of follow up. Mean survival after the procedure was 3.8 months. CONCLUSIONS: Electrical fulguration of esophageal tumors is a valid therapeutic alternative in aphagic patients.

Slowed reaction time in HIV-1-seropositive intravenous drug users without AIDS.

One hundred and fourteen subjects with a history of intravenous drug abuse (65 subjects infected with the human immunodeficiency virus, HIV, and 49 seronegative controls) were evaluated with a reaction time (RT) test which included one measure of simple RT and three measures of complex RT. All seropositive patients were in HIV stages A or B. The multivariate analysis of covariance controlled for age, educational level and Montgomery-Asberg Depression Rating Scale score, showed differences between seropositive subjects and controls: the seropositive group scored slower than the control group on two RT tasks, simple RT and a more complex RT measure. Our results suggest that computerized RT measures may be more sensitive than conventional neuropsychological tests in detecting subtle cognitive and motor retardation in the early stages of HIV infection, thus extending the findings of other studies to the intravenous drug-user population.

Cutaneous metastases as initial manifestation of dedifferentiated chondrosarcoma of bone. An autopsy case with review of the literature.

Metastases of chondrosarcoma to the skin are uncommon. We report a case of dedifferentiated chondrosarcoma that manifested as cutaneous metastases and had an outcome of three weeks. A 69-year-old male presented with two cutaneous nodules, one in the chest and other in the inguinal area. The punch biopsy of the latter showed a poorly differentiated mesenchymal metastatic tumor. Shortly before death, an X-ray revealed a proximal epiphyseal lesion in the right humerus, radiographically interpreted as chondrosarcoma. The autopsy showed this lesion to be a dedifferentiated chondrosarcoma whose nonchondroid mesenchymal part was akin, histologically and immunohistochemically, to the cutaneous metastases. While ten previous reports of chondrosarcoma metastatic to the skin are known, we believe that this is the first case to report the cutaneous metastases of the dedifferentiated variety. Furthermore, skin metastasis preceding the diagnosis of chondrosarcoma has not been previously reported. The fact that one part of this kind of tumor can be highly undifferentiated or, else, differentiated along lines not usually reminiscent of bone tumors, can make the diagnosis of such cases extremely difficult. Most chondrosarcomas metastatic to the skin arise in bones of the extremities, including the hand. The most common type of tumor is conventional chondrosarcoma. These metastases can be either single or multiple with a slight predilection for the head and neck region. Most patients die in a mean time of 6 months after the appearance of cutaneous metastases.

Factors associated with neuropsychological performance in HIV-seropositive subjects without AIDS.

BACKGROUND: Previous research has suggested that several factors may influence the presence of cognitive impairment in human immunodeficiency virus (HIV) infection. The objective of this study was to assess the impact of cognitive reserve capacity and other variables on neuropsychological performance in early HIV infection. METHODS: The neuropsychological performance of 100 HIV-seropositive subjects without AIDS (71 men and 29 women) was compared with that of 63 seronegative controls (51 men and 12 women). Measures included a neuropsychological battery, a medical examination and a psychiatric assessment. Cognitive reserve scores were based on a combination of years in school, a measure of educational achievement, and an estimate of pre-morbid intelligence. RESULTS: HIV-positive subjects had longer reaction time latencies than HIV-negative subjects. Those in the HIV-positive group with low cerebral reserve scores showed the poorest performance on the neuropsychological tests. The prevalence of cognitive impairment was significantly higher in the HIV-positive group (27%) than in the controls (32%). Multiple regression analysis and logistic regression analysis were used to identify factors associated with global neuropsychological performance and cognitive impairment. Older age, lower cerebral reserve scores and not being on zidovudine treatment were associated with lower global neuropsychological scores and with the presence of cognitive impairment. CONCLUSIONS: Our results suggest that although cognitive impairment is not characteristic of early HIV infection, there is a subgroup of subjects who perform more poorly than expected. A lower reserve capacity, older age and not being on zidovudine treatment are factors that lower the threshold for neuropsychological abnormalities in cases of early HIV infection.

Interferon alpha treatment of chronic hepatitis C in HIV-infected patients receiving zidovudine: efficacy, tolerance and response related factors.

BACKGROUND/AIMS: In our area most of the human immunodeficiency virus (HIV) infected patients are intravenous drug users; HIV and hepatitis C virus infections often coexist in these patients. Due to the repercussions of both infections, we designed a trial to evaluate the efficacy, response-related factors and tolerance during an eight-month regime of recombinant interferon alpha-2b on hepatitis C virus infection. METHODOLOGY: We included 79 patients in an open, prospective and multicentric trial with zidovudine and interferon alpha-2b. Response to interferon treatment was evaluated by biochemical and histopathological criteria. RESULTS: A complete response (alanine aminotransferase normalization) was obtained in 57.4% of patients. The significant response-related factors were: degree of histopathological activity, CD4+ cell number and initial leukocyte number. CONCLUSIONS: Recombinant interferon therapy seems to be effective for chronic hepatitis C in HIV infected patients; the best response was in those with active chronic hepatitis and CD4+ cell counts > or = 200/mm3. General tolerance was variable, although side effects were not different from those seen in non-HIV patients. The most common side effect was flu-like syndrome (constitutional manifestations), with no interference on treatment continuity; however, hematological toxicity prevents the indiscriminate use of interferon.

[Normative data for the neuropsychological evaluation of intravenous drug users]. / Datos normativos para la exploración neuropsicológica de usuarios de drogas por vía parenteral.

BACKGROUND: There are many recent epidemiological studies that find that intravenous drug users' (IDU's) performance in several measures of neuropsychological function are not the same than that of the general population, whether they are seropositive to HIV-1 infection or not. Consequently, it has been stated the need to establish appropriate norms for this population. The purpose of this study is to provide normative data on a battery of neuropsychological tests from a IDU group. SUBJECTS AND METHODS: This report provide normative data from a group of 116 IDU, on a battery of neuropsychological tests stratified by age group (mean = 30.9; SD = 4.5), and educational level (mean = 8; SD = 2.4). Comparisons between the means of the different groups according to age and education, and also with respect to sex are made. The analysis includes estimation of partial correlations between neuropsychological test scores and age and education. RESULTS: The analysis demonstrates that education is an important determinant of performance for most of these tests, while there are no differences in performance between the two age-groups. With respect to sex, females out-performed men on a measure of motor speed and coordination. CONCLUSIONS: This report provides norms that may be of use as a reference for clinical evaluation and research in drug user populations. It also emphasizes the need to establish normative data controlling for variables like educational level, from a population with special characteristics such as IDU population.

Atypical coccidioidomycosis in an AIDS patient successfully treated with fluconazole.

Cervical lymphadenopathy due to Coccidioides immitis occurred as the sole opportunistic infection in a Spanish patient with the acquired immunodeficiency syndrome. Twelve years earlier the patient had lived in the desert regions of the southwestern USA. After an initial course of high doses of fluconazole, the patient recovered without any sequelae. This is the first case of coccidioidomycosis in Spain.

Neuroleptic malignant syndrome in the acquired immunodeficiency syndrome.

Patients infected by the human immunodeficiency virus are predisposed to many infectious and noninfectious complications and often receive a variety of drugs. Furthermore, they seem to have a particular susceptibility to idiosyncratic adverse drug reactions. It is therefore surprising that only a few cases of the neuroleptic malignant syndrome have been described in patients with the acquired immunodeficiency syndrome. A high index of suspicion is required to diagnose the neuroleptic malignant syndrome in these patients, as its usual manifestations, including fever and altered consciousness, are frequently attributed to an underlying infection.