bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gender difference in HIV‐1 RNA viral loads
Authors: Donnelly CA , Bartley LM , Ghani AC , Le Fevre AM , Kwong GP , Cowling BJ , Van Sighem AI , De Wolf F , Rode RA , Anderson RM 
Published: May 2005

ObjectivesTo test and characterize the dependence of viral load on gender in different countries and racial groups as a function of CD4 T‐cell count.MethodsPlasma viral load data were analysed for >30 000 HIV‐infected patients attending clinics in the USA [HIV Insight™ (Cerner Corporation, Vienna, VA, USA) and Plum Data Mining LLC (East Meadow, NY, USA) databases] and the Netherlands (Athena database; HIV Monitoring Foundation, Amsterdam, Netherlands). Log‐normal regression models were used to test for an effect of gender on viral load while adjusting for covariates and allowing the effect to depend on CD4 T‐cell count. Sensitivity analyses were performed to test the robustness of conclusions to assumptions regarding viral loads below the lower limit of quantification (LLOQ).ResultsAfter adjusting for covariates, women had (nonsignificantly) lower viral loads than men (HIV Insight™:−0.053 log10 HIV‐1 RNA copies/mL, P=0.202; Athena: −0.005 log10 copies/mL, P=0.667; Plum:−0.072 log10 copies/mL, P=0.273). However, further investigation revealed that the gender effect depended on CD4 T‐cell count. Women had consistently higher viral loads than men when CD4 T‐cell counts were at most 50 cells/μL, and consistently lower viral loads than men when CD4 T‐cell counts were greater than 350 cells/μL. These effects were remarkably consistent when estimated independently for the racial groups with sufficient data available in the HIV Insight™ and Plum databases.ConclusionsThe consistent relationship between gender‐related differences in viral load and CD4 T‐cell count demonstrated here explains the diverse findings previously published.
Better maintained adherence on switching from twice‐daily to once‐daily therapy for HIV: a 24‐week randomized trial of treatment simplification using stavudine prolonged‐release capsules
Authors: Portsmouth SD , Osorio J , McCormick K , Gazzard BG , Moyle GJ 
Published: May 2005

BackgroundAdherence to antiretroviral therapy is critical to treatment outcomes. Adherence studies in other therapeutic areas of medicine suggest that once‐daily regimens support improved adherence when compared to twice‐daily therapy. An expansion in the range of once‐daily antiretrovirals is making once‐daily therapy possible for persons with HIV infection.MethodsA 24‐week randomized open‐label simplification study of twice‐daily regimens based on stavudine immediate release or zidovudine to an all once‐daily regimen based on the stavudine prolonged‐release capsule (PRC), in persons with complete virological suppression on regimens also including efavirenz and lamivudine, was carried out. Subjects were assessed for adherence [using the Medication Event Monitoring System® (MEMS®) cap; Aardex Corporation, Union City, CA, USA], quality of life, tolerability and efficacy.ResultsForty‐three patients were randomly assigned: 21 remained on their original regimen and 22 switched to once‐daily therapy with stavudine PRC. Although high levels of adherence and good quality of life were present at study enrolment, adherence declined to a significantly lesser extent at week 24 in the group that switched to once‐daily therapy. Efficacy was maintained in both groups and there were no differences in tolerability or toxicity.ConclusionsSubjects switching from twice‐daily therapy to once‐daily therapy demonstrate less of a decline in adherence over 24 weeks. A once‐daily regimen including stavudine PRC is as effective and tolerable as a regimen containing the twice‐daily formulation.
The use of a triple nucleoside‐nucleotide regimen for nonoccupational HIV post‐exposure prophylaxis
Authors: Winston A , McAllister J , Amin J , Cooper DA , Carr A 
Published: May 2005

ObjectivesNonoccupational post‐exposure prophylaxis (NPEP) for HIV is recommended after high‐risk sexual exposure. Because of the high incidence of intolerable side effects observed with protease inhibitor‐ and zidovudine‐based NPEP regimens, our unit changed standard NPEP treatment to 28 days of tenofovir‐lamivudine‐stavudine (TDF‐3TC‐d4T). The aim of this study was to compare side effects and numbers of individuals completing NPEP before and after this change.MethodsParameters were compared amongst individuals commencing the following NPEP regimens: zidovudine‐lamivudine (ZDV‐3TC), zidovudine‐lamivudine‐nelfinavir (ZDV‐3TC‐NFV) and TDF‐3TC‐d4T.ResultsA total of 385 individuals received ZDV‐3TC (n=36), ZDV‐3TC‐NFV (n=225) or TDF‐3TC‐d4T (n=137) as NPEP for the first time between June 1999 and November 2003. Noncompletion rates were 25%, 32% and 15%, respectively (P=0.001), with odds ratios for noncompletion being 2.0 [95% confidence interval (CI) 0.8–4.8] and 2.7 (95% CI 1.6–4.8) in the first two groups compared with the TDF‐3TC‐d4T group (P=0.008). Adverse events were less common in the TDF‐3TC‐d4T group, with significantly lower rates of nausea and headache, but significantly higher rates of peripheral neuropathy and asymptomatic raised transaminases. There was no HIV seroconversion in any group.ConclusionsTDF‐3TC‐d4T is significantly better tolerated than ZDV‐3TC or ZDV‐3TC‐NFV as NPEP and results in greater numbers of individuals completing 28 days of treatment.
Determinants of clinical progression in antiretroviral‐naïve HIV‐infected patients starting highly active antiretroviral therapy. Aquitaine Cohort, France, 1996–2002
Authors: Bonnet F , Thiébaut R , Chêne G , Neau D , Pellegrin J‐L , Mercié P , Beylot J , Dabis F , Salamon R , Morlat P ,   for the Groupe d'Epidemiologie Clinique du SIDA en Aquitaine (GECSA)
Published: May 2005

ObjectivesTo determine the factors associated with clinical progression (AIDS events and death) in antiretroviral‐naïve patients who have begun highly active antiretroviral therapy (HAART).MethodsHIV‐infected patients naïve to antiretroviral therapy were included in a prospective hospital‐based cohort who began HAART between June 1996 and December 2001. Progression was explained by baseline characteristics using Cox proportional hazards models.ResultsOverall, data for 709 patients were analysed. In multivariate analysis, factors associated with an increased risk of progression were CD4 count <50 cells/μL [hazard ratio (HR)=13.0 (95% confidence interval 3.8–44.3)] and between 50 and 199 cells/μL [HR=5.1 (1.6–16.3)], when compared with patients with CD4 count>350 cells/μL; AIDS events before HAART prescription [HR=2.1 (1.2–3.7)]; CD8 count < 400 cells/μL [HR=1.8 (1.1–3.0)]; and older age (HR=1.2 by 10 years (1.0–1.5)]. In a second model including CD4 percentage, factors associated with progression were CD4<10% [HR=6.3 (2.2–17.9)] and 10%<CD4 <15% [HR=4.2 (1.4–12.5)], when compared with patients with CD4>20%; CD8 count; AIDS events before HAART prescription; and older age. In a third model including the CD4:CD8 ratio, factors associated with progression were CD4:CD8<15% [HR=8.2 (2.3–28.8)] and 15%<CD4:CD8<30% [HR=4.6 (1.3–16.0)], when compared with patients with CD4:CD8>45%; AIDS events before HAART prescription; and older age. The Akaike information criteria for model analysis were 803, 805 and 815, respectively.ConclusionsConsideration of CD4 level in terms of CD4:CD8 ratio or CD4 percentage can be a good alternative to absolute CD4 count. Other prognostic factors such as older age, CD8 count <400 cells/μL and AIDS events also have to be considered in the decision to initiate HAART.
Predicting short‐term disease progression among HIV‐infected patients in Asia and the Pacific region: preliminary results from the TREAT Asia HIV Observational Database (TAHOD)
Authors: Zhou J , Kumarasamy N ,   on behalf of the TREAT Asia HIV Observational Database
Published: May 2005

ObjectivesHIV disease progression has been well documented in Western populations. This study aimed to estimate the short‐term risk of AIDS and death from the TREAT Asia HIV Observational Database (TAHOD), a prospective, multicentre cohort study in Asia and the Pacific region.MethodsProspective data were analysed to estimate short‐term disease progression. Endpoints were defined as the time from study entry to diagnosis with AIDS or death. Antiretroviral treatment was fitted as a time‐dependent variable. Predictors of disease progression were assessed using Cox proportional hazards models, and prognostic models were developed using Weibull models.ResultsA total of 1260 patients with prospective follow‐up data contributed 477 person‐years of follow‐up, during which 18 patients died and 34 were diagnosed with AIDS, a combined rate of 10.1 per 100 person‐years. Compared with patients receiving antiretroviral treatment, patients not on treatment had a higher rate of disease progression (17.6 vs. 8.1 per 100 person‐years, respectively). Baseline CD4 count was the strongest predictor of disease progression. Prognostic models, using either a baseline CD4 count as the sole marker or markers including baseline haemoglobin, AIDS‐related symptoms and previous or current antiretroviral treatment, were successful at identifying patients at high risk of short‐term disease progression.ConclusionsSimilar to the situation in Western countries, baseline CD4 count was the strongest predictor of short‐term disease progression. Prognostic models based on readily available clinical data and haemoglobin level should be useful in estimating short‐term clinical risk in HIV‐infected patients in Asia and the Pacific region.
Making Sense of Lamotrigine Serum Levels
Authors: Abou-Khalil Bassel W. 
Published: May 2005

Correlating Lamotrigine Serum Concentrations with Tolerability in Patients with Epilepsy Hirsch LJ, Weintraub D, Du Y, Buchsbaum R, Spencer HT, Hager M, Straka T, Bazil CW, Adams DJ, Resor SR Jr, Morrell MJ Neurology 2004;63:1022–1026 Objective To correlate lamotrigine (LTG) serum concentrations (levels) with tolerability in patients with epilepsy. Methods The charts of 811 outpatients with epilepsy who had received LTG and were seen at the Columbia Comprehensive Epilepsy Center after January 1, 2000, were reviewed. Data gathered included levels, dosage, duration of use, concomitant antiepileptic drugs (AEDs), clinical toxicity, specific side effects, and efficacy. Rates of toxicity, specific side effects, and efficacy were calculated and correlated with serum levels. Results In total, 3,731 LTG levels were recorded. A regimen was categorized as toxic if the patient experienced side effects that led to a dosage change or discontinuation of LTG. Of 3,919 AED regimens, 9.4% were toxic, and 30.7% of patients had at least one toxic regimen. Toxicity increased with increasing LTG levels ( P < 0.0001): With levels less than 5.0 μg/mL, 7% of patients were toxic; with levels of 5 to 10 μg/mL, 14%; with 10 to 15 μg/mL, 24%; with 15 to 20 μg/mL, 34%; and with more than 20 μg/mL, 59%. The correlation between levels and tolerability was independent of concurrent medication. Increasing efficacy, as measured by seizure freedom for a 6-month period, occurred up to levels of more than 20 μg/mL. Conclusions A correlation exists between LTG serum level and tolerability, independent of the use of other AEDs. Adverse effects requiring a dose change are uncommon with the most frequently encountered LTG concentrations (<10 μg/mL) and occur in only 7.4% of patients at levels obtained during the majority of clinical trials (<5 μg/mL). An initial target range of 1.5 to 10 μg/mL is suggested, although higher levels, up to more than 20 μg/mL, are often tolerated and can lead to additional efficacy in refractory patients.
Valproate Poses Risk to Unborn Child
Authors: Meador Kimford 
Published: May 2005

The Longer Term Outcome of Children Born to Mothers with Epilepsy Adab N, Kini U, Vinten J, Ayres J, Baker G, Clayton-Smith J, Coyle H, Fryer A, Gorry J, Gregg J, Mawer G, Nicolaides P, Pickering L, Tunnicliffe L, Chadwick DW J Neurol Neurosurgsychiatry 2004;75:1575–1583 Objectives To determine the prevalence of cognitive delay and possible associated dysmorphic features in children exposed to antiepileptic drugs (AEDs) in utero. Methods In a retrospective study of children born to mothers with epilepsy, in regional epilepsy clinics in Liverpool and Manchester, U.K., the children were aged between 6 months and 16 years and born to mothers with epilepsy. Structured interviews, hospital records, clinical examination, and psychometric tests (Wechsler) were used to assess exposure and intelligence quotient (IQ). Blinded assessment of photographs was used to score children with characteristic dysmorphic features. Results In total, 249 children aged 6 and older were studied: 41 were exposed to sodium valproate (VPA), 52 to carbamazepine, 21 to phenytoin, 49 to polytherapy, and 80 were unexposed. Mean verbal IQ was significantly lower in the VPA group compared with that in unexposed and other monotherapy groups. Multiple regression analysis showed that both VPA exposure and frequent tonic-clonic seizures in pregnancy were significantly associated with a lower verbal IQ, despite adjusting for other confounding factors. A significant negative correlation was found between dysmorphic features and verbal IQ in children exposed to VPA. Conclusions This study identifies VPA as a drug carrying potential risks for developmental delay and cognitive impairment and is the first to suggest that frequent tonic-clonic seizures have a similar effect. Our results must be interpreted with caution, given their retrospective nature. Women with epilepsy need careful counseling about individual risk benefit of AED treatment before pregnancy.
Calcium Channel “Gaiting” and Absence Epilepsy
Authors: Noebels Jeffrey L. 
Published: May 2005

Dysfunction of the Brain Calcium Channel Cav2.1 in Absence Epilepsy and Episodic Ataxia Imbrici P, Jaffe SL, Eunson LH, Davies NP, Herd C, Robertson R, Kullmann DM, Hanna MG Brain 2004;127(Pt 12):2682–2692 The molecular basis of idiopathic generalized epilepsy remains poorly understood. Absence epilepsy with 3-Hz spike–wave EEG is one of the most common human epilepsies and is associated with significant morbidity. Several spontaneously occurring genetic mouse models of absence epilepsy are caused by dysfunction of the P/Q-type voltage-gated calcium channel CaV2.1. Such mice exhibit a primary generalized spike–wave EEG, with frequencies in the range of 5 to 7 Hz, often associated with ataxia, evidence of cerebellar degeneration and abnormal posturing. Previously, we identified a single case of severe primary generalized epilepsy with ataxia associated with CaV2.1 dysfunction, suggesting a possible link between this channel and human absence epilepsy. We now report a family in which absence epilepsy segregates in an autosomal dominant fashion through three generations. Five members exhibit a combination of absence epilepsy (with 3-Hz spike–wave) and cerebellar ataxia. In patients with the absence epilepsy/ataxia phenotype, genetic marker analysis was consistent with linkage to the CACNA1A gene on chromosome 19, which encodes the main pore-forming α1A subunit of CaV2.1 channels (CaV2.1 α1). DNA sequence analysis identified a novel point mutation resulting in a radical amino acid substitution (E147K) in CaV2.1 α1, which segregated with the epilepsy/ataxia phenotype. Functional expression studies using human CACNA1A cDNA demonstrated that the E147K mutation results in impairment of calcium channel function. Impaired function of the brain calcium channel CaV2.1 may have a central role in the pathogenesis of certain cases of primary generalized epilepsy, particularly when associated with ataxia, which may be wrongly ascribed to anticonvulsant medication.
Regulation of Brain Water: Is there a Role for Aquaporins in Epilepsy?
Authors: Dudek F. Edward , Rogawski Michael A. 
Published: May 2005

Aquaporin-4 Is Increased in the Sclerotic Hippocampus in Human Temporal Lobe Epilepsy Lee TS, Eid T, Mane S, Kim JH, Spencer DD, Ottersen OP, de Lanerolle NC Acta Neuropathol (Berl) 2004;108:493–502 The hippocampus of patients with mesial temporal lobe epilepsy is often hardened and shrunken, a condition known as sclerosis. MRI reveals an increase in the T2-weighted signal, whereas diffusion-weighted imaging shows a higher apparent diffusion coefficient in sclerotic hippocampi, indicating increased water content. As water transport appears to be coupled to K+ clearance and neuronal excitability, the molecular basis of the perturbed water homeostasis in the sclerotic hippocampus was explored. The expression of aquaporin-4 (AQP-4), the predominant water channel in the brain, was studied with quantitative real-time polymerase chain reaction analysis, light-microscopic immunohistochemistry, and high-resolution immunogold labeling. A significant increase in AQP-4 was observed in sclerotic, but not in nonsclerotic, hippocampi obtained from patients with medically intractable temporal lobe epilepsy. This increase was positively correlated with an increase in the astrocyte marker glial fibrillary acidic protein. AQP-4 was localized to the plasma membranes of astrocytes including the perivascular endfeet. Gene expression associated with increased AQP-4 was evaluated by high-throughput gene-expression analysis with Affymetrix GeneChip U133A, and related gene networks were investigated with Ingenuity Pathways Analysis. AQP-4 expression was associated with a decrease in expression of the dystrophin gene, a protein implicated in the anchoring of AQP-4 in perivascular endfeet. The decreased expression of dystrophin may indicate a loss of polarity in the distribution of AQP-4 in astrocytes. We conclude that the perturbed expression of AQP-4 and dystrophin may be one factor underlying the loss of ion and water homeostasis in the sclerotic hippocampus and hypothesize that the reported changes may contribute to the epileptogenic properties of the sclerotic tissue.
Neuroleptic dysphoria: revisiting the concept 50 years later
Authors: Awad A. G. , Voruganti L. N. P. 
Published: May 2005

Objective:  To review the concept of neuroleptic dysphoria, its historical development and the current state of the art.Method:  This paper is based on extensive but selective literature review and also draws on our extensive clinical and research experiences.Results:  Although the construct of neuroleptic dysphoria was recognized shortly following the introduction of the first antipsychotic, chlorpromazine, it took several years for the concept to receive adequate research and clinical attention. Without having direct evidence to link neuroleptic dysphoria to dopamine, it was generally understood that dopamine played a significant role in its genesis. In recent neuroimaging studies and dopamine depletion strategies, the role of dopamine in the genesis of neuroleptic dysphoria has been directly confirmed.Conclusion:  Neuroleptic dysphoria is a valid construct, which has significant implications for treatment and outcome. It is now clear that it relates to dopamine activities in the nigrostriatal complex. Recent research has also raised the issue of whether neuroleptic dysphoria is a variant of extrapyramidal symptoms. Meanwhile, the role of dopamine in both the genesis of neuroleptic dysphoria and addictive behaviour has raised the issue of both conditions being different facets of the schizophrenic disease process. The recent interface of addiction and psychiatry research may have opened a new science: the science of subjective tolerability disorders.
Subjective well‐being under neuroleptic treatment and its relevance for compliance
Authors: Naber D. , Karow A. , Lambert M. 
Published: May 2005

Objective:  To review the concept of ‘subjective well‐being under neuroleptic treatment’, its development and clinical relevance, particularly regarding compliance.Method:  The manuscript includes a review of the limited literature and recent open and controlled clinical trials.Results:  The patients’ perspective of antipsychotic treatment was largely neglected for a long time. Scientific interest in this field of strong clinical relevance started mainly with the development of atypical antipsychotics. Recent research indicates that subjective well‐being (SW) is a major determinant of medication compliance in schizophrenia. There are several self‐report instruments with sufficient internal consistency and good construct validity. Effects of antipsychotic treatment on psychopathology and SW are only partly related. Most patients strongly prefer the atypical over typical antipsychotics. The assessment of SW is helpful for selecting the optimal drug for the individual patient.Conclusion:  SW, under antipsychotic treatment, is a valid construct; its assessment provides an independent outcome variable, which is relevant to compliance.
Levels of Recent Thymic Emigrant Cells Decrease in Children Undergoing Partial Thymectomy during Cardiac Surgery
Authors: Madhok Ashish B. , Chandrasekran A. , Parnell Vincent , Gandhi Mysore , Chowdhury Devyani , Pahwa Savita 
Published: May 2005

ABSTRACT

The human thymus is required for establishment of a T-cell pool in fetal life, but postnatal thymectomy is not known to cause immunodeficiency. T-cell emigration from thymus (thymic recent emigrants [TRECs]) is a continuous thymic-dependent process. We studied TREC levels pre- and post-partial thymectomy in children undergoing cardiac surgery. TRECs were quantitated by real-time PCR in peripheral blood lymphocytes of 24 children (0 to 12 years). TREC values were 47916 ± 9271 pre-partial thymectomy and 33157 ± 8479 post-partial thymectomy in 11 paired patients (
P
= 0.014). Interval between pre- and post-partial thymectomy was 8.8 days ± 5.8 days. Another group of 8 children had 30384 ± 9748 TRECs 16 days to 6 years post-partial thymectomy. There was a significant drop in TREC values post-partial thymectomy in the immediate postoperative period compared to prethymectomy TREC levels. While decreased thymic output may persist, the long-term implications were not evaluated in this patient population.
Duplex Microsphere-Based Immunoassay for Detection of Anti-West Nile Virus and Anti-St. Louis Encephalitis Virus Immunoglobulin M Antibodies
Authors: Johnson Alison J. , Noga Amanda J. , Kosoy Olga , Lanciotti Robert S. , Johnson Alicia A. , Biggerstaff Brad J. 
Published: May 2005

ABSTRACT
West Nile (WN) virus was introduced into the United States in 1999, when the first human cases of WN fever and encephalitis appeared in New York City. From there, the virus has spread throughout North America, in some areas cocirculating with the related flavivirus St. Louis encephalitis (SLE) virus. Public health laboratories currently use an immunoglobulin M (IgM) antibody capture enzyme-linked immunosorbent assay (MAC-ELISA) as a primary test for human serodiagnosis, followed by a confirmatory plaque-reduction neutralization test (PRNT). The MAC-ELISAs take 2 days to perform; therefore there is a need for a more rapid test. This report describes a duplex microsphere-based immunoassay (MIA) that shortens the test processing time to about 4.5 h. The assay employs two sets of microspheres coupled to a single flavivirus group-reactive antibody, which are used to capture the WN and SLE viral antigens independently. Immunoglobulin G-depleted serum is concurrently assayed for IgM antibodies to each of the viral antigens. The results are standardized and classified by using quadratic discriminant analysis so that a single result, anti-WN IgM-positive, anti-SLE IgM-positive, negative, or nonspecific, can be determined. The duplex MIA results compared favorably to those of the plaque-reduction neutralization test and MAC-ELISA. The assay proved to be reproducible, produced accurate classifications as to the infecting virus, and was specific.