Hearing impairment and deafness among HIV infected children and adolescents in Harare, Zimbabwe.

Background: Among HIV-infected children ear infections are recurrent and chronic, which may lead to hearing loss. Objective: To determine the prevalence, cause and severity of hearing impairment among HIV-infected children aged 5-17 years attending for HIV care in Harare. Design and Setting: An analytical cross-sectional survey conducted at Newlands Clinic, an opportunistic infections clinic in Harare. Materials and Methods: Participants underwent a standardised otoscopic examination of the ear and Pure Tone Audiometry (PTA). Factors associated with hearing impairment were investigated using multivariate logistic regression. Results: Three hundred and eighty (380) participants (55% female and mean age 11 years (SD: 3.3 years)) were consecutively recruited. The vast majority of participants (n=338; 89% were taking antiretroviral therapy (ART) for a median of 3 (IQR: 2-5) years at recruitment, and the most recent median CD4 Count (i.e. CD4 count measured within 6 months of the study recruitment) was 725 (IQR: 497-1000) cells/µL, with no difference by ART status. 61% (n= 231) of participants had an abnormal ear examination. Of the 359 participants who underwent audiometry, the prevalence of hearing impairment was 32.3% (95%CI: 27.5%-37.4%) based on a PTA threshold ≥26Db. Hearing impairment was associated with a recent CD4 count <350cell/µL (OR 2.1, P<0.037). Conclusion: There is a high prevalence of hearing impairment among HIV-infected children and adolescents. Low CD4 count remains a risk factor even among those who are on ART. We recommend that HIV infected children and adolescents, particularly those with low CD4 counts, should have routine evaluation of hearing as part of HIV care.

Intravenous thrombolysis in patients with stroke attributable to small artery occlusion.

BACKGROUND: Intravenous thrombolysis (IVT) for stroke seems to be beneficial independent of the underlying etiology. Recent observations raised concern that IVT might cause harm in patients with strokes attributable to small artery occlusion (SAO). OBJECTIVE: The safety of IVT in SAO-patients is addressed in this study. METHODS: We used the Swiss IVT databank to compare outcome and complications of IVT-treated SAO-patients with IVT-treated patients with other etiologies (non-SAO-patients). Main outcome and complication measures were independence (modified Rankin scale 0.8). Fatal ICH occurred in 3.3% of the non-SAO-patients but none amongst SAO-patients. Ischaemic stroke within 3 months after IVT reoccurred in 1.5% of SAO-patients and in 2.3% of non-SAO-patients (P = 0.68). CONCLUSION: IVT-treated SAO-patients died less often and reached independence more often than IVT-treated non-SAO-patients. However, the variable 'SAO' was a dependent rather than an independent outcome predictor. The absence of an excess in ICH indicates that IVT seems not to be harmful in SAO-patients.

Thrombolysis in stroke patients aged 80 years and older: Swiss survey of IV thrombolysis.

This databank-based, multicenter study compared all stroke patients with IV tissue plasminogen activator aged > or = 80 years (n = 38) and those < 80 years old (n = 287). Three-month mortality was higher in older patients. Favorable outcome (modified Rankin scale < or = 1) and intracranial hemorrhage (asymptomatic/symptomatic/fatal) were similarly frequent in both groups. Logistic regression showed that stroke severity, time to thrombolysis, glucose level, and history of coronary heart disease independently predicted outcome, whereas age did not.

Particle-scale investigation of PAH desorption kinetics and thermodynamics from sediment.

Dredged sediment from Milwaukee Harbor showed two primary classes of particles in the <2 mm size range: a lighter-density coal- and wood-derived fraction with 62% of total PAHs and a heavier-density sand, silt, and clay fraction containing the remaining 38% of the PAHs. Room-temperature PAH desorption kinetic studies on separated sediment fractions revealed slow desorption rates for the coal-derived particles and fast desorption rates for the clay/silt particles. The effect of temperature on PAH release was measured by thermal program desorption mass spectrometry to investigate the desorption activation energies for PAHs on the different sediment particles. Three activated diffusion-based models and an activated first-order rate model were used to describe the thermal desorption of PAHs for four molecular weight classes. PAH binding with the coal-derived particles was associated with high activation energies, typically in the range of 115-139 kJ/mol. PAHs bound to the clay/silt material had much lower activation energy, i.e., in the range of 37-41 kJ/ mol for molecular weight 202. Among the desorption models tested, a spherical diffusion model with PAHs located like a rind on the outer 1-3 microm region best described the PAH thermal desorption response for coal-derived particles. This internal PAH distribution pattern on coalderived particles is based on prior direct measurement of PAH locations at the subparticle scale. These studies reveal that heterogeneous particle types in sediment exhibit much different amounts and binding of PAHs. PAHs associated with coal-derived particles aged over several decades in the field appear to be far from reaching an equilibrium sorption state due to the extremely slow diffusivities through the polymer-like coal matrix. These results provide an improved mechanistic perspective for the understanding of PAH mobility and bioavailability in sediments.

Succession of phenotypic, genotypic, and metabolic community characteristics during in vitro bioslurry treatment of polycyclic aromatic hydrocarbon-contaminated sediments.

Dredged harbor sediment contaminated with polycyclic aromatic hydrocarbons (PAHs) was removed from the Milwaukee Confined Disposal Facility and examined for in situ biodegradative capacity. Molecular techniques were used to determine the successional characteristics of the indigenous microbiota during a 4-month bioslurry evaluation. Ester-linked phospholipid fatty acids (PLFA), multiplex PCR of targeted genes, and radiorespirometry techniques were used to define in situ microbial phenotypic, genotypic, and metabolic responses, respectively. Soxhlet extractions revealed a loss in total PAH concentrations of 52%. Individual PAHs showed reductions as great as 75% (i.e., acenapthene and fluorene). Rates of (14)C-PAH mineralization (percent/day) were greatest for phenanthrene, followed by pyrene and then chrysene. There was no mineralization capacity for benzo[a]pyrene. Ester-linked phospholipid fatty acid analysis revealed a threefold increase in total microbial biomass and a dynamic microbial community composition that showed a strong correlation with observed changes in the PAH chemistry (canonical r(2) of 0.999). Nucleic acid analyses showed copies of genes encoding PAH-degrading enzymes (extradiol dioxygenases, hydroxylases, and meta-cleavage enzymes) to increase by as much as 4 orders of magnitude. Shifts in gene copy numbers showed strong correlations with shifts in specific subsets of the extant microbial community. Specifically, declines in the concentrations of three-ring PAH moieties (i.e., phenanthrene) correlated with PLFA indicative of certain gram-negative bacteria (i.e., Rhodococcus spp. and/or actinomycetes) and genes encoding for naphthalene-, biphenyl-, and catechol-2,3-dioxygenase degradative enzymes. The results of this study suggest that the intrinsic biodegradative potential of an environmental site can be derived from the polyphasic characterization of the in situ microbial community.

Colocalization of androgen, estrogen and cholinergic receptors on cultured astrocytes of rat central nervous system.

By means of immunohistochemical and electrophysiological methods, we have investigated the presence of androgen receptors on astrocytes in explant and primary cultures from various regions of rat central nervous system. Our studies have shown that a great number of astrocytes and neurones express androgen receptors as recognized by a specific monoclonal antibody. Immunoreactivity was mainly distributed over the soma of the astrocytes, the nuclei being intensely stained. In contrast, glial processes were only faintly stained or not stained. Double-immunostaining studies have provided evidence for a colocalization of androgen and estrogen alpha- and beta-receptors on many astrocytes. Furthermore, there was also a coexistence of glial androgen receptors with cholinergic muscarinic and nicotinic sites. Our immunohistochemical findings are supported by electrophysiological investigations demonstrating that 5alpha-androstan, 17beta-estradiol as well as the cholinergic agonists muscarine and nicotine caused hyperpolarizations on the same astrocytes. Our studies suggest that there is a coexistence of functional receptors for androgen, estrogen as well as for the cholinergic agonists on glial cells. Further investigations are needed to elucidate the physiological role of glial androgen, estrogen and cholinergic receptors and to define their function in neurodegenerative diseases.

Treatment-induced decline of human immunodeficiency virus-1 p24 and HIV-1 RNA in lymphoid tissue of patients with early human immunodeficiency virus-1 infection.

We report detailed quantitative analysis of human immunodeficiency virus-1 (HIV-1) p24 and HIV-1 RNA in tonsil biopsies from 13 patients with early, asymptomatic HIV infection before and during combination antiretroviral therapy. Using fluorescent microscopy in conjunction with reverse transcriptase-polymerase chain reaction of frozen tissue sections, we show that plasma and tissue viral loads decreased by approximately 3 logs during the 1-year treatment period, with good correlation between the HIV-1 p24 and HIV-1 RNA response in tissue. The decrease of tissue viral load was delayed compared to plasma viral load, possibly explained by the observation that the amount of follicular dendritic cell-associated virus correlated best with the area under the curve of plasma HIV-1 RNA throughout the last 12 weeks. Before and during treatment, the relative proportions of HIV-1 on follicular dendritic cells and within mononuclear cells remained constant, suggesting similar decay characteristics in these two lymphoid tissue compartments. However, viral p24 or RNA remained almost always detectable in tissue despite full suppression of HIV-1 RNA in plasma, and increased even after short-term rebounds in plasma viral load. Thus, full and sustained suppression of viral replication was required to efficiently decrease viral load in lymphoid tissue, but complete abolition of residual viral replication was not achieved.

Human immunodeficiency virus type 1 p24 concentration measured by boosted ELISA of heat-denatured plasma correlates with decline in CD4 cells, progression to AIDS, and survival: comparison with viral RNA measurement.

Human immunodeficiency virus type 1 (HIV-1) RNA and p24 antigen concentrations were determined in plasma samples from 169 chronically infected patients (median CD4 cell count, 140 cells/microL; range, 0-1500 cells/microL). p24 quantification involved heat-mediated immune complex dissociation and tyramide signal amplification-boosted ELISA, which has a diagnostic sensitivity similar to that of RNA quantification by a commercial polymerase chain reaction kit. In Cox's proportional hazard models adjusted for CD4 cell count, both RNA (P<.005) and p24 (P=.043) levels were significant predictors of progression to AIDS. Measurement of p24 was superior to measurement of RNA in the model for survival (P=.032 vs. P=.19). p24 level was a significant predictor of CD4 cell decline in models adjusted for CD4 cell counts and was superior or equivalent to RNA level, depending on the group analyzed. Stratification by CD4 cell counts at baseline showed that the superiority of p24 measurement was more pronounced at lower levels of CD4 cells (<200/microL). p24 level may be of interest as a simple and inexpensive predictive marker of disease progression.

Effects of early antiretroviral treatment on HIV-1 RNA in blood and lymphoid tissue: a randomized trial of double versus triple therapy. Swiss HIV Cohort Study.

To assess the effects of early initiation of antiretroviral therapy on cell-free and cell-associated viral load in blood and lymphoid tissue, we performed a randomized, open-label, multicenter trial comparing a double (zidovudine + lamivudine) and triple (zidovudine + lamivudine + ritonavir) drug combination in treatment-naive, asymptomatic patients with CD4 counts >400 cells/microl. HIV-1 RNA was measured in plasma, peripheral blood mononuclear cells, and sequential tonsil or lymph node biopsies (27 patients); the study follow-up was 2 years. Among 42 randomized patients, the proportion with plasma HIV-1 RNA <50 copies/ml was 16% and 74% at week 24 (p<.001) in those randomized to double and triple therapy, respectively, necessitating frequent treatment intensification in the double arm. After a rapid decline within 4 weeks in both arms, cell-associated HIV-1 RNA decreased further only in those patients with sustained suppression of plasma viral load, but remained almost always detectable at low levels, indicating persisting transcription of viral RNA. CD4 counts increased by 200 to 250 cells/microl at week 96 in both arms without significant differences (intent-to-treat analyses). Thus, even if treatment is initiated early in asymptomatic patients with preserved CD4 counts, three drugs are necessary to achieve sustained decreases of HIV load in blood and lymphoid tissue.

Randomized, placebo-controlled trial of Chinese herb therapy for HIV-1-infected individuals.

CONTEXT: Alternative medicine or complementary remedies that have not been scientifically tested are nonetheless widely used to treat chronic illnesses, particularly if curative options are limited. OBJECTIVES: To assess the effectiveness of Chinese medicinal herbs in reducing symptoms and improving the quality of life of HIV-infected persons. DESIGN: Prospective, placebo-controlled double-blind study. SETTING: University-based HIV outpatient clinic. PATIENTS: 68 HIV-infected adults with CD4 cell counts <0.5 x 10(9)/L. INTERVENTION: Participants were randomized to receive four daily doses of seven pills containing a standardized preparation of 35 Chinese herbs or placebo for 6 months. MAIN OUTCOME MEASURES: Symptoms, HIV disease progression, HIV-1 RNA plasma viral loads, CD4 and CD8 cell counts, and scores on standard questionnaires for quality of life, depression, anxiety, and coping. RESULTS: Intervention and placebo groups were equivalent at baseline regarding, respectively, previous antiretroviral therapy (74% versus 79%), median CD4 cell counts (0.20 x 10(9)/L versus 0.25 x 10(9)/L), and median HIV-1 plasma viral loads (35,612 copies/ml versus 52,027 copies/ml). At enrollment, none of the study subjects was seriously ill or depressed, and average coping and quality of life scores were in the normal range. In all, 53 (78%) participants completed the study. Patients taking Chinese herbs reported significantly more gastrointestinal disturbances (79% versus 38%; p = .003) than those receiving placebo. No therapy-related toxicities were observed. At completion of the study, no significant differences between the intervention and placebo groups were found regarding plasma viral loads, CD4 cell counts, symptoms, and psychometric parameters. HIV-1 RNA level was unchanged at study end. Among participants who were not on concomitant antiretroviral therapy, median CD4 cell counts declined by 0.05 x 10(9)/L in both the intervention and placebo groups. CONCLUSIONS: This standardized formulation of Chinese herbs for HIV-infected individuals did not improve quality of life, clinical manifestations, plasma virus loads, or CD4 cell counts. The data suggest that this formulation of Chinese herbs is not effective when administered in a Western medicine setting.

A randomized trial of interferon-alpha2a and zidovudine versus bleomycin and zidovudine for AIDS-related Kaposi's sarcoma. Swiss HIV Cohort Study.

The efficacy and toxicity of interferon-alpha2a (9MU/d) and bleomycin (15 mg every 2 weeks), each combined with zidovudine (2x250 mg/d), was compared in a randomized study in 26 men with progressing AIDS-related Kaposi's sarcoma (KS). The median CD4 count was 113/microl. Complete or partial response was achieved in one (8%) of 12 evaluable patients on interferon and in 2 (20%) of 10 patients on bleomycin (P = 0.43) during 4.7 and 5.3 months of treatment, respectively. The tolerability was comparable. During extended follow up, survival time was 24 and 13 months in the interferon and bleomycin arm, respectively. In a multivariate Cox regression analysis, CD4 lymphocytes <200/microl (relative risk 3.74; 95% CI: 1.30-10.8) and randomization to interferon (relative risk 0.37; 95% CI: 0.15-0.90) were significantly predictive of mortality. New AIDS-related events occurred more frequently in patients who had received bleomycin. The antiviral activity of interferon-alpha or the chemotherapy-mediated increase in the risk for opportunistic infections may explain these differences.

Highly sensitive methods for quantitation of human immunodeficiency virus type 1 RNA from plasma, cells, and tissues.

Precise and sensitive quantitation of viral RNA in specimens from human immunodeficiency virus (HIV) type 1 (HIV-1)-infected individuals has become an indispensable tool for the monitoring of the efficacy of highly active antiretroviral combination therapy. The present report describes reproducible and efficient protocols with enhanced sensitivity for quantitation of HIV-1 RNA from plasma, peripheral blood mononuclear cells, and tissues with Qiagen silica columns for RNA purification combined with the Roche Amplicor HIV-1 Monitor test for quantitative reverse transcription-PCR (RT-PCR). Extraction of RNA from 0.5 ml of plasma resulted in the detection of fewer than 20 HIV RNA copies/ml of plasma, equivalent to the centrifugation-based boosted RT-PCR assay. Silica extraction of cellular RNA resulted in the detection of fewer than 3 HIV-1 RNA copies/microg of total RNA. These techniques facilitate direct comparisons of viral loads between liquid and cellular specimens. Application of these sensitive methods may improve the assessment of the response to new antiretroviral regimens.

Database search based on Bayesian alignment.

The size of protein sequence database is getting larger each day. One common challenge is to predict protein structures or functions of the sequences in databases. It is easy when a sequence shares direct similarity to a well-characterized protein. If there is no direct similarity, we have to rely on a third sequence or a model as intermediate to link two proteins together. We developed a new model based method, called Bayesian search, as a means to connect two distantly related proteins. We compared this Bayesian search model with pairwise and multiple sequence comparison methods on structural databases using structural similarity as the criteria for relationship. The results show that the Bayesian search can link more distantly related sequence pairs than other methods, collectively and consistently over large protein families. If each query made one error on average against SCOP database PDB40D-B, Bayesian search found 36.5% of related pairs, PSI-Blast found 32.6%, and Smith-Waterman method found 25%. Examples are presented to show that the alignments predicted by the Bayesian search agree well with structural alignments. Also false positives found by Bayesian search at low cutoff values are analyzed.

[Chronic hepatitis B and C in HIV-infected patients]. / Chronische Hepatitis B und C bei HIV-infizierten Patienten.

BACKGROUND AND AIM: This retrospective study examined the prevalence of co-infections with hepatitis B virus (HBV) and hepatitis C virus (HCV) and the frequency of chronic hepatitis in HIV-infected patients with respect to both the different risk groups and the serological results. PATIENTS AND METHODS: All Zurich participants of the Swiss HIV Cohort Study were evaluated who had available results of hepatitis B and C serology and ALT. RESULTS: Of the total 279 patients, 52% belonged to the intravenous drug user, 34% to the homosexual, and 11% to the heterosexual risk category. Serologically, previously acquired infection with HBV alone could be demonstrated in 92 (33%), HCV alone in 9 (3%), and both HBV and HCV in 130 (47%) patients. Only 3% of patients with sexually acquired HIV infection had anti-HCV antibodies, whereas co-infection with HBV and HCV was present in 87% of intravenous drug users. Among the 222 patients with previous HBV contact, 25 (11%) had positive HBsAg and 91 (41%) had "anti-HBc alone", both assumed to represent active HBV infection. 66 (24%) of 279 patients had chronic hepatitis with ALT elevation lasting > or = 6 months. Chronic hepatitis was present in 46% of those with active HBV and HCV co-infection, in 36% of those with HCV infection alone and in 18% of those with active HBV infection alone (P < 0.001). Of the 66 cases of chronic hepatitis, 58 were associated with HCV infection, and only 2 cases had no serological signs of active HBV or HCV infection. CONCLUSION: In patients with sexually acquired HIV infection, HBV had frequently been co-transmitted. In contrast, almost all of those infected by means of intravenous drug use had a co-infection with both HBV and HCV. The latter seems to play the strongest role in the development of chronic hepatitis with persistent ALT elevation. A chronic ALT elevation was almost always associated with serologically active HBV or HCV infection.

Antibody response in six HACEK endocarditis cases under therapy.

The antibody response to bacteria of the so-called HACEK group, i.e. Haemophilus spp., Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens and Kingella kingae, was measured in sera of six patients with endocarditis. The corresponding isolates from their blood cultures were identified by conventional methods, including reactions for nitrate reduction and catalase as well as acid production from sugars. Crude antigens were prepared by glycine extraction and sonification of the blood culture isolates, and used to determine titers by complement fixation. A patient with Haemophilus parainfluenzae bacteremia received a short course of antibiotic therapy, and relapsed with spondylitis and endocarditis 5 months later. Titers of sera against his own isolate rose from 1:40 to 1:320 and fell to 1:40 after therapy within one year. A patient with C. hominis endocarditis had a similarly prolonged course. The complement fixation titer against his own isolate was already 1:240 before antibiotics were administered. Another patient with C. hominis endocarditis presented a titer of 1:320 2 weeks after the diagnosis. These three patients revealed C-reactive protein values over 50 mg/l in the first serum sample. Decrease of both antibody titers and C-reactive protein values correlated with clinical improvement. Two patients with prosthetic valve replacement 5 months earlier developed C. hominis and K. kingae endocarditis, respectively. At admission, C-reactive protein values were 64 and 82, respectively, and therapy was instituted immediately. The first sera were received 3 and 6 weeks, respectively, after isolation of the corresponding blood culture isolates and revealed already low titers, i. e. 1:80 and 1:60, respectively. A woman with A. actinomycetemcomitans endocarditis received immediate therapy and did not develop titers against her own isolate. CRP was 100 at admission and remained over 50 5 weeks later. We conclude that the complement fixation assay with individual antigen preparations was easy to perform and allowed monitoring of the antibody response in 5 of 6 HACEK endocarditis cases under therapy, but the usefulness of this method to find culture-negative HACEK endocarditis needs to be established.

Predictors of unprotected sexual contacts in HIV-infected persons in Switzerland.

Predictors of sexual risk behavior with regular and casual partners among HIV-infected heterosexual and gay persons were addressed. Sociodemographic data as well as self- and interviewer-reported data on sexual behavior were obtained from 117 asymptomatic HIV-infected persons enrolled in the Zurich part of the Swiss HIV Cohort Study (SHCS). Participants who reported sexual intercourse at least once (vaginal and/or anal) without condom use in the 6 months prior to interview were considered to have risk behavior. Sexual risk behavior was analyzed separately in contacts with regular and casual partners. In the 6-month preinterview period, 92% (108 of 117) of the HIV-infected study population reported sexual contacts, and 30/117 (26%) had at least one unprotected vaginal and/or anal contact. Among 93 persons using condoms, 25% of the heterosexual and 10% of the homosexual participants reported breakage of the condom. The main predictor for unprotected sexual behavior with regular partners was an elevated number of contacts. Predictors for sexual risk behavior with casual partners were the combination of alcohol and sexual encounters and the change of sexual behavior since the epidemic of AIDS. These findings did not differ between persons with hetero- and homosexual behavior. Considering that these contacts may have passed the virus on to the seronegative population, that the probability of unsafe sex increased with the growing number of contacts, and that the number of condom breakages was remarkable, it is imperative that this group be educated and motivated to take the active role in insisting on safer sex practices in each encounter.

Frequent chronic hepatitis B virus infection in HIV-infected patients positive for antibody to hepatitis B core antigen only. Swiss HIV Cohort Study.

Persons with immune deficiency may present with atypical results in serological tests for hepatitis B virus (HBV). Frozen serum specimens that were sequentially obtained over time from a cohort of 57 HIV-infected patients, all of whom tested positive only for antibody to hepatitis B core antigen (anti-HBcAg), were therefore retested for HBV markers, including HBV DNA. The results were assessed for their time course and correlated with clinical data and alanine aminotransferase (ALT) values. Forty-eight patients were male; intravenous drug users constituted the principal risk group (n = 30), followed by homosexual men (n = 22). Thirty-three persons tested positive for antibody to hepatitis C virus (anti-HCV). During a median of 31 months from the first to the last serum, anti-HBcAg remained the sole marker of HBV infection in 98.2% of the patients. Polymerase chain reaction (PCR) to detect DNA for HBV core and HBV surface gene was positive in 126 (62.4%) and 121 (59.9%) of all 202 serum samples, respectively. Over time, HBV DNA was detected at least once in 51 (89.5%) patients. In contrast, decomplexed hepatitis B surface antigen (HBsAg) was detected at least once in 14 (24.6%) patients. Among patients positive for HBV DNA and negative for anti-HCV, eight (36.4%) of 22 had chronic hepatitis (ALT elevation > or = 6 months) that was attributable only to persisting HBV infection. Similarly, 12 (41.4%) of 29 patients positive for both HBV DNA and anti-HCV had chronic viral hepatitis, but their ALT values were significantly higher. In HIV-infected patients, anti-HBcAg as the sole serological HBV marker detected must be considered indicative of chronic HBV infection and is in part associated with chronic hepatitis and ALT elevation.

Biodegradation kinetics of naphthalene in nonaqueous phase liquid-water mixed batch systems: comparison of model predictions and experimental results.

A model is formulated to describe dissolution of naphthalene from an insoluble nonaqueous phase liquid (NAPL) and its subsequent biodegradation in the aqueous phase in completely mixed batch reactors. The physicochemical processes of equilibrium partitioning and mass transfer of naphthalene between the NAPL and aqueous phases were incorporated into the model. Biodegradation kinetics were described by Monod's microbial growth kinetic model, modified to account for the inhibitory effects of 1,2-naphthoquinone formed during naphthalene degradation under certain conditions. System parameters and biokinetic coefficients pertinent to the NAPL-water systems were determined either by direct measurement or from nonlinear regression of the naphthalene mineralization profiles obtained from batch reactor tests with two-component NAPLs comprised of naphthalene and heptamethylnonane. The NAPLs contained substantial mass of naphthalene, and naphthalene biodegradation kinetics were evaluated over the time required for near complete depletion of naphthalene from the NAPL. Model predictions of naphthalene mineralization time profiles compared favorably to the general trends observed in the data obtained from laboratory experiments with the two-component NAPL, as well as with two coal tars obtained from the subsurface at contaminated sites and composed of many different PAHs (polycyclic aromatic hydrocarbon compounds). The effects of varying the NAPL mass and the naphthalene mole fractions in the NAPL are discussed. It was observed that the time to achieve a given percent removal of naphthalene does not change significantly with the initial mass of naphthalene in a fixed volume of the NAPL. Significant changes in the mineralization profiles are observed when the volume (and mass) of NAPL in the system is changed.

Improvement in immune function due to treatment with indinavir despite severe immune deficiency.

To study the virological, immunological and clinical effects of the protease inhibitor indinavir in human immunodeficiency virus (HIV)-infected patients with CD4 counts < 50 cells/mm3, indinavir was added to prior treatment with nucleoside analogues in a prospective open-label study in 23 HIV-infected patients with median CD4 count of 10 cells/mm3 and median serum HIV-1 RNA load of 27,508 copies/ml. Addition of indinavir induced a decrease in HIV-1 RNA levels to < 400 copies/ml in 15 patients that was maintained until week 36 of the study in 8 (35%) patients. The median increase in CD4 cell counts was 92 cells/mm3 (range 55-258 cells/mm3) and in CD8 counts was 245 cells/mm3 (range 51-1552 cells/mm3) at week 30. The treatment induced a significant CD8 T cell expansion, consisting in the first 6 weeks of predominantly memory CD45RO+ cells and followed by expansion of naive cells from week 12 on, and a significant decrease in the proportion of activated CD8/CD38 cells. In addition, significant increases in T cell proliferation following stimulation with phytohaemagglutinin and significant decreases in the rates of spontaneous apoptosis of CD4+ and CD8+ T cells were observed. In conclusion, the addition of indinavir induced restoration of both memory and naive CD8 T cells. Corresponding evidence of improving T cell function, as assessed by enhanced lymphoproliferative capacity and diminished propensity to undergo apoptosis, provides evidence for treatment-induced regeneration of immune function even in patients with severe immunodeficiency.

Exchange blood transfusion in severe falciparum malaria: retrospective evaluation of 61 patients treated with, compared to 63 patients treated without, exchange transfusion.

The rationale for exchange blood transfusion (ET) in severe falciparum malaria is threefold: reduction of parasitaemia, reduction of presumptive 'toxic' factors, and improvement of the rheological quality of the blood. We evaluated the records of 61 patients treated with ET to describe the present status of malaria treatment in Germany, Austria and Switzerland and to assess the efficacy of ET. Clinical data of 61 patients treated with ET were compared to data of 63 patients treated in 2 hospitals where ETs were generally not performed. We found that exchange transfusion is applied according to the clinician's subjective impression rather than strict guidelines. Logistic regression analysis adjusting for the differences in clinical parameters between patients treated with or without ET did not identify treatment as a prognostic indicator (odds ratio for relative risk of death with ET: 1.3; 95% CI: 0.4-4.9). Exchange transfusion did not significantly improve the unfavourable prognosis in cases of severe falciparum malaria. However, failure to reach statistical significance may be due to the retrospective design of the study and therefore non-systematic approach.