Rainforest aerosols as biogenic nuclei of clouds and precipitation in the Amazon.

The Amazon is one of the few continental regions where atmospheric aerosol particles and their effects on climate are not dominated by anthropogenic sources. During the wet season, the ambient conditions approach those of the pristine pre-industrial era. We show that the fine submicrometer particles accounting for most cloud condensation nuclei are predominantly composed of secondary organic material formed by oxidation of gaseous biogenic precursors. Supermicrometer particles, which are relevant as ice nuclei, consist mostly of primary biological material directly released from rainforest biota. The Amazon Basin appears to be a biogeochemical reactor, in which the biosphere and atmospheric photochemistry produce nuclei for clouds and precipitation sustaining the hydrological cycle. The prevailing regime of aerosol-cloud interactions in this natural environment is distinctly different from polluted regions.

Evolution of organic aerosols in the atmosphere.

Organic aerosol (OA) particles affect climate forcing and human health, but their sources and evolution remain poorly characterized. We present a unifying model framework describing the atmospheric evolution of OA that is constrained by high-time-resolution measurements of its composition, volatility, and oxidation state. OA and OA precursor gases evolve by becoming increasingly oxidized, less volatile, and more hygroscopic, leading to the formation of oxygenated organic aerosol (OOA), with concentrations comparable to those of sulfate aerosol throughout the Northern Hemisphere. Our model framework captures the dynamic aging behavior observed in both the atmosphere and laboratory: It can serve as a basis for improving parameterizations in regional and global models.

Determination of terephthalic acid isopropylamide in urine with a liquid chromatography/mass spectrometry (LC/MS) method.

A sensitive and simple liquid chromatography/mass spectrometry (LC/MS) method was developed for the determination of terephthalic acid isopropylamide, the final metabolite of procarbazine in human urine. A solid-phase extraction with C(18) cartridges was used followed by LC/MS with a single mass spectrometer (SSQ 7000 from Finnigan). Terephthalic acid isobutylamide was the internal standard. The quantification limit was 30 ng/mL in urine (6 x noise). This assay was applied for drug monitoring of terephthalic acid isopropylamide in urine after oral administration of procarbazine in children and adolescents with Hodgkin lymphomas.

Size matters more than chemistry for cloud-nucleating ability of aerosol particles.

Size-resolved cloud condensation nuclei (CCN) spectra measured for various aerosol types at a non-urban site in Germany showed that CCN concentrations are mainly determined by the aerosol number size distribution. Distinct variations of CCN activation with particle chemical composition were observed but played a secondary role. When the temporal variation of chemical effects on CCN activation is neglected, variation in the size distribution alone explains 84 to 96% of the variation in CCN concentrations. Understanding that particles' ability to act as CCN is largely controlled by aerosol size rather than composition greatly facilitates the treatment of aerosol effects on cloud physics in regional and global models.

Lactic acidosis in Gabonese children with severe malaria is unrelated to dehydration.

BACKGROUND: Hyperlactatemia is an important and common complication of severe malaria. We investigated changes in fluid compartment volumes in patients with severe malaria and control patients with the use of bioimpedence analysis. METHODS: We estimated extracellular water and total body water volumes in a total of 180 children: 56 with severe malaria, 94 with moderate malaria, 24 with respiratory tract infection, and 6 with severe diarrhea. RESULTS: There was a mean (+/-SD) decrease in total body water volume of 17+/-24 mL/kg (or 3% of total body water volume) in patients with severe malaria. This compares with a mean (+/-SD) decrease in total body water volume of 33+/-28 mL/kg (or 6% of total body water volume) in patients with severe diarrhea. There was no increase in extracellular water volume in patients with severe malaria, suggesting no significant intravascular volume depletion in patients with severe malaria. There was no relationship between lactatemia and any changes in fluid compartment volumes. CONCLUSIONS: The changes in fluid volumes that were observed are unlikely to be of physiological significance in the pathophysiology of severe malaria.

Nucleation particles in diesel exhaust: composition inferred from in situ mass spectrometric analysis.

Mass spectrometric measurements of size and composition of diesel exhaust particles have been performed under various conditions: chassis dynamometer tests, field measurements near a German motorway, and individual car chasing. Nucleation particles consisting of volatile sulfate and organic material could be detected both at the chassis dynamometer test facility and during individual car chasing. We found evidence that if nucleation occurs, sulfuric acid/water is the nucleating agent. Low-volatile organics species condense only on the preexisting sulfuric acid/water clusters. Nucleation was found to depend strongly on various parameters such as exhaust dilution conditions, fuel sulfur content, and engine load. The latter determines the fraction of the fuel sulfur that is converted to sulfuric acid. The organic compounds (volatile and low-volatile) condense only on preexisting particles, such as both sulfuric acid nucleation particles and larger accumulation mode soot particles. On the latter, sulfuric acid also condenses, if the conditions for nucleation are not given. The overall ratio of sulfate to organic (volatile and low-volatile) is also strongly dependent on the engine load. It was found that the production of nucleation particles even at high engine load can be suppressed by using low-sulfur fuel.

Global air pollution crossroads over the Mediterranean.

The Mediterranean Intensive Oxidant Study, performed in the summer of 2001, uncovered air pollution layers from the surface to an altitude of 15 kilometers. In the boundary layer, air pollution standards are exceeded throughout the region, caused by West and East European pollution from the north. Aerosol particles also reduce solar radiation penetration to the surface, which can suppress precipitation. In the middle troposphere, Asian and to a lesser extent North American pollution is transported from the west. Additional Asian pollution from the east, transported from the monsoon in the upper troposphere, crosses the Mediterranean tropopause, which pollutes the lower stratosphere at middle latitudes.

Amodiaquine-artesunate versus amodiaquine for uncomplicated Plasmodium falciparum malaria in African children: a randomised, multicentre trial.

BACKGROUND: Increasing drug resistance limits the choice of efficacious chemotherapy against Plasmodium falciparum malaria in Africa. Amodiaquine still retains efficacy against P falciparum in many African countries. We assessed the safety, treatment efficacy, and effect on gametocyte carriage of adding artesunate to amodiaquine in three randomised trials in Kenya, Sénégal, and Gabon. METHODS: We enrolled 941 children (400 in Kenya, 321 in Sénégal, and 220 in Gabon) who were 10 years or older and who had uncomplicated P falciparum malaria. Patients were randomly assigned amodiaquine (10 mg/kg per day for 3 days) plus artesunate (4 mg/kg per day for 3 days) or amodiaquine (as above) and placebo (for 3 days). The primary endpoints were parasitological cure rates at days 14 and 28. Analysis was by intention to treat and by an evaluability method. FINDINGS: Both regimens were well tolerated. Six patients in the amodiaquine-artesunate group and five in the amodiaquine group developed early, drug-induced vomiting, necessitating alternative treatment. By intention-to-treat analysis, the day-14 cure rates for amodiaquine-artesunate versus amodiaquine were: 175/192 (91%) versus 140/188 (74%) in Kenya (D=16.7% [95% CI 9.3-24.1], p<0.0001), 148/160 (93%) versus 147/157 (94%) in Sénégal (-1.1% [-6.7 to 4.5], p=0.7), and 92/94 (98%) versus 86/96 (90%) in Gabon (8.3% [1.5-15.1], p=0.02). The corresponding rates for day 28 were: 123/180 (68%) versus 75/183 (41%) in Kenya (27.3% [17.5-37.2], p<0.0001), 130/159 (82%) versus 123/156 (79%) in Sénégal (2.9% [-5.9 to 11.7], p=0.5), and 80/94 (85%) versus 70/98 (71%) in Gabon (13.7% [2.2-25.2], p=0.02). Similar rates were obtained by evaluability analysis. INTERPRETATION: The combination of artesunate and amodiaquine improved treatment efficacy in Gabon and Kenya, and was equivalent in Sénégal. Amodiaquine-artesunate is a potential combination for use in Africa. Further investigations to assess the potential effect on the evolution of drug resistance, disease transmission, and safety of amodiaquine-artesunate are warranted.

Reassessment of the resistance of Plasmodium falciparum to chloroquine in Gabon: implications for the validity of tests in vitro vs. in vivo.

Increasing resistance of Plasmodium falciparum to antimalarial drugs presents a major risk factor for people living in endemic areas of tropical Africa. In Lambaréné, Gabon, regular surveillance of chloroquine sensitivity of P. falciparum in vitro has been carried out since 1992 using the WHO standard microtest. Results indicated that from 1994 onwards chloroquine resistance in vitro decreased significantly and that by 2000, about 70% of parasite isolates seemed to be sensitive to chloroquine in vitro. In 2001, we conducted a clinical study to reassess the efficacy of chloroquine in vivo for the treatment of uncomplicated P. falciparum malaria. Twenty-six patients aged 4-15 years were included in this study. Most unexpectedly, the study demonstrated high-grade resistance to chloroquine in vivo (failure rate on day 28 of 100%). As a consequence, tests of parasite susceptibility to chloroquine in vitro were repeated using the same protocol except for the replacement of previously used commercially available predosed WHO culture plates by independently dosed plates. All tested P. falciparum isolates were highly resistant to chloroquine, correlating well with our clinical findings. We concluded that high level resistance of P. falciparum to chloroquine persists in the study area. Neglect or absence of quality controls of essential test material can lead to invalid study results and wrong conclusions and should always be suspected in the case of major fluctuations in the sensitivity patterns of an antimalarial drug in vitro. In addition, our results highlight the supreme value of tests in vivo in providing reliable estimates of the efficacy of an antimalarial in a specific area.

The prevalence of parasite infestation and house dust mite sensitization in Gabonese schoolchildren.

BACKGROUND: Allergic diseases seem less prevalent in communities in less developed parts of the world, where parasite infections are highly prevalent. Altogether not much is known about the association between chronic infections with tissue and blood-dwelling parasites and atopy. METHODS: In an area in Gabon endemic for blood and tissue parasites, 520 schoolchildren were parasitologically examined and skin prick-tested for a set of common environmental aeroallergens. Levels of allergen-specific IgE and polyclonal IgE were measured. RESULTS: In schoolchildren schistosome and filarial infections increased with age, whereas malaria was more prevalent in younger children. In contrast to allergen sensitization that increased with age, skin test reactivity tended to decline. The number of children with mite-specific IgE antibodies (47%) by far exceeded the number responding to skin prick testing (11%). Mite sensitization was found to be the highest in children infected with schistosomes and/or filariae whereas skin test reactivity was lowest. The multiple logistic regression showed that the risk of a positive skin test was 8-fold higher with increasing levels of mite-specific IgE but was reduced by 72% when infected with blood stage helminths. CONCLUSIONS: Chronic blood and tissue parasite infections that are often capable of modulating immune responses in the host are negatively associated with skin test reactivity in a sensitized population.

High prevalence of human antibodies to recombinant Duffy binding-like alpha domains of the Plasmodium falciparum-infected erythrocyte membrane protein 1 in semi-immune adults compared to that in nonimmune children.

We used a panel of nine fusion proteins that contain different Duffy binding-like alpha (DBL-alpha) domains of Plasmodium falciparum-infected erythrocyte membrane protein 1 to assess the levels of antibody activity in serum samples obtained from semi-immune or nonimmune individuals from Lambaréné, Gabon. Recognition was measured in terms of either the prevalence or the magnitude of the response. A strong correlation between the immune status of the patients and reactivity with recombinant proteins was observed, which was interpreted as a reflection of the number of infections acquired over time. The antibody responses were predominantly directed toward variable epitopes of the DBL-alpha domain. Antibody responses could be reduced by preincubation of the sera with various fusion proteins. A portion of individuals who exhibited high-level responses to all fusion proteins also had antibodies which recognized conserved epitopes. The possibility that a synergizing effect of anti-DBL-alpha domain antibodies could support chemotherapy is discussed.

Artesunate and praziquantel for the treatment of Schistosoma haematobium infections: a double-blind, randomized, placebo-controlled study.

Recently, artemisinin derivatives have been shown to be efficacious in chemoprophylaxis of and chemotherapy for Schistosoma japonicum and S. mansoni infections. Therefore, a double-blind, randomized, placebo-controlled study was carried out to investigate the efficacy and tolerability of artesunate plus placebo and the combination of artesunate and praziquantel in the treatment of S. haematobium infections in Gabon. The 300 infected schoolchildren included in the study were randomized to receive artesunate plus placebo (n=90), praziquantel plus placebo (n=90), artesunate and praziquantel (n=90), or only placebo (n=30). End points were efficacy, assessed as cure on day 56, and tolerability. All treatment regimens were well tolerated. The praziquantel plus placebo-treated group attained a cure rate of 73%, artesunate plus placebo a rate of 27%, the combination of artesunate and praziquantel a rate of 81%, and placebo alone a rate of 20%. In summary, earlier findings of efficacy of artemisinin derivitives against S. mansoni and S. japonicum could not be confirmed in S. haematobium infections.

Atopy and malaria.

The last decades have seen a dramatic rise in the prevalence of allergic diseases throughout the industrialised world. The "hygiene hypothesis" postulates that this is due to a reduced exposure to infections during childhood. A cohort study in children from Gabon gave us the unique opportunity to examine the relationship between exposure to P. falciparum and atopy. 91 children, who had been closely followed for an average of 5 years and of whom the exact incidence of malaria attacks was known, underwent a skin-prick test with mite antigen. 16 children (18%) had a positive reaction. Gender or age had no effect on the outcome of the test. However, those tested positive had had less infections and a lower incidence of malaria than children tested negative (p = 0.017). Survival analysis shows that children with a high exposure to P. falciparum were at lower risk of an atopic skin reaction (p = 0.001). We postulate that the low exposure to the malaria parasite contributes to the development of an imbalanced immune system with a subsequent higher reactivity to the allergen tested. Immuno-suppression is commonly seen during a malaria attack and this correlates positively with the level of anti-inflammatory cytokines such as interleukin-10. High exposure to parasite antigens might counterbalance pro-inflammatory immune reactions and thus protect against allergic diseases. A better understanding of the relationship between parasitic infection and allergy will help us to develop strategies to prevent allergic disease without being exposed to infectious diseases.

Malaria chemoprophylaxis with tafenoquine: a randomised study.

BACKGROUND: Tafenoquine is an analogue of primaquine with an improved therapeutic and safety profile. It has a long half-life and activity against liver-stage malaria parasites, so may be useful for chemoprophylaxis. In this randomised, double-blind study we assessed the efficacy and safety of tafenoquine in different doses. METHODS: 2144 individuals aged 12-20 years living in Lambaréné, Gabon, an endemic area for Plasmodium falciparum malaria, were invited to take part. 535 attended, and 426 eligible participants were randomly assigned tafenoquine (250 mg, 125 mg, 62.5 mg, or 31.25 mg) or placebo daily for 3 days. 417 received initial curative treatment with halofantrine, and 410 completed the assigned prophylaxis regimen. During follow-up of 70 days, adverse events were recorded and thick blood smears were examined weekly. The primary and secondary endpoints were the number of individuals with positive blood smears by day 56 and day 77, respectively. Analyses were per-protocol. FINDINGS: Eight positive blood smears were recorded by day 56 (four/82 participants in the placebo group; four/79 tafenoquine 31.25 mg group). By day 77, 34 positive blood smears had been recorded (14/82 placebo; 16/79 tafenoquine 31.25 mg; three/86 tafenoquine 62.5 mg; one/79 tafenoquine 125 mg; none/84 tafenoquine 250 mg). Numbers of adverse events did not differ significantly between the treatment groups. INTERPRETATION: Tafenoquine is effective and well tolerated. It has the potential to replace currently used drugs for malaria chemoprophylaxis.

[Qualitative marginal gap research on amalgam fillings]. / Qualitative Randspaltuntersuchungen an Amalgamfüllungen.

Using x-ray spectroscopy the inorganic contents of the interface tooth restoration of conventional and gamma-2-reduced amalgam fillings were analysed after short and long clinical application. Qualitative difference did not exist between interface layer of both amalgam types. The amalgam elements mercury, silver and copper were not detected, but tin occurred everywhere. Zinc and oxygen were frequently analysed in the interface layer. Calcium, phosphorus, sodium and magnesium were detected, too.

[The corrosion behavior of antimony in a Ag-Sn-Cu-Sb amalgam]. / Zum Korrosionsverhalten des Antimons in Ag-Sn-Cu-Sb-Amalgam.

Specimen of amalgam containing antimony were stored in solutions with different pH and different content of rhodanide until 21 days. The most antimony were solved within 24 hours. After 7 days an increase of the antimony concentration were not observed in physiological pH. An inhibition of corrosion by rhodanide existed only after incubation from 21 days. The quantity of antimony (10-21 micrograms) were analysed by mean of atomic absorption spectroscopy. It represent not a risk for the health. The natural presence of this element in environment and in human body is discussed to the analysed quantity of solved antimony.

[Effect of surface treatment and thermal stress on the adaptation of Germadent amalgam fillings]. / Zum Einfluss der Oberflächenbearbeitung und thermischer Belastung auf die Adaptation von Germadent-Amalgamfüllungen.

Surfaces of amalgam-fillings (Germadent) applied to extracted human teeth were treated in four variants. The adaptation of the fillings to the cavosurface margins was measured with SEM before and after thermal stress. Burnishing lead to a clear reduction of leakages, in contrast to carving. Fillings polished after carving, and especially after burnishing, have smallest marginal leakage. Thermal charges cause a small deterioration of marginal adaptation.