In vitro activity and interaction of clindamycin combined with dihydroartemisinin against Plasmodium falciparum

Combination regimens are considered a valuable tool for the fight against drug-resistant falciparum malaria. This study was conducted to evaluate the antimalarial potential of clindamycin in combination with dihydroartemisinin in continuously cultured and in freshly isolated Plasmodium falciparum parasites, measuring the inhibition of Plasmodium falciparum histidine-rich protein II synthesis. Interaction analysis revealed a synergistic or additive mode of interaction at various concentration ratios in all continuously cultured parasites at the 50% effective concentration (EC(50)) level. Antagonism was not found for any of the culture-adapted parasites. In fresh P. falciparum isolates, a fixed clindamycin-dihydroartemisinin combination exhibited additive activity at the EC(50) and EC(90) levels. The drug mixture showed no significant activity correlation to other commonly used antimalarials. The clindamycin-dihydroartemisinin combination appears to be a promising candidate for clinical investigation.     

Detection of primary aldosteronism using the captopril test

In order to evaluate whether changes in the plasma concentration of aldosterone (PA) following the administration of captopril, an inhibitor of angiotensin-converting enzyme, will establish the diagnosis of primary aldosteronism we have used this test in 9 healthy subjects and in 22 patients with various forms of hypertension, including 5 patients with primary aldosteronism due to idiopathic adrenal hyperplasia (n = 4) or aldosterone-producing adenoma (n = 1). The response of PA to captopril (25 mg orally) was investigated on an outpatient basis, following a rest period of 120 minutes in the supine position. In healthy subjects PA decreased from a mean basal value of 11.5 +/- 5.9 ng/dl to less than 6.4 ng/dl (4.9 +/- 1.4 ng/dl [p less than 0.01]). Similarly, captopril induced a fall in PA concentration to less than 6.4 ng/dl in patients with essential hypertension, with renal artery stenosis or with an afunctional kidney. Post-captopril concentrations of plasma aldosterone were about twice the normal level in 3 of 4 patients with idiopathic adrenal hyperplasia and about four-fold raised above normal in the patient with an aldosterone-producing adenoma. In spite of a false-negative result in one patient with idiopathic adrenal hyperplasia, the administration of captopril appears to be of use in recognizing patients with primary aldosteronism on an outpatient basis.     

Antibody responses to pneumococcal and hemophilus vaccinations in splenectomized patients with hematological malignancies or trauma

In this study we addressed the question of whether an underlying hematological malignancy may affect the immune response to vaccination against bacterial polysaccharide antigens (e.g. Haemophilus influenzae type b, Streptococcus pneumoniae) in splenectomized patients. Between 1993 and 2003, 44 splenectomized adults from the outpatient clinic for infectious diseases were prospectively included in the study: 23 patients suffered from hematological malignancies (HM) and had undergone splenectomy; 21 were splenectomized following trauma (T) and served as the control group. Each patient received an intradeltoid injection with 0.5 ml of a single lot of a 23-valent pneumococcal polysaccharide vaccine, and 0.5 ml of a polyribosyl ribitol phosphate capsular polysaccharide vaccine of H. influenzae type b (Hib) into the opposite arm. Blood samples for determination of pneumococcal and Hib antibodies were taken prior to vaccination and again 6-8 weeks later. In assessing responses to the 23-valent pneumococcal polysaccharide vaccine, we found significant differences in antibody titer increase between the HM and T groups (median IgG increase 1.27 [0.7; 2.39] vs. 3.9 [2.1; 15.3], P < 0.001; and median IgM increase 1.33 [1.0;2.67] vs. 5.25 [2.3; 7.78], P < 0.001). In the HM group, only 8/23 and 6/23 showed a titer increase of twice or more the base value for IgG and IgM respectively, whereas in the trauma group an adequate response was shown by 16/21 and 16/20 respectively. Patients with splenectomy and hematological malignancies responded poorly to the 23-valent polysaccharide vaccine. Response to the conjugated Hib vaccine was slightly better, but still significantly lower than in individuals with posttraumatic splenectomy. Data suggest that vaccination response to the polysaccharide vaccines should be evaluated at least in the high-risk group.