Pharmacokinetics and clinical evaluation of aztreonam in pediatrics

Pharmacokinetics, in vitro, and in vivo effect of aztreonam (SQ 26,776, AZT), a newly synthesized monobactam antibiotic, were investigated in pediatric patients. The pharmacokinetics were studied in 12 children without renal or hepatic impairment, each of whom received single 10, 20 and 40 mg/kg intravenous doses of drug. Serial samples of serum and urine were assayed for AZT. Serum pharmacokinetics of AZT were described by an open, linear, two-compartment kinetic model. After intravenous administration, AZT was eliminated primarily by urinary excretion of unchanged drug (60.4%). The average biological half-lives of AZT in serum were 1.33 (10 mg/kg, n = 1), 1.69 +/- 0.40 (20 mg/kg, n = 8), and 1.51 +/- 0.61 (40 mg/kg, n = 3) hours. The antibacterial activity of AZT against E. coli and P. aeruginosa was equal or slightly stronger than that of CPZ, LMOX, and CTX. It had no antimicrobial activity against Gram-positive cocci. In vivo effect of AZT was evaluated in 13 children with various infections. The result was excellent in 7 cases, good in 1 case, fair in 3 cases and poor in 1 case, with effective ratio of 66.7%. Exanthema or elevation of GOT and GPT were noticed in 3 patients.     

Increased [18F]fluorodeoxyglucose accumulation in right ventricular free wall in patients with pulmonary hypertension and the effect of epoprostenol

OBJECTIVES: We examined whether right ventricular (RV) [(18)F]fluorodeoxyglucose (FDG) accumulation is increased in patients with pulmonary hypertension using gated positron emission tomography (PET) and whether RV FDG accumulation changes after therapy with epoprostenol. BACKGROUND: Myocardial glucose utilization is increased in animal models with ventricular pressure overload. METHODS: We performed gated FDG-PET in 24 patients with pulmonary hypertension. The RV standardized uptake value (SUV) of FDG was corrected for the partial volume effect based on the wall thickness measured by electron-beam computed tomography or magnetic resonance imaging. RESULTS: The corrected RV SUV of FDG was significantly correlated with the pulmonary vascular resistance, mean pulmonary artery pressure, right atrial pressure, RV wall stress, and plasma brain natriuretic peptide levels, but not with the RV wall thickness and mass. After pulmonary vasodilator therapy with epoprostenol for three months, the corrected RV SUV of FDG significantly decreased in the responders, but not in the non-responders, and the percentage change of the corrected RV SUV of FDG was significantly correlated with the percentage change of the pulmonary vascular resistance (r = 0.78; p < 0.01) and RV systolic wall stress (r = 0.76; p < 0.05). CONCLUSIONS: The RV FDG accumulation corrected for the partial volume effect was significantly increased in accordance with the severity of the RV pressure overload (i.e., the RV peak-systolic wall stress) in patients with pulmonary hypertension. Furthermore, the corrected RV FDG accumulation was decreased after the treatment with epoprostenol in accordance with the degree of reduction in the pulmonary vascular resistance and RV peak-systolic wall stress.     

NADH augments blood flow in physiologically activated retina and visual cortex

The mechanism(s) that increase retinal and visual cortex blood flows in response to visual stimulation are poorly understood. We tested the hypothesis that increased transfer of electrons and protons from glucose to cytosolic free NAD(+), reducing it to NADH, evoked by increased energy metabolism, fuels redox-signaling pathways that augment flow. The near-equilibrium between free cytosolic NADH/NAD(+) and lactate/pyruvate ratios established by lactate dehydrogenase predicts that transfer of additional electrons and protons from injected lactate to NAD(+) will augment the elevated blood flows in stimulated retina and cortex, whereas transfer of electrons and protons from NADH to injected pyruvate will attenuate the elevated flows. These predictions were tested and confirmed in rats. Increased flows evoked by stimulation also were prevented by inhibition of nitric oxide synthase. These findings support an important role for cytosolic free NADH in fueling a signaling cascade that increases *NO production, which augments blood flow in photostimulated retina and visual cortex.     

In utero diagnosis of bladder perforation with urinary ascites. A case report

Prenatal sonographic diagnosis of fetal obstructive uropathy is relatively common. However, the complication of spontaneous rupture of the obstructed bladder in utero causing fetal urinary ascites is extremely rare. This case report describes an unusual case of congenital bladder perforation and urinary ascites diagnosed in utero. The pertinent literature is reviewed.     

HIV type 1 infection in Pygmy hunter gatherers is from contact with Bantu rather than from nonhuman primates

To investigate the route of zoonotic transmission of HIV-1, we isolated three and seven HIV-1 strains from 449 Pygmy hunter gatherers and 169 neighboring Bantu, respectively, in southern Cameroon. Phylogenetic analysis based on pol-integrase and env-C2V3 sequences revealed that strains from Pygmies were 1CRF02_AG/CRF02_AG, 1 subtype G/CRF02 AG (pol/env), and 1 CRFll_cpx/CRF11_cpx, and that those from Bantu were 2 CRF02_AG/CRF02_AG, 1 CRF02_AG/CRF01_AE/A, 1 CRF02_AG/subtype A, 1 G/A, 1G/CRF02_AG, and 1 unclassified fH. CRF02_AG and CRF11_cpx have been identified in Cameroon. The results suggest that HIV-1 has been introduced into Pygmies through their neighboring Bantu rather than directly from nonhuman primates.