Population pharmacokinetics of amikacin in intensive care unit patients studied by NPEM algorithm

Summary— The population pharmacokinetics of amikacin was studied in 40 intensive care unit patients (212 plasma concentrations) by NPEM algorithm using a one-compartment model. The population was best characterized by the following pharmacokinetic parameters: renal clearance relative to creatinine clearance (C_s = 0.96 ± 0.33), and either the total volume of distribution (V_d = 23.9 ± 7.0 I) or the volume of distribution relative to body weight (V_s = 0.36 ± 0.10 1·kg⁻¹. The volume of distribution was increased with respect to the usual value of 0.25 1·kg⁻¹. The statistical distribution of these pharmacokinetic parameters was approximately gaussian, with no significant correlation between volume of distribution and clearance. The medians and standard deviations of C_s and V_s were used as reference population values to estimate the pharmacokinetics of amikacin in a second group of 29 patients by the bayesian method, with two blood samples per patient. For each patient, the fitted parameters were able to predict the plasma concentrations of amikacin during the next 72 h with no significant bias and good precision (2.9 mg·1⁻¹ for peaks and 0.5 mg·1⁻¹ for troughs). This study confirms the ability of the NPEM algorithm to provide reference population values for use in bayesian monitoring of aminoglycoside therapy.     

Hydrogen MR imaging of the head at 0.35 T and 0.7 T: effects of magnetic field strength

To determine whether hydrogen magnetic resonance imaging at 0.7 T provides added clinical value over imaging at 0.35 T, images of the heads of patients with various intracranial disorders were obtained at these field strengths. Measurements of tissue contrast (C), signal-to-noise (S/N) ratio, and T1 and T2 relaxation times were determined. For a given spin-echo sequence with equal imaging time, resolution, and data sampling window, the product C X S/N was somewhat lower for the lower field strength. Under conditions of imaging with equal chemical shift artifact, C X S/N at 0.35 T was equal to or greater than that measured at 0.7 T. With an increase in field strength, T1 of pathologic areas and surrounding normal tissues increased, resulting in a corresponding loss of absolute signal level and decrease in contrast. Lesions were equally well seen at both 0.35 T and 0.7 T. The increased T1 and decreased C X S/N for higher magnetic fields--when measured with a fixed imaging time, resolution, chemical shift, and sequence--suggest that such field strengths may not improve tissue contrast, diagnostic ability, or clinical throughput when compared with lower field strength systems.     

Melatonin does not inhibit estradiol-stimulated proliferation in MCF-7 and BG-1 cells

Melatonin, an indolic pineal hormone, is produced primarily at night in mammals and is important in controlling biological rhythms. Previous research suggested that melatonin can attenuate proliferation in the estrogen-responsive MCF-7 breast cancer cell line. We tested whether these anti-proliferative effects may have physiological consequences upon two estrogen-responsive cell lines, MCF-7 (a breast cancer cell line) and BG-1 (an ovarian adenocarcinoma cell line). Melatonin (10(-9)- 10(-5) M) attenuated proliferation of MCF-7 and BG-1 cells by >20% in the absence of estrogen. However, 17beta-estradiol exposure negated the ability of melatonin to inhibit proliferation. To substantiate this finding, cells were estrogen starved followed by multiple treatments with estradiol and melatonin. Melatonin did not inhibit estradiol- stimulated proliferation under this protocol. Estradiol increased MCF-7 and BG-1 cell cycle transition from G1 to S phase, however, melatonin did not inhibit this transition nor did it down-regulate estradiol- induced pS2 mRNA levels measured by northern blotting, further indicating that melatonin was unable to attenuate estradiol-induced proliferation and gene expression. We also examined the effects of melatonin on estradiol-induced proliferation in MCF-7 cell xenografts in athymic nude mice. Melatonin at a dose 28 times greater than 17beta- estradiol did not inhibit estradiol-induced proliferation in vivo. Furthermore, pinealectomy did not increase proliferation. Therefore, we conclude that melatonin does not directly inhibit estradiol-induced proliferation.      

Infant feeding, wheezing, and allergy: a prospective study

The determinants of wheezing and allergy were investigated in 453 children with a family history of allergic disease. A randomised controlled trial examined the effects of withholding cows' milk protein during the first three months of life and replacing cows' milk with soya milk. The children were followed up to the age of 7 years. Withholding cows' milk did not reduce the incidence of allergy or wheezing. Children who had ever been breast fed had a lower incidence of wheeze than those who had not (59% and 74% respectively). The effect persisted to age 7 years in the non-atopics only, the risk of wheeze being halved in the breast fed children after allowing for employment status, sex passive smoking, and overcrowding. Allergic disease was not associated with exposure to tobacco smoke, house dust mite antigen, or cats. Breast feeding may confer long term protection against respiratory infection.     

Abstracts of selected papers from the 1st ISOQOL Pan-Pacific Conference, Tokyo, Japan, April 13–15 2001

Abstract List

Abstracts of selected papers from the 1st ISOQOL Pan-Pacific Conference, Tokyo, Japan, April 13–15 2001     

Avoided and avoidable risks of cancer

Despite the considerable efforts and funds devoted to cancer research over several decades, cancer still remains a mainly lethal disease. Cancer incidence and mortality have not declined at the same rate as other major causes of death, indicating that primary prevention remains a most valuable approach to decrease mortality. There is general agreement that environmental exposures are variously involved in the causation of the majority of cancer cases and that at least half of all cancers could be avoided by applying existing etiologic knowledge. There is disagreement, however, regarding the proportion of cancer risks attributable to specific etiological factors, including diet, occupation and pollution. Estimates of attributable risks are largely based today on unverified assumptions and the calculation of attributable risks involves taking very unequal evidence of various types of factors and treating them equally. Effective primary prevention resulting in a reduction of cancer risk can be obtained by: (i) a reduction in the number of carcinogens to which humans are exposed; or (ii) a reduction of the exposure levels to carcinogens. Exposure levels that could be seen as sufficiently low when based on single agents, may actually not be safe in the context of the many other concomitant carcinogenic and mutagenic exposures. The list of human carcinogens and of their target organs might be quite different if: (i) epidemiological data were available for a larger proportion of human exposures for which there is experimental evidence of carcinogenicity; (ii) more attention was paid to epidemiological evidence that is suggestive of an exposure-cancer association, but is less than sufficient, particularly in identifying target organs; and (iii) experimental evidence of carcinogenicity, supported by mechanistic considerations, were more fully accepted as predictions of human risk.