BACKGROUND: Developments in accelerator mass spectrometry (AMS) now permit
the determination of femtogram amounts of 26Al in blood and in various
tissues with good precision and free of external contamination. METHODS: In
the present study we used trace quantities of 26Al to investigate the
intestinal absorption and compartmentalization of aluminium in rats with
renal failure (Nx, 5/6 nephrectomy) and in pair- fed controls (C). Single
oral doses of 20 ng 26Al were administered to six animals in each group
and, subsequently, 24-h post-load 26Al was analysed in serum, urine, bone,
liver, and spleen by means of AMS. RESULTS: Serum concentrations of 26Al
were significantly lower in uraemic rats compared to controls, whereas
urinary excretion was comparable (Nx, 7.11 +/- 5.78 pg/day vs C, 9.46 +/-
6.10 pg/day), suggesting a higher fraction of ultrafiltrable serum 26Al in
uraemia. The target tissues of cellular transferrin-mediated 26Al uptake,
liver and spleen, tended to show a larger degree of aluminium accumulation
in controls (0.26 +/- 0.31 pg/g vs Nx, 0.14 +/- 0.10 pg/g and 0.37 +/- 0.27
pg/g vs Nx, 0.25 +/- 0.27 pg/g respectively). In contrast, in bone, a site
of extracellular aluminium deposition, 26Al concentrations were more
elevated in uraemia (1.22 +/- 0.59 pg/g vs C: 0.68 +/- 0.30 pg/g).
Estimated total 26Al accumulation in all measured target tissues was
significantly higher in uraemic rats (28.15 +/- 9.90 pg vs C: 17.03 +/-
7.03 pg) and total recovery of 26Al from tissue and urine was 26.58 +/-
6.74 pg in controls and 35.75 +/- 7.03 pg in uraemic animals, suggesting a
fractional absorption of 0.133% and 0.175% respectively. CONCLUSIONS: Our
data suggest that fractional absorption from a dietary level dose of 26Al
is about 0.13%. Compartmentalization occurs in transferrin-dependent target
tissues such as liver and spleen; however, in quantitative terms
extracellular deposition in bone is more important. Uraemia has a
significant effect on the intestinal absorption and compartmentalization of
aluminium. It enhances fractional absorption and increases subsequent
extracellular deposition of aluminium in bone. However, at the same time
uraemia does not increase transferrin-dependent cellular accumulation of
aluminium in liver and spleen.
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SUMMARY This double-blind, randomised, cross-over study investigated the antihypertensive efficacy of ramipril and enalapril was completed by 30 patients with mild-to-moderate essential hypertension. After a four-week placebo run-in phase, the patients received either 2.5mg ramipril or 10mg enalapril once daily for four weeks. The dosages were increased to 5mg ramipril and 20mg enalapril for a further four weeks. After a placebo washout phase of four weeks, the patients were crossed over to the alternative treatment. The decrease in average 24-hour ambulatory diastolic blood pressure from week 0 to week 8 was 1.6mmHg greater with ramipril than enalapril (90% confidence interval 0.6-2.7mmHg). The corresponding reduction in for systolic blood pressure was also greater with ramipril than enalapril by 2.4mmHg (90% confidence interval: 0.5-4.2mmHg). For the difference in the drop of 24-hour ambulatory diastolic blood pressure between ramipril and enalapril the lower level of the 90% confidence interval (CI) is above the clinically relevant difference of -3mmHg. This is an indication that ramipril (2.5 and 5mg dose) is at least as effective as enalapril (10 and 20mg dose) in decreasing blood pressure in patients with mild-to-moderate essential hypertension. The duration of adequate antihypertensive effect was relatively long for both ramipril and enalapril; however, ramipril tended to have a more prolonged antihypertensive effect. Ramipril had a higher diastolic and systolic trough/peak ratio than enalapril, resulting in a more uniform antihypertensive effect over the 24-hour treatment period. Both ramipril and enalapril were well tolerated and the two treatment groups had similar safety profiles. 相似文献
A group of unique Epstein-Barr virus-containing cell lines was derived from the bone marrow of three patients with X-linked agammaglobulinemia. Efforts to obtain cell lines from the peripheral blood of these patients were uniformly unsuccessful. Immunofluorescence analyses as well as biosynthetic studies with [(35)S]methionine indicated unusual patterns of Ig synthesis in many of these bone marrow derived lines. Seven of the lines were of particular interest in that two produced no Ig of any type; two others showed no Ig by fluorescence but small amounts by [(35)S]methionine labeling; one expressed only cytoplasmic μ chains without any evidence of light chain synthesis, and two produced primarily μ chains with only slight amounts of light chains. One of the lines without membrane or cytoplasmic Ig studied in detail grew like a typical lymphoid line and was carried in intermittent culture over a period of 2 yr without Ig expression. One line grew quite differently and resembled the round cell type described previously, which has been obtained from a variety of sources. The cell line with cytoplasmic μ chains and no light-chain expression had the characteristic properties of pre-B cells. Three normal type Ig-producing cell lines also were obtained from the patients. The accumulated evidence obtained in the present study indicates that these unusual cell lines represent normal precursor cells of the B-cell lineage; these grew out in these cases because of the virtual absence of mature B cells that ordinarily overgrow the culture system. However, the possibility that in certain instances they reflect abnormal Ig synthesis characteristic of the disease has not been ruled out. 相似文献
Purpose: The cytoprotective agent amifostine has been shown to reduce the radiation-induced acute and chronic xerostomia in head and neck cancer patients. The purpose of this study was to evaluate whether or not amifostine also reduces the incidence of dental caries associated with the radiation-induced xerostomia.
Methods and Materials: The dental status before and 1 year after radiotherapy was retrospectively compared in 35 unselected patients treated as part of the prospective randomized and multicenter open-label Phase III study (WR-38) at the University Hospitals of Heidelberg, Freiburg, and Erlangen. The WR-38 study compared radiotherapy in head and neck cancer with and without concomitant administration of amifostine.
Results: Patient and treatment characteristics (particularly the radiation dose and percentage of parotids included in the treatment volume) were equally distributed between the patients who received (n = 17) or did not receive (n = 18) amifostine. Fifteen patients of the amifostine group showed no deterioration of the dental status 1 year after radiotherapy as compared to 7 patients who did not receive the cytoprotector (p = 0.015, two-tailed Fisher exact test).
Conclusion: Our data suggest a protective effect of amifostine on the dental health after radiotherapy of the head and neck. The dental status should be used as a primary endpoint in future studies on amifostine. 相似文献
PURPOSE: To evaluate the influence of blood hemoglobin concentration on the radiosensitivity of acutely reacting normal tissues. METHODS AND MATERIALS: Weekly scores (EORTC/RTOG criteria) for acute reactions of skin and mucosa are available for 60 patients with cancer of the head and neck undergoing a standard conventional radiotherapy. The prognostic significance of blood hemoglobin levels on the development of acute reactions is studied by multivariate analysis (Cox Proportional Hazards Model). Further, the incidence and the time to development of these reactions is looked at in cohorts of patients with different mean blood hemoglobin concentrations during radiotherapy. Patients are therefore classified into a "severely anemic group" (hemoglobin < 11.0 g/100 mL), and into a cohort with a blood hemoglobin value equal or above 11.0 g/100 mL. RESULTS: Normal tissue scoring and monitoring of blood hemoglobin levels allows for a detailed analysis of possible correlations. A decrease in the mean blood hemoglobin value of 1 g/100 mL predicts a reduced risk to develop a skin reaction of Grade 2 or 3 (RR = 0.9; p = 0.08; RR = 0.8; p = 0.26, respectively) or a mucosa reaction of Grade 3 (RR = 0.8; p = 0.16), independent from the radiation dose, the treatment time and from previous surgery within the radiation volume (multivariate analysis). Likewise, patients with severe anemia develop grade 3 mucositis or dermatitis less often (0%; 13%) as compared to those with blood hemoglobin concentrations equal or above 11.0 g/100 mL (21%; 19%). Skin and mucosa reactions further tend to occur later in the course of radiation. The observations are not statistically significant and possible reasons will be discussed. CONCLUSIONS: A decreased blood hemoglobin concentration may-perhaps by an impaired tissue oxygenation-reduce the radiosensitivity of normal tissue such as skin and mucosa. However, the data is preliminary and needs further confirmation. 相似文献