Ultrasensitive analysis of the intestinal absorption and compartmentalization of aluminium in uraemic rats: a 26Al tracer study employing accelerator mass spectrometry

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.      

Non-prescribed drug use during methadone treatment by clinic- and community-based patients

We investigated the efficacy of methadone maintenance treatment in clinic-based (n= 10) and community-based (n= 10) patients by studying the relationships between dose, plasma concentrations of methadone and non-prescribed drug-use using logistic regression. We found that clinic-based patients had significantly reduced odds of having a urine sample test positive for illicit drugs when compared to community-based patients (OR = 0.20; 95% confidence interval 0.10–0.38: p < 0.001). There was no relationship between either methadone dose or plasma methadone concentration and testing positive for non-prescribed drugs (including cocaine, cannabis, amphetamine, ecstasy, benzodiazepines). We looked specifically at the misuse of opiate drugs. Location was again important and clinic-based patients had significantly reduced odds of having a urine sample test positive for opiate drugs (OR= 0.36, 95% confidence internal 0.13–0.71: p～0.004). Opiate drug use in our patients was also significantly related to plasma methadone concentration, increasing noticeably when the drug concentration < 0.48 nmol/L (p～0.04). We found no relationship between methadone dose and odds of having a positive urine drug test in either clinic- or community-based patients.     

The Effect of Etiocholanolone on Granulocyte Kinetics

The effect of etiocholanolone on granulocyte kinetics in 12 hematologicallynormal patients has been investigated using the technic of ³H-DFP labelingof autologous blood in vitro.

Baseline determinations of the total blood granulocyte pool (TBGP), thecirculating pool (CGP), and the marginated pool (MGP) were performed.The values for the total blood granulocyte pools were similar to those previously reported. Following the administration of etiocholanolone, there was a98 per cent increase in the TBGP, which was considered to be due to mobilization of granulocytes from the bone marrow reserve. There was no change inthe ratio of CGP to MGP.

These studies suggest that etiocholanolone may be a useful agent for theestimation of bone marrow reserve.

Submitted on November 21, 1966 Accepted on April 13, 1967     

Acute toxicity and first clinical results of intensive postinduction therapy using a modified busulfan and cyclophosphamide regimen with autologous bone marrow rescue in first remission of acute myeloid leukemia [see comments]

The combination of high-dose busulfan (16 mg/kg) and 200 mg/kg cyclophosphamide is gaining increasing significance as a preparative regimen prior to autologous, syngeneic, or allogeneic marrow transplantation. A new regimen of high-dose busulfan in conjunction with a reduced dose of 120 mg/kg cyclophosphamide has recently been described as a preparative regimen prior to allogeneic transplantation. To determine the drug-related nonhematologic toxic effects of this new regimen without confounding factors associated with allogeneic transplantation, we conducted a pilot study using this new regimen in 20 patients with acute myeloid leukemia (AML) in first remission prior to autologous unpurged marrow transplantation. All patients experienced transient non-life-threatening acute drug-related toxicity with skin reactions in 20 (100%), nausea and vomiting in 20 (100%), oral mucositis in 18 (90%), hepatic functional impairment in 17 (85%), hemorrhagic cystitis in three (15%), and generalized seizures in two (10%) of these patients, respectively. Two procedural, fatal complications resulted from infectious causes that were not directly related to the speed of hematopoietic reconstitution or the toxicity of the preparative regimen. The 3-year event-free survival estimate (55% +/- 11%) and probability of leukemic recurrence (38% +/- 11%) attained with this new regimen in recipients of autografts in first remission of AML are promising and challenge comparisons with preparative regimens employing combinations of cytotoxic agents or total body irradiation (TBI).     

牛津单髁膝关节置换：长期结果

牛津膝置换是使用最广泛的膝关节单髁置换（UKR）。牛津膝在37年前开始应用,拥有一个全匹配的活动衬垫,因而磨损率非常低。牛津膝最主要的使用指征是膝关节前内侧骨关节炎,这种病人至少占所有需要行膝关节置换术患者的50％。由于这一系统的设计特点,传统UKR的反指征,如年龄、活动量、肥胖、髌股关节损害和软骨钙质沉着症等对于牛津膝均不是反指征。与全膝关节置换（TKR）相比,牛津膝提供更快的康复、更好的功能、更大的活动度和更好的术后满意度,发生并发症更少、程度更轻,病残率和死亡率更低。一个持续超过30年的研究显示在90％的病例中,牛津膝为患者终生提供了优或良的临床结果,且不需要翻修。在最近15年,牛津膝通过微创手术入路植入,涉及6000多例使用该入路牛津膝置换的9个研究报道显示,10年生存率约95％。在许多这样的研究中,医生们在拟行膝关节置换的患者中约50％使用了牛津单髁膝置换。     

Regional myocardial dysfunction: evaluation of patients with prior myocardial infarction with fast CT

A prototype ultrafast cine computed tomographic (CT) scanner, designed specifically for cardiac imaging, was used to evaluate a preliminary series of patients with prior myocardial infarction (n = 21) and a control group without coronary artery disease (n = 5). Multilevel 50-msec CT scan exposures were obtained during peripheral intravenous bolus injections of contrast medium. A comparison was made between cine-CT scans and standard left ventriculographic images in assessing segmental left ventricular motion. Results indicate that cine CT, performed at sufficiently rapid speeds (20 scans per second) to allow useful analysis of regional ventricular wall motion, can provide adequate image quality. Analysis of 110 segments revealed a good correlation (90.9%) between the two techniques in characterizing normal from abnormal regional wall motion. Cine CT, based on this initial study, demonstrates considerable potential for evaluating not only cardiac chamber dimensions but also segmental wall dynamics.     

The staphylococcal scalded skin syndrome

Histochemical and electron microscopic studies were carried out on the newborn mouse model of the staphylococcal scalded skin syndrome to investigate the mechanism of action of the staphylococcal epidermolytic toxin that causes it. Histochemical studies showed that an intra-epidermal split develops below the subcorneal zone which is rich in catabolic enzymes (the so-called esterase-acid phosphatase-rich band). However, histochemical alterations in the enzyme pattern could not be demonstrated. The earliest change revealed by electron microscopy was a widening of the intercellular space, with the formation of microvilli at the level between the stratum spinosum and stratum granulosum where the split later occurs. A clearing of the peripheral cytoplasm along the cell membranes was also revealed. In pre-split areas, adhesion between cell membranes of adjacent cells seems to be lost; desmosomes continue to hold the cells together but the split develops when these are broken by mechanical pressure. Later, damaged cell membranes may be seen. Extracellular keratinosomes remain unchanged. Although these findings do not agree with the already divergent results of other studies, they help support the findings of all groups that cases of the Lyell syndrome produced by staphylococci do not occur through necrolysis; it is therefore inappropriate to continue applying the term ‘toxic epidermal necrolysis’ to such cases.