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.      

Guanylnucleotide specificity for muscarinic receptor inhibitory coupling to cardiac adenylate cyclase.

The guanylnucleotide specificity of muscarinic acetylcholine receptor (MR) inhibitory coupling to cardiac adenylate cyclase (AC) was investigated under low MgCl2 (i.e., 0.5 mM) conditions. In purified cardiac sarcolemma, carbachol maximally inhibited AC activity 60% in the presence of GTP. Carbachol-dependent inhibition in the presence of guanosine 5'-O-(3-thiotriphosphate (GTP gamma S) or guanylylimidodiphosphate [Gpp(NH)p] was of lesser magnitude (i.e., 30%) and was evident only during short incubation periods. Of greater interest, carbachol maximally inhibited AC activity in the presence of GDP and guanosine 5'-O-(2-thiodiphosphate (GDP beta S) by 35 and 60%, respectively. Control studies ruled out transphosphorylation of GDP and GDP beta S by nucleoside diphosphate kinase or guanylnucleoside triphosphate contamination as reasons for the inhibitory effects of GDP and GDP beta S. Furthermore, isoproterenol stimulated AC in the presence of GTP, GTP gamma S, and Gpp(NH)p but not in the presence of GDP or GDP beta S. Therefore, GDP and GDP beta S may serve as agonists on MR-activated Gi but not on beta-adrenergic receptor-activated Gs in these membranes. Time course studies revealed that carbachol-dependent inhibition of AC in the presence of either GTP or GDP occurred without a detectable lag period, and this inhibition was rapidly reversed by atropine. In contrast, a 1-2-min lag time was required for carbachol- and GDP beta S-dependent inhibition of AC to occur, and inhibition, once developed, was only partially and slowly reversed by atropine. Preincubation of sarcolemma with carbachol and GDP beta S, in the absence of ATP or under nonphosphorylating conditions, eliminated the lag time for inhibition of AC activity. Although it is unlikely that GDP and GDP beta S have physiological relevance of MR-Gi-AC coupling, these studies provide unique insights into this coupling mechanism in cardiac membranes.     

Qualitative microscopy of implanted vein grafts. Effects of graft integrity on morphologic fate.

This is an investigation of the relationship between graft preparation techniques and the subsequent fate of vein grafts. Vein grafts intentionally injured by warm saline storage demonstrated endothelial and smooth muscle cell damage. In the acute postimplantation period, platelet adhesion/activation and white cell infiltration were present. By 7 days the endothelium had "healed," but the underlying smooth muscle cells had modulated and were of the synthetic phenotype. This persisted at 30 days, but by 60 days the graft wall remodeled with smooth muscle cells that were of the contractile phenotype, with an organized extracellular matrix. None of these injurious responses were noted in optimally prepared papaverine-treated vein grafts. Optimal preparation of vein grafts is effective in minimizing endothelial and smooth muscle cell injury before and after arterial reconstruction. Prevention of vein graft injury during harvesting prevents the morphologic changes characteristic of the "arterialization response."     

Women supporting women: Supportive/educative groups for ethnically diverse,urban, impoverished women dealing with depression and anxiety

Depression and anxiety are mental health issues that disproportionately affect urban, ethnically diverse, impoverished women. Using community based participatory research and in the context of long-term partnerships between a nursing department and underserved neighborhoods that are predominately Black, Hispanic, and White respectively, supportive/educative groups were offered. The study employed a quasi-experimental, nonequivalent comparison group pretest-posttest design. Seventy-two women aged 17–88?years participated. Repeated measures ANOVA indicated a significant increase in knowledge for self-care for depression and anxiety and a significant decrease in anxiety and depression symptomatology from before to after the group sessions.     

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。