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.      

Minocycline as a cause of acute eosinophilic pneumonia]

A rare side effect of minocycline is acute eosinophilic pneumonia. In the literature only ten cases have been reported. We report two cases of minocycline which induced (eosinophilic) alveolitis. A high fever, dry cough, dyspnoea and fatigue are the main features of the clinical picture. Peripheral blood eosinophilia and elevated total IgE content were seen in one patient. Bronchoalveolar lavage in this patient revealed eosinophilia. Transbronchial lung biopsies showed infiltration with eosinophilic granulocytes in both patients. Airway macrophages contained brown-black pigment granules. In the acute stage an important decrease in diffusion capacity was observed. The pulmonary and systemic symptoms promptly cleared up after discontinuation of minocycline. Provocation with minocycline was positive, because both patients noticed the same symptoms within one day.     

Interdigestive small bowel motility and duodenal bacterial overgrowth in experimental acute pancreatitis

The objective of this study is to investigate the effects of an acute necrotizing pancreatitis (ANP), without biliary obstruction, on the migrating motor complex (MMC), small bowel bacterial overgrowth (SBBO), bacterial translocation (BT) and infection of the pancreas simultaneously. Rats were divided into four groups: mild pancreatitis, control, ANP and sham operated control. Jejunal myoelectrodes were used to measure MMCs. Blood, peritoneal fluid, bile, and abdominal organs were harvested for microbial culturing 72 h after induction of pancreatitis. The splenic portion of the pancreas was taken for histology. During ANP the MMC cycle length was significantly increased from 14.1 +/- 0.2 to 22.4 +/- 1.9 min (P < 0.05). The duodenum of ANP rats was in contrast with the other groups characterized by Enterobacteriacae (> 3 log 10 CFU g-1 in seven of 12 rats, P < 0.05). A positive correlation (r = 0.78, P < 0.01) existed between duodenal Gram-negative and anaerobic flora and the MMC cycle. Correlation between MMC cycle length and BT to the pancreas was positive as well (r = 0.70, P < 0.01). A positive correlation (r = 0.85, P < 0.01) was found between the severity of pancreatitis and duodenal bacterial overgrowth. During ANP without biliary obstruction, the jejunal MMC is disturbed and consequently SBBO occurs. The correlation between the severity of pancreatitis, the disturbance of the MMC and SBBO suggests an important pathophysiological role of the proximal small bowel in the infection of pancreatic necrosis.     

Surgical treatment of ulcerative colitis and familial adenomatous polyposis: recent developments]

Reconstructive surgery for ulcerative colitis and familial adenomatous polyposis nowadays usually takes the form of an ileoanal pouch, involving making a reservoir of the terminal portion of the ileum which subsequently is anastomosed to the anal canal. This method results in definite cure in many cases, but is associated with a morbidity of 15-30% and fails in 10%. A new surgical treatment includes complete removal of the affected large bowel mucosa, guaranteeing oroanal intestinal continuity, limiting complications and providing good function of the reservoir or of the new rectum. In creation of an ileoneorectal anastomosis, complete removal of the affected mucous membrane is followed by preparing a functional 'neorectum' by means of pedicle grafting of ileal mucous membrane on to the uncovered muscular wall of the rectum. This operation gave good results in a small-scale clinical trial.     

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).     

Surgical treatment of acute pancreatitis

Background

Acute pancreatitis remains an unpredictable, potentially lethal disease with significant morbidity and mortality rates. New insights in the pathophysiology of acute pancreatitis have changed management concepts. In the first phase, characterized by a systemic inflammatory response syndrome, organ failure, not related to infection but rather to severe inflammation, dominates the focus of treatment. In the second phase, secondary infectious complications largely determine the clinical outcome. As infection is associated with increased mortality in acute pancreatitis, numerous prophylactic strategies have been explored in the past two decades.

Purpose

This review describes the strategies that have been developed to lower the infection rate, in an attempt to lower mortality. Antibiotic prophylaxis has been the subject of many RCT’s without showing convincing evidence of their efficacy. Probiotics, although theoretically capable of lowering the rate of infection, also had no effect on infectious complications, and consequently, no effective strategy to lower the rate of infectious complications is currently available. In the second part of this review, new approaches for necrosectomy that have been designed by different centers around the world are discussed. All the interventional techniques have in common their aim to lower the invasive character, hypothesizing that lowering the surgical trauma will improve survival and lower complication rates. Recent advances include postponing intervention as a strategy to facilitate necrosectomy and improve prognosis and the “step-up approach” in case of infected necrosis. The step-up approach includes percutaneous catheter drainage as the first step, to be followed by necrosectomy, either through a minimally invasive approach or by open necrosectomy, as the next step.

Conclusions

All attempts to develop treatment strategies to lower the infection rate in acute pancreatitis have failed. Accumulating evidence is emerging to show that the combination of centralization, the use of catheter drainage as the first step of invasive treatment, and the development of minimally invasive techniques, improve the outlook for patients with infected necrosis. It is uncertain at this point in time as to which of the three effects is dominant in the improvement of prognosis.     

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。     

The influence of anesthesia-controlled time on operating room scheduling in Dutch university medical centres

Background

Predicting total procedure time (TPT) entails several elements subject to variability, including the two main components: surgeon-controlled time (SCT) and anesthesia-controlled time (ACT). This study explores the effect of ACT on TPT as a proportion of TPT as opposed to a fixed number of minutes. The goal is to enhance the prediction of TPT and improve operating room scheduling.

Methods

Data from six university medical centres (UMCs) over seven consecutive years (2005-2011) were included, comprising 330,258 inpatient elective surgical cases. Based on the actual ACT and SCT, the revised prediction of TPT was determined as SCT × 1.33. Differences between actual and predicted total procedure times were calculated for the two methods of prediction.

Results

The predictability of TPT improved when the scheduling of procedures was based on predicting ACT as a proportion of SCT.

Conclusions

Efficient operating room (OR) management demands the accurate prediction of the times needed for all components of care, including SCT and ACT, for each surgical procedure. Supported by an extensive dataset from six UMCs, we advise grossing up the SCT by 33% to account for ACT (revised prediction of TPT = SCT × 1.33), rather than employing a methodology for predicting ACT based on a fixed number of minutes. This recommendation will improve OR scheduling, which could result in reducing overutilized OR time and the number of case cancellations and could lead to more efficient use of limited OR resources.