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.      

Velocity and flow quantitation in the superior sagittal sinus with ungated and cine (gated) phase-contrast MR imaging

Normal blood flow and velocity in the superior sagittal sinus were measured in 30 patients. A fast two-dimensional ungated phase-contrast (PC) pulse sequence was compared with a peripherally gated cine PC technique for velocity and flow quantitation. The same imaging parameters were used for both methods. Measured values for mean velocity and flow obtained with the two methods were compared by using regression analysis and t testing. For blood flow, the correlation coefficient was 0.976. For velocity measurements, r was 0.950. Mean flow was 285 mL/min ± 19 with the ungated PC method and 281 mL/min ± 19 with the cine PC method. The mean velocities measured with the two methods were 12.94 cm/sec ± 1.1 and 13.59 cm/sec ± 1.1, respectively. There was no significant difference (paired t test) between the methods for mean flow or velocity data. This was true even though flow in the superior sagittal sinus is moderately pulsatile, as shown with the cine PC technique. The ungated PC method provided these data in 13 seconds versus 3.5 minutes for the cine PC method.     

Neurologic complications of cardiac transplantation

The neurologic evaluation of an individual cardiac transplant recipient often does not lead to a succinct bedside diagnosis. There are few consistent clinical observations. The onset of seizures in the early postoperative period is associated with embolic cerebral infarction. Seizures occur most commonly, however, as a neurotoxic manifestation of cyclosporine. The onset of an acute delirium or psychosis in the first week after cardiac transplantation usually has multiple causative factors and is reversible. A postoperative brachial plexopathy or mononeuropathy can be identified with a neurologic examination, confirmed by appropriate electrophysiologic testing and is usually reversible. The onset of periorbital inflammation, ophthalmoplegia, and nasal turbinate or sinus invasion and necrosis is consistent with phycomycosis. Most patients, however, present with nonspecific findings of impaired mentation with or without focal neurologic signs. These patients require a fairly systematic search for potentially treatable neurologic complications (see Table 3). In a medically stable patient an aggressive diagnostic approach, at times including stereotaxic brain aspirate or biopsy, is indicated. In the severely ill patient with multiple organ failure, empirical therapy for the most probable treatable disorder is justified.     

Contrast on T2-weighted images of the lumbar spine using fast spin-echo and gated conventional spin-echo sequences

A prospective study in 31 patients was designed to compare contrast quantitatively using axial conventional, gated spin-echo T2-weighted (T2W) (SE) (asymmetrical echo TE 30 and 80 ms) and axial dual-echo fast spin-echo (FSE) sequences (TE_eff20 and 120 ms) to image lumbar discs, nerve roots, and cerebrospinal fluid CSF. We used two quantitative measures, percent (%) contrast and contrast-to-noise ratio (CNR), to compare the sequences. The FSE sequence had greater % contrast and CNR on the first and second echo images for both disc and nerve root detection using these scan parameters. An axial FSE sequence, therefore, provided contrast characteristics similar to those of gated axial T2W SE sequence in the lumbar spine, with a 60% saving in acquisition time. The FSE sequence is now our standard axial T2W study for the lumbar spine.     

Pulsed magnetization transfer spin-echo MR imaging

Cross relaxation between macromolecular protons and water protons is known to be important in biologic tissue. In magnetic resonance (MR) imaging sequences, selective saturation of the characteristically short T2 macromolecular proton pool can produce contrast called magnetization transfer contrast, based on the cross-relaxation process. Selective saturation can be achieved with continuous wave irradiation several kilohertz off resonance or short, intense 0° pulses on resonance. The authors analyze 0° binomial pulses for T2 selective saturation, present design guidelines, and demonstrate the use of these pulses in spin-echo imaging sequences in healthy volunteers and patients. Using the phenomenologic Bloch equations modified for two-site exchange, the authors derive the analytic expressions for water proton relaxation under periodic pulsed saturation of the macromolecular protons. This relaxation is shown to be monoexpo-nential, with a rate constant dependent on the saturation pulse repetition rate and the individual and cross-relaxation rates.     

Benign versus pathologic compression fractures of vertebral bodies: assessment with conventional spin-echo, chemical-shift, and STIR MR imaging

Differentiation of benign from pathologic compression fractures of vertebral bodies was evaluated with magnetic resonance imaging in a prospective study of 53 patients. Twenty-six patients had 34 benign posttraumatic compression fractures. Twenty-seven patients had metastatic disease to the vertebral column and seven pathologic fractures. T1- and T2-weighted spin-echo (SE) sequences (1.5 T) were performed in all patients. A presaturation technique was used to obtain "fat" and "water" images to better assess the degree of normal fatty marrow replacement in fractured vertebrae. Short inversion-time inversion-recovery (STIR) images were also obtained. Discrimination between benign and pathologic compression fractures was generally possible with the SE sequences. Chronic benign fractures demonstrated isointense marrow signal intensity (SI), compared with that of normal vertebrae with all sequences. Pathologic fractures showed low SI on T1-weighted images and high SI on T2-weighted images. Fat images revealed complete replacement of normal fatty marrow, shown as absent SI in the involved vertebral body. Water and STIR images showed diffuse high SI in pathologic fractures, with STIR images having the highest contrast between abnormal and normal marrow. Acute benign compression fractures also demonstrated high SI on T2-weighted, water, and STIR images, but the SI was less pronounced and the pattern was generally more inhomogeneous than that of pathologic compressions. In general, fat images showed only partial replacement of normal fatty marrow by low SI, in contrast to the complete absence of marrow SI typical of pathologic fractures.     

The activity of a transient potassium current in retinal glial (Müller) cells depends on extracellular calcium

The modulating effects of varying extracellular concentrations of Ca2+ ([Ca2+]e) and of other divalent cations on the fast transient (A-type) K+ current (I(A)) of freshly isolated Muller glial cells from rabbit and human retinae were studied with the whole-cell patch-clamp method. The I(A) of Miller cells was voltage-independently blocked by extracellular 4-aminopyridine (4AP) with a 50 % reduction achieved at 0.94 mM 4AP. The I(A) amplitude was elevated by increased extracellular [K+]. Elevation of the [Ca2+]e had three effects on the glial I(A): (i) it concentration-dependently shifted both the activation and inactivation curves towards less negative membrane potentials, (ii) it increased the peak current amplitude, and (iii) it slowed down the activation and inactivation kinetics. Particularly at depolarized membrane potentials, the I(A) was enlarged and broadened when the [Ca2+]e was increased. Various divalent cations also exerted these effects, although at different concentrations. While Zn2+, Cd2+, Cu2+ and Pb2+ modulated the I(A) in the micromolar range, Mg2+ and Ba2+ had effects in the millimolar range. Extracellular acidification produced a positive shift in the voltage dependence of I(A) gating. However, alterations of the extracellular pH did not abolish the Ca2+ effects on I(A); this indicates that protons and Ca2+ ions mediate their effects on glial K(A) channels by different mechanisms or binding sites, respectively. Physiological (i.e., activity-dependent) changes of the extracellular concentration of divalent cations and of the extracellular pH should influence the retinal excitability via modulation of glial K+ currents. The activation of glial I(A) by divalent cations at depolarized voltages supports a repolarization and, therefore, the maintainance of a hyperpolarized glial membrane potential during periods of increased neuronal activity.     

Arginine-vasopressin influences the mitogen-induced development of T and B effector cells

Using a solid phase enzyme-linked immunospot assay (ELISPOT) for enumerating antibody and interleukin secreting cells it could be demonstrated that arginine-vasopressin (AVP) inhibits the activation process of in vitro cultivated murine spleen lymphocytes. Lipopolysaccharide stimulated B cells could be influenced by high AVP concentrations (10[-5] M), while ConA induced Th1 cells respond also to a lower AVP level (10[-8] M) and such response by the IL-4 secreting Th2 cells may be demonstrated only after the activation with suboptimal doses of Con A. These observations suggest that AVP is not only able to suppress immunological reactions by stimulating proopiomelanocortin processing and secretion of adrenocorticotropic hormone, but also by a direct binding to lymphocytes and, moreover, that the susceptibility in monitoring this signal among the murine lymphocyte subpopulations is different.     

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).