Direct injections of calcitriol into enlarged parathyroid glands in chronic dialysis patients with severe parathyroid hyperfunction

Summary: Severe secondary hyperparathyroidism in chronic dialysis patients has been recently treated by supraphysiological concentration of calcitriol achieved through pulse therapy. However, there are many patients resistant to this therapy, who usually have larger parathyroid gland(s). to overcome this resistance, calcitriol was injected directly into the enlarged glands under ultrasonographic guidance. We injected 70–90% of the calculated gland volume of calcitriol solution (1 μg/mL) into the glands of 7 patients three times per week for 2 weeks. the parathyroid hormone (PTH) levels decreased significantly after 2 weeks of direct injections of calcitriol. Following a further 4 weeks of calcitriol pulse therapy, PTH levels remained suppressed and serum alkaline phosphatase activity and the volume of parathyroid glands also decreased. During the long-term follow up, five patients remained well controlled with calcitriol pulse therapy, while two patients needed ethanol injections to control hyperparathyroidism. Although we could not completely rule out a toxic effect of the vehicle, direct injection of calcitriol into parathyroid glands may be another treatment option for chronic dialysis patients. Our data further support the important role of resistance of parathyroid cells to calcitriol in the pathogenesis of parathyroid hyper function in uraemic patients.     

Aniracetam,a Pyrrolidinone-type Cognition Enhancer,Attenuates the Hydroxyl Free Radical Formation in the Brain of Mice with Brain Ischaemia

We demonstrate here that aniracetam has the ability to block the formation of cytotoxic hydroxyl radicals (· OH) during ischaemia-reperfusion of mouse brain. The fact that brain ischaemia for 40 min followed by reperfusion increased ·OH was evidenced by detection of a peaked increase at 20 min after an ischaemic insult in the formation of 2,3-dihydroxy-benzoate (DHBA) from salicylate in cerebroventricular perfusate, a means of monitoring ·OH formation. A clearcut increase in dopamine was also observed during and after brain ischaemia. The ischaemia-reperfusion mice given aniracetam at an intraperitoneal dose of 30 or 100 mg kg^?1 showed a smaller increase in the formation of DHBA than those given the vehicle only. Aniracetam at 100 mg kg^?1 significantly suppressed the formation of DHBA by approximately 80%, becoming evident at 20 min after reperfusion and thereafter. Protection against death in mice insulted with a 40-min brain ischaemia (3/13 vs 13/25) was observed following 100 mg kg^?1 aniracetam. The increase in the dopamine levels was substantially reduced following aniracetam treatment and the reduction became significant at 20 min after reperfusion and thereafter in parallel with attenuation by aniracetam of DHBA formation. This finding suggests that the inhibitory activity of aniracetam in attenuating the hydroxyl free-radical formation in ischaemic mice is probably due, at least in part, to its palliative action on the dopaminergic neurons.     

High-performance Liquid Chromatographic Determination of Trazodone and 1-m-Chlorophenylpiperazine with Ultraviolet and Electrochemical Detector

A high-performance liquid chromatographic (HPLC) assay was developed for the determination of trazodone and its metabolite, 1-m-chlorophenylpiperazine (m-CPP), in plasma. The high level of trazodone in plasma was detected by ultraviolet absorbance at 254 nm and the low level of m-CPP in plasma was detected by coulometric electrochemical detection at 840 mV on the series arrangement of two detectors. Pilsicainide as an internal standard for both compounds was monitored by both detectors. Trazodone and m-CPP in plasma were extracted by a rapid and simple procedure based on CN bonded-phase extraction, and C₈ reversed-phase HPLC separation. Determination was possible for trazodone in the concentration range 100–2000 ng mL^?1 and for m-CPP in the concentration range 5–100 ng mL^?1. The recoveries of trazodone and m-CPP added to plasma were 81·0–84·2 and 68·0–73·2%, respectively, with coefficients of variation of less than 7·3 and 8·2%, respectively. The method is applicable to high level monitoring of trazodone and low level monitoring of m-CPP in plasma of healthy volunteers and patients treated with trazodone.     

3D Turbo Spin-echo MRI-based Mechanical Thrombectomy at Middle Cerebral Artery Bifurcations

We describe three cases with acute middle cerebral artery (MCA) occlusion. From the pre-operative MRI, including three-dimensional turbo spin-echo sequences using T1WI and T2WI, we assessed both thrombus configuration and arterial anatomy at the MCA bifurcations. For efficient endovascular thrombectomy, we identified the applied MCA segment 2 (M2) branch, in which the main thrombus was buried. Sufficient recanalization after a single pass was achieved and the patients made a marked recovery. Although mechanical thrombectomy for M2 occlusion has not been of proven benefit, the endovascular procedure based on three-dimensional turbo spin-echo imaging is useful for more complete thrombus removal at MCA bifurcations.     

Bile acids influence hepatic chemiluminescence in normal and oxidative-stressed rats†

The aim of the present study was to clarify whether bile acids influence chemiluminescence (CL) in the liver in vivo. Hepatic CL was determined on the surface of the liver of anaesthetized rats by using a photon counter. In normal rats, hepatic CL was significantly decreased 30 min after enteral administration of chenodeoxycholic acid (CDCA) or deoxycholic acid (DCA), but returned to its initial level 3 h later, after part of the CDCA administered was metabolized. Ursodeoxycholic acid (UDCA) and cholic acid had no effect on CL. In contrast, hepatic CL was markedly increased 30 min after CDCA or DCA administration in rats given either buthionine sulphoximine (BSO), an inhibitor of γ-glutamylcysteine synthetase, or diethyldithiocarbamate (DDC), an inhibitor of both superoxide dismutase and glutathione peroxidase. Chenodeoxycholic acid further increased the CL of BSO- or DDC-treated rats during inhalation of oxygen via a tracheal cannula. Coadministration of UDCA eliminated the effects of CDCA on the hepatic CL of normal and BSO- or DDC-treated rats with or without oxygen inhalation. We conclude that cytotoxic bile acids, such as CDCA, increase CL in the antioxidants-depleted or oxidative-stressed liver in vivc, but that UDCA prevents CDCA from developing CL.     

Effects of interleukin-12 on natural killer cell cytotoxicity and the production of interferon-7 and tumour necrosis factor-a in patients with myelodysplastic syndromes

The effects of Interleukin 12 (IL-12) on natural killer (NK) cell cytotoxicity and on the production of interferon-7 (IFN-7) and tumour necrosis factor-a (TNF-a) were examined in 15 patients with myelodysplastic syndromes (MDS), which are well known to have immunologic defects, and in 11 normal subjects. The NK cell cytotoxicity of all of the normal subjects was augmented by incubation with IL-12 alone, and co-incubation with interleukin 2 (IL-2) further augmented it (type A response). The MDS patients showed varied responses to IL-12/IL-2. Seven patients showed the type A response, resulting in augmented NK cell cytotoxicity which was similar to that in the normal subjects. In five other patients the cytotoxicity was not increased by IL-12 alone, but the combination of IL-12 and IL-2 did augment the cytotoxicity (type B response). The augmented cytotoxicity in these type B patients was lower than that in the normal subjects. In the final three MDS patients the cytotoxicity was low and not affected by IL- 12 and/or IL-2 (type C response). AH patients with refractory anaemia with excess blasts (RAEB) and patients with RAEB in transformation showed a type B or C response. Conversely, six of eight refractory anaemia patients showed a type A response. In MDS patients there was a positive correlation between the percentage of CD3CD56⁺ cells in pre-incubated cells and the cytotoxicity of cells incubated with IL-12/IL-2. The combination of IL-12 and IL-2 augmented IFN-7 and TNF-Q production by nonadherent mononuclear cells in a synergistic or cumulative manner, respectively, in most patients. These results suggest that IL-12, alone or with IL-2, may modulate these important immunologic functions in most MDS patients.     

Current Density Distribution by Ring and Diagonally Arranged Half‐Ring Electrodes in Bipolar and Overlapping Biphasic Impulse Stimulation

Background: We have studied the acute and long‐term efficacy of overlapping biphasic impulse (OLBI) stimulation for atrial pacing with VDD pacemakers and demonstrated the feasibility of DDD pacing in OLBI with diagonally arranged half‐ring (Half‐Ring) electrodes. We made two three‐dimensional computational analysis models to verify our clinical studies. Methods and Results: Model I was composed of a heart, a pacemaker, and a human body. Model II was a cube with dimensions of 20 by 20 by 20 mm quarried from Model I for the detailed study of current density distributions. Laplace's equation was solved using the finite element method and the current density J was calculated. For Model I, the distal and proximal voltages were ?10 V, 0 V in bipolar and ?5 V, +5 V in OLBI, using Ring electrodes. In Model II, the actual measurements of electrode impedances obtained from the clinical study (1,180 Ω for Ring and 630 Ω for Half‐Ring) were added to the analysis conditions. Model I showed that OLBI produced more concentrated current density distributions than those by bipolar. According to Model II, at the atrial myocardium position current density produced by Half‐Ring was larger than that by Ring electrodes, 70 μA/mm² versus 30 μA/mm² in OLBI configuration. It also indicated that even if electrode impedances were equal between Half‐Ring and Ring electrodes, the maximum current density produced by Half‐Ring would be greater than that by Ring electrodes. Conclusions: It was considered that OLBI configuration with Half‐Ring electrodes provides more effective current density distributions. (PACE 2010; 33:1063–1073)     

Longitudinal study on forces transmitted from denture base to retainers of lower free-end saddle dentures with Aker''s clasps

The aim of this study was to make a longitudinal analysis of the forces transmitted from denture base to retainers of lower free-end saddle dentures with Aker's clasps using a newly developed transducer. The experimental apparatus consisted of two components, a metal framework and a denture base embedded with a force-detecting unit. This device was the transducer, which could detect changes in lateral and vertical forces transmitted from denture base to retainers at the same time. Forces were measured on several separate occasions from the insertion of new dentures to about 4 months afterwards. The result are summarized as follows: (i) the maximal mean value of vertical forces transmitted from denture base to retainers was decreased after 1 week of insertion of new dentures, then increased and reached a constant level (about 10N) 4-6 weeks after the insertion of new dentures; (ii) there were large differences in the maximal mean value of lateral forces between subjects.