Meta-Analysis of Trials on Prophylactic Use of Levosimendan in Patients Undergoing Cardiac Surgery

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Early influx of macrophages determines susceptibility to experimental allergic encephalomyelitis in Dark Agouti (DA) rats

Experimental allergic encephalomyelitis (EAE) is characterized by inflammatory infiltrates of myelin antigen(s) specific T cells and consecutive demyelination. Injection of encephalitogen into the footpads induces disease in genetically susceptible Dark Agouti rats (DA) but not in Albino Oxford (AO) rats although mild inflammatory infiltrates are observed in both strains early after disease induction. In addition, only DA rats develop disease when cells from (AO×DA) F(1) hybrids are passively transferred into sub-lethally radiated AO and DA parent hosts. The aim of the study was therefore to examine the participation of accessory cells, macrophages, dendritic cells and microglia in EAE development at the level of the target tissue in these two strains using specific membrane markers. We demonstrate here that in the induction phase of EAE in DA rats, macrophages (CD68(+); CD45(hi)CD11b(+)) are the first detectable infiltrating cells in the subpial regions of the spinal cord but were not found in AO rats. During the same period, resident microglial cells which are of the ramified variety are observed in both DA and AO rats. In DA rats at the peak of disease, when profuse influx of T cells is seen, macrophages and dendritic cells appear in the parenchyma of the CNS. In addition, at that time, microglial cells are activated. FACS analyses also reveal a significant increase in CD45(hi)CD11c(+) dendritic cells and CD45(hi)D11b(+) macrophages compared with levels in na?ve and immunized AO rats. During resolution of disease in DA rats, the expression of microglia and macrophage markers is comparable with those in na?ve non-immunized DA and immunized AO rats. We conclude that an initial influx of macrophages is indispensible for the development of EAE in DA rats. The presence of dendritic cells and myeloid dendritic cells at the peak of disease supports the role of these cells in EAE especially in relapses and chronicity. The activation pattern of microglia in DA rats does not indicate their role as antigen presenting cells in disease induction since they are ramified at the induction phase and only become activated after the overwhelming influx of T cells.     

Antidepressant-like effect of magnetic resonance imaging-based stimulation in mice

INTRODUCTION: It has been reported that a novel type of magnetic resonance imaging (MRI) scan called echo planar magnetic resonance spectroscopic imaging (EP-MRSI) may show antidepressant effects. We examined whether the two routine diagnostic protocols of MRI [T1 and echo planar diffusion weighted imaging (EPI-DWI)], have antidepressant-like effects in an animal model of depression. METHODS: The effects of standard EPI-DWI and T1 MRI on immobility, swimming and climbing times in the modified forced swimming test (FST) in mice were examined. After exposure to the first session of modified forced swimming test, we randomly divided the mice into four groups. The first group (T1 MRI group, n=21) received a 15-minute stimulation of T1 sequence. The second group (EPI-DWI MRI group, n=21) received a 15-minute stimulation of EPI-DWI protocol. The third group (sham group, n=21) spent 15 min in a tunnel similar to the MRI gantry in terms of size, temperature and light intensity and received recorded sounds from a normal session of EPI-DWI with similar duration and intensity. The fourth group acted as controls (n=21).The second session of the modified FST was conducted twelve hours later. The mean of immobility, swimming and climbing times in this session were compared to the control group. RESULTS: T1 weighted and EPI-DWI MRI groups showed a reduction in immobility time compared to the control group (P value<0.002, P value<0.017 respectively). This effect is comparable to that seen in the FST after the administration of antidepressant agents. The climbing time in the group subjected to EPI-DWI MRI was longer than the control group (P value<0.035). Previous studies showed similar effects after the administration of antidepressant drugs affecting the catecholamine systems. The swimming time in the T1 MRI group was significantly longer than the control group (P value<0.037). Previous studies showed qualitatively similar effect to that of anti-depressant drugs affecting the serotoninergic systems. The swimming, climbing and immobility times in the sham and control groups showed no significant difference. CONCLUSIONS: Our findings raise the possibility that MRI-based stimulation may have antidepressant-like effects in mice. This is likely to be through different mechanisms in T1 weighted and EPI-DWI protocols. However the possible biological basis of this effect is not yet understood and we would advocate further studies of MRI-based stimulation effects on transmitters in the different organs in the body specially the brain.     

Multimodal imaging in photic retinopathy

Letter to the Editor     

Detection of gastric contents in tracheal fluid of infants by lactose assay

We designed an in vitro assay to detect the presence of lactose in the tracheal aspirates of premature, ventilator-dependent infants. This method was employed to identify recurrent, unrecognized aspiration, which could prolong the requirements for ventilator support and contribute to the development of chronic lung disease. One hundred five determinations of lactose were performed on the tracheal fluid obtained from 42 ventilator-dependent infants who were receiving enteral feedings. There was a wide range of lactose levels (0 to 3,270 nmol lactose/ml tracheal aspirate). Six infants had samples that were highly suggestive of aspiration (greater than 200 nmol lactose/ml tracheal aspirate). Twenty infants had questionably positive samples (25 to 200 nmol lactose/ml tracheal aspirate), and 16 infants had samples that were considered negative for aspiration (less than 25 nmol lactose/ml tracheal aspirate).     

A phase I/II trial of rAd/p53 (SCH 58500) gene replacement in recurrent ovarian cancer

PURPOSE: To determine the safety, gene transfer, host immune response, and pharmacokinetics of a replication-deficient adenovirus encoding human, recombinant, wild-type p53 (SCH 58500) delivered into the peritoneal cavity (i.p.) alone and sequentially in combination with platinum-based chemotherapy, of patients with recurrent ovarian, primary peritoneal, or fallopian tube cancer containing aberrant or mutant p53. METHODS: SCH 58500 was administered i.p. to three groups of patients with heavily pretreated recurrent disease. Group 1 (n=17) received a single dose of SCH 58500 escalated from 7.5 x 10(10) to 7.5 x 10(12) particles. Group 2 (n=9) received two or three doses of SCH 58500 given alone for one cycle, and then with chemotherapy for two cycles. The SCH 58500 dose was further escalated to 2.5 x 10(13) particles/dose in group 2. A third group (n=15) received a 5-day regimen of SCH 58500 given at 7.5 x 10(13) particles/dose per day i.p. alone for cycle 1 and then with intravenous carboplatin/paclitaxel chemotherapy for cycles 2 and 3. RESULTS: No dose-limiting toxicity resulted from the delivery of 236/287 (82.2%) planned doses of SCH 58500. Fever, hypotension abdominal complaints, nausea, and vomiting were the most common adverse events. Vector-specific transgene expression in tumor was documented by RT-PCR in cells from both ascitic fluid and tissue biopsies. Despite marked increases in serum adenoviral antibody titers, transgene expression was measurable in 17 of 20 samples obtained after two or three cycles of SCH 58500. Vector was detectable in peritoneal fluid by 24 hours and persisted for as long as 7 days whereas none was detected in urine or stool. There was poor correlation between CT scans and CA125 responses. CA125 responses, defined as a greater than 50% decrement in serum CA125 from baseline, were documented in 8 of 16 women who completed three cycles of the multidose regimen. CONCLUSION: CT scans are not a valid measure of response to i.p. SCH 58500 due to extensive adenoviral-induced inflammatory changes. Intraperitoneal SCH 58500 is safe, well tolerated, and combined with platinum-based chemotherapy can be associated with a significant reduction of serum CA125 in heavily pretreated patients with recurrent ovarian, primary peritoneal, or fallopian tube cancer.     

Iodine-131 MIBG scintigraphy in small cell lung cancer

There is a well documented relationship between small cell carcinoma of the lung and the amine precursor uptake and decarboxylation system of endocrine cells (APUD). We attempted to exploit this association by employing the unique radiopharmaceutical,¹³¹I-MIBG, which is recognized and taken up by the APUD system to monitor disease activity in patients with small cell carcinoma of the lung. A total of eight patients with biopsy proven, metastatic small cell carcinoma of the lung were studied.¹³¹I-MIBG was synthesized in our laboratory by reacting metaiodobenzylamine synthesized in our laboratory by reacting metaiodobenzylamine hydrochloride with cyanamide with subsequent solid phase radioiodination. A dose of 0.5 mCi radiopharmaceutical was injected and images obtained on a large field of view gamma camera with a high energy parallel hole collimator at 2, 24, and either 48 or 72 h. Images were compared with known focal areas of metastatic disease demonstrable on computed tomographic scan, chest roentgenogram or bone scan. We were unable to detect reproducible correlations between the images produced by conventional radiographic techniques and the images produced by our radiopharmaceutical. We conclude that this agent will probably not be useful for localization of metastatic small cell lung carcinoma.This work was supported by a Pilot Research Grant from the Education and Research Foundation of the Society of Nuclear Medicine     

Modulation of P2 auditory-evoked responses by the spectral complexity of musical sounds

We investigated whether N1 and P2 auditory-evoked responses are modulated by the spectral complexity of musical sounds in pianists and non-musicians. Study participants were presented with three variants of a C4 piano tone equated for temporal envelope but differing in the number of harmonics contained in the stimulus. A fourth tone was a pure tone matched to the fundamental frequency of the piano tones. A simultaneous electroencephalographic/magnetoencephalographic recording was made. P2 amplitude was larger in musicians and increased with spectral complexity preferentially in this group, but N1 did not. The results suggest that P2 reflects the specific features of acoustic stimuli experienced during musical practice and point to functional differences in P2 and N1 that relate to their underlying mechanisms.