Dose response relationships for radiation induced chromosome aberrations in human lymphocytes in vivo and in vitro

Chromosome aberrations have been analysed in cultured lymphocytes from a patient undergoing whole-body treatment with split doses of gamma-rays up to a cumulative dose of 1.4 Gy. The dependence on dose of the yield of dicentrics was best fitted to the linear-quadratic relationship with a linear component predominating in the low dose range (below 0.56 Gy). These observations were compared with the data obtained when blood samples were exposed in vitro to low acute doses of gamma-rays (from 0.05 up to 2.0 Gy). The frequencies of induced chromosome aberrations were similar in both cases and little deviation was found between the dose response curves (a/b ratio equal to 0.56 and 0.69 Gy, respectively in vivo and in vitro). These results confirm that in vitro calibration curves can be utilized confidently for the biological estimate of an in vivo absorbed dose.     

Assessment of myocardial viability in rats: Evaluation of a new method using superparamagnetic iron oxide nanoparticles and Gd-DOTA at high magnetic field.

The aim of this study was to detect salvageable peri-infarction myocardium by MRI in rats after infarction, using with a double contrast agent (CA) protocol at 7 Tesla. Intravascular superparamagnetic iron oxide (SPIO) nanoparticles and an extracellular paramagnetic CA (Gd-DOTA) were used to characterize the peri-infarction zone, which may recover function after reperfusion occurs. Infarcted areas measured from T1-weighted (T1-w) images post Gd-DOTA administration were overestimated compared to histological TTC staining (52% +/- 3% of LV surface area vs. 40% +/- 3%, P=0.03) or to T2-w images post SPIO administration (41% +/- 4%, P=0.04), whereas areas measured from T2-w images post SPIO administration were not significantly different from those measured histologically (P=0.7). Viable and nonviable myocardium portions of ischemically injured myocardium were enhanced after diffusive Gd-DOTA injection. The subsequent injection of vascular SPIO nanoparticles enables the discrimination of viable peri-infarction regions by specifically altering the signal of the still-vascularized myocardium.     

Effects of hyperthermia on natural killer cells: inhibition of lytic function and microtubule organization.

Cells with natural killer activity (NK) may play an important role in host defence against tumour cells. The lytic function of NK cells is very sensitive to hyperthermic inactivation. However, cells with NK activity isolated from rat spleen and exposed to 41-42.5 degrees C for 30 min could partially recover their cytotoxic activity after incubation at 37 degrees C. The recovered cytotoxicity was still NK-specific, as it only resulted in the lysis of YAC-1 sensitive targets, and could not lyse NK-resistant P815 mastocytoma cells. Conjugate formation assay using NK cells labelled with specific monoclonal antibody (mAb) 3.2.3 indicated that the binding of NK cells to targets was not significantly affected by heat treatment. Compared to controls, however, microtubule organizing centre (MTOC) reorientation towards the region of intercellular contact was reduced by 40% in heated effector cells. This was accompanied by a greater inhibition (62-77%) of NK lytic activity. Kinetic analysis indicated that MTOC reorientation capacity recovered following incubation at 37 degrees C. MTOC recovery was maximal 4 h after treatment whereas that of lytic activity peaked at 6 h. These data indicate that NK cells recover NK-specific lytic activity after heat inactivation. Moreover, our study demonstrates that hyperthermia interferes with post-binding MTOC reorientation, and further supports a role for microtubule in secretory processes involved in NK-mediated cytolysis.     

Maturation of long-term potentiation in the hippocampal dentate gyrus of the freely moving rat

The ability of the perforant path/dentate granule cell synapse of the hippocampal formation to establish and maintain enhanced levels of synaptic transmission in response to tetanization (long-term potentiation, LTP) was investigated in freely moving rats at 15, 30, and 90 days of age. Measures of (1) the slope of the population excitatory postsynaptic potential (EPSP), and (2) the population spike amplitude (PSA) obtained before, and at several times following tetanization, were used to evaluate the magnitude and duration of LTP as a function of age. Significant enhancement of both EPSP slope and PSA measures was obtained from animals of all three ages in response to perforant path tetanization. The initial degree of enhancement was essentially the same across the age groups, ranging from +27% to +38% of pretetanization levels for EPSP slope measures and +60% to +75% of pretetanization levels for PSA measures, obtained 15 min after tetanization. The duration of this enhancement obtained from animals of the preweaning group was significantly longer than that obtained from either 30- or 90-day-old animals. Enhanced measures of both EPSP slope and PSA decayed to baseline levels in these older animals 18 to 24 h after tetanization, while animals tetanized at 15 days of age maintained potentiated levels of both measures for a period of 5 days following tetanization. Tetanization of 15-day-old animals resulted in a significant reduction in the latency to EPSP onset without affecting the time-based relationships among the other measured parameters, which included latency of the population spike onset, population spike minimum, and population spike offset. Tetanization had no effect on the latency measure of any of these parameters in either of the two older age groups. The primarily postnatal development of the dentate granule cell population suggests that both functionally immature GABAergic modulation of granule cell activity and the differential development of components of the N-methyl-D-aspartate receptor complex may be involved in the age-related differences in the induction and expression of the LTP phenomenon. This study represents the first developmental characterization of LTP in the perforant path/dentate granule cell synapse in freely moving rats during early development. The results indicate that LTP can be reliably established and maintained in behaving rats as young as 15 days of age. Whereas the degree of potentiation at this age is equivalent to that obtained from juveniles and young adults, the duration of the effect significantly outlasts that obtained from older animals in which development of the dentate gyrus is more functionally mature. © 1994 Wiley-Liss, Inc.     

Retrocostoxyphoid hernia in children. Apropos of 6 cases. Review of the literature

Six further cases of retrocostoxiphoid hernia in children are reported, the postoperative course being uncomplicated following supraumbilical laparotomy. The relevant literature is reviewed and emphasis placed on the value of peritoneography for establishing diagnosis prior to operation.     

BioArgos: a fully automated blood culture system.

BioArgos (Sanofi Diagnostics Pasteur, Marnes-la-Coquette, France) is a fully automated blood culture system that detects carbon dioxide production by infrared spectroscopy through a glass bottle. This hands-off system was compared with the BACTEC NR-660 system (Becton Dickinson Diagnostic Instrument Systems, Towson, Md.). A total of 336 microorganisms belonging to 74 taxa were tested in simulated blood cultures by both systems. Experimental data showed no significant differences between the two systems. The inclusive detection times (+/- the standard deviations) were 33.2 +/- 28.7 and 35.0 +/- 30.6 h with BioArgos and BACTEC, respectively. Anaerobes were detected earlier with BioArgos, whereas detection of some organisms that need oxygen to grow was slightly delayed. In conclusion, BioArgos is as reliable and accurate as BACTEC NR-660 and shows better practicability owing to noninvasive detection, reduction of vial manipulation, and absence of daily maintenance.     

Disposition of sandostatin, a new synthetic somatostatin analogue, in rats

The distribution, excretion, and metabolism of Sandostatin, a long-acting octapeptide analogue of somatostatin, have been studied in the rat after iv administration. Similar plasma levels and excretion values were observed by using radioimmunoassay and HPLC-liquid scintillation techniques. For the latter technique Sandostatin was radiolabeled with either 14C or 3H. The plasma pharmacokinetics of Sandostatin were as follows: Vdss = 0.4 liter/kg, C/t = 4.2 ml/min, and t1/2 2.0 hr; this half-life was by far longer than that of somatostatin. The in vitro protein binding amounted to 59% in rat plasma; no Sandostatin was taken up by blood cells. The tissue concentrations of Sandostatin were similar when determined either by radioimmunoassay or by quantitative whole-body autoradiography; this suggests that the distribution of 3H or 14C radioactivity observed 0.5 hr after iv administration mostly represented unchanged Sandostatin. Kidney and liver were the only tissues in which Sandostatin levels were higher than in blood; high radioactivity levels were observed in the blood vessel walls, whereas levels in brain were insignificant. Unchanged drug accounted for most of the radioactivity found in plasma, urine, and bile, whereas only traces of unchanged drug were detected in feces. These results demonstrated the metabolic stability of Sandostatin in the tissues, primarily in the liver, and suggested an extensive degradation in the intestinal tract. The degradation products consisted of smaller peptides and free amino acids. About 50% and 20% of the applied dose were excreted as unchanged Sandostatin in bile and urine, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Septicemias in cancer patients during parenteral nutrition: contributing factors and detection by weekly blood cultures

Infections constitute the main complication of parenteral nutrition, particularly in cancer patients, but prediction of catheter-related septicemias (CRS) has been little investigated. We have evaluated, in 200 consecutive episodes of parenteral nutrition (PN) in cancer patients, the factors contributing to infectious complications, and the predictive value of weekly blood cultures performed through the nutrition catheter. The median duration of PN was 22 days with a total of 5816 patient-days of PN, neutropenia (neutrophils < 1,000/mul) being present in 872 (15%). Catheters were placed either in a jugular vein (71% single-lumen silicone catheters, 18.5% double-lumen Hickman-Broviac catheters) or in a femoral vein (10.5%). We observed 62 episodes of septicemia of which 22 were CRS (11% incidence for the 200 cycles) and 40 were non-CRS (20% incidence); CRS were mostly due to Staphylococcus epidermidis (14 22 ). Neutropenic patients as a group did not suffer more CRS than non-neutropenic patients, but the risk of CRS was slightly increased when expressed per day of neutropenia (8 CRS/872 days vs 14 CRS/4942 days without neutropenia, P < 0.05). On the other hand, a femoral insertion site was associated with a much higher incidence of CRS (9 CRS/21 femoral catheters vs 13 CRS/179 jugular catheters, P < 0.0001). It was possible to evaluate 20 episodes of CRS for their predictability by weekly blood cultures: the sensitivity for detecting CRS due to Staphylococcus epidermidis was 67%, the specificity 92%, the negative predictive value 98% and the positive predictive value 36%. The simple and widely available procedure of routine surveillance blood cultures performed through the PN catheter should be further investigated, because it could help the clinician to determine the origin of recent fever, particularly to exclude CRS and avoid unnecessary removal of PN catheters.