Experimental antitumour activity of S 16020-2 in a panel of human tumours

OBJECTIVE: To compare the effects of inhaled nitric oxide (NO) and extracorporeal membrane oxygenation (ECMO) on oxygenation, hemodynamics, and lymphatic drainage in an oleic acid lung injury model in sheep. DESIGN: Prospective, randomized study. SETTING: Animal research laboratory. ANIMALS: Thirty female sheep, weighing 35 to 40 kg. INTERVENTIONS: Acute lung injury was induced by central venous injection of oleic acid (0.5 mL/kg body weight). A chronic lymph fistula had been prepared through a right thoracotomy 3 days before the experiment. Animals were assigned randomly to the NO group (n = 14) or the ECMO group (n = 16). When a lung injury score of > 2.5 was achieved, the animals were given NO in dosage increments of 2, 5, 10, 20, and 40 parts per million (ppm), or placed on ECMO with an FIO2 of 0.21 (ECMO-21) and then 1.0 (ECMO-100) at the oxygenator. Mechanical ventilator parameters were kept constant to isolate the effects of NO and ECMO on systemic and pulmonary hemodynamics, cardiac output, oxygenation parameters, lymph/plasma protein ratio, and lymph flow. Measurements and calculations were performed after 1 hr at each individual step of NO concentration or FIO2. MEASUREMENTS AND MAIN RESULTS: In the ECMO group, PVRI and MPAP did not change and were significantly different from the NO group. In the NO group, there was a dose-dependent decrease in venous admixture, maximal at 10 ppm NO and decreasing from 40 +/- 6% to 23 +/- 10% (p < .05). This decrease was significantly different from the ECMO group, where there was no change. There was a significant increase in PaO2/FIO2 in the NO group, maximal at 10 ppm NO (84 +/- 11 to 210 +/- 90, p < .05), but a greater increase in PaO2/FIO2 on ECMO-21 (81 +/- 14 to 265 +/- 63) and a further increase on ECMO-100 (398 +/- 100) (p < .05). The lymph/plasma protein ratio remained unchanged in both groups after induction of lung injury by oleic acid. However, lymph flow decreased by 11 +/- 6% in the NO group, whereas it increased by 14 +/- 17% in the ECMO group (p < .05). CONCLUSIONS: In an oleic acid-induced sheep model of acute lung injury, there were significant differences between the effects of NO and ECMO on acute pulmonary hypertension, hypoxemia, hypercarbia, and lymph flow. NO significantly decreases pulmonary hypertension, whereas pulmonary hemodynamics were not substantially affected by ECMO. Both interventions reversed hypoxemia, but ECMO did so to a greater degree, and only ECMO improved hypercarbia. Only NO decreased lymph flow, possibly as an effect of decreased microvascular filtration pressure. This study did not attempt to evaluate the impact of these interventions on ventilatory requirements, barotrauma, or outcome. However, this model suggests that NO therapy may moderate pulmonary hypertension and improve lymph flow in acute lung injury. Clinical studies are needed to assess whether NO therapy might be beneficial in treatment of severe acute lung injury in older children and adults.     

Comparative action spectrum for ultraviolet light killing of mouse melanocytes from different genetic coat color backgrounds

PURPOSE: This study reports the authors' experience with long-term follow-up of 100 consecutive peripherally inserted, subcutaneous arm ports for central venous access. MATERIALS AND METHODS: One hundred patients with subcutaneous arm ports inserted by interventional radiologists were retrospectively studied. Data were collected from the patients' medical records and from telephone canvassing. Using each insertion period as an observation, the complication rates per 100 catheter days were determined with 95% confidence intervals (CIs). RESULTS: One hundred subcutaneously implanted ports were placed in 98 patients; three devices (three patients) were lost to follow-up, leaving 97 devices in 95 patients. Total exposure time was 23,842 days (mean, 246 days; range, 2-865 days). Seven infectious and two noninfectious complications occurred with seven (7.2%) devices in six patients (6.3%), yielding 0.038 complications per 100 catheter days at risk (95% CI; 0.011-0.069) and 0.029 infections per 100 catheter days at risk (95% CI; 0.008-0.058). A successful clinical outcome was defined as a functional port at removal, time of death, or at study closure (minimum of 6 months of follow-up), which was not removed because of a complication. This successful outcome was achieved in 91 ports (93.8%). Procedural-related complications, defined as those occurring up to 30 days after insertion, occurred in only one port (thrombophlebitis and catheter tip infection-day 9). All other patients received several months of service from their port. Fifteen devices were placed in 13 patients with HIV for 3,486 days, with a total complication rate of 0.11 per 100 catheter days (95% CI; 0.0-0.28), all of which were infections. Devices in HIV-positive patients were associated with higher total complication (20% vs 4.9%) and infection rates (20% vs 3.7%) than devices in patients without HIV infection. This gives a relative risk 8.17 x (P = .04) greater for infectious complications for devices placed in HIV-infected individuals. CONCLUSIONS: Subcutaneous arm ports placed by interventional radiologists are effective for central venous access with excellent functionality (93.8% achieved a successful long-term outcome) and a very low procedural complication rate. Although infections were more frequent in HIV-infected individuals, these devices are associated with a very low incidence of both immediate and long-term complications, including infection, for all patients.     

Racial and ethnic disparities in the use of cardiovascular procedures: associations with type of health insurance

This is the first report showing VIP fibers in the optic chiasm and the optic nerves of intact rats. These fibers form a fan-shaped dorso-medial bundle in the optic nerves. After colchicine injection into the vitreous body VIP fibers could be followed farther in the optic nerve toward the eye when compared to intact rats. After removal of eyes (enucleation) the VIP fiber-bundle became more prominent and VIP immunoreactive perikarya appeared in the supraoptic and para ventricular nuclei. When five-nine months after the enucleation Phaseolus vulgaris leucoagglutinin was administered to the paraventricular or supraoptic area, the anterogradely transported tracer was demonstrated in the optic nerve. These observations suggest the existence of a hypothalamic projection to the eye, which is, at least in part, VIP immunoreactive.     

Unusual fatty acid compositions of the hyperthermophilic archaeon Pyrococcus furiosus and the bacterium Thermotoga maritima

The fatty acid compositions of the hyperthermophilic microorganisms Thermotoga maritima and Pyrococcus furiosus were studied and compared. A total of 37 different fatty acids were identified in T. maritima, including the novel 13,14-dimethyloctacosanedioic acid. In contrast, a total of 18 different fatty acids were characterized, as minor components, in P. furiosus, and these included saturated, monounsaturated, and dicarboxylic acids. This is the first report of fatty acids from an archaeon.     

Tryptophan depletion and HIV infection: a metabolic link to pathogenesis

HIV-1-infected patients have low circulating tryptophan concentrations despite evidence of adequate dietary intake of this essential amino acid. A chronic increase in inducible tryptophan oxidation is the basis of HIV-1-associated tryptophan depletion. This metabolic process results in the irretrievable loss of tryptophan molecules from the available pool. Such sustained disruption of normal tryptophan metabolism over time disturbs the many metabolic processes involving this amino acid, and has been implicated in some features of AIDS pathogenesis. Normal T-cell function is adversely affected by tryptophan depletion, but the extent of the effect in HIV-1-infected patients is still unclear. Attempting to directly supplement tryptophan is not advised given the potential increase in circulating concentrations of neurotoxic intermediates. Although only preliminary data are available, evidence suggests that antiretroviral and nicotinamide treatments can boost plasma tryptophan concentrations in HIV-1-infected patients and impact the secondary effects of tryptophan depletion. Additional study of this metabolism could lead to improved treatment strategies for patients with HIV infection. In this review I focus on the potential links between disturbed tryptophan metabolism and pathogenesis.