Effect of high-dose fentanyl on renal function in dogs

OBJETIVOS: Estudamos os efeitos de alta dose de fentanil (F) em atributos de função renal (FR) do cão. DESENHO: Anestesiamos com pentobarbital sódico (PS) 16 cães divididos aleatoriamente em 2 grupos: manutenção com PS (Gi) e PS com F (0,05 mg.kg-1) (G2). INTERVENÇÃO: os cães foram ventilados artificialmente e tiveram cateterizadas as veias femorais esquerda e direita e a artéria femoral esquerda para infusão de drogas e coleta de dados hemodinâmicos e de sangue para dosagens laboratoriais. Coletou-se urina durante todo experimento. MENSURAÇÃO: Determinaram-se os valores de atributos de FR.. RESULTADOS: PS não mudou a FR e o comportamento de G1 deveu-se à expansão do volume extracelular. O F diminuiu significativamente freqüência cardíaca, pressão arterial média, clearance de creatinina, volume urinário, clearance osmolar e excreção fracionária de sódio e potássio. CONCLUSÕES: A diminuição da FR foi provavelmente devida às alterações hemodinâmicas induzidas pelo F, não se descartando possível ação da aldosterona.

A comparison of the effect of high- and low-dose fentanyl on the incidence of postoperative cognitive dysfunction after coronary artery bypass surgery in the elderly

Background. Postoperative cognitive dysfunction (POCD) after coronary artery bypass graft surgery is a common complication for which, despite many clinical investigations, no definitive etiology has been found. The current use of both high and low-dose fentanyl as anesthetic techniques allowed us to investigate the effect of fentanyl on the incidence of POCD. Methods. Three hundred fifty patients scheduled to undergo elective coronary artery bypass graft surgery were randomized to receive either high-dose fentanyl (50 mu g/kg) or low-dose fentanyl (10 mu g/kg) as the basis of the anesthetic. All patients underwent neuropsychological testing before surgery and at 1 week, 3 months, and 12 months after surgery. Results. One hundred sixty-eight patients in the low-dose group and 158 patients in the high-dose group were included in the final analysis. Neuropsychological testing was performed on 88%, 93%, and 92% of patients at 1 week, 3 months, and 12 months, respectively. There was no difference between group mean scores at any of the three testing times. Analysis of individual patients by the 20% rule did not detect any differences between groups. The one SD rule, which has fewer false-positive results, detected significantly more patients with POCD in the low-dose group than in the high-dose group at 1 week (23.6% vs. 13.7%; P = 0.03) but not at the other testing times. Patients with POCD spent an average of 1.2 days longer in the hospital than those without POCD (P = 0.021). Conclusions: High-dose fentanyl is not associated with a difference in the incidence of POCD at 3 or 12 months after surgery. Low-dose fentanyl leads to shorter postoperative ventilation times and may be associated with a greater incidence of POCD 1 week after surgery. Early POCD is associated with an increased duration of stay in the hospital.

A phase II study of the modulation of 5-fluorouracil and folinic acid with high-dose infusional hydroxyurea in metastatic colorectal carcinoma

Background: Hydroxyurea (HU), an inhibitor of ribonucleotide reductase, may potentiate the activity of 5-fluorouracil (5-FU) and folinic acid (FA) by reducing the deoxyribonucleotide pool available for DNA synthesis and repair. However as HU may inhibit the formation of 5-fluoro-2-deoxyuridine-5- monophosphate (FdUMP), one of the principal active metabolites of 5-FU, the scheduling of HU may be critical. In vitro experiments suggest that administration of HU following 5-FU, maintaining the concentration in the region of I mM for six or more hours, significantly enhances the efficacy of 5-FU. Patients and methods: 5-FU/FA was given as follows: days 1 and 2 - FA 250 mg/m 2 (max. 350 mg) over two hours followed by 5-FU 400 mg/m 2 by intravenous bolus (ivb) over 15 minutes and subsequently 5-FU 400 mg/m 2 infusion (ivi) over 22 hours. HU was administered on day 3 immediately after the 5-FU with 3 g ivb over 15 minutes followed by 12 g ivi over 12 hours. Results: Thirty patients were entered into the study. Median survival was nine months (range 1-51 + months). There were eight partial responses (28%, 95% CI: 13%-47%). The median duration of response was 6.5 (range 4-9 months). Grade 3-4 toxicities included neutropenia (grade 3 in eight patients and grade 4 in five), anaemia (grade 3 in one patient) and diarrhoea (grade 3 in two patients). Neutropenia was associated with pyrexia in two patients. Phlebitis at the infusion site occurred in five patients. The treatment was complicated by pulmonary embolism in one patient and deep venous thrombosis in another. Conclusion: HU administered in this schedule is well tolerated. Based on these results and those of other phase II studies, a randomised phase III study of 5-FU, FA and HU versus 5-FU and FA using the standard de Gramont schedule is recommended.

ANNEALING BEHAVIOUR OF HIGH DOSE As** plus IMPLANTS.

The annealing behaviour of doses up to 4. 10**1**6 ions/cm**2 implanted at ion currents up to 10ma is described. Differences between rapid isothermal and furnace annealing in the measured sheet resistances are due to different amounts of diffusion and to loss of dopant by evaporation. Implantation at high currents (10ma) does not appear to affect the quality of the regrown material provided the temperature rise during implantation is small.

Fabrication of a Low-Loss SSC Using High-Dose Electron Beam Lithography Exposure With Negative PMMA Resist

A silicon-on-insulator optical fiber-to-waveguide spot-size converter (SSC) using Poly-MethylMethAcrylate (PMMA) is presented for integrated optical circuits. Unlike the conventional use of PMMA as a positive resist, it has been successfully used as a negative resist with high-dose electron exposure for the fabrication of ultrafine silicon wire waveguides. Additionally, this process is able to reduce the side-wall roughness, and substantially depresses the unwanted propagation loss. Exploiting this technology, the authors demonstrated that the SSC can improve coupling efficiency by as much as over 2.5 dB per coupling facet, compared with that of SSC fabricated with PMMA as a positive resist with the same dimension.

Aggregation and precipitation in high dose as ion implanted Ge0.5Si0.5 alloy

Thermally stimulated redistribution and precipitation of excess arsenic in Ge0.5Si0.5 alloy has been studied by X-ray photoelectron spectroscopy (XPS), cross sectional transmission electron microscopy (XTEM) and X-ray energy disperse spectrometry (EDS). Samples were prepared by the implantation of 6 X 10(6) As+ cm(-2) and 100 keV with subsequent thermal processing at 800 degrees C and 1000 degrees C for 1 h. The XPS depth profiles from the implanted samples before and after the thermal annealing indicate that there is marked redistribution of the elements in heavily arsenic-implanted Ge0.5Si0.5 alloys during the annealing, including: (1) diffusion of As from the implanted region to the surface; (2) aggregation of Ge in the vicinity of the surface. A high density of precipitates was observed near the surface which were by XTEM and EDS identified as an arsenide. It is suggested that most of the implanted As in Ge0.5Si0.5 alloy exists in the form of GeAs.

Alleviation of pre-exposure of mouse brain with low-dose C-12(6+) ion or Co-60 gamma-ray on male reproductive endocrine damages induced by subsequent high-dose irradiation

Irradiation has been widely reported to damage organisms by attacking on proteins, nucleic acid and lipids in cells. However, radiation hormesis after low-dose irradiation has become the focus of research in radiobiology in recent years. To investigate the effects of pre-exposure of mouse brain with low-dose C-12(6+) ion or Co-60 gamma (gamma)-ray on male reproductive endocrine capacity induced by subsequent high-dose irradiation, the brains of the B6C3F(1) hybrid strain male mice were irradiated with 0.05 Gy of C-12(6+) ion or Co-60 gamma-ray as the pre-exposure dose, and were then irradiated with 2 Gy as challenging irradiation dose at 4 h after pre-exposure. Serum pituitary gonadotropin hormones, follicle-stimulating hormone (FSH) and luteinizing hormone (LH), testosterone, testis weight, sperm count and shape were measured on the 35th day after irradiation. The results showed that there was a significant reduction in the levels of serum FSH, LH, testosterone, testis weight and sperm count, and a significant increase in sperm abnormalities by irradiation of the mouse brain with 2 Gy of C-12(6+) ion or Co-60 gamma-ray. Moreover, the effects were more obvious in the group irradiated by C-12(6+) ion than in that irradiated by Co-60 gamma-ray. Pre-exposure with low-dose C-12(6+) ion or Co-60 gamma-ray significantly alleviated the harmful effects induced by a subsequent high-dose irradiation.

Adaptive hormetic response of pre-exposure of mouse brain with low-dose C-12(6+) ion or Co-60 gamma-ray on growth hormone (GH) and body weight induced by subsequent high-dose irradiation

The brain of the Kun-Ming strain mice were irradiated with 0.05 Gy of C-12(6+) ion or Co-60 gamma-ray as the pre-exposure dose, and were then irradiated with 2 Gy of 12C6+ ion or Co-60 gamma-ray as challenging irradiation dose at 4 h after per-exposure. Body weight and serum growth hormone (GH) concentration were measured at 35th day after irradiation. The results showed that irradiation of mouse brain with 2 Gy of C-12(6+) ion or Co-60 gamma-ray significantly diminished mouse body weight and level of serum GH. The relative biological effectiveness values of a 2 Gy dose of C-12(6+) ion calculated with respect to Co-60 gamma-ray were 1.47 and 1.34 for body weight and serum GH concentration, respectively. Pre-exposure with a low-dose (0.05 Gy) of C-12(6+) ion or Co-60 gamma-ray significantly alleviated reductions of mouse body weight and level of serum GH induced by a subsequent high-dose (2 Gy) irradiation. The data suggested that low-dose ionizing irradiation can induce adaptive hormetic responses to the harmful effects of pituitary by subsequent high-dose exposure.