69 research outputs found
Benchmarking of DFT methods using experimental free energies and volumes of activation for the cycloaddition of alkynes to cuboidal Mo3S4 clusters
Here, the kinetics of the concerted [3 + 2] cycloaddition reaction between the [Mo3(μ3‐S)(μ‐S)3Cl3(dmen)3]+ (dmen = N,N′‐dimethyl‐ethylenediamine) ([1]+) cluster and various alkynes to form dithiolene derivatives is thoroughly studied, with measurements at different temperatures and pressures allowing the determination of the free energies and volumes of activation. These parameters, together with the available single‐crystal X‐ray diffraction structures, are used to test a number of commonly used density functional theory (DFT) methods from Jacob's ladder, as well as the effects associated with the size of the basis sets, the way in which solvent effects are taken into account, or the inclusion of dispersion effects. Overall, a protocol that leads to average deviations between experimental and computed ΔV and ΔG values similar to the uncertainty of the experimental measurements is obtained
Impact of renal retransplantation on graft and recipient survival
The aim of this study was to evaluate the influence of
retransplantation in graft and recipient survival. METHODS: We carried out a
retrospective study in 419 renal transplants and studied the influence of
retransplantation in graft and patient survival. A homogeneity study was
performed between the two groups with a Student`s T and a chi-square tests. Graft
survival analysis was performed with Kaplan-Meyer and log rank tests. RESULTS: Of
419 transplants, 370 (88.3%) were first transplantations, 45 (10.7%) second
transplantations and 4(1%) third ones. Mean follow-up of the whole group was 72.5
months (+/-54.1 SD). There were no differences in follow-up between groups (Mean
Follow-up 73.1 months +/-54.4 SD in first transplantations vs. 61.6 months
+/-51.2 SD in repeat transplantation. p >0.05). The actuarial graft survival
showed no differences between patients with first transplantation and those with
a repeat one. [3 and 5 year SV of 89% (95% CI: 87-91%) and 84%(95% CI: 82-86%) Vs
88% (95% CI; 83-93%) and 85% (95% CI:i; 80-90%) respectively]. After adjusting
for all the heterogeneity variables we still did not find differences on graft
survival. The actuarial recipient survival showed no differences between patients
with first transplantation and those with a repeat one. [3 and 5 year SV of 98%
and 96% Vs.97%]. CONCLUSIONS: There are no differences of graft and recipient
survival between patients with a first transplantation and those with a repeat
one
Priapismo maligno: un caso manejado de forma conservadora
Priapism is an urological emergency which requires investigation, especially to differentiate between ischemic and non-ischemic priapism. Initial management is carried out through aspiration and gasometry of blood from the corpus cavernosum. We report the case of a 69-year-old patient with urothelium carcinoma of the bladder T2 G3 and metastasis in urethra/corpus cavernosum who requested an emergency consultation because of edema and a penile erection lasting several days. Due to the poor prognosis and the imaging test, a conservative management was carried out
Perforación duodenal espontánea en paciente intervenido de prostatectomía radical
Radical prostatectomy is a well known treatment for prostate cancer, with a low incidence of early postoperative complications. Our case is a 54 year old patient diagnosed with prostate adenocarcinoma, Gleason score 3+3=6 with 8 ng/ml of PSA, treated by retropubic prostatectomy, who suffered spontaneous perforation of the duodenum. We chose a conservative management, resolved in 30 days. When dealing with a surgical patient all kinds of complications must be taken into account by performing the minimum tests that will enable a sure diagnosis to be achieved. The usual treatment is surgery or conservative management, depending on the case and the patient
Imatinib inhibits proliferation of Ewing tumor cells mediated by the stem cell factor/KIT receptor pathway, and sensitizes cells to vincristine and doxorubicin-induced apoptosis
Purpose and Experimental Design: The stem cell factor/
KIT receptor loop may represent a novel target for molecular-
based therapies of Ewing tumor. We analyzed the in
vitro impact of KIT blockade by imatinib in Ewing tumor
cell lines.
Results: KIT expression was detected in 4 of 4 Ewing
tumor cell lines and in 49 of 110 patient samples (44.5%) by
immunohistochemistry and/or Western blot analysis. KIT
expression was stronger in Ewing tumors showing EWSFLI1
nontype 1 fusions. Despite absence of c-kit mutations,
constitutive and ligand-inducible phosphorylation of KIT
was found in all tumor cell lines, indicating an active receptor.
Treatment with KIT tyrosine kinase inhibitor imatinib
(0.5–20 M) induced down-regulation of KIT phosphorylation
and dose response inhibition of cell proliferation (IC50,
12–15 M). However, imatinib administered alone at doses
close to IC50 for growth inhibition (10 M) did not induce a
significant increase in apoptosis. We then analyzed if blockade
of KIT loop through imatinib (10 M) was able to
increase the antitumor in vitro effect of doxorubicin (DXR)and vincristine (VCR), drugs usually used in Ewing tumor
treatment. Addition of imatinib decreased in 15–20 and
15–36% of the proliferative rate of Ewing tumor cells exposed
to DXR and VCR, respectively, and increased in 15
and 30% of the apoptotic rate of Ewing tumor cells exposed
to the same drugs.
Conclusions: Inhibition of Ewing tumor cell proliferation
by imatinib is mediated through blockade of KIT receptor
signaling. Inhibition of KIT increases sensitivity of
these cells to DXR and VCR. This study supports a potential
role for imatinib in the treatment of Ewing tumor
Randomized crossover pharmacokinetic evaluation of subcutaneous versus intravenous granisetron in cancer patients treated with platinum-based chemotherapy
BACKGROUND:
5-HT3-receptor antagonists are one of the mainstays of antiemetic treatment, and they are administered either i.v. or orally. Nevertheless, sometimes neither administration route is feasible, such as in patients unable to admit oral intake managed in an outpatient setting. Our objective was to evaluate the bioavailability of s.c. granisetron.
PATIENTS AND METHODS:
Patients receiving platinum-based chemotherapy were randomized to receive 3 mg of granisetron either s.c. or i.v. in a crossover manner during two cycles. Blood and urine samples were collected after each cycle. Pharmacokinetic parameters observed with each administration route were compared by analysis of variance.
RESULTS:
From May to November 2005, 31 patients were included and 25 were evaluable. Subcutaneous granisetron resulted in a 27% higher area under the concentration-time curve for 0-12 hours (AUC(0-12h)) and higher levels at 12 hours, with similar values for AUC(0-24h). The maximum concentration was lower with the s.c. than with the i.v. route and was observed 30 minutes following s.c. administration.
CONCLUSION:
Granisetron administered s.c. achieves complete bioavailability. This is the first study that shows that s.c. granisetron might be a valid alternative to i.v. delivery. Further trials to confirm clinical equivalence are warranted. This new route of administration might be especially relevant for outpatient management of emesis in cancer patients
Case of emphysematous pyelonephritis in kidney allograft: Conservative treatment
Emphysematous pyelonephritis is an acute necrotizing infection with gas in the kidney and perinephric space that carries a bad prognosis. Apart from its predisposing clinical entities, diabetes mellitus and immune-incompetence are quite common in patients with this infection. We report a case of a 53-year-old kidney transplant recipient diabetic male, suffering from recurrent fever, abdominal pain and nausea episodes. Immediate broad-spectrum antibiotics were administered and percutaneous drainage was performed after the diagnosis. The bacteria involved were Stahpylococcus epidermidis and Escherichia coli. After 4 weeks of antibiotic treatment and abscesses drainage, the case was resolved. Consecutives urine cultures and ultrasonographies confirm the complete resolution of the disease. We discuss the predisposing factors, clinical presentation and management
Carcinoma microcítico de pulmón
El cáncer microcítico de pulmón es uno de los tumores sólidos más
agresivos, por su rápido crecimiento y por su tendencia a metastatizar
desde fases tempranas. Sin embargo, también es uno de los tumores
más sensibles a los tratamientos de quimioterapia y radioterapia, con
los cuales algunos pacientes con enfermedad limitada pueden sobre-
vivir a largo plazo. Estas características han hecho de este tumor un
modelo clínico sobre el cual se han probado múltiples estrategias de
tratamiento, incluyendo tratamientos concomitantes con quimioterapia
y radioterapia, esquemas de quimioterapia alternante o de altas dosis
con soporte hematológico o la utilización de radioterapia holocraneal
profi
láctica. Además en los últimos años el cáncer microcítico de pulmón
también se ha empleado como plataforma de desarrollo de tratamientos
dirigidos contra dianas específi
cas o de inmunoterapia. INGLÉS: Small cell lung cancer is one of the most aggressive solid tumors because of its rapid growth and early tendency to spread to distant organs. Nonetheless, it is also one of the most sensitive tumors to chemotherapy and radiotherapy, which can give patients with limited disease a chance to become long-term survivors. These characteristics have made this tumor a clinical model to explore various treatment strategies, including concomitant chemotherapy and radiotherapy, alternant chemotherapy, high-dose chemotherapy with hematologic support, or use of whole-brain prophylactic radiotherapy. In addition, in recent years, small cell lung cancer has been used as a platform to develop some new targeted therapy agents or immunotherapeutic approaches
Randomized pharmacokinetic study comparing subcutaneous and intravenous palonosetron in cancer patients treated with platinum based chemotherapy
BACKGROUND:
Palonosetron is a potent second generation 5- hydroxytryptamine-3 selective antagonist which can be administered by either intravenous (IV) or oral routes, but subcutaneous (SC) administration of palonosetron has never been studied, even though it could have useful clinical applications. In this study, we evaluate the bioavailability of SC palonosetron.
PATIENTS AND METHODS:
Patients treated with platinum-based chemotherapy were randomized to receive SC or IV palonosetron, followed by the alternative route in a crossover manner, during the first two cycles of chemotherapy. Blood samples were collected at baseline and 10, 15, 30, 45, 60, 90 minutes and 2, 3, 4, 6, 8, 12 and 24 h after palonosetron administration. Urine was collected during 12 hours following palonosetron. We compared pharmacokinetic parameters including AUC0-24h, t1/2, and Cmax observed with each route of administration by analysis of variance (ANOVA).
RESULTS:
From October 2009 to July 2010, 25 evaluable patients were included. AUC0-24h for IV and SC palonosetron were respectively 14.1 and 12.7 ng × h/ml (p = 0.160). Bioavalability of SC palonosetron was 118% (95% IC: 69-168). Cmax was lower with SC than with IV route and was reached 15 minutes following SC administration.
CONCLUSIONS:
Palonosetron bioavailability was similar when administered by either SC or IV route. This new route of administration might be specially useful for outpatient management of emesis and for administration of oral chemotherapy
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