A randomized trial of three renal transplant induction antibodies: early comparison of tacrolimus, mycophenolate mofetil, and steroid dosing, and newer immune-monitoring

BACKGROUND: New trends in immunosuppression in clinical transplantation include the use of antibody induction agents in protocols that emphasize reduction or avoidance of steroids and calcineurin inhibitors. METHODS: In a randomized trial using three different antibody induction agents in 90 first renal transplant recipients from cadaver donors, group A received Thymoglobulin, group B received Alemtuzumab, and group C received Daclizumab. Maintenance immunosuppression included tacrolimus and mycophenolate in all three arms, and methylprednisolone in groups A and C only (standard clinical institutional practice). The targeted trough level of tacrolimus was between 8 and 10 ng/mL for groups A and C, respectively, with a targeted mycophenolate dose of 1 g twice daily. However, in group B, the target tacrolimus trough level was 4 to 7 ng/mL to reduce long-term nephrotoxicity, with 500 mg twice-daily doses of mycophenolate, without steroid maintenance. RESULTS: In this 15-month median postoperative interval report, there were no notable differences in demographics and patient and graft survivals. Acute rejection rates at 1 year were equivalent, that is, 5 of 30 in all three groups (16.6%). In group B, there was slightly lower renal function at 1 month, but no difference at 1 year. There was also significantly more leukopenia, but a greater percentage of T-regulatory cells and number of Fox-P3 mRNA copies by flow cytometry and semiquantitative polymerase chain reaction analysis, respectively, in group B. CONCLUSIONS: This preliminary analysis indicates that 80% of the patients in group B remained steroid-free 1 year postoperatively, with lower tacrolimus trough levels and no difference in other adverse events.     

Fluoroquinolone resistance in penicillin-resistant Streptococcus pneumoniae clones, Spain

Among 2,882 Streptococcus pneumoniae sent to the Spanish Reference Laboratory during 2002, 75 (2.6%) were ciprofloxacin-resistant. Resistance was associated with older patients (3.9% in adults and 7.2% in patients > or =65 years of age), with isolation from noninvasive sites (4.3% vs. 1.0%), and with penicillin and macrolide resistance. Among 14 low-level resistant (MIC 4-8 microg/mL) strains, 1 had a fluoroquinolone efflux phenotype, and 13 showed single ParC changes. The 61 high-level ciprofloxacin-resistant (MIC > or =16 microg/mL) strains showed either two or three changes at ParC, ParE, and GyrA. Resistance was acquired either by point mutation (70 strains) or by recombination with viridans streptococci (4 strains) at the topoisomerase II genes. Although 36 pulsed-field gel electrophoresis patterns were observed, 5 international multiresistant clones (Spain23F-1, Spain6B-2, Spain9V-3, Spain14-5 and Sweden15A-25) accounted for 35 (46.7%) of the ciprofloxacin-resistant strains. Continuous surveillance is needed to prevent the dissemination of these clones.     

Murine typhus with renal involvement in Canary Islands, Spain

Murine typhus and "murine-typhus-like" disease are reemerging infectious diseases. In Canary Islands (Spain), a rather distinct clinical pattern characterized by higher incidence of complications, especially renal damage (including acute failure and urinalysis abnormalities), is apparent and highly suggestive. It could be related to different strains of Rickettsia typhi or other cross-reactive species.     

Ruthenium (II) nitrofurylsemicarbazone complexes: new DNA binding agents

Complexes of the type [Ru(II)Cl(2)(DMSO)(2)L], where L are 5-nitrofurylsemicarbazone derivatives, were prepared in an effort to combine the potential anti-tumor activity of the metal and the free ligands. The new complexes are excellent DNA binding agents for calf thymus DNA. So, their in vitro anti-tumor activity was tested in cellular models and the complexes were found to be non-cytotoxic on the tumor cell lines assayed, neither in aerobic conditions nor in the bio-reductive assay performed. Redox behavior, lipophilicity and stability were studied in order to explain the lack of cellular cytotoxic effects. The complexes resulted 10-100 times more hydrophilic than the parent ligands thus the bio-activity of these compounds would be compromised by their inadequate lipophilic properties.     

A comparison of current neuroblastoma chemotherapeutics

Neuroblastoma is the most common solid tumour in childhood. Modern management includes a biopsy to perform genetic studies. Based on clinical data and Myc-N amplification (MNA), patients are divided in three prognostic groups: the low-risk (Stage 1, 2, 4S without MNA) has an event-free survival (EFS) of > 90% with surgery alone; the intermediate-risk (Stage 3, > 1 year of age, without MNA and Stage 3 and 4 infants without MNA) has an EFS of approximately 80% with mild chemotherapy and surgery; the high-risk group includes Stage 4, > 1 year of age and any stage and age with MNA. These patients are treated with chemotherapy, surgery, megatherapy, irradiation and 13-cis-retinoic acid. With this complex therapy, a 5-year EFS of 30-50% can be obtained.     

Cytomegalovirus prophylaxis with valganciclovir in kidney, pancreas-kidney, and pancreas transplantation

Cytomegalovirus, seen in more than 50% of solid organ transplant recipients, is responsible for numerous direct and indirect consequences, including infection with opportunistic pathogens and allograft rejection. Prophylaxis with intravenous ganciclovir has been the gold standard for prevention; however, intravenous treatment is expensive and carries risks of its own. Oral ganciclovir, to be effective, must be given in large, divided doses. Valganciclovir, the valine ester of ganciclovir, at 900 mg/day, provides oral bioavailability equivalent to that of intravenous ganciclovir and superior to that of oral ganciclovir. This retrospective study assessed the efficacy of 3 months prophylaxis with valganciclovir in kidney, simultaneous pancreas-kidney, and pancreas transplantation. Of 161 patients, all of whom received potent immunosuppressive regimens and were followed for a mean of 440 days, only one developed cytomegalovirus infection, at 120 days post-transplantation. Two patients died, and two others lost their grafts. There were seven incidents of acute rejection. Only seven patients discontinued treatment early, five because of leukopenia. These results suggest that prophylaxis with 900 mg/day of valganciclovir for at least 3 months safely and effectively prevents cytomegalovirus infection in kidney, simultaneous pancreas-kidney and pancreas transplant recipients on highly potent immunosuppression.     

Oxidative stress status in an institutionalised elderly group after the intake of a phenolic-rich dessert

The elderly population undergoes a series of physiological and sociological changes common to old age with a high probability of suffering degenerative illness and malnutrition. A dessert rich in phenolic compounds has been designed by using concentrated juices of grape, cherry, blackberry, blackcurrant and raspberry with the aim of it being used as a complementary food in adulthood. In the present study, we investigated the effect of the intake of this dessert (a jar of 200 g daily for a period of 2 weeks), with an antioxidant activity equivalent to ten servings of fruits and vegetables, on several markers of oxidative and antioxidant status in DNA and plasma in a group of elderly individuals. Non-smoking institutionalised elderly subjects were recruited from a pool of volunteers in an old-age home in Murcia (Spain). Twenty-two subjects (six men and sixteen women) participated in the study. The study was designed as a randomised intervention trial with a period of 2 weeks. At days 1 and 15, blood samples were collected to analyse total antioxidant capacity, biochemical parameters, antioxidant vitamins, LDL peroxidation, and DNA damage in peripheral blood lymphocytes. The conclusion of the present study is that a 2-week intervention with our dessert enriched with natural polyphenol compounds in elderly individuals does not give enough time to find changes in the antioxidant and oxidative status. Also, the view that the marked antioxidant ability of polyphenols in vitro does not translate to analogous effects in vivo was confirmed. Moreover, a highly oxidative stress status during ageing was confirmed, together with the need to perform follow-up nutritional studies to improve this situation.     

1, 2, 4-Triazine N-oxide derivatives: studies as potential hypoxic cytotoxins. Part II

New 1, 2, 4-Triazine N-oxide and N, N'-dioxide derivatives were synthesized in order to obtain compounds as selective hypoxic cell cytotoxins. The starting heterocycles have been prepared using a standard microwave oven in a clean and good-yielded process. The reactivity of methyl-1, 2, 4-triazine N(4)-oxide and N(1), N(4)-dioxide with different electrophilic agents has been studied. The desired products were obtained only when iminium electrophiles were employed. The regioselectivity of this process has been studied by means of experimental and theoretical (at ab initio level) procedures. Theoretically was expected that the most stable intermediates where the benzylic-like anion from position 5. A fact which agreed with the experimental observed regioselectivity. The new compounds were tested for their cytotoxicity in oxia and hypoxia. Some of them proved to be less active in hypoxic conditions than tirapazamine, 3-amino-benzo[1, 2-e]1, 2, 4-triazine N(1), N(4)-dioxide. Derivative 19, 6-methyl-5-[2-(5-nitrothienyl)ethenyl)-1, 2, 4-triazine N(4)-oxide, was the most cytotoxic compound, but it was non-selective.     

Design and evaluation of an exhaled breath sampler for biological monitoring of organic solvents.

We designed a breath sampler based on a tube which collects the final portion of exhaled air. The passage of successive fractions through a layer of activated charcoal is controlled by a three-way valve. This system was validated in a controlled atmosphere of n-hexane and toluene at four concentrations between 12 and 110 mg m-3 and 12 and 115 mg m-3, respectively. Uptake volumes of 0.1, 0.2 and 0.31 were tested at relative humidities of 46% and 98%. There were no significant differences in the recoveries obtained under any of the conditions tested. We confirmed the reproducibility between successive samples in volunteers and exposed workers, and found no significant differences between the different sampling conditions studied. Our system enriches the sample in an adsorbent cartridge by collecting successive fractions of end-exhaled breath from one or more exhalations until the amount required by the analytical method has been accumulated. It is portable, economical and highly operative in the field.