Current status of DNA vaccines and their route of administration

This review is aimed at bringing DNA vaccines into perspective with regard to other currently available vaccines and vaccine strategies in development. It is concluded that, encouragingly, DNA vaccines still offer significant potential, with more recent developments such as improved vectors and delivery systems likely to have an important impact; and in addition, the potential safety of DNA as a vaccine is becoming increasingly apparent. Strategies for oral delivery may be suitable for some applications, with all nonparenteral routes likely to require suitable carriers or adjuvants. The diversity of experimental data attests to the increasing interest in vaccination for the treatment and prevention of disease.     

New PET imaging agent for the serotonin transporter: [(18)F]ACF (2-[(2-amino-4-chloro-5-fluorophenyl)thio]-N,N-dimethyl-benzenmethanamine)

A new F-18-labeled phenylthiophenyl derivative specific for imaging of serotonin transporters (SERT) in the brain by positron emission tomography (PET) is described. Fluorinated phenylthiophenyl derivative, ACF, 2-[(2-amino-4-chloro-5-fluorophenyl)thio]-N,N-dimethyl-benzenmethanamine, was prepared by first coupling 2,5-dichloro-4-nitroaniline with 2-mercapto-N,N-dimethylbenzamide. The amino group of the coupled adduct was converted to a fluoro group through a Schiemann reaction. Subsequently, a one pot reduction of both nitro and amide groups by BH(3)-tetrahydrofuran yielded the nonradioactive ACF (yield 25%). In vitro binding assays using cell membrane homogenates of LLC cells expressing SERT, dopamine transporters (DAT), or norepinephrine transporters (NET) showed excellent binding affinity and selectivity for SERT (K(i) = 0.05, 3020, and 650 nM for SERT, DAT, and NET, respectively). For preparation of the [(18)F]ACF, the NH(2) group of the initially coupled adduct was converted to the trimethylammonium salt, which was replaced by [(18)F]fluoride in the presence of Kryptofix 222 and potassium carbonate. The final product, [(18)F]ACF, was obtained after a borane and stannous chloride reduction reaction. The combined two step reaction gave a radiochemical yield of 10-15% (EOB) and a radiochemical purity of >99%. Synthesis of the novel PET tracer, [(18)F]ACF, as a probe for binding to SERT in the brain was successfully achieved. The new tracer [(18)F]ACF showed excellent brain penetration and selective localization after an iv injection in rats (brain uptake at 2, 30, 60, 120, and 240 min was 3.27, 1.28, 0.69, 0.21, and 0.06% dose/organ, respectively). The hypothalamus/cerebellum ratio at 60 min post iv injection was 3.55. This specific localization in the hypothalamus was blocked by pretreatment of (+)McN5652. This novel ligand is a potential PET tracer for in vivo evaluation of SERT in the brain.     

The development of polyplex-based DNA vaccines

DNA immunisation provides new possibilities for the development of effective vaccines for the prophylaxis and treatment of several diseases and infections. Application of such vaccines for mucosal (secretory or local) vaccination provides a powerful means to gain protection against local infection that enters and colonises the mucosa whilst inducing concomitant systemic immunity. This review examines the current and potential applications for polyplex-based mucosal vaccination strategies, notably those aimed at gaining expression of transgenes within dendritic cells, in order to gain both T-helper and cytotoxic T cell (CTL) responses. Emphasis is given to the development of polyplex-based oral vaccines in conjunction with microparticulate systems.     

Primary renal lymphoma and hypercalcemia in a child

Renal lymphoma is most frequently due to secondary lymphomatous infiltration of the kidneys in advanced stage disease. Rarely, are the kidneys the tissue of origin. We describe a 15-year-old male presenting with hypercalcemia and acute renal failure, due to a bilateral "primary B-cell lymphoma of the kidneys". The diagnosis was established by percutaneous needle biopsy of the right kidney. His disease was metastatic to multiple bones. His presenting features radiological findings and biopsy results are unique. We report his case, and review the pediatric literature.     

Origin of a central nervous system lymphoid neoplasm in an immunocompromised host with acute lymphoblastic leukemia

We describe a case of relapsed pediatric pre-B acute lymphoblastic leukemia (ALL) with a simultaneous presentation of an intracerebral lymphoid mass. Cytogenetic, immunophenotypic and molecular analysis (immunoglobulin heavy chain and T-cell receptor gene rearrangements) revealed that the brain neoplasm was distinct from the relapsed leukemia. We discuss the etiology of this extremely rare event, and raise issues about the clonality of lymphoid neoplasms and the behavior of hematopoietic cells within the central nervous system (CNS).     

What is the impact of cytoreductive nephrectomy in patients with metastatic renal cell carcinoma?

The impact of cytoreductive nephrectomy in patients with metastatic renal cell carcinoma (RCC) is discussed herein with consideration of prolonged survival and quality of life. A nephrectomy can be indicated in a patient with good performance status and pulmonary metastases when adjuvant immunotherapy is an option. In contrast, in a patient with poor performance status and/or metastases including multiple organs, a nephrectomy is not indicated. To relieve symptoms, options other than nephrectomy should be considered.     

Imbalance Between Apostain Expression and Proliferative Index can Predict Survival in Primary Glioblastoma

Summary. Summary.   Background: Cell proliferation and cell death are opposing processes in tumour growth, with tumour progression reflecting the balance between proliferating and apoptotic cells. The purpose of the present study is to verify the hypothesis that an imbalance between apoptosis and proliferation can predict survival in patients with primary glioblastoma.   Methods: After the immunohistochemical study of Apostain and MIB-1 expression, the index of apoptosis (AI), the index of proliferation (PI), and the ratio AI/PI was recorded for each tumour specimen, in a series of 32 primary glioblastomas. Studies of correlation between AI and PI, between AI and survival, between PI and survival, and between the ratio AI/PI and survival, were performed using the Spearman rank correlation test. Furthermore, a comparative study of survival was performed for subgroups of patients with ratio AI/PI greater or lesser than 1, using the log rank test.   Findings: In the present series, values of AI and PI showed a wide distribution, with a mean±SD of 8.16±7.2, and of 12.69±21.1, respectively. The values for the ratio AI/PI ranged between 0.01 and 6.03 (mean±SD: 1.44±1.60). Statistical study failed to obtain correlation between AI and PI. Survival of patients not correlated with AI neither with PI. The ratio between AI and PI did not correlate with survival either. Nevertheless, when survival for the subgroups of patients showing a ratio AI/PI greater or lesser than 1 was compared, a significant difference was found (p: 0.02). Survival ranged between 50 and 81 weeks (mean of 58.5±11.05 weeks) for the 12 cases showing a ratio AI/PI greater than 1, and it ranged between 8 and 85 weeks (mean: 38.20±25.37 weeks) for the 20 cases showing a ratio AI/PI lesser than 1.   Interpretation: Our present results suggest that a clear imbalance between cell proliferation and apoptosis can predict outcome in patients operated on for a primary glioblastoma.     

Preemptive diclofenac reduces morphine use after remifentanil-based anaesthesia for tonsillectomy

BACKGROUND: We investigated the effect of preincisional rectal diclofenac on pain scores and postoperative morphine requirements of children undergoing tonsillectomy after remifentanil-propofol anaesthesia in a randomized clinical trial. METHODS: Induction and maintenance of anaesthesia were with remifentanil and propofol. Forty children were randomly assigned into two groups before incision. The diclofenac group (n=20) received diclofenac suppositories (approximately 1 mg x kg(-1)) and the control group (n=20) received no treatment. Following discontinuation of remifentanil, patient-controlled analgesia (PCA) with morphine (a loading dose 50 micro g x kg(-1), a background infusion 4 micro g x kg(-1) x h(-1) and a demand dose 20 micro g x kg(-1) with 5-min intervals) was started. We assessed pain score [verbal analogue scales (VAS), 0-10] and sedation level at 5-min intervals and recorded the total morphine consumption of the first hour in the PACU. Patients were discharged to the ward with a new PCA morphine programme (a demand dose 20 micro g.kg-1 with a lockout time of 30 min, for 4 h), and total morphine consumption was recorded. RESULTS: The mean VAS score of the diclofenac group was significantly lower than the control group on arrival in the PACU (2.85 +/- 0.77, 7.60 +/- 0.83, respectively, P < 0.01) and it remained significantly lower in the PACU stay of the children. The mean total morphine consumption of the diclofenac group was less than the control group in the PACU (130.33 +/- 11.26 and 169.92 +/- 9.22, respectively, P=0.012) and the ward (50.80 +/- 11.38 and 87.77 +/- 10.55, respectively, P=0.021). CONCLUSIONS: Preemptive diclofenac given rectally reduced pain intensity and morphine requirements of children anaesthetized with remifentanil for tonsillectomy.