[Risk assessment of irradiation of tissue with metal implants].

Authors examine the influence of metal implants on the distribution of ionizing radiation in tissue. In vivo measurements in a patient are seldom possible. The risk can be assessed with sufficient accuracy on the basis of various experimental dosimetric methods, histological changes in the irradiated volume and the tolerance to the physical stress, published in the available literature.

Bone marrow micrometastases in patients with stage I-II localised prostate cancer.

Prostate cancer commonly metastasises to the bones. Detection of bone marrow micrometastases (BMM) may give important information that helps define treatment strategies. This study was undertaken to analyse BMM in early prostate cancer patients and to determine the accuracy of immunohistochemical (IHC) and morphological methods in detecting cancerous cells.

Population pharmacokinetics of everolimus in de novo renal transplant patients: impact of ethnicity and comedications.

Background: Everolimus is a macrolide immunosuppressant intended for acute rejection prophylaxis after kidney transplantation.

Methods: A total of 5260 blood samples were collected in the context of two randomized, double-blind, multicenter efficacy trials in 673 patients over a 6-month period after kidney transplantation. The data were evaluated in a nonlinear mixed-effects model.

The search for novel adjuvants for early life vaccinations: can "danger" motifs show us the way?

Potent but safe adjuvants are required to circumvent the many limitations of the newborn immune system to induce rapidly effective and long lasting immunity to subunit vaccines. By the use of pattern recognition receptors, antigen-presenting cells (APC) can very efficiently be activated by "danger" motifs expressed by various pathogens. APC activated by "danger" motifs, such as immunostimulatory sequences of bacterial DNA, can not only transmit the activation signal from the innate immunity to the adaptive compartment, but also shape the antigen-specific immune responses.

Impaired T cell proliferation, increased soluble death-inducing receptors and activation-induced T cell death in patients undergoing haemodialysis.

Haemodialysis is a widespread option for end-stage renal disease (ESRD). Long-term success of dialysis is, however, limited by a high rate of serious bacterial and viral infections. We compared T cell functions in ESRD patients undergoing haemodialysis (n = 20), or were not dialysed and received conventional medical treatment (n = 20).

[Radical radiotherapy of prostate carcinoma].

Radiotherapy is an effective treatment modality of prostate carcinoma. Considering the limited radiosensitivity of this tumour it is necessary to use relatively high doses of radiation. Modern technology offers the possibility to perform high-dose radiotherapy with acceptable toxicity.

Induction of adult-like antibody, Th1, and CTL responses to measles hemagglutinin by early life murine immunization with an attenuated vaccinia-derived NYVAC(K1L) viral vector.

Although initially developed in adult animals, novel viral vectors expressing recombinant measles antigens must eventually prove their success in the early life setting, where the efficacy of the currently used live-attenuated measles virus vaccine is limited. The immunological requirements for vaccine candidates include the generation of protective antibody responses as well as the induction of Th1 and cytotoxic T lymphocytes (CTL) responses, which is challenging in the neonatal setting. Here, we report that young BALB/c mice immunized with a single dose of a vaccinia-based NYVAC(K1L) vector generate adult-like antihemagglutinin (HA) antibody responses as well as adult-like Th1 and CTL responses.

A population pharmacokinetic screen to identify demographic-clinical covariates of basiliximab in liver transplantation.

Background: Basiliximab is a high-affinity interleukin-2 receptor (CD25) chimeric monoclonal antibody used for immunoprophylaxis in organ transplantation. It was assessed in a randomized, double-blind, placebo-controlled efficacy trial in de novo liver allograft recipients who received 40 mg of basiliximab (20 mg on days 0 and 4) in addition to baseline immunosuppression with cyclosporine (INN, ciclosporin) microemulsion and corticosteroids.

Methods: Serial blood samples (8.

Relation of prenephrectomy CD profiles and serum cytokines to the disease outcome and response to IFN-alpha/IL-2 therapy in renal cell carcinoma patients.

Immune parameters, including cytokine levels and CD profiles were determined in 78 renal cell carcinoma patients (RCC) prior to nephrectomy. The values were correlated with the outcome of disease and response to cytokine-based treatment during a 3-year follow-up. Significantly lower frequency of progressions and higher proportion of survivors were recorded in 24 treated patients compared to 43 untreated ones (22.

Differential influence of azathioprine and mycophenolate mofetil on the disposition of basiliximab in renal transplant patients.

Pharmacokinetic sampling was performed in two multicenter trials in which basiliximab (anti-CD25 monoclonal antibody) was administered with triple immunosuppression consisting of cyclosporine microemulsion, corticosteroids, and either azathioprine or mycophenolate mofetil. Blood samples were collected over 12 wk post-transplant from 31 azathioprine-treated and 66 mycophenolate mofetil-treated patients. Empirical Bayes estimates of each patient's basiliximab disposition parameters were derived and the duration of CD25 saturation was estimated as the time over which serum concentrations exceeded 0.

[Papillomaviruses and human tumors].

The report summarizes the main results obtained in the course of our research project. The results of immunological and epidemiological studies provide further proofs that human papillomaviruses (HPV) are the etiological agents in cervical neoplasia. In addition, they raise hopes that immunological methods may be utilized in diagnostics of cervical cancer and for monitoring the clinical course of this disease in the near future.

RAD in stable lung and heart/lung transplant recipients: safety, tolerability, pharmacokinetics, and impact of cystic fibrosis.

Background: RAD is a novel macrolide with potent immunosuppressive and antiproliferative activities. This study characterizes the safety, tolerability, and pharmacokinetics of two different single oral doses of RAD in stable lung and heart/lung transplant recipients with and without cystic fibrosis (CF).

Methods: This was a Phase I, multicenter, randomized, double-blind, two-period, two-sequence, crossover study.

Delayed and deficient establishment of the long-term bone marrow plasma cell pool during early life.

Early life antibody responses are characterized by a rapid decline, such that antigen-specific IgG antibodies decline to baseline levels within months following infant immunization. This generic observation remains unexplained. Here, we have analyzed the induction and organ-localization of antigen-specific IgG antibody-secreting cells (ASC) following immunization of 1-week-old or adult BALB/c mice with tetanus toxoid (TT), a T-dependent antigen.

Metastatic MHC class I-negative mouse cells derived by transformation with human papillomavirus type 16.

In the endeavour to develop a model for studying gene therapy of cancers associated with human papillomaviruses (HPVs), mouse cells were transformed with the HPV type 16 (HPV16) and activated H-ras oncogenes. This was done by cotransfection of plasmid p16HHMo, carrying the HPV16 E6/E7 oncogenes, and plasmid pEJ6.6, carrying the gene coding for human H-ras oncoprotein activated by the G12V mutation, into secondary C57BL/6 mouse kidney cells.

Pharmacokinetics and tolerability of 40-0-[2-hydroxyethyl]rapamycin in de novo liver transplant recipients.

Background: 40-0-[2-Hydroxyethyl]rapamycin (RAD), a novel macrolide with potent immunosuppressive and antiproliferative activities, prevents rejection in animal allotransplantation models. This phase I trial assessed the effects of bile diversion, administration route, and time after transplant on RAD pharmacokinetics after single-dose administration in de novo liver allograft recipients. The influence of RAD on cyclosporine (CsA) pharmacokinetics and the safety of RAD were also evaluated.

Longitudinal assessment of everolimus in de novo renal transplant recipients over the first post-transplant year: pharmacokinetics, exposure-response relationships, and influence on cyclosporine.

Objective: Our objective was to characterize the steady-state pharmacokinetics of everolimus and cyclosporine (INN, ciclosporin) when coadministered in de novo kidney allograft recipients during the first year after transplantation.

Method: This study was a multicenter randomized double-blind study of 101 patients who were randomly assigned 1:1:1 to receive everolimus tablets at doses of 0.5 mg, 1 mg, or 2 mg twice daily with cyclosporine and prednisone.

Adjuvant effects of CpG oligodeoxynucleotides on responses against T-independent type 2 antigens.

Oligodeoxynucleotides containing CpG motifs (CpG-ODN) are potent in vitro B-cell activators and they have been successfully used to increase in vivo antibody responses to T-dependent peptide and protein antigens. In contrast, the use of CpG-ODN to enhance in vivo antibody responses to various T-independent type 2 (TI-2) antigens has recently generated contradictory results. In this study, we compared the CpG-ODN stimulatory effect on antibody responses of adult and young BALB/c mice to trinitrophenylaminoethyl-carboxymethyl (TNP) -Ficoll and to polysaccharides (PS) from several distinct serotypes of Streptococcus pneumoniae (SPn).

Rapidly progressive glomerulonephritis and carcinoma of the hypopharynx.

We report on a 50-year-old man with rapidly progressive glomerulonephritis and carcinoma of the hypopharynx. Because cancer treatment was followed by remission of proteinuria and complete restoration of renal function, a causal relationship between tumor and glomerular injury seems possible.

Rare somatic p53 mutation identified in breast cancer: a case report.

Most p53 mutations occur in the central part of the p53 gene that codes for the DNA-binding domain. Missense mutations are prevalent. However, 10-25% of all mutations occur outside exons 5-8 and include a prevalence of frameshift, nonsense and splice site mutations.

Listeria monocytogenes modulates macrophage cytokine responses through STAT serine phosphorylation and the induction of suppressor of cytokine signaling 3.

Macrophage activation as part of natural resistance to infection is caused by stimulation with IFN-gamma and by the invading microorganisms or microbial products. Infection of macrophages with the Gram-positive bacterium Listeria monocytogenes for short periods before activation with IFN-gamma increased the phosphorylation of transcription factor STAT1 at S727 and thereby the expression of IFN-gamma-induced genes. By contrast, persistent infection with viable bacteria or treatment with heat-killed Listeria diminished IFN-gamma-stimulated transcription and the phosphorylation of STAT1 at Y701.

Twelve months of lamivudine treatment for chronic hepatitis B virus infection in renal transplant recipients.

Background: Chronic hepatitis B virus (HBV) infection increases morbidity and mortality in renal transplant recipients (RTR). Lamivudine has shown promising results in patients with chronic hepatitis B, but experience with its use in RTR is limited.

Methods: In a prospective, open labeled, uncontrolled trial, 19 HBsAg(+) RTR were treated with lamivudine for 12 months.

[Serum cobalt and serum chromium level in 2 patients with chronic renal failure after total hip prosthesis implantation with metal-metal gliding contact].

Purpose: The influence of chronic renal failure on serum cobalt and serum chromium in two patients with metal-on-metal bearing (Metasul) and cementless total hip arthroplasty (Alloclassic) is investigated.

Methods: Serum cobalt and serum chronium levels were determined in the postoperative course using atomic absorption spectrometry.

Results: Maximum values are found to be more than 100-fold elevated when compared to the reported median serum cobalt concentrations in patients with the same prosthesis type and no known renal disease.

Long-term oral ganciclovir prophylaxis for prevention of cytomegalovirus infection and disease in cytomegalovirus high-risk renal transplant recipients.

Background: Although specific therapy is available with ganciclovir, cytomegalovirus (CMV) disease remains a major problem after renal transplantation especially in CMV seronegative recipients of organs of seropositive donors (D+R-).

Methods: In an open-labeled prospective controlled trial we evaluated the effect of long-term oral ganciclovir prophylaxis (3 g/day for 3 months posttransplantation) in a cohort of 31 CMV-high risk (D+R-) renal transplant recipients (GC) compared with a cohort of 28 high-risk patients with targeted CMV prophylaxis (CO) receiving i.v.

Product equivalence study comparing the tolerability, pharmacokinetics, and pharmacodynamics of various human immunoglobulin-G formulations.

In this randomized, double-blind, parallel-group study, a commercially available human immunoglobulin-G product, IVIG, was compared with two test formulations: (1) IVIG-N, which is a nanofiltered formulation of IVIG, and (2) IVIG-L, which is a nanofiltered, liquid, ready-for-use IgG formulation containing nicotinamide, L-proline, and L-isoleucine as stabilizers. Three groups of 10 healthy subjects each received a single 0.6 g/kg dose of one of the formulations infused over 3.

Longitudinal follow-up of antibody response to selected antigens of human papillomaviruses and herpesviruses in patients with invasive cervical carcinoma.

A group of 21 cervical-carcinoma patients was followed longitudinally. All patients had undergone intensive radiotherapy. In the course of a more than 5-year observation period, 2 patients died of cervical cancer, 1 from other causes, 3 were lost from follow-up, and 15 survived without any signs of the disease.