Epidemiology of human trichinellosis in Poland--currently and in the past

Since the XIX century human trichinellosis has remained an unsolved problem of public healthcare in Poland. This paper describes the past situation and analyses current changes in the epidemiological pattern of trichinellosis in Poland. Epidemiological data from the last 60 years, point out that the number of human cases as well as the number of deaths caused by trichinellosis has decreased significantly. Up to 90s the main source of Trichinella infection for people was pork. Among other implemented control measures, the introduction of the artificial digestion method in the early 80s to detect trichinellosis in pigs resulted in a shift in the sources of Trichinella infection in humans - pork was replaced with wild boar meat. In the years 1990-1995 the number of outbreaks due to pork consumption was 3.5-times higher than in the years 2000-2005. In the early nineties pork was the source of infection causing about 71% of all outbreaks; in 2000-2005 that number has fallen to only 12%. On the other hand wild boar meat was responsible for 23% of the outbreaks in 1990-1995 and as many as 88% of all outbreaks in the years 2000-2005. Moreover the number of persons infected in the outbreaks significantly decreased. The study of wild animals demonstrated that wild boars in Poland are infected not only with T. spiralis but also with Trichinella britovi. These results and EU recommendations indicate a requirement of determining the Trichinella species which cause infections in outbreaks. In the 3 trichinellosis outbreaks in 2005 the infected meat products were examined with molecular tools. T. spiralis species larvae were the etiological agents of infection in all these outbreaks. The current epidemiological situation of trichinellosis in Poland indicates a need of increasing the awareness of risks related to wild boar meat consumption among the general public. Introducing the artificial digestion method as an obligatory method for wild boar meat examination is also necessary.     

Bone marrow versus sentinel lymph node involvement in breast cancer: a comparison of early hematogenous and early lymphatic tumor spread

The early spread of tumor cells in primary breast cancer patients may occur either through lymphatic or hematogenous dissemination. Lymph node (LN) status and presence of disseminated tumor cells (DTC) in bone marrow (BM) are independent predictors of poor outcome. It is unknown which factors determine one or the other route of tumor cell spread and whether lymphatic and hematogenous tumor cell dissemination are two independent processes. This study is aimed to compare the DTC status in clinically node-negative (N0) breast cancer patients with their sentinel LN status and to investigate predictors of BM and LN involvement. The DTC status of 1,345 clinically N0 breast cancer patients who underwent SLN biopsy during initial surgery was investigated. BM and LN status were compared and predictors of hematogenous and lymphatic tumor cell spread were investigated. DTCs were present in the BM of 181 (13%) patients. LN involvement was found in 348 (26%) patients. There was no correlation between LN and BM status: 137 of 997 nodal-negative patients (14%) had BM involvement and 44 of 348 nodal-positive patients (13%) were positive for DTCs (P = 0.649). The presence of DTCs was not influenced by tumorbiological factors. Conversely, a high correlation between nodal status and tumor size, histology, ER-status and lymph vessel invasion was found. Hematogenous and lymphatic tumor spread seem to be because of independent pathways of cancer progression.     

The risk of breast cancer in women with a BRCA1 mutation from North America and Poland

Women with a BRCA1 mutation face a high lifetime risk of breast cancer. It is unknown to what extent environmental factors modify the inherent genetic risk. If women from different countries, but with similar mutations, experience different levels of cancer risk, nongenetic risk modifiers are likely to be present. Study subjects were a cohort of 1477 women with a BRCA1 mutation, from Canada (n = 358), the United States (n = 256) and Poland (n = 863). The women were followed for a mean of 4.3 years and 130 incident cases of breast cancer were recorded. Annual cancer incidence rates were calculated, and based on these, penetrance curves were constructed for women from North America and Poland. In a Cox proportional hazards model, residence in Poland, versus North America, was associated with an adjusted hazard ratio of 0.54 (95% CI 0.34-0.86; p = 0.01). The risk of breast cancer to age 70 was estimated to be 49% for women from Poland and 72% for women from North America. Among women with BRCA1 mutations, the risk of breast cancer in women who reside in Poland is less than that of women who reside in North America. The reasons for the difference are unknown, but this observation suggests that environmental factors or genetic modifiers are important in determining risk.     

Mafosfamide as a new anticancer agent: preclinical investigations and clinical trials

Mafosfamide (4-thioethane sulfonic acid salt of 4-hydroxy-cyclophosphamide, MAF) belongs to a new generation of the oxazaphosphorine agents. MAF is a cyclophosphamide analog which spontaneously degrades to 4-hydroxy-cyclophosphamide. The effects of MAF on various types of cancer cells were determined during preclinical investigations and clinical trials. The positive results from in vitro and in vivo anticancer studies promoted MAF to a good candidate for phase I trials. Clinical experience with intrathecal MAF, used for patients with neoplastic meningitis due to leukemia, lymphoma, and solid tumors, indicated good tolerability and efficacy. The recommended phase II doses of intrathecally administered MAF were determined. Clinical trials using intrathecal MAF are now underway. To obtain a better therapeutic index, a strategy to alternate dosing between the intraventricular and intralumbar routes is also being tested. MAF is an attractive agent for regional cancer therapy. The current available knowledge on MAF as a new anticancer agent is based on a collection of the original published studies, conference abstracts and relevant articles.     

Results of a phase II open-label, non-randomized trial of cisplatin chemotherapy in patients with BRCA1-positive metastatic breast cancer

ABSTRACT: INTRODUCTION: The purpose of this investigation was to evaluate the efficacy of cisplatin chemotherapy in BRCA1 mutation carriers with metastatic breast cancer. METHODS: In a phase II, open-label study, 20 patients with metastatic breast cancer who carried a mutation in BRCA1 were treated with cisplatin 75 mg/m2 intravenously every 3 weeks as part of a 21-day cycle for 6 cycles. Restaging studies to assess response were performed after cycles 2 and 6, and every three months thereafter. RESULTS: Between July 2007 and January 2009, 20 patients were enrolled. Baseline characteristics were as follows: 65% had prior adjuvant chemotherapy, 55% had prior chemotherapy for metastatic breast cancer; mean age was 48 years (ranges 32 to 70); 30% estrogen receptor (ER) or progesterone receptor (PR)+, 70% ER/PR/Human Epidermal Growth Factor Receptor 2 (HER2)- and 0% HER2+. Overall response rate was 80%; nine patients experienced a complete clinical response (45%) and seven experienced a partial response (35%). Overall survival was 80% at one year, 60% at two years and 25% at three years. Four of the 20 patients are alive four years after initiating treatment. The median time to progression was 12 months. The median survival from the start of cisplatinum treatment was 30 months. Cisplatin-related adverse events, including nausea (50%), anemia (5%) and neutropenia (35%) were mostly mild to moderate in severity. CONCLUSIONS: This phase II study demonstrates that cisplatin chemotherapy has high activity in women with a BRCA1 mutation and metastatic breast cancer and is generally well tolerated. TRIAL REGISTRATION: This trial is registered retrospectively on the clinical trials website ClinicalTrials.gov. The identifier is NCT01611727.     

Discriminant analysis involving serum cytokine levels and prediction of the response to therapy of patients with Hodgkin lymphoma

Current standard diagnostic methods do not identify patients with Hodgkin lymphoma (HL), who are at high risk of failure after the first-line treatment. In HL patients, serum cytokine levels are frequently elevated and correlate with clinical and pathological features of the disease as well as with disease-free survival and overall survival. The aim of this study was to investigate if pretreatment serum cytokine and cytokine receptor concentrations evaluated by discriminant analysis could be predictive of response to standard first-line treatment in HL. The study involved 48 previously untreated patients with histologically confirmed classical HL and no EBV infection. Treatment included chemotherapy and involved field radiotherapy or radiotherapy alone. At the end of treatment, 71?% of patients reached complete response (CR), and 29?%, in partial response. To identify parameters predictive of nonachievement of CR after the first-line treatment, the discriminant analysis was used. The following variables were included in the analysis: clinical stage, sex, age, histologic subtype, bulky mediastinal mass, systemic symptoms and the number of involved nodal areas, lactate dehydrogenase (LDH) activity, and serum levels of 12 cytokines/cytokine receptors. The resulting classifying function assigned a discriminant power to the following variables: the levels of vascular endothelial growth factor, interleukin-8, macrophage colony stimulating factor, basic fibroblast growth factor, soluble tumor necrosis factor receptor I, and LDH activity. The accuracy of predicting CR and non-CR was 94 and 43?%, respectively.     

The use of transglutaminase in the reduction of immunoreactivity of wheat flour

The immune response of wheat flour modified by the treatment with transglutaminase under different conditions of temperature, incubation periods and the ratio of enzyme/wheat flour was investigated. The particular wheat protein fractions were examined for the immune reaction by the use of an indirect non-competitive ELISA. Commercially available antibodies, namely, monoclonal antihuman IgG and monoclonal antihuman IgE conjugates with alkaline phosphatase and human sera with elevated IgG as well as rabbit sera against QQQPP peptide were tested. The highest decrease in gliadins immunoreactivity was observed for wheat flour modified under following conditions: temperature 37°C, 18 h of incubation and the ratio enzyme/wheat flour 1:10 000. For all rabbit sera examined the residual immunoreactivity of glutenins was found to be below 30% of the level measured for the untreated protein. The large decrease in allergenicity of glutenins leads to the conclusion that wheat flour modified by treatment with transglutaminase may be used as a constituent of food products destined for people with a classic food allergy, i.e. the allergy elicited by that protein fraction.     

Correlation between early neonatal diet and atopic symptoms up to 5-7 years of age in very low birth weight infants: follow-up of randomized, double-blind study

The influence of early feeding on the risk of atopic diseases has been studied in full-term newborns, not in very low birth weight infants (VLBW). The study evaluated effect of early feeding of VLBW infants with either cow's milk-based formula (CMF) or extensively hydrolyzed milk formula (HF) on incidence of atopic diseases and markers of atopy at 5-7 years of age. This was a follow-up of the randomized, double-blind study evaluating the influence of different enteral feeding protocols on the early morbidity of VLBW infants. In the original study 80 children were randomly allocated into 2 groups receiving during first month of life HF (experimental group) or CMF (control group). At the age of 5-7 years, 62 children among 74 available (84%) with mean birthweight 1124g were evaluated according to standardized ISAAC (International Study of Asthma and Allergies in Childhood) protocol. Total IgE level, specific IgE, lymphocyte CD4+CCR4+/CD4+CXCR3+ ratio and skin prick tests (SPT) were done. Prevalence of obvious allergic diseases was not significantly different between the studied groups (HF: 12/33; CMF: 6/29; RR [relative risk] HF vs CMF: 1.76; 95%CI [confidence interval]: 0.76–4.09). Comparison of atopic status across groups revealed similar rate of positive markers of atopy: IgE (RR: 2.57 95%CI: 0.91–8,08), SPT (RR: 5.13; 95%CI: 0.93–31.6), lymphocyte CD4+CCR4+/CD4+CXCR3+ ratio (OR: 2.32; 95%CI: 0.78–7.53) in the both studied groups. Based on the carried out follow-up study we were unable to confirm the usefulness of hydrolyzed formula in prevention of allergy in an unselected cohort of very low birth weight infants.     

Optimizing photodynamic therapy: in vivo pharmacokinetics of liposomal meta-(tetrahydroxyphenyl)chlorin in feline squamous cell carcinoma.

PURPOSE: The aim of the present study was to optimize and simplify photodynamic therapy using a new liposomal formulation of the photosensitizer meta-(tetrahydroxyphenyl)chlorin [m-THPC (Foscan); liposomal m-THPC (Fospeg)] and to reduce systemic reactions to the photosensitizer. EXPERIMENTAL DESIGN: To examine the pharmacokinetics of liposomal m-THPC, we determined tissue and plasma variables in feline patients with spontaneous squamous cell carcinoma. In vivo fluorescence intensity measurements of tumor and skin were done with a fiber spectrophotometer after i.v. injection of m-THPC or liposomal m-THPC in 10 cats. Blood samples, drawn at several time points after photosensitizer administration, were analyzed by high-performance liquid chromatography. RESULTS: None of the liposomal m-THPC-treated cats showed side effects during or after drug injection. Fluorescence intensities, fluorescence ratios (tumor fluorescence divided by skin fluorescence), and bioavailability in the tumor were 2 to 4 times higher with liposomal m-THPC compared with m-THPC. Liposomal m-THPC concentration in the tumor increased constantly to reach a maximum at 4 hours after injection. Plasma concentration and bioavailability were approximately 3 times higher with liposomal m-THPC compared with m-THPC measured at the time points of highest plasma concentration. The distribution half-life was shorter with liposomal m-THPC, resulting in maximal tumor accumulation up to 5.5 times earlier. Maximal tumor accumulation and maximal fluorescence ratio with liposomal m-THPC occurred at the same time point, indicating maximal selectivity. In both groups, all cats responded to therapy. CONCLUSIONS: Liposomal m-THPC was well tolerated by all cats and seems to have superior pharmacokinetic properties compared with m-THPC. The efficacy of the drug warrants further study.