Electrochemotherapy of chest wall breast cancer recurrence

Chest wall breast cancer recurrence after mastectomy is a disease difficult to treat. Its incidence varies between 5% and 30% in different subset of patients. When possible, radical surgical therapy represents the main treatment approach, however when the disease progresses and/or treatments are not successful, ulceration, bleeding, lymphedema and psychological distress of progressive disease significantly decrease the quality of the remaining life of a patient. When surgical excision of chest wall recurrence is not possible, other local treatments such as radiotherapy, radiotherapy with hyperthermia, topical chemotherapy and electrochemotherapy might be taken into account. Electrochemotherapy provides safe, efficient and non-invasive locoregional treatment approach for chest wall breast cancer recurrence. Several clinical studies have demonstrated high efficacy and a good safety profile of electrochemotherapy applied in single or multiple consecutive sessions, till clinical response was reached. Electrochemotherapy can be performed either with cisplatin injected intratumorally or with bleomycin given intratumorally or intravenously. Furthermore, it can be effectively used in heavily pre-treated areas, after surgery, radiotherapy or systemic chemotherapy. These are the advantages that might demand its use especially in patients with pre-treated extensive disease and in frail elderly patients. With development of the technology electrochemotherapy could even be suggested as a primary local therapy in patients not suitable for surgical removal of the primary tumor.     

Urinary Screening for Early Detection of Kidney Diseases

Objective

Urinary screening is a simple inexpensive tool to evaluate kidney functions. The authors carried out urinary screening of school children for early detection of kidney diseases.

Methods

Children in the age group 5–15 y were screened for urinalysis. They were divided in 2 groups; group-1 included 5–10 y and group-2 included >10–15 y old children.

Results

Urine samples of 3340(78%) out of 4283 enrolled children were tested. Abnormal samples were found in 5.75%; with proteinuria in 4.59%, pyuria in 3.29% and hematuria in 4.31%. Males constituted 47.71% in group-1 and 54.64% in group-2. Low body mass index was found in 94.1% group-1 and 78.99% group-2 children. Mild proteinuria was found in 1.2% group-1 and 2.56% group-2 children. Severe proteinuria was more in group-2 (0.77% vs. 0.06%) with female preponderance. Glucosuria was found in 1 boy of group-2. Urobilinogen was more in group-2 (0.65% vs. 0.24%) with male preponderance. Nitrituria was found in 9 girls. Pyuria (2.02% vs. 1.27%) and hematuria were more in group-2 (3.04% vs. 1.87%) with female preponderance. Combined proteinuria and hematuria (0.42% vs. 0.24%) as well bacteruria and fungaluria were more in group-2 (4.11% vs. 1.39%). Six of 192 children with abnormal urinary findings were treated; 1 for urinary calculus and 5 for urinary tract infection.

Conclusions

Abnormal urinary findings were more common in children >10 y of age. Thus urinary screening program of children can become useful for early detection of kidney diseases and contribute towards building up of a healthy nation.

     

Seliciclib (CYC202, R‐roscovitine) enhances the antitumor effect of doxorubicin in vivo in a breast cancer xenograft model

We sought to determine whether seliciclib (CYC202, R‐roscovitine) could increase the antitumor effects of doxorubicin, with no increase in toxicity, in an MCF7 breast cancer xenograft model. The efficacy of seliciclib combined with doxorubicin was compared with single agent doxorubicin or seliciclib administered to MCF7 cells and to nude mice bearing established MCF7 xenografts. Post‐treatment cells and tumors were examined by cell cycle analysis, immunohistochemistry and real‐time PCR. Seliciclib significantly enhanced the antitumor effect of doxorubicin without additional murine toxicity. MIB1 (ki67) immunohistochemistry demonstrated reduced proliferation with treatment. The levels of p21 and p27 increased after treatment with doxorubicin or seliciclib alone or in combination, compared to untreated controls. However, no changes in p53 protein (DO1, CM1), survivin or p53 phosphorylation (SER¹⁵) were observed in treated tumors compared with controls. In conclusion, the CDK inhibitor seliciclib (R‐roscovitine) enhances the antitumor effect of doxorubicin in MCF7 tumors without increased toxicity with a mechanism that involves cell cycle arrest rather than apoptosis. © 2008 Wiley‐Liss, Inc.     

Single-nucleotide polymorphisms may cause erroneous results in primer-introduced restriction enzyme analyses: a case of molecular misdiagnosis of homozygous vs heterozygous familial hypercholesterolemia

PCR amplification followed by a primer introduced restriction analysis PCR (PIRA-PCR) is a widely used method to detect point mutations. Usually the artificial RFLP is created by siting one nucleotide mismatch near the 3; end of the primer. This does not alter the hybrization of the primer to the target DNA sequence. Unfortunately, unexpected single nucleotide polymorphisms (SNPs) may lead to additional mismatches and result in no amplification of the allele having unexpected SNP. We describe a warning example in which heterozygous familial hypercholesterolemia patient had an unexpected SNP and this led to his misdiagnosis.     

Reliability of a multidimensional questionnaire for adults with treated complete cleft lip and palate

The purpose of this study was to evaluate the reliability of a multidimensional questionnaire for Swedish adults with treated complete unilateral or bilateral cleft lip and palate (CLP). The questionnaire was designed to be used in the evaluation of adults with treated CLP after treatment. Before any conclusions were drawn from the results of the study we assessed the test-retest reliability of the questionnaire. The questionnaire included 168 questions and assessed the following domains: aesthetics, functions associated with CLP, satisfaction with treatment and perceived need for treatment, quality of life, depression and non-specific physical symptoms, body image, and jaw function. The subjects answered the questionnaire twice at a 2-3-week interval. Sixty-one adults (38 men, 23 women) mean age 24 years (range 20-29) participated in the study. The response rate for the questionnaire was acceptable at 75%. The test-retest reliability varied among the different domains. The reliability of questions regarding aesthetics, functions associated with CLP, and treatment satisfaction was good to excellent (intraclass correlation coefficient (ICC) = 0.51 to 0.89). Good to excellent (ICC = 0.61 to 1.0) reliability was also found for the quality of life in various life domains and the wellbeing scales. The reliability of the body image scale was moderate (kappa = 0.43-0.60) for most items and lower than that of other scales used in this study. The reliability of the mean depression symptom score (ICC = 0.93) and the mean non-specific physical symptoms score (ICC = 0.85) were excellent. The reliability of the mandibular function impairment was good (ICC = 0.67). The conclusion of the study is that an overall reliability was good for the multidimensional questionnaire.     

Desmin-lacZ transgene expression and regeneration within skeletal muscle transplants

The purpose of this study was to investigate the initiation and time course of the regeneration process in fragments of skeletal muscle transplants as a function of muscle tissue age at implantation. The appearance of desmin occurs at the very beginning of myogenesis. The transgenic desminnls lacZ mice used in the study bear a transgene in which the 1 kb DNA 5′ regulatory sequence of the desmin gene is linked to a reporter gene coding for Escherichia coliβ-galactosidase. The desmin lacZ transgene labels muscle cells in which the desmin synthesis programme has commenced. We implanted pectoralis muscle fragments from fetal transgenic embryos and mature and old transgenic mice into mature non-transgenic mice. Early events of myogenesis occurring during regeneration started sooner in transplants from 4-month-old (day 3 post-implantation) muscle than in those from 24-month-old (day 5-6 post-implantation) muscle, and they lasted longer in those from young (day 17 post-implantation) than in those from old (day 14 post-implantation) muscle fragments. In adult muscle, transgene activation proceeded from the periphery toward the centre of the transplant. In transplants from fetal 18-day-old pectoralis, myotubes with transgene activity were observed from day 1 to day 19. Desmin immunoreactivity, which appeared about one day after transgene activation, was followed by myosin expression. In adult transplants, the continuity of laminin labelling was disrupted around degenerative fibres, illustrating alteration of the extracellular matrix. Our data suggest that satellite cells from old muscle tissue have lower proliferative capacity and/or less access to trophic substances released by the host (damaged fibres, vascularization) than those from fetal or young adult muscle This revised version was published online in July 2006 with corrections to the Cover Date.     

Biological constants in migrants

Until now, clinical chemists, clinicians, physicians dealing with the problem of migrant biology dispose only reference limits established for an autochtone population. But can these really be applied? We compared 28 blood constituents of a migrant population with those of the french population. We defined five geographic areas: Italy, the Iberian Peninsula, Northern Africa, Northern and Central Europe and the Near and Middle East.