Factors correlated to successful surgical treatment of 181 non-palpable invasive breast carcinomas

Surgical treatment of non-palpable solitary invasive carcinoma consists of localization, tumorectomy and sentinel lymph node biopsy which can successfully be performed with the use of isotopes (SNOLL). The aim of our study was to find out the success rate of SNOLL and the factors that correlated with complete excision of invasive carcinoma. Solitary non-palpable carcinoma was preoperatively diagnosed in 181 cases. After peritumoral injection of nanocolloid labeled with 99mTc under mammographic (N=79) or ultrasound (N=102) guidance, tumorectomy and sentinel node biopsy were performed. Clear surgical margins were obtained in 82% of cases. Surgical margins were likely to be clear (p<0.05) if: (1) the patients were older than 50 years, (2) the weight of surgical specimens >50 g, (3) the tumor radiologic diameter was ≤20 mm, (4) invasive carcinoma was ductal rather than other types of invasive carcinomas. Only one surgical procedure was sufficient for surgical treatment of 75% of cases with non-palpable solitary invasive carcinoma.     

Estrogen metabolism genotypes, use of long-term hormone replacement therapy and risk of postmenopausal breast cancer

Association between long-term hormone replacement therapy (HRT) use and increased risk of breast cancer is still under debate. Functionally relevant genetic variants within the estrogen metabolic pathway may alter exposure to exogenous sex hormones and affect the risk of postmenopausal breast cancer. We investigated the associations of common polymorphisms in 4 genes encoding key proteins of the estrogen metabolic pathway, duration of HRT use and their interactions with breast cancer risk. We studied 530 breast cancer cases and 270 controls of the same age and ethnicity participating in a case-control study of postmenopausal women. Duration of HRT use was ascertained through a postal questionnaire. Genotyping was conducted for CYP1B1 (rs1056836), COMT (rs4680), GSTP1 (rs1695) and MnSOD (rs4880) polymorphisms by PCR-based RFLP and TaqMan? allelic discrimination method. Adjusted odds ratios and 95% confidence intervals were calculated using logistic regression analysis. HRT use was significantly associated with decreased breast cancer risk (p<0.001). None of the polymorphisms studied was associated with breast cancer risk. A significant interaction was observed between MnSOD 47T>C and HRT use (pinteraction=0.036); the risk of breast cancer associated with long-term vs. short-term HRT use was decreased in women homozygous for the wild-type allele and increased in women with at least one variant allele of the MnSOD 47T>C polymorphism. Our results suggest that MnSOD 47T>C polymorphism in interaction with long-term HRT use may modify the risk of breast cancer.     

Combined effect of CYP1B1, COMT, GSTP1, and MnSOD genotypes and risk of postmenopausal breast cancer

Objective

Estrogen plays a key role in breast cancer development and functionally relevant genetic variants within the estrogen metabolic pathway are prime candidates for a possible association with breast cancer risk. We investigated the independent and the combined effects of commonly occurring polymorphisms in four genes encoding key proteins of estrogen metabolic pathway on their potential contribution to breast cancer risk.

Methods

We studied 530 breast cancer cases and 270 controls of the same age and ethnicity participating in a case-control study of postmenopausal women. Genotyping was conducted for CYP1B1 (rs1056836), COMT (rs4680), GSTP1 (rs1695), and MnSOD (rs4880) polymorphisms by polymerase chain reaction based restriction fragment length polymorphism and TaqMan allelic discrimination method. Adjusted ORs and 95% CIs were calculated using logistic regression.

Results

None of the 4 genetic variants examined contributed to breast cancer risk individually. When the combined effects of the risk genotypes were investigated, significant associations were observed among women with two high-risk genotypes in CYP1B1 and COMT (OR, 2.0; 95% CI, 1.1 to 3.5) and two high-risk genotypes in COMT and MnSOD (OR, 2.0; 95% CI, 1.0 to 3.8), compared to those with low-risk genotypes.

Conclusion

Our results suggest that individual susceptibility to breast cancer incidence may be increased by combined effects of the high-risk genotypes in CYP1B1, COMT, and MnSOD estrogen metabolic genes.     

New paradigm in training of undergraduate clinical skills: the NEPTUNE-CS project at the Split University School of Medicine

Clinical skills' training is arguably the weakest point in medical schools' curriculum. This study briefly describes how we at the Split University School of Medicine cope with this problem. We consider that, over the last decades, a considerable advancement in teaching methodologies, tools, and assessment of students has been made. However, there are many unresolved issues, most notably: (i) the institutional value system, impeding the motivation of the teaching staff; (ii) lack of a strong mentoring system; (iii) organization, timing, and placement of training in the curriculum; (iv) lack of publications pertinent to training; and (v) unwillingness of patients to participate in student training. To improve the existing training models we suggest increased institutional awareness of obstacles, as well as willingness to develop mechanisms for increasing the motivation of faculty. It is necessary to introduce changes in the structure and timing of training and to complement it with a catalog, practicum, and portfolio of clinical skills. At Split University School of Medicine, we developed a new paradigm aimed to improve the teaching of clinical skills called "Neptune-CSS," which stands for New Paradigm in Training of Undergraduate Clinical Skills in Split.     

Chemokines CXCL10, CXCL11, and CXCL13 in acute disseminated encephalomyelitis,non-polio enterovirus aseptic meningitis,and neuroborreliosis: CXCL10 as initial discriminator in diagnostic algorithm?

We investigated potential diagnostic usefulness of serum and cerebrospinal fluid (CSF) concentrations of chemokines CXCL10, CXCL11, and CXCL13 in pediatric patients with acute disseminated encephalomyelitis (ADEM) (n?=?23), non-polio enterovirus aseptic meningitis (NPEV AM) (n?=?20), and neuroborreliosis (NB) (n?=?21) and children with acute infectious diseases with neurological symptoms but with excluded neuroinfection/neuroinflammation (controls, n?=?20). CSF levels of CXCL10 and CXCL11 were higher in patients with NPEV AM than those in other children, and CXCL10 levels showed a high discriminative potential (area under the receiver operating characteristic curve, ROC, 0.982) with high specificity and sensitivity (both 95%). CSF levels of CXCL13 were higher in NB patients than those in other children; however, discriminative potential (area under ROC curve 0.814) and diagnostic properties were moderate (sensitivity 67%, specificity 97%). Data suggest usefulness of chemokine quantification as a diagnostic aid in children with suspected ADEM, NPEV AM, or NB.     

Classification of loratadine based on the biopharmaceutics drug classification concept and possible in vitro-in vivo correlation

Loratadine was studied both in vitro and in vivo (in healthy humans) to classify it according to the Biopharmaceutics Classification System (BCS) in order to gain more understanding of the reasons for its highly variable nature with respect to plasma time profiles, and to determine the most appropriate dissolution test conditions for in vitro assessment of the release profile of the drug from solid dose forms. Based on the solubility of loratadine determined under various pH conditions and its permeability through Caco-2 monolayers, loratadine was classified as a Class II drug. Plasma profiles were predicted by convolution analysis using dissolution profiles obtained under various pH and hydrodynamic conditions as the input function and plasma time data obtained from a syrup formulation as the weighting function. The predicted profiles based on dissolution studies done at gastric pH values were in reasonable agreement with the mean bio-data suggesting dissolution testing should be done at gastric pH values. However, the bio-data were highly variable and it is suggested this may be due, at least in part, to high individual gastric pH variability and dissolution occurring in the intestine on some occasions, and therefore, dissolution testing should also be done in simulated intestinal fluid.     

The anxiolytic CRF<Subscript>1</Subscript> antagonist DMP696 fails to function as a discriminative stimulus and does not substitute for chlordiazepoxide in rats

Rationale. Compounds with a mechanism of action different from benzodiazepines may retain the anxiolytic effects of benzodiazepines with fewer side effects. CRF₁ antagonists have anxiolytic-like effects but may have different discriminative stimulus (DS) effects compared with benzodiazepines. Objective. The present study evaluated the similarity of DS effects of a CRF₁ antagonist DMP696 to the benzodiazepine chlordiazepoxide and the ability of DMP696 to produce DS effects on its own using drug discrimination procedures, as well as its anxiolytic-like effects after acute or chronic administration. Methods. Rats were trained to discriminate chlordiazepoxide (5.0 mg/kg, IP, 30 min prior to session) from vehicle under a fixed-ratio 10 schedule of food reinforcement and drug- or vehicle-lever selection following administration of DMP696 was determined. The effects of DMP696 on latency to exit a dark chamber (defensive withdrawal model of anxiety) were used as an index of anxiolytic-like activity. Results. In chlordiazepoxide-trained rats, DMP696 (1.0–100 mg/kg, PO) resulted in most of the animals selecting the vehicle lever, as did another anxiolytic, the 5-HT_1A partial agonist buspirone (0.3–10 mg/kg, IP). DMP696 reduced exit latency in defensive withdrawal at 10 mg/kg administered either acutely or chronically for 14 days. Thus, the doses of DMP696 studied in drug discrimination were up to 10-fold higher than those active in the anxiety model. In addition, DMP696 (10–60 mg/kg, PO) could not be established as a DS under the conditions used in this study. In a subsequent study, chlordiazepoxide was established as a DS in these same animals. Conclusions. Lack of substitution of DMP696 for the chlordiazepoxide DS in rats and its inability to acquire DS properties suggest that the DS effects of DMP696 differ from those of benzodiazepines. Electronic Publication     

The influence of different types of antibodies on in vitro fertilization results

PROBLEM: The influence of anti-sperm (ASA), anti-phospholipid (APA), and antizonal (AZA) antibodies on in vitro fertilization (IVF) results and the need for intracytoplasmic sperm injection (ICSI) were assessed. METHOD OF STUDY: Forty-four couples with infertility of immunologic origin were investigated. ASA in serum and ovulatory mucus were studied by a tray agglutination test (TAT) and indirect mixed anti-globulin reaction test (MAR) test, AZA were studied by passive hemagglutination and commercial enzyme-linked immunosorbent assay (ELISA; BioGen, Germany), and APA were tested by ELISAs in immunoglobulin isotypes IgG and IgM. RESULTS: Because of failed or very low fertilization after standard IVF in the previous cycle, ICSI had to be used in five out of 15 cases with ASA (33.3%), in 16 out of 18 couples with AZA (89.4%), and in only one case if APA were present (9%). Clinical pregnancy rate was 60% in cases with ASA, 38.5% with AZA, and 27.3% per embryo transfer (ET) if APA were detected. CONCLUSIONS: Immunologic infertility can be treated by IVF with very good results. The most important group are women with AZA, in whom IVF ICSI without any delay is recommended.