Accumulation of genetic alterations in brain metastases of sporadic breast carcinomas is associated with reduced survival after metastasis.

Tumor progression is characterized by stepwise accumulation of genetic alterations. To identify alterations associated with breast cancer metastasis, an analysis of comparative loss of heterozygosity (LOH) was performed on 38 primary sporadic breast carcinomas and 16 distant metastases. Two loci at 5q21 and 18q21 were chosen because of their reported increased deletion frequency in metastatic tumors. LOH at 17q21, 13q12-13, 17p13.1 and 11q22-23 was analyzed to determine whether there is a specific involvement of these breast cancer-associated gene loci in the metastatic process. Our data show that distant metastases are characterized by markedly increased LOH frequency at all loci examined. In both gene locus groups, significantly more distant metastases are affected by combined LOH. Furthermore, a significantly reduced postmetastatic survival time has been observed in patients with brain metastases affected by synchronous allelic loss at the four breast cancer-associated gene loci. Our results suggest that cumulative LOH of breast cancer-related gene loci is associated with a more aggressive phenotype of metastatic breast tumors.     

Efficacy of percutaneous abscess drainage in patients with vancomycin-resistant enterococci

OBJECTIVE: We reviewed a 4-year experience draining fluid collections infected with vancomycin-resistant enterococci to determine the outcome of percutaneous intervention in patients with this highly resistant and increasingly common organism. MATERIALS AND METHODS: Charts of patients from whom vancomycin-resistant enterococci had been isolated during percutaneous drainage were reviewed to determine patient response to drainage, catheter management, and outcome of treatment. RESULTS: Twenty-one patients underwent percutaneous drainage of 28 fluid collections from which vancomycin-resistant enterococci were isolated, including 16 intraabdominal abscesses, seven biliary or urinary obstructions, and five empyemas. The drainage of 27 (96%) of 28 collections were technically successful. In seven patients, drainage provided the first isolation of vancomycin-resistant enterococci from the patient. Five patients also had blood cultures with positive findings for vancomycin-resistant enterococci, and 14 collections were coinfected with other bacteria or with fungi. Twenty collections (71%) or obstructions were successfully treated with percutaneous drainage. Drainage was unsuccessful in treating eight collections in seven patients. CONCLUSION: Despite high-level antibiotic resistance, fluid collections infected with vancomycin-resistant enterococci can be successfully drained percutaneously, resulting in a favorable likelihood of recovery for patients.     

Phase I/II trial of intravenous Doxil and whole abdomen hyperthermia in patients with refractory ovarian cancer.

OBJECTIVE: A phase I/II study of Doxil combined with whole abdomen hyperthermia was conducted in patients with refractory ovarian cancer. Liposomal doxorubicin combined with hyperthermia has been shown to increase both liposomal delivery and drug extravasation into tumour xenografts resulting in enhanced cytotoxic effects. PATIENTS AND METHODS: Thirty patients with either recurrent or persistent epithelial ovarian cancer were enrolled. All patients had either measurable or assessable disease. Patients received intravenous (IV) Doxil at a dose of 40 mg m-2 as a 1-h infusion followed by whole abdomen hyperthermia. The phase I portion of the study was performed to determine the maximal tolerated dose (MTD) of hyperthermia. Quality of life (QoL) was performed at baseline, prior to each cycle and every 3 months. Plasma pharmacokinetic studies were performed with the first cycle. RESULTS: Ten patients participated in the phase I portion of the study which demonstrated that the MTD of hyperthermia was 60 min after either average vaginal and rectal temperatures of 40 degrees C had been achieved or after 30 min of power application, whichever was shorter. All 30 patients were either paclitaxel and/or platinum resistant initially or developed resistant disease. The median number of prior chemotherapeutic regimens was three (range 2-8) and six patients had been previously treated with Doxil. There were three partial responses for a response rate of 10% (95% CI: [2%, 27%]) and eight patients (27%; 95% CI: [12%, 46%]) had disease stabilization. The median time to progression or death was 3.4 months (95% CI: [2.6, 5.2]) and the median survival was 10.8 months (95% CI: [8.8, 17.4]). Twelve patients (40%) experienced palmar-plantar erythrodysesthesia (PPE), but only four (13%) experienced grade 3-4 PPE toxicity. Doxil systemic exposure was higher in those with grade 3-4 PPE compared to those with no PPE. None of the patients had grade 3-4 thermal toxicity due to hyperthermia. QoL was not decreased in patients responding to therapy. CONCLUSIONS: Therapy with intravenous Doxil and whole abdomen hyperthermia for patients with platinum/paclitaxel resistant ovarian cancer is feasible and does not negatively impact quality of life.     

Detection of pharyngeal perforation: comparison of aqueous and barium-containing contrast agents

OBJECTIVE: We sought to assess the value of aqueous and barium-containing contrast agents in the detection of pharyngeal perforation. SUBJECTS AND METHODS: Visual and objective in vitro comparisons of an iodinated aqueous contrast agent, a 50% weight/volume barium suspension, and a 100% weight/volume barium suspension were performed. Moreover, to exclude pharyngeal perforation after surgery, we prospectively examined 109 patients by pharyngography, using the aqueous contrast agent and the 100% weight/volume barium suspension. All patients with a pharyngeal perforation were followed up clinically to exclude complications due to barium application. RESULTS: As opposed to the 100% weight/volume barium suspension, in vitro comparison between the aqueous contrast agent and the 50% weight/volume barium suspension yielded no substantial differences. Seventeen perforations could be detected with the aqueous contrast agent. Although 10 of 17 perforations could be slightly better visualized with the 100% weight/volume barium suspension, two perforations were missed with this agent. Five perforations were equally well detected with both. CONCLUSION: Because of a higher radiopacity, 100% weight/volume barium suspensions may more sharply delineate perforations. However, in contrast to aqueous contrast media, narrow pharyngeal perforations can be missed. Thus, the use of a 100% weight/volume barium suspension does not improve the detection of pharyngeal perforation.     

Chronic inhalation exposure to mainstream cigarette smoke increases lung and nasal tumor incidence in rats.

An animal model of lung carcinogenicity induced by chronic inhalation of mainstream cigarette smoke would be useful for research on carcinogenic mechanisms, smoke composition-response relationships, co-carcinogenicity, and chemoprevention. A study was conducted to determine if chronic whole-body exposures of rats would significantly increase lung tumor incidence. Male and female F344 rats (n = 81 to 178/gender) were exposed whole-body 6 h/day, 5 days/week for up to 30 months to smoke from 1R3 research cigarettes diluted to 100 (LS) or 250 (HS) mg total particulate matter/m(3), or sham-exposed to clean air (C). Gross respiratory tract lesions and standard lung and nasal sections were evaluated by light microscopy. A slight reduction of survival suggested that the HS level was at the maximum tolerated dose as commonly defined. Cigarette smoke exposure significantly increased the incidences of non-neoplastic and neoplastic proliferative lung lesions in females, while nonsignificant increases were observed in males. The combined incidence of bronchioloalveolar adenomas and carcinomas in females were: HS = 14%; LS = 6%; and C = 0%. These incidences represented minima because only standard lung sections and gross lesions were evaluated. Mutations in codon 12 of the K-ras gene occurred in 4 of 23 (17%) tumors. Three mutations were G to A transitions and one was a G to T transversion. The incidence of neoplasia of the nasal cavity was significantly increased at the HS, but not the LS level in both males and females (HS = 6%, LS = 0.3%, C = 0.4% for combined genders). These results demonstrate that chronic whole-body exposure of rats to cigarette smoke can induce lung cancer.     

Neue Systematik der Epilepsien und aktuelle Therapieempfehlungen

Monatsschrift Kinderheilkunde - Die aktuelle Klassifikation der Epilepsien aus dem Jahr 2017 gleicht stark der Version des Jahres 1989. Die Versuche einer Reklassifikation in den Jahren 2001, 2006...     

Do gender and birth height of infant affect calorie of human milk? An association study between human milk macronutrient and various birth factors

Objective: The purpose of this study is to analyze the macronutrient of human milk (HM) and to find out the various maternal–infantile factors that can affect HM composition.

Methods: 478 HM samples were collected from healthy and exclusively breast-feeding mothers who delivered healthy term neonates within 3 months. Macronutrient of the samples was analyzed and the birth data were collected.

Results: In multivariate logistic regression analysis, various maternal–infantile factors were found to be associated with HM composition changes; higher fat: cesarean section (OR?=?2.47, p?p?=?0.004); higher protein: postpartum age (OR?=?0.89, p?p?=?0.005) and female infant (OR?=?0.56, p?=?0.012); higher calorie: postpartum age (OR?=?0.95, p?=?0.003), female infant (OR?=?0.33, p?=?0.017), and birth height (OR?=?0.74, p?p?=?0.029), birth height (OR?=?0.73, p?=?0.001), and postpartum age (OR?=?0.95, p?=?0.005) were found as independent risk factors for higher HM calorie.

Conclusion: Various maternal–infantile factors were found to affect HM composition. Interestingly, delivery mode, gender of infant, and birth height were associated with changes in HM macronutrient as well as postpartum age.     

Excavation of lead compounds that inhibit mast cell degranulation by combinatorial chemistry and activity-guided

An allergic reaction ensues after antigen binds to mast cell or basophil high affinity IgE receptor, Fc epsilonRI, resulting in degranulation of various inflammatory mediators that produce various allergic symptoms. In this study, i) we isolated the active component for the inhibition of mast cell degranulation from the extract of leaves of Castanea crenata and identified it as quercetin; ii) we established the total synthesis procedure of quercetin; iii) using quercetin as positive control, we excavated some lead compounds that possess inhibitory activities for mast cell degranulation by screening the chemical libraries of 1,3-oxazolidine derivatives prepared by solid phase combinatorial chemistry. Some of 1,3-oxazolidine compounds possessing acetyl and 3',4'-dichlorophenyl group displayed strong inhibitory activities on Fc epsilonRI-mediated mast cell degranulation, suggesting that they can be used as lead compounds for the development of anti-allergic agents.