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Selected AbstractsTherapy of metastasized Merkel cell carcinoma with liposomal doxorubicin in combination with radiotherapyJOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT, Issue 6 2009Marion Wobser Summary Background: Merkel cell carcinoma is a rare skin cancer of neuroendocrine origin, which is characterized by a high rate of recurrence, metastatic spread and mortality. Because of its rarity, evidence-based therapeutic regimens are difficult to establish. Merkel cell carcinoma is known to be both radio- and chemosensitive. Toxicity is a key factor in assessing any regimen, as the patients are usually elderly and likely to have other significant medical problems. Patients and Methods: We retrospectively evaluated five patients with metastatic Merkel cell carcinoma to see if liposomal doxorubicin (Caelyx® or Myocet®) in combination with radiotherapy exhibited clinical anti-tumoral effects accompanied by acceptable side effects. Results: The outpatient chemotherapy regimen was tolerated without major side effects and produced good response rates. All patients achieved at least tumor stabilization; four of five had a partial remission. Effects of therapy were usually seen in the first cycle of therapy but the responses were of short duration with an average interval of two months until progression. Conclusions: As combined radiochemotherapy with liposomal doxorubicin is well tolerated even in older patients with other illnesses and can be given on an outpatient basis, it is an attractive option for metastatic Merkel cell carcinoma. Based on response rate or overall survival, it offers no advantages compared to polychemotherapy. [source] Whole-Genome Scan for Linkage to Bone Strength and Structure in Inbred Fischer 344 and Lewis Rats,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 9 2005Imranul Alam Abstract A genome-wide genetic linkage analysis identified several chromosomal regions influencing bone strength and structure in F2 progeny of Fischer 344 x Lewis inbred rats. Introduction: Inbred Fischer 344 (F344) and Lewis (LEW) rats are similar in body size, but the F344 rats have significantly lower BMD and biomechanical strength of the femur and spine compared with LEW rats. The goal of this study was to identify quantitative trait loci (QTL) linked to bone strength and structure in adult female F2 rats from F344 and LEW progenitors. Materials and Methods: The 595 F2 progeny from F344 x LEW rats were phenotyped for measures of bone strength (ultimate force {Fu}; energy to break {U}; stiffness {S}) of the femur and lumbar vertebra and structure (femur midshaft polar moment of inertia {Ip}; femur midshaft cortical area; vertebral area). A genome-wide scan was completed in the F2 rats using 118 microsatellite markers at an average interval of 20 cM. Multipoint quantitative linkage analysis was performed to identify chromosomal regions that harbor QTL for bone strength and structure phenotypes. Results: Evidence of linkage for femur and lumbar strength was observed on chromosomes (Chrs) 1, 2, 5, 10, and 19. Significant linkage for femoral structure was detected on Chrs 2, 4, 5, 7, and 15. QTLs affecting femoral strength on Chrs 2 and 5 were also found to influence femur structure. Unique QTLs on Chrs 1, 10, and 19 were found that contributed to variability in bone strength but had no significant effect on structure. Also, unique QTLs were observed on Chrs 4, 7, and 15 that affected only bone structure without any effect on biomechanics. Conclusion: We showed multiple genetic loci influencing bone strength and structure in F344 x LEW F2 rats. Some of these loci are homologous to mouse and human chromosomes previously linked to related bone phenotypes. [source] Clinical evaluation of a single-wavelength fractional laser and a novel multi-wavelength fractional laser in the treatment of photodamaged skin,LASERS IN SURGERY AND MEDICINE, Issue 6 2009Laurel Naversen Geraghty BA Abstract Background and Objectives Nonablative fractional lasers are well recognized for rejuvenating photoaged skin. We previously reported favorable outcomes with short follow-up after the use of 1,440-nm Nd:YAG laser energy used alone or in combination with a 1,320-nm laser to effect rejuvenation and wrinkle reduction. We now report longer follow-up data. Study Design/Materials and Methods Nineteen Caucasian subjects (average age 47±8.4; range 33,62) exhibiting mild-to-moderate photoaging of the face and neck were treated four times (average interval 18.1± 4.1 days; range 11,37 days) with the 1,440-nm Nd:YAG fractional laser (average fluence 3.7±0.3,J/cm2) or the 1,320/1,440-nm multiplex Nd:YAG fractional laser (1,320-nm average fluence 8.4±0.4,J/cm2; 1,440-nm average fluence 2.3±0.2,J/cm2). Outcomes were assessed by subjects and the treating physician using a quartile scale to evaluate skin tightening, surface texture, rhytids, dyschromia, erythema, and global appearance after 1, 3, and 6 months. Retroauricular punch biopsies from three patients were used to evaluate wound healing. Three patients withdrew from the study prior to evaluation, one missed the 1-month evaluation, and one missed the 6-month evaluation. Results Assessment by subjects and the treating physician revealed clinical improvement for all outcomes after 1, 3, and 6 months. The differences between the treatment groups were not statistically significant. Subjects demonstrated the greatest average 6-month improvements in surface texture and global skin appearance. Subjects treated with the multiplex laser reported more skin tightening than the group treated only with the 1,440-nm laser. Histological evaluation revealed wound healing within 10 days and significant neocollagenesis at 3 months. No adverse events were reported in any subject. Conclusion The 1,440-nm Nd:YAG and 1,320/1,440-nm multiplex Nd:YAG lasers safely and effectively produced improved surface texture, rhytids, dyschromia, erythema, global skin appearance, and skin tightening. Histopathologic findings correlated with clinical observations. Lasers Surg. Med. 41:408,426, 2009. © 2009 Wiley-Liss, Inc. [source] Antibody response to Pseudomonas aeruginosa in children with cystic fibrosisPEDIATRIC PULMONOLOGY, Issue 4 2009Lucimar G. Milagres PhD Abstract Cystic fibrosis (CF) is the most frequent life threatening autosomal recessive disease in white subjects. The primary cause of morbidity and mortality in children with CF is chronic pulmonary infection, mainly caused by Pseudomonas aeruginosa. The purpose of this study was to assess the value of the measurement of antibodies to P. aeruginosa in diagnosing lung infection by the bacteria in CF patients. We assessed P. aeruginosa antibody titers in CF patients from Rio de Janeiro, Brazil, using cell lysate antigens as well as recombinant PcrV, a Type III Secretion System protein. Sputum (more than 70% of the specimens) or oropharyngeal swabs were obtained whenever patients were regularly followed for their pulmonary disease. Blood samples were obtained with an average interval of 6 months for a period of 2 years. The ELISA cut-offs were assigned as the positive 95% confidence interval of the mean antibody levels from non-fibrocystic controls. Our data showed that most CF patients (81%) of whom were not chronically infected by P. aeruginosa (Groups I and II), had their first serology positive for rPcrV. Cell-lysate ELISA was able to detect P. aeruginosa antibodies before positive culture in the first serum sample of 44% of the patients from Groups I and II. When serum reactivity to rPcrV and cell lysate were combined, 94% of CF patients from Groups I and II (n,=,16) had the first serology positive for P. aeruginosa over a mean time of 20 months before the first isolation of P. aeruginosa. In conclusion, longitudinal P. aeruginosa serology should become part of respiratory care follow-up, in conjunction with other lung parameter functions. Pediatr Pulmonol. 2009; 44:392,401. © 2009 Wiley-Liss, Inc. [source] The second generation of the International Equine Gene Mapping Workshop half-sibling linkage mapANIMAL GENETICS, Issue 3 2003G. Guérin Summary A low-density, male-based linkage map was constructed as one of the objectives of the International Equine Gene Mapping Workshop. Here we report the second generation map based on testing 503 half-sibling offspring from 13 sire families for 344 informative markers using the crimap program. The multipoint linkage analysis localized 310 markers (90%) with 257 markers being linearly ordered. The map included 34 linkage groups representing all 31 autosomes and spanning 2262 cM with an average interval between loci of 10.1 cM. This map is a milestone in that it is the first map with linkage groups assigned to each of the 31 automosomes and a single linkage group to all but three chromosomes. [source] Genetic linkage map of the pearl oyster, Pinctada martensii (Dunker)AQUACULTURE RESEARCH, Issue 1 2009Yaohua Shi Abstract Genetic linkage maps were constructed with amplified fragment length polymorphism (AFLP) and microsatellite markers for the pearl oyster, Pinctada martensii (Dunker), the main bivalve used for marine pearl production in Asia. Twenty-four AFLP and 84 microsatellite primer pairs were used for linkage analysis in a full-sib family with two parents and 78 offspring. Of the 2357 AFLP fragments generated, 394 (16.7%) were polymorphic and segregating. Most (340 or 86.2%) of the markers segregated according to expected Mendelian ratios. Female and male linkage maps were constructed using 230 and 189 markers, including 15 and 10 microsatellites respectively. The female map consisted of 110 markers in 15 linkage groups, covering 1415.9 cM, with an average interval of 14.9 cM. The male map consisted of 98 markers in 16 linkage groups, with a total length of 1323.2 cM and an average interval of 16.1 cM. When unlinked doublets were considered, genome coverages were 78.5% for the female and 73.5% for the male map. Although preliminary, the genetic maps constructed here should be useful for future linkage and quantitative trait loci mapping efforts. [source] Description and characterization of a chamber for viewing and quantifying cancer cell chemotaxisCYTOSKELETON, Issue 1 2005Lilian Soon Abstract Direct observations of cancer cell invasion underscore the importance of chemotaxis in invasion and metastasis. Yet, there is to date, no established method for real-time imaging of cancer chemotaxis towards factors clinically correlated with metastasis. A chamber has been designed and tested, called the Soon chamber, which allows the direct observation and quantification of cancer cell chemotaxis. The premise for the design of the Soon chamber is the incorporation of a dam, which creates a steep gradient while retaining stability associated with a pressure-driven system. The design is based on the characteristics of cancer cell motility such as relatively low speeds, and slower motility responses to stimuli compared to classical amoeboid cells like neutrophils and Dictyostelium. We tested MTLn3 breast carcinoma cells in the Soon chamber in the presence of an EGF gradient, obtaining hour-long time-lapses of chemotaxis. MTLn3 cells migrated further, more linearly, and at greater speeds within an EGF gradient compared to buffer controls. Computation of the degree of orientation towards the EGF/buffer source showed that MTLn3 cells were significantly more directional toward the EGF gradient compared to buffer controls. Analysis of the time-lapse data obtained during chemotaxis demonstrated that two populations of cancer cells were present. One population exhibited oscillations in directionality occurring at average intervals of 12 min while the second population exhibited sustained high levels of directionality toward the source of EGF. This result suggests that polarized cancer cells can avoid the need for oscillatory path corrections during chemotaxis. Cell Motil. Cytoskeleton 62:27,34, 2005. © 2005 Wiley-Liss, Inc. [source] | |||||||||||||