Anatomical parameters of cardiopulmonary system in three different lines of chickens: further evidence for involvement in ascites syndrome.

The present study was designed to compare the anatomical parameters of the cardiopulmonary system in three different lines of chickens with different susceptibility to ascites syndrome. Eggs from three different genetic lines-commercial broiler and layer lines and one native to Iran--were incubated and hatched, and 1-day-old chicks used. The relative heart and lung weights, the volumes of the heart, lung and thorax cavity, the incidence of ascites, and the related physiological parameters in these chickens were followed. Lung weight as a percentage of body weight, the relative lung and heart volume, and the volumes of the thorax cavity, before and after removing heart and lung tissues, were lower in fast-growing broiler chickens compared with the layer and native chickens. Additionally, most of these parameters (e.g. relative lung weight, lung volume and thorax cavity) were significantly decreased with age in broiler chickens but were increased in layer and native chickens, which was concomitant with the incidence of ascites in broiler chickens. Our data indicate that all cardiopulmonary parameters investigated are extremely unfavourable to broiler chickens and suggest a reduction in gas exchange area in broilers, and therefore higher susceptibility to pulmonary hypertension and ascites.     

Identification of novel DRBI*13 (DRB1*1333), DRB1*04(DRB1*0426) and DRB5* (DRB5*0109) alleles

Abstract: Three novel HLA class H alleles (DRB1*1333, DRB1*O426, DRB5*0109) are described here. The 3 novel alleles were initially detected as previously unidentified SSO hybridization patterns using the CANTYPE reverse hybridization assay. Sequences were determined by cloning/sequencing. DRB1*1333 is identical to DRB1*1303 except for a single nucleotide substitution (ACC→AAC), changing codon 77 from Thr to Asn. This polymorphism is typical for DRB1*03 alleles. DRB1*0426 is identical to DRB1*0401 except for a single nucleotide substitution (GCC→ACC) at codon 58, changing the encoded Ala to Thr. DRB5*0109 is identical to DRB5*0101, except for a single nucleotide substitution (GAC→AAC), changing codon 70 from Asp to Asn. Both latter polymorphisms were so far undetected in DRB alleles. DRB1*1333 could have arisen from a gene conversion event, but DRB1*0426 and DRB5*0109 most likely were generated by point mutation events. For all 3 alleles, the sequence was confirmed by the original hybridization pattern (DRB1*1333) or by hybridization to a newly designed probe (DRB1*0426 and DRB5*0109). Ethnic backgrounds were Lebanese for DRB1*1333 and Caucasian for DRB1*0426 and DRB5*0109.     

Genotype-phenotype correlation and frequency of the 3199del6 cystic fibrosis mutation among I148T carriers: results from a collaborative study.

PURPOSE: We expect that the mutation panel currently recommended for preconception/prenatal CF carrier screening will be modified as new information is learned regarding the phenotype associated with specific mutations and allele frequencies in various populations. One such example is the I148T mutation, originally described as a severe CF mutation. After implementation of CF population-based carrier screening, we learned that I148T exists as a complex allele with 3199del6 in patients with clinical CF, whereas asymptomatic compound heterozygotes for I148T and a second severe CF mutation were negative for 3199del6. METHODS: We performed reflex testing for 3199del6 on 663 unrelated specimens, including I148T heterozygotes, compound heterozygotes, and a homozygous individual. RESULTS: Less than 1% of I148T carriers were also positive for 3199del6. Excluding subjects tested because of a suspected or known CF diagnosis or positive family history, 0.6% of I148T-positive individuals were also positive for 3199del6. We identified 1 I148T homozygote and 6 unrelated compound heterozygous individuals with I148T and a second CF variant (2 of whom also carried 3199del6). In addition, one fetus with echogenic bowel and one infertile male were heterozygous for I148T (3199del6 negative). CONCLUSIONS: Reflex testing for 3199del6 should be considered whenever I148T is identified. Reflex testing is of particular importance for any symptomatic patient or whenever one member of a couple carries a deleterious CF mutation and the other member is an I148T heterozygote. Further population data are required to determine if I148T, in the absence of 3199del6, is associated with mild or atypical CF or male infertility.     

Efficacy of different irrigation technique in simulated curved root canals

The aim of this study was to assess the influence of the canal curvature on the efficacy of sonically, ultrasonically, and laser-activated irrigation in removing a biofilm-mimicking hydrogel (BMH) from simulated canal irregularities. Transparent resin blocks containing a curved root canal (40° or 60°) were used as test models. A 4-mm groove at 1 mm from the apex was filled with BMH. Five different irrigation procedures were performed (n=20): needle irrigation (NI), EndoActivator (EA), Eddy, ultrasonically activated irrigation (UAI) (Irrisafe), and laser-activated irrigation (LAI) using a pulsed erbium laser (PIPS approach). All protocols were executed for 3×20s. Images of the groove were taken before and after irrigation, and the percentage BMH removal was calculated using image analysis software. In the 40° canal curvature model, the highest BMH removal was observed for UAI (99.9%), yielding a significantly better removal than that of EA (57.2%) and NI (53.8%), but not of LAI (96.8%) and Eddy (99.4%). In the 60° canal curvature model, UAI removed 99.5%, which resulted in significantly greater hydrogel removal than all other groups (P < 0.05). The difference between LAI (82.5%) and Eddy (78.1%) was not statistically significant, but both were more effective than EA (13.5%) and NI (7.3%). Canal curvature negatively affects the cleaning efficacy of different irrigation methods. The effect was most pronounced for the sonic techniques, while this was not the case for UAI. This could be ascribed to the prebent ultrasonic tip. Despite the position of the laser tip at the orifice level, fluid streaming during LAI resulted in substantial BMH removal beyond the curve.

     

Fibrodysplasia ossificans progressiva: Still turning into wood after 300 years?

Fibrodysplasia ossificans progressiva (FOP), a rare autosomal dominant disorder, is characterized by symmetrical congenital skeletal abnormalities and progressive heterotopic ossification of the connective tissues. At present, more than 300 years after the first report by Patin in 1648 in which he described the woman who turned to wood, its pathogenesis remains largely unknown and its therapy is limited to symptom-modifying trials. However, significant progress has been recently made and new data on the molecular organization and regulation of normal and disordered bone induction are likely to lead to a more specific therapy. FOP is believed to be a genetic disorder characterized by a disturbed expression of the endochondral osteogenesis programme, and the remarkable clues from the fly reported by Kaplan et al. [8] in 1990 suggest a gain-of-function mutation in the genetic regulation of bone morphogenetic proteins.     

Resection of lung metastases: long-term results and prognostic analysis based on 5206 cases--the International Registry of Lung Metastases

The International Registry of Lung Metastases was established in 1991 to asses the long-term results of pulmonary metastasectomy. The Registry has accrued 5206 cases of lung metastasectomy, from 18 departments of thoracic surgery in Europe (n = 13), USA (n = 4) and Canada (n = 1). Of these patients 4572 (88%) underwent complete surgical resection. The primary tumor was epithelial in 2260 (43%), sarcoma in 2173 (42%), germ cell in 363 (7%), and melanoma in 328 (6%) patients. The disease-free interval was 0 to 11 months in 1729 (33%) cases, 12 to 35 months in 1857 (36%) and more than 36 months in 1620 (31%). Single metastases accounted for 2383 (46%) cases and multiple lesions for 2726 (52%). Mean follow up was 46 months. Analysis was performed by Kaplan-Meier estimates of survival, relative risk of death and multivariate Cox model. The actuarial survival after complete metastasectomy was 36% at 5 years, 26% at 10 years and 22% at 15 years (median 35 months); the corresponding values for incomplete resection were 13% at 5 years and 7% at 10 years (median 15 months). Among complete resections, the 5-year survival was 33% for patients with a disease free-interval of 0 to 11 months and 45% for those with a disease-free interval of more than 36 months; 43% for single lesions and 27 for four or more lesions. Multivariate analysis showed a better prognosis for patients with germ cell tumors, disease-free interval of 36 months and more and single metastases. These results confirm that lung metastasectomy is a safe and potentially curative procedure.     

Randomized parallel study of doxorubicin plus paclitaxel and doxorubicin plus cyclophosphamide as neoadjuvant treatment of patients with breast cancer.

PURPOSE: This randomized, noncomparative, parallel-group study was designed to evaluate the pathologic complete response (pCR) rate of combined doxorubicin plus paclitaxel (AP) and doxorubicin plus cyclophosphamide (AC) as neoadjuvant chemotherapy in patients with previously untreated breast cancer who were unsuitable for conservative surgery. PATIENTS AND METHODS: A total of 200 patients with T2-3, N0-1, M0 disease were randomly assigned in a 2:1 ratio to receive preoperative chemotherapy with either doxorubicin 60 mg/m(2) plus paclitaxel 200 mg/m(2) as a 3-hour infusion (AP) or doxorubicin 60 mg/m(2) plus cyclophosphamide 600 mg/m(2) (AC) every 3 weeks for 4 courses followed by surgery. RESULTS: A pCR (eradication of invasive carcinoma in tumor and in axillary lymph nodes) was found in 16% and 10% of patients in the AP and AC arms, respectively, by study center pathologists, and in 8% and 6% of patients, respectively, by independent pathologists. Patients with pCRs tended to have unifocal disease, tumors with negative hormonal receptor status, and less differentiation (Scarff, Bloom, and Richardson scale grade 3). Breast-conserving surgery was performed in 58% and 45% of patients in the AP and AC arms, respectively. An objective clinical response was achieved in 89% of patients in the AP arm and 70% in the AC arm. At a median follow-up of 31 months, disease-free survival (DFS) was higher in patients who reached pCR versus those without pCR (91% v 70%). CONCLUSION: The encouraging pathologic and clinical responses of patients with breast cancer after neoadjuvant chemotherapy with doxorubicin plus paclitaxel warrant additional investigation of paclitaxel in the neoadjuvant setting of breast cancer management.