Mutational analysis of <Emphasis Type="BoldItalic">hMsh6</Emphasis> in Israeli HNPCC and HNPCC-like Families

Germline mutations in DNA mismatch repair (DNA-MMR) genes, mainly hMlh1 and hMsh2, underlie Hereditary Non-Polyposis Colorectal Cancer (HNPCC). Germline hMSH6 gene mutations have been reported in a small subset of HNPCC families. In the present study, ethnically diverse individuals with HNPCC and HNPCC-like features were genotyped for hMsh6 germline mutations using exon-specific PCR, DGGE, and DNA sequencing. The study encompassed 92 individuals representing 88 unrelated families who were previously analyzed for Msh2 and Mlh1 mutations: Jewish Ashkenazim (n = 44), non-Ashkenazim (n = 27), Israeli Moslem-Arab (n = 15), Druze (n=3), and Cypriot non-Jews (n = 3). Of the study population, 71 had colon cancer (CRC), mean age at diagnosis was 50.9±13.2 years (range16–73 years), 5 had endometrial cancer (two with concurrent CRC), (mean 43.6±3.26 years, range 38–45 years), and unaffected individuals (n = 18) were first degree relatives within HNPCC families and were genotyped at a mean age of 48.3±11.7 years (range 30–69 years). Of the 92 individuals analyzed, none showed a truncating hMsh6 mutation, and 6 (6.6%) harbored one of three germline missense mutations: a previously reported one (V878A), and two novel mutations (V509A, S227I). The pathogenic significance of these three missense mutations is yet unclear. In addition, 5 polymorphisms were detected, 2 of which were novel. We conclude that the rate of pathogenic hMsh6 mutations in HNPCC families of Jewish and Mediterranean origin is low, and that mutations in other genes probably account for the phenotype in these families.     

Cytogenetic analysis of the spontaneous murine B-cell leukemia (BCL1

Cytogenetic studies were carried out on the spontaneous transplantable murine B cell leukemia (BCL₁) of BALB/c mice, a recently discovered model of chronic lympholytic leukemia. BCL₁ tumor cells appear as medium to large size mature lymphocytes located predominantly in the blood (up to 500,000/mm³) and in the x50 enlarged spleen. BCL₁ cells obtained from the spleen show a certain degree of spontaneous proliferation unlike peripheral blood lymphocytes (PBL), but both show a good in vitro response to the B-cell mitogen lipopolysaccharide (LPS). Out of 213 spontaneously dividing spleen cells and LPS stimulated PBL studied, the majority (75.5%) showed a rather stable and complex female karyotype consisting of 36 chromosomes. No normal representative of chromosome Nos. 6, 8, 12 and 15 was present and only one normal representative was found for chromosome Nos. 4, 5, 9, 14 and X. Two deleted chromosomes and seven characteristic marker chromosomes, originating from complex chromosomal rearrangements could be identified in each cell. Of special interest was the t(12:15) translocation, which had been found in several murine plasmacytomas. No direct correlation between the chromosomal changes and the phenotypic characteristics of BCL₁ tumor cells could be made. However, the highly specific karyotype may serve as a useful marker in identifying single BCL₁ tumor cells.     

Hospital-based group practice and comprehensive care for children of indigent families

The replacement of a community hospital's pediatric outpatient clinics with a physicians' group practice is described, and the effects of this development on the receipt of services by children of indigent families are analyzed. An expanded patient population, frequent telephone utilization, decreased emergency room use, and satisfactory parental perceptions are found. A comparative measure of effectiveness is obtained from a record review of the preventive care received by infants delivered by the hospital's staff obstetricians. The latter data show the group practice to be more successful than the clinics in initiating and maintaining well-child care in its facility, and in achieving the timed completion of immunizations and screening procedures. The experience indicates an acceptance by low-income families of an outpatient service that emphasizes the physician-patient relationship with limited use of outreach services and nonphysician providers. It also inidicates that such a system of care can be provided to a heterogeneous patient population within the same facility.     

Fatal varicella associated with selective natural killer cell deficiency

A 2-year-old girl with recurrent severe varicella infections had a fatal outcome. Studies of cellular and humoral immunity were normal. No natural killer (NK) cells were detected, and NK activity was markedly decreased. The interleukin (IL)15/IL15R signaling pathway was intact. This case emphasizes the role of NK cells in controlling herpes viral infection.     

Orbital hydatid cyst manifested as expanding exophthalmos following blunt orbital trauma

A 14-year-old boy suffered right blunt orbital trauma. X-ray revealed a compressed fracture of the right ethmoidal sinuses. Three months after the trauma, progressive, painless right proptosis developed. Ocular examination revealed a severe proptosis and pronounced down displacement of the right globe without signs of orbital inflammation. A well-demarcated, extraconal right orbital cystic mass was seen on computerized tomography scan. The cyst contents were aspirated and found to contain echinococcal scolices and "hydatid sand." Hypertonic saline was injected and the cyst was excised. Progressive proptosis after blunt orbital trauma in patients from endemic areas should be suspected of being an orbital hydatid cyst.     

Renal cell carcinoma invading the right ovarian vein: multidetector computed tomography and ultrasound Doppler findings

Multidetector computed tomography (MDCT) and Doppler ultrasound findings of a renal cell carcinoma invading the right ovarian vein are presented. An MDCT study performed for evaluation of macroscopic hematuria showed a heterogeneously enhancing malignant thrombus in the right ovarian vein that was in continuity with inferior vena cava and right renal vein thrombi of identical characteristics. Further investigation with Doppler ultrasound confirmed these findings and showed arterial blood flow of low resistance within the ovarian vein and inferior vena cava thrombi. To the authors' knowledge, this is the first report of MDCT and Doppler ultrasound findings of a renal cell carcinoma invading the right ovarian vein.     

The benefit of the operating microscope for access cavity preparation by undergraduate students

Although studies show the operating microscope (OM) provides benefits for endodontists, the benefit to undergraduates has not been evaluated as completely as for specialists. The purpose of this study was to determine whether using the OM would improve students' performance in endodontic access cavity preparation and canal identification. Thirty-six dental students prepared access cavities and located canals in extracted maxillary molars, before and after training, which varied according to group. The standard group received a lecture and practice in preparation of access cavities. The microscope group received identical instruction using the OM. The control group received lectures only. All groups received equal content and instruction time (2 hr 20 min). Faculty graded preparations according to a multidimensional 5-point rating scale. Using the OM, the microscope group improved significantly in access cavity preparation (p <0.05) and significantly outperformed both standard and control groups in accuracy of identifying canals (p <0.05).     

Treatment outcome in endodontics-The Toronto Study. Phases I and II: apical surgery

This study prospectively assessed the 4 to 8 yr outcome of apical surgery performed by graduate students in phases I and II of the Toronto Study. The study cohort included 155 teeth in 138 patients. Outcome was assessed by a blinded and calibrated examiner. Clinical and radiographic measures were used for a dichotomous outcome: healed (no signs and symptoms, Periapical Index score /= 3). The recall rate was 85% and the overall healed rate 74%. Healed rate was significantly higher for teeth with small (相似文献   

Variables associated with successful vaginal birth after one cesarean section: a proposed vaginal birth after cesarean section score

The objective of this study was to define the variables associated with vaginal birth after cesarean section (VBAC) and to develop a scoring system for the prediction of successful VBAC. We searched our computerized database for parturients with a history of one low-transverse cesarean section (CS) who were delivered during the year 2000. Variables were categorized according to the time period in which they were obtained: (1) first prenatal visit, (2) at the onset of labor, and (3) during labor. Univariate and multiple stepwise logistic regression models were fitted to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Of the 475 parturients with a history of one previous CS, 136 underwent elective CS and 339 underwent a trial of VBAC, of whom 82% were successful. Of the variables that can be obtained at the onset of labor, five were significantly associated with successful VBAC: abnormal presentation as the indication for the primary CS (OR, 7.4; 95% CI 2.8 to 19.2), a previous VBAC (OR, 7.2; 95% CI, 2.1 to 24.8), cervical dilation (OR, 2.5; 95% CI, 1.3 to 4.9), gestational age < or = 41 weeks (OR, 2.8; 95% CI, 1.1 to 7.1), and lower gestational age at the primary CS (OR, 1.2; 95% CI, 1.02 to 1.4). In the proposed VBAC score, each of the four most significant variables was assigned a score ranging between 0 and 3 based on the probability for VBAC. A score < or = 2 was associated with a success rate of 42%, a score between 3 and 6 was associated with a rate of 81%, and a score between 7 and 10 was associated with a 98% successful VBAC rate (p < 0001). The proposed VBAC score may help obstetricians when counseling their patients regarding the individual likelihood of a successful VBAC.