Cytogenetic and molecular genetic analysis of tumorigenic human bronchial epithelial cells induced by radon alpha particles

To establish a cell culture model for lung carcinogenesis, independent populations of the human papillomavirus 18-immortalized human bronchial epithelial cell line BEP2D were treated with high linear energy transfer radon-simulated alpha-particles, expanded and xenotransplanted into Nu/Nu mice. Six independent cell lines were established from tumors that developed from three separate radiation treatments as follows: treatment (Tx) 1 (30 cGy--two doses), H2BT, Tx 2 (30 cGy-- single dose), R30T1L, R30T2 and R30T3L, Tx 3 (30 cGy--single dose), H1ATN and H1ATBA1. Cytogenetic analysis revealed common changes in all tumor lines: loss of the Y chromosome (ch), one of three copies of ch8, one of three copies of ch14, and one of two copies of ch4p16-pter and ch11p15-pter. Analysis of polymerase chain reaction-amplified short tandem repeats of informative loci confirmed the loss of chY in all lines and loss of heterozygosity (LOH) at eight loci spanning the length of ch8 in all lines from Tx's 1 and 2. Our data support previous studies indicating the presence of tumor suppressor genes on ch8. LOH also was confirmed on ch14 at locus D14S306 in all cell lines from Tx 2 and in one of two lines from Tx 3. This region, 14q12-q13, may contain changes in one of the five known somatostatin receptor genes (SSTR1). No LOH was detected at any of the informative loci tested for on ch4 or ch11.      

Mycobacterial infection in an inner city children's hospital

Childhood tuberculosis is perceived by many as a disease of the past. Experience in a children's hospital serving a deprived population suggested that tuberculosis and other mycobacterial infections were not declining in clinical practice. Fifty three tuberculous and 11 atypical mycobacterial infections were identified between 1978 and 1992. There was no decline in tuberculosis and nine of the 11 atypical infections occurred in the last five years. Altogether 40% of cases of tuberculosis were in non-Asian children; 32% had arrived in the UK or visited family overseas in the previous year; and 38% had a history of tuberculosis contact, usually a close adult relative. Nationally, the previous decline in tuberculosis in all ages has reversed. In the local health districts in London's east end, childhood tuberculosis has also stopped declining and seems to be increasing. It is regrettable that BCG vaccination has been abolished by some districts in the UK, against current recommendations. Childhood tuberculosis is still common in the practice described here, including among children who do not fall into conventionally recognised high risk groups. Inner city dwellers and junior doctors are both highly mobile populations, adding to the risk that paediatricians, particularly those in training, may encounter tuberculosis with little or no previous experience of the condition.     

MR imaging of blood vessels using three-dimensional reconstruction: methodology

Multisection, dual-echo magnetic resonance (MR) transaxial images of blood vessels contain both anatomic and qualitative information about flow. Even so, the images are produced as a series of two-dimensional tomographic sections from which full visualization of connected structures is difficult. A computer algorithm was developed that automatically detects flowing blood based on pixel intensity and calculated T2 and provides reconstructed views of vessels while analyzing and displaying flow characteristics. Images of abdominal vessels, aortic aneurysms, and the heart were encoded by flow and color to demonstrate depth. In addition, these data were reconstructed to derive a more accurate assessment of patency. With this technique, transaxial images can be used to analyze flow patterns, determine patent areas, and visualize all levels of vessels in a single image.     

A retrospective review of 15 years of radical radiotherapy with or without concurrent cisplatin and/or 5-fluorouracil for the treatment of locally advanced cervical cancer

Radiation therapy is the standard of care treatment for locally advanced cervical cancer in the United States. In 1999 the addition of concomitant chemotherapy to radical radiotherapy became standard. The addition of cisplatin (CDDP) with or without 5-fluorouracil (5-FU) chemotherapy to radiation therapy was based on the near simultaneous reporting of five randomized, controlled clinical trials which all showed an improvement in survival with a magnitude of approximately 35%. The purpose of our study was to test the hypothesis that the addition of chemotherapy improved survival in our patients. We identified 291 patients treated with primary 'intent-to-cure' radiation therapy for locally advanced carcinoma of the cervix between 1985 and 2000. We analyzed patients using a stepwise Cox regression, including as possible predictors: clinical stage, age at diagnosis, use of concurrent chemotherapy with radiation and method of teletherapy delivery. We also examined survival as a function of CRT with a CDDP and/or 5-FU containing regimen using the Kaplan-Meier estimates of overall survival. The use of concurrent CDDP and/or 5-FU chemotherapy with radiation (CRT) was not associated with an increase in disease free survival (p=0.734) or overall survival (p=0.989). In this retrospective study there was no disease free or overall survival benefit from the addition of CDDP and/or 5-FU chemotherapy to radical radiotherapy for the treatment of locally advanced cervical carcinoma, although there was a trend favoring CRT.     

Randomized trial of McRoberts versus lithotomy positioning to decrease the force that is applied to the fetus during delivery

OBJECTIVE: In an effort to reduce shoulder dystocia incidence and morbidity, some obstetricians use prophylactic maternal hip hyperflexion (McRoberts maneuver), with the hope of facilitating delivery and decreasing the traction needed for delivery. The objective of this study was to evaluate whether the delivery force is reduced with the prophylactic McRoberts maneuver in a prospective, objective manner. STUDY DESIGN: Between April 2002 and July 2003, we randomly assigned multiparous women with term, cephalic singleton gestations to delivery in the lithotomy or McRoberts position. A single physician used a force-measuring system that consisted of a custom glove with force sensors to record the amount of force that was exerted on the fetal head. The primary outcomes of the study were peak force (pounds; highest force needed to accomplish entire delivery), peak force for delivery of anterior shoulder (pounds), and peak force rate (pounds per second; the duration required to reach the peak force). RESULTS: The peak force was not different between the patients in the lithotomy position (n=13) versus the McRoberts position (n=14; 7.2 +/- 0.8 lbs vs 8.0 +/- 0.7 lbs; P = .5). The peak force for delivery of the anterior shoulder (6.7 +/- 0.8 lbs vs 7.1 +/- 0.7 lbs; P = .7) and peak force rate (32.3 +/- 7.0 lbs/sec vs 29.1 +/- 3.5 lbs/sec; P = .7) were not different between the patients in the lithotomy position versus the McRoberts position, respectively. There was no difference between the groups for gestational age, birth weight, incidence of diabetes mellitus, or operative vaginal delivery. The subjective degree of difficulty of the delivery correlated with the peak force (R2 = 0.53; P = .001). CONCLUSION: The use of the McRoberts maneuver before clinical diagnosis of shoulder dystocia provides no reduction in the force that is used in traction on the fetal head during vaginal delivery in multiparous patients. The acceptance of this maneuver to be used prophylactically requires re-evaluation.     

Intraventricular hemorrhage and periventricular leukomalacia in preterm infants

OBJECTIVE: To evaluate whether intraventricular hemorrhage and periventricular leukomalacia are characterized by different risk factors. METHODS: In a cohort of 653 consecutive singleton neonates born after preterm membrane rupture, spontaneous preterm labor, or indicated preterm delivery at 24 to 33 weeks of gestation from January 1, 1993, to December 31, 2002, we evaluated the obstetric and histopathologic placental variables in reference to the development of intraventricular hemorrhage (n = 44), periventricular leukomalacia (n = 19), or no ultrasonographic cerebral lesion (n = 589). Excluded were stillbirths and congenital anomalies. Statistical analysis included Fisher exact test, Student t test, and stepwise logistic regression analysis with a 2-tailed P <.05 considered significant. RESULTS: Multivariate analysis showed that occurrence of neonatal intraventricular hemorrhage and periventricular leukomalacia were associated only with spontaneous prematurity (odds ratio = 1.9; 95% confidence interval 1.1-3.4) and gestational age at delivery in weeks (odds ratio = 0.8; 95% confidence interval 0.7-0.9). Neonates with intraventricular hemorrhage did not differ from those with periventricular leukomalacia in any obstetric or neonatal variable, but there was a higher risk of neurodevelopmental delay associated with periventricular leukomalacia. CONCLUSION: Among premature infants born at less than 34.0 weeks of gestation, intraventricular hemorrhage and periventricular leukomalacia share common clinical characteristics, with spontaneous preterm delivery and gestational age at delivery as the only independent antenatal predictors.     

Factors affecting the decision regarding amniocentesis in women at genetic risk because of age 35 years or older

OBJECTIVE: To evaluate the effects of anamnestic factors and sonographic findings on the patient's decision regarding amniocentesis in a cohort of women at genetic risk because of advanced age. METHODS: All women 35 years of age or older registered for prenatal care between January 1990 and December 1998 were asked about their attitude towards genetic amniocentesis during the course of individual genetic counseling and once again after ultrasound examination inclusive of markers of aneuploidies (nuchal fold thickness greater than 6 mm, renal pyelectasis, choroid plexus cysts, and hyperechogenic bowel). Their attitudes towards genetic amniocentesis before and after ultrasound examination were compared using chi-square, Fisher's exact test, Mann-Whitney U-test, and logistic regression analysis, with a two-tailed p < 0.05 or an odds ratio (OR) with 95% confidence interval (CI) not inclusive of the unity considered significant. RESULTS: Among the 1486 women in the cohort, 1368 (97%) expressed an opinion towards genetic testing at the time of counseling: 501 (37%) were in favor and 867 (63%) were against having the procedure. After ultrasonographic examination, 33% (446/1368) of women opted for amniocentesis, 36% (146/402) after abnormal findings and 31% (300/966) after normal ultrasound findings. Significantly more women with abnormal than normal ultrasound findings opted for diagnostic testing in both groups. Overall, only 8% (115/1368) of women changed their attitude towards diagnostic testing after ultrasonographic examination. Normal sonographic findings were three times more likely to change the attitude of women initially interested in amniocentesis than abnormal sonographic findings did in women a priori not interested in the procedure (20% versus 7%, p < 0.001, OR = 3.2, 95% CI 1.8; 5.8). CONCLUSIONS: In a cohort of women at genetic risk because of advanced age, the key determinant of the choice regarding genetic amniocentesis is the a priori opinion of the woman towards the procedure, which was expressed by 93% of women. Ultrasonography plays a secondary role in changing or confirming women's attitude towards invasive diagnostic testing. Normal sonographic findings affect women's decisions more powerfully than abnormal sonographic findings, suggesting that ultrasonography has an important reassuring function for the woman.     

Diffusion-weighted MR imaging of pyogenic ventriculitis

OBJECTIVE: The purpose of this study was to describe the features of pyogenic ventriculitis (ventricular empyema, pyocephalus) on diffusion-weighted MR imaging. CONCLUSION: Markedly increased signal intensity of dependent intraventricular fluid on diffusion-weighted MR imaging and an apparent diffusion coefficient that is less than that of normal cerebral white matter indicate restricted water diffusion in purulent fluid and suggest the diagnosis of pyogenic ventriculitis.