Production and characterization of a monoclonal antibody reactive with a specific neoantigenic determinant (comprising B beta 54-118) in degradation products of fibrin and of fibrinogen

Balb/c mice were immunized with a mixture of fibrin degradation products (XDPs) prepared by complete lysis of a human blood clot by tissue-type plasminogen activator and purified by immunoaffinity chromatography. Spleen cells of the mice were fused with P3 X 63 Ag 8653 myeloma cells. A clone (FDP 14) was selected that produces monoclonal antibodies (MoAbs) of the IgG1 kappa type that react with a neoantigenic determinant exposed in these XDPs, but not in intact fibrinogen or in fibrin monomers. Furthermore, the MoAb is reactive with some pure, individual degradation products of fibrinogen (fragments X, Y, E, and the N-terminal disulphide knot) and with the fibrinogen B beta-chain but not with A alpha- and gamma-chains or with fragments D, FCB-2 and FCB-3. Comparison of the known primary structures of these fibrinogen fragments indicates that the stretch B beta 54-118 comprises at least an important part of the epitope recognized by FDP-14. Apparently, this stretch contributes importantly to a neoantigenic determinant that is not functional in intact fibrinogen and fibrin monomer and that can be made functional by reduction of fibrinogen, or by digestion with plasmin or CNBr.     

Expression of BRCA1 gene in ewe mammary epithelial cells during pregnancy: regulation by growth hormone and steroid hormones.

OBJECTIVE: Steroid hormones (estradiol and progesterone) in association with prolactin and growth hormone are involved in lobulo alveolar development of the mammary gland during pregnancy. We hypothesized that the BRCA1 gene may be induced by these different hormones. METHODS AND RESULTS: In this study, we have demonstrated by Northern blot and in situ hybridization, that the expression of ovine (o) BRCA1 mRNA in mammary epithelial cells increased dramatically during a short period in the second half of pregnancy (days 70 to 112) and decreased at the end of pregnancy. The increase in oBRCA1 mRNA expression is concomitant with rapid lobulo alveolar growth. Using an in vivo protocol to artificially induce mammary gland development, we demonstrated by the real-time RT-PCR method that growth hormone in association with estrogen, progesterone and hydrocortisone induces an increase of BRCA1 mRNA expression in the ewe mammary gland. Moreover, we showed that estradiol and progesterone induce oBRCA1 expression in primary cultures of ewe mammary gland. CONCLUSIONS: These results suggest that BRCA1 is a potential regulator of the effects of steroid hormones and growth hormone in the induction of mammary epithelial cell proliferation.     

Spondylometaphyseal dysplasia, corner fracture type: a heritable condition associated with coxa vara

The authors present the radiographic features of a previously incompletely delineated bone dysplasia, which they call spondylometaphyseal dysplasia, corner fracture type. This is a dominant heritable condition associated with short stature and developmental coxa vara. The progressive hip deformity usually causes significant disability requiring surgical correction. Developmental coxa vara, simulated corner fractures of long tubular bones, and vertebral body abnormalities result in a diagnostic constellation. Knowledge of these distinctive radiologic features allows accurate diagnosis, which in turn should lead to appropriate genetic counseling and possibly to earlier, more efficacious surgical treatment of the coxa vara.     

Effacement of the fetal cisterna magna in association with myelomeningocele

The cisterna magna is effaced in association with myelomeningocele. The authors retrospectively investigated the size of the fetal cisterna magna as a predictor of fetal myelomeningocele in 67 pregnant women (17-38 menstrual weeks) referred for prenatal sonography because of an elevated serum alpha-fetoprotein level (n = 61) or a suspicion of fetal ventriculomegaly on previously obtained sonograms (n = 6). Twenty fetuses had myelomeningocele, 14 had isolated ventriculomegaly, and 33 were normal. A normal-sized cisterna magna (range, 4-9 mm in depth) was present in all normal fetuses. In 19 of 20 fetuses with myelomeningocele, the views of the posterior fossa were adequate, and in each of these the cisterna magna was effaced (n = 18) or very small (n = 1). The cisterna magna was effaced in five of 13 (38%) fetuses with isolated ventriculomegaly in whom the posterior fossa was adequately imaged. Although effacement of the cisterna magna is a nonspecific finding, the high negative predictive value of this sign is useful during routine screening of the fetal neural axis.     

Exploring the surgeon volume outcome relationship among women with breast cancer

BACKGROUND: A relationship between higher surgeon volume and lower mortality has been described for breast cancer, but selection bias has not been rigorously evaluated. We studied potential bias in the surgeon volume-outcome relationship by comparing the relationship of surgeon volume to breast cancer mortality and to mortality from other causes of death. METHODS: We conducted an observational cohort study from tumor registry and Medicare claims data on 12 216 women, 66 years or older, with stage I or II breast cancer, who were operated on by 1856 surgeons. Breast cancer mortality and other-cause mortality were determined from death certificate sources and surgeon volume from Medicare claims. RESULTS: Treatment by a high-volume surgeon was associated with younger patient age, white race, less comorbidity, and residence in a more affluent zip code. Patients treated by low-, medium-, and high-volume surgeons had small differences in breast cancer mortality (17.4, 15.7, and 13.0 deaths per 1000 person-years, respectively; P = .03) but larger differences in non-breast cancer mortality (46.0, 36.8, and 31.7 deaths per 1000 person-years, respectively; P < .001). After adjustment for multiple patient and disease factors, women treated by high-volume surgeons, compared with those treated by low-volume surgeons, were not less likely to die of breast cancer (relative risk, 0.94; 95% confidence interval, 0.76-1.16) but were significantly less likely to die of other causes (relative risk, 0.86; 95% confidence interval, 0.75-0.98). CONCLUSIONS: The surgeon volume-outcome relationship for these patients with breast cancer was attributable not to mortality from breast cancer but to other causes of death. The lack of specificity of this relationship raises the possibility of selection bias as an explanatory factor.     

Perceived accessibility versus actual physical accessibility of healthcare facilities.

This study addressed how healthcare clinics perceive themselves in regard to accessibility for persons with spinal cord injuries (SCI). All 40 of the clinics surveyed reported that they were wheelchair accessible; however, there was significant variability in the number of sites that actually met the guidelines of the Americans with Disability Act. In general, a person using a wheelchair could enter the building, the examination room, and the bathroom. The majority of sites did not have an examination table that could be lowered to wheelchair level. Most reported limited experience in working with persons with (SCI), yet they claimed to be able to assist with difficult transfers. Only one site knew about autonomic dysreflexia. Problems of accessibility appeared to be seriously compounded by the clinics' perception of how they met physical accessibility guidelines without consideration of the actual needs of persons with SCI. This study addressed the perception of accessibility as reported by clinic managers versus actual accessibility in healthcare clinics in a Midwestern metropolitan area for persons using wheelchairs.     

Challenging behaviors should not be considered depressive equivalents in individuals with intellectual disabilities. II. A replication study

Previous research has proposed behavioral equivalents for depression, but evidence for behavioral equivalents has been contradictory. The relationship between a measure of depression and several proposed behavioral equivalents of depression was assessed in 693 adults living in a large residential setting. Most were adults with severe or profound intellectual disability. The frequency of language-based measures of depression was very low. A scale to assess depression was constructed based on an item analysis of a larger pool of items. Both item and factor analysis and correlations between scores on the depression scale and individual maladaptive behavior items showed little or no relationship between proposed behavioral equivalents and depression. No support was found for behavioral equivalents of depression. This replicated the findings of Tsiouris, Mann, Patti, and Sturmey (2003). Practitioners are cautioned against using maladaptive behaviors as evidence of depression in people with severe or profound intellectual disabilities.     

Disparities in colon cancer screening in the Medicare population

BACKGROUND: Colorectal cancer is the third most common cancer in the United States, but the rate of screening remains low. Since 2001, Medicare has provided coverage of colonoscopy for colorectal cancer screening in individuals at average risk, but little is known about the effect of this coverage on screening or disparities in screening practices. METHODS: We examined the Medicare physician/supplier billing claims file for New York, Florida, and Illinois for the years 2002 and 2003. Using a previously employed algorithm, we identified the rates of colorectal screening tests in individuals at average risk. We performed multivariate logistic regression analysis to calculate the effects of sex, racial/ethnic, and socioeconomic characteristics on screening. We also looked for interactions between socioeconomic and demographic variables. RESULTS: A total of 596 470 Medicare beneficiaries were included in the study. Approximately 18.3% of the population had undergone a screening colon test during the study period. Nonwhite persons were less likely to be screened for colorectal cancer than were white persons (relative risk [RR], 0.52; 95% confidence interval [CI], 0.50-0.53). The lowest RR of screening colonoscopy in women compared with men was in the oldest age group and the highest income tertile (RR for whites, 0.64; 95% CI, 0.59-0.70). Higher income level was associated with screening colonoscopy in white patients (men: RR, 1.19; 95% CI, 1.14-1.25; women: RR, 1.09; 95% CI, 1.05-1.15) but not in nonwhite patients (men: RR, 0.97; 95% CI, 0.78-1.22; women: RR, 0.94; 95% CI, 0.78-1.14). CONCLUSION: Despite the expansion of Medicare coverage for colorectal cancer screening, there still remain significant disparities between sex and racial/ethnic groups in screening practices.