Narrowing racial gaps in breast cancer chemotherapy initiation: the role of the patient–provider relationship

Chemotherapy improves breast cancer survival but is underused more often in black than in white women. We examined associations between patient–physician relationships and chemotherapy initiation and timeliness of initiation among black and white patients. Women with primary invasive, non-metastatic breast cancer were recruited via hospitals (in Washington, DC and Detroit) and community outreach between July 2006 and April 2011. Data were collected via telephone interviews and medical records. Logistic regression models evaluated associations between chemotherapy initiation and independent variables. Since there were race interactions, analyses were race-stratified. Factors associated with time from surgery to chemotherapy initiation and delay of ≥90 days were evaluated with linear and logistic regressions, respectively. Among eligible women, 82.8 % were interviewed and 359 (90.9 %) of those had complete data. The odds of initiating chemotherapy were 3.26 times (95 % CI: 1.51, 7.06) higher among black women reporting greater communication with physicians (vs. lesser), after considering covariates. In contrast, the odds of starting chemotherapy were lower for white women reporting greater communication (vs. lesser) (adjusted OR 0.22, 95 % CI: 0.07, 0.73). The opposing direction of associations was also seen among the sub-set of black and white women with definitive clinical indications for chemotherapy. Among those initiating treatment, black women had longer mean time to the start of chemotherapy than whites (71.8 vs. 55.0 days, p = 0.005), but race was not significant after considering trust in oncologists, where initiation time decreased as trust increased, controlling for covariates. Black women were also more likely to delay ≥90 days than whites (27 vs. 8.3 %; p = 0.024), but this was not significant after considering religiosity. The patient–physician dyad and sociocultural factors may represent leverage points to improve chemotherapy patterns in black women.     

Biological organization of hydroxyapatite crystallites into a fibrous continuum toughens and controls anisotropy in human enamel

Enamel forms the outer surface of teeth, which are of complex shape and are loaded in a multitude of ways during function. Enamel has previously been assumed to be formed from discrete rods and to be markedly aniostropic, but marked anisotropy might be expected to lead to frequent fracture. Since frequent fracture is not observed, we measured enamel organization using histology, imaging, and fracture mechanics modalities, and compared enamel with crystalline hydroxyapatite (Hap), its major component. Enamel was approximately three times tougher than geologic Hap, demonstrating the critical importance of biological manufacturing. Only modest levels of enamel anisotropy were discerned; rather, our measurements suggest that enamel is a composite ceramic with the crystallites oriented in a complex three-dimensional continuum. Geologic apatite crystals are much harder than enamel, suggesting that inclusion of biological contaminants, such as protein, influences the properties of enamel. Based on our findings, we propose a new structural model.     

Human ameloblastoma tumors express the amelogenin gene.

Instructive signals are responsible for the regulation of the expression of gene products characteristic of many cell lineages during normal development and potentially during neoplasia. The odontogenic origin of ameloblastomas is based largely on the similarity in histologic appearance between the tumor and the developing tooth organ. A pathognomonic pattern for odontogenic tissue-specific gene expression in ameloblastomas has not been previously shown. In these studies, the gene expression parameters for human ameloblastomas have been characterized with the techniques of messenger RNA phenotyping in combination with Northern and in situ hybridization analysis of messenger RNA. The results of these studies confirm that amelogenin, a gene transcribed solely by differentiated ameloblasts, was expressed by epithelial cells from human ameloblastomas. This observation suggests that the instructive signals required for ameloblast differentiation are shared during normal development and tumorigenesis of odontogenic epithelium.     

Amelogenin post-secretory processing during biomineralization in the postnatal mouse molar tooth

The primary structures, molecular genetics and biosynthesis of the amelogenin protein of the developing tooth are established, but knowledge of their subsequent post-secretory processing and its relation to enamel biomineralization is fragmentary. Preparations of tooth matrix proteins were isolated from molars (M1) of mice from birth to 15 days and analysed by SDS-PAGE and immunochemical methods. Amelogenin proteins, isolated and partially purified by HPLC, were characterized by amino acid analysis and SDS-PAGE. At birth a 26 kDa amelogenin was present that during subsequent developmental stages generated a series of 20-25 kDa amelogenins differing in apparent size by approximately 1 kDa. Amino acid analyses showed that all these amelogenins have amino-terminal TRAP sequences; analyses for both glycosylation and phosphorylation were negative. It is suggested that these post-secretory amelogenins are generated by a sequence of specific carboxy-terminal cleavages, and that the observed post-secretory processing of amelogenin is functionally linked to the structure of the enamel matrix and the control of crystallite development.     

Polyoma virus-induced murine odontogenic tumors.

Neonatal mouse pups were injected subcutaneously with polyoma virus to induce odontogenic tumors. This treatment resulted in a spectrum of tumors that arose in organs dependent upon epithelial-mesenchymal interactions for their organogenesis, which included the teeth, salivary glands, thymus, and lacrimal glands. In addition, several odontogenic tumors with a histologic resemblance to ameloblastoma were identified and analyzed with respect to the presence of markers specific for various stages of ameloblast differentiation. Immunodetection analyses of the odontogenic tumors identified fibronectin and laminin, typical of basement membrane organization during early tooth organogenesis. These same tumors failed to express amelogenin, a gene whose expression is limited to differentiated ameloblasts. In contrast, a 47 kDa enamelin-like polypeptide was identified with the use of an antienamelin antibody. These data were interpreted to suggest that the polyoma virus truncated the differentiation pathway for these odontogenic tissues at an early stage of their development and retained the expression of basement membrane components and the enamelin-like polypeptides, yet excluded expression of amelogenin gene products. This observation suggests that polyoma viral transformation may dysregulate odontogenic tissue interactions and produce tumors composed of cells arrested at a specific stage in their development.     

Significant ocular findings are a feature of heritable bone dysplasias resulting from defects in type II collagen

BACKGROUND/AIMS: The type II collagenopathies are a phenotypically diverse group of genetic skeletal disorders caused by a mutation in the gene coding for type II collagen. Reports published before the causative mutations were discovered suggest heritable bone dysplasias with skeletal malformations may be associated with a vitreoretinopathy. METHODS: A retrospective notes search of patients with a molecularly characterised type II collagenopathy chondrodysplasia who had been examined in the ophthalmology clinic was conducted. RESULTS: 13 of 14 patients had a highly abnormal vitreous appearance. One patient aged 11 presented with a total retinal detachment. Two other children aged 2 and 4 had bilateral flat multiple retinal tears on presentation. 10 of 12 patients refracted were myopic. Two patients had asymptomatic lens opacities: one associated with bilateral inferiorly subluxed lenses and the other with a zonule and lens coloboma. CONCLUSION: Heritable skeletal disorders resulting from a mutation in the gene coding for type II collagen are associated with abnormal vitreous, myopia and peripheral cataract with lens subluxation. In bone dysplasias resulting from a defect of type II collagen there is likely to be a high risk of retinal detachment with a propensity to retinal tears at a young age.     

Long-term outcomes of radiotherapy for pituitary adenomas

PURPOSE: To evaluate long-term local control and toxicity for pituitary adenomas treated with fractionated radiotherapy (RT). METHODS AND MATERIALS: The records of 100 patients with pituitary adenomas treated between 1983 and 2003 were retrospectively reviewed. Thirty-one patients had hormone-secreting tumors; 69 patients were treated with surgery and postoperative RT. Median follow-up was 6.7 years (range, 0.6-20.2 years) for all patients and 6.2 years (range, 2-20.2 years) for living patients. The mean dose delivered was 45 Gy (range, 43-50.4 Gy). RESULTS: The 10-year actuarial local control rates for nonsecreting and secreting adenomas were 98% and 73%, respectively (p = 0.0015). Actuarial 10-year cause-specific survival (CSS) rates were 95% and 88%, and overall survival rates were 66% and 79% for nonsecreting and secreting adenomas, respectively. Involvement of the sphenoid sinus was found to be significantly associated with decreased 10-year CSS (p = 0.0453). When compared with the two- or three-field techniques, stereotactic RT was associated with improved CSS (p = 0.0775). CSS was not significantly associated with hormone excretion, extent of surgery, or whether RT was administrated postoperatively or for salvage after a postsurgical recurrence. New cases of hypopituitarism occurred in 35 patients. One patient experienced vision loss, and one patient developed a post-treatment glioma. CONCLUSIONS: This is one of the most mature series in the literature that documents excellent results with fractionated RT for pituitary adenoma. We recommend 45 Gy at 1.8 Gy per fraction using stereotactic noncoplanar fields.