Patient and provider factors associated with the noninitiation of tamoxifen for young women at high-risk for the development of breast cancer.

We sought to identify factors associated with disparities in tamoxifen utilization among young patients at high-risk for developing breast cancer. We identified 67 premenopausal, high-risk women age 35-45, without surgical prophylaxis, who did not initiate tamoxifen. Factors associated with noninitiation were examined. About 37% of patients had no documented provider-based discussion regarding initiation. Type of high-risk diagnosis was the only factor associated with a provider-based discussion (P = .03). For patients offered tamoxifen, primary reasons for noninitiation were perceived minimal benefit (66.7%), fertility concerns (16.7%), and concerns about side effects (7.1%). Implementation of comprehensive educational strategies regarding the benefits of tamoxifen should be facilitated to improve initiation among young high-risk patients.

Case report: mediastinal hematoma secondary to hypertension, presenting as a retropharyngeal space abscess.

The majority of retropharyngeal hematomas described in the literature have been associated with anticoagulation therapy, tumors, aneurysm, infection or cervical spine injury. We present a case of a 55-year-old African American female with acute chest pain, sore throat, and dysphagia. Her past medical history was significant for uncontrolled hypertension and cervical spine arthritis. Physical exam was significant for posterior pharyngeal edema and her labs indicated mild leukocytosis. Contrast-enhanced CT scan of the neck demonstrated an extensive retropharyngeal fluid collection with mediastinal extension, concerning for an abscess. A trans-oral and trans-cervical incision and drainage of the presumed abscess revealed clotted blood and venous ooze. Penrose drains were placed in the retropharyngeal space to allow for spontaneous drainage over the next two days. The patient was kept intubated for 8 days to ensure a secure airway while venous ooze was allowed to self-tamponade. Antihypertensive medications were utilized to control her labile blood pressures. To our knowledge this is the first case report of uncontrolled chronic hypertension as the etiology of a spontaneous mediastinal venous hematoma with presentation as a retropharyngeal space fluid collection. When evaluating retropharyngeal space occupying lesion with mediastinal extension, consideration should be given to mediastinal venous plexus bleeding. Treatment involves securing the airway, drainage, and control of blood pressure.

Insulin like growth factor-1 (IGF-1) decreases ischemia-reperfusion induced apoptosis and necrosis in diabetic rats.

Previous evidence supports the view that insulin, as well as insulin like growth factor-1 (IGF-1) provides neurotropic support for neurons in the central nervous system (CNS) and peripheral nervous system (PNS). In the present study we evaluated the effects of the intravenous infusion of IGF-1 on both necrosis and apoptosis in the CNS of streptozotocin induced diabetic animals before and/or following middle cerebral artery occlusion (MCAO) with reperfusion. The lesion volume was used as an index of necrosis and the sensorimotor cortex (layers 5 and 6) as well as the CA1 and CA3 regions of the hippocampus were analyzed for apoptosis using TUNEL staining and Caspase-3 immunoreactivity. A large lesion volume was produced in diabetic animals after 2-h MCAO and 24-h reperfusion. Diabetic animals also had an elevated basal level of apoptotic cells that are bilaterally distributed. Apoptosis was further increased over basal after 2-h MCAO and 24-h reperfusion. The acute administration of IGF-1 30-min before or 2 h after MCAO followed by 24-h reperfusion decreased the lesion volume as well as the number of apoptotic cells in the cortical penumbra. Apoptosis as assessed by TUNEL and caspase-3 immunoreactivity was decreased in select sensorimotor cortex and hippocampal areas. We conclude that treatment with IGF-1 before or after ischemic insult significantly decreases both lesion volume and apoptosis in selected areas of the cortex and hippocampus.

Effects of hyperglycemia on the differential expression of insulin and insulin-like growth factor-I receptors in human normal peritoneal and adhesion fibroblasts.

OBJECTIVE: To determine whether the insulin receptor (IR), insulin-like growth factor-I receptor (IGF-IR), and IGF-I are expressed differentially in fibroblasts isolated from normal peritoneal and adhesion tissue before and after 24-hour treatment with increasing glucose concentrations. DESIGN: Prospective experimental study. SETTING: University medical center. PATIENT(S): Primary cultures of fibroblasts established from peritoneal and adhesion tissues of the same patients. INTERVENTION(S): Glucose treatment of the primary cultured fibroblasts for 24 hours with increasing concentrations of glucose (100-850 mg/dL). MAIN OUTCOME MEASURE(S): Real-time polymerase chain reaction was used to measure messenger RNA (mRNA) levels for IR, IGF-IR, and IGF-I. Enzyme-linked immunosorbent assay was used to determine protein levels. RESULT(S): At the normal glycemic level (100 mg/dL), adhesion fibroblasts have significantly higher mRNA levels of the IR (7.96 +/- 0.15 vs. 6.97 +/- 0.16; P<.05), IGF-IR (7.72 +/- 0.22 vs. 6.88 +/- 0.06; P<.05), and IGF-I (7.04 +/- 0.10 vs. 5.92 +/- 0.10; P<.05) when compared with normal fibroblasts, respectively. Data are expressed as log(mRNA/microg RNA). Normal fibroblasts respond to increasing glucose concentrations by increasing the expression levels of the IR, IGF-IR, and IGF-I, whereas adhesion fibroblasts respond by decreasing the expression of the IR, IGF-IR, and IGF-I. CONCLUSION(S): The differential expression of the IR, IGF-IR, and IGF-I in adhesion fibroblasts may contribute to the pathogenesis of fibrosis observed in diabetic patients.

Cerebral ischemia-induced apoptosis and necrosis in normal and diabetic rats: effects of insulin and C-peptide.

Neuronal apoptosis has been demonstrated to be a significant factor in neurological deficiencies associated with diabetes, and these deficiencies are exaggerated following ischemia. Diabetic rats have an increased basal level of apoptosis compared to non-diabetics and it has been previously demonstrated that infarct volumes were greater in diabetic animals following middle cerebral artery occlusion (MCAO) when compared to non-diabetics. In this study, we evaluated both the acute and chronic effects of insulin and/or C-peptide on CNS necrosis and apoptosis in non-diabetic and streptozotocin-induced diabetic rats following MCAO with reperfusion. Two brain areas, the sensori-motor cortex (layers-5 and 6) and the CA1 and CA3 sectors (pyramidal cell layers) of the hippocampus, were analyzed for apoptosis using TUNEL and Caspase-3 immunoreactivity. The chronic administration of a low maintenance concentration of insulin (2 U/kg), or the acute administration of insulin (2 U/kg) with or without C-peptide, did not alter the lesion volume or basal levels of apoptosis or the apoptotic levels in animals subjected to 2-h MCAO followed by 24-h reperfusion. However, both the acute or chronic administration of a high concentration of insulin (12 U/kg) significantly decreased lesion volume and apoptosis subsequent to 2-h MCAO followed by 24-h reperfusion. High dose insulin treatment also decreased the basal level of apoptosis. We conclude that in diabetic rats subjected to ischemia and reperfusion chronic insulin treatment decreased the basal apoptotic level, and both acute and chronic insulin decreased the MCAO-induced lesion volume and apoptosis. Maintenance insulin concentrations with or without C-peptide were without effect.

Cerebral ischemia induced apoptosis and necrosis in normal and diabetic rats.

Stroke is the third leading cause of death and disability, and the risk for ischemic stroke is greater in diabetics. Previous studies have demonstrated both structural and functional nervous system changes in diabetes, and these changes may be enhanced by apoptosis. In the present study, we evaluated several indexes of both necrosis and apoptosis in the CNS of normals and two different models of diabetes (insulinopenic and insulin-resistant). Studies were conducted following middle cerebral artery occlusion (MCAO) with or without reperfusion. The sensory motor cortex (layer-5 and -6) and the CA1 and CA3 sectors of the hippocampus were analyzed following MCAO. We observed that both insulinopenic and insulin-resistant diabetic rats have increased basal level of apoptosis that is uniformly and bilaterally distributed as indicated by both caspase-3 activity and TUNEL staining. Twenty-four hours after MCAO, apoptosis was further increased in both diabetic models. Reperfusion after a 2 h MCAO compared to 24 h MCAO was associated with a decrease in TUNEL staining and caspase-3 activity in the control animal but exacerbated apoptosis, especially in the hippocampus of insulin-resistant diabetic rats. MCAO-induced lesion volumes were greater in insulinopenic rats compared to insulin-resistant and control rats. We conclude that both insulinopenic and insulin-resistant diabetic animals have increased apoptosis in the CNS in response to MCAO, and restoration of blood flow especially in the insulinopenic diabetic animals paradoxically exacerbates this process. Furthermore, restoration of blood flow did not decrease lesion volume in insulinopenic diabetic animals.