Progesterone stimulates proliferation and promotes cytoplasmic localization of the cell cycle inhibitor p27 in steroid receptor positive breast cancers.

Progestins are reported to increase the risk of more aggressive estrogen receptor positive, progesterone receptor positive (ER+ PR+) breast cancers in postmenopausal women. Using an in vivo rat model of ER+ PR + mammary cancer, we show that tumors arising in the presence of estrogen and progesterone exhibit increased proliferation and decreased nuclear expression of the cell cycle inhibitor p27 compared with tumors growing in the presence of estrogen alone. In human T47D breast cancer cells, progestin increased proliferation and decreased nuclear p27 expression. The decrease of nuclear p27 protein was dependent on activation of Src and PI3K by progesterone receptor isoforms PRA or PRB. Importantly, increased proliferation and decreased nuclear p27 expression were observed in invasive breast carcinoma compared with carcinoma in situ. These results suggest that progesterone specifically regulates intracellular localization of p27 protein and proliferation. Therefore, progesterone-activated pathways can provide useful therapeutic targets for treatment of more aggressive ER+ PR+ breast cancers.

Progesterone decreases levels of the adhesion protein E-cadherin and promotes invasiveness of steroid receptor positive breast cancers.

Progestins are reported to increase the risk of invasive breast cancers in postmenopausal women receiving hormone therapy with estrogen plus progestin. We report here that estrogen and progesterone receptor positive (ER+PR+) rat mammary tumors arising in the presence of estrogen and progesterone exhibit increased invasiveness and decreased expression of E-cadherin protein compared with tumors growing in the presence of estrogen alone. A similar decrease of E-cadherin expression was observed in human ER+PR+ invasive ductal carcinoma compared with ductal carcinoma in situ. In agreement with findings in the rat, estrogen plus progestin R5020 treatment decreased E-cadherin expression in vitro in T47D human breast cancer cells. Decrease of E-cadherin protein was mediated by progesterone receptor B (PRB) and dependent on the activation of the Wnt pathway. These results suggest that progesterone signaling via PRB contributes to tumor invasiveness and can provide an important therapeutic target for treatment of invasive ER+PR+ breast cancers.

Appendicitis and benign appendiceal mucocele presenting as large bowel obstruction.

INTRODUCTION: Appendiceal mucocele is most commonly encountered incidentally during appendectomy. METHODS: We report a case of large bowel obstruction presenting as a closed loop with an appendiceal mucocele as the lead point, superimposed on a chronic ileal stricture that had been misdiagnosed as irritable bowel syndrome. RESULTS: The patient underwent ileocecal resection and primary anastomosis. She did well postoperatively, and her irritable bowel syndrome disappeared. CONCLUSIONS: Appendiceal mucocele can present in a variety of ways, and surgeons should be alert for atypical presentations. Moreover, some patients with intermittent abdominal pain deserve anatomic investigation before being dismissed as having irritable bowel.

Reduction of radiation dose in pediatric brain CT is not associated with missed injuries or delayed diagnosis.

Increased accuracy of CTs in the identification of traumatic injuries compared with physical examination or conventional radiography is well documented. Our goal was to identify the most effective strategy for decreasing radiation exposure while retaining the benefits of computerized imaging. Based on a literature review and our trauma registry, the mortality risk of untreated injuries was compared with that of patients who received treatment of injuries diagnosed by CT. Because automated exposure control of tube current is not routinely used with brain CT, this region was identified as the initial focus for a dose-saving algorithm. CT settings were adjusted for children studies and the new settings were implemented into four protocols based on age. Images were compared and reviewed by radiologists for the ability to identify traumatic injuries. Effective dose (ED) was estimated using Monte Carlo simulations. The lifetime incidence and mortality for thyroid cancer and leukemia were assessed. In-hospital mortality of unidentified injury in trauma patients is 8.0%. Forty dose-saving CTs were performed and no injuries were missed. The ED decreased by 5.2-, 4.5-, 2.62-, and 2.5-fold in each group. Decreasing the ED is achievable, theoretically decreases the cancer risk and does not increase the missed injury rate.

A modern analysis of a historical pediatric disaster: the 1927 Bath school bombing.

BACKGROUND: Children have unique anatomy and physiology that may necessitate a unique approach to a pediatric surge. An analysis of the Bath school bombings of 1927, the largest pediatric terrorist disaster in U.S. history, provides an opportunity to gain perspective on pediatric patterns of injury and future disaster preparedness. MATERIALS AND METHODS: Eighty-nine contemporary newspaper accounts, the official coroner's inquest, interviews, online resources, and the Michigan state archives of the disaster were reviewed with respect to the demographics, pattern of injury, gender, age, duration of hospitalization, relative distance of each classroom from the blast, and severity of injuries sustained using the Injury Severity Scale (ISS). RESULTS: Eighty-seven children and three teachers were unable to safely evacuate the building; 36 children (41%) were dead on-site, 40 sustained mild injuries (76.9%), nine sustained moderate injuries (17.3%), and one sustained serious injuries (1.9%). Mean ISS scores decreased with increasing relative distance of each classroom from the primary blast, while the classrooms involved in structural collapse had the highest initial mortality and ISS score. Patterns of injury sustained imply a predominance of crush and penetrating trauma. CONCLUSIONS: Mean ISS scores and initial mortality by classroom were a function of proximity to the blast and structural collapse. The pattern of injury closely approximates those of other pediatric disasters such as Columbine, Oklahoma City, and 911. The absence of severe abdominal trauma and one reported hospital mortality may reflect an initial under-triage of patients, possibly due to the medical technology of the times.

Hematocrit, systolic blood pressure and heart rate are not accurate predictors for surgery to control hemorrhage in injured patients.

Hematocrit (Hct), systolic blood pressure (SBP), and heart rate (HR) are considered to closely correlate with hypovolemia in injured patients. The clinical importance of these parameters in the early recognition of occult but clinically significant hemorrhage remains to be demonstrated. We undertook this study to assess the clinical importance of these parameters in the early recognition of occult hemorrhage in injured patients. A retrospective study of 7880 patients admitted to a Level I trauma center was carried out. Patients who underwent surgery were divided into the hemorrhage (n = 160) and no-hemorrhage group (n = 228). Hematocrit, SBP, and HR were correlated and receiver operating characteristic (ROC) curves were plotted. The ROC curves for Hct, SBP, and HR showed suboptimal areas under the graph. Even for different Hct thresholds and for hypotension and tachycardia, low predictive values were found. Although Hct, SBP, and HR levels were significantly altered among patients who require surgery for hemorrhage, the low predictive values of each parameter renders them as clinically unreliable individual tools for recognition of hemorrhagic patients who need surgery. Although useful in aggregate, as a pattern, or as indications for further diagnostic studies, these common parameters have limited usefulness individually.

Anatomic variations of the first extensor compartment and abductor pollicis longus tendon in trapeziometacarpal arthritis.

Anatomic variation of the trapeziometacarpal joint stabilizing structures is one of the concepts proposed to explain the pathogenesis of trapeziometacarpal arthritis. We undertook this study to test the hypothesis that septation of the first extensor compartment or variation of the abductor pollicis longus (APL) tendon (supernumerary insertions) are more frequently associated with the progression or severity of trapeziometacarpal arthritis. Septation within the first extensor compartment was significantly associated with trapeziometacarpal arthritis (p = 0.013), whereas supernumerary APL insertions (trapezium or thenar) did not reveal a significant association (p = 0.811 and p = 0.937, respectively). The results of this study do not support a role for variations of APL tendon insertions in trapeziometacarpal arthritis. Yet, the presence of septation within the first extensor compartment may play an important role in the pathogenesis of trapeziometacarpal arthritis.

A new model for health care delivery.

BACKGROUND: The health care delivery system in the United States is facing cost and quality pressures that will require fundamental changes to remain viable. The optimal structures of the relationships between the hospital, medical school, and physicians have not been determined but are likely to have a large impact on the future of healthcare delivery. Because it is generally agreed that academic medical centers will play a role in the sustainability of this future system, a fundamental understanding of the relative contributions of the stakeholders is important as well as creativity in developing novel strategies to achieve a shared vision. DISCUSSION: Core competencies of each of the stakeholders (the hospital, the medical school and the physicians) must complement the others and should act synergistically. At the same time, the stakeholders should determine the common core values and should be able to make a meaningful contribution to the delivery of health care. SUMMARY: Health care needs to achieve higher quality and lower cost. Therefore, in order for physicians, medical schools, and hospitals to serve the needs of society in a gratifying way, there will need to be change. There needs to be more scientific and social advances. It is obvious that there is a real and urgent need for relationship building among the professionals whose duty it is to provide these services.

Reduction and maintenance of scapholunate dissociation using the TwinFix screw.

OBJECTIVE: Closed reduction and internal fixation of the scapholunate dissociation are currently performed using K-wires or a headless bone screw. We present an alternative for this fixation by means of a cannulated screw with dynamic adjustable interfragmentary compression and discuss the advantages of using this type of technique. METHODS: Closed reduction of the scapholunate interval was achieved using a K-wire centered through the scaphoid and lunate bones followed by delivery of a cannulated compression screw to maintain the scapholunate interval. RESULTS: Nine months after the surgery, the hand active range of motion was significantly improved. Only minimal pain was experienced with high loadings of the wrist and the patient achieved much improvement in his wrist strength. CONCLUSIONS: The technique we present is simple to perform and represents an attractive alternative to the conventional procedures to achieve the reduction of the scapholunate diastasis and the maintenance of the scapholunate interval.