Increased β-adrenergic signaling promotes fracture healing through callus neovascularization in mice.

Traumatic brain injury (TBI) leads to skeletal changes, including bone loss in the unfractured skeleton, and paradoxically accelerates healing of bone fractures; however, the mechanisms remain unclear. TBI is associated with a hyperadrenergic state characterized by increased norepinephrine release. Here, we identified the β-adrenergic receptor (ADRB2) as a mediator of skeletal changes in response to increased norepinephrine.

Transcript-dependent effects of the CALCA gene on the progression of post-traumatic osteoarthritis in mice.

Osteoarthritis represents a chronic degenerative joint disease with exceptional clinical relevance. Polymorphisms of the CALCA gene, giving rise to either a procalcitonin/calcitonin (PCT/CT) or a calcitonin gene-related peptide alpha (αCGRP) transcript by alternative splicing, were reported to be associated with the development of osteoarthritis. The objective of this study was to investigate the role of both PCT/CT and αCGRP transcripts in a mouse model of post-traumatic osteoarthritis (ptOA).

Tranexamic Acid Attenuates the Progression of Posttraumatic Osteoarthritis in Mice.

Background: Posttraumatic osteoarthritis (OA) is a common disorder associated with a high socioeconomic burden, particularly in young, physically active, and working patients. Tranexamic acid (TXA) is commonly used in orthopaedic trauma surgery as an antifibrinolytic agent to control excessive bleeding. Previous studies have reported that TXA modulates inflammation and bone cell function, both of which are dysregulated during posttraumatic OA disease progression.

The selective norepinephrine reuptake inhibitor reboxetine promotes late-stage fracture healing in mice.

Impaired fracture healing is of high clinical relevance, as up to 15% of patients with long-bone fractures display non-unions. Fracture patients also include individuals treated with selective norepinephrine reuptake inhibitors (SNRI). As SNRI were previously shown to negatively affect bone homeostasis, it remained unclear whether patients with SNRI are at risk of impaired bone healing.

Increased beta2-adrenergic signaling is a targetable stimulus essential for bone healing by promoting callus neovascularization.

Traumatic brain injury (TBI) is associated with a hyperadrenergic state and paradoxically causes systemic bone loss while accelerating fracture healing. Here, we identify the beta2-adrenergic receptor (Adrb2) as a central mediator of these skeletal manifestations. While the negative effects of TBI on the unfractured skeleton can be explained by the established impact of Adrb2 signaling on bone formation, Adrb2 promotes neovascularization of the fracture callus under conditions of high sympathetic tone, including TBI and advanced age.

The role of sphingosine-1-phosphate in bone remodeling and osteoporosis.

Osteoporosis is a systemic bone disease that affects more than 200 million people worldwide and is caused by the disruption of the equilibrium between osteoclastic bone resorption and osteoblastic bone formation. Sphingosine-1-phosphate (S1P) is a natural, bioactive sphingolipid that has been shown to play a major role in cardiovascular and immunological pathologies by regulating biological and cellular processes, including migration, differentiation, proliferation and survival. Recent studies also suggest a central role for S1P in bone diseases, including osteoporosis; however, the effects of S1P, particularly in bone metabolism, remain to be further elucidated.

Systemic calcitonin gene-related peptide receptor antagonism decreases survival in a porcine model of polymicrobial sepsis: blinded randomised controlled trial.

Background: Calcitonin gene-related peptide (CGRP) and procalcitonin, which are overexpressed in sepsis, exert distinct immunomodulatory effects mediated through the CGRP receptor. The CGRP receptor antagonist olcegepant improves survival in murine sepsis. This study evaluated whether CGRP receptor antagonism is similarly beneficial in a porcine model of polymicrobial sepsis.

An optimized protocol for a standardized, femoral osteotomy model to study fracture healing in mice.

Fracture healing represents a dynamic and complex process which depends on the balanced activities of a broad array of different cell types and signaling pathways. Here, we describe a femoral osteotomy protocol for mice, using an external fixator to stabilize the fractured bone. Depending on experimental requirements, the size of the osteotomy gap can be adjusted.

Glucose Metabolism in Osteoblasts in Healthy and Pathophysiological Conditions.

Bone tissue in vertebrates is essential to performing movements, to protecting internal organs and to regulating calcium homeostasis. Moreover, bone has also been suggested to contribute to whole-body physiology as an endocrine organ, affecting male fertility; brain development and cognition; and glucose metabolism. A main determinant of bone quality is the constant remodeling carried out by osteoblasts and osteoclasts, a process consuming vast amounts of energy.

Crosstalk of Brain and Bone-Clinical Observations and Their Molecular Bases.

As brain and bone disorders represent major health issues worldwide, substantial clinical investigations demonstrated a bidirectional crosstalk on several levels, mechanistically linking both apparently unrelated organs. While multiple stress, mood and neurodegenerative brain disorders are associated with osteoporosis, rare genetic skeletal diseases display impaired brain development and function. Along with brain and bone pathologies, particularly trauma events highlight the strong interaction of both organs.

Reconstructive plastic surgery in the treatment of vulvar carcinomas.

Objective: The results obtained using plastic surgery reconstruction in 207 patients with a primary or recurrent vulvar carcinoma were analyzed with regard to the surgical procedures applied, pre-treatment and post-operative findings, along with the long-term oncological disease course.

Study Design: Standardized data concerning the surgical procedures applied and clinical factors were collected in a databank and statistically analyzed.

Results: The flaps employed were termed either 'local' (cutaneous or fasciocutaneous; n=84) or 'regional' (myocutaneous, n=123).

[Plastic reconstructive procedures of vulvar carcinoma: results and complications].

Purpose: This study describes the results of the plastic reconstructive measures in 207 patients with a primary or a recurrent vulvar cancer. These procedures were analysed in sight of surgical excision, previous therapy, and detailed postoperative results.

Methods: All procedures and clinical parameters were recorded standardized in a data bank and analysed using statistical methods.

Surgical therapy of recurrent vulvar cancer.

Objective: The success of various surgical interventions in 201 cases with recurrent vulvar carcinoma was examined in the light of patients' pretreatment, surgical therapy, plastic reconstruction, and postoperative disease course.

Study Design: A databank of standardized clinical data was analyzed using statistical procedures.

Results: Therapy was selected on an individual basis according to tumor status.

Reconstructive surgery following resection of primary vulvar cancers.

Objective: This study describes the surgical treatment and follow-up of 213 patients with primary vulvar cancer; particular attention is given to reconstructive surgical procedures.

Methods: The clinical and pathological parameters of the patients were recorded according to standardized procedures, and the data concerning type of operation, surgical reconstruction and postoperative course of disease (recurrence-free and overall survival) were analyzed.

Results: In about one-third of the cases, plastic surgery reconstruction involving skin-flaps was performed.

The impact of treatment for genital cancer on quality of life and body image--results of a prospective longitudinal 10-year study.

Objective: To evaluate the impact of treatment for genital cancer on quality of life and body image to determine patients' therapy-related needs for quality improvement of medical care before and after surgery.

Methods: We started to evaluate women with cervical cancer planned for pelvic exenteration in 1993 and integrated women planned for a Wertheim-Meigs surgery in 1995 before surgery, 4 and 12 months after surgery. Thanks to funding since 1999, more than 400 patients with a diagnosis of genital (n = 185) or breast (n = 217) cancer participated in this prospective study until July 2003.

The physician-patient relationship before cancer treatment: a prospective longitudinal study.

Objectives: To evaluate quality of life before surgery for genital cancer to determine risk factors that might influence the physician-patient relationship.

Methods: From 1993 until 2003, 129 women with cervical cancer entered this prospective study. Patients were contacted 1 to 5 days before surgery by a psychologist or psychotherapeutically trained physician on the surgical ward.

Early postpartum hyponatremia in a patient with transient Sheehan's syndrome.

In modern day health care, Sheehan's syndrome is a rare disorder affecting the postpartum period. We present a case of a 33-year-old woman with atonic hemorrhage developing a transient Sheehan's syndrome associated with hyponatremia six days postpartum. Evaluation of cranial computer tomography and magnetic resonance imaging of the pituitary demonstrated normal finding.

p53 expression and resistance against paclitaxel in patients with metastatic breast cancer.

Purpose: Paclitaxel is an important agent in the pharmacological treatment of metastatic breast cancer. Despite its efficacy in selected patients, the majority of patients have a resistance against paclitaxel. The aim of this study was to identify the responding patients and hence prevent the other patients from ineffective treatment.

[Valence of immunohistochemical analysis of endometrial carcinoma biopsy specimen].

Objective: We compared immunohistological examination of endometrium biopsy specimen with the results of the immunohistological examination of tumor specimen to analyse the valence of this preoperative examination according to the clinico-pathological findings and overall-survival.

Material And Method: Between 1985 and 1995 193 women were treated of an endometrial carcinoma at the University hospital Mainz. In this group we evaluated 41 patients with enough preoperative endometrial biopsy material for a retrospective immunohistochemical analysis and complete follow-up data.

Multivariate independent prognostic factors in endometrial carcinoma: a clinicopathologic study in 181 patients: 10 years experience at the Department of Obstetrics and Gynecology of the Mainz University.

The aim of this study was to evaluate the biologic outcome of endometrial carcinomas as compared to clinical and pathologic parameters and to identify multivariate independent prognostic factors. Charts were abstracted from patients with endometrial carcinoma from 1985 to 1995. Data on clinicopathologic variables, adjuvant treatment, site of recurrence, and survival were collected.

Antigen-driven T-cell selection in patients with cervical cancer as evidenced by T-cell receptor analysis and recognition of autologous tumor.

We characterized the T-cell receptor (TCR) repertoire in freshly harvested tumor lesions, in short-term-expanded CD4(+) tumor infiltrating lymphocytes (TIL) as well as in CD4(+) and CD8(+) peripheral blood lymphocytes (PBL) from three patients with cervical cancer. Skewing of the T-cell repertoire as defined by measuring the length of the complementarity-determining region 3 (CDR3) of the TCR VA and VB chains was observed in CD8(+) PBL, in freshly harvested tumor tissue, as well as in CD4(+) TIL. Comparative analysis of the TCR repertoire revealed unique monoclonal TCR transcripts within the tumor lesion which were not present in PBL, suggesting selection of TCR clonotypes due to antigenic stimulation.

Improved assessment of T-cell receptor (TCR) VB repertoire in clinical specimens: combination of TCR-CDR3 spectratyping with flow cytometry-based TCR VB frequency analysis.

Antigen-specific T-cell responses may be described by combining three categories: (i) the specificity and effector functions of a T-cell population, (ii) the quantity of T-cell responses (i.e., the number of responding T cells within the CD4/CD8 population), and (iii) the "quality" of T cells (defined by the T-cell receptor [TCR] structure).

[Endometrial carcinoma in patients with diabetes mellitus].

Objective: The purposes of this study were to analyze the relationship between clinical and pathological risk factors in endometrial cancer and additional diabetes mellitus and to clarify the correlation between additional diabetes mellitus and survival of patients with this disease. -

Material And Methods: This analyze included 181 patients with endometrial carcinoma who were treated between 1985 and 1995 at the University hospital Mainz. Patients with sarcoma were excluded.

Carcinoma of the neovagina: case report and review of the literature.

Background: Carcinoma of the vagina is a rare disease, and it is even more rare in the neovagina. Nevertheless, it has been well described. The aim of this report was to analyze the reported cases and to add observations concerning a risk profile for this rare occurrence of carcinoma.