Primary reconstruction of open depressed skull fractures with titanium mesh

Open skull fractures have been traditionally managed in 2 stages: urgent craniotomy and elevation of the fracture with removal of contaminated bone, debridement, and delayed cranioplasty. Primary, single-stage repair of these injures has been said to entail risks such as infections. Recent experience, however, disproved these concerns.We used a primary single-stage reconstruction for patients presenting with open depressed skull fractures. All patients received antibiotic prophylaxis. The patients underwent elevation of the compound fracture and craniotomy if necessary. Debridement was performed, followed by skull reconstruction using a 0.6-mm titanium mesh.We present 5 consecutive male patients (age, 32.2 +/- 15.6 years) who underwent primary reconstruction of open depressed skull fractures. Clinical and radiologic follow-up was performed 2 months after surgery. The duration of the surgery was 2 +/- 1.6 hours. The size of the implanted mesh was 13 +/- 13.1 cm. No infection was detected in our series, with a follow-up period of 22 +/- 6.5 months (range, 16-29 months). The cosmetic result was defined in 4 patients as "excellent" and in 1 patient as "good."Primary reconstruction of open skull fractures with titanium mesh is feasible, safe, and cosmetically preferable than the conventional staged approach. The introduction into clinical practice can be warranted.

Restorative neuroscience: concepts and perspectives

There is increasing interest in the search for therapeutic options for diseases and injuries of the central nervous system (CNS), for which currently no effective treatment strategies are available. Replacement of damaged cells and restoration of function can be accomplished by transplantation of cells derived from different sources, such as human foetal tissue, genetically modified cell lines, embryonic or somatic stem cells. Preclinical and clinical trials have shown promising results in neurodegenerative disorders, like Parkinson's and Huntington's disease, but also ischaemic stroke, intracerebral haemorrhage, demyelinating disorders, epilepsy and traumatic lesions of the brain and spinal cord. Other studies have focused on finding new ways to activate and direct endogenous repair mechanisms in the CNS, eg, by exposure to specific neuronal growth factors or by inactivating inhibitory molecules. Neuroprotective drugs may offer an additional tool for improving neuronal survival in acute or chronic CNS diseases. Importantly however, a number of scientific issues need to be addressed in order to permit the introduction of these experimental techniques in the wider clinical setting.

Cell replacement therapy for intracerebral hemorrhage

Intracerebral hemorrhage (ICH), for which no effective treatment strategy is currently available, constitutes one of the most devastating forms of stroke. As a result, developing therapeutic options for ICH is of great interest to the medical community. The 3 potential therapies that have the most promise are cell replacement therapy, enhancing endogenous repair mechanisms, and utilizing various neuroprotective drugs. Replacement of damaged cells and restoration of function can be accomplished by transplantation of cells derived from different sources, such as embryonic or somatic stem cells, umbilical cord blood, and genetically modified cell lines. Early experimental data showing the benefits of cell transplantation on functional recovery after ICH have been promising. Nevertheless, several studies have focused on another therapeutic avenue, investigating novel ways to activate and direct endogenous repair mechanisms in the central nervous system, through exposure to specific neuronal growth factors or by inactivating inhibitory molecules. Lastly, neuroprotective drugs may offer an additional tool for improving neuronal survival in the perihematomal area. However, a number of scientific issues must be addressed before these experimental techniques can be translated into clinical therapy. In this review, the authors outline the recent advances in the basic science of treatment strategies for ICH.

Functions and effects of creatine in the central nervous system

Creatine kinase catalyses the reversible transphosphorylation of creatine by ATP. In the cell, creatine kinase isoenzymes are specifically localized at strategic sites of ATP consumption to efficiently regenerate ATP in situ via phosphocreatine or at sites of ATP generation to build-up a phosphocreatine pool. Accordingly, the creatine kinase/phosphocreatine system plays a key role in cellular energy buffering and energy transport, particularly in cells with high and fluctuating energy requirements like neurons. Creatine kinases are expressed in the adult and developing human brain and spinal cord, suggesting that the creatine kinase/phosphocreatine system plays a significant role in the central nervous system. Functional impairment of this system leads to a deterioration in energy metabolism, which is phenotypic for many neurodegenerative and age-related diseases. Exogenous creatine supplementation has been shown to reduce neuronal cell loss in experimental paradigms of acute and chronic neurological diseases. In line with these findings, first clinical trials have shown beneficial effects of therapeutic creatine supplementation. Furthermore, creatine was reported to promote differentiation of neuronal precursor cells that might be of importance for improving neuronal cell replacement strategies. Based on these observations there is growing interest on the effects and functions of this compound in the central nervous system. This review gives a short excursion into the basics of the creatine kinase/phosphocreatine system and aims at summarizing findings and concepts on the role of creatine kinase and creatine in the central nervous system with special emphasis on pathological conditions and the positive effects of creatine supplementation.

Proliferation and apoptosis in mammary epithelium during the rat oestrous cycle

AIM: During each oestrous cycle, the mammary gland is subject to changes in ovarian hormone levels. It responds with limited proliferation, differentiation and regression. To understand the processes resulting in these changes, particularly the regulation of cell death, we examined protein levels in mammary epithelium during the oestrous cycle of the Sprague-Dawley rat. METHODS: Studies of serum hormone levels, vaginal smears, uterine weight and morphology, mammary gland morphology, proliferation and apoptotic indices, and protein levels during the stages of the Sprague-Dawley rat oestrous cycle were used to examine the response of mammary epithelium to the oestrous cycle. RESULTS: Proliferation of mammary epithelium was greater in diestrus and proestrus, while apoptosis was increased in metestrus and diestrus. Growth factor-, hormone- and anchorage-mediated cell survival signalling, indicated by activation of Stat5A, FAK and Akt 1 and expression of anti-apoptotic Bcl-2 family members, was greater in proestrus and reduced in metestrus. In contrast, the levels of pro-apoptotic Bcl-2 family members and proteins associated with apoptosis in mammary epithelium (TGFbeta3, pStat3) were increased during metestrus and diestrus. CONCLUSION: Decreases in growth factor, hormone and cell attachment survival signals corresponded with increased apoptosis during the second half of the oestrous cycle. The protein levels detected during oestrus suggest parallels to apoptosis in mammary involution.

Lhermitte-Duclos disease with atypical vascularization--case report and review of the literature

OBJECTIVE: A case of Lhermitte-Duclos disease (LDD, dysplastic gangliocytoma) with atypical vascularization is reported. LDD is a rare cerebellar mass lesion which may be associated with Cowden's syndrome and the PTEN germline mutation. CASE MATERIAL: A 61-year-old male presented 15 years before with a transient episode of unspecific gait disturbance. Initial magnetic resonance (MR) imaging revealed a right-sided, diffuse, nonenhancing cerebellar mass lesion. No definitive diagnosis was made at that time, and the symptoms resolved spontaneously. 15 years later, the patient presented with acute onset of vomiting associated with headache and ataxic gait. MR imaging showed a progression of the lesion with occlusive hydrocephalus. The lesion depicted a striated pattern characteristic for LDD with T1-hypointense and T2-hyperintense bands, nonenhancing with contrast. After resection of the mass lesion, the cerebellar and hydrocephalic symptoms improved rapidly. The pathological examination confirmed the diagnosis of dysplastic gangliocytoma (WHO Grade I) with enlarged granular and molecular cell layers, reactive gliosis and dysplastic blood vessels. No other clinical features associated with Cowden's syndrome were present. CONCLUSIONS: This case illustrates that LDD with atypical vascularization is a slow-growing posterior fossa mass lesion which may remain asymptomatic for many years. Timing of surgical treatment and extent of resection in patients with LDD is controversial. The typical features on standard T1-/T2-weighted MR imaging allow a diagnosis without surgery in most cases. The authors believe that the decision to treat in these cases should be based on clinical deterioration.

GPI-specific phospholipase D (GPI-PLD) is expressed during mouse development and is localized to the extracellular matrix of the developing mouse skeleton

Glycosylphosphatidylinositol-specific phospholipase D (GPI-PLD) is abundant in serum and has a well-characterized biochemistry; however, its physiological role is completely unknown. Previous investigations into GPI-PLD have focused on the adult animal or on in vitro systems and a putative role in development has been neither proposed nor investigated. We describe the first evidence of GPI-PLD expression during mouse embryonic ossification. GPI-PLD expression was detected predominantly at sites of skeletal development, increasing during the course of gestation. GPI-PLD was observed during both intramembraneous and endochondral ossification and localized predominantly to the extracellular matrix of chondrocytes and to primary trabeculae of the skeleton. In addition, the mouse chondrocyte cell line ATDC5 expressed GPI-PLD after experimental induction of differentiation. These results implicate GPI-PLD in the process of bone formation during mouse embryogenesis.

Tenascin-W is found in malignant mammary tumors, promotes alpha8 integrin-dependent motility and requires p38MAPK activity for BMP-2 and TNF-alpha induced expression in vitro

Tenascins represent a family of extracellular matrix glycoproteins with distinctive expression patterns. Here we have analyzed the most recently described member, tenascin-W, in breast cancer. Mammary tumors isolated from transgenic mice expressing hormone-induced oncogenes reveal tenascin-W in the stroma around lesions with a high likelihood of metastasis. The presence of tenascin-W was correlated with the expression of its putative receptor, alpha8 integrin. HC11 cells derived from normal mammary epithelium do not express alpha8 integrin and fail to cross tenascin-W-coated filters. However, 4T1 mammary carcinoma cells do express alpha8 integrin and their migration is stimulated by tenascin-W. The expression of tenascin-W is induced by BMP-2 but not by TGF-beta1, though the latter is a potent inducer of tenascin-C. The expression of tenascin-W is dependent on p38MAPK and JNK signaling pathways. Since preinflammatory cytokines also act through p38MAPK and JNK signaling pathways, the possible role of TNF-alpha in tenascin-W expression was also examined. TNF-alpha induced the expression of both tenascin-W and tenascin-C, and this induction was p38MAPK- and cyclooxygenase-dependent. Our results show that tenascin-W may be a useful diagnostic marker for breast malignancies, and that the induction of tenascin-W in the tumor stroma may contribute to the invasive behavior of tumor cells.

Psychoedukative und bewältigungsorientierte Gruppentherapie für SchizophreniepatientInnen

Anliegen: Es sollte evaluiert werden, in wieweit Patienten mit Schizophrenie oder einer schizoaffektiven Erkrankung von einem psychoedukativen, bewältigungsorientierten Therapieprogramm profitieren können. Methode: Für die Evaluation wurde ein kontrolliertes prospektives Studiendesign herangezogen. Zum Einsatz kam in der Experimentalgruppe das “Therapiemanual zur Psychoedukation und Krankheitsbewältigung” (PKB), das neben gezielter Information über die Erkrankung und die Pharmakotherapie Strategien vermittelt, wie Frühwarnsignale erkannt und der Umgang mit ihnen erlernt werden können. Darüber hinaus werden auch Aspekte zu „gesundem“ Verhalten behandelt. Als Kontrollgruppe diente eine Patientengruppe mit supportiven Gesprächen bzw. eine Gruppe mit dem Schwerpunkt der Arbeitsrehabilitation. Um die Effekte der PKB zu evaluieren, wurden der psychopathologische Status, wissensbezogene sowie soziale Variablen zu verschiedenen Messzeitpunkten (vor der Therapie, nach Therapieende, 12 Monate nach Therapieende) erhoben. Als abhängige Variablen dienten der Wissensstand über die Erkrankung, Rehospitalisierungen, soziale Integration und Bewältigungsstrategien. Ergebnisse: 82 Patienten nahmen an der Studie teil. Sowohl in der Experimentalgruppe als auch in der Kontrollgruppe wurde eine signifikante Verbesserung des Allgemeinzustandes und der Psychopathologie beobachtet. Die Ergebnisse der Gruppen unterschieden sich insofern, dass in der Experimentalgruppe weniger Rehospitalisierungen im ersten Jahr nach Studienende vermerkt wurden und die Teilnehmer sich anderer Copingstrategien bedienten (signifikant weniger depressive Krankheitsverarbeitung und Bagatellisierung). Schlussfolgerungen: In der Behandlung von Schizophrenie können unterschiedliche Interventionen wirksam sein. Fragestellungen, welche Patienten von welcher Art der therapeutischen bzw. rehabilitativen Intervention profitieren können, sollten weiterhin Gegenstand intensiver Forschung sein.

Intraoperative hypothermia during vascular neurosurgical procedures

Increasing evidence in animal models and clinical trials for stroke, hypoxic encephalopathy for children, and traumatic brain injury have shown that mild hypothermia may attenuate ischemic damage and improve neurological outcome. However, it is less clear if mild intraoperative hypothermia during vascular neurosurgical procedures results in improved outcomes for patients. This review examines the scientific evidence behind hypothermia as a treatment and discusses factors that may be important for the use of this adjuvant technique, including cooling temperature, duration of hypothermia, and rate of rewarming.

Novel autoantigens immunogenic in COPD patients

Background Chronic obstructive pulmonary disease (COPD) is a respiratory inflammatory condition with autoimmune features including IgG autoantibodies. In this study we analyze the complexity of the autoantibody response and reveal the nature of the antigens that are recognized by autoantibodies in COPD patients. Methods An array of 1827 gridded immunogenic peptide clones was established and screened with 17 sera of COPD patients and 60 healthy controls. Protein arrays were evaluated both by visual inspection and a recently developed computer aided image analysis technique. By this computer aided image analysis technique we computed the intensity values for each peptide clone and each serum and calculated the area under the receiver operator characteristics curve (AUC) for each clone and the separation COPD sera versus control sera. Results By visual evaluation we detected 381 peptide clones that reacted with autoantibodies of COPD patients including 17 clones that reacted with more than 60% of the COPD sera and seven clones that reacted with more than 90% of the COPD sera. The comparison of COPD sera and controls by the automated image analysis system identified 212 peptide clones with informative AUC values. By in silico sequence analysis we found an enrichment of sequence motives previously associated with immunogenicity. Conclusion The identification of a rather complex humoral immune response in COPD patients supports the idea of COPD as a disease with strong autoimmune features. The identification of novel immunogenic antigens is a first step towards a better understanding of the autoimmune component of COPD.

Mammary epithelial-specific knockout of the ephrin-B2 gene leads to precocious epithelial cell death at lactation

The family of Eph receptor tyrosine kinases and their membrane bound ligands, the ephrins, are involved in a wide variety of morphogenic processes during embryonic development and adult tissue homeostasis. Receptor-ligand interaction requires direct cell-cell contact and results in forward and reverse signaling originating from the receptor and ligand, respectively. We have previously shown that EphB4 and ephrinB2 are differentially expressed during the development of the adult mammary parenchyma. Overexpression of EphB4 in the mammary epithelium of transgenic mice leads to perturbations in mammary epithelial morphology, motility and growth. To investigate the role of ephrinB2 signaling in mammary gland biology, we have established transgenic mice exhibiting conditional ephrinB2 knockout in the mammary epithelium. In homozygote double transgenic CreLox mice, specific knockout of ephrinB2 occurred in the mammary epithelium during the first pregnancy-lactating period. Abolishing ephrinB2 function led to severe interference with the architecture and functioning of the mammary gland at lactation. The morphology of the transgenic lactating glands resembled that of involuting controls, with decreased epithelial cell number and collapsed lobulo-alveolar structures. Accordingly, massive epithelial cell death and expression of involution-specific genes were observed. Interestingly, in parallel to cell death, significant cell proliferation was apparent, suggestive of tissue regeneration.

Deregulated ephrin-B2 expression in the mammary gland interferes with the development of both the glandular epithelium and vasculature and promotes metastasis formation

Eph receptor tyrosine kinases and their membrane-bound ephrin ligands play key roles during morphogenesis and adult tissue homeostasis. Receptor-ligand interactions result in forward and reverse signalling from the receptor and ligand respectively. To delineate the role(s) of forward and reverse signalling in mammary gland biology we have established transgenic mice exhibiting mammary epithelial-specific overexpression of either the native ephrin-B2 or a dominant negative ephrin-B2 mutant incapable of reverse signalling. During pregnancy and lactation overexpression of the native ephrin-B2 resulted in precocious differentiation, whereas overexpression of mutated ephrin-B2 caused delayed epithelial differentiation and in disturbed tissue architecture. Both transgenes affected also mammary vascularisation. Whereas ephrin-B2 induced superfluous but organised capillaries, mutant ephrin-B2 overexpression resulted in an irregular vasculature with blind-ending capillaries. Mammary tumours were not observed in either transgenic line, however, the crossing with NeuT transgenic animals revealed that mutated ephrin-B2 expression significantly accelerated tumour growth and imposed a metastatic phenotype.