Apoptosis induction and reduced proliferation in human osteoblasts by rhBMP-2, -4 and -7.

BACKGROUND: The role of bone morphogenetic proteins (BMPs) in bone healing has been demonstrated in numerous in vivo animal models. BMP-2, -4 and -7 have also been shown to stimulate the differentiation of human and animal stem cells into osteoblasts in vitro. There are, however, contradictory reports of BMPs causing apoptosis and inhibition of proliferation of osteoblastic cells. Therefore, a more complete understanding of the effects of BMP-2, -4 and -7 on human osteoblasts is required. METHODS: Cells of the immortalised human fetal osteoblastic line hFOB 1.19 were exposed to recombinant human (rh) BMP-2, -4 and -7. In addition, primary human osteoblasts were exposed to rhBMP-7. Cell proliferation was measured using a colorimetric assay. Apoptotic cells were detected using the TUNEL assay. RESULTS: The hFOB cells exposed in a dose-dependent manner to rhBMP-2, -4 and -7 had significantly lower rates of proliferation than non-treated cells, (p<0.01 for rhBMP-2, -4 and -7). The proliferation results for rhBMP-7 were replicated using primary human osteoblasts. Additionally, rhBMP-2, -4 and -7 induced a significantly higher rate of apoptosis in the hFOB cells, with a temporal and dose-dependent pattern (p<0.05), irrespective of the presence of serum growth factors. CONCLUSIONS: Despite interest in the potential clinical application of BMPs to improve bone healing, further studies are necessary to determine their full biological function before they can be used confidently in humans.

Treatment of Periprosthetic Femoral Fractures Vancouver Type B2: Revision Arthroplasty Versus Open Reduction and Internal Fixation With Locking Compression Plate.

INTRODUCTION: The Vancouver algorithm recommends revision arthroplasty (RA) for Vancouver type B2 (VTB2) fractures. However, open reduction and internal fixation (ORIF) using locking compression plates (LCP) may be a valid and less invasive alternative treatment. MATERIALS AND METHODS: Between January 2007 and March 2017, we retrospectively recruited all patients treated with either ORIF with LCP or RA for VTB2 fractures in our clinic. All of the following were reviewed: the length of hospital stay, the operating time, the need for blood transfusions during and/or after surgery, implant-related and patient-related complications, need for revision surgery, and the radiological outcome. Additionally, the functional outcome was investigated. RESULTS: Fifty-nine patients were recruited. Thirty-five (59.3%) patients underwent RA, while 24 (40.7%) patients received ORIF with LCP. The median surgical time was 137.50 minutes in the LCP group compared to 160.00 minutes in the RA group (P = .051). Three (12.5%) patients in the LCP group and 10 (28.6%) patients in the RA group experienced an implant-associated complication (P = .131). Patient-related complications occurred in 3 (12.5%) patients in the LCP group versus 6 (17.1%) patients in the RA group (P = .628). The mean preoperative Parker mobility score was 9 points in both groups and decreased in both groups to a mean of 5 points in the LCP and 7 points in the RA group. DISCUSSION: Open reduction and internal fixation with LCP seems to be a less invasive procedure for VTB2 fractures in comparison to RA. It is a bone-sparing procedure that can be advantageous for further revision operations. Moreover, some fractures can only be anatomically reduced by ORIF with LCP, whereas for proximal fractures with a radiologically unambiguously loosened stem RA might be advantageous. CONCLUSION: In line with previously published studies, our data suggest that ORIF using LCP is a valid treatment option for VTB2 fractures.

Contemporary damage control surgery outcomes: 80 patients with severe abdominal injuries in the right upper quadrant analyzed.

BACKGROUND: Damage control laparotomy (DCL) is a well-established surgical strategy in the management of the severely injured abdominal trauma patients. The selection of patients by intra-abdominal organs involvement for DCL remains controversial. The aim of this study was to assess the injury to the abdominal organs that causing severe metabolic failure, needing DCL. METHODS: Severely injured abdominal trauma patients with a complex pattern of injuries were reviewed over a 52-month period. They were divided into DCL and definitive repair (DR) group according to the operative strategy. Factors identifying patients who underwent a DCL were analyzed and evaluated. RESULTS: Twenty-five patients underwent a DCL, and 55 patients had DR. Two patients died before or during surgery. The number and severity of overall injuries were equally distributed in the two groups of patients. Patients who underwent a DCL presented more frequently hemodynamically unstable (p = 0.02), required more units of blood (p < 0.0001) and intubation to secure the airway (p < 0.0001). The onset of metabolic failure was more profound in these group of patients than DR group. The mean Basedeficit was - 7.0 and - 3.8, respectively, (p = 0.003). Abdominal vascular (p = 0.001) and major liver injuries (p = 0.006) were more frequently diagnosed in the DCL group. The mortality, complications (p < 0.0001), hospital (p < 0.0001), and ICU stay (p < 0.009) were also higher in patients with DCL. CONCLUSION: In severely injured with an intricate pattern of injuries, 31% of the patients required a DCL with 92% survival rate. Severe metabolic failure following significant liver and abdominal vascular injuries dictates the need for a DCL and improves outcome in the current era.

Pharmacological blocking of the osteoclastic biocorrosion of surgical stainless steel in vitro.

In vitro studies suggest that human osteoclasts (OC) are able to corrode surgical stainless steel 316L (SS). The aim of this study was to investigate whether osteoclastic biocorrosion can be blocked pharmacologically. Human OCs were generated in vitro from peripheral blood monocytic cells (PBMCs) in the presence of OC differentiation cytokines. The osteoclastic viability, differentiation, and resorptive function (on both bone and SS) were assessed using standard colorimetric cell viability assay 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenil)-2H-tetrazolium, inner salt (MTS), fluorescence microscopy, tartrate-resistant acid phosphatase expression (flow cytometry), and scanning electron microscopy. OCs cultured on SS were exposed to nontoxic concentrations of bafilomycin A1, amiloride hydrochloride, or zoledronic acid. The extent of biocorrosion was quantified using atomic emission spectrometry (to measure the concentration of metal ions released into the supernatant) and scanning electron microscopy. PBMCs differentiated into mature and functional OC in the presence of all the drugs used. Osteoclastic resorption of SS was noted with differences in the resorption pattern for all drug treatments. Under the drug treatments, single areas of osteoclastic resorption were larger in size but less abundant when compared with positive controls. None of the drugs used were able to inhibit osteoclastic biocorrosion of SS.

[Cervicobrachialgia - an update under special consideration of the surgical management]. / Zervikobrachialgie - ein Update unter besonderer Berücksichtigung der chirurgischen Therapie.

The classic cervicobrachialgia results acutely from cervical nerve root compression by disc herniation or subacutely by radicular compression after progressive spondylotic changes of the cervical spine. The clinical presentation includes local and radiating pain syndromes that can be accompanied by sensorimotor deficits. Besides the medical history and a targeted clinical examination, supplementary radiographic means should be undertaken to confirm diagnosis. If no urgent surgical indication exists, conservative therapy should be initiated. However, with varying results of conservative and surgical therapy, chronic impairment can occur.

[Inferior vena cava thrombosis after laparoscopy]. / Thrombose der Vena cava Inferior nach Diagnostischer Laparoskopie.

HISTORY AND FINDINGS: A previously healthy 43-year-old woman was admitted because of pain in the lower abdomen. Abdominal and transvaginal ultrasound revealed a cystic structure in the right ovary, providing the indication for an exploratory laparoscopy. A hemorrhagic corpus luteum was enucleated. Laboratory tests had merely shown a raised C-reactive protein level and marginally elevated leukocytes. A family history of thrombotic episodes had been elicited. FURTHER COURSE, DIAGNOSIS AND TREATMENT: Although heparin had been applied increasing swelling developed in both thighs and lower legs at day six, indicating thrombosis of the inferior vena cava. Laboratory tests revealed a mutation in factor V (Leiden). Computed tomography showed complete thrombotic IVC occlusion. Thrombolytic treatment with recombinant tissue plasminogen was initiated, direct thrombus aspiration attempted and a filter inserted in the IVC. Low molecular heparin was infused, replaced by oral anticoagulation with phenprocoumon. Subsequent Doppler ultrasound examination demonstrated almost complete resolution of the thrombus, except for a few small residual thrombi. CONCLUSION: This case demonstrates that even minor laparoscopic interventions carry the risk of an IVC thrombosis as a late complication, indicating appropriate measures to prevent thrombosis.

[Deep brain stimulation - options and limits]. / Tiefe Hirnstimulation - Möglichkeiten und Grenzen.

Deep brain stimulation (DBS) is meanwhile an established procedure. It has been employed for several neurological diseases with impressive therapeutic responses to some extent. Stimulation of the ventral intermediate nucleus of the thalamus can distinctively improve tremor associated with essential tremor or Parkinson disease. Similarly, stimulation of the subthalamic nucleus or the globus pallidus internus can substantially diminish bradykinesia, rigidity, and tremor. Additionally, by means of a reduced dopaminergic therapy, it can lead to an improvement of the L-Dopa induced dyskinesias in patients with Parkinson disease. In recent years, DBS has also been used for other neurological and psychiatric diseases. Yet, the exact mechanism of action on a neuronal level remains uncertain. Regardless of the underlying disease and the surgical electrode positioning, a meticulous patient selection and correct indication is of paramount importance for the therapeutic success.

[Intracerebral haemorrhage - when is a surgical treatment reasonable?]. / Intrazerebrale Blutung - wann ist eine chirurgische Behandlung sinnvoll?

Intracerebral haemorrhages (ICH) are responsible for 10-17% of all strokes and are associated with a high mortality and morbidity. More than 50% of the primary cases of ICH are associated with an underlying arterial hypertension and up to 30% with a cerebral amyloidosis. In supratentorial ICH, primary treatment generally should be conservative, as clinical studies could not show favourable outcomes after surgical haematoma evacuation. However, in patients with infratentorial haemorrhages and neurologic deterioration, early surgical evacuation should be considered. Modern therapeutic strategies and the focus of current and recent clinical research include early haemostasis, improvement of intensive care, and less invasive neurosurgical interventions, with the aim to reduce secondary brain damage. This review provides an overview of the clinical presentation of ICH and includes up-to-date recommendations concerning diagnostic and therapeutic options.

[The lumbar disc herniation - management, clinical aspects and current recommendations]. / Lumbaler Bandscheibenvorfall - Management, klinische Aspekte und aktuelle Empfehlungen.

Lumbar disc herniation has a high prevalence and strong social-medical impact. Patients suffer from lower back pain that radiates from the spine. Loss of sensation or paresis adds to the clinical picture. The diagnosis should be confirmed by imaging in patients considered for surgery. High remission rates initially warrant conservative treatment (adequate analgesia and physiotherapy) in many patients. If this treatment does not lead to significant alleviation within 5-8 weeks, surgery should be performed to reduce the risk of chronic nerve affection. Posterior interlaminar fenestration is the intervention primarily conducted for this diagnosis. A relapse in the same region occurs in up to 10% of patients after months through years, which sometimes necessitates a reoperation if symptoms are pertinent.

[Adult syringomyelia - a syndrome of different origins]. / Die Adulte Syringomyelie - ein Krankheitsbild mit Verschiedenen Ursachen.

Syringomyelia describes an intra-medullary cyst in the spinal cord. In the adult patient, the pathology mostly results from Chiari-I-malformation or from severe spinal trauma. The clinical picture varies broadly, but symptoms often include pain and progressive neurologic deficits. During the clinical course, muscular atrophy and loss of pain and temperature sensation may develop in the affected region. Today, magnet resonance imaging helps to detect syringomyelia at an early stage. The interdisciplinary therapeutic approach includes an adequate pain treatment and physiotherapy, in selected cases a surgical intervention by an experienced surgeon. If not treated surgically, most symptomatic patients experience progressive neurologic deficits that may lead to severe paragplegia and chronic neuropathic pain.

[Infected urachal cyst in adulthood: case report and literature review]. / Infizierte Urachuszyste im Erwachsenenalter : Fallvorstellung und Literaturübersicht.

Normally, the urachus is obliterated at the latest in early infancy and degenerates to a fibrous band extending from the bladder to the umbilicus. Urachal anomalies may develop through an absent or incomplete obliteration, which more commonly cause clinical problems in children. Urachal cysts (UC) represent the most common form in adulthood. They most likely remain asymptomatic until complications occur. We report the case of a 32-year-old man with abscess formation in the abdominal wall as a complication of an infected ruptured UC.

[Craniopharyngioma--a "geographical malignant" tumour]. / Das Kraniopharyngeom--ein "geographisch maligner" Tumor.

The craniopharyngioma is a rare dysontogenetic tumour that originates from either scattered cells of the craniopharyngeal duct or from metaplastically mutated anterior pituitary parenchyma cells. Despite being classified as a WHO-Class-I tumour, the histologically benign craniopharyngioma may display an aggressive behaviour. Like other congenital tumours, it usually becomes manifest within the first two decades of life. Patients typically complain of headache and a chiasma syndrome with bitemporal hemianopsy may develop depending on tumour localisation. In children, anterior pituitary insufficiency often manifests as growth restriction. Additionally, diabetes insipidus and other hormonal disturbances may develop. Therapeutically either radical total removal or subtotal resection in combination with postoperative radiation is recommended. In cystic tumors, stereotactic cyst drainage and adjuvant radiation may be a possible alternative. The prognosis is best in patients who are diagnosed early.

[Carpal tunnel syndrome--modern diagnostic and management]. / Karpaltunnelsyndrom - moderne Diagnostik und Management.

The carpal tunnel syndrome is the most common entrapment neuropathy (about 3% of the adults are affected). It is characterized by pain and paresthesia along the distribution of the median nerve. Thenar muscle atrophy with corresponding muscle weakness is a late manifestation of advanced disease. Electrophysiological tests are helpful in suggesting the diagnosis. An imaging with a magnetic resonance tomography may be used in the diagnosis of atypical cases. Ergonomic manoeuvres, oral steroids and steroidal injections may alleviate symptoms in mild cases. Surgical decompression of the carpal tunnel is the classical treatment of severe cases as well as for those who do not respond to conservative treatment. After surgery patients usually show excellent results. The following article discusses clinical aspects, diagnosis and current therapeutic options.

[Trigeminal neuralgia - pathophysiology, clinical aspects and treatment]. / Trigeminusneuralgie - Pathophysiologie, klinische Aspekte und Therapie.

The trigeminal neuralgia is characterised by paroxysmal appearing fulgurous stabbing pain. Its medical condition is caused through a local-circumscribed demyelinisation of the trigeminal nerve with consecutive conduction of salting impulses on afferent pain fibres. It is essential to differentiate the symptomatic from the idiopathic trigeminal neuralgia. As primary management, a pharmacological treatment with anticonvulsants is recommended in order to attenuate the ectopic-generated pain impulses. Different neurosurgical procedures are available in cases of resistance to therapy. Thereby, causal surgery in form of microvascular decompression is not only the operative treatment of choice, but because of the excellent results also a fundamental support of the theory of vascular compression. A comprehensive knowledge about diagnosis and management of trigeminal neuralgia is essential to treat patients efficiently and successfully. This synopsis summarises the current recommendations concerning diagnostics and therapeutic options.

[Metal ions: important co-players in aseptic loosening]. / Metallionen: Wichtige Mitspieler in der aseptischen Lockerung.

AIM: The aims of this review were to discuss the different mechanisms of biocorrosion of orthopaedic metal implants in the human body, as well as the effects of the released metal ions on bone metabolism and the immune system in regard to their involvement in the pathophysiological mechanisms of aseptic loosening and metal hypersensitivity. Implant failure due to aseptic loosening is thought to occur in about 10-15% of cases. METHODS: A review of the literature (using PubMed with the search terms: biocorrosion, metal ions and bone metabolism) was performed. Additionally, we discuss our research results in the field of aseptic loosening. RESULTS: Despite a great effort in developing new implants, metal devices used in orthopaedic and trauma surgery remain prone to biocorrosion by several mechanisms including the direct corrosion by osteoclasts, leading to the production of significant amounts of wear particles and metal ions. In addition to the well documented increased osteolytic activity caused by large (in the nanometer range) wear particles, increasing evidence strongly suggests that the released metal ions contribute to the pathophysiological mechanism of aseptic loosening. Metal ions stimulate both the immune system and bone metabolism through a series of direct and indirect pathways leading to an increased osteolytic activity at the bone-implant interface. CONCLUSION: To date, revision surgery remains the only option for the treatment of a failed orthopaedic implant caused by aseptic loosening. A better understanding of the complex pathophysiological mechanisms (including the effects caused by the released metal ions) of aseptic loosening may have a significant potential in developing novel implants and therapies in order to reduce the incidence of this complication.

[Aneurysmal subarachonid haemorrhage]. / Aneurysmatische Subarachnoidalblutung.

The most characteristic symptom of an aneurysmal subarachnoid haemorrhage (aSAH) is a sudden onset of severe headache, which can be accompanied by meningism, impaired consciousness, and vegetative symptoms. A cerebral CT scan is the initial diagnostic tool of choice if aSAH is suspected. The localisation and morphology of the aneurysm is depicted in a CT-angiography and/or conventional panangiography. Until definitive exclusion of the aneurysm by either microsurgical clipping or endovascular coiling, rebleeding should be avoided implicitly. The postoperative phase, especially in patients with severe aSAH is embossed with the occurrence of disease-specific complications (cerebral vasospasm, intracranial hypertension, seizure disorder, hydrocephalus) and consecutively increased risk for secondary brain injury. Furthermore, many patients present systemic complications such as electrolyte disturbances and cardiac dysfunctions. Early identification and therapy of cerebral and systemic complications are very important in order improve functional outcome.

[Glioblastoma multiforme--new hope due to modern therapeutical approaches]. / Glioblastoma multiforme--Neue Hoffnungen dank moderner Therapieansätze.

Glioblastoma multiforme (GBM) is the most frequently encountered malignant cerebral tumor. Despite significant improvements in the treatment of GBM, this disease remains associated with a high morbidity and mortality, with more than half of all affected patients dying within the first year after diagnosis. Typical symptoms include focal neurological symptoms, seizures, personality changes and neurocognitive symptoms. GBM can be identified by means of cerebral imaging modalities and subsequently confirmed histopathologically through biopsy or resection. At present, surgical resection followed by radiotherapy with concomitant chemotherapy with temozolomide and subsequent adjuvant chemotherapy with temozolomide is considered the standard therapy for patients with GBM. Currently, many interdisciplinary studies with glioblastoma patients are accomplished with the aim to further improve the prognosis of the affected patients.

[Idiopathic normal pressure hydrocephalus]. / Idiopathischer Normaldruckhydrozephalus.

Normal pressure hydrocephalus (NPH) is characterized by the classic triad of symptoms including gait disturbance, urinary incontinence, and dementia. Gait impairment represents the cardinal symptom. NPH is associated with a radiological verifiable ventriculomegaly in the absence of elevated cerebrospinal fluid (CSF) pressure. Because many patients do not present with classical clinical and radiological findings, its diagnosis and management represents a challenge for the general practitioner, neurologist and neurosurgeon. Various supplemental preoperative tests, including lumbar CSF tap test or CSF outflow resistance determination, can improve the accuracy of predicting a response to surgical intervention. CSF shunt results in significant symptoms in the majority of appropriately evaluated patients. The following article discusses clinical aspects, diagnosis and current therapeutic options.

[Chronic low Back Pain - A Dreaded Vicious Circle!]. / Chronische Kreuzschmerzen - Ein gefürchteter Circulus vitiosus!

Up to 10% of patients with low back pain develop chronic low back pain. By definition, this is a pain that has persisted for longer than three months. Patients with chronic low back pain suffer from a disease, which has serious effects on the psycho-social and physiological integrity of the persons concerned. Pain syndromes of the lumbar region are among the greatest health care system problems in industrialised countries with direct and indirect annual costs of 150 to 250 billion Swiss francs. Despite intensive treatment some patients remain symptomatic. Out of it results a complaint-driven functional under-utilisation, which leads to an alleviation of the performance and increased inactivity - the beginning of a vicious circle. A multimodal treatment concept including physio- and psychotherapy, supported by a targeted medicamentous therapy, normally improves physical functions and achieves a significant discomfort reduction. If resistance to therapy persists, it is suggestive to consider precociously minimal-invasive or invasive therapeutic options.

[Fluorescence guided resection of malignant brain tumors - breakthrough in the surgery of brain tumors]. / Fluoreszenzgestützte Resektion bösartiger Hirntumoren - Durchbruch bei der Hirntumor-Operation.

Malignant gliomas, among others the glioblastoma multiforme, are the most frequent brain tumors. The glioblastoma itself represents the most unfavorable tumor. In Switzerland, about 450 humans contract a glioblastoma each year. The median survival time is under 12 months, thus the prognosis is dismal despite a combination of surgery, radiotherapy and chemotherapy. Surgical resection presents the major constituent in the management of patients with a glioblastoma. Postoperative radio- and chemotherapy have beneficial effects on the survival time and quality of life. Surgical removal of glioblastomas is challenging due to their infiltrative growth pattern. Therefore, the target extent of resection can only be achieved partially. For some time now, a new in Germany developed method is used in the Neurosurgical Clinic of the Cantonal Hospital in St. Gallen: The 5-ALA-guided microsurgical resection method allows a targeted and secure surgical resection of the tumor. A preoperative administered substance colors the tumor and makes it better visible for the neurosurgeon. Consequently, the healthy brain tissue can be better distinguished from the tumor. This permits not only a larger complete surgical resection of the tumor but also minimizes the resection of healthy tissue.