Ventilator-associated lung injury: a search for better therapeutic targets.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) represent a continuum of injury that may arise from a number of primary insults. Localised injury may progress due to trauma from mechanical ventilation, a finding that has led to intense debate in the clinical and experimental literature over optimal ventilator management. The implementation of low tidal volume strategies has led to an improvement in outcomes; however, mortality remains unacceptably high. In the current review, ventilator-associated lung injury is examined, as it relates to the pathophysiological changes beyond direct airway trauma in ALI and ARDS, and an attempt is made to provide a historical perspective to outline potential current and future pitfalls in the use of surrogate end-points and the discovery of potential biomarkers. The systemic responses that lead to multi-organ dysfunction, the leading causes of morbidity and mortality in ALI and ARDS, are caused by pro-inflammatory signalling cascades and the activation of such diverse mediators as reactive oxygen species, immune response elements, apoptotic constituents and coagulation proteins. These areas are examined, including key mediators, and possible future areas of interest are discussed, including the potential of an "acute lung injury chip" to integrate measured surrogate biomarkers with real-time clinical information to improve patient outcomes.

Recurrent arachnoid cyst of Meckel's cave mimicking a brain stem ischaemia. Report of a rare case.

UNLABELLED: A 44-years old man developed TIA-like symptoms with dysaesthesia around the mouth, vertigo and diplopia. MRI revealed a cystic space-occupying lesion on the right Meckel's cave, which spread out into cerebellopontine angle in a further examination. Therefore surgical exploration was performed using a suboccipital approach. An arachnoidal cyst was found and removed including its wall. About three months later the patient suffered again from dysaesthesias of the right side of the face and a new MRI revealed a recurrence of the lesion, with extension into the cerebellopontine angle, too. Surgical revision was done using the same approach and the recurrent cyst was removed. Postoperatively, there were a transient hypaesthesia in the distribution area of the right trigeminal nerve and a light pulmonary embolism occurred as a complication. No symptoms have returned during an observation period of 15 months. CONCLUSION: An arachnoidal cyst must be considered as a rare cause, when a lesion is found at the Meckel's cave with intermittent clinical symptoms of a trigeminal nerve affection. As surgical treatment we favour fenestration and cyst wall resection.

The role of endothelins in the regulation of pituitary function.

The different members of the endothelin peptide family exhibit potent, long-lasting vasoconstrictive effects and thus play a central role in blood pressure regulation. However, endothelins have also been shown to modulate renal, cardiac and immune functions under physiological and pathophysiological conditions. In addition, endothelins are thought to be involved in the progression of some types of tumours. Soon after their discovery in 1988, it was shown that endothelins affect hormone release in the pituitary. Moreover, the intrapituitary production and expression of both endothelins and endothelin receptors have been described. This review summarises the present day knowledge concerning the expression and regulation of intrapituitary endothelins and their receptors. In addition, the effects of endothelins on hormone production by anterior, intermediate and posterior pituitary cell types are reviewed and their importance for pituitary physiology and pathophysiology is discussed.

A new method for surgical repair of impression fractures of the cranial vault and frontal sinus with rivet-like titanium clamps.

Conventional methods of stabilizing fragments in cranial impression fracture include the use of threads, wires, plates, etc. A new approach to facilitate this surgery is the use of titanium clamps, presented here in five cases, including one with frontal sinus fracture. Surgery was performed on admission day, with the exception of the sinus fracture. Compared with the use of mini- and microplates, the procedure was simple and short. The fixation was very rigid and the esthetic result excellent in all five cases. Skin irritation was minimal, compared with that from miniplates. Computed tomography and MRI compatibility due to artifacts are identical to those with miniplates.

[Lumbar lateral recess stenosis. Clinical symptoms, diagnostic modalities and surgical management]. / Die lumbale Rezessusstenose. Klinische Symptome, Diagnostik und operative Therapie.

BACKGROUND: In spite of its importance for lumbar radicular syndroms only a few reports about lumbar lateral recess stenosis exist in literature. Most important clinical symptom is radicular pain, which may be exercise-dependent. Confirmation of diagnosis and differentiation from disc herniation requires imaging like CT, MRI or post-myelo-CT. Surgical treatment options include selective decompression techniques like foraminotomy, medial facettectomy and undercutting as well as hemilaminectomy, laminotomy and wide laminectomy or fusion. METHOD: We treated 35 patients with selective decompression techniques. RESULTS: In the follow-up 5 up to 18 months after surgery 25 patients for themselves described the results as good or excellent. Therefore, individually tailored selective microsurgical decompression is an appropriate and successful treatment strategy for lumbar lateral recess stenosis, if conservative treatment fails.

New concepts in vascular nitric oxide signaling.

Low levels of nitric oxide (NO) control the activities of guanylate cyclase and mitochondrial respiration. Increasing NO levels interact with multiple signaling systems through the formation of peroxynitrite and other oxidation products. Signaling mechanisms linked to NO participate in the prevention of acute responses such as vasoconstriction, thrombosis and the recruitment of inflammatory cells. In contrast, processes related to vascular remodeling, and responses to injury that are associated with the progression and adaptation to disease processes, are not as well understood. Many of the opposing processes involved in these adaptations may originate from the diverse signaling mechanisms that NO and its oxidized products can regulate in a cell-specific manner in the vessel wall.

Cerebellopontine angle meningiomas (cpam)--clinical characteristics and surgical results.

INTRODUCTION: About 10% of the tumourous lesions in the cerebellopontine angle are meningiomas according to the literature. Evidently, these tumours differ from the other lesions by their clinical presentation as well as by the surgical results, which will be presented in the following article. PATIENT MATERIAL: We report on 26 patients (22 females, 4 males: age distribution 45-81 years, mean 63 years) operated on CPAM's in the last 8 years. Clinical history lasted from 2 weeks to 9 years (mean 17 months). Cerebellar symptoms were the most frequent findings (n = 22), followed by cranial nerve (V, VII, and VIII) deficits (n = 12) and signs of increased intracranial pressure (n = 7). In 3 clinically asymptomatic cases the lesion was found incidentally, and there was 1 patient with a recurrent lesion. The radiological procedures included CT-scan in 17 patients, MR-imaging in 18, MR-angiography in 2 cases and angiography in 2 cases. Hydrocephalus was demonstrated in 8 cases. Tumour size ranged from 2.8 to 7 cm (mean 4.2 cm). All patients underwent osteoclastic craniotomy with complete tumour removal. Temporary CSF-drainage was necessary in 8 cases, monitoring was done in 9 patients. RESULTS: Postoperative follow-up period ranged from 3 months to 5 years (mean 2.5 years). After 1 month, 14 patients were discharged home and 12 were transferred into other hospitals in good condition. Improvement was achieved in 19 cases, 5 patients were equal to their preoperative situation, in one case a temporary deterioration with tetraparesis and in 1 case deterioration of hearing was found. After an average follow-up of 2.5 years, 22 patients were self-sufficient without or with minimal neurological deficits at home, 2 were moderately disabled and 2 died in the meantime due to other diseases. Among the operative complications, we observed 3 CSF-fistulas, 1 requiring surgical reexploration as well as 1 rebleeding and additionally 1 meningitis. Non-surgical complications were found in 5 patients. CONCLUSIONS: Cerebellar ataxia and impairment of hearing are the clinical leading symptoms of CPAM's. At diagnosis, these tumours are impressively large, but the operative results are very favourable with low morbidity and excellent prognosis.

Anterior cervical spine fusion using RABEA-Titan-Cages avoiding iliac crest spongiosa: first experiences and results.

INTRODUCTION: In cervical discectomy using the ventral approach both, the necessity of replacement of the removed disc space itself as well as the material of the graft, if used, is still a matter of discussion. New approaches are titan-cages, usually filled with autologeous spongiosa. We present in the following study our first experiences using the hollow RABEA-Titan-Cages without filling with spongiosa to avoid the iliac crest complications. MATERIAL AND METHODS: 63 patients (33 male, 30 female, age 25-79 years, mean 52 years) were operated on a degenerative cervical disc herniation by ventral discectomy and replacement of the disc by the cage for fusion. The mean follow-up was 8 months. The preoperative symptoms were radiculopathies (n = 43) and myelopathies (n = 20). The diagnosis was confirmed by CT, MRI, myelography/CT and functional plain x-ray examination excluding instability. Level of the disc herniation: C3/4 n = 3, C4/5 n = 4, C5/6 n = 21, C6/7 n = 23, C7/Th1 n = 5, and 7 cases with 2 levels. In 30 cases we found hard discs, in 13 cases soft discs and in 20 patients combined lesions. All patients were intra- and postoperatively controlled by x-ray examination. RESULTS: Free of complaints were 17 patients, a marked improvement was found in 33 cases, a minor improvement in 10 cases, from those 4 patients additionally suffered from depression or alcoholism and 1 patient had a trauma in the history. 3 patients showed no change. Minor neck pain was reported in 5 cases. The mean postoperative hospitalisation was 8 days. Surgery related complications: temporary radicular palsies n = 5, hoarseness/problems with swallowing n = 5. In 2 cases (3%) with osteoporosis surgical revision of the cage was necessary (one case with ventral dislocation and one case with recurrent nerve root compression). In all other cases the x-ray control proved the correct placement of the cages intra- and postoperatively on discharge. CONCLUSION: For the anterior cervical fusion, the hollow RABEA-Titan-Cages present good clinical results and help to avoid complications from the iliac crest donor site. For long-term results, a longer follow-up and a increased number of patients is required.

A rare fatal course of disease in a patient with spontaneous pituitary apoplexy. Case report and literature review.

A rare fatal course of a spontaneous pituitary apoplexy is described and its histological and pathophysiological causes are discussed. A review of the literature gives an overview of the historical and epidemiological data.

The mapping and continuous monitoring of the intrinsic motor nuclei during brain stem surgery.

A comprehensive technique was developed for continuous electrophysiological monitoring of intrinsic brain stem motor function during surgery to remove space-occupying lesions in the fourth ventricle and brain stem. The technique is analogous to that used during surgery in the cerebellopontine angle; motor nuclei and peripheral pontine fiber tracts of Cranial Nerves III-XII are identified by the electrical stimulation of structures in the operative field and the evaluation of the compound muscle action potentials recorded from the corresponding muscles of the head. Nerve function is monitored continuously by recording the ongoing electromyographic activity in these same muscles. Broadcasting electromyographic responses through a loudspeaker gives the surgeon immediate feedback on the status of the motor nuclei being monitored. Advantages of this technique include 1) the positive, objective identification of the nuclei and fiber tracts; 2) the continuous feedback on the status of these structures; 3) a safe approach through the fourth ventricle to the lesions in the brain stem; 4) the positive identification of the boundaries between the neoplasm and the motor structures of the rhomboid fossa; and 5) a warning to the surgeon of potentially harmful nerve manipulations (contact, dissection, transection) during surgery. After this technique was used in 16 consecutive operations to remove cavernomas (n = 9), gliomas (n = 4), and other types of tumors (n = 3), surgical and neurological results showed the method to be reliable and simple to perform.

Intracavitary treatment of intrasellar cystic craniopharyngeomas with 90-Yttrium by trans-sphenoidal approach--a technical note.

Intracavitary irradiation of intrasellar cystic craniopharyngeomas by stereotactic cyst puncture and injection of radioactive solutions is not yet possible. Therefore we designed a new method which allows such intracavitary irradiation. Its principle is a transphenoidal approach with only a small bony opening of the sella floor, followed by cyst puncture, exclusion of cyst leakage by Metrizamid injection under x-ray control, injection of Y-90-colloid solution at a dosage which delivers a radiation of 200 Gy to the cyst wall, and finally tight closure of the puncture site using fibrin glue and gelfoam. This method has been used in three patients with good results (follow-up 12-15 months) and without complications. Even though long-term follow-up is not yet available, our preliminary results suggest that this method will be useful for future patients with intrasellar cystic craniopharyngeomas.

Endothelin expression in normal human anterior pituitaries and pituitary adenomas.

Endothelins (ETs) are important regulators of growth and function in many endocrine tissues. This study was designed to verify the expression of ETs in a series of normal human pituitaries and pituitary adenomas. We examined 13 normal pituitaries and 58 pituitary adenomas for the presence of immunoreactive (ir) ET-1 and ET-3. No ir-ET-1 was detected in any of the 13 normal pituitaries, whereas ir-ET-3 was observed in 4 of 13 (31%) cases. In contrast, 48% (28 of 58) of pituitary adenomas display immunoreactivity for ET-1, whereas 31% (18 of 58) show immunoreactivity for ET-3. With respect to the type of tumors, staining was as follows: nonfunctioning adenomas: ET-1, 14 of 33; ET-3, 9 of 33; somatotropinomas: ET-1, 8 of 16; ET-3, 6 of 16; corticotropinomas: ET-1, 5 of 5; ET-3, 2 of 5; and prolactinomas; ET-1, 1 of 4; ET-3, 1 of 4. Using double immunostaining, we found the colocalization of ET-3 in normal pituitaries and of ET-1 and ET-3 in pituitaries adenomas in each hormone-secreting cell. In Cushing adenomas, ET-1 was coexpressed in corticotropic cells in all 5 cases (100%). In the same tumors, by reverse transcriptase polymerase chain reaction, we investigated the presence of ET-1 and ET-3 messenger ribonucleic acids and found that they are expressed, respectively, in 18 of 21 and 7 of 11 tumors examined. Our findings demonstrate that pituitary adenomas frequently display ET-1 as well as ET-3 immunoreactivity, in contrast to normal pituitaries, in which only ET-3 was found.(ABSTRACT TRUNCATED AT 250 WORDS)

The treatment of spondylotic cervical myelopathy by ventral discectomy. Long term results on 121 patients.

The pathophysiology of spondylotic cervical myelopathy is still a matter of discussion. This paper presents a series of 126 patients operated on using a ventral approach. In 47% of the patients only a spondylotic narrowing of the spinal canal was present and in 35% an additional disc herniation was found. In 13% of the cases however a soft disc without spondylotic spures was found and in 5% a dislocation of vertebral bodies. We found a marked male preponderance of 77%, mean age was 51.6 years, ranging from 25-50 years. Most patients were operated on at the levels of C4/5 and C5/6. Observation time covered a period of 3-10 years. The outcome was rated relatively to the preoperative degree of disablement using a questionnaire for the patients and their family doctors. We found a marked difference in the answers, especially in rating deterioration, which was stated by patients in 34%, by physicians only in 12%. Another finding was the time-related outcome. We found best results with 75% improvement and 5% deterioration between 3-6 months postoperatively, with increasing time the results decreased to 33% improvement, 33% identical statys and in 33% a deterioration related to the preoperative status must be noted.

Diagnosis and results of different treatment regimens in patients with spinal abscesses.

Bacterial abscesses involving the spinal canal are associated with a high morbidity and mortality. Most frequently, these lesions are found in the epidural, rarely in the subdural space. In this report, our clinical material consists of a series of 16 patients treated during the last seven years. The clinical presentation included local neurological signs (back pain, para-/tetraparesis, bladder dysfunction), disturbances of consciousness (ranging from drowsiness to deep coma) and general inflammatory signs (meningism, fever). All patients presented with risk factors (septic foci, chronic diseases, and iatrogenic causes). Laboratory investigations revealed typically pathological blood sedimentation rate, leucocytosis and CSF-pleocytosis. Radiologically, the diagnosis was confirmed by myelography, CT and preferably MRI. The abscesses were located epidurally in 14 and subdurally in 2 cases. The surgical treatment included laminectomy, or multiple flavectomies in extensive lesions. Drainage systems (either simple silicon outflow drains or suction-/irrigation systems) were installed in all cases, as well as antibiotic treatment. Results of treatment: Following an observation period of 0.5-6 years, we found complete recovery in six (38%) cases, six (38%) others were mildly disabled and four (25%) patients died. Focussing on the results of the two different drainage systems, we found a statistically significant superiority of the inflow-/outflow system. Complications included mandatory re-exploration, post-inflammatory hydrocephalus, syringomyelia, spinal instability, surgical treatment of peripheral septic foci and therapy resistant septicaemia. In conclusion, we propose that spinal epi- or subdural abscesses require surgical evacuation, using a suction-/irrigation drainage system, as well as antibiotic and intensive care treatment.

An association of the RB gene with osteosarcoma: molecular genetic evaluation of a case of hereditary retinoblastoma.

A 24-year-old male patient with hereditary retinoblastoma and a poorly differentiated osteoblastic osteogenic sarcoma was found to carry a mutant RB1 allele in all cells. This findings was most likely a point mutation or microdeletion because Southern blot analysis of peripheral blood DNA failed to disclose any structural aberration of the RB1 gene. A somatic mutation (deletion) affecting the other allele was found in the osteosarcoma cells. Management of tumor by external radiotherapy in early age is questioned because the effect of irradiation is to significantly increase the total incidence of second tumors above the already high incidence in non-irradiated patients.

Surgical observations in extremely lateral lumbar disc herniation.

About 10% of lumbar disc herniations are localized in an extreme lateral position referred to as "extracanalicular". The clinical syndrome is a typical one with compression signs of the lateral, extra-foraminal nerve root and minimal lumbar pain. A reliable diagnosis can be made only since high resolution spinal computed tomography has become available. Surgical treatment will be rendered difficult by the "hidden" localisation of the disc fragments. A total number of 15 patients has been operated on in our department during the last year. In 10 patients, we used the lateral microsurgical approach proposed by REULEN, in five cases a combined procedure with lateral sequestrotomy and medial nucleotomy. In the first group, re-sequestration occurred in three cases and further surgery including medial nucleotomy was performed then. A good result with remission could be achieved in 13 cases, whereas in two cases with additional spondylolisthesis, lumbar back pain continued, but the radicular symptoms were reduced.

Non-specific granulomas of the pituitary: report of six cases treated surgically.

Granulomatous lesions of the pituitary gland are very rare. In our department, six patients with these lesions have been operated on since 1988. The records of these patients were analysed and are reported in the following. Three of the patients were admitted because of severe and rapid development of visual disturbances caused by a suprasellar extending lesion. Endocrinological examination most often found posterior lobe insufficiency, was followed by anterior lobe dysfunction. CT and MRI demonstrated a cystic lesion with semiliquid content, where mild contrast enhancement of the walls of the tumor was observed in all cases. Surgery was performed using the transphenoidal approach. Rapid relief of visual impairment was observed in the three patients with chiasmal compression. In one patient, recurrent chiasm syndrome due to lesion regrowth required additional surgery with transcranial resection of the capsule. Unfortunately, visual impairment persisted postoperatively in one eye. Endocrinological follow-up demonstrated unchanged or even worsened pituitary functions in all cases. Our study revealed no consistent predictive preoperative finding. Therefore, we consider an indication for decompression surgery to be given in all patients with chiasmal syndrome and for diagnostic surgery for all patients with intrasellar lesions.

Benign symptomatic lesions of the pineal gland. Report of seven cases treated surgically.

Seven patients with non-neoplastic symptomatic lesions of the pineal gland have been operated on in our department since 1988. Clinical symptoms were slight and there were intermittent signs of a space occupying lesions in the quadrigeminal area, i.e. visual and gait disturbances. In three patients, obstructive hydrocephalus with related symptoms was found. Diagnosis was confirmed by use of MRI in sagittal planes, revealing a cystic lesion in five and a solid tumour in two patients. All patients were operated on without complications using an infratentorial supracerebellar approach. Histological examination showed glial cysts of the pineal gland in five patients. In the two solid specimens, normal pineal tissue was found. These lesions seem to be of special interest, as the only pathological property are their size: Both lesions--"too large pineal glands"--caused obstruction of the outlet of the third ventricle with subsequent hydrocephalus. Surgical treatment was curative in all cases with prompt relief of the symptoms. Clinical symptoms and signs, diagnostic and pathological findings, as well as the surgical results of these cases will be reported.

Nd:YAG-laser in the microsurgery of frontobasal meningiomas.

Forty-three patients with big frontobasal meningiomas underwent a microsurgical removal of the tumor. The 1.32 microns Nd:YAG-laser has proved useful in this prospective series particularly with the contactless shrinkage of the tumors and the necrotization of the dural and bony attachments. Tumor shrinkage was achieved by radiating the tumor surface with the Nd:YAG-laser. This technique facilitated the microsurgical dissection and reduced the blood loss by half. The Nd:YAG-laser necrotization of the dural and bony attachments reduced the recurrence rate following grade two resections from 20% to zero. The postoperative quality of life was excellent with a complete rehabilitation in 76% of the patients. The use of the 1.32 microns Nd:YAG-laser improved significantly the results of microsurgery for frontobasal meningioma.

Surgical treatment of patients with midline arachnoid cysts.

Usually, arachnoid cysts are found in the Sylvian fissure (about 85%); midline arachnoid cysts are rare. Typical clinical symptoms are increased intracranial pressure, caused by a concomitant hydrocephalus, as well as visual and/or endocrinological disturbances. Six patients were examined, treated with one of two different surgical methods (cyst shunting or open treatment, either craniotomy/cyst membrane resection or laser endoscopy). Better results were observed following open treatment methods.