Activation of B-Raf and regulation of the mitogen-activated protein kinase pathway by the G(o) alpha chain.

Many receptors coupled to the pertussis toxin-sensitive G(i/o) proteins stimulate the mitogen-activated protein kinase (MAPK) pathway. The role of the alpha chains of these G proteins in MAPK activation is poorly understood. We investigated the ability of Galpha(o) to regulate MAPK activity by transient expression of the activated mutant Galpha(o)-Q205L in Chinese hamster ovary cells. Galpha(o)-Q205L was not sufficient to activate MAPK but greatly enhanced the response to the epidermal growth factor (EGF) receptor. This effect was not associated with changes in the state of tyrosine phosphorylation of the EGF receptor. Galpha(o)-Q205L also potentiated MAPK stimulation by activated Ras. In Chinese hamster ovary cells, EGF receptors activate B-Raf but not Raf-1 or A-Raf. We found that expression of activated Galpha(o) stimulated B-Raf activity independently of the activation of the EGF receptor or Ras. Inactivation of protein kinase C and inhibition of phosphatidylinositol-3 kinase abolished both B-Raf activation and EGF receptor-dependent MAPK stimulation by Galpha(o). Moreover, Galpha(o)-Q205L failed to affect MAPK activation by fibroblast growth factor receptors, which stimulate Raf-1 and A-Raf but not B-Raf activity. These results suggest that Galpha(o) can regulate the MAPK pathway by activating B-Raf through a mechanism that requires a concomitant signal from tyrosine kinase receptors or Ras to efficiently stimulate MAPK activity. Further experiments showed that receptor-mediated activation of Galpha(o) caused a B-Raf response similar to that observed after expression of the mutant subunit. The finding that Galpha(o) induces Ras-independent and protein kinase C- and phosphatidylinositol-3 kinase-dependent activation of B-Raf and conditionally stimulates MAPK activity provides direct evidence for intracellular signals connecting this G protein subunit to the MAPK pathway.

Isolated glossopharyngeal and vagus nerves palsy due to fracture involving the left jugular foramen.

This report describes a case of delayed post-traumatic glossopharyngeal and vagus nerves palsy (i.e. dysphonia and swallowing dysfunction). A high resolution CT study of the cranial base detected a fracture rim encroaching on the left jugular foramen. Treatment consisted in supportive measures with incomplete recovery during a one-year follow-up period. Lower cranial nerves palsies after head trauma are rare and, should they occur, a thorough investigation in search of posterior cranial base and cranio-cervical lesions is warranted. The presumptive mechanism in our case is a fracture-related oedema and ischemic damage to the nerves leading to the delayed occurrence of the palsy.

Effect of interface conditions between ultrahigh molecular weight polyethylene and polymethyl methacrylate bone cement on the mechanical behaviour of total shoulder arthroplasty.

The aim of this study was to investigate the effect of the interface condition between polymethyl methacrylate (PMMA) bone cement and the ultrahigh molecular weight (UHMWPE) glenoid component on cement stresses and glenoid component tilting in a finite element (FE) model. The background of this research is that most FE models assume bonding between the PMMA bone cement and the UHMWPE component, although it is very doubtful that this bonding is present. An FE model of a cemented glenoid component was developed and a joint compression force and subluxation force of 725 and 350 N respectively were applied. The maximal principal stresses in the cement layer ranged between 21.30 and 32.18 MPa. Glenoid component tilting ranged between 0.943 degrees and 0.513 degrees. It was found that the interface condition has a large effect on the maximal principal stresses and glenoid component tilting. Whether adhesion between the UHMWPE component and PMMA bone cement occurs is unknown beforehand and, as a result, design validation using the FE technique should be carried out both by using contact elements in combination with a coefficient of friction as well as by a full bonding at this interface.

A broader vision for managed care, Part 2: A typology of community benefits.

Applying a "community benefit" standard to managed care is difficult because prevailing definitions of community benefit have been drawn largely from the hospital industry, which has different operating practices and capabilities than managed care plans do. To formulate a more comprehensive and appropriate typology for managed care, we describe four different conceptual perspectives on community benefit and identify actual plan practices that match each perspective. We propose a "balanced model" for encouraging community benefit through public and private policies.

Growing-fracture of the orbital roof with post-traumatic encephalocele in an adult patient. Case report.

Growing fractures are a rare entity, usually occurring in paediatric age. Localisation at the orbital region is even rarer. We report the case of a growing fracture of the orbital roof with post-traumatic encephalocele in an adult patient, the 1(st) similar case in adulthood at our knowledge. Clinical and neuroimaging aspects are described, underlining the role of MRI in displaying intraorbital encephalocele. Surgical treatment with relevant technical notes is discussed as well.

Regional brain injury epidemiology as the basis for planning brain injury treatment. The Romagna (Italy) experience.

AIM: Neurosurgical services for traumatic brain injury (TBI) should be based upon the understanding of the epidemiology of TBI in the region as well as the clinical parameters. Our objective was to measure incidence and epidemiologic factors associated with TBI in the Romagna region of Northeastern Italy and correlate those parameters with neurosurgical imaging and related clinical features. METHODS: Guidelines for brain injury management in our region were derived following meetings of all physicians involved in the treatment of brain injury. An epidemiologic study was undertaken in 1998. The study population was all patients admitted for hospital care in the Region following a TBI with a discharge diagnosis of pertinent International Classification Disease, 9(th) revision, codes. Data on the extent, diagnoses, severity, external causes and hospital course were abstracted from the hospital record and computer entered for analyses. RESULTS: Using data for the population of Romagna of about 1000000 persons we identified, in the full year 1998, 2430 TBI patients or an incidence rate of 250 per 100000 resident population. There were, in addition, 460 nonresident patients who were admitted in the region. External causes of injury were generally similar to reports from other places in Western Europe, with the exception of a very low frequency of cases stemming from violence. Age specific incidence rates were highest among young children, persons aged 15-24, and those aged 65 and older. Computerized tomography scans were given to 1732 patients and intracranial traumatic lesions were identified in 497 (28.6%) patients or a rate of 38 /100000. We performed 128 craniotomies, an incidence rate of 11/100000. The case fatality rate (CFR) was 2.8% among admitted patients with the highest rate among those aged 75 or older. CONCLUSION: Incidence of TBI in Italy is similar to other published European series. The number of minor brain injuries admitted for hospital care remains high and can be significantly reduced with better use of CT scans in adults whenever possible. The workload for a neurosurgical unit servicing a population of 1 million is limited and does not justify the opening of new units for trauma care or the use of craniotomies outside the Neurosurgical Unit.

Evolving lesions in traumatic subarachnoid hemorrhage: prospective study of 110 patients with emphasis on the role of ICP monitoring.

We have consecutively studied 110 patients with traumatic subarachnoid hemorrhage (tSAH) on the first Computed Tomography (CT) scan (obtained in each case within 3 hours from injury). The only exclusion criteria were brain death on admission, and severe hypotension due to extracranial injuries. All CTs were reviewed by one of us and the "worst" CT examination was determined. We defined the worst CT examination as that showing the most extensive degree of parenchymal-associated damage. Intracranial pressure was monitored in 25 severely head injured patients. Seventy-four patients (66%) showed an evolution from the initial CT scan (worst CT not corresponding to the admission CT). The outcome was favorable in 53 cases (73%) of patients with evolving lesions and in 32 cases (89%) with non evolving lesion. In the 25 severely head injured patients, Intra-cranial Pressure (ICP) monitoring (in combination with scheduled repeat CT scan) was helpful to identify the timing of the worst parenchymal damage and of surgery in those patients with an initial normal intracranial pressure in spite of an evolving lesion.

[Myocutaneous flaps in general surgery. The authors' personal experience]. / I lembi miocutanei in chirurgia generale. Esperienza personale.

Today, myocutaneous flaps are the safest way to repair every kind of tissue loss. The authors report a personal series of 28 cases, which results sufficient to rule out the possibilities of these technique either as "en principle" or as an adjuvant procedure.

Spontaneous cerebrospinal fluid rhinorrhoea in anteromedial temporal occult encephalocele.

A 75-year-old man was admitted because of a spontaneous rhinorrhoea without a previous history of head injury. Computed tomography showed bone rarefaction of the floor of the middle cranial fossa and magnetic resonance imaging demonstrated a right temporal encephalocele. This was treated via extradural approach, and the bone defects were plugged with temporalis fascia, muscle and the fibrin glue. No recurrence of rhinorrhoea was observed at the follow-up (1 year).

Integration of image transmission into a protocol for head injury management: a preliminary report.

Neurosurgical care is limited in many parts of the world to one or two hospitals serving a large geographic area. The quality of neurosurgical response to emergencies depends on the reliability and completeness of the information received from referral hospitals. The aim of this study is to show how application of guidelines for head injury management in an entire area can be usefully combined with transmission of images from the peripheral to the central hospital. From January 1998 to December 2000, 1665 CT examinations were sent via image transfer to the Neurosurgical Unit; 637 first examinations (47%) and 206 second examinations (70%) were related to acute trauma cases. Out of 637 first examinations, 150 patients were actually transferred to the Neurosurgery Unit (23%), whereas of 206 second examinations, only 10 patients were secondarily transferred (5%). In the absence of the outcomes of patients located outside the Neurosurgical Unit, we studied in detail these 10 patients. They are, in fact, the only way for us to partially measure the impact of our system. Only in a single case could the death be attributed to a delay in transferring the patient. We then studied the factors influencing the decision of patient transfer. Mean GCS was 11 both for transferred and non transferred cases. The mean age of all patients was 52 years (median 48, SD 20.5 years); mean age of non-transferred patients was 54 years and for transferred patients it was 41 years (p < 0.01). The same statistically significant difference concerning age applied to any type of pathology sent via image link. In conclusion our data show that it is feasible to co-ordinate in an entire area the treatment of head injured patients. Available systems for CT images link are reliable and mostly useful. Unnecessary transfers can be avoided and the neurosurgeons can evaluate the images of a number of patients who have always been treated outside our Units. This results in more work for the neurosurgeons on duty, but also in a better quality service for the whole area. The lack of follow-up for patients not admitted to Neurosurgery is the limitation on a quality assessment of the system.

Time course of CT evolution in traumatic subarachnoid haemorrhage: a study of 141 patients.

BACKGROUND: Evidence of tSAH on an admission CT scan seems to be an early predictor of evolving posttraumatic lesions. Detection of these changes requires serial CT scanners. The goal of our study was to determine the optimal timing of follow-up CT scans in head injured patients with traumatic subarachnoid haemorrhage (tSAH). METHOD: We reviewed the initial and follow-up CT scans in 141 patients with closed head injuries and evidence of tSAH on the initial CT scan. We used the Marshall classification to determine diffuse and focal injuries. The "worst CT scan", defined as the CT examination in which midline shift, cistern compression and/or intracranial focal lesions were greater, was also determined. Any worsening of the admission CT findings, occurring when the "worst CT examination" did not correspond to the initial CT study, was considered as a "CT evolution". Any "CT evolution" associated with a variation from a lower to a higher score in the Marshall classification score was indicated as a "significant CT evolution". FINDINGS: The median time between injury and the first CT scan was 1.3 (IQR 1.5) hours. A CT evolution was found in 83/141 (58.9%) patients in whom the median time between the initial and worst CT scans was 27.7 hours (IQR 69.2 hours). The worst CT studies were seen more often at 12-24 hours and at 24-48 hours after the admission CT scan than in later studies. A similar temporal profile was observed when the timing of the "worst CT scan" was evaluated in 38/83 (45.8%) subjects with a "significant CT evolution". INTERPRETATION: Our findings show that an early admission CT scan did not represent the full extent of the posttraumatic damage in more than half of our patients. They also suggest that to identify these changes in head injured patients with tSAH, CT scans should be repeated at 12-24 and possibly also at 24-48 hours from the admission CT examination to allow early detection and evacuation of evolving intracranial lesions.