A respiratory therapist-driven weaning protocol incorporating daily screens, spontaneous breathing trials (SBT), and prompts to caregivers has been associated with superior outcomes in mechanically ventilated medical patients. To determine the effectiveness of this approach in neurosurgical (NSY) patients, we conducted a randomized controlled trial involving 100 patients over a 14-mo period. All had daily screens of weaning parameters. If these were passed, a 2-h SBT was performed in the Intervention group. Study physicians communicated positive SBT results, and the decision to extubate was made by the primary NSY team. Patients in the Intervention (n = 49) and Control (n = 51) groups had similar demographic characteristics, illness severity, and neurologic injuries. Among all patients, 87 (45 in the Control and 42 in the Intervention group) passed at least one daily screen. Forty (82%) patients in the Intervention group passed SBT, but a median of 2 d passed before attempted extubation, primarily because of concerns about the patient's sensorium (84%). Of 167 successful SBT, 126 (75%) did not lead to attempted extubation on the same day. The median time of mechanical ventilation was 6 d in both study groups, and there were no differences in outcomes. Overall complications included death (36%), reintubation (16%), and pneumonia (9%). Tracheostomies were created in 29% of patients. Multivariate analysis showed that Glasgow Coma Scale (GCS) score (p < 0.0001) and partial pressure of arterial oxygen/fraction of inspired oxygen ratio (p < 0.0001) were associated with extubation success. The odds of successful extubation increased by 39% with each GCS score increment. A GCS score > or = 8 at extubation was associated with success in 75% of cases, versus 33% for a GCS score < 8 (p < 0.0001). Implementation of a weaning protocol based on traditional respiratory physiologic parameters had practical limitations in NSY patients, owing to concerns about neurologic impairment. Whether protocols combining respiratory parameters with neurologic measures lead to superior outcomes in this population requires further investigation.

MTLE is associated with network rearrangement within, but not restricted to, the temporal lobe ipsilateral to the onset of seizures. Networks involving key components of the medial temporal lobe and structures traditionally not removed during surgery may be associated with seizure control after surgical treatment of MTLE.

Temporal lobe epilepsy (TLE) is the most common form of focal epilepsy. Previous research has demonstrated several trends in human tissue that, undoubtedly, contribute to the development and progression of TLE. In this study we examined resected human hippocampus tissue for a variety of changes including gliosis that may contribute to the development and presentation of TLE. The study subjects consisted of 6 TLE patients and 3 sudden-death controls. Clinicopathological characteristics were evaluated by H&E staining. Immunohistological staining and Western blotting methods were used to analyze the samples. Neuronal hypertrophy was observed in resected epileptic tissue. Immunohistological staining demonstrated that activation of astrocytes was significantly increased in epileptic tissue as compared corresponding regions of the control group. The western blot data also showed increased CX43 and AQP4 in the hippocampus and downregulation of Kir4.1, α-syntrophin, and dystrophinin, which are the key constituents of AQP4 multi-molecular complex. These tissues also demonstrated changes in inflammatory factors (COX-2, TGF-β, NFkB) suggesting that these molecules may play an important role in TLE pathogenesis. In addition we detected increases in metabotropic glutamate receptor (mGluR) 2/3, mGluR5 and kainic acid receptor subunits KA1 (Grik4) and KA2 (Grik5) in patients' hippocampi. We noted increased expression of the α1c subunit comprising Class C L-type Ca2+ channels and calpain expression in these tissues, suggesting that these subunits may have an integral role in TLE pathogenesis. These changes found in the resected tissue suggest that they may contribute to TLE and that the Kainic acid receptor (KAR) and deregulation of GluR2 receptor may play an important role in TLE development and disease course. This study identifies alterations in number of commonly studied molecular targets associated with astrogliosis, cellular hypertrophy, water homeostasis, inflammation, and modulation of excitatory neurotransmission in hippocampal tissue from TLE patients.

Spring-assisted surgery is a safe, effective, minimally invasive treatment of scaphocephaly. It combines the low morbidity and the operative time of a strip craniectomy with dynamic reshaping techniques while the implanted spring gradually distracts the skull, improving head shape. Our 7 years of experience has shown that SAS effectively corrected cranial shape including frontal bossing with maintained results over time.

Summary:The objective of this study was to determine whether brief focal ischemia induces ischemic tolerance in rat brain. Focal ischemia was produced in Wistar rats by occluding the middle cerebral artery (MCA) for 20 min at a distal site. Following recovery for 24 h, the animals were SUbjected to a lO-min episode of forebrain ischemia using a combination of bilateral carotid artery occlusion and systemic hypotension. Histologic injury, assessed af ter a survival period of 3-4 days, consisted of selective neuronal necrosis bilaterally in cerebral cortex, striatum, hippocampus, and thalamus superimposed upon a small cortical infarct adjacent to the site of MCA occlusion. However, the intensity of neuronal necrosis in the MCA territory of the neocortex ipsilateral to MCA occlusion was markedly less than that in the contralateral MCA cortex. In contrast, the extent of neuronal necrosis in subcortical structures was similar in both hemispheres.Pretreatment of the brain with a sublethal stress has been reported to increase neuronal tolerance to a subsequent episode of cerebral ischemia (Chopp et aI., 1989; Kitagawa et aI. , 1990; Kirino et aI. , 1991). This induction of "ischemic tolerance" is analogous to the acquisition of thermotolerance demonstrated in many types of cells (Gerner and Schneider, 1975;Henle and Leeper, 1976 Abbreviations used: bFGF, basic fibroblast growth factor; FAM, formaldehyde/glacial acetic acid/absolute methanol (8:1:1); hsp72, heat-shock protein 72; MCA, middle cerebral ar tery; PBS, phosphate-buffered saline; SSC, saline-sodium ci trate. 545Unexpectedly, animals in which the MCA was manipu lated, but not occluded, also exhibited a marked reduc tion of neuronal necrosis in the ipsilateral MCA neocor tex following forebrain ischemia. However, in animals with craniotomy alone, forebrain ischemia caused a sim ilar extent of neuronal necrosis in the MCA neocortex of both hemispheres. Transient occlusion of the MCA in duced the focal expression of the 72-kDa heat-shock pro tein (hsp72) in the MCA territory of the neocortex. Lim ited expression of hsp72 was also detected following sham occlusion, but not after craniotomy alone. These results demonstrate focal induction of ischemic tolerance in rat neocortex that may be related to expression of heat shock proteins.

The underlying cause of neocortical involvement in temporal lobe epilepsy (TLE) remains a fundamental and unanswered question. Magnetic resonance imaging has shown a significant loss in temporal lobe volume, and it has been proposed that neocortical circuits are disturbed functionally because neurons are lost. The present study used design-based stereology to estimate the volume and cell number of Brodmann's area 38, a region commonly resected in anterior temporal lobectomy. Studies were conducted on the neocortex of patients with or without hippocampal sclerosis (HS). Results provide the surprising finding that TLE patients have significant atrophy of neocortical gray matter but no loss of neurons. Neurons are also significantly larger, dendritic trees appear sparser, and spine density is noticeably reduced in TLE specimens compared with controls. The increase in neuronal density we found in TLE patients is therefore attributable to large neurons occupying a much smaller volume than in normal brain. Neurons in the underlying white matter are also increased in size but, in contrast to other reports, are not significantly elevated in number or density. Neuronal hypertrophy affects HS and non-HS brains similarly. The reduction in neuropil and its associated elements therefore appears to be a primary feature of TLE, which is not secondary to cell loss. In both gray and white matter, neuronal hypertrophy means more perikaryal surface area is exposed for synaptic contacts and emerges as a hallmark of this disease. Key words: temporal lobe epilepsy; stereology; Brodmann's area 38; ectopia; cortical atrophy; neuronal hypertrophy; hippocampal sclerosisHippocampal sclerosis (HS) is the most frequently encountered pathologic abnormality in intractable epilepsy. There is however increasing evidence of more widespread temporal lobe pathology in HS patients (Nakasato et al., 1992;Sisodiya et al., 1995) and prevalent temporal lobe hypometabolism in patients with temporal lobe epilepsy (TLE) (Rausch et al., 1994). Moreover, magnetic resonance imaging (MRI) studies show a reduction in temporal lobe volume both ipsilateral and contralateral to the seizure focus (Lee et al., 1995Marsh et al., 1997). Volume reduction is also independent of the presence of HS (Sisodiya et al., 1997), which indicates that it underlies a broader spectrum than mesial temporal disease alone.Pathologic studies of TLE neocortex are dominated by those focused on readily detectable lesions and gross developmental abnormalities (Choi and Matthias, 1987;Haines et al., 1991;Raymond et al., 1995). There are far fewer investigations of subtle morphological abnormalities in the neocortex than in the hippocampus (Mathern et al., 1995), even though such studies might be expected to answer basic questions about epileptogenic activity originating outside the hippocampus and gross volume reductions in the temporal lobe.A common view of cortical pathology in TLE is that of neuronal loss. This notion is based on reports of reduced numbers of inhibitory neurons (DeFelip...

SUMMARYSurgical resection of the hippocampus is the most successful treatment for medication-refractory medial temporal lobe epilepsy (MTLE) due to hippocampal sclerosis. Unfortunately, at least one of four operated patients continue to have disabling seizures after surgery, and there is no existing method to predict individual surgical outcome. Prior to surgery, patients who become seizure free appear identical to those who continue to have seizures after surgery. Interestingly, newly converging presurgical data from magnetic resonance imaging (MRI) and intracranial electroencephalography (EEG) suggest that the entorhinal and perirhinal cortices may play an important role in seizure generation. These areas are not consistently resected with surgery and it is possible that they continue to generate seizures after surgery in some patients. Therefore, subtypes of MTLE patients can be considered according to the degree of extrahippocampal damage and epileptogenicity of the medial temporal cortex. The identification of these subtypes has the potential to drastically improve surgical results via optimized presurgical planning. In this review, we discuss the current data that suggests neural network damage in MTLE, focusing on the medial temporal cortex. We explore how this evidence may be applied to presurgical planning and suggest approaches for future investigation.

Abstract-Angiotensin-converting enzyme (ACE) inhibitors reduce the progression of atherosclerosis in animal models and reinfarction rates after myocardial infarction in humans. Although expression of components of the renin-angiotensin system has been reported in human coronary arteries, no data regarding their presence in carotid arteries, a frequent site for the occurrence of atherosclerosis plaques, are available. The following study sought to determine whether ACE mRNA and protein can be detected in human carotid atheromatous lesions. Twenty-four intact endarterectomy specimens were obtained from patients with severe carotid occlusive disease (17 males and 7 females, aged 68Ϯ1 years) and fixed within 30 minutes. Carotid artery specimens contained advanced Stary type V and VI lesions, and human ACE mRNA expression and protein were localized in cross sections by the combination of in situ hybridization and immunohistochemistry. Cell type-specific antibodies were used to colocalize ACE to smooth muscle cells, endothelial cells, macrophages, or lymphocytes. ACE protein was localized in the intima, whereas the overlying media was largely free of ACE staining. In less complicated lesions, ACE staining was modest and could be visualized in scattered clusters of macrophages and on the luminal side of carotid artery vascular endothelium. Smooth muscle cells were largely negative. ACE staining increased as lesions became more complex and was most prominent in macrophage-rich regions. The shoulder regions of plaques contained numerous ACE-positive macrophage foam cells and lymphocytes. In these areas, microvessels were positive for endothelial cell and smooth muscle cell ACE expression. However, microvessels in plaques free of inflammatory cells were stained only faintly for ACE expression. Labeling for ACE mRNA mirrored the pattern of protein expression, localizing ACE mRNA to macrophages and microvessels within the intima. In conclusion, atherosclerosis alters carotid artery ACE production, increasing transcription and translation within regions of plaque inflammation. These data provide another important mechanism by which inflammation associated with increased ACE expression may contribute to the progression of atherosclerosis. Key Words: carotid arteries Ⅲ angiotensin-converting enzyme Ⅲ macrophages Ⅲ immunohistochemistry Ⅲ hybridization A ngiotensin II (Ang II) has been implicated in the pathobiology of atherosclerosis and the arterial response to injury and restenosis 1-4 via mechanisms that include vascular hypertrophy, extracellular matrix production, and induction of cytokines. 5 In animal models of atherosclerosis, angiotensin-converting enzyme (ACE) inhibition reduces lesion progression, 6 -8 whereas blockade of the Ang II type 1 receptor (AT 1 ) inhibits monocyte activation, 4,9 LDL oxidation, 10,11 and fatty streak formation. 6,9,11 It has been reported that both ACE and immunoreactive Ang II may be found within the walls of atherosclerotic coronary arteries. 1,12 In the present study, we extend these obs...