Carboxyhaemoglobin formation and ECG changes during hysteroscopic surgery, transurethral prostatectomy and tonsillectomy using bipolar diathermy.

Diathermy is known to produce a mixture of waste products including carbon monoxide. During transcervical hysteroscopic surgery, carbon monoxide might enter the circulation leading to the formation of carboxyhaemoglobin. In 20 patients scheduled for transcervical hysteroscopic resection of myoma or endometrium, carboxyhaemoglobin was measured before and at the end of the surgical procedure, and compared with levels measured in 20 patients during transurethral prostatectomy, and in 20 patients during tonsillectomy. Haemodynamic data, including ST-segment changes, were recorded. Levels of carboxyhaemoglobin increased significantly during hysteroscopic surgery from median (IQR [range]) 1.0% (0.7-1.4 [0.5-4.9])% to 3.5% (2.0-6.1 [1.3-10.3]%, p < 0.001), compared with levels during prostatectomy or tonsillectomy. Significant ST-segment changes were observed in 50% of the patients during hysteroscopic surgery. Significant correlations were observed between the increase in carboxyhaemoglobin and the maximum ST-segment change (ρ = -0.707, p < 0.01), between the increase in carboxyhaemoglobin and intravasation (ρ = 0.625; p < 0.01), and between intravasation and the maximum ST-segment change (ρ = -0.761; p < 0.01). The increased carboxyhaemoglobin levels during hysteroscopic surgery appear to be related to the amount of intravasation and this could potentially be a contributing factor to the observed ST-segment changes.

How safe is the intravasation limit in hysteroscopic surgery?

BACKGROUND: Transcervical resection of myomas (TCR-M) is considered a safe hysteroscopic procedure if intravasation is limited. Complications may occur if gas formation during myoma resection leads to gaseous embolism. However, the incidence of emboli during transcervical myoma resection is unknown. Therefore in this study the occurrence of physiological changes that indicate the formation of emboli was retrospectively determined in patients undergoing hysteroscopic myoma resection. In addition, these changes were related to the amount of fluid intravasation. METHODS: The anesthesia records and operation files of 234 patients were screened for physiological changes that indicate embolism, as measured with standard intraoperative monitoring. These patients underwent surgery for intrauterine myomas with either a monopolar resectoscope with electrolyte-free distension fluid containing 3% sorbitol (limited to 1500-mL intravasation) or a bipolar resectoscope with normal saline solution (limited to 2500-mL intravasation). The patients were grouped according to the amount of fluid intravasation during the operation: Group 1: 500 mL or less, group 2: 500-1000 mL, group 3: 1000-1500 mL, and group 4: 1500-2500 mL. RESULTS: Physiological changes that could be attributed to gaseous embolism were observed in 33% to 43% of patients with 1000 to 2500 mL fluid intravasation during transcervical myoma resection. Nearly half of those patients had cardiovascular disturbances that indicated the formation of emboli. CONCLUSION: During transcervical resection of myomas, physiological changes that could be attributed to gaseous embolism frequently occurred. Therefore cardiovascular disturbances that indicate gaseous embolism during transcervical resection of myomas may occur despite the limitation of intravasation according to current view.

Increased virus replication in mammalian cells by blocking intracellular innate defense responses.

The mammalian innate immune system senses viral infection by recognizing viral signatures and activates potent antiviral responses. Besides the interferon (IFN) response, there is accumulating evidence that RNA silencing or RNA interference (RNAi) serves as an antiviral mechanism in mammalian cells. Mammalian viruses encode IFN antagonists to counteract the IFN response in infected cells. A number of IFN antagonists are also capable of blocking RNAi in infected cells and therefore serve as RNA-silencing suppressors. Virus replication in infected cells is restricted by these innate antiviral mechanisms, which may kick in earlier than the viral antagonistic or suppressor protein can accumulate. The yield of virus vaccines and viral gene delivery vectors produced in mammalian producer cells may therefore be suboptimal. To investigate whether blocking of the innate antiviral responses in mammalian cells leads to increased viral vector production, we expressed a number of immunity suppressors derived from plant and mammalian viruses in human cells. We measured that the yield of infectious human immunodeficiency virus-1 particles produced in these cells was increased 5- to 10-fold. In addition, the production of lentiviral and adenoviral vector particles was increased 5- to 10-fold, whereas Sindbis virus particle production was increased approximately 100-fold. These results can be employed for improving the production of viral gene transfer vectors and viral vaccine strains.

Dutch Dataset Pain Rehabilitation in daily practice: Content, patient characteristics and reference data.

BACKGROUND: No core set of measurement tools exists to collect data within clinical practice. Such data could be useful as reference data to guide treatment decisions and to compare patient characteristics or treatment results within specific treatment settings. METHODS: The Dutch Dataset Pain Rehabilitation was developed which included the six domains of the IMMPACT core set and three new domains relevant in the field of rehabilitation (medical consumption, patient-specific goals and activities/participation). Between 2010 and 2013 the core set was implemented in 32 rehabilitation facilities throughout the Netherlands. RESULTS: A total of 8200 adult patients with chronic pain completed the core set at first consultation with the rehabilitation physician. Adult patients (18-90 years) suffering from a long history of pain (38% >5 years) were referred. Patients had high medical consumption and less than half were working. Although patients were referred with diagnosis of low back pain or neck or shoulder pain, a large group (85%) had multisite pain (39% 2-5 painful body regions; 46% >5 painful body regions). Scores on psychosocial questionnaires were high, indicating high case complexity of referred patients. Reference data for subgroups based on gender, pain severity, pain locations and on pain duration are presented. CONCLUSIONS: The data from this clinical core set can be used to compare patient characteristics of patients of other treatment setting and/or scientific publications. As treatment success might depend on case complexity, which is high in the referred patients, the advantages of earlier referral to comprehensive multidisciplinary treatment were discussed. SIGNIFICANCE: A detailed description of case complexity of patients with chronic pain referred for pain rehabilitation. Insight in case complexity of patients within subgroups on the basis of gender, pain duration, pain severity and pain location. These descriptions can be used as reference data for daily practice in the field of pain rehabilitation and can be used to evaluate, monitor and improve rehabilitation care in care settings nationwide as well as internationally.

Broad resistance to tospoviruses in transgenic tobacco plants expressing three tospoviral nucleoprotein gene sequences.

Transgenic tobacco plants have been obtained expressing nucleoprotein (N) gene sequences of three different tospoviruses known to affect vegetable crops: tomato spotted wilt virus (TSWV), tomato chlorotic spot virus (TCSV), and groundnut ringspot virus (GRSV). The chimeric plant transformation vector used comprised the three viral N gene sequences, each with a copy of the CaMV 35S promoter and the nos terminator. Despite the high levels of homology between the different N gene sequences (74-82%) and the presence of repeated promoter and terminator sequences in this construct, unrearranged copies of this triple N gene construct were stably maintained in both Escherichia coli and Agrobacterium tumefaciens plasmids used during the cloning process, as well as in several generations of transgenic tobacco plants. A transgenic tobacco line was obtained that exhibited high levels of resistance to all three tospoviruses, showing the possibility of producing transgenic plants with a broad resistance to tospoviruses by introducing tandemly cloned viral N gene sequences. DNA analysis of this transgenic plant line shows that the multivirus resistance trait is confined to a single genetic locus, which is very convenient for further breeding purposes.

Engineered RNA-mediated resistance to tomato spotted wilt virus is sequence specific.

Transgenic plants were produced that expressed a wide range of randomly chosen sequences of the tripartite tomato spotted wilt virus (TSWV) RNA genome or its complement. Testing the progenies of these plants revealed that only transgenic expression of N or NS(M) gene sequences resulted in resistance to TSWV.

The nucleotide sequence of the S RNA of Impatiens necrotic spot virus, a novel tospovirus.

Impatiens necrotic spot virus (INSV) shares a number of properties with tomato spotted wilt virus (TSWV), the type species of the genus tospovirus within the family Bunyaviridae. INSV, however, differs from TSWV in plant host range and serology. In order to define the genomic structure and the taxonomic status of this TSWV-like virus, the nucleotide sequence of its genomic S RNA segment has been determined. The molecular data obtained demonstrate that, like TSWV, INSV has an ambisense S RNA molecule, encoding a non-structural protein in viral sense and the nucleocapsid protein in viral complementary sense. The level of nucleotide sequence homology between their S RNAs, as well as the divergence in amino acid sequence homology of their gene products, confirm previous conclusions from serological studies that INSV and TSWV represent distinct virus species within the newly created genus, tospovirus.

Spectophotometric quantification of cell-cell adherence by an enzyme-linked immuno-cell adhesion assay.

In the present study a spectophotometric method was developed to determine the number of T cells binding to human epidermal keratinocytes (KC). In this cell adhesion assay the adherent T cells were detected with a cell-specific monoclonal antibody conjugated to horseradish peroxidase and the coloured substrate quantified in an ELISA reader at 492 nm. A correlation was demonstrated between the number of T cells and the extinction values measured. The enzyme-linked immuno-cell adhesion assay (ELICAA) was used to quantify KC/T lymphocyte adherence in a series of experiments designed to evaluate its reliability and reproducibility. Compared with the 51Cr-labelled adherence assay, the ELICAA was a safe, rapid and accurate method avoiding the use of radioactive material.

Effect of ischemic pretreatment on heat shock protein 72, neurologic outcome, and histopathologic outcome in a rabbit model of spinal cord ischemia.

OBJECTIVE: In the present study, we investigated the effect of ischemic pretreatment on heat shock protein 72 concentration and neurologic and histopathologic outcome after transient spinal cord ischemia. METHODS: In 28 New Zealand White rabbits, an aortic occlusion device was placed infrarenally. The animals were randomly assigned to 2 groups: ischemic pretreatment (n = 14 animals) and control (n = 14 animals). The duration of ischemic pretreatment was 6 minutes. After 24 hours, the aorta was occluded for 26 minutes in both groups of animals. Neurologic function was assessed 24 and 48 hours after the definite ischemic insult. At 48 hours, the animals were killed for histopathologic evaluation of the spinal cord. In a separate set of animals, heat shock protein 72 levels were determined in the lumbar spinal cord after both a 6- and 10-minute ischemic period, with the use of a Western blot analysis. RESULTS: No significant difference in neurologic outcome between the groups was observed at 24 and 48 hours. The incidence of paraplegia and severe paresis at 48 hours was 79% in the control group and 92% in the ischemic pretreatment group. There was no difference in histopathologic scores between the groups. Heat shock protein 72 could be clearly detected 1 and 2 days after 6- or 10-minute periods of spinal cord ischemia. CONCLUSIONS: In the present rabbit study, ischemic pretreatment could not induce tolerance against a moderately severe spinal cord ischemic insult, despite increased heat shock protein 72 levels after the preconditioning stimulus.

Efficacy of transcranial motor-evoked myogenic potentials to detect spinal cord ischemia during operations for thoracoabdominal aneurysms.

OBJECTIVE: Motor-evoked myogenic potentials after transcranial electrical stimulation monitor the vulnerable motoneuronal system of the spinal cord. This study reports our initial experiences with motor-evoked potentials to assess the adequacy of spinal cord perfusion during operations for thoracoabdominal aneurysms. METHODS: In 20 patients undergoing thoracoabdominal aneurysm operations, myogenic motor-evoked potentials were recorded. In 18 patients retrograde aortic perfusion was used. When spinal cord ischemia was detected, distal flow or mean arterial pressure was increased in an attempt to restore cord perfusion. By means of sequential crossclamping, motor-evoked potentials were also used to identify intercostal or lumbar arteries that needed to be reimplanted. RESULTS: Reproducible motor-evoked potentials could be recorded in all patients. During retrograde perfusion, nine patients showed a rapid decrease in the amplitude of motor-evoked potentials to less than 25% of baseline, indicating spinal cord ischemia. In five patients ischemic changes in motor-evoked potentials could be reversed by increasing distal and proximal blood pressures. In four patients ischemic changes during crossclamping necessitated segmental artery reimplantation. In three of these four patients intercostal or lumbar arteries were reattached. In one patient reimplantation of segmental arteries was not possible; this patient awoke paraplegic. Segmental arteries were ligated after confirmation of intact motor-evoked potentials during aortic clamping in eight patients. None of these patients had a neurologic deficit. The absence of motor-evoked potentials at the end of the procedure always indicated a postoperative motor deficit. CONCLUSION: During operations for thoracoabdominal aneurysms, monitoring of motor-evoked potentials is an effective technique to detect spinal cord ischemia within minutes. This modality can be used to guide the management of distal aortic perfusion techniques and may also help to identify segmental arteries that need to be reattached.

Injury to the major airways during subtotal esophagectomy: incidence, management, and sequelae.

OBJECTIVE: The objective of this study was to gain insight into the incidence and sequelae of injury to the major airways during subtotal esophagectomy. METHODS: We performed an analysis of 383 consecutive patients undergoing this procedure between 1993 and 1999. Indications were adenocarcinoma (220), squamous cell carcinoma (121), and other (42). Transhiatal resection was done in 269 (70%) patients and transthoracic resection in 114 (30%). RESULTS: There were 4 men and 2 women (median age 57 years; range 45 to 68 years) with injury to the major airways, recognized during surgery in 5 patients and on the first postoperative day in the other. Five lesions occurred during transhiatal resection (5 of 269 = 1.8%) and 1 during transthoracic resection (1 of 114 = 0.8%; P =.67). The injury occurred proximal to the carina in 5 patients and in the left main bronchus in the other. All injuries could be closed primarily. The defect was covered with pericardium in 1 patient and with pleura in 2 patients. In all cases the gastric tube was placed over the defect. Pulmonary complications developed in 4 patients. Patients with tracheal injury required artificial ventilation for a longer period (median 6 days vs 1 day; P =.02) and stayed longer in the intensive care unit (median 11 vs 3 days; P <.01) than patients without such injury, although hospital time was not significantly prolonged (median 23 vs 16 days; P =.09). There was no associated mortality. CONCLUSION: Tracheobronchial injury is a rare complication of subtotal esophagectomy. It can be managed effectively by primary closure and apposition of vital tissue (gastric tube) to the defect. It is associated with pulmonary complications, leading to prolonged assisted ventilation and stay in the intensive care unit, but mortality is rare.

The influence of regional spinal cord hypothermia on transcranial myogenic motor-evoked potential monitoring and the efficacy of spinal cord ischemia detection.

OBJECTIVE: Myogenic motor-evoked responses to transcranial electrical stimulation (transcranial myogenic motor-evoked potentials) can rapidly detect spinal cord ischemia during thoracoabdominal aortic aneurysm repair. Recent evidence suggests that regional spinal cord hypothermia increases spinal cord ischemia tolerance. We investigated the influence of subdural infusion cooling on transcranial myogenic motor-evoked potential characteristics and the time to detect spinal cord ischemia in 6 pigs. METHODS: Regional hypothermia was produced by subdural perfusion cooling. A laminectomy and incision of the dura were performed at L2 to advance 2 inflow catheters at L4 and L6, to cool the lumbar subdural space with saline solution. Two temperature probes were advanced at L3 and L5, and 1 cerebrospinal fluid pressure line was advanced at L4. Spontaneous cerebrospinal fluid outflow was allowed. Spinal cord ischemia was produced by clamping a set of critical lumbar arteries, previously identified by transcranial myogenic motor-evoked potentials and lumbar artery clamping. The time between the onset of ischemia and detection with transcranial myogenic motor-evoked potentials (amplitude < 25%) was determined at cerebrospinal fluid temperatures of 37 degrees C and 28 degrees C. Thereafter, the influence of progressive cerebrospinal fluid cooling on transcranial myogenic motor-evoked potential amplitude and latency was determined. RESULTS: The time necessary to produce ischemic transcranial myogenic motor-evoked potentials, after the clamping of critical lumbar arteries, was not affected at moderate subdural hypothermia (3.8 +/- 0.9 min) compared with subdural normothermia (3.2 +/- 0.5 min; P =.6). Thereafter, progressive cooling resulted in a transcranial myogenic motor-evoked potential amplitude increase at 28 degrees C to 30 degrees C and was followed by a progressive decrease. Response amplitudes decreased below 25% at 14.0 degrees C +/- 1.1 degrees C. The influence of cerebrospinal fluid temperature on transcranial myogenic motor-evoked potential amplitude was best represented by a quadratic regression curve with a maximum at 29.6 degrees C. In contrast, transcranial myogenic motor-evoked potential latencies increased linearly with decreasing subdural temperatures. CONCLUSIONS: Detection of spinal cord ischemia with transcranial myogenic motor-evoked potentials is not delayed at moderate subdural hypothermia in pigs. At a cerebrospinal fluid temperature of 28 degrees C, transcranial myogenic motor-evoked potential amplitudes are increased. Further cerebrospinal fluid temperature decreases result in progressive amplitude decreases and latency increases.

Epidural versus subdural spinal cord cooling: cerebrospinal fluid temperature and pressure changes.

BACKGROUND: Regional spinal cord cooling can increase the tolerable duration for spinal cord ischemia resulting from aortic clamping. We compared the efficacy of epidural and subdural cooling and the effect of the resulting cerebrospinal fluid-pressure (CSF) increases on spinal cord motor neuron function. METHODS: In 8 pigs, CSF temperature and pressure were assessed in the subdural space at L4, T15, and T7. Saline was infused at 333, 666, and 999 ml/h at four consecutive locations: L4 subdural, L4 epidural, T15 subdural, and T15 epidural. First, the influence of CSF-pressure increases during normothermic infusion on transcranial motor evoked potentials (tc-MEPs) was assessed. Then, hypothermic infusion (4 degrees C) was performed to assess CSF-temperature changes. RESULTS: During normothermic infusion, baseline CSF pressures increased uniformly from 6 +/- 4 mm Hg to 34 +/- 18, 42 +/- 17, and 50 +/- 18 mm Hg with increasing infusion rates (p < 0.001), and did not differ between epidural or subdural infusion. Tc-MEPs indicated spinal cord ischemia in 6 animals when CSF pressures reached 65 +/- 11 mm Hg. During hypothermic infusion, CSF temperatures decreased from 37 degrees to 35 +/- 1.2 degrees, 31 +/- 2.2 degrees, and 28 +/- 2.8 degrees C, but increasing CSF-temperature gradients were observed between the infusion location and distant segments. Subdural cooling resulted in lower CSF temperatures (p < 0.001), but caused larger CSF-pressure increases (p < 0.001). CONCLUSIONS: Subdural and epidural infusion cooling produce localized spinal cord hypothermia in pigs. The concurrent pressure increases, however, are uniformly distributed and can result in tc-MEP evidence of ischemia.

Development of spinal cord ischemia after clamping of noncritical segmental arteries in the pig.

BACKGROUND: Blood flow to the thoracolumbar spinal cord is thought to be critically dependent on the arteria radicularis magna. We investigated whether spinal cord blood supply becomes dependent on other, noncritical, segmental arteries if spinal cord perfusion pressure (SCPP) is decreased. The SCPP is equal to the mean arterial pressure (MAP) minus the cerebrospinal fluid (CSF) pressure (SCCP = MAP - CSF). METHODS: The thoracoabdominal aorta was exposed in 10 pigs. Functional integrity of spinal cord motor pathways was assessed with myogenic motor-evoked potentials after transcranial electrical stimulation (tc-MEPs). Using this technique, a group of segmental arteries not critical for spinal cord blood supply was identified. Before, during, and after clamping of the noncritical segmental arteries, spinal cord ischemia was produced by decreasing SCPP by means of increasing CSF pressure, and the SCPP threshold at which tc-MEPs showed evidence of spinal cord ischemia was determined. Ischemic SCPP thresholds, obtained during and after clamping of the noncritical segmental arteries, were compared with the ischemic threshold obtained before clamping (control value). RESULTS: Before noncritical segmental arteries were clamped, ischemic tc-MEP changes occurred when the SCPP was below 15 +/- 5 (SD) mm Hg. With a total of 9 +/- 3 (SD) segmental arteries clamped, the ischemic SCPP threshold was 48 +/- 14 mm Hg (p < 0.01). After the release of all clamps, ischemia occurred at a SCPP of 15 +/- 5 (SD) mm Hg. CONCLUSIONS: In this porcine experiment, clamping of originally noncritical segmental arteries significantly reduced the tolerance of the spinal cord to a decrease in SCPP.

Effects of sustained-release chlorhexidine acetate on the human dental plaque flora.

The aim of this study was to determine the effect on the human dental plaque flora of a varnish containing chlorhexidine diacetate. The in vitro release of chlorhexidine acetate from the varnish preparation was relatively fast on the first day, followed by a substantial decline in the subsequent three days. In a clinical experiment, 26 volunteers were randomly distributed over four experimental groups. After a dental prophylaxis, the subjects were treated with a single application of a placebo varnish (group I), a fluoride varnish (group II), a chlorhexidine varnish (group III), or a fluoride-plus-chlorhexidine varnish (group IV). Saliva and pooled plaque samples from approximal surfaces were taken before (baseline) and one, two, three, four, and six weeks after the treatments. No suppression was found of total cultivable flora or S. sanguis after the experimental treatments. Application of the fluoride varnish did not suppress the A. viscosus/naeslundii or S. mutans levels in the dental plaque. Chlorhexidine suppressed A. viscosus/naeslundii until two weeks after the treatment. S. mutans was significantly suppressed until four weeks after a single chlorhexidine application. While in some subjects S. mutans was effectively suppressed over the whole experimental period, in others S. mutans recovered quickly. In five subjects in whom S. mutans recovered quickly, the dentition was treated twice with chlorhexidine varnish, with an interval of one week between the treatments. After two chlorhexidine treatments, S. mutans in saliva and on the teeth was suppressed more strongly than after a single treatment. However, the second chlorhexidine treatment could not prevent the return of S. mutans in the approximal areas to its original level.

Human growth factor (huGRO), interleukin-8 (IL-8) and interferon-gamma-inducible protein (gamma-IP-10) gene expression in cultured normal human keratinocytes.

HuGRO, IL-8 and gamma-IP-10 belong to a recently described superfamily of genes encoding a group of cytokines with inflammatory, growth regulating and/or leukocyte chemotactic properties (chemokines). We studied huGRO, IL-8 and gamma-IP-10 gene expression in unstimulated and stimulated (TNF alpha, INF gamma, TNF alpha + IFN gamma, IL-1 beta, PMA and LPS) normal human keratinocytes by Northern blot analysis. The mRNA for none of the three chemokines was detectable in unstimulated keratinocytes, but considerably elevated levels of huGRO and IL-8 mRNA, but not of gamma-IP-10 mRNA, were found in the presence of cycloheximide, indicating that huGRO and IL-8 mRNA, but not gamma-IP-10 mRNA, are constitutively produced. gamma-IP-10 mRNA was exclusively induced by IFN gamma, with a strong and transient rise between 8 and 18 h, and superinduced by the combination of IFN gamma and TNF alpha, indicating marked synergism. Both huGRO and IL-8 mRNA were induced by TNF alpha and PMA (a strong and transient rise between 2 and 8 h), but not by IFN gamma or LPS. The combination of TNF alpha and IFN gamma did not show a synergistic effect. In addition, IL-1 beta transiently upregulated huGRO mRNA but failed to induce IL-8 mRNA. Using specific oligonucleotides for alpha, beta and gamma huGRO, TNF alpha was found to induce all three forms, alpha and beta to an equal extent and gamma to a lesser extent.(ABSTRACT TRUNCATED AT 250 WORDS)

Chemokine IP-10 expression in cultured human keratinocytes.

IP-10, a member of the CXC family of chemokines, is considered to play an important role in inflammation via its T-cell chemotactic and adhesion-promoting properties. Elevated IP-10 levels in the epidermis of psoriasis, delayed-type hypersensitivity reactions, cutaneous T-cell lymphoma and fixed drug eruptions prompted us to study its expression in keratinocytes. IP-10 mRNA could be detected using the sensitive RT-PCR method, but not by Northern blotting in RNA preparations from unstimulated normal cultured keratinocytes, indicating a low steady-state level of IP-10 mRNA. Upon stimulation with IFN-gamma, IP-10 mRNA was found to accumulate in high amounts in a time- and dose-dependent manner. Superexpression was found with the combination of IFN-gamma and TNF-alpha or IL-1, although these latter cytokines by themselves did not induce accumulation of IP-10 mRNA. Nuclear run-on experiments performed to investigate the regulation of IP-10 mRNA expression, showed a very high constitutive transcriptional activity of the IP-10 gene in unstimulated keratinocytes, which was not affected by stimulation with IFN-gamma, TNF-alpha, or a combination of IFN-gamma and TNF-alpha. Protein kinase C (PKC) was shown to be involved in IP-10 mRNA expression since the PKC inhibitor H7 decreased IP-10 mRNA accumulation. A protein was isolated from culture supernatants of stimulated keratinocytes using HPLC techniques and, by sequence analysis, was found to be identical to IP-10. The dynamics of secretion of IP-10 protein as monitored by ELISA was shown to parallel the mRNA expression.

Spinal cord monitoring with myogenic motor evoked potentials: early detection of spinal cord ischemia as an integral part of spinal cord protective strategies during thoracoabdominal aneurysm surgery.

Spinal cord ischemia during resection of thoracoabdominal aortic aneurysms (TAA) can result in lower limb neurological deficits. Spinal cord monitoring can only improve outcome if ischemia is detected before irreversible damage has occurred and protective measures are readily available. Monitorin( spinal cord function with motor evoked potentials (MEPs) is a relatively new technique. With MEP. recorded from the muscle (myogenic MEPs), the vulnerable spinal motoneuronal system is exclusively monitored and ischemia is detected within minutes. Using a strategy aimed at maintaining and restoring spinal cord blood supply (distal aortic perfusion, sequential aortic clamping, and selective segmental artery reattachment), early detection of ischemia allows protective measures to be applied and adjusted immediately, ie, reattaching or safely ligating intercostal arteries, increasing proximal o distal aortic pressures as required, or inducing hypothermia. Recent improvements in the technique fo eliciting myogenic MEPs include multi-pulse stimulation paradigms and the use of a circumferentia cathode. This results in robust and reproducible signals, which are less susceptible to anesthetic interference and allow the use of a constant level of neuromuscular blockade. In conclusion, monitoring myogenic MEPs during a TAA repair has become clinically feasible. The fast detection of spinal cord ischemia allows timely guidance of protective measures.

Theoretical analysis of the release of drug from completely dissolving carriers containing drug particles.

The approach of "controlled supply of slow-release particles" is evaluated for a dissolving carrier system containing drug particles. Drug dissolution from this system is calculated after solving a convolution integral. The effects of geometry and relative dissolution time between drug particles and carrier device on drug dissolution kinetics are considered. Minima in the deviation of the dissolution profiles from linearity as a function of relative dissolution time are found. The impacts of geometry on the minima are discussed. Incorporation of a second system of isometric drug particles in an isometric carrier shows less deviation from constant-release kinetics when suitable values of the parameters affecting drug release are used in the calculations. A substantially constant rate of release of drug can be realized for a system of two carriers, each containing "slow-release" drug particles. The initial deviation from linearity in the sigmoidally shaped profile of drug dissolved in time from one of the two carriers is eliminated by the release of dissolved drug from the second carrier. About 80% of the drug content is dissolved at a constant rate by the combination of the two carriers.

Pharmacologic adjuncts to protect the spinal cord during transient ischemia.

Despite numerous strategies that aim to maintain and restore adequate spinal cord perfusion during thoracoabdominal aortic aneurysm repair, a lower limb neurologic deficit remains a distinct possibility. When critical intercostal arteries originate either at or below the level of repair, transient spinal cord ischemia might occur. Pending on the severity and duration of ischemia, irreversible damage evolves. Therefore, it would be advantageous if adjuncts were available that could enhance neuronal tolerance and improve neuronal survival after episodes of spinal cord ischemia. The beneficial effect of permissive or induced hypothermia is well established. This review focuses on pharmacologic adjuncts. The cascade that leads to neuronal death after ischemia consists of several pathways that act both parallel and sequential. The ischemic cascade provides logical pathogenetic determinants for pharmacologic interventions. Indeed, neuroprotection was attributed to numerous agents in experimental spinal cord ischemia. The clinical use of most of these agents is hampered by their toxicity and side effects. The current status of pharmacologic protection against spinal cord ischemia is summarized, and future directions are provided.