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AIM: The “2023 Guideline for the Management of Patients With Aneurysmal Subarachnoid Hemorrhage” replaces the 2012 “Guidelines for the Management of Aneurysmal Subarachnoid Hemorrhage.” The 2023 guideline is intended to provide patient-centric recommendations for clinicians to prevent, diagnose, and manage patients with aneurysmal subarachnoid hemorrhage. METHODS: A comprehensive search for literature published since the 2012 guideline, derived from research principally involving human subjects, published in English, and indexed in MEDLINE, PubMed, Cochrane Library, and other selected databases relevant to this guideline, was conducted between March 2022 and June 2022. In addition, the guideline writing group reviewed documents on related subject matter previously published by the American Heart Association. Newer studies published between July 2022 and November 2022 that affected recommendation content, Class of Recommendation, or Level of Evidence were included if appropriate. STRUCTURE: Aneurysmal subarachnoid hemorrhage is a significant global public health threat and a severely morbid and often deadly condition. The 2023 aneurysmal subarachnoid hemorrhage guideline provides recommendations based on current evidence for the treatment of these patients. The recommendations present an evidence-based approach to preventing, diagnosing, and managing patients with aneurysmal subarachnoid hemorrhage, with the intent to improve quality of care and align with patients’ and their families’ and caregivers’ interests. Many recommendations from the previous aneurysmal subarachnoid hemorrhage guidelines have been updated with new evidence, and new recommendations have been created when supported by published data.

OBJECTIVE Postoperative urinary retention (POUR) is a common complication after spine surgery and is associated with prolongation of hospital stay, increased hospital cost, increased rate of urinary tract infection, bladder overdistention, and autonomic dysregulation. POUR incidence following spine surgery ranges between 5.6% and 38%; no reliable prediction tool to identify those at higher risk is available, and that constitutes an important gap in the literature. The objective of this study was to develop and validate a preoperative risk model to predict the occurrence of POUR following routine elective spine surgery. METHODS The authors conducted a retrospective chart review of consecutive adults who underwent lumbar spine surgery between June 1, 2017, and June 1, 2019. Patient characteristics, preexisting ICD-10 codes, preoperative pain and opioid use, preoperative alpha-1 blocker use, details of surgical planning, development of POUR, and management strategies were abstracted from electronic medical records. A binomial logistic model and a multilayer perceptron (MLP) were optimized using training and validation sets. The models’ performance was then evaluated on model-naïve patients (not a part of either cohort). The models were then stacked to take advantage of each model’s strengths and to avoid their weaknesses. Four additional models were developed from previously published models adjusted to include only relevant factors (i.e., factors known preoperatively and applied to the lumbar spine). RESULTS Overall, 891 patients were included in the cohort, with a mean of 59.6 ± 15.5 years of age, 52.7% male, BMI 30.4 ± 6.4, American Society of Anesthesiologists class 2.8 ± 0.6, and a mean of 5.6 ± 5.7 comorbidities. The rate of POUR was found to be 25.9%. The two models were comparable, with an area under the curve (AUC) of 0.737 for the regression model and 0.735 for the neural network. By combining the two models, an AUC of 0.753 was achieved. With a regression model probability cutoff of 0.24 and a neural network cutoff of 0.23, maximal sensitivity and specificity were achieved, with specificity 68.2%, sensitivity 72.9%, negative predictive value 88.2%, and positive predictive value 43.4%. Both models individually outperformed previously published models (AUC 0.516–0.645) when applied to the current data set. CONCLUSIONS This predictive model can be a powerful preoperative tool in predicting patients who will be likely to develop POUR. By using a combination of regression and neural network modeling, good sensitivity, specificity, and NPV are achieved.

Severe traumatic brain injury (TBI) is a major contributor to disability and mortality in the industrialized world. Outcomes of severe TBI are profoundly heterogeneous, complicating outcome prognostication. Several prognostic models have been validated for acute prediction of 6-month global outcomes following TBI (e.g., morbidity/mortality). In this preliminary observational prognostic study, we assess the utility of the International Mission on Prognosis and Analysis of Clinical Trials in TBI (IMPACT) Lab model in predicting longer term global and cognitive outcomes (7-10 years post injury) and the extent to which cerebrospinal fluid (CSF) biomarkers enhance outcome prediction.Very long-term global outcome was assessed in a total of 59 participants (41 of whom did not survive their injuries) using the Glasgow Outcome Scale-Extended and Disability Rating Scale. More detailed outcome information regarding cognitive functioning in daily life was collected from 18 participants surviving to 7-10 years post injury using the Cognitive Subscale of the Functional Independence Measure. A subset (n = 10) of these participants also completed performance-based cognitive testing (Digit Span Test) by telephone. The IMPACT lab model was applied to determine its prognostic value in relation to very long-term outcomes as well as the additive effects of acute CSF ubiquitin C-terminal hydrolase-L1 (UCH-L1) and microtubule associated protein 2 (MAP-2) concentrations.The IMPACT lab model discriminated favorable versus unfavorable 7- to 10-year outcome with an area under the receiver operating characteristic curve of 0.80. Higher IMPACT lab model risk scores predicted greater extent of very long-term morbidity (β = 0.488 p = 0.000) as well as reduced cognitive independence (β = - 0.515, p = 0.034). Acute elevations in UCH-L1 levels were also predictive of lesser independence in cognitive activities in daily life at very long-term follow-up (β = 0.286, p = 0.048). Addition of two CSF biomarkers significantly improved prediction of very long-term neuropsychological performance among survivors, with the overall model (including IMPACT lab score, UCH-L1, and MAP-2) explaining 89.6% of variance in cognitive performance 7-10 years post injury (p = 0.008). Higher acute UCH-L1 concentrations were predictive of poorer cognitive performance (β = - 0.496, p = 0.029), whereas higher acute MAP-2 concentrations demonstrated a strong cognitive protective effect (β = 0.679, p = 0.010).Although preliminary, results suggest that existing prognostic models, including models with incorporation of CSF markers, may be applied to predict outcome of severe TBI years after injury. Continued research is needed examining early predictors of longer-term outcomes following TBI to identify potential targets for clinical trials that could impact long-ranging functional and cognitive outcomes.

Major vascular surgical procedures are commonly performed on patients with significant comorbidities. Regional anesthetic techniques may be used as the primary mode of anesthesia or to supplement general anesthesia for open or endovascular surgical procedures. This chapter focuses on the management of thoracic and abdominal aortic repair, as well as revascularization of the lower extremities. Although general anesthesia is still used in a majority of these surgeries, neuraxial and regional options allow for the reduction of opioid administration and provide hemodynamic stability while maintaining safety. An understanding of vascular anatomy, the surgical procedure, as well as neuraxial or regional anesthesia technique, is critical for success. Finally, anticoagulant medication management, coordination of the timing of the procedure, and postoperative management are crucial to reduce the risk of complications in this challenging patient population.

Perioperative stroke is associated with considerable morbidity and mortality. Stroke recognition and diagnosis are challenging perioperatively, and surgical patients receive therapeutic interventions less frequently compared with stroke patients in the outpatient setting. These updated guidelines from the Society for Neuroscience in Anesthesiology and Critical Care provide evidence-based recommendations regarding perioperative care of patients at high risk for stroke. Recommended areas for future investigation are also proposed.

Francis Robicsek was an outstanding cardiothoracic and vascular surgeon, anthropologist, biomedical engineer, philanthropist, art lover, and collector. During a career of almost 55 years, he managed to influence almost every aspect of cardiothoracic and vascular surgery. He is best known for his novel approach to the treatment of sternal instability, the Robicsek weave, which is currently the reference standard. His accomplishments include over 35,000 surgical interventions, 672 medical publications, 734 lectures, 4 textbooks on Mayan culture, and approximately 100 pupils. His remains one of the most fascinating stories in modern surgery.

Emergency visits, hospitalizations, and deaths due to traumatic brain injury (TBI) have increased significantly over the past few decades. While the primary early brain trauma is highly deleterious to the brain, the secondary injury post-TBI is postulated to significantly impact mortality. The presence of blood, particularly hemoglobin, and its breakdown products and key binding proteins and receptors modulating their clearance may contribute significantly to toxicity. Heme, hemin, and iron, for example, cause membrane lipid peroxidation, generate reactive oxygen species, and sensitize cells to noxious stimuli resulting in edema, cell death, and increased morbidity and mortality. A wide range of other mechanisms such as the immune system play pivotal roles in mediating secondary injury. Effective scavenging of all of these pro-oxidant and pro-inflammatory metabolites as well as controlling maladaptive immune responses is essential for limiting toxicity and secondary injury. Hemoglobin metabolism is mediated by key molecules such as haptoglobin, heme oxygenase, hemopexin, and ferritin. Genetic variability and dysfunction affecting these pathways (e.g., haptoglobin and heme oxygenase expression) have been implicated in the difference in susceptibility of individual patients to toxicity and may be target pathways for potential therapeutic interventions in TBI. Ongoing collaborative efforts are required to decipher the complexities of blood-related toxicity in TBI with an overarching goal of providing effective treatment options to all patients with TBI.

This study compared cerebrospinal fluid (CSF) levels of microtubule-associated protein 2 (MAP-2) from adult patients with severe traumatic brain injury (TBI) with uninjured controls over 10 days, and examined the relationship between MAP-2 concentrations and acute clinical and radiologic measures of injury severity along with mortality at 2 weeks and over 6 months. This prospective study, conducted at two Level 1 trauma centers, enrolled adults with severe TBI (Glasgow Coma Scale [GCS] score ≤8) requiring a ventriculostomy, as well as controls. Ventricular CSF was sampled from each patient at 6, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, and 240 h following TBI and analyzed via enzyme-linked immunosorbent assay for MAP-2 (ng/mL). Injury severity was assessed by the GCS score, Marshall Classification on computed tomography (CT), Rotterdam CT score, and mortality. There were 151 patients enrolled—130 TBI and 21 control patients. MAP-2 was detectable within 6 h of injury and was significantly elevated compared with controls (p

Midline shift following severe traumatic brain injury (sTBI) detected on computed tomography (CT) scans is an established predictor of poor outcome. We hypothesized that lateral ventricular volume (LVV) asymmetry is an earlier sign of developing asymmetric intracranial pathology than midline shift. This retrospective analysis was performed on data from 84 adults with blunt sTBI requiring a ventriculostomy who presented to a Level I trauma center. Seventy-six patients underwent serial CTs within 3 h and an average of three scans within the first 10 d of sTBI. Left and right LVVs were quantified by computer-assisted manual volumetric measurements. LVV ratios (LVR) were determined on the admission CT to evaluate ventricular asymmetry. The relationship between the admission LVR value and subsequent midline shift development was tested using receiver operating characteristic (ROC) analysis, and odds ratio (OR) and relative risk tests. Sixty patients had no >5 mm midline shift on the initial admission scan. Of these, 15 patients developed it subsequently (16 patients already had >5 mm midline shift on admission scans). For >5 mm midline shift development, admission LVR of >1.67 was shown to have a sensitivity of 73.3% and a specificity of 73.3% (area under the curve=0.782; p1.67 as exposure yielded an OR of 7.56 (p

Perioperative stroke is associated with considerable morbidity and mortality. Stroke recognition and diagnosis are challenging perioperatively, and surgical patients receive therapeutic interventions less frequently compared with stroke patients in the outpatient setting. These updated guidelines from the Society for Neuroscience in Anesthesiology and Critical Care provide evidence-based recommendations regarding perioperative care of patients at high risk for stroke. Recommended areas for future investigation are also proposed.

This study assessed whether early levels of biomarkers measured in CSF within 24-h of severe TBI would improve the clinical prediction of 6-months mortality. This prospective study conducted at two Level 1 Trauma Centers enrolled adults with severe TBI (GCS ≤8) requiring a ventriculostomy as well as control subjects. Ventricular CSF was sampled within 24-h of injury and analyzed for seven candidate biomarkers (UCH-L1, MAP-2, SBDP150, SBDP145, SBDP120, MBP, and S100B). The International Mission on Prognosis and Analysis of Clinical Trials in TBI (IMPACT) scores (Core, Extended, and Lab) were calculated for each patient to determine risk of 6-months mortality. The IMPACT models and biomarkers were assessed alone and in combination. There were 152 patients enrolled, 131 TBI patients and 21 control patients. Thirty six (27 %) patients did not survive to 6 months. Biomarkers were all significantly elevated in TBI versus controls (p

Traumatic brain injury (TBI) remains a significant cause of morbidity and mortality, and advanced age is an independent predictor of worse outcome. Mortality is nearly double that of younger TBI patients, regardless of injury severity. In addition, geriatric patients are more prone to complications, have longer hospital stays, and require long-term rehabilitative services, the cost of which can be a significant burden. These observations are often attributed to anatomic and physiologic changes that occur with age, as well as patient comorbidities and the medications required to treat those conditions. Although current diagnostic and treatment guidelines have led to improved outcomes in the general population, data regarding the specific management of geriatric patients remain sparse. The identification and management of TBI has been the focus of both basic science and clinical investigations. Recent advances in molecular biology have identified specific markers of brain cell damage that may offer insight to the nature and progression of injury, lead to improved monitoring and diagnostic capability, and potentially guide therapy. This review highlights some of the latest technology that may pave the way for advanced diagnostic and treatment modalities.

Hemophilia B is a rare X-linked disorder that may cause dramatic bleeding. Women account for only 3.2% of those clinically affected. The X-linked inheritance frequently delays the diagnosis in women and may expose the patient to an increased risk of adverse events. There is limited experience with these patients during labor and delivery. A 28-year-old primiparous woman with hemophilia B (bleeding phenotype) delivered a male infant by an unplanned cesarean delivery under general anesthesia following treatment with factor IX and normalization of her coagulation parameters, guided by thromboelastography. Postpartum vaginal bleeding required transfusion of two units of packed red blood cells. Factor IX supplementation continued for one week. Once diagnosed with hemophilia B, a multidisciplinary approach and advanced antenatal planning can increase the likelihood of a safe delivery. Neuraxial approaches and cesarean delivery are recommended only after normalization of the coagulation profile. The male fetus of a hemophilia A or B patient requires special attention. Operative vaginal delivery and invasive fetal monitoring should be avoided. Thromboelastography is an excellent technique to assess parturients with bleeding disorders or peripartum hemorrhage and may be underused.

Ubiquitin C-terminal hydrolase (UCH-L1), also called neuronal-specific protein gene product (PGP 9.3), is highly abundant in neurons. To assess the reliability of UCH-L1 as a potential biomarker for traumatic brain injury (TBI) this study compared cerebrospinal fluid (CSF) levels of UCH-L1 from adult patients with severe TBI to uninjured controls; and examined the relationship between levels with severity of injury, complications and functional outcome.This study was designed as prospective case control study.This study enrolled 66 patients, 41 with severe TBI, defined by a Glasgow coma scale (GCS) score ofor =8, who underwent intraventricular intracranial pressure monitoring and 25 controls without TBI requiring CSF drainage for other medical reasons.: Two hospital system level I trauma centers.Ventricular CSF was sampled from each patient at 6, 12, 24, 48, 72, 96, 120, 144, and 168 hrs following TBI and analyzed for UCH-L1. Injury severity was assessed by the GCS score, Marshall Classification on computed tomography and a complicated postinjury course. Mortality was assessed at 6 wks and long-term outcome was assessed using the Glasgow outcome score 6 months after injury. TBI patients had significantly elevated CSF levels of UCH-L1 at each time point after injury compared to uninjured controls. Overall mean levels of UCH-L1 in TBI patients was 44.2 ng/mL (+/-7.9) compared with 2.7 ng/mL (+/-0.7) in controls (p.001). There were significantly higher levels of UCH-L1 in patients with a lower GCS score at 24 hrs, in those with postinjury complications, in those with 6-wk mortality, and in those with a poor 6-month dichotomized Glasgow outcome score.These data suggest that this novel biomarker has the potential to determine injury severity in TBI patients. Further studies are needed to validate these findings in a larger sample.

Background/Aims: During the placement of electrodes for deep brain stimulation (DBS), patients are commonly in a seated position, awake, and spontaneously breathing. Air may be entrained through bone or dural veins causing venous air emboli (VAE) and this phenomenon can result in significant hemodynamic changes. Although VAEs have been described in many types of neurosurgical procedures, their incidence during DBS surgery is unknown. Methods: Following approval from the Institutional Review Board, the University of Florida Movement Disorders Center database comprising 286 DBS leads placed since 2002 was reviewed. Intraoperative cough, which has been associated with VAE, as well as hemodynamic instability were the focus of the review. Additionally, a prospective evaluation of the incidence of VAE using precordial Doppler ultrasound was undertaken over a 3-month period (June 2007–August 2007). Results: The retrospective review revealed a 3.2% incidence of cough per lead. Prospective monitoring in 21 consecutive patients with 22 leads yielded the detection of 1 VAE, and an incidence of 4.5% per lead. Conclusion: VAEs are rare but potentially serious complications of DBS surgery unless recognized. Patient positioning and the occurrence of cough are two important predictors to consider in VAE. Precordial Doppler is a safe, non-invasive monitor that can be used in the early detection of VAE in these procedures.

Self-inflating manual resuscitators (SIMRs) can mislead caregivers because the bag, unlike a Mapleson-type device, reinflates even without patient exhalation. We added a whistle as an audible indicator to the exhalation port of a SIMR. In randomized order, each participant provided two sets of breaths via mask ventilation with a SIMR, one with and one without audible feedback, to a Human Patient Simulator modified to log lung volume changes. The last three breaths in each set were used to compare average tidal volume (Vt) under both conditions. Eighty-seven advanced cardiac life support trainees (54 males, 33 females) with clinical experience averaging 6.4 +/- 9.4 yr were recruited. Average Vt delivered with the standard SIMR was 486 +/- 166 mL and 624 +/- 96 mL with the modified SIMR. Average Vt delivered by a modified SIMR was significantly larger by 40% when it followed standard SIMR use and 19% when using the modified SIMR first. Use of a SIMR with an audible indicator of exhalation significantly (P < 0.001) increased mask ventilation of a patient simulator, suggesting that mask ventilation of a patient with a SIMR may also be increased by objective, real-time feedback of exhaled Vt.

An understanding of the basic pharmacodynamic and pharmacokinetic characteristics of medications is paramount in the management of the critically ill neuroscience patient. Furthermore, the influence or alterations a neurologic disease process or injury may exert on these basic and specific drug principles must be considered when designing pharmacotherapy regimens and monitoring plans. Known potential adverse medication reactions, such as the potential for elevation in intracranial pressure with hydralazine, may be of little clinical concern in the average medical or surgical intensive care unit patient but of more severe consequence in the neurologically injured patient. The critical care pharmacist is a key member of the interdisciplinary team and a valuable resource in navigating the many medication issues or needs of the neuroscience patient.

Ubiquitin C-terminal hydrolase-L1 (UCH-L1) is a neuron-specific enzyme that has been identified as a potential biomarker of traumatic brain injury (TBI). The study objectives were to determine UCH-L1 exposure and kinetic metrics, determine correlations between biofluids, and assess outcome correlations in severe TBI patients. Data were analyzed from a prospective, multicenter study of severe TBI (Glasgow Coma Scale [GCS] score ≤ 8). Cerebrospinal fluid (CSF) and serum data from samples taken every 6 h after injury were analyzed by enzyme-linked immunosorbent assay (ELISA). UCH-L1 CSF and serum data from 59 patients were used to determine biofluid correlations. Serum samples from 86 patients and CSF from 59 patients were used to determine outcome correlations. Exposure and kinetic metrics were evaluated acutely and up to 7 days post-injury and compared to mortality at 3 months. There were significant correlations between UCH-L1 CSF and serum median concentrations (r(s)=0.59, p0.001), AUC (r(s)=0.3, p=0.027), Tmax (r(s)=0.68, p0.001), and MRT (r(s)=0.65, p0.001). Outcome analysis showed significant increases in median serum AUC (2016 versus 265 ng/mL*min, p=0.006), and Cmax (2 versus 0.4 ng/mL, p=0.003), and a shorter Tmax (8 versus 19 h, p=0.04) in those who died versus those who survived, respectively. In the first 24 h after injury, there was a statistically significant acute increase in CSF and serum median Cmax((0-24h)) in those who died. This study shows a significant correlation between UCH-L1 CSF and serum median concentrations and biokinetics in severe TBI patients, and relationships with clinical outcome were detected.

In this study we assessed the clinical utility of quantitative assessments of alphaII-spectrin breakdown products (SBDP145 produced by calpain, and SBDP120 produced by caspase-3) in cerebrospinal fluid (CSF) as markers of brain damage and outcome after severe traumatic brain injury (TBI). We analyzed 40 adult patients with severe TBI (Glasgow Coma Scale [GCS] scoreor=8) who underwent ventriculostomy. Patients requiring CSF drainage for other medical reasons served as controls. CSF samples were taken at admission and every 6 h thereafter for a maximum of 7 days and assessed using novel quantitative fragment-specific ELISAs for SBDPs. Outcome was assessed using the 3-month Glasgow Outcome Scale. Mean CSF levels of SBDPs were significantly higher in TBI patients than in controls at all time points examined. Different temporal release patterns of CSF SBDP145 and SBDP120 were observed. SBDP145 provided accurate diagnoses at all time points examined, while SBDP120 release was more accurate 24 h after injury. Within 24 h after injury, SBDP145 CSF concentrations significantly correlated with GCS scores, while SBDP120 levels correlated with age. SBDP levels were significantly higher in patients who died than in those who survived. SBDP145 levels (6 ng/mL) and SBDP120 levels (17.55 ng/mL) strongly predicted death (odds ratio 5.9 for SBDP145, and 18.34 for SBDP120). The time course of SBDPs in nonsurvivors also differed from that of survivors. These results suggest that CSF SBDP levels can predict injury severity and mortality after severe TBI, and can be useful complements to clinical assessment.

Traumatic brain injury (TBI) produces alphaII-spectrin breakdown products (SBDPs) that are potential biomarkers for TBI. To further understand these biomarkers, the present study examined (1) the exposure and kinetic characteristics of SBDPs in cerebrospinal fluid (CSF) of adults with severe TBI, and (2) the relationship between these exposure and kinetic metrics and severity of injury. This clinical database study analyzed CSF concentrations of 150-, 145-, and 120-kDa SBDPs in 38 severe TBI patients. Area under the curve (AUC), mean residence time (MRT), maximum concentration (C(max)), time to maximum concentration (T(max)), and half-life (t(1/2)) were determined for each SBDP. Markers of calpain proteolysis (SBDP150 and SBDP145) had a greater median AUC and C(max) and a shorter MRT than SBDP120, produced by caspase-3 proteolysis in the CSF in TBI patients ( p < 0.001). AUC and MRT for SBDP150 and SBDP15 were significantly greater in patients with worse Glasgow Coma Scale (GCS) scores at 24 h after injury compared to those whose GCS scores improved (AUC p=0.013, MRT p=0.001; AUC p=0.009, MRT p=0.021, respectively). A positive correlation was found between patients with longer elevations in intracranial pressure (ICP) measurements of 25mmHg or higher and those with a greater AUC and MRT for all three biomarkers. This is the first study to show that the biomarkers of proteolysis differentially associated with calpain and caspase-3 activity have distinct CSF exposure profiles following TBI that suggest a prominent role for calpain activity. Further studies are being conducted to determine if exposure and kinetic metrics for biofluid-based biomarkers can predict clinical outcome.

Cyclic nucleotide phosphodiesterases (PDEs) are the only enzymes that inactivate intracellular cyclic AMP (cAMP). Because the functions of T-lymphocytes are modulated by cAMP levels, the isozymes of PDE in these cells are potential targets for new drugs designed to modify the body's immunity through selective alteration of T-lymphocyte PDE activity. Cyclic GMP and 3(2 H )-pyridazinone-4, 5-dihydro-6-[4-(1 H -imidazol-1-yl)phenyl]-5-methyl-monohydrochloride (CI-930) selectively inhibit the catalytic activity of one of the two high affinity cAMP-PDE isozyme families known to occur in mammals, whereas d , l -1,4-[3-butoxy-4-methoxybenzyl]-2-imidazolidinone (Ro 20-1724) selectively inhibits the other. The objectives of this investigation were: (1) to determine whether human T-lymphocytes contain one or both of these pharmacologically distinguishable high-affinity cAMP-PDEs, and (2) to determine the effects of selective inhibitors of these PDEs on lymphocyte blastogenesis. High-affinity cAMP-PDE was found in both the soluble and particulate fractions of T-lymphocyte sonicates. Cyclic GMP and CI-930 inhibited PDE in the particulate fraction better than in the soluble fraction, but the converse was found for Ro 20-1724. CI-930 or Ro 20-1724, used alone, attenuated T-lymphocyte blastogenesis, but neither suppressed it completely. In combination, the same PDE inhibitors caused greater suppression of blastogenesis than either produced alone. The results indicate that human T-lymphocytes contain both CI-930- and Ro 20-1724-inhibitable isozymes. Either of the isozymes can modulate human T-lymphocyte blastogenesis, but inhibition of both isozymes produces synergistic antiblastogenic effects.

The effects of controlled cooling on phrenic nerve signal conduction were investigated by cooling an isolated segment of the phrenic nerve with a constant but variable temperature probe. The conduction of a standard electrical stimulus applied to the nerve proximal to the cooled section was measured by detector electrodes sutured to the diaphragm. Nerve conduction of the applied stimulus ceased between 10° and 12° C but returned within seconds after the probe was removed. The delay in the return of conduction increased as nerve temperature decreased until at a temperature of 4° C the ability to conduct did not return after 4 hours. The amount of fat surrounding the nerve and the blood flow rate along the cooled portion of the nerve were observed to ameliorate the effects of low temperature on stimulus conduction. Total body cooling also appears to offer some protection against loss of conduction.

The role of systemic autoimmunity in human traumatic brain injury (TBI) and other forms of brain injuries is recognized but not well understood. In this study, a systematic investigation was performed to identify serum autoantibody responses to brain-specific proteins after TBI in humans. TBI autoantibodies showed predominant immunoreactivity against a cluster of bands from 38-50 kDa on human brain immunoblots, which were identified as GFAP and GFAP breakdown products. GFAP autoantibody levels increased by 7 days after injury, and were of the IgG subtype predominantly. Results from in vitro tests and rat TBI experiments also indicated that calpain was responsible for removing the amino and carboxyl termini of GFAP to yield a 38 kDa fragment. Additionally, TBI autoantibody staining co-localized with GFAP in injured rat brain and in primary rat astrocytes. These results suggest that GFAP breakdown products persist within degenerating astrocytes in the brain. Anti-GFAP autoantibody also can enter living astroglia cells in culture and its presence appears to compromise glial cell health. TBI patients showed an average 3.77 fold increase in anti-GFAP autoantibody levels from early (0-1 days) to late (7-10 days) times post injury. Changes in autoantibody levels were negatively correlated with outcome as measured by GOS-E score at 6 months, suggesting that TBI patients with greater anti-GFAP immune-responses had worse outcomes. Due to the long lasting nature of IgG, a test to detect anti-GFAP autoantibodies is likely to prolong the temporal window for assessment of brain damage in human patients.

Owing to similarities between human immunodeficiency virus and feline retrovirases, the feline model was chosen for the study to investigate the efficacy of timely topical treatment of accidental human immunodeficiency virus infection in the operating room. Cats were subcutaneously inoculated with either feline leukemia virus or feline immunodeficiency virus. An effort was made to neutralize the virus in loco either by infiltration of the inoculation site with povidone-iodine or with monoclonal antibodies, or by cauterization and excision. The animals were periodically monitored for feline leukemia virus antigens or for feline immunodeficiency virus antibodies. The results indicated that in the feline model, the development of generalized virus infection may be prevented by local measures if applied immediately.

Particulate matter comparable in size with that of human immunodeficiency virus was subcutaneously injected into experimental animals. Such matter remained at the inoculation site long enough to suggest the possibility that human immunodeficiency virus can be destroyed in loco before it invades the host's circulation. These findings may be useful in developing a method to prevent acquired immunodeficiency syndrome after accidental injury with human immunodeficiency virus-contaminated instruments.

The cyclic nucleotide phosphodiesterase (EC 3.1.4.17) in extracts of purified human peripheral blood T-lymphocytes was examined by ion exchange high pressure liquid chromatography. Four peaks of activity were isolated. The first peak of activity selectively hydrolyzed cyclic GMP. The following 3 peaks of activity (Ia, IIa and IIIa) were selective for cyclic AMP. The selective low K m cyclic AMP-phosphodiesterase inhibitor, Ro 20-1724 (d,l-1,4-[3-butoxy-4-methoxybenzyl]-2-imidazolidinone), did not inhibit the activity in Ia whereas it did inhibit the activity in IIa and IIIa (IC 50 = 17 μM). The authors conclude that ion exchange high pressure liquid chromatography described in this communication is a useful method for the isolation of different forms of cyclic nucleotide phosphodiesterase activity from human T-lymphocytes.

A simple method for the positioning of a temporary pacemaker electrode in the course of open-heart operation is presented. Instead of using "back stitching," we recommend that after the wire electrode is passed through the myocardium, it should be driven through a small pledget of Silastic rubber material to hold it in position.