Predicting the difficult neuraxial block: a prospective study.

Anticipated technical difficulty is one factor that can influence the anesthesiologist's decision to perform neuraxial (spinal or epidural) blockade. Problems during the procedure may be associated with patient dissatisfaction, neurologic sequelae, or hematoma. We designed this study of 595 neuraxial blocks to determine whether any patient characteristics would be useful in predicting a difficult neuraxial block. Before the procedure, the following data were noted: demographic data, body habitus (normal, thin, muscular, obese), spinal landmarks (good = easily palpable spinous processes, poor = difficult to palpate spinous processes, none = unable to positively identify spinous processes), and spinal anatomy (assessed by inspection and examination as normal or deformed). We noted the technique, approach, needle type, needle gauge, etc. We also recorded whether the procedure was completed at the first (first-level success) or second spinal level and the total number of new skin punctures (attempts) necessary to complete the procedure. Of all the factors considered, the quality of landmarks best correlated with technical difficulty as measured by both first-level success and number of attempts. Abnormal spinal anatomy correlated with difficulty as measured by number of attempts. Body habitus also correlated with difficulty, but only as measured by number of attempts. There was no association between either measure of difficulty and any of the following: age, sex, spinal versus epidural, approach, needle type, needle gauge, or training level of the provider. Thoracic epidurals were less difficult than lumbar epidurals by both measures of difficulty. We conclude that body habitus does not seem to be the best predictor of technical difficulty. An examination of the patient's back for the quality of landmarks and obvious anatomical deformity better predicts the ease or difficulty of neuraxial block. Other factors seem to have little or no influence on the difficulty of neuraxial block procedures. Implications: We studied a number of factors, including equipment, technique, and patient characteristics, that may indicate the ease or difficulty of performing neuraxial (spinal and epidural) blocks. Of these factors, only patient characteristics had significant predictive value. We found that an examination of the patient's back for the quality of landmarks and obvious anatomical deformity better predicts the ease or difficulty of neuraxial block than does body habitus.     

Fearful faces in schizophrenia: the relationship between patient characteristics and facial affect recognition

Although schizophrenia has often been associated with deficits in facial affect recognition, it is debated whether the recognition of specific emotions is affected and if these facial affect-processing deficits are related to symptomatology or other patient characteristics. The purpose of the present study was to explore whether particular patient characteristics are associated with the recognition of specific facial expressions in patients with schizophrenia. Sixty-four patients with a DSM-IV diagnosis of schizophrenia were assessed with a computerized test of degraded facial affect recognition. Linear regression analysis showed that, in particular, negative symptoms and male sex were associated with worse recognition of fearful faces. Furthermore, diagnosis of nonparanoid schizophrenia and later age of onset were associated with worse recognition of neutral faces. Findings are explained in the light of a neuroanatomical dysfunction accounting for both negative symptoms, such as reduced emotional expression and social-emotional dysfunction, for which men seem more vulnerable than women.     

Can nasal drug delivery bypass the blood-brain barrier?: questioning the direct transport theory

The connection between the nasal cavity and the CNS by the olfactory neurones has been investigated extensively during the last decades with regard to its feasibility to serve as a direct drug transport route to the CSF and brain. This drug transport route has gained much interest as it may circumvent the blood-brain barrier (BBB), which prevents some drugs from entering the brain. Approximately 100 published papers mainly reporting animal experiments were reviewed to evaluate whether the experimental design used and the results generated provided adequate pharmacokinetic information to assess whether the investigated drug was transported directly from the olfactory area to the CNS. In the analysis the large anatomical differences between the olfactory areas of animals and humans and the experimental conditions used were evaluated. The aim of this paper was to establish the actual evidence for the feasibility of this direct transport route in humans. Twelve papers presented a sound experimental design to study direct nose to CNS transport of drugs based on the authors' criteria. Of these, only two studies in rats were able to provide results that can be seen as an indication for direct transport from the nose to the CNS. No pharmacokinetic evidence could be found to support a claim that nasal administration of drugs in humans will result in an enhanced delivery to their target sites in the brain compared with intravenous administration of the same drug under similar dosage conditions.     

Association of ethnicity with the minimum alveolar concentration of sevoflurane

BACKGROUND: Selective breeding produces animal strains with varying anesthetic sensitivity. It thus seems unlikely that various human ethnicities have identical anesthetic requirements. Therefore, the authors tested the hypothesis that the minimum alveolar concentration of sevoflurane differs significantly as a function of ethnicity. METHODS: The authors recruited 90 American Society of Anesthesiologists physical status I and II adult patients belonging to three Jewish ethnic groups: European, Oriental, and Caucasian (from the Caucasus Mountain region). All were scheduled to undergo surgery requiring a skin incision exceeding 3 cm. Without premedication, anesthesia was induced with 6-8% sevoflurane in 100% oxygen, and tracheal intubation was facilitated with succinylcholine. The skin incision was made after a predetermined end-tidal concentration of sevoflurane of 2.0% was maintained for at least 10 min in the first patient in each group. Blinded investigators observed the patient for movement during the subsequent minute. The concentration in the next patient was increased by 0.2% when patients moved, or decreased by the same amount when they did not. Results are presented as means [95% confidence intervals]. RESULTS: Morphometric and demographic characteristics were similar among the groups; however, mean arterial pressure was slightly greater in European Jews. Minimum alveolar concentration for sevoflurane was greatest in Caucasian Jews (2.32% [2.27-2.41%]), less in Oriental Jews (2.14% [2.06-2.22%]), and still less in European Jews (1.9% [1.82-1.99%]) (P < 0.001). CONCLUSIONS: The results suggest that minimum alveolar concentration varies as a function of ethnicity. However, the extent to which confounding characteristics contribute, including lifestyle choices and environmental factors, remains unknown.     

Amino acid regions 572-579 and 657-666 of the spacer domain of ADAMTS13 provide a common antigenic core required for binding of antibodies in patients with acquired TTP

Antibodies directed against ADAMTS13 have been detected in the majority of patients with acquired thrombotic thrombocytopenic purpura (TTP). We have previously localized a major antigenic determinant within the spacer domain of ADAMTS13. To identify the amino acid residues of the spacer domain that are involved in binding of anti-ADAMTS13 antibodies, we constructed a series of fifteen hybrids (designated A-O) in which 5-10 amino acids of the spacer domain were exchanged for the corresponding region of ADAMTS1. Plasma from six patients with antibodies directed against the spacer domain was analyzed for reactivity with the ADAMTS13/ADAMTS1 chimeras. Exchange of amino acid residues 572-579 (hybrid C) and 657-666 (hybrid M) completely abolished the binding of antibodies from all six patients analyzed. Regions 580-587 (D), 602-620 (G, H), 629-638 (J), and 667-767 (N) contributed to binding of antibodies from patients 2, 4, and 5 (epitope present within regions CDGHJMN). Antibodies derived from patient 1 required region 602-620 (G, H) for binding (CGHM-epitope). For antibodies of patient 3, residues 564-571 (B), 580-587 (D), and 629-638 (J) were required (BCDJM-epitope), whereas replacement of residues 602-610 (G) and 629-638 (J) greatly diminished binding of antibodies from patient 6 (CGJM-epitope). Despite the presumably polyclonal origin of the antibodies present in plasma of patients, our results suggest that residues 572-579 (C) and 657-666 (M) comprise a common antigenic core region that is crucial for binding of anti-ADAMTS13 antibodies. Other regions that spatially surround this antigenic core further modulate binding of antibodies to the spacer domain.     

Identification of their epitope reveals the structural basis for the mechanism of action of the immunosuppressive antibodies basiliximab and daclizumab

Interleukin-2 (IL-2) and its receptor (IL-2R) play a major role in cellular immunity. The monoclonal antibodies basiliximab and daclizumab directed against the IL-2R subunit CD25 are widely used to prevent graft or host rejection after allogeneic tissue transplantation. Although these antibodies have been used for this purpose for many years, their common epitope within the CD25 protein is unknown. We screened a random phage display library to isolate peptides specifically binding to basiliximab. A striking amino acid sequence motif was enriched. This motif is homologous to the peptide ERIYHFV comprising amino acid positions 116 to 122 within the extracellular domain of CD25, suggesting that this is the basiliximab epitope. Basiliximab and daclizumab binding of selected phage was specific, as no binding was observed to isotype antibody controls. Phage binding could be inhibited by the cognate peptide. In cells expressing mutant CD25, binding of basiliximab was abolished when two or more amino acids of the suspected epitope were changed. In contrast, basiliximab binding remained unaffected in cells expressing CD25 versions with mutations outside this epitope. We therefore conclude that the (116)ERIYHFV(122) string within CD25 is the epitope recognized by basiliximab and daclizumab. This epitope overlaps with the interaction site of CD25 and IL-2, thus revealing the structural basis for the inhibition of IL-2R binding by this class of immunosuppressive antibodies.     

Accuracy of seizure detection using abbreviated EEG during polysomnography.

The purpose of this study was to determine the validity of abbreviated EEG montages for seizure detection during polysomnography. Three electroencephalographers reviewed files containing seizures or nonepileptic events using 8- and 18-channel montages. Files were rated as to whether they contained seizures and assigned a "probability of seizure" score from 0% to 100% reflecting the confidence that it was a seizure. Readers then localized seizures as temporal, frontal, parieto-occipital, or nonlocalized and provided a probability of correct localization with 0% to 100% confidence. Data were analyzed using the Adjusted McNemar Test method of Obochuwski. The probability of seizure score was measured using the receiver operating characteristic curve. Observed agreement was 78% and 84% for 8- and 18-channel montages, respectively. Readers were better able to distinguish seizures from nonepileptic events using the 18-channel montage (P = 0.004). Seizures localized to the temporal and parieto-occipital regions were more likely to be correctly identified and localized. Readers were able to correctly localize 27% and 49% of seizures using the 8- and 18-channel montages, respectively (P < 0.001). Abbreviated EEG montages are inadequate in the differentiation of seizures and nonepileptic events arising from sleep during polysomnography. This seems to be particularly true in frontal lobe epilepsy.     

Dendritic cells: biology of the skin

Allergic contact dermatitis results from a T-cell-mediated, delayed-type hypersensitivity immune response induced by allergens. Skin dendritic cells (DCs) play a central role in the initiation of allergic skin responses. Following encounter with an allergen, DCs become activated and undergo maturation and differentiate into immunostimulatory DCs and are able to present antigens effectively to T cells. The frequency of allergic skin disorders has increased in the past decades. Therefore, the identification of potential sensitizing chemicals is important for skin safety. Traditionally, predictive testing for allergenicity has been conducted in animal models. For regulatory reasons, animal use for sensitization testing of compounds for cosmetic purposes is shortly to be prohibited in Europe. Therefore, new non-animal-based test methods need to be developed. Several DC-based assays have been described to discriminate allergens from irritants. Unfortunately, current in vitro methods are not sufficiently resilient to identify allergens and therefore need refinement. Here, we review the immunobiology of skin DCs (Langerhans' cells and dermal dendritic cells) and their role in allergic and irritant contact dermatitis and then explore the possible use of DC-based models for discriminating between allergens and irritants.