Facilitation of penicillin haptenation to serum proteins.

Traditionally, penicillin binding to serum proteins was believed to be a passive chemical process; however, it appears to be facilitated by serum factors. The objectives of this in vitro investigation were to examine facilitated penicillin haptenation, to study the kinetics of haptenation, and to determine the nature of haptenation-facilitating factors. The model involved addition of [3H]benzylpenicillin to serum or albumin solutions (at pH 7.3 to 7.4) and incubation at 37 degrees C for up to 72 h. The extent of penicillin binding to proteins in serum was found to be four- to fivefold higher than with solutions having comparable concentrations of purified albumin, total protein, or total immunoglobulin. Ultrafiltration of serum reduced penicillin binding to serum proteinssubstantially. An ultrafiltrable haptenation-facilitating factor(s) was found to be less than 0.5 kDa but was not calcium or magnesium. Finally, the extent of penicillin binding was related to albumin purity, as binding substantially increased with albumin purity. These findings suggest that there is a factor(s) in serum that facilitates covalent binding of penicillin to serum proteins. The factor(s) can be removed and then restored to increase penicillin binding to albumin. It appears that at least one component of the facilitation factor is less than 0.5 kDa, which suggests that it is not a peptide and that it is some simple serum component other than calcium or magnesium

Lipopolysaccharide-reactive immunoglobulin E is associated with lower mortality and organ failure in traumatically injured patients

Antilipopolysaccharide (anti-LPS) immunoglobulin G (IgG) and IgM have been associated with protection from LPS effects in vivo. We investigated the presence of IgE and anti-LPS in 32 patients that had experienced severe traumatic injury and in 35 healthy volunteers; we also investigated whether IgE anti-LPS was associated with important clinical events. Plasma samples were collected daily from patients in the intensive care unit and on one occasion from volunteers; the samples were assayed for IgE anti-LPS. IgE anti-LPS was assayed by enzyme-linked immunosorbent assay with monoclonal anti-human IgE as the capture antibody. Detection was accomplished with biotin-labeled LPS (Escherichia coli J5 mutant) followed by streptavidin-peroxidase with 2,2\u27-azino(3-ethylbenzthiazoline)sulfonic acid as the substrate. The assay was demonstrated to be specific for IgE and LPS-biotin by nonreactivity of control sera with high-titer anti-LPS IgG and IgM and by inhibition with unlabeled LPS. IgE anti-LPS was detected in 1 of 35 healthy controls (2.9%o) and 25 of 32 traumatically injured patients (78%) (P \u3c 0.001). The presence of IgE anti-LPS was associated with a lower incidence of death (P = 0.026) and of renal failure (P = 0.0012). There was no apparent temporal relationship between detection of IgE anti-LPS and clinical events. IgG anti-LPS was detected more frequently in patients that were positive for IgE anti-LPS (P = 0.06) but was not associated with clinical events. The inability to detect IgE anti-LPS may be related to adverse clinical events through depletion of specific IgE due to LPS exposure after trauma or through saturation of the assay by IgE with other specificities. We have reported increased total IgE concentrations in these patients (J. T. DiPiro, R. G. Hamilton, T. R. Howdieshell, N. F. Adkinson, and A. R. Mansberger, Ann. Surg. 215:460-466, 1992)

Self‐reported drug allergy in a general adult Portuguese population

Clin Exp Allergy. 2004 Oct;34(10):1597-601. Self-reported drug allergy in a general adult Portuguese population. Gomes E, Cardoso MF, Praça F, Gomes L, Mariño E, Demoly P. Serviço de Imunoalergologia, Hospital Maria Pia, Porto, Portugal. [email protected] Abstract AIM: To estimate the prevalence of self-reported drug allergy in adults. METHODS: Cross-sectional survey of a general adult population from Porto (all of whom were living with children involved in the International Study of Asthma and Allergies in Childhood-phase three), during the year 2002, using a self-administered questionnaire. RESULTS: The prevalence of self-reported drug allergy was 7.8% (181/2309): 4.5% to penicillins or other beta-lactams, 1.9% to aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs) and 1.5% to other drugs. In the group 'allergic to beta-lactams', the most frequently implicated drug was penicillin G or V (76.2%) followed by the association of amoxicillin and clavulanic acids (14.3%). In the group 'allergic to NSAIDs', acetylsalicylic acid (18.2%) and ibuprofen (18.2%) were the most frequently identified drugs, followed by nimesulide and meloxicam. Identification of the exact name of the involved drug was possible in less than one-third of the patients, more often within the NSAID group (59.5%). Women were significantly more likely to claim a drug allergy than men (10.2% vs. 5.3%). The most common manifestations were cutaneous (63.5%), followed by cardiovascular symptoms (35.9%). Most of the reactions were immediate, occurring on the first day of treatment (78.5%). Only half of the patients were submitted to drug allergy investigations. The majority (86.8%) completely avoided the suspected culprit drug thereafter. CONCLUSIONS: The results showed that self-reported allergy to drugs is highly prevalent and poorly explored. Women seem to be more susceptible. beta-lactams and NSAIDs are the most frequently concerned drugs. PMID: 15479276 [PubMed - indexed for MEDLINE

Comparison of Wound Outcomes for Absorbable versus Non-absorbable Suture after Carpal Tunnel Release

Background and Hypothesis:Carpal tunnel release (CTR) is a common hand surgery procedure. Despite the large volume of CTRs performed worldwide (400,000-600,000 cases/year), there is no consensus as to the optimal suture material for incision closure. In this study, we sought to compare outcomes of absorbable and non-absorbable suture for skin closure after CTR. Our hypothesis was that that there is no statistically or clinically significant difference in wound-related outcomes between the cohorts. Project Methods:All patients who underwent primary open carpal tunnel release (CTR) at a large, public county hospital in Indianapolis, IN were identified by CPT code (64721). All patients were treated by one of two fellowship-trained hand surgeons. The most recent 50 patients treated between September 2022 and May 2023 by each surgeon were identified. Surgeon “A” uses 4-0 vicryl rapide for closures (absorbable). Surgeon “B” uses 4-0 nylon for closures (non-absorbable). Adverse events (AE) were defined as infection, dehiscence, or suture granuloma observed at any follow-up appointment. This study was approved by the Institutional Review Board. Results:100 patients were identified - 4 patients were lost to follow-up and were excluded from the study. Of the remaining 96 patients, 46 received absorbable suture and 50 non-absorbable suture. Of the 46 patients who received absorbable suture, 8 experienced AE (17.4%). None of the 50 patients who received non-absorbable suture experienced an AE. There was a statistically significant difference in AE between the absorbable and non-absorbable suture cohorts (p=0.002). Patients with absorbable suture averaged 1.61 follow-up appointments, whereas those with non-absorbable suture averaged 2.32 (p=.0008). Conclusion and Potential Impact:In this study, absorbable suture resulted in more wound-related complications after CTR. However, patients with non-absorbable suture had more post-operative follow-up appointments. These findings should be considered when selecting suture material for skin closure after CTR

Meta-analysis of genome-wide association studies of asthma in ethnically diverse North American populations.

Asthma is a common disease with a complex risk architecture including both genetic and environmental factors. We performed a meta-analysis of North American genome-wide association studies of asthma in 5,416 individuals with asthma (cases) including individuals of European American, African American or African Caribbean, and Latino ancestry, with replication in an additional 12,649 individuals from the same ethnic groups. We identified five susceptibility loci. Four were at previously reported loci on 17q21, near IL1RL1, TSLP and IL33, but we report for the first time, to our knowledge, that these loci are associated with asthma risk in three ethnic groups. In addition, we identified a new asthma susceptibility locus at PYHIN1, with the association being specific to individuals of African descent (P = 3.9 × 10(-9)). These results suggest that some asthma susceptibility loci are robust to differences in ancestry when sufficiently large samples sizes are investigated, and that ancestry-specific associations also contribute to the complex genetic architecture of asthma

The Effects of Postoperative Physician Phone Calls for Hand and Wrist Fractures: A Prospective, Randomized Controlled Trial

Background: In this study, we sought to determine if postoperative physician phone calls following hand and wrist fracture surgery improve patient outcomes, satisfaction, and treatment adherence. Methodology: We prospectively enrolled 24 consecutive adult patients who underwent outpatient surgery for isolated hand and wrist fractures at a single, metropolitan, safety-net hospital over one year to receive an additional physician phone call starting on postoperative day one. We measured preoperative and postoperative Brief Michigan Hand Questionnaire (bMHQ) composite score, overall satisfaction on a five-point Likert scale, compliance with treatment recommendations, presence of complications, discharge instructions reading level, and clarity of discharge and follow-up instructions. The surgical team was blinded to the treatment arm. Results: The bMHQ score improved 26% after surgery; however, there was no difference in absolute score change between groups (12.2 vs. 6.5, p = 0.69). Most patients were satisfied throughout all stages of care, but postoperative satisfaction did not differ between groups (1.4 vs. 2.5, p = 0.21). There was a stronger correlation between patient hand function and satisfaction starting one month after surgery (R2 = 0.502, p = 0.002) than preoperatively (R2 = 0.252, p = 0.029). Immediately following surgery, most patients stated that discharge instructions were clear, and the average readability was below the average patient education level. Despite this, 13% removed their splint or Kirschner wires, 67% did not follow up within a week of recommendation, 62% did not complete postoperative treatment, and 33% had complications. Conclusions: Postoperative phone calls by physicians did not improve compliance with recommendations, patient-rated outcome measures, or clinical outcomes among our hand and wrist fracture patient population

Hierarchical heterogeneity across human cortex shapes large-scale neural dynamics

The large-scale organization of dynamical neural activity across cortex emerges through long-range interactions among local circuits. We hypothesized that large-scale dynamics are also shaped by heterogeneity of intrinsic local properties across cortical areas. One key axis along which microcircuit properties are specialized relates to hierarchical levels of cortical organization. We developed a large-scale dynamical circuit model of human cortex that incorporates heterogeneity of local synaptic strengths, following a hierarchical axis inferred from MRI-derived T1w/T2w mapping, and fit the model using multimodal neuroimaging data. We found that incorporating hierarchical heterogeneity substantially improves the model fit to fMRI-measured resting-state functional connectivity and captures sensory-association organization of multiple fMRI features. The model predicts hierarchically organized high-frequency spectral power, which we tested with resting-state magnetoencephalography. These findings suggest circuit-level mechanisms linking spatiotemporal levels of analysis and highlight the importance of local properties and their hierarchical specialization on the large-scale organization of human cortical dynamics

Default mode network electrophysiological dynamics and causal role in creative thinkingDefault Mode Network Electrophysiological Dynamics and Causal Role in Creative Thinking

The default mode network (DMN) is a widely distributed, intrinsic brain network thought to play a crucial role in internally directed cognition. The present study employs stereo-EEG in 13 human patients, obtaining high resolution neural recordings across multiple canonical DMN regions during two processes that have been associated with creative thinking: spontaneous and divergent thought. We probe these two DMN-associated higher cognitive functions through mind wandering and alternate uses tasks, respectively. Our results reveal DMN recruitment during both tasks, as well as a task-specific dissociation in spatiotemporal response dynamics. When compared to the fronto-parietal network, DMN activity was characterized by a stronger increase in gamma band power (30-70 Hz) coupled with lower theta band power (4-8 Hz). The difference in activity between the two networks was especially strong during the mind wandering task. Within the DMN, we found that the tasks showed different dynamics, with the alternate uses task engaging the DMN more during the initial stage of the task, and mind wandering in the later stage. Gamma power changes were mainly driven by lateral DMN sites, while theta power displayed task-specific effects. During alternate uses task, theta changes did not show spatial differences within the DMN, while mind wandering was associated to an early lateral and late dorsomedial DMN engagement. Furthermore, causal manipulations of DMN regions using direct cortical stimulation preferentially decreased the originality of responses in the alternative uses task, without affecting fluency or mind wandering. Our results suggest that DMN activity is flexibly modulated as a function of specific cognitive processes and supports its causal role in divergent thinking. These findings shed light on the neural constructs supporting different forms of cognition and provide causal evidence for the role of DMN in the generation of original connections among concepts