Exposure to Smoke From Wildfire, Prescribed, and Agricultural Burns Among At-Risk Populations Across Washington, Oregon, and California.

Wildfires, prescribed burns, and agricultural burns all impact ambient air quality across the Western U.S.; however, little is known about how communities across the region are differentially exposed to smoke from each of these fire types. To address this gap, we quantify smoke exposure stemming from wildfire, prescribed, and agricultural burns across Washington, Oregon, and California from 2014 to 2020 using a fire type-specific biomass burning emissions inventory and the GEOS-Chem chemical transport model. We examine fire type-specific PM2.5 concentration by race/ethnicity, socioeconomic status, and in relation to the Center for Disease Control's Social Vulnerability Index. Overall, population-weighted PM2.5 concentrations are greater from wildfires than from prescribed and from agricultural burns. While we found limited evidence of exposure disparities among sub-groups across the full study area, we did observe disproportionately higher exposures to wildfire-specific PM2.5 exposures among Native communities in all three states and, in California, higher agricultural burn-specific PM2.5 exposures among lower socioeconomic groups. We also identified, for all three states, areas of significant spatial clustering of smoke exposures from all fire types and increased social vulnerability. These results provide a first look at the differential contributions of smoke from wildfires, prescribed burns, and agricultural burns to PM2.5 exposures among demographic subgroups, which can be used to inform more tailored exposure reduction strategies across sources.

Quantifying fascial tension in ventral hernia repair and component separation.

BACKGROUND: Excessive fascial tension is a major cause of ventral hernia recurrence. Although hernias are commonly characterized by area, the tension experienced by fascia is directly proportional to the surrounding tissue stiffness. We demonstrate an accurate and simple technique for intra-operative measurement of fascial closing tension and quantify the decrease in tension following Component Separation (CS). METHODS: A tensiometer was created using a spring with a known recoil constant (k) and a surgical clamp. Using Hooke's law (Force = kX; X = spring displacement), fascial tension was calculated. This method was first validated on a bench-top model and then applied to the anterior fascia of 4 fresh cadavers (8 hemi-abdomens) over a range of simulated hernia defect sizes. When fascia could no longer reach midline, CS was performed and measures repeated. Tissue stiffness was calculated by plotting defect size versus resulting tension. RESULTS: Fascial defects ranged from 1- to 18-cm wide with average midline closing tension prior to release 36.1 N (range 17-48) and 8.2 N (range 5-11) after CS, a mean 76% decrease (range 70%-85%). Mean R2 values between defect size and tension for the synthetic and cadaver models were 0.99 (p < 0.01) and 0.91 (p = 0.01; all hemi-abdomen measurements significant). Inter-rater Pearson's correlation consistently found R2 values > 0.95 (p < 0.01) for each hemi-abdomen, showing high precision and reproducibility. CONCLUSION: We have applied a cheap, simple, and precise method to sterilely assess fascial tension during herniorrhaphy and also quantified the decrease in tension following component separation. This technique may be rapidly translated into the operating room with minimal equipment to provide objective data critical for intraoperative decision-making.

Relapse to cocaine-seeking after hippocampal theta burst stimulation.

Treatment efforts for cocaine addiction are hampered by high relapse rates. To map brain areas underlying relapse, we used electrical brain stimulation and intracranial injection of pharmacological compounds after extinction of cocaine self-administration behavior in rats. Electrical stimulation of the hippocampus containing glutamatergic fibers, but not the medial forebrain bundle containing dopaminergic fibers, elicited cocaine-seeking behavior dependent on glutamate in the ventral tegmental area. This suggests a role for glutamatergic neurotransmission in relapse to cocaine abuse. The medial forebrain bundle electrodes supported intense electrical self-stimulation. These findings suggest a dissociation of neural systems subserving positive reinforcement (self-stimulation) and incentive motivation (relapse).

Building Capability for Clinical Pharmacology Research in Sub-Saharan Africa.

A strong scientific rationale exists for conducting clinical pharmacology studies in target populations because local factors such as genetics, environment, comorbidities, and diet can affect variability in drug responses. However, clinical pharmacology studies are not widely conducted in sub-Saharan Africa, in part due to limitations in technical expertise and infrastructure. Since 2012, a novel public-private partnership model involving research institutions and a pharmaceutical company has been applied to developing increased capability for clinical pharmacology research in multiple African countries.

Management of T3N1 glottic carcinoma: therapeutic outcomes.

OBJECTIVE: The aim of the current study was to determine the best total laryngectomy (TL) approach to the treatment of T3N1 glottic cancer, to study the impact of early nodal disease on stage III glottic cancers, and to describe the preliminary results in a group of patients recently treated for laryngeal preservation (LP). METHODS: A retrospective study of Tumor Research Project data were performed on previously untreated patients with T3N1 glottic squamous cell carcinoma who were treated with curative intent by TL and neck dissection (ND) with or without adjuvant radiation therapy (TL +/- RT) from April 1, 1955 to October 8, 1999 at Washington University School of Medicine/Barnes Jewish Hospital. A preliminary analysis of a similar group of patients more recently treated for LP (1-1-2000 to 1-1-2005) is reported. RESULTS: Forty-two patients with T3N1 glottic carcinoma were treated with TL and ND (TL/ND-16) and TL with ND and TL (TL/ND/RT-26). The 5 year observed survival (OS) and disease-specific survival (DSS) for TL/ND were similar at 62.5%. The 5 year OS and DSS for TL/ND/RT were 53.8% and 58.3%, respectively. There was no survival difference between the two methods. The overall local-regional control rate was 73.9% (11/42 recurrences). The overall recurrence rate was 38%, with 7.1% recurrence at both the primary site and neck. Recurrence was not related to treatment method. The overall salvage rate (5 year DSS after retreatment) was 20% with 50% salvage for patients with neck recurrence. No patients with local recurrence were survivors. The incidence of second primary cancers was 6.8%. More recently, 26 similar patients were treated with LP techniques. Preliminary results showed a 3 year OS of 63.5% and DSS of 76.8%. Local-regional control was 85.4%. LP was 88.5%. CONCLUSIONS: The two TL modalities had statistically similar results in terms of survival, recurrence, and complications. Decreased DSS was seen in older patients (>65 years) and in patients with involved resection margins, recurrent disease, and distant metastasis. Patients with T3N1 glottic cancer had an 8% decrease in DSS compared to patients with T3N0 disease. Previously patients with T3N1 disease have been treated with TL resulting in loss of natural voice in all patients. Preliminary results on 26 patients with T3N1 disease, treated between 2000 and 2005 with voice preservation intent, indicate that the OS, DSS, and local-regional control rates were similar to the TL group, whereas 88.5% of patients maintained natural voice and natural breathing. Use of LP techniques should be the initial therapeutic approach for patients with T3N1 glottic cancer.

Plasmacytoma of the breast. An unusual case of recurrent myeloma.

An unusual case of multiple myeloma is presented in which recurrence of the disease after a four-year remission was heralded by an infiltrating plasmacytoma of the breast. The clinical and histologic features of this neoplasm are presented and compared with ten previously reported cases of plasmacytoma of the breast.

Regional differentiation of cranial suture-associated dura mater in vivo and in vitro: implications for suture fusion and patency.

Despite its prevalence, the etiopathogenesis of craniosynostosis is poorly understood. To better understand the biomolecular events that occur when normal craniofacial growth development goes awry, we must first investigate the mechanisms of normal suture fusion. Murine models in which the posterior frontal (PF) suture undergoes programmed sutural fusion shortly after birth provide an ideal model to study these mechanisms. In previous studies, our group and others have shown that sutural fate (i.e., fusion vs. patency) is regulated by the dura mater (DM) directly underlying a cranial suture. These studies have led to the hypothesis that calvarial DM is regionally differentiated and that this differentiation guides the development of the overlying suture. To test this hypothesis, we evaluated the messenger RNA (mRNA) expression of osteogenic cytokines (transforming growth factor beta1 [TGF-beta1] and TGF-beta3) and bone-associated extracellular matrix (ECM) molecules (collagen I, collagen III, osteocalcin, and alkaline phosphatase) in freshly isolated, rat dural tissues associated with the PF (programmed to fuse) or sagittal (SAG; remains patent) sutures before histological evidence of sutural fusion (postnatal day 6 [N6]). In addition, osteocalcin protein expression and cellular proliferation were localized using immunohistochemical staining and 5-bromo-2'deoxyuridine (BrdU) incorporation, respectively. We showed that the expression of osteogenic cytokines and bone-associated ECM molecules is potently up-regulated in the DM associated with the PF suture. In addition, we showed that cellular proliferation in the DM associated with the fusing PF suture is significantly less than that found in the patent SAG suture just before the initiation of sutural fusion N6. Interestingly, no differences in cellular proliferation rates were noted in younger animals (embryonic day 18 [E18] and N2). To further analyze regional differentiation of cranial suture-associated dural cells, we established dural cell cultures from fusing and patent rat cranial sutures in N6 rats and evaluated the expression of osteogenic cytokines (TGF-beta1 and fibroblast growth factor 2 [FGF-2]) and collagen I. In addition, we analyzed cellular production of proliferating cell nuclear antigen (PCNA). These studies confirmed our in vivo findings and showed that dural cell cultures derived from the fusing PF suture expressed significantly greater amounts of TGF-beta1, FGF-2, and collagen I. In addition, similar to our in vivo findings, we showed that PF suture-derived dural cells produced significantly less PCNA than SAG suture-derived dural cells. Finally, coculture of dural cells with fetal rat calvarial osteoblastic cells (FRCs) revealed a statistically significant increase in proliferation (*p < 0.001) in FRCs cocultured with SAG suture-derived dural cells as compared with FRCs cocultured alone or with PF suture-derived dural cells. Taken together, these data strongly support the hypothesis that the calvarial DM is regionally differentiated resulting in the up-regulation of osteogenic cytokines and bone ECM molecules in the dural tissues underlying fusing but not patent cranial sutures. Alterations in cytokine expression may govern osteoblastic differentiation and ECM molecule deposition, thus regulating sutural fate. Elucidation of the biomolecular events that occur before normal cranial suture fusion in the rat may increase our understanding of the events that lead to premature cranial suture fusion.

Adenovirus-mediated gene therapy of osteoblasts in vitro and in vivo.

Modulation of biological pathways governing osteogenesis may accelerate osseous regeneration and reduce the incidence of complications associated with fracture healing. Transforming growth factor beta1 (TGF-beta1) is a potent growth factor implicated in the regulation of osteogenesis and fracture repair. The use of recombinant proteins, however, has significant disadvantages and has limited the clinical utility of these molecules. Targeted gene therapy using adenovirus vectors is a technique that may circumvent difficulties associated with growth factor delivery. In this study, we investigate the efficacy of replication-deficient adenoviruses containing the human TGF-beta1 and the bacterial lacZ genes in transfecting osteoblasts in vitro and osseous tissues in vivo. We demonstrate that adenovirus-mediated gene therapy efficiently transfects osteoblasts in vitro with the TGF-beta1 virus causing a marked up-regulation in TGF-beta1 mRNA expression even 7 days after transfection. Increased TGF-beta1 mRNA expression was efficiently translated into protein production and resulted in approximately a 46-fold increase in TGF-beta1 synthesis as compared with control cells (vehicle- or B-galactosidase-transfected). Moreover, virally produced TGF-beta1 was functionally active and regulated the expression of collagen IalphaI (5-fold increase) and the vascular endothelial growth factor (2.5-fold increase). Using an adenovirus vector encoding the Escherichia coli LacZ gene, we demonstrated that adenovirus-mediated gene transfer efficiently transfects osteoblasts and osteocytes in vivo and that transfection can be performed by a simple percutaneous injection. Finally, we show that delivery of the hTGF-beta1 gene to osseous tissues in vivo results in significant changes in the epiphyseal plate primarily as a result of increased thickness of the provisional calcification zone.

Mechanisms of fibroblast growth factor-2 modulation of vascular endothelial growth factor expression by osteoblastic cells.

Normal bone growth and repair is dependent on angiogenesis. Fibroblast growth factor-2 (FGF-2), vascular endothelial growth factor (VEGF), and transforming growth factor-beta (TGFbeta) have all been implicated in the related processes of angiogenesis, growth, development, and repair. The purpose of this study was to investigate the relationships between FGF-2 and both VEGF and TGFbeta in nonimmortalized and clonal osteoblastic cells. Northern blot analysis revealed 6-fold peak increases in VEGF mRNA at 6 h in fetal rat calvarial cells and MC3T3-E1 osteoblastic cells after stimulation with FGF-2. Actinomycin D inhibited these increases in VEGF mRNA, whereas cycloheximide did not. The stability ofVEGF mRNA was not increased after FGF-2 treatment. Furthermore, FGF-2 induced dose-dependent increases in VEGF protein levels (P < 0.01). Although in MC3T3-E1 cells, TGFbeta1 stimulates a 6-fold peak increase in VEGF mRNA after 3 h of stimulation, we found that both TGFbeta2 and TGFbeta3 yielded 2- to 3-fold peak increases in VEGF mRNA levels noted after 6 h of stimulation. Similarly, both TGFbeta2 and TGFbeta3 dose dependently increased VEGF protein production. To determine whether FGF-2-induced increases in VEGF mRNA may have occurred independently of TGFbeta, we disrupted TGFbeta signal transduction (using adenovirus encoding a truncated form of TGFbeta receptor II), which attenuated TGFbeta1 induction of VEGF mRNA, but did not impede FGF-2 induction ofVEGF mRNA. In summary, FGF-2-induced VEGF expression by osteoblastic cells is a dose-dependent event that may be independent of concomitant FGF-2-induced modulation of TGFbeta activity.

Polybrene neutralization as a means of monitoring heparin therapy for extracoporeal cirulation.

Dose-response effects of heparin and protamine in 34 adult patients undergoing cardiac operations were monitored by an in vitro analysis utilizing hexadimetharine bromide (Polybrene) neutralization. Heparin administered prior to cannulation for cardiopulmonary bypass in a dose of 3.0 mg (300 units) per kilogram of body weight, and 1.5 mg (150 units) per kilogram for each subsequent hour of bypass, routinely produced circulating heparin concentrations greater than 1.0 units per milliliter of plasma. A protamine dose equal to 80% of the total number of milligrams of heparin given resulted in no detectable plasma heparin in 23 of the 34 patients one-half hour after administration. No patient required protamine in an amount greater than the total number of milligrams in the heparin dose to achieve heparin neutralization. Modest postoperative chest tube drainage (mean, 784 ml in 48 hours) in these patients provides clinical support for low-dose protamine administration for heparin neutralization at the conclusion of cardiopulmonary bypass.

Skin metastases from transitional cell bladder cancer.

Three cases of transitional cell bladder cancer metastatic to skin are described. This manifestation of transitional cell uroepithelial malignancy was previously believed to be quite uncommon. The authors' experience suggests that this occurrence is not that rare and that it may reflect increased longevity in successfully treated patients, allowing previously unusual manifestations of metastatic disease to become evident. The role of aspiration skin biopsy is discussed.

Validation and characterization of the L5178Y/TK+/- mouse lymphoma mutagen assay system.

The current status of the L5178Y/TK+/- leads to TK-/- mouse-lymphoma mutagenicity assay is described. Dose-survival-mutagenic response data are shown for 43 chemicals. Mutagenicity and cytotoxicity in the presence or absence of non-induced and/or Aroclor-induced rat-liver S-9 are compared for most of these chemicals, 25 of these for which usuable carcinogenicity data exist have been used to construct an approximately linear relationship between oncogenic potency in vivo and mutagenic potency in this system in vitro; linearity between these two endpoints extends over a greater than 100,000-fold range in potencies. Several carcinogens which are negative or difficult to detect in the standard Ames assay are mutagenic in this mammalian cell system. These include natulan, sodium saccharin (lot S-1022), p,p'-DDE (metabolite of DDT), dimethylnitrosamine, diethylnitrosamine and diethylstilbestrol. Characterization of the TK-/- mutants suggests that two mutagenic mechanisms contribute to their final yield. Large-colony TK-/- mutants probably represent point or gene mutations affecting the TK locus. In addition, a class of small-colony TK(/- mutants are described and characterized as being heritably growth-deficient; this and other properties suggest that these small-colony TK-/- mutants originate by a heritable and viable chromosomal aberration. Most carcinogens and mutagens tested produce both classes of TK-/- mutants in this system; the relative proportions of small- and large-colony mutants are both mutagen- and dose-dependent. Comparative studies have been done at the rapidly-expressing TK locus and the slowly-expressing HGPRT locus in these cells. Several carcinogens detected at the TK locus are non- or very weakly mutagenic at the HGPRT locus. This findings is consistent with the induction of slow-growing specific locus mutants by a chromosomal mechanism and their subsequent dilution during this long expression time.

Specific gene mutations in L5178Y cells in culture.

The predominant test system uses a near-diploid L5178Y mouse lymphoma cell line and is based on the quantitation of forward mutations occurring at the heterozygous thymidine kinase (TK) locus (TK+/- leads to TK-/-). (Other markers, such as ouabain- or methothrexate-resistance and alanine independence, in other L5178Y mouse lymphoma cells were also examined, but our criteria for the acceptability of data or the paucity of data considerably reduced the value of these mutagenesis test systems to this study.) The biochemical basis for the L5178Y/TK+/- assay depends on the ability of TK-competent cells to phosphorylate 5-bromo-2'-deoxyuridine or trifluorothymidine. The phosphorylated product or its metabolites kill these cells, thus, medium containing 5-bromo-2'-deoxyuridine or trifluorothymidine is capable of selecting for cells that are lacking the TK enzyme (TK-/-). TK-/- cells eventually give rise to a bimodal distribution of colony sizes. The relative proportion of small and large colonies appears to be characteristic of the mutagen, its dose, and the length of the expression period. A total of 108 references were reviewed and 48 chemical agents were evaluated. Of these, in vivo carcinogenicity data existed for 44 and covered a wide variety of chemical classes (43 compounds) and a complex mixture. In this system, 39 agents were positive, 1 was negative, and 4 yielded inconclusive results. The 44 test substances evaluated were insufficient to single out agents or agent classes for which the assay was particularly well suited; however, with the exception of thymidine analogs, the system seems to be versatile. The correlation of the TK locus assay results with the carcinogenicity data revealed that 2 agents were definite false positives (sodium azide and methotrexate) and 1 agent was a definite false negative (1,1-dimethylhydrazine). Further evaluation suggested that 4-acetylaminofluorene and diphenylnitrosamine were questionable false positives, while benzo[e]pyrene was a questionable false negative. (The term questionable was used to imply uncertainties concerning the mutagenicity and/or carcinogenicity data). Thus, the assay is of value in the battery approach to mutagenicity/carcinogenicity screening.

Management of juvenile angiofibromata.

Twenty-eight angiofibromata, treated between 1971 and 1988, were reviewed according to their patterns of invasion, blood supply, treatment modality, and clinical course. All patients were males, and two patients were black. The average age was 14.8 years. Nasopharyngeal masses, epistaxis, and facial asymmetry were the most common presenting symptoms. Tumors extended along predetermined pathways following the vascularity of the external carotid system. CNS extension arose via the superior orbital fissure or direct extension from the sphenoid sinus. Angiography described the neoplastic vascularity, CT with contrast demonstrated tumor location and extracranial extension, and MRI best demonstrated CNS invasion. All lesions were reclassified according to the American Joint Committee staging system. Twenty-seven patients were operated upon; four with cryotherapy and 23 following embolization. Two tumors recurred and needed additional surgery. One patient with CNS invasion was treated with estrogen and radiotherapy for cure. Tumor staging is not particularly helpful in decision making, because surgery must be individualized according to tumor location and extent. Surgical approaches for specific tumor locations are discussed.

Mimetic surgery for the paralyzed face.

One hundred ten patients with facial nerve paralyses were treated by various surgical methods. Eighty-six patients had total facial nerve paralyses and 24 had segmental paralyses. In the total paralysis group, 62 patients had oncologic procedures or tumor induced paralysis. In the segmental paralysis group, 14 patients had malignancies. Two patients had idiopathic facial nerve paralysis. In the total paralysis group, 59 had neural reconstructions, 7 neuromuscular pedicles, and 20 muscle-fascia transpositions. The segmental paralysis group was divided into an upper facial palsy group (n = 11) and lower facial palsy group (n = 13). Five patients had neural transpositions, 5 had muscle-fascia transpositions, and 14 had plastic reconstructions. The results were analyzed by various methods and grading systems. The data indicate that neural repairs produce better results than muscle-fascia transpositions or plastic reconstructions. Within the repairs, the procedures are listed in an hierarchical order of cosmetic and functional results. The average follow-up for the entire group was 2.8 years. The average follow-up for the neural repair group was 3.2 years, and for the muscle fascia transpositions, 14.1 months.

Surgical management of cutaneous carcinomas at the inner canthus.

Surgical management of carcinomas at the inner canthus is based on three criteria which are listed in a descending order of importance: tumor resectability with adequate margins, preservation of vision, and acceptable cosmetic result. The lesions resected are to create trapezoid or rectangular defects which can be closed simply with primary closures or with Z- or W-plasties. In medium sized defects skin is borrowed from the glabella, upper nasal dorsum, or nasolabial sulci and used as rotational flaps. In more extensive lesions, through and through defects, or when lined flaps are required, nondelayed midline forehead pedicled or island flaps are employed. For very large defects, sliding cheek flaps, sickle forehead flaps, horizontal forehead flaps, and (in rare instances) scalping flaps where the distal segment is the temporal, hairless skin is used. Tumors which extend intracranially and are deemed resectable are removed with a combined intracranial approach. The latter may be via a transfrontal sinus resection or a combined lateral rhinotomy and frontal craniotomy resection. Regional lymph node metastasis normally requires a superficial parotidectomy, radical neck dissection (including submaxillary, angular, and mandibular nodes), and occasionally postauricular lymph node dissection. Distant metastases are contraindications for major surgical procedures.

Parotid masses: evaluation, analysis, and current management.

Two hundred thirty-one sequential parotid masses seen from January 1982 to July 1986 were reviewed for their clinical presentation, diagnostic evaluation, pathologic findings, and therapeutic approach. The results were compared with the previously reported findings on parotid masses. There were 146 (63.2%) benign tumors, 50 (21.6%) malignancies, and 35 (15.2%) nonmalignant lesions. Tumors were classified according to their histopathologic diagnosis. An asymptomatic mass was the most common presentation. Radiological evaluation was mainly with computed tomography. The primary surgical procedure was parotidectomy with facial nerve preservation. A selected group of patients was referred for radiation therapy. Our study demonstrated that non-neoplastic lesions contribute a significant number of masses in the differential diagnosis of parotid tumors. Metastatic squamous cell carcinoma was the most frequently encountered malignancy. Deep lobe tumors were twice as common as previously reported.

Ossification patterns of the tympanic facial canal in the human fetus and neonate.

Dehiscences in the bony facial canal are comparatively common in the human adult. The highest incidence occurs in the tympanic segment of the facial nerve near the region of the oval window. Thirty-three fetal temporal bones, ranging from 16 to 40 weeks' gestation, and four from 1, 2, 4 and 12 weeks' postpartum neonates, were studied to evaluate the normal patterns of ossification of the fallopian canal of the tympanic facial nerve segment in the human. The tympanic facial nerve segment elongates three-fold during this period (from 1 mm to 3 mm). The ossification starts at 21 weeks' gestation anteriorly from apical otic ossification centers and at 26 weeks from canalicular ossification centers near the stapedius muscle. The ossification proceeds in an anterior-to-posterior direction as two periosteal shelves of bone surround the facial nerve. The superior periosteal bony ledge contributes 75% of the circumference of the fallopian canal. The anterior ossification center forms over 83% of the fallopian canal length. The two centers fuse post partum near the region of the oval window. The anatomic location of the facial nerve, nerve branching, and neural vasculature precede ossification. In 80% of the paired temporal bones, this ossification pattern appears to be symmetrical. The patterns and incidence of bony dehiscences within the tympanic fallopian canal segment can be explained by these observations. This study demonstrates that fallopian canal dehiscences are not congenital anomalies, but variations of normal developmental anatomic processes.

Rabbit facial nerve regeneration in autologous nerve grafts after antecedent injury.

OBJECTIVE: The effect of incomplete antecedent injuries on subsequent facial nerve regeneration within cable graft repairs is not known. The purpose of this study is to compare facial nerve regeneration after an immediate and delayed neural cable graft repair. METHOD: Rabbit facial nerve regeneration after complete transectional injuries of the buccal division was compared in two experimental models. In one, a 10-mm segment of the nerve was transected, rotated 180 degrees, and immediately repaired as a cable graft (N=8). In the second, a preliminary nerve crush was allowed to recover over a 4-week period and a 10-mm segment of nerve centered on the crush site was then transected, rotated 180 degrees, and delay repaired as a cable graft (N = 7). Data are presented as total numbers of regenerating myelinated axons that traverse the surgical repair to innervate the cable graft and distal nerve stumps, as well as the percentage of regenerating neurites compared with preoperative pooled and individual controls. Subpopulations of regenerating neurons are delineated to quantify the pattern of neural innervation. RESULTS: Five weeks after cable graft repair both groups had similar myelinated outgrowth from the proximal nerve stump across the proximal anastomosis to innervate the cable graft (3995 +/- 1209 vs. 3284 +/- 651; P = .89). However, the delayed repair group had more intrafascicular regeneration within cable grafts (2261 +/- 931 vs. 1660 +/- 1169; P = .02) and distal nerve stump (1532 +/- 281 vs. 445 +/- 120; P = .004) than the immediate repair group. The immediate repair group had greater extrafascicular nerve regeneration in the cable graft (2335 +/- 1954 vs. 437 +/- 236; P = .001) and more myelin and axonal debris in pre-existing neural fascicles of the cable graft (P = .02) and distal nerve stump (463 +/- 187 vs. 103 +/- 87; P = .02). CONCLUSIONS: Antecedent priming lesions do not enhance axonal survival as determined by regenerating myelinated axonal counts. However, antecedent injuries enhance the efficiency of neural innervation of the affected mimetic musculature by increasing the number of myelinated intrafascicular neural regenerants in the cable graft and distal nerve stump. This is accomplished by two factors: increased perineural fibrosis and decreased intrafascicular myelin and axonal debris.