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Objective: To review the design and function of pacemakers and implantable cardioverter defibrillators with particular attention to those aspects that are of clinical relevance to perioperative and critical care physicians.Main Points: Pacemakers and implantable cardioverter defibrillators are complex devices that interact with cardiac function in ways that can significantly influence hemodynamics. A basic appreciation of device technology is essential to understanding both the normal patterns of pacemaker and implantable cardioverter defibrillator usage and the ways in which iatrogenic influences may result in adverse outcomes. The most important concern for pacemaker patients who enter the hospital is exposure to electromagnetic interference. Exposure is mainly from surgical cautery, but other sources are also present. With awareness of these concerns and an understanding of how to prevent adverse interactions, it is possible to safely care for these patients in the critical care setting. Despite recommended precautions, undesirable outcomes may occur and the clinician must be prepared to intervene in an appropriate manner to prevent patient injury. [ABSTRACT FROM AUTHOR]

Objective: To use an extremity magnetic resonance system to perform kinematic magnetic resonance imaging (MRI) of the patellofemoral joint to qualitatively assess the effect of bracing on patellar position. Design and Setting: Subjects underwent kinematic MRI of the symptomatic extremity with a 0.2-Tesla extremity magnetic resonance system. Images were obtained using a knee coil and a T1-weighted, spin echo pulse sequence. Subjects: Seven female patients with patellofemoral joint symptoms. Measurements: Four different axial sections were obtained for each position: extension and 3 positions of flexion up to 36°. An appropriate-sized patellofemoral brace was applied, and the kinematic MRI procedure was repeated. Results: Six patients had lateral displacement of the patella, and 1 patient had medial displacement of the patella. After application of the brace, 6 patients (5 with lateral displacement and 1 with medial displacement, 86%) exhibited correction (5) or improvement (1 with lateral displacement) in the abnormal patellar positions, and 1 patient had worsening of the abnormal position of the patella. Conclusions: We used kinematic MRI to determine the presence of abnormal patellar positioning. Application of the brace counteracted the abnormal patellar positions in most of the patients studied. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the utility of meniscus allografts in combination with other procedures to delay knee arthroplasty in patients older than 50 years previously advised joint arthroplasty., Methods: A total of 108 meniscus allograft transplants using the arthroscopic 3-tunnel technique between 1997 and 2019 in patients older than 50 years were retrospectively reviewed with a 2-year minimum follow-up period. Inclusion criteria were patients recommended for knee arthroplasty with pain and preservation of some joint space by standing flexion radiographs. Exclusion criteria were lack of joint space, failure to comply with rehabilitation protocol, and failure to complete research questionnaires. International Knee Documentation Committee composite and isolated pain scale were evaluated longitudinally. Time from meniscus allograft transplant to arthroplasty was measured, with failure defined as allograft excision or revision, progression to arthroplasty, or same or increased pain., Results: Eighty-six of 108 (79.6%) patients met eligibility criteria. Over the follow-up mean 8.55 (range 0.68 to 25.2) years, 42 of 87 (48.2%) grafts progressed to arthroplasty with mean time of 8.64 (median 8.05) years. Concomitant procedures did not have significant impact on survival; however, survival medians were higher among paste graft and chondroplasty and lower among osteotomy groups. At the time of reporting, 41 of 84 (48.8%) patients had intact meniscus transplants, demonstrating significant improvements (P < .001) in pain and function as assessed by International Knee Documentation Committee Score. These improvements were sustained 10 years postoperatively, correlated to a mean of 65.8 years of age. At least 50% of patients achieved Minimal Clinically Important Difference through 10 years postoperatively., Conclusions: Meniscus allografts in combination with other arthroscopic interventions delay knee arthroplasty and improve knee symptoms of pain and function in a population of knee arthroplasty candidates older than 50 years. Influences of concomitant procedures cannot be defined., Level of Evidence: Level IV, therapeutic case series, retrospective., Competing Interests: Disclosures The authors (K.R.S., A.W.W., S.S., T.J.T., C.F.-D., M.D., E.M., H.C., V.L., S.W., M.V.) declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Purpose: ACL reconstruction has a significant failure rate. To address the need for inexpensive strong tissue, a treatment process to "humanize" porcine tissue was developed and tested in primates and humans. This report describes the long-term outcomes from the first human clinical trial using a porcine xenograft ACL reconstruction device., Methods: The study was performed with Z-Lig™ xenograft ACL device in 2003 as a pilot clinical feasibility study. This device was processed to slow its immune-mediated destruction by enzymatic elimination of α-gal epitopes and by partial crosslinking to slow the infiltration of macrophages into the biotransplant., Results: Ten patients underwent reconstruction with the Z-Lig™ device. Five of 10 patients failed due to subsequent trauma (n = 3), arthrofibrosis (n = 1), and surgical technical error (n = 1). One patient was lost to follow-up after the 12-year evaluation. Each remaining patient reported a stable fully athletic knee. Physical exams are consistent with a score of less than one on the ACL stability tests. MRIs demonstrate mature remodeling of the device. There is no significant degradation in patient-reported outcome scores, physical exams, or MRI appearance from 12 to 20-year follow-ups., Conclusions: The studies in a small group of patients have demonstrated that implantation of porcine ligament bioprosthesis into patients with torn ACLs can result in the reconstruction of the bioprosthesis into autologous ACL that remains successful over 20 years. The possibility of humanizing porcine tissue opens the door to unlimited clinical material for tissue reconstructions if supported by additional clinical trials., Level of Evidence: IV, case series., (© 2023. European Society of Sports Traumatology, Knee Surgery, Arthroscopy (ESSKA).)

Objective: Patients undergoing articular cartilage paste grafting have been shown in studies to have significant improvement in pain and function in long-term follow-ups. We hypothesized that ex vivo impacting of osteochondral autografts results in higher chondrocyte matrix production versus intact osteochondral autograft plugs., Design: This institutional review board-approved study characterizes the effects of impacting osteochondral plugs harvested from the intercondylar notch of 16 patients into a paste, leaving one graft intact as a control. Cell viability/proliferation, collagen type I/II, SOX-9, and aggrecan gene expression via qRT-PCR (quantitative reverse transcription-polymerase chain reaction) were analyzed at 24 and 48 hours. Matrix production and cell morphology were evaluated using histology., Results: Paste samples from patients (mean age 39.7) with moderate (19%) to severe (81%) cartilage lesions displayed 34% and 80% greater cell proliferation compared to plugs at 24 and 48 hours post processing, respectively ( P = 0.015 and P = 0.021). qRT-PCR analysis yielded a significant ( P = 0.000) increase of aggrecan, SOX-9, collagen type I and II at both 24 and 48 hours. Histological examination displayed cell division throughout paste samples, with accumulation of aggrecan around multiple chondrocyte lacunae., Conclusions: Paste graft preparation resulted in increased mobility of chondrocytes by matrix disruption without loss of cell viability. The impaction procedure stimulated chondrocyte proliferation resulting in a cellular response to reestablish native extracellular matrix. Analysis of gene expression supports a regenerative process of cartilage tissue formation and contradicts long-held beliefs that impaction trauma leads to immediate cell death. This mechanism of action translates into clinical benefit for patients with moderate to severe cartilage damage.

Background: For many songbirds in North America, we lack movement details about the full annual cycle, notably outside the breeding season. Understanding how populations are linked spatially between breeding and overwintering periods (migratory connectivity) is crucial to songbird conservation and management. We assessed migratory connectivity for 2 breeding populations of Gray Catbirds (Dumetella carolinensis) west of and within the Rocky Mountains by determining migration routes, stopover sites, and overwintering locations. Additionally, we compared apparent annual survivorship for both populations., Methods: We deployed 39 archival light-level geolocators and 21 Global Positioning System (GPS) tags on catbirds in the South Okanagan Valley, British Columbia, Canada, and 32 geolocators and 52 GPS tags in the Bitterroot River Valley, Montana, USA. These devices allowed us to determine migration routes, stopover sites, overwintering locations, and migratory connectivity. Migratory connectivity was quantified using Mantel's correlation. We used mark-recapture of colour banded catbirds in both sites to estimate apparent annual survivorship., Results: We retrieved 6 geolocators and 19 GPS tags with usable data. Gray Catbirds from both populations passed through the Rocky Mountains eastward before heading south towards their overwintering locations in northeastern Mexico and Texas. Stopover sites during fall migration occurred primarily in Montana, Kansas, Oklahoma, and Arkansas. Overwintering locations spanned Texas and 5 states in northeastern Mexico. Individual catbirds used up to 4 distinct sites during the overwintering period. Catbirds separated by almost 500 km during the breeding season overlapped during the non-breeding season, suggesting weak migratory connectivity among western populations (Mantel's correlation = 0.013, P-value = 0.41). Catbird apparent annual survivorship estimates were higher in British Columbia (0.61 ± 0.06 females; 0.64 ± 0.05 males) than in Montana (0.34 ± 0.05 females; 0.43 ± 0.04 males), though the main driver of these differences remain unclear., Conclusions: Our results provide high precision geographic details during the breeding, migration, and overwintering phases of the annual cycle for western Gray Catbirds. Notably, we found that western catbirds followed the Central Flyway as opposed to the Pacific Flyway. We document that catbirds used multiple sites over winter, contrary to the popular belief that this phase of the annual cycle is stationary for most songbirds.

This review describes the first studies on successful conversion of porcine soft-tissue bioprostheses into viable permanently functional tissue in humans. This process includes gradual degradation of the porcine tissue, with concomitant neo-vascularization and reconstruction of the implanted bioprosthesis with human cells and extracellular matrix. Such a reconstruction process is referred to in this review as "humanization". Humanization was achieved with porcine bone-patellar-tendon-bone (BTB), replacing torn anterior-cruciate-ligament (ACL) in patients. In addition to its possible use in orthopedic surgery, it is suggested that this humanization method should be studied as a possible mechanism for converting implanted porcine bioprosthetic heart-valves (BHV) into viable tissue valves in young patients. Presently, these patients are only implanted with mechanical heart-valves, which require constant anticoagulation therapy. The processing of porcine bioprostheses, which enables humanization, includes elimination of α-gal epitopes and partial (incomplete) crosslinking with glutaraldehyde. Studies on implantation of porcine BTB bioprostheses indicated that enzymatic elimination of α-gal epitopes prevents subsequent accelerated destruction of implanted tissues by the natural anti-Gal antibody, whereas the partial crosslinking by glutaraldehyde molecules results in their function as "speed bumps" that slow the infiltration of macrophages. Anti-non gal antibodies produced against porcine antigens in implanted bioprostheses recruit macrophages, which infiltrate at a pace that enables slow degradation of the porcine tissue, neo-vascularization, and infiltration of fibroblasts. These fibroblasts align with the porcine collagen-fibers scaffold, secrete their collagen-fibers and other extracellular-matrix (ECM) components, and gradually replace porcine tissues degraded by macrophages with autologous functional viable tissue. Porcine BTB implanted in patients completes humanization into autologous ACL within ~2 years. The similarities in cells and ECM comprising heart-valves and tendons, raises the possibility that porcine BHV undergoing a similar processing, may also undergo humanization, resulting in formation of an autologous, viable, permanently functional, non-calcifying heart-valves.

Corrective lower limb osteotomies are innovative and efficient therapeutic procedures for restoring axial alignment and managing unicompartmental knee osteoarthritis. This review presents critical insights into the up-dated clinical knowledge on osteotomies for complex posttraumatic or congenital lower limb deformities with a focus on high tibial osteotomies, including a comprehensive overview of basic principles of osteotomy planning, biomechanical considerations of different implants for osteotomies and insights in specific bone deformity correction techniques. Emphasis is placed on complex cases of lower limb osteotomies associated with ligament and multiaxial instability including pediatric cases, computer-assisted navigation, external fixation for long bone deformity correction and return to sport after such osteotomies. Altogether, these advances in the experimental and clinical knowledge of complex lower limb osteotomies allow generating improved, adapted therapeutic regimens to treat congenital and acquired lower limb deformities.

Purpose: The purpose of this study is to evaluate the clinical outcomes of the articular cartilage paste graft procedure at a minimum of 10 years from surgery. It is hypothesized that articular cartilage paste grafting can provide patients with a durable repair of severe full-thickness osteochondral injuries, measured by persistence of procedure-induced benefit and subjective outcome scores at 10 or more years., Methods: Seventy-four patients undergoing paste grafting at a mean age of 45.3 ± 10.8 years (range 13-69 years) were followed up at a mean of 16.8 ± 2.4 years (range 10.6-23.2 years) post-operatively using validated subjective outcome measures; Kaplan-Meier survival analysis was performed to estimate expected population benefit time., Results: Kaplan-Meier estimated median benefit time of 19.1 years (mean: 16.6 ± 0.9 years) for all patients undergoing paste grafting. Thirty-one (41.9 %) patients had progressed to arthroplasty at a mean of 9.8 ± 5.6 years (range 0.4-20.6 years). Ninety percent of patients reported that the procedure provided good to excellent pain relief. Median IKDC subjective score increased significantly at most recent follow-up (70.1) compared to preoperative (55.7, p = 0.013). Median WOMAC scores decreased significantly from 26 to 14 (p = 0.001). Median Tegner score increase from 4 to 6 was not found to be significant (ns). VAS pain averaged 23/100 at most recent follow-up., Conclusions: Patients who underwent the paste grafting reported improved pain, function, and activity levels for an expected mean of 16.6 years, and for those who ultimately progressed to knee replacement, surgical treatment including the paste graft was able to delay arthroplasty until a mean age of 60.2 years, an age at which the procedure is commonly performed. Full-thickness articular cartilage loss can be successfully treated, reducing pain, and improving function, using this single-step, inexpensive arthroscopic procedure., Level of Evidence: IV.

This review describes a novel method developed for processing porcine tendon and other ligament implants that enables in situ remodeling into autologous ligaments in humans. The method differs from methods using extracellular matrices (ECMs) that provide postoperative orthobiological support (i.e., augmentation grafts) for healing of injured ligaments, in that the porcine bone-patellar-tendon-bone itself serves as the graft replacing ruptured anterior cruciate ligament (ACL). The method allows for gradual remodeling of porcine tendon into autologous human ACL while maintaining the biomechanical integrity. The method was first evaluated in a preclinical model of monkeys and subsequently in patients. The method overcomes detrimental effects of the natural anti-Gal antibody and harnesses anti-non-gal antibodies for the remodeling process in two steps: Step 1. Elimination of α-gal epitopes-this epitope that is abundant in pigs (as in other nonprimate mammals) binds the natural anti-Gal antibody, which is the most abundant natural antibody in humans. This interaction, which can induce fast resorption of the porcine implant, is avoided by enzymatic elimination of α-gal epitopes from the implant with recombinant α-galactosidase. Step 2. Partial cross-linking of porcine tendon with glutaraldehyde-this cross-linking generates covalent bonds in the ECM, which slow infiltration of macrophages into the implant. Anti-non-gal antibodies are produced in recipients against the multiple porcine antigenic proteins and proteoglycans because of sequence differences between human and porcine homologous proteins. Anti-non-gal antibodies bind to the implant ECM, recruit macrophages, and induce the implant destruction by directing proteolytic activity of macrophages. Partial cross-linking of the tendon ECM decreases the extent of macrophage infiltration and degradation of the implant and enables concomitant infiltration of fibroblasts that follow the infiltrating macrophages. These fibroblasts align with the implant collagen fibers and secrete their own collagen and other ECM proteins, which gradually remodel the porcine tendon into human ACL. This ligamentization process lasts ∼2 years and the biomechanical integrity of the graft is maintained throughout the whole period. These studies are the first, and so far the only, to demonstrate remodeling of porcine tendon implants into permanently functional autologous ACL in humans.

The Gene Expression Database (GXD; www.informatics.jax.org/expression.shtml) is an extensive and well-curated community resource of mouse developmental expression information. Through curation of the scientific literature and by collaborations with large-scale expression projects, GXD collects and integrates data from RNA in situ hybridization, immunohistochemistry, RT-PCR, northern blot and western blot experiments. Expression data from both wild-type and mutant mice are included. The expression data are combined with genetic and phenotypic data in Mouse Genome Informatics (MGI) and made readily accessible to many types of database searches. At present, GXD includes over 1.5 million expression results and more than 300 000 images, all annotated with detailed and standardized metadata. Since our last report in 2014, we have added a large amount of data, we have enhanced data and database infrastructure, and we have implemented many new search and display features. Interface enhancements include: a new Mouse Developmental Anatomy Browser; interactive tissue-by-developmental stage and tissue-by-gene matrix views; capabilities to filter and sort expression data summaries; a batch search utility; gene-based expression overviews; and links to expression data from other species., (© The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Objective: To determine the validity of the hip and knee osteoarthritis guidelines., Methods: A systematic search of PubMed using a combination of Mesh and text terms with limitations to guidelines was performed to identify hip and knee osteoarthritis guidelines. The study was performed from April 17, 2014 to October 1, 2014. Guidelines were reviewed for graded levels of evidence, methods used to grade the evidence, and disclosures of conflicts of interest. Additionally, guidelines were also assessed for key quality measures using the AGREE II system for assessing the quality of guidelines., Results: A total of 13 guidelines relevant to the diagnosis and/or treatment of hip/knee osteoarthritis was identified. The 180 recommendations reviewed were supported by 231 pieces of evidence. In total, 35% (n = 80; range: 0-26) were supported by level A evidence, 15% (n = 35; range: 0-10) were by level B, and 50% (n = 116; range: 0-62) were by level C. Median age of the guidelines was 4 years (±4.8; range: 0-16) with no comments on planned updates. In total, 31% of the guidelines included patients in the development process. Only one guideline incorporated cost consideration, and only 15% of the guidelines addressed the surgical management of osteoarthritis. Additionally, 46% of guidelines did not comment on conflicts of interest (COI). When present, there was an average 29.8 COI. Notably, 82% of the COI were monetary support/consulting., Conclusions: In total, 50% of the hip/knee osteoarthritis guideline recommendations are based on lower quality evidence. Nearly half the guidelines fail to disclose relevant COI and when disclosed, multiple potential COI are present. Future hip/knee osteoarthritis guideline development committees should strive to improve the transparency and quality of evidence used to formulate practice guidelines., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: The purpose of this study was to evaluate the efficacy of meniscus allograft transplantation in an active patient population with moderate to severe cartilage damage and the procedure's ability to allow sports participation postoperatively., Methods: Forty-nine patients with moderate to severe cartilage damage who underwent meniscus allograft transplantation were included in this study; those with symptoms related to articular cartilage damage also underwent articular cartilage repair. Kaplan-Meier (KM) survival estimate, potential hazards to survival, and subjective clinical outcomes were analyzed. For KM survival, failure was defined as progression to knee arthroplasty, surgical removal of the meniscus transplant without revision, a self-reported follow-up pain level that was more than preoperative level, or constant moderate pain with no relief from non-operative treatment., Results: The mean follow-up time was 8.6 ± 4.2 years. The mean age at surgery was 45.3 ± 12.9 years. Meniscus transplantation was performed in 37 medial cases and 12 lateral cases. There were 41 patients with Outerbridge Grade IV and 8 with Grade III. Thirty-six (73.5%) patients were able to participate in sporting activities postoperatively. Eleven (22.4%) meniscus transplants failed at an average of 5.2 ± 4.4 years. The KM mean estimated survival time was 12.6 ± 0.7 years. No tested risks were found to affect sports participation or procedure success., Conclusions: Meniscus transplantation is a viable surgical option for patients with severe cartilage damage and missing or irreparable menisci to provide significant improvements in pain and function levels in the medium to long term with the majority of patients achieving their goal of participation in sporting activities. These results indicate that symptomatic patients may be able to participate in sports activities for an average of 12.6 years following meniscus transplantation., Level of Evidence: Case series, Level IV.

Background: Revision of failed surgical treatments of osteochondritis dissecans (OCD) lesions remains a challenge without an obvious solution. The aim of this study was to evaluate seven consecutive patients undergoing osteochondral grafting of a failed OCD repair., Methods: The mean time from surgery to the latest evaluation was 7.0 years. IKDC, WOMAC, Tegner, and MRI studies were collected both preoperatively and during follow-up. Evaluation of the graft was assessed using the magnetic resonance observation of cartilage repair tissue (MOCART) grading system., Results: Over the course of the study period, five patients required additional surgery with a study median of one additional surgery (range, zero to 3). At most recent follow-up, there was significant improvement from preoperative values in median IKDC (p=0.004), WOMAC (p=0.030), and Tegner (p=0.012). Complete cartilage fill and adjacent tissue integration of the paste graft were observed by MRI evaluation in five of the seven (71.4%) patients. Definitive correlation between clinical outcomes and MRI scores was not observed., Conclusions: This study shows promising results of osteochondral grafting as a viable option for the revision of failed OCD lesion repairs; however, more patients are needed to fully support its efficacy in these challenging failed revision cases., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Objectives: To better understand the effects of misinformation on eyewitnesses of different ages, older and younger adults experienced an event under intentional and incidental learning conditions in a naturalistic experiment using multiple memory tests., Method: Following exposure to the event, which was a brief interruption of a group testing session, participants completed several memory tests. For half of the participants, misinformation was embedded in the first cued recall test. On subsequent free recall and cued recall tests, basic scores and misinformation-based memory errors were examined., Results: As expected, younger adults had higher recall scores than older adults. Older and younger adults made the same number of misinformation errors in free recall and in cued recall with intentional learning. However, in the incidental condition, younger adults made more misinformation errors likely due to the information processing strategies they employed after incidental learning., Discussion: Misinformation effects were quite strong, even with a realistic scene and intentional learning. Older adult suggestibility was no worse than that of younger adults. When misinformation was combined with incidental learning, younger adults may have used strategic processing to encode misinformation to their detriment.

The Gene Expression Database (GXD; http://www.informatics.jax.org/expression.shtml) is an extensive and well-curated community resource of mouse developmental expression information. GXD collects different types of expression data from studies of wild-type and mutant mice, covering all developmental stages and including data from RNA in situ hybridization, immunohistochemistry, RT-PCR, northern blot and western blot experiments. The data are acquired from the scientific literature and from researchers, including groups doing large-scale expression studies. Integration with the other data in Mouse Genome Informatics (MGI) and interconnections with other databases places GXD's gene expression information in the larger biological and biomedical context. Since the last report, the utility of GXD has been greatly enhanced by the addition of new data and by the implementation of more powerful and versatile search and display features. Web interface enhancements include the capability to search for expression data for genes associated with specific phenotypes and/or human diseases; new, more interactive data summaries; easy downloading of data; direct searches of expression images via associated metadata; and new displays that combine image data and their associated annotations. At present, GXD includes >1.4 million expression results and 250,000 images that are accessible to our search tools.

The International Knockout Mouse Consortium (IKMC) aims to mutate all protein-coding genes in the mouse using a combination of gene targeting and gene trapping in mouse embryonic stem (ES) cells and to make the generated resources readily available to the research community. The IKMC database and web portal (www.knockoutmouse.org) serves as the central public web site for IKMC data and facilitates the coordination and prioritization of work within the consortium. Researchers can access up-to-date information on IKMC knockout vectors, ES cells and mice for specific genes, and follow links to the respective repositories from which corresponding IKMC products can be ordered. Researchers can also use the web site to nominate genes for targeting, or to indicate that targeting of a gene should receive high priority. The IKMC database provides data to, and features extensive interconnections with, other community databases.

As stagnant water contacts copper pipe and lead solder (simulated soldered joints), a corrosion cell is formed between the metals in solder (Pb, Sn) and the copper. If the resulting galvanic current exceeds about 2 μA/cm(2), a highly corrosive microenvironment can form at the solder surface, with pH < 2.5 and chloride concentrations at least 11 times higher than bulk water levels. Waters with relatively high chloride tend to sustain high galvanic currents, preventing passivation of the solder surface, and contributing to lead contamination of potable water supplies. The total mass of lead corroded was consistent with predictions based on the galvanic current, and lead leaching to water was correlated with galvanic current. If the concentration of sulfate in the water increased relative to chloride, galvanic currents and associated lead contamination could be greatly reduced, and solder surfaces were readily passivated.

Two decades of uncharacteristically severe wildfires have caused government and private land managers to actively reduce hazardous fuels to lessen wildfire severity in western forests, including riparian areas. Because riparian fuel treatments are a fairly new management strategy, we set out to document their frequency and extent on federal lands in the western U.S. Seventy-four USDA Forest Service Fire Management Officers (FMOs) in 11 states were interviewed to collect information on the number and characteristics of riparian fuel reduction treatments in their management district. Just under half of the FMOs surveyed (43%) indicated that they were conducting fuel reduction treatments in riparian areas. The primary management objective listed for these projects was either fuel reduction (81%) or ecological restoration and habitat improvement (41%), though multiple management goals were common (56%). Most projects were of small extent (93% < 300 acres), occurred in the wildland-urban interface (75%), and were conducted in ways to minimize negative impacts on species and habitats. The results of this survey suggest that managers are proceeding cautiously with treatments. To facilitate project planning and implementation, managers recommended early coordination with resource specialists, such as hydrologists and fish and wildlife biologists. Well-designed monitoring of the consequences of riparian fuel treatments on fuel loads, fire risk, and ecological effects is needed to provide a scientifically-defensible basis for the continued and growing implementation of these treatments.

Purpose: Successful meniscus transplantation may depend on accurate sizing. Meniscal sizing is currently determined by measuring a combination of bony landmarks and soft-tissue insertion points through images obtained radiographically or by magnetic resonance imaging (MRI). The literature widely reports inaccuracy in sizing resulting from radiographic errors in magnification, erroneous identification of bony landmarks, and difficulty in differentiating between the soft-tissue and bone interface. In our meniscus transplantations we have observed that when the height and weight of the recipient matched those of the donor, the meniscal size appeared to be a match at surgical implantation; we designed this study to confirm this observation., Methods: The MRI-based meniscal sizing of 111 patients (63 male and 38 female patients; mean age, 44 years [range, 15 to 76 years]), totaling 147 menisci (87 lateral and 60 medial), was compared with the height, weight, gender, and body mass index (BMI) of each patient. MRI scans were obtained with a 1.0-Tesla MRI system (ONI Medical Systems, Wilmington, MA). Sizing was performed by an independent musculoskeletal MRI radiologist as established by the literature. Statistical methods include nonparametric Pearson correlation (r) between MRI-based lateral meniscal width, lateral meniscal length, medial meniscal width, medial meniscal length, total tibial plateau width, and patient height, weight, gender, and BMI. Significance at the P = .05 level was used., Results: Height was found to have a linear relationship to total tibial plateau, which has a good predictive correlation with meniscal dimensions of r > 0.7. Female patients generally present with smaller dimensions than male patients. High-BMI groups present with significantly larger meniscal dimensions than low-BMI groups at any given height., Conclusions: Height, weight, and gender are easily obtained variables and are proportional to meniscal tissue dimensions. These exploratory statistics establish correlations between height, weight, gender, total tibial plateau width, and meniscal size., Clinical Relevance: Height, weight, and gender should be considered by both tissue banks and surgeons as fast and cost-effective variables by which to predict meniscal dimensions.

Purpose: This study proposes treatment methods to provide a mechanically competent, immunocompatible, and sterile porcine graft for human knee ligament reconstruction., Methods: The anterior cruciate ligament (ACL) was reconstructed by using treated porcine patellar tendon grafts or controls of untreated porcine grafts or allografts in 20 rhesus monkeys. Animals were stratified into 2-, 6-, and 12-month postreconstruction cohorts. Serologic and histologic assessments were performed to evaluate host immunological and cellular response. Healing and functional integrity of the ACL reconstructions were assessed by tensile biomechanical testing., Results: Untreated porcine grafts were acutely resorbed and rejected, whereas treated porcine grafts and allografts were incorporated by the host as functional grafts. Temporal histologic assessment of treated porcine grafts and rhesus grafts revealed gradual host cellular infiltration and graft collagen remodeling through a similar mechanism of ligamentization. Biomechanical evaluations support graft functional integration with no difference between allograft and treated graft reconstructions., Conclusion: Rhesus allograft and treated porcine grafts presented with similar healing profiles in a long-term evaluation of ACL reconstruction., Clinical Relevance: Immunochemical modification and sterilization of porcine patellar tendon grafts may improve initial biocompatibility and long-term functionality of xenografts in musculoskeletal applications.

Background: Understanding anti-non-gal antibody response is of significance for success in xenotransplantation. Long-term anti-non-gal response in humans was studied in patients transplanted with porcine patellar tendon (PT) lacking alpha-gal epitopes, for replacing ruptured anterior cruciate ligament (ACL)., Methods: Porcine PTs were treated with recombinant alpha-galactosidase to eliminate alpha-gal epitopes and with glutaraldehyde for moderate cross-linking of collagen fibers. The processed pig PTs were implanted to replace ruptured ACL in patients., Results: In five of six evaluable subjects, the xenografts have continued to function for over two years and passed all functional stability assessments. Thus, processed porcine PT seems to be appropriate for replacing ruptured human ACL. Enzyme-linked immunosorbent assay and Western blot studies indicated that all subjects produced anti-non-gal antibodies against multiple pig xenoproteins, but not against human ligament proteins. Production of anti-non-gal antibodies peaked two to six months posttransplantation and disappeared after two years., Conclusions: These antibodies contribute to a low-level inflammatory process that aids in gradual xenograft replacement by infiltrating host fibroblasts that align with the pig collagen "scaffold" and secrete collagen matrix. The assays monitoring anti-non-gal antibodies will help to determine whether long-term survival of live organ xenografts requires complete suppression of this antibody response.

Purpose: We present meniscus allograft survival data at least 2 years from surgery for 45 patients (47 allografts) with significant arthrosis to determine if the meniscus can survive in an arthritic joint., Type of Study: Prospective, longitudinal survival study., Methods: Data were collected for 31 men and 14 women, mean age 48 years (range, 14 to 69 years), with preoperative evidence of significant arthrosis and an Outerbridge classification greater than II. Failure is established by previous studies as allograft removal. No patient was lost to follow-up., Results: The success rate was 42 of 47 allografts (89.4%) with a mean failure time of 4.4 years as assessed by Kaplan-Meier survival analysis. Statistical power is greater than 0.9, with alpha = 0.05 and N = 47. There was significant mean improvement in preoperative versus postoperative self-reported measures of pain, activity, and functioning, with P = .001, P = .004, and P = .001, respectively, as assessed by a Wilcoxon rank-sum test with P = .05., Conclusions: Meniscus allografts can survive in a joint with arthrosis, challenging the contraindications of age and arthrosis severity. These results compare favorably with those in previous reports of meniscus allograft survival in patients without arthrosis., Level of Evidence: Level IV.

Purpose: To prospectively assess clinical outcomes and regeneration of osteoarthritic cartilage lesions treated with an articular cartilage paste grafting technique., Type of Study: Prospective, longitudinal case series., Methods: We treated 125 patients (136 procedures; 34% female, 66% male; mean age, 46 years; range, 17 to 73 years) with an Outerbridge classification of grade IV lesions with an articular cartilage paste graft. Clinical data were recorded 2 to 12 years from surgery, with 20 of 145 patients lost to follow-up over 12 years (13.7%). Clinical outcomes were captured annually with validated Western Ontario and McMaster Universities Arthritis Index (WOMAC), International Knee Documentation Committee (IKDC), and Tegner subjective questionnaires. Regenerated cartilage biopsy specimens were obtained at second-look arthroscopy from 66 patients and evaluated as to quality and quantity of defect fill by a blinded, independent histopathology reviewer., Results: Preoperative versus postoperative validated pain, functioning, and activity measures improved significantly (P< .001). Clinically, 18 of the 125 patients were considered failures (14.4%), with 10 patients undergoing subsequent joint arthroplasty and 8 who reported worse pain after surgery. Regional histologic variation occurred. Forty-two of 66 biopsy specimens (63.6%) showed strong and consistent evidence of replacement of their articular surface, and 18 of 66 biopsy specimens (27.3%) showed development of areas of cartilage., Conclusions: Paste grafting is a low-cost, 1-stage arthroscopic treatment for patients with Outerbridge classification grade IV arthritic chondral lesions. The procedure offers excellent, long-lasting, pain relief, restored functioning, and possibility of tissue regeneration for patients with painful chondral lesions in both arthritic and traumatically injured knees., Level of Evidence: Level IV, case series.

This technical note describes an improved arthroscopic technique of meniscal transplantation that simplifies the surgical procedure and secures the allograft to the tibia at 3 sites. The technique is useful for both medial and lateral meniscal transplantation and has been used in our clinic for over 60 meniscal transplantation procedures.

Torn meniscal cartilages and the consequences of missing meniscus tissue represent the major indications for operative arthroscopy of the knee. After recognizing the importance of the meniscus, clinicians made the shift away from complete meniscectomy to partial meniscectomy aided by the development of arthroscopic instrumentation. Despite extensive basic science data showing the importance of a complete meniscus for normal force transference, meniscus repair occurs in less than 10% of all meniscal tears found at arthroscopy. This paper will discuss the reasons for the common clinical approach and compare that approach with an aggressive approach of salvaging and replacing meniscus tissue, and will offer speculations about future directions for meniscus repair, reconstruction, and replacement.

Background: Studies on transplantation of porcine meniscus and articular cartilage into monkeys are important for evaluating the possible use of such tissues in humans. In addition, such studies shed light on the chronic xenograft rejection process in primates. Transplantation of porcine cartilage into cynomolgus monkeys for 2 months results in a many-fold increase in anti-Gal activity and in a strong cellular inflammatory response of T lymphocytes and macrophages within the implants. The objective of this study was to determine whether elimination of Galalpha1-3Galbeta1-4GlcNAc-R (alpha-gal epitopes) from the xenograft may alter the immune response and the inflammatory reaction., Methods: Porcine meniscus and articular cartilage specimens were treated with recombinant alpha-galactosidase (100 U/ml), and the absence of alpha-gal epitopes was assessed by the binding of the monoclonal anti-Gal antibody M86. The treated cartilage specimens were transplanted into the suprapatellar pouch of cynomolgus monkeys. The immune response to cartilage was monitored in the serum and the inflammatory reaction was assessed in the xenografts, which were explanted after 2 months., Results: Incubation with alpha-galactosidase resulted in complete removal of alpha-gal epitopes from the cartilage. The increase in anti-Gal activity in the transplanted monkeys was marginal. However, most monkeys produced antibodies to antigens specific to porcine cartilage. The inflammatory response within the alpha-galactosidase-treated xenografts was much lower than in nontreated cartilage and the proportion of T lymphocytes within the cellular infiltrates was greatly reduced., Conclusions: Treatment of cartilage xenografts with alpha-galactosidase successfully removes alpha-gal epitopes from porcine cartilage. Transplantation of the treated cartilage results in the production of only anti-porcine cartilage-specific antibodies and a reduced inflammatory response consisting primarily of macrophages infiltrating into the cartilage.

A collagen scaffold was designed for use as a template for the regeneration of meniscal cartilage and was tested in ten patients in an initial, Food and Drug Administration-approved, clinical feasibility trial. The goal of the study was to evaluate the implantability and safety of the scaffold as well as its ability to support tissue ingrowth. The study was based on the findings of in vitro and in vivo investigations in dogs that had demonstrated cellular ingrowth and tissue regeneration through the scaffold. Nine patients remained in the study for at least thirty-six months, and one patient voluntarily withdrew after three months for personal reasons. The collagen scaffold was found to be implantable and to be safe over the three-year period. Histologically, it supported regeneration of tissue in meniscal defects of various sizes. No adverse immunological reactions were noted on sequential serological testing. On second-look arthroscopy, performed either three or six months after implantation, gross and histological evaluation revealed newly formed tissue replacing the implant as it was resorbed. At thirty-six months, the nine patients reported a decrease in the symptoms. According to a scale that assigned 1 point for strenuous activity and 5 points for an inability to perform sports activity, the average score was 1.5 points before the injury, 3.0 points after the injury and before the operation, and 2.4 points at six months postoperatively, 2.2 points at twelve months, 2.0 points at twenty-four months, and 1.9 points at thirty-six months. According to a scale that assigned 0 points for no pain and 3 points for severe pain, the average pain score was 2.2 points preoperatively and 0.6 point thirty-six months postoperatively. One patient, who had had a repair of a bucket-handle tear of the medial meniscus and augmentation with the collagen scaffold, had retearing of the cartilage nineteen months after implantation. Another patient had debridement because of an irregular area of regeneration at the scaffold-meniscus interface twenty-one months after implantation. Magnetic resonance imaging scans demonstrated progressive maturation of the signal within the regenerated meniscus at three, six, twelve, and thirty-six months. These findings suggest that regeneration of meniscal cartilage through a collagen scaffold is possible. Additional studies are needed to determine long-term efficacy.

Transplantation of discordant xenograft tissues usually results in antibody-mediated hyperacute rejection response. It has been speculated that because cartilage has a limited vascular, neural, and lymphatic supply, it might be immunologically privileged and may not undergo hyperacute or chronic rejection. Moreover, porcine and bovine cartilage were found to express very low amounts of alpha-galactosyl epitopes (Gal alpha1-3Gal beta1-4GlcNAc-R). To evaluate animal cartilage for possible human transplantation, xenograft meniscal cartilage was transplanted from pigs and cows into the suprapatellar pouches of six cynomolgus monkeys (group 1). In a second group of six monkeys (group 2), porcine meniscal cartilage and porcine articular cartilage plugs were evaluated. During the 2-month evaluation period in group 1, all monkeys displayed an extensive humoral response to the xenograft, as indicated by the increase in production of antibodies against bovine and porcine cartilage. Upon explant, all meniscal cartilage samples in this group demonstrated histological evidence of chronic rejection, including fibroplasia, encapsulation, mononuclear infiltrates, foreign body giant cells, and eosinophilic infiltrates. There was no difference between the response seen in untreated tissues and that seen in tissues treated with UV irradiation or ozone oxidation. In group 2, the menisci explanted after 1 month displayed extensive infiltration of eosinophils alone or eosinophils mixed with mononuclear cells. The mononuclear infiltrates consisted primarily of CD4+ and CD8+ T cells and of macrophages. The articular cartilage plugs demonstrated only a small area of fibrous encapsulation and leukocyte infiltration at the periphery. This study suggests that xenograft cartilage tissue does not appear to be immunoprivileged and is unsuitable for human implantation due to a chronic rejection mechanism, which is evident already within 1 month after transplantation. In addition, this study may serve as a general model for the primate immune response against xenografts in the absence of hyperacute rejection.

The recent advances in avoiding hyperacute rejection by producing transgenic pigs with complement regulatory proteins call for the analysis of posttransplantation changes in anti-Gal activity in the absence of hyperacute rejection. Transplantation of cynomolgus monkeys with porcine or bovine meniscus and articular cartilage enabled the study of anti-Gal IgG response to xenografts that are not subjected to hyperacute rejection. The cartilage implants were kept in suprapatellar pouches of the recipients for 1 or 2 months and anti-Gal activity was measured in the serum at various time intervals after transplantation. Within 2 weeks after transplantation, titer of anti-Gal IgG, in all transplanted monkeys, increased by 20- to 100-fold, as measured in ELISA with synthetic alpha-galactosyl epitopes linked to bovine serum albumin or with mouse laminin. Furthermore, binding of serum anti-Gal to porcine endothelial cells increased by 10-fold or more after transplantation. Complement-mediated cytotoxicity also increased by two- to eightfold after transplantation. The elevated activity of anti-Gal was maintained for the 2-month period during which the grafts were kept in the monkeys, and returned to the pretransplantation level 6 months after graft removal. All these data suggest that the primate immune system responds vigorously to alpha-galactosyl epitopes on xenografts by activating many B lymphocytes that produce increased amounts of anti-Gal IgG, which may also be of high affinity. These antibodies are likely to bind to the xenograft cells, even if these cells express low numbers of alpha-galactosyl epitopes. Such antibody binding may play an important role in chronic rejection of xenografts.

We reviewed the films of 1760 patients who had magnetic resonance image scanning of the knee joint to assess the most common pathologic changes associated with an incidental finding of a Baker's cyst. Of the 1760 knees scanned, Baker's cysts were noted in 238. The cysts were classified as small (55%), medium (30%), or large (15%) and were primarily found on the medial side of the knee (94%). The menisci were evaluated and changes were classified as complete tears, where signal contacts the surface, or degenerative intrasubstance tears. One hundred eleven (47%) complete meniscal tears were found, and 88 (37%) degenerative tears. The majority of tears were found in the posterior horn of the medial meniscus (65 complete tears and 45 degenerative tears). Thus, 199 tears were found in 170 knees, and 106 of the 170 knees (62%) had tears of the posterior horn of the medial meniscus. Baker's cysts are frequent findings on physical examinations and on magnetic resonance imaging scans of the knee. They are thought to be due to intraarticular pathologic changes, usually posterior meniscal tears. This study documents the association between Baker's cysts and meniscal tears and notes that a complete tear is not necessary for the cyst to be present.

Replacement of the meniscus cartilage presents challenges not easily met by the application of technology or transplantation biology. No studies have demonstrated definitely that there are benefits to a replaced meniscus. Regeneration of the body's own meniscus cartilage may be successful, but confirmation of this phenomenon awaits further data.

Autogenous replantation of meniscal cartilage (resection of 80% of the meniscus cartilage followed by immediate replantation) was performed in 14 dogs as a control arm of a meniscal replacement study. The purpose was to assess the ability of the excised tissue to heal to the intact rim and function as a meniscus cartilage. This procedure is an idealized model of allografting meniscus cartilage in that the tissue is fresh, autogenous, and perfectly sized. If this procedure did not succeed, it seemed likely to the authors that allografting meniscal cartilage would have diminished chances for success. Evaluation of these replant failures led us to speculate that the causes and mechanisms might include slow or incomplete revascularization, inadequate mechanical fixation or stabilization, and, perhaps, some type of rejection phenomenon not examined or confirmed in the present study. We believe these mechanisms will be particularly deleterious for allografted meniscal cartilages and recommend further extensive evaluation of meniscal allografts before wide clinical use.

Objectives: To compare the effectiveness of several hemostatic agents and to evaluate a new hemostatic agent (ReClot) in controlling splenic hemorrhage., Design: Rabbits were anesthetized and catheters placed. A celiotomy was performed and a splenic injury produced; hemostatic agent and compression were applied., Experimental Groups: In group 1 (n = 8), the splenic laceration was compressed with a dry sponge and 75 g of pressure until hemorrhage ceased. In groups 2, 3, and 4 (n = 10 each), splenic injury was treated with Avitene, Collastat, and ReClot, respectively. Hemostatic agent was applied to the splenic laceration and a dry sponge and pressure were applied as described for group 1. In group 5 (n = 9), a splenic laceration was produced, ReClot applied, and aggressive fluid resuscitation was initiated; the volume of crystalloid was adjusted to maintain mean arterial pressure., Results: Application of a hemostatic agent reduced total blood loss compared with that measured in the control group, but there was no difference in blood loss among experimental groups treated with a hemostatic agent. The time required to achieve control of blood loss was less in the ReClot-treated group compared with the Avitene- and Collastat-treated groups., Conclusions: The hemostatic agent ReClot had a significant advantage over other hemostatic agents for the time required to achieve control of splenic bleeding. Aggressive fluid resuscitation did not limit the ability of ReClot to produce hemostasis.

Meniscal replacement by allograft and meniscal regeneration through collagen meniscal scaffolds have been recently reported. To evaluate the effectiveness of a replaced or regrown meniscal cartilage, a method for measuring the size and function of the regenerated tissue in vivo is required. To solve this problem, we developed and evaluated a magnetic resonance imaging (MRI) technique to measure the volume of meniscal tissues. Twenty-one intact fresh cadaver knees were evaluated and scanned with MRI for meniscal volume sizing. The sizing sequence was repeated six times for each of 21 lateral and 12 medial menisci. The menisci were then excised and measured by water volume displacement. Each volume displacement measurement was repeated six times. The MRI technique employed to measure the volume of the menisci was shown to correspond to that of the standard measure of volume and was just as precise. However, the MRI technique consistently underestimated the actual volume. The average of the coefficient of variation for lateral volumes was 0.04 and 0.05 for the water and the MRI measurements, respectively. For medial measurements it was 0.04 and 0.06. The correlation for the lateral menisci was r = 0.45 (p = 0.04) and for the medial menisci it was r = 0.57 (p = 0.05). We conclude that 3D MRI is precise and repeatable but not accurate when used to measure meniscal volume in vivo and therefore may only be useful for evaluating changes in meniscal allografts and meniscal regeneration templates over time.

Meniscal replacement by allograft and prosthesis is under laboratory and investigational clinical practice. In order to succeed, a replacement must duplicate the exact mechanical function of the original meniscal cartilage. The technique of replacement described in this article permits minimal disruption of the joint tissues, accurate placement of the meniscal horns, and secure fixation of the meniscal synovial junction.

We sought to create a regeneration template for the meniscal cartilage of the knee to induce complete meniscal regeneration, and to develop the technique for implanting the prosthetic appliance in vivo. We designed a resorbable collagen-based scaffold and conducted in vitro and in vivo studies. In vivo, the scaffold was implanted in the knees of immature swine and mature canines and evaluated clinically, histologically, and biochemically. Because the canine stifle joint meniscus is more clinically relevant to the human meniscus, this paper emphasizes those results. We studied 24 mixed breed dogs (14 males and 10 females) with an average weight of 25.5 kg (range, 20 to 35) that were obtained from a USDA-licensed supplier. The dogs were deemed clinically and radiographically skeletally mature. None of the dogs had a preexisting knee joint abnormality. All dogs underwent an 80% subtotal resection of the medial meniscus bilaterally. A collagen template was implanted in one stifle (N = 24). The contralateral side served as a control: 12 dogs had a total resection alone and the other 12 dogs had an immediate replantation of the autologous meniscus. Results were tabulated at 3, 6, 9, and 12 months. At final evaluation, before the animals were euthanized, the results were submitted for statistical analysis as well as histologic and biochemical analyses. The results demonstrated that a copolymeric collagen-based scaffold can be constructed that is compatible with meniscal fibrochondrocyte growth in vitro and in vivo, that does not inhibit meniscal regeneration in an immature pig, and that may induce regeneration of the meniscus in the mature dog.(ABSTRACT TRUNCATED AT 250 WORDS)

Prosthetic meniscal replacement offers the ability to stabilize the meniscectomized knee and provide prophylaxis against early degenerative arthritis. Since prosthetic meniscal replacement may be performed in the setting of normal articular cartilage, a prosthesis will be required to match the exact joint configuration, induce the same lubricity, produce the same coefficient of friction, and absorb and dampen the same joint forces (without incurring significant creep or abrasion) as does the normal meniscus. This feat is currently beyond the capabilities of artificial materials alone. Alternatively, collagen-based prostheses acting as resorbable regeneration templates offer the possibility of inducing regrowth of new menisci. This paper presents a summary of hypotheses, considerations, and laboratory evidence for the use of collagen-based, resorbable matrices as regeneration templates.

Recent studies of murine tumor models and certain human tumor cell lines have provided evidence for intratumor heterogeneity in expression of extracellular matrix receptors and in the elaboration of matrix-degrading enzymes. However, little is known about possible intratumoral heterogeneity in the production of matrix macromolecules. We have, therefore, examined the biosynthesis and secretion of matrix proteins by cells derived from a polyclonal human cell line (JH-17) established from a large cell undifferentiated carcinoma of the lung. For the present studies, we focused on the production of collagens and structural glycoproteins by two phenotypically different aneuploid clones, designated C13 and C22. These clones were distinctive in their inability to grow in soft agar or to form tumors in nude mice and had identical DNA contents. Tumor cells were labeled with [3H]proline and the newly synthesized proteins accumulating in the culture medium were identified using biochemical and immunologic techniques. Clone C13 secreted at least three genetically distinct collagens, including type V procollagen (PC), type IV procollagen, and a type VIII-like collagen. By contrast, the clone C22 synthesized fibronectin, and a single bacterial collagenase-sensitive and pepsin-resistant component consistent with type I trimer. These studies emphasize the potential diversity of matrix proteins synthesized by neoplastic cells and suggest that there is intratumoral heterogeneity in matrix protein biosynthesis in vivo. These studies further suggest that tumor-derived matrix may be altered during tumor progression or cell selection in vivo.

A procedure is described for short-term cryopreservation of primary human tumor cells and tissue slices for later analysis by flow cytometry. Cells were mechanically dispersed into a freezing medium, which was then frozen at either -20 degrees C or -70 degrees C for delayed cell cycle analysis. The results show that a correlation coefficient of greater than 0.95 exists between cell cycle kinetic analyses performed immediately after surgical excision of the tumor and on cells frozen from 1 to 30 days at -70 degrees C in this freezing solution. Somewhat lower levels of correlation exist for cells frozen at -20 degrees C in this freezing medium. This procedure has also been successfully used to preserve freshly isolated breast carcinoma cells shipped from distant laboratories for analysis in the flow cytometer, thus expanding the data base on certain types of breast carcinoma.

This study investigated two hypotheses: (1) sufficient cells may be obtained by needle aspiration of breast nodules to produce good flow cytometric DNA profiles; and (2) benign breast lesions do not produce aneuploid G0G1 peaks, and therefore a distinct aneuploid peak is sufficient for a diagnosis of malignancy. Breast specimens received in Surgical Pathology between December 1985 and February 1987 were aspirated, and the cells stained with propidium iodide for flow cytometric DNA analysis. A total of 344 specimens were aspirated, of which 204 (59%) were malignant and 140 (41%) benign. One hundred fifty-three malignant and 111 benign specimens contained sufficient cells for analysis. Cytologic smears were available for 177 malignant and 123 benign specimens. DNA histograms were considered diagnostic of malignancy if an aneuploid peak was present which contained at least 20% of the cells in the distribution, and had a DNA index greater than or equal to 1.2. Using these criteria, 73 of 153 (48%) carcinomas could be identified. None of the benign lesions satisfied these criteria. One fibroadenoma with atypical hyperplasia produced a distinct peak which contained less than 5% of the cells in the histogram, and had a DNA index of 1.25. Flow cytometric analysis provides objective data that complement the subjective cytologic interpretation of fine needle aspirates.

A simple method is described which combines a sodium dodecyl sulfate polyacrylamide gel electrophoresis (SOS-PAGE) in the first demension with a second electrophoresis, at right angles to the first, into an agarose matrix. The proteins, separated by SDS-PAGE, are exposed to appropriate antisera after the second stage electrophoresis and immunoprecipitates form in the agarose corresponding to the relative electrophoretic mobilities of proteins in the first stage SDS-PAGE separation. The method thus provides a simple, reproducible means for correlating antigenicity with apparent molecular weight of proteins. The technique is qualtitative, but requires smaller quantities of antisera than more conventional immunoelectrophoretic methods such as rocket electrophoresis.

Collagenase dissociation, performed on 40 human breast cancers, yielded between 1 million and 50 million cells from less than 1 g of tissue from each tumor. Approximately 60% of cells (mean) was considered viable as judged by trypan blue exclusion and phase microscopy. On subsequent flow cytometric analysis, 20 cancers (50%) were considered diploid, three were tetraploid, and the remainder, hyperdiploid. Thymidine labeling (TLI) and flow cytometry following mechanical dissociation also were performed on 23 of these 40 tumors. Among this group of 23 cases, the median percentage of S-phase cells obtained by collagenase dissociation was 5.4, by TLI was 5.7, and by mechanical dissociation was 9.7. There was excellent correlation between the percentage of S-phase cells obtained by collagenase and TLI (r = 0.847, p = 0.0001) but only fair correlation between the percentage of S-phase cells obtained by mechanical dissociation and TLI (r = 0.597, p = 0.0027). The percentage of S-phase cells obtained by either collagenase or mechanical dissociation predicted whether a tumor was above or below median TLI in 19 of 23 cases (p = 0.0018). Estrogen receptor positivity or negativity did not predict whether a tumor was above or below median TLI (r = 0.283, p = 0.130) or above or below median S-phase fraction following collagenase dissociation (r = 0.218, p = 0.182), nor did quantitative estrogen receptor correlate significantly with TLI (r = 0.283, p = 0.13) or S-phase fraction (r = 0.218, p = 0.18).