Outcomes of posterior component separation with transversus abdominis release for repair of abdominally based breast reconstruction donor site hernias.

PURPOSE: Abdominally based autologous breast reconstruction (ABABR) is common after mastectomy, but carries a risk of complex abdominal wall hernias. We report experience with posterior component separation (PCS) and transversus abdominis release (TAR) with permanent synthetic mesh repair of ABABR-related hernias. METHODS: Patients at Cleveland Clinic Foundation and Penn State Health were identified retrospectively. Outcomes included postoperative complications, hernia recurrence, and patient-reported outcomes (PROs): Hernia Recurrence Inventory, HerQLes Summary Score, Patient-Reported Outcome Measurement Information System (PROMIS) Pain Intensity 3a Survey, and the Decision Regret Scale (DRS). RESULTS: Forty patients underwent PCS/TAR repair of hernias resulting from pedicled (35%), free (5%), muscle-sparing TRAMs (15%), and DIEPs (28%) from August 2014 to March 2021. Following PCS, 30-day complications included superficial surgical site infection (13%), seroma (8%), and superficial wound breakdown (5%). Five patients (20%) developed clinical hernia recurrence. At a minimum of 1 year, 17 (63%) reported a bulge, 12 (44%) reported pain, median HerQLes Quality Of Life Scores improved from 33 to 63/100 (p value < 0.01), PROMIS 3a Pain Intensity Scores improved from 52 to 38 (p value < 0.05), and DRS scores were consistent with low regret (20/100). CONCLUSION: ABABR-related hernias are complex and technically challenging due to missing abdominal wall components and denervation injury. After repair with PCS/TAR, patients had high rates of recurrence and bulge, but reported improved quality of life and pain and low regret. Surgeons should set realistic expectations regarding postoperative bulge and risk of hernia recurrence.

Staged abdominal wall reconstruction in the setting of complex gastrointestinal reconstruction.

PURPOSE: Literature on one- versus two-staged abdominal wall reconstruction (AWR) with complex gastrointestinal reconstruction (GIR) is limited to single-arm case series with a focus on patients who complete all planned stages. Herein, we describe our experience with both one- and two-staged approaches to AWR/GIR, with attention to those who did not complete both intended stages. METHODS: A retrospective review of prospectively collected data was conducted to identify patients who underwent a one- or two-stage approach to GIR/AWR from 2013 to 2020. The one-stage approach included GIR and definitive sublay mesh herniorrhaphy. The two-stage approach included Stage 1 (S1)-GIR and non-definitive herniorrhaphy and Stage 2 (S2)-definitive sublay mesh herniorrhaphy. RESULTS: Fifty-four patients underwent GIR/AWR: 20 (37.0%) underwent a planned 1-stage operation while 34 (63.0%) underwent S1 of a planned 2-stage approach. Patients assigned to the 2-stage approach were more likely to be smokers, have a history of mesh infection, have an enterocutaneous fistula, and a contaminated wound class (p<0.05). Of the 34 patients who underwent S1, 12 (35.3%) completed S2 during the mean follow-up period of 44 months while 22 (64.7%) did not complete S2. Of these, 10 (45.5%) developed hernia recurrence but did not undergo S2 secondary to elective nonoperative management (40%), pending preoperative optimization (30%), additional complex GIR (10%), hernia-related incarceration requiring emergent surgery (10%), or unrelated death (10%). No differences in outcome including SSI, SSO, readmission, and recurrence were noted between the 12 patients who completed the two-stage approach and the 20 patients who completed a one-stage approach, despite increased risk factors for complications in the 2-stage group (p>0.05). CONCLUSION: Planned two-stage operations for GIR/AWR may distribute operative complexity and post-operative morbidity into separate surgical interventions. However, many patients may never undergo the intended definitive S2 herniorrhaphy. Future evaluation of 1- versus 2-stage GIR/AWR is needed to clarify indications for each approach. This work must also consider the frequent deviations from intended clinical course demonstrated in this study.

Outcomes of redo-transversus abdominis release for abdominal wall reconstruction.

BACKGROUND: Transversus abdominis release (TAR) is increasingly used to address complex ventral hernias; consequently, associated complications are seen more frequently. Our hernia center has a growing experience with redo-transversus abdominis release (redo-TAR) to address large, complex hernia recurrences after failed TAR. Here, we describe our outcomes after abdominal wall reconstruction with redo-TAR. STUDY DESIGN: Adults undergoing elective open, redo-TAR at our institution from January 2015 to February 2021 were queried from a prospectively collected database in the Abdominal Core Health Quality Collaborative. The primary outcome was 30-day wound morbidity. Secondary outcomes were long-term composite hernia recurrence and patient-reported quality of life. RESULTS: Sixty-five patients underwent redo-TAR. Median age was 60 years, 50.8% were female, and median BMI 31.8 kg/m2. Median recurrent hernias were 16 cm wide by 25 cm long. Frequent mechanisms of recurrence included linea semilunaris injury (27.7%), mesh fracture (18.5%), infection (16.9%), and posterior sheath disruption (15.4%). Wound complications occurred in 33.8% and 16.9% required procedural intervention. With median clinical and PRO follow-up of 12 and 19 months, respectively, the composite hernia recurrence rate was 22.5% and patients reported significantly improved quality of life (HerQLes: median + 36.7, PROMIS: median - 9.5). CONCLUSION: Redo-TAR may be performed as a salvage procedure to reconstruct complex defects after failed TAR, however, in our center, it is associated with increased wound morbidity and fairly high composite recurrence rates. Despite this, patients report improvements in quality of life and pain. Tracking outcomes after TAR will facilitate understanding how to manage its failures.

Comparative effectiveness of surgeon-performed transversus abdominis plane blocks and epidural catheters following open hernia repair with transversus abdominis release.

PURPOSE: Recovery protocols aim to limit narcotic administration following ventral hernia repair (VHR). However, little is known about the contribution of a protocol's individual components on patient outcomes. We previously reported that surgeon-performed transversus abdominis plane block (TAP-block) is more effective than ultrasound-guided TAP-block following VHR. This study evaluates the effectiveness of two postoperative analgesia modalities: epidural catheter and surgeon-performed TAP-block following VHR performed with transversus abdominis release (TAR). METHODS: A retrospective analysis was performed on data prospectively collected between 2012 and 2019. All patients undergoing open VHR with TAR performed by a single surgeon were identified. Parastomal hernia repairs and any patients receiving ultrasound-guided TAP blocks or paraspinal blocks were excluded. Primary outcome was length of stay (LOS) with secondary outcomes including pain scores, opioid requirements, and 30-day morbidity. Linear regression was used to model LOS. RESULTS: One hundred thirty-five patients met inclusion criteria (63 epidural, 72 TAP-block). The majority (67.4%) of patients were modified ventral hernia working group grade 2. The only statistically significant difference in postoperative pain scores between the groups was on postoperative day 2 (TAP block 3.19 versus epidural 4.11, p = 0.0126). LOS was significantly shorter in the TAP block group (4.7 versus 6.2 days, p = 0.0023) as was time to regular diet (3.2 versus 4.7 days, p < 0.0001). After controlling for confounders, epidural was associated with increased LOS by 1.3 days (p = 0.0004). CONCLUSION: Epidural use following VHR with TAR is associated with increased LOS and increased time to regular diet without reducing pain or opioid use when compared to surgeon-performed TAP block.

Watchful waiting is an appropriate option for peritoneal dialysis candidates with an asymptomatic ventral hernia.

PURPOSE: Expert consensus recommends that all ventral hernias be repaired prior to, or concomitantly with, peritoneal dialysis (PD) catheter insertion. We examined the clinical outcomes of patients undergoing initial PD catheter insertion, with asymptomatic ventral hernias that were not repaired and rather managed using a watchful waiting approach. METHODS: A single-center, retrospective review of patients undergoing PD catheter insertion from 2005-2019 was performed. Patients who did not undergo repair of a pre-existing ventral hernia at the time of their initial PD catheter insertion were included. The primary endpoint was ventral hernia repair following PD catheter insertion. RESULTS: Forty-one patients were included. Most patients presented with an umbilical hernia (78%). Six patients (15%) underwent ventral hernia repair at a median postoperative interval of 12 months [IQR 8-16], due to abdominal discomfort and hernia enlargement (n = 2) and incarceration (n = 2). Two patients remained asymptomatic, yet underwent ventral hernia repair at the time of renal transplantation. The cumulative incidence of ventral hernia repair within 12 and 24 months of PD catheter insertion was 13% and 21%, respectively. CONCLUSION: Watchful waiting may be an acceptable option for select patients with asymptomatic ventral hernias at the time of initial PD catheter placement. These findings highlight the need to better identify factors associated with asymptomatic ventral hernias that do not warrant concomitant repair to aid surgeons in the decision-making process.

Non-coated versus coated mesh for retrorectus ventral hernia repair: a propensity score-matched analysis of the Americas Hernia Society Quality Collaborative (AHSQC).

PURPOSE: The outcomes of utilizing anti-adhesive barrier-coated mesh in the retrorectus position during open ventral hernia repair are unknown. We compared the wound-related outcomes between non-coated (NCM) and coated mesh (CM) placed in the retrorectus space. METHODS: Patients undergoing elective, open, clean ventral hernia repair with retrorectus mesh were retrospectively identified in the Americas Hernia Society Quality Collaborative. Propensity score matching was performed based on clinically relevant demographic and operative covariates. The primary outcome was wound morbidity, defined as surgical site infection (SSI), surgical site occurrence (SSO), and SSO requiring procedural intervention (SSOPI). RESULTS: 3609 patients were included (3281 NCM, 328 CM). Following 2:1 propensity score matching, rates of myofascial release remained the only statistically different matching parameter; external oblique releases were performed more frequently in the CM group (8% vs. 15%; p = 0.03). Rates of SSI (3% vs. 4%; p = 0.16) were similar between groups. Increased rates of SSO (13% vs. 18%; p = 0.045) and SSOPI (4% vs. 8%; p = 0.038) were observed in the CM group. The CM group had a higher rate of postoperative seroma (3% vs. 7%; p = 0.027) compared to the NCM group. CONCLUSION: Barrier-coated mesh in the retrorectus position was associated with increased wound morbidity requiring procedural intervention. Due to a lack of clinical benefit, the use of more costly barrier-coated mesh in the retrorectus position is not justified for routine, open ventral hernia repairs at this time.

Toll-like receptors and their therapeutic potential in Parkinson's disease and α-synucleinopathies.

Toll-like receptors (TLRs) are pattern recognition receptors which mediate an inflammatory response upon the detection of specific molecular patterns found on foreign organisms and on endogenous damage-related molecules. These receptors play a major role in the activation of microglia, the innate immune cells of the CNS, and are also expressed in peripheral tissues, including blood mononuclear cells and the gut. It is well established that immune activation, in both the brain and periphery, is a feature of Parkinson's disease as well as other α-synucleinopathies. Aggregated forms of α-synuclein can act as ligands for TLRs (particularly TLR2 and TLR4), and hence these receptors may play a critical role in mediating a detrimental immune response to this protein, as well as other inflammatory signals in Parkinson's and related α-synucleinopathies. In this review, the potential role of TLRs in contributing to the progression of these disorders is discussed. Existing evidence comes predominantly from studies in in vitro and in vivo models, as well as analyses of postmortem human brain tissue and pre-clinical studies of TLR inhibitors. This evidence is evaluated in detail, and the potential for therapeutic intervention in α-synucleinopathies through TLR inhibition is discussed.

Emersion and Terrestrial Locomotion of the Northern Snakehead (Channa argus) on Multiple Substrates.

Most fishes known for terrestrial locomotion are small and/or elongate. Northern snakeheads (Channa argus) are large, air-breathing piscivores anecdotally known for terrestrial behaviors. Our goals were to determine their environmental motivations for emersion, describe their terrestrial kinematics for fish 3.0-70.0 cm and compare kinematics among four substrates. For emersion experiments, C. argus was individually placed into aquatic containers with ramps extending through the surface of the water, and exposed to 15 ecologically-relevant environmental conditions. For kinematic experiments, fish were filmed moving on moist bench liner, grass, artificial turf, and a flat or tilted rubber boat deck. Videos were digitized for analysis in MATLAB and electromyography was used to measure muscular activity. Only the low pH (4.8), high salinity (30 ppt), and high dCO2 (10% seltzer solution) treatments elicited emersion responses. While extreme, these conditions do occur in some of their native Asian swamps. Northern snakeheads >4.5 cm used a unique form of axial-appendage-based terrestrial locomotion involving cyclic oscillations of the axial body, paired with near-simultaneous movements of both pectoral fins. Individuals ≤3.5 cm used tail-flip jumps to travel on land. Northern snakeheads also moved more quickly on complex, three-dimensional substrates (e.g., grass) than on smooth substrates (e.g., bench liner), and when moving downslope. Release of snakeheads onto land by humans or accidentally by predators may be more common than voluntary emersion, but because northern snakeheads can respire air, it may be necessary to factor in the ability to spread overland into the management of this invasive species.

Emersión y locomoción terrestre de la cabeza de serpiente del norte (Channa argus) en múltiples sustratos (Emersion and terrestrial locomotion of the northern snakehead (Channa argus) on multiple substrates) La mayoría de los peces conocidos por locomoción terrestre son pequeños y/o alargados. Las cabezas de serpiente del norte (Channa argus) son grandes pesces piscívoros que respiran aire, anecdóticamente conocidos por sus comportamientos terrestres. Nuestros objetivos fueron determinar sus motivaciones ambientales para la emersión, describir su cinemática terrestre para peces de 3, 0 a 70, 0 cm y comparar la cinemática entre cuatro sustratos. Para los experimentos de emersión, C. argus se colocó individualmente en contenedores acuáticos con rampas que se extienden a través de la superficie del agua y fueron expuesto a quince condiciones ambientales ecológicamente pertinentes. Para los experimentos cinemáticos, los peces se filmaron moviéndose sobre un revestimiento de banco húmedo, césped, césped artificial y una cubierta de bote de goma plana o inclinada. Los videos se digitalizaron para su análisis en MATLAB y se usó electromiografía para medir la actividad muscular. Solo los tratamientos de bajo pH (4, 8), alta salinidad (30 partes por mil) y alto dCO2 (solución de agua de Seltz 10%) provocaron respuestas de emersión. Aunque son extremas, estas condiciones si ocurren en algunos de sus pantanos asiáticos nativos. Las cabezas de serpiente del norte >4, 5 cm usaron una forma única de locomoción terrestre basada en movimientos apéndiculares-axiales que involucra oscilaciones cíclicas del cuerpo axial, junto con movimientos casi simultáneos de ambas aletas pectorales. Los individuos de ≤3, 5 cm usaron saltos de cola para moverse en tierra. Las cabezas de serpiente del norte también se movían más rápidamente en sustratos tridimensionales complejos (ej., césped) que en sustratos lisos (ej., revestimiento de banco), y al moverse cuesta abajo. La liberación de cabezas de serpiente en la tierra por humanos o accidentalmente por depredadores puede ser más común que la emersión voluntaria, pero debido a que las cabezas de serpiente del norte pueden respirar aire, puede ser necesario tener en cuenta la capacidad de propagarse por tierra en el manejo de esta especie invasora. Translated to Spanish by YE Jimenez (yordano_jimenez@brown.edu).

A call for standardization of wound events reporting following ventral hernia repair.

INTRODUCTION: Postoperative wound events following ventral hernia repair are an important outcome measure. While efforts have been made by hernia surgeons to identify and address risk factors for postoperative wound events following VHR, the definition of these events lacks standardization. Therefore, the purpose of our study was to detail the variability of wound event definitions in recent ventral hernia literature and to propose standardized definitions for postoperative wound events following VHR. METHODS: The top 50 cited ventral hernia, peer-reviewed publications from 1995 through 2015 were identified using the search engine Google Scholar. The definition of wound event used and the incidence of postoperative wound events was recorded for each article. The number of articles that used a standardized definition for surgical site infection (SSI), surgical site occurrence (SSO), or surgical site occurrence requiring procedural intervention (SSOPI) was also identified. RESULTS: Of the 50 papers evaluated, only nine (18%) used a standardized definition for SSI, SSO, or SSOPI. The papers that used standardized definitions had a smaller variability in the incidence of wound events when compared to one another and their reported rates were more consistent with recently published ventral hernia repair literature. CONCLUSION: Postoperative wound events following VHR are intimately associated with patient quality of life and long-term hernia repair durability. Standardization of the definition of postoperative wound events to include SSI, SSO, and SSOPI following VHR will improve the ability of hernia surgeons to make evidence-based decisions regarding the management of ventral hernias.

Acute bone response to whole body vibration in healthy pre-pubertal boys.

The skeleton responds to mechanical stimulation. We wished to ascertain the magnitude and speed of the growing skeleton's response to a standardised form of mechanical stimulation, vibration. 36 prepubertal boys stood for 10 minutes in total on one of two vibrating platforms (high (>2 g) or low (<1 g) magnitude vibration) on either 1, 3 or 5 successive days (n=12 for each duration); 15 control subjects stood on an inactive platform. Blood samples were taken at intervals before and after vibration to measure bone formation (P1NP, osteocalcin) and resorption (CTx) markers as well as osteoprotegerin and sclerostin. There were no significant differences between platform and control groups in bone turnover markers immediately after vibration on days 1, 3 and 5. Combining platform groups, at day 8 P1NP increased by 25.1% (CI 12.3 to 38.0; paired t-test p=0.005) and bone resorption increased by 10.9% (CI 3.6 to 18.2; paired t-test p=0.009) compared to baseline. Osteocalcin, osteoprotogerin and sclerostin did not change significantly. The growing skeleton can respond quickly to vibration of either high or low magnitude. Further work is needed to determine the utility of such "stimulation-testing" in clinical practice.

The effect of thermal variance on the phenotype of marine turtle offspring.

Temperature can have a profound effect on the phenotype of reptilian offspring, yet the bulk of current research considers the effects of constant incubation temperatures on offspring morphology, with few studies examining the natural thermal variance that occurs in the wild. Over two consecutive nesting seasons, we placed temperature data loggers in 57 naturally incubating clutches of loggerhead sea turtles Caretta caretta and found that greater diel thermal variance during incubation significantly reduced offspring mass, potentially reducing survival of hatchlings during their journey from the nest to offshore waters and beyond. With predicted scenarios of climate change, behavioral plasticity in nest site selection may be key for the survival of ectothermic species, particularly those with temperature-dependent sex determination.

Leaf litter species evenness influences nonadditive breakdown in a headwater stream.

Species loss directly affects the magnitude and stability of various ecosystem processes, and species composition can drive this phenomenon. Much of the evidence that species loss affects ecosystem processes comes from experiments where species richness was manipulated while holding abundance/biomass of individual species constant. Given that species rarely coexist in equal proportions, neglecting evenness might under/overestimate the role of important species combinations. We examined leaf litter breakdown in a small stream based on species-specific input rates of leaf litter from the four dominant species (Liriodendron tulipifera, Fraxinus pennsylvanica, Fagus grandifolia, Quercus prinus), comprising 71% of inputs over peak leaf fall, for a full-factorial litter mixture study. Our experimental approach departed from previous mixture studies in that while we created all two-, three-, and four-species combinations holding species-specific mass constant, we also created a complementary set of mixtures that reflected the natural proportion we estimated from the survey. We found that species richness and evenness alone did not explain variation in breakdown rate, but an interaction between the two did, and mixtures reflecting ambient evenness lost mass nearly 33% faster than single species treatments. Analysis of individual treatments revealed that the emergent effect of mixing species was nearly twice as common in uneven vs. even mixtures. The compositional effects of litter diversity on breakdown uncovered in previous studies might be more pronounced if evenness, and not just richness, is considered when evaluating the role of species loss in these ecosystems.

Himematsutake (Iwade Strain 101) extract (ABM-FD): genetic toxicology and a 3-month dietary toxicity study in rats.

Agaricus blazei Murrill, an edible mushroom, is used as a functional food due to medicinal effects of (1-->6)-beta-D-glucan protein complex which has been shown to have anti tumour activity in mice. A 13week oral subchronic study in rats performed at 500, 1000 or 2000mg/kg/day caused, at the highest dose, reduced erythrocyte numbers and high mean cell volume in males, high creatinine and urea concentrations in both sexes and low spleen weights in females, but no histopathological change. The findings suggested low level chronic toxicity at 2000mg/kg/day and a no observed adverse effect level (NOAEL) of 1000mg/kg/day. Genotoxicity tests on the aqueous extract were negative in the bacterial reverse mutation test, either with or without S9 mix, up to 5000microg/plate and in a rat bone marrow micronucleus test up to 2g/kg bodyweight. The extract was positive at acceptable levels of toxicity in an L5178Y mouse lymphoma assay following 24h exposure in the absence of S9 and this was associated with an increase in the number of small colonies, suggesting possible clastogenic activity or aneuploidy, rather than point mutation. The aqueous extract of A. blazei is therefore of low subchronic toxicity and did not cause any direct effect upon the DNA molecule and the weak positive in the L5178 mouse lymphoma test was likely due to large deletions or the loss of the whole chromosomes rather than to direct damage to the DNA.

Intact fetal cell isolation from maternal blood: improved isolation using a simple whole blood progenitor cell enrichment approach (RosetteSep).

Isolation and analysis of intact fetal cells in maternal blood is an attractive method of non-invasive prenatal diagnosis; however, detection levels are not optimal. The poor sensitivity and inconsistent recovery of fetal cells is compounded by small numbers of circulating fetal cells and loss of fetal cells during enrichment procedures. Optimizing selection criteria by utilizing less complicated methods for target cell enrichment is essential. We report here salutary results using a simple density-based depletion method that requires neither MACS (magnetic-activated cell sorting) nor flow cytometric separation for enrichment of progenitor cells. Maternal blood samples (n = 81) were obtained from women prior to invasive prenatal genetic diagnostic procedures and processed randomly within 24 h using one of two density-based enrichment methods. For progenitor cell enrichment, samples (n = 49) were labeled with a RosetteSep progenitor antibody cocktail to remove unwanted mature T-cells, B-cells, granulocytes, natural killer cells, neutrophils and myelomonocytic cells. For CD45-negative cell enrichment, samples (n = 14) were labeled with RosetteSep CD45 antibody to remove unwanted maternal white cells. The desired cellular fraction was collected and analyzed by either fluorescent in situ hybridization (FISH) or real-time PCR for the presence of intact fetal cells and to quantify Y-chromosome-specific DYS1 sequences, respectively. Overall, FISH and real-time PCR correct detection rates for the progenitor cell enrichment approach were 53% and 89% with 3% (1 out of 30 cases) and 0% false-positive detection, respectively. Fetal sequences were detected in the range from 0.067 to 1.167 genome equivalents per milliliter of blood. No fetal cells were detected using the CD45-negative enrichment method. Flow cytometric analysis of cord blood showed that a unique myeloid population of cells was recovered using RosetteSep trade mark progenitor enrichment compared with the CD45-negative enrichment method. Sensitivity of the RosetteSep progenitor enrichment approach for detection of fetal cells in this pilot study shows great promise with recovery of cells that are suitable for FISH and automated microscope scanning. This simple and rapid method may also allow expansion in culture and characterization of the fetal cell type(s) that circulate in maternal blood, hence, greatly improving reliability of non-invasive prenatal diagnosis.

Immune parameters relevant to neural xenograft survival in the primate brain.

The lack of supply and access to human tissue has prompted the development of xenotransplantation as a potential clinical modality for neural cell transplantation. The goal of the present study was to achieve a better understanding of the immune factors involved in neural xenograft rejection in primates. Initially, we quantified complement mediated cell lysis of porcine fetal neurons by primate serum and demonstrated that anti-C5 antibody treatment inhibited cell death. We then developed an immunosuppression protocol that included in vivo anti-C5 monoclonal antibody treatment, triple drug therapy (cyclosporine, methylprednisolone, azathioprine) and donor tissue derived from CD59 or H-transferase transgenic pigs and applied it to pig-to-primate neural cell transplant models. Pre-formed alphaGal, induced alphaGal and primate anti-mouse antibody (PAMA) titers were monitored to assess the immune response. Four primates were transplanted. The three CD59 neural cell recipients showed an induced anti-alphaGal response, whereas the H-transferase neural cell recipient exhibited consistently low anti-alphaGal titers. Two of these recipients contained surviving grafts as detected by immunohistochemistry using selected neural markers. Graft survival correlated with high dose cyclosporine treatment, complete complement blockade and the absence of an induced PAMA response to the murine anti-C5 monoclonal antibodies.

Topoisomerase II alpha and II beta expression in childhood acute lymphoblastic leukaemia: relation to prognostic factors and clinical outcome.

BACKGROUND/AIMS: Many regimens used in the treatment of childhood acute lymphoblastic leukaemia (ALL) include Daunorubicin or Etoposide, which act as topoisomerase poisons. It has been suggested that there may be a relation between topoisomerase expression and response to topoisomerase poisons, based mainly on results from in vitro studies. Therefore, the aim of this study was to investigate this relation in a clinical setting and determine whether topoisomerase II alpha and II beta might be of predictive value in ALL. METHODS: Cellular expression of topoisomerases II alpha and II beta was assessed in 177 cases of ALL by immunohistochemistry using monoclonal antibodies to the two enzymes. The percentages of cell nuclei showing positive staining for topoisomerase II alpha and II beta expression were assessed. RESULTS: Taking the series as a whole, a clear separation of survival curves was seen with the established prognostic markers white blood cell (WBC) count, CD10 status, and sex. However, topoisomerase II alpha and II beta expression showed no relation to survival. No association was found between the topoisomerases and the prognostic markers CD10 and WBC count; however, topoisomerase II alpha expression was found to be related to sex, with expression being lower in girls (p = 0.002). CONCLUSIONS: These results suggest that the response to topoisomerase poisons cannot be predicted by the assessment of topoisomerase II alpha and II beta expression as defined by immunohistochemistry.

Intranigral transplantation of solid tissue ventral mesencephalon or striatal grafts induces behavioral recovery in 6-OHDA-lesioned rats.

Parkinson's disease (PD) is characterized by a degeneration of the dopamine (DA) pathway from the substantia nigra (SN) to the basal forebrain. Prior studies in unilateral 6-hydroxydopamine (6-OHDA)-lesioned rats have primarily concentrated on the implantation of fetal ventral mesencephalon (VM) into the striatum in attempts to restore DA function in the target. We implanted solid blocks of fetal VM or fetal striatal tissue into the SN to investigate whether intra-nigral grafts would restore motor function in unilaterally 6-OHDA-lesioned rats. Intra-nigral fetal striatal and VM grafts elicited a significant and long-lasting reduction in apomorphine-induced rotational behavior. Lesioned animals with ectopic grafts or sham surgery as well as animals that received intra-nigral grafts of fetal cerebellar cortex showed no recovery of motor symmetry. Subsequent immunohistochemical studies demonstrated that VM grafts, but not cerebellar grafted tissue expressed tyrosine hydroxylase (TH)-positive cell bodies and were associated with the innervation by TH-positive fibers into the lesioned SN as well as adjacent brain areas. Striatal grafts were also associated with the expression of TH-positive cell bodies and fibers extending into the lesioned SN and an induction of TH-immunolabeling in endogenous SN cell bodies. This finding suggests that trophic influences of transplanted fetal striatal tissue can stimulate the re-expression of dopaminergic phenotype in SN neurons following a 6-OHDA lesion. Our data support the hypothesis that a dopaminergic re-innervation of the SN and surrounding tissue by a single solid tissue graft is sufficient to improve motor asymmetry in unilateral 6-OHDA-lesioned rats.