Parenchymal involvement on CT pulmonary angiography in SARS-CoV-2 Alpha variant infection and correlation of COVID-19 CT severity score with clinical disease severity and short-term prognosis in a UK cohort.

AIM: To determine if there is a difference in radiological, biochemical, or clinical severity between patients infected with Alpha-variant SARS-CoV-2 compared with those infected with pre-existing strains, and to determine if the computed tomography (CT) severity score (CTSS) for COVID-19 pneumonitis correlates with clinical severity and can prognosticate outcomes. MATERIALS AND METHODS: Blinded CTSS scoring was applied to 137 hospital patients who had undergone both CT pulmonary angiography (CTPA) and whole-genome sequencing of SARS-CoV-2 within 14 days of CTPA between 1/12/20-5/1/21. RESULTS: There was no evidence of a difference in imaging severity on CTPA, viral load, clinical parameters of severity, or outcomes between Alpha and preceding variants. CTSS on CTPA strongly correlates with clinical and biochemical severity at the time of CTPA, and with patient outcomes. Classifying CTSS into a binary value of "high" and "low", with a cut-off score of 14, patients with a high score have a significantly increased risk of deterioration, as defined by subsequent admission to critical care or death (multivariate hazard ratio [HR] 2.76, p<0.001), and hospital length of stay (17.4 versus 7.9 days, p<0.0001). CONCLUSION: There was no evidence of a difference in radiological severity of Alpha variant infection compared with pre-existing strains. High CTSS applied to CTPA is associated with increased risk of COVID-19 severity and poorer clinical outcomes and may be of use particularly in settings where CT is not performed for diagnosis of COVID-19 but rather is used following clinical deterioration.

Assessing the safety of del Nido cardioplegia solution in adult congenital cases.

PURPOSE: del Nido cardioplegia solution (CPS) has been successfully used for myocardial protection in the pediatric population. We propose this solution can be used safely in adult congenital patients. The proposed benefit of this solution is the avoidance of the need for repetitive interruption of the operation to administer multiple doses of standard cardioplegia. METHODS: As part of a quality improvement initiative, 47 consecutive adult patients (mean age 40.9 years, range 18-71) undergoing congenital heart surgery were given del Nido CPS. Cardiac function was assessed pre- and post-operatively by echocardiography (ECHO). Inotrope use, troponin levels and restoration of cardiac rhythm were also evaluated. RESULTS: The average duration of the longest ischemic time was 52.5 minutes ± 15.57 minutes. In patients receiving a single dose (40%, n=19) of CPS, the average ischemic time was 49.8 minutes ± 18.8 minutes. No patients demonstrated any ventricular electrical activity while the aorta was cross-clamped. Post-operative ECHO showed that 94% (n=44) had no change in ejection fraction from the pre-operative ECHO. Patients requiring inotropic support at the time of leaving the operating room (OR) was 43% (n=20). The percentage of patients requiring inotropic support twenty-four hours post-operatively was 17% (n=8). Spontaneous restoration of cardiac rhythm (without the need for defibrillation) after cross-clamp removal occurred in 91% (n=43) of patients. The average troponin T level post-op was 1.86 ± 2.9 µg/L. CONCLUSIONS: del Nido CPS can be used for myocardial protection during adult congenital cardiac surgery without any apparent adverse effects. In addition, we were able to change our re-dosing protocol to 45 minutes with del Nido CPS compared to 20 minutes with our adult 4:1 blood CPS.

Carboxyhemoglobinemia in a pediatric cardiopulmonary bypass patient derived from a contaminated unit of allogenic blood.

A 4.3 kg, three-month-old patient, diagnosed with a perimembranous ventricular septal defect, presented for cardiac surgery. Upon initiation of cardiopulmonary bypass (CPB), the patient developed carboxyhemoglobinemia (11.1%). Potential sources for the unexpected acquired carboxyhemoglobinemia were sought quickly. Testing of residual blood from the unit of packed red blood cells (PRBCs) used to prime the CPB circuit revealed a carboxyhemoglobin (COHb) of 15.1 %. A decrease in cerebral oximetry (rSO(2)) on CPB was initially felt to be a result of the elevated COHb levels. When ventilation of the oxygenator with 100% oxygen (O(2)) failed to decrease COHb levels, a partial exchange transfusion was performed with reduction in COHb to 7.1%. The operation was completed successfully and the patient's COHb levels returned to normal within 75 minutes. Post case analysis of events and data collected during the case revealed a broader differential for explaining the compromised patient's O(2) delivery than the transient acquired carboxyhemoglobinemia. A partial obstruction of the superior vena cava could have triggered the drop in rSO(2) on CPB. Follow-up of the donor blood confirmed the donor had previously undiagnosed carboxyhemoglobinemia as a result of chronic carbon monoxide exposure from a faulty vehicle exhaust system.

A clinical evaluation of the Dideco Kids D100 neonatal oxygenator.

In August 2006, Duke University Perfusion Services had the opportunity to be the first institution in the United States to clinically evaluate the Dideco D100 Neonatal Oxygenator. The device was used on six pediatric patients to facilitate correction or palliation of their cardiac defects, which included two arterial switch operations, two truncus arteriosus repairs, one stage 1 Norwood and one repair of total anomalous pulmonary venous return. The average patient weight was 3.1 kg. The average cardiopulmonary bypass (CPB) time was 135 minutes and the average cross-clamp time was 61 minutes. Arterial and venous blood gasses were drawn and used to calculate oxygen transfer. The average oxygen transfer was 14.8 +/- 10.3 ml/O2/min. The Dideco D100 Oxygenator is the first oxygenation device designed specifically for neonates. The Dideco D100 is a microporous hollow-fiber device. It has a static priming volume of 31 ml and a maximum rated flow of 700 ml/min. The integral hard-shell venous reservoir has a minimum operating level of 10 ml and a reservoir capacity of 500 ml. For this evaluation, the Dideco Kids D100 Neonatal Oxygenator performed adequately on patients weighing up to 5 kg. This device provides an excellent first step towards offering very small children appropriate circuitry without having to sacrifice safety or performance.

Type 1 growth factor receptor expression in node positive breast cancer: adverse prognostic significance of c-erbB-4.

BACKGROUND: There is a clear need to define biological markers that will predict the response to treatment in breast cancer, and several recent studies suggest that the expression of type 1 growth factor receptors may prove important in this regard. The type 1 growth factor receptors are a family of transmembrane receptors comprising epidermal growth factor receptor (EGFR), c-erbB-2, c-erbB-3, and c-erbB-4. Both EGFR and c-erbB-2 are associated with poor prognosis in certain tumours. AIMS: There is very little information concerning expression patterns of the full range of type 1 growth factor receptors, especially with respect to c-erbB-3 and c-erbB-4. Therefore, this study was designed to compare the expression of each, and to assess whether expression of any of the factors was related to patient survival in a clinical series. METHODS: Type 1 growth factor receptor expression was investigated by means of immunohistochemistry in a series of node positive patients with breast cancer (n = 66), and statistical analysis was carried out to determine associations between variables and survival analysis for each variable. RESULTS: There were several correlations between variables, and overexpression of EGFR, c-erbB-2, and c-erbB-4 was found to be associated with adverse clinical outcome, although the results were significant only for c-erbB-4 (p = 0.002). CONCLUSION: Although patient numbers are small, this is the first report describing c-erbB-4 as an adverse prognostic marker. These findings are in contrast to previous investigations and may relate to the fact that the patients studied all had advanced stage disease and had undergone similar chemotherapy regimens in the context of a clinical trial.

High-level expression of recombinant Fc chimeric proteins in suspension cultures of stably transfected J558L cells.

Recombinant Fc chimeric proteins are useful tools for studying protein function, including the analysis of molecular interactions by techniques such as expression cloning. Here we describe a method we have used to express the IgLON family proteins, CEPU1 and OBCAM, as recombinant Fc chimeric proteins in stably transfected mouse J558L myeloma cells. The use of this cell line provided the opportunity to maximize protein production, as it secretes antibodies in large quantities and can be grown to high density in small volumes of culture medium. Isolation of recombinant OBCAMFc from the adherent COS7 cell line suggested a minimum level of expression of 0.07 mg OBCAMFc/100 mL culture medium, while the J558L cell line expressed OBCAMFc at approximately 11.4 mg/100 mL culture medium. Purification of IgLON-Fc expressed by J558L cells was simpler than purification from COS7 cells because of the lower volume of culture medium generated. Furthermore, contamination of J558L expressed IgLONFc with bovine IgG from the culture medium was negligible. The method presented, which utilizes a commercially available small-scale bioreactor, provides the nonspecialist protein expression laboratory with the means to produce recombinant proteins quickly and easily in milligram quantities.

Identification and characterization of CEPU-Se-A secreted isoform of the IgLON family protein, CEPU-1.

CEPU-1/Neurotrimin is a neuronal glycoprotein thought to play a role in axon guidance and cell-cell recognition. It is a member of the IgLON family, has three C2 domains, and is attached to the plasma membrane by a GPI-anchor. We report here the characterisation of an alternatively-spliced isoform of CEPU-1 that is secreted. This isoform, termed CEPU-Se, is coexpressed with CEPU-1 in retina, cerebellum, and DRG neurons. In the cerebellum CEPU-1/CEPU-Se is expressed predominantly on granule cells and in the molecular layer. Divalent but not monovalent CEPU-Se interacts with CEPU-1 and other IgLONs, suggesting that the ability of CEPU-Se to modify the activity of the IgLON family may require an additional cofactor. CEPU-Se does not support the outgrowth of DRG neurons or the extension of established growth cones; however, neurite outgrowth on laminin is unaffected by CEPU-Se. Our data suggest that CEPU-Se may act to modulate the ability of CEPU-1, LAMP, and OBCAM to influence neurite outgrowth.

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.

Vascular control for resection of suprahepatic intracaval Wilms' tumor: technical considerations.

The surgical resection of Wilms' tumor can be complicated by tumor thrombus extension into the inferior vena cava. In cases of suprahepatic Wilms' tumor thrombus that may extend into the right atrium, a median sternotomy and cardiopulmonary bypass (CPB) are used to facilitate tumor resection. However, if the tumor can be localized and controlled below the atrium, resection without the use of cardiopulmonary bypass may limit morbidity. The authors describe a novel approach to tumor thrombectomy for a Wilms' tumor extending to the suprahepatic vena cava without the use of CPB. The authors used transesophageal echocardiography to localize the tumor thrombus and detect any tumor or air embolization and a minimal lower sternotomy to obtain intrapericardial control of the inferior vena cava. This technique may be useful in selected cases of Wilms' tumor as an alternative to median sternotomy and use of cardiopulmonary bypass.

Co-localisation, heterophilic interactions and regulated expression of IgLON family proteins in the chick nervous system.

The chick glycoprotein GP55 has been shown to inhibit the growth and adhesion of DRG and forebrain neurons. GP55 consists of several members of the IgLON family, a group of glycoproteins including LAMP, OBCAM, CEPU-1 (chick)/neurotrimin (rat) and neurotractin (chick)/kilon (rat) thought to play a role in the guidance of growing axons. IgLONs belong to the Ig superfamily and have three C2 domains and a glycosyl phosphatidylinositol anchor which tethers them to the neuronal plasma membrane. We have now completed the deduced amino acid sequence for two isoforms of chicken OBCAM and used recombinant LAMP, OBCAM and CEPU-1 to raise antisera specific to these three IgLONs. LAMP and CEPU-1 are co-expressed on DRG and sympathetic neurons, while both overlapping and distinct expression patterns for LAMP, OBCAM and CEPU-1 are observed in retina. Analysis of IgLON mRNA expression reveals that alternatively spliced forms of LAMP and CEPU-1 are developmentally regulated. In an attempt to understand how the IgLONs function, we have begun to characterise their molecular interactions. LAMP and CEPU-1 have already been shown to interact homophilically. We now confirm that OBCAM will bind homophilically and also that LAMP, OBCAM and CEPU-1 will interact heterophilically with each other. We propose that IgLON activity will depend on the complement of IgLONs expressed by each neuron.

Expression of topoisomerase IIIalpha in normal and neoplastic tissues determined by immunohistochemistry using a novel monoclonal antibody.

Topoisomerases are nuclear enzymes that modulate the topological structure of DNA in order to facilitate cellular events such as replication and transcription. These enzymes are also the cellular targets of certain classes of chemotherapeutic agents termed topoisomerase poisons. A new human topoisomerase isoform, IIIa, was discovered in 1996, which is thought to have roles in genome stability and possibly chromosome separation during mitosis. It is possible that novel or existing anti-topoisomerase agents target topoisomerase IIIa, suggesting that this enzyme may have potential as a prognostic marker and chemotherapeutic target. In order to study expression patterns of topoisomerase IIIa we have produced a novel monoclonal antibody to human topoisomerase IIIa (TOPO3a-1A4), and used it to assess topoisomerase IIIa expression in a wide range of normal and neoplastic tissues. We have found that topoisomerase IIIa is expressed in a wide range of tissue types, with especially high concentrations in endothelial cells and stromal fibroblasts. No general relationship was observed between expression of topoisomerase IIIa and proliferation. Expression in neoplastic tissues often paralleled their normal counterparts, although certain tumours showed either increased (e.g. colonic adenoma) or reduced (e.g. gastric carcinoma, small cell carcinoma of bronchus) expression. If topoisomerase IIIa is found to be a target for chemotherapeutic agents, clinical response in different tumour types may be related to topoisomerase IIIa expression, which may be assessed using TOPO3a-1A4.

The role of antibodies in dysfunction of pig-to-baboon pulmonary transplants.

OBJECTIVE: Pulmonary transplantation has become the preferred treatment for end-stage lung disease, but application of the procedure is limited because of a paucity of donors. One way to solve donor limitations is to use animal organs as a donor source or xenotransplantation. The current barrier to pulmonary xenotransplantation is the rapid failure of the pulmonary xenograft. Although antibodies are known to play a role in heart and kidney xenograft rejection, their involvement in lung dysfunction is less defined. This project was designed to define the role of antibodies in pulmonary graft rejection in a pig-to-baboon model. METHODS: Orthotopic transgenic swine left lung transplants were performed in baboons depleted of antibodies by one of three techniques before transplantation: (1) ex vivo swine kidney perfusion, (2) total immunoglobulin-depleting column perfusion, and (3) ex vivo swine lung perfusion. Results were compared with those of transgenic swine lung transplants in unmodified baboons. RESULTS: All three techniques of antibody removal resulted in depletion of xenoreactive antibodies. Only pretransplantation lung perfusion improved pulmonary xenograft function compared with lung transplantation in unmodified baboons. CONCLUSIONS: The pathogenesis of pulmonary injury in a swine-to-primate transplant model is different from that in renal and cardiac xenografts. Depletion of antibodies alone does not have a beneficial effect and may actually be detrimental.

Monoclonal antibodies recognizing CD5, CD10 and CD23 in formalin-fixed, paraffin-embedded tissue: production and assessment of their value in the diagnosis of small B-cell lymphoma.

AIMS: Assessment of the expression of antigens CD5, CD10 and CD23 can be of value in the differential diagnosis of small B-cell lymphoma. Correct subclassification is important since optimal treatment regimes differ between the subtypes. The aim of this study was to generate monoclonal antibodies recognizing these antigens in paraffin-embedded tissue and to assess their efficacy using a panel of cases of small B-cell lymphoma of various subtypes. METHODS AND RESULTS: For each antibody synthetic recombinant protein and conventional murine hybridoma technology was employed. Monoclonal antibodies effective in formalin-fixed, paraffin-embedded tissue were successfully generated, designated NCL-CD5-4C7, NCL-CD10-270 and NCL-CD23-1B12, respectively. A series of 58 cases of small B-cell lymphoma including examples of each subtype (lymphocytic, follicle centre cell, mantle cell, marginal zone and lymphoplasmacytoid) was assembled and immunostaining for the respective antigens carried out using the monoclonal antibodies produced. Our results indicate that the antibodies are specific for their respective antigens and give the predicted phenotypic profile in the small B-cell lymphoma subtypes. CONCLUSIONS: These novel monoclonal antibodies may be of value in routine diagnostic practice.

Mini-circuit cardiopulmonary bypass with vacuum assisted venous drainage: feasibility of an asanguineous prime in the neonate.

Conventional cardiopulmonary bypass (CPB) in neonates results in increased transfusion requirements and hemodilution. There has been little advancement in CPB for the neonatal population. There is evidence that increased priming volumes and blood product transfusion enhances inflammatory response to CPB and increases myocardial and pulmonary dysfunction. We have devised a miniaturized CPB circuit that utilizes vacuum-assisted venous drainage (VAVD) in an effort to decrease priming volume and avoid transfusion requirements. The purpose of this study was to evaluate the safety and efficacy of this miniaturized CPB system and determine the feasibility of an asanguineous prime. Ten 1-week-old piglets were randomized to five mini- and five conventional CPB pump circuits. Subjects were supported with CPB at 100 ml/kg/min, cooled to 28 degrees C, exposed to 10 min aortic crossclamp with cardioplegic arrest, rewarmed to 37 degrees C, weaned from bypass, and subjected to modified-ultrafiltration (MUF) for approximately 10 min. This method was chosen to simulate a situation with all the elements of clinical CPB. Blood transfusion trigger was a hematocrit <15 on CPB. Serum samples were obtained pre-CPB, at 15 min of CPB onset, immediately post-CPB completion, and immediately post-MUF. Indices of hemolysis (SGOT, LDH), production of inflammatory mediators (interleukin (IL)-8, tumor necrosis factor-alpha (TNFalpha)), and physiologic parameters of inflammation were measured. The overall blood requirement was significantly less in the mini-circuit compared to conventional CPB (47.0+/-5.8 ml vs 314.2+/-31.6 ml; p < 0.0001). The only significant blood requirement in the mini-circuit was to replace the volume removed for samples. During the study, mean arterial pressure (MAP) (p = 0.004), static pulmonary compliance (p = 0.04), platelets (p = 0.0003), and white blood cells (p = 0.003) significantly decreased across the groups. Lung water content (p = 0.02), TNFalpha levels (p = 0.05), and SGOT (p = 0.009) increased significantly during the study, across the groups. Among all parameters tested, except for blood requirement and hematocrit post-CPB, there were no significant differences between the two circuits. VAVD makes asanguineous prime in neonates feasible. When used in this study to miniaturize a conventional-CPB circuit, VAVD with a reconfigured neonatal CPB console and circuit resulted in no detrimental effects, and allowed for markedly decreased priming volumes and blood transfusion requirements.

Intermittent perfusion protects the brain during deep hypothermic circulatory arrest.

BACKGROUND: Deep hypothermic circulatory arrest (DHCA) has been shown to cause impairment in recovery of cerebral blood flow (CBF) and cerebral metabolism (CMRO2) proportional to the duration of the DHCA period. This effect on CMRO2 may be a marker for brain injury, because CMRO2 recovers normally after cardiopulmonary bypass (CPB) when DHCA is not used. The aim of this study was to investigate the effects of intermittent perfusion during DHCA on the recovery of CMRO2 after CPB and to correlate these findings with electron microscopy (EM) of the cerebral microcirculatory bed. METHODS: Fifteen neonatal piglets were placed on CPB and cooled to 18 degrees C. Each animal then underwent either: (1) 60 minute continuous CPB (control), (2) 60 minute uninterrupted DHCA (UI-DHCA), or (3) 60 minute DHCA with intermittent perfusion (1 minute every 15 minutes) (I-DHCA). All animals were then rewarmed and weaned from CPB. Measurements of CBF and CMRO2 were taken before and after CPB. A further 9 animals underwent CPB without DHCA (2 animals) or with DHCA (7 animals), under various conditions of arterial blood gas management, intermittent perfusion, and reperfusion time. RESULTS: UI-DHCA resulted in significant impairment to recovery of CMRO2 after CPB (p < 0.05). Regardless of the blood gas strategy used, the EM after UI-DHCA revealed extensive damage characterized by perivascular intracellular and organelle edema, and vascular collapse. I-DHCA, on the other hand, produced a pattern of normal CMRO2 recovery identical to controls, and the EM was normal for both these groups. CONCLUSIONS: Intermittent perfusion during DHCA is clinically practical and results in normal cerebral metabolic and ultrastructural recovery. Furthermore, the correlation between brain structure and CMRO2 suggests that monitoring CMRO2 during the operation may be an outstanding way to investigate new strategies for neuroprotection designed to reduce cerebral damage in children undergoing correction of congenital cardiac defects.

Song as an indicator of parasitism in the sedge warbler.

We studied female choice and reproductive success in a marked population of sedge warblers Acrocephalus schoenobaenus, from 1995 to 1996. Three genera of parasitic blood protozoans, namely Haemoproteus sp. Trypanosoma sp. Plasmodium sp., were identified from blood samples taken from all breeding adults. Relatively high prevalence values of 19.5% in 1995 and 37.5% in 1996 were associated with increased levels of white blood cells relative to the number of red blood cells. Compared with nonparasitized males, parasitized males had significantly lower repertoire sizes in both years of the study; in one year, they also spent less time in song flights and weighed less. They also provisioned their broods at a lower rate. Parasitized females produced the same clutch size as nonparasitized females, although their broods were smaller at 7 days old. We suggest that haematozoan infections may reduce the expression of sexually selected song traits. Furthermore, such infections may influence the standard of parental care provided by males, although further research is needed to determine whether this is mediated through genetic resistance to parasitism or the effects of parasitism upon immediate body condition. Copyright 1999 The Association for the Study of Animal Behaviour.

Identification of chURP, a nuclear calmodulin-binding protein related to hnRNP-U.

In a screen for myosin-like proteins in embryonic chicken brain, we have identified a novel nuclear protein structurally related to hnRNP-U (heterogeneous nuclear ribonuclear protein U). We have called this protein chURP, for chicken U-related protein. In this screen, chURP was immunoreactive with two myosin antibodies and, in common with the unconventional myosins, bound calmodulin in vitro in both the presence and absence of calcium ions. Determination of 757 amino acids of the chURP sequence revealed that it shares 41% amino acid identity with human and rat hnRNP-U, although chURP and hnRNP-U appear not to be orthologous proteins. ChURP is ubiquitously expressed in the nuclei of all chick tissues and, as one of a growing number of calmodulin-binding proteins to be identified in the nucleus, further highlights the potential of calmodulin as a regulator of nuclear metabolism.

Effects of ischemia on pulmonary dysfunction after cardiopulmonary bypass.

BACKGROUND: Pulmonary hypertension and lung injury secondary to cardiopulmonary bypass (CPB) are probably caused by a combination of ischemia and inflammation. This study was undertaken to investigate the potential ischemic effects of cessation of pulmonary arterial flow during CPB on pulmonary injury. METHODS: Twenty neonatal piglets (2.5 to 3.1 kg) were randomly assigned to two groups. Group A (n = 10) underwent 90 minutes of CPB at full flow (100 mL x kg(-1) x min(-1)) and clamping of the main pulmonary artery (PA). Group B (n = 10) underwent 90 minutes of partial CPB (66 mL x kg(-1) x min(-1)) with continued mechanical ventilation and without clamping of the PA. All hearts were instrumented with micromanometers and a PA ultrasonic flow probe. Endothelial function was assessed by measuring endothelial-dependent relaxation (measured by change in pulmonary vascular resistance after PA infusion of acetylcholine) and endothelial-independent relaxation (measured by change in pulmonary vascular resistance after ventilator infusion of nitric oxide and PA infusion of sodium nitroprusside). RESULTS: All groups exhibited signs of pulmonary injury after CPB as evidenced by significantly increased pulmonary vascular resistance, increased alveolar-arterial O2 gradients, and decreased pulmonary compliance (p<0.05); however, pulmonary injury was significantly worse in group A (p<0.05). CONCLUSIONS: This study suggests that although exposure to CPB alone is enough to cause pulmonary injury, cessation of PA flow during CPB contributes significantly to this pulmonary dysfunction.

Methylprednisolone reduces the inflammatory response to cardiopulmonary bypass in neonatal piglets: timing of dose is important.

INTRODUCTION: Cardiopulmonary bypass produces an inflammatory response that can cause significant postoperative pulmonary dysfunction and total body edema. This study evaluates the efficacy of preoperative methylprednisolone administration in limiting this injury in neonates and compares the effect of giving methylprednisolone 8 hours before an operation to the common practice of adding methylprednisolone to the cardiopulmonary bypass circuit prime. METHODS: A control group of neonatal pigs (control; n = 6) received no preoperative medication. One experimental group (n = 6) received methylprednisolone sodium succinate (30 mg/kg) both 8 and 1.5 hours before the operation. A second experimental group received no preoperative treatment, but methylprednisolone (30 mg/kg) was added to the cardiopulmonary bypass circuit prime. All animals underwent cardiopulmonary bypass and 45 minutes of deep hypothermic circulatory arrest. Hemodynamic and pulmonary function data were acquired before cardiopulmonary bypass and at 30 and 60 minutes after bypass. RESULTS: In the control group, pulmonary compliance, alveolar-arterial gradient, and pulmonary vascular resistance were significantly impaired after bypass (P <.01 for each by analysis of variance). In the group that received methylprednisolone, compliance (P =.02), alveolar-arterial gradient (P =.0003), pulmonary vascular resistance (P =.007), and extracellular fluid accumulation (P =.003) were significantly better after bypass when compared with the control group. Results for the group that received no preoperative treatment fell between the control group and the group that received methylprednisolone. CONCLUSIONS: When given 8 hours and immediately before the operation, methylprednisolone improves pulmonary compliance after bypass, alveolar-arterial gradient, and pulmonary vascular resistance compared with no treatment. The addition of methylprednisolone to the cardiopulmonary bypass circuit prime is beneficial but inferior to preoperative administration.

NCL-CD10-270: a new monoclonal antibody recognizing CD10 in paraffin-embedded tissue.

CD10 (CALLA) antigen is expressed in a wide variety of epithelial and nonepithelial tissues, but its most significant application is in the diagnosis and classification of certain types of malignant lymphoma and leukemia. CD10 is expressed in a high percentage of cases of acute lymphoblastic leukemia (ALL), follicular lymphoma, Burkitt's lymphoma, and some hematopoietic tumors. Although the antigen is not lineage specific, CD10 expression is widely used to define subgroups within B-ALL and is a useful tool for detecting the presence of leukemic blasts in the bloodstream. Currently available monoclonal antibodies to CD10 have been found to be effective only in fresh-frozen tissue and for techniques such as flow cytometry. We have used a recombinant protein corresponding to the whole of CD10 to generate a monoclonal antibody that is effective in paraffin-embedded tissue sections. We have used this antibody to assay for the presence of CD10 on a range of normal and pathological tissues. Strong staining was seen in lymphoid germinal centers, renal tubules, glomeruli, syncytiotrophoblast, hepatic parenchymal canaliculi, B-lineage ALL, follicle center cell lymphoma, and a proportion of cases of large-B-cell lymphoma. We believe that this antibody will be of value in the characterization of malignant lymphoma, in particular the differential diagnosis of small-B-cell lymphoma and subtyping of lymphoblastic leukemia, as well as the investigation of the significance of expression of CD10 in other normal and pathological tissues.