Actividad citotóxica y antiproliferativa de un extracto rico en fucoidan de Lessonia trabeculata sobre células de adenocarcinoma mamario murino 4T1

Introducción. Los tumores neoplásicos se caracterizan por su invasividad y metástasis. Las células neoplásicas tienen heterogeneidad genética, por lo cual pueden desarrollar resistencia a los quimioterápicos. Por esta razón, las plantas continúan siendo una fuente importante de nuevos productos anticancerígenos. Objetivo. Evaluar la actividad citotóxica y antiproliferativa de un extracto rico en fucoidan de Lessonia trabeculata nativa (EFLt) sobre la línea celular de adenocarcinoma mamario murino, triple negativo 4T1. Métodos. La citotoxicidad y la IC50 se determinaron en monocapas de 4T1 empleando el reactivo MTT. Para demostrar la actividad antiproliferativa se aplicaron los métodos de cierre de herida y anticlonogénico utilizando las IC50 del EFLt y Dox (doxorubicina). El cierre de herida fue evaluado mediante barrido de tiempos discretos; el efecto anticlonogénico fue evaluado 7 días postratamiento mediante el conteo de colonias y se determinó la fracción de sobrevivencia. Adicionalmente, se evaluaron la citotoxicidad y actividad antiproliferativa combinando las IC50 de EFLt y Dox. El porcentaje de migración y conteo de colonias se realizó con el programa ImageJ. Resultados. La IC50 del EFLt (950 μg/mL) produjo 56% de citotoxicidad, 80,3% de inhibición de la migración celular, 68% de inhibición en la formación de colonias. La IC50 de Dox fue 0,5 μg/mL. Conclusiones. El EFLt ejerce citotoxicidad dependiente de la concentración y tiene efecto antiproliferativo sobre 4T1. Se requiere continuar los ensayos en modelos de mayor complejidad que permitan esclarecer el potencial antitumoral del EFLt.

Introduction. Neoplastic tumors are characterized by invasiveness and metastasis. Neoplastic cells are genetically heterogeneous and can develop resistance to chemotherapeutic agents. For this reason, plants continue to be an important source of new anticancer products. Objective. To determine the cytotoxic and antiproliferative activity of a fucoidan-rich extract of native Lessonia trabeculata (EFLt) on the tripe negative murine mammary adenocarcinoma cell line 4T1. Methods. Cytotoxicity and IC50 were determined in 4T1 monolayers using the MTT reagent. To demonstrate antiproliferative activity, "wound" closure and anticlonogenic methods were applied using the IC50 of EFLt and Doc (doxorubicin). "Wound" closure was evaluated by discrete times sweep to determine percentage inhibition of cell migration; the anticlonogenic effect was evaluated by colony counting 7 days after treatment and the survival fraction was determined. In addition, cytotoxicity and antiproliferative activity were evaluated by combining the IC50 of EFLt and Dox. Percent migration and colony counts were performed using ImageJ software. Results. The IC50 (950 μg/mL) of EFLt was 56% cytotoxicity, 80,3% inhibition of cell migration, 68% inhibition of colony formation.The ICof Dox was 0,5 μg/mL. Conclusions. EFLt exerts concentration-dependent cytotoxicity and antiproliferative effect on 4T1. Further studies in more complex models are needed to elucidate the anti-tumor potential of EFLt.

Comparison of etomidate and methohexital as anesthetic agents for continuation and maintenance electroconvulsive therapy: A retrospective analysis of seizure quality and safety.

BACKGROUND: The ideal hypnotic agent for electroconvulsive therapy (ECT) is still under debate and previous studies comparing etomidate and methohexital have produced conflicting results. This retrospective study compares etomidate and methohexital as anesthetic agents in continuation and maintenance (m)ECT with regard to seizure quality and anesthetic outcomes. METHODS: All subjects undergoing mECT at our department between October 1st, 2014 and February 28th, 2022 were included in this retrospective analysis. Data for each ECT session were obtained from the electronic health records. Anesthesia was performed with either methohexital/succinylcholine or etomidate/succinylcholine. Standard seizure quality parameters, anesthesiological monitoring data, pharmacological interventions and side-effects were recorded. RESULTS: 573 mECT treatments in 88 patients were included (methohexital n = 458, etomidate n = 115). Seizures lasted significantly longer after using etomidate (electroencephalography: +12.80 s [95 %-CI:8.64-16.95]; electromyogram +6.59 s [95 %-CI:4.14-9.04]). Time to maximum coherence was significantly longer with etomidate (+7.34 s [95 %-CI:3.97-10.71]. Use of etomidate was associated with longer procedure duration (+6.51 min [95 %-CI:4.84-8.17]) and higher maximum postictal systolic blood pressure (+13.64 mmHg [95 %-CI:9.33-17.94]). Postictal systolic blood pressure > 180 mmHg, the use of antihypertensives, benzodiazepines and clonidine (for postictal agitation), as well as the occurrence of myoclonus was significantly more common under etomidate. CONCLUSIONS: Due to longer procedure duration and an unfavorable side effect profile, etomidate appears inferior to methohexital as an anesthetic agent in mECT despite longer seizure durations.

Incremento de la viabilidad, producción de especies reactivas de oxígeno, IL-1 y TNF-α en células mononucleares de sangre periférica humana tratadas con fucoidan de Lessonia trabeculata

Las algas pardas constituyen una fuente de alto contenido de polisacáridos como los fucoidanos que poseen importantes propiedades inmunomoduladoras. El objetivo fue determinar la viabilidad de células mononucleares de sangre periférica humana (CMSPh), producción de óxido nítrico (NO), especies reactivas de oxígeno (ROS) y de las citoquinas proinflamatorias IL-1α, IL-6, TNF-α e IFN-γ en cultivos tratados con fucoidan de Lessonia trabeculata. Se empleó fucoidan de Lessonia trabeculata proveniente de la bahía San Nicolás de Marcona-Ica. Las CMSPh se aislaron empleando Ficoll-Hypaque, se distribuyeron a una concentración de 1x105 células/pocillo en medio RPMI-1640 completo y se trataron con diferentes concentraciones de fucoidan durante 24 y 48 h. La actividad citotóxica se determinó por la reducción de MTT, la producción de NO por la reacción de Griess y las ROS por la reducción del NBT. La producción de citoquinas se cuantificó por ELISA. El fucoidan de L. trabeculata estimuló la proliferación de CMSPh y produjo el incremento de ROS a concentraciones de 100-2000 μg/mL respecto al control (p<0.001), la reacción para nitritos resultó negativa. El fucoidan incrementó la producción de IL-1α y TNF-α a concentraciones de 100 y 10 μg/mL respectivamente, mientras que la producción de IL-6 e IFN-γ no mostró diferencias significativas. Se concluye que el fucoidan de L. trabeculata estimula la proliferación de CMSPh, producción de especies reactivas de oxígeno y las citoquinas proinflamatorias IL-1α y TNF-α que poseen importantes propiedades inmunomoduladoras.

Brown algae are a source of high content of polysaccharides such as fucoidans that have important immunomodulatory properties. The aim was to determine the viability of human peripheral blood mononuclear cells (hPBMC), production of nitric oxide (NO), reactive oxygen species (ROS) and the proinflammatory cytokines IL-1α, IL-6, TNF-α and IFN -γ in cultures treated with fucoidan from Lessonia trabeculata. Fucoidan from Lessonia trabeculata from San Nicolás de Marcona-Ica Bay was used. The hPBMC were isolated using Ficoll-Hypaque, distributed at a concentration of 1x105 cells/well in complete RPMI-1640 medium and treated with different concentrations of fucoidan for 24 and 48 h. The cytotoxic activity was determined by the reduction of MTT, NO production by the Griess reaction and ROS by the reduction of NBT. The production of cytokines was quantified by ELISA. The fucoidan of L. trabeculata stimulated the proliferation of hPBMC and produced the increase of ROS at concentrations of 100-2000 μg/mL with respect to the control (p <0.001), the reaction for nitrites was negative. Fucoidan increased the production of IL-1α and TNF-α at concentrations of 100 and 10 μg/mL respectively, while the production of IL-6 and IFN-γ did not show significant differences. It is concluded that the fucoidan of L. trabeculata stimulates the proliferation of hPBMC, production of reactive oxygen species and the proinflammatory cytokines IL-1α and TNF-α that possess important immunomodulatory properties.

[Etiological structure of influenza and other ARVI in St. Petersburg during epidemic seasons 2012-2016.]

The etiological structure of influenza and other acute respiratory viral infections including their rate of incidence in St. Petersburg and Leningrad region during 4 epidemic seasons has been studied. Seasonality of some respiratory viruses was shown and peaks of circulation of RSV, adenovirus, parainfluenza viruses, rhinovirus, bocavirus, metapneumovirus and coronavirus were marked. The interference of influenza A viruses and RSV, RSV and rhinoviruses was highlighted. A high incidence of adenovirus infection in organized communities and RSV infection in children was revealed.

Synthesis and Study of Fe-Doped Bi2S3 Semimagnetic Nanocrystals Embedded in a Glass Matrix.

Iron-doped bismuth sulphide (Bi2-xFexS3) nanocrystals have been successfully synthesized in a glass matrix using the fusion method. Transmission electron microscopy images and energy dispersive spectroscopy data clearly show that nanocrystals are formed with an average diameter of 7-9 nm, depending on the thermic treatment time, and contain Fe in their chemical composition. Magnetic force microscopy measurements show magnetic phase contrast patterns, providing further evidence of Fe incorporation in the nanocrystal structure. The electron paramagnetic resonance spectra displayed Fe3+ typical characteristics, with spin of 5/2 in the 3d5 electronic state, thereby confirming the expected trivalent state of Fe ions in the Bi2S3 host structure. Results from the spin polarized density functional theory simulations, for the bulk Fe-doped Bi2S3 counterpart, corroborate the experimental fact that the volume of the unit cell decreases with Fe substitutionally doping at Bi1 and Bi2 sites. The Bader charge analysis indicated a pseudo valency charge of 1.322|e| on FeBi1 and 1.306|e| on FeBi2 ions, and a spin contribution for the magnetic moment of 5.0 µB per unit cell containing one Fe atom. Electronic band structures showed that the (indirect) band gap changes from 1.17 eV for Bi2S3 bulk to 0.71 eV (0.74 eV) for Bi2S3:FeBi1 (Bi2S3:FeBi2). These results are compatible with the 3d5 high-spin state of Fe3+, and are in agreement with the experimental results, within the density functional theory accuracy.

GENETIC DIVERSITY OF ADENOVIRUSES CIRCULATING AMONG THE MILITARY IN THE NORTH-WEST REGION.

The contribution of adenovirus (AV) infections to the overall structure of acute viral respiratory infections among young people of draft age can reach as high as 64.6%. Wide dissemination, the incidence of AV-associated pneumonias and lethal outcomes in the case of some complicated infections illustrate the urgency of studying the antigenic diversity of AVs circulating among the military. 991 nasopharyngeal swabs from patients hospitalized in military health facilities with symptoms of acute respiratory infections from 2014 to 2017 were detected by real-time PCR. Sanger sequencing was performed using forward and reverse primers matching the fiber gene. AVs were detected in 326 samples. In 80 of those, AVs were present in combination with other respiratory viruses, as follows: 26 with respiratory syncytial viruses (RSV), 49 with rhinoviruses, 2 with bocaviruses, 1 with RSV and rhinovirus, 1 with parainfluenza virus, and 1 with metapneumovirus. 31 samples were sequenced. Thirty AVs belonged to group E (serotype 4), and 1 AV belonged to group B (serotype 7).

FDG-PET/CT findings in systemic mastocytosis: a French multicentre study.

INTRODUCTION: Mastocytosis is a clonal haematological disease characterized by uncontrolled proliferation and the activation of mast cells. The value of FDG-PET/CT (FDG-PET) in mastocytosis has yet to be determined. METHODS: We retrospectively identified patients with an established diagnosis of systemic mastocytosis (SM), according to the WHO criteria, who underwent PET using the French Reference Centre for Mastocytosis database. Semi-quantitative and visual analysis of FDG-PET was performed and compared to the clinico-biological data. RESULTS: Our cohort included 19 adult patients, median age 65 years [range 58-74], including three with smouldering SM (SSM), three with aggressive SM (ASM), 10 with an associated clonal haematological non-mast-cell lineage disease (SM-AHNMD), and three with mast cell sarcoma (MCS). FDG-PET was performed at the time of the SM diagnosis (15/19), to evaluate lymph node (LN) activity (3/19) or the efficacy of therapy (1/19). FDG uptake was observed in the bone marrow (BM) (9/19, 47%), LN (6/19, 32%), spleen (12/19, 63%), or liver (1/19, 5%). No significant FDG uptake was observed in the SSM and ASM patients. A pathological FDG uptake was observed in the BM of 6/10 patients with SM-AHNMD, appearing as diffuse and homogeneous, and in the LN of 5/10 patients. All 3 MCS patients showed intense and multifocal BM pathological uptake, mimicking metastasis. No correlation was found between the FDG-PET findings and serum tryptase levels, BM mast cell infiltration percentage, and CD30 and CD2 expression by mast cells. CONCLUSIONS: FDG uptake does not appear to be a sensitive marker of mast cell activation or proliferation because no significant FDG uptake was observed in most common forms of mastocytosis (notably purely aggressive SM). However, pathological FDG uptake was observed in the SM-AHNMD and in MCS cases, suggesting a role of FDG-PET in their early identification and as a tool of therapeutic assessment in this subgroup of patients.

Dose matters! Optimisation of guideline adherence is associated with lower mortality in stable patients with chronic heart failure.

AIMS: Guidelines have been published for improving management of chronic heart failure (CHF). We examined the association between improved guideline adherence and risk for all-cause death in patients with stable systolic HF. METHODS: Data on ambulatory patients (2006-2010) with CHF and reduced ejection fraction (HF-REF) from the Austrian Heart Failure Registry (HIR Austria) were analysed. One-year clinical data and long-term follow-up data until all-cause death or data censoring were available for 1014 patients (age 65 [55-73], male 75%, NYHA class I 14%, NYHA II 56%, NYHA III/IV 30%). A guideline adherence indicator (GAI [0-100%]) was calculated for each patient at baseline and after 12 ± 3 months that considered indications and contraindications for ACE-I/ARB, beta blockers, and MRA. Patients were considered ΔGAI-positive if GAI improved to or remained at high levels (≥ 80%). ΔGAI50+ positivity was ascribed to patients achieving a dose of ≥ 50% of suggested target dose. RESULTS: Improvements in GAI and GAI50+ were associated with significant improvements in NYHA class and NT-proBNP (1728 [740-3636] to 970 [405-2348]) (p<0.001). Improvements in GAI50+, but not GAI, were independently predictive of lower mortality risk (HR 0.55 [95% CI 0.34-0.87; p=0.01]) after adjustment for a large variety of baseline parameters and hospitalisation for heart failure during follow-up. CONCLUSIONS: Improvement in guideline adherence with particular emphasis on dose escalation is associated with a decrease in long-term mortality in ambulatory HF-REF subjects surviving one year after registration.

Detection of asymptomatic aortic involvement in ANCA-associated vasculitis using FDG PET/CT.

Large vessel involvement in ANCA-associated vasculitis is very rare. We report here on the case of two patients with ANCA-associated vasculitis and asymptomatic aortic arch involvement diagnosed using FDG-PET/CT. Because aortic involvement in ANCA-associated vasculitis is a potentially life-threatening condition, its early detection can be crucial. FDG-PET/CT may also provide new insights into large vessel involvement as part of the spectrum of ANCA-associated vasculitis.

Low dose beta-blocker prevents ovariectomy-induced bone loss in rats without affecting heart functions.

Findings from animal studies have suggested that bone remodeling is under beta-adrenergic control. However, the level of adrenergic inhibition required to achieve the most favorable effects on the skeleton remains unknown. To address this question, we compared the effects of low (0.1 mg/Kg/day), medium (5 mg/Kg/day) or high (20 mg/Kg/day) doses of propranolol given 5 days per week for 10 weeks in ovariectomized (OVX) rats. Characteristics of bone microarchitecture, biomechanical properties and bone turnover were investigated, whilst heart functions were assessed by echocardiography and catheterization of the left ventricle. We first confirmed the expression of Adrbeta2R and the absence of Adrbeta1R on osteoblasts by PCR and confocal microscopy. We then showed that low dose propranolol prevented OVX induced bone loss by increasing bone formation (+30% of MAR vs. placebo, P = 0.01) and decreasing bone resorption (-52% of osteoclast surface on bone surface vs. placebo, P = 0.01). Consequently, rats receiving 0.1 mg/kg/day propranolol displayed higher stress (+27%), intrinsic energy (+28.7%) and Young's Modulus in compression versus placebo (all, P < 0.05). No significant effects on heart hemodynamic parameters were found in rats receiving this dose. In contrast, medium and high doses of propranolol had a negative effect on heart functions but no significant protective effects on bone mass in ovariectomized rats. These results, consistent with the dominant nature of the high bone mass phenotype and normal heart function of Adrbeta2R-deficient mice, suggest that low doses of beta-blockers may have a therapeutic utility in the treatment of osteoporosis with high selectivity for bone tissues.

Ophthalmic artery Doppler velocimetry in healthy pregnancy.

OBJECTIVES: To establish normative data for ophthalmic artery Doppler parameters throughout a healthy pregnancy, to investigate the possible correlation between these Doppler measurements and gestational age, and to test intraobserver variability. METHODS: A prospective cross-sectional study was performed to assess various Doppler parameters in 276 healthy women between 20 and 39 weeks of gestation. The following measurements were obtained: pulsatility and resistance indices (PI, RI), peak systolic velocity (PSV), peak diastolic velocity (PDV), end diastolic flow velocity (EDFV), and peak ratio (PR). Quantile regression was used to estimate reference values throughout pregnancy and P<0.05 was considered significant. The intraclass correlation coefficient (Intra-CC) was used to calculate intraobserver variability. RESULTS: The 5th and 95th prediction intervals for each gestational age are presented. No significant correlation was detected between Doppler indices and gestational age. Intra-CC was excellent (0.996). CONCLUSIONS: Reference values were generated for ophthalmic artery Doppler measurements, and they did not vary significantly during healthy pregnancy.

Heart rate variability in rats with chronic hypoxic pulmonary hypertension.

The precise role of pulmonary hypertension as a possible factor inducing a decrease in heart rate variability is poorly known. Spectral analysis of heart rate variability (HRV) was carried out in 21 Wistar rats before and after exposure to normoxia (N = 10) or to 3 weeks of hypobaric hypoxia inducing chronic pulmonary hypertension and right ventricular hypertrophy (N= 11). Continuous ECG was recorded in conscious animal at rest. Compared to the control group, rats exposed to hypoxia had a similar heart rate but a lower overall HRV (total power, 27.9 +/- 15.2 vs. 57.6 +/- 24.7 ms2, P < 0.01). Low frequency power (0.25-0.8 Hz) and high frequency power (0.8-3 Hz) were similar in both groups suggesting that HRV was decreased in the very low frequency power (0-0.25 Hz). The effects of atropine and propranolol on heart rate and HRV were similar in rats exposed or not to hypoxia. HRV is decreased in rats with hypoxic induced pulmonary hypertension, mainly in the very low frequency band, suggesting an increase in sympathetic activity. However, this decrease is moderate and the modulation of HRV with pharmacologic autonomic blockade remains similar to that of normal rats.

Mean xenograft survival of 14.6 days in a small group of hDAF-transgenic pig hearts transplanted orthotopically into baboons.

INTRODUCTION: In a discordant orthotopic xenotransplantation model (pig-to-baboon) donor pigs expressing human decay accelerating factor (hDAF) as a regulator of complement activity were used to prevent hyperacute xenograft rejection (HXR). We investigated a modified immunosuppressive therapy consisting of ERL080 (Novartis Pharma AG, Base, Switzerland), cyclosporin A (Neoral), steroids, and a cyclophosphamide (CyP) induction protocol with several reduced doses to prevent acute vascular rejection (AVR). METHODS: Donor hearts were harvested from hDAF-transgenic pigs (18.8 +/- 2.6 kg, Imutran Ltd., a Novartis Pharma AG Company). Four adult baboons (25.6 +/- 2.7 kg) with high titers of xenoreactive antibodies (XAb) served as recipients. Serological and hemodynamic parameters were measured. Finally, myocardial tissue was sampled for histological and immunohistochemical examinations. RESULTS: In the first baboon, an acute graft failure occurred after 1 hour due to preservation injury. The second succumbed after 11.1 day due to an acute renal failure. The third died after 13.1 days of an ileus. The fourth baboon had continuously excellent cardiac function (mean echocardiographic ejection fraction, 69.2%), but succumbed on day 20 due to anemia. Corrected mean xenograft survival (excluding the first baboon because of a technical failure) was 14.6 +/- 2.6 days. XAb decreased after day 3 to constantly low levels (<1:64 titer) after CyP induction. White blood cell count decreased from 10.3 +/- 0.8 to 0.9 +/- 0.3 G/L after day 3. Macroscopically and histologically no typical signs of HXR or severe AVR could be detected. CONCLUSIONS: These results confirm that hDAF transgen blocks HXR in this life-supporting model. AVR was prevented by using a modified quadruple immunosuppressive drug combination (Neoral, ERL080, steroids, and several small single doses of CyP). An optimum "fine-tuning" of immunosuppression is required to achieve the best risk-benefit ratio.

Combination of hDAF-transgenic pig hearts and immunoadsorption in heterotopic xenotransplantation of immunosuppressed baboons.

INTRODUCTION: Hyperacute xenograft rejection (HXR) and acute vascular rejection (AVR) after xenotransplantation are triggered by xenoreactive antibodies (XAb) and an activated complement cascade. In a heterotopic (abdominal) xenotransplantation model we combined immunoadsorption (IA, Ig-Therasorb column) and a quadruple immunosuppressive drug therapy in recipient baboons with donor pig hearts transgenic for human decay accelerating factor (hDAF). METHODS: According to XAb titers between 6 and 14 cycles of IA were performed preoperatively in 4 recipient baboons (18.6 +/- 2.5 kg). Hearts of hDAF-transgenic donor pigs (6.1 +/- 1.1 kg, Imutran Ltd., a Novartis Pharma AG Company, Basel, Switzerland) were heterotopically transplanted using the abdominal technique in baboons. Immunosuppression consisted of cyclophosphamide (CyP) induction therapy, ERL080 (Novartis Pharma AG), cyclosporin A (CyA, Neoral), and steroids. Blood levels of mycophenolate, CyA, immunoglobulins (Ig), anti-pig-antibodies, complement factors, and cardiac enzymes were determined. Abdominal electrocardiography (ECG), echocardiography, and palpation were used for monitoring of the pig hearts. Myocardial tissue specimens were examined using immunohistochemistry, light microscope (LM), and electron microscope (EM). RESULTS: Ten cycles of IA alone removed 78% of XAb and accordingly IgM, IgG, IgA, complement C3, and C4. None of the xenografts was hyperacutely rejected, but xenograft failure occurred after 5.0 +/- 1.3 days (range, 2.4-8.0 days) because of an AVR associated with a rapid XAb increase within 24 hours. White blood cell count (10.3 +/- 2.2 G/L) showed a maximum of 13.1 +/- 2.1 (day 1) and constant levels (1.4 +/- 0.3-2.1 +/- 1.3 G/L) between day 3 and 6. Histology (LM/EM) showed massive hemorrhage, necrosis, and vascular thrombi as signs of AVR. CONCLUSION: Although HXR was prevented by using IA and hDAF-transgenic donor hearts, AVR was not avoided due to insufficient immunosuppressive regimen used and a missed postoperative IA treatment as a result of an inefficient control of XAb production.

[Contribution of lymphoscintigraphy in the exploration of lymphedema in children]. / Intérêt de la lymphoscintigraphie dans l'exploration des lymphoedèmes de l'enfant.

OBJECTIVES: The objectives of this work were a) to assess the feasibility of lymphoscintigraphy in very young children, and b) to assess its usefulness in understanding the underlying pathophysiology. PATIENTS AND METHODS: Forty-one children (age range 3 months-16 years) with primary lymphedema of the lower and/or upper limbs underwent lymphosinctigraphy using 99mTC-labeled colloid (Nanocis or Nanocol) injected subcutaneous at the foot and/or hand level. Recording time, which depended on the child's age, included at least static images during the thirty minutes following injection and four hours later. RESULTS: Abnormal activity of the lymph collectors, nodes, and interstitial space were analyzed according to age (> or < 2 years). Abnormal findings were classed as simple hypoplasia (n=18) or other type of lymph disease: diffuse lymphatic dysplasia (n=6), mixed vascular dysmorphism (n=5), amniotic bride disease (n=1), and hypoplasia revealed by occurrence of a minor factor (n=11). These observations demonstrate the role of lymphoscintigraphy in the diagnosis and prognostic evaluation of lymphedema in children. CONCLUSION: Lymphoscintigraphy is a useful technique for very young children with lymphedema providing further information contributing to overall exploration.

The value of immunoscintigraphy in the detection of recurrent colorectal cancer.

The aim of this prospective study was to determine whether anti-carcinoembryonic antigen (anti-CEA) scintigraphy is a useful additional technique in the diagnosis recurrence of colorectal cancer. Forty patients with suspected recurrence of colorectal cancer, underwent immunoscintigraphy (IS) and helical computed tomography (CT) in the 2 weeks before surgery. Surgical findings were used to evaluate the performance of the imaging techniques. Suspected areas on IS and CT were systematically explored. Helical CT was found to be superior to IS for the liver, the sensitivity and specificity of CT being 100% and 90%, respectively, vs 53% and 100% for IS. However, IS was better than CT for the detection of extra-hepatic abdominal recurrence: sensitivity and specificity of IS were 100 and 82% respectively vs 33 and 82% for CT. Seven cases of peritoneal carcinomatosis were overlooked by helical CT. Our results indicate that IS improves detection of extra-hepatic abdominal recurrence of colorectal cancer. Immunoscintigraphy is valuable as a guide to the treatment strategy and operative procedures.

Technetium-99m ECD single photon emission computed tomography in brain trauma: comparison of early scintigraphic findings with long-term neuropsychological outcome.

OBJECTIVE: The aim of this study was to assess the prognostic value of early brain scintigraphy in head injury in relation to long-term neuropsychological behavior. Twenty-four patients underwent technetium-99m (Tc-99m) ethyl cysteinate dimer single photon emission computed tomography (SPECT) within 1 month of the trauma. Scintigraphic abnormalities were evaluated both visually and semiquantitatively using the brain-to-cerebellum ratio method. The clinical neuropsychological investigation was conducted to evaluate abnormalities related to motor deficit, frontal behavior, and memory and language disorders. All patients had abnormalities on SPECT scan. One year after trauma, 14 patients (58%) had neuropsychological sequelae. The brain-to-cerebellum ratios in the left basal ganglia and brain stem were significantly decreased in patients with memory disorders (P = .03 and P = .02, respectively). Moreover, SPECT visual analysis indicated that low uptake in the basal ganglia, thalamus, and brain stem was associated with subsequent motor deficit, frontal behavior, and language and memory disorders. The authors conclude that brain SPECT can be valuable in predicting the neuropsychological behavior of survivors of severe head injury.

Prevention of hyperacute xenograft rejection in orthotopic xenotransplantation of pig hearts into baboons using immunoadsorption of antibodies and complement factors.

To prevent hyperacute xenograft rejection (HXR) caused by preformed natural antibodies (XNAb) after orthotopic heart xenotransplantation (oXHTx) of landrace pig hearts into baboons, we used immunoadsorption of immunoglobulins IgG, IgM and IgA and complement with the reusable Ig-Therasorb column. In addition to functional data, tissue was sampled for histological, immunohistochemical and electron microscopical analysis. We performed three oXHTx of landrace pig hearts to baboons using extracorporeal circulation (ECC) connected to the immunoadsorption unit. Intraoperative treatment consisted of four cycles of immunoabsorption (IA). One oXHTx of a baboon without IA served as a control. A mismatch of donor and recipient heart size was prevented by selecting a 30-40% lower body weight of donor pigs than recipients. Four cycles of IA removed more than 80% of IgG, IgM and IgA, 86% of antipig antibodies and 66% of complement factors C3 and C4 from plasma. The graft of the control animal failed after 29 min. Orthotopic xenotransplantation with IA was selectively terminated after 100 min, 11 h and 21 h, respectively without any histological signs of HXR in light and electron microscopy. After weaning off from ECC these donor xenografts showed sufficient function with normal ECG and excellent cardiac output in echocardiography and invasive measurement (1.93 +/- 0.035 l/min). The myocardium of the control xenograft demonstrated more deposits of Ig and complement components (C3, C4) than in the IA group. Baboons survive HXR after orthotopic pig heart xenotransplantation due to antibody depletion by reusable Ig-Therasorb column treatment. Long-term survival in an orthotopic baboon xenotransplantation model after IA, especially in combination with transgenic pig organs, could be a reliable preclinical trial for future clinical xenotransplantation programs.

Localization of the ventricular preexcitation site in Wolff-Parkinson-White syndrome with Doppler tissue imaging.

PURPOSE: The objective of this study was to evaluate the ability of Doppler tissue imaging (DTI) to localize the ventricular emergence site of accessory atrioventricular pathways (Wolff-Parkinson-White syndrome). METHODS: Thirty-three patients were studied prospectively by Doppler tissue imaging (128XP and Sequoia 256 echocardiographic systems; Acuson, Mountain View, Calif) before investigation of Wolff-Parkinson-White syndrome and after radiofrequency ablation of the accessory pathways. The normal appearance of the ventricular contractions was defined in a group of 10 control subjects. The preexcitation zone was determined as a zone of maximum acceleration in "DTI acceleration mode" or as a coded contraction zone in "DTI velocity mode," at the time of the delta wave or before the onset of the QRS complex. RESULTS: The earliest ventricular activation site was correctly localized for 12 of the 15 left-sided pathways (8 anterior or anterolateral, 2 lateral or posterolateral, 2 inferior). When wall motion abnormalities were detected in the left ventricle by DTI, the left-sided localization was confirmed by electrophysiologic exploration. For the right-sided pathways, the localization was correct in only 4 of 11 cases (3 posteroseptal and 1 anterolateral). After effective ablation in all patients, the abnormalities corresponding to the electrophysiologic data disappeared totally in only 11 of 16 patients. CONCLUSION: In the presence of Wolff-Parkinson-White syndrome, DTI localizes contraction abnormalities associated with early activation of a part of the ventricle. However, the interpretation of the images remains difficult because the normal coding of the contraction of the ventricular walls depends on the incidence for which they are investigated. This noninvasive examination seems to be an effective tool for localizing the left-sided accessory pathways of the left ventricle, in particular in the anterior, anterolateral, or inferior walls.

Fourier phase analysis of SPECT equilibrium radionuclide angiography in symptomatic patients with mitral valve prolapse without significant mitral regurgitation: assessment of biventricular functional abnormalities suggesting a cardiomyopathy.

BACKGROUND: Ventricular premature beats are common in patients with mitral valve prolapse (MVP). The purpose of this study was to determine whether symptomatic patients with MVP had certain functional characteristics and if ventricular arrhythmia (VA) could be explained by functional extravalvular abnormalities. Single photon emission computed tomography equilibrium radionuclide angiography with Fourier phase analysis was preferred to the planar radionuclide method. Only patients without significant mitral regurgitation were studied. METHODS AND RESULTS: A total of 23 symptomatic patients with MVP (13 men, 10 women, mean age, 47+/-14 years) without mitral regurgitation underwent single photon emission computed tomography equilibrium radionuclide angiography. Symptoms were present in 20 patients, and VA was present in 14 patients. Ejection fraction, regional wall motion, and Fourier phase analysis were examined in both ventricles and compared with results for normal subjects. Ventricular abnormalities were observed in 20 (87%) patients: decreased left ventricular and right ventricular ejection fractions, increased standard deviations of the mean phase and focal wall motion, and/or delayed phase abnormalities. Abnormalities were less frequent but more marked in the right ventricular free wall, the infundibulum, or the septum compared with left ventricular delayed abnormalities, which were more frequent but limited. In 12 of 14 patients with VA, phase-delayed areas were observed in the ventricle where the origin of ventricular premature beats was suspected on the basis of their electrocardiographic morphologic features. A relation was found between late potentials and delayed-phase areas (right ventricle or septum) and left bundle branch block morphologic features of VA. CONCLUSIONS: Symptomatic patients with MVP frequently have ventricular dysfunction in 1 or both ventricles, sometimes limited but more marked in the presence of severe VA even without significant mitral regurgitation, suggesting structural modification. The use of a sensitive, accurate, and 3-dimensional method such as single photon emission computed tomography equilibrium radionuclide angiography may be of interest for a noninvasive investigation, especially in young symptomatic patients with MVP and VA.