Neuregulin-2 ablation results in dopamine dysregulation and severe behavioral phenotypes relevant to psychiatric disorders.

Numerous genetic and functional studies implicate variants of Neuregulin-1 (NRG1) and its neuronal receptor ErbB4 in schizophrenia and many of its endophenotypes. Although the neurophysiological and behavioral phenotypes of NRG1 mutant mice have been investigated extensively, practically nothing is known about the function of NRG2, the closest NRG1 homolog. We found that NRG2 expression in the adult rodent brain does not overlap with NRG1 and is more extensive than originally reported, including expression in the striatum and medial prefrontal cortex (mPFC), and therefore generated NRG2 knockout mice (KO) to study its function. NRG2 KOs have higher extracellular dopamine levels in the dorsal striatum but lower levels in the mPFC; a pattern with similarities to dopamine dysbalance in schizophrenia. Like ErbB4 KO mice, NRG2 KOs performed abnormally in a battery of behavioral tasks relevant to psychiatric disorders. NRG2 KOs exhibit hyperactivity in a novelty-induced open field, deficits in prepulse inhibition, hypersensitivity to amphetamine, antisocial behaviors, reduced anxiety-like behavior in the elevated plus maze and deficits in the T-maze alteration reward test-a task dependent on hippocampal and mPFC function. Acute administration of clozapine rapidly increased extracellular dopamine levels in the mPFC and improved alternation T-maze performance. Similar to mice treated chronically with N-methyl-d-aspartate receptor (NMDAR) antagonists, we demonstrate that NMDAR synaptic currents in NRG2 KOs are augmented at hippocampal glutamatergic synapses and are more sensitive to ifenprodil, indicating an increased contribution of GluN2B-containing NMDARs. Our findings reveal a novel role for NRG2 in the modulation of behaviors with relevance to psychiatric disorders.

Interobserver agreement in assigning IOTA color score to adnexal masses using three-dimensional volumes or digital videoclips: potential implications for training.

OBJECTIVE: To estimate the interobserver agreement between a trainer and trainees in assigning the International Ovarian Tumor Analysis (IOTA) color score to adnexal masses using three-dimensional (3D) volumes and videoclips. METHODS: Fifty-one digital videoclips and 3D volumes of a non-consecutive series of adnexal masses were used for this study. One trainer and four trainees evaluated first the 3D volume and 1 week later a videoclip from the same mass. They had to assign IOTA color scores according to their impression of the amount of color content in each case. Interobserver agreement between trainer and trainees was assessed using Cohen's weighted kappa index with 95% CIs and percentage of agreement. RESULTS: When using 3D volumes, interobserver agreement was good for three out of four pairs of comparisons and very good for one (kappa values of 0.70, 0.68, 0.81 and 0.71 for trainees A, B, C and D, respectively). When using videoclips, interobserver agreement was very good for two out of four pairs of comparisons and good for two (kappa values of 0.84, 0.80, 0.68 and 0.86 for Trainees A, B, C and D, respectively). CONCLUSION: Evaluation of IOTA color scores in adnexal masses using either videoclips or 3D volumes is reproducible even in the hands of trainees after a short training program.

Dose-escalated SBRT for borderline and locally advanced pancreatic cancer. Feasibility, safety and preliminary clinical results of a multicenter study.

Background: Pancreatic Stereotactic Body Radiotherapy (SBRT) allows for the administration of a higher biologically effective doses (BED), that would be essential to achieve durable tumor control. Escalating treatment doses need a very accurate tumor positioning and motion control during radiotherapy.The aim of this study to assess the feasibility and safety of a Simultaneous Integrated Boost (SIB) dose-escalated protocol at 45 Gy, 50 Gy and 55 Gy in 5 consecutive daily fractions, in Border Line Resectable Pancreatic Cancer (BRCP) /Locally Advanced Pancreatic Cancer (LAPC) by means of a standard LINAC platform. Methods: Patients diagnosed of BRPC/LAPC, candidates for neoadjuvant chemotherapy and SBRT, in four university hospitals of the province of Las Palmas (Canary Islands, Spain) were included in this prospective study. Radiotherapy was administered using standard technology (LINACS) with advanced positioning (Lipiodol® and metallic stent used as fiducial markers) and tumor motion control (4D, DBH, Calypso®). There were 3 planned dose-escalated SIB groups, 45 Gy/5f (9 patients) 50 Gy/5f (9 + 9 patients) and 55 Gy/5f (9 patients). The defined primary end points of the study were the safety and feasibility of the proposed treatment protocol. Secondary endpoints included radiological tumor response after SBRT, local control and survival. Results: From June 2017 to December 2022, sixty-two patients were initially assessed for eligibility in the study in the four participating centers, and 49 were candidates for chemotherapy (CHT). Forty-one were referred to radiotherapy after CHT and 33 finally were treated by escalated-dose SIB, 45 Gy (9 patients) 50 Gy (16 patients), 55 Gy(8 patients). All patients completed the scheduled treatment and no acute or late severe (≥grade3) gastrointestinal toxicity was observed.Local response was analyzed by CT/MRI two months after the end of SBRT. Ten patients (31,25 %) achieved objective response (2/9:45 Gy, 5/15:50 Gy, 3/8:55 Gy). Follow-up was closed as July 2023. Freedom from local progression at 1-2y were 89,3% (95 %CI:83,4-95,2%) and 66 % (95 %CI:54,6-77,4%) respectively. The 1-2y survival rates were 95,7% (95 %CI:91,4-100 % and 48,6% (95 %CI:37,7-59,5%) respectively. Conclusion: These promising results should be confirmed by further studies with larger sample size and extended follow-up period.

Stereoscopic particle image velocimetry measurements of the three-dimensional flow field of a descending autorotating mahogany seed (Swietenia macrophylla).

An experimental investigation of near field aerodynamics of wind dispersed rotary seeds has been performed using stereoscopic digital particle image velocimetry (DPIV). The detailed three-dimensional flow structure of the leading-edge vortex (LEV) of autorotating mahogany seeds (Swietenia macrophylla) in a low-speed vertical wind tunnel is revealed for the first time. The results confirm that the presence of strong spanwise flow and strain produced by centrifugal forces through a spiral vortex are responsible for the attachment and stability of the LEV, with its core forming a cone pattern with a gradual increase in vortex size. The LEV appears at 25% of the wingspan, increases in size and strength outboard along the wing, and reaches its maximum stability and spanwise velocity at 75% of the wingspan. At a region between 90 and 100% of the wingspan, the strength and stability of the vortex core decreases and the LEV re-orientation/inflection with the tip vortex takes place. In this study, the instantaneous flow structure and the instantaneous velocity and vorticity fields measured in planes parallel to the free stream direction are presented as contour plots using an inertial and a non-inertial frame of reference. Results for the mean aerodynamic thrust coefficients as a function of the Reynolds number are presented to supplement the DPIV data.

[Rolandic epilepsy clinical variants and their influence on the prognosis]. / Variantes clínicas de epilepsia rolándica y su implicación en el pronóstico.

INTRODUCTION: Benign epilepsy with central-temporal spikes (BECTS) is the most common epileptic syndrome in childhood. It is an age-dependent, genetically determined and benign condition. The aim of this study is to describe the clinical course and prognosis in 60 patients with BECTS diagnosed in our hospital. PATIENTS AND METHODS: We made a retrospective review of patients diagnosed with BECTS in a University Hospital (1995-2009). They were divided into 2 groups: 1) Patients who met all BECTS classical criteria. 2) Patients who met all the criteria but one (less than 4 years; diurnal seizures; atypical EEG abnormalities). RESULTS: A total of 60 patients, 34 males and 26 females were included, with 31 patients in group 1 and 29 in group 2. The mean age at onset in group 1: 7.45 years, group 2: 6.55 years. Medical treatment was indicated in 32.2% of patients in group 1 and 41.3% in group 2. The outcome was favourable in the majority: 58% in group 1 and 62.1% in group 2 were free of seizures after 1 year. Average age in which it disappeared: 8.54 years in group 1 and 7.84 years in group 2. There were no statistically significant differences in any of these parameters. CONCLUSIONS: Unlike that published by some authors, we have not identified any poor outcome factors in patients with BECTS in this study, meaning that an accurate diagnosis correlates with a good prognosis and excellent neurological outcome.

Effectiveness of trivalent seasonal and monovalent influenza A(H1N1)2009 vaccines in population with major chronic conditions of Navarre, Spain: 2010/11 mid-season analysis.

We defined a cohort of people with major chronic conditions (152,585 subjects) in Navarre, Spain, using electronic records from physicians, to obtain 2010/11 mid-season estimates of influenza vaccine effectiveness. The adjusted estimates of the effectiveness of the 2010/11 trivalent influenza vaccine were 31% (95% confidence interval (CI): 20­40%) in preventing medically attended influenza-like illness, and 58% (95% CI: 11­80%) in preventing laboratory-confirmed influenza. Having received the monovalent influenza A(H1N1)2009 vaccine in the 2009/10 season had an independent preventive effect against medically attended influenza-like illness (17%, 95% CI: 1­30%), and having received both vaccines had 68% (95% CI: 23­87%) effectiveness in preventing laboratory-confirmed influenza.

Asymmetric hysteresis loop in magnetostatic-biased multilayer nanowires.

The hysteresis of multilayer nanowires composed by a soft magnetic cylindrical wire, a non-magnetic spacer layer and an external hard magnetic shell is investigated. The external magnetic shell originates a non-homogeneous magnetic field on the inner wire, which is responsible for a displacement and a change of the width of the hysteresis curve of the wire. Moreover, different reversal modes occur at each branch of the hysteresis loop, which can be understood by analyzing the interaction magnetostatic field along the wire. Our results open the possibility of controlling two parameters of the hysteresis loop, the coercivity and the bias, providing an interesting system to be investigated.

[Proximal carpectomy versus four-cornered arthrodesis in patients with lesions SLAC and SNAC]. / Carpectomía de fila proximal versus artrodesis de cuatro esquinas en pacientes con lesiones de SLAC y SNAC.

Advanced scafosemilunar collapse (SLAC) and advanced scaphoid pseudoarthrosis (SNAC) collapse are the result of trauma causing scaphoid fracture and the consequent pseudoarthrosis resulting in abnormal kinematics of the wrist and a scapholunate ligament injury, respectively. Current surgical options for SLAC/SNAC treatment include partial arthrodesis, carpal proximal row resection. MATERIAL AND METHODS: Retrospective, cross-cutting and descriptive study was carried out in the period from January 2010 to December 2015. 52 patients operated on with 4-cornered arthrodesis and 19 patients with carpectomy were studied. RESULTS: 71 patients, 62 male patients and 9 female patients were analysed. For the carpectomy procedure were 5 female patients, for patients with four-corner arthrodesis 48 male patient and 4 female patient were included. 48 patients with SNAC and 23 patients with SLAC were identified. 19 carpectomies and 52 arthrodesis of four corners of the total patients 65 of them were carried without any complications, 3 patients with delay of consolidation two with residual pain, and one with superficial infectious process. DISCUSSION: The four-corner arthrodesis technique involves longer surgery and costs in relation to carpectomy, however arthrodesis has a faster return to pain-improvement work with respect to carpectomy; the final decision will depend on the case, the patients activity.

Las lesiones por el colapso escafosemilunar avanzado y el colapso avanzado por seudoartrosis del escafoides son consecuencia de un traumatismo que origina la fractura de escafoides y la consecuente seudoartrosis, resultando en una cinemática anormal de la muñeca y en una lesión de ligamento escafosemilunar, respectivamente. Las opciones quirúrgicas actuales para el tratamiento incluyen artrodesis parcial y carpectomía de la línea proximal del carpo. Material y métodos: Estudio retrospectivo, transversal y descriptivo en el período comprendido de Enero de 2010 a Diciembre de 2015. Se estudiaron 52 pacientes operados con artrodesis de cuatro esquinas y 19 pacientes manejados con carpectomía. Resultados: Del total de 71 pacientes, 62 fueron masculinos y nueve femeninos. Para el procedimiento de carpectomías, fueron 14 varones y cinco mujeres, para los pacientes con artrodesis de cuatro esquinas se incluyeron 48 masculinos y cuatro femeninos. Se identificaron 48 pacientes con colapso avanzado por seudoartrosis del escafoides y 23 pacientes con colapso escafosemilunar avanzado. Se realizaron 19 carpectomías y 52 artrodesis de cuatro esquinas del total de pacientes, 65 de ellos cursaron sin ninguna complicación, tres pacientes con retardo de la consolidación, dos con dolor residual, y uno con proceso infeccioso superficial. Discusión: La técnica de artrodesis de cuatro esquinas implica mayor tiempo de cirugía y de costos en relación con la carpectomía; sin embargo, la artrodesis tiene una reincorporación más rápida al trabajo con mejoría del dolor con respecto a la carpectomía; la decisión final en nuestra institución dependerá del caso y de la actividad del paciente.

Long-term prognosis of childhood absence epilepsy. / Epilepsia ausencia infantil. Pronóstico a largo plazo.

INTRODUCTION: Childhood absence epilepsy (CAE) is considered easily manageable with medication provided that a strict patient classification system is employed. It accounts for 10% of all childhood epilepsy cases starting before the age of 15 and it is most frequent in school-aged girls. The aim of this study is to analyse long-term outcomes of patients diagnosed with CAE according to the Loiseau and Panayiotopoulos criteria and treated during childhood. METHODS: We conducted a retrospective study including 69 patients with CAE who are currently older than 11; data were gathered from medical histories, EEG records, and telephone questionnaires. RESULTS: 52 patients met the Loiseau and Panayiotopoulos criteria. Mean age is now 17.16 years. Female-to-male ratio was 1.65:1; mean age at onset was 6 years and 2 months; mean duration of treatment was 3 years and 9 months. A family history of epilepsy was present in 30.8% of the patients and 7.7% had a personal history of febrile convulsions. Absence seizures were simple in 73.5% of the patients and complex in 26.5%. Response rates to first-line treatment were as follows: valproic acid, 46.3%; and valproic acid plus ethosuximide, 90.9%. The rate of response to second-line therapy (ethosuximide or lamotrigine) was 84.2%; 4% of the patients experienced further seizures after treatment discontinuation, 78.8% achieved seizure remission, and 25% needed psychological and academic support. CONCLUSIONS: Our data show that epileptic patients should be classified according to strict diagnostic criteria since patients with true CAE have an excellent prognosis. The relapse rate was very low in our sample. Despite the favourable prognosis, psychological and academic support is usually necessary.

[Transition from child to adult epilepsy. Difficulties with an objective that cannot be delayed]. / Transicion de la epilepsia del niño al adulto. Dificultades en un objetivo no demorable.

Paediatric care of a chronic process is limited by the moment when the clinical and therapeutic follow-up must be continued by a specialist from the area for adults. The delay in the transition from paediatrics to adult medicine can be due to causes attributable to the patient or his/her relatives, or the professional who diagnosed the disease. The former arises from the uncertainty of facing the unknown, which becomes more intense when the diagnosis and treatment have been difficult, as there is a fear of upsetting the stability of the patient. The latter concerns the paediatric specialist, who created ties of dependence with the patient due to the difficulties involved in the process, and perhaps even owing to a wish to avoid playing a less important role in it. Delaying the transition gives rise to problems that are detrimental for the child, because after adolescence there will still be a harmful dependence on the family and the paediatrician, which will delay the necessary knowledge of their own illness and of the limitations that can condition them. As a result this can prevent them from developing mechanisms for coming to terms with the reality of their own life situation. Later on, when it comes to taking the necessary step into adult medicine, immaturity appears, which increases the difficulties due to a lack of knowledge of both the disease and the tell-tale signs of alarm, revealing insecurity in the different situations that arise. The problem can be solved by a slow progressive change which must be coordinated in mixed outpatient departments with the presence of specialists for both paediatric and adult patients. This publication offers an analysis of this problem and a review of the solutions recommended to implement them in the best possible way.

TITLE: Transicion de la epilepsia del niño al adulto. Dificultades en un objetivo no demorable.La atencion pediatrica de un proceso cronico se ve limitada por el momento a partir del cual el seguimiento clinico y terapeutico debe continuarlo el especialista del area con dedicacion al adulto. El retraso de la transicion de la pediatria a la medicina del adulto puede originarse por causas familiares o del paciente, o bien por el profesional que diagnostico la enfermedad. La primera emana de la incertidumbre ante lo desconocido, mas intensa cuanto mayor ha sido la dificultad diagnostica y terapeutica, al temer que el paciente se desestabilice. La segunda atañe al especialista pediatrico, que creo lazos de dependencia con el paciente por las dificultades del proceso, e incluso por el deseo de no perder protagonismo en el mismo. Demorar la transicion genera problemas perjudiciales para el niño, pues superada la adolescencia mantendra una nociva dependencia familiar y del pediatra, retrasando el necesario conocimiento de la propia enfermedad y de las limitaciones que pueden condicionarle, e impidiendole desarrollar mecanismos para enfrentarse a su realidad vital. Mas adelante, cuando llega el necesario paso a la medicina del adulto, aflora la inmadurez, que incrementa las dificultades por desconocer tanto la enfermedad como los signos de alarma, revelando inseguridad en las situaciones que vayan apareciendo. El problema se soluciona con un cambio lento y progresivo, que debe coordinarse en consultas mixtas atendidas por especialistas pediatricos y de adultos. En esta publicacion se analiza esta problematica y se revisan las soluciones aconsejadas para su mejor desarrollo.

Pesticide residues in propolis from Spain and Chile. An approach using near infrared spectroscopy.

This study analyses the presence of pesticides in 106 samples of raw propolis from Spain and Chile. The components detected and quantified using gas chromatography mass spectrometry were as follows: triamidefon present in 70.1% of the samples with concentrations between 0.35 and 42.17mg/kg, and dicofol detected in 7.5% of the samples with concentrations between 0.39 and 2.83mg/kg. Diclorofluanid, procymidone, folpet, propham and metazachlor were also detected but only in a small number of samples. Near infrared spectroscopy with a remote reflectance fibre-optic probe was used to detect samples contaminated with triadimefon via partial least squares discriminant, with a R2 value of 0.71. In addition, the presence of the pesticide triadimefon in propolis was quantified using the modified partial least squares (MPLS) regression method. The calibration results showed a coefficient of determination (R2) of 0.81, a root mean square error (RMSE) of 0.36, and a ratio of performance to deviation (RPD) of 2.5.

5-HT3A -driven green fluorescent protein delineates gustatory fibers innervating sour-responsive taste cells: A labeled line for sour taste?

Taste buds contain multiple cell types with each type expressing receptors and transduction components for a subset of taste qualities. The sour sensing cells, Type III cells, release serotonin (5-HT) in response to the presence of sour (acidic) tastants and this released 5-HT activates 5-HT3 receptors on the gustatory nerves. We show here, using 5-HT3A GFP mice, that 5-HT3 -expressing nerve fibers preferentially contact and receive synaptic contact from Type III taste cells. Further, these 5-HT3 -expressing nerve fibers terminate in a restricted central-lateral portion of the nucleus of the solitary tract (nTS)-the same area that shows increased c-Fos expression upon presentation of a sour tastant (30 mM citric acid). This acid stimulation also evokes c-Fos in the laterally adjacent mediodorsal spinal trigeminal nucleus (DMSp5), but this trigeminal activation is not associated with the presence of 5-HT3 -expressing nerve fibers as it is in the nTS. Rather, the neuronal activation in the trigeminal complex likely is attributable to direct depolarization of acid-sensitive trigeminal nerve fibers, for example, polymodal nociceptors, rather than through taste buds. Taken together, these findings suggest that transmission of sour taste information involves communication between Type III taste cells and 5-HT3 -expressing afferent nerve fibers that project to a restricted portion of the nTS consistent with a crude mapping of taste quality information in the primary gustatory nucleus.

[An unusual cause of failure of weaning from mechanical ventilation in an infant]. / Una causa inusual de fracaso del destete de la ventilación mecánica en un lactante.

The weaning process is a critical phase in patients undergoing mechanical ventilation. This process can be hampered by numerous causes, such as neuromuscular diseases and spinal muscular atrophy (SMA). We present a 6-month-old boy with respiratory distress, fever, marked hypotonia without motor developmental milestones, and areflexia. The patient showed progressive respiratory distress requiring mechanical ventilation. Definitive weaning was not achieved and the boy died from respiratory failure. Partial autopsy was performed with a diagnosis of SMA and genetic study of the parents. Neuromuscular diseases are an infrequent cause of respiratory insufficiency in suckling infants. The differential diagnosis is made between axonal and motor neuron diseases. The diagnosis was confirmed by muscular biopsy and genetic study.

Molecular analysis of complex cases of alpha- and beta-thalassemia in Mexican mestizo patients with microcytosis and hypochromia reveals two novel alpha(0) -thalassemia deletions - -(Mex1) and - -(Mex2).

INTRODUCTION: Alpha-thalassemia (α-thal) is a common monogenic disorder worldwide. In mixed ethnic populations, α-thal and beta-thalassemia (ß-thal) can be expected, sometimes giving complex phenotypes, which without molecular analysis are not easily explained. We performed the molecular identification of α- and ß-thal alleles in 51 Mexican patients with microcytosis, hypochromia, and normal or low levels of HbA2 . METHODS: Common deletional alleles (-α(3.7) , -α(4.2) , - -(SEA) , - -(MED) , - -(FIL) , - -(THAI) , -α(20.5) ) and α-triplication were studied by gap-PCR and nondeletional alleles (α(IVSI) ((-5nt)) , α2 (NcoI) , α1 (NcoI) ) by ARMS. ß-thal alleles Cd39 (C>T), IVS1:1 (G>A), IVS1:110 (G>A), and Spanish δß-thal were also investigated. DNA sequencing was performed on HBA2, HBA1, and HBB genes. Negative samples were subjected to MLPA. RESULTS: In 35 subjects, we identified the mutations, -α(3.7) , - -(SEA) , - -(FIL) , α(IVSI) ((-5nt)) , and ααα(anti3.7) and two novel deletion alleles - -(Mex1) (6.8-8.9 kb) and - -(Mex2) (77.6-135.7 kb). Four individuals also had a ß-thal allele (Cd39/IVS1:110). No α-thal alleles were observed in 16 subjects, but three had a ß-thal mutation Cd39, IVS1:110, and Spanish δß-thal. CONCLUSION: α-thal is relatively common in Mexican patients, the combination with ß-thal is sometimes unexpected, and this underlines the importance of performing molecular analysis for both α- and ß-genes defects in patients showing microcytic hypochromic anemia.

Blue- and green-absorbing visual pigments of Drosophila: ectopic expression and physiological characterization of the R8 photoreceptor cell-specific Rh5 and Rh6 rhodopsins.

Color discrimination requires the input of different photoreceptor cells that are sensitive to different wavelengths of light. The Drosophila visual system contains multiple classes of photoreceptor cells that differ in anatomical location, synaptic connections, and spectral sensitivity. The Rh5 and Rh6 opsins are expressed in nonoverlapping sets of R8 cells and are the only Drosophila visual pigments that remain uncharacterized. In this study, we ectopically expressed Rh5 and Rh6 in the major class of photoreceptor cells (R1-R6) and show them to be biologically active in their new environment. The expression of either Rh5 or Rh6 in "blind" ninaE(17) mutant flies, which lack the gene encoding the visual pigment of the R1-R6 cells, fully rescues the light response. Electrophysiological analysis showed that the maximal spectral sensitivity of the R1-R6 cells is shifted to 437 or 508 nm when Rh5 or Rh6, respectively, is expressed in these cells. These spectral sensitivities are in excellent agreement with intracellular recordings of the R8p and R8y cells measured in Calliphora and Musca. Spectrophotometric analyses of Rh5 and Rh6 in vivo by microspectrophotometry, and of detergent-extracted pigments in vitro, showed that Rh5 is reversibly photoconverted to a stable metarhodopsin (lambda(max) = 494 nm), whereas Rh6 appears to be photoconverted to a metarhodopsin (lambda(max) = 468 nm) that is less thermally stable. Phylogenetically, Rh5 belongs to a group of short-wavelength-absorbing invertebrate visual pigments, whereas Rh6 is related to a group of long-wavelength-absorbing pigments and is the first member of this class to be functionally characterized.

T-kininogen can either induce or inhibit proliferation in Balb/c 3T3 fibroblasts, depending on the route of administration.

T-kininogen (T-KG) is a precursor of T-kinin, the most abundant kinin in rat serum, and also acts as a strong and specific cysteine proteinase inhibitor. Its expression is strongly induced during aging in rats, and expression of T-KG in Balb/c 3T3 fibroblasts results in inhibition of cell proliferation. However, T-KG is a serum protein produced primarily in the liver, and thus, most cells are only exposed to the protein from the outside. To test the effect of T-KG on fibroblasts exposed to exogenous T-KG, we purified the protein from the serum of K-kininogen-deficient Katholiek rats. In contrast to the results obtained by transfection, exposure of Balb/c 3T3 fibroblasts to exogenously added T-KG leads to a dose-dependent increase in [3H]-thymidine incorporation. This response does not require kinin receptors, but it is clearly mediated by activation of the ERK pathway. As a control, we repeated the transfection experiments, using a different promoter. The results are consistent with our published data showing that, under these circumstances, T-KG inhibits cell proliferation. We conclude that T-KG exerts opposite effects on fibroblast proliferation, depending exclusively on the way that it is administered to the cells (transfection versus exogenous addition).

Exercise electrocardiographic variables: a critical appraisal.

To compare four recently proposed methods of analyzing the exercise electrocardiogram with the conventional analysis of ST segment depression, 303 consecutive patients without myocardial infarction who had been referred for coronary arteriography underwent stress electrocardiography and stress thallium imaging. The specificity for the prediction of a greater than 50% coronary obstruction of 0.5, 1.0, 1.5 and 2.0 mm ST segment depression measured in the conventional way was 0.59, 0.73, 0.88 and 0.94, respectively. The specificity of a thallium perfusion defect was 0.79. Sensitivities of the conventional ST depressions, thallium defect, the change in the sum of the R amplitudes and the slope adjusted for heart rate increase were calculated and compared at the cited levels of specificity. R wave changes had a significantly lower sensitivity than did the conventionally analyzed ST depression at each level of specificity. Slope-adjusted ST depression had a slightly higher sensitivity than that of conventional ST depression only at a specificity of 0.73 (0.68 versus 0.65, p = 0.07). R wave-adjusted ST depression was significantly more sensitive than conventional ST depression only at a specificity of 0.94 (0.45 versus 0.36, p = 0.01). Heart rate-adjusted ST depression was more sensitive than conventional ST depression at all of the specificities except 0.59. This pattern of superior accuracy of heart rate-adjusted ST depressions was preserved for the prediction of multivessel coronary disease. Heart rate adjustment is a simpler and more accurate modification of the conventional electrocardiographic analysis than are the other three methods studied.

Computer-assisted versus unassisted analysis of the exercise electrocardiogram in patients without myocardial infarction.

Computer-assisted interpretation of the exercise electrocardiogram has been advocated to improve the accuracy of diagnosing coronary artery disease. Its accuracy was compared with a blinded visual interpretation of exercise-induced ST depression in 271 consecutive subjects without prior myocardial infarction who were referred for coronary angiography. The sensitivity of the visual and computer readings was 0.51 and 0.51, respectively, at a specificity of 0.87. Receiver operating characteristic curves were generated for the visual and computer ST depression in lead V5. Analysis of the areas under these curves showed no significant difference between them, indicating that computer-assisted analysis was not superior to unmodified visual analysis. A similar analysis was applied to two other computer indexes reported to be superior to visual assessments (treadmill exercise score and ST index). These computer indexes were not superior to a conventional visual analysis of leads I, II, V2, V4 and V5 in predicting severe disease (greater than 50% luminal narrowing). These results suggest that computer-assisted interpretation does not improve the accuracy of exercise electrocardiography in diagnosing coronary artery disease in subjects without prior myocardial infarction.