Ablación exitosa con radiofrecuencia a través de la cúspide coronariana derecha de un complejo ventricular prematuro parahisiano / Successful radiofrequency ablation through the right coronary cups of a parahisian premature ventricular complexes

Resumen Los complejos ventriculares prematuros (CVP) son hallazgos frecuentes en individuos con o sin enfermedad estructural cardiaca. Los CVP cuyo origen se localiza en la región parahisiana son poco frecuentes y su manejo a través de ablación con catéter de radiofrecuencia es un reto, pues su localización favorece un alto riesgo de desarrollo de bloqueo aurículo-ventricular. Se describen dos casos de pacientes con CVP parahisianos llevados a ablación con catéter de radiofrecuencia.

Abstract Premature ventricular complexes (PVC) are common findings in patients with or without structural heart disease. Parahisian PVC are uncommon and their management through radiofrequency catheter ablation remains a challenge, since their location favors a high risk for developing atrioventricular block. Two cases of patients with parahisian PVC undergoing radiofrequency catheter ablation are described.

Implante de un electrodo de estimulación ventricular izquierdo mediante doble canulación del seno coronario, técnica de snare y acceso retrógrado de la vena posterolateral / Implant of a left ventricular pacing electrode by double cannulation of the coronary sinus, snare technique and retrograde access of the posterolateral vein

Resumen El implante percutáneo de un electrodo de estimulación ventricular izquierdo a través del seno coronario para resincronización cardiaca siempre ha implicado un reto y más aún en pacientes con anatomía venosa coronaria compleja. Este caso demuestra cómo una técnica de doble canulación del seno coronario con uso de catéter multi-snare permite la colocación exitosa de un electrodo de estimulación ventricular izquierdo mediante acceso retrógrado a una vena posterolateral estenótica.

Abstract The percutaneous implantation of a left ventricular pacing electrode through the coronary sinus for cardiac resynchronization has always been a challenge, especially in patients with a complex coronary venous anatomy. This case shows how double cannulation of the coronary sinus using a multisnare catheter allows a left ventricular pacing electrode to be placed through retrograde access to a stenotic posterolateral vein, with a good clinical outcome.

Quality of attachment, trauma, psychopathology, and frequency of non-suicidal self-injury in Mexican adolescents suffering from psychosocial vulnerability: Description of a risk profile / Calidad del vínculo, trauma, psicopatología y frecuencia de autolesiones no suicidas en adolescentes Mexicanos que padecen vulnerabilidad psicosocial: Descripción de un perfil de riesgo

Abstract Introduction Suffering from psychosocial vulnerability, particularly during adolescence, increases the likelihood of experiencing adverse life circumstances, psychiatric conditions, and non-suicidal self-injury (NSSI). Objective We studied: 1. record-based demographic and clinical characteristics, as well as the frequency of NSSI in adolescents, beneficiaries of services for vulnerable population of one of six Non-Governmental Organizations (NGO's), we compared by beneficiary type: internal (IB) versus external (EB); 2. predictive relationship of NSSI with depression, difficulties in emotion regulation (DER) and suicidal ideation (administered measures); 3. Comparison of average scores on measures by: quality of attachment (QOA) and presence/absence of NSSI. Method A convenience sample of 255 adolescents (45.5% women, ages 11-15) answered instruments in institutional facilities (Mexico City and Puebla), where 181 (71%) resided as IB and 74 (29%) resided in family home (EB). The mental health staff of each NGO specified according to the record: demographics, psychiatric diagnoses, history of trauma, and QOA between the minor and his attachment figure. Results 42% denied NSSI episodes, 16.9% indicated a non-significant pattern, and 35.6% reported a significant and recent pattern. IB presented higher scores in all measurements, higher report of interpersonal trauma, depressive, anxiety, and behavior disorders. Minors with positive QOA obtained significantly lower scores. Discussion and conclusion Compared to EB's, adolescents residing in NGOs have a higher risk profile, particularly those without a positive QOA, a fact that is associated with a greater presence of psychopathology and significant and recent NSSI.

Resumen Introducción Padecer vulnerabilidad psicosocial, particularmente durante la adolescencia, incrementa la probabilidad de experimentar circunstancias vitales adversas, afecciones psiquiátricas y autolesiones no suicidas (ALNS). Objetivo Se estudiaron: 1. características demográficas y clínicas con base en expediente, así como la frecuencia de ALNS en adolescentes, usuarios de servicios para población vulnerable de una de seis Organizaciones No Gubernamentales (ONG's), se comparó por tipo de beneficiario: interno (BI) versus externo (BE); 2. relación predictiva de ALNS con depresión, dificultades en la regulación emocional (DRE) e ideación suicida (medidas administradas); 3. comparación de puntajes promedio de las mediciones por: calidad del vínculo (CV) y presencia/ausencia de ALNS. Método Una muestra de conveniencia de 255 adolescentes (45.5% mujeres, edades 11-15), contestaron instrumentos en instalaciones institucionales (Ciudad de México y Puebla), donde 181 (71%) residían como BI y 74 (29%) residían en casa de familiar (BE). El personal de salud mental de cada ONG especificó conforme a expediente: demografía, diagnósticos psiquiátricos, historial de trauma y CV entre el menor y su figura de apego. Resultados 42% negó episodios de ALNS, 16.9% indicó una pauta no significativa y 35.6% reportó un pauta significativa y reciente. Los BI presentaron puntuaciones superiores en todas las mediciones, mayor reporte de trauma interpersonal, trastornos depresivos, de ansiedad y conducta. Los menores con CV positiva obtuvieron puntuaciones significativamente menores. Discusión y conclusión En comparación con los BE, los adolescentes que residen en las ONG's presentan un perfil de mayor riesgo, particularmente, aquellos sin una CV positiva, hecho que se asocia con mayor presencia de psicopatología y ALNS reciente y significativa.

Características clínicas y sociodemográficas de y sociodemográficas de pacientes fallecidos por pacientes fallecidos por COVID-19 en Colombia / Clinical and sociodemographic characteristics of patients who died from COVID-19 in Colombia

Introducción: desde el 6 de marzo 2020 se confirmó el primer contagiado de la enfermedad coronavirus 2019 (COVID-19) en Colombia, se extendió por todo su territorio con un compromiso clínico variable. Es de vital importancia conocer las Características de los pacientes afectados letalmente. Objetivos: describir las características clínicas y sociodemográficas de pacientes fallecidos por COVID-19 en Colombia hasta el 15 de mayo 2020. Materiales y métodos: estudio de corte transversal. Se tomaron datos de los pacientes fallecidos por COVID-19 en todo el territorio colombiano, registradas en las bases de datos reportadas por el Instituto Nacional de Salud desde el 6 de marzo a 15 de mayo 2020. Resultados: hasta el 15 de mayo 2020 se reportaron un total de 546 muertes, 60.8% de los fallecidos eran hombres. La edad mediana fue 69 años (RIC: 59-79) siendo 73.3% pacientes con 60 años o más, 86.8% tenían factores de riesgo conocidos, los más comunes fueron hipertensión arterial (37.9%), diabetes mellitus (18.7%), enfermedad pulmonar obstructiva crónica (17.3%) y antecedente de cardiopatía (15.2%), 3.3% eran casos provenientes del extranjero. Las principales zonas afectadas a nivel nacional fueron Bogotá (29.8%), Cali (12.2%), Cartagena (11.1%) y Leticia (6.2%). Conclusiones: la letalidad en Colombia por COVID-19 es de 3.8%. La mayoría de los pacientes tuvo una condición clínica asociada siendo la hipertensión arterial la más frecuente, pero enfermedad pulmonar obstructiva crónica e hipotiroidismo son relevantes en nuestra población.

Introduction: the first case of Coronavirus disease 2019 (COVID-19) was confirmed in Colombia on March 6 2020, and spread through the country with diverse clinical presentations. It is critical to identify the characteristics of individuals with fatal outcomes. Objectives: to describe the clinical and sociodemographic characteristics of patients who died from COVID-19 in Colombia up to May 15 2020. Material and Methods: a cross-sectional study. Data on patients who died from COVID-19 in Colombia recorded and reported by the National Health Institute from March 6 to May 15 2020 were used. Results: a total of 546 deaths were reported as of May 15 2020, of which 60.8% were males. The median age was 69 years (IQR: 59-79), 73.3% were patients aged 60 years or older and 86.8% had underlying risk factors, the most common being hypertension (37.9%), diabetes mellitus (18.7%), chronic obstructive pulmonary disease (17.3%) and a past history of heart disease (15.2%), 3.3% were cases that had arrived from abroad. Nationally, the most affected areas were Bogotá (29.8%), Cali (12.2%), Cartagena (11.1%) and Leticia (6.2%). Conclusions: the COVID-19 mortality rate in Colombia is 3.8%. Most patients had an associated clinical condition being hypertension the most frequent one, but chronic obstructive pulmonary disease and hypothyroidism are relevant in our population.

Herramientas de sistemas inteligentes en el diagnóstico de los síndromes coronarios agudos: una revisión sistemática / Intelligent systems tools in the diagnosis of acute coronary syndromes: A systemic review

Resumen Antecedentes: El infarto agudo de miocardio representa la primera causa de muerte no trasmisible a nivel mundial. Su diagnóstico es una tarea altamente compleja que se ha intentado modelar mediante métodos automáticos. Se expone una revisión sistemática de estudios de pruebas diagnósticas de los síndromes coronarios agudos mediante sistemas inteligentes. Métodos: Revisión sistemática de la literatura a partir de Medline, Embase, Scopus, IEEE/IET Electronic Library, ISI Web Of Science, Latindex y LILACS de la evaluación diagnóstica de los síndromes coronarios agudos mediante sistemas inteligentes. Fue realizada por 2 revisores de manera independiente y las discrepancias se resolvieron por una tercera persona. Se extrajeron las características operativas de cada herramienta. Resultados: En total, 35 artículos cumplieron los criterios de inclusión. En 22 (62.8%) se utilizaron redes neuronales. Cinco comparan varias herramientas de sistemas inteligentes. En 13 se abarcaba todos los síndromes coronarios agudos y en 22 solo los infartos. En 21 los datos de entrada fueron la clínica y el electrocardiograma, en 10 solo el electrocardiograma. La mayoría utilizan como referente estándar el contexto clínico. Se encontraron altos niveles de precisión diagnóstica con un mejor rendimiento en el caso de redes neuronales y máquinas de soporte de vectores en comparación con las herramientas estadísticas de reconocimiento de patrones y árboles de decisiones. Conclusiones: Encontramos una amplia evidencia de que los abordajes a través de las herramientas de sistemas inteligentes alcanzan un alto nivel de precisión por lo que deberían ser consideradas como herramientas para el soporte de las decisiones diagnósticas de los síndromes coronarios agudos.

Abstract Background: Acute myocardial infarction is the leading cause of non-communicable deaths worldwide. Its diagnosis is a highly complex task, for which modelling through automated methods has been attempted. A systematic review of the literature was performed on diagnostic tests that applied intelligent systems tools in the diagnosis of acute coronary syndromes. Methods: A systematic review of the literature is presented using Medline, Embase, Scopus, IEEE/IET Electronic Library, ISI Web of Science, Latindex and LILACS databases for articles that include the diagnostic evaluation of acute coronary syndromes using intelligent systems. The review process was conducted independently by 2 reviewers, and discrepancies were resolved through the participation of a third person. The operational characteristics of the studied tools were extracted. Results: A total of 35 references met the inclusion criteria. In 22 (62.8%) cases, neural networks were used. In five studies, the performances of several intelligent systems tools were compared. Thirteen studies sought to perform diagnoses of all acute coronary syndromes, and in 22, only infarctions were studied. In 21 cases, clinical and electrocardiographic aspects were used as input data, and in 10, only electrocardiographic data were used. Most intelligent systems use the clinical context as a reference standard. High rates of diagnostic accuracy were found with better performance using neural networks and support vector machines, compared with statistical tools of pattern recognition and decision trees. Conclusions: Extensive evidence was found that shows that using intelligent systems tools achieves a greater degree of accuracy than some clinical algorithms or scales and, thus, should be considered appropriate tools for supporting diagnostic decisions of acute coronary syndromes.

[Intelligent systems tools in the diagnosis of acute coronary syndromes: A systemic review]. / Herramientas de sistemas inteligentes en el diagnóstico de los síndromes coronarios agudos: una revisión sistemática.

BACKGROUND: Acute myocardial infarction is the leading cause of non-communicable deaths worldwide. Its diagnosis is a highly complex task, for which modelling through automated methods has been attempted. A systematic review of the literature was performed on diagnostic tests that applied intelligent systems tools in the diagnosis of acute coronary syndromes. METHODS: A systematic review of the literature is presented using Medline, Embase, Scopus, IEEE/IET Electronic Library, ISI Web of Science, Latindex and LILACS databases for articles that include the diagnostic evaluation of acute coronary syndromes using intelligent systems. The review process was conducted independently by 2 reviewers, and discrepancies were resolved through the participation of a third person. The operational characteristics of the studied tools were extracted. RESULTS: A total of 35 references met the inclusion criteria. In 22 (62.8%) cases, neural networks were used. In five studies, the performances of several intelligent systems tools were compared. Thirteen studies sought to perform diagnoses of all acute coronary syndromes, and in 22, only infarctions were studied. In 21 cases, clinical and electrocardiographic aspects were used as input data, and in 10, only electrocardiographic data were used. Most intelligent systems use the clinical context as a reference standard. High rates of diagnostic accuracy were found with better performance using neural networks and support vector machines, compared with statistical tools of pattern recognition and decision trees. CONCLUSIONS: Extensive evidence was found that shows that using intelligent systems tools achieves a greater degree of accuracy than some clinical algorithms or scales and, thus, should be considered appropriate tools for supporting diagnostic decisions of acute coronary syndromes.

A Randomized Controlled Study of Cognitive-Behavioral Therapy for Posttraumatic Stress in Street Children in Mexico City.

The study aimed to evaluate cognitive-behavioral therapy (CBT) for posttraumatic stress (PTS), depression, anxiety, and anger in street children by a randomized controlled trial of CBT versus a waitlist control. It was conducted in 8 residential facilities for street children in Mexico City, with assessments at baseline, posttreatment, and 3 months later. Children who reported at least moderate posttraumatic stress, and fulfilled the study requirement were enrolled in the study (N = 100, 12-18 years old, 36 boys). There were 51 children randomized to CBT and 49 to the waitlist condition. Randomization was stratified by gender. CBT consisted of 12 individual 1-hour sessions administered weekly by 2 trained, master's-level clinicians. Outcome measures included self-reports of PTS, depression, anxiety, and anger; global improvement was assessed by the independent evaluator. Compared to participants in the waitlist condition participants in CBT showed a significant reduction in all symptoms, with effects sizes of 1.73 to 1.75. At follow up there was attrition (n = 36), and no change from posttreatment scores. The study did find statistically significant improvement in symptoms in the CBT group compared to the waitlist condition; symptoms remained stable at 3 months. The study found that CBT for trauma in a sample of street children provided a reduction of a broad range of mental health symptoms.

[Studying the tumor growth inhibitory effect of modified GnRH-III-anthracycline bioconjugates in subcutaneous vs. orthotopic models in vivo]. / Módosított GnRH-III-antraciklin biokonjugátumok daganatnövekedést gátló hatásának tanulmányozása in vivo szubkután vs. ortotopikus rendszerekben.

Targeted tumor therapy is a perspective procedure to specifically destroy the cancer tissues with eliminating or at least decreasing the side effects of anticancer drugs. For this purpose the drug molecule is attached to a targeting moiety (e.g. peptide hormones) that recognizes tumor specific or overexpressed receptors on cancer cells. The in vitro cytostatic or cytotoxic assays do not give proper information whether the tumor growth inhibitory effect of the conjugate is better than the activity of the free drug. Only in vivo studies are adequate to answer this question. However, the selection of the appropriate tumor model is important to eliminate the false positive results. In our studies a gonadotropin-releasing hormone analog (GnRH-III) was applied as targeting moiety in drug conjugates. The in vivo antitumor activity of these conjugates was investigated on mice bearing subcutaneously or orthotopically szigdeveloped tumors. The subcutaneously implanted tumor model which is isolated from its surroundings may provide false results in tumor growth inhibition. In contrast, the orthotopically developed tumor is a better model representing appropriate anatomical and clinical status of cancer. Therefore, the orthotopical colon cancer developed in our laboratory is a suitable model for the study of the antitumor activity of the conjugates prepared for targeted tumor therapy.

Propiedades psicométricas de la escala "Dificultades en la Regulación Emocional" en español (DERS-E) para adolescentes mexicanos / Psychometric properties of the "Difficulties in Emotion Regulation Scale" in spanish (DERS-E) in Mexican adolescents

Introduction Emotional Dysregulation (ED) is the decreased capacity to experiment and differentiate an ample range of emotions, as well as to monitor, evaluate and modify intense emotional states. ED is associated with the most frequent emotional problems such as depression, anxiety, and with maladaptive behaviors thought to serve an emotion and impulsivity regulating function, including deliberate self-harm. The Difficulties in Emotion Regulation Scale (DERS) was developed for adults, has good internal consistency (Cronbach's α=0.93), and good test-retest reliability (r=0.88). Objectives To translate and determine the psychometric properties of the Spanish version of the DERS (DERS-E) in a nonclinical Mexican adolescent's sample. Method 455 students of a public junior high school in Mexico City participated; the mean age was 13.1 ±.95 years old. The scale was administrated in groups of 40 students, who concurrently answered the Spanish version of the following measures: i) Self-injury Schedule; ii) Beck Depression Inventory; and iii) Plutchik's Impulsivity Scale. Results The first confirmatory factorial analysis (CFA) showed that the data did not replicate the original six-factor structure with 36 items (χ2=22339.4, df= 6, p<0.05). An exploratory factorial analysis showed that the data adjusted with a 24 items and 4-factor model (corroborated with a second CFA: χ2=259.729, df=230, p>0.05); the subscales Cronbach' a were from .85 to .68. The validity through contrasted groups and the correlation with concurrent scales showed significant results (Pearson's r of .51 to .76, p<0.05). Conclusions The DERS-E with adolescents did not replicate the factorial structure of the original scale, but showed a similar and multidimensional structure of four factors and showed good psychometric properties with respect to internal consistency and concurrent validity.

La desregulación emocional (DE) es la capacidad disminuida para experimentar y diferenciar un amplio rango de emociones, así como para monitorear, evaluar y modificar estados emocionales intensos. La DE se ha asociado a los más frecuentes padecimientos, como depresión, ansiedad y conductas desadaptativas, incluidas la impulsividad y las autolesiones no suicidas. La escala Difficulties in Emotion Regulation Scale (DERS por sus siglas en inglés) fue desarrollada para evaluar estas dificultades en adultos, posee una buena consistencia interna (α de Cronbach=0.93) y buena confiabilidad test-retest (r=0.88). Objetivos Traducir y determinar las propiedades psicométricas de la DERS en español (DERS-E) en una muestra no clínica de adolescentes mexicanos. Método Participaron 455 estudiantes de una escuela secundaria pública de la Ciudad de México, de los cuales 226 eran hombres (49.7%) y 229 mujeres (50.3%); la edad promedio fue de 13.1±.95 años. La escala fue administrada grupalmente (grupos de 40 estudiantes), quienes contestaron concurrentemente los inventarios de: i) Autolesiones, ii) Depresión de Beck, iii) Impulsividad de Plutchik. Resultados El primer análisis factorial confirmatorio (AFC) mostró que los datos no replicaban la estructura original de seis factores con 36 reactivos (χ²=22339.4, gl=6, p<0.05). Un análisis factorial exploratorio mostró que los datos se ajustaban a un modelo de 24 reactivos y cuatro factores (corroborados con un segundo AFC: χ²=259.729, gl=230, p>0.05). Las alphas de Cronbach de cada subescala tuvieron un rango entre .85 y .68. La validez por medio de grupos contrastados y la correlación con las medidas concurrentes mostraron resultados significativos (r de Pearson de .51 a .76, p<0.05). Discusión y conclusiones La DERS-E con adolescentes no replicó la estructura factorial de la escala original, pero sí presentó una estructura similar, multidimensional, con cuatro factores y mostró buenas características psicométricas, tanto de consistencia interna como de validez concurrente.

In-vivo antitumour effect of daunorubicin-GnRH-III derivative conjugates on colon carcinoma-bearing mice.

Targeted cancer chemotherapy is a novel approach developed for the specific delivery of anticancer drugs. Tumour targeting can be achieved by combining a chemotherapeutic agent with a targeting moiety that recognizes tumour-specific or highly expressed receptors on cancer cells. We used the gonadotropin-releasing hormone-III (GnRH-III) as a targeting moiety to which the chemotherapeutic agent daunorubicin (Dau) was attached through an oxime bond either directly or by inserting a GFLG tetrapeptide spacer. The in-vivo toxicity of Dau-GnRH-III derivative conjugates was evaluated on healthy BDF-1 female mice, and their tumour growth inhibitory effect was determined on C26 murine and HT-29 human colon carcinoma-bearing mice. Both oxime bond-containing conjugates were well tolerated and exerted significant antitumour activity on C26 colon carcinoma-bearing mice at a dose of 30 mg Dau content in conjugate/kg body weight. Furthermore, the conjugates inhibited the tumour growth more than the free drug at a dose that was still not toxic. Similar tumour growth inhibitory effects were obtained on HT-29 human colon carcinoma-bearing mice using three treatments with 15 mg Dau content in conjugate/kg. The tumour growth inhibitions according to the tumour volume and the tumour weight were 44/41% and 58/50%, respectively. Considering the results, both of the investigated Dau-GnRH-III derivative conjugates were well tolerated and had significant antitumour effect on colon carcinoma-bearing mice.

Enhanced enzymatic stability and antitumor activity of daunorubicin-GnRH-III bioconjugates modified in position 4.

Here, we report on the synthesis, enzymatic stability, and antitumor activity of novel bioconjugates containing the chemotherapeutic agent daunorubicin attached through an oxime bond to various gonadotropin-releasing hormone-III (GnRH-III) derivatives. In order to increase the enzymatic stability of the bioconjugates (in particular against chymotrypsin), (4)Ser was replaced by N-Me-Ser or Lys(Ac). A compound in which (4)Lys was not acetylated was also prepared, with the aim of investigating the influence of the free ε-amino group on the biochemical properties. The in vitro cytostatic effect of the bioconjugates was determined on MCF-7 human breast, HT-29 human colon, and LNCaP human prostate cancer cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Their stability/degradation (1) in human serum, (2) in the presence of rat liver lysosomal homogenate, and (3) in the presence of digestive enzymes (trypsin, chymotrypsin, and pepsin) was analyzed by liquid chromatography in combination with mass spectrometry. The results showed that (1) all synthesized bioconjugates had in vitro cytostatic effect, (2) they were stable in human serum at least for 24 h, and (3) they were hydrolyzed in the presence of lysosomal homogenate. All compounds were stable in the presence of (1) pepsin and (2) trypsin (except for the (4)Lys containing bioconjugate). In the presence of chymotrypsin, all bioconjugates were digested; the degradation rate strongly depending on their structure. The bioconjugates in which (4)Ser was replaced by N-Me-Ser or Lys(Ac) had the highest enzymatic stability, making them potential candidates for oral administration. In vivo tumor growth inhibitory effect of two selected bioconjugates was evaluated on orthotopically developed C26 murine colon carcinoma bearing mice. The results indicated that the compound containing Lys(Ac) in position 4 had significantly higher antitumor activity than the parent bioconjugate.

Development of an oxime bond containing daunorubicin-gonadotropin-releasing hormone-III conjugate as a potential anticancer drug.

Here, we report on the synthesis and biological properties of a conjugate in which daunorubicin (Dau) as chemotherapeutic agent was attached through an oxime bond to gonadotropin-releasing hormone-III (GnRH-III) as targeting moiety. In vitro toxicity and the cytostatic effect of the conjugate on MCF-7 human breast and C26 murine colon cancer cell lines were determined, and the results were compared with those obtained for the free daunorubicin, as well as with the doxorubicin containing derivative. In vivo antitumor effect of daunorubicin-GnRH-III was studied on Balb/c female mice transplanted with C26 tumor. Our data indicate that the daunorubicin-GnRH-III conjugate had a lower toxic effect than the free daunorubicin and it was essentially nontoxic up to 15 mg (Dau content)/kg body weight. The treatment of the C26 tumor bearing mice with the conjugate led to tumor growth inhibition and longer survival time in comparison with the controls and with the administration of the free drug. When mice were treated twice with the conjugate (on days 4 and 7 after tumor transplantation), 46% tumor growth inhibition was obtained. In this case, the increase of the median survival time was 38% compared to the controls.

The antitumour effect of the somatostatin analogue TT-232 depends on the treatment regimen.

The somatostatin analogue TT-232, containing a five residue ring structure, has a strong antitumour activity both in vitro and in vivo. This peptide has no effect on growth hormone (GH) release, but exhibits a remarkable tyrosine kinase inhibitory effect and induced apoptosis. We studied the effect of TT-232 in different routes of administration and treatment schedules on various types of mouse tumour models. The infusion treatment with inserted Alzet osmotic minipumps proved to be superior to both twice daily subcutaneous (s.c.) or intravenous (i.v.) injections in a 2 weeks period. In the case of S-180 tumour the infusion treatment resulted in 77-100% tumour growth inhibition and in 40-60% of mice long-term and tumour-free survivors. With the P-388sc tumour the infusion of TT-232 resulted in 20-40% of animals long-term and tumour-free survivors and in 76-100% tumour growth inhibition. In the very aggressive Colon-26 (C-26) and MXT, the TT-232 treatment resulted in 71-75% tumour growth inhibition and increased survival time by about 50%.