An international survey in Latin America on the practice of interventional cardiology during the COVID-19 pandemic, with a particular focus on myocardial infarction.

INTRODUCTION: A reduction in the number of interventional cardiology procedures has emerged as a result of the COVID-19 pandemic. A survey was performed to quantify this decrease and the impact on the management of myocardial infarction in Latin America. METHODS: A telematic survey was conducted for all countries in Latin America. Diagnostic catheterisations, coronary and structural interventions, as well as the incidence and delay to reperfusion therapy of myocardial infarction (STEMI), were recorded. Two periods were compared: from 24 February to 8 March 2020 (pre-COVID-19) and another 2­week period that varied according to country (COVID-19). RESULTS: Responses were obtained from 79 centres in 20 countries. There was a significant decrease in the number of diagnostic procedures (-65.2%), coronary interventions (-59.4%), structural therapeutics (-86.1%) and STEMI care (-51.2%). A decrease was noted in the incidence of STEMI, but also a delay in the time to STEMI reperfusion. While there was a variation in activity in interventional cardiology between countries, patient behaviour was rather homogeneous. CONCLUSIONS: A significant reduction in healthcare activity has been noted during the COVID-19 pandemic, including STEMI care, with the risk of increased mortality and/or morbidity following STEMI. Healthcare providers should encourage patients with suspected symptoms of STEMI to call for emergency care to ensure rapid diagnosis and timely reperfusion treatment.

Levels of anti-Müllerian hormone in premenopausal women with the antiphospholipid syndrome and its association with the risk of clinical complications.

OBJECTIVE: The study aims to investigate the ovarian reserve in premenopausal women with antiphospholipid syndrome (APS) and to evaluate whether it is associated with cumulative organ damage or the risk of clinical complications. METHODS: This single-center study was conducted in 23 premenopausal female patients (10 with primary APS and 13 with secondary APS) and 24 healthy volunteers. Serum anti-Müllerian hormone (AMH) levels were measured by enzyme-linked immunoassay. Disease-specific organ damage (DIAPS score) and the risk of clinical complications (aGAPSS score) were additionally evaluated in APS patients. RESULTS: Serum AMH levels were similar in APS patients (median 6.06, interquartile range 4.31-7.54 ng/ml) and in controls (4.87, 2.64-6.40 ng/ml; P = 0.116), and no differences were observed between the primary (6.60, 5.49-8.88 ng/ml) and secondary (6.06, 3.91-7.30 ng/ml; P = 0.532) forms of the syndrome. In individuals with APS, serum AMH levels correlated inversely with the aGAPSS score (rho-0.421, 95% confidence intervals -0.716 to -0.001; P = 0.045), while no associations were observed with the DIAPS score (rho-0.001, -0.423 to 0.422; P = 0.996). CONCLUSIONS: Ovarian reserve is not reduced in premenopausal women with APS. In addition, serum AMH levels may reflect the risk of APS-related clinical complications but not the burden of disease-specific organ damage.

Pro-inflammatory caspase-1 activation during the immune response in cells from rainbow trout Oncorhynchus mykiss (Walbaum 1792) challenged with pathogen-associated molecular patterns.

In response to pathogens, the higher vertebrate innate immune system activates pro-inflammatory caspase-1 which is responsible for the processing and secretion of several important cytokines involved in the host's defence against infection. To date, caspase-1 has been described in few teleost fish, and its activity has been demonstrated through substrate cleavage and inhibition by pharmacological agents. In this study, the detection of the active form of caspase-1 during the immune response in salmonid fish is described, where two antibodies were produced. These antibodies differentially recognize the structural epitopes of the inactive pro-caspase-1 and the processed active form of the caspase. Firstly, caspase-1 activation was demonstrated in vitro by ELISA, Western blotting and immunocytochemistry in rainbow trout macrophages exposed to different pathogen-associated molecular patterns plus the pathogen Aeromonas hydrophila. This activity was clearly abrogated by a caspase inhibitor and seems to be unrelated to IL-1ß secretion. Caspase-1 activation was then validated in vivo in gill cells from fish challenged with Aeromonas salmonicida. These results represent the first demonstration of caspase-1 activation in salmonids, and the first evidence of the putative regulatory role which this protease plays in inflammatory response in this fish group, as described for some other teleosts and mammals.

Expression, functionality, and localization of apurinic/apyrimidinic endonucleases in replicative and non-replicative forms of Trypanosoma cruzi.

Trypanosoma cruzi is the etiological agent of Chagas disease. The parasite has to overcome oxidative damage by ROS/RNS all along its life cycle to survive and to establish a chronic infection. We propose that T. cruzi is able to survive, among other mechanisms of detoxification, by repair of its damaged DNA through activation of the DNA base excision repair (BER) pathway. BER is highly conserved in eukaryotes with apurinic/apirimidinic endonucleases (APEs) playing a fundamental role. Previous results showed that T. cruzi exposed to hydrogen peroxide and peroxinitrite significantly decreases its viability when co-incubated with methoxyamine, an AP endonuclease inhibitor. In this work the localization, expression and functionality of two T. cruzi APEs (TcAP1, Homo sapiens APE1 orthologous and TcAP2, orthologous to Homo sapiens APE2 and to Schizosaccaromyces pombe Apn2p) were determined. These enzymes are present and active in the two replicative parasite forms (epimastigotes and amastigotes) as well as in the non-replicative, infective trypomastigotes. TcAP1 and TcAP2 are located in the nucleus of epimastigotes and their expression is constitutive. Epimastigote AP endonucleases as well as recombinant TcAP1 and TcAP2 are inhibited by methoxyamine. Overexpression of TcAP1 increases epimastigotes viability when they are exposed to acute ROS/RNS attack. This protective effect is more evident when parasites are submitted to persistent ROS/RNS exposition, mimicking nature conditions. Our results confirm that the BER pathway is involved in T. cruzi resistance to DNA oxidative damage and points to the participation of DNA AP endonucleases in parasite survival.

Scorpion sting envenomation outbreak in Mexico. Strategies for prevention and control.

In Mexico occurs 25% of all worldwide cases of scorpion sting envenomation (SSE). An outbreak of SSE was identified in Villa Unión, Sinaloa, Mexico. The objective of this study is to describe the outbreak, and prevention and control strategies implemented. The design was a cross-sectional study. Eligibility criteria included confirmed cases (n = 425) identified from the date the outbreak was recognized (from November 08, 2023 to July 10, 2023). The cases from Villa Unión (n = 231) were included for the analysis of epidemiological and clinical findings. The research followed the recommendations of the Initiative Reporting of studies Conducted Using Observational Routinely collected Data (RECORD). Of the total cases (n = 425), 398 (93.6%) were from the municipality of Mazatlán, and 231 (58%) were from Villa Unión. The incidence rate was 13.64 per 1000 persons. The average cases per week was 51.5(SD ± 12). The male-to-female ratio was 3:4, the average age was 30.7(SD ± 19) years. Most of cases occurred in the 25-44 age group. The sting occurred mostly inside houses (n = 200, 86.5%). The predominant symptoms were local pain (95.2%), and local paresthesia (75.8%). The Case fatality rate was 0%. Implementation of prevention and control strategies based on field epidemiological research and scientific evidence are necessary to reduce the incidence and prevent fatal complications.

Development of a new antibody for detecting natural killer enhancing factor (NKEF)-like protein in infected salmonids.

The main cellular responses of innate immunity are phagocytic activity and the respiratory burst, which produces a high amount of reactive oxygen species. Natural killer enhancing factor (NKEF) belongs to the peroxiredoxin family that has an antioxidant function and enhances cytotoxic cell activity. This molecule may play a key role in macrophage and cytotoxic cell communication during the innate immune response of fish against pathogens. In fish, the NKEF gene has been characterized in some species as showing an up-regulation in infected fish, suggesting a trigger effect upon NK-like cells. To detect and localize this molecule in salmonids at protein level, a monospecific polyclonal antibody was generated. A probable NKEF-like protein epitope region was identified and characterized using bioinformatic tools, and the sequence was chemically synthesized using Fmoc strategy, analysed by RP-HPLC and its molecular weight confirmed by mass spectrometry. The synthetic peptide was immunized and antibodies from ascitic fluid were obtained. The resulting antibody is a versatile tool for detecting NKEF by different immune techniques such as ELISA, Western blotting and immunohistochemistry. Analysis of NKEF-like protein is a useful method for characterizing immune properties of this molecule in fish during response to pathogens.

Evolutionary history and identification of conservation units in the giant otter, Pteronura brasiliensis.

The giant otter, Pteronura brasiliensis, occupies a range including the major drainage basins of South America, yet the degree of structure that exists within and among populations inhabiting these drainages is unknown. We sequenced portions of the mitochondrial DNA (mtDNA) cytochrome b (612bp) and control region (383 bp) genes in order to determine patterns of genetic variation within the species. We found high levels of mtDNA haplotype diversity (h = 0.93 overall) and support for subdivision into four distinct groups of populations, representing important centers of genetic diversity and useful units for prioritizing conservation within the giant otter. We tested these results against the predictions of three hypotheses of Amazonian diversification (Pleistocene Refugia, Paleogeography, and Hydrogeology). While the phylogeographic pattern conformed to the predictions of the Refugia Hypothesis, molecular dating using a relaxed clock revealed the phylogroups diverged from one another between 1.69 and 0.84 Ma, ruling out the influence of Late Pleistocene glacial refugia. However, the role of Plio-Pleistocene climate change could not be rejected. While the molecular dating also makes the influence of geological arches according to the Paleogeography Hypothesis extremely unlikely, the recent Pliocene formation of the Fitzcarrald Arch and its effect of subsequently altering drainage pattern could not be rejected. The data presented here support the interactions of both climatic and hydrological changes resulting from geological activity in the Plio-Pleistocene, in shaping the phylogeographic structure of the giant otter.

Celecoxib: Antiangiogenic and Antitumoral Action / Celecoxib: Acción Antiangiogénica y Antitumoral

SUMMARY: Angiogenesis, a process by which new blood vessels are generated from pre-existing ones, is significantly compromised in tumor development, given that due to the nutritional need of tumor cells, pro-angiogenic signals will be generated to promote this process and thus receive the oxygen and nutrients necessary for its development, in addition to being a key escape route for tumor spread. Although there is currently an increase in the number of studies of various anti-angiogenic therapies that help reduce tumor progression, it is necessary to conduct a review of existing studies of therapeutic alternatives to demonstrate their importance.

La angiogénesis, proceso por el cual se generan nuevos vasos sanguíneos a partir de otros preexistentes, se encuentra comprometida de forma importante en el desarrollo tumoral, dado que por necesidad nutritiva de las células tumorales se generarán señales pro angiogénicas para promover este proceso y así recibir el oxígeno y los nutrientes necesarios para su desarrollo, además de ser una ruta de escape clave para la diseminación tumoral. Si bien, actualmente existe un aumento en la cantidad de estudios de diversas terapias anti angiogénicas que ayudan a reducir el avance tumoral, es necesario realizar una revisión de los estudios existentes de alternativas terapéuticas para demostrar su importancia.

Analysis of previous training with simulated models on the success rate of ultrasound-guided supraclavicular block. Prospective cohort study. / Análisis del entrenamiento previo con modelos simulados en el porcentaje de éxito del bloqueo supraclavicular guiado por ultrasonido. Estudio de cohorte prospectivo.

INTRODUCTION: The teaching based on simulation and acquisition of skills is changing the paradigm of education and restructuring the clinical residences, with the aim of acquiring better skills, increasing procedural success, reducing complications, as well as providing safe, effective, and efficient and focused care of the patient. Peripheral nerve blocks have advanced as techniques for anatomical repairs, use of neurostimulator, and ultrasound. The posgraduate anaesthesiology program implemented a teaching program that included phases of theoretical teaching, training with simulated models, and application in real scenarios. OBJECTIVE: To analyse the success, the management of the ultrasound equipment and the incidence of complications of ultrasound-guided supraclavicular blocks (BSE) in the clinical scenario, performed by residents of anaesthesiology previously trained with a theoretical and simulated model. METHODS: Prospective cohort study among residents of anaesthesiology (R1, R2, R3, R4), who received previous theoretical-practical training on simulated models. The evaluation was performed by expert anaesthesiologists, with video analysis of the ultrasound screen performed at the time of BSE initiation. RESULTS: The evaluation included 16 residents, who performed 156 BSE. None had previous experience in ultrasound-guided blocks. The success of the block was 96.15%. The team management was excellent (from 86% to 95%), with no significant differences among the residents. (P=.61) The incidence of complications was 0.64%, corresponding to arterial puncture. CONCLUSIONS: In BSE, previous training with a theoretical and simulated model could increase the probability of success and reduce complications. With adequate training, first year residents managed to successfully carry out the procedure.

Split cricoideo anterior posterior: una novedosa técnica para evitar la traqueotomía en parálisis cordal bilateral en pacientes pediátricos / Posterior anterior cricoid split: a cutting-edge technique to avoid tracheostomy in bilateral cordal paralysis in pediatric patients

Introducción: La parálisis cordal bilateral en aducción es la segunda causa de estridor congénito y genera una grave obstrucción de la vía aérea, debutando con estridor. La traqueotomía ha sido durante mucho tiempo el gold estándar para el tratamiento de esta afección, no exenta de complicaciones. Existen procedimientos que intentan evitar la traqueotomía, como el split cricoideo anterior posterior endoscópico (SCAPE). Objetivo: Presentar experiencia con SCAPE en pacientes pediátricos como tratamiento alternativo de parálisis cordal bilateral en aducción. Material y Método: Análisis retrospectivo de los resultados quirúrgicos obtenidos en pacientes con parálisis cordal bilateral en aducción tratados con SCAPE entre enero de 2016 y diciembre de 2019 en el Hospital Guillermo Grant Benavente de Concepción, Chile. Resultados: Siete pacientes se sometieron a SCAPE. Todos los pacientes presentaban insuficiencia respiratoria severa, cinco requirieron asistencia ventilatoria mecánica. Seis pacientes tenían el diagnóstico de parálisis cordal bilateral (PCB) congénita y uno PCB secundaria a tumor de tronco cerebral. Cuatro pacientes presentaron comorbilidad de la vía aérea: dos pacientes presentaron estenosis subglótica grado I y dos pacientes presentaron laringomalacia que requirió manejo quirúrgico. Los días promedio de intubación fueron once días. Ningún paciente requirió soporte ventilatorio postoperatorio, sólo un paciente recibió oxigenoterapia nocturna debido a hipoventilación secundaria a lesión de tronco. Ningún paciente ha presentado descompensación respiratoria grave. Un 40% ha recuperado movilidad cordal bilateral. Conclusión: Split cricoideo anteroposterior endoscópico es una alternativa eficaz para tratar el PCB en pacientes pediátricos. Nuestro estudio evidencia que es una alternativa a la traqueotomía, con excelentes resultados y menor morbimortalidad.

Introduction: Bilateral vocal fold paralysis in adduction is the second cause of congenital stridor and generates a serious obstruction of the airway. Tracheostomy has long been the gold standard for the treatment of this condition, but it has inherent complications. There are procedures that try to avoid tracheotomy, such as the endoscopic anterior posterior cricoid split (EAPCS). Aim: Present our experience with EAPCS in pediatric patients as a treatment for bilateral vocal fold paralysis in adduction. Material and Method: Retrospective analysis of the surgical results obtained in patients with bilateral vocal cord paralysis in adduction treated with EAPCS between January 2016 and December 2019 at Guillermo Grant Benavente Hospital in Concepción, Chile. Results: Seven patients underwent EAPCS. All patients had severe respiratory failure, five required mechanical ventilation assistance. Six patients were diagnosed with congenital bilateral cord palsy (BCP) and one BCP secondary to a brainstem tumor. Four patients had airway comorbidity: two patients had grade I subglottic stenosis and two patients had laryngomalacia that required surgical management. The average days of intubation were eleven days. No patient required post op invasive/non-invasive ventilation, only one patient received nocturnal oxygen therapy due to hypoventilation secondary to trunk injury. None of the patients has presented severe respiratory decompensation. Forty percent have recovered bilateral chordal mobility. Conclusion: SCAPE is a cutting-edge and effective alternative to treat PCB in pediatric patients. Our study shows that it is an alternative to tracheotomy, with excellent results and lower morbidity and mortality.

Tuberculosis in recipients of solid-organ transplants during 1995-2015 in Cali, Colombia.

SETTING: Tuberculosis (TB) in solid-organ transplants (SOTs) is an important opportunistic infection associated with mortality and graft loss. SOT recipients carry a higher risk of contracting active TB than the general population. Clinical and radiographic presentations are non-specific, and sputum smear and culture have low yields. TB patients with SOTs require standard anti-tuberculosis treatment. However, rifampicin (RMP) use is associated with a 30% rate of acute graft rejection (AGR) and a 20% rate of transplant loss. OBJECTIVE: To determine treatment outcomes in SOT recipients with active TB. DESIGN: A retrospective study of clinical and microbiological data and TB treatment outcomes. RESULTS: Among the 2349 transplants assessed, active TB was detected in 31 recipients; 55% had pulmonary TB and 40% were sputum smear-positive. In 32% of the patients, TB was diagnosed 30 days after symptom onset, 77% of the patients were cured and 10% died. AGR occurred in 13%. CONCLUSION: TB was diagnosed in <30 days. Anti-tuberculosis treatment without RMP (80% vs. 67%; P = 0.48, OR 0.5, 95%CI 0.07-3.55) and with moxifloxacin yielded higher treatment success rates and a lower risk of AGR.

La enfermedad periodontal, diabetes tipo 2 y el riesgo cardiovascular / Periodontal disease, type 2 diabetes and cardiovascular risk

JUSTIFICACIÓN: recientes estudios promovidos por la Federación Dental Internacional y el Consejo General de Dentistas demuestran que existe una relación bidireccional entre la salud oral y la diabetes tipo 2 (DM2). Tanto en la periodontitis como en la DM2, los procesos inflamatorios están aumentados, lo que produce alteraciones microvasculares que provocan que la presencia de una de las dos afecte y empeore el cuadro de la otra enfermedad, lo que puede llevar a un aumento del 20 % del riesgo cardiovascular en estos pacientes. La labor del farmacéutico comunitario podría ayudar a detectar de manera precoz los problemas gingivales y con ello prevenir futuras complicaciones sistémicas derivadas de una enfermedad periodontal (EP) no controlada.OBJETIVO: diseño de un protocolo de cribado para la detección de EP en pacientes con DM2.MATERIAL Y MÉTODOS: se elaboró un protocolo sistematizado "ad hoc" para el desarrollo de una entrevista demográfica, además de una recogida de variables y síntomas de alarma. Fueron seleccionados tras la consulta de documentos hallados mediante una búsqueda bibliográfica en PUBMED, Biblioteca Cochrane Plus y documentos del grupo de Epidemiología de la Sociedad Española de Diabetes. En el registro se incorporaron variables correspondientes a las características de los pacientes: demográficas (edad y sexo), relacionadas con el hábito tabáquico y clínicas (años de tratamiento de la DM2, grupo de fármaco antidiabético, tratamiento cardiovascular, salud dental y sintomatología asociada). RESULTADOS Población diana: pacientes mayores de 18 años que en su plan de tratamiento presenten al menos un medicamento antidiabético frente a DM2. (AU)

Plasmocitoma extramedular solitario rinosinusal: reporte de caso y revisión de literatura / Solitary extramedullary plasmacytoma of the rhinosinusal cavity: a case report and literature review

Resumen El plasmocitoma extramedular solitario (PES) es una neooplasia maligna infrecuente caracterizada por una proliferación aislada de células plasmáticas monoclonales en tejido extramedular. La localización más frecuente es en cabeza y cuello con predominio en el territorio rinosinusal, sin embargo, estas lesiones malignas representan menos del 1% de los tumores de esta región anatómica. El diagnostico requiere una alta sospecha clínica, análisis histopatológico acucioso, estudios serológicos y exámenes radiológicos sistémicos de acuerdo a los criterios diagnósticos establecidos en la literatura internacional. Se analiza el caso de un paciente masculino con un PES que se presentó como un tumor de fosa nasal derecha y obstrucción nasal de meses de evolución con hallazgos clínicos e imagenológicos inespecíficos. El diagnóstico definitivo se realizó mediante biopsia endoscópica nasal y estudio histopatológico. El tratamiento fue abordado de manera multidisciplinaria entre otorrinolaringología, hematología y radiooncología. De acuerdo a las guías internacionales, se decidió realizar radioterapia localizada con buen resultado clínico precoz. El PES requiere un abordaje multidisciplinario para lograr un diagnóstico y tratamiento oportuno, siendo imprescindible la exclusión del mieloma múltiple debido a las diferencias terapéuticas y en pronóstico clínico. El tratamiento puede realizarse con radioterapia y/o cirugía, siendo la radioterapia el pilar de tratamiento.

Abstract Solitary extramedullary plasmacytoma (SEP) is a rare malignant neoplasm characterized by isolated proliferation of monoclonal plasma cells in extramedullary tissue. The most frequent location is in the head and neck with a predominance in the rhinosinusal territory; however, these malignant lesions represent less than 1% of the tumors in this anatomical region. The diagnosis requires a high clinical suspicion, careful histopathological analysis, serological studies and systemic radiological examinations according to the diagnostic criteria established in the international literature. We analyze the case of a male patient with SEP that presented as a tumor of the right nostril and nasal obstruction of months of evolution with nonspecific clinical and imaging findings. The definitive diagnosis was made by nasal endoscopic biopsy and histopathological study. The treatment was approached by multidisciplinary teamwork. According to international guidelines, it was decided to perform localized radiotherapy with good early clinical results. SEP requires a multidisciplinary approach to achieve a timely diagnosis and treatment, being essential exclusion of multiple myeloma due to the therapeutic differences and prognosis. Treatment can be done with radiation therapy and/or surgery; radiation therapy is the mainstay of treatment.

Efectos de la suplementación con vitamina D en el control del asma en pacientes adultos: una revisión sistemática / Effects of vitamin D supplementation on asthma control in adult patients: a systematic review

INTRODUCCIÓN: El asma es una enfermedad crónica inflamatoria de la vía aérea e inmunomediada en su patogénesis. La vitamina D es un inmunomodulador que regula el perfil secretor de citoquinas, entre otras funciones celulares. Una asociación entre la suficiencia de vitamina D y mejoría en la función pulmonar, control de asma y número de exacerbaciones se ha propuesto en adultos, importante dada la elevada prevalencia de insuficiencia de vitamina D globalmente. OBJETIVO: Conocer los efectos de la suplementación con vitamina D en el control del asma en adultos. MÉTODOS: Se realizó una revisión sistemática de la literatura a través de una búsqueda en la base de datos PubMed y EMBASE. Los desenlaces primarios fueron cambios en VEF1, control sintomático, frecuencia de exacerbaciones, además de eventos adversos y FEM como desenlaces secundarios. La calidad de evidencia de los desenlaces fue evaluada a través del modelo GRADE. RESULTADOS: Siete estudios fueron seleccionados después de remover duplicados y aplicar los criterios de inclusión y exclusión, con calidad de evidencia muy baja aplicando sistema GRADE. DISCUSIÓN: No se encontraron diferencias estadísticamente significativas tras la suplementación con vitamina D en los desenlaces evaluados en general, pero dada la calidad de evidencia muy baja y que no se reportaron efectos adversos serios, es necesario tomar cautelosamente estos resultados. Asímismo no se puede descartar la utilidad de esta terapia como tratamiento auxiliar a los pacientes asmáticos con este déficit vitamínico.

BACKGROUND: Asthma is an airway chronic disease, with an important inflammatory component within its pathogenesis, driven by a dysregulated immune response. Vitamin D is an immunomodulator that regulates cell proliferation, differentiation and cytokine secretion profile. An association between vitamin D sufficiency and improvement in pulmonary function, asthma control and a decrease in exacerbations have been proposed in the adult population, which falls into importance given the high prevalence of vitamin D insufficiency globally. OBJECTIVE: To know vitamin D supplementation effects in asthma control in adults. METHODS: Through a PubMed and EMBASE database search, a systematic review of the literature was conducted. Primary outcomes were: changes in FEV1, symptomatic control, exacerbation frequency and PEF and adverse events as secondary outcomes. Outcome evidence quality assessment was made using the GRADE model. Results: Seven studies were selected after taking out duplicates, applying inclusion and exclusion criteria. In all cases, evidence quality assessed by the GRADE system yielded very low quality. CONCLUSIONS: No statistically significant differences were found after vitamin D supplementation in the overall evaluated outcomes. Nonetheless, a cautious interpretation of studies is mandatory, because evidence quality was very low and no serious adverse events were reported. Hence this treatment usefulness as an ancillary therapy for vitamin D deficient asthmatic patients cannot be dismissed.

Mdr1 gene expression in childhood acute lymphoblastic leukemias and lymphomas: a critical evaluation by four techniques.

Expression of the multidrug resistance gene mdr1 is reported to be an important determinant of responsiveness to therapy and survival in some cancers. Many different methods have been used to evaluate mdr1 expression in these studies. This paper compares four methods for determination of mdr1 expression. We studied the mdr1 gene expression in 36 freshly established cell lines from 28 children with acute lymphoblastic leukemia (16 T-ALL, six BCP-ALL, two B-ALL (L3), two biphenotypic leukemias, two Burkitt's lymphomas). Leukemic specimens were obtained at the time of diagnosis in 16 cases, and after chemotherapy in 20 cases. In all the samples, mdr1 mRNA was measured by slot blotting and reverse transcriptase polymerase chain reaction (rt-PCR), and the presence of the mdr1 product, P-glycoprotein, was detected by immunohistochemistry with the MRK-16 monoclonal antibody. In situ mdr1 RNA hybridization was performed in 30 cases. Complete agreement was noted between all the techniques in 14 cases (39%). Results differed on a single test result in another 39% of the cases. These 78% of cases were considered assessable, and the consensus result was presumed to be correct. By this consensus criterion, immunohistochemistry yields both false negative (11%), and false positive (11%) results. RNA slot blotting has a high (21%) false positive rate. In situ mRNA hybridization and rt-PCR have the highest concordance, 80%. The 28 patients from whom these cell lines were derived appear to represent a very poor prognosis group, since there are only two patients (with Burkitt's lymphoma) who are long-term survivors. Nonetheless, a complete clinical response to therapy was correlated with absence of mdr1 expression in assessable cases (p = 0.04). These four methods of determining mdr1 expression often yield discordant results. Therefore, the use of at least two methods for evaluating mdr1 expression is advisable. Rt-PCR is recommended because of its relative simplicity and specificity. This should be supplemented by a technique (immunohistochemistry or flow cytometry) able to detect heterogeneity of P-glycoprotein expression among cells.

Altered cortisol response and hippocampal atrophy in pediatric HIV disease.

The hippocampus is a major center for the regulation of the hypothalamic-pituitary-adrenal axis. There is experimental evidence that chronic exposure to high levels of glucocorticoids may be toxic to the hippocampus. We observed elevated mean basal and 60-min cortisol (F) levels in response to adrenocorticotropin stimulation (0.25 mg cortrosyn, i.v. bolus infusion) in 15 children with HIV infection. Furthermore, in eight of the children for whom data was available, in addition to high peripheral cortisol levels, neurologic dysfunction and hippocampal atrophy were noted on CT scan. These preliminary data suggest that in HIV-infected children an altered cortisol secretion may be associated with specific central nervous system damage.

Comparison of "host cell infiltrates" in patients with follicular lymphoma with and without spontaneous regression.

The "host cell infiltrates" in five patients with low-grade follicular lymphoma who had spontaneous regression without therapy were studied with the use of immunohistochemical methods applied to frozen sections. These infiltrates were compared with the "host cell infiltrates" in six patients with follicular lymphoma with progressive disease. The group with progressive disease was selected to be similar to the group with spontaneous regression in age, sex, histologic characteristics, and stage of disease. The patients with spontaneous regression had significantly more T-helper cells in the host cell infiltrate than the control patients. There were no statistically significant differences between the two groups in numbers of cytotoxic/suppressor T-cells, macrophages, Tac-positive cells, Leu-7-positive cells, or proliferating cells.