Brain metastasis models: What should we aim to achieve better treatments?

Brain metastasis is emerging as a unique entity in oncology based on its particular biology and, consequently, the pharmacological approaches that should be considered. We discuss the current state of modelling this specific progression of cancer and how these experimental models have been used to test multiple pharmacologic strategies over the years. In spite of pre-clinical evidences demonstrating brain metastasis vulnerabilities, many clinical trials have excluded patients with brain metastasis. Fortunately, this trend is getting to an end given the increasing importance of secondary brain tumors in the clinic and a better knowledge of the underlying biology. We discuss emerging trends and unsolved issues that will shape how we will study experimental brain metastasis in the years to come.

Nuevo método de liberación de antibióticos del cemento óseo (polimetilmetacrilato): redefiniendo los límites / New method for antibiotic release from bone cement (polymethylmethacrylate): redefining boundaries

Introducción. La creciente resistencia a antimicrobianos está impulsando la adición de antibióticos con elevada actividad antiestafilocócica al polimetilmetacrilato (PMMA), para su uso en los espaciadores de cemento en la infección periprotésica. El linezolid o el levofloxacino ya han sido utilizados en estudios in vitro; sin embargo, la rifampicina ha demostrado un efecto deletéreo sobre las propiedades mecánicas del PMMA, inhibiendo su polimerización. El objetivo de nuestro estudio fue aislar la rifampicina durante el proceso de polimerización mediante técnicas de microencapsulación, con el fin de obtener un PMMA apto para la fabricación de espaciadores articulares. Material y método. Se sintetizaron microcápsulas de rifampicina con alginato y PHBV, utilizando Rifaldin®. Se estudió la concentración de rifampicina mediante espectrofotometría UV-visible. Se realizaron ensayos de compresión, dureza y tiempo de fraguado con probetas de cemento CMW®1 solo, con rifampicina y microcápsulas de PHBV y alginato. Resultados. El rendimiento de producción, la eficiencia y el rendimiento de microencapsulación fueron mayores con alginato (p=0,0001). El cemento con microcápsulas mostró mayor resistencia a la compresión que el cemento con rifampicina (91,26±5,13, 91,35±6,29 y 74,04±3,57MPa en alginato, PHBV y rifampicina, respectivamente) (p=0,0001). El tiempo de fraguado disminuyó, siendo la curva de dureza del cemento con microcápsulas de alginato similar a la de control. Discusión y conclusiones. La microencapsulación con alginato es una técnica adecuada para introducir rifampicina en el PMMA preservando las propiedades de compresión y el tiempo de fraguado. Su obtención permitiría fabricar espaciadores que liberasen localmente rifampicina para el tratamiento de la infección periprotésica (AU)

Introduction. The increasing antimicrobial resistance is promoting the addition of antibiotics with high antistaphylococcal activity to polymethylmethacrylate (PMMA), for use in cement spacers in periprosthetic joint infection. Linezolid and levofloxacin have already been used in in-vitro studies, however, rifampicin has been shown to have a deleterious effect on the mechanical properties of PMMA, because it inhibits PMMA polymerization. The objective of our study was to isolate the rifampicin during the polymerization process using microencapsulation techniques, in order to obtain a PMMA suitable for manufacturing bone cement spacers. Material and method. Microcapsules of rifampicin were synthesized with alginate and PHBV, using Rifaldin®. The concentration levels of rifampicin were studied by UV-visible spectrophotometry. Compression, hardness and setting time tests were performed with CMW®1 cement samples alone, with non-encapsulated rifampicin and with alginate or PHBV microcapsules. Results. The production yield, efficiency and microencapsulation yield were greater with alginate (P = .0001). The cement with microcapsules demonstrated greater resistance to compression than the cement with rifampicin (91.26±5.13, 91.35±6.29 and 74.04±3.57 MPa in alginate, PHBV and rifampicin, respectively) (P = .0001). The setting time reduced, and the hardness curve of the cement with alginate microcapsules was similar to that of the control. Discussion and conclusions. Microencapsulation with alginate is an appropriate technique for introducing rifampicin into PMMA, preserving compression properties and setting time. This could allow intraoperative manufacturing of bone cement spacers that release rifampicin for the treatment of periprosthetic joint infection (AU)

New method for antibiotic release from bone cement (polymethylmethacrylate): Redefining boundaries. / Nuevo método de liberación de antibióticos del cemento óseo (polimetilmetacrilato): redefiniendo los límites.

INTRODUCTION: The increasing antimicrobial resistance is promoting the addition of antibiotics with high antistaphylococcal activity to polymethylmethacrylate (PMMA), for use in cement spacers in periprosthetic joint infection. Linezolid and levofloxacin have already been used in in-vitro studies, however, rifampicin has been shown to have a deleterious effect on the mechanical properties of PMMA, because it inhibits PMMA polymerization. The objective of our study was to isolate the rifampicin during the polymerization process using microencapsulation techniques, in order to obtain a PMMA suitable for manufacturing bone cement spacers. MATERIAL AND METHOD: Microcapsules of rifampicin were synthesized with alginate and PHBV, using Rifaldin®. The concentration levels of rifampicin were studied by UV-visible spectrophotometry. Compression, hardness and setting time tests were performed with CMW®1 cement samples alone, with non-encapsulated rifampicin and with alginate or PHBV microcapsules. RESULTS: The production yield, efficiency and microencapsulation yield were greater with alginate (P = .0001). The cement with microcapsules demonstrated greater resistance to compression than the cement with rifampicin (91.26±5.13, 91.35±6.29 and 74.04±3.57 MPa in alginate, PHBV and rifampicin, respectively) (P = .0001). The setting time reduced, and the hardness curve of the cement with alginate microcapsules was similar to that of the control. DISCUSSION AND CONCLUSIONS: Microencapsulation with alginate is an appropriate technique for introducing rifampicin into PMMA, preserving compression properties and setting time. This could allow intraoperative manufacturing of bone cement spacers that release rifampicin for the treatment of periprosthetic joint infection.

Using peptides to increase transport across the intestinal barrier.

The oral route is the preferred for the administration of drugs; however, it has some serious limitations. One of the main disadvantages is poor permeability across the intestinal barrier. Various approaches are currently being adopted to overcome this issue. In this review, we describe the alternatives that use peptides to enhance intestinal absorption. First, we define the various sources of peptide enhancers followed by the analysis of the absorption mechanism used. We then comment on the possible toxic effects derived from their use as permeation enhancers, as well as potential formulation strategies. Finally, the advantages and drawbacks of peptides as intestinal enhancers are examined.

[Alkaline phosphatase isoenzymes in the serum of patients with renal insufficiency]. / Isoenzimas de fosfatasa alcalina en el suero de pacientes con insuficiencia renal.

OBJECTIVE: The aim of this study was to test the utility of serum alkaline phosphatase isoenzymes determination from patients with renal insufficiency. MATERIAL AND METHODS: Serum levels of alkaline phosphatase isoenzymes were determined in a group of 58 patients: 22 of them suffering acute renal insufficiency (ARI) and 36 with chronic renal failure (CRF) undergoing regular hemodialysis, results obtained were compared from a population of 30 healthy adults. Intestinal, bone, liver, macromolecular and intestinal variant isoenzymes, were separated by electrophoresis on agarose gel and quantified using a densitometer. RESULTS: Were found a significant increase the total alkaline phosphatase activity in both pathologic groups (p < 0.05 in ARI and p < 0.01 in CRF). Isoenzymatic profiles showed: increase of the bone fraction (p < 0.05 in ARI and p < 0.001 in CRF), decrease of the liver isoenzyme (p < 0.001) in both groups, macromolecular fraction elevated in acute patients (p < 0.05) and a significant increase of the intestinal and intestinal variant isoenzyme in the chronic patients (p < 0.001). CONCLUSION: The renal insufficiency modified the normal distribution of alkaline phosphatase isoenzymes and the study of their serum levels could be an effective non-invasive marker, for the evaluation of bone disease and intestinal disorders associated with renal failure.

Pharmacokinetics of ciprofloxacin as a tool to optimise dosage schedules in community patients.

OBJECTIVE: To evaluate the dosage regimens of ciprofloxacin prescribed for outpatients by applying the principles of antibacterial therapy. DESIGN: Retrospective analysis of prescription and demographic data. SETTING: Community pharmacy in Valladolid, Spain. PATIENTS: Fifty male and female patients aged 18-93 years and with bodyweight 41-95kg. METHODS: Prescribed dosage regimen, age, weight, height, type of infection, comorbidity and coadministered drugs were recorded for each patient. Plasma concentration curves were simulated from literature values of the pharmacokinetic parameters of the drug and the age and weight of the patients. Urine concentrations were estimated from simulated plasma concentrations, literature values of renal clearance and an average urinary flow rate of 2 L/day. The potential efficacy of the prescribed treatment was evaluated from the ratio of the simulated peak plasma concentration (C(max)) to the literature value of the minimum inhibitory concentration (MIC) for the bacterium most probably responsible for the infection (C(max) /MIC). The ratio of area under the plasma concentration-time curve over 24 hours to MIC (AUC24 /MIC) was also estimated for non-urinary infections. RESULTS: Demographic variables such as age or bodyweight do not seem to be taken in consideration when ciprofloxacin is prescribed, at least in the patients considered here, leading to wide interindividual variability in plasma concentrations. This may not be relevant for urinary infections, since ciprofloxacin concentrates in the urine, leading to high Cmax /MIC ratios in all patients. Simulated plasma concentration-time curves revealed consistent underdosing for systemic infections in young patients over 60kg, for whom the plasma concentrations achieved led to Cmax /MIC and AUC24 /MIC ratios lower than those associated with clinical efficacy and minimal spread of bacterial resistance. CONCLUSIONS: The standard regimen of ciprofloxacin 250mg every 12 hours prescribed for urinary infections may not be the best choice, since a more convenient regimen of 500mg once daily leads to a higher Cmax /MIC ratio, which is associated with a more significant postantibiotic effect and higher efficacy of fluoroquinolones. For non-urinary infections, the age and weight of patients should be taken into account to achieve optimum plasma concentrations.

Isoenzimas de fosfatasa alcalina en el suero de pacientes con insuficiencia renal / Alkaline phosphatase isoenzymes in the serum of patients with renal insufficiency

Objetivo: estudiar la utilidad clínica de la determinación sérica de las isoenzimas de fosfatasa alcalina en pacientes con insuficiencia renal.Material y métodos: se midieron las isoenzimas de fosfatasa alcalina en un grupo de 58 pacientes: 22 con insuficiencia renal aguda (IRA) y 36 con fallo renal crónico (IRC) y sometidos a hemodiálisis, comparándose los resultados con los de una población de 30 adultos sanos. Las isoenzimas intestinal, ósea, hepática, macromolecular e intestinal variante se separaron por electroforesis sobre gel de agarosa, cuantificándose por densitometría. Resultados: la actividad total de fosfatasa alcalina se mostró significativamente aumentada en ambos grupos patológicos (p<0,05 en IRA y p<0,01 en IRC). Los perfiles isoenzimáticos mostraron: un incremento de la fracción ósea (p<0,05 en IRA y p<0,001 en IRC), descenso de la fracción hepática (p<0,001) en ambos grupos, fracción macromolecular aumentada en pacientes con IRA (p<0,05) y un aumento significativo de la fracción intestinal e intestinal variante en pacientes con IRC (p<0,001).Conclusión: la insuficiencia renal modifica la distribución sérica de isoenzimas de fosfatasa alcalina, su cuantificación podría servir de marcador, no invasivo, para valorar las complicaciones óseas e intestinales asociadas al fallo renal. (AU)

Pharmacokinetic/pharmacodynamic modelling of ciprofloxacin 250 mg/12 h versus 500 mg/24 h for urinary infections.

A simulation study was performed to evaluate and compare the standard dosage regimen of 250 mg/12 h versus 500 mg/24 h of ciprofloxacin for the treatment of urinary tract infections (UTIs). Pharmacokinetic parameters reported for healthy young and old individuals were used for the simulation of drug levels in urine, at different mean urine flow rates (1-2.5 L/day). Pharmacokinetic/pharmacodynamic analysis of the results revealed that 500 mg ciprofloxacin once a day produced a more favourable profile in urine than 250 mg/12 h, particularly in the elderly, due to the slower elimination of the drug in this group of patients. Circadian rhythms were also considered for the simulation of drug levels in urine. According to the results, 500 mg once a day administered in the morning would be a better choice than 250 mg/12 h at least for uncomplicated UTI; nevertheless, clinical assays are needed to prove this hypothesis.

Atención farmacéutica en antibioterapia: fluoroquinolonas / Antibiotherapy pharmaceutical care: fluoroquinolones

El incremento progresivo de microorganismos resistentes causantes de infecciones de difícil tratamiento ha llevado a la implantación de diversos programas destinados a evitar el abuso y mal uso de los antibióticos, al ser ésta una causa directamente relacionada con la aparición de resistencias. El objetivo de este estudio ha sido el de evaluar las pautas posológicas de las fluoroquinolonas prescritas en el ámbito comunitario en relación con su potencial eficacia, así como establecer un protocolo de actuación farmacéutica destinado a prevenir y evitar los PRMs más probables para este grupo de fármacos. Para ello se ha aplicado una metodología, previamente descrita, basada en la simulación de curvas de niveles de fármaco en sangre u orina considerando la variabilidad famacocinética asociada a las características demográficas de los pacientes. Los resultados obtenidos demuestran que las pautas de dosificación prescritas corresponden a unos estándares preestablecidos, independientemente de la edad o peso del paciente para el que se prescribe la quinolona. En consecuencia, las concentraciones de fármaco simuladas difieren significativamente de unos casos a otros, lo que puede no tener trascendencia clínica en infecciones urinarias debido a las altas concentraciones alcanzadas en orina, pero sí en infecciones de otro tipo, ya que los niveles en plasma simulados para ciprofloxacino son, en algunos casos, inferiores a los recomendados para optimizar la eficacia del tratamiento y minimizar la aparición de resistencias (AU)

Progressive resistance emergence responsible for infections with complicated treatments has lead to the establishment of different types of programs aimed at controlling the misuse of these drugs since the latter has been related to the emerging resistance. The aim of this study was to evaluate the dosage patterns of the fluoroquinolone prescriptions for the community patients in relation with its potential efficacy as well as to establish a protocol to be applied at the community pharmacy to avoid the most probable FRM for this group of drugs. The methodology used has been previously described and, briefly, it consists in the simulation of the urine and plasma drug levels taking into account the variability in pharmacokinetics, according to the demographics of the patient.The results show that a standard dosage pattern is prescribed with no consideration of the age and body weight, leading to a significant inter-variability in the simulated levels of the drug. This may not show clinical implications for urinary infections since these drugs concentrate in urine and reach sufficiently high values in this fluid. Nevertheless, despite urine levels simulated plasma concentrations of ciprafloxacin are in some cases lower than the recommended values for improving efficacy and reducing resistance emergence (AU)

[Isoamylases and isolipases values in the serum from patients wtih renal insufficiency]. / Valoración de isoamilasas e isolipasas en el suero de pacientes con insuficiencia renal.

OBJECTIVE: The aim of this study is to test the utility os serum isoamylases and isolipases as determined from patients with renal insufficiency. MATERIAL AND METHODS: Serum levels of isoamylases and isolipases were determined in a group of sixty-eight patients with renal disease, 32 of them suffering acute insufficiency and 36 with chronic renal failure undergoing regular hemodialysis, results obtained were compared from a population of 44 healthy adults. We used a new method for isolipases determination in serum based on its separation on agarose gel. Two forms of lipase, L1 and L2, were identified by this method and quantitated by densitometry. RESULTS: Were found a significant increase of pancreatic isoamylase P2 and P/S isoenzymatic ratio in acute patients (p < 0.001) as chronic (p < 0.05). In both groups, the isolipase L1 activity and L1/L2 isoform ratio were showed significantly elevated (p < 0.01). We studied the relationship between isoamylases and isolipases establishing the P2/L2 ratio (normal range < 0.6) showing, in the two pathologic groups, significantly elevated values compared with the control group (p < 0.001) and a positive and significant correlation between the P2/L2 and P/S isoform ratios (r = 0.76, p < 0.05 in acute patients; r = 0.58, p < 0.05 in chronic patients). CONCLUSION: The combined study of serum levels of isoamylases and isolipases could be an effective marker for diagnosis and evolution of associated pancreatitis with acute or chronic renal failure.

Valoración de isoamilasas e isolipasas en el suero de pacientes con insuficiencia renal / Isoamylases and isolipases valoration in the serum from patients with renal insufficiency

Objetivo: Estudiar la utilidad clínica de la determinación de isoamilasas e isolipasas en el suero de pacientes con insuficiencia renal.Material y métodos: Determinamos los niveles séricos de isoamilasas e isolipasas en un grupo de 68 pacientes con enfermedad renal, 32 con insuficiencia aguda y 36 con fallo renal crónico y sometidos a hemo diálisis, comparándose los resultados con los de una población de 44 adultos sanos. Utilizamos un nuevo método para la determinación sérica de isolipasas basado en su separación electroforética sobre gel de agarosa. Dos formas de lipasa, L1 y L2, fueron identificadas por este método y cuantificadas por densitometría.Resultados: Encontramos un aumento significativo de la isoamilasa pancreática P2 y del cociente isoenzimatico P/S tanto en los pacientes agudos (p<0,001) como en los crónicos (p<0,05). En ambos grupos la actividad de la isolipasa L1 y el cociente L1/L2 se mostraron significativamente elevados (p<0,01). Estudiamos la relación entre isoamilasas e isolipasas estableciendo el cociente P2/L2 (rango normal <0,6) encontrando, en los dos grupos patológicos, valores significativamente elevados respecto al grupo control (p<0,001) y una correlación positiva y estadísticamente significativa entre los cocientes P2/L2 y P/S (r=0,76, p<0,05 en pacientes agudos; r = 0,58, p<0,05 en crónicos).Conclusión: El estudio combinado de isoamilasas e isolipasas séricas podría ser un marcador efectivo para el diagnóstico y evolución de la pancreatitis asociada al fallo renal agudo o crónico (AU)

[Alkaline phosphatase isoenzymes in serum and bronchoalveolar lavage from patients with bronchopulmonary disease]. / Isoenzimas de fosfatasa alcalina en el suero y lavado broncoalveolar de pacientes con patología broncopulmonar.

OBJECTIVE: In this study, we are looking at the principal isoenzymes of alkaline phosphatase (ALP), as injury markers of cellular membranes from bronchial epithelium, in 80 patients diagnosed with bronchopulmonary pathology from different ethology, using serum samples and bronchoalveolar lavage fluid (BAL). METHOD: Patients were grouped according to age as following: 26 preterm neonates suffering respiratory distress syndrome requiring mechanical ventilation; 32 children ranging from 2 to 12 years old, and 22 adults (30-65 years old) examined by bronchoscopy for the purpose of diagnosis. Results obtained from all pathological groups were compared with a control group showing similar characteristics. Isoenzymes were separated by electrophoresis on agarose gel and were quantified by desitometry. Total protein was measured in BAL; ALP activity was expressed in UI/mg x 10-3 of protein. RESULTS: We found that macromolecular ALP fraction was significantly increased in the serum of neonates with distress (p < 0.01), in the patients 2-12 years and adults affected by pulmonary pathology (p < 0.001). The electrophoresis of ALP isoenzymes showed a unique isoenzymatic band corresponding with its macromolecular fraction in the BAL fluid. CONCLUSIONS: We conclude that increased macromolecular fraction of alkaline phosphatase found in the serum of patients diagnosed with respiratory problems could have its origin in damaged pulmonary tissue.

Isoenzimas de fosfatasa alcalina en el suero y lavado broncoalveolar de pacientes con patología broncopulmonar / Alkaline phosphatase isoenzymes in serum and bronchoalveolar lavage from patients with bronchopulmonary disease

Objetivo: Se estudiaron las principales isoenzimas de la fosfatasa alcalina (ALP) como marcadores de lesión de las membranas celulares del epitelio bronquial, utilizando suero y líquido procedente del lavado broncoalveolar (LBA), en 80 enfermos con patología broncopulmonar de etiología diversa. Método: Los enfermos se clasificaron, atendiendo a su edad, en tres grupos, comparándose los resultados de cada grupo patológico con un grupo control de características similares: 26 recién nacidos prematuros, con distress respiratorio grave, que precisaron ventilación mecánica; 32 niños entre 2-12 años con broncopatía obstructiva y 22 adultos (30-65 años) sometidos a broncoscopia y LBA con fines diagnósticos. Las isoenzimas se separaron por electroforesis sobre gel de agarosa y se cuantificaron por densitometría. En el LBA se midieron proteínas totales, expresándose la actividad de ALP en UI/mg de proteína ¥ 10-3. Resultado: Encontramos la fracción macromolecular de ALP significativamente aumentada en el suero de los neonatos con distress (p<0,01), en los enfermos de 2-12 años y en los adultos patológicos estudiados (p<0,001). La electroforesis de isoenzimas de ALP en el LBA mostró una única banda isoenzimática, correspondiente a su fracción macromolecular. Conclusiones: El aumento de la fracción macromolecular de la ALP en el suero de los enfermos con problemas respiratorios podría tener su origen en el tejido pulmonar dañado. Fosfatasa Alcalina. Isoenzimas. Enfermedad Broncopulmonar. Lavado Broncoalveolar (AU)

[Creatine kinase BB activity in the serum and bronchial aspirate of preterm newborns with respiratory distress syndrome]. / Actividad de la isoenzima CKBB en suero y broncoaspirado de recién nacidos pretérmino con síndrome de distrés respiratorio.

OBJECTIVE: The aim of this study was to test the utility of serum creatine kinase (CK) isoenzyme determinations as a marker of tissue injury in preterm newborns with respiratory distress syndrome (RDS). PATIENTS AND METHODS: Two groups of neonates were studied, 26 suffering from RDS who required mechanical ventilation and 20 healthy newborns with gestational ages, hours of life and birth weights similar to the first group. The activity of CK and its isoenzymes was determined in the bronchial aspirate and serum samples that were obtained before and 24 hours after exogenous surfactant therapy. The isoenzymes were separated by electrophoresis on agarose gel and their activity expressed as a percentage of the total CK. Total proteins were quantified in the bronchial aspirate and CK enzymatic activity expressed in U/mg of protein x 10-3. RESULTS: The CK-BB isoenzyme was significantly increased (p < 0.001) in the serum of infants with RDS compared with the control group. In the bronchial aspirate, the isoenzymatic study showed that the CK-BB isoenzyme represented 98-100% of the total enzymatic CK activity. CONCLUSIONS: The study shows significant differences in the CK isoenzyme patterns of neonates with RDS compared to controls. An increase in serum levels of the CK-BB isoenzyme could be an effective marker of tissue injury in lung disease in the newborn.

[Serum creatine kinase MM isoforms and lactate dehydrogenase isoenzymes in patients with non-traumatic acute rhabdomyolysis]. / Isoformas de creatin quinasa-MM e isoenzimas de lactico deshidrogenasa en el suero de pacientes con rabdomiolisis aguda no traumática.

We studied lactate-dehydrogenase (LD) isoenzymes and creatinekinase MM (CKMM) isoforms MM1, MM2 and MM3, in the serum of 18 patients with nontraumatic acute rhabdomyolysis, to test the utility of these markers in the diagnosis and disease evolution. The isoenzymes were separated by electrophoresis on agarose gel and were quantified with a densitometer. We studied the correlation between CKMM isoforms calculating the MM3/MM1 ratio, establishing the reference values from control group of 36 healthy adults. MM3 and MM3/MM1 ratio values were significantly increased in patients with rhabdomyolysis (p < 0.001) and progressively decreased coinciding with signs of getting better, showing 10 days after similar values of control group. LD4 and LD5 isoenzymes were significantly increased (p < 0.001) keeping elevated until 8-10 days when they showed a significant decrease compared with admission values (p < 0.05) but keeping elevated respect to control (p < 0.01).

[Lactate dehydrogenase isoenzymes in the serum and bronchial aspirate of newborn infants with respiratory difficulty of different etiologies]. / Isoenzimas de lactato deshidrogenasa en el suero y aspirado bronquial de recién nacidos con dificultad respiratoria de etiología diversa.

OBJECTIVE: To study the usefulness of lactate dehydrogenase isoenzymes serum determination as tissue injury markers in newborns with respiratory distress. DESIGN AND METHODS: Ninety four neonates were studied and classified in two groups: 64 suffering various types of respiratory problems, and 30 healthy newborns of a similar birth weight and gestational age. LDH activity and its isoenzymes was determined in the serum of all the infants and in 23 samples of the bronchial aspirate of infants who required ventilation support. The isoenzymes were separated by electrophoresis on agarose gel and their activity was expressed as percentage of the total LDH. RESULTS: LDH1 and LDH2 isoenzymes were decreased, and LDH4 and LDH5 isoenzymes were significantly increased (p > 0.001) in infants serum with respiratory distress, compared with controls. We compared LDH isoenzymes values found in bronchial aspirate with their values found in serum of ventilate infants, and we found a significant levels of LDH2 and LDH3 were lower, and those of LDH5 were higher (p < 0.001) in bronchial aspirate than in serum and a positive correlation (r = 0.47, p < 0.01) between LDH5 values in both samples. CONCLUSIONS: The study shows significantly differences in the LDH isoenzyme profiles of neonates with respiratory distress compared with controls. The increase in serum of LDH4 and particularly of LDH5 isoenzymes could be an effective marker of tissue damage in lung disease in the newborn.

[Serum CK-BB. A biochemical marker in neonatal necrotizing enterocolitis]. / CK-BB sérica. Marcador bioquímico en la enterocolitis necrotizante neonatal.

OBJECTIVE: We performed a prospective study of 72 preterm neonates with high-risk predisposing them to necrotizing enterocolitis (NEC) in which isoenzyme CK-BB activity in serum was measured at birth and after establishment of feeding with the purpose being to investigate whether CK-BB isoenzyme measurement may be useful in the diagnosis of NEC and an efficient marker in the evolution of the disease. DESIGN AND METHODS: In 12 neonates with NEC, CK-BB was measured in serum, at the beginning of symptoms and every 48 hours until remission of the acute episode. Control data were obtained from 26 healthy preterm and 20 preterm neonates with diarrhoea of several etiologies. Fourteen infants were excluded from the study due to complications. Electrophoresis on an agarose gel was used determine CK isoenzymes and these are expressed as the percentage of total CK activity. RESULTS: There were no differences in CK-BB values between the control groups. At the beginning of symptoms, the CK-BB in serum was significantly greater in neonates with NEC (p < 0.001) than in the control groups and were continuously elevated until complete recovery from NEC. CONCLUSION: The CK-BB was shown as a useful marker in the diagnosis and evolution of NEC.

[Pulmonary hypoplasia in the newborn infant]. / Hipoplasia pulmonar en el recién nacido.

Incidence of pulmonary congenital malformations is studied among 46,966 babies born in a twelve year period, with special reference to 27 cases of pulmonary hypoplasia. 59.25% of these newborns were males and only 51.89% of them were born at term with normal weight. 74.0% of mortality took place in the first day of life. Hypoplasia was bilateral in 59.25% of cases and associated to other malformations in 96.29%.