KRAS mutation analysis: a comparison between primary tumours and matched liver metastases in 305 colorectal cancer patients.

BACKGROUND: KRAS mutation is a negative predictive factor for treatment with anti-epidermal growth factor receptor antibody in metastatic colorectal cancer (CRC). KRAS mutation analysis is usually performed on primary tumour tissue because metastatic tissue is often not available. However, controversial data are available on the concordance of test results between primary tumours and corresponding metastases. We assessed the concordance of KRAS mutation status in a study of 305 primary colorectal tumours and their corresponding liver metastases. METHODS: Patients with histologically confirmed CRC who underwent surgical resection of the primary tumour and biopsy or surgical resection of the corresponding liver metastasis were included. KRAS mutation analysis was performed for codons 12 and 13. RESULTS: KRAS mutation was detected in 108 out of 305 primary tumours (35.4%). In 11 cases (3.6%), we found a discordance between primary tumour and metastasis: 5 primary tumours had a KRAS mutation with a wild-type metastasis, 1 primary tumour was wild type with a KRAS mutation in the metastasis, and in 5 cases the primary tumour and the metastasis had a different KRAS mutation. CONCLUSION: We observed a high concordance of KRAS mutation status of 96.4% (95% CI 93.6-98.2%) between primary colorectal tumours and their corresponding liver metastases. In only six patients (2.0%; 95% CI 0.7-4.2%), the discordance was clinically relevant. In this largest and most homogenous study to date, we conclude that both primary tumours and liver metastases can be used for KRAS mutation analysis.

[Acute intermittent porphyria and inappropriate ADH syndrome]. / Porfiria aguda intermitente y síndrome de secreción inadecuada de ADH.

A 44-year-old woman complained of abdominal pain of 4 days' duration accompanied by vomiting and painful urination. The admitting physician noted neurologic signs consistent with axonal polyneuropathy and hyponatremia. In the absence of other explanations for the syndrome, SIADH was diagnosed. Because of the nonspecific nature of the observations, the patient was assessed by various specialists and admitted to the anesthetic recovery unit due to worsening of neurologic signs and suspicion of acute intermittent porphyria. The diagnosis was confirmed by laboratory findings of elevated d-aminolevulinic acid and porphobilinogen levels and normal stool porphyrins. The patient improved with intravenous hematin infused over 4 days.

Porfiria aguda intermitente y síndrome de secreción inadecuada de ADH / Acute intermittent porphyria and aldehyde dehydrogenase deficiency

Presentamos el caso de una mujer de 44 años con uncuadro abdominal de cuatro días de evolución, acompañadode vómitos alimenticios y orina colúrica. Durantesu ingreso se asoció clínica neurológica, consistente polineuropatíaaxonal e hiponatremia que en ausencia deotras causas se diagnosticó de síndrome de secreción inadecuadade ADH. Fue valorada por diferentes especialistaspor la clínica inespecífica del cuadro e ingreso en launidad de reanimación, por empeoramiento de la clínicaneurológica y con la sospecha de porfiria aguda intermitente.El diagnóstico se verificó con los datos analíticos,ácido deltaaminolevulínico y porfobilinógeno elevadoscon coproporfirinas en heces normal. Se instauró tratamientocon hematina intravenosa durante cuatro díascon mejoría del cuadro(AU)

A 44-year-old woman complained of abdominal pain of4 days’ duration accompanied by vomiting and painfulurination. The admitting physician noted neurologic signsconsistent with axonal polyneuropathy and hyponatremia.In the absence of other explanations for the syndrome,aldehyde dehydrogenase deficiency was diagnosed. Becauseof the nonspecific nature of the observations, the patientwas assessed by various specialists and admitted to theanesthetic recovery unit due to worsening of neurologicsigns and suspicion of acute intermittent porphyria. Thediagnosis was confirmed by laboratory findings of elevatedd-aminolevulinic acid and porphobilinogen levels andnormal stool porphyrins. The patient improved withintravenous hematin infused over 4 days(AU)

Morbilidad neonatal en el parto instrumentado / Neonatal morbidity in instrumental delivery

Introducción: El gran aumento en la utilización de diversos tipos de instrumentación obstétrica durante la extracción fetal, así como del número de cesáreas, es un tema muy controvertido en la actualidad. El objetivo de este trabajo es valorar la relación entre diferentes tipos de instrumentación y la incidencia de traumatismos obstétricos específicos. Población y métodos: Estudio de casos y controles, realizado sobre una muestra de estudio de 103 recién nacidos, en los que como diagnóstico al alta figuró alguno de los relacionados con traumatismos perinatales: cefalohematoma, hemorragia subaponeurótica, subaracnoidea, epidural, subdural, parenquimatosa, fractura de clavícula y parálisis braquial. Resultados: El vacuum fue el instrumento más utilizado, y constituyó un factor de riesgo respecto a la cesárea en la producción de cefalohematomas, hemorragias subgaleales, subaracnoideas, subdurales y fracturas de clavícula. Discusión: El vacuum es, en números absolutos, el instrumento que se asocia a un mayor número de traumatismos. El alto porcentaje de traumatismos con el vacuum podría estar relacionado con el elevado número de inducciones que terminan en vacuextracción, lo que hace suponer que la modalidad de parto (espontáneo frente a inducido) es un factor esencial, asociado a la morbilidad del expulsivo; pero hay otros factores significativos además de las inducciones, como el tipo de campana usada durante la vacuextracción, el peso fetal, la anestesia epidural y la maniobra de Kristeller

Introduction: The marked increase in the use of diverse types of obstetric instrumentation during fetal delivery, as well as in the number of cesarean sections, is currently a highly controversial topic. The objective of this report is to assess the relationship between different types of instruments and the incidence of specific obstetric injuries. Population and methods: Study of cases and controls, carried out in a study sample of 103 newborns with a discharge diagnosis of perinatal trauma, such as cephalhematoma, subgaleal hemorrhage, subarachnoid hemorrhage, epidural hemorrhage, subdural hemorrhage, cerebral hemorrhage, clavicular fracture and brachial plexus injuries. Results: The vacuum extractor was the most widely used instrument, and is considered to be a risk factor with respect to cesarean section in the provocation of cephalhematoma, subgaleal hemorrhage, subarachnoid hemorrhage, subdural hemorrhage and clavicular fracture. Discussion: The vacuum extractor is also, in absolute numbers, the instrument associated with a greater number of traumas. The high percentage of traumas produced with the vacuum extractor could be related to the high number of inductions that end in vacuum extraction. This fact suggests that the modality of delivery (spontaneous versus induced) is an essential factor, associated with perinatal morbidity, but that there are other important factors besides induction, including the type of cup used during vacuum extraction, fetal weight, epidural anesthesia and Kristeller’s maneuver

Morbilidad neonatal en el parto instrumentado: mención especial a la ventosa obstétrica / Neonatal morbidity in instrumental delivery: special mention of the obstetric vacuum extractor

El aumento de las lesiones en el periparto, asociadas al cada vez más creciente uso de instrumentación, ha llevado a plantear en numerosas ocasiones intensos debates sobre las indicaciones y la problemática derivada de su cada vez mayor indicación en la práctica obstétrica diaria. El vacuum es un instrumento bastante seguro, de modo que las lesiones pueden existir, pero son mucho menos frecuentes con una correcta aplicación, y la gravedad de las mismas se ve influida no sólo por la instrumentación, sino también por una serie de factores que hay que tener en cuenta en el periparto, siendo uno de los principales el desarrollo de la vacuextracción. Entre la lesiones que nos encontramos asociadas al uso del vacuum aparecen desde algunas de elevada incidencia pero de escasa significación clínica como el cefalohematoma o el hematoma subgaleal, hasta otras de escasa frecuencia pero de extrema gravedad y riesgo vital para el recién nacido, como el hematoma epidural o el subdural

The rise in the incidence of injuries during childbirth associated with the increasingly widespread use of instrumentation has, on a number of occasions, led to intense debates on the indications and the problems derived from the extension of these indications in routine obstetric practice. Vacuum devices are fairly safe instruments. Thus, lesions can occur, but are much less common with a correct application, and their severity is influenced not only by the instrumentation, but also by a series of additional factors that must be taken into account during the delivery. One of the major ones is, of course, the development of vacuum extraction. The lesions associated with the use of vacuum devices range from those in which the incidence is high but the clinical significance is minor, such as cephalhematoma or the subgaleal hematoma, to others, like epidural or subdural hemorrhage, that are highly uncommon but are extremely serious and even life threatening for the newborn

Coloboma palpebral bilateral: una malformación ocular poco frecuente / Bilateral palpebral coloboma: an infrequent ocular malformation

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[Application of four ELISA techniques (two for IgM and two for IgG) for serological diagnosis of an outbreak of Q fever]. / Aplicación de cuatro técnicas de ELISA (dos para IgM y dos para IgG) en el diagnóstico serológico de un brote de fiebre Q.

OBJECTIVE: To evaluate four ELISAs (commercialized by Panbio and Serion) for IgM and IgG detection in an outbreak of Q fever. METHODS: Fifty-three serum samples corresponding to 29 persons were processed. An indirect immunofluorescence assay was used as the reference method. RESULTS: The sensitivity and specificity for IgM were 100% and 74% (Panbio), and 91% and 88% (Serion). IgG sensitivity was 72% (Panbio) and 89% (Serion). The specificity of both techniques for IgG was 97%. CONCLUSIONS: Both ELISAs seem to be good IgM screening methods for use during Q fever outbreaks.

Aplicación de cuatro técnicas de ELISA (dos para IgM y dos para IgG) en el diagnóstico serológico de un brote de fiebre Q / Application of four Elisa techniques (two for IgM and two for IgG) for serological diagnosis of an outbreak of Q fever

Objetivo. Evaluar cuatro técnicas de análisis de inmunoabsorción ligada a enzimas (ELISA) (comercializadas por Panbio y Serion) para la detección de inmunoglobulinas (IgM e IgG) en un brote de fiebre Q. Métodos. Se procesaron 53 muestras de suero correspondientes a 29 personas. El método de referencia fue inmunofluorescencia indirecta (IFI). Resultados. La sensibilidad y especificidad en la detección de IgM fueron del 100 y del 74% (Panbio) y del 91 y el 88% (Serion). La sensibilidad para IgG fue del 72% (Panbio) y del 89% (Serion). Las dos técnicas obtuvieron para IgG una especificidad del 97%. Conclusiones. Ambos ELISA parecen ser buenos métodos de cribado para la detección de IgM en brotes (AU)

Objective. To evaluate four ELISAs (commercialized by Panbio and Serion) for IgM and IgG detection in an outbreak of Q fever. Methods. Fifty-three serum samples corresponding to 29 persons were processed. An indirect immunofluorescence assay was used as the reference method. Results. The sensitivity and specificity for IgM were 100% and 74% (Panbio), and 91% and 88% (Serion). IgG sensitivity was 72% (Panbio) and 89% (Serion). The specificity of both techniques for IgG was 97%. Conclusions. Both ELISAs seem to be good IgM screening methods for use during Q fever outbreaks (AU)

[Culture-confirmed whooping cough in a tertiary center over a twelve-year period]. / Tos ferina confirmada por cultivo en un hospital terciario.

OBJECTIVE: To study the characteristics of patients diagnosed with whooping cough at a tertiary center in Barcelona, Spain. MATERIAL AND METHODS: We performed a retrospective study of patients aged less than 18 years treated for pertussis-like cough or clinically-suspected whooping cough over a 12-year period (1989-2000). Only patients with isolated Bordetella spp. were included. The variables of age, sex, vaccination status, hospitalization, clinical manifestations, severity, and lethality were analyzed. RESULTS: One hundred sixty-one patients with positive Bordetella spp. culture were identified. Of these, complete information was available in 149 (79 boys and 70 girls) with a median age of 3 months (range: 13 days-17 years); 77.2 % were aged 6 months or less. All the isolated strains corresponded to B. pertussis except three that corresponded to B. parapertussis. Three epidemic cycles (in 1989, 1992 and 2000) were observed during the study period. A total of 72.5 % of cases occurred between May and September. Bordetella spp. was associated with other bacteria in 28.2 % of the patients, viruses in 13.4 % and a bacterium and a virus in 4.7 %. One hundred twenty-one patients required hospitalization, of which 14.9 % were admitted to the intensive care unit. Age was the only factor associated with risk for hospitalization, which was more frequent in younger infants (p < 0.0001). Paroxysmal cough with cyanosis was present in 53.4 % of the patients, leucocytosis with lymphocytosis occurred in 67.5 % and apneas were present in 21.5 %. Chest X-ray revealed atelectasis in 34.1 %. The mean length of hospital stay was 11 days (range: 1-70 days). Three boys aged less than 3 months with malignant pertussis syndrome died (lethality: 2 %). More than half the patients (59.7 %) were not vaccinated (55.4 % for being under the age of 3 months) and only 16 % had received three or more vaccination doses. CONCLUSIONS: Whooping cough continues to be a severe disease in infants, with a high admission rate during the first 6 months of life. New preventive strategies are required to protect infants who have not yet developed full immunity to this infection.

Tos ferina confirmada por cultivo en un hospital terciario / Culture-confirmed whooping cough in a tertiary center over a twelve-year period

Objetivo: Estudiar las características de los pacientes diagnosticados de tos ferina en un hospital terciario de Barcelona. Material y métodos: Estudio retrospectivo de los pacientes menores de 18 años que han consultado por tos pertusoide o por sospecha clínica de tos ferina, durante un período de 12 años (1989-2000). Sólo se han incluido en el estudio los casos con aislamiento de Bordetella spp. Se han analizado las siguientes variables: edad, sexo, estado vacunal, hospitalización, manifestaciones clínicas, gravedad y letalidad. Resultados: Se identificaron 161 pacientes con cultivo positivo a Bordetella spp., pero sólo se dispone de información completa de 149 casos. Todas las cepas aisladas correspondieron a B. pertussis, excepto tres a B. parapertussis. Se observaron 3 ciclos epidémicos durante el período del estudio, correspondiendo a los años 1989, 1992 y 2000. El 72,5 por ciento de los casos se presentaron entre los meses de mayo y septiembre. Bordetella spp. se asoció a otras bacterias en el 28,2 por ciento de los pacientes, a virus en el 13,4 por ciento y a una bacteria y a un virus en el 4,7 por ciento. Los 149 pacientes, 79 varones y 70 mujeres, tenían una mediana de edad de 3 meses (límites, 13 días-17 años) y el 77,2 por ciento una edad igual o inferior a 6 meses. Requirieron hospitalización 121 enfermos, de los que el 14,9 por ciento ingresaron en la unidad de cuidados intensivos. La edad fue el único factor asociado al riesgo de hospitalización, superior en los lactantes más pequeños (p < 0,0001). Se presentó tos paroxística acompañada de cianosis en el 53,4 por ciento de los pacientes y leucocitosis con linfocitosis en el 67,5 por ciento; en el 21,5 por ciento se produjeron apneas. En la radiografía de tórax había imágenes de atelectasia en el 34,1 por ciento de los enfermos. La media de la estancia hospitalaria fue de 11 días (límites, 1-70 días). Fallecieron 3 varones menores de 3 meses de edad con un síndrome de tos ferina maligna (letalidad, 2 por ciento). El 59,7 por ciento de los pacientes no estaban vacunados (55,4 por ciento porque eran menores de 3 meses) y sólo el 16 por ciento habían recibido tres o más dosis de vacuna. Conclusiones: La tos ferina continúa siendo una enfermedad grave en el lactante y con un porcentaje elevado de hospitalización durante el primer semestre de la vida. Es necesario desarrollar nuevas estrategias preventivas para proteger a los lactantes que aún no han desarrollado inmunidad completa frente a esta infección (AU)

Expression of Tcf/Lef and sFrp and localization of beta-catenin in the developing mouse lung.

Recent evidence that Wnts and other genes in the Wnt signaling pathway are expressed in embryonic and adult mouse lung suggests that this pathway is important for cell fate decisions and differentiation of lung cell types. We therefore examined the expression and protein distribution of several Wnt pathway components during prenatal mouse lung development using whole-mount in situ hybridization and immunohistochemistry. Between embryonic days 10.5 and 17.5 (E10.5-E17.5), beta-catenin was localized in the cytoplasm, and often also the nucleus, of the undifferentiated primordial epithelium (PE), differentiating alveolar epithelium (AE; present from E14.5 onward), and adjacent mesenchyme. Tcf1, Lef1, Tcf3, Tcf4, sFrp1, sFrp2 and sFrp4 were also expressed in the PE, AE, and adjacent mesenchyme in specific spatio-temporal patterns.

Functional overexpression of wild-type p53 correlates with alveolar cell differentiation in the developing human lung.

At 15 weeks after conception (a.c.), the human pulmonary acinus is lined by distal low-columnar and more proximal cuboidal cells that are successive stages in alveolar type II cell differentiation (pseudoglandular period of lung development). From 16 weeks a.c. onward, there are also 'flatter' cells that are intermediate stages in the differentiation of cuboidal type II cells into squamous type I cells (canalicular period). We investigated the role of wild-type p53 protein and the proliferation marker Ki-67 in the differentiation of type II and type I cells in these two periods. Serial sections from fetal lungs (n = 30) were immunoincubated with antibodies against p53 and Ki-67. The presence of prospective type II and type I cells was confirmed using immunohistochemistry for surfactant protein SP-A as a differentiation marker and light and electron microscopy. The p53 and Ki-67 positive nuclei were quantified per alveolar cell phenotype (i.e., low-columnar; cuboidal; flatter). The occurrence of cell apoptosis was studied using propidium iodide (PI) and 4',6'-diamino-2-phenylindol dihydrochloride (DAPI) staining. The combined increase in p53 expression and decrease in Ki-67 expression during alveolar epithelial cell differentiation suggests that wild-type p53 protein plays a role in the differentiation of alveolar type II and type I cells in the human lung, and that this function is mediated through cell cycle arrest. The rare incidence of apoptotic nuclei in alveolar type II cells, together with their absence in alveolar type I cells, supports the view that p53 is involved in the differentiation, rather than the death, of alveolar epithelial cells.

Regulation of inhibin/activin subunits and follistatin mRNA expression in the rat pituitary at early estrus.

In the rat pituitary, activin stimulates whereas inhibin prevents FSH synthesis and secretion. Besides, the activin binding protein follistatin neutralizes the action of activin. The control of the FSH secondary surge at early estrus is not completely understood. To investigate the regulation of the inhibin/activin alpha-, betaA- and betaB-subunits and follistatin mRNA expression in the pituitary during the time of the FSH secondary surge, cyclic rats treated with LHRH antagonist (ANT) and ovine LH (oLH), progesterone (P), the anti-steroid RU486, adrenalectomy (ADX) or ADX plus corticosterone (B), were killed at early estrus. The serum concentrations of FSH were measured and the mRNA levels of the above mentioned transcripts were analysed and quantitated by using RNase protection assays. ANT abolished the FSH secondary surge and increased mRNA for alpha- and betaA-subunits and follistatin, but reduced that for betaB-subunit. Both oLH and P reversed these effects. RU486 blocked the effect of oLH on FSH levels and prevented the reduction in the mRNA for follistatin. ADX in ANT+oLH-treated rats reduced the serum FSH concentrations, enhanced mRNA for betaA- and betaB-subunits and, similar to RU486, blocked the drop in follistatin mRNA. Finally, replacement of B in ADX animals reversed these effects. These results demonstrate that, in the cyclic rat, the preovulatory secretion of LH and the surges of P and B on proestrus regulate the synthesis of inhibin/activin subunits and follistatin mRNA in the rat pituitary at early estrus, probably by reducing inhibin and follistatin and increasing activin. Moreover, these effects of LH, P and B at the pituitary level, together with the decrease in the amount of inhibin coming from the ovary, might be responsible for the occurrence of the FSH secondary surge.

Comparison of the effects of antiprogestins RU38486, ZK98299 and ORG31710 on periovulatory hypophysial, ovarian and adrenal hormone secretion in the rat.

The antiprogestin (AP) RU38486 (RU) blocks progesterone (P) and glucocorticoid (G) actions. Administration of 4 mg RU on proestrous morning to cyclic rats dissociates LH and FSH secretion on proestrous afternoon, early estrus and on estrous afternoon. In order to ascertain which action blocked by RU is predominant in the control of periovulatory LH and FSH secretion, a study was made on the effects of: a) 1 or 4 mg of ZK98299 (ZK) (type I P antagonist; Schering), b) 2 or 8 mg of Org31710 (OR) (type II P antagonist lacking anti-G actions; Organon) or c) 1 or 4 mg of RU (type II P antagonist; Exelgyn) to 4-day cyclic rats on proestrous morning on serum concentrations of LH, FSH, inhibin-alpha (I), estradiol-17beta (E), progesterone (P) and corticosterone (B) at 18:30 h on proestrus and at 02:00 and 18:30 h on estrus. Controls, receiving 0.2 ml oil, had elevated serum concentrations of all six hormones on proestrous afternoon; at early estrus, only serum concentrations of FSH and P remained elevated, and, on estrous afternoon, all hormones but I and B, that peaked again, had reached their lowest serum levels. All AP treatments except 1 mg ZK had the same effects. On proestrous afternoon serum LH concentrations were reduced and serum FSH concentrations were suppressed whereas serum levels of I, E, P and B were unaffected. At early estrus, basal serum concentrations of LH and E increased while FSH secretion was abolished. Serum levels of I, P and B did not differ from controls. AP treatments increased basal LH concentration, hyperstimulated FSH secretion and reduced serum I concentration on the afternoon of estrus. E, P and B serum levels did not differ from controls at this stage. Treatment with 1 mg ZK was less effective in reducing serum FSH on proestrous afternoon and at early estrus, and had no effect on serum concentrations of any hormone on estrous afternoon. These results indicate that blockade of P receptor activation by P is, predominantly, the mechanism of AP action on periovulatory gonadotropin secretion in rats.