PRL-3 is essentially overexpressed in primary colorectal tumours and associates with tumour aggressiveness.

Phosphatase PRL-3 has been involved in different types of cancer, especially in metastases from colorectal carcinoma (CRC). In this study, we explored both isoforms of PRL-3 as a biomarker to predict the recurrence of stage IIIB-C CRC. Overexpression of PRL-3 was investigated in primary human colorectal tumours (n=20) and hepatic metastases (n=36) xenografted in nude mice, samples characterised by absence of human non-tumoral cells, showing a high degree of expression in metastases (P=0.001). In 27 cases of matched normal colonic mucosa/primary tumour/hepatic metastases, PRL-3 overexpression occurs in primary tumours vs normal mucosa (P=0.001) and in hepatic metastases vs primary tumours (P=0.045). Besides, our results in a series of 80 stage IIIB-C CRC primary tumours showed that high levels of PRL-3 were an independent predictor of metastasis (P<0.0001; OR: 9.791) in multivariate analysis of a binary logistic regression and that PRL-3 expression tightly correlates with parameters of bad outcome. Moreover, PRL-3 expression associated with poor outcome in univariate (P<0.0001) and multivariate Cox models (hazard ratio: 3.322, 95%, confidence interval: 1.405-7.852, P=0.006). In conclusion, PRL-3 is a good marker of aggressiveness of locally advanced CRS and a promising predictor of distant metastases. Nevertheless, for prognosis purposes, it is imperative to validate the cutoff value of PRL-3 expression in a larger and consecutive series and adjuvant setting.

Möbius sequence, hypogenitalism, cerebral, and skeletal malformations in two brothers.

Two brothers born to a healthy, consanguineous Spanish couple have a syndrome of Möbius sequence with involvement of cranial nerves V, VI, VII, IX, and XII, central nervous system malformations; characteristic face with creased earlobes, short philthrum, and a short, arched upper lip, skeletal anomalies with short sternum and delayed bone maturation, hypogenitalism, and profound mental retardation. We suggest that this is a new multiple congenital anomalies condition and mental retardation (MCA/MR) syndrome with autosomic recessive inheritance.

Single aberrant umbilical artery in a fetus with severe caudal defects: sirenomelia or caudal dysgenesis.

We describe a 1,000-g twin fetus with absent kidneys and ureters, anal atresia and minimal evidence of external genitalia, and hypoplastic lower limbs with absent feet. A postmortem arteriogram showed a large single umbilical artery in direct continuation with the abdominal aorta, a unique anomaly almost always related to sirenomelia. We discuss the possible diagnosis of this case as sirenomelia or caudal dysgenesis, and the controversy as to whether they are two related or separate entities.

Localization of non-specific X-linked mental retardation gene (MRX73) to Xp22.2.

Clinical and molecular studies are reported on a family (MRX73) of five males with non-specific X-linked mental retardation (XLMR). A total of 33 microsatellite and RFLP markers was typed. The gene for this XLMR condition was been linked to DXS1195, with a lod score of 2.36 at theta = 0. The haplotype and multipoint linkage analyses suggest localization of the MRX73 locus to an interval of 2 cM defined by markers DXS8019 and DXS365, in Xp22.2. This interval contains the gene of Coffin-Lowry syndrome (RSK2), where a missense mutation has been associated with a form of non-specific mental retardation. Therefore, a search for RSK2 mutations was performed in the MRX73 family, but no causal mutation was found. We hypothesize that another unidentified XLMR gene is located near RSK2.

X-linked hydrocephalus: another two families with an L1 mutation.

X-linked hydrocephalus is a variable condition caused by mutations in the gene encoding for L1CAM. This gene is located at Xq28. Clinically the spectrum ranges from males with lethal congenital hydrocephalus to mild/moderate mental retardation and spastic paraplegia. Few carrier females show minimal signs of the syndrome. Although most cases are familial, de novo situations have been reported. We report two new families with the syndrome and a L1 mutation. Family 1 has two patients and family 2 a single patient. Clinical diagnosis in all three affected boys was beyond doubt. Prenatal testing through chorionic villus biopsy is possible only with a demonstrated L1 mutation. In lethal sporadic cases neuropathology is very important in order to evaluate for features of the syndrome. We stress the importance of further clinical reports including data on neuropathology and DNA analysis in order to further understand the mechanisms involved in this disorder.

[The effect of moderate intake of alcohol during pregnancy on the weight of the newborn]. / Efecto del consumo moderado de alcohol durante el embarazo sobre el peso del recién nacido.

BACKGROUND: There is currently no doubt concerning the detrimental effects of the intake of high doses of alcohol during pregnancy. Nonetheless, there has been some controversy regarding the effects of intake of low or moderate quantities of alcohol. The aim of the present study, carried out within the framework of a more extensive European study (EUROMAC), was to specifically analyze the relation between moderate intake of alcohol in pregnant women and the weight of the newborns. METHODS: A prospective cohort study including 1,005 women who attended prenatal consultation in the Hospital La Fe of Valencia between 12 and 18 weeks of pregnancy during 1989 was performed. All the subjects were asked on alcohol intake during the week prior to the interview with data on other sociodemographic and biologic variables being collected. Variance analysis was carried out to evaluate the association of the weight of the newborn with alcohol intake as well as with each of the control variables. Multiple lineal regression analysis was performed by the minimum squares method to evaluate possible effects of confusion and interaction. RESULTS: Following adjustment for parity, weight of the mother prior to pregnancy, sex of the newborn, age at pregnancy and tobacco consumption, only a slight reduction in the weight of the newborns was observed in the category of intake greater than 90 g/week, however this difference was not statistically significant. CONCLUSIONS: The low or moderate intake of alcohol during the first months of pregnancy has no detectable effect on fetal growth.

[Lip pits and Van der Woude syndrome. Description of a new familial case]. / Lip pits e sindrome di Van der Woude. Descrizione di un nuovo caso familiare.

The authors describe the case of a family in which two siblings affected by cleft palate and cheiloschisis were diagnosed as suffering from van der Woude's syndrome (VWS). The diagnosis was largely determined by the finding of mucous cysts (lip-pits) on the lower lip of the two patients and their mother. Classification as VWS enabled genetic counseling as to the risk of recurrence to be modified from multifactorial to autosomal dominant. The authors also consider aspects of differential diagnosis among van der Woude syndrome, pterygo -popliteal syndrome and labio or palatoschisis syndrome with filiform fusion of the eyelids.

Novel (60%) and recurrent (40%) androgen receptor gene mutations in a series of 59 patients with a 46,XY disorder of sex development.

BACKGROUND: Androgen receptor (AR) gene mutations are the most frequent cause of 46,XY disorders of sex development (DSD) and are associated with a variety of phenotypes, ranging from phenotypic women [complete androgen insensitivity syndrome (CAIS)] to milder degrees of undervirilization (partial form or PAIS) or men with only infertility (mild form or MAIS). OBJECTIVE: The aim of the study was to characterize the contribution of the AR gene to the molecular cause of 46,XY DSD in a series of Spanish patients. SETTING: We studied a series of 133 index patients with 46,XY DSD in whom gonads were differentiated as testes, with phenotypes including varying degrees of undervirilization, and in whom the AR gene was the first candidate for a molecular analysis. METHODS: The AR gene was sequenced (exons 1 to 8 with intronic flanking regions) in all patients and in family members of 61% of AR-mutated gene patients. RESULTS: AR gene mutations were found in 59 individuals (44.4% of index patients), of whom 46 (78%) were CAIS and 13 (22%) PAIS. Fifty-seven different mutations were found: 21.0% located in exon 1, 15.8% in exons 2 and 3, 57.9% in exons 4-8, and 5.3% intronic. Twenty-three mutations (40.4%) had been previously described and 34 (59.6%) were novel. CONCLUSIONS: AR gene mutation is the most frequent cause of 46,XY DSD, with a clearly higher frequency in the complete phenotype. Mutations spread along the whole coding sequence, including exon 1. This series shows that 60% of mutations detected during the period 2002-2009 were novel.

Nuclear IKK activity leads to dysregulated notch-dependent gene expression in colorectal cancer.

Nuclear functions for IkappaB kinase (IKK), including phosphorylation of histone H3 and nuclear corepressors, have been recently described. Here, we show that IKK is activated in colorectal tumors concomitant with the presence of phosphorylated SMRT (silencing mediator of retinoic acid and thyroid hormone receptor) corepressor that is aberrantly localized in the cytoplasm. In these tumors, IKKalpha associates to the chromatin of specific Notch targets, leading to the release of SMRT. Abrogation of IKK activity by BAY11-7082 or by expressing dominant negative IKKalpha restores the association of SMRT with Notch target genes, resulting in specific gene repression. Finally, BAY11-7082 significantly reduces tumor size in colorectal cancer xenografts (CRC-Xs) implanted in nude mice.

[Salmonellosis in children. II: management and follow-up (author's transl)]. / Salmonelósis en niños. II. Tratamiento y evolución.

The clinical records of 185 cases of Salmonellosis have been reviewed retrospectively, in order to study a relation between the evolution and the treatment given, so as to be able to determine the therapeutic criteria. 139 cases showed as gastroenteritis, 48 of which received antibiotic treatment and 91 did not. Statistic differences were observed in favour of the non treated cases where, the average time of hospitalization, the negative copro-cultive and the onset of complications were more favourable. All the cases with Tipho-Paratific fever were treated with antibiotics without finding any significant differences in the clinical evolution not withstanding the antibiotic used. The data here obtained is compared with that previously reported. According to the results a treatment planning is suggested.

[Salmonella infection in children. Epidemiological and clinical considerations (author's transl)]. / Salmonellosis en niños Parte I: Características epidemiológicas y clínicas.

An analysis of data on Salmonella infection treated at the Children's Hospital "La Fe", in Valencia, from 1974--75 is presentd. A patient population of 211 selected cases were divided into two groups: Gastroenteritis (GEC), 155 cases, and typhoid-paratyphoid fever (T-P F), 56 cases. Hospitalization was required in 79% of the cases. The following parameter were studied: Locality and district of origin with respect to residence, conditions of hygiene, size of family: age, sex, seasonal incidence, previous time of illness, presenting symptoms and physical sings and complementary studies. The following conclusions were obtained: Salmonella infection are and endemic problem in Valencia. Their incidence is maximal during the months of June to October. Epidemiological environment was positive in 15% of the cases. Higher morbidity in children less than two years of age. Most frequent presenting symptoms: Diarrhea, fever and vomiting as often in GEC as in T-P F. In 38.7% of GEC cases, the diarrhea was bloody; 21.9% of GEC cases began with fever. Salmonella paratyphi B was the agent most frequently responsible. Data concerning sex, family size, conditions of hygiene and white blood cells offer little discriminatory information. Results obtained are concordant with those described in the literature.

Subdural hematomas in neonates. Surgical treatment.

7 cases of acute subdural hematomas diagnosed and surgically treated during the first week of life are presented. 5 of them are alive and well at 6 and 7 months and 3, 4 and 6 years of follow-up. Free interval, raised intracranial pressure, lateralizing signs, fall of hematocrit and presence of blood in CSF were constant. Subdural puncture was negative in 6 cases, including a hemophilic patient (hemophilia B). Clinical diagnosis was ratified by means of neuroradiological procedures. The authors conclude that craniectomy is the treatment of choice and subdural tapping a useless procedure.

[Spontaneous resolution of a congenital depressed skull fracture]. / Fractura hundimiento craneal congénita con resolución espontánea.

Congenital depressed skull fracture is rare and in most cases its etiology remains unclear. We present a female newborn infant with a congenital depressed skull fracture and no evidence of antepartum or intrapartum traumatism. The baby had normal neurological status and the depressed fracture healed spontaneously in a few weeks. Based on our experience of this case and a literature review, we conclude that congenital depressed skull fractures should be managed conservatively if the skull depression is less than 2cm, there is no previous trauma, no local edema or hematoma, and if the neonate shows normal neurological status.

Urethral obstruction sequence and lower limb deficiency: evidence for the vascular disruption hypothesis.

We reviewed five unreported examples and 23 previously reported cases of urethral obstruction sequence with associated lower limb deficiency. There was no evidence of amniotic bands or exposure to vasoactive drugs during pregnancy in any case. In three infants a gangrenous lesion at the distal part of the affected leg was found; in another three infants, necrotic tissue was noted in the stump of the affected leg. This type of lesion can be explained only on a vascular ischemic basis. In five cases, signs of compression of the external iliac artery by the grossly distended bladder, by grossly distended ureters, or both were found. A vascular disruption in the territory of the external iliac artery caused by compression by the distended urinary tract is the proposed mechanism for the associated limb deficiency.

Non-immunological hydrops fetalis and intrapericardial teratoma: case report and review.

A large intrapericardial teratoma was found at necropsy in a 38-week stillborn fetus, in which prenatal diagnosis of hydrops fetalis and an echogenic cardiac mass had been made. Clinical and pathological data are reported. In utero intrapericardial teratomata lead to different outcomes depending on whether fetal hydrops is associated. When generalized fetal hydrops is not present, the outcome is good, even in cases with large pericardial effusions. When generalized fetal hydrops occurs, it often results in a poor outcome. In our literature review, we have found eight perinatal deaths in nine similar cases reported.