Thanatophoric dysplasia type II with encephalocele and semilobar holoprosencephaly: Insights into its pathogenesis.

Thanatophoric dysplasia (TD) is a lethal form of short-limb skeletal dysplasia that is associated with macrocephaly, and variably cloverleaf skull. Two types of TD are clinically recognized, TD1 and TD2, mainly distinguished by their radiographic characteristics. The differences between the two are principally observed in the femur, which appears curved in TD1, while it remains straight but with a proximal medial spike in TD2, and are a less severe overall affectation in TD2. Both types of TD are caused by mutations in different functional domains of the FGFR3 gene. However, whereas several mutations in the different domains of FGFR3 cause TD1, the K650E mutation involving the change of a lysine to glutamic acid ("Lys650Glu") has been found in all TD2 cases to date. Here we describe a newborn infant with TD2 associated with brain defects that have either been infrequently observed (encephalocele) or not hitherto described (holoprosencephaly). Based on recent studies, we consider encephaloceles described in TD to be pseudoencephaloceles, since they are secondary to the intracranial pressure generated by severe hydrocephaly and to severe cranial structural anomalies. Finally, to analyze the mechanisms of holoprosencephaly observed in the case described here, we include a concise review on the current understanding of how FGFs and their receptors are expressed in the rostral signaling center (particularly Fgf8). In addition, we evaluated recent observations that FGF ligands and receptors (including FGFR3) act in concert to organize the whole telencephalon activity, rather than independently patterning different areas.

[Incidence and mortality due to cancer in Navarre, 1998-2002. Trends in the last 30 years]. / Incidencia y mortalidad por cáncer en Navarra, 1998-2002. Evolución en los últimos 30 años.

Between 1998-2002, 16,952 new cases of cancer were registered in Navarre. In men, the most frequently diagnosed cancers were in the following order: prostate, lung, colon and rectum, bladder and stomach, which accounted for 63.2%. In women, the sites were breast, colon and rectum, corpus uteri, stomach and ovary, which accounted for 57.6% of the cases. In the same period, 1998-2002, 4,127 men and 2,470 women died from cancer. Sixty percent of all deaths due to malign tumours in men were due to cancer of the lung, prostate, colon and rectum, stomach and bladder. In women this was due to cancers of colon and rectum, breast, stomach, pancreas and lung, which accounted for 49% of the cases. In men in Navarre there has been an increase in the incidence rates of cancer of the prostate, kidney and non-Hodgkin lymphoma. Avoidable cancers such as those related to smoking (lung, oral cavity and pharynx or pancreas) continue to rise, and represent a greater global risk of dying from cancer in the latest period studied than in the decades of the 1970s and 1980s. From 1995 up to the present, mortality due to cancer has moved from occupying the second place to become the first cause of death among men in Navarre. The global risk of death due to cancer in men is now equal to the first period studied, 1975-1977. Amongst women the global risk of death due to cancer fell by 25% between 1975 and 2002, basically at the cost of breast and stomach cancer. Tumours related to smoking increased both in mortality and in incidence and appear as a significant health problem amongst women in Navarre. Breast cancer has increased in incidence, with lower mortality figures than those of the first period 1975-1977. Invasive cancer of the cervix remains at very low rates in comparison with many European countries, including Spain. In both sexes colorectal and skin cancer has increased, while the incidence and mortality of stomach cancer continues to fall.

Threonines at position 174 and 235 of the angiotensinogen polypeptide chain are related to familial history of hypertension in a Spanish-Mediterranean population.

This study investigates the association between the allelic distribution of two polymorphisms of the angiotensinogen (AGT) gene (T174M and M235T in the polypeptide chain) and blood pressure (BP) in a Mediterranean population in the south-west of Europe. The sample consists of 1322 participants from urban and rural areas, from the province of Albacete (218,462 inhabitants), located in the south-east of Spain. The subsample of this study, adjusted by age (over 18 years old) and sex, consists of 401 individuals. A case-control study is conducted which analyses 205 individuals from the group with the highest BP (fifth quintile) and 196 from the group with the lowest BP (first quintile). In addition, a comparative and associated analysis of these polymorphisms with BP level and family history of hypertension is carried out. The T174 allele proved to be more common in the fifth quintile group, although not statistically so. When the presence of threonine was analysed in both polymorphism positions (174 and 235), the TTTT genotype was found to be more common in the fifth quintile than in the first quintile. Moreover, the TTTT genotype was significantly more common in individuals with a family history of hypertension, indicating that it could be considered a predisposing factor to high BP in individuals from such families. In addition, the T174M-T235T genotype was more common in the first quintile group, and showed significant association (P=0.05) with the group that had no family history of hypertension.

Ovarian endometriosis and clear cell carcinoma, leiomyomatosis peritonealis disseminata, and endometrial adenocarcinoma: an unusual, pathogenetically related association.

A 42 year-old female with a preoperative clinical diagnosis of ovarian cancer underwent laparotomy which revealed leiomyomatosis peritonealis disseminata (LPD) in the peritoneum and omentum and a left ovarian endometriotic cyst associated with a clear cell carcinoma. A grade 1, superfically invasive villoglandular endometrial endometrioid adenocarcinoma was also found. Microscopically, the endometriotic cyst wall contained an extensive peripheral band-like condensation of stromal cells. These cells were strongly positive for alpha inhibin and may have been the hormonal source responsible for the induction of the simultaneous LPD and endometrial adenocarcinoma. It is proposed that endometriosis is not only a precursor of clear cell carcinoma but, through secondary hormonal induction of the surrounding ovarian stroma, may also provide a hormonal stimulus for diverse proliferative processes.

[Value of the expression of p21RAS, P53, Bcl-2 oncoproteins and Ki-67(MIB-1) antigen of cellular proliferation in the diagnosis and prognosis of thyroi]. / Aplicación de las oncoproteínas p21RAS, p53, Bcl-2 y del factor de proliferación celular Ki-67(MIB-1) en el diagnóstico y pronóstico de tumores tiroid.

INTRODUCTION: The thyroid gland is a good organ for the study of genetic alterations in tumoural development and progress. The study of oncogenes and antigens of cellular proliferation is of interest. MATERIAL AND METHODS: 36 cases of thyroid adenomas, 58 papillary carcinomas, 32 follicular carcinomas, 2 anaplastic carcinomas and 12 medullary carcinomas were selected. Clinical and histological prognostic factors were studied and an immunohistochemical study with Ki-67 (MIB-1), p53, Bcl-2 and p21 RAS antibodies was performed. RESULTS: The proliferative rate Ki-67 (MIB-1) showed statistical differences in adenomas and follicular carcinomas. The p53 protein did not appear in adenomas, but was shown in those carcinomas with bigger histological dedifferentiation. A relationship was also established with greater age, larger size and progression of the tumour. The Bcl-2 protein was high in the normal thyroid, in the adenomas and in the carcinomas, decreasing in correlation with histological dedifferentiation, and totally disappearing in the anaplastic carcinomas. In medullary carcinomas its disappearance was correlated with mortality. The intense expression of the p21 RAS protein in papillary carcinomas is statistically correlated with advanced clinical studies. CONCLUSIONS: The differences in the proliferative rate between adenomas and follicular carcinomas can be of help in differential diagnosis. The p53 manifestation and the loss of the Bcl-2 expression are correlated with the histological redifferentiation process. An intense manifestation of p21 RAS in papillary carcinoma is correlated with tumoural progression.

[Psoas muscle abscess. Description of a series of 19 cases]. / Absceso del músculo psoas. Descripción de una serie de 19 casos.

Abscess of the psoas muscle (PA) is every more frequently observed in recent years. The PA diagnosed in the authors' center over a period of 91 months are presented, analyzing the main clinical features, microbiologic causal agents, risk factors, treatment and the differences between primary and secondary PA. A total of 19 cases of which 14 were secondary PA (73.7%) and 5 primary PA (26.3%) were diagnosed. The main foci of infection of the former were the bone and the genitourinary tract, with intestinal infection being rare. The most frequent clinical data were lumbar pain with possible irradiation to the lower limb, fever, and leucocytosis with neutrophilia. Gram negative and enteric anaerobes were the bacteria most often identified, followed by Staphylococcus aureus and Mycobacterium tuberculosis. In a high percentage of patients (57.8%) a history of immunodeficiency was reported. In regard to treatment, surgical drainage was performed in 5 cases (26.3%), while ten cases (52.6%) were treated by DPCT. Four patients (21%) were exclusively treated with antibiotics. Recurrence was observed in three cases (15.3%) of the DPCT group requiring new drainage. Of all the cases, 18 were cured while one death occurred, being attributed to the underlying tumoral disease of advanced stage. The authors believe DPCT to be a good therapeutic option in both primary and secondary PA, thereby avoiding the risks of major surgery. In the cases with no underlying immunodeficiency the existence of secondary PA should be discarded as occurred in 7 out of 8 cases with no history of immunodeficiency in this series of patients.

Salivary duct carcinoma: clinicopathological and immunohistochemical studies.

Nine cases of salivary duct carcinoma were reviewed clinically, histologically and immunohistochemically, with special evaluation of biomarkers with prognostic significance (p53, Ki67, c-erbB-2 and DNA content). Eight tumours occurred in the parotid gland and one in the submandibular gland. The average age of the patients (8 males and 1 female) was 62.8 years (range = 47-74 years). Tumour size ranged from 1 to 6 cm (mean = 3.46 cm). Recurrences were found in 33.3% (3 patients), regional metastases in 44.4% (4 patients) and systemic metastases in 33.3% (3 patients). Three patients died of their disease (median survival = 12.3 months), one is alive with the disease (follow-up of 222 months) and 5 are alive without evidence of disease (mean follow-up of 75 months). p53 protein nuclear immunostaining was positive in 66.6% and c-erbB-2 overexpression was observed in 100% of the tumours. Ki 67 positivity ranged from 6.75% to 47.5% of tumour cells (mean = 21.3%). DNA aneuploidy was found in 4 tumours (44.4%) and DNA diploidy in 5 (55.5%). Our results seem to indicate that Ki67 immunostaining can be useful in the evaluation of the biological behaviour of these tumours, as well as the presence of a high proliferative index of aneuploid cells and the presence of distant metastases.

Fusocellular gonadal stromal tumour of the testis with epithelial and myoid differentiation.

We describe an unusual fusocellular gonadal stromal tumour with a benign behaviour in the left testis from a 16-year-old man. The neoplasm consisted of a non-encapsulated proliferation of irregularly arranged, fusiform cell bundles in fibrous connective tissue. The tumour cells contained a slightly infolded nucleus, some dilated rough endoplasmic reticulum cisternae, abundant filament bundles which connected to subplasmalemmal electron-dense bodies, pinocytotic vesicles and a discontinuous basal lamina. The intercellular spaces were narrow and the tumour cells were joined by desmosomes. These cells were immunoreactive for muscle actin, alpha-actinin and vimentin. Focal immunostaining for collagen type IV was observed around the cells. No immunoreactivity for keratins, desmin S-100 protein or XIIIa factor was found. The findings suggest that the tumour arose from the peritubular myoid cells.

[New etiopathogenic, diagnostic and therapeutic aspects in primary pulmonary hypertension]. / Nuevos aspectos etiopatogénicos, diagnósticos y terapéuticos en la hipertensión pulmonar primaria.

Primary Pulmonary Hypertension (PPH) is a rare disease of unknown aetiology that is diagnosed only when the underlying causing factors are undetermined. Usually is discovered in its late stage, when pulmonary vascular resistances are severely compromised and the pathologic changes already well developed, resulting in right heart failure and death within several years of the onset of symptoms. The data published in the last years have provided new insights into the disease knowledge. In this article currents concepts about aetiology, pathogenesis and open lung biopsy value are reviewed; clinical manifestations and diagnostic methods are described; the usefulness of medical treatment to improve quality of life in these patients, mainly anticoagulation and vasodilator therapy with high-dose nifedipine, and how lung transplantation has increasingly become an option for selected patients with PPH, is also analysed.

A quantitative approach to the classification of hypospermatogenesis in testicular biopsies for infertility.

Absolute counts of germ cells were performed in 110 testicular biopsy specimens from 59 patients with either idiopathic infertility or varicocele and in a series of five autopsy specimens from age-matched controls. The tubular diameter, thickness of the tubular wall, and density of Leydig cells were measured. The following patterns were identified by germ-cell counts in the biopsy specimens: normal cell population, mild decrease in germ cells with normal ratio of cell types, advanced hypospermatogenesis with abnormal ratio of cell types, and Sertoli cell only. This sequence of progressive hypospermatogenesis was remarkably similar in both series. A separate category of maturation arrest was not recognized. Cell counts also correlated between right- and left-sided samples from the same patient in both series of biopsies. Reduction of tubular diameter, thickening of the tubular wall, and increase in Leydig cell density were often seen in severe stages of germ-cell impairment, although with an irregular distribution.

[Peritoneal hydatidosis with fistulization into the sigmoid colon]. / Hidatidosis peritoneal fistulizada a sigma.

A case is presented of peritoneal hydatidosis with fistulization into the sigmoid in a patient who had previously undergone surgery for hepatic hydatidosis. The clinical picture made its debut as an alteration in intestinal habit followed by the appearance of diarrheic syndrome and expulsion of hydatid membranes. The natural history of peritoneal hydatidosis, its complications and therapeutic guidelines are discussed.

[Idiopathic varicocele in children]. / Varicocele idiopático en el niño.

The authors present their experience with ten children operated on for left-sided idiopathic varicocele over a period of seven years. The treatment was high ligature of the spermatic vein with a favorable outcome in all cases. The histology of the testes, seen in biopsy, demonstrated a variable degree of damage. For this reason the authors recommend that this operation should be done in childhood in order to avoid problems of subfertility or infertility in adult life.