Role of calcifying nanoparticle in the development of hyperplasia and vascular calcification in an animal model.

OBJECTIVE: Calcifying nanoparticles (NPs) have been detected recently in calcified human arterial specimens and are involved in the process of calcification. This study was designed to test the hypothesis that human-derived NPs could worsen the response to arterial endothelial injury and induce vascular calcification. METHODS: The right carotid artery of 24 New Zealand rabbits was injured with an angioplasty balloon. Animals were perfused intravenously with saline (100 mL) during the experiment and divided into three groups: group-A, control; group-B, exposed to NPs (2 mL) obtained from calcified aortic valves; and group-C, exposed to NPs (2 mL) and treated postoperatively with atorvastatin (2.5 mg/kg/24 h). At 30 days, both carotid arteries were removed and examined histologically. Blood measurements were monitored during the study. RESULTS: The intimal hyperplasia area was significantly larger in the injured right carotid artery compared with the left unoperated carotid artery in all groups. There was no significant variation in medial area between groups. Morphometrically, the intima/media ratio (IMR) was significantly higher in damaged carotids compared with controls. A significant increase of IMR was found in group-B (1.81 ± 0.41) compared with group-A (0.38 ± 0.59; p = .004) or group-C (0.89 ± 0.79; p = .035). Differences between groups C and A were not significant (p = .064). Calcifications were observed in six animals, all of which had been exposed to NPs (4 in group-B, 2 in group-C, p = .027). Plasma levels of cholesterol and triglycerides remained stable. CONCLUSIONS: This research confirms the ability of systemic inoculation of human-derived NPs to accelerate hyperplasia and stimulate calcification in localized areas of arteries previously submitted to endothelial damage, while it was harmless in healthy arteries. Atorvastatin was demonstrated to slow down this process.

[Gastrointestinal stromal tumors (GISTs): clinical aspects]. / Tumores de la estroma gastroinestinal (GIST): aspectos clínicos.

INTRODUCTION: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors in the gastrointestinal tract. One of their features is the expression of the c-KIT/CD117 receptor. AIMS AND METHODS: We will focus on describing the symptoms, clinical studies prior to diagnosis, histologic and immunohistochemical characteristics, as well as the progression of disease in a group of patients. RESULTS: Seventeen cases were diagnosed between December 1999 and April 2005. Mean age of patients was 64.5 (+/-11.9); 47% were women. Tumor location was as follows: 52.9% in the jejunum or ileum, 29.4% were gastric, 11.7% were in the duodenum, and 5.8% were located in the mesentery. Tumor size was 6.0 cm on average (+/-5.0); 47% were asymptomatic, and to a lesser degree caused abdominal pain or digestive bleeding; 94.1% of tumors expressed CD117. Most of them were discovered while performing a laparotomy or ultrasound scan; 94.1% of tumors were removed; 35.2% (6 out of 17) of patients suffering from GIST met consensus criteria for aggressive behavior. Over 25.6 months (+/-22.5) metastasis or tumor relapse occurred in 23.5% (4 out of 17) of patients--those with more frequent high-risk criteria, symptomatic and bigger tumors, and tumors not expressing CD117. The three patients with tumor relapse were prescribed imatinib mesylate. Three patients died because of the tumor, and four from other causes unrelated to GIST. CONCLUSIONS: GIST was diagnosed in around 12 cases per million a year. Its diagnosis was usually an incidental finding during a medical evaluation, and tumors were malignant in nearly one fourth of cases. We can predict its outcome depending on different aspects.

[Spermatic cord liposarcoma. Association with prostate cancer. Report of a case and review of literature]. / Liposarcoma de cordón espermático. Asociación con carcinoma de próstata. Comunicación de un caso y revisión de la literatura.

Spermatic Cord Liposarcoma are uncommon soft tissue neoplasm. Association with others tumors is so exceptional. We describe and relation between liposarcoma and prostate cancer in a 66 years old patient who had a left paratesticular tumor with low speed growth and 12 cm of length; nodule in prostate gland was detected. Ecography demostrate an hipoecoic tumor in the spermatic cord; Prostate Specific Antigen (PSA) was 1276 ng./ml. and bone gammagraphy reported metastatic lesions. We made an radical orquiectomy and pathological diagnosis including inmunohistoquimical process was sclerosing dedifferenciated liposarcoma. We discuss clinical and pathologic behaviour of this lesions and diagnosis and treatment options.

Identification of three novel mutations in hereditary protein S deficiency.

We report the application of single-stranded conformation polymorphism (SSCP) analysis to the screening of 15 functionally important Protein S (PS) gene (PS alpha) regions (4.243 Kb) in 6 unrelated families with PS deficiencies. Direct sequencing of the fragments with altered migration patterns led to the identification of the corresponding molecular alterations. A missense mutation, G to T transversion at codon Cys598, and two different alterations, leading either to allelic exclusion, or premature termination of the protein translation: a G to A transition at codon Trp465 and a 1 nt (T) insertion at codon 265, were identified. The 1 nt insertion was observed in three apparently unrelated families but with a common geographical origin and the mutated allele was undetectable in platelet mRNAs of affected individuals. Family analysis confirmed, in each case, a perfect cosegregation of the mutation with the PS deficiency. We conclude that these alterations represent the causative mutations.

Molecular genetic analysis of factor XI deficiency: identification of five novel gene alterations and the origin of type II mutation in Portuguese families.

Coagulation factor XI (FXI) deficiency is an inherited autosomal recessive mild bleeding disorder. In this study, we report the molecular genetic analysis of FXI deficiency in six unrelated families of Portuguese origin. The Jewish type II mutation was found in two families, of seemingly Portuguese origin. Haplotype analysis in these families demonstrated that this mutation is of Jewish origin. In the remaining families, five novel FXI mutations have been identified. Two of these mutations (FXI IVS K -10T-->A and FXI 1026G-->T, cd 324) affect the FXI pre-mRNA splicing. A further two (FXI 307 ins AAGCAAT, cd 85 and FXI 1072 del A, cd 340) introduce frameshifts leading to premature termination codons. The FXI splicing mutation, 1026G-->T cd 324, was found in compound heterozygosity with missense mutation FXI K518N. Analysis of the FXI mRNA from the latter genotype demonstrated new donor splice site usage. All reported mutations most likely result in functional null-alleles. In addition, three novel polymorphisms have been identified: at nt -138 in intron A, at codon D125 in exon 5 and at codon T249 in exon 8.

Prognostic factors in neuroendocrine lung tumors: a Spanish Multicenter Study. Spanish Multicenter Study of Neuroendocrine Tumors of the Lung of the Spanish Society of Pneumonology and Thoracic Surgery (EMETNE-SEPAR).

BACKGROUND: This study examines the experience of the Spanish Multicenter Study of Neuroendocrine Tumors of the Lung through the clinical data and behavior of patients treated for this pathologic process. METHODS: From 1980 to 1997, 361 cases of neuroendocrine carcinomas (NEC) were treated surgically. Patients were enrolled in a protocol using the pathologic and follow-up reports. According to Dreslers' criteria, the cases were segregated into grade 1 (typical carcinoid), grade 2 (atypical carcinoid), grade 3 large cell type, and grade 3 small cell type. Several variables were reviewed in all patients. Statistical analysis was performed to determine whether clinical characteristics and differentiation were associated with significant differences in the prognosis. RESULTS: A total of 261 cases of NEC were identified with grade 1, 43 with grade 2, and with grade 3: 22 of large and 35 of small cells. Five-year survival for different grades was as follows: grade 1, 96%; 2, 72%; 3 large cell type, 21%; and 3 small cell type, 14%. When a comparative analysis between typical and atypical carcinoids was performed a significant difference for mean age, tumor size, nodal metastases, and recurrence was observed. However, female sex, nodal metastases, and recurrence rate differed between atypical carcinoids and grade 3 NEC of large cells. A difference in recurrence rate was found between patients with both types of grade 3 NEC. CONCLUSIONS: The progressive deterioration of tumor organization highlights that neuroendocrine tumors constitute a continuous spectrum. A careful observation of pathologic findings is necessary to individualize their prognostic factors.

Glial fibrillary acidic protein (GFAP) in spinal cord of postnatal rat. An immunoperoxidase study in semithin sections.

The presence and distribution of gliofibrillary acidic protein (GFAP) was studied in the postnatal spinal cord of the rat. On birth GFAP can be seen in astrocytic bodies and their processes of ventral columns; perivascular glial membrane was initially seen within white and gray matter; most of the fibers were transversally oriented. There are many mitotic cells, some of them with GFAP in their cytoplasm, while others lack it, thus providing strong evidence to identify two cellular populations as astrocytes and, possibly, oligodendrocytes and to state that neuroglial cells differentiate to astrocytes before myelination gliosis. The glia limitans membrane is continuous from the 5th day onwards and in 17-day-old animals the astrocytic framework of the spinal cord has reached its adult appearance.

Glial fibrillary acidic (GFA) protein in rat spinal cord. An immunoperoxidase study in semithin sections.

The distribution of glial fibrillary acidic (GFA) protein was examined in cervical spinal cord of adult rat, according to the immunocytochemical peroxidase-antiperoxidase (PAP) method in semithin sections (1-2 microns). We have found astroglial cells in proximal regions of both ventral and dorsal roots. The presence of astrocytic processes reaching the central canal, only in the dorsal region suggest that they are the only radial glia cells which remain attached to the central canal.

Tonsillar metastasis from adenocarcinoma of the stomach.

Metastatic carcinoma of the tonsil is rare with only some 100 cases having been reported in the literature, of which nine have resulted from stomach carcinoma. Tonsillar metastases rarely become apparent before the diagnosis of the primary neoplasm. We describe here the clinical and histopathological findings of a case of unilateral palatine tonsil metastasis as the first sign of a signet-ring cell carcinoma of the stomach. This has not been reported previously.

[Adult Wilms' tumor]. / Tumor de Wilms del adulto.

Wilms' tumor is a malignant embryonic renal neoplasm that is exceptional in adults. There are not clinical data or radiographic investigations that can distinguish it from renal cell carcinoma. So the diagnostic is based in the pathological evaluation. It may be cystic and must be consider in the differential diagnosis of cystic lesions of the kidney. The prognosis of Wilms' tumor in adults is worse than in children because of the high recurrence, the lower response rate to chemotherapy regimens and the advanced stage at the time of clinical presentation, like an asymptomatic abdominal mass in 75% of the cases. We report a new case of nephroblastoma in a 29 years old woman presenting like a renal colic, with a cystic configuration by abdominal ultrasound initially, that changed into a solid renal mass later. There is not a definitive treatment protocol currently but some authors suggest a combination chemotherapy with carboplatin and etoposide because it is very effective in recurrent or refractory adult Wilms' tumor. Our patient remains asymptomatic and without evidence of recurrence 18 months after the surgery.

[Etiologic considerations regarding superior vena cava syndrome]. / Consideraciones etiológicas sobre el síndrome de vena cava superior.

Literature review indicates a change in the etiological trends of the Superior Cava Syndrome. While during the first half of the twentieth century, aortic aneurysms, malignant tumors and mediastinitis were its main causes, nowadays talking about obstruction of the superior cava is the same than talking about obstruction secondary to a malignant cause (85-90%). Benign affections account for 10-15% and, among them, intravenous iatrogenic foreign bodies constitute a new chapter as cause of thrombosis. Given that small cells simplex carcinoma is the most common cause of SCS and given that benign processes or other chemosensitive tumors can be present, it is currently necessary to secure the histologic diagnosis before starting the treatment.

[Papillary carcinoma of the choroid plexus: apropos 3 cases]. / Carcinoma papilar de los plexos coroideos: a propósito de tres casos.

Choroid plexus carcinoma are tumors arising from epithelial cells of the choroid plexus. They distinguish from the benign choroid plexus papilloma because of their invasive capacity and cellular pleomorphism. This is a rare neoplasm and only infrequently occurs in adults. We report three cases of choroid plexus carcinoma, two women of 61 and 58 years old and a third one a child of 3 years old. We performed a review of the literature with special attention to the epidemiologic, histologic, clinic and therapeutic issues.

[Neck schwannomas]. / Schwannomas de cuello.

Given the rareness of cervical schwannomas, they are often mistaken for other kinds of lesions. We present 2 clinical cases, make comments on the clinical-pathological features involved and point out the essential elements that ensure the differential diagnosis of these tumours.

[Mixed tumor in cervical salivary heterotopy]. / Tumor mixto en heterotopia salival cervical.

This paper presents a case, infrequent and clinically unsuspected, of pleomorphic adenoma in the upper region of the neck in front of the sternocleidomastoid, independent of the salivary glands. The tumor developed within an heterotopic salivary gland of seromucose type, the histopathologic study of the surgical piece being decisive in the diagnosis. The characteristics of salivary heterotopias of the neck, and their diagnostic difficulties and histogenetic problems are reviewed.

[Are the guidelines guiding us reliable? Evaluation of the Spanish clinical practice guidelines]. / Las guías que nos guían son fiables? Evaluación de las guías de práctica clínica españolas.

BACKGROUND AND OBJECTIVE: There is a large proliferation of clinical practice guidelines (CPG), there being doubts on inconsistencies between the recommendations made and internal incongruencies, that affect the role of the guidelines as instruments helping the clinicians. This study aims to analyze the quality of a group of Spanish CPG and to assess the feasibility of use and consistency of the AGREE Instrument in its Spanish version, designed to evaluate the CPG. METHOD: A total of 278 CPG produced in Spain between January 1990 and December 2002 were identified. The originals of 61 guidelines were recovered from their authors and passed to the AGREE Instrument independently by four raters. Quality of the guidelines feasibility and reproducibility of AGREE were analyzed. RESULTS: For all the attributes of AGREE except in the editorial independence, more than 60% of the guidelines evaluated obtained a poor quality score, there being no domain in which more than 10% of the guidelines was excellent. The worst grading areas are those of applicability, participation and rigour of development of the guidelines. Of the 61 guidelines evaluated, the reviewers graded 25 as "very poor quality", 26 as "non recommendable" and 6 and 4 as "recommendable" or "highly recommendable", respectively. Interrater consistency was high. CONCLUSIONS: The mean quality of the Spanish guidelines evaluated is very low. The AGREE Instrument in its Spanish version is consistent for the Spanish guidelines and easy to use.

Intermediate filament aggregates in mitoses of primary cutaneous neuroendocrine (Merkel cell) carcinoma.

Primary cutaneous neuroendocrine carcinomas express different kinds of intermediate filaments and frequently in a 'paranuclear globular' pattern. We have observed the same pattern not only in interphase but also in mitotic cells, which are very frequent in these tumours. We report a quantitative and morphological study of eight primary cutaneous neuroendocrine carcinomas stained with different antibodies against cytokeratins (CAM 5.2 and anticytokeratin 20), neurofilaments (70 kDa and 200 kDa) and peripherin. We have found a predominance of CAM 5.2 expression in interphase cells and of neurofilament proteins in mitotic cells; 87.02% of the interphase cells were positive with CAM 5.2 whereas only 6.08% were positive for neurofilaments (P < 0.01); 35.41% of the mitotic cells were positive with CAM 5.2, whereas 50% were positive for neurofilaments (P < 0.01). A correlation between a globular pattern of intermediate filament proteins and prognosis has not been found. We describe for the first time the division of neoplastic cells with a globular pattern; the presence of intermediate filament proteins with a globular pattern in all mitotic stages; and the uneven distribution of this formation between the two daughter cells.