Tumor-like presentation of herpetic cervicitis: A case report.

The case of a 20-year-old immunocompetent woman with necrotizing cervicitis of the cervix caused by a primary infection with herpes simplex virus type 2 is presented, along with its respective evolution in images. Cervical cancer was included in the differential diagnoses, but biopsies ruled out malignancy and laboratory tests demonstrated the viral etiology of the cervical inflammation. After initiating specific treatment, the cervical lesions completely healed within 3 weeks. This case highlights the need to consider herpes simplex infection in the differential diagnosis of cervical inflammation and tumor formation. Additionally, it provides images that can aid in diagnosis and allow for the observation of its clinical evolution.

Role of circulating tumor cells as prognostic marker in resected stage III colorectal cancer.

BACKGROUND: The prognostic role of circulating tumor cells (CTC) in early colorectal cancer (CRC) has not been determined yet. We evaluated the potential prognostic value of CTC in stage III CRC patients. PATIENTS AND METHODS: Prospective multicenter study of 519 patients with stage III CRC recruited between January 2009 and June 2010. CTC were enumerated with the CellSearch System after primary tumor resection and before the start of adjuvant therapy. A total of 472 patients were included in the analysis. RESULTS: CTC ≥1, ≥2, ≥3 and ≥5 were detected in 166 (35%), 93 (20%), 57 (12%) and 34 (7%) patients, respectively. Median follow-up was 40 months. In the overall population, CTC ≥1 (disease-free survival (DFS): HR 0.97, P = 0.85; overall survival (OS): HR 1.03, P = 0.89), ≥2 (DFS: HR 1.07, P = 0.76; OS: HR 1.02, P = 0.95), ≥3 (DFS: HR 0.96, P = 0.87; OS: HR 0.74, P = 0.41) and ≥5 (DFS: HR 0.72, P = 0.39; OS: HR 0.48, P = 0.21) were not associated with worse DFS and OS. No clinicopathological characteristics were significantly associated with the presence of CTC. In patients with disease relapse, the proportion with CTC ≥1 was not significantly different between those with single versus multiple metastatic locations (37.9% versus 31.4%, P = 0.761). In the multivariate analysis, CTC ≥1 was not an independent prognostic factor for DFS (HR 0.97, P = 0.87) and OS (HR 0.96, P = 0.89). CONCLUSION: CTC detection was not associated with worse DFS and OS in patients with stage III CRC. Given the scarcity of CTC in these patients, it is likely that CTC determined by CellSearch system does not have a prognostic role in this setting. However, a longer follow-up is needed.

Nuevas estrategias en el tratamiento del trauma raquimedular: actualización bibliográfica / New strategies in treatment of spinal cord injury: literature update

Better understanding of spinal cord injury pathophysiology has allowed the development of new areas of investigation, focused in reducing the injury and stimulating cord regeneration. The preliminary results of these investigations have generated great expectation in the scientific world, together with ambiguous information for patients with these injuries. In this article, we present a review of the available literature in this area, describing several non-pharmacological interventions, together with new drugs, immune therapies to block processes that inhibit cord regeneration and the renowned cell therapy. After evaluating the available articles included in this review, we observed a progress towards an increased efficacy of these treatments, but with limitations due to methodological flaws in the study protocols, which do not allow us to make applicability recommendations of them in humans.

Los recientes avances en el entendimiento de la fisiopatología del traumatismo raquimedular, han permitido el desarrollo de investigación enfocada en intervenciones orientadas a disminuir la lesión y estimular la regeneración medular. El entusiasmo por este nuevo conocimiento ha generado expectativa en el mundo científico co e información ambigua en los pacientes con este tipo de lesiones. En este trabajo revisamos la literatura reciente y la que se está llevando a cabo a este respecto, encontrando la descripción de algunas intervenciones no farmacológicas diferentes a la cirugía, nuevos medicamentos, terapias de bloqueo inmunológico de procesos que inhiben la regeneración medular y la reconocida terapia celular. Al evaluar los trabajos incluidos en esta revisión, observamos un avance hacia el aumento de la efectividad de los tratamientos pero con la limitación debida a las falencias metodológicas en la investigación que impiden hacer recomendaciones de aplicabilidad de los mismos en humanos.

[Haemophilia in the German risk adjustment scheme]. / Die Hämophilie im morbiditätsorientierten Risikostrukturausgleich.

Haemophilia presents a challenge to every risk adjustment scheme even if it uses diagnostical or pharmaceutical data. The German adjustment scheme developed by the Bundesversicherungsamt realizes fairly cost homogenous groups for many expensive diseases. It does not regard haemophilia. This holds true for the original classification system (grouper) from 2009 and for the improved classification procedure in 2010. The extreme peak costs that can originate from haemophilia cases can present a existential risk for small health plans. The chances to form cost-homogeneous subgroups of the haemophilia disease by more specific coding or other measures seem low because of the small number of cases affected by this disease. The complementary (re-)installation of a expenditure-oriented risk sharing is regarded as suited for improvement of the performance of the German risk adjustment scheme. This also corresponds to international experience and practice.

[pulmonary thromboembolism in hospitalized patients during the period 1994-2000: an autopsy study]. / Tromboembolismo pulmonar en pacientes hospitalizados entre 1994-2000: serie de autopsia.

BACKGROUND: Pulmonary thromboembolism (PTE) has been for a long time a significant cause of morbidity and mortality in hospitalized patients. The utility of Low-Molecular Weight Heparins (LMWH) in these patients in the last decade of the XX century has decreased the incidence of this disease. We try to know if the massive useful of LMWH as thromboprophylasis is diminishing its incidence in autopsies. MATERIAL AND METHODS: Retrospective study of all the autopsies in adults in the Hospital Clínico San Carlos (Madrid) in a period of 6 years (from January 1994 to December 1999). There were reviewed those necropsies which had pathological data of pulmonary thromboembolism and several items were studied: anatomopathological, epidemiological, clinical and therapeutical. RESULTS: 483 necropsies were performed in this period; 40 (8.3%) had PE. Most of them were older than 50 years (85%) and the most important risk factors associated were bedridden, chronic cardiovascular diseases and malignant neoplasias. Only Pre-mortem diagnosis was only suspected in 5 patients (12.5%) and 15 of them (37.5%) had a fatal pulmonary embolism despite receipt of thromboprophylasis with LMWH. CONCLUSIONS: PTE is still an important cause of mortality in hospitalized patients. The increased of life expect, survival of chronic cardiovascular and malignant disease made PTE a frequent possibility situation in hospitalized patients. Receipt of LMWH as thromboprophylaxis is not always effective to avoid PTE.

El acoso psicológico: riesgo laboral más frecuente de lo reportado / Psychological harassment: a more frequent labor risk than reported

Objetivo: revisar el acoso psicológico como una forma de violencia laboral a la cual está expuesta la población trabajadora en Colombia y en el mundo. Materiales y métodos: revisión narrativa del acoso psicológico en el trabajo, con énfasis en la situación actual colombiana. Resultados: el acoso psicológico en el trabajo se ha definido como un comportamiento irracional repetido con respecto a una persona o grupo de personas; crece y se desarrolla en el entorno laboral, afectando la salud psicológica, física y social de quien lo padece, de su familia y de quien lo ejecuta, así como el funcionamiento de las empresas. En Colombia, la prevalencia del acoso psicológico se ha reportado en un 19,8 por ciento; de agresión verbal en 12,8 por ciento; el jefe es el agresor más frecuente, con el 40 por ciento. Discusión: el evento estudiado es un fenómeno reciente aunque no novedoso, cuya tendencia mundial es creciente; en Colombia, los estudios realizados reportan proporciones superiores con relación a otros países y no existe legislación que lo controle. Conclusiones: el acoso psicológico en el trabajo es un riesgo laboral que debe prevenirse desde la salud pública para mitigar los daños causados a trabajadores, familia, empresa y sociedad.

Phase II study of weekly irinotecan (CPT-11) as second-line treatment of patients with advanced colorectal cancer.

This phase II trial studied the antitumor effect and toxicity of weekly irinotecan (CPT-11, 125 mg/m(2) 60 min iv infusion, weekly for 4 wk plus 2 wk rest) as second-line chemotherapy in patients with advanced colorectal cancer (CRC) resistant or refractory to prior 5-fluorouracil (5-FU) therapy. Sixty-nine patients with adenocarcinoma (57% in the colon and 43% in the rectum) were enrolled. The median number of treatment cycles received per patient was 4 (range, 1-6). Overall response rate was 18% (95% CI, 9-26), with 4 complete responses (6%) and 8 partial responses (12%), and a median duration of response of 8.1 mo (95% CI, 4.2-12.1). Stable disease was observed in 19 patients (28%). The median time to disease progression was 5.2 mo (95% CI, 4.3-6.1), and the median overall survival was 13.3 mo (95% CI, 9.8-16.8 months). The toxicity profile was favorable: grade 3/4 delayed diarrhea was observed in 10 patients (14.5%) in one cycle each, and grade 3/4 neutropenia in 6 patients (8.7%) and 6 cycles (3.3%). No febrile neutropenia or infection was documented. Grade 3/4 nausea and vomiting were reported in 1 (1.4%) and 7 patients (10.1%), respectively. In conclusion, this phase II trial showed a response rate and a toxicity profile of weekly CPT-11 in line with the results of prior phase II studies.

Combined vascular and extracellular pH imaging of solid tumors.

The unique physiological environment of solid tumors, frequently characterized by areas of poor flow, hypoxia, high lactate and low extracellular pH (pHe), influences vascularization, invasion and metastasis. Thus, vascularization and the physiological and metabolic environment play permissive (and conversely preventive) roles in invasion and metastasis. By using a multi-parametric approach of combined vascular and spectroscopic imaging, we can begin to evaluate which combinations of vascular, metabolic and physiological regions in a solid tumor represent the highest 'metastatic threat'. Here, we present measurements of pHe, vascular volume and permeability from co-localized regions within a solid tumor. These studies were performed for a group of metastatic (MDA-MB-231) and non-metastatic (MCF-7) human breast cancer xenografts. In this study, we have demonstrated the feasibility of such an approach, and presented methods of analyses to detect differences in patterns of combined parameters obtained from spatially co-registered regions in a solid tumor.

Extraction and LC determination of lysine clonixinate salt in water/oil microemulsions.

A new reversed-phase high performance liquid chromatography method has been developed and validated for the quantitative determination of lysine clonixinate salt in water/oil microemulsions. The mobile phase was acetonitrile-buffer phosphate pH 3.3. Detection was UV absorbance at 252 nm. The precision and accurately of the method were excellent. The established linearity range was 5-60 microg ml(-1) (r(2)=0.999). Microemulsions samples were dispersed with chloroform and extracted lysine clonixinate salt with water. This easy method employing chloroformic extraction has been done three times. The recovery of lysine clonixinate salt from spiked placebo and microemulsion were >90% over the linear range.

Mapping extracellular pH in rat brain gliomas in vivo by 1H magnetic resonance spectroscopic imaging: comparison with maps of metabolites.

The value of extracellular pH (pH(e)) in tumors is an important factor in prognosisand choice of therapy. We demonstrate here that pH(e) can be mappedin vivo in a rat brain glioma by (1)H magnetic resonance spectroscopic imaging (SI) of the pH buffer (+/-)2-imidazole-1-yl-3-ethoxycarbonylpropionic acid (IEPA). (1)H SI also allowed us to map metabolites, and, to better understand the determinants of pH(e), we compared maps of pH(e), metabolites, and the distribution of the contrast agent gadolinium1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraaceticacid (Gd-DOTA). C6 cells injected in caudate nuclei of four Wistar rats gave rise to gliomas of approximately 10 mm in diameter. Three mmols of IEPA were injected in the right jugular vein from t = 0 to t = 60 min. From t = 50 min to t = 90 min, spin-echo (1)H SI was performed with an echo time of 40 ms in a 2.5-mm slice including the glioma (nominal voxel size, 2.2 microl). IEPA resonances were detected only within the glioma and were intense enough for pH(e) to be calculated from the chemical shift of the H2 resonance in almost all voxels of the glioma. (1)H spectroscopic images with an echo time of 136 ms were then acquired to map metabolites: lactate, choline-containing compounds (tCho), phosphocreatine/creatine, and N-acetylaspartate. Finally, T(1)-weighted imaging after injection of a bolus of Gd-DOTA gave a map indicative of extravasation. On average, the gradient of pH(e) (measured where sufficient IEPA was present) from the center to the periphery was not statistically significant. Mean pH(e) was calculated for each of the four gliomas, and the average was 7.084 +/- 0.017 (+/- SE; n = 4 rats), which is acid with respect to pH(e) of normal tissue. After normalization of spectra to their water peak, voxel-by-voxel comparisons of peak areas showed that N-acetylaspartate, a marker of neurons, correlated negatively with IEPA (P < 0.0001) and lactate (P < 0.05), as expected of a glioma surrounded by normal tissue. tCho (which may indicate proliferation) correlated positively with pH(e) (P < 0.0001). Lactate correlated positively with tCho (P < 0.0001), phosphocreatine/creatine (P < 0.001), and Gd-DOTA (P < 0.0001). Although lactate is exported from cells in association with protons, within the gliomas, no evidence was observed that pH(e) was significantly lower where lactate concentration was higher. These results suggest that lactate is produced mainly in viable, well-perfused, tumoral tissue from which proton equivalents are rapidly cleared.

In vivo imaging of extracellular pH using 1H MRSI.

Tumor pH is physiologically important since it influences a number of processes relevant to tumorigenesis and therapy. Hence, knowledge of localized pH within tumors would contribute to understanding these processes. The destructiveness, poor spatial resolution, and poor signal-to-noise ratio (SNR) of current technologies (e.g., microelectrodes, 31P magnetic resonance spectroscopy) have limited such studies. An extrinsic chemical extracellular pH (pHe) probe is described that is used in combination with 1H magnetic resonance spectroscopic imaging to yield pHe maps with a spatial resolution of 1 x 1 x 4 mm3. The principle of the technique is demonstrated on a phantom. Further data are shown to demonstrate its application in vivo, and results agree with previously reported pH values. The accuracy of the reported pH measurements is <0.1 pH units, as derived from a detailed analysis of the errors associated with the technique, the description of which is included.

N-2-(azol-1(2)-yl)ethyliminodiacetic acids: a novel series of Gd(III) chelators as T2 relaxation agents for magnetic resonance imaging.

The synthesis, physicochemical properties, and toxicological implications of a novel series of N-2-(azol-1(2)-yl)ethyliminodiacetic acids, useful as contrast agents for magnetic resonance imaging are reported. Compounds were prepared by alkylation of methyl iminodiacetate with N-2-bromoethylazoles and subsequent hydrolysis. Stability constants of the corresponding Gd(III) complexes and T1 and T2 relaxivities were determined and interpreted in terms of optimized geometries obtained by semiempirical PM3 calculations. Compounds show increased T2 relaxivity and decreased toxicity in vitro as compared to EDTA-Gd(III) complexes.

Vascular density as a prognostic indicator for invasive ductal breast carcinoma.

Estimated vascular density obtained with the aid of antibodies against endothelial cells has been claimed to be an independent prognostic indicator for invasive ductal breast carcinoma. Since 1991 most studies have counted the number of vessels with the optic microscope. We have performed immunohistochemical staining for Factor VIII on formaldehyde-fixed, paraffin-embedded primary invasive ductal carcinomas from 112 patients, with a minimal follow-up time of 60 months, who had received postoperative chemoradiation therapy. We have performed a manual count with a 20x objective of the vessels in the vascular hot-spot identified in a 4x field. We analysed the association of this factor with epidemiological risk factors, histopathological features, hormonal receptor status and p53 and c-erbB-2 expression and the influence on prognosis. In univariate analysis vascular density is a significant prognostic indicator in both node-negative and node-positive patients, together with staging, Baak's morphometric multiparametric index, tumour size and histological grade. However, in multivariate analysis only tumour staging and vascular density are independent prognostic factors in breast carcinoma.

Vascular enumeration as a significant prognosticator for invasive breast carcinoma.

PURPOSE: Vascular enumeration has been claimed to be an independent prognosticator for invasive breast cancer. Most of the studies have performed a manual count of the vessels. Few investigators have used image analyzers to reduce subjectivity in the measures. The aim of this retrospective study was to compare the manual vessel count to the counts obtained with an image analyzer and to estimate their possible prognostic influence. MATERIALS AND METHODS: We selected 112 patients with invasive ductal carcinoma, treated with radical mastectomy followed by chemotherapy and with a minimal follow-up time of 60 months (5 years). After immunostaining with factor VIII, we performed a double count of the vessels. First, we performed a manual count following Gasparini's criteria, and second, we used an image analyzer (Microm, Barcelona, Spain) to count the vessels in eight adjacent microscopic fields with a 20x objective, to reach a total area of 0.98 mm2. The image analyzer calculated the total number of vessels, their size and also the percentage of the field occupied by the vessels. RESULTS: In our series, vascular enumeration showed no significant association with histologic grade (Bloom-Scarff-Richardson grading), tumor size, or staging. CONCLUSION: Vascular enumeration with both methods was an independent prognosticator for relapse-free-survival (RFS) in both node-negative and -positive patients in the univariate analysis, but only vascular enumeration with the image analyzer was an independent prognostic factor in the multivariate analysis, together with lymph node metastases.

Immunohistochemical expression of p53 and c-erbB-2 in breast carcinoma: relation with epidemiologic factors, histologic features and prognosis.

We have performed immunohistochemical staining for p53 and c-erbB-2 on formaldehyde-fixed, paraffin-embedded primary invasive ductal carcinomas from 112 patients, with a minimal follow-up time of 60 months. All of them had received postoperative chemoradiation therapy. We have analyzed the association of these factors with epidemiologic risk factors, histopathologic features and hormonal receptor status and the influence on prognosis. Our results indicate that the expression of c-erbB-2 protein defines a group of node-negative patients with poor prognosis. The overexpression of c-erbB-2 has shown a significant association with estrogen receptor status (those tumors expressing c-erbB-2 are usually estrogen receptor negative), presence of fibrosis and lymphoplasmacytoid infiltrates. P53 expression has shown no relation either with prognosis or with any other histopathologic or clinical feature. The only factors with prognostic influence in our series have been tumor size, the presence of node metastases, TNM stage and the prognostic morphometric index (Baak's index), apart from c-erbB-2 in node-negative patients. However, only the TNM stage showed an independent association with prognosis after a multivariate analysis. In summary, in our experience the expression of p53 protein has no prognostic influence on breast carcinoma, and TNM stage remains to be as the most powerful prognostic factor in these patients.

[Pseudomyxoma peritonei]. / Seudomixoma peritoneal.

Pseudomyxoma peritonei is an infrequent clinical entity, characterized by peritoneal implantations organized in cyst of mucine or free peritoneal mucine. Most arise from cystadenoma or cystadenocarcinoma of the ovary and appendix, and fewer from other tumours and locations. It is more common in females, and it is usually diagnosed over the fifth decade. Three cases of pseudomyxoma peritonei are presented, two associated to appendicular carcinoma and one to carcinoma of the ovary, and the data published about this disease are reviewed.

Alternating chemotherapy for small-cell lung cancer. A twelve-week schedule of six drugs.

We have treated sixty-two patients (21 with limited disease, 41 with extensive disease), on an outpatient-basis schedule of six drugs administered weekly for twelve weeks. Cyclophosphamide, 400 mg/m2, adriamycin, 20 mg/m2 and vincristine, 2 mg, full dose, were administered during weeks 1, 5 and 9; cisplatin, 50 mg/m2 and etoposide, 100 mg/m2 during weeks 2, 6 and 10; adriamycin and vincristine at the same doses during weeks 3, 7 and 11; methotrexate 30 mg/m2, during weeks 4, 8 and 12. After the first 28 patients vincristine was replaced by teniposide (VM-26) due to neurotoxicity. The overall response rate was 64.5% (complete remission 13 p., partial remission 27 p.). Toxicity grade 3-4, mainly nausea and vomiting or neutropenia, was recorded in 17 patients. Alopecia grade 1-2 was universal. One toxic death occurred from sepsis. The overall survival was 8 months (range 1-40), (95% CL: 53-77%); 8 months in limited disease (range 1-40), and 7 months in extensive disease (range 1-23). Time to treatment failure was 6 months (7 limited disease, 5 extensive disease). In conclusion, the results of this alternating schedule are poorer than those attained with standard, high-dose treatments, mainly in limited disease, but could be a less toxic option for patients with extensive disease.

Synthesis and transport applications of 3-aminobicyclo[3.2.1] octane-3-carboxylic acids.

The isomeric 3-aminobicyclo[3.2.1]octane-3-carboxylic acids were synthesized and compared with the widely used (1R,2S,4S)-2-aminobicyclo[2.2.1]heptane-2-carboxylic acid as to specificity to the Na+-independent membrane transport system L of the Ehrlich ascites tumor cell and of the rat hepatoma cell line HTC. The presence of an additional methylene group in the ring system leads to an optically symmetrical amino acid, with the advantages that the product is devoid of isomeric contamination. Hence, optical resolution is not necessary to secure a homogeneous test substrate for discrimination of amino acid transport systems. Through its inhibitory action on the cellular uptake of known system-specific amino acids, the bicyclo[3.2.1]octane amino acid proved more reactive than the bicycloheptane analogue with the Na+-independent amino acid transport system of the test cells and not perceptibly reactive with the accompanying Na+-dependent systems. Recent evidence of the presence of a second component of Na+-independent amino acid transport, beyond system L, increases the importance of securing a variety of possibly discriminatory model substrates.