Coexistencia de artritis séptica y microcristalina: un reto diagnóstico. A propósito de 25 casos

ObjectiveSeptic arthritis is a medical emergency and crystal-induced arthritis is a risk factor for its development. If both occur simultaneously, crystal-induced arthritis may mask the diagnosis of infection and delay antibiotic therapy.MethodRetrospective analysis of patients with coexistence of septic and crystal-induced arthritis. We included only patients with isolation of crystals in synovial fluid analysis and positive culture of synovial fluid and/or blood culture.ResultsA total of 25 patients (17 men and 8 women) with a mean age of 67 years. The most commonly affected joint was the knee. In synovial fluid cytological studies, the most frequently identified crystals were monosodium urate. Risk factors included diabetes and chronic renal failure. The most frequently isolated germs were methicillin-sensitive S. aureus (48%), methicillin-resistant S. aureus (12%) and Mycobacterium tuberculosis (12%). In all, 36% of subjects required surgical drainage (excluding those caused by M. tuberculosis). Clinical outcome was favorable in 56%, although intercurrent complications were usual (40%). Mortality was 8%.ConclusionsCoexistence of septic and crystal-induced arthritis represents a diagnostic challenge and requires a high index of suspicion. Gout was the most prevalent crystal-induced arthritis. S. aureus was the most commonly causative pathogen, with a high rate of methicillin-resistant S. aureus infection. If treated early, the outcome is usually favorable, making synovial fluid microbiological study imperative.     

Economic Issues in the Treatment of BPH

The long-term cost of effective management for benign prostatic hyperplasia (BPH) remains an important issue in pharmacoeconomics because about 25% of men aged 50 yr and older experience voiding problems due to BPH. With the ageing population and the increase in the percentage of patients with BPH for whom any type of treatment can be considered, a substantial increase in total costs to society can be expected. The up-front costs of interventional approaches to BPH are being replaced by a pattern of long-term medical and preventive therapy. The age-adjusted rate of transurethral resection of the prostate (TURP) reached a high point in 1987 and TURP rates, but not costs, have been in decline ever since. Mean 1-yr treatment costs (medical therapy and TURP) have been estimated in a pan-European study to be 858 Euros per patient, 75% of which were medication costs. Using a 2-yr time frame for treatment, Medicare costs for finasteride, terazosin, and TURP have been estimated as $3874, $2161, and $1820, respectively. The available models of the total long-term cost for all therapies for BPH remain compromised by a lack of inclusion of indirect costs, the lack of true long-term data and, critically, the lack of human cost information (patient preference). Only medical therapy provides a preventive as well as symptomatic potential and, if all of the issues were fully incorporated, it is likely that medical therapy would be increasingly recognised as economically preferable.     

Small-cell neuroendocrine carcinoma of the ampullary region. A clinicopathologic, immunohistochemical, and ultrastructural study of three cases.

We report the clinicopathologic, immunohistochemical, and ultrastructural features of three small-cell neuroendocrine carcinomas of the ampullary region of the duodenum. All patients were men; their ages were 51, 62, and 66 years. The therapy consisted of pancreatoduodenectomy. All patients died of the disease; median survival was 10 months from the diagnosis. The histological appearance was identical to pulmonary and extrapulmonary small-cell carcinoma. The neuroendocrine differentiation was demonstrated ultrastructurally by the presence of dense-core granules, and by the positive immunoreaction for neuron-specific enolase and Leu-7 in each case. One case expressed a focal positivity for chromogranin A (PHE-5) and argyrophilic granules. The same case showed the presence of neurofilaments on frozen material. Neurofilament proteins could not be demonstrated in any case in paraffin sections. Neoplastic cells exhibited cytoplasmic immunostaining for cytokeratins (CAM 5.2) in all cases. In one case, a large number of neoplastic cells (60-70%) exhibited nuclear Ki-67 positivity. We postulate that the disease's histogenesis was from epithelial stem cell expressing both epithelial and neuroendocrine characteristics. The clinical behavior of small-cell neuroendocrine carcinomas of the ampullary region appears to be extremely aggressive, with early metastases and fatal outcome.     

Temporal coupling between transport and grasp components during prehension movements: effects of visual perturbation.

The temporal coupling between the transport and grasp components of prehension movements was investigated through two experiments. In Experiment 1, six normal subjects were required to reach and grasp each of three spheres located at three different distances (Blocked trials). In Experiment 2, a visual perturbation paradigm was used in which the location of the object to be reached and grasped could change at the beginning of arm movement (Perturbed trials). The same subjects participated in both experiments. Kinematics of wrist trajectory (transport component) and of distance between thumb and index finger (grasp component) were analyzed. The results of Experiment 1 showed that the two components could be temporally coupled during their time course. In Experiment 2, the visual perturbation affected both the components, but different times were required by each component to reorganize the movement towards the new target. These different times caused the decoupling of those events that appeared synchronized in Experiment 1. Finally, evidence was found to suggest that planning of grip formation takes into account not only the perceived characteristics of the object, but also the time planned by the transport component to reach the object.     

Modulation of laminin synthesis in human neuroblastoma cells during retinoic acid induced differentiation.

A comparable pattern of morphological neuronal differentiation was induced in the human neuroblastoma cell line SMS-KCNR by treatment with either retinoic acid (RA) or exogenous laminin (LM). LM expression and synthesis by SMS-KCNR was increased upon RA treatment which involved the cell bound, rather than the secreted protein. These data suggest an involvement of LM in the neuroblastoma differentiation process manifested both as an ability of LM to induce a morphological neuronal differentiation and as a selective control on LM metabolism during RA induced neuronal differentiation.     

Diagnostic utility of S100A1 expression in renal cell neoplasms: an immunohistochemical and quantitative RT-PCR study.

S100A1 is a calcium-binding protein, which has been recently found in renal cell neoplasms. We evaluated the diagnostic utility of immunohistochemical detection of S100A1 in 164 renal cell neoplasms. Forty-one clear cell, 32 papillary, and 51 chromophobe renal cell carcinomas, and 40 oncocytomas, 164 samples of normal renal parenchyma adjacent to the tumors and 13 fetal kidneys were analyzed. The levels of S100A1 mRNA detected by quantitative RT-PCR analysis of frozen tissues from seven clear cell, five papillary, and six chromophobe renal cell carcinomas, four oncocytomas, and nine samples of normal renal tissues adjacent to neoplasms were compared with the immunohistochemical detection of protein expression. Clear cell and papillary renal cell carcinomas showed positive reactions for S100A1 in 30 out of 41 tumors (73%) and in 30 out of 32 (94%) tumors, respectively. Thirty-seven renal oncocytomas out of 40 (93%) were positive for S100A1, whereas 48 of 51 (94%) chromophobe renal cell carcinomas were negative. S100A1 protein was detected in all samples of unaffected and fetal kidneys. S100A1 mRNA was detected by RT-PCR in all normal kidneys and renal cell neoplasms, although at very different levels. Statistical analyses comparing the different expression of S100A1 in clear cell and chromophobe renal cell carcinomas observed by immunohistochemical and RT-PCR methods showed significant values (P<0.001), such as when comparing by both techniques the different levels of S100A1 expression in chromophobe renal cell carcinomas and oncocytomas (P<0.001). Our study shows that S100A1 protein is expressed in oncocytomas, clear cell and papillary renal cell carcinomas but not in chromophobe renal cell carcinomas. Its immunodetection is potentially useful for the differential diagnosis between chromophobe renal cell carcinoma and oncocytoma. Further, S100A1 protein expression is constantly detected in the normal parenchyma of the adult and fetal kidney.     

A subset of high-grade pulmonary neuroendocrine carcinomas shows up-regulation of matrix metalloproteinase-7 associated with nuclear β-catenin immunoreactivity,independent of EGFR and HER-2 gene amplification or expression

Nuclear translocation of β-catenin has been correlated with epidermal growth factor receptor (EGFR) overexpression/activation in nonsmall cell lung cancer. Less is known on β-catenin transactivation in high-grade pulmonary neuroendocrine tumors and on the status of β-catenin activating EGFR and human epidermal growth factor receptor 2 (HER-2) or β-catenin target genes cyclin D1 and matrix metalloproteinase-7 (MMP-7). β-catenin immunoreactivity was evaluated in 51 large-cell neuroendocrine carcinomas (LCNEC) and 45 small-cell lung carcinomas (SCLC). Nineteen cases were assessed for β-catenin gene exon 3 mutations, expression of MMP-7, and expression/gene amplification of EGFR, HER-2, and cyclin D1. β-catenin was expressed in all 96 high-grade neuroendocrine tumors, the vast majority (94%) showing >50% immunopositive cells. A disarrayed immunoreactivity, however, was commonly encountered consisting in variably altered membrane-associated patterns of staining along with progressive accumulation of cytoplasmic immunoreactivity. In LCNEC, but not in SCLC, the disarrayed patterns correlated with EGFR and HER-2 protein expression. β-catenin nuclear accumulation was found in nine tumors, including seven LCNEC and two SCLC, and was always associated with disarrayed immunoreactivity and increased MMP-7, but not cyclin D1 expression. These cases, however, did not show β-catenin gene mutations or EGFR and HER-2 gene amplification or expression. No association was found between nuclear β-catenin and any clinicopathological variable including patients' survival. The subcellular compartmentalization of β-catenin is profoundly altered in high-grade pulmonary neuroendocrine tumors. A minor subset of these tumors shows β-catenin nuclear accumulation in association with increased expression of MMP-7, but not of cyclin D1, independent of EGFR and HER-2 gene amplification or expression. The authors have no significant financial or other relationship with the manufacturers of any commercial products or commercial services presented in this paper     

Mediastinal large-cell lymphoma with sclerosis

Summary The Southern blot hybridization technique has been applied to study the configuration of immunoglobulin and T-cell receptor genes in 6 cases of the so called mediastinal large cell lymphoma with sclerosis. This lymphoma has been recently recognized as a separate entity among non-Hodgkin lymphomas mainly affecting young adult patients. The B-cell origin of this neoplasm was suggested by means of immunohistochemical analysis. However, the immunophenotypical B-cell related markers used do not always exhibit lineage fidelity. The Southern blot analysis demonstrated the presence of unique heavy and k-light chain immunoglobulin gene rearrangements, establishing genotypically their B-cell origin.This work was supported by the Associazione Italiana per la Ricerca sul Cancro, Milano, Italy, and Progetto finalizzato Oncologia (contratto n^o 86.00461.44), CNR, Rome, Italy. Aldo Scarpa and Maurizio Lestani are supported by a Scholarship from the Associazione Italiana per la Ricerca sul Cancro, Milano, Italy     

K-ras gene mutational analysis supports a monoclonal origin of biphasic pleomorphic carcinoma of the lung.

We investigated 27 pleomorphic carcinomas of the lung for exon 1 K-ras gene mutations using polymerase chain reaction-single-strand conformation polymophism analysis and direct sequencing. All pleomorphic carcinomas were biphasic, that is, composed of an adeno-, squamous- or large-cell-carcinomatous component associated with a spindle- and/or giant-cell component. Of 27 cases, six (22%) showed K-ras codon 12 mutations, which is a figure higher than that previously reported on in pure sarcoma-like pleomorphic carcinomas. Five tumors displayed the same mutation in both the epithelial and the sarcomatoid components, whereas in one tumor the mutation was restricted to the epithelial component. All mutations occurred in smokers, and were transversions, including GGT (glycine) to TGT (cysteine) change in two cases, to GCT (alanine) in two and to GTT (valine) in two. No significant relationships were found between the occurrence and type of mutations and patients' survival or any other clinicopathological variable, suggesting that K-ras mutations are early events in the development of these tumors. Our results indicate that most, though not all, biphasic pleomorphic carcinomas of the lung are monoclonal in origin, and that cigarette smoking may have a causative role in the development of K-ras alterations in these tumors, as all mutations are transversions.