AIDS-related cardiac tamponade: Is surgical drainage justified?

In order to evaluate the usefulness of surgical drainage in the treatment of patients with acquired immunodeficiency syndrome (AIDS)-related cardiac tamponade, we reviewed our experience with subxiphoid pericardiostomy on 5 consequent such patients. One patient died in the immediate postoperative period and the remaining 4 died within 21 weeks after the operation. Similar results have been reported by other authors who found that surgical drainage has no diagnostic or therapeutic benefit over pericardiocentesis in this particular group of patients. Based on our limited experience and the data of the literature, we feel that surgical drainage cannot be justified as the primary method of treatment of AIDS-related cardiac tamponade. (C) 2004 by The Society of Thoracic Surgeons

Benign retroperitoneal neural sheath tumors in patients without von Recklinghausen's disease

Benign retroperitoneal neural sheath tumors in patients without von Recklinghausen’s disease are quite rare and usually presented as isolated case reports. There are two types of benign neural sheath neoplasms: schwannoma and neurofibroma. Confusion exists in the nomenclature of these tumors due to the disagreement upon their cell of origin. In a collective report from two institutions, three cases with benign retroperitoneal neural sheath tumors are presented, and the histological features, diagnostic and therapeutic options are discussed

p53-Dependent ICAM-1 overexpression in senescent human cells identified in atherosclerotic lesions

Most normal somatic cells enter a state called replicative senescence after a certain number of divisions, characterized by irreversible growth arrest. Moreover, they express a pronounced inflammatory phenotype that could contribute to the aging process and the development of age-related pathologies. Among the molecules involved in the inflammatory response that are overexpressed in senescent cells and aged tissues is intercellular adhesion molecule-1 (ICAM-1). Furthermore, ICAM-1 is overexpressed in atherosclerosis, an age-related, chronic inflammatory disease. We have recently reported that the transcriptional activator p53 can trigger ICAM-1 expression in an nuclear factor-kappa B (NF-kappa B)-independent manner (Gorgoulis et al, EMBO J. 2003; 22: 1567 - 1578). As p53 exhibits an increased transcriptional activity in senescent cells, we investigated whether p53 activation is responsible for the senescence-associated ICAM-1 overexpression. To this end, we used two model systems of cellular senescence: ( a) human fibroblasts and (b) conditionally immortalized human vascular smooth muscle cells. Here, we present evidence from both cell systems to support a p53-mediated ICAM-1 overexpression in senescent cells that is independent of NF-kappa B. We also demonstrate in atherosclerotic lesions the presence of cells coexpressing activated p53, ICAM-1, and stained with the senescence-associated beta-galactosidase, a biomarker of replicative senescence. Collectively, our data suggest a direct functional link between p53 and ICAM-1 in senescence and age-related disorders

Wound infections after minor limb lacerations: Risk factors and the role of antimicrobial agents

Background: The requirement for antimicrobial agents in patients with minor limb lacerations was prospectively studied. Methods: The development of wound infections in patients with minor limb lacerations who received amoxicillin plus clavulanate acid treatment (group ii, 52 patients) mas studied and compared with patients who did not (group B, 48 patients). Results: Wound infection occurred in 6 (11.5%) and 10 (21%) patients in groups A and B, respectively (p > 0.10). Statistically significant risk factors for the development of infection were diabetes mellitus (odds ratio [OR], 15.8; p < 0.001), lower limb lacerations (OR, 33.5; p < 0.001), lacerations caused by compressive forces (OR, 21.6; p = 0.007), laceration length from 5 to 8 cm (OR, 7.04; p = 0.001), ragged laceration edge (OR, 2.55; p = 0.049), and skin tension (OR, 2.00; p = 0.006), Conclusion: The use of antimicrobial agents in minor limb injuries was not associated with a significant reduction of infection rate. Routine antimicrobial treatment is discouraged

Transcription factor E2F-1 acts as a growth-promoting factor and is associated with adverse prognosis in non-small cell lung carcinomas

Numerous upstream stimulatory and inhibitory signals converge to the pRb/E2F pathway, which governs cell-cycle progression, but the information concerning alterations of E2F-1 in primary malignancies is very limited. Several in vitro studies report that E2F-1 can act either as an oncoprotein or as a tumour suppressor protein. In view of this dichotomy in its functions and its critical role in cell cycle control, this study examined the following four aspects of E2F-1 in a panel of 87 non-small cell lung carcinomas (NSCLCs), previously analysed for defects in the pRb-p53-MDM2 network: firstly, the status of E2F-1 at the protein, mRNA and DNA levels; secondly, its relationship with the kinetic parameters and genomic instability of the tumours; thirdly, its association with the status of its transcriptional co-activator CBP, downstream target PCNA and main cell cycle regulatory and E2F-1-interacting molecules pRb, p53 and MDM2; and fourthly, its impact on clinical outcome. The protein levels of E2F-1 and its co-activator CBP were significantly higher in the tumour area than in the corresponding normal epithelium (p < 0.001). E2F-1 overexpression was associated with increased E2F-1 mRNA levels in 82% of the cases examined. The latter finding, along with the low frequency of E2F-1 gene amplification observed (9%), suggests that the main mechanism of E2F-1 protein overexpression in NSCLCs is deregulation at the transcriptional level. Mutational analysis revealed only one sample with a somatic mutation at codon 371 (Glu –> Asp) and one carrying a polymorphism at codon 393 (Gly –> Ser). Carcinomas with increased E2F-1 positivity demonstrated a significant increase in their growth indexes (r = 0.402, p = 0.001) and were associated with adverse prognosis (P = 0.033 by Cox regression analysis). The main determinant of the positive association with growth was the parallel increase between E2F-1 staining and proliferation (r = 0.746, p < 0.001), whereas apoptosis was not influenced by the status of E2F-1. Moreover, correlation with the status of the pRb-p53-MDM2 network showed that the cases with aberrant pRb expression displayed significantly higher E2F-1 indexes (p = 0.033), while a similar association was noticed in the group of carcinomas with deregulation of the p53-MDM2 feedback loop. In conclusion, the results suggest that E2F-1 overexpression may contribute to the development of NSCLCs by promoting proliferation and provide evidence that this role is further enhanced in a genetic background with deregulated pRb-p53-MDM2 circuitry. Copyright (C) 2002 John Wiley & Sons, Ltd

Growth index is independent of microvessel density in non-small-cell lung carcinomas

Induction of angiogenesis is essential for carcinogenesis and facilitates the processes of tumor development and metastasis. Vascular endothelial growth factor (VEGF) is an important angiogenic regulator under physiologic and pathologic conditions. To elucidate the role of angiogenesis in malignant growth, we evaluated angiogenesis and VEGF expression in a panel of 68 non-small-cell lung carcinomas (NSCLCs) and examined their relation with the kinetic parameters, ploidy, and p53 protein status, which have been analyzed previously. Angiogenesis was estimated as microvascular density (MVD) of the tumor area by CD31 immunodetection. Expression of VEGF was also immunohistochemically evaluated. All possible associations were assessed through a series of statistical methods. The mean MVD value was 39 microvessels/mm(2), and high VEGF immunoreactivity was observed in all specimens, with a mean percentage of positive cells of 73%. The relation between MVD and VEGF expression was not statistically significant (P = 0.065). No association was observed between MVD or VEGF levels with the proliferation index, apoptotic index, tumor ploidy status, p53 expression, and overall survival. We conclude that in a subset of NSCLCs, angiogenesis may be associated with VEGF, but other factors also participate in this process. Angiogenesis and growth (proliferation and apoptosis) are independent and probably differentially operated procedures, with only growth partially controlled by p53 protein expression. Copyright 2002, Elsevier Science (USA). All rights reserved

Additional characterization of a hexanucleotide polymorphic site in the first intron of human H-ras gene: comparative study of its alterations in non-small cell lung carcinomas and sporadic invasive breast carcinomas

Intron 1 of the human I-I-l ns gene possesses a polymorphism consisting of repetitions of the GGGCCT consensus. Three alleles have been reported at this locus. We confirmed that two, pi and PZ, display four and two repeats, respectively, with their internal sequence structure similar to that previously described. The third, P3, previously assigned as a three-unit repetition allele according to its electrophoretic mobility and with no other information regarding its internal structure, was also found. Sequence analysis of the P3 allele revealed that it consists of three perfect repeats of the GGGCCT consensus. This polymorphism is present only in human c-H-ras gene, although single hexanucleotide repeats are found scattered within intron 1 of this gene in rodents. Analysis of this locus in matched tumor/distant normal samples from. (i) 38 patients with nonsmall-cell lung carcinoma (NSCLC), and (ii) 35 patients with sporadic invasive breast carcinoma, revealed: (1) 6.6% and 19% loss of heterozygosity (LOH) respectively, and (2) 10.5% and 2.9% hexanucleotide instability (III) respectively, detected by the presence of shifted in length alleles. Shifted alleles exhibited altered internal sequence structure in comparison to normal ones, suggesting complex mutational events. The same pattern of alterations was also detected in tissues adjacent to lung adenocarcinomas and dysplasias adjacent to squamous cell carcinomas (7.7% LOH, 5.9% III), implying that abnormalities at this locus may be early events in lung carcinogenesis. The frequency of alterations (LOH vs. HI) was significantly different among NSCLC and breast cancer (P=.005), probably due to the different tumor biology of each system. Finally, altered mRNA expression of H-ras gene was detected in all cases with HI, but this finding was also observed in samples without I-II. In view of reports showing that elements in intron 1 of H-ras gene potentially influence its transcriptional regulation, from our results we cannot exclude that the hexanucleotide locus could be an element with possible involvement in expressional regulation of this gene. (C) 2001 Elsevier Science Tnc. All rights reserved

Relationship of the K-ras/c-mos expression patterns with angiogenesis in non-small cell lung carcinomas

Background: Neo-angiogenesis is an acquired capability vital for a tumor to grow and metastasize. Evidence has shown that the mitogen-activated protein (MAP) kinase pathway is involved in this process. Alterations of K-ras and c-mos, two pivotal components of this pathway, have been implicated in non-small cell lung carcinogenesis. In the present report, we examine, in a series of non-small cell lung carcinomas (NSCLCs), the status of K-ras and c-mos oncoproteins in correlation with the tumor neo-angiogenesis state and the major angiogenic factor, vascular endothelial growth factor (VEGF). Materials and Methods: c-mos and p-ERK1/2 status was evaluated immunohistochemically in a total of 65 NSCLCs, whereas the presence of K-ras mutations was examined by reverse transcriptase-polymerase chain reaction (RT-PCR) restriction fragment length polymorphism (R-FLP) in available matched normal tumor material from 56 cases. Microvessel density (MVD) was estimated by immunodetection of CD31 endothelial marker, and VEGF expression was assessed by immunohistochemistry. All possible associations were examined by a series of statistical methods. Results. Expression of oncogenic activated K-ras and c-mos overexpression was observed in 12 of 49 (25%) and in 16 of 61 (26%) informative cases, respectively. Only 1 of the 25 deregulated for K-ras or c-mos cases exhibited both alterations, suggesting a mutually exclusive relationship between activated K-ras and c-mos overexpression. (p = 0.074) in a subset of NSCLCs. In these cases, the MAPK kinase kinase/MEK/ERK pathway was found to be activated. MVD and VEGF expression were 36.9 +/- 10.6 mv/mm(2) and 73.1 +/- 20.0%, respectively. The most intriguing finding was that the [K-ras(No)/c-mos(P)] profile was significantly associated with low MVD levels compared to normal cases (p = 0.004); by contrast, no correlation was found: between the other K-ras/c-mos patterns and MVD. Furthermore, the former group exhibited the lowest VEGF levels. Conclusions: The mutually exclusive relationship between mutated K-ras and c-mos overexpression in a subset of NSCLCs implies a common signal transduction pathway in lung carcinogenesis. The effect of this pathway on NSCLC neo-angiogenesis seems to depend upon the status of c-mos, which acts as a molecular “switch,” possibly exerting a negative selective pressure on tumor progression