RESUMEN
The mechanisms of p53-dependent apoptosis involve a set of genes that possess the ability to modulate oxidative stress. One of them PIG3, is induced by p53 through a microsatellite in its promoter region. This microsatellite was found to acquire its full structure and p53-functional dependence only in Hominoidea (apes and humans) and has been proposed to represent an evolutionary adaptation of tumor suppressor mechanisms. Microsatellite instability and genetic constitution, comprising the presence of the low repetition allele (10 TGYCC repeats), at this locus have been hypothesized to provide an increased risk for cancer development. Therefore, in the present analysis we examined this polymorphism in two common human cancers, lung and breast and compared it with corresponding control cases. Furthermore, for lung cancer we employed two different ethnic groups, Greek and British. Analysis of this locus in this types of tumors showed: (1) a very low frequency of microsatellite instability and loss of heterozygosity (1.4% and 4%, respectively) in the examined carcinomas, (2) the homozygous presence of the 10 repeats allele only in the control cases, and (3) a non-significant increase of the most frequent allele (15 repeats) in the cancer groups as compared to control ones. The last two observations were found in both Greek and British populations. Taken together, these data do not support the notion that this PIG3 polymorphism is associated with an increased risk for cancer susceptibility. Larger studies including other types of cancer should also be performed.
Asunto(s)
Neoplasias de la Mama/genética , Neoplasias Pulmonares/genética , Polimorfismo Genético , Proteínas Proto-Oncogénicas/genética , Proteína p53 Supresora de Tumor/fisiología , Secuencia de Bases , Cartilla de ADN , Genética de Población , Genotipo , Humanos , Péptidos y Proteínas de Señalización Intracelular , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factores de RiesgoRESUMEN
It is well established that p16(INK4A) protein acts as a cell cycle inhibitor in the nucleus. Therefore, cytoplasmic localization of p16 (INK4A) usually is disregarded by investigators as nonspecific. Three recent studies reported findings that differ from the current view concerning p16(INK4A) immunohistochemical localization. All three demonstrated that breast and colon cancers expressing cytoplasmic p16(INK4) represent distinct biological subsets. We previously detected in a percentage of non-small cell lung carcinomas simultaneous nuclear and cytoplasmic p16(INK4A) staining. In view of the reports concerning breast and colon carcinomas, we conducted an ultrastructural re-evaluation of our cases to clarify the specificity of p16(INK4A) cytoplasmic expression. We observed p16 (INK4A) immunolocalization in both the nucleus and the cytoplasm of a proportion of tumor cells. Diffuse dense nuclear staining was detected in the nucleoplasm, whereas weaker granular immunoreactivity was observed in the cytoplasm near the rough endoplasmic reticulum. Negative tumor cells also were visible. In the tumor-associated stromal, cells p16(INK4A) immunoreactivity was detected only in the nuclei. We have demonstrated that p16(INK4A) cytoplasmic staining is specific and suggest that it represents a mechanism of p16(INK4A) inactivation similar to that observed in other tumor suppressor genes.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/ultraestructura , Inhibidor p16 de la Quinasa Dependiente de Ciclina/metabolismo , Citoplasma/metabolismo , Citoplasma/ultraestructura , Proteínas Nucleares/metabolismo , Artefactos , Carcinoma de Pulmón de Células no Pequeñas/patología , Núcleo Celular/metabolismo , Núcleo Celular/ultraestructura , Inhibidor p16 de la Quinasa Dependiente de Ciclina/ultraestructura , Humanos , Inmunohistoquímica , Microscopía Electrónica de Transmisión , Proteínas Nucleares/ultraestructura , Células Tumorales CultivadasRESUMEN
BACKGROUND: Deregulation of MHC class II molecules consists of a favorable mechanism of tumor evasion from immune surveillance. Among these molecules, HLA-DR antigens are the predominant ones in cancer. In the present study we sought to investigate the ability of tumor infiltrating immune cells (TIICs) to express HLA-DR antigen in the primary tumor site and reactive regional lymph nodes (LNs) in non small cell lung cancer (NSCLC). MATERIALS AND METHODS: Material consisting of 60 NSCLCs with corresponding regional LNs was studied by immunohistochemistry for human leukocyte antigen D-region related (HLA-DR) expression. Control reactive LNs, regional to several different malignant and non-malignant disorders, were also included in the study. RESULTS: Primary tumor site investigation revealed positive HLA-DR cancer cells in 22% of cases, whereas TIICs rarely expressed HLA-DR antigens. The lack of HLA-DR expression in TIICs was gradually attenuated as the distance from the primary tumor site decreased. Regional LN investigation showed that all follicles (paracapsular and deep cortical ones) were HLA-DR-negative in 60% of the LNs; in the remaining 40%, the paracapsular follicles remained negative, while all deep cortical ones were positive. Interestingly, LNs possessing only HLA-DR-negative follicles were more proximal to the primary tumor site compared to those that had only the paracapsular follicles negative. All control reactive LNs, regional to several distinct malignant and non-malignant disorders, were found to be HLA-DR-positive. CONCLUSION: The impairment of HLA-DR expression, detected both in neoplastic and by-stander immune cells, may justify the immunosuppression observed in NSCLC. This phenomenon may be due to a putative soluble factor in the tumor environment secreted by cancer cells.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/inmunología , Antígenos HLA-DR/inmunología , Neoplasias Pulmonares/inmunología , Linfocitos Infiltrantes de Tumor/inmunología , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Antígenos HLA-DR/biosíntesis , Humanos , Tolerancia Inmunológica/inmunología , Inmunohistoquímica , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/metabolismo , Neoplasias Pulmonares/metabolismo , Ganglios Linfáticos/inmunología , Ganglios Linfáticos/metabolismo , Linfocitos Infiltrantes de Tumor/metabolismo , Macrófagos/inmunología , Macrófagos/metabolismoRESUMEN
Intron 1 of the human H-ras gene possesses a polymorphism consisting of repetitions of the GGGCCT consensus. Three alleles have been reported at this locus. We confirmed that two, P1 and P2, 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 non-small-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 (HI) 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% HI), 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 HI. 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.
Asunto(s)
Neoplasias de la Mama/genética , Carcinoma de Pulmón de Células no Pequeñas/genética , Genes ras , Intrones , Neoplasias Pulmonares/genética , Oligonucleótidos/genética , Polimorfismo Genético , Secuencia de Bases , Neoplasias de la Mama/patología , Cartilla de ADN , Humanos , Invasividad Neoplásica , Reacción en Cadena de la PolimerasaRESUMEN
Little is known about the status of the mitogen-activating protein kinase pathways in lung cancer. One of the key molecules taking part in these pathways is the product of the c-mos proto-oncogene, which plays an important role in oocyte maturation. In vitro investigations in somatic cells have shown that c-mos expression has opposing effects on the cell cycle, which suggests that this proto-oncogene may represent an important determinant of aberrant cell function (genomic instability and altered kinetics). A recent study suggests that these effects may be p53 dependent. In view of the apparent link between c-mos and p53, we investigated in a series of 56 non-small cell lung carcinomas: a) the status of c-mos; b) its relationship to genomic instability (aneuploidy) and two kinetic parameters of the tumors, proliferation and apoptotic indexes (AI); and c) its association with p53 alterations and their concomitant relationship with the above parameters. We found c-mos overexpression in 27% of the tumors. Expression was higher in stages II/III (34%) than in stage I (17%; P = 0.018). Complete concordance was observed between c-mos overexpression and elevated c-mos mRNA levels. Because c-mos gene amplification was not detected, its deregulated expression may be attributable to increased transcription. Of the c-mos positive [c-mos(P)] cases, 77% were associated with aneuploidy. Sequencing showed two silent mutations and one missense (R-->L) at codon 22, located in a region critical for c-mos stability. In contrast to the findings of some in vitro studies, c-mos(P) tumors had a lower mean AI score than the c-mos negative [c-mos(N)] tumors had, implying that induction of apoptosis may have been defective. Indeed, 86% of the tumors overexpressing c-mos showed p53 alterations. The carcinomas with concomitant alterations of c-mos and p53 [c-mos(P)/p53 positive] had significantly lower AI values (P < 0.001) and were more frequently associated with aneuploidy (P = 0.015) than the c-mos(N)/p53 negative tumors but not the c-mos(N)/p53 positive tumors, which suggests that p53 status is the main determinant of ploidy status and apoptosis in our series. This finding also strengthens the concept that wild-type p53 plays a "safeguard" role in preventing oncogene-mediated activation.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/genética , Neoplasias Pulmonares/genética , Proteínas Proto-Oncogénicas c-mos/genética , Anciano , Aneuploidia , Apoptosis , Secuencia de Bases , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , División Celular , Análisis Mutacional de ADN , ADN de Neoplasias/química , ADN de Neoplasias/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Inmunohistoquímica , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Mutación , Estadificación de Neoplasias , Fosforilación , Polimorfismo Conformacional Retorcido-Simple , Proto-Oncogenes Mas , Proteínas Proto-Oncogénicas c-mos/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Análisis de Supervivencia , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
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 (RFLP) in available matched normal tumor material from 56 cases. Microvessel density (MVD) was estimated by immunodetection of CD3, 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/mm2 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.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/fisiopatología , Genes mos , Genes ras , Neoplasias Pulmonares/fisiopatología , Neovascularización Patológica , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Factores de Crecimiento Endotelial/metabolismo , Regulación Neoplásica de la Expresión Génica , Humanos , Inmunohistoquímica , Neoplasias Pulmonares/patología , Linfocinas/metabolismo , Sistema de Señalización de MAP Quinasas/fisiología , Modelos Biológicos , Proteínas Proto-Oncogénicas c-mos/metabolismo , Factor A de Crecimiento Endotelial Vascular , Factores de Crecimiento Endotelial Vascular , Proteínas ras/metabolismoRESUMEN
BACKGROUND: Recent in vitro studies provide evidence that the cell cycle molecules pRb, p53 and MDM2 form a tightly regulated protein network. In this study, we examined the relationship of this protein network in a series of non-small cell lung carcinomas (NSCLCs), with the kinetic parameters, including proliferative activity or proliferation index (PI) and apoptotic index (AI), and ploidy status of the tumors. MATERIAL AND METHODS: A total of 87 NSCLCs were examined using immunohistochemical and molecular methods in order to estimate the status of the pRb-p53-MDM2 network. The kinetic parameters and the ploidy status of the tumors were assessed by in situ assays. The possible associations between alterations of the network, kinetic parameters and ploidy status of the carcinomas were assessed with a series of statistical methods. RESULTS: Aberrant expression of pRb (Ab) and overexpression of p53 (P) and MDM2 (P) proteins were observed in 39%, 57%, and 68% of the carcinomas, respectively. The comprehensive analysis revealed that concurrent alterations in all three cell cycle regulatory molecules were the most frequent pattern, pRb(Ab)/p53(P)/MDM2(P); this "full abnormal" phenotype represented approximately 27% of the cases. This immunoprofile obtained the highest PI/AI value; whereas, the "normal" phenotype was the lowest one (p = 0.004). Furthermore, the pattern pRb(Ab)/p53(P)/MDM2(P) acquired the highest PI (p < 0.001) and lowest AI (p < 0.001) scores. Interestingly, the groups of carcinomas with impaired expression of one or two molecules attained PI/AI ratio values clustered in a narrow range placed in the middle of the scores exhibited by the "normal" and "full abnormal" phenotypes. These tumors had significantly lower AI, but similar PI values, compared with those noticed in the normal pattern. In addition, it was observed that the pRb(Ab)/p53(P)/MDM2(P) phenotype was also significantly associated with aneuploidy (p = 0.002) and a tendency was observed when the expression of two components was altered (p = 0.055). CONCLUSIONS: Our findings suggest that simultaneous deregulation of all members of the pRb-p53-MDM2 network confers an additive effect on tumor growth. The apoptotic pathway seems to be more susceptible to its defects than the cell proliferation machinery. The findings of the ploidy analysis, which are in parallel with those regarding the proliferative activity and the apoptotic rate study, further support the concept that these molecules constitute a tightly regulated network participating in cell cycle control and chromosomal stability.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Neoplasias Pulmonares/metabolismo , Proteínas Nucleares , Proteínas Proto-Oncogénicas/metabolismo , Proteína de Retinoblastoma/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Alelos , Aneuploidia , Apoptosis , Secuencia de Bases , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , División Celular , Cartilla de ADN/genética , Diploidia , Expresión Génica , Genes de Retinoblastoma , Genes p53 , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Modelos Biológicos , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas c-mdm2 , ARN Mensajero/genética , ARN Mensajero/metabolismo , ARN Neoplásico/genética , ARN Neoplásico/metabolismo , Proteína de Retinoblastoma/genética , Células Tumorales Cultivadas , Proteína p53 Supresora de Tumor/genéticaAsunto(s)
Aorta Torácica/lesiones , Aneurisma de la Aorta Torácica/cirugía , Implantación de Prótesis Vascular/métodos , Traumatismos Torácicos/complicaciones , Accidentes de Tránsito , Angiografía , Aorta Torácica/diagnóstico por imagen , Aorta Torácica/cirugía , Aneurisma de la Aorta Torácica/diagnóstico por imagen , Aneurisma de la Aorta Torácica/etiología , Materiales Biocompatibles , Prótesis Vascular , Femenino , Humanos , Persona de Mediana Edad , Tereftalatos Polietilenos , Traumatismos Torácicos/diagnóstico por imagen , Traumatismos Torácicos/cirugíaRESUMEN
Deletions in the 5q14 region have been described in a variety of neoplasms, such as testicular germ cell tumors, ovarian, gastric and lung cancer. The high frequency of allelic losses observed in this region implies the presence of putative tumor suppressor gene(s) (TSGs). In the present study, we investigated in a series of 56 non-small cell lung carcinomas (NSCLCs) the allelic imbalance (Alm) within the 5q14 region, employing the D5S644 marker, and its relationship with p53 abnormalities, the kinetic parameters [proliferation index (PI) and apoptotic index (AI)] and the ploidy status of the carcinomas. AI at D5S644 was found at a frequency of 51.2%. The rather high percentage of Alm in stage I tumors suggests an early involvement in NSCLC development. LOH at 5q14 was associated with decreased AR in lung tumors insinuating the presence of a putative TSG(s) (P=0.008). Simultaneous alterations of both p53 and D5S644 locus were the most frequent pattern observed (37.5%). Cases demonstrating this profile also exhibited a marked decrease in AI (P=0.001). These findings imply a synergistic mechanism of co-operation between different TSGs. However, proliferation activity was dependent only on p53 status, leading to the assumption that the putative TSG(s) present at 5q14 may probably be involved in normal apoptotic procedures. Further studies are needed to identify the candidate gene(s).
Asunto(s)
Apoptosis/genética , Carcinoma de Pulmón de Células no Pequeñas/genética , Cromosomas Humanos Par 5/genética , ADN de Neoplasias/análisis , Genes p53/genética , Pérdida de Heterocigocidad , Neoplasias Pulmonares/genética , Anciano , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , División Celular , Cartilla de ADN/química , Femenino , Frecuencia de los Genes/genética , Humanos , Etiquetado Corte-Fin in Situ , Pérdida de Heterocigocidad/genética , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Repeticiones de Microsatélite/genética , Persona de Mediana Edad , Estadificación de Neoplasias , Ploidias , Pronóstico , Tasa de SupervivenciaRESUMEN
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 A, 52 patients) was 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.
Asunto(s)
Amoxicilina/uso terapéutico , Antibacterianos/uso terapéutico , Ácido Clavulánico/uso terapéutico , Traumatismos de la Pierna/complicaciones , Penicilinas/uso terapéutico , Infección de Heridas/etiología , Infección de Heridas/prevención & control , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Riesgo , Infección de Heridas/epidemiologíaRESUMEN
This is the case of a patient with metastatic disease diagnosed 40 years after a radical mastectomy which was followed by radiation treatment for breast cancer. The patient had nonspecific symptoms for 3 years, and a lymph node biopsy revealed the underlying cause to be recurrent breast cancer. Excision of the largest metastases combined with chemotherapy resulted in a further 3-year remission.
Asunto(s)
Adenocarcinoma/secundario , Neoplasias de la Mama/patología , Ganglios Linfáticos/patología , Mastectomía Radical , Adenocarcinoma/diagnóstico , Adenocarcinoma/terapia , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/terapia , Femenino , Estudios de Seguimiento , Humanos , Escisión del Ganglio Linfático , Ganglios Linfáticos/efectos de los fármacos , Ganglios Linfáticos/cirugía , Metástasis Linfática , Recurrencia Local de NeoplasiaRESUMEN
OBJECTIVE: We reviewed our experience of 343 descending and thoracoabdominal aortic aneurysm repairs to determine the impact of the adjuncts distal aortic perfusion and cerebral spinal fluid drainage on neurological deficit and death. MATERIALS AND METHODS: Between January 1991 and March 1996, 104 (30%) patients were operated for thoracoabdominal aortic aneurysm type I, 118 (34%) for type II, 68 (20%) for type III or type IV, and 53 (15%) for descending thoracic type. Before September 1992, simple cross-clamp was used for 94 (27%) patients. After September 1992, adjuncts were used for 186 (54%) patients. RESULTS: Overall neurological deficit was 33/343 (10%). Neurological deficit for simple cross-clamp patients compared to adjunct patients was 15/94 (16%) vs. 12/186 (7%) (O.R. 0.36, p < 0.01). For types I and II the incidence was 11/52 (21%) vs. 12/141 (9%) (O.R. 0.35, p < 0.02) and for type II, nine out of 22 (41%) vs. 11/85 (13%) (O.R. 0.21, p < 0.003). Overall 30-day mortality was 43/343 (13%), including patients presenting with rupture. Excluding these patients, overall 30-day mortality was 33/322 (10%). CONCLUSION: Cerebral spinal fluid drainage and distal aortic perfusion decreased the incidence of neurological deficit and were particularly effective for patients at highest risk with type II thoracoabdominal aortic aneurysm.
Asunto(s)
Aneurisma de la Aorta Abdominal/líquido cefalorraquídeo , Aneurisma de la Aorta Torácica/líquido cefalorraquídeo , Disección Aórtica/líquido cefalorraquídeo , Enfermedades del Sistema Nervioso/prevención & control , Complicaciones Posoperatorias/prevención & control , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Disección Aórtica/complicaciones , Disección Aórtica/cirugía , Aorta Abdominal/cirugía , Aorta Torácica/cirugía , Aneurisma de la Aorta Abdominal/complicaciones , Aneurisma de la Aorta Abdominal/cirugía , Aneurisma de la Aorta Torácica/complicaciones , Aneurisma de la Aorta Torácica/cirugía , Niño , Drenaje/instrumentación , Drenaje/métodos , Drenaje/estadística & datos numéricos , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Enfermedades del Sistema Nervioso/epidemiología , Perfusión/instrumentación , Perfusión/métodos , Perfusión/estadística & datos numéricos , Complicaciones Posoperatorias/epidemiología , Resultado del TratamientoRESUMEN
PURPOSE: The effect of retrograde cerebral perfusion on the incidence of stroke and death among patients undergoing repair of aneurysms of the ascending aorta and transverse arch was determined. MATERIALS AND METHODS: Between January 1991 and March 1995, 161 patients were operated on for aneurysms of the ascending aorta and transverse arch. Thirty-three of the patients (20%) had an aneurysm of the ascending aorta only and 128 (80%) had aneurysms of both the ascending aorta and the transverse arch. All the patients underwent cardiopulmonary bypass, profound hypothermia, and circulatory arrest, and 120 (74%) also underwent retrograde cerebral perfusion. Median pump time was 143 minutes (range, 21 to 461 minutes). Median circulatory arrest time was 42 minutes (range, 8 to 111 minutes), and median myocardial ischemic time was 71 minutes (range, 14 to 306 minutes). RESULTS: The overall 30-day mortality rate was 6% (9 patients) and the incidence of stroke was 4% (7 patients). The use of retrograde cerebral perfusion demonstrated a protective effect against stroke (3 of 120 patients, or 3%) compared with no retrograde cerebral perfusion (4 of 41 patients, or 9%; odds ratio, 0.24; confidence interval, 0.06 to 0.99; p < 0.049). This was most significant in patients more than 70 years of age; none of the 36 elderly patients who received retrograde cerebral perfusion had a stroke, compared with 3 of the 13 (23%) who did not (p < 0.003). Only pump time was associated with an increased risk of stroke (odds ratio, 1.01; 95% confidence interval, 1.00 to 1.02; p < 0.005). Pump time also was associated with increased mortality (odds ratio, 1.01; 95% confidence interval, 1.00 to 1.02; p < 0.008). CONCLUSION: Retrograde cerebral perfusion decreased the incidence of stroke in patients undergoing repair of aneurysms of the ascending aorta and transverse arch.
Asunto(s)
Aneurisma de la Aorta/terapia , Trastornos Cerebrovasculares/prevención & control , Reperfusión/métodos , Adulto , Anciano , Anciano de 80 o más Años , Aorta , Aneurisma de la Aorta/mortalidad , Aneurisma de la Aorta Torácica/mortalidad , Aneurisma de la Aorta Torácica/terapia , Puente Cardiopulmonar , Trastornos Cerebrovasculares/diagnóstico , Distribución de Chi-Cuadrado , Intervalos de Confianza , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Tasa de SupervivenciaRESUMEN
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.
Asunto(s)
Neoplasias de la Vaina del Nervio/cirugía , Neurofibromatosis 1/cirugía , Neoplasias Retroperitoneales/cirugía , Anciano , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Índice Mitótico , Neoplasias de la Vaina del Nervio/patología , Neurilemoma/patología , Neurilemoma/cirugía , Neurofibroma/patología , Neurofibroma/cirugía , Neurofibromatosis 1/patología , Neoplasias Retroperitoneales/patología , Espacio Retroperitoneal/patología , Espacio Retroperitoneal/cirugíaRESUMEN
The plasma concentration of lipoprotein(a) [Lp(a)] is highly correlated with the incidence of cardiovascular and peripheral vascular disease. A positive physiological role for Lp(a) has not yet been clearly identified, although elevated plasma levels in pregnant women, long-distance runners, subjects given growth hormone, patients after cardiovascular surgery, and patients with cancer, diabetes, or renal disease suggest its involvement in tissue synthesis and repair. The hypothesis that Lp(a) is involved in repair/reinforcement of the aorta was tested in 38 patients undergoing surgery for aortic aneurysm. In 29 patients 1 day before surgery, the mean plasma Lp(a) protein level was 10.7 mg/dl. At about 1, 2, and 8 weeks after surgery, the level was 14.1, 15.1, and 15.2 mg/dl, respectively. These levels are significantly higher than those of a comparable group of normal subjects (6.4 mg/dl; n = 274). Specimens of resected aortic aneurysm showed extensive medial degeneration, discontinuous elastic fibers, and deposition of mucopolysaccharides; these specimens were treated with a detergent-containing buffer to extract entrapped lipoproteins. The mean Lp(a) protein level in aortic wall extracts was 14.6 ng/mg tissue; these individual values were significantly associated with plasma Lp(a) levels before surgery (r2 = 0.31, p = 0.0003). The mean Lp(a) protein level in aortic thrombus extracts was substantially higher at 69.6 ng/mg tissue; these individual levels also were significantly associated with plasma Lp(a) concentrations before surgery (r2 = 0.68, p < 0.0001). The observations that: (i) plasma Lp(a) protein is about 1.7-fold higher in patients with aortic aneurysms than in normal subjects; and (ii) that Lp(a) protein in the aneurysmic thrombus is about 4.8-fold higher than in the aortic wall suggest that this lipoprotein plays a significant and direct role in thrombus formation and in reinforcement of the aneurysmic aortic wall.
Asunto(s)
Aorta/patología , Aneurisma de la Aorta Abdominal/cirugía , Lipoproteína(a)/sangre , Trombosis/fisiopatología , Adolescente , Adulto , Anciano , Aorta/química , Femenino , Histocitoquímica , Humanos , Lípidos/sangre , Lipoproteína(a)/fisiología , Masculino , Persona de Mediana Edad , Músculo Liso Vascular/química , Análisis de Regresión , Factores de Riesgo , Cicatrización de Heridas/fisiologíaRESUMEN
BACKGROUND: Adenosine perfusion scintigraphy is a powerful technique for diagnosing coronary artery disease and risk stratifying patients with recent myocardial infarction. METHODS AND RESULTS: We investigated the use of adenosine 201Tl tomography to risk stratify 106 patients undergoing vascular arterial reconstruction consisting of lower limb arterial grafting in 44, aortic aneurysmectomy in 36, and carotid endarterectomy in 26 patients. Abnormal tomograms occurred in 57 patients (54%), 47 (82%) of whom had reversible perfusion defects. There were three postoperative deaths, all in the group that underwent aortic aneurysmectomy. Another patient with an aortic aneurysm had unstable angina and one patient who underwent lower limb arterial surgery had pulmonary edema after surgery. No patient without transient defects had an event (negative predictive value 100%). Cardiac events occurred only in patients with transient perfusion defects. However, only 5 of 47 such patients had events (positive predictive value 11%). The perfusion defect size (23% +/- 14% vs 8.9% +/- 135; p = 0.034) and the ischemic fraction (20% +/- 16% vs 5.6% +/- 8.9%; p = 0.009) were 2.5- and 3.5-fold larger, respectively, in patients with than in those without events. A history of diabetes mellitus or previous infarction did not enhance the predictive value of the test. CONCLUSION: Thus absence of reversible hypoperfusion during adenosine scintigraphy ensures virtual absence of postoperative cardiac events. Patients undergoing aortic aneurysmectomy may be targeted preferentially for risk-stratification strategies in the future.
Asunto(s)
Adenosina , Arterias/cirugía , Corazón/diagnóstico por imagen , Radioisótopos de Talio , Tomografía Computarizada de Emisión de Fotón Único , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , RiesgoRESUMEN
We present the case of a young patient with abdominal pain of 3 weeks' duration and a preoperative presumptive diagnosis of acute appendicitis, diverticulitis, colon perforation, or possibly neoplasm. Even after resection of a large mass involving the right colon, the diagnosis was not confirmed until surgical pathology identified torsion, partial necrosis, and inflammation of an epiploic appendix of the right colon.
Asunto(s)
Colitis/diagnóstico , Adulto , Colitis/patología , Colitis/cirugía , Colon/irrigación sanguínea , Colon/patología , Diagnóstico Diferencial , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/cirugía , Humanos , Infarto/diagnóstico , Infarto/cirugía , Masculino , Necrosis , Trombosis/diagnóstico , Trombosis/cirugía , Anomalía TorsionalRESUMEN
The purpose of this study was to evaluate the use of retrograde cerebral perfusion via the superior vena cava during profound hypothermia and circulatory arrest (CA) in pigs. In three groups of 5 pigs each, group A (control) underwent cardiopulmonary bypass and normothermic CA for 1 hour, group B underwent cardiopulmonary bypass, profound hypothermia, and CA (15 degrees C nasopharyngeal) for 1 hour, and group C underwent the same procedure as group B plus retrograde cerebral perfusion. In group A none awoke. In group B, 2 of 5 did not awake and 3 of 5 awoke unable to stand, 2 with perceptive hind limb movement and 1 moving all extremities. In group C all awoke, 4 of 5 able to stand and 1 of 5 unable to stand but moving all limbs. In neurologic evaluation group B had significantly lower Tarlov scores than group C (p = 0.0090). Group B mean wake-up time, plus or minus standard error of the mean, was 124.6 +/- 4.6 minutes versus 29.2 +/- 5.1 in group C (p = 0.0090). In group B late phase CA cerebral blood flow dropped 30.9% +/- 4.8%, but in group C it rose 24.7% +/- 9.3% (p = 0.0007, pooled variance t test, two-tailed). In group B late phase CA brain oxygenation decreased 46.0% +/- 13.9% but it increased 26.1% +/- 5.4% in group C (p = 0.0013). This difference was reduced somewhat during rewarming (B, -21.2% +/- 14.9%; C, 16.4% +/- 4.7%; p = 0.043). Group B rewarming jugular venous O2 saturation was 30.8% +/- 2.5% versus 56.0% +/- 4.4% in group C (p = 0.0011). We conclude that in pigs retrograde cerebral perfusion combined with profound hypothermia during CA significantly reduces neurologic dysfunction, providing superior brain protection.
Asunto(s)
Circulación Cerebrovascular , Paro Cardíaco Inducido , Hipotermia Inducida , Animales , Velocidad del Flujo Sanguíneo , Encéfalo/metabolismo , Encéfalo/patología , Dióxido de Carbono/sangre , Puente Cardiopulmonar , Enfermedades del Sistema Nervioso Central/etiología , Concentración de Iones de Hidrógeno , Venas Yugulares , Flujometría por Láser-Doppler , Oxígeno/sangre , Oxígeno/metabolismo , Porcinos , Vena Cava SuperiorRESUMEN
Here we describe a case of angina pectoris in a patient for whom an extensive cardiovascular workup was done, with negative results. Eventually, the cause of his symptoms was found to be pernicious anemia. Although angina is an uncommon manifestation of pernicious anemia, a review of the literature suggests that the correlation between anemia and angina has been well described. Our case highlights an important differential diagnosis to consider for patients with exercise-induced chest pain and serves to emphasize the attention that should be focused on simple screening laboratory studies. The emphasis in this case is the sequence in which the studies are done. A simple complete blood count with proper interpretation and intervention at the outset of evaluation could possibly have prevented a number of unnecessary, invasive, and costly studies.
Asunto(s)
Anemia Perniciosa/diagnóstico , Angina de Pecho/diagnóstico , Anciano , Anemia Perniciosa/sangre , Diagnóstico Diferencial , Estudios de Seguimiento , Humanos , Masculino , Vitamina B 12/sangreRESUMEN
A 62-year-old woman who underwent an aortic valve replacement for severe aortic valve stenosis developed postoperative thrombocytopenia and adult respiratory distress syndrome, simultaneously. Both complications resolved promptly after discontinuing heparin therapy. The presence of a heparin-related antiplatelet antibody was detected by in vitro testing. The time course of clinical events suggests the possibility of a heparin-induced, immune-mediated injury to both the pulmonary vascular endothelium and the platelet membrane as an underlying pathophysiologic mechanism.