Neuroendocrine and biologic features of primary tumors and tissue in pulmonary large cell carcinomas

BACKGROUND: Because biological behavior in lung tumors with neuroendocrine differentiation is highly dependent on cell death (apoptosis) and angiogenesis, p21(waf1/cip1) and microvessel density have been targeted as potentially useful tumor markers. We sought to validate the importance of p21(waf1/cip1) and microvessel density and study their interrelationship, analyzing clinical factors, subclassifications, and tumor and stromal markers. METHODS: We examined p21(waf1/cip1) and other markers in tissue from 61 patients with surgically excised large cell carcinomas. The amount of tumor staining for p21(waf1/cip1) and microvessel density was evaluated by immunohistochemistry and morphometry. The study outcome was survival time until death from recurrent lung cancer. RESULTS: Multivariate Cox model analysis demonstrated that after surgical excision, histologic subtypes were significantly related to survival time (p = 0.02), but quantitative staining of the tumor for p21(waf1/cip1) and microvessel density added prognostic information and these variables were more strongly prognostic than histologic subtype (p = 0.00). Cut points at the median staining of 3.5% and 3.0% for p21(waf1/cip1) and microvessel density, respectively, divided patients into two groups with distinctive survival times. Patients with p21(waf1/cip1) staining of more than 3.5% and microvessel density staining of more than 3.0% had a median survival time of 14 months. CONCLUSIONS: Tumor staining for p21(waf1/cip1) and microvessel density in resected large cell carcinomas and certain other types of lung tumors was strongly related to survival. Patients with more than 3.0% staining in their tumors were at high risk of death from lung cancer and may be an appropriate target for prospective studies of adjuvant chemotherapy after surgical resection.     

Better surgical prognosis for patients with complete atrioventricular septal defect and Down's syndrome

Background

Several studies have shown that Down's syndrome is not a risk factor for biventricular repair of complete atrioventricular septal defects. However, few data are available about the comprehensive outcome of all the cardiac surgical procedures in patients with trisomy 21, including palliative surgery.

Methods

This is a retrospective study of 206 consecutive patients who underwent cardiac surgery from January 1992 to January 2002. Data about mortality and morbidity were analyzed and the impact of Down's syndrome was evaluated.

Results

Overall mortality was 7.7%. Actuarial survival was 94% among patients with Down's syndrome versus 86% of the group with normal karyotype (p = 0.12). The presence of unbalanced ventricles was the only independent risk factor affecting survival at multivariate analysis (p < 0.0001). The need for a Norwood type surgery was more frequent among non-Down patients (12.0% vs 1.5%, p = 0.02) as was the prevalence of pulmonary artery banding operations (22.9% vs 9.3%, p = 0.04). Cumulative mortality after palliation was higher in non-Down patients (44% vs 2.9%, p = 0.0001). Freedom from reoperation was lower in the group with normal chromosomes in respect to patients with Down's syndrome (81.4% vs 94.6%, p = 0.04), due to the higher prevalence of anomalies of the mitral valve (4.9% vs 1.8%, p = 0.03) or left ventricular outflow tract (7.3% vs 0%, p = 0.01).

Conclusions

Down patients showed a decreased risk for biventricular repair and lower mortality and morbidity in cases of complex cardiac malformations requiring complex palliative operations.     

The effect of maintenance immunosuppression medication on the change in kidney allograft function

BACKGROUND: The optimum maintenance immunosuppression regimen for kidney transplant recipients is uncertain. In this study we determined the effect of maintenance immunosuppression medications on the rate of kidney allograft function loss defined by the annualized change in glomerular filtration rate (GFR). METHODS: We studied 40,963 first kidney only transplant recipients between 1987 and 1996 with allograft survival of at least two years in the United States Renal Data System. Linear regression methods were applied to serial GFR estimates after transplantation to determine the annualized change in GFR. Patients were classified according to the type of maintenance calcineurin and purine metabolism inhibitor received after transplantation. Multiple linear regression was used to determine the independent effect of maintenance immunosuppression medications on the annualized change in GFR (mL/min/1.73m2/year). RESULTS: Compared to patients who received cyclosporine microemulsion (Neoral), a slower decline in GFR was observed in tacrolimus-treated patients (1.60 mL/min/1.73m2/year, 95% CI 1.22-1.97, P < 0.001) and patients who did not receive calcineurin inhibitors (0.82 mL/min/1.73m2/year, 95% CI 0.08-1.56, P= 0.03). In contrast, compared to compared to patients who received Neoral, a faster decline in GFR was observed in patients who received the original oil-based formulation of cyclosporine (Sandimmune) (-0.16 mL/min/1.73m2/year, 95% CI -0.003 to -0.32, P= 0.04) and patients with unknown calcinuerin inhibitor exposure (-2.11 mL/min/1.73m2/year, 95% CI -2.27 to -1.95, P < 0.001). Compared to patients who received azathioprine, patients who received mycophenolate mofetil (MMF) had a slower decline in GFR (0.61 mL/min/1.73m2/year, 95% CI 0.14-1.08, P= 0.01) and patients with unknown purine metabolism inhibitor exposure had a faster decline in GFR (-0.61 mL/min/1.73m2/year, 95% CI -0.75 to -0.47, P < 0.001.) In a subgroup analysis of patients who received a transplant after 1993, the decline in GFR was slower for tacrolimus compared to neoral treated patients (1.64 mL/min/1.73m2/year, 95% CI 1.15-2.14, P < 0.001) but was not different for MMF compared to azathioprine-treated patients (0.24 mL/min/1.73m2/year, 95% CI -0.38-0.85, P= 0.45). CONCLUSION: Tacrolimus and MMF were the calcineurin inhibitor and purine metabolism inhibitor associated with the most favorable effects on rates of change in allograft function. Because most transplant recipients establish a low baseline level of allograft function, the effect of immunosuppression medication on GFR decline should be considered when selecting a maintenance immunosuppression regimen.     

Identification and characterization of an antigen recognized by monoclonal antibody TRA 54 in mouse epididymis and vas deferens

Spermatozoa in testicular fluid are known to have weak forward motility and cannot fertilize eggs. The epididymis is known to participate in sperm maturation leading fertilization, but little is known about the specific epididymal molecules involved in the modification of sperm. In this study, we characterized the new pattern of expression of an antigen previously identified in testicular germ cells by monoclonal antibody (mAb) TRA 54. This antigen is expressed in epididymal and vas deferens epithelial cells in mice older than 24 days but not during younger developmental stages. Evaluation by immunohistochemistry shows that antigen expression is limited to the cytoplasm of a specific cell population of epithelia along the epididymal regions and vas deferens of adult mice. The molecules synthesized and released by epididymal and vas deferens epithelia into their lumen seem to bind on spermatozoa moving down through the ducts. Immunoblot analysis showed that the molecules recognized by mAb TRA 54 in testis and epididymis were similar and share a common epitope involving carbohydrate domains. Interestingly, the antigens identified in epididymal and vas deferens epithelial cells were expressed independently of testicular germ cells and are produced in an androgen-dependent manner. Finally, the molecules recognized by mAb TRA 54 seem to play an important role in spermatogenesis, as well as in epididymal function related to spermatozoa maturation and ability to fertilize.     

Bone Mineral Density in Menopausal Women with Primary Hyperparathyroidism before and after Parathyroidectomy

The relationship between osteoporosis and primary hyperparathyroidism (pHPT) has not been definitely established because both diseases occur predominantly in postmenopausal women, and because PTH has a paradoxical effect on bone. We have investigated the prevalence of reduced bone mineral density (BMD) in women with pHPT, its relationship with metabolic parameters, and its course after parathyroidectomy. A prospective observational study was carried out on perimenopausal and postmenopausal women consecutively diagnosed and operated on for pHPT. Demographic data were recorded, as well as, PTH, Ca, calciuria/24h, P, vitamin D, adenoma weight. The BMD was measured at three sites: femoral neck (FN), proximal femur (PF), and lumbar spine (LS). Fifty-two patients were included with a mean age of 61 ± 12 years. The prevalence of reduced BMD ( 1SD, T-score) was 80%–100% depending on site. Parathyroid hormone was higher in patients with osteoporosis (319 ± 181 pg/ml) than in those with osteopenia (230 ± 83 pg/ml) or normal BMD (148 ± 81 pg/ml; p < 0,04). Twenty-eight patients were investigated 1 year after parathyroidectomy. The BMD improved significantly at all sites, particularly in patients with osteoporosis. Age correlated inversely with BMD increases at the femoral sites (r= –0,47; p = 0,02) but not at the LS. 25-OHD₃ plasma levels correlated inversely with BMD increases at PF (r= –0,76; p < 0,0001). In pHPT, there is a high prevalence of BMD abnormalities. No metabolic variables had a definite influence on BMD values but a tendency was observed for lower BMD in severe pHPT. One year after parathyroidectomy, there were significant BMD increases that were more marked at femoral sites, in younger patients, in patients with preoperative osteoporosis, and in those with lower plasma levels of 25-OHD₃.This article was presented at the International Association of Endocrine Surgeons meeting, Uppsala, Sweden, June 14–17, 2004.     

Virtual colon dissection with CT colonography compared with axial interpretation and conventional colonoscopy: preliminary results

OBJECTIVE: The aim of this study was to determine whether a new virtual colon dissection 3D visualization technique for CT colonography has a shorter analysis time and better sensitivity for detection of colonic polyps than interpretation of axial CT images. SUBJECTS AND METHODS. CT colonography was performed in 22 patients using 4-MDCT followed by conventional colonoscopy on the same day. The CT colonography data sets were analyzed by virtual colon dissection, which virtually bisects and unfolds the colon along its longitudinal axis to inspect the inner colonic surface for polyps. The same CT data sets were independently evaluated using axial interpretation. All data sets were independently interpreted by two radiologists in a blinded manner. RESULTS: Conventional colonoscopy revealed 31 colonic lesions in 20 patients. Twenty two of the lesions were smaller than 10 mm; nine were 10 mm or larger. Two of the original 22 patients were excluded, one because of residual stool and fluid and the other because of an impassable stenosing rectal wall cancer. For virtual colon dissection, the per-lesion sensitivity was 42% for observer 1 and 68% for observer 2; for axial interpretation, the respective sensitivities were 48% and 61%. For polyps 10 mm or larger, the respective sensitivities were 67% and 89% for virtual colon dissection and 89% and 100% for axial interpretation. The average time for reconstruction and analysis of virtual colon dissection was 36.8 min versus 29.2 min for axial images. Virtual colon dissection was feasible in both the supine and the prone positions in 45.5% of colonic segments, in either the supine or the prone position in 24.5%, and in neither position in 30% of segments. CONCLUSION: Although virtual colon dissection may facilitate detection of colonic polyps in isolated cases, its detection rate is not superior to axial interpretation, which is mainly attributable to failed rendering of insufficiently distended colonic segments or regions with residual feces. Virtual colon dissection is also the more time-consuming of the two procedures. With further improvement of path-finding and image segmentation, however, virtual colon dissection has the potential to be a useful interpretation tool for CT colonography.     

Magnetic resonance imaging characteristics of six radiofrequency electrodes in a phantom study

PURPOSE: To evaluate and compare visibility and artifacts in magnetic resonance (MR) compatible radiofrequency (RF) electrodes for MR-guided RF ablation. MATERIAL AND METHODS: Six different MR compatible electrodes for RF ablation including two internally cooled single needles, one internally cooled cluster needle, two expandable needles and one perfused needle were tested in a phantom study at 0.2 Tesla and at 1.5 Tesla field strength. Fluoroscopic, T1- and T2-weighted fast spin echo (FSE) and gradient echo (GE) sequences, which are usually used for MR-guided interventions, were evaluated. Qualitative and quantitative evaluations were performed. Length, width, noise, tip artifacts, global artifacts and global visualization of the RF electrodes that showed all sequences at different angles. RESULTS: Qualitative analysis showed that electrodes were well visualized at all angles and sequences and on both MR imagers. Quantitative analysis showed that artifact-induced widening of the shaft was increased in all electrodes by: a). use of fluoroscopic sequences, GE sequences, and fat saturation, b). increasing the angle between the needle and main magnetic field, and c). high field strength (1.5 T). Expandable needles produced fewer tip artifacts but broader signal voids along the shaft compared to nonexpandable needles. Cluster electrodes produced less widening than the other electrodes. CONCLUSION: Visibility and artifacts in all six MR compatible RF electrodes are satisfactory and these electrodes could be used for MR-guided radiofrequency ablation procedures.     

Knowledge about transplantation and attitudes toward organ donation: a survey among medical students in northeast Brazil

During the registration for the second semester of 2002, 779 of the 1001 students from the Medical School, Federal University of Bahia, Brazil, answered an anonymous multiple-choice questionnaire including demographic variables, knowledge about transplantation issues, and willingness to donate organs. Mean age was 21.9 +/- 2.9 years (range: 17 to 51 years); 59.5% were men. Regarding the knowledge of which organs and tissues could be transplanted, 99.1% answered kidneys, 96.1% heart, 88.2% liver, 41.1% lung, 24.0% pancreas, 9% bowel, 98.3% corneas, 89.5% bone marrow, 38.1% heart valves, 47.7% skin, and 18.5% bone and tendons. Regarding the criteria of death, 82.4% answered that it is the lack of all brain activity, 8.2% cardiac arrest, 5.2% irreversible coma, and 4.2% did not know. As to the Brazilian transplantation law, 47.3% did not know, 51% had heard about it, and 1.7% answered that they knew the law in detail. As to the willingness to donate organs, 538 (69.2%) were donors. Of 239 nondonors, 51.1% answered the reason for not donating was the lack of confidence in the heath system, 14.3% had no knowledge of the matter, 17.7% were concerned about organ removal before brain death, and 1.7% for religious reasons. The percentage of those willing to donate organs was greater among spiritualists than among Catholics and Protestants. The results of this study support a greater emphasis on providing information regarding transplantation in medical schools to improve the knowledge of future heath care professionals about transplantation and organ donation issues.