Toward a more complete recognition of immunoreactive antigens in squamous cell lung carcinoma

There is very limited knowledge about the antibody response against tumor-expressed antigens in lung cancer. To arrive at a more complete picture of lung cancer antigens, we generated 2 cDNA libraries from squamous cell lung carcinoma and isolated 15 immunogenic antigens using autologous sera. Among the antigens most frequently identified were the lymphoid blast crisis oncogene (LBC), an unknown hypothetical protein and the p53-binding protein (TP53 BP), which have already been associated with tumor development. Of the immunogenic antigens, 6 map to chromosomes that are frequently altered in squamous cell lung carcinoma. SEREX database analysis showed that 7 of the identified immunogenic antigens have been associated with the humoral immune response in other human tumors. Screening with heterologous sera of patients with lung carcinoma identified 4 antigens, including human protein kinase C and TP53 BP, which have also been found by autologous screening. Only 1 of the 15 identified antigens reacted with any of the 36 control sera, which were taken from individuals without known disease. Sera from adenocarcinoma and large cell carcinoma of the lung were not reactive for the antigens. In summary, using 2 newly established cDNA libraries, we isolated 15 novel antigens, which were subsequently evaluated for the frequency of their corresponding antibodies in autologous, normal and heterologous sera; their chromosomal localization; and their correlation with survival after surgery.     

Galectin-1 modulates human glioblastoma cell migration into the brain through modifications to the actin cytoskeleton and levels of expression of small GTPases

We show that high-grade astrocytic tumors with high levels of galectin-1 expression are associated with dismal prognoses. The immunohistochemical analysis of galectin-1 expression of human U87 and U373 glioblastoma xenografts from the brains of nude mice revealed a higher level of galectin-1 expression in invasive areas rather than non-invasive areas of the xenografts. Nude mice intracranially grafted with U87 or U373 cells constitutively expressing low levels of galectin-1 (by stable transfection of an expression vector containing the antisense mRNA of galectin-1) had longer survival periods than those grafted with U87 or U373 cells expressing normal levels of galectin-1. Galectin-1 added to the culture media markedly and specifically increased cell motility levels in human neoplastic astrocytes. These effects are related to marked modifications in the organization of the actin cytoskeleton and the increase in small GTPase RhoA expression. All the data obtained indicate that galectin-1 enhances the migratory capabilities of tumor astrocytes and, therefore, their biological aggressiveness.     

Use of electrical impedance scanning in the differentiation of sonographically suspicious and highly suspicious lymph nodes of the head–neck region

Sonographic differentiation between inflammatory and malignant lymph nodes is difficult, due in part to almost unchanged morphology of small lymph node metastases; however, as cancer cells exhibit altered dielectric properties, measurement of local electrical field distortions may be useful as adjunct to ultrasound in detection of malignancy. In this study, we evaluated the ability of electrical impedance scanning (EIS) to differentiate cervically located sonographically suspicious or highly suspicious lymph nodes. Seventy patients with 106 sonographically suspicious lymph nodes (mean size 20 x 13 x 13 mm, mean depth 8 mm) were examined using TransScan TS2000 (Siemens, Erlangen, Germany; manufactured by TransScan Research and Development Co., Israel). Included in the study were cervical ( n=64), inframandibular/periparotideal ( n=32) and nuchal/supraclavicular ( n=10) nodes. The EIS results were compared with histopathological ( n=100) and serological ( n=6) findings. Sixty-two of 64 malignant lymph nodes were correctly detected using EIS; 19 of 42 inflammatory/benign lymph nodes were correctly identified as benign (true positive 96.9%, true negative 45.2%; accuracy 71.3%, negative predictive value 90.5%, positive predictive value 59.6%). The high tumour detection rate achieved in this study suggests that EIS may be of value as an adjunctive technique in differentiation of lymph nodes of the head-neck region. Software changes to reduce the high number of false-positive markers are, however, necessary to improve the value in the evaluation during a regular clinical routine.     

Correlation of bone mineral density with strength and microstructural parameters of cortical bone in vitro

The aim of this study was to evaluate the influence of microstructural parameters, such as porosity and osteon dimensions, on strength. Therefore, the predictive value of bone mineral density (BMD) measured by quantitative computed tomography (QCT) for intracortical porosity and other microstructural parameters, as well as for strength of cortical bone biopsies, was investigated. Femoral cortical bone specimens from the middiaphysis of 23 patients were harvested during total hip replacement while drilling a hole (dia. 4.5 mm) for the relief of the intramedullary pressure. In vitro structural parameters assessed in histological sections as well as BMD determined by quantitative computed tomography were correlated with yield stress, and elastic modulus assessed by a compression test of the same specimens. Significant correlations were found between BMD and all mechanical parameters (elastic modulus: r = 0.69, p < 0.005; yield stress: r = 0.64, p < 0.005). Significant correlations between most structural parameters assessed by histology and yield stress were discovered. Structural parameters related to pore dimensions revealed higher correlation coefficients with yield stress (r = -0.69 for average pore diameter and r = -0.62 for fraction of porous structures, p < 0.005) than parameters related to osteons (r = 0.60 for osteon density and average osteonal area, p < 0.005), whereas elastic modulus was predicted equally well by both types of parameters. Significant correlations were found between BMD and parameters related to porous structures (r = 0.85 for porosity, 0.80 for average pore area, and r = 0.79 for average pore diameter in polynomial regression, p < 0.005). Histologically assessed porosity correlated significantly with parameters describing porous structures and haversian canal dimensions. Our results indicate a relevance of osteon density and fraction of osteonal structures for the mechanical parameters of cortical bone. We consider the measurement of BMD by quantitative computed tomography to be helpful for the estimation of bone strength as well as for the prediction of intracortical porosity and parameters related to porous structures of cortical bone.     

Temporary Vena Cava Filters and Ultrahigh Streptokinase Thrombolysis Therapy: A Clinical Study

Purpose: To assess the efficacy of temporary vena cava filters in patients undergoing ultrahigh-dose streptokinase thrombolysis for iliocaval thrombosis and to determine therapy success and filter and therapy complications. Methods: Forty-five patients were studied regarding extension and characteristics of thrombosis, duration, success, and complications of thrombolysis therapy, filter type, access route, pulmonary embolisms, and filter complications. Results: Complete recanalization was achieved in 57% of cases. Filters were inserted predominantly via a transbrachial route. One fatal pulmonary embolism (2%) occurred 1 day after starting thrombolysis. No other pulmonary embolism was noted. Other complications were induced by thrombolysis alone (n = 12), thrombolysis and filter (n = 9), and filter alone (n = 11). Conclusion: Fatal pulmonary embolisms as a complication of ultrahigh-dose treatment of pelvic or caval thrombosis can not safely be prevented by the temporary vena cava filters currently available. Filter design needs to be improved.     

Feasibility of C-Arm-Supported CT Fluoroscopy in Percutaneous Abscess Drainage Procedures

Purpose: Evaluation of C-arm-supported CT fluoroscopy to facilitate percutaneous abscess drainage procedures. Methods: Prospectively, 40 percutaneous drainage procedures were performed either with C-arm-supported CT fluoroscopy or with CT fluoroscopy alone. Hybrid imaging was performed on the CT couch after complementing a CT fluoroscopy scanner with a C-arm fluoroscopy unit. Procedure times, drainage revisions during follow-up, and postinterventional drainage periods were analyzed. Results: When compared with exclusive CT fluoroscopic guidance, a median procedure time of 9 ± 3.7 min versus 14.8 ± 7.3 min was required for C-arm-supported CT fluoroscopy (p < 0.005, t-test). During follow-up, eight drainage catheters had to be revised within the exclusive CT fluoroscopy group, while only two revisions were necessary within the C-arm-supported CT fluoroscopy group. With C-arm-supported CT fluoroscopy, postinterventional drainage periods were reduced (median 13 vs 19 days; p < 0.001, t-test). Conclusion: Compared with exclusive cross-sectional image guidance, C-arm-supported CT fluoroscopy seems to improve placement of abscess drainage catheters to possibly reduce procedure times, drainage catheter revisions, and postinterventional drainage periods.     

Langzeitverlauf der primär konservativ behandelten akuten Sigmadivertikulitis Eine retrospektive Analyse

Aim: The aim of this study was to analyze the outcome of patients with sigmoid diverticulitis who primarily received conservative treatment. Method: During the years 1991–1995 88 patients (57 female, 31 male, average age 65.7 years) received conservative treatment for sigmoid diverticulitis in our clinic. Performing a retrospective analysis in 1998 we investigated clinical symptoms as well as diagnostic and therapeutic approaches. Results: 76.1% (67/88) of the patients showed no complications. During the observation period a relapse occurred in 42.6% of the patients (26/61). Complications were detected in 23.9% of the patients (21/88). Within the group of patients with complications, 75% relapsed and 76.2% underwent surgery following medical therapy. 14.3% of the patients (5/35) receiving surgical treatment had non-fatal complications. Two patients (5.7%) died postoperatively. 15 out of the 16 initially operated patients (93.7%) remained symptom-free following surgery. Conclusions: Patients with complicated sigmoid diverticulitis should receive surgical treatment, whereas conservative treatments is indicated in uncomplicated cases. In light of the high rate of recurrence, however, elective sigmoid resection should be considered individually following a diagnosis of diverticulitis.     

Büschelartiges Hämangiom (“tufted angioma”) des Unterarms Fallbericht und Literaturübersicht

Background: Tufted angioma represents a benign vascular lesion of the skin. The knowledge of this distinctive entity is important in distinction of clinically more aggressive and malignant neoplasms respectively. Case report. We report a 8-months-old girl who developed a deep seated tufted haemangioma on her right forearm. Sonography and MRI showed a good vascularized tumor with interseptal spreading. Histological examination of the incisional biopsy revealed a cellular capillary haemangioma with morphological features of rare tufted haemangioma. Discussion. Characteristic morphological features of tufted haemangioma allow accurate diagnosis and differential diagnosis to clinically more aggressive and malignant neoplasms of skin and soft tissues, wheras radiological methods are rather unspecific and do not distinguish reliably between these vascular lesions. It is of special clinical importance that tufted haemangioma represents an enlarging but biologically benign vascular neoplasm.     

Preclinical activity of a new platinum analogue,lobaplatin, in cisplatin-sensitive and -resistant human testicular,ovarian, and gastric carcinoma cell lines

Lobaplatin [1,2-diamminomethylcyclobutane-platinum(II) lactate] is a new platinum compound with interesting preclinical activity and apparently no nephro- or neurotoxicity that is currently undergoing clinical phase II studies. Little is known about the cross-resistance between cisplatin and lobaplatin. The activity of this new compound in comparison with cisplatin and carboplatin was evaluated in cisplatin-sensitive and cisplatin-resistant human testicular, gastric, and ovarian carcinoma cell lines using 96 h continuous drug exposure in a sulforhodamine-B assay. In three cisplatin-sensitive testicular carcinoma cell lines, lobaplatin and cisplatin showed comparable antitumor activity. The 50% growth-inhibitory concentrations (IC₅₀ values) determined for cisplatin ranged from 0.1 to 0.4 μM, and those found for lobaplatin ranged from 0.25 to 0.5 μM. Carboplatin showed markedly lower cytotoxicity in all cell lines tested. Lobaplatin was not cross-resistant to cisplatin in a 10-fold cisplatin-resistant testicular carcinoma cell line and showed only weak cross-resistance in a 20-fold cisplatin-resistant ovarian carcinoma cell line. In contrast, complete cross-resistance between cisplatin and lobaplatin occurred in two cisplatin-resistant human gastric carcinoma cell lines, which were 3.3- and 9-fold resistant to cisplatin and 3.1- and 6.5-fold resistant to lobaplatin, respectively. Furthermore, lobaplatin showed significant activity against cisplatin-resistant human ovarian and testicular carcinoma xenografts in vivo. These data indicate a high level of activity for lobaplatin at clinically achievable concentrations in drug-sensitive testicular, ovarian, and gastric carcinoma cell lines and a lack of complete cross-resistance to cisplatin. Further clinical development of lobaplatin is clearly warranted.     

Biological monitoring of standardized exposure to ethylbenzene: evaluation of a biological tolerance (BAT) value

The results of standardized 8 h lasting exposures of n=18 volunteers to ethylbenzene (EthBz) at levels of 25 and 100% of the maximum allowable concentrations at the workplace (MAK) value of 100 ppm as well as the results of field studies are considered to evaluate a biological tolerance (BAT) value for EthBz. On the basis of the relationship between the external and internal exposure a BAT value of 1.5 mg/l has been set for the EthBz concentration in blood as the most sensitive and specific parameter of exposure to this aromatic hydrocarbon. The interpretation of EthBz blood values has to take into account the short half-life of t _1/2=0.5 ± 0.08 h in the first hour after the end of exposure in which this aromatic hydrocarbon is eliminated from the blood. The additional determination of the EthBz metabolites mandelic acid (MA) and phenylglyoxylic acid (PGA), respectively, excreted in post shift urine as well as in urine samples at the beginning of the next shift shows good correlations with the external exposure. The biological half-life of MA was calculated to t _1/2=5.3 ± 1.1 h. Because the time of sampling can vary the relationship between the levels of MA to PGA the total concentration of the excreted metabolites depends less on this influence and is therefore better suited for monitoring exposed persons. On the basis of the standardized experiments a BAT value has been proposed of 2 g MA plus PGA corrected per gram creatinine. Both BAT values are adjusted to data which result from earlier standardized exposures during 30 min to EthBz under physical activity of 50 watt on a bicycle ergometer. Received: 10 August 1999 / Accepted: 2 November 1999