Pregnancy and uncomplicated vaginal delivery only 13 months after cardiac transplantation (case report)

Summary Background Pregnancy is prossible in female patients who underwent cardiac transplantation but is associated with unpredictable risks. Methods A 23-year old female patient underwent cardiac transplantation because of dilatative cardiomyopathy. Results Against our advice, she became pregnant 4 months after transplantation. Following an uneventful pregnancy, spontaneous vaginal delivery occurred 13 months after transplantation. The patient gave birth to a healthy new-born in good physical condition. Thereafter, the patient refused to attend any further routine follow-up control. 9 months after delivery, the patient was admitted to hospital in severe cardiac shock. Biopsy showed a serious, acute rejection which was treated with a course of methylprednisolone. Clinically, the patient recovered within 1 week, but died from acute myocardial infarction 1 day after discharge from hospital. Conclusions Only women without a history of rejection episodes, with good kidney function, good graft function, and high compliance should be counselled to become pregnant.      

Adjuvant TACE inhibitor treatment improves the outcome of TLR2<Superscript>-/-</Superscript>mice with experimental pneumococcal meningitis

Background  

Streptococcus (S.) pneumoniae meningitis has a high lethality despite antibiotic treatment. Inflammation is a major pathogenetic factor, which is unresponsive to antibiotics. Therefore adjunctive therapies with antiinflammatory compounds have been developed. TNF484 is a TNF-alpha converting enzyme (TACE) inhibitor and has been found efficacious in experimental meningitis. Toll-like receptor 2 (TLR2) contributes to host response in pneumococcal meningitis by enhancing bacterial clearing and downmodulating inflammation. In this study, TNF484 was applied in mice, which lacked TLR2 and exhibited a strong meningeal inflammation.     

Valproic acid induced encephalopathy--19 new cases in Germany from 1994 to 2003--a side effect associated to VPA-therapy not only in young children.

Valproic acid (VPA) is a broad-spectrum antiepileptic drug and is usually well-tolerated. Rare serious complications may occur in some patients, including haemorrhagic pancreatitis, bone marrow suppression, VPA-induced hepatotoxicity and VPA-induced encephalopathy. The typical signs of VPA-induced encephalopathy are impaired consciousness, sometimes marked EEG background slowing, increased seizure frequency, with or without hyperammonemia. There is still no proof of causative effect of VPA in patients with encephalopathy, but only of an association with an assumed causal relation. We report 19 patients with VPA-associated encephalopathy in Germany from the years 1994 to 2003, none of whom had been published previously.     

Human peripheral Null lymphocytes I. Isolation,immunological and functional characterization

A Null lymphocyte-enriched population was isolated from human peripheral blood of healthy donors using a combination of Ficoll density gradient centrifugation followed by elimination of mononuclear phagocytes, passage through Ig-anti-Ig columns and sedimentation of E rosettes. After each separation step lymphocyte fractions were examined for morphology, cell surface markers, mitogen responsiveness and effector functions in antibody-dependent (ADCC) and spontaneous cellular cytotoxicity (SCMC) reactions against an allogeneic melanoma cell line. The final Null lymphocyte preparation was recovered at a rate of 1 to 3 % from the population passed through Ig-anti-Ig columns (fraction FFF-C). The marker analysis revealed over 99 %of surface Ig-negative lymphoid cells; 50 to 60 % of these cells were ‘real Null’ cells lacking immunological cell surface markers, 7 % formed EA, 13 % EAC and 24 %E rosettes. Regarding the mitogen responses, passage through Ig-anti-Ig columns drastically reduced concanavalin A (Con A), pokeweed mitogen (PWM)and tuberculin (PPD) responses, whereas the phytohemagglutinin (PHA) response was reduced in absolute counts but not in the stimulation index. Compared to the T cell-enriched lymphocyte fraction, the Null cells showed significantly diminished proliferative responses to PHA and Con A and slightly increased reactivity to PWM and PPD. Although depleted of high affinity Fc receptor lymphocytes, the Null cell fractions exhibited good ADCC and SCMC activities being about 4 to 6 times higher than in the T cell fraction.     

Characterization of hemagglutinin variant strains of adenovirus 15 and 9

Summary Five adenovirus 15/Hx and one Ad9/Hx strain with a common novel hemagglutinin were compared serologically and by DNA restriction analysis with six endonucleases with the related prototypes. The five Ad15/Hx strains represented five different genome types.With 1 FigureAided by grants from the Deutsche Forschungsgemeinschaft (Wi 2/21-1), Bundesministerium für Jugend, Familie und Gesundheit, and Förderverein der Deutschen Vereinigung zur Bekämpfung der Viruskrankheiten e. V., FRG.     

Diffuse optical tomography of breast cancer during neoadjuvant chemotherapy: a case study with comparison to MRI

We employ diffuse optical tomography (DOT) to track treatment progress in a female subject presenting with locally advanced invasive carcinoma of the breast during neoadjuvant chemotherapy. Three-dimensional images of total hemoglobin concentration and scattering identified the tumor. Our measurements reveal tumor shrinkage during the course of chemotherapy, in reasonable agreement with magnetic resonance images of the same subject. A decrease in total hemoglobin concentration contrast between tumor and normal tissue was also observed over time. The results demonstrate the potential of DOT for measuring physiological parameters of breast lesions during chemotherapy.     

Prognostic value of MMP-2, -9 and TIMP-1,-2 immunoreactive protein at the invasive front in advanced head and neck squamous cell carcinomas

In head and neck cancer as well as in other carcinomas, tumor expansion and spread to distant sites require the secretion of destructive enzymes that degrade the extracellular matrix. A variety of proteases contribute to matrix destruction. Characteristics of the invasive tumor front may reflect tumor prognosis better than do other parts of the tumor. Therefore, it was the aim of the present study to (i) compare central and peripheral tumor zones for differences in the expression of matrix-metalloproteinases (MMP) -2 and -9 and their naturally occurring inhibitors (tissue inhibitor of matrix-metalloproteinases (TIMP) -1 and -2), (ii) examine the morphological potential of malignancy, and (iii) correlate these findings with clinicopathological parameters. The study population consisted of 106 surgical specimens of advanced head and neck squamous cell carcinomas. The invasive front was graded for malignancy, and immunohistochemical staining with MMP-2, MMP-9, TIMP-1 and TIMP-2 antibodies was performed. Both MMP-2 and MMP-9 were found to be significantly overexpressed at the tumor front. The MMP-2-positive invasive front exhibited diminished overall survival times. In multivariate analysis, MMP-2 expression retained its correlation with overall survival in addition to nodal status and total malignancy score. Expression of TIMP-2 correlated with local tumor invasion. We conclude that the expression of MMP-2 at the invasive front is a marker of poor survival and appears to be associated with early recurrence in initially lymph node-negative patients.     

Crossing the barrier: Evolution and spread of a major class of mosaic pbp2x in Streptococcus pneumoniae, S. mitis and S. oralis

A paradigm for Streptococcus interspecies gene transfer is represented by the mosaic pbp genes encoding the target enzymes for beta-lactam antibiotics, the penicillin-binding proteins, in Streptococcus pneumoniae. We investigated a collection of oral streptococci from three continents by comprehensive multi-locus sequence typing analysis in order to trace the origin of a mosaic block belonging to a dominant family of mosaic pbp2x implicated in penicillin resistance of S. pneumoniae. One widespread family of mosaic pbp2x occurred in all three distinct clusters of S. pneumoniae, Streptococcus mitis and Streptococcus oralis, documenting independent inter- and intraspecies recombination events. Moreover, potential ancestor genes of this mosaic block could be identified in two penicillin-susceptible S. mitis strains from South Africa and Spain, facilitating the identification of pbp2x mutations relevant for resistance development.     

Establishment and characterization of the permanent human cell line C3842 derived from a secondary chondrosarcoma in Ollier’s disease

The permanent human cell line C3842 was established from a secondary chondrosarcoma in a typical case of Olliers disease. In the present study, we analyzed the morphological, cytogenetic and molecular biological characteristics of the cultured cells in comparison with the original tumor and investigated the invasion properties of the tumor model using functional imaging of proteolysis, matrigel assay and chick chorioallantoic membrane assay. C3842 cells exhibit the typical features of malignant cartilage tumor cells in vitro, including the expression of collagen types II, IX, XI and aggrecan. The proteolytic ability of C3842 cells is attributed to the expression of several proteases, such as cathepsin B, urokinase plasminogen activator and matrix-metalloproteinase-2, which enable the cells to degrade collagen type I and to permeate matrigel matrix. In accordance with the biological features in vivo, C3842 cells are not able to invade through the epithelium of the chick chorioallantoic membrane. In conclusion, the cell line C3842 provides the first model of a secondary chondrosarcoma in Olliers disease in vitro, which is characterized by distinct features of such malignant cartilage tumors.