Skin lesions, malaise, and heart failure in a renal transplant recipient.

A male Caucasian patient developed nodular erythematous skin lesions, malaise, and clinical signs of progressive heart failure 4 months after renal transplantation. Bronchoscopy with bronchoalveolar lavage performed for a small infiltrate seen on a computed tomography scan revealed Trypanosoma, which had at this point not been suspected as a cause. Parasitemia was present, and reactivation rather than transmission of Chagas' disease was established by performing polymerase chain reaction and serology in the donor and recipient. Treatment with benznidazole and allopurinol successfully reduced parasitemia, but the clinical course was fatal owing to progression of severe myocarditis. The patient had never lived in an endemic area, but had an extensive travel history in South America. The last visit was more than 5 years before transplantation. In non-endemic countries (United States, Europe), reactivation after transplantation has only been very rarely reported. Given the rising numbers of transplantations in patients with a migration background and extensive travel histories, specific screening procedures have to be considered.

[Disease with generalized pain. Guillain-Barré syndrome]. / Erkrankung mit generalisierten Schmerzen. Guillet-Barré Syndrom.

A 43-year-old women is suffering from immobilizing generalized muscular pain. Initial diagnostic course doesn't lead to diagnosis. Some days later after appearing of a facial palsy a Guillain-Barré syndrome is diagnosed after lumbar puncture showing a increased protein and normal white-cell count. Because the patient is seriously affected with immobilization a treatment with intravenous immunoglobulin is established, leading to a quick improvement. Pain as a leading symptom of Guillain- Barré syndrome and has a potential for leading to misdiagnosis effecting delay in therapy in possible harmful disease.

Differential microglial regulation in the human spinal cord under normal and pathological conditions.

As the primary intrinsic immune effector cells of the central nervous system, microglia are involved in virtually all pathological processes of the brain and spinal cord including inflammatory, neurodegenerative, traumatic, neoplastic and vascular diseases. Despite this important role, there is a lack of data concerning microglial distribution and protein expression in the human spinal cord. In this study, we immunohistochemically investigated 10 normal human spinal cords to establish reference data and compared these results with 15 pathological human spinal cords deriving from distinct pathologies. Each spinal cord was evaluated at eight different levels for three white and two grey matter areas for both constitutive (MHC-II, CD68, IL-16, AIF-1, LCA, CD4) and reactive (MRP-8, MRP-14) microglial antigens. Whereas previous studies revealed significant regional differences in microglial distribution and protein expression in human brain, normal spinal cord displayed a uniform expression pattern, reaching levels of up to 17% MHC-II positive cells of the total cell population. This datum formed the basis for the further evaluation of microglia expression levels in pathological spinal cords, where levels of up to 45% positive cells were observed. Our results represent important reference values for future neuropathological diagnostic and therapeutical approaches in spinal cord pathologies.

[The NEN (Nicolet Electronic Naviation System) ENT navigation system. Initial clinical application]. / Das NEN-HNO-Navigationssystem. Erste klinische Anwendung.

BACKGROUND: Intraoperative computer navigation will soon play an important role in procedures performed on the anterior and lateral skull base. Electromagnetic systems compared to optical systems offer some advantages such as small hardware dimension and free unimpaired mobility of the surgeon. PATIENTS AND METHODS: The NEN navigational system (Nicolet Electromagnetic Navigation System) was used in 22 patients who underwent microscopic/endoscopic surgery for polypoid rhinosinusitis. It is the prototype of a new system, which localizes the surgical probe via the measurement of pulsed electromagnetic DC fields. This system was modified for the needs of head and neck surgery. Preoperative imaging data consisted of an axially oriented spiral computed tomography (CT) resulting in a slice thickness of 1 mm with a radiation dose slightly higher than a routine coronary CT scan of the paranasal sinuses. RESULTS: The data acquired during clinical application was used to optimize navigation accuracy. The number and positions of the markers were gradually modified and improved. Six markers including the volume of the paranasal sinus system (three non-coplanar frontal markers, one on each of the mastoid processes and one median marker on parietooccipital junction) offered the best navigation precision. Additionally, all surgical instruments measured as ferromagnetic, i.e., nasal specula, were replaced by titanium instruments. An adapter affixed to the maxilla-designed to hold a second sensor used to track the patient's head was developed. With these modifications, it was possible to improve navigation accuracy to 1.5 mm in the plane of the sphenoid bone while retaining free head movement of the patient. CONCLUSION: For routine procedures such as microscopic/endoscopic endonasal sinus surgery, the systems have to be cost effective and easy to operate.

[Assessment of the risk of occipitocervical dislocation in inflammatory rheumatic diseases]. / Zur Risikobeurteilung occipito-cervicaler Dislokationen bei entzündlich-rheumatischen Krankheiten.

In this mainly retrospective study we examined by means of tomographic and computer tomographic findings various manifestations and courses of cranio-cervical subluxations in chronic inflammatory rheumatic diseases and the resulting neurological complications. Even in marked cranio-cervical subluxations neurological complications are rarely observed. More serious anterior atlanto-axial subluxation represents the highest risk for spinal cord injury as a result of the mobility of the atlas. A subsequent vertical (upward) atlanto-axial subluxation occurring particularly in serious courses of illness reduces this risk since it is generally to be found together with a fixation of the atlas. This also applies to a possible pseudobasilar invagination. As a result of our studies we found ways of using CT to achieve further information. We could also derive guidelines for the indication of operative treatment. In view of the further development of surgical methods and variations in operative risk dependent on the preoperative situation, these recommendations can only be provisional.

Interactions of tumor cells with human amnion membrane: a model for studying tumor invasion in vitro.

The human amnion membrane consisting of a single layer of epithelium attached to the continuous basement membrane and the underlying collagenous stroma has been used to study tumor invasion in vitro by means of electron microscopy. Three cell lines utilized in these experiments were established from surgical specimens of human squamous cell carcinomas of the tongue and larynx. The cultivation of amnion membrane for 48h or longer leads to some alterations in the morphological appearance. All three carcinomas form aggregates which appear firmly attached to the amnion epithelium and are able to establish contacts to the basement membrane within 96h. In two cases the basement membrane reveals local defects and some cells have extended processes into the collagenous tissue. However, none of the tumor cells of the three carcinomas have broken through the basement membrane and grown into the collagenous stroma. Some differences of interaction between amnion epithelial cells and tumor cells of the three carcinomas are apparent. These ultrastructural findings show, that the amnion membrane model allows morphological analysis of various steps of tumor invasion under standardized conditions.

Interaction of human carcinoma cells with an epithelial layer and the underlying basement membrane. A new model.

We have developed a new in-vitro model to study the interaction of malignant tumour cells with a normal epithelium and a subsequent invasion and penetration of the epithelium. The system involves the culture of human amnions obtained after caesarean section. The amnion with its intact basement membrane and the underlying collagenous stroma was cultured on an agar coated grid, tumour cells were added on top of the amnoin and co-cultured for up to 7 days. We report on human tumour cell lines, HeLa I also broke through the basement membrane and grew into the collagenous stroma. Normal cells were accepted by the amnoin and the amnoin epithelium grew over the fibroblasts. This system should provide a useful model to study the factors controlling tumour cell invasion, such as the role of proteolytic and collagenolytic enzymes, cell adhesion and locomotion.

Tumor metastases and cell-mediated immunity in a model system in DBA/2 mice. VII. Interaction of metastasizing and nonmetastasizing tumors with normal tissue in vitro.

Three mouse tumors known to metastasize in vivo and 3 nonmetastasizing mouse tumors that grow only locally in vivo were examined for their ability to adhere to and invade normal syngeneic lung organ cultures in vitro. All 3 metastasizing tumors adhered to and invaded the normal lung cultures. In contrast, tumors that grow only locally in vivo neither adhered to nor invaded the normal lung tissue. The described system is ideally suited to correlate the in vivo invasiveness of a given tumor with its potential to metastasize in vivo and to study in vitro how to influence the interaction of metastasizing tumor cells with normal tissue.

Can cell morphology in monolayer reveal its behaviour in aggregates?

The morphology of HeLa cells was altered to stellate shape by 0.2-1.0 mM butyric acid. At similar concentrations butyric acid did not alter the ability of HeLa cells to aggregate, but did inhibit the remodelling of the aggregates. Papaverine at 10 micrometers, on the other hand, had no effect on cells in monolayer, but severely inhibited the ability of cells to aggregate and the remodelling of the aggregates. Our results show that the effect of a drug on the morphology of HeLa cells in monolayer does not predict its effect in aggregates of cells which more faithfully approximate the behaviour of cells in tissue than the monolayer.

[The influence of beta-sympathomimetics and so-called Ca++-antagonistic inhibitors on human heart muscle in vitro (author's transl)]. / Der Einfluss von beta-Sympathomimetika und sog. Catt-antagonistischer hemmstoffe auf den menschlichen Herzmuskel in vitro

In an in vitro assay on fetal human heart muscle it was demonstrated for the first time that overstimulation by beta-sympathomimetics could cause elective parenchymal necrosis. Fenoterolhydrobromide, which is used for tocolysis on a longterm scale, induces in vitro necroses of individual heart muscle fibers according to a pathogenetic principle postulated by Flekkenstein. The combination of Fenoterolhydrobromide with a Ca++-antagonist prevents elective parenchymal necroses by reducing the Ca++-influx into the heart muscle fibers. These results suggest that elective necroses of heart muscle fibers may be not only of coronarogenic but also of metabolic origin.

Patterns of invasive growth in vitro. Human decidua graviditatis confronted with established human cell lines and primary human explants.

Human decidua graviditatis was used as a receptor tissue to demonstrate invasive properties of human cells in vitro. In the confrontation between decidua and established cell lines of tumors and of normal origin as well as primary explanted cells, we noted differences in the cells' interactions with decidual tissue. The two original tumor cell lines, HeLa (carcinoma) and AFi (sarcoma), and a spontaneously transformed lymphoblastoid cell line showed aggressiveness, i.e., invasion, rapid proliferation, injury, and destruction of the decidual tissue. Strain HeLa S3 and two established cell lines, FL (amnion) and Girardi Heart, which are regarded as transformed cells because of their increased mitotic rate and polyploidy, exhibited various degrees of aggressiveness but did not invade. Freshly explanted fetal lung and endometrium caused no injury to the receptor tissue and were included in the decidual tissue.

The effects of betamimetic drugs used for tocolysis on the fetal myocardium.

During the last five years tocolysis with betamimetic drugs, e.g. Fenoterol has become a standard method for the treatment of impending premature births. We studied the effect of Fenoterol in vitro on organ cultures of human fetal hearts. At a concentration in the nutrient medium corresponding to the dose used in clinical application, light and electron microscopy demonstrated myocardia damage. In contrast the combined use of Fenoterol and the calcium antagonist Verapamil in a ratio of 1:40 showed no pathological findings either clinically or in vitro. The results are documented with light and electron photomicrographs.