Extraosseous osteosarcoma arising from the small intestinal mesentery.

Extraskeletal osteosarcoma (EOS) is a highly aggressive and exceedingly rare mesenchymal tumor. Due to the rare nature of the disease, the diagnosis can be difficult and is often confirmed only after diagnostic laparotomy and histopathology. We describe the clinical history, radiologic and histomorphologic presentation, and clinical management of a 61-year-old patient who presented with abdominal pain. Abdominal ultrasound and computerized tomography (CT) scan revealed a calcified intra-abdominal mass. Following an explorative laparotomy, histology showed a large extraosseous osteosarcoma of the small bowel mesentery. Therapy according to the Cooperative Sarcoma Study-96 (COSS-96) was commenced. Diagnosis, management, and outcome in the context of the current literature are discussed. To our knowledge, this is the first description of an extraosseous osteosarcomas in the small bowel mesentery in the literature.

Clinical results of immunoscintigraphy in a variety of malignant tumors with special reference to immunohistochemistry.

Radioimmunoscintigraphy was performed in 52 patients with a variety of malignant tumors (colorectal, melanoma, lung, testicular, ovarian, bladder, carcinoid). Respective antibodies or their F(ab')2 fragments against CEA (n = 23), melanoma antigen 225.28 S (n = 18), TPA (n = 4), beta HCG (n = 5) and HMFG2 (n = 2) were selected by immunohistochemistry of the primary tumor. Most patients were suspected of recurrence or of hitherto unknown distant or local metastases. Overall accuracy was 61% (32/52). False negatives amounted to 33% (17/52). Useful additional clinical information-not available by CT, ultrasonics or serum levels of tumor markers-was obtained in 17 out of 52 patients (= 33%). From these results it seems obvious that antibodies used for radioimmunoscintigraphy should be selected on the basis of immunohistochemistry.

The use of semifluorinated alkanes in blood-substitutes.

Semifluorinated alkanes are useful for blood-substitutes in two different ways: as co-surfactant to stabilize emulsions with perfluorocarbons as oxygen-carrier and as oxygen-carrier instead of perfluorocarbons. Semifluorinated alkanes act as co-surfactants in low concentrations because they are enriched at the interface perfluorodecalin/water. Emulsions with semifluorinated alkanes dissolve about the same amount of oxygen as emulsions with perfluorocarbons. The stability of these emulsions depends on the nature of the alkyl and the perfluoroalkyl chain. Semifluorinated alkanes do not eliminate hydrogen fluoride under clean-up conditions of perfluorocarbons. According to toxicity tests against human carcinoma cells semifluorinated alkanes with alkyl chains are harmless in the examined range from C6 to C10.

Fusion from without induced by herpes simplex virus type 1.

Strains ANG and ANG path of herpes simplex virus type 1 (HSV1) produced fusion from without (FFWO) of cells in culture. FFWO required 45 min to become complete. In contrast, fusion from within (FFWI) was not detected until 3-4 h after infection, depending on the cell type. FFWO was temperature dependent: at 0 degrees no fusion could be observed, but increase of temperature increased the degree of fusion. The pH optimum for FFWO was 7.8-8.5. The FFWO activity of the virus was found to be slightly more heat stable at 46 degrees than was infectivity. FFWO was produced in Vero, CV-1 and BSC1 cells, but not in BHK clone 13 or in primary or secondary rabbit kidney cells. FFWO was linked to the presence of virus particles and perhaps to other sedimentable, infected-cell material but not to soluble factors. Actinomycin D, cycloheximide, and UV irradiation did not block this activity, indicating no direct activity of the HSV1 genome for FFWO.

[Tactics and results of surgical treatment of hyperparathyroidism]. / Taktik und Ergebnisse in der operativen Behandlung des Hyperparathyreoidismus.

Following a brief overview on parathyroid surgery, ontogenesis, anatomy and physiology of the parathyroids are described. Clinical symptoms and signs of hyperparathyroidism are as variable as the topography of parathyroid bodies may be. While parathyroid hyperfunction can easily be demonstrated by determination of serum calcium and parathyroid hormone levels, preoperative localization of adenoma or hyperplastic gland remains unsatisfactory in spite of great technical efforts. Therefore, the operative procedure has to be standardized and rational. Methylen blue staining of parathyroid bodies was proven to be helpful. Clinical results of 58 patients are presented.

Differences in humoral immunogenicity between herpes simplex virus types 1 and 2.

Infection of NMRI mice with increasing doses of six different strains of herpes simplex virus type 1 (HSV-1) induced increasing levels of neutralizing antibodies. In contrast, three strains of HSV-2, irrespective of the dose, induced only marginal antibody responses. Only strain HG 52 (HSV-2) at high doses of infection stimulated antibody formation. The virus content of some organs in 6- to 8-week-old mice appeared to be lower after HSV-2 than after HSV-1 infection. Application of immune-modulating drugs [silica or poly(I) X poly(C) coupled via L-lysine to CM-cellulose] resulted in little augmentation of antibody formation if compared to HSV-1 infection. Secondary infections with HSV-1 or HSV-2 after a primary dose of HSV-1 were followed by a marked booster response. In contrast, a primary infection with HSV-2 suppressed secondary responses of HSV-1 and HSV-2, thus indicating fundamental differences between the antibody-stimulating potency of HSV-1 and HSV-2 strains.

Kinetics and genetics of herpes simplex virus-induced antibody formation in mice.

The kinetics of antibody synthesis was investigated after intraperitoneal, subcutaneous, and footpad infection of various strains of mice with herpes simplex virus. Immunoglobulin M antibodies appeared 5 days after and immunoglobulin G antibodies appeared 10 to 12 days after intraperitoneal infection with herpes simplex virus type 1. The major histocompatibility complex and the background genome of inbred mice were not found to have a systematical influence on antibody synthesis. Female mice, however, consistently produced more antibodies than did male if the infection was done intraperitoneally, but not if it was done subcutaneously or into footpads. Castration considerably increased the amount of antibodies produced by male mice. The difference in antibody formation between females and males could be abolished by injection of silica; moreover, antibody titers were enhanced by this treatment. This has also been found by immunization with a Formalin-inactivated herpes simplex virus vaccine. The effect of silica in enhancing antibody formation could be observed up to 12 days after infection. Infectious virus could be detected up to 2 days after infection, and herpes simplex virus type 1 antibody-stimulating antigens could be detected up to 4 days in ultrasonicates of macrophages. The assumption is made that androgen-sensitive cell populations, including macrophages and their soluble products, are involved in antibody-depressing mechanisms.

Loss of surface fibronectin after infection of cultured cells by HSV-1 and 2.

Fibronectin is lost from the surface of HSV infected cells during cell rounding. In order to investigate also the fate of fibronectin during the process of HSV-induced cell-fusion, BHK, Vero as well as primary or secondary rabbit kidney cells were infected with HSV-1 strains producing cell-fusion. By immunofluorescence and immunoelectron microscopy a considerable loss of fibronectin after HSV infection could be demonstrated leaving only irregular clumps of fibronectin containing virus particles on the cell surface. Decrease and disarrangement of fibronectin was similar during cell rounding and cell fusion. Loss of Fibronectin was closely connected with the two types of the cytopathic effect (CPE) and could not be prevented by protease inhibitors. The immediate-early protein 175K is essential for induction of CPE and loss of fibronectin. The damage to the cell membrane during HSV infection shows certain analogous mechanisms with events induced by Cytochalasin B and might be explained by the loss of hypothetical fibronectin receptors.

Suppression and enhancement of humoral antibody formation by herpes simplex virus types 1 and 2.

Intraperitoneal infection of mice and rats by herpes simplex virus type 2 (HSV-2) but not type 1 (HSV-1) resulted in suppression of antibody formation on subsequent challenge with HSV-1 or HSV-2. Application of silica considerably enhanced antibody formation after primary HSV-1 infection, but only slightly after primary HSV-2 infection. Suppression induced by HSV-2 was, however, reduced significantly by injection of silica 21 days later, on the day of the second injection of HSV-2. Suppression could be detected soon after infection by HSV-2. The degree of this suppression depended on the dose of the injected virus and was abolished by u.v. irradiation of the virus prior to inoculation. Likewise the weak antibody response induced by HSV-2 was abolished for both neutralizing and ELISA antibodies. Infections with HSV-1 evoked considerable numbers of HSV-specific antibody-producing B cells, when assessed by an enzyme-linked immunospot assay. The B cell response to HSV-2, however, was very weak. Silica considerably enhanced the number of specific antibody-producing B cells only during primary HSV-1 infections. The present results in combination with earlier data demonstrate the central role of macrophages, which seem to be the primary target affected by silica, for enhancement and suppression of HSV-induced antibody generation.

On the perfluorocarbon emulsions of second generation.

For formulation of perfluorocarbon-emulsions (PFC-emulsions) of second generation new perfluorocarbons (F-dimorpholines, F-dipiperidines and F-cyclohexylmorpholine) were synthesized, acting both as oxygen carriers and as interfacial active compounds (IFACs). The stabilizing effect of these IFACs is interpreted and a new theory is introduced. Also new classes of fluorosurfactants were synthesized and tested for biocompatibility. In PFC mixtures compounds of the type RFRH (RF = CmF2m + 1, RH = CnH2n + 1) are acting as IFACs but also as anchor-groups for lipophilic surfactants.

On the perfluorocarbon emulsions of second generation.

Perfluorocarbon-emulsions of second generation were prepared by means of new perfluorocarbons (F-dimorpholines, F-dipiperidines and F-cyclohexylmorpholine), acting both as oxygen carriers and as interfacial active compounds (IFACs). The stabilizing effect of these IFACs is interpreted and a new theory is introduced. Also new classes of fluorosurfactants were synthesized and tested for biocompatibility. In PFC mixtures compounds of the type RFRH (RF = CmF2m + 1, RH = CnH2n + 1) are acting as IFACs but also as anchor-groups for lipophilic surfactants.

Enhancement of antibody formation against herpes simplex virus in mice by the T-cell mitogen bestatin.

The influence of the T-lymphocyte-stimulating dipeptide bestatin on the induction of neutralizing antibodies against herpes simplex virus type 1 in the mouse was investigated. Dose-response experiments revealed two active ranges from 1 ng/kg to 100 ng/kg and from 10 micrograms/kg to 10 mg/kg or more. Bestatin (10 mg/kg) enhanced antibody levels after primary infection, if injected between day 5 and day 8 after infection with a maximum effect at day 5. Following secondary infections, bestatin was most effective at day 1 after secondary infection. Moreover, the antibody-generating potency of a formalinized herpes simplex virus type 1 vaccine was elevated considerably. Bestatin and silica seemed to be effective systemically. Treatment of mice with silica before virus infection and additionally with bestatin at day 1 after infection resulted in an additive effect on antibody production. Comparable effects could be obtained when polyinosinic acid X polycytidylic acid or indomethacin was combined with bestatin at day 1. It was assumed that certain factors released by macrophages 'sensitize' the antibody-producing system for the enhancing activity of bestatin at day 1. Indeed, culture fluids of macrophages obtained from mice either pretreated with silica or infected by herpes simplex virus were active in enhancing antibody formation upon injection into mice at day 1 in combination with bestatin. Bestatin did not induce interferon activity. No influence of bestatin on the virus content of organs or on mortality was observed.