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Since musculoskeletal tumours comprise a large heterogeneous group of entities with different biological behaviour, clinical diagnosis of such lesions can be very difficult. The aim of this prospective study was to assess the usefulness of 2-[F-18]-fluoro-2-deoxy-d-glucose (FDG) positron emission tomography (PET) in the non-invasive evaluation of soft tissue tumours. One hundred and two patients with suspected soft tissue neoplasms were investigated by FDG-PET. The uptake of FDG was evaluated semiquantitatively by determining the tumour to background ratio (TBR). All patients underwent biopsy, resulting in the histological detection of 39 high-grade sarcomas, 16 intermediate-grade sarcomas, 11 low-grade sarcomas, 25 benign tumours, 10 tumour-like lesions such as spontaneous myositis ossificans (n = 6) and one non-Hodgkin lymphoma. All lesions except for two lipomas disclosed an increased FDG uptake. Sarcomas showed significantly higher TBR values than latent or active benign lesions (P0.001) and aggressive benign lesions (P0.05). Using a TBR cut-off level of 3.0 for malignancy, sensitivity of FDG-PET was 97.0%, specificity 65.7% and accuracy 86. 3%. From our data there are three main conclusions: (1) Except for patients with pseudotumoral myositis ossificans, lesions with a TBR3 were sarcomas (91.7%) or aggressive benign tumours (8.3%). (2) Tumours with a TBR1.5 were latent or active benign lesions, exclusively. (3) The group with intermediate TBR values (3 and1. 5) comprised primarily latent or active benign lesions, but also four aggressive benign tumours and two low-grade sarcomas. Our data suggest that FDG-PET represents a useful tool for the evaluation of the biological activity of soft tissue neoplasms.

Im Rahmen einer prospektiven Studie an 168 Patienten mit Weichteil- oder Knochentumoren, darunter 71 Sarkomen, wurde unter farbdopplersonographischer Kontrolle eine Vollschnittbiopsie mit dem Hochgeschwindigkeitssystem Autovac® gewonnen. Das Ultraschallmonitoring erlaubte eine gezielte Punktion auch von kleinen oder tiefer gelegenen Lasionen und ermoglichte im Falle des Vorliegens von Nekrosen das Aufsuchen vitaler Tumoranteile. Eine adaquate histologische Beurteilung einschlieslich Tumortypisierung und Grading war bei der grosen Mehrzahl der Weichteilsarkome, Weichteilmetastasen, malignen Lymphome, Plasmocytome und osteolytischen Skelettmetastasen moglich. Benigne Weichteil- und Knochentumoren waren dagegen nur zu 66 % diagnostizierbar. In der Gruppe der ossaren Sarkome war trotz histologischem Malignitatsnachweis eine exakte Tumortypisierung aufgrund zu geringer Materialmenge haufig nicht moglich. Mit einer Genauigkeit von 97 % fur das Kriterium Malignitat und von 94 % fur die Diagnose Weichteilsarkom liefert die Methode Ergebnisse, die denen der Incisionsbiopsie, dem Standardverfahren bei Weichteil- und Knochentumoren unklarer Dignitat, vergleichbar sind. In Anbetracht der bekannten Nachteile und onkologischen Risiken des offenen Verfahrens stellt die Nadelbiopsie – bei Einhaltung der fur die Incisionsbiopsie geltenden Kautelen – fur Weichteiltumoren und osteolytische Skelettlasionen die Methode der Wahl dar.

The contribution of hepatitis C virus (HCV) infection to liver disease after bone marrow transplantation (BMT) was retrospectively evaluated in 61 patients treated with BMT. HCV genome, as well as antibodies to HCV, was analyzed in sera collected before and serially after BMT. Six patients had been infected with HCV before BMT and three patients acquired the infection during or shortly after BMT. All patients infected before BMT died within 10 weeks after transplantation. Five of these six patients (83%) died of veno-occlusive disease (VOD), compared with nine of 52 patients (17%) not infected with HCV (P < .005). Risk factors for VOD other than HCV were not more prevalent in these patients compared with uninfected patients. Parallel to the development of VOD, replication of HCV increased, as demonstrated by rising concentrations of viral RNA in serum. HCV infection acquired during or after BMT caused only mild acute hepatitis C, which progressed to chronic hepatitis C in one patient surviving 10 years after BMT. These data suggest that patients with liver disease caused by HCV infection are at high risk of developing lethal VOD after BMT.

We report on the systhesis of (La,RE) 2- x Sr x CuO 4 for various RE=Pr, Nd, Sm, Eu, Gd, Dy, Ho and Er as a function of the RE and Sr concentrations. The sample characterization by means of powder X-ray diffraction and EDX is described. We present our results on the solubility limit of the various RE in the T structure of La 2- x Sr x CuO 4 and discuss the systematic influence of RE and Sr doping on the structural properties. We furthermore show that doping with RE does not influence the charge carrier concentration of the samples.

A full-term 46,XY female newborn presented with respiratory failure due to a right-sided diaphragmatic hernia. During surgical repair, exploration revealed isolated dextrocardia and hypoplasia of the right lung. Neither gonads nor wolffian or müllerian structures could be palpated. Cardiac catheterization demonstrated defects of the ventricular septum, hypoplasia of the right pulmonary artery, persistence of the left vena cava superior and a patent ductus arteriosus. Anthropometric data were normal at birth, but fell below the 3rd percentile during follow-up. Body proportions displayed a predominance of the upper compared to the lower segment. Endocrine studies indicated no defect of steroid biosynthesis and no functional gonadal tissue. Using genetic analyses of various loci within the testis-determining region of the Y chromosome, a mutation could not be detected. The patient died from pneumonia at the age of 19 months. Postmortem examination confirmed the diagnosis of gonadal agenesis.

Background Sarcoidosis is a common granulomatous systemic inflammatory disease mainly affecting the interstitial lung tissue and perihilar lymph nodes. Since its first description by Bernier 1889 its etiology has remained obscure. Method Sarcoidosis of the right middle ear in a 38-year-old woman was diagnosed by biopsy. Result After mastoidectomy and treatment with prednisolone the patient has been free of relapse for two years. Conclusion According to our knowledge this is the second reported case of sarcoidosis of the middle ear. In both cases the interstitial lung tissue has been involved as well. This finding increases the importance of excluding sarcoidosis in differential diagnosis of chronic otitis media.

Clinical diagnosis of skeletal tumors can be difficult, because such lesions compose a large, heterogeneous group of entities with different biologic behaviors. The aim of this prospective study was to assess the value of PET in grading tumors and tumorlike lesions of bone.Two hundred two patients with suspected primary bone tumors were investigated using FDG PET. Uptake of FDG was evaluated semiquantitatively by determining the tumor-to-background ratio (T/B). All patients underwent biopsy, resulting in the histologic detection of 70 high-grade sarcomas, 21 low-grade sarcomas, 40 benign tumors, 47 tumorlike lesions, 6 osseous lymphomas, 6 plasmacytomas, and 12 metastases of an unknown primary tumor.All lesions, with the exception of 3 benign tumors, were detected by increased FDG uptake. Although sarcomas showed significantly higher T/Bs than did latent or active benign lesions (P0.001), aggressive benign lesions could not be distinguished from sarcomas. Using a T/B cutoff level for malignancy of 3.0, the sensitivity of FDG PET was 93.0%, the specificity was 66.7%, and the accuracy was 81.7%.FDG PET provides a promising tool for estimating the biologic activity of skeletal lesions, implicating consequences for the choice of surgical strategy.

In patients with systemic sclerosis (SSc) treatment-related mortality after autologous stem cell transplantation (ASCT) appears to be increased as compared to patients with hematological malignancies. In our phase I/II study on ASCT in autoimmune diseases a patient with SSc died on day 2 after ASCT. Here we report the results of the autopsy which revealed advanced pulmonary and cardiac fibrosis as the most probable cause of death. In spite of detailed technical examination before enrollment, the cardiopulmonary function tests did not reflect the advanced stage of the disease. We conclude that in selected patients with SSc, biopsies should be performed to reduce mortality after ASCT.

In a prospective study we investigated 168 patients with musculoskeletal tumors, including 71 sarcomas, by core needle biopsy using the high-speed device Autovac. Monitoring with colour-coded duplex sonography allowed a well-aimed puncture of smaller or deeply localized lesions and also permitted the discrimination of necrotic and viable parts of the tumor. Adequate material for histologic diagnosis including grading and determination of tumor subtype was obtained from soft tissue sarcomas, soft tissue metastases, malignant lymphomas, plasmacytomas, and osteolytic skeletal secondaries. In contrast, in benign soft tissue and bone tumors the diagnosis could be established in only 66% of cases. Although skeletal sarcomas were identified as malignant mesenchymal lesions, a complete histologic classification of tumor subtype frequently was not possible due to an insufficient tissue specimen. With an accuracy of 97% for the diagnosis of malignancy and of 94% for the diagnosis of soft tissue sarcoma the results of core needle biopsies were comparable to those of incisional biopsies, the reference standard in the diagnosis of musculoskeletal tumors. Regarding the known disadvantages and the oncological risks of incisional biopsies, needle biopsy should replace the open procedure as the primary means of diagnosis in soft tissue and osteolytic bone tumors.

Sarcoidosis is a common granulomatous systemic inflammatory disease mainly affecting the interstitial lung tissue and perihilar lymph nodes. Since its first description by Bernier 1889 its etiology has remained obscure.Sarcoidosis of the right middle ear in a 38-year-old woman was diagnosed by biopsy.After mastoidectomy and treatment with prednisolone the patient has been free of relapse for two years.According to our knowledge this is the second reported case of sarcoidosis of the middle ear. In both cases the interstitial lung tissue has been involved as well. This finding increases the importance of excluding sarcoidosis in differential diagnosis of chronic otitis media.

Experiments were designed to examine the wound healing characteristics at the aorta-endograft interface. Thoracic aneurysms were induced in sheep and excluded by endovascular placement of a selfexpanding stent graft (Corvita Endovascular Graft). After a follow-up of 1, 4, or 12 weeks sheep were sacrificed and the corresponding segments of the aorta were subjected to histological examinations. Histomorphological evaluation of all groups underlined sufficient exclusion of lesions of the aortic wall by endovascular grafting. There was no evidence of proximal or distal leakage, graft dislocation or migration. The results appeared to be evidence that the endoluminal stent graft may be incorporated by the host aortic tissue.

Cytomegalovirus (CMV) PCR from stool specimens was adopted as a diagnostic tool for patients with suspected CMV colitis. After being established, the method was evaluated in 17 AIDS patients and 19 other immunocompromised patients by comparison of PCR results with clinical, histological, and microbiological or virological data. CMV PCR was positive in 4 symptomatic patients with proven CMV colitis and negative in 15 of 16 patients without characteristic histopathology. Neither CMV immunoglobulin G seropositivity nor intestinal symptoms alone were significantly associated with positive PCR results, but severe active systemic CMV infection may lead to a positive PCR. Absence of CMV DNA in stool samples may prove useful in ruling out CMV related colitis.

Inflammatory pseudotumors (synonym: plasma cell granulomas) of the lung and trachea are a group of non-neoplastic lesions of unknown etiology which may occur at any age. The complex histomorphology und proliferative capacity of these pseudotumors may result in diagnostic difficulties during intraoperative frozen section analysis. Four cases of inflammatory pseudotumors of the respiratory tract (three pulmonal, one tracheal pseudotumors) are reported. One patient (16 years, female) suffered from sudden chest pain with dyspnoe, caused by obstruction of the right main bronchus due to an intraluminal pseudotumor. Because of the intraoperative diagnosis of a malignant histiocytoma, sleeve resection of the right main bronchus with bronchotracheal anastomosis was performed. Eight years postoperative, the patient is still disease-free. Another patient (52 years, male) developed multiple inflammatory pseudotumors in both lungs with direct infiltration of the mediastinum. After three thoracotomies, there is still residual disease in the mediastinum. The third patient (52 years, male) developed an inflammatory pseudotumor in the right upper lobe after irradiation therapy for hypopharyngeal carcinoma several years before. The last case in this series is a patient (43 years, male) with suspected bronchial carcinoma in the left lower lobe. The intraoperative frozen section analysis interpreted this lesion as an bronchioloalveolar carcinoma, but the diagnosis was corrected in the paraffin embedded specimens. Clinical presentation, size and number of these tumors are very variable. Despite their rarity, inflammatory pseudotumors should be considered in the differential diagnosis.

Alternaria alternata and Aspergillus terreus were isolated from cutaneous nodules in a 5-year-old girl with agranulocytosis of unknown origin. Histopathological examination supported the diagnosis of an infection with two opportunistic moulds. Aspergillus terreus was also isolated from the secretions of the maxillary sinuses of the patient. In spite of antimycotic therapy, the child eventually died from respiratory failure.

The contribution of hepatitis C virus (HCV) infection to liver disease after bone marrow transplantation (BMT) was retrospectively evaluated in 61 patients treated with BMT. HCV genome, as well as antibodies to HCV, was analyzed in sera collected before and serially after BMT. Six patients had been infected with HCV before BMT and three patients acquired the infection during or shortly after BMT. All patients infected before BMT died within 10 weeks after transplantation. Five of these six patients (83%) died of veno-occlusive disease (VOD), compared with nine of 52 patients (17%) not infected with HCV (P.005). Risk factors for VOD other than HCV were not more prevalent in these patients compared with uninfected patients. Parallel to the development of VOD, replication of HCV increased, as demonstrated by rising concentrations of viral RNA in serum. HCV infection acquired during or after BMT caused only mild acute hepatitis C, which progressed to chronic hepatitis C in one patient surviving 10 years after BMT. These data suggest that patients with liver disease caused by HCV infection are at high risk of developing lethal VOD after BMT.

To elucidate the role of T lymphocytes in primary infection with Yersinia enterocolitica, we investigated the elimination rate of this pathogen, the histomorphology of tissue lesions, and the immune responses of athymic T-cell-deficient C57BL/6 nude mice and their euthymic littermates after parenteral infection with Y. enterocolitica of serotype O:8. While a low inoculum of 3 x 10(2) Y. enterocolitica cells (about 0.01 times the median lethal dose for normal C57BL/6 mice) was cleared by normal C57BL/6 mice within 7 to 10 days, athymic nude C57BL/6 mice developed progressive infections after this inoculum, leading to death on days 20 to 25 postinfection (p.i.). While normal C57BL/6 mice experienced short-term transient infections, nude mice exhibited a biphasic, progressive infectious process. Thus, in the early phase (days 1 to 7 p.i.), a rapid influx of CD11b/18-positive cells (Mac-1 antigen) and natural killer cells was evident in the spleens and livers of the nude mice. The late phase (from day 8 p.i. onward) was characterized by a rapid progression of the infection and a further influx of CD11b/18-positive cells into the liver accompanied by an increase in bacterial counts and development of tissue lesions particularly in the liver and spleen. In normal mice, granuloma-like lesions composed of CD11b/18-, CD4-, and CD8-positive cells could be observed. However, granulomata were not found in nude mice. Yersinia-specific immunoglobulin G antibodies appeared on day 15 p.i. in the sera of normal mice, while nude mice failed to develop significant antibody titers. Adoptive transfer of Yersinia-specific T cells into athymic nude mice mediated resistance to Y. enterocolitica infection and restored both the ability of granuloma formation and the production of specific antibodies. In summary, the data presented herein strongly suggest that T lymphocytes play an essential role in the defense of C57BL/6 mice against Y. enterocolitica.

The authors report on a female patient, 32 years old, suffering for eight years from recurrent and progressive abdominal pain, combined with chronic anemia, due to iron deficiency. Neither anamnesis and clinical course, nor technical examinations elucidated the etiology. Finally an explorative laparotomy with segmental resection of the small intestine led to diagnosis and healing of the rare "idiopathic small bowel ulcer". Possible differential diagnoses were lacking. This case report demonstrates the need of an invasive and aggressive diagnostic approach after excluding all common causes of disease, related to the symptoms, in order to prevent patients from suffering for years.

We report on 9 infants with severe combined immunodeficiency (SCID), who additionally showed signs of Omenn syndrome with an exfoliative dermatopathy, alopecia, enlarged lymph nodes, a hepatomegalia and a striking blood eosinophilia. The immunological evaluation revealed the characteristic abnormalities of SCID with cellular and humoral immunodeficiency. All patients however had the unusual finding of mature T cells in the peripheral blood. By HLA typing these cells were noted to be of maternal origin in 5 patients. In the other 4 patients the T cells were of host origin. We asked for additional differences between both patient groups.Both patient groups were analyzed and compared with regard to case histories, clinical, laboratory and histopathological parameters.No clinical or laboratory differences could be detected. The histomorphologic analysis of patients with or without maternal T cells was identical. The skin biopsies showed dense cell infiltrations of lymphocytes, histiocytes and eosinophils, in the enlarged lymph nodes the latter two cell types predominated. Therefore the only difference between the 2 patient groups was the presence or absence of maternal T cells.Since the Omenn syndrome is found in association with maternal as well as patient derived T cells, we postulate that the peculiar symptoms of this syndrome are the result of a T cell induced inflammatory reaction, similar but not identical to a graft versus host reaction, occurring on the basis of an inborn SCID.

A case of dentinogenic ghost cell tumor, that has originated peripherally in the jaw, is presented and the literature reviewed with particular reference to the origin of the tumor. The total number of central and peripheral cases reported in the English literature is 10 and although mucosal infiltration is common, peripheral origin of the neoplasm could be verified in only 3 cases.

In (La RE)SrCuO with RE = Nd, Eu, Gd, Dy, Tb we find, besides the known tetragonal → orthorhombic transition, a further low temperature (LT) structural phase transition. Its occurance and also the low temperature structure depend on RE and Sr content. We find well defined and sharp transitions especially in La1.85-xNdxSr0.15CuO4, for which we present a detailed phase diagram including structural and superconducting properties. For a Sr content of 0.15 there is a competition between superconductivity and the low temperature phase transition: There is no bulk superconductivity in the LT phase and, vice versa, there is no complete LT-transition, if the transition temperature of the structural transition extrapolated from the Nd-concentration dependence is smaller than Tc. For Sr content sufficiently far away from 0.15 the LT-transition smears out and bulk superconductivity occurs.

45 patients with oral cancer preoperatively received regional intraarterial chemotherapy (RIAC). All patients developed stomatitis or glossitis limited to the region of cytostatic perfusion. Between 1 and 19 days (median 4 days) after RIAC the tumor was removed by hemiglossectomy, partial resection of the floor of the mouth etc. The tissue alterations induced by chemotherapy in these surgical specimens were analyzed histomorphologically. Stomatitis due to RIAC was characterized by necrosis, ulceration and severe epithelial dysplasia of mucous membranes. Approximately 2 weeks after chemotherapy both the inflammatory changes and the dysplasia had disappeared completely. The differences between spontaneous premalignant dysplasia of the oral cavity and dysplasia induced by RIAC are discussed.

Most inborn immunodeficiency syndromes clinically become overt by complicating infections, e.g. by BCG-infection after BCG-vaccination. The diagnostic approach often is hampered by an atypical histomorphological picture of the infection caused by the underlying immune defect. We examined biopsies of different organs in 18 infants with severe combined immunodeficiency syndrome and BCG-infection. A number of unusual histomorphological patterns of BCG-infection were found not yet published previously. There was a correlation between histomorphological features and immunological data or clinical course in most cases.

1. The Omen-syndrome is not a disease on its own, but a complication of congenital SCID. 2. In contrast to patients with classical SCID, patients with Omenn-syndrome possess mature T-cells, which are either of maternal or of host origin. 3. These T-cells are involved in the pathogenesis of the characteristic tissue changes, in particular of skin and lymph nodes (Langerhans-histiocytosis with eosinophilia). 4. The detection of immunodeficiency in Omenn-syndrome is difficult since the lymph nodes are enlarged in contrast to patients with classical SCID. The histomorphological analysis of lymph nodes in Omenn-syndrome is considerably complicated by secondary changes closely resembling dermatopathic lymphadenopathia.

In the present survey the pathohistologic substrate of the major thyroid diseases (functional disturbances, goiters, inflammations, tumors) occurring in childhood is described. In this context the functional morphology (correlation of structure and function) and the immunohistology of the thyroid is reported in detail. Finally, it is discussed under which conditions histologic studies of the thyroid are meaningful for the diagnosis.

Reticular Dysgenesis (RD) basically represents a lymphopenic severe combined immunodeficiency (SCID) in association with congenital agranulocytosis. It is presumed that RD results from a primary defect of pluripotent hematopoietic stem cells (HSC). Alternatively RD might be due to an alloreaction induced by T-cells derived from intrauterine transfusion of maternal cells into an immunoincompetent host. In the past 15 years, among 49 newborns with SCID taken care of in the University Hospital of Ulm, 5 children (4 boys, 1 girl) exhibited the characteristics of RD. In 3 of 4 cases studied, maternal T-cells were detected by HLA-typing. All 3 children showed signs of graft-versus-host-disease (GvHD), confirmed histologically. However, 9 of 45 newborns with SCID without congenital agranulocytosis also disclosed maternal T-cell-engraftment; 5 of the 9 had signs of GvHD. Therefore, it is unlikely that RD is caused by GvHD secondary to maternofetal transfusion. The fact that erythropoiesis, thrombopoiesis and the monocyte-macrophage-system basically are intact argues against a global maturation defect of HSC in RD.

An ischemic colitis of the descending Colon and Sigma in 3 patients following aorto-iliacal reconstruction was caused by embolism of cholesterol crystals. In all cases the stump pressure of the inferior mesenteric artery measured more than 40 Torr as an empiric value. Therefore a good collateral blood flow could be expected. Nevertheless a malperfusion of the left Colon occurred. These cases of postoperative ischemic colitis were caused by multiple cholesterol crystal emboli in the arterioles of the colon descendens and Sigma. The mobilisation and embolism of arteriosclerotic material during aorto-iliac reconstruction must be responsible for the unfortunate event. Awareness of a bowel ischemia following abdominal aortic surgery and immediate endoscopic control should lead to an early diagnosis and a higher survival rate. A decision to redo operation with left hemicolectomy is required at an early stage.

The impact of aggressive chemotherapy on reproductive and endocrine gonadal function was prospectively studied in 44 patients with germ cell tumors. Diagnostic procedures to determine gonadal toxicity consisted of hormone determinations, semen analyses, interviews with a standardized questionnaire, and gonadal histology. After chemotherapy all patients showed elevated serum levels of follicle-stimulating hormone (FSH) and azoospermia due to germ cell and stem cell loss. Recovery of spermatogenesis, as indicated by normalization of serum FSH levels and sperm density, occurred in 77% of the patients 25-60 months after cessation of chemotherapy. In all patients serum testosterone and luteinizing hormone (LH) values remained within normal limits after therapy indicating resistance of Leydig cells to cytotoxic drugs. Three patients fathered four healthy children after completion of chemotherapy. These data suggest significant reproductive dysfunction in all men treated for germ cell tumors. However, most patients showed late and complete recovery of spermatogenesis. In contrast, endocrine gonadal function was unaffected after chemotherapy in all patients. FSH and LH are feasible markers to assess drug-induced gonadal toxicity.

In einer retrospektiven Analyse wurden Patienten, bei welchen wegen eines Rectumcarcinoms eine anteriore Rectumresektion oder eine abdomino-perineale Rectumexstirpation vorgenommen wurde, erfast. Dabei wurde fur jedes Operationsverfahren die Rate der Operationsletalitat, der postoperativen Komplikationen, der Wiedererkrankung (loco-regionare Rezidive, Fernmetastasen) und der Mortalitat in Korrelation zu der Tumorlokalisation, dem Tumorstaging und dem Tumorgrading gesetzt. Gleichzeitig wurde unter diesen Aspekten ein Vergleich zwischen diesen beiden Operationsverfahren bei Carcinomen des mittleren Rectumdrittels (7–11 cm) vorgenommen. Es zeigte sich, das im Gesamtkrankengut wie auch bei den Patienten mit einem Carcinom im mittleren Rectumdrittel die Rate an Wiedererkrankungen und postoperativen Komplikationen bei den anterioren Rectumresektionen niedriger war als bei den abdomino-perinealen Rectumexstirpationen, was jedoch auf die unterschiedliche Verteilung der Tumorstadien zuruckgefuhrt werden mus.

Anhand von zwei verschiedenen operativen Versuchsmodellen (distale Choledochusligatur; Pfeffersches Modell in der Modifikation von Nevalainen) soll die Bedeutung des Komplementsystems bei der Entstehung der akuten Pankreatitis tierexperimentell untersucht werden. Es konnte gezeigt werden, das auch bei nicht immunologisch induzierter akuter Pankreatitis eine Komplementdepression festgestellt werden kann. Ferner wurde gezeigt, das auch nach vorausgegangener Dekomplementierung durch Anwendung der genannten Versuchsmodelle eine akute Pankreatitis zu induzieren ist, jedoch von deutlich geringerem Ausmas. Es wird gefolgert, das das Komplementsystem wesentlich an der Progredienz und Intensitat des entzundlichen Geschehens Anteil hat.

This paper is a survey of the histomorphology of experimental listeriosis based on cooperative studies performed within the past ten years. The influence of various parameters of the infectious agent (pathogenic Listeria monocytogenes serovar 4b, nonpathogenic Listeria innocua serovar 6b etc.) as well as of the host (euthymic NMRI-mice conditioned with dextran sulfate 500 or cyclosporin A, athymic nude mice etc.) on the course, morphology and outcome of the Listeria infection was investigated. From the experimental models used and the studies performed much could be learned concerning the factors that determine the histomorphological manifestations of listeriosis in humans.

Experimental listeriosis in phenotypically normal (nu/+) euthymic NMRI mice has a characteristic morphology and short-term course. In contrast, listeric infection in congenitally dysthymic nude (nu/nu) mice does not proceed in clear-cut phases, develops more slowly, displays a chronic tendency from the beginning, and shows a considerably different morphology. The inability of nude mice to effectively control and terminate infection by Listeria monocytogenes obviously results from the lack of T lymphocytes.

NMRI mice were experimentally infected with Listeria monocytogenes serotypes 1/2b, 3a, 4b, and 4d and Listeria innocua serotype 6b by different means. The course of infection was monitored, using bacteriological and histological methods. The following typical features of experimental infection with the various L. monocytogenes and L. innocua serotypes were observed. (i) On the basis of the mean lethal dose, L. monocytogenes 4b, 4d, and 1/2b proved to be mouse pathogenic, although to different degrees, L. monocytogenes 3a and L. innocua can be regarded as nonpathogenic for NMRI mice. The virulence of L. monocytogenes serotype 4d was increased 1,000-fold after adaptation to mice. (ii) Primary infection with any serotype of L. monocytogenes or L. innocua resulted in protection against a lethal challenge with the most virulent serotype, 4b. This protective immunity could be transferred by spleen cells. Compared with the duration of immunity achieved by infection with L. monocytogenes serotype 4b, the protection induced by infection with L. innocua was short lived and dose dependent. The data obtained also suggest that immunity after experimental infection with any serotype of L. monocytogenes or L. innocua is produced only when the animal host is filled with bacteria. (iii) The distribution of the germs in the internal organs of the mouse shortly after infection was dependent on the route of infection rather than on the serotype used. (iv) The main difference among the Listeria serotypes tested was their ability to multiply within the host and to induce a granulomatous inflammation. The results indicate that mouse pathogenicity and virulence of Listeria spp. cannot be defined only by the capacity of the bacteria to infect or kill conventional mice. Such a definition should include an analysis of the immune system of the host, a kinetic study of experimental infection, and a histomorphological evaluation of the lesions induced.

Immunological reconstitution by transplantation of HLA-haploidentical, paternal bone marrow was attempted in four infants with severe combined immunodeficiency who lacked HLA-identical donors. To prevent graft-versus-host disease, T lymphocytes were removed from the grafts by agglutination with soybean agglutinin and rosette formation with sheep red blood cells. None of the patients received conditioning treatment before transplantation. Normal, donor-derived cellular immune functions developed in all four patients within several months of transplantation. Threatening complications of graft-versus-host reactions were not seen. All four patients remain in excellent health 12-15 months after discharge home, with persisting normal T-cell functions.

Es wird uber morphologische Untersuchungen bei der experimentellen Echinokokkose berichtet. Nach i.p. Infektion von Gerbils (Meriones unguiculatus) mit Echinococcus multilocularis—Larven konnte die Entwicklung der Cysten in den inneren Organen der Versuchstiere rasterelektronenmikroskopisch in allen Einzelheiten beobachtet werden.

A girl aged 12 years and 10 months presented with deepening of the voice first noted 7 months earlier. Pubertal development was almost completed. The girl had regular monthly menses and no signs of hirsutism, clitoris enlargement or Cushing's disease. Serum testosterone was about threefold above normal, whereas dehydroepiandrosterone was in the upper normal range. The 17-ketosteroids as well as the gas-chromatographically analyzed 5 alpha and 5 beta derivatives of testosterone from urine were slightly increased. Other serum and urinary steroids were normal. Dynamic tests of the endocrine function exhibited inconclusive results. Ultrasonography revealed no ovarian cysts. A small, left-sided adrenal mass was identified by computed axial tomographic scan and removed by surgery. There were no signs of local metastasis nor of vascular extension. The histopathological diagnosis was adrenocortical carcinoma. 5 months after surgery, the preoperatively elevated steroid levels had returned to normal.

The binding of the synthetic immunoadjuvant N-acetyl-muramyl-l-alanyl-d-isoglutamine (MDP, for muramyl dipeptide) to human and rabbit sera containing peptidoglycan (PG) antibodies was investigated. Studies were performed by employing the corresponding 14C or 125I-labeled compounds in Farr-type binding and inhibition assays. Whereas MDP did not react with naturally occurring or experimentally induced PG-antibodies, the analog of MDP MDP-l-Lys-d-Ala did bind to hyperimmune rabbit anti-PG sera, but not to the human sera tested. These studies indicate that the radioimmunoassays employed basically are applicable for the selection of nonimmunogenic MDP analogs possessing immunoadjuvant activity.

Although the parenteral injection of dextran sulfate 500 (DS 500; 50 mg/kg body weight) into 22-month-old NMRI mice resulted in a complete loss of resistance when administered 1 day before the sublethal (4.5 X 10(3)) infection with Listeria monocytogenes, the consequences in aged animals were less dramatic than in young adult (2- to 3-month-old) controls. This was documented by prolonged survival times as well as reduced numbers of Listeriae in spleen. This indicates that aged mice possess an increased paghocytic capacity, as compared to young adult animals. In aged mice the DS 500-induced loss of resistance could be completely abolished by pretreatment with 3 X 10(9) heat-killed Bordetella pertussis organisms 4 days before the DS 500 injection, i.e., 5 days before listeric infection. This indicates that aged NMRI mice possess remarkable reserves in phagocytic activity.

Summary Unlike the acute and short-term course of experimental listeriosis in phenotypically normal (nu/+) mice, Listeria monocytogenes infection in conventionally raised athymic Nude mice results in chronic inflammation with persistence of bacteria and lesions in the internal organs such as liver and spleen. Although it could be shown that germfree Nude mice had no intestinal microbial flora and lacked measurable serum immunoglobulins, neither the course nor the histomorphology of experimental listeriosis, differed significantly from that of their conventionally raised littermates. The results indicate that the typical response of Nude mice to Listeria infection is primarily determined by inborn factors and not by prior antigenic stimulation.

The nature and extent of bacterially induced allergies are difficult to define. Since peptidoglycan, the main component of the cell wall of almost all bacteria, has been available in a highly purified, chemically and immunologically well-defined form, investigation of the allergological significance of this cell component is feasible. Intracutaneous tests were carried out on 181 test subjects with five different peptidoglycan (PG) preparations from Staphylococcus aureus, Staphylococcus epidermidis and Streptococcus Pyogenes. The results of the investigation were compared with the result of determination of serum PG antibodies and serum IgE concentrations. It was shown that test subjects with dual and later reactions to three different staphylococcal PGs displayed significantly higher PG antibody titers than test subjects with negative reactions. Such a relationship could not be found with the cutaneous reactions to streptococcal PG. The total serum IgE values were very much higher in test subjects with immediate reactions to staphylococcal PG than in test subjects with a negative reaction. Typical Arthus reaction or late granulomatous reactions were not observed. Humoral antibodies are involved at least in part in the elicitation of dual and late reactions. Thus, there are interesting parallels to allergy to fungal spores and organic dusts.

The purpose of this survey on the interrelationship of causative agents, mediators and the histomorphology of inflammation is to show to what extent endogenous biochemical factors determine the inflammatory reaction. There is overwhelming evidence, today, that such factors are involved in the manifestation of acute as well as chronic, non-specific as well as well as specific inflammation. In fact, the histomorphological pattern of many inflammatory reactions more directly reflects the activity of the mediators than of the causative agents involved. Therefore, knowledge of the properties of mediators of inflammation does not only provide new insights into the underlying pathomechanisms but may also help in the understanding and interpretation of the histomorphology of inflammatory lesions.

Es wurden die Ergebnisse einer Untersuchung uber das Vorkommen beta-hamolytischer Streptokokken bei 342 Bonner Schulkindern mitgeteilt. Die Gesamtzahl betrug fur den Herbst-Winter-Zeitraum 1965/1966 20,46% bei 10,52% Gruppe A-Streptokokken. Die weitere Aufschlusselung ergab fur die Gruppe A-Rate einen Schwankungsbereich von 5,78–30%. Daruber hinaus wurden Befunde vorgelegt, welche darauf hinweisen, das die meisten der isolierten Gruppe A-Streptokokkenstamme wahrscheinlich infektios bzw. pathogen waren. Es wurde angeregt, ahnliche Untersuchungen in verschiedenen Teilen Westdeutschlands durchzufuhren, um die Haufigkeit des Vorkommens und die Bedeutung von Gruppe A-Streptokokken bei Schulkindern zu ermitteln und somit einen zuverlassigen Masstab fur Kontrollmasnahmen zu erhalten.

Um eine evtl. Dissoziation von Ag-Ak-Komplexen in vivo (Kaninchen) nachzuweisen, wurden 1. Komplexe injiziert, deren Ak-Teil aus speciesgleichen Tieren (Kaninchen) stammte, 2. Komplexe verwendet, deren Antigenkomponente in ihrer antigenen Wirksamkeit weitgehend bekannt ist (C-Streptokokken) und 3. nur zwei verschiedene Arten von Komplexen (Agglutinat und Pracipitat) gepruft. Bei Injektion des Pracipitates konnten weder gegen den Komplex, noch gegen den Ag-Teil des Komplexes, noch gegen die Antikorperkomponente des Komplexes pracipitierende oder agglutinierende Antikorper nachgewiesen werden. Dagegen gelang es bei Verwendung eines Agglutinates aus inaktivierten C- Streptokokken und dem homologen, artspezifischen Antikorper in den Kaninchen gegen den Ag-Teil des Komplexes wirksame Antikorper festzustellen, wahrend das Serum gegen den Komplex selbst keine Antikorper enthielt. Es scheint somit auch in vivo eine Dissoziation von Ag-Ak-Komplexen unter bestimmten Umstanden vorzukommen.

Die wesentlichen Probleme, welche bei der diagnostischen Anwendung der Imnrunofluorescenz und hier besonders beim Nachweis von den im Gewebe lokalisierten Bakterien auftreten, werden beschrieben.