Gliosarcoma with extensive extracranial metastatic spread and familial coincidence: A case report.

Gliosarcoma is a rare histopathological subtype of glioblastoma. Metastatic spreading is unusual. In this report, we illustrate a case of gliosarcoma with extensive extracranial metastases with confirmation of histological and molecular concordance between the primary tumor and a metastatic lesion of the lung. Only the autopsy revealed the extent of metastatic spread and the hematogenous pattern of metastatic dissemination. Moreover, the case bared a familial coincidence of malignant glial tumors as the patient's son was diagnosed with a high-grade glioma shortly after the patient's death. By molecular analysis (Sanger and next generation panel sequencing), we could confirm that both patient's tumors carried mutations in the TP53 gene. Interestingly, the detected mutations were located in different exons. Altogether, this case draws attention to the fact that sudden clinical aggravation could be caused by the rare phenomenon of metastatic spread and should therefore be always taken into consideration, even at an early disease stage. Furthermore, the presented case highlights the contemporary value of autoptic pathological examination.

[Oncocytoma versus chromophobe renal cell carcinoma: Is there something in between?]. / Onkozytom versus chromophobes Nierenkarzinom: Gibt es etwas dazwischen?

The differentiation of oncocytic tumors of the kidneys is often difficult, particularly in renal biopsies. Differential diagnoses are chromophobe renal cell carcinoma (ChRCC), renal oncocytoma (RO), the oncocytic variant of papillary renal cell carcinoma (OPRCC), the eosinophilic variant of clear cell renal cell carcinoma (CCRCC) and hybrid oncocytic chromophobe tumors (HOCT). In difficult cases that cannot be resolved by morphology alone, immunohistochemistry is usually helpful. The RO and ChRCC show positive reactions for CD117, they are negative for vimentin and alpha-methylacyl-CoA racemase (AMACR), while CCRCC are positive for vimentin and OPRCC are positive for AMACR. To distinguish between RO and ChRCC, CK7, claudin-7 (both strongly positive in ChRCC and negative or patchy positive in RO) and epithelial cell adhesion molecule (EpCAM) can be used (positive in ChRCC, negative in RO); however, a diagnosis may remain difficult in some cases even with the use of immunohistochemistry. Thus, numerous new methods are being developed in the field of molecular pathology and computer-based morphometric tumor analysis; however, these new methods have not yet been applied in routine diagnostics.

[Vancouver classification of renal tumors: Recommendations of the 2012 consensus conference of the International Society of Urological Pathology (ISUP)]. / Vancouver-Klassifikation von Nierentumoren : Empfehlungen der Konsenskonferenz der Internationalen Gesellschaft für Uropathologie (ISUP) 2012.

The 2012 consensus conference of the International Society of Urological Pathology (ISUP) has formulated recommendations on classification, prognostic factors and staging as well as immunohistochemistry and molecular pathology of renal tumors. Agreement was reached on the recognition of five new tumor entities: tubulocystic renal cell carcinoma (RCC), acquired cystic kidney disease-associated RCC, clear cell (tubulo) papillary RCC, microphthalmia transcription factor family RCC, in particular t(6;11) RCC and hereditary leiomyomatosis-associated RCC. In addition three rare forms of carcinoma were considered as emerging or provisional entities: thyroid-like follicular RCC, succinate dehydrogenase B deficiency-associated RCC and anaplastic lymphoma kinase (ALK) translocation RCC. In the new ISUP Vancouver classification, modifications to the existing 2004 World Health Organization (WHO) specifications are also suggested. Tumor morphology, a differentiation between sarcomatoid and rhabdoid and tumor necrosis were emphasized as being significant prognostic parameters for RCC. The consensus ISUP grading system assigns clear cell and papillary RCCs to grades 1-3 due to nucleolar prominence and grade 4 is reserved for cases with extreme nuclear pleomorphism, sarcomatoid and/or rhabdoid differentiation. Furthermore, consensus guidelines were established for the preparation of samples. For example, agreement was also reached that renal sinus invasion is diagnosed when the tumor is in direct contact with the fatty tissue or loose connective tissue of the sinus (intrarenal peripelvic fat) or when endothelialized cavities within the renal sinus are invaded by the tumor, independent of the size. The importance of biomarkers for the diagnostics or prognosis of renal tumors was also emphasized and marker profiles were formulated for use in specific differential diagnostics.

[Integration of the functional signal of intraoperative EMG of the facial nerve in to navigation model for surgery of the petrous bone]. / Integration des intraoperativen EMG-Signals des N. facialis in das Navigationsmodell der Felsenbeinchirurgie.

UNLABELLED: PROBLEM DEFINITION: The goal of this work is the integration of the information of the intraoperative EMG monitoring of the facial nerve into the radiological data of the petrous bone. The following hypotheses are to be examined: (I) the N. VII can be determined intraoperatively with a high reliability by the stimulation-probe. A computer program is able to discriminate true-positive EMG signals from false-positive artifacts. (II) The course of the facial nerve can be registered in a three-dimensional area by EMG signals at a nerve model in the lab test. The individual items of the nerve can be combined into a route model. The route model can be integrated into the data of digital volume tomography (DVT). MATERIAL AND METHODS: (I) Intraoperative EMG signals of the facial nerve were classified at 128 measurements by an automatic software. The results were correlated with the actual intraoperative situation. (II) The nerve phantom was designed and a DVT data set was provided. Phantom was registered with a navigation system (Karl Storz NPU, Tuttlingen, Germany). The stimulation probe of the EMG-system was tracked by the navigation system. The navigation system was extended by a processing unit (MiMed, Technische Universität München, Germany). Thus the classified EMG parameters of the facial route can be received, processed and be generated to a model of the facial nerve route. The operability was examined at 120 (10 x 12) measuring points. RESULTS: The evaluation of the examined algorithm for classification EMG-signals of the facial nerve resulted as correct in all measuring events. In all 10 attempts it succeeded to visualize the nerve route as three-dimensional model. The different sizes of the individual measuring points reflect the appropriate values of Istim and UEMG correctly. DISCUSSION: This work proves the feasibility of an automatic classification of an intraoperative EMG signal of the facial nerve by a processing unit. Furthermore the work shows the feasibility of tracking of the position of the stimulation probe and its integration into amodel of the route of the facial nerve (e. g. DVT). The rediability, with which the position of the nerve can be seized by the stimulation probe, is also included into the resulting route model.

Comparative pharmacokinetics of enrofloxacin and ciprofloxacin in chickens.

The pharmacokinetics of enrofloxacin (EFX) and ciprofloxacin (CFX) was investigated in broiler chickens. Each antimicrobial was administered intravenously at a dose of 5 mg/kg body weight. Blood was taken in different preset times: prior and at 0.03, 0.06, 0.13, 0.25, 0.5, 1, 2, 4, 8, 12 and 24 h following drug administration. The concentrations of EFX and CFX in plasma were determined by high pressure liquid chromatography (HPLC). Plasma concentrations vs. time were analysed by a compartmental independent pharmacokinetic model that provided the most important kinetic parameters. Statistically significant differences between the two antimicrobials were found for most of the pharmacokinetic parameters: Area under the curve (AUC), area under first moment curve (AUMC), mean residence time (MRT), total body cleareance (ClB), volume of distribution beta (Vd beta) and volume of distribution at the steady state (Vd(ss)). Both antimicrobials were widely distributed in chickens throughout the body with a mean Vd(ss) of 1.98+/-0.18 L/kg for EFX, and 4.04+/-0.69 L/kg for CFX. The ClB for CFX was five times higher than that obtained for EFX. AUC, MRT and the diminished half time for EFX were two-four times higher than those obtained for CFX. These results indicate that CFX remains in the body for less time than the other quinolone. This characteristic of CFX suggests the advantage of a shorter withdrawal time for food producing animals treated with this antimicrobial.

Splice variants of the nuclear dot-associated Sp100 protein contain homologies to HMG-1 and a human nuclear phosphoprotein-box motif.

Sp100 and PML are interferon-inducible proteins associated with a new class of nuclear domains (known as nuclear dots or PML bodies) which play a role in tumorigenesis, virus infections, and autoimmunity. While PML is extensively alternatively spliced, only two splice variants are known for Sp100. Here we describe the identification and characterization of several Sp100 splice variant proteins and support their existence by elucidation of the 3'-end of the Sp100 gene. Some of the splice variants contain a domain of significant sequence similarity with two previously described highly related interferon-inducible nuclear phosphoproteins as well as to suppressin and DEAF-1, which altogether define a novel protein motif, termed HNPP-box. One class of splice variants contains an almost complete and highly conserved copy of the DNA-binding high mobility group 1 protein sequence and thus represent novel HMG-box proteins. When expressed transiently, both major classes of Sp100 splice variant proteins localize in part to nuclear dots/PML bodies and in addition to different nuclear domains. Furthermore, PML was occasionally redistributed. These data indicate that alternatively spliced Sp100 proteins are expressed, differ in part in localization from Sp100, and might bind to chromatin via the HMG domain.

[Psychotic women and their children]. / Psychotische Frauen und ihre Kinder.

OBJECTIVE: The study collected information on the situation of children of psychotic mothers. METHODS: Case reports of a total of 279 female patients with schizophrenia or puerperal psychosis were analysed retrospectively. RESULTS: 128 of these patients gave birth to 218 children. Approximately 80% of the children grew up with their families, and only 8% had to be transferred to foster families or foster homes. Two case vignettes illustrate child care problems in a community psychiatric setting. CONCLUSIONS: Child care is exercised even in families where mothers suffer from psychotic illness. However, many of these mothers do not receive the help they require.

Pregnancy in women on chronic dialysis. A single-center experience with 17 cases.

Successful pregnancy outcome is an uncommon occurrence in women requiring chronic dialytic treatment, and the most adequate dialysis therapy in the management of these pregnant patients has not been established. During the period 1988-1995, we studied the outcome of 17 pregnancies in dialyzed females, with an average age of 28.2 +/- 5.9 years (range: 18-38 years). Seven women had adequate urine volume (>800 ml/24 h). Five patients started dialysis after conception and the remaining 12 pregnancies were diagnosed after 6-72 months on dialysis. Fourteen women were maintained on hemodialysis (HD) and 3 on continuous ambulatory peritoneal dialysis (CAPD). The HD schedule was increased to 3 h 5-6 times weekly, and CAPD was increased to six 2-liter exchanges/day. Mean serum urea was 78.6 +/- 27.4 mg/dl (range 45-110); serum creatinine was 6.5 +/- 3.7 mg/dl (3.3-9.8 mg/dl); and hematocrit was 28.9 +/- 3.3 vol% (22-35 vol%). Anemia was partially controlled with rHuEpo in 8 patients. Significant problems were polyhydramnios in 7 cases (5 HD/2 CAPD), oligohydramnios in 1 (HD), gestational diabetes in 2 (CAPD), premature labor with spontaneous abortion at the 19th, 22nd and 28th weeks of gestation (2 HD/1 CAPD), hypertension in 8 (7 HD/1 CAPD), and sterile eosinophilic peritonitis in 1 case (CAPD). Mean gestational age at delivery in 14 successful pregnancies (12 HD/2 CAPD) was 32.3 +/- 2.6 weeks (27-36 weeks) and mean baby weight was 1,400.7 +/- 579.1 g (range 720-2,650 g). No congenital fetal abnormality was observed. Respiratory distress was observed in 6 infants, with 2 deaths (1 HD/1 CAPD) in the first week after delivery. In this study, successful pregnancies were reported in 70.6% of dialyzed women with uremia, with hemodialysis having a rate of fetal survival of 78.6% and CAPD with 33.3%.

[The incidence of endemic sprue/celiac disease in Berlin (West). A prospective study with short discussion of a case]. / Inzidenz der einheimischen Sprue/Zöliakie in Berlin (West). Eine prospektive Untersuchung mit kurzer Falldiskussion.

This study was carried out between June 1986 and May 1988 in Berlin (West). In cooperation with 5 Pathological Departments, we prospectively recorded every bioptical diagnosis of total/subtotal villus atrophy (group S) or of partial villus atrophy (group SV). In addition, we registered anamnestic, clinical and laboratory findings from these patients. The diagnosis of coeliac disease was considered verified if the patient showed an unequivocal improvement of his clinical conditions and laboratory findings within three months on a gluten-free diet. In total, 42 patients were registered, among them were 29 with mucosal alterations typical for coeliac disease and 13 whose biopsies showed partial villus atrophy. The diagnosis of coeliac disease could be verified in 28 patients, among them one woman with intestinal lymphoma after longstanding untreated coeliac disease. A second patient with complete villus atrophy had intestinal lymphoma but without preceeding coeliac disease. Our findings show that the incidence of coeliac disease in Berlin is 1 out of 2113 newborn children. This figure is similar to the data reported from France, yet being clearly lower than those from Western Ireland, Switzerland and Sweden. Women are affected twice as often as men. 20 out of 28 patients were children under five years of age. The most common symptoms were meteorism/flatulence, recurrent diarrhea, loss of body weight, or inappropriate growth. 70% of the patients suffered from anaemia, the D-Xylose-test was pathological in 92% of the patients.

A comparison of glutathione reductase and glutathione peroxidase activities in patients with rheumatoid arthritis and healthy adults.

A 30% increase in erythrocyte glutathione peroxidase (GP) activity was found in patients with rheumatoid arthritis when compared with healthy controls (p = 0.001) whereas the increase in glutathione reductase (GR) was statistically insignificant. No correlation was found between the activities of the enzymes and the erythrocyte sedimentation rate (ESR). The enzyme activities were independent of age, sex, or type of drug treatment of the patients. A possible interpretation of the results is presented.

[Incidence of endemic sprue in Berlin (West). A retrospective study based on biopsy findings]. / Inzidenz der einheimischen Sprue in Berlin (West). Eine retrospektive Untersuchung anhand bioptischer Befunde.

The incidence of celiac disease in Berlin (West) during the years 1979-1984 has been studied retrospectively by investigating the records of the local Pathological Institutes, which examine small intestinal biopsies, for the occurrence of abnormal specimens typical of celiac disease (group 1) or consistent with the diagnosis of celiac disease (group 2). Group 1 exhibited a constant average incidence of 0.74 per 100,000 inhabitants per year, while group 2 showed a small increase between 1979 and 1984, averaging 1.03 per 100,000 inhabitants per year. Classified according to age the highest incidence was seen in the 0-5 year-olds, namely 8.04 in group 1 and 10.00 in group 2. For those children born and examined during the period of investigation the values ranged between 15.8 and 64.7 per 100,000 births. Girls, with an average frequency of 1:1919 births were more often affected than boys, who averaged 1:4219 births. These figures obtained in Berlin (West) indicate only the lower ranges of incidences and will have to be further supplemented by a prospective study.

Semiquantitative and morphometric investigations on the histopathology of chronic hepatitis non-A, non-B.

Ninety-five cases (202 liver biopsies) with chronic hepatitis Non-A, Non-B (NANB) were investigated histologically. The alterations were analysed semiquantitatively. The histological indices (e. g. volume of the portal tracts, number of acidophilic bodies) of various case groups of chronic hepatitis NANB were determined morphometrically and the results were checked for internal statistical significance and for correlations with comparison groups of chronic hepatitis B. The large number of acidophilic bodies and sinusoidal cells are the sole characteristic histological sign of hepatitis NANB which enable its differential diagnosis, especially from hepatitis B. The chronic post-transfusion hepatitis NANB has a relatively good prognosis and in 80% of the cases shows the course of a chronic persistent hepatitis (CPH). In sporadic hepatitis NANB a chronic aggressive hepatitis (CAH) is present in 60%. The frequency of cirrhosis based on an already chronic stage is 12.6%. An indication for immunosuppressive therapy of sporadic chronic aggressive hepatitis NANB can only be established individually after a sufficiently long observation of the biochemical and histological alterations.

[Laparoscopy findings of the yellow spot, a focal fatty liver infiltration]. / Laparoskopische Beobachtungen zum "Gelben Fleck", einer fokalen Leberverfettung.

From 1976 to 1982 in 279 patients amongst 3719 laparoscopies focal fatty liver infiltrates were found at the right and/or left liver edge next to the insertion point of the round ligament. These so-called "yellow spots" mainly could be recognized in case of normal liver tissue and in cases suffering from chronic hepatitis insofar as a cirrhotic transformation or a significant fibrosis had not taken place. The localization and the shape of these focal lesions indicate, that an abnormality in the portal blood supply of the corresponding area may play an etiologic role for the development of the fatty infiltration.

[Ketoconazole-induced hepatitis. Case report]. / Ketoconazol-induzierte Hepatitis. Eine Kasuistik.

Since Oct. 1981 a new systemic antifungal drug Ketoconazole is available in the Federal Republic of Germany that has proven effective even in severe cases with fungal infections. This case-study will call attention on a rare but important side effect, namely Ketoconazole induced hepatitis. As an acute icteric viral hepatitis, type Non-A-Non-B-hepatitis possibly misdiagnosed only a carefully compiled history of the recent intake of drugs points at the real cause of hepatitis. In our case-report we observed a considerable increase in serum enzymes, especially GOT, GPT and GLDH after a drug-challenge with two tablets. We recommend so-called liver functions tests 2 to 3 weeks after beginning of therapy and further-on in monthly intervals. Histologically at that time toxic hydropic changes of the liver cells and a mesenchymal reaction with portal and intralobular mainly eosinophilic infiltration could be established. The serum enzymes came to normal only after 12 weeks.

[Laparoscopic aspect and clinical relevance of cholangiofibromas]. / Laparoskopischer Aspekt und klinische Relevanz von Cholangiofibromen.

In a current series of 1160 laparoscopies in 38 cases (3.2%) we found cholangiofibromas. The picture of single, sporadic and multiple cholangiofibromas as well as cholangiofibromatosis is both described and documented by laparoscopic photography. Clinically it seems remarkable that only patients with alcohol- or drug-induced liver injury showed such alterations. The prevalence of cholangiofibromas in toxic liver damage suggests that we are here not dealing with embryonal aberrations (hamartomas) but apparently with cellular inductive phenomena.

[Propafenon-induced cholestatic liver injury--a further example for allergic drug hepatitis (author's transl)]. / Propafenon-induzierte cholestatische Hepatitis. Ein weiteres Beispiel für eine medikamentös induzierte "allergische" Leberschädigung.

In the course of cholestatic liver injury after propafenonhydrochloride medication, a high increase of the glutamatedehydrogenase up to the twenty fold of the normal range was followed by a marked raise of SGOT and SGPT. Cholestatic enzymes like gamma-glutamyl transpeptidase and alkaline phosphatase reached their maxima a week later. Within two weeks the hepatic cell enzymes and within four weeks the cholestatic enzymes have returned spontaneously to normal.

Morphometric investigations on the portal tracts of the liver, the differentiation of variable progression in chronic persistent hepatitis.

Morphometric investigations were carried out on the portal tracts of the liver in different forms of chronic hepatitis. The investigation groups each contained 25 liver biopsies, which were subdivided into cases with normal liver, a subsiding acute virus hepatitis, three different forms of chronic persistent hepatitis (CPH) and chronic aggressive hepatitis type IIa (CAH IIa). Determinations of the volume and surface of the portal tracts and their components enabled three forms of COH (type Ia, Ib, Ic) to be characterised. Preliminary clinical and semiquantitative histological investigations were correlated with a significant difference in the histological characteristics and prognosis. HBsAg-positive and HBsAg-negative cases showed no significant morphologically detectable differences in all grups investigated. Morphometry is suitable for investigation of pathological changes in liver tissue, especially the portal tracts.

[Chronic persistent hepatitis. Histological and clinical study of different forms of the course of CPH]. / Die chronisch persistierende Hepatitis. Histologische und klinische Untersuchungen verschiedener Verlaufsformen.

Among 4903 liver biopsies were found 96 cases (241 biopsies) of non-active hepatitis persisting for longer than one year (up to 12 years). Three forms of the course of chronic persistent hepatitis could be delimited in morphological terms taking into account clinical laparoscopic and clinical chemical data. The type Ia presents the picture of a largely subsided, lobular accentuated acute virus hepatitis. The type Ib corresponds to a chronic inflammation with emphasis on the portal system without destruction of the limiting plate, without fibrosis and with only slight intralobular involvement. The type Ic is characterized by a portal and slight septal fibrosis with round-cell infiltrates and a slight facultative periportally active inflammation as well as a moderate intralobular mesenchyme reaction. The typing permits a clear subdivision and a differentiated prognosis: 10% of the cases of type Ic pass into an active chronic hepatitis of the type IIa.