Enhancement of peroxisomal enzymes, cytochrome P-452 and DNA synthesis in putative preneoplastic foci of rat liver treated with the peroxisome proliferator nafenopin

The peroxisome proliferator (PP) nafenopin (NAF) enhanced tumordevelopment in rat liver through promotion of a subtype of putativepreneoplastic cell foci, characterized by weak cytoplasmic basophilia(1,2). In order to elucidate the selective growth advantageof these weakly basophilic foci (WBF) we investigated the effectsof NAF on their metabolic phenotype and DNA synthesis. In WBF,as well as in other foci subpopulations and in hepatocellularcarcinomas the occurrence of five NAF-inducible enzymes, i.e.of peroxisomal ß-oxidation (acyl-CoA oxidase, bifunctionalprotein and thiolase), catalase and cytochrome P-452 was studiedby immunohistochemical methods. In untreated livers almost allfoci were stained with the same intensity as the surroundingtissue. When NAF was applied, most of the liver foci showedconsiderably less staining than the non-focal parenchyma inwhich pronounced enzyme induction had occurred. However, thesubpopulation of WBF showed a more heterogeneous pattern ofenzyme expression varying from less to even more than in theadjacent tissue. A similarly broad range of expression of peroxisomalenzymes was found in hepatocellular carcinomas. On average,however, the tumors exhibited less staining and lower activityof peroxisomal ß-oxidation than the surrounding parenchyma.WBF always showed higher rates of DNA synthesis than other focisubtypes and unaltered liver. In     

Assessment of Photoinduced Frontal Polymerization Processes for a Stable 1K System

Frontal polymerization (FP) has attracted increasing interest in recent years in various applications. This polymerization method can be very promising for the polymerization of thick materials with high fillers content in the range of 50–80% (weight) by local application of a reasonable amount of energy. In this work, recent advances in controllable and predictive behavior for photoinduced frontal photopolymerization are reported. Here, tert-butyl peroxybenzoate (Luperox-P) is selected to initiate thermal polymerization at depth because its high polymerization ability and its decomposition temperature is in a promising range, i.e., neither extremely high (monomer decomposition) nor very low (storage stability issues). Thermal imaging experiments are used to follow the temperatures in the samples in real time. The number of cured layers and the depth of cure are also determined. This paper investigates various factors such as the contents of both photo and thermal initiators, the light intensity, the fiber contents, the irradiation time, etc., resulting in a statistical design of experiments with the factors: 1) content of Luperox P and 2) the irradiation time used to investigate the influence on photoinduced frontal polymerization. Markedly, FP appears to be fully controllable for a storage-stable, tunable 1K system.     

Hypoglycaemic effects of the novel antidiabetic agent repaglinide in rats and dogs

1. Repaglinide, a novel compound with a nonsulphonylurea structure, is currently being clinically tested as a therapeutic agent. In the present study, the hypoglycaemic effects of repaglinide in rats and dogs were investigated.
2. Whereas the R-enantiomer, AG-EE 624 ZW, showed only weak hypoglycaemic activity, the S-enantiomer, repaglinide, turned out to be a potent hypoglycaemic compound in rats after oral as well as after intravenous administration. Only 50% of the dose of repaglinide was needed to be equieffective with the racemic mixture AG-EE 388 ZW. The corresponding ED₅₀ values calculated for the effects after 120 min p.a. (intravenous administration) were 3.4 μg kg⁻¹ (repaglinide) and 6 μg kg⁻¹ (AG-EE 388 ZW).
3. When compared to glimepiride or glibenclamide, repaglinide displayed a 18 to 25 times higher potency in fasted rats. The ED₅₀ values calculated for the effects after 120 min p.a. (oral administration) were 10 μg kg⁻¹ (repaglinide), 182 μg kg⁻¹ (glimepiride) and 255 μg kg⁻¹ (glibenclamide).
4. In glucose loaded rats (0.5, 1.0, 2.0 and 3.0 g kg⁻¹ glucose, p.o.) repaglinide exerted a very strong antihyperglycaemic activity which was even more pronounced than under normoglycaemic conditions. So for a reduction in blood glucose of 1 mmol l⁻¹, 10.3, 9.3, 7.0 8.4 and 7.2 μg kg⁻¹ repaglinide were needed after glucose loads of 0.0, 0.5, 1.0, 2.0 and 3.0 g kg⁻¹, respectively.
5. In beagle dogs repaglinide again showed a pronounced hypoglycaemic effect (ED₅₀ 28.3 μg kg⁻¹) which lasted for up to 24 h. However, insulin levels were only transiently increased.
6. The in vivo data presented are well supported by recently published in vitro findings. From its activity profile, repaglinide appears to be a promising new therapeutic agent.

     

Orbital immunocytoma simulating Hodgkin‘s disease by mimicking Hodgkin- and Reed-Sternberg-like cells

Purpose. The present case report describes primaryorbital immunocytoma (IgM-) mimicking Hodgkinsdisease of the diffuse, lymphocyte predominance type byexpressing Hodgkin simulating cells as well asReed-Sternberg simulating cells (both: H-RScells). Patients and methods. The patient (87a; male)was admitted to hospital with increasing left upper eyelidprotrusion. Computed tomography revealed an unspecificaccumulation of soft tissue within the orbit. A biopsy wastaken. Light microscopical sections were stained with PAS, Giemsa andhaematoxylin-eosin. Immunohistochemistry was performedfollowing standard procedures. Results. By means oflight microscopy, Hodgkins disease of the diffuse,lymphocyte predominance type was indicated.This initial diagnosis was mainly based onmorphological criteria, e.g. the presence of H-RS-like cells.Since staging work-up produced no evidence of systemicdisease, immunohistochemistry was performed. It revealedthat the misleading cells were H-RS simulating cells. Finally, the diagnosis made was thatof immunocytoma (IgM-); stage I EA. Conclusion.The diagnosis of Hodkins disease of the diffuse, lymphocytepredominance type is normally based on morphologicalcriteria. However, in very rare cases immunocytomas simulate this variant ofHodgkins disease by expressing misleading H-RS simulatingcells. Thus, immunohistochemical investigations shouldgenerally be included in the criteria for the diagnosis ofHodgkins disease of the diffuse, lymphocyte predominance type. As far as we areaware, primary immunocytoma mimicking this variant ofHodgkins disease within the orbit has never been reported.     

DNA measurement,proliferation markers,and other factors in pituitary adenomas

To assess the proliferative activity of pituitary adenomas, 36 surgically removed adenomas were studied by light microscopical parameters; mitotic count; expression of PCNA, Ki-67, cathepsin D, and EGF; and image cytometry. Three adenomas (9%) showed high, 11 (34%) medium, 17 (53%) moderate, and 1 (3%) low structural differentiation. In 10 adenomas (31%), no mitosis was observed. The average was 2.4 mitoses/100 HPF; the highest count was 7.1 mitoses/100 HPF. Eleven adenomas (33.3%) were PCNA-negative; in 20 adenomas (60.6%), between 0.05 and 3.9, and in 2 adenomas (6.0%), between 10.5 and 16.4 PCNA-positive nuclei were observed. Only a recurrent null-cell adenoma (9%) was Ki-67-negative. Three adenomas (9.1%) were EGF-negative, 28 (84.8%) showed up to 10% positive cells, and 2 (6.1 %) showed between 10 and 30% positive cells; 19 adenomas (68%) were cathepsin D-negative, including all endocrine-inactive adenomas. Half the adenomas had an euploid DMA stem line. Endocrine-inactive adenomas displayed a higher rate of euploid DNA stem lines than endocrine-active adenomas. The S-phase fraction varied between 2.97 and 28%, with a mean value of 14.4%. Half the adenomas showed an S-phase fraction of 11.65% or lower.     

Percutaneous burrhole trephination of the skull: a study of 519 cases

We want to report on our experiences with the percutaneous trephination using a 2.35 mm round dental drill with serrated saws around it, a Rosenbohrer. It is a methodically similar activity as described by J. Zentner [11].From 1981 to 1992 519 patients were treated and 546 trephinations were performed.At the beginning this treatment was only used in connection with intracerebral bleedings and biopsies.In a considerable short time the indication could be extended to the subdural hematoma, tumor cyst, obstructive hydrocephalus as well as to the abscess and the subdural epyema.The rate of infection was 1.28% and the risk of bleeding 0.36%.In our opinion the advantages of this small electrical trephination are the easy handling, the universal use and mobility and the avoidable risk of anesthesia as well as the sterilisation at the same time and the stopping of blood, caused by the contact surface friction.     

The treatment of spondylotic cervical myelopathy by ventral discectomy. Long term results on 121 patients

The pathophysiology of spondylotic cervical myeolopathy is still a matter of discussion. This paper presents a series of 126 patients operated on using a ventral approach. In 47% of the patients only a spondylotic narrowing of the spinal canal was present and in 35% an additional disc herniation was found. In 13% of the cases however a soft disc without spondylotic spures was found and in 5% a dislocation of vertebral bodies. We found a marked male preponderance of 77%, mean age was 51.6 years, ranging from 25–50 years. Most patients were operated on at the levels of C4/5 and C5/6. Observation time covered a period of 3–10 years. The outcome was rated relatively to the preoperative degree of disablement using a questionnaire for the patients and their family doctors. We found a marked difference in the answers, especially in rating deterioration, which was stated by patients in 34%, by physicians only in 12%. Another finding was the time-related out-come. We found best results with 75% improvement and 5% deterioration between 3–6 months postoperatively, with increasing time the results decreased to 33% improvement, 33% identical statys and in 33% a deterioration related to the preoperative status must be noted.     

Cell death and disposal in retinoblastoma: an electron microscopic study

Background: Tumor necrosis and cell death are common features of retinoblastoma. In non-malignant retinal cells after ischemia, as well as in many nonretinal tumors, cell death occurs in at least two ways. We investigated whether similar patterns of cell death could be demonstrated in retinoblastoma cells. Methods: Nine globes with retinoblastoma from eight patients were studied. Paraffin sections stained with HE or the Feulgen method were examined by light microscopy. Several samples from each tumor were selected for electron microscopic study. Results: Ultrastructurally, two main types of cell death were identified. Type I was characterized by progressive lysis of the cytoplasm and karyoplasm. Nuclear chromatin either dissolved or was transformed into compact clumps becoming extracellular dense bodies. Phagocytosis of cell remnants by neighboring tumor cells, or occasional macrophages, was common. Type II was characterized by progressive condensation and shrinkage of the cytoplasm and nucleus. Type II was subdivided in two forms distinguished mainly by characteristic patchy vs crescentic chromatin condensation. Small parts of condensed cytoplasm were engulfed by neighboring tumor cells. Compact cell remnants then underwent either phagocytosis by neighboring retinoblastoma cells or progressive intercellular disaggregation. Conclusion: Retinoblastoma cells may undergo at least two types of cell death. Type I fits the definition of necrosis, while both forms of type II exhibited several features consistent with apoptosis. The types of cell death observed in retinoblastoma exhibited similarities to patterns observed in ischemic retina, as well as in other malignant tumors. Type II cell death (apoptosis) may play a role in limiting tumor growth.Presented in part at the 1993 ARVO Meeting in Sarasota, Fla., USA     

Multileafkollimator: Erweiterte Qualit?tssicherung an einem GE-Linearbeschleuniger

Hintergrund: Ein Multileafkollimator stellt durch die Vielzahl der Lamellen sehr viel höhere Ansprüche an die Konstanzprüfverfahren als ein konventionelles Blendensystem. Zur täglichen Kontrolle der Lamellenpositionierung wird ein Qualitssicherungskonzept vorgestellt. Methode: Zwei Feldkonfigurationen, die bei maximaler Öffnung der Blockblenden sowohl maximale Öffnung als auch "Overtravel" einzelner Lamellen enthalten, werden in täglichem Wechsel online vom Verifikationssystem zum Linearbeschleuniger übertragen. Im Lichtfeld des Linearbeschleunigers erfolgt eine visuelle Kontrolle der Lamellenpositionen mit Hilfe eines speziellen Prüfkörpers. Abschließend wird die Lamellenpositionierung mittels eines Electronic-Portal-Imaging-Systems dokumentiert und nach Überlagerung eines Gitters mit einer Referenzaufnahme verglichen. Ergebnisse: Die Methode stellt eine schnelle und effektive Möglichkeit dar, die Funktionsfähigkeit des gesamten Systems durch Simulation des "Routinebetriebs" zu überprüfen. Schlußfolgerung: Der Arbeits- und Zeitaufwand für die Qualitätssicherung an einem Multileafkollimator unterscheidet sich nur unwesentlich von dem eines konventionellen Blendensystems. Background: In comparison to a conventional collimator, a multileaf collimator demands a great deal of quality assurance procedures due to its large number of leaves. A concept for daily quality assurance is presented, mainly concerning the positioning accuracy of the leaves. Material and Methods: Two leaf configurations including maximal opening as well as overtravel of single leaves, at a maximal opening of the jaws, are transmitted online in daily exchange from our record- and verify system to the linac. Aiming at a special test phantom a visual control of the positioning accuracy is performed. The leaf positioning is documented by an electronic portal imaging system and is compared with a reference shot by superposition of a grid. Results: This method of quality assurance offers a fast and effective possibility to guarantee the proper function of the whole system by simulating the routine treatment situation. Conclusions: Compared to a conventional collimator only a slightly greater workload is needed for quality assurance of a multileaf collimator.     

Noise-Induced Endocrine Effects and Cardiovascular Risk

Noise has the potential to cause stress reactions. Chronic noise-induced stress accelerates the ageing of the myocardium and thus increase the risk of myocardial infarction. The involved pathomechanisms include acute increase of catecholamines or cortisol under acute noise exposure and an interaction between endocrine reactions and intracellular Ca/Mg shifts. Chronic noise exposure of animals on a diet with suboptimal magnesium content led to increase of connective tissue and calcium, and decrease of magnesium in the myocardium. These changes were correlated to noradrenaline and normal ageing. Post mortem studies of hearts from victims of ischemic heart diseases confirmed the importance of Ca/Mg shifts in humans. Recent epidemiological studies support the importance of noise as a risk factor in circulatory and heart diseases, especially in myocardial infarction.