[Chemotherapy of juvenile angiofibroma--an alternative?]. / Chemotherapie des juvenilen Angiofibroms--eine Alternative?

Since February 1979, 22 juvenile angiofibromas have been treated among 312 tumors of the skull base managed in the ENT Department, Fulda. According to a general staff consensus the treatment of choice was complete surgical removal. This was achieved in 20 cases with one operation and in one case with two operations. In addition to removal of tumor, functional and aesthetic aspects had to be considered as aims of operative treatment, including among others preservation of the facial skeleton, infraorbital nerve, nasolacrimal drainage system and vision. In rare cases complete excision of the tumor is not possible. The value of cytostatic therapy is demonstrated in one patient with uncommonly advanced disease. Considering the extensive regression of tumor achieved in this case after chemotherapy with Adriamycin and decarbazine, one has to raise the question if the chemotherapeutic approach was more than just palliative. From our experience chemotherapy should be considered a possible alternative to radiation in the management of unresectable juvenile angiofibromas.

Radiotherapy alone versus chemotherapy with ifosfamide/vindesine followed by radiotherapy in unresectable locally advanced non-small cell lung cancer.

In a German multicenter trial, previously untreated patients with unresectable stages IIIA and IIIB non-small cell lung cancer were randomly assigned to receive either radiotherapy alone (arm A) or chemotherapy followed by radiotherapy (arm B). Chemotherapy in arm B consisted of ifosfamide 1,500 mg/m2 intravenously on days 1 to 5 and 29 to 33, and vindesine 3 mg/m2 intravenously on days 1 and 5 and 29 and 33. Radiotherapy started on day 1 in arm A and on day 56 in arm B. Single doses of 2 Gy were given 5 days a week for 3 weeks and after a 2-week interval for an additional 2 weeks. The total radiation dose was 50 Gy. Concurrent to radiotherapy, cisplatin was given as a radiosensitizer at a dose of 20 mg/m2 once a week. From July 1986 to March 1989, 85 patients were randomized, of whom 78 were evaluable. Main prognostic factors were well balanced. Of the patients receiving chemotherapy, 25% had a partial remission after two cycles, 46% showed no change, and 29% had progressive disease. After radiotherapy, response rates were 49% in arm A and 58% in arm B, including a 10% complete remission rate in both groups. After two thirds of the projected sample size had been included, an analysis of survival was performed and showed a statistically significant advantage for the treatment group including chemotherapy (P = .016). Median survival was 9.0 months versus 13.7 months and 2-year survival was 12% versus 24%, both in favor of the group receiving chemotherapy. These results caused premature discontinuation of patient accrual according to the study protocol and the recommendations of the Ethics Review Board of the Philipps-University Hospital. The results of this trial indicate that chemotherapy is able to prolong survival of patients with locally advanced unresectable non-small cell lung cancer and should be considered for treatment of these patients.

[Peridural anesthesia using high volume prilocaine--success rate and patient acceptance. A prospective study of 630 anesthetized patients]. / Periduralanaesthesien mit hohen Volumina Prilocain--Erfolgsquoten und Patientenakzeptanz. Eine prospektive Studie über 630 Anaesthesien.

In a prospective clinical study the follow-up course of 630 lumbar single-shot and continuous epidural anesthetics in young patients (average age 24.5 years) with 20-25 ml prilocaine 2% (epinephrine concentration 1:200,000) and 0.1 mg fentanyl was examined critically. The patients were interviewed postoperatively about this method of anesthesia. In 89% of cases the patients had been found suitable for surgery without any additional medication; 9% of the patients needed 0.1-0.15 mg fentanyl and 2.5-5 mg midazolam i.v. Only in 10/630 cases was supplementary anesthesia needed. During anesthesia a drop in blood pressure by 30% or more of the original value was recorded in 1.4% of patients; 5 patients had obvious simultaneous bradycardia. Nausea and vomiting were observed in 2.5% of cases; in 6 patients the level of peridural anesthesia was as high as T4-5. Postoperatively, 19% of the patients complained of discomfort in the area of the lumbar vertebral column. It subsided significantly 2 days after surgery; in 5.6% of cases patients had micturition disorder needing treatment. In 93% of cases the patients considered the method of anesthesia quite acceptable; in the same circumstances 96.5% said they would prefer epidural block to general anesthesia. The main reasons for this were the possibility of observing the surgical operation (26.8%) and the likelihood of speedy recovery on the same day (24.3%). Epidural block is preferred to any form of general anesthesia according to the experience we have gained in these young patients without essential concomitant diseases and with exact consideration to the contraindications for all operations distal of segments T9 and T10.

Genetic engineering of polysaccharide structure: production of variants of xanthan gum in Xanthomonas campestris.

Xanthan gum is an extracellular heteropolysaccharide produced by the bacterium Xanthomonas campestris. Xanthan has wide commercial application as a viscosifier of aqueous solutions. Previously, through genetic engineering, a set of mutants defective in the xanthan biosynthetic pathway has been obtained. Certain mutants were shown to synthesize and polymerize structural variants of the xanthan repeating unit and thus produce "variant xanthans". Initial studies of solution viscosities of these polymers, presented here, indicate that the variants have rheological properties similar to, but not identical with, xanthan. These results indicate that acetylation and pyruvylation can affect the viscometric properties of xanthan. Specifically, the presence of pyruvate increases viscosity, whereas acetate decreases viscosity. In addition, the elimination of sugar residues from xanthan side chains also has a major effect on viscosity. Compared to wild-type xanthan, polymer lacking the terminal mannose (polytetramer) is a poor viscosifier. In contrast, polymer lacking both the terminal mannose and glucuronic acid (polytrimer) is a superior viscosifier, on a weight basis. There is a negative effect of acetylation on the viscosity of polytetramer xanthan, but there is seemingly no effect of acetylation on polytrimer xanthan viscosity. The further study of these materials should provide insight into the relationship between xanthan structure and rheological behavior.

CHOP-VP16 chemotherapy and involved field irradiation for high grade non-Hodgkin's lymphomas: a phase II multicentre study.

Sixty previously untreated patients with high grade non-Hodgkin's lymphomas stages II-IV received cyclophosphamide 750 mg m2 i.v., doxorubicin 50 mg m2 i.v., and vincristine 2 mg i.v. on day 1, prednisolone 100 mg p.o. on days 1-5 and etoposide 100 mg m2 i.v. on days 3-5 (CHOP-VP16). After four courses an involved field irradiation with a total dose of 25 Gy was employed and followed by two additional courses of CHOP-VP16. The overall response rate was 93%, with 49 patients (82%) achieving a complete remission (CR). Seven patients had a partial response and four patients showed no response. During a median follow-up period of 55 months, 22 of the 49 patients with CR relapsed, seven of them achieving a second complete remission with the same drug regimen. A maintained complete remission of up to 68 months was seen in 55% of all patients initially achieving CR. The median survival is 43 months. Mean side-effects of this drug regimen were alopecia (89%), nausea/vomiting (76%) and leukopenia (61%). No therapy-related deaths were seen. The results of this study demonstrate that this combined modality treatment produces high complete remission rates and that more than half of these patients achieve long-term disease-free survival.

Extraction of proteins within ultrathin-layer polyacrylamide electrophoresis (SDS-PAGE) and isoelectric focusing (PAGIF) of cryostat sections and tissue culture specimens.

Separations on a micro- and ultramicroscale by electrophoresis and isoelectric focusing of protein quantities between 10(-6) and 10(-12) g have notable interest, particularly in cytology and histology. We performed the methods of ultrathin-layer polyacrylamide horizontal electrophoresis, isoelectric focusing and protein mapping with some modifications in order to study protein extraction and applied them for cryostat sectioned muscle tissues and singular dorsal root ganglia of the chicken in tissue culture. Further we established an extraction chamber for histological specimens. The basis for ultrathin-layer electrophoresis is the ultrathin (0.12 mm-0.36 mm) polyacrylamide gel on glass plates or microscopic slides. This method allows a considerable reduction of the amount of proteins at the range of 10(-9) g and is thus appropriate for direct extraction of proteins within electrophoresis (10 min, 5 mA 200 V) or isoelectric focusing (10 min, 10 mA, 500 V) of cryostat-sections (7-20 micron thickness) or tissue culture specimens. The advantages of these techniques for extraction of soluble proteins in immunohistochemistry as well as for handling to obtain optimal resolution (compared with electrophoresis of conventional extracted proteins) will be demonstrated.

[Coronary heart disease and heart valve diseases in patients with terminal kidney insufficiency]. / Koronare Herzkrankheit und Herzklappenerkrankungen bei Patienten mit terminaler Niereninsuffizienz.

Cardiac catheterisation and coronary angiography were performed in 100 patients preceding a planned renal transplantation. Coronary heart disease was revealed in 64 patients: stenoses of 50-70% in 28, 71-90% in 16, over 90% in 20 patients. For stenoses above 50% the sensitivity of clinical symptoms was 0.52, their specificity 0.64. For stenoses over 70% the specificity was 0.58; over 90% it was 0.70. Typical symptoms of angina were less common in dialysis patients with coronary heart disease than is usual in other patients with coronary heart disease. Total duration of dialysis as well as frequency and severity of coronary heart disease did not correlate. In 19 of the 100 patients valvar disease was also present, with a discrepancy between the severity of clinical and of hemodynamic findings. Incidence and severity of valvar disease increased with the duration of dialysis. Transplantation was postponed in 11 patients (bypass operation in 3, balloon dilatation in 2, valve replacement in 6). Transplantation was advised against in four (severe coronary heart disease in 2, cardiomyopathy in 2).

[Multicenter study of the treatment of highly malignant non-Hodgkin's lymphomas with polychemotherapy (CHOPV) and irradiation]. / Multizentrische Studie zur Behandlung hochmaligner Non-Hodgkin-Lymphome mit Polychemotherapie (CHOPV) und Bestrahlung.

In a multicenter study 46 untreated patients with highly-malignant non-Hodgkin's lymphomas stage II-IV received 6 courses of the following drug combination: cyclophosphamide 750 mg/m2 i.v. day 1, adriamycin 50 mg/m2 i.v. day 1, vincristine 2 mg i.v. day 1, prednisolone 100 mg p.o. days 1-5, and etoposide 100 mg/m2 i.v. days 3-5. Between courses 4 and 5 an involved field irradiation with a total dose of 25 Gy was employed. The overall response rate was 91%, with 38 patients achieving a complete remission (82%), 4 patients achieving a partial remission (9%), and 4 patients showing no response (9%). During a median follow-up period of 34 months 16 out of 38 patients relapsed, 4 of them achieving a second complete remission with the same drug regimen. A maintained complete remission up to 52 months was seen in 51% of all patients initially achieving CR. The overall survival curve shows a plateau at 60% at 30 months, while disease-free survival shows a plateau at 51% at 36 months. Mean side effects of this drug regimen were alopecia (89%), nausea/vomiting (76%), and leukopenia (61%). No therapy-related deaths were reported. The results of this study demonstrate that this treatment produces high complete remission rates and that the majority of these patients achieves long-term disease-free survival.

Architectonic differentiation of the lateral geniculate body of the cat.

The cell layers of the lateral geniculate nucleus (LGN) of the cat have been reinvestigated in relation to the localization of the degeneration of optic terminals. After unilateral enucleation the degenerated crossed and uncrossed optic terminals form five continuous alternate strips in all the five layers of the LGN with the Fink-Heimer method. The crossed terminals end in the layers A, B0, and B2, and the uncrossed terminals in the layers A1, and B1 without overlapping. The cyto- and myeloarchitectonic study of complete frontal, sagittal, and horizontal serial sections has shown that the former B layer and the nuclei interlaminares centralis pars ventralis and medialis of Thuma built up three continuous parallel layers, which we propose to call B0, B1, and B2. The layer B0 containing large cells and more single fibers than the layers A and A1, extends on the medial, ventral and caudal side of layer A1. The layer B1 containing smaller cells and less single fibers than the layer B0, surrounds the layer B0 from medial, ventral and caudal. It comprises in the medial part of the ventral extent a pale spot with especially small nerve cells. The layer B2 containing medium-sized cells in less dense arrangement and many small dark fiber bundles split up from optic tract extends medially and ventrally of layer B1. The caudal pole of the LGN is covered cap-like by the layers B0, and B1 and incompletely by B2. This new interpretation of the LGN's layers in the cat is more regular and easier to compare with the stratification of the LGN of other species including primates.

Progression of coronary and valvular heart disease in patients on dialysis.

Coronary heart disease and end-stage renal disease: Coronary heart disease is frequent in patients with end-stage renal disease. Without invasive procedures coronary heart disease is often not diagnosed in patients with end-stage renal disease. We have no evidence for accelerated progression of coronary heart disease under conditions of dialysis. Valvular heart disease and end-stage renal disease: Valvular heart disease shows an increasing frequency depending on the period of dialysis. Valvular heart disease is often unnoticed and constantly underestimated without invasive investigation. Valvular heart disease often indicates a bad prognosis in our patients with end-stage renal disease.

Terminals of intralaminar thalamic neurons in the pallidum externum of Saimiri sciureus.

Stereotactic coagulations of intralaminar thalamic nuclei in 6 squirrel monkeys Saimiri sciureus produced dark degenerations only of type IV synapses in pallidum externum, according to the classification of Hassler and Chung often preserving the slightly asymmetric contact and subsynaptic densities. Other type IV boutons underwent semidark degeneration, whereas others showed crystalloid degeneration. Some of type IV boutons show the deposition of many dense core vesicles and mitochondria with loss of most synaptic vesicles. Enlarged type IV boutons are sometimes overcrowded with irregularly shaped lysosomes. Thus, a monosynaptic connections of intralaminar thalamic nuclei to pallidum externum could be demonstrated.

Identification of eight types of synapses in the pallidum externum and internum in squirrel monkey (Saimiri sciureus).

The electron microscopic study of the neuronal structures of the pallidum externum (Pa.e) and internum (Pa.i) in squirrel monkey (Saimiri sciureus) has revealed in both segments a frequent large type of nerve cell and a rare small one, probably an interneuron. With respect to the small cells, only one axosomatic synapse inserts on the slender rim of cytoplasm; the clear nucleus is always invaginated and contains a small nucleolus. Eight types of synapses can be differentiated in Pa.e and Pa.i. The axodendritic type I P with pleomorphic vesicles and an inconspicuous symmetric contact to a central dendrite, make up 65% of all synapses in Pa.e and 79% in Pa.i. These synapses are commonly arranged in a rosette pattern around the dendrite. Two subtypes of the type I P are found in both segments--the one with invaginated boutons (subtype I Piv) and the other (subtype I Pol) oligovesicular. The type III SR synapses are characterized by small round or slightly oval vesicles and a strongly asymmetric contact (12% in Pa.e and 8.1% in Pa.i). The predominantly axosomatic type II EF synapses are characterized by elongated vesicles as well as by encapsulation in thin astrocytic processes (5% in Pa.e, 8.5% in Pa.i). The boutons of type IV Sph characterized by large uniformly spherical vesicles undergo symmetric synaptic contacts (in Pa.e 6% and in Pa.i 0.5%). The type V Osl stiletto-shaped bouton with ovoid vesicles undergoes a symmetric contact with a dendrite (in Pa.e 5% and in Pa.i 1.1%). Two types of dendrodendritic and dendrosomatic synapses are found: the type VI DE containing sparsely distributed elongated vesicles suspended on neurofilaments, undergoing a symmetric contact, and the type VII DC with clustering mostly round vesicles near the presynaptic component of the asymmetric contact. The rare axodendritic type VIII My arising from a myelinated axon, exhibits small elongated vesicles and symmetric contact. The synaptic types I, III, IV, and VI are similar to the same types in the substantia nigra, whereas types II, V and VII resemble the equivalent types in the motor thalamic VA and ventro-oralis anterior nuclei.

Types of synapses and degeneration in the thalamic nucleus ventralis oralis posterior after cerebellar lesions in the squirrel monkey.

The thalamic nucleus ventralis oralis posterior (V.o.p) of Saimiri sciureus corresponds to the posterior basal part of the ventral lateral nucleus and is characterized by medium-sized nerve cells. Electron microscopic study revealed seven different types of synapses and the size of vesicles in each has been quantitatively determined. The synapse of type I LR (Large with Rounded vesicles) is considerably larger than the similar type IV MR (Medium-sized with Rounded vesicles) both contain round to ovoid vesicles and a large amount of mitochondria. Their contacts are asymmetric with presynaptic aggregations of synaptic vesicles. The type I LR synapses may also form button-like contacts (adhering junctions) without presynaptic accumulation of synaptic vesicles. The type II F (large with Flattened vesicles) symmetric synapses are formed by large boutons containing flattened vesicles and are partially encircled by astrocytic processes. The type III SR (Small with Rounded vesicles) bouton possesses small, nearly round till ovoid dense vesicles and forms a strongly asymmetric contact. In the type V SO (Small with Ovoid vesicles) bouton, the pleomorphic vesicles are larger than in type III and form asymmetric contacts with relatively small dendrites. Finally, two types of dendritic terminals were distinguished (VI and VII), which can be differentiated chiefly by the distribution of synaptic vesicles; VI DE (Dendritic terminal with Evenly distributed vesicles) and VII DC (Dendritic terminal with Clustered vesicles). Following hemicerebellectomy (4 experiments), only the type I LR and type IV MR synapses were found to be degenerated in the thalamic nucleus V.o.p. Similar degeneration was found in the ventral intermediate nucleus (V.im) which corresponds to the most rostral part of the VPL nucleus (VPLo). After three days survival, the forms of degeneration were largely neurofilamentous or pale, becoming mostly dark after four days. Degeneration of these same types of synapses appeared also in the nucleus ventralis oralis internus (V.o.i) and in the nucleus dorsalis intermedius (D.im), which lies above the ventral intermediate and ventrocaudal nuclei of the thalamus. These results are in good agreement with the findings in the light microscopic investigations if one considers the cyto- and myeloarchitectonic boundaries between the V.o.p and V.im.

Effects of frontal motor cortex ablation on the ultrastructure of cat substantia nigra.

3,4 and 5 days after the removal by suction of the left motor and premotor cortex in cats, the presence of ultrastructural changes in the substantia nigra was investigated. Whereas after 3 days dark bouton degeneration was rare, after 4- and 5-day survival it was regularly found for a distinct type of synapse containing in its bouton densely packed small round vesicles and possessing an asymmetric synaptic junction with a dendrite. Often these darkly degenerated boutons contained dense bodies which were also observed in the same type of synapse not yet exhibiting a dark axoplasm. Various inclusions, especially glycogen depots, were present in these boutons suggesting that they were in the process of degeneration. The glial reaction was comparatively severe. In addition, darkly shrunken dendrites contacted both, by intact and by altered boutons were frequently encountered as well as single degenerated neuronal perikarya. The nature of this effect, i.e. whether transneuronal or retrograde, could not be clarified. All these alterations were found bilaterally after the unilateral cortex ablation, and were confined to the substantia nigra pars compacta along its whole anterior-posterior extent. In the pars reticulata, solely traversing myelinated axons in the process of degeneration were observed. Thus, the results are in agreement with the older studies and with evidence from primates demonstrating that the substantia nigra receives a bilateral projection from the motor and premotor cortex.