Four-year follow-up of acromegalic patients treated with the new long-acting formulation of Lanreotide (Lanreotide Autogel).

Lanreotide Autogel (Ipsen) is a long-acting somatostatin analogue (SA) in a new galenic formulation suitable for subcutaneous (s.c.) injection. In our department, 11 patients with therapy-resistant acromegaly were treated with Lanreotide Autogel for 48 months. 10/11 patients had previously undergone transsphenoidal surgery. For a median duration of 1.4 years prior to Lanreotide Autogel, the patients received Lanreotide PR 30 mg every 7, 10, or 14 days. 60, 90, or 120 mg of Lanreotide Autogel was administered by deep s.c. injection every 28 days, with the higher dosage being given to those with the previously shortest injection interval under Lanreotide PR. Dose was adjusted on the basis of Growth Hormone (GH) level after 4, 8, and 12 months with a minimum dose of 60 mg and a maximum dose of 120 mg. The efficacy of Lanreotide Autogel treatment was evaluated by measuring GH concentrations (4 hour profiles) and IGF-I levels. Before switching to Lanreotide Autogel, the multiple of the upper limit of normal (xULN) of IGF-I levels was 1.2 (median) and the median GH level was 1.3 microg/l. 3 out of 11 patients had an IGF-I within the age- and sex-adjusted normal range. After 48 months of treatment with Lanreotide Autogel, six patients had an IGF-I within the normal range. Median GH levels were at 1.3 microg/l and xULN of IGF-I was at 1.0 compared to Lanreotide PR 30 mg treatment (p < 0.001). At the end of the study, 8 patients received 120 mg Lanreotide Autogel, 2 patients 90 mg and 1 patient 60 mg, respectively. There was slight but significant deterioration of glucose metabolism with an increase of HbA1c. In conclusion, the new galenic formulation of Lanreotide improves not only the control of biochemical markers of acromegaly compared to the conventional PR formulation, but is also easier to administer given its deep s.c. method of administration. Glucose metabolism has to be followed carefully in patients on high-dose Lanreotide Autogel.

Early ultrastructural changes of myocardial endothelial cells in traumatic haemorrhagic shock in rats.

The aim of this study was to assess early traumatic haemorrhagic shock (THS)-induced changes in myocardial endothelial cells (mECs) both morphologically and morphometrically. The mECs of capillaries of the left ventricular myocardium were investigated by electron microscopy 15, 30, 60, and 120 min after a standardised THS and compared to a control group. With the use of a computer-assisted image analysis system, we measured the following morphometric parameters--height, area, circumference, cytoplasmic processes, and interendothelial junctions--and determined the number and distribution of cytoplasmic vesicles in every mEC. THS induced a significantly increased formation of cytoplasmic processes and a redistribution of cytoplasmic vesicles towards the cell centre, with the changes peaking between 15 and 60 min. There was no evidence of an increase in mEC height or area/circumference ratio used as indicators for early mEC oedema, although the latter dropped significantly after 15 min. No increase in damaged mitochondria was observed and the interendothelial junctions remained close. The THS-induced ultrastructural changes represent early mEC activation. Irreversible damage of mECs does not occur.

Swelling of capillary endothelial cells contributes to traumatic hemorrhagic shock-induced microvascular injury: a morphologic and morphometric analysis.

The endothelial cell (EC) response during the first 2 h after traumatic hemorrhagic shock (THS) was analyzed in the rat mesentery by electron microscopy. Using a computer-assisted image analysis system, we interactively measured THS-induced changes of the area and the mean height of EC as well as the number of swollen EC occluding the capillary lumen. Analysis distinguished between capillaries presenting with the lumen blocked by corpuscular blood cells and capillaries with an open lumen. THS resulted in a significant increase in EC height of capillaries with an open lumen, but not of capillaries with lumen blocked by blood cells when compared with the control group (p < 0.05). This phenomenon was found to be most prominent 60 min after THS. In addition, THS was accompanied by a significantly increased number of swollen EC which occluded capillaries with an open lumen. From these results we conclude that swelling of EC contributes to THS-induced microvascular injury. Occlusion of the capillary lumen by EC swelling may be regarded as the morphological correlate of the THS-induced 'no-reflow' phenomenon.

Cytoskeletal alterations in endothelial cells of mesenteric microcirculatory bed in experimental traumatic haemorrhagic shock.

The purpose of our investigations was to answer the question of whether an increased number of cytoskeletal structures (CSS) in endothelial cells (EC) of the mesenteric terminal vascular bed will be seen in the early phase of a traumatic haemorrhagic shock (THS). A THS was induced in 32 adult R-rats according to a standardized model (fracture of right heel and withdrawal of one third blood volume through carotid catheter). Eight animals each time were killed 15, 30, 60, and 120 minutes after shock induction. Tissue samples of mesenteric microvessels were taken and flatly embedded in Epon. The mesenterium of 8 animals was used as control. CSS formed in the perinuclear and/or peripheric regions of endothelial cytoplasm were visually evaluated and divided into 3 degrees on the basis of 1,500 micrographs. Results were statistically analyzed. A significantly higher degree of CSS (microfilaments, intermediate filaments and microtubules) in EC was found in all shock groups as compared with the control group. CSS are frequently clearly seen in oedematous and swollen EC as well as in EC rich in organelles. Capillaries with stasis are especially predisposed to CSS. Different factors as changed interaction between vascular content and EC, hypoxia and ischemia as well an increased metabolic activity of EC have to be considered as possible causes.

[Ultrastructural changes in the endothelial cells of the mesenterial terminal blood stream track during the first two hours of a traumatic hemorrhagic shock (THS)]. / Ultrastrukturelle Veränderungen der Endothelzellen der mesenterialen Endostrombahn in den ersten zwei Stunden eines traumatisch-haemorrhagischen Schocks (THS).

Ultrastructural changes of endothelial cells of the mesenteric microcirculatory bed were morphometrically and statistically examined on a total of 32 male R-rats 15, 30, 60, and 120 min after a traumatic-haemorrhagic shock (THS). Significant changes of various parameters were observed at all times after shock compared with a control group (8 animals). The findings can be divided into 2 main forms of reaction, namely activation and injury. At all times overlapping occurred and endothelial cells were considerably heteromorphic. Severe, possible irreversible injuries were rare.

[Increase in the cytoskeleton of endothelial cells in mesenteric microvessels in experimental traumatic hemorrhagic shock]. / Zunahme des Zytoskeletts an den Endothelzellen der Endstrombahn des Mesenteriums bei einem experimentellen traumatisch-hämorrhagischen Schock.

Traumatic haemorrhagic shock in male rats caused an increase of cytoskeletal, especially filaments, in the numerous endothelial cells of the mesenteric microvessels during an examination period of 15 minutes to 2 hours. The filaments become ultrastructurally visible especially in endothelial cells with an enhanced "activity", in case of attachment of cells and in narrow capillaries with stasis. Additional investigations of these findings with other results will be carried out.

[Hemangiopericytoma of the uterus]. / Ein Hämangioperizytom des Uterus.

Uterine hemangiopericytoma is reported in a 49 years old woman. It is a very rare tumour. The treatment of choice is total hysterectomy with bilateral salpingo-oophorectomy. Uterine hemangiopericytoma are of low malignancy with favourable prognosis and do seldom recur.

Alterations in the intestinal microvillous surface area during the whole life span of the female rat ileum.

The present EM morphometric analysis is a continuation of a series of studies in which the changes of the microvillous surface area of the small intestine was investigated in the course of the entire life span of the female rat. It was concluded from the present data that the alterations of the ileal microvillous surface area are more balanced in the young, pregnant, lactating, adult, old and senile animals than that was observed in the case of the duodenum and jejunum. Positive correlations were found between the parameters height and surface area and, density and surface area measures of the microvilli. Microvillous width and density revealed an inverse relationship mainly in the case of the young and adult animals.

[Morphometric and densitometric studies on the ultrastructure of endothelial cells in capillaries in tumor bearing rats]. / Morphometrische und densitometrische Untersuchungen zur Ultrastruktur von Endothelzellkernen an Blutkapillaren bei tumortragenden Ratten.

The permeability of tumor capillaries to higher molecular substances like albumin and beta-globulin is increased. The comparison of permeability is associated with a modification of the ultrastructure of the capillary wall, especially of endothelial cells and their nuclei. On micrographs of blood capillaries Zajdela-Ascites-Hepatoma pregnanted rats we've studied a) morphometrically the surface and the volume of endothelial cell nuclei in relation to the time after tumor implantation, b) densitometrically the Hetero-Euchromatin-ratio in the nuclei of the same cells in relation to tumor time too. We've got the following results: The surface of the endothelial cell nuclei is increasing in the first four days, then it's decreasing to the 8th day. The volume of the same nuclei is increasing to the 4th experimental day too, then it's relatively steady. At the 6th experimental day the largest part of Heterochromatin is "euchromatinized". It will be possible to distinguish the functionally and the degeneratively nucleus' swelling with morphometrically methods. The reasons of modifications in the ultrastructure of blood capillary endothelial cell nuclei might be a) the increased demandings to the permeability of capillary wall, b) the increased activity of the MMS/RHS and c) local immunity reactions against the tumor.

[On the angio-architecture of intramuscularly implanted Yoshida-sarcoma in untreated and lithium carmine-treated rats (author's transl)]. / Zur Angioarchitektur des intramuskulär implantierten Yoshida-Sarkoms bei unbehandelten und bei mit Lithiumkarmin behandlten Ratten

Investigations were made on the angio-architecture of intramuscularily implanted Yoshida-sarcomas in untreated Wistar-rats and in animals treated with lithium carmine. The injected quantity of lithium carmine led to RES-activation according to the data in the literature. The presentation of the vessels was made by corrosion technique using the synthetic material KALLOCRYL after rinsing the vessels with the proper ester. The pre-existent vessels in the surrounding of the tumor showed an adaptation the expansive growth of the tumor. After starting the experiment the tumor-owned vessels showed an increasing tendency to grow out. The vessels of the treated animals rected in a more regularly and orientated course than those of the untreated animals. In the following time vascularisation in the untreated animals was considerably decreasing, whereas a clear vascularisation was evident in the treated animals until the end of the study. These different findings may be the expression of a local vascular reaction in the implanted tumor following RES-activation induced by lithium carmine.