[Possibilities of medical treatment in acromegaly]. / Moznosti medikamentózni lécby akromegalie.

Active acromegaly deteriorates the quality of life and shortens the life expectancy. Surgery is the first-line therapy in the majority of patients, followed by radiotherapy in unsuccessful cases. The surgery cure rate is only one half in the case of macroadenomas and it takes years before radiotherapy normalizes GH and IGF-I levels. In the interim, medical therapy is necessary. Second-generation dopamine agonists (cabergoline) are successful in about one third of patients, especially in those with lower basal IGF-I levels and with adenomas co-secreting prolactin. Somatostatin analogues octreotide and lanreotide are the gold standard of medical treatment - both are available in a form applicable as once-monthly injections. They successfully control disease activity in the majority of patients and induce tumour shrinkage in part of adenomas. Surgical debunking of macroadenomas improves the results of therapy with somatostatin analogues and it is not necessary to discontinue this therapy before radiotherapy. The potential of higher efficiency represent new analogues, binding not only to somatostatin receptor subtype 2, but also to subtype 5 and "dopastatins" that are able to bind both to the somatostatin and the dopamine D2 receptors. The advent of the GH receptor antagonist pegvisomant provides the possibility to normalise IGF-I in virtually every patient. Combined treatment with somatostatin analogues probably enables reduction from daily to weekly injections.

[Evaluation of the results of surgery of intracranial supratentorial tumors in 363 children over the past 50 years (1948-1997)]. / Zhodnocení výsledku u 363 detí operovaných pro nitrolebecní supratentoriální nádory za 50 let (1948-1997).

At the Department of Neurosurgery, Hradec Králové, in the course of 50 years (1948-1997) 363 children, 199 boys and 164 girls (1.2:1) aged under 18 years were operated on for intracranial supratentorial tumours. The average age in children at the time of first operation was 9.3 years; most frequently they participated those of 8 and 11 to 14 years of age. Children aged 1, 2 and 3 years constituted 4.7%, 4.4% and 5% of operations. The tumours were located in: cerebral hemispheres 123 (33.8%), lateral ventricles 17 (4.7%), IIIrd ventricle 5 (1.4%), hypothalamus 26 (7.2%), thalamus 19 (5.2%), basal ganglia 24 (6.6%), sellar region 86 (23.7%), chiasmatic region 38 (10.5%) and pineal region 19 (5.2%). 223 of tumours (61.4%) were located in the midline and 140 of them (38.6%) laterally (in hemispheres and lateral ventricles of the brain). 268 of tumours were histologically verified (73.8%) and 95 of cases were evaluated according to the neurosurgeon's point of view and/or to the clinical and CT controls (26.2%), because of the biopsy (especially in the pre-CT era) was highly riskfull. Histological typing of tumours was retrospectively reevaluated according to the present WHO classification. Summarized 53 types of tumours were differentiated. The most frequent lesions were various variants of astrocytic gliomas (135 = 37.2%). Further on the craniopharyngiomas dominated (73 = 20.1%). The tumours were operated on through craniotomies 299 times, by primarily drainage operations 52 times, functions 6 times, stereotactically 8 times and or by combination of these operations 82 times. Reoperation was needed for postoperative complications in 1.7% (6 times) and for delayed recurrence in 11.3% (41 times). The postoperative mortality (up to 1 month after initial surgery) was in 156 children operated on in pre-CT era (between 1948 and 1977), as compared with 207 children operated on in the era of CT (between 1978 and 1997) in astrocytomas 3.8:0%, pilocytic astrocytomas 6.5:2.8%, craniopharyngiomas 15.4:0% and in all tumours 12.2:2.9%. 16 children with orbital tumours (the average age 5.8 years) operated on with orbitofrontal approach were also evaluated. 14 of them survive for 5-37 years (on the average 16.6 years). The chronological development of diagnostic and operative processes of supratentorial tumours in children's care is discussed. The prognostic elements of present histobiological classification of tumours are positively evaluated.

Cerebral angiogenesis shows nestin expression in endothelial cells.

The class VI intermediate filament protein nestin has been generally considered as a specific marker for neural precursor cells or developing muscles. In the prenatal developing rat central nervous system (CNS), we localized immunoreactivity for the nestin in blood vessels. Although the widespread nestin expression in cerebral blood vessels persisted in early postnatal periods, it was down-regulated in the adulthood. However, when the adult rat brains were subjected to procedures that trigger neovascularization, e.g. grafting fetal nervous tissue or C6 glioma, the abundant immunoreactivity was detected in all newly formed vessels and adjacent host vasculature. Our results demonstrate that nestin expression in endothelial cells lining cerebral vessels accompanies the process of angiogenesis.

Posterior cranial fossa surgery in 454 children. Comparison of results obtained in pre-CT and CT era and after various types of management of dura mater.

At the Department of Neurosurgery, Hradec Kralové, 454 children (aged under 18 years) were operated on for posterior cranial fossa lesions in a period of 49 years (1948-1996). The majority (402) had tumours: cerebellar astrocytomas 149 (37.1%), medulloblastomas 139 (34.6%), brain stem gliomas 46 (11.4%), ependymomas 28 (7.0%), and others 40 (9.9%). Postoperative mortality was compared for the pre-CT era (1948-1977) and the CT era (1978-1996): astrocytomas (8.6%:4.7%), medulloblastomas (14.9%:2.9%), brain stem gliomas (21.7%:19.0%), ependymomas (18.2%:6.3%), and others (40.0%:7.4%). The initially high mortality was due to insufficient intracranial decompression, brain oedema and disturbances of cerebrospinal fluid circulation. Obstructive hydrocephalus was treated in 53 children with tumours and 25 with aqueduct stenoses, by Torkildsen's drainage in 5.5%, and/or by catheterisation of aqueduct in 12.3%. The main postoperative complications of medial posterior fossa surgery in 429 children operated on were: pseudomeningocele (12.3%), active hydrocephalus (6.2%) and CSF leakage (4.6%). Only 8.2% had shunts placed for these complications. We presume that this low percentage of shunts used results from a frequent use of duraplasties and drains installed at the primary operation. The dura mater was initially (1948-1954) left open (50 cases), and later (1955-1958) also sutured (37 cases), and from 1958, onward, and especially from 1961, reconstructed by a medial approach by means of various grafts (377 cases). In all, duraplasty was performed in 81.6% of cases. The grafts used for dura mater reconstruction were prepared from autogeneic (1.6%), allogeneic (72.3%), xenogeneic (24.8%), or synthetic (1.3%) material. They were successful in 99.2% of cases (all materials). Our own suture technique for posterior fossa duraplasty is presented.

Immunohistochemical detection of intermediate filament nestin.

Using Rat-401 monoclonal antibody and peroxidase immunohistochemistry we have detected IF nestin in developing and adult rat tissues. Although epitope recognized by Rat-401 antibody is relatively resistant to aldehyde fixation and paraffin embedding, the embedding of tissue samples into polyester wax and microwave antigen retrieval of histological sections enabled us to enhance sensitivity of immunohistochemical detection and to identify cells expressing low levels of nestin. Our findings confirm that nestin is predominantly distributed in developing neural, myogenic and mesenchymal cells, i.e. cell types that have been previously described to express this intermediate filament. Furthermore, we made original findings on identification of nestin expression in additional cell types, e.g. newly formed endothelial cells of extra- and intraembryonic blood vessels, epithelial cells of the developing lens, and cells apposed to to hair follicles.

Choroid plexus cyst of the left lateral ventricle with intermittent blockage of the foramen of Monro, and initial invagination into the III ventricle in a child.

A cyst of the choroid plexus of the left lateral ventricle with intermittent blockage of the foramen of Monro and initially with invagination of the III ventricle in a child is described. In a 6-week-old boy a ventriculoatrial shunt was implanted for correction of an active asymmetrical hydrocephalus of unknown origin. When he was 3 months of age a water-soluble contrast CT ventriculography revealed a noncolloid cyst localised predominantly in the upper portion of the III ventricle. At that time the ventricular catheter obstructed with choroid plexus was removed; new bilateral catheters in a parieto-occipital region were implanted. In the course of the next 4 years, first the atrial catheter had to be extracted and then the peritoneal catheter was changed, in both cases because of obstruction. Periods of normal life alternated with periods of transient and intermittent symptoms of increased intracranial pressure, papilloedema, and myoclonic jerks. Repeated computed tomography (CT) and magnetic resonance imaging (MRI) showed stabilised hydrocephalus with an enlarged left lateral ventricle. When the boy was 16 years old MRI revealed a choroid plexus cyst in the left lateral ventricle 2 cm in diameter, with a ballvalve type of obstruction of the foramen of Monro. CT stereoendoscopic resection of the wall of a large cyst filled with cerebrospinal fluid was performed, and two additional adnexal small cysts were coagulated using the bipolar coagulator, Diomed 25 laser and scissors; the symptoms then regressed, except for superior bilateral altitudinal anopsia. Light and electron microscopy of the cyst wall is reported. The cyst was composed of collagenic connective tissue lined with a basal lamina lacking in epithelial cells. The preoperative and postoperative MRI are presented. Choroid plexus cysts localised in the anterior part of lateral ventricles are very rare, and all reported cases have been in male patients. According to the literature our case is only the third ever described in a child.

Angiogenesis of extra- and intraembryonic blood vessels is associated with expression of nestin in endothelial cells.

For a long time, intermediate filament protein nestin was recognized as a specific constituent of the cytoskeleton of developing neural cells and skeletal muscle. Recent reports by other investigators demonstrated that nestin may also be expressed in other cell types. Here we give evidence that nestin is expressed by endothelial cells of developing blood vessels in the rat. Using anti-Rat-401 monoclonal antibody we identified high levels of nestin in the endothelium lining all blood vessels of E14-15 rat foetuses. Immunoreactivity for nestin was detected in both extraembryonic (chorion, placenta, umbilical cord) and intraembryonic blood vessels. In the body of the foetus, we observed nestin-positive endothelial cells in vessels located in the areas of the mesenchyme as well as in vessels supplying the developing organs (central nervous system, liver, lung, spleen, heart, digestive tube). The strongest positive signal was given by the endothelium of newly vascularized tissues. In contrast to the developing tissues, expression of nestin by vascular endothelial cells was greatly reduced in adult tissues.

Detailed evaluation of 2959 allogeneic and xenogeneic dense connective tissue grafts (fascia lata, pericardium, and dura mater) used in the course of 20 years for duraplasty in neurosurgery.

Surgical experience with 2959 allogeneic and xenogeneic dense connective tissue grafts (1767 of fascia lata, 909 of pericardium, and 283 of dura mater), used in 2665 neurosurgical operations performed in the course of 20 years (1976 to 1995) is reported. Duraplasty using either allogeneic or xenogeneic grafts has had a similar, and favourable clinical outcome. Nevertheless, the pliable deep frozen fascia lata grafts, which could be used in any location, have been reserved for sella turcica plugging, anterior cranial base plasty, aneurysmal wrapping, and surgery of lipomyelomeningocele. Pericardium and dura mater grafts were in the majority of cases used over the brain convexity and posterior cranial fossa. Ovine pericardium proved to be superior to bovine and allogeneic pericardia because of its workability, flexibility, reduced thickness, and better transparency. Postsurgical complications occurred in 7.3%, and they were: 1) cerebrospinal fluid fistulas in 2.8%; 2) meningites in 2.3% (aseptic 1.4%, bacterial 0.8%, and tumoural 0.1% meningites); 3) pseudomeningoceles in 2.2%; 4) wound infections in 0.6%; 5) malresorptive hydrocephalus in 0.5%; and 6) adhesions to nerve tissue in 0.5%. The majority of complications healed without surgery. Forty-eight grafts (1.6%) failed to fulfil the requirements of the surgeon, and 46 of them were re-operated upon. Though another thirty-nine grafts healed successfully, 39 shunts (1.5%) had to be performed for malresorptive hydrocephalus (0.9%), and/or for a big pseudomeningocele (0.6%). So, the pure complication rate in 2665 duraplasties was 3.1%. The complex evaluation of the allogeneic and xenogeneic grafts (fascia, pericardium, and dura mater), used for duraplasty in neurosurgery during the last 20 years proved them, as remarkably good, with a success rates of 96.9%.