Inhibition of hormone secretion in GH-secreting pituitary adenomas by receptor-subtype specific somatostatin analogues in vitro.

The aim of the study was to determine the inhibitory effects of somatostatin analogues with relative specificity to somatostatin receptor subtype 2 (SSTR2) (BIM-23197), subtype 5 (SSTR5) (BIM-23268), and their combination on GH and PRL secretion in acromegalic adenomas in vitro. Three types of answer were observed: 1. In one resistant adenoma no inhibition was achieved. 2. The GH secretion in six adenomas was suppressed significantly more (p < 0.01 or p < 0.001 using Mann-Whitney U-test in concentration range of 10(-12) to 10(-8) mol/l) with SSTR2 specific analogue BIM-23197 with no additive effect of compounds combination. 3. In three adenomas the potency of BIM-23197 and BIM-23268 was almost equal and the combination of these SSTR2 and SSTR5 specific compounds had statistically significant additive effect (p < 0.05 or p < 0.01 in concentration range of 10(-12) to 10(-8) mol/l). PRL secretion of five adenomas was more suppressed with SSTR5 specific BIM-23268 (statistically significant in concentrations 10(-10) to 10(-8) mol/l). In conclusion the somatostatin analogue BIM-23268 had an additive effect on suppression of GH secretion in a subset of adenomas, where both SSTR2 and SSTR5 were involved. This effect was not observed in the majority of tumours, where the inhibitory effect seems to be mediated via SSTR2 only.

[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.

Cholinesterases in dexrazoxane-treated daunorubicin cardiomyopathy in rabbits.

Changes in cholinesterases activities in daunorubicin cardiomyopathy and in dexrazoxane (DRZX)-treated daunorubicin cardiomyopathy were investigated in rabbits. Acetyl- and butyrylcholinesterase (AChE and BuChE) were determined using Ellman's method. In the serum, a significant decrease of BuChE was observed in the daunorubicin group (9.05 at the beginning and 7.15 microcat/l at the end of the experiment). After DRZX, no significant changes were found and a significant increase in BuChE was observed in the control group (10.26-12.38 microcat/l). AChE activity in the left and right cardiac ventricles was not significantly different between the groups while in the septum there was a significantly lower AChE activity found in the daunorubicin group only. BuChE activity was significantly decreased in the left (15.64 ncat/g) and right (19.27 ncat/g) heart ventricles, in the septum and in the liver in the daunorubicin group. A significant decrease in serum total protein and albumin was demonstrated only in the daunorubicin group. Our results support the hypothesis about the influence of daunorubicin on protein (and enzyme) synthesis in the liver and heart. A protective effect of DRZX on cholinesterases activity was observed. The changes in cholinesterase activities may thus reflect their possible role in cardiomyopathy.

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.

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.

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%.

Ovine pericardium: a new material for duraplasty.

The authors report on their 2 1/2-year clinical experience using a dural substitute, ovine pericardium, stabilized with 0.3% glutaraldehyde, flat freeze-dried, and sterilized with gamma-irradiation. Packaging of the ovine pericardium in double-plastic transparent bags allows simple storage in operating rooms and the opportunity for the surgeon to choose an ideal graft according to its shape, size, and plasticity. The ovine pericardia were examined histologically and by transmission and scanning electron microscopy in their native, freeze-dried, and irradiated forms. The final product is composed solely of pericardium fibrosum interwoven with artificially formed extracellular microcavities that serve as natural pores for the ingrowth of host tissue. The surfaces of the grafts appear smooth on the inner and rough on the outer sides. Sixteen grafts were examined macroscopically at autopsy and four of these were also examined histologically to illustrate their successful healing with no adhesion to the underlying brain. As a new dural substitute, ovine pericardium proved to be superior to bovine and allogeneic pericardia because of its workability, flexibility, and reduced thickness. In a study of 120 grafts, all but one healed without complications.

Changes of some biochemical and hematological parameters following administration of daunorubicin in rabbits.

The effects of the repeated i.v. administration of daunorubicin (50 mg/m2, once weekly, max. 9 weeks) were investigated in rabbits in vivo to analyze biochemical and hematological changes. Noninvasive polygraphic records were used to evaluate the function of the heart. The administration of daunorubicin induced changes especially in levels of protein (decrease in total protein and albumin) and of some ions (decrease in calcium, magnesium and phosphorus) as well as in hematological parameters (decrease in erythrocytes, leukocytes and thrombocytes). The results obtained correlate with data on mechanisms of daunorubicin toxicity.