[First Experience with Cranioplasty Using the Polyetheretherketone (PEEK) Implant - Retrospective Five-Year Follow-up Study]. / První zkusenosti s kranioplastikou pomocí implantátu z polyetereterketonu (PEEK) ­ retrospektivní studie pri petiletém sledování.

PURPOSE OF THE STUDY Cranioplasty is currently the most common neurosurgical procedure. The purpose of this study is to describe the first experience with successful use of the Cranio-Oss (PEEK) custom implant for cranioplasty. MATERIAL AND METHODS In the period 2012 to 2013, a total of 26 cranioplasties were performed. In fourteen patients, their own bone flap was used for reconstruction. In four cases, a synthetic Cranio-Oss bone implant made of PEEK was used. In six patients, the defect was covered by an intraoperatively-made Palacos implant and in two cases, minor defects were covered with a titanium mesh. The patients were followed up for at least five years. Cranio-Oss is a cranial implant made from polyetheretherketone (PEEK), a synthetic biocompatible material. The implant is created using the CAD/CAM method in the shape of the bone defect based on the CT scan. Creating optimal roughness of the implant surface and of the surface of the contact area attached to the bone bed is controlled and included already in the strategy for machining individual areas of the implant during its manufacturing at a 5-axis machining centre. RESULTS The Cranio-Oss implant was used in four younger patients to cover larger and complex-shaped defects. The mean age of patients in this group was 47 years. The implant was fixed to the skull by micro-plates. In all the cases the wound healed well with good cosmetic results without the necessity of revision with respect to the used implant. The follow-up CT scans always showed the implant in situ with no signs of malposition. DISCUSSION Autologous bone flap is the most suitable material for defect reconstruction after craniectomy. This option is affordable and represents one of the best methods of reconstruction of defects after craniectomy in terms of cosmetic results. In some cases, the original skull cannot be used for cranioplasty (e.g. if destructed by tumourous process, infected or in comminuted fractures). In such cases, the defect needs to be managed using a synthetic implant. In case of extensive defects, the most suitable option is a custom made implant from advanced biomaterials. CONCLUSIONS Authors prefer using autologous bone flaps during cranioplasty. In cases where this method is unavailable, a synthetic bone substitute has to be used. The first medium-term experience with the use of a Cranio-Oss implant made of PEEK showed that it is a suitable alternative to the patient's own bone. No complications associated with this synthetic implant were reported and its use to manage skull defects can be strongly recommended. With respect to legal and accreditationrelated difficulties connected with bone fragments storage and thanks to the continuous cost reduction of synthetic implants will their importance grow in the future. Key words: decompressive craniectomy, bone substitute, craniotrauma.

Atomic nuclei: moments of inertia and quadrupole moments.

Moments of inertia and quadrupole moments of deformed even even nuclei were calculated in the closely packed spheron model.

Nasal prosthesis supported with self-tapping implants with bioactive surface--a case report.

Nasal prosthesis using dental implants and magnetic abutments is a method of choice in replacement of missing hard and soft facial tissues. Nose form, coloration, and texture must be as indiscernible from the surrounding natural tissues as possible. Rehabilitation efforts can be successful only when patients can appear in public without fear of attracting unwanted attention. This case report evaluates on a step-by-step basis the materials and methods including implants insertion.

Identification of imidazo[1,2-b]pyridazine TYK2 pseudokinase ligands as potent and selective allosteric inhibitors of TYK2 signalling.

As a member of the Janus (JAK) family of non-receptor tyrosine kinases, TYK2 mediates the signaling of pro-inflammatory cytokines including IL-12, IL-23 and type 1 interferon (IFN), and therefore represents an attractive potential target for treating the various immuno-inflammatory diseases in which these cytokines have been shown to play a role. Following up on our previous report that ligands to the pseudokinase domain (JH2) of TYK2 suppress cytokine-mediated receptor activation of the catalytic (JH1) domain, the imidazo[1,2-b]pyridazine (IZP) 7 was identified as a promising hit compound. Through iterative modification of each of the substituents of the IZP scaffold, the cellular potency was improved while maintaining selectivity over the JH1 domain. These studies led to the discovery of the JH2-selective TYK2 inhibitor 29, which provided encouraging systemic exposures after oral dosing in mice. Phosphodiesterase 4 (PDE4) was identified as an off-target and potential liability of the IZP ligands, and selectivity for TYK2 JH2 over this enzyme was obtained by elaborating along selectivity vectors determined from analyses of X-ray co-crystal structures of representative ligands of the IZP class bound to both proteins.

In vivo effects of recombinant human interleukin 2 on antitumor and antiviral natural immunity in induced or natural murine immunodeficiency states.

We have examined the ability of in vivo treatment of mice with recombinant interleukin 2 (rIL-2) to affect natural immunity measured against tumor (YAC-1) or virally infected (herpes simplex type 1) target cells. rIL-2 treatment leads to significant increases in natural killer/lymphocyte-activated killer (NK/LAK) function and spleen cells recovered. This effect is dose dependent and strain related. The latter parameter correlated with the pretreatment NK activity level of the strain. The rIL-2 induced NK/LAK augmentation is also kinetically restricted as treatment must have occurred within 48-72 h of assay to be effective. The rIL-2 therapy effectively enhances both antitumor and antiviral NK/LAK activity and results in a noticeable increase in asialo-GM1-positive cells in the spleens of treated mice as well as a significant increase in IL-2 receptor expression as monitored by either cytometry or radioligand binding. In vivo treatment of mice with an antibody directed to the ASGM1 determinant effectively reduces the rIL-2 augmentation of both antitumor and antiviral activity even though this treatment does not affect the pretreatment level of antiviral activity. Various natural and induced immunodeficiency states (immunotherapy, irradiation, immunosuppressive drugs, cytoreductive drugs) have been examined for the ability of in vivo treatment with rIL-2 to enhance NK/LAK activity. In vivo rIL-2 administration is differentially effective in enhancing NK/LAK activity in these situations. Notably, in these induced immunodeficiency states, although NK/LAK activity is commonly enhanced, the number of spleen cells recovered often is only marginally affected. Thus, as expected, a limiting aspect in this use of a natural immunomodulator is the number of potentially responsive cells present in the immunodeficiency condition. In addition, correlations between rIL-2 effect, several of the immunodeficiency states, and vascular leak syndrome are briefly discussed.

Molecular cloning and characterization of a human adenocarcinoma/epithelial cell surface antigen complementary DNA.

A human adenocarcinoma-associated antigen (KSA) defined by the monoclonal antibody KS1/4 has become the focus of several site-directed strategies for tumor therapy. KSA, a 40,000 Da cell surface glycoprotein antigen, is found at a high density in all adenocarcinomas examined to date and in corresponding normal epithelial tissues. Here we describe the cloning and sequencing of overlapping complementary DNA clones which encode the entire KSA as expressed in UCLA-P3, a human lung adenocarcinoma cell line. We have deduced the 314-amino acid sequence and have compared it to the N-terminal amino acid sequence data of the affinity-purified antigen. The KSA is synthesized as a 314-residue-long preproprotein that is then processed to a 232-residue-long antigen. KSA appears to have a single transmembrane domain of 23 residues that separates the highly charged 26-residue cytoplasmic domain from the extracellular domain. The N-terminal region of the propeptide is rich in cysteines and contains three potential N-glycosylation sites. Computer-assisted analyses at both the DNA and protein levels have found no significant similarities of this protein to known sequences, but a GC-rich 5' terminus is evident. Northern blot analysis shows that transcription of KSA can be detected in RNA isolated from normal colon but not in RNA isolated from normal lung, prostate, or liver.

In vivo selection of human tumor cells resistant to monoclonal antibody-Vinca alkaloid immunoconjugates.

UCLA-P3 human lung adenocarcinoma cells were grown in nude mice and given repetitive treatments of a monoclonal antibody-Vinca alkaloid immunoconjugate. Although this therapy resulted in a greater than 4-fold reduction in mean tumor mass of the established tumors, some animals experienced a reinitiation of tumor growth after cessation of conjugate treatment. Two such animals were treated again with high doses of monoclonal antibody-Vinca but one of the tumors was no longer regressed by the drug conjugate. The tumor was excised, enzymatically dissociated, and grown in tissue culture. Cultured cells were reimplanted in nude mice and subjected to further therapy with a monoclonal antibody-Vinca conjugate. The resulting tumors were also refractory to the immunoconjugate therapy. This cycle was repeated for a total of three times and resulted in the serial in vivo selection of three conjugate resistant variants. The mechanism responsible for the in vivo resistance of human tumor cells to the monoclonal antibody-Vinca immunoconjugate is unknown but does not appear to involve antigen modulation, altered tumor cell growth rate, or an apparent decrease in tumor targeting in vivo. The resistance was also not accompanied by any detectable elevation in multidrug resistance 1 mRNA or P-glycoprotein expression. Significantly, the resistance pattern was observed only in vivo and was not maintained by cells grown in vitro.

Effect of plasma-sprayed hydroxyapatite coating on the osteoconductivity of commercially pure titanium implants.

Formation of a calcium phosphate layer was studied on the surfaces of plasma-sprayed hydroxyapatite (PSHA) and sandblasted commercially pure (cp) titanium in simulated body fluid with ion concentrations similar to those of human blood plasma. The PSHA surface induced the formation of calcium phosphate surface layers, while the precipitation of calcium phosphate on sandblasted cp titanium was not detected. Histologic evaluation of in vivo tests demonstrated that implants with a PSHA coating enabled the growth of bone tissue into gaps with a depth of up to 1 mm without significant formation of intermediate fibrous tissue. In comparison to sandblasted cp titanium, implants with PSHA coating exhibited greater tolerance to unfavorable conditions during healing, such as gaps at the interface or primary instability of the implant. In the case of good primary stability of the implant, filling of the gap with fibrous tissue was observed for sandblasted cp titanium implants over the greater part of the surface of gaps with a depth of 0.3 mm. Direct contact of cp titanium implants with bone was achieved only when the press-fit implantation model was used.

[Diagnostic and therapeutic procedures in intraabdominal injuries.]. / Diagnostické a lécebné postupy u nitrobrisního poranení

The authors evaluated the diagnostic and therapeutic procedure in 25 patients with blunt and in 12 with penetrating abdominal injuries hospitalized between Jan. 1, 1995 and Aug. 30, 1997 at the intensive care unit of the Surgical Clinic Prague 10. The diagnostic algorithm included in addition to the basic clinical examination also computed tomography. The most frequently injured organ in blunt injuries was the spleen (12 times) and liver (11 times). Twenty-three patients were operated. In casualties with penetrating injuries there were 8 with piercing wounds and 4 with shotgun wounds. The most frequently injured organ was the small intestine (4 times). Two patients of the group died. Key words: blunt and penetrating abdominal injuries, diagnosis, treatment.

[Experience with the lateral lumbar approach in epidural anesthesia]. / Dalsí zkusenosti s laterálním bederním prístupem u epidurálního znecitlivení.

Based on a detailed analysis of X-ray pictures of the lumbo-sacral spine and experience assembled during epidural anaesthesia in 116 men, mean age 67 years, and 84 women, mean age 68 years, the authors describe in more detailed the formerly recommended method of a lateral lumbar approach. To make it as successful and as safe as possible it is essential during puncture to be aware of the typical resistance of the yellow ligament, frequently after previous contact with bone and to obtain the positive sign of the "hanging drop" after penetration of the ligament. If in exceptional instances in the depth the elastic resistance of the yellow ligament is lacking before the positive sign of the "hanging drop", it is better to perform the puncture of the epidural space in another intervertebral space. This practically rules out the false positive sign of the "hanging drop" in case of the possible presence of a tougher ligamentous septum in the paravertebral muscles in older patients. This rules out also the even rarer possible penetration of the needle to the dura mater, exactly in the middle of the yellow ligament through the opening for the blood vessel where are only individual elastic fibres, practically without resistance, with a positive "hanging drop".

[Differences in patient sensitivity to currently used non-depolarized curaremimetics and factors which affect it]. / Rozdílná citlivost nemocných na soucasne uzívaná nedepolarizacní kurarimimetika a cinitelé, kterí ji ovlivnují.

A whole number of factors which affect the depth as well as duration of the block after administration of non-depolarizing myorelaxants, both positively and negatively. However, the effect in one patient can be predicted only with difficulty--as this paper showed--as neither the hydration level, age nor kalemia concentration had any effect on the depth of the neuromuscular block. Neither in patients, otherwise healthy, is it possible to predict the degree of the neuromuscular block after administering a standard dose of curaremimetic. The depth of the block can only be established by an objective method--mechano-myoscopic block monitoring. For this purpose, the authors use a Czechoslovak-made neuromuscular stimulator LSN 110. The determination of the actual block depth can help to control relaxation according to the needs of the surgeon or anaesthesiologist, and according to the individual patient's sensibility. A different sensibility response to myorelaxants was found in pipecuronium, vecuronium and even in atracurium. It corresponds approximately to gaussian curve of frequency.

[The positive effect of the 10 degree Trendelenburg position in patients undergoing epigastric surgery with lumbo-thoracic epidural anesthesia]. / Príznivý vliv 10 stupnu Trendelenburgovy polohy u nemocných operovaných v nadbrisku v lumbotorakálním epidurálním znecitlivením.

The authors administered to 60 patients, mean age 71 years, epidural anaesthesia on account of operations in the epigastrium. A solution of 0.5% bupivacaine without adrenaline in doses calculated according to Bromage for 18 segments was administered from a lateral approach in the upper part of the lumbar spine. After administration of the anaesthetic they tilted the patients to a 15-20 degrees Trendelenburg position. They adjusted the slope of the patients to ensure that the anaesthesia reached eventually the radicular zone of Th3. They made use of the finding that the anaesthetic solution in the epidural space tends to decline. After fixation of the anaesthetic to the nervous tissue, 30 patients were slowly changed to a horizontal position and the same number of patients was left throughout the operation in a Trendelenburg position. The authors made sure that the systolic blood pressure did not drop below 13.3 kPa in normotonics and beneath 60% of the initial value in hypertonic patients. There were no substantial differences in the ephedrine consumption per kg body weight within three hours after the puncture of the epidural space in the two groups. The total consumption of Hartmann solution, ketamine and diazepam was, however, significantly lower in patients who during operation were in the 10 degrees Trendelenburg position. The variations of blood pressure during traction of anatomical structures in the epigastrium were smaller in the latter patients. No serious disorders of the cardiac rhythm were recorded. None of the patients of the group died within seven days after operation.(ABSTRACT TRUNCATED AT 250 WORDS)

[Methods of determining clinically sufficient decurarization and its evaluation]. / Metody stanovení klinicky dostatecné dekurarizace a jejich zhodnocení.

Mechanomyoscopy as an objective method for determining the degree of decurarisation is particularly useful in the case of uncooperative patients and those who are incapable of adequate neck flexion mostly for spinal column diseases. The authors use for that purpose a Czechoslovak-made neuromuscular stimulator (LSN 110), with constant 50 Hz frequency of stimulation, 0.3 ms impulse duration, max. 50 mA and, depending on skin impedance, 5-140 V. The stimulator switch is manually controlled. The absence of muscular fatigue (fade) on single as well repeated stimulation lasting only a fraction of a second necessary to elicit muscular response does not rule out residual curarisation despite the fact that less than 70% of the cholinergic receptors are blocked. The only reliable sign of clinically sufficient decurarisation is the ability of the muscles of the hand to maintain contraction on tetanic stimulation of the motor point of the ulnar nerve in the wrist for at least 5 seconds without fatigue, and that even on a repeated exercise. This corresponds to a block of less than 60% of the cholinergic receptors. The patient's ability to raise his or her head and to keep it raised at 4 fingerbreaths for a period of 4 seconds is also a manifestation of clinically sufficient decurarisation. The value of forced expiratory volume is not conclusive evidence of sufficient decurarisation, it only gives a rough idea of its degree. The final decision is up to the an anaesthesiologist, his knowledge and experience based on objective data.

[The role of ultrasonographic examination in the diagnosis of thyroid gland disorders]. / Prínos ultrasonografického vysetrení k diagnóze afekcí stítné zlázy.

The authors compared the results of ultrasonographic examinations of thyroid processes with clinical and histological findings of operated patients. The results proved the importance of ultrasonographic examinations as one in the complex of examination methods before operation of the thyroid gland for the assessment of the preoperative diagnosis.

[Catheterization of the central venous system by way of the cubital veins]. / Kanylace centrálního zilního reciste cestou loketních zil.

The authors elaborated and tested in 100 patients the described method and were successful in 97%. After local anaesthesia they incise the skin in the inner portion of the skinfold in the cubital fossa and, if necessary, extend it to the bicipital ridge. The best vein as regards access is the v. basilica or the strongest branch of the brachial vein, on both sides. They isolate the vein and insert a thread underneath it. The ends of the thread are grasped by a forceps and thus the vein is fixed. After compressing the arm with a rubber band with subsequent venostasis they puncture the vein on the index finger with sharp scissors. A polyvinyl catheter cut obliquely at the end with an external diameter of 1.5 mm, containing a drip infusion of saline, is inserted slowly into the vein of the sitting patient without positioning of the head, 40-60 cm centrally, with the free hand. The position of the tip of the catheter is checked by X-ray. If there is a venous spasm (the catheter cannot be inserted, its tip is beyond the thoracic cavity or it forms a loop or is bent) the arm is compressed as high as possible. At a short distance the authors insert a catheter into the vein and administer in a drop infusion 40-60 ml 0.3% Xanidil (xanthinolium nicotinicum) solution. After relaxation of the spasm they connect the infusion with the saline, release the rubber band and complete the cannulation. In case of an unintentional injury of the vein they suture it but never use ligatures.(ABSTRACT TRUNCATED AT 250 WORDS)

[Traumatic ruptures of the diaphragm]. / Traumatické ruptury bránice.

The authors present a group of three traumatic ruptures of the diaphragm and call attention to the possibility of this injury in blunt injuries of the chest or abdomen. In the diagnostic part they describe the complex character of diagnosis of rupture of the diaphragm even when modern non-invasive examination methods are used, some of which (CT) may give false positive results. The authors describe typical symptoms leading to the diagnosis.

[Stab and gunshot thoracoabdominal injuries]. / Bodná a strelná poranení torakoabdominální.

The authors give an account of their experience with the treatment of punctures and gunshot injuries of the chest and abdomen in 43 patients hospitalized at the Surgical Clinic of the Third Medical Faculty, Charles University Prague 10 between 1989 and 1992. Injuries of the chest were recorded 15 times, abdominal injuries in 25 patients and concurrent injuries of the chest and abdomen in three patients. To ensure treatment of penetrating injuries the authors present an algorithm which comprises differentiated care as well as some non-interventional diagnostic methods (ultrasonography, computed tomography). Based on analysis of their own results and data in the literature, the authors recommend in casualties with penetrating chest injuries and abdominal injuries early indicated surgical revision which alone ensures adequate treatment with minimal diagnostic errors. They also draw attention to the necessity to ensure effective first aid and rapid transport of casualties to prevent the development of irreversible changes as a result of haemorrhage, as observed in a single patient who died after a piercing heart injury.

Antibacterial, cytotoxicity and physical properties of laser--silver doped hydroxyapatite layers.

Hydroxyapatite layers with silver doping from 0.06 at.% to 14 at.% were prepared by laser deposition. The films' physical properties such as morphology, composition, crystallinity, Young's modulus and microhardness were measured. Films were amorphous or polycrystalline in dependence on deposition temperature (from RT to 600 °C). Antibacterial properties were tested using Escherichia coli and Bacillus subtilis cells. The antibacterial efficacy changed with silver doping from 4% to 100%. Cytotoxicity was studied by a direct contact test. Depending on doping and crystallinity the films were either non-toxic or mildly toxic.