Antisense anti IGF-I cellular therapy of malignant tumours: immune response in cancer patients.

The treatment of cancer by antisense anti-IGF-I cellular therapy inducing immune response has evoked interest among many promising strategies. Here, we reported some results obtained from patients with cancer, mainly glioblastoma treated by this strategy, which was also extended to patients with colon carcinoma, ovary cystadenocarcinoma and prostate adenocarcinoma. It was shown that, in the phase I of clinical trial, patients vaccinated with their own tumour cells treated by antisense IGF-I presented a slight increase of temperature. Their peripheral blood lymphocytes showed a shift in the percentage of CD8 effector cells as judged by expression of cell surface markers CD8+ CD28+. Particularly, in two treated patients with glioblastoma, the survival time was 19 and 24 months respectively in comparison to the range of 12 to 15 months observed in the case of classical treatment such as surgery, radiation or chemotherapy. These results, although preliminary, gave indication that the reported strategy could deserve consideration owing to its safety. Furthermore, the increase in the percentage of peripheral blood monomorphonucleated cells (PBMNCs) with effector phenotype, i.e., CD8+ CD28+ in vaccinated patients might explain their prolonged survival time.

Spectral characteristics of longitudinal corneal apex velocities and their relation to the cardiopulmonary system.

PURPOSE: To study the naturally occurring kinetic characteristics of corneal surface. METHODS: The right eyes of three subjects (young, early presbyope, and presbyope) were examined. Cardiac signal and longitudinal corneal apex movements were simultaneously measured with electrocardiography (ECG) and a high-speed videokeratoscope, respectively. Time, frequency, and combined time-frequency representations of the acquired signals were derived to establish their temporal and spectral contents. Coherence analysis was used to assess the correlation between the corneal apex velocities and the cardiopulmonary system. RESULTS: In all measurements, longitudinal corneal apex velocity signals showed close correlation with the corresponding ECG signals. The signatures of the pulse frequency, which was inferred from the ECG spectra and their variations in time, were clearly visible in the spectral content of corneal apex velocities. For the young subject, the correlation was the strongest and all of the spectral content of the pulse signal including the harmonics was propagating to the corneal apex velocities. For the other two subjects, there was a clear propagation of the pulse signal itself but not of all pulse harmonics. CONCLUSIONS: Longitudinal movements of the corneal apex are closely related to the cardiopulmonary system. The differences in propagation of pulse harmonics to the corneal apex velocities for different subjects suggest that the frequency characteristics of apex velocity could be related to pulsative variations in the intraocular pressure and biomechanical properties of the eye. These findings could potentially be used in noninvasive assessment of the hemodynamic status of the eye with high-speed videokeratoscopy.

Modelling the elastic properties of the anterior eye and their contribution to maintenance of image quality: the role of the limbus.

PURPOSE: The elastic moduli of the cornea, sclera, and limbus for different corneal eccentricities (e) and varying levels of intraocular pressure (IOP) were modelled in order to determine how the rheological properties, especially those of the limbus, need to alter to maintain optical image quality when the eye is subjected to small variations in IOP. METHODS: Finite element analysis (FEA) was used to construct eyeball models with four different corneal eccentricities (e=0, 0.33, 0.5, 0.65). Three values for Young's modulus of the cornea were tested in all models (0.2 megapascal (MPa), 1.2 and 10 MPa). For each corneal modulus, scleral moduli of 3, 4, 5, 7, and 10 times that of the corneal modulus were selected. The limbal modulus was varied to optimise image quality of the eye model subjected to IOP variations of +/-0.8 mmHg for three different levels of IOP (8, 16, and 32 mmHg). RESULTS: The elastic modulus of the limbal ring increases with an increase in corneal modulus and rises to a peak when the ratio of scleral to corneal moduli is between 5 and 7 depending on corneal eccentricity. Different levels of IOP produce only slight differences in the relative moduli required to maintain optical image quality. CONCLUSIONS: The significance of a peak in the value of Young's modulus of the limbus is not clear but suggests that there may be an optimal limbal modulus that must be balanced with the moduli of cornea and sclera for preservation of image quality.

Measurement of pupil reactivity using fast pupillometry.

Analysis of human eye pupil reactivity is a very valuable diagnostic method used mainly for evaluation of the condition of the autonomic nervous system and the visual system. The paper presents an experimental pupillometer built in the Institute of Physics of the Wroclaw University of Technology. The apparatus makes it possible to record and analyze pupillary light reflex and spontaneous changes in the pupil diameter during a session in the dark. The detector system used in the pupillometer allows us to record the pupil diameter at a rate of 90 Hz with a linear accuracy of 0.008 mm. In this paper, the proposed detection method, the principle of operation and calibration of the apparatus and the possibilities of the measurement system are presented.

IGF-I triple helix gene therapy of rat and human gliomas.

PURPOSE: IGF-I anti-gene technology was applied in treatment of rat and human gliomas using IGF-I triple helix approach. MATERIAL AND METHODS: CNS-1 rat glioma cell and primary human glioblastoma cell lines established from surgically removed glioblastomas multiforme were transfected in vitro with IGF-I antisense (pMT-Anti-IGF-I) or IGF-I triple helix (pMT-AG-TH) expression vectors. The transfected cells were examined for immunogenicity (immunocytochemistry and flow cytometry analysis) and apoptosis phenomena (electron microscopy). 3 x 10(6) transfected cells were inoculated subcutaneously either into transgenic Lewis rats or in patients with glioblastoma. The peripheral blood lymphocytes (PBL) derived from "vaccinated" patients were immunophenotyped for the set of CD antigens (CD4, CD8 etc). RESULTS: Using immunocytochemistry and Northern blot techniques, the transfected "antisense" and "triple-helix" cells showed total inhibition of IGF. Transfected cultures were positively stained either for both MHC-I and B7 antigens--60% of cloned lines, or for MHC-I only--40% of cloned lines. Moreover "triple helix" cells as compared to "antisense" cells showed slightly higher expression of MHC-I or B7. Transfected cells also showed the feature of apoptosis in 60%-70% of cells. In in vivo experiments with rats bearing tumors, the injection of "triple helix" cells expressing both MHC-I and B7 interrupted tumor growth in 80% of cases. In contrast, transfected cells expressing only MHC-I stopped development in 30% of tumors. In five patients with surgically resected glioblastoma who were inoculated with "triple helix" cells, PBL showed an increased percentage of CD4 + CD25+ and CD8 + CD11b-cells, following two vaccinations. CONCLUSIONS: The anti-tumor effectiveness of IGF-I anti-gene technology may be related to both MHC-I and B7 expression in cells used for therapy. The IGF-I antigene therapy of human glioblastoma multiforme increases immune response of treated patients.

Enhanced lipid peroxidation processes in patients after brain contusion.

Erythrocyte superoxide dismutase (SOD-1) activity and cerebrospinal fluid (CSF), blood plasma low-density lipoprotein (LDL) and erythrocyte thiobarbituric acid reactive substance (TBARS) concentrations were determined in 30 patients with brain contusion and in 37 control patients with low back pain due to noninflammatory degenerative lumbar disc disease. In comparison to controls, during 10-day follow-up patients with brain contusion had significantly increased erythrocyte SOD-1 activity and CSF, blood plasma (LDL), and erythrocyte TBARS concentrations. The highest CSF TBARS concentrations were observed in five patients who died 2, 7, or 8 days following head injury. A significant negative correlation was found between erythrocyte SOD-1 activity or TBARS concentrations, in the blood plasma LDL fraction and erythrocytes, and The Glasgow Coma Scale score. These results suggest that enhanced lipid peroxidation processes, which seem to correlate with the severity of head injury, accompany brain contusion.

[Endothelin in the plasma and cerebrospinal fluid of patients after head injury]. / Endotelina w osoczu i plynie mózgowo--rdzeniowym chorych po urazie glowy.

UNLABELLED: Endothelin (ET) is identified as a potent vasoconstrictor peptide. It can cause a cerebral vasospam after subarachnoid hemorrhage. Its long-lasting vasoconstricting activity has been well documented. The role of ET in response to head injury is not clear. ET can participate in astrocyte activation and oxidative stress after trauma. The aim of this presentation was to investigate ET in the plasma and cerebrospinal fluid of patients after head injury and estimation of relation between the ET csf level and clinical condition of the patients and also relation of ET csf level and changes in the CT-scan and usefulness of ET as independent prognostic factor. We examined 30 patients at Day 1 after trauma (28 male, 2 female, aged 19-34 y, mean 30, 4, GCS ranged 8-15). CT-examination showed post-traumatic changes in 19 cases (11 with brain edema only, 8 with brain contusion). We measured ET by immunoenzymatic method using standard kits (Biomedica). The ET plasma level reached 1.12 +/- 0.63 fmol/ml (in the control group--0.44 +/- 0.19 fmol/ml) and c ET csf level 1.03 +/- 0.49 (in the control group--0.07 +/- 0.09 fmol/ml). W confirmed the correlation between the ET level and patients consciousness (by GCS) (p < 0.01). The ET csf level was highest in the patients with brain contusion in CT-scan (p < 0.02). Using multivariate analyses, we showed that ET can be used as a prognostic factor of results of treatment (p < 0.02). CONCLUSIONS: The ET level is elevated in the plasma of patients after head injury. ET is also present and strongly elevated in the cerebrospinal fluid of the same patients. The ET level in cerebrospinal fluid is associated with clinical condition of patients and elevated in cases with brain edema and structural brain damage. The ET level in cerebrospinal fluid is related to post-traumatic changes of the brain such as oedema and structural damage present in the CT-scan. ET can be used as a prognostic factor of results of treatment.

[Von Willebrand factor in patients with subarachnoid hemorrhage]. / Czynnik von Willebranda u chorych z krwotokiem podpajeczynówkowym.

UNLABELLED: Von Willebrand factor (vWF) plays an important role in the coagulation system. It affects platelet aggregation in the place of vessel endothelium damage. The importance of vWF in cerebrovascular disease is not clear. The aim of this presentation was to evaluate the vWF level in the plasma and cerebrospinal fluid of patients after subarachnoid hemorrhage including cases with cerebral vasospasm and cerebral infarct. We investigated 66 patients (38 persons graded I-III H&H and 28 persons graded IV H&H). The control group consists of 8 subjects. VWF was measured by ELISA method using standard kit Asserachrom (Boehringer). The vWF level in the plasma reached 288.81 +/- 99.66% (in the control group, 98.84 +/- 14.53%) without significant differences regarding clinical condition of patients. In the cerebrospinal fluid the vWF level was significantly different in I-III H&H patients and in IV H&H patients (1.21 +/- 0.52% and 9.18 +/- 7.58%, respectively, p < 0.001) and in the control group (0.13 +/- 0.33%). Our data indicate that there is correlation (Pearson, p < 0.01) between the level of vWF and neurological condition (GCS) of patients. There is also correlation (p < 0.01) between the level of VWF and the presence of clinical disorders (cerebral vasospasm, delayed neurological deficit (DIND) and cerebral infarct). Based on multivariate analysis, we confirmed that vWF is an independent prognostic factor of cerebral vasospasm (p < 0.01) and ischemic complications (p < 0.02). CONCLUSIONS: vWF is elevated in the plasma of patients after subarachnoid hemorrhage in early stage of the disease. VWF is present in the cerebrospinal fluid of patients with SAH and its level is higher in patients with poor neurological condition. The VWF elevation in csf is correlated with clinical condition of patients and also the presence of cerebral vasospasm and cerebral infarct. VWF can be used as an independent prognostic factor of cerebral vasospasm and ischemic complications.

Stabilometric evaluation of equilibrium in patients with damage to the cervical spine.

The purpose of the present article is the stabilometric evaluation of patients with disorders of the cervical spine. The research involved 106 persons with spinal damage in the cervical segment due either to degenerative disease or traumatic injury. The examinations, performed on a Freyss stabilometric platform, involved the evaluation of particular parameters of platform movement. Head torque was also measured by using a special attachment. Improvement in posture coordination was demonstrated in the period from one month to one year after surgical fixation of the spine, as was the negative impact of an orthopedic collar on vestibulospinal reflexes. The results here recorded are associated with changes in cervical proprioception, reliably evaluated by comparing traditional platform movement results with the parameters used to evaluate shifts is head position.

Functional evaluation of treatment outcome in fractures of the cervical spine.

Introduction. Fractures of the cervical spine are becoming more and more frequent, which is causing the number of disabled persons to increase. Proper handling of the patient on the scene of the accident, proper transport to the hospital, and the correct interpretation of indications for surgical intervention can contribute to reducing the number of complications and improving treatment outcome.
Material and method. Our research involved 132 patients, 86 men and 46 women, operated as a result of traumatic injury to the spine and spinal cord with neurological deficits of varying degree. The patients were evaluated neurologically before surgery and divided into three groups on the deficits discovered. Their functional status was tested by means of the Functional Independence Measure (FIM) before surgery (Exam I), one week after surgery (Exam II), and approximately 6 months after surgery (Exam III).
Results. Improvement occurred in our patients in all the measured parameters, depending on the preoperative status of the patient. The greatest improvement in respect to functional independence was gained by those patients who prior to surgery presented with the largest neurological deficits; however, due to the very low preoperative level of functioning exhibited by these patients their condition, even after considerable improvement, was less than fully satisfactory. Somewhat less improvement took place in the patients with a moderate level of neurological deficit, while the least improvement occurred in the patients who presented with minimal neurological deficits. The condition of the patients in this last group was close to normal.
Conclusions. The proposed surgical method in many cases facilitated a rapid return to health; within only a few days after surgery these patients obtain more complete sphincter control, greater motor capability, more self-sufficiency, and better social functioning. The treatment outcomes are dependent on the patient's preoperative status.

Corneal shape change during accommodation.

PURPOSE: To investigate whether accommodation induces any changes in central corneal curvature. METHODS: Shape changes were measured on 14 subjects using a keratometer modified to enable a change in focus to occur without a change in vergence. All subjects were emmetropic and their ages ranged from approximately 20 to 28 years. RESULTS: In 11 of the 14 subjects a difference in central corneal curvature, of around 0.4 D in at least one principal meridian, was found when focus was changed between distant and near targets. In 9 subjects the curvature was greater for near focus in at least one meridian. In 5 subjects the change in one meridian was opposite in effect to what would be expected, i.e. the curvature was greater at distance than at near. CONCLUSION: The study suggests that accommodation may have some effect on corneal shape.

[Evaluation of tear film stability by means of laser interferometry]. / Pomiar stabilnosci filmu lzowego za pomoca prototypowego interferometru laserowego.

PURPOSE: The paper presents a new method for evaluation of the tear film stability on the human eye. METHODS: The tear film distribution on the cornea is measured by the lateral shearing interference technique. The eye is kept open during approximately a two-minute recording, when the blinking has to be prevented. Continuous recording and viewing of interferograms enables registration of the changes in disturbances of interference fringes during elapsed time. The changes in fringes are caused by evaporation of tears from the ocular surface and appearance of the breakups. CONCLUSIONS: The noninvasive tear breakup time (NITBUT) can be evaluated by comparing the recorded consecutive interferograms.

[Cerebral aneurysms and current methods of treatment]. / Tetniaki tetnic mózgowych i nowoczesne metody ich zaopatrywania.

The authors discuss briefly aneurysms cerebral arteries. In the light of the pertinent literature the hypotheses of their development are reviewed. These aneurysms are probably lesions acquired by individuals with special predispositions, acquired or inborn. The problems of aneurysm diagnosis are reviewed and the methods are discussed of their management, both surgical and intravascular (embolization). Both methods are tentatively compared. In certain cases each method may be an excellent alternative for the other, and in other cases they are mutually complementary extending thus the range of therapeutic possibilities.

[Electronystagmographic and videonystagmographic studies in cerebello-pontine angle tumors]. / Diagnostyka elektronystagmograficzna i videonystagmograficzna w guzach kata mostowo-mózdzkowego.

Otoneurological investigations were carried out in 24 patients with cerebello-pontine angle tumors demonstrated in computed tomography. Standardized history taking was followed by electronystagmographic and videonystagmographical tests. In no case correct electrophysiological results were obtained. Eye-tracking test and gaze nystagmus were most frequently abnormal and together with other data these abnormalities indicated the location of the process. A more extensive use of videonystagmography was postulated.

New approximation for the whole profile of the human crystalline lens.

This paper presents a new approximation for the whole profile of the human crystalline lens by the use of only one analytical function for both unaccommodated lens and the lens on accommodation. Approximation of the anterior and posterior lens profile is composed of hyperbolic cosine functions and is given in polar coordinates. Each of the hyperbolic cosines is modulated by the function of hyperbolic tangent type. The curvature of the hyperbolic cosine in polar coordinates is discussed and some results concerning the stability of its central radius of curvature are shown. Fitting of the hyperbolic cosine type curve to various results of the lens curvature measurements is presented. Examples of profiles of the lens under accommodation are given. It is shown that this approximation can be used for the description of iso-indical profiles inside the lens.

Cerebrospinal meningitis with the presence of Acinetobacter spp.

The study was conducted on 16 strains of Acinetobacter sp. which were isolated from cerebrospinal fluid. The diagnostic material was analysed with the use of automatic BacT/Alert system (Organon Teknika). The analysis was performed in the Department of Microbiology, Medical University in Bydgoszcz. API 20NE system (bioMérieux) enabled the identification of 14 strains (87.5%) as A. baumannii, 1 strain as A. haemolyticus and 1 strain as A. lwoffii. The micro-organisms were isolated from patients whose age ranged between 4 and 66 years. These patients were treated in the departments of Neurosurgery (75.0%), Neurology (18.8%) and Intensive Therapy (6.2%). The infection of cerebrospinal fluid was caused by injury and subsequent exposure to the bacteria present in external environment. Antibiotic-sensitivity of these micro-organisms was evaluated with the help of disc-diffusion method, observing standardisation conditions outlined by NCCLS. All the strains proved sensitive to carbapenems, 15 strains were sensitive to netilmicin, 7 strains--to tobramycin and 7 strains--to amikacin. All the strains displayed multiple resistance. The only exception was A. haemolyticus. The use of two-discs allowed for the detection of ESBLs in 7 A. baumannii strains. Positive results were most frequently obtained after the combination of sublactam and aztreonam. Due to microscopic resemblance between Acinetobacter spp., and bacteria of Neisseria, Moraxella and Haemophilus genus, microbiological diagnostics should not be restricted to microscopic assessment of cerebrospinal fluid and quick serological tests evaluating the antigens of the most frequent aetiological factors. Considering multiple resistance of Acinetobacter spp. to antibiotics, the treatment should be based on sensitivity tests and the ability of a given antibiotic to penetrate into cerebrospinal fluid. In our opinion, both reasonable antibiotic policy as well as observing the principles of hygiene and monitoring infections play equally important roles in the prevention of infections with Acinetobacter spp. Such combined measures may help to prevent the spreading of multiple resistant strains in hospital environment.

Fixation of the cervical spine using a titanium plate.

Surgery of the cervical spine has been developing since the early twentieth century, but significant progress began with the appearance of the anterior approach, thanks to Bailley, Bedgley and Cloward, who developed a special set of instruments to facilitate operations using the anterior approach. In 1967 Haftek became the first surgeon to perform this operation in Poland; since that time the anterior approach has come to be in more and more general use. The first goal of the operation is to remove fragments of bone and intervertebral discs compressing the spinal cord; the second goal is to achieve good fixation of the operated segment of the cervical spine. In the earlier period external immobilization was applied, using campolite collars, Florida collars, Schanz collars, or HALO stabilizers. Currently immobilizing is done with titanium plates, which are well suited to the purpose of internal fixation of the spine.

Surgical treatment of pathologiesof the craniocervical functions.

Spinal fractures at the craniocervical function require surgical treatment. Surgical can be preceded by direct traction of the cranium in order to set the fragments prior to fixation. This paper presents various methods of fixation from the posterior titanium loops.

Fixation of high thoracic spine fractures. A case report.

Fractures of the thoracic spine are very frequently accompanied by spinal cord compression syndromes, including symptoms that would indicate complete severance of the spinal cord. The indicates a very small reverse of space, especially in the upper and middle segments of the thoracic spine. Even a few millimeters of dislocation among the fragments of broken vertebrae can disrupt the proper anatomical relations and produce neurological deficits. Early intervention - in the form of complete immobilization of the damaged spinal segment, the administration of Solu-Medrol in a dosage consistent with the NASCIS II recommendations, and early surgical treatment with full decompression of the nerve elements - can lead to improvement. Despite the natural splinting provided by the ribs and the sternum, the thoracic spine requires good fixation after the decompression operation, followed in short order by intensive rehabilitation.