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.

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.

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.

[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.

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.

[Cases of cavernous hemangioma discovered in patients with post traumatic intracerebral hematoma]. / Przypadki haemangioma cavernosum ujawnione u chorych z pourazowym krwiakiem sródmózgowym.

Cavernous haemangioma has various forms. The cases with spontaneous intracerebral haemorrhage are most common, but post-traumatic intracerebral haematoma was not reported. The aim of this report is to present cases of cavernous haemangioma with unusual clinical course. In seven patients with post-traumatic intracerebral haematoma, fragments of histologically confirmed cavernous haemangioma tissue situated in the place of haematoma were found. In one case, delayed intracerebral haematoma twenty four hours after trauma and initial CT-scan was observed. On the initial CT-scan in this patient only traumatic changes in the brain without haematoma or tumour were present. In our cases, cavernous haemangioma was situated most frequently in frontal and temporal region, shown as haematoma usually 24 hours after trauma, mainly in men in age range 30-44 years with disorders of consciousness (GCS 11). As the result of operation, the majority of patients (6 out of 7) were discharged as self-independent. The authors reviewed the literature for cavernous haemangioma. The tumour may be present in any region of the brain including infratentorial region. The lesion is disclosed most frequently in children as spontaneous brain haemorrhage and rarely as seizures or intracranial hypertension. Final diagnosis is based on cerebral angiography or MRI. CT-scans are not typical and before the appearance of haematoma do not suggest the presence of tumour. Surgical removal of haematoma with tumour fragments is the main method of therapy, but radiation is possible in order to diminish the mass. The authors conclude that in each patient with post-traumatic intracerebral haematoma, the presence of cavernous haemangioma is possible.

[Advances in diagnostic procedures and treatment of spinal neoplasms]. / Postepy w diagnostyce i leczeniu nowotworów kregoslupa.

In the years 1958-1995 in the Department of Neurosurgery in Bydgoszcz we treated operatively 160 patients (100 men and 60 women aged 5-81 yrs) with spinal tumours causing spinal cord compression. Our material was useful in estimating the evolution in diagnostic procedures, treatment and limit of contraindications to surgery. We utilized previously analyzed patients' data from the years 1958-1987 (100 patients) and compared this with results from the years 1988-1995 (60 patients). In the years 1988-1995 we operated on twice as many patients per year than in the period 1958-1987 owing to better diagnostic and operative procedures and decrease of contraindications to treatment. In about 60 percent of patients the tumours were totally and subtotally removed. In recent period we performed 10 initial procedures of transpedicular stabilization. In most cases the extensiveness of tumours did not reach the level of three spinal segments. We confirmed good early results of treatment, particularly in cases with total resection of tumours, in about half the patients with spinal neoplasm, although the most common histological diagnoses were carcinoma (89 cases). In thirty percent of cases with carcinoma only pain was diminished.

[Cases of "delayed" subdural posttraumatic hygromas]. / Przypadki "odroczonych" pourazowych wodniaków podtwardówkowych.

The authors present 6 cases of uni- or bilateral subdural hygromas that appeared a few weeks following severe head injury. Such hygromas were named by the authors as "delayed" ones. Surgical evacuation of hygroma resulted in patient's status improvement in all 6 cases, based on well-known theories of posttraumatic hygromas origin, the authors try to explain patomechanism of the "delayed" hygromas.

[Otolaryngologic symptoms from tumors of the posterior cranial fossa]. / Objawy otolaryngologiczne w guzach tylnego dolu czaszki.

The aim of the paper was the estimation of the otolaryngological signs in the patients with the tumor of posterior cranial cavity. Each one was underwent the otoneurological diagnosis inclusive of electronystagmography. The most frequent symptoms we noticed were headache, vertigo together with cerebellar signs and disorder of the VII, VIII and IX-th cranial nerves, The ENG seemed to be a useful method in a localizing process of intracranial damages.

Influence of culture conditions on expression of antigens in Bordetella bronchiseptica.

Bordetella (B.) bronchiseptica isolates from the respiratory tract of rat and pig in their virulent phase-I and their spontaneously developed avirulent phase-III were investigated. The strains were cultured on Bordet-Gengou agar, on nutrition agar with 10% horse blood, and with 5% sheep blood, on yeast agar, on minimal nutrition agar (MM) and Simmon's citrate agar with glycerol, starch, and nicotinic acid. Antigenic modulation was induced by MgSO4 on Bordet-Gengou agar. The B. bronchiseptica strains were cultivated at 37 degrees C for 48 h. The influence of different MgSO4 concentrations after five passages (1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 50, 100 mM/ml and low (20 degrees C) and high (42 degrees C) temperatures on antigenic modulation was investigated on Bordet-Gengou (B-G) agar. B. bronchiseptica colonies were characterized in relation to morphology, haemolysis, slide agglutination with B. bronchiseptica phase-I polyclonal antibodies, haemagglutination with horse and calf erythrocytes and polypeptide and LPS patterns in SDS-PAGE. Cultivation of B. bronchiseptica phase-I on B-G agar and ACMM agar at 37 degrees C for 48 h resulted in strong phase-I antigenic patterns, and, on peptone-rich media, in antigenic modulation. The morphology of B. bronchiseptica phase-I-strain colonies on peptone media was different from that of B-G and ACMM agar. The LPS pattern of both strains resembled that of phase-III strains. MgSO4 concentrations of 1 mM/ml (strain 1636 I) and 3 mM/ml (Ratte I) were able to induce LPS-pattern-like phase III.

Measurement of elastic modulus of the central bovine cornea by means of holographic interferometry. Part II. Results.

BACKGROUND: The structural and elastic properties of the cornea play an important role in the outcome of corneal refractive surgery. A way to describe the elastic properties is to calculate Young's modulus. The tangent Young's modulus (Eit) represents the first part of the viscoelastic response of the intact cornea due to intraocular pressure increase. METHOD: The tangent Young's modulus (Eit) of the central cornea of 16 fresh enucleated intact bovine eyes determined from the immediate response was calculated by means of holographic interferometry. The stress was an increase of the intraocular pressure. In 16 eyes the change of intraocular pressure was 10 Pa (group I), starting with an intraocular pressure of 1340 Pa (about 10 mm Hg). In 6 of these 16 eyes there was a second pressure increase of 20 Pa starting at the same intraocular pressure of 1340 Pa (about 10 mm Hg) (group II). RESULTS: The mean value for the Young's modulus in group I was 1.58 x 10(5) Pa. For group II the Young's modulus was 1.60 x 10(5) Pa. The difference was not significant. The values for the Young's moduli of the cornea of intact eyes are about 100 times smaller than calculations based on experiments with strips of the cornea. CONCLUSION: It is necessary to consider the localization of the corneal tissue to avoid influences of corneal hydration or dehydration and to define the existing intraocular pressure if Young's modulus of the cornea is to be calculated.

[Cranioplasty of bone defects with "Codubix" plates]. / Plastyka ubytków kosci czaszki plytkami "Codubix".

Codubix plates made of polypropylene-polyester fabric were used for reconstructive cranioplasty of cranial vault defects after trauma. This method protected well the brain against secondary trauma with a good cosmetic result of the operation. By eliminating the necessity of use of patient's own bones the duration of operation was shortened, the patient avoided postoperative pain, and the possibility of postoperative complications was reduced. During a two-year period of follow-up no complications were observed.

[Results of surgical treatment of intracranial aneurysms]. / Wyniki leczenia operacyjnego tetniaków sródczaszkowych.

In the years 1986-1990 in the Department of Neurosurgery Military Hospital in Bydgoszcz 61 patients were treated surgically for intracranial aneurysms. Good results were obtained in 60.7% of cases and bad in 21.3%. Death from extracranial causes occurred in 6 cases. The number of past bleedings from the aneurysms, the clinical state of the patients, the timing of the operation, intraoperative rupture of the aneurysms were factors having a significant unfavourable influence on the early postoperative results.

[Use of gelatin-resorcinol-formaldehyde glue in the surgical treatment of cerebrospinal rhinorrhea]. / Zastosowanie kleju zelatynoworezorcynowo-formaldehydowego (GRF) w chirurgicznym leczeniu przetok plynu mozgowo-rdzeniowego.

The introduction of tissue adhesives in neurosurgery for treating cerebrospinal fluid fistulas has been a major advance in the operative technique. The authors describe the use of gelatin-resorcin-formaldehyde adhesive (GRF) in the surgical treatment of cerebrospinal fluid fistulas. The method of preparation of GRF, the technique of adhesive application, its clinical use and advantages are described.