PubMed Health⌕ Search

Biomedical subjects

H D Herrmann

Publications and source records attributed to H D Herrmann.

At least 55 records · Page 3Linked to original sources

Growth factor biology and oncogene activation in human gliomas and their implications for specific therapeutic concepts.

The failure of most available treatment modalities to improve the survival time and the quality of survival in patients with gliomas calls for the intense biological analysis of glial neoplasia. The untimely activation of cellular protooncogenes is often related to the process of neoplasia. Several protein growth factors as well as their cellular receptors have been identified as products of proto-oncogenes. Furthermore, these growth factors have been identified as glial mitogens in normal glial cell cultures as well as in tumors. The analysis of growth factor biology gains additional weight by the demonstration of autocrine growth factor secretion by tumor cells. The role of epidermal growth factor (EGF) and its receptor system in glial cell proliferation and differentiation is presented, with the speculation that the EGF receptor system may integrate the biological actions of many different factors, of which EGF itself may be least important. The literature on platelet-derived growth factor and insulin-like growth factors is reviewed, and the biology of fibroblast growth factor is presented in perspective with such phenomena as neovascularization and cell-matrix interactions.

Epidermal Growth Factor↗

Spectrum of karyotypic aberrations in cultured human meningiomas.

Twenty-two unselected cases of meningioma were initiated in tissue culture on an extracellular matrix derived from bovine corneal endothelial cells. The cultures were available for karyotypic analysis at passages 1 to 5, representing cultivation periods of up to two months. Histologically, the meningiomas were meningiotheliomatous (16 cases), fibrous (1 case), angiotheliomatous (1 case), microcystic (2 cases), and parenchymatous (2 cases). Two of the meningotheliomatous cases had histological signs of malignancy, another case showed increased signs of proliferation, and two cases were recurrences, one after a complete course of irradiation. In five cases no structural chromosome aberrations were found. Monosomy of chromosome 22 was found in six cases and was associated with other random aberrations. Clonal or random aberrations without monosomy 22 were present in 11 cases, including one case with trisomy 7 and another case with a stable translocation marker, t(4;7). In these latter two cases, EGF-receptor binding was not elevated, compared to other meningiomas. Our results illustrate that, in addition to the frequent involvement of chromosome 22, numerous other individual clonal karyotype aberrations exist in meningioma cell populations, reflecting the heterogeneity of biological and pathological findings.

Adult↗

Clinical efficacy of perioperative antimicrobial prophylaxis in neurosurgery--a prospective randomized study involving 159 patients.

In a randomized study 87 patients received perioperative antibiotic prophylaxis with 2 x 2 g ceftriaxone (Rocephin) at the beginning of the operation and in the following morning. Seventy-two patients received no antibiotic prophylaxis. In patients receiving the prophylaxis, a lower incidence of infections was observed postoperatively in addition to a reduction in wound-healing disorders. Respiratory tract infections were more successfully prevented than urinary tract infections. The number of pathogenic bacteria detected in the group on receiving prophylaxis decreased. The positive effect of the perioperative administration of antibiotics was more evident in protracted operations, such as brain surgery, than in operations involving the spinal cord.

Bacteria↗

Biological and karyotypic characterization of a new cell line derived from human gliosarcoma.

A cell line (NCE-G28) was established from the biopsy material of a human gliosarcoma of low histological differentiation. The initial cultures showed a mixed population of cells which in later stages became more uniform due to loss of slower growing constituents. The cells have been growing steadily for 20 months. A suspension of NCE-G28 cells injected s.c. as well as i.p. into nude mice produced solid tumors in all cases. Histologically these tumors closely resembled the original tumor. The original tumor, the nude mouse tumor, and NCE-G28 cells were immunochemically positive for glial fibrillary acidic protein as well as for neural plasma membrane antigen A2B5 expression. Two cell strains, 9B2C and 9B2E, were obtained by cloning of the initial cultures and another strain, NCE-G28T, was derived after explantation of a mouse heterotransplant. The two subclones were negative for glial fibrillary acidic protein expression but stained for cell surface fibronectin. NCE-G28T cells initially were positive for glial fibrillary acidic protein but lost this property within 8 months of cultivation. Karyotype analysis of NCE-G28 and the three strains revealed hyperdiploidy and six structurally altered marker chromosomes five of which were shared by nearly all cells. Receptors for epidermal growth factor were detected in all cell lines with the highest levels (about 300,000 receptors/cell) in the parental cell line. The epidermal growth factor receptors had an affinity of 2.5 nM (Kd) and by affinity cross-linking analysis a molecular weight of 170,000 was found. Initially, NCE-G28 cells responded to epidermal growth factor as well as fibroblast growth factor with increased rates of proliferation, while platelet derived growth factor had no effect. In higher passages the growth factor sensitivity was reduced. Using antibodies directed against synthetic protooncogene peptides the production of c-sis immunoreactive material was detected. NCE-G28 cells produce an autocrine factor which stimulated proliferation. This factor is present in conditioned medium and is active on cultured meningiomas and other glioma cell lines. NCE-G28 cells can be maintained in serum-free defined medium on plastic coated with fibronectin or an extracellular matrix from bovine corneal endothelial cells. The NCE-G28 cell line with its strains provide an in vitro model system in which the complexity of gliosarcoma cell populations and the interaction of the cloned cellular constituents can be studied.

Aged↗

Glioma biology in vitro: goals and concepts.

Gliomas are heterogeneous in their cellular composition, affecting therapeutic efforts such as surgical removal, radiotherapy, chemotherapy and immunotherapy. 106 gliomas were taken into culture in our laboratory and 12 cell lines could be established there from. Experiments were carried out in as many early cultures as possible and with the constant experimental system of the cell lines. To subdivide and possibly classify the heterogeneous group of gliomas the following approaches emerged: Immunostaining of cells for glial markers such as GFAP, A4, A2B5, Leu 7 as well as fibronectin will allow one to distinguish different groups of glial cultures. Performance of growth factor sensitivity tests allows the assessment of major aspects of growth control in cultured gliomas. Cytogenetic evaluation in early cultures and correlation with the expression of oncogenes may yield useful information on mechanisms of escape from normal growth control. One of our cell lines (NCE-G28) in which cells switch from GFAP to fibronectin expression and transiently express the x-hapten may serve as a model to study crucial aspects of cellular differentiation. Using different extracellular matrices for the initiation of cultures even from very benign lesions with low proliferative potential it is possible to include these into comparative studies with glioblastomas.

Animals↗

Floating thrombus in the internal carotid artery disclosed by B-mode ultrasonography.

In a 44-year-old patient with transient cerebral ischaemia a large floating thrombus in the carotid bifurcation was detected by B-mode ultrasonography. To prevent further embolization the floating thrombus was removed by endarterectomy. The sonography findings were confirmed by operation and microscopy. Although migrating clots have long been recognized as a frequent cause of cerebrovascular accident, comparable cases have been rarely published. The problems involved in visualizing thrombi in the carotid artery by B-mode ultrasonography are discussed.

Adult↗

Brain tumours in children. A plea for an interdisciplinary working group.

A considerable number of high risk brain tumours require an interdisciplinary approach with surgery, radiation and chemotherapy rather than one single therapeutic regimen. Children with a medulloblastoma must be subdivided into four different risk groups depending on the size of the tumour, on the age of the child and on cerebral spinal fluid cytology findings. The treatment protocol for ependymomas depends on the location of the tumour and on histological grading. Pineal region tumours can be successfully removed; further therapy depends on the type of the tumour. Children with hemispheric high grade astrocytomas gain substantially from local radiation therapy. The GPO (Gesellschaft für Pädiatrische Onkologie) has most recently taken the initiative to found a pediatric neuro-oncology working group in order to establish and to evaluate different treatment modalities.

Antineoplastic Agents↗

Growth factors in cultured human glioma cells: differential effects of FGF, EGF and PDGF.

Primary cell cultures were initiated from surgically obtained specimens from human gliomas. After 4-10 passages in vitro the cells from 18 individual cases were seeded onto cluster dishes and left to attach for 24 h in medium containing fetal calf serum. Thereafter the medium was changed to serumfree, defined conditions and the following growth factors were added: EGF 1.5 x 10-8 M, PDGF 35 ng/ml, FGF 80 pg/ml. The growth factors were added fresh every 2 days. After 9 or 11 days in culture, the cells on one multiwell-plate were counted. In 8 cases another set which was cultured also in a multiwell-plate but on glass cover slides was immunostained for glial fibrillary acidic protein (GFAP), fibronectin (FN), A2B5 and galactocerebroside (galC). The proliferative response pattern in consequence to the growth factor addition varied greatly between different cases. In all cases a pronounced proliferative response was accompanied by marked changes on the culture morphology. Usually the best proliferative response was obtained with PDGF (10 cases) or FGF (8 cases) whereas EGF was most effective only in one case. Two cases showed only minimal response, one of which was an oligodendroglioma D according to Ludwig and another a gliosarcoma which was re-evaluated after 1 year in culture. It could be noted, however, that FGF had a tendency to be less effective in the group of malignant astrocytomas. The staining pattern of the cultures with the afore mentioned markers was not affected by the growth factor treatment. The proliferative response usually resulted in increased staining for fibronectin and never an induction of GFAP. A2B5 staining was positive only in one case of gliosarcoma and galC staining was regularly negative.

Cell Division↗

[The biology of gliomas: growth factors and oncogene expression. A current review].

In recent years several proteins with in vitro cell growth promoting activity were chemically identified and termed growth factors. Their role in normal glial development has been studied in vitro in different defined systems. In addition it has been tried to elucidate their role in the biology of gliomas. Some clues were obtained from the study of growth factor receptors and the expression of oncogenes. It has to be assumed that from the correlation and synthesis of results obtained from studies of growth factors, oncogene expression, gliogenesis and cytogenetics there will emerge useful biological concepts for specific therapeutic approaches.

Animals↗

Intramedullary spinal cord tumors resected with CO2 laser microsurgical technique: recent experience in fifteen patients.

We have operated upon 15 intramedullary spinal cord tumors with the aid of a CO2 laser attached to the microscope. The operative technique is described. Most of the tumors were localized within the cervical spinal cord. Nine tumors were benign gliomas: 4 ependymomas, 1 subependymoma, 3 astrocytomas, and 1 ganglioglioma. Six were removed totally, and 3 were removed subtotally. The remaining 6 tumors consisted of 3 hemangioblastomas, 1 intramedullary neurofibroma, 1 lipoma, and 1 primary intramedullary melanoma. Neurological function postoperatively compared to the preoperative function of the upper extremities was unchanged in 13 patients (86.5%), improved in 1, and worse in 1 patient. In the lower extremities, the preoperative neurological status was unchanged in 11 patients (73.3%), improved in 1 patient, and worse in 3 patients (20%). Magnetic resonance imaging was superior to myelography and computed tomography in localizing these lesions. Enhancement with paramagnetic substances (e.g., gadolinium-DTPA) helps to localize solid tumor within cysts. Histological evaluation of small tissue biopsies or frozen section histology is unreliable. The entire lesion should be exposed in all cases, and an attempt should be made to remove the tumor totally or, if this is not possible, to resect as much of the center of the tumor as is possible until the cord is decompressed. The decision to administer further treatment is based on the histological features of the tumor.

Adolescent↗

Clinical and laboratory findings in patients with multiple meningiomas.

A series of eight patients with multiple meningiomas is presented. Up to 14 meningiomas were diagnosed in one patient. The clinical and laboratory findings suggest that multiple meningiomas do not constitute a disease entity of their own featuring disease-specific clinical or laboratory findings. In our series we find a female predominance with seven female and one male patient. The histological findings were mixed, even within the individual cases. There are no consistent patterns of steroid receptor levels or chromosomal aberrations in the more recent cases in which these parameters could be investigated.

Adult↗

Pineal region tumours of childhood.

In Germany, the relative frequency of pineal region tumours seems to be much higher than hitherto assumed. At the University Hospital Hamburg, from 1980-1985 17 children with pineal region tumours were encountered amongst 102 children with CNS tumours. Two-cell-type germinoma is the most frequent pineal region tumour. Cerebrospinal fluid cytology is highly successful in identifying this germ cell tumour. Surgical removal has become a reasonably safe procedure in the treatment of pineal region tumours and was successful in all 10 cases so treated. In addition, our patients with two-cell-type germinomas received craniospinal axis radiation. All children, treated by both surgical removal and craniospinal axis radiation are so far relapse-free and are functioning on a pretreatment level.

Brain Neoplasms↗

Cerebellar haemorrhage as a complication after supratentorial craniotomy.

Four cases are presented, in whom cerebellar haemorrhages appeared as a complication following supratentorial craniotomy for a giant aneurysm, for tumours in three cases. Two patients died. Intracranial hypotension in combination with disturbed blood coagulation is discussed as possible pathogenesis. Because this seems to be a rare complication--similar cases have not yet been described in the literature--its timely diagnosis may be missed.

Adult↗

Does the timing of aneurysm surgery neglect the real problems of subarachnoid haemorrhage?

In 1984, in connection with the introduction of the calcium antagonist nimodipine, a new strategy for the treatment of subarachnoid haemorrhage (SAH) due to ruptured aneurysm was developed in our hospital. With no rigid regard to "timing" all patients undergo surgery as soon as possible. The only exception being those in Hunt and Hess grades IV and V without space-occupying intracranial haemorrhage and those bearing aneurysms of the vertebrobasilar circulation that are difficult of access. As soon as the risk of rebleeding has been eliminated surgically an active therapy against the possible consequences of SAH--cerebral vasospasm and simultaneous disturbances of autoregulation--is started. It consists in lowering the increased intracranial pressure, raising of mean arterial pressure and improving of rheological properties of the blood in order to prevent delayed build-up of neurological deficit due to ischaemia. It goes without saying that calcium antagonists are given from the very beginning of the patient's treatment even before operation. The advantages of this therapeutic concept are demonstrated by two series of non-selected consecutive patient material. The first series (A; n = 135) was treated between 1981 and 1984 before the change in treatment strategy, the second (B; n = 183) from 1984 to 1986 after that change. The overall mortality in series A was 27%, that in series B 20%. Operative mortality could be reduced from 22% to 16% in patients having undergone early operation and from 6% to 2% in patients with late surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Initiation of primary cell cultures from human intracranial tumors on extracellular matrix from bovine corneal endothelial cells.

Tissue specimens from 105 human gliomas and 57 human meningiomas were obtained at surgery, dissociated into single cells and small cell aggregates and then plated onto plain plastic tissue culture dishes and dishes which had been precoated with an extracellular matrix (ECM) derived from bovine corneal endothelium. In 80% of the glioma cases we observed a marked improvement in initial plating efficiency, colony formation and speed of attachment when cells were plated on ECM. In 5 cases cells attached only to the ECM-coated dishes but remained afloat in the untreated dishes. In addition it could be noted that over the first 2 days, those cells which had been initiated on ECM showed more signs of morphological differentiation, i.e., extension of cytoplasmic processes or formation of fiber networks between cell groups. If adaptation occurred and proliferation began in vitro, either immediately or after a several days' lag phase, both the ECM-cultured cells as well as those which slowly had adapted to culture on plastic could be passed on to untreated culture ware and perpetuated thereon. In the case of well-differentiated low-grade gliomas where no growth in culture took place, the cultures on ECM could at least be used for initial experiments in the primary cultures (P0). Meningiomas usually attached well to both, plastic or ECM. In 50% of our cases the plating efficiency was higher on ECM but after successful initial culture, the delay until the cells on plastic reached confluence in comparison with those on ECM was 1 or 2 days. Again there were 2 cases in which the cells would not plate on plastic. Here the cells which after 1 day were still afloat plated to more than 80% within the first 2 h after transfer to ECM. In all cases the cells from plastic and ECM cultures were indistinguishable and could be passed onto untreated dishes henceforth. In later culture stages ECM offers several advantages: It is easier to shift cells to serum-free defined culture conditions, the cells will grow at a faster rate on ECM when in higher passages and the maximal number of passages possible is higher on ECM.

Animals↗

Transnasal surgery in the treatment of craniopharyngiomas.

The results of transnasal-transsphenoidal surgery in 31 patients with craniopharyngioma are evaluated. To assess the value of transnasal surgery in cases with visual impairment, the results are compared to cases operated transcranially. There was only one death occurred on the 5th postoperative day. Two patients developed rhinoliquorrhoea, and one a transient oculomotor palsy. Recurrences leading to re-operation occurred frequently after mere cyst aspiration and only once after subtotal tumour removal. Normal glandotrope functions of the hypophysis were preserved in 75%, disturbed functions were normalized in 19% of primary transnasal surgery. Visual disturbances were normalized or improved in 94% cases after transnasal surgery, whereas an improvement was observed in only 65% after transcranial surgery. A deterioration never appeared after transnasal surgery, but in 26% after transcranial operations.

Adolescent↗

Aspects of personality in patients with pituitary adenomas.

In 24 patients suffering from pituitary tumours, aspects of personality as covered by the FPI (Freiburger Personality Inventory), the Giessen test and the STAI (State-Trait-Anxiety Inventory) were investigated in order to find out changes or problems which demand special treatment. The most interesting result concerns state- and trait-anxiety scores being increased pre-surgically and normalizing to some extent after treatment. Most of the other explored aspects did not show but tendencies which demand further investigation. Relationships between hormone levels and tumour size could not be shown. As a result of this investigation, special psychological treatment should be considered in acromegaly and Cushing's disease.

Acromegaly↗