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Biomedical subjects

G F Walter

Publications and source records attributed to G F Walter.

At least 37 records · Page 2Linked to original sources
PubMed1999

The interactive use of networking multimedia--innovative education resource for professionals and patients.

The combination of new and rapidly developing interactive multimedia computers and applications with electronic networks will require a restructuring of our traditional approach to strategic planning and organizational structure. Worldwide telecommunication networks (using satellites, cable) are now facilitating the global pooling of healthcare information and medical knowledge independent of location. The development of multimedia information and communication systems demands cooperative working teams of authors, who are able to master several areas of medical knowledge as well as the presentation of these in different multimedia forms. The assemblage of telematics and services offers a base for multimedia applications, for example teleteaching, telelearning, telepublishing, teleconsulting, teleconferencing, telemedicine etc. The expansion of the internet will also lead to the formation of interdisciplinary "Global Education Networks". The theory and practice of education are undergoing dramatic changes. Lifelong learning and adaptation of medical practice to new knowledge and new techniques will be even more important in the future.

Computer-Assisted Instruction↗
PubMed1998

[Basic fibroblast growth factor (b-FGF) in the perimatrix of cholesteatoma].

UNLABELLED: The growth of a cholesteatoma requires angioneogenesis in the connective tissue of the perimatrix. Angioneogenesis is also needed for wound healing as a host response to tissue injury. Normal wound repair is conducted through a wide number of growth factors. Basic fibroblast growth factor (b-FGF) plays a pivotal role in wound repair. This cytokine exerts its effects through stimulation of a wide range of target cells. B-FGF is chemotactic and mitogenic for fibroblasts, endothelial cells and keratinocytes. In addition, b-FGF can stimulate the production of collagenase and plasminogen activators to enhance fibroblast proliferation and angioneogenesis. Its necessity for normal wound repair has been confirmed by several workers. METHOD: In order to demonstrate angioneogenesis in the cholesteatoma perimatrix the distribution of b-FGF as the pivotal cytokine of the process was investigated in the perimatrix of 18 cholesteatoma specimens. RESULTS: B-FGF could be observed in 12 of 18 specimens (66%) in close approximation to histological signs of inflammation and wound healing. Areas with b-FGF also exhibited proliferation of the covering squamous epithelium. Cholesteatoma matrix tissue without inflammation or any sign of wound healing did not express b-FGF (6 of 18). CONCLUSION: Histological changes and distribution pattern of b-FGF in the perimatrix of cholesteatoma in the present study indicate that the perimatrix cells and substances of the wound healing cascade may play an important role in cholesteatoma development, angiogenesis and growth.

Cholesteatoma, Middle Ear↗
PubMed1998

Time-dependent expression of donor- and host-specific major histocompatibility complex class I and II antigens in allogeneic dopamine-rich macro- and micrografts: comparison of two different grafting protocols.

Neural transplantation, as a therapeutic approach to Parkinson's disease, still requires allogeneic graft material and raises questions of immunosuppression and graft rejection. The present study investigated the time course of major histocompatibility complex (MHC) expression and astrocytic response in allogeneic dopaminergic grafts, comparing two different grafting protocols. Adult 6-hydroxydopamine-lesioned Lewis 1.W rats received intrastriatal cell suspension grafts from the ventral mesencephalon of DA rat fetuses, either as single 1-microliter macrograft via metal cannula or as four micrografts of 250 nl/deposit via a glass capillary. No immunosuppression was administered. Immunohistochemistry was performed at 1, 3, 6, and 12 weeks after grafting, using antibodies against donor- and host-specific MHC class I and II antigen, glial fibrillary acidic protein (GFAP) and tyrosine hydroxylase (TH). Most animals showed good allograft survival up to 12 weeks after transplantation with no signs of rejection. Reinnervation of the lesioned striatum by TH-positive neurites was observed from 3-6 weeks on. Expression of donor-specific MHC class I was comparably low in both allogeneic grafting groups, while host MHC class I and II reaction as well as astrocytic response tended to be higher in the macrografted animals. Donor MHC class II was not observed at any time point. It is concluded that intraparenchymal allografts of fetal mesencephalic cell suspensions can survive well in the rat Parkinson model without immunosuppression for at least 12 weeks, and that the expression of moderate amounts of donor-specific MHC class I antigen does not suffice to initiate a rejection process. In addition, the microtransplantation approach may reduce the level of trauma and subsequent MHC and GFAP expression and may, thereby, minimize the risk of graft rejection.

Animals↗
PubMed1998

Retroperitoneal ectopic neural mass: "abdominal brain"--presentation of two cases and proposal of classification of paraneuraxial neural ectopia.

An encapsulated mass of brain tissue was found in the retroperitoneum of a fetus of gestational week 15 and a boy of age 3 years. The masses possessed fibrous tissue that bound them to the spine and intraspinal connective tissue, respectively, but there was no evidence of direct continuity of the ectopic brain tissue with the normal central nervous system. There was no dysraphism. In our fetal case, possible Foix-Alajouanine anomaly was additionally found. The ectopic neural tissue in the retroperitoneal region may be termed "abdominal brain." In the literature, an identical state has been described in the head (paracranial region) but there are no other records of the paraspinal region. Despite the different locations of the masses (head/paracranial or retroperitoneum/paraspinal), these ectopic brain masses should belong to the same disorder spectrum of the paraneuraxial neural ectopia, a new concept.

Cell Differentiation↗
PubMed1998

Somatic mutation analysis of the APP and Presenilin 1 and 2 genes in Alzheimer's disease brains.

The molecular basis for sporadic Alzheimer disease (AD) remains largely unknown. We hypothesized that in some cases of sporadic AD, a somatic mutation in an embryonic cell committed to neuronal development within the amyloid precursor protein (APP), the presenilin 1 (PS-1) or the presenilin 2 (PS-2) genes (genes known to be involved in familial AD) may result in AD phenotype. Using PCR, denaturing gradient gel electrophoresis (DGGE), restriction enzyme digest and direct DNA sequencing, we analyzed these genes in 99 brain tissues from patients with histopathologically proven AD. One brain sample showed a mutation within the PS-1 gene, His163 Arg, later shown to be a germline mutation. No other migration abnormalities were demonstrated in any sample in exon 16 or 17 of the APP gene or the coding exons of the PS-1 gene. Restriction digest pattern was normal with regard to the predominant PS-2 gene mutation (N141I). A known mutation in the APP gene, as well as novel mutations within the PS-1 gene were easily detected by DGGE (Reznick Wolf et al. manuscript submitted). We conclude that the genes that are involved in familial AD do not display somatic mutations in the brains of sporadic AD patients, and that other molecular mechanisms are probably involved in the pathogenesis of sporadic AD.

Alzheimer Disease↗
PubMed1998

[Enteroparesis caused by progressive fibrosis of the muscularis propria].

We would like to present the case of a 54-year-old patient who was admitted to the hospital with complaints of recurrent vomitus after food intake and associated weight loss. Endoscopy. barium X-ray of the small bowel and scintigraphy showed enteroparesis. Full-thickness biopsies achieved by explorative laparotomy revealed the pathological changes. The inner circular muscular layer was atrophic and replaced by fibrosis. The pathological findings were consistened with either visceral myopathy or isolated intestinal progressive systemic sclerosis. A sporadic nonfamilial type of visceral myopathy seems to be the most likely diagnosis in this case. Progressive systemic sclerosis seems to be unlikely as the patient presented with isolated gastrointestinal involvement and lack of appropriate autoantibodies. The diseases progression made an enteral supplementation impossible. Therefore a parenteral nutrition was started, which was characterized by a complicated clinical course. Persisting gastrointestinal complaints, recurrent port infections and lack of perspectives led to patient's diminished motivation for adequate sterile use of the port-system. This case report shows that besides the use of modern port-systems and antibiotics the psychological situation of patients treated with total parenteral nutrition is of great interest for optimal patient care.

Diagnosis, Differential↗
PubMed1997

[Rhabdomyolysis in antiretroviral therapy with Lamivudin].

HISTORY AND CLINICAL FINDINGS: Six weeks after antiretroviral treatment with lamivudin (a nucleoside analogue) had been started (300 mg daily) in a 31-year-old man with AIDS developed pain and weakness in his muscles. On admission he had myalgia on pressure and movement as well as weakness of the entire body musculature, especially of the arms. The history and findings suggested bacterial or HIV-associated myositis. INVESTIGATIONS: Creatinekinase activity (4442 U/l) and myoglobin concentration (3250 micrograms/l) were greatly increased, while creatine (96 mumol/l) and C-reactive protein (22 mg/l) levels were only slightly raised. Serology was negative for acute and bacterial infections and autoimmune myositis. Magnetic resonance imaging and biopsy indicated marked rhabdomyolysis without myositis. DIAGNOSIS, TREATMENT AND COURSE: After excluding other causes, lamivudin and other drugs were discontinued, drug-induced rhabdomyolysis being suspected. This and the administration of prednisolone (100 mg daily) improved the symptoms. Creatinekinase activity and myoglobin level became normal within 14 days. On renewed administration of lamivudin creatinekinase and myoglobin concentrations in serum doubled to 180 U/l and 110 micrograms/l, respectively. Cessation of medication once again restored them to normal. CONCLUSION: Rhabdomyolysis is a serious but rare side effect of lamivudin treatment. Appropriate biochemical monitoring should therefore be undertaken when it is used in the treatment of HIV-positive patients.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Cerebellar neurocytoma in an infant: an important differential diagnosis from cerebellar neuroblastoma and medulloblastoma?

A benign small cell tumor of the cerebellum of an infant boy is reported. The tumor exhibited cytological features strongly resembling those of central neurocytoma but in a pattern as usually seen in cerebellar nodular neuroblastoma or in desmoplastic medulloblastoma. It is suggested to call this tumor cerebellar neurocytoma, distinguishable from medulloblastoma or cerebellar neuroblastoma as most important differential diagnoses.

Cerebellar Neoplasms↗
PubMed1996

The expression of nerve growth factor receptor on Schwann cells and the effect of these cells on the regeneration of axons in traumatically injured human spinal cord.

To investigate the effects of Schwann cells and nerve growth factor receptor (NGFR) on the regeneration of axons, autopsy specimens of spinal cord from 21 patients with a survival time of 2 h to 54 years after spinal cord trauma were studied using immunohistochemistry and electron microscopy. Regenerating sprouts of axons could be observed as early as 4 days after trauma. At 4.5 months after trauma, many regenerating nests of axons appeared in the injured spinal cord. The regeneration nests contained directionally arranged axons and Schwann cells. Some axons were myelinated. In injured levels of the spinal cord, the Schwann cells exhibited an increased expression of NGFR within spinal roots. These results show that an active regeneration process occurs in traumatically injured human spinal cord. The NGFR expressed on Schwann cells could mediate NGF to support and induce the axon regeneration in the central nervous system.

Adolescent↗
PubMed1996

[Inhibition of angiogenesis and growth of malignant gliomas in the athymic nude rat model: immunotherapy against "basic fibroblast growth factor"].

An important feature of malignant progression in human gliomas is increased polymorphism of tumor cells associated with karyotypic heterogenity and a variety of secondary changes, one of which is increased angiogenesis. The capability of brain tumors for angiogenesis most probably is the earliest sign for malignancy in 95% of cases and occurs before typical changes of histology appear. Malignant brain tumors are known to produce several angiogenic growth factors. One of the most potent of these factors is the basic fibroblast growth factor (bFGF). In an experimental study human U87 MG glioma cells (2.10(5) cells/50 microliters) were implanted through a burrhole into the cerebral cortex in a group of 25 nude rats. After 3 weeks we found a reproducible extensive tumor growth with extensive neovascularization. Immunohistochemical evaluations proved a high expression of bFGF in the tumor. A parallel group of xenotransplanted rats were treated with 33 micrograms of rabbit anti-bFGF antibodies during tumor cell implantation. Thereafter, the same dosages of antibodies were administrated intracranially twice a week for 3 weeks. We found a significant inhibition of tumor vascularization and growth compared to other groups who had no treatment or who received irrelevant immunoglobulins or saline as a control. Our results indicate that inhibition of tumor angiogenesis might contribute to inhibition of tumor growth in malignant gliomas.

Animals↗
PubMed1996

[Time limited immunosuppression in allogenic nerve transplant in the rat].

A rejection response of peripheral nerve allografts eliminates the Schwann cells without destroying the tubular architecture and leads to a regeneration of inferior quality. Under immunosuppression this rejection is prevented, and allogenic Schwann cells persist in the grafts, leading to a better regeneration result. In adult rats of the strains DA and LEW.1W, a 2,5 cm segment of the sciatic nerve was grafted. Under Cyclosporin A regeneration was allowed to take place for 12 weeks. Thereafter, immunosuppression was discontinued in one group and gradually reduced in another. Regeneration quality was compared after an additional six weeks in comparison to an autologous control. Best regeneration was observed in the autologous control; no statistical differences were observed between the two experimental groups. Gradual reduction of immunosuppression did not result in an atraumatic replacement of donor derived Schwann cells by recipient derived ones. Allogenic nerve grafting needs continuous immunosuppression, which to date precludes it from clinical application.

Animals↗
PubMed1995

Morphometric changes in free neurovascular latissimus dorsi flaps: an experimental study.

This study was designed to investigate regeneration of reinnervated, free transplanted muscles. We used a rat model, consisting of eight rats per group, in which the latissimus dorsi muscle was transplanted orthotopically and then harvested and evaluated after 2 and 12 weeks. Age-matched control animals were used to oppose non-operated muscles. At date of removal the patency of the vascular anastomoses was checked clinically and histologically. Electrophysiological measurements were also performed and conventional and enzyme histochemical histological slides manufactured. Two weeks after the free neurovascular flap transfer the muscle was not yet innervated, and histologically a dissolved pattern of type 1 and type IIA muscle fibres was found. The muscle fibres demonstrated a decrease of more than 50% cross-sectional area. After 12 weeks the muscles were reinnervated again; muscle contraction was positive with electrical stimulation and the cross-sectional area had regained 80% of the activity of normal muscle fibres. With enzyme histochemical staining the typical type grouping of reinnervated muscles could be demonstrated.

Animals↗
PubMed1995

Preservation of peripheral nerve grafts: a comparison of normal saline, HTK organ preservation solution, and DMEM Schwann cell culture medium.

The regeneration of peripheral nerve grafts was evaluated in a rat model, after pretreating the grafts with Schwann cell culture medium, HTK organ preservation solution, and normal saline, under cold ischemic conditions for different time periods. Following orthotopic replantation of the grafts into donor animals, the quality of regeneration was assessed after 6 weeks, compared to positive controls (autologous transplantation) and negative controls (acellular grafts). The regenerative quality in the Schwann cell culture groups with ischemic periods of 32 and 72 hr was comparable to normal controls. Significantly minor regeneration was detected in specimens undergoing 14 and 120 hr of ischemia in the Schwann cell culture medium and in the HTK and normal saline groups, regardless of ischemic time. Among the conclusions was that controlled proliferation of Schwann cells seems to be a basic principle for preservation of peripheral nerve grafts.

Animals↗
PubMed1995

In vivo inhibition of angiogenesis and growth of the human U-87 malignant glial tumor by treatment with an antibody against basic fibroblast growth factor.

The effectiveness of in vivo suppression of neovascularization and growth of malignant glial tumors by in situ administration of an antibody directed against basic fibroblast growth factor (bFGF), a strong mitogen for cells of mesodermal origin, was tested. One hundred fifty congenitally athymic nude rats (han rnu/rnu) were implanted intracerebrally with U-87MG tumor cells, known constitutive producers of bFGF. The animals were randomly assigned to six groups of 25 animals each. Animals were treated by in situ application of saline (Group F), control antibody (Group D), or polyclonal anti-bFGF antibody (Group B). In additional groups a putative effect on tumor growth caused by the treatment application device itself (between growth control Groups A and E), and the effect of heat-inactivated tumor cells (negative control Group C) were tested. After 3 weeks of treatment, tumor progression and degree of neovascularization were morphometrically recorded. In the untreated Groups A and E massive tumor growth was recorded, consisting of 19.9% +/- 0.4% and 27.1% +/- 0.5%, respectively, of the total brain cross-sectional area. In Group C, no tumor growth occurred. In control Groups D and F tumor progression consisted of 18.6% +/- 0.4% and 18.5% +/- 0.4%, respectively, of the total brain cross-sectional area; whereas in the anti-bFGF treated Group B, significantly smaller tumor masses measuring 7.2% +/- 0.1% were recorded. New blood vessels were located both peritumorally and intratumorally and defined as numerical density and area fraction (number/area and area/area). Significantly more new blood vessels were found in Groups A, D, E, and F, ranging from 41,380/mm2 +/- 464/mm2 to 53,442/mm2 +/- 150/mm2 peritumorally and 51,846/mm2 +/- 495/mm2 to 64,660/mm2 +/- 183/mm2 intratumorally than in the anti-bFGF treated Group B, which numbered 8220/mm2 +/- 225/mm2 peritumorally and 16,554/mm2 +/- 236/mm2 intratumorally. The authors conclude that treatment with anti-bFGF antibody is effective in inhibiting tumor-induced angiogenesis and correlated tumor progression. However, owing to the character of the experimental system used, one cannot exclude the possibility that application of the specific anti-bFGF antibody also counteracts device-induced neovascularization. The authors suggest that combined surgical excision and adjuvant immunotherapy of tumors such as glioblastoma and other malignant brain tumors that express bFGF might prevent tumor recurrence.

Animals↗
PubMed1995

[Muscle-specific changes in free latissimus dorsi transplantation in the rat model].

The aim of this study is to gain further knowledge concerning the regeneration of reinnervated, freely transplanted muscles. Therefore, we used a rat model, consisting of eight rats per group, in which the latissimus dorsi muscle was transplanted orthotopically, after a period of time of two and twelve weeks harvested, then evaluated histologically and enzyme-histochemically. As controls we used a group of non-operated muscles. At date of removal, the patency of the vascular anastomoses was checked clinically and histologically. Additionally, electrophysiological measurements and conventional and enzyme-histochemical histologies were performed. Two weeks after the free neurovascular flap transplantation, the muscle was not innervated yet, histologically a dissolved pattern of type 1 and type 2 muscle fibers was found. After twelve weeks of time, the muscles were reinnervated again, muscle contraction was positive after electrical stimulation and the typical pattern of fibers was reestablished.

Animals↗
PubMed1994

Immunolocalization of granulocyte-colony-stimulating factor in human glial and primitive neuroectodermal tumors.

Granulocyte-colony-stimulating factor (G-CSF) is a hematopoietic cytokine that regulates the differentiation of myeloid progenitors and the function of mature neutrophils. It is produced in vitro by monocytes/macrophages, mesothelial cells, fibroblasts and endothelial cells after appropriate induction by inflammatory mediators like IL-1 and TNF. Normal as well as tumorous glial cells can also be induced to produce CSFs in vitro. However, little is yet known about the in vivo expression of G-CSF as a mediator in inflammation and malignancy within the human central nervous system. The aim of the present study was to investigate by immunostaining the expression of the G-CSF protein within non-tumorous and tumorous glial tissues, and primitive neuroectodermal tumors. Using the murine monoclonal anti-G-CSF TM 82/60 antibody, we found high G-CSF expression in astrocytoma WHO grades I and II and reactive brain tissue, low expression in astrocytoma WHO grade III, and none in glioblastoma, oligodendroglioma WHO grades II and III, and medulloblastoma. In consecutive sections of the tissue samples, G-CSF protein was localized in GFAP-positive glial cells, but not in macrophages/microglial cells, which expressed HLA-DR, detected by the antibody CR3/43. Computer-assisted microdensitometric evaluation of the intensity of immunostaining for G-CSF and statistic analysis of the data revealed significant differences between the diagnostic entities studied (p < 0.0001). We conclude that in vivo expression of G-CSF is a characteristic of reactive as well as tumorous astrocytes, with the latter losing this feature at higher degrees of dedifferentiation.

Adolescent↗