Biomedical subjects

G Ritter

Publications and source records attributed to G Ritter.

At least 55 records · Page 3Linked to original sources

PubMed1996

Induction of antibodies reactive with GM2 ganglioside after immunization with lipopolysaccharides from Camplyobacter jejuni.

Ganglioside GM2, expressed on the surface of some human cancers, is a promising target for immune therapy, since GM2 antibodies are cytotoxic, can be induced in humans by vaccination, and the presence of GM2 antibodies is associated with a better prognosis in melanoma patients. In our efforts to induce long-lived, cytotoxic GM2 antibodies, we investigated lipopolysaccharides (LPS) containing "GM2-like" oligosaccharides. LPS were prepared from Campylobacter jejuni serotypes O:1, O:23, or O:36 (all sharing the oligosaccharide structure GalNAcbeta1-4Gal(113NeuAc)-Hex with ganglioside GM2), and tested for their ability to induce GM2-reactive antibodies. Immunization of NZW rabbits (2 animals per vaccine) with LPS from C. jejuni serotype O:1 in Freund's adjuvant resulted in production of high-titer IgG antibodies reactive with purified bovine brain GM2 in ELISA, dot-blot immune strains and immune thin-layer chromatography, and with GM2 derived from various human tumors by immune thin-layer chromatography. These rabbit antibodies bound to cancer cell lines expressing GM2 on their cell surface, as determined by mixed hemadsorption assays, mediating strong antibody-dependent cellular cytotoxicity (ADCC) with tumor cells expressing cell-surface GM2. Antibodies induced by vaccination with C. jejuni serotype O:1 were higher-titer (IgG ELISA titer > 1:60,000) than antibodies induced by immunization with purified GM2 (IgG ELISA titer > 1:200). Immunization with LPS from C. jejuni serotype O:36 resulted in production of moderately high-titer IgM and low-titer IgG GM2 antibodies. Immunization with LPS from C. jejuni serotype O:23 did not elicit GM2-reactive antibodies. No clinical symptoms were observed in animals immunized with these LPS preparations, with purified GM2 ganglioside, or with LPS derived from C. jejuni serotype O:19 (containing a GM1-like oligosaccharide). Our results indicate that lipopolysaccharides sharing carbohydrate epitopes with gangliosides may be useful immunogens for inducing antibodies to ganglioside antigens.

Animals↗

PubMed1996

[Long-term outcome of managing medial femoral neck fractures with ceramic head endoprostheses].

Total hip replacement is often recommended for the treatment of femoral neck fractures in elderly patients. A less invasive approach with shorter operating time is the replacement of the femoral head only, leaving the acetabular cartilage in situ. Hemiarthroplastic hip replacement using a metallic head prosthesis was not successful in the past, because the majority of patients developed protrusio acetabuli after surgery. In the present study hemiarthroplastic hip replacement using an Al2O3-ceramic head was shown to be a useful method for the treatment of femoral neck fractures in elderly patients. From 1985 to 1990 277 patients were treated with hemiarthroplasty. The average age at the time of accident and operation was 81.7 years. At the time of follow-up in 1993 only 77 survivors were available for examination. A standardized score was calculated assessing activity, gait, hip pain, etc., with the patients obtaining an average score of 58 out of possible 78 points. Only three patients had hip pain, and in four cases the roentgenographic examination revealed protrusio acetabuli. Two of these four patients underwent revision surgery for replacement of the cup, leaving the stem in situ. In view of the small number of approach-related complications, hemiarthroplastic hip replacement using an Al2O3-ceramic head is the recommended surgical treatment for femoral neck fractures in elderly patients. In the rare patient with protrusio acetabuli, revision surgery can be performed to replace the cup, leaving the stem in situ.

Activities of Daily Living↗

PubMed1996

The control of ichthyophthiriasis by a medicated food containing quinine: efficacy tests and ultrastructure investigations.

The present report demonstrates that a medicated food containing quinine kills the skin-inhabiting trophozoite stage of Ichthyophthirius multifiliis in ornamental fish. Artificially infected swordtails. (Xiphophorus helleri), black mollies (Poecilia sphenops), and black neons (Hyphessobrycon herbertaxelrodi) were used in the trials. The fish were maintained in groups of 10 or 20 inside aquaria (20 or 60 l) at 25 degrees C. Ultrastructure investigations by means of transmission electron microscopy revealed clear deleterious effects of quinine on the trophozoite stages. Following the initial application the outer limiting membrane of the trophozoite was broken at places. Within the nephridial plasma the plasma bridges were broken in part. After 2 days of treatment the lumen of the alveolar sac became enlarged. The food vacuoles in treated trophozoites were more electron-dense than those in the untreated controls. Numerous lipid droplets were found close to the vacuoles. The degree of damage in the nephridial plasma was intensified. When feeding was prolonged for 3 or more days, all kinds of damage became more extensive as seen in the trophozoites after 1 or 2 days of treatment. In addition food vacuoles in the final stages of digestion were no longer detectable. In long-term feeding tests, when typical ornamental fish species were fed three times daily ad libitum with the medicated food over a 12-week period, the animals showed no adverse clinical symptom. From the toxicological as well as the ecological and economical point of view the feeding of flakes containing quinine has considerable advantages as compared with conventional bath treatment.

Administration, Oral↗

PubMed1996

Dramatically different phenotypes in mouse models of human Tay-Sachs and Sandhoff diseases.

We have generated mouse models of human Tay-Sachs and Sandhoff diseases by targeted disruption of the Hexa (alpha subunit) or Hexb (beta subunit) genes, respectively, encoding lysosomal beta-hexosaminidase A (structure, alpha) and B (structure, beta beta). Both mutant mice accumulate GM2 ganglioside in brain, much more so in Hexb -/- mice, and the latter also accumulate glycolipid GA2. Hexa -/- mice suffer no obvious behavioral or neurological deficit, while Hexb -/- mice develop a fatal neurodegenerative disease, with spasticity, muscle weakness, rigidity, tremor and ataxia. The Hexb -/- but not the Hexa -/- mice have massive depletion of spinal cord axons as an apparent consequence of neuronal storage of GM2. We propose that Hexa -/- mice escape disease through partial catabolism of accumulated GM2 via GA2 (asialo-GM2) through the combined action of sialidase and beta-hexosaminidase B.

Animals↗

PubMed1996

Results of three-phase bone scintigraphy and radiography in 20 cases of neonatal osteomyelitis.

Neonatal osteomyelitis, a rare, potentially crippling disease, requires early diagnosis and effective therapy. This study of 20 neonates analysed the diagnostic value of three-phase bone scintigraphy (motivated by its controversial role), plain radiography and local clinical signs in neonatal osteomyelitis and complicating septic arthritis. The sensitivities for detecting focal skeletal involvement were as follows: bone scintigraphy 90%, radiography 65%, clinical local signs 20%. Reliable scintigraphic signs were localized hyperperfusion (phase I), vasodilation (phase II) and hot or cold lesions on 3-h images. Radionuclide angiography definitely increased the validity of bone scintigraphy. During follow-up, the reduction or normalization in focal hyperperfusion was the first and most sensitive sign of an adequate response to antibiotic treatment; persistence (or recurrence) of focal hyperperfusion, increasing relative uptake ratios and the appearance of new foci of bone involvement indicated escape from antibiotic therapy. Radiography revealed no pathological signs in 35% of cases, soft tissue changes in 20% and effusion of the hip joint in 45%. Local clinical signs were not a reliable predictor of scintigraphic or radiographic findings. We consider bone scintigraphy in neonatal osteomyelitis to be a successful, efficient and cost-effective diagnostic modality, not only for early diagnosis, but also during follow-up.

Bone and Bones↗

PubMed1996

The home health visit: an appropriate unit for Medicare payment?

To contain costs and increase incentives for efficient provision of care, prospective payment methods are being proposed for Medicare home health services. Although a shift to per episode payment is much discussed, the methods rely on the home health visit as a fundamental building block in setting rates and ceilings. Some propose setting fixed per visit prices in the interim until episode payment can be developed. Findings from the evaluation of a Health Care Financing Administration (HCFA) demonstration of per visit payment suggest that this could shorten to the length of visits provided to Medicare beneficiaries. Because of home health agencies' discretion over visit length, we question whether the visit is the appropriate basic unit for developing prospectives payment methods for Medicare home health.

Centers for Medicare and Medicaid Services, U.S.↗

PubMed1995

Analysis of the antibody response to immunization with purified O-acetyl GD3 gangliosides in patients with malignant melanoma.

Gangliosides expressed in malignant melanoma are potential targets for immunotherapy. Immunization of melanoma patients with vaccines containing purified GM2 ganglioside has resulted in induction of GM2 antibodies, and high titers of GM2 antibodies have correlated with increased survival. Melanoma ganglioside 9-O-acetyl GD3 is another candidate for ganglioside vaccine construction because of its limited expression in normal human tissues. As purification of 9-O-acetyl GD3 from human melanoma (9-O-acetylated on the terminal sialic acid) is not practical for broad application, we investigated the antibody response of melanoma patients to O-acetyl GD3 from several additional sources: hamster melanoma (7-O-acetyl GD3), bovine buttermilk (mixture of 7-O-acetyl GD3, 9-O-acetyl GD3 and 7,9-di-O-acetyl GD3) and chemically modified GD3 from bovine brain (9-O-acetylated on the subterminal sialic acid). Only immunization with the buttermilk-derived O-acetyl GD3 preparation resulted in consistent production of IgM antibodies. However, the induced antibodies reacted with the immunogen and with 7-O-acetyl GD3 derived from hamster melanoma but not with 9-O-acetyl GD3 or human melanoma cells expressing 9-O-acetyl GD3 on their cell surface. In contrast, all O-acetyl GD3 derivatives used for immunization were recognized by murine MAbs that reacted with 9-O-acetyl GD3, and immunization of mice with buttermilk-derived O-acetyl GD3 resulted in the production of antibodies that reacted with human melanoma cells expressing 9-O-acetyl GD3. Apparently, the human and murine immune systems preferentially recognize different epitopes on these molecules.

Adjuvants, Immunologic↗

PubMed1995

Serological response patterns of melanoma patients immunized with a GM2 ganglioside conjugate vaccine.

Gangliosides, such as GM2, GD2, GD3, and 9-O-acetyl GD3, are receiving attention as targets for antibody-based and vaccine-based therapies of melanoma. GM2 appears to be a particularly immunogenic ganglioside in humans, as indicated by the presence of naturally occurring IgM anti-GM2 antibodies in approximately 5% of humans and the fact that immunization with irradiated GM2-expressing melanoma cells or purified GM2 adherent to bacillus Calmette-Guérin elicits GM2 antibodies of low to moderate titers in a high proportion of vaccinated patients. To develop vaccines that consistently induce high titers of IgM as well as IgG anti-GM2 antibodies, vaccines containing GM2 conjugated to keyhole limpet hemocyanin as the carrier protein and QS-21 as the adjuvant have been constructed. The serological response of vaccinated patients was monitored by ELISA using purified GM2 ganglioside for IgM and IgG anti-GM2 antibodies and for GM2 cell surface-reactive antibodies by immune adherence assays and cytotoxic tests (IgM antibodies) and mixed hemadsorption assays (IgG antibodies). The majority of vaccinated patients developed IgM and IgG antibodies detectable by ELISA. In most cases, the results of IgM ELISA correlated with assays for cell surface-reactive IgM antibodies. This was not true for IgG anti-GM2 antibodies, where strong discrepancies were seen between high titers in ELISA and little or no reactivity in mixed hemadsorption tests for cell surface-reactive antibodies. These IgG antibodies (and the less frequent IgM antibodies that show similar discrepancies) may be directed against GM2 determinants that are buried, hidden, or not present on GM2-expressing target cells. With regard to a major objective of ganglioside vaccines--i.e., generation of cytotoxic antibodies--the GM2-keyhole limpet hemocyanin/QS-21 vaccine is clearly superior to the previously tested GM2/bacillus Calmette-Guérin vaccine. However, variability in patient response and lack of persistence of high-titered IgM cytotoxic antibodies in many patients are problems that remain to be solved.

Adjuvants, Immunologic↗

PubMed1995

Effect of the new oral antidiabetic agent (-)-BM 13.0913.Na on insulin resistance in lean and obese Zucker rats.

The new antidiabetic agent (-)-BM 13.0913.Na (BM) was administered to 12-week-old lean and obese Zucker rats, an animal model of insulin resistance, at a daily dose of 50 mg/kg for 14 days. Hyperinsulinemic-euglycemic clamps were performed on treated and untreated lean and obese Zucker rats. Basal hepatic glucose production (HGP) rates were similar in lean and obese untreated animals. Insulin-induced suppression of HGP was significantly less effective in obese animals. In addition, these animals exhibited the characteristic impaired glucose utilization. In obese animals, drug treatment improved insulin suppression of HGP and total glucose utilization (GU) during clamp studies. Furthermore, drug treatment decreased insulin levels during clamp studies, suggesting an acceleration of insulin clearance. Drug treatment also decreased basal plasma insulin levels and serum and liver concentrations of cholesterol in both fasted lean and obese rats. Additionally, blood glucose, plasma nonesterified fatty acids (NEFA), and serum triglyceride levels were reduced in fasted obese rats, but only minor changes in liver triglycerides were observed in lean and obese rats. On the basis of these results, we suggest that BM is an effective antidiabetic agent that may reduce abnormalities of glucose and lipid metabolism.

Administration, Oral↗

PubMed1995

[Effectiveness of oral rifampicin against mycobacteriosis in tropical fish].

In vitro studies have shown that rifampicin is an effective antibiotic for mycobacteria infections. Two species of tropical fish, the Firemouth Cichild Cichlasoma meeki and the Congo Tetra Phenacogrammus interruptus, were used to determine whether oral application of rifampicin might serve as an effective treatment for mycobacteriosis in tropical fish. Fish of the two species were infected with M. marinum under controlled conditions. Six or twelve weeks after infection, treatment was begun with medicated fish food containing rifampicin in combination with tetracyclin. Histological examination of epithelial cell granuloma in the anterior and posterior kidneys, as well as in liver and spleen, showed that antibiotic treatment could somewhat reduce the intensity of, but could not successfully eliminate infection. In addition, after treatment, acid-resistant rods could still be isolated from histological samples and M. marinum could be cultured from organ samples.

Administration, Oral↗

PubMed1994

[Neurologic-psychiatric expert assessment in 1989 to 1991 social law].

With 100 Social Court proceedings instituted in Germany (according to the territory of 1989), there could be shown the law-suits not being based on substantial arguments in two thirds and, therefore not having chances of success in foro. Among medical expert testimonies concerning with psychiatric matters female plaintiffs predominated; in contrast, neurologic testimonies were predominantly requested for males. The proportion of foreigners amounted to 5-15% depending from the matter on which testimony was requested. Mean age of the plaintiffs was approximately 50 years, they had been retired from business life on an average of 3 years before. Two thirds of the plaintiffs briefed an attorney or a representation of interests for instituting legal proceedings; the latter did not result in charges to the plaintiffs. Medical examinations to elaborate the testimony included tests employing technical measures such as neuroimaging in about one third of the cases. Relating to the latter, there is an increasing tendency obviously.

Adult↗

PubMed1994

A comparative trial of anti-glycoconjugate antibody assays: IgM antibodies to GM1.

IgM class antibodies against the ganglioside GM1 have been found in a subgroup of patients with lower motor neuron syndromes and multifocal motor neuropathies (MMN). The pathogenic relevance of these antibodies is still unclear, but some MMN patients with IgM antibodies against GM1 seem to profit from immunosuppressive therapy. A reliable test for IgM antibodies against GM1 may be useful for identifying these patients. We have assessed the comparability of the ELISA tests used for the determination of IgM against GM1 by sending coded serum samples to nine laboratories. In three samples high-titre IgM antibodies against GM1 were detected by all laboratories. This result was confirmed by dot blot immunodetection and thin-layer chromatography immuno-overlay. Seven samples were read as negative by nearly all laboratories. Major discrepancies between laboratories were noted in the analysis of one sample with results ranging from negative to "high titre".

Adolescent↗

PubMed1994

[Results of implantation of uncemented porous metal hip prostheses].

72 patients having cementless spongy-metal hip prosthesis were reexamined by clinical and radiological check up two to seven years after implantation (average 43 months). In case of five patients hip prosthesis had to be changed due to loosening (no bony ingrowth n = 2, loosening of acetabular component due to technical faults n = 3). In correlation to clinical results 88% could be considered as excellent or good, 9% acceptable and 3% as inadequate. 10% of the patients complained about thigh pain. The typical radiological bony reactions of the surrounding bone are described. An evaluation of the radiological results can only be done under consideration of the clinical problems involved. In view of the positive results obtained in the recent time the use of spongy-metal hip prosthesis can be recommended for cementless hip joint replacement in case of younger patients. Especially in case of cemented hip joints which have become loose it will be an advantage to use spongy-metal hip prosthesis.

Adult↗

PubMed1994

Specificity and structure of murine monoclonal antibodies against GM1 ganglioside.

Anti-GM1 antibodies have been implicated in the pathogenesis of several neurological diseases, but the role of these antibodies is still controversial. An animal model could provide insight into the mechanisms of these human disorders, but obtaining specific anti-GM1 monoclonal antibodies (mAbs) has been extremely difficult because of the weak immunogenicity of GM1 ganglioside. Four murine mAbs against GM1 were elicited by immunization of mice with lyso GM1 coupled to BSA and GM1 glycolipid. All four IgM,k mAbs bound strongly to GM1, three antibodies (125, 360 and 494) also bound very weakly to asialo GM1 (GA1) and one (156) bound weakly to GD1b. Three antibodies (125, 360 and 494) were encoded by the same VH and V kappa genes. The VH gene exhibited 97% homology to VHOX1, a member of the VHQ52N gene family, the D segment was probably derived from DQ52 and JH was identical to JH2. The V kappa gene was approximately 99% homologous to V kappa RF and J kappa was germline J kappa 2. The VH gene of mAb 156 exhibited 98% homology to VH205.12, of the VHJ558 gene family, the D segment was derived from DFL16.1, and JH was germline JH2. The V kappa and J kappa genes of mAb were identical to V kappa 8 and J kappa 1, respectively. The genes encoding these anti-GM1 antibodies were close to germline sequences and have been used to encode other antibodies. This suggests that the unresponsiveness of mice to immunization is probably due to inactivation of self-reactive B cells. These rare anti-GM1 mAbs will be valuable reagents for studies of the pathogenesis of autoimmune neuropathy in animals, and also for analyzing the tissue distribution and functions of GM1.

Amino Acid Sequence↗

PubMed1994

Improved survival in stage III melanoma patients with GM2 antibodies: a randomized trial of adjuvant vaccination with GM2 ganglioside.

PURPOSE: To perform a double-blind randomized trial with American Joint Commission on Cancer (AJCC) stage III melanoma patients for the following reasons: (1) to confirm our previous finding that patients with antibodies against the melanoma differentiation antigen GM2 have an improved prognosis, and (2) to demonstrate clinical benefit from GM2 antibody induction. PATIENTS AND METHODS: One hundred twenty-two patients with AJCC stage III melanoma who were free of disease after surgery were randomized: 58 to receive treatment with the GM2/BCG vaccine, and 64 to receive treatment with bacille Calmette-Guèrin (BCG) alone. All patients were pretreated with low-dose cyclophosphamide (Cy). RESULTS: GM2 antibody was detected in 50 of 58 patients treated with GM2/BCG and seven of 64 patients treated with BCG alone. With a minimum follow-up period of 51 months, there was a highly significant increase in the disease-free interval (P = .004) and a 17% increase in overall survival (P = .02) in these 57 antibody-positive patients, confirming our earlier experience. Exclusion of all patients with preexisting GM2 antibodies (one in the GM2/BCG group and five in the BCG group) from statistical analysis resulted in a 23% increase in disease-free interval (P = .02) and a 14% increase in overall survival (P = .15) at 51 months for patients treated with the GM2/BCG vaccine. However, when all patients in the two treatment groups were compared as randomized, these increases were 18% for disease-free interval and 11% for survival in the GM2/BCG treatment group, with neither result showing statistical significance. CONCLUSION: (1) Vaccination with GM2/BCG induced immunoglobulin M (IgM) antibodies in most patients. (2) GM2 antibody production was associated with a prolonged disease-free interval and survival. (3) Comparison of the two arms of this trial as randomized fails to show a statistically significant improvement in disease-free interval or survival for patients treated with GM2/BCG vaccines.

Adolescent↗

PubMed1994

Stability of frailty in the social/health maintenance organization.

Although many long-term care (LTC) programs assume that the disabilities of their frail elderly participants are stable in nature, there has been suggestive evidence to the contrary. This study tests stability of disability among social/health maintenance organization (S/HMO) members who were judged eligible for admission into a nursing home. Identified persons were reassessed quarterly. By the end of 1 year, less than 50 percent were still considered to be nursing home eligible. Logit analysis revealed an increased likelihood of instability for persons who were newly identified as functionally disabled after hospitalization. Policy implications for capitated managed-care programs for the elderly are discussed.

Aged↗

PubMed1994

[Bone remodeling after reamed and unreamed intramedullary nailing. A histomorphometric study].

Experimental findings after unreamed nailing have indicated certain advantages for new bone formation in comparison to reamed nailing. It would be of interest to establish whether any essential differences can be determined in the extent and course of callus formation. To investigate this question, thin sections of bone from 16 tibiae (nailing after transverse osteotomy in sheep) were examined histomorphometrically the progress at the periosteal and interfragmentary surfaces of the remodelling callus being recorded separately after 4, 6 and 8 weeks. After unreamed nailing, more extensive and earlier formation of interfragmentary callus was observed. At 4 weeks postoperatively the remodelled periosteal bone surface was 158 mm2, which was 1.6 times that after the unreamed procedure (95 mm2). By 4 weeks after unreamed nailing the periosteal callus surface was already greater than 6 weeks after reamed nailing. On the basis of these experimental results the use of unreamed nailing can be recommended, especially for open fractures and fractures with severe soft tissue damage.

Animals↗

PubMed1994

[Rotational stability of the thoracolumbar spine after interlaminar ultrasound window, hemilaminectomy and laminectomy. A comparative experimental study].

Intraoperative spinal sonography to check whether fragments have been successfully repositioned requires enlargement of the natural interlaminar window to 8 x 10 mm. The present study was performed to measure any rotational instability caused by such a laminotomy and compare it with that resulting when the conventional methods of checking the spinal canal, e.g. hemilaminectomy and laminectomy, are applied. The investigations were carried out in 10 human vertebral columns, in the area of T-12, L-2 and L-4. Torsional loads of up to 20 Nm were applied to the spines and axial rotations were recorded. Laminotomy, hemilaminectomy and laminectomy were done step by step. The loading-unloading cycles were achieved with initial axial rotation and decreasing torsional moment after measurement the dorsal manipulations. It was shown that interlaminar fenestration causes a hardly measurable instability. A laminotomy to 10 x 20 mm, allowing direct repositioning of the posterior vertebral surface, causes a 6% loss of stability. A significant decrease is caused by hemilaminectomy, with a 20% loss and by laminectomy, with 27% loss of rotational stability compared with the intact spine. Rotational instability of the spine causes severe pain and often has to be treated by spondylodesis. The present investigations show that the spinal canal should not be checked by hemilaminectomy or laminectomy. For this we now use intraoperative ultrasound.

Biomechanical Phenomena↗