[Staphylococcal infections in implantation surgery--pathogenetic mechanisms].
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Biomedical subjects
Publications and source records attributed to G Peters.
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Experimental studies on dogs with staphylococcal osteomyelitis showed that it is possible to reduce florid bone suppuration by the use of hydroxyapatite granules containing an antibiotic or antiseptic. In our series the use of flucloxacillin hydroxyapatite granules was superior to other treatment methods. Twelve patients were treated with thorough sequestrectomy, reliable wound closure and suitable stabilization supplemented with an implant of antibiotic or antiseptic hydroxyapatite granules, and an autologous spongiosa graft for large bone cavities or for discontinuity between the bone ends. The results of this preliminary study showed the treatment to be effective.
Forty-four patients were evaluated for ototoxicity following treatment with the chemotherapeutic agent cis-platinum. Statistically significant hearing changes at 2,000 Hz (p less than 0.001); 4,000 Hz (p less than 0.05); and 8,000 Hz (p less than 0.001) were observed. Chi-square analysis demonstrated that at 8,000 Hz patients who had lower than average thresholds prior to chemotherapy were more likely to experience greater threshold shift than those patients whose pre-chemotherapy thresholds were higher than average. In this patient sample, there was no significant correlation shown between serum creatinine levels and ototoxicity.
The effect of sodium selenite on experimental myocardial infarction was investigated in 47 domestic pigs, with a major emphasis on the hemodynamic antiarrhythmic effects of selenium. Intravenous sodium selenite administered in a dose of 1-2 mg/kg body weight produced a favorable pharmacologic effect. The hemodynamic action consisted in an increase of heart rate, and the maximum aortic flow rate, cardiac output, minute volume of the heart and coronary flow, as well as a decrease in total peripheral resistance. Selenium's antiarrhythmic effect was manifested in reduced occurrence of ventricular extrasystoles and flutter, and the disappearance of "late potentials" in the peri-infarction area.
Staphylococcus epidermidis infection of plastic catheters is often associated with heavy deposits of slime. To test whether this slime affects the human cellular immune response, its effect on the lympho-proliferative response of mononuclear cells to polyclonal stimulators was measured. Slime drastically reduces this response. Its inhibitory action was not immediate but took place over a few days and resulted in destruction of affected cells. The effect is dose related. This inhibition of cellular response may contribute to S epidermidis infection of implanted prostheses.
Insulin is degraded in plasma or serum from NMMAA-diabetic rats, at 37 degrees C in vitro, as shown by losses of both immunoreactivity and biological activity on fat pad tissue. The rate of insulin degradation was not notably influenced by plasma pH, in the range 7.2-8.3. Presumably due to destruction of insulin in the course of the 120 min bioassay incubation at 37 degrees C and pH 7.4, the potency of crystalline insulin on fat pad tissue was apparently lower in the presence of serum from NMMAA-poisoned rats than with control serum. Although plasma from control rats also lost some insulin within 120 min at 37 degrees C, the loss was much less pronounced. At 0 degree C, no loss of insulin occurred in serum samples from the poisoned animals. Therefore, the radioimmunoassay, which is performed at 0 degree C, yields valid measurements of insulin concentrations in these samples. Our observations provide an explanation for the erroneously low values of insulin detected by bioassay in serum from NMMAA-diabetic rats.
Infections of pacemaker electrodes and/or aggregate pockets are usually caused by staphylococci, primarily Staphylococcus epidermidis. From in vitro experiments it can be demonstrated that staphylococci are able to adhere to the plastic electrode sheath, to multiply there, and to form microcolonies. Furthermore, the staphylococci produce a slimy amorphous substance with which they are completely covered after a 24-hour incubation. No difference was noticed between the in vitro experiment situation and that occurring in pacemaker infection in humans. This slimy material may be responsible for the maintenance of the infection and the protection of the enclosed bacterial cells against natural host defense mechanisms and antibiotic treatment.
Mouse mammary tumor virus, a type-B retrovirus, was shown to mediate fusion of cultured cells following low-pH treatment. Fusion could be demonstrated both with virus-infected cells or with uninfected cells carrying freshly absorbed virus. Although the fusion response was variable between different cell lines, one line of MMTV-infected mink lung cells, designated MGR4, was particularly susceptible to fusion at reduced pH. Since expression of MMTV in these cells is strongly regulated by glucocorticoids, it was possible to demonstrate that cell fusion was dependent on MMTV-encoded functions. With MGR4 cells, a pH threshold for membrane fusion was observed, centered on pH 5.5, at which 50% of the cells were fused. At lower pHs virtually all of the cells in the monolayer fused. These results are similar to those described for other virus groups and are consistent with the idea that most enveloped animal viruses infect cells by a common mechanism involving membrane fusion triggered by low pH.
Approximately 50% of tumors induced by mouse mammary tumor virus (MMTV) contain an acquired provirus within a limited region of chromosomal DNA, termed int-2. We have extended our previous characterization of this locus and have mapped provirus integration sites in 21 independent tumors. Although integration occurs at multiple sites, proviruses within int-2 are distributed into two oppositely oriented groups whose transcription is directed away from a central domain. Provirus insertion in int-2 is accompanied by expression of RNA derived, at least in part, from this central domain. Since the RNA is not detected in normal mammary tissue, we conclude that MMTV integration activates the expression of a cellular gene within int-2 and that this event may contribute to tumorigenesis.
The extracellular slime substance produced by Staphylococcus epidermidis was investigated. Slime production was assessed by bacterial agglutination in the presence of concanavalin A (Con A) or poly-L-lysine and by bacterial adherence to polyethylene. Media for slime production was optimized using these criteria. A phenol-saline extract of crude slime was separated into four fractions on a DEAE-sepharose column. Total protein and sugar content and the monosaccharide constituents were determined. Crude slime and the phenol-saline extract showed a strong precipitation reaction with Con A and poly-L-lysine (double diffusion). Fractions I and II containing mannose as the most abundant sugar reacted with Con A and two other mannose-specific lectins (Lens culinaris, Pisum sativum). This reaction could be inhibited by mannose. Fractions III and IV were precipitated by poly-L-lysine, probably due to a reaction with glucuronic acid which was only present in these fractions. Precoating of polyethylene with crude slime, phenol-saline extract and fractions III and IV resulted in a marked inhibition of attachment of staphylococcal cells. Production of the extracellular slime substance was completely inhibited by subinhibitory concentrations of the glycosylation inhibitor tunicamycin, whereas penicillin had no influence. Extracellular slime substance produced by S. epidermidis seems to be a complex of glycoconjugate character and plays an important role in the attachment to synthetic polymers. The production of slime by staphylococci can be easily determined using mannose specific lectins and poly-L-lysine.
Staphylococcus epidermidis infections on foreign bodies made of plastic are caused by special and complex mechanisms. The staphylococcal cells are able to adhere to and grow on polymer surfaces in vivo and in vitro. In the course of colonization they produce an extracellular substance ('slime') which eventually covers them. It is thought that the staphylococcal slime has several biological functions, including promoting adhesion and protection against both antibiotics and host defence mechanisms. In patients, the removal of a colonized device should be accompanied by the parenteral administration of highly effective antistaphylococcal drugs, such as vancomycin.
Two regions of mouse DNA which constitute common provirus integration sites in tumors induced by mouse mammary tumor virus have been identified and designated int-1 and int-2. By examining a series of hamster-mouse somatic cell hybrids, we mapped the int-2 locus to mouse chromosome 7 and confirmed the previous assignment of int-1 to chromosome 15. This constitutes proof that int-1 and int-2 are discrete genetic loci. It is therefore possible that proviral activation of two distinct cellular genes may result in the same neoplastic disease.
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The releasing kinetic of antibiotics from tricalcium phosphate beads was studied in animal experiments. The porous TCP-beads were filled with antibiotics and coated with biodegradable substances for delaying the release of the antibiotics. There were high tissue levels of antibiotics in the surrounding bone for many days. This method gains an increase in therapeutic safety in treatment of osteomyelitis. The coated TCP-antibiotic beads are used simultaneously as bone graft and for treatment of the bone infection. There is no need for further operation.
We have prepared specific probes for unique-sequence cellular DNA adjacent to each of the newly integrated proviruses in tumors induced by mouse mammary tumor virus (MMTV). The use of such probes to screen a large number of independent mammary tumors in the BR6 strain of mouse has indicated that in at least 17 out of the 40 tumors examined so far, an MMTV provirus has integrated into a common chromosomal domain. A 10 kb Eco RI fragment of single copy DNA from this region has been isolated and partially characterized by restriction enzyme mapping. Of the proviruses located within this fragment in different tumors, all but one are complete, in the same orientation, and clustered within about 3 kb of cellular DNA. These findings are consistent with an insertional mutagenesis model for tumorigenesis by MMTV, in which the integration of a provirus in a particular region of cellular DNA may activate a neighboring oncogene. The region we describe here appears to be different from that reported for mammary tumors in the C3H strain of mouse.
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