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Biomedical subjects

D S Terman

Publications and source records attributed to D S Terman.

51 records · Page 3Linked to original sources

Renal failure following gentamicin in combination with clindamycin.

Acute renal failure (ARF) occurred concomitantly with the administration of gentamicin in combination with clindamycin in three patients in whom no other known predisposing cause of ARF could be demonstrated. The evidence for combined nephrotoxicity consisted of the temporal relationship between administration of the antibiotics and the development of ARF, and the prompt improvement in renal function upon cessation of therapy. Complete or partial recovery of renal function occured in all patients. Renal function should be carefully monitored in patients receiving this antibiotic combination.

Acute Kidney Injury↗

Degradation of circulating DNA by extracorporeal circulation over nuclease immobilized on nylon microcapsules.

Studies were undertaken to determine whether deoxyribonuclease I, (DNase I) once immobilized on activated nylon microspheres, would be capable of degrading circulating DNA in vitro and in vivo in an extracorporeal circulation system in dogs. Nylon microspheres were prepared and after gentle hydrolysis and glutaraldehyde treatment, demonstrated a retention of up to 4.73 mg of Dnase I. In vitro studies showed that DNase I immobilized on microspheres degreded a significant percentage of 125I-native DNA (nDNA) within 15 min. Mongrel dogs were injected with 125I-nDNA and a variation in initial t 1/2 in individual animals was observed. Therefore, for experimental studies, 125I-nDNA was injected and decay was recorded during a control period in which untreated microcapsules were utilized in the extracorporeal system. DNase I microspheres were then introduced into the extracorporeal circuit which resulted in an acceleration of degradation of acid precipitable 125I-nDNA. When 200 mug of unlabeled DNA with 125I-nDNA was injected, a similar augmentation of DNA degradation was noted after extracorporeal circulation over DNase I microcapsules. This effect could not be attributed to release of DNase I from the microspheres since no 131I-DNase was detected in the serum or organs of the dogs at the conclusion of the experiments. 125I-nDNA:anti-DNA complexes were passively injected into dogs and after a similar control period of circulation over untreated microcapsules. DNase I microspheres were introduced. Results showed a rapid acceleration in the degradation rate of 125I-nDNA:anti-DNA complexes precipitable with (NH4)2SO4. Extracorporeal circulation over nylon microspheres resulted in no significant alteration of the host's hematocrit or platelet count, and little residual cellular debris on the microcapsules. These data suggest that DNAase immobilized on nylon microspheres may have a potential role in the specific therapy of systemic lupus erythematosus, when it is desirable to hydrolyze DNA circulating free or in combination with antibody.

Animals↗

Specific removal of DNA antibodies in vivo with an extracorporeal immuno-adsorbent.

The selective removal of circulating antibody specific for DNA was affected with an immuno-absorbent consisting of DNA-cellulose incorporated into agar gel. Antisera to DNA obtained from patient with systemic lupus erythematosus was circulated in vitro through experimental and control columns by a dual channel haemodialysis pump and serial aliquots were withdrawn and assayed for antibody. A 65% reduction in DNA binding of serum was achieved at a flow rate of 210 ml/min over a 4-hr period with no release of 125I-labelled DNA from the column into the serum. For in vivo studies, 2-6-3-8 kg rabbits were actively immunized with methylated bovine serum albumin conjugated to single-stranded DNA (MBSA-ssDNA). Whole blood was pumped from the femoral artery through an immuno-adsorbent composed of ssDNA-cellulose in an agar matrix. Results showed significant reductions in ssDNA binding activity over various periods after connection of the rabbit's circulation to the immuno-adsorbent with only minimal changes in BSA binding during the same period. Little release of incorporated 125I-labelled DNA from the column as assayed in the blood and tissues of the experimental animals occurred during the procedure. The immuno-adsorbent columns showed no residual cellular debris or thrombotic material. These results suggest that this immuno-adsorbent system may be used to specifically withdraw circulating DNA antibodies in vivo. Such a system may have clinical potential for specific therapy of systemic lupus erythematosus.

Adsorption↗

Specific extraction of antigen in vivo by extracorporeal circulation over antibody immobilized in collodion-charcoal.

A novel extracorporeal immunoadsorbent is described in which anti-bovine serum albumin (anti-BSA) was entrapped in collodion membranes adherent to activated charcoal particles. This immunoadsorbent was capable of specifically removing circulating BSA in vitro and in vivo in an extracorporeal system in dogs. In preparation of the immunoadsorbent, up to 81.2% of added anti-BSA was retained on collodion-charcoal. In vitro circulation studies demonstrated that anti-BSA collodion-charcoal removed 812% more 125I-BSA than control colloidon-charcoal. For in vivo studies, an extracorporeal circulation system was established and arterial blood was passaged through a continuous flow celltrifuge wherein plasma which was separated from formed elements of the blood was circulated over anti-BSA and control rabbit gamma-globulin collodion-charcoal. 125I-BSA was passively infused into mongrel dogs, and plasma was then circulated over extracorpeal immunoadsorbents for 2 hr. Results showed up to 896% greater uptake of circulating 125I-BSA on the charcoal containing immobilized anti-BSA compared to control charcoal. There was no evidence of release of anti-BSA from the immunoadsorbent since 125I-anti-BSA cpm on the charcoal before and after the experiments were unchanged. In addition, there were no significant alterations in hematocrit, leukocyte counts, serum sodium, potassium, calcium, magnesium, or creatinine levels before and after in vivo procedures. These data suggest that this immunoadsorbent consisting of anti-BSA immobilized in collodion membranes adherent to charcoal particles may specifically withdraw circulating antigens in vivo with minimal release of entrapped antibodies and no significant alteration in the host hematologic and biochemical status.

Animals↗

Specific removal of bovine serum albumin (BSA) antibodies in vivo by extracorporeal circulation over BSA immobilized on nylon microcapsules.

Studies were undertaken to determine whether BSA, once immobilized on activated nylon microspheres, would be capable of specifically removing circulating BSA antibody in vitro and in vivo in an extracorporeal circulation system in dogs. Nylon microspheres were prepared and, after gentle hydrolysis and glutaraldehyde treatment, demonstrated a retention of up to 34.5 mg of BSA. In vitro studies showed that BSA immobilized on microspheres removed a significant percentage of BSA-binding activity. For in vivo studies, an extracorporeal circulation system was established and mongrel dogs were then injected with anti-BSA and anti-HSA antibodies. After an equilibration period, BSA microspheres were introduced into the extracorporeal circulation system. After the insertion of BSA microcapsules, serum exhibited a sharp reduction in BSA binding over the next 15 min, with a more gradual diminution over the ensuing 60 to 90 min. There was no significant reduction in anti-HSA binding over the same time frame. This effect could not be attributed to release of BSA from the microspheres since no 125I-BSA was detected in the serum or organs of the dogs at the conclusion of the experiments. After extracorporeal circulation over nylon microspheres, there were only minimal changes in the host's hematocrit or leukocyte counts and no significant thrombotic material or cellular debris was recoverable on the capsules. These data suggest that antigen immobilized on nylon microspheres may specifically withdraw circulating antibodies in vivo with minimal release of its antigenic material and little alteration in the host's hematologic status.

Animals↗

Localization of neuroblastoma in vivo with tumor-specific antibodies.

Studies of the mouse C-1300 neuroblastoma were undertaken in order to isolate tumor-specific antibodies and harness them for detection of tumors in vivo. Preliminary investigations demonstrated the strain-growth specificity of the neuroblastoma in A/Jax male mice and established the requirement for tumor viability for successful adoptive passage. Intradermally passaged tumor permitted extended survival of mice so that serum could be sampled at intervals for the presence of tumor-specific antibodies. By means of an indirect radioimmunoassay with glutaraldehyde-fixed identified in the serum of tumor-bearing hosts 6 days after inoculation, with a steady increase in antibody levels observed through Day 22. An eluate in which immunoglobulin G antibodies were identified by immunoelectrophoresis was obtained from purified tumor cells by acid buffer incubation. These antibodies were labeled with 125-I, absorbed with normal tissues, and injected into tumor-bearing mice. A selectively collimated single-probe isotope localization was positioned over the intradermal tumor, while the rest of the animal was shielded with lead. With this device, 125-neuroblastoma eluate was significantly taken up in the neuroblastoma but not in the mouse head or in a reticulum cell sarcoma control. Increasing uptake of MOPC 141 125-I-immunoglobulin G was not observed in either tumor. These studies suggest that the mouse neuroblastoma may provide a source of tumor-specific, antibodies and that, with sensitive monitoring devices, these antibodies may be utilized to localize occult neoplastic tissue in vivo.

Animals↗