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Biomedical subjects

R H Rubin

Publications and source records attributed to R H Rubin.

At least 145 records · Page 8Linked to original sources
PubMed1991

Prevention of cytomegalovirus infection in the pediatric renal transplant recipient.

Cytomegalovirus (CMV) infection is the most important single infectious complication of organ transplantation, affecting more than 70% of transplant recipients. Its emergence as a major pathogen has coincided with the use of cytotoxic therapy. Manifestations of serious CMV disease include: pneumonia, hepatitis, gastrointestinal disease, leukopenia and chorioretinitis. CMV is associated with superinfection with opportunistic organisms, graft failure and increased mortality. Serious infection most frequently occurs with primary CMV infection in which latently infected cells from CMV-positive donors are given to seronegative recipients. Pediatric patients who have a lower pre-transplant rate of CMV seropositivity are at particularly high risk of developing serious CMV disease. Preventative efforts range from the ideal but impractical use of only CMV-negative donors (organ and blood products), to the use of CMV hyperimmune globulin and antiviral chemotherapy. Data support the use of prophylactic hyperimmune globulin and preliminary information supports the use of prophylactic high-dose acyclovir in renal transplant patients. Prophylactic gancyclovir alone or with hyperimmune globulin and pre-transplant vaccination with live-attenuated Towne strain CMV vaccine remain investigational.

Antiviral Agents↗
PubMed1991

Non-tumor applications of radioimmune imaging.

The application of radioimmune imaging techniques to the evaluation of non-neoplastic disease is largely based on the same principles as tumor imaging; specificity and high affinity of antibodies. Currently the most common non-tumor applications of antibody imaging are the detection of clots (peripheral and pulmonary emboli), myocardial necrosis (myocardial infarction, myocarditis and cardiac transplant rejection) and focal sites of infection/inflammation. In the area of injection imaging, both antigen-specific and non-specific properties of antibodies have been successfully exploited in imaging studies. While the number of non-tumor applications of antibodies are far fewer than the number of tumor studies, in many cases, they appear to be more reliable. The basis for the reliability of antibodies for detecting non-neoplastic lesions is probably related to the availability of abundant antigen, lack of antigen modulation and enhanced permeability at the lesion site. These observations suggest that there will be rapid proliferation of work in this area.

Animals↗
PubMed1991

Imaging of Pneumocystis carinii pneumonia with 111In-labelled non-specific polyclonal IgG: an experimental study in rats.

The relative sensitivity of imaging with 67Ga-citrate (67Ga) and non-specific human polyclonal IgG radiolabelled with 111In (111In-IgG) for the detection of Pneumocystis carinii pneumonia (PCP) was determined in rats. Pneumocystis carinii pneumonia was induced by low protein diet and dexamethasone. The course of the disease was monitored by serial imaging with 111In-IgG and 67Ga. Diffuse accumulation of both radiopharmaceuticals was observed in the lungs of infected animals (infection was verified by histological examination of the lungs), however, accumulation of 111In-IgG was consistently higher. In rats with early PCP, 111In-IgG imaging revealed pulmonary accumulation in animals with normal chest radiographs and 67Ga scans. In animals successfully treated for PCP, decreased pulmonary accumulation of 111In-IgG coincided with histological improvements. Several animals developed superinfection with bacteria or fungi. These animals had striking focal accumulation of 111In-IgG, in addition to the pattern of generalized uptake. Gallium concentration in these animals did not show this focal accumulation. These observations suggest that 111In-IgG may be useful for detecting PCP and pulmonary abscesses in the immunocompromised host.

Animals↗
PubMed1991

Comparison of 99Tcm-labelled monoclonal anti-granulocyte antibody and 111In-labelled IgG for the detection of focal sites of infection in rats.

The abilities of 99Tcm-labelled monoclonal anti-human granulocyte antibody (AGAb) and 111In-labelled nonspecific polyclonal human immunoglobulin (IgG) to localize at focal sites of inflammation were compared in rats with deep thigh infection due to E. coli. The radiolabelled antibodies were coadministered followed 4-6 and 24 h later by imaging and biodistribution studies. At 4-6 h after injection, the target to background ratio (T/B, lesion to contralateral leg) and percentage residual activity (% RA, counts in the lesion/total body counts) were nearly identical for both antibody preparations. At 24 h, T/B and % RA increased significantly (P less than 0.001) for both proteins but differences between the agents were not significant. In vitro analysis of the binding of AGAb and human polyclonal IgG to rat granulocytes showed a low level of binding with both agents. These results suggest that the primary mechanism of localization, by either antibody preparation in this model, is not antigen related. 111In-labelled nonspecific human IgG and 99Tcm-AGAb are equivalent reagents for the detection of focal sites of infection in the rat.

Animals↗
PubMed1991

The impact of infection on the outcome of transplantation.

The risk of infection in the transplant patient is determined by two factors: the net state of immunosuppression and the environmental exposures the patient encounters. Those infections that do occur in the transplant patient are strongly modulated by the type, intensity, duration, and sequence of immunosuppressive agents administered. A central role in the pathogenesis of all forms of infection in the transplant patient is played by the immunomodulating viruses, particularly cytomegalovirus. Prevention of infection is far better than treatment; when prevention fails and clinical disease develops, patient and allograft survival are directly related to the speed with which diagnosis is made and specific therapy instituted. In order to prevent disease, both antimicrobial prophylaxis and preemptive therapy are being increasingly employed, particularly to blunt the side effects of intensive antirejection therapy.

Bacterial Infections↗
PubMed1991

Imaging focal sites of bacterial infection in rats with indium-111-labeled chemotactic peptide analogs.

Four DTPA-derivatized chemotactic peptide analogs: ForNleLFNleYK-DTPA (P1), ForMLFNH(CH2)6NH-DTPA (P2), ForNleLFK(NH2)-DTPA (P3), and ForNleLFK-DTPA (P4), were synthesized and evaluated for in vitro bioactivity and receptor binding. The peptides were radiolabeled with 111In by transchelation and their biodistribution determined in rats at 5, 30, 60 and 120 min after injection. Localization at sites of infection was determined by scintillation camera imaging in animals with deep-thigh infection due to Escherichia coli. Images were recorded from 5 min to 2 hr after injection. All peptides maintained biologic activity (EC50 for O2-production by human PMN's: 3-150 nM) and the ability to bind to the oligopeptide chemoattractant receptor on human PMN's (EC50 for binding: 7.5-50 nM); biologic activity and receptor binding were highly correlated (r = 0.99). For all the peptides, blood clearance was rapid (half-lives: 21.5, 33.1, 31.6, and 28.7 min for P1, P2, P3, and P4, respectively). Biodistributions of the individual peptides were similar with low levels of accumulation in the heart, lung, liver, spleen, and gastrointestinal tract. In the kidney, P1 had much greater accumulation than other organs. All peptides yielded high quality images of the infection sites within 1 hr of injection. This study demonstrates that 111In-labeled chemotactic peptide analogs were effective agents for the external imaging of focal sites of infection.

Animals↗
PubMed1990

Effect of isoelectric point on biodistribution and inflammation: imaging with indium-111-labelled IgG.

Electrostatic effects play an important role in protein interactions and may alter the biodistribution of antibodies. To study the effect of molecular charge of the biodistribution and infection imaging properties of human polyclonal immunoglobulin G (IgG), its isoelectric point was varied by changing the level of diethylene triamine penta-acetic acid (DTPA) substitution: 0.8, 0.9, 3.7, 5.1 and 5.9 DTPA/IgG. Biodistributions of the different IgG preparations were determined at 10 min, 1, 6, 24, and 48 h post injection in normal rats, and infection imaging properties were determined in rats with Escherichia coli thigh infections. The biodistribution was significantly affected by pI. The immunoglobulin preparations with 0.9 and 3.7 DTPA/IgG showed faster clearance from the circulation and generally lower accumulation in most organs. The images had a target-to-background ratio of approximately 1.3-2.3:1. These results suggest that even though targeting is not affected by the level of DTPA substitutions, preparations with 0.9 and 3.7 DTPA/IgG may be superior imaging agents because of reduced accumulation by background organs.

Animals↗
PubMed1990

P&T Committee review of fluconazole: an effective alternative to antifungal therapy.

Fluconazole is a new antifungal agent available in both oral and parenteral formulations. According to the experts in this roundtable discussion, fluconazole represents a major clinical advance in the treatment of candidiasis and cryptococcosis in cancer patients, patients with AIDS, organ transplant recipients, and other patients at risk for opportunistic mycoses. The pharmacokinetic profile for fluconazole permits infrequent dosing and also makes it ideal for tissue site infections. Fluconazole's low toxicity gives it an advantage over currently available antifungal therapy and will permit prompt presumptive treatment of selected infections.

Antifungal Agents↗
PubMed1990

Approach to immunization in the immunosuppressed host.

An ever-increasing population of immunocompromised individuals, including not only the burgeoning AIDS population but also those patients whose host defenses have been damaged by a wide variety of diseases and their therapies, requires prophylaxis against infectious diseases. Existing vaccines can provide some benefit, but the clinician must always be alert to the fact that vaccine response cannot be assumed and such adjunctive measures as antimicrobial prophylaxis (i.e., amantadine during community-wide influenza outbreaks or penicillin prophylaxis against pneumococcal infection in certain asplenics) and/or intravenous immunoglobulin administration should be considered in some patients. In the future, in addition to developing new vaccines, a major effort should be devoted to the development of immunoadjuvants that would increase the effectiveness of vaccine administration.

HIV Infections↗
PubMed1990

Technetium-99m-human polyclonal IgG radiolabeled via the hydrazino nicotinamide derivative for imaging focal sites of infection in rats.

The biologic behavior of human polyclonal immunoglobulin (IgG) radiolabeled with technetium-99m (99mTc) by a novel method, via a nicotinyl hydrazine derivative, was evaluated in rats. Technetium-99m- and indium-111-IgG were co-administered to normal rats and biodistribution was determined at 2, 6, and 16 hr. The inflammation imaging properties of the two reagents were compared in rats with deep-thigh infection due to Escherichia coli. Blood clearance of both antibody preparations was well described by a bi-exponential function: (99mTc-IgG: t1/2 = 3.82 +/- 0.89 and 57.52 +/- 1.70 hr. 111In-IgG: 3.93 +/- 0.117 and 40.71 +/- 1.26 hr). Biodistributions in the solid organs were similar, however, small but statistically significant differences were detected: 99mTc-IgG greater than 111In-IgG in lung, liver, and spleen; 99mTc-IgG less than 111In-IgG in kidney and skeletal muscle (p less than 0.01). At all three imaging times, target-to-background ratio and percent residual activity for the two compounds were remarkably similar. These studies establish that human polyclonal IgG labeled with 99mTc via a nicotinyl hydrazine modified intermediate is equivalent to 111In-IgG for imaging focal sites of infection in experimental animals.

Animals↗
PubMed1990

Localization of Fc and Fab fragments of nonspecific polyclonal IgG at focal sites of inflammation.

Intact IgG, Fc, Fab, and 1/2Fc (reduced and alkylated Fc) were coupled to DTPA, labeled with indium-111 and administered to rats to compare the ability of fragments of IgG to localize at focal sites of inflammation. Two sets of experiments were performed: First, 1, 6, 24, and 48 hr after injection, biodistribution was determined in healthy animals; second, localization at sites of inflammation was determined by scintillation camera imaging of animals with deep-thigh infection due to Escherichia coli. The biodistribution studies demonstrated differences in kidney and liver localization: IgG less than Fc less than Fab less than 1/2Fc (kidney), Fc less than 1/2Fc less than IgG less than Fab (liver). The imaging studies revealed that target-to-background ratio (T/B) and percent residual activity (%RA) for IgG was significantly greater (p less than 0.01) than 1/2 Fc or Fab, and T/B for IgG was greater (p less than 0.01) than Fc. These studies suggest that the Fc portion of IgG is the fragment with the best imaging properties.

Animals↗
PubMed1989

111In-labeled nonspecific immunoglobulin scanning in the detection of focal infection.

We performed radionuclide scanning after the intravenous injection of human IgG labeled with indium-111 in 128 patients with suspected focal sites of inflammation. Localization of 111In-labeled IgG correlated with clinical findings in 51 infected patients (21 with abdominal or pelvic infections, 11 with intravascular infections, 7 with pulmonary infections, and 12 with skeletal infections). Infecting organisms included gram-positive bacteria, gram-negative bacteria, Pneumocystis carinii, Mycoplasma pneumoniae, and Candida albicans. No focal localization of 111In-labeled IgG was observed in 63 patients without infection. There were five false negative results, and nine results were unusable. Serial scans were carried out in eight patients: continued localization correctly predicted relapse in six, and the absence of localization indicated resolution in two. To determine whether 111In-labeled IgG localization was specific for inflammation, we studied 16 patients with cancer. Focal localization occurred in 13 of these patients (5 with melanomas, 5 with gynecologic cancers, and 1 each with lymphoma, prostate cancer, and malignant fibrous histiocytoma). No localization was seen in patients with renal or colon cancer or metastatic medullary carcinoma of the thyroid. We conclude that 111In-labeled IgG imaging is effective for the detection of focal infection and that serial scans may be useful in assessing therapeutic efficacy. This technique may also be helpful in the evaluation of certain cancers.

Abdomen↗