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Biomedical subjects

C D Russell

Publications and source records attributed to C D Russell.

At least 37 records · Page 2Linked to original sources
PubMed1996

Intraperitoneal radioimmunotherapy of ovarian cancer with lutetium-177-CC49.

UNLABELLED: Twelve ovarian cancer patients who failed chemotherapy entered a Phase I trial of intraperitoneal 177Lu-CC49 antibody. METHODS: Patients had disease confined to the abdominal cavity +/- retroperitoneal lymph nodes, adequate organ function and no previous radiation. RESULTS: Side effects included mild discomfort with administration (1/12), delayed transient arthralgia (2/12), and mild marrow suppression (calculated marrow doses of 11-54 cGy). The maximum tolerated dose has not been reached with levels of 10, 18, 25 and 30 mCi/m2. Radioimmunoscintigraphy revealed localization consistent with tumor in 11 of 12 patients. One of eight patients with gross disease had > 50% tumor reduction after therapy, while six progressed and one went off study with stable disease. Of patients with microscopic or occult disease, one relapsed at 10 mo and three remain without evidence of disease after 18 mo. CONCLUSION: Intraperitoneal radioimmunotherapy with 177Lu-CC49 is well tolerated and appears to have antitumor activity against chemotherapy-resistant ovarian cancer in the peritoneal cavity.

Adenocarcinoma↗
PubMed1996

Phase II study of dual 131I-labeled monoclonal antibody therapy with interferon in patients with metastatic colorectal cancer.

The combination of COL-1 (anti-CEA) and CC49 (anti-TAG-72) has shown an increase in binding and distribution in colon cancer by immunoperoxidase staining compared to either antibody alone. To overcome tumor heterogeneity and allow delivery of higher radiation dose, 131I-labeled COL-1 and CC49 at a total dose of 75 mCi/m2 (2775 MBq/m2) were simultaneously administered to 14 patients with metastatic colon cancer. alpha-IFN (3 x 10(6) IU) was given s.c. on days -5 to +3 to increase carcinoembryonic antigen and TAG-72 antigen expression. Most patients had mild symptoms during IFN therapy, including mild neutropenia, fever, and malaise, which rapidly subsided after IFN cessation. No acute allergic reactions occurred with radioimmunotherapy; two patients experienced transient, delayed grade 2 arthralgias. Transient neutropenia and/or thrombocytopenia, which was maximal at 4-6 weeks, were consistent side effects without adverse events. All patients had tumor localization, and 13 of 14 patients achieved 4+ (highest grade) localization readings to at least one known site of disease. No objective responses occurred; 4 patients were stable and 10 progressed. Tumor dose estimates varied from 393 to 1327 cGy, including liver and extrahepatic sites. Combining two complementary antibodies and IFN administration appeared to increase localization intensity and radiation doses at tumor sites as compared to historical controls. The amount of radiation delivered to tumor sites was still below that required to cause tumor regressions in metastatic colorectal cancer.

Adult↗
PubMed1995

Techniques for measuring renal transit time.

A variety of techniques have been used for quantitative estimation of renal transit time. We compared different indices of transit time in a group of 30 patients having baseline and ACE inhibitor technetium-99m mercaptoacetyltriglycine (MAG3) renography prior to arteriography: peak time, mean transit time, and the ratio of background-subtracted counts at 20 min to those at 3 min. Each index was calculated from whole-kidney ROI, cortical ROI, and cortical factor (by factor analysis). The strongest correlations between angiographic percent of stenosis and transit time index were observed for the peak time (Spearman p=0.469, n=53, P <0.005) and for the R20/3 (again p=0.469, n=53, P <0.005) using the whole-kidney ROI and using only the baseline data without captopril. (Spearman's p is simply the correlation coefficient calculated from rank in list, which allows for nonlinear correlation.) Thus simple indices of transit time (whole-kidney peak time and R20/3) correlated as well with the observed pathology as did more complicated methods that required deconvolution, factor analysis, or selection of a cortical ROI.

Adult↗
PubMed1995

Radionuclide evaluation of renal transplants.

Chronic renal failure caused by hypertension or by parenchymal kidney disease is a very common global health problem. Patients with chronic renal failure have two therapeutic options, dialysis and transplantation, of which transplantation has become a preferred modality. This review article is an update of a more comprehensive previous review (Semin Nucl Med, 181-198, 1988) and concentrates on the changes that have taken place in this field in recent years. These changes comprise new criteria for the selection of transplant candidates, newer techniques for the diagnosis of medical and surgical complications after transplantation, the use of new tracers (Tc-99m MAG3), and new antirejection regimens.

Female↗
PubMed1995

Comparison of single-injection multisample renal clearance methods with and without urine collection.

UNLABELLED: Single-injection renal clearance methods based on plasma clearance alone, without urine collection, are sometimes met with skepticism. They require data extrapolation to infinite time, which is hard to justify a priori. It has been asserted that they are less accurate for rapidly cleared tubular agents than for slowly cleared glomerular filtration rate agents. In this study, we compare urine-based and urine-free methods for the tubular agents 99mTc-MAG3 and 131I-OIH. METHODS: In 18 patients, dual-tracer plasma data were obtained from 4 to 90 min after injection (nine samples). Urine was also collected for 90 min (in two voidings). The urine counts wre corrected for residual bladder activity by pre- and postvoid dual-channel gamma camera images. RESULTS: When comparing the two methods of clearance calculations, the difference between urine-based and urine-free measurements 1 +/- 5 ml/min for 99mTc-MAG3 and 23 +/- 8 for 131I-OIH (mean +/- s.e. of the mean). For 99mTc-MAG3, the regression line did not differ significantly from the line of identity. The correlation coefficient was 0.94 for both agents. CONCLUSION: Urine collection is not necessary to measure renal clearance, even for the rapidly cleared tubular agents, except at low clearance levels (when the small absolute error corresponds to a large percentage error).

Glomerular Filtration Rate↗
PubMed1994

Quantitation of renal parenchymal retention of technetium-99m-MAG3 in renal transplants.

UNLABELLED: When imaging renal transplants with tubular agents, such as mercaptoacetyltriglycine, marked parenchymal retention is a hallmark of acute rejection (AR) or acute tubular necrosis (ATN). (AR can be distinguished from ATN by the time course on serial studies.) The quantitative relationship of retention to uptake can be measured by dividing the background-corrected renal activity at 20 min by that at 3 min. METHODS: The diagnostic value of this ratio (R20/3) was tested in a series of 555 renograms. Because patients with mild disease have minimal abnormalities, the patients were ranked by their estimated severity of disease (1-4 for abnormal and 0 for normal). RESULTS: R20/3 was found to correlate strongly with severity of ATN (Spearman's rho = 0.879, p < 0.001, n = 168) and also with severity of AR (rho = 0.888, p < 0.001, n = 267). There were two (3%) false-positive results in 64 normal patients. CONCLUSION: If 0.8 is taken as the upper limit of normal for R20/3, then among patients with disease severity 3 or 4, there were no false-negative findings in 104 patients with ATN or in 203 patients with AR. R20/3, despite its simplicity, is an effective diagnostic parameter.

Graft Rejection↗
PubMed1994

Treatment of metastatic prostate carcinoma with radiolabeled antibody CC49.

UNLABELLED: A Phase II trial of 75 mCi/m2 131I-anti-TAG-72 high-affinity antibody CC49 was studied in 15 patients with hormone-resistant metastatic prostate cancer. METHODS: Patients had adequate renal, liver and hematopoietic function. No previous cytotoxic chemotherapy was allowed and previous radiation was limited to 20% of the active bone marrow. RESULTS: No acute adverse reactions occurred, but all patients had evidence of an immune response to CC49 by 4 wk. Six of 10 symptomatic patients had bone pain relief, but no patients met the radiographic or PSA criteria for objective response. Positive imaging of bone and/or soft-tissue lesions was noted for 13 of the 15 patients. CONCLUSIONS: CC49 had a high frequency of tumor localization with evidence of anti-tumor effects (pain relief).

Adenocarcinoma↗
PubMed1993

Lipoprotein lipase regulation by insulin and glucocorticoid in subcutaneous and omental adipose tissues of obese women and men.

There are marked variations in the activity of lipoprotein lipase (LPL) among adipose depots, particularly in women. Consistent with data on LPL activity, the level of expression of LPL mRNA was lower in omental (OM) than subcutaneous (SQ) adipose tissue of women. To investigate the cellular basis of these differences, OM and SQ adipose tissues obtained at surgery from obese men and women were placed in organ culture for 7 d with varying concentrations of insulin and dexamethasone. Insulin increased levels of LPL mRNA and LPL activity in abdominal SQ but not OM adipose tissue. Dexamethasone also increased LPL mRNA and LPL activity, and these effects were more marked in the OM adipose tissue, particularly in men. When insulin and dexamethasone were added together, synergistic increases in LPL activity were seen in both depots, and this was in part explained at the level of LPL mRNA. The SQ depot was more sensitive to the effects of submaximal doses of dexamethasone in the presence of insulin. The maximum activity of LPL induced by insulin or insulin plus dexamethasone was higher in the SQ than in the OM depot of women, and this was associated with higher levels of LPL mRNA. Rates of LPL synthesis paralleled LPL mRNA levels. These data show that insulin and glucocorticoids influence human adipose tissue LPL activity at the level of LPL gene expression, as well as posttranslationally, and that responsiveness to these hormonal effects is dependent on adipose depot and gender.

Abdomen↗
PubMed1993

Direct localization comparison of murine and chimeric B72.3 antibodies in patients with colon cancer.

To compare radiolocalization of murine B72.3 (m-B72.3) and mouse/human chimeric B72.3 (ch-B72.3) antibodies, five patients with biopsy confirmed adenocarcinoma of the colon received both radiolabeled antibodies 4 or 7 days before laparotomy. Following antibody administration, preoperative gamma camera images showed localization to sites of disease in four of the five patients. Autoradiography of resected specimens showed that both labeled antibodies localized specifically to the tumor with only minimal amounts in normal tissues. Radioactivity from each isotope in biopsy specimens of tumor and normal tissues was quantitated by scintillation gamma counting. Comparison of the percentages of injected activities for each antibody in resected tumor and normal tissue yields tumor to normal tissue radiolocalization ratios of 2.7-13.3 and 0.9-6.3 for murine and chimeric antibodies, respectively. The higher ratios for murine antibody were due to lower normal tissue levels, reflecting its faster clearance from the circulation, whereas the quantitative uptake of labeled antibody was always greater with the chimeric antibody. The chimera to murine antibody ratios in tumor of 1.1-2.7 suggest modest enhancement of tumor localization with chimeric antibody because of its longer half-life.

Aged↗
PubMed1993

Optimum sample times for single-injection, multisample renal clearance methods.

The best choice of sample times for measuring renal function in adults by single-injection multisample plasma clearance methods was determined by Monte Carlo simulation, using a two-compartment model with parameters chosen to fit average values (from published clinical studies) for each of the three radiopharmaceuticals 99mTc-MAG3, 99mTc-DTPA and 131I-ortho-iodohippurate. Random errors were added and the simulated data were then fit to a two-exponential model using a weighted nonlinear curve fitting method. The calculated clearance values were compared with the original values to determine random and systematic errors for different selections of sample time for each radiopharmaceutical at various levels of renal function. The results show that for research-level accuracy with a GFR agent such as 99mTc-DTPA, plasma sampling must begin by 10 min after injection and continue at least 3 hr (in adults). With an ERPF agent such as 99mTc-MAG3 or 131I-OIH, sampling must begin by 5 min and continue for at least 90 min. Six logarithmically distributed samples are sufficient.

Glomerular Filtration Rate↗
PubMed1992

Renal transplant hypertension caused by iliac artery stenosis.

A captopril renal study performed with both radiohippuran and 99mTc-MAG3 demonstrated the typical changes of a hemodynamically significant renal artery stenosis in a hypertensive renal allograft recipient. Arteriography demonstrated high grade stenosis not of the renal artery but of the iliac artery. After successful angioplasty, the patient's hypertension resolved.

Captopril↗
PubMed1992

Phase I trial of iodine-131-chimeric B72.3 (human IgG4) in metastatic colorectal cancer.

Twelve patients with metastatic colorectal cancer participated in a Phase I trial of 131I-labeled chimeric B72.3 (human IgG4). Consecutive groups of patients received 18 mCi/m2, 27 mCi/m2 and 36 mCi/m2. No acute side effects related to antibody administration were noted. Bone marrow suppression was the only side effect; it was dose-dependent and correlated with whole-body radiation dose estimates. The lowest dose level produced no marrow suppression, whereas 27 mCi/m2 resulted in Grade 1 and 2 marrow suppression in two of three patients. The maximum tolerated dose was 36 mCi/m2 with all six patients at this dose level having at least Grade 1 and two patients with Grade 3 and 4 marrow suppression. Eight of 12 patients had radioimmune imaging of tumor sites at 5-22 days. Seven patients had an antibody response to initial infusion. On retreatment, whole-body kinetics and imaging were altered for patients with a high anti-ch-B72.3 response. Thus, chimeric B72.3 (IgG4) has limited utility as a means of delivering multiple therapeutic doses of 131I in the majority of patients; alternative strategies including second generation anti-TAG-72 monoclonal antibodies, other radioisotopes and other chimeric human isotypes will need to be pursued.

Adenocarcinoma↗
PubMed1991

Diagnosis of renovascular hypertension after renal transplantation.

Hypertension in renal transplant recipients is an important risk factor for graft function and cardiovascular morbidity and mortality. The mechanisms of posttransplant hypertension are not well understood. Most of the time, the nature of this hypertension is multifactorial. Rejection, both acute and chronic, recurrent renal disease, graft renal artery stenosis, native kidney disease and drug therapy with steroids and cyclosporin have all been implicated. Where a single cause can be identified, the therapy can be rational and often very successful. For this reason, the diagnosis of graft renal artery stenosis is important, because percutaneous transluminal angioplasty or surgery can lead to the cure of hypertension and improvement of the graft function. Noninvasive testing, using captopril renography for the diagnosis of hemodynamically significant renal artery stenosis, presently yields encouraging results.

Captopril↗
PubMed1991

Simplified methods for renal clearance in children: scaling for patient size.

Development and validation of simplified renal clearance methods has required a research data base of multiple blood samples drawn over a substantial time interval, which is difficult to obtain for children. While the medical risks entailed in drawing multiple samples may be negligible, the problems of parental and institutional consent make such studies more difficult in the pediatric population. Scaling for patient size permits combining data from patients of different age and limits the number of studies required. A scaling technique is presented and evaluated here. With scaling, adult data can be used successfully to predict pediatric responses and to develop pediatric methods based on adult data alone. Inclusion of pediatric data improves the fit and permits development of generic methods that work with both adults and children.

Adolescent↗