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Biomedical subjects

L G Hunsicker

Publications and source records attributed to L G Hunsicker.

At least 55 records · Page 3Linked to original sources
PubMed1992

A controlled clinical trial of angiotensin-converting enzyme inhibition in type I diabetic nephropathy: study design and patient characteristics. The Collaborative Study Group.

A placebo-controlled, double-blind clinical trial has been initiated to determine whether angiotensin-converting enzyme inhibitor (ACEI) therapy with captopril (25 mg three times daily) slows the progressive loss of renal function in patients with type 1 diabetes mellitus. Entry criteria include; (1) ages 18 to 50 yr; (2) onset of insulin-dependent diabetes before the age of 30 yr, insulin dependent for at least 7 yr; (3) 24-h urine protein excretion > 500 mg, plus: (a) diabetic retinopathy or (b) if no retinopathy, a renal biopsy diagnosis of diabetic nephropathy; (4) serum creatinine (SCr) < 2.5 mg/dL; (5) informed consent. Patients follow strict medical management protocols. Systemic blood pressure is controlled to predefined goals (< 140-90 mm Hg). The primary outcome of the Study is a doubling of the patients' entry SCr to at least 2 mg/dL confirmed by a > 50% decrease in GFR by radioactive iothalamate clearance technique. Baseline characteristics of the cohort at entry into the Study are (mean +/- SD): male/female, 52%/48%; age, 35 +/- 8 yr; duration of diabetes, 21 +/- 7 yr; duration of proteinuria, 2.8 +/- 3.3 yr; duration of retinopathy, 4.5 +/- 4.1 yr; 50% of cohort presented with hypertension, duration, 4 +/- 4.7 yr; blood pressure, 139/86 +/- 19/12; SCr, 1.35 +/- 0.44 mg/dL; GFR 78 +/- 32 mL/min; BUN, 24 +/- 11 mg/dL; proteinuria, 3.1 +/- 3.3 g/day; cholesterol, 236 +/- 50 mg/dL; total glycosylated hemoglobin, 11.1 +/- 2.1%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Design and statistical issues of the Modification of Diet in Renal Disease Trial. The Modification of Diet in Renal Disease Study Group.

The Modification of Diet in Renal Disease Trial is a multicenter randomized clinical trial for men and women aged 18-70 years with chronic renal disease who are not on dialysis and who have not had a kidney transplant. Study participants are randomized in a 2 x 2 factorial design to diets containing different amounts of protein and phosphorus and to two levels of blood pressure control. The prescribed modifications differ depending on the level of a patient's kidney function. The primary outcome variable to compare diet or blood pressure groups is each patient's slope (or the change) in glomerular filtration rate with time. This paper describes the study design with particular emphasis on sample size determination. Special statistical analysis issues that arise with slope as the outcome are also discussed.

Adolescent↗
PubMed1990

Utility of radioisotopic filtration markers in chronic renal insufficiency: simultaneous comparison of 125I-iothalamate, 169Yb-DTPA, 99mTc-DTPA, and inulin. The Modification of Diet in Renal Disease Study.

Assessment of glomerular filtration rate (GFR) with inulin is cumbersome and time-consuming. Radioisotopic filtration markers have been studied as filtration markers because they can be used without continuous intravenous (IV) infusion and because analysis is relatively simple. Although the clearances of 99mTc-diethylenetriamine-pentaacetic acid (DTPA), 169Yb-DTPA, and 125I-iothalamate have each been compared with inulin, rarely has the comparability of radioisotopic filtration markers been directly evaluated in the same subject. To this purpose, we determined the renal clearance of inulin administered by continuous infusion and the above radioisotopic filtration markers administered as bolus injections, simultaneously in four subjects with normal renal function and 16 subjects with renal insufficiency. Subjects were studied twice in order to assess within-study and between-study variability. Unlabeled iothalamate was infused during the second half of each study to assess its effect on clearances. We found that renal clearance of 125I-iothalamate and 169Yb-DTPA significantly exceeded clearance of inulin in patients with renal insufficiency, but only by several mL.min-1.1.73m-2. Overestimation of inulin clearance by radioisotopic filtration markers was found in all normal subjects. No differences between markers were found in the coefficient of variation of clearances either between periods on a given study day (within-day variability) or between the two study days (between-day variability). The true test variability between days did not correlate with within-test variability. We conclude that the renal clearance of 99mTc-DTPA, 169Yb-DTPA, or 125I-iothalamate administered as a single IV or subcutaneous injection can be used to accurately measure GFR in subjects with renal insufficiency; use of the single injection technique may overestimate GFR in normal subjects.

Creatinine↗
PubMed1989

Increased frequency of posttransplant lymphomas in patients treated with cyclosporine, azathioprine, and prednisone.

We have documented seven B cell lymphomas over a six-month period in 132 (5.3%) kidney and heart allograft recipients immunosuppressed with cyclosporine, azathioprine, and prednisone (triple therapy). This is a significant increase (P less than 0.0001) over the number of such tumors seen by us previously. Only 2 lymphomas had occurred in 669 cadaver and 29 living-related kidney allografts treated with azathioprine and prednisone alone (0.3%). In 160 cadaver kidney recipients treated with cyclosporine and prednisone there have been no lymphomas. Similarly in 14 living-related kidney recipients who were transplanted since the introduction of triple therapy for cadaver grafts, but continued to receive only azathioprine and prednisone, no lymphomas occurred. There seemed to be a clear relationship between this increase and the use of triple therapy. This led us to examine other possible contributing factors. A case control study has not shown any other factor that differs in patients in whom lymphomas developed. We have only been able to demonstrate Epstein Barr virus nuclear antigen in the cells of one tumor. Four of these 7 tumors were monoclonal, one polyclonal, and two indeterminate. All patients had their immunosuppression withdrawn and six received intravenous acyclovir. Three patients have shown some response but four patients died. Triple therapy is being used by many centers to reduce the level of cyclosporine toxicity. We wish to sound a note of caution that this may result in an increased incidence of posttransplant lymphomas.

Adult↗
PubMed1989

Appearance of type II diabetes mellitus in type I diabetic recipients of pancreas allografts.

To determine the cause of hyperglycemia appearing after pancreas transplantation in type I diabetic recipients, we performed 65 oral glucose tolerance tests with serum insulin and C-peptide determinations in 32 patients with pancreas grafts functioning two or more months following transplantation. We correlated these results with estimates of graft size obtained by magnetic resonance imaging (MRI) and values of urinary amylase as a measure of pancreatic exocrine function. A total of 33 studies were obtained in 20 patients at times of normal glucose tolerance, and normal ranges for serum insulin and C-peptide levels were established; 32 studies in 17 patients during periods of glucose intolerance revealed values of serum insulin and C-peptide that were within the normal range, though the time to peak values was delayed to 2 hr, characteristic of type II diabetes. Only 3 of 17 patients examined by MRI had significant pancreatic allograft atrophy. These patients also had low urinary amylase excretion, and the only values for serum C-peptide that were below the normal range. The other 14 hyperglycemic patients had normalized pancreas grafts, normal urinary amylase excretion, and normal values for serum insulin and C-peptide. In our experience, then, in 76% of patients with hyperglycemia more than 2 months following pancreas transplantation, the cause was appearance of type II diabetes rather than destruction of the allograft with recurrence of type I diabetes. This observation has important implications for the definition of pancreas allograft failure and for the management of pancreas allograft recipients with hyperglycemia.

Amylases↗
PubMed1989

Pancreatic transplants: evaluation with MR imaging.

Eighty-eight magnetic resonance (MR) imaging studies of 31 pancreas transplants in 30 patients were performed. The postoperative graft usually appears enlarged and inhomogeneous, with patchy areas of increased signal intensity on T2-weighted images that may last 3-4 weeks. During acute rejection, T1-weighted images of graft abnormalities show a decrease in signal intensity, similar to that of muscle, and T2-weighted images show an increase in signal intensity, equal to or higher than that of the bladder. The pattern of abnormal signal is most frequently multifocal but can be diffuse, and the graft may be enlarged. During recovery from rejection, the graft parenchyma shows a decrease in signal intensity (less than that of the bladder) on T2-weighted images when compared with that of acute rejection. During chronic rejection the graft is small and shows low signal intensity, slightly higher than or similar to that of muscle, on both T1- and T2-weighted images. MR imaging appears to be useful for detection of early pancreas allograft rejection and complications in conjunction with clinical findings, laboratory data, and other radiologic procedures.

Acute Disease↗
PubMed1989

Application of magnetic resonance imaging in pancreas transplant.

Various imaging methods have been used in the differential diagnosis of pancreas-transplant dysfunction. As early as 1977, angiography and radionuclide studies ([75Se]seleno-DL-methionine) were used to evaluate pancreas allografts. More recently, the use of 99mTc-labeled DTPA, computed tomography, and ultrasonography has been described, and abnormal findings associated with rejection have been reported with these imaging methods. However, no attempt has been made to determine the ability of each method to detect rejection and to differentiate graft dysfunction caused by rejection from dysfunction by other causes. We summarize our experience with the application of magnetic resonance imaging (MRI) in pancreas transplantation and a comparative study of radionuclide 99mTc-DTPA scans, ultrasonography, and MRI in the detection and differentiation of pancreas-graft dysfunction.

Adult↗
PubMed1988

Pancreatic transplant imaging.

Forty-four clinical episodes of suspected (pancreas) transplant rejection in 17 pancreatic transplantation patients were reviewed retrospectively. The clinical impression of acute graft rejection, chronic rejection, or nonrejection in each episode was correlated with the results of 19 nuclear medicine, 12 ultrasound (US), and 44 magnetic resonance (MR) imaging studies. US was found to be a moderately sensitive (82%) method of detecting graft rejection. US also was effective in identifying intra- and peripancreatic fluid accumulations. Nuclear medicine imaging was also a sensitive technique (86%) and the only modality that provided physiologic information regarding graft perfusion. MR imaging allowed correct prediction of the presence or absence of graft rejection in 39 of 44 cases (sensitivity, 100%; specificity, 76%) and was an effective means of detecting pathologic fluid collections. Nuclear medicine, US, and MR imaging are all believed to be sensitive methods of detecting graft rejection and are complementary adjuncts to the clinical evaluation of pancreatic transplants.

Diagnostic Imaging↗
PubMed1987

Glomerular sieving of high molecular weight proteins in proteinuric rats.

To characterize the permeability of the glomerular capillary wall to high molecular weight proteins in normal and proteinuric rats, we determined the glomerular sieving coefficients (GSC) of radioiodinated marker proteins of known size and charge by means of a paired label, tissue accumulation method previously validated in this laboratory. In one group of rats (Series A) the GSCs of 125I-anionic IgG (aIgG-molecular weight [mol wt] 150,000, pI 4.9) and 131I-neutral IgG (nIgG-pI 7.4 to 7.6) were measured simultaneously. In Series B, the GSC of a second anionic marker, 131I-human ceruloplasmin (Crp-mol wt 137,000, pI 4.9) was compared to that of 125I-nIgG. As in the previous report, the labeled proteins were not degraded or deiodinated during the 20 minute clearance period for GSC determination. Within Series A and B, three subgroups of rats were studied: control saline-infused rats, rats made acutely proteinuric by infusion of the polycation hexadimethrine (HDM), and rats with chronic doxorubicin (Adriamycin-Adria) nephrosis. In the control rats, GSCs for the anionic markers aIgG (Series A) or Crp (Series B) were significantly greater than that of nIgG (both series). These large proteins crossed the filtration barrier by a different pathway from that available to smaller neutral molecules the size of albumin, which in our previous study had a much higher GSC than a native, anionic albumin marker. In a third group of control rats only (Series C), the GSCs of native anionic bovine albumin (BSA) and nIgG were compared directly. The GSC of BSA (0.0029) was only slightly larger than the GSC of nIgG (0.0025), indicating that most of the native albumin crosses the glomerular capillary wall via a nonselective pathway similar to that available to nIgG. The results in the control groups are compatible with recently-described heteroporous models of glomerular size selectivity. In the HDM proteinuric rats of both series, the filtration of all three markers was significantly increased, although the GSCs of the anionic markers continued to exceed that of nIgG. The finding of increased nIgG filtration in HDM rats confirms our previous observation that HDM, although it binds to and neutralizes anionic sites in glomerular basement membrane, induces a structural change which leads to altered pore size distribution. Adria rats also had increased GSCs of all markers, although the increase was not as great as in HDM rats, and the GSCs of the anionic and neutral markers became equal.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Charged compounds of the glomerular filter and their role in normal and disordered permselectivity.

Infusion into rats of the polycation hexadimethrine (HDM) leads to onset of massive proteinuria, which recovers when the infusion is stopped. Several lines of evidence indicate that the proteinuria results from binding of HDM to polyanions of the glomerular filter, with neutralization of shielding of their charges. To determine the mechanism of this proteinuria, we measured the glomerular sieving coefficients of anionic and neutral forms of albumin and IgG in control and proteinuric rats. Surprisingly, these studies revealed a marked defect in size dependence, but not in charge dependence, of glomerular permselectivity in hexadimethrine-treated animals, indicating that binding of HDM induces a structural change in the glomerular filter. In vitro studies of binding of tritiated HDM and cationized ferritin to glomerular basement membrane (GBM) indicate that the binding is not dependent on proteoglycans such as heparan sulfate, nor on sialoproteins such as podocalyxin, but is dependent on charged carboxyl groups of GBM.

Animals↗