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H Benediktsson

Publications and source records attributed to H Benediktsson.

At least 37 records · Page 2Linked to original sources
PubMed1995

Post-transplant hypertension and chronic renal allograft failure.

Chronic renal allograft dysfunction is often associated with hypertension, but it is unknown to what extent this affects graft structure and function. We investigated the effect of antihypertensive drug treatments on the course and histopathology of chronic renal allograft rejection in a rat model. Recipient animals were treated with a combination of reserpine, hydralazine and hydrochlorothiazide, the angiotensin converting enzyme inhibitor cilazapril, or the angiotensin II receptor blocker L158,809. Systemic blood pressures and tubular stop-flow pressures were measured on day 50 after transplantation; the histopathology was assessed semiquantitatively in kidneys not used for micropuncture studies. Grafts removed from untreated recipients showed inflammation and structural vascular and glomerular lesions consistent with chronic rejection. All treatment regimens decreased the systemic and glomerular capillary pressures and were associated with improved graft survival, decreased proteinuria and a tendency to improved graft function; the histopathology showed a significant amelioration of glomerular mesangiolysis and glomerulosclerosis but no effect was found on the tubulointerstitial lesions; the angiotensin receptor blocker also inhibited graft atherosclerosis. We conclude that hemodynamic and angiotensin II-mediated processes may play a pivotal role in the expression of immune-mediated glomerular lesions of chronic allograft dysfunction.

Animals↗
PubMed1994

Cardiac allograft atherosclerosis in the rat. The effect of histocompatibility factors, cyclosporine, and an angiotensin-converting enzyme inhibitor.

Cardiac transplant atherosclerosis is thought to result from immune-mediated vessel wall injury. The present experiments were designed to test whether CsA alone or in combination with the ACE-inhibitor cilazapril has any effect on graft atherosclerosis in a rat cardiac transplant model. Cardiac grafts were transplanted heterotopically into either syngeneic or allogeneic recipients and followed by daily palpation; long-surviving grafts were removed after 100 days and the extent and degree of atherosclerosis was assessed using computerized morphometry. Atherosclerosis was more extensive in grafts removed from untreated allogeneic recipients compared with syngeneic recipients; CsA treatment increased the extent of atherosclerosis in syngeneic transplants. The extent and degree of vascular occlusion in allogeneic grafts from recipients treated with 15 mg/kg of CsA every other day was not different from that in grafts removed from recipients that received initially higher CsA doses. Cilazapril had no effect on the extent of graft atherosclerosis but decreased the degree of luminal narrowing in grafts from CsA-treated recipients significantly. Some grafts showed neovascularization in the subendocardial region adjacent to organized intraventricular clots, suggesting the release of angiogenic factors from such clots; such growth factors may contribute to the atherosclerotic vessel wall reaction in this model. We conclude that CsA promotes the development of graft atherosclerosis in heterotopically transplanted syngeneic cardiac grafts in the rat. We furthermore found that cilazapril has a beneficial effect on the degree of atherosclerosis in CsA-treated recipients.

Animals↗
PubMed1994

Partial characterization of the enhanced survival of female NZB/W mice treated with lithium chloride.

Previous investigations have indicated that initiation of LiCl treatment (4 mg/day) of female NZB/W mice at 10 weeks of age led to enhanced survival of 50% of the mice to > 11 months of age (Lithium, 3, 61-67, 1992). The present results indicate that this enhancement of survival is dose dependent in that 2 mg 7LiCl/day was less effective than 4 mg 7LiCl/day. Daily treatment of groups of mice with 2 or 4 mg LiCl per day starting at 8 weeks of age led to the survival of 40% and 70%, respectively, of the mice at 40 weeks of age, a time when only 10% of the untreated mice remained alive. Initiation of treatment with 2 mg 7LiCl/day after the disease process was evident (24 weeks of age) led to diminished effectiveness. Parallel experiments with mice treated with 4 mg 7LiCl/day revealed 60% long-term survivors in the early treatment groups and 33% in the delayed treatment groups. Cessation of treatment in both groups led to some additional deaths, but 20-27% of the mice remained alive at 60 weeks of age, even though animals had detectable levels of anti-ssDNA antibodies in their serum. Additional experiments with 2 and 4 mg 7LiCl/day in NZB/W mice pretreated with C. parvum-PER, a treatment previously shown to enhance survival (Int. J. Immunopharmac., 14, 35-41, 1992), indicated that the effect of the two modalities was not additive. The results presented indicate that treatment of NZB/W mice with LiCl leads to very effective prolongation of survival by unique mechanisms, possibly involving alteration of the effector phase of autoimmune damage to the kidney or the susceptibility of kidney elements to immune-mediated damage leading to renal failure.

Animals↗
PubMed1993

International standardization of criteria for the histologic diagnosis of renal allograft rejection: the Banff working classification of kidney transplant pathology.

A group of renal pathologists, nephrologists, and transplant surgeons met in Banff, Canada on August 2-4, 1991 to develop a schema for international standardization of nomenclature and criteria for the histologic diagnosis of renal allograft rejection. Development continued after the meeting and the schema was validated by the circulation of sets of slides for scoring by participant pathologists. In this schema intimal arteritis and tubulitis are the principal lesions indicative of acute rejection. Glomerular, interstitial, tubular, and vascular lesions of acute rejection and "chronic rejection" are defined and scored 0 to 3+, to produce an acute and/or chronic numerical coding for each biopsy. Arteriolar hyalinosis (an indication of cyclosporine toxicity) is also scored. Principal diagnostic categories, which can be used with or without the quantitative coding, are: (1) normal, (2) hyperacute rejection, (3) borderline changes, (4) acute rejection (grade I to III), (5) chronic allograft nephropathy ("chronic rejection") (grade I to III), and (6) other. The goal is to devise a schema in which a given biopsy grading would imply a prognosis for a therapeutic response or long-term function. While the clinical implications must be proven through further studies, the development of a standardized schema is a critical first step. This standardized classification should promote international uniformity in reporting of renal allograft pathology, facilitate the performance of multicenter trials of new therapies in renal transplantation, and ultimately lead to improvement in the management and care of renal transplant recipients.

Graft Rejection↗
PubMed1993

Glomerular capillary pressures in long-surviving rat renal allografts.

Many renal transplants undergo gradual deterioration in structure and function in the months or years after transplantation. The processes that underlie this progressive decline have not been defined, and may include immunological and nonimmunological mechanisms. The present experiments were designed to investigate the glomerular capillary hydrostatic pressure in long-surviving rat renal transplants with or without chronic rejection. Stop-flow glomerular pressures were measured in F344 renal allografts with chronic rejection, syngeneic F344 grafts, and long-surviving syngeneic and allogeneic LEW grafts without chronic rejection; control measurements were done in nontransplanted intact animals or after subtotal renal ablation. Renal ablation or transplantation resulted in increased glomerular pressure in F344 but not LEW kidneys; the glomerular pressure in syngeneic F344 grafts was not different from that in allogeneic F344 grafts. There was no correlation between the mean arterial pressure and the glomerular capillary pressure. Our data suggest that the glomerular capillary pressure is determined by local intrarenal factors. The glomerular capillary pressure in allotransplanted kidneys resembles that of the donor kidney after subtotal renal ablation. The importance of increased glomerular pressure in the progressive decline of graft function of chronic rejection remains to be established.

Animals↗
PubMed1992

Macrophage subpopulations in normal and transplanted heart and kidney tissues in the rat.

The purpose of the present study was to investigate the phenotype of macrophages that infiltrate normal and transplanted rat tissues. The macrophage monoclonal antibodies ED1, ED2, ED3, 52-1D4, ER15, and OX43, together with antibodies against lymphocyte and class II MHC antigens, were used in an indirect immunofluorescence technique with sections of normal tissues and heart and renal grafts that experienced long-term survival or rejection. A small number of ED1- and ED3-positive interstitial cells were detected in normal heart and renal tissues and their number increased dramatically in rejection. Normal heart tissue contained a population of ED2-positive cells with dendritic morphology that was not detected in renal tissue. Following transplantation, a diffuse increase of rounded ED2-positive cells was observed in heart grafts; no ED2-positive cells were detected in grafts removed after 20-30 days from nonimmunosuppressed recipients. Grafts from CsA-treated animals or grafts that survived greater than 50 days in nonimmunosuppressed recipients exhibited the interstitial dendritic pattern of ED2-positive cells. Only very few rounded ED2-positive cells were observed in renal allografts; if present, they were mostly located in the medulla. OX43, which bound in normal tissues to vessel endothelium and a population of macrophages, stained in allografts an additional small population of graft-infiltrating cells, and in F344 renal allografts a population of multinucleated giant cells. We conclude that the posttransplant macrophage infiltration pattern of heart and renal allografts, defined by the monocyte/macrophage antibodies ED1, ED3, 52-1D4, and ER15, is very similar for both types of organs, although the antibody ED2 and the endothelial-macrophage antibody OX43 revealed remarkable differences between the two types of organ allografts.

Animals↗
PubMed1992

Ultrasound guided needle biopsy of brain tumors using an automatic sampling instrument.

All ultrasound (US) guided needle biopsies of brain tumors performed during an 8-year period were reviewed. Tissue samples were obtained in 112 of 115 biopsy procedures, and a histologic diagnosis was established in 99 cases (88.4%). The rate of major complications was 8.0%. The mortality is similar as in reports on stereotactic and CT-guided biopsy procedures while the morbidity is higher in our material. There are no large series available on US guided intracranial biopsy with adequate reports of complications. A modified biopsy technique is introduced here using a cutting needle and an automatic sampling instrument. The modified technique, which has been used in all cases since 1985, yielded diagnostic material in 91.5%. This method consistently provides a tissue core which is essential for a confident histopathologic diagnosis.

Biopsy, Needle↗
PubMed1992

Enhancement of true-positive rates for nonpalpable carcinoma of the breast through mammographic selection.

A retrospective review of 332 needle localization biopsies for nonpalpable mammographic abnormalities was performed. Twenty-one invasive and 12 noninvasive carcinomas were identified in this population, for a true positive biopsy rate of 10 percent. A review of all needle localization mammograms performed on these patients by a radiologist specializing in mammography identified 225 mammograms with a low probability of malignancy. In this group, there were four in situ and six invasive carcinomas (true positive biopsy rate of 4 percent). In the remaining 107 mammograms with a high probability of malignancy, there were eight in situ and 15 invasive carcinomas (true positive biopsy rate of 21.4 percent). In the low probability group, fine needle aspiration or excisional biopsy were recommended for six of the ten neoplasms and follow-up mammograms at three to six months for the remaining four (two in situ and two invasive carcinomas). Using selectivity, 225 biopsies could have been avoided at a savings of $97,368 (Canadian dollars) in fees for physicians alone while still identifying 29 of 33 neoplasms (87 percent of all neoplasms) and possibly delaying diagnosis for three to six months or longer in four of 33 neoplasms (13 percent, two in situ and two invasive) for which follow-up mammograms were recommended.

Adult↗
PubMed1991

Granular cell neoplasm of the extrahepatic biliary tree: morphological, ultrastructural, and immunohistochemical study and review of the literature.

A recent case of a biliary granular cell tumor of the cystic duct prompted a literature review and an extensive pathological examination of the tumor in question. A total of 44 cases have been described mostly in black females. Most cases present with biliary symptoms, and simple surgical resection allows complete control of this benign condition. Granular cell tumors are most likely derived from neural crest cells.

Adult↗
PubMed1991

Cyclosporine-associated reduction in systolic myocardial function in the rat.

The cardiotoxic effect of cyclosporine in the inbred rat was investigated in the isolated perfused heart model. Diastolic and systolic function was studied in 5 groups of (Lewis x Brown Norway) F1 rats treated with different doses of cyclosporine for different time intervals and in a group which received the vehiculum cremophor. Of the cyclosporine-treated rats, one group was studied four weeks after drug discontinuation to assess reversibility of the effect. To control for the nephrotoxic side effects of cyclosporine, a group of animals that had undergone 1.5-1.75 renal ablation was included. Left ventricular pressures were measured with a balloon catheter; stepwise increases in preload were obtained by small increments in the balloon volume. Over the range of left ventricular volumes studied, no differences were found in diastolic pressure between the groups. Peak systolic pressures were significantly lower in hearts obtained from cyclosporine treated rats which had received 15 or 7.5 mg/kg/24 h subcutaneously for three weeks (P less than 0.05). Our results indicate that cyclosporine treatment resulted in a reversible decrease in myocardial contractile force apparently unrelated to decreases in renal function or to changes in mean arterial pressure.

Analysis of Variance↗
PubMed1991

Mercury from dental "silver" tooth fillings impairs sheep kidney function.

In humans Hg vapor is released from "silver" amalgam fillings that contain 50% Hg by weight. Previous studies show that when 12 such fillings are placed in sheep teeth, the kidneys will concentrate amalgam Hg at levels ranging from 5 to 10 micrograms Hg/g renal tissue 4-20 wk after placement. In the present study 12 occlusal fillings were placed in each of six adult female sheep under general anesthesia, using standard dental procedures. Glass ionomer occlusal fillings (12) were inserted in two control sheep. At several days before dental surgery, and at 30 and 60 days after placement of fillings, renal function was evaluated by plasma clearance of inulin and by plasma and urine electrolytes, urea, and proteins. An average plasma inulin clearance rate of 69.5 +/- 7.2 ml/min before amalgam placement was reduced to 32.3 +/- 8.1 ml/min by 30 days and remained low at 27.9 +/- 8.7 ml/min after 60 days. Inulin clearance did not change in controls. After amalgam placement urine concentration of albumin decreased from 93.0 +/- 20.5 to 30.1 +/- 15.3 mg/l and urine Na+ concentration increased steadily from 24.8 +/- 7.7 to 82.2 +/- 20.3 mmol/l at 60 days. Concentrations of K+, urea, gamma-glutamyl transpeptidase, alkaline phosphatase, and total protein did not change significantly from 0 to 60 days in urine. Plasma levels of Na+, K+, urea, and albumin remained unchanged from 0 to 60 days after amalgam. Renal histology remained normal in amalgam-treated animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗