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Biomedical subjects

G Petrusevska

Publications and source records attributed to G Petrusevska.

18 recordsLinked to original sources

ANCA-GBM dot-blot test in diagnosis of patients with glomerulonephritis.

Patients with rapidly progressive glomerulonephritis who are positive for anti-neutrophil cytoplasmic antibody (ANCA) or anti-glomerular basement membrane (GBM) antibodies may develop chronic renal failure leading to end-stage renal disease (ESRD) within days or weeks. The early serologic detection of auto-antibodies associated with ANCA and anti-GBM diseases will be helpful in preventing ESRD. We evaluated the combined ANCA-GBM dot-blot strip assay (Biomedical Diagnostics, Brugge, Belgium) in 30 consecutive patients with biopsy proven glomerulonephritis (GN). MPO- and PR3-ANCA were detected in 5 and 2 samples, respectively. Three samples were positive for both MPO- and PR3-ANCA (all 3 had focal segmental necrotizing GN). One patient was diagnosed as having Goodpastures' syndrome (the only anti-GBM positive result) and two had Wegener's granulomatosis (the two PR3-ANCA positive results). Two additional samples were equivocal: positive for MPO-ANCA and PR3-ANCA, respectively. Patients positive only for MPO-ANCA had only limited extrarenal organ manifestations. Anti-PR3 positive patients with necrotizing glomerulonephritis had a more dramatic deterioration of their renal function at diagnosis. Radiographically, these patients had nodular or pneumonia-like lesions. Acute respiratory failure necessitating mechanical ventilation was developed in one GBM positive patient. In conclusion, the ANCA-GBM dot-blot is a useful screening tool in situations where conventional ANCA testing is not readily available.

Adult↗

Protocol biopsies in kidney transplant recipients: histologic findings as prognostic markers for graft function and outcome.

The aim of the present study was to identify subclinical and borderline rejections as well as histological markers of chronic allograft nephropathy (CAN) among protocol biopsies performed at 1 and 6 months after living related kidney transplantation to assess their possible implications for graft function. Twenty paired allograft biopsies performed at 1 and 6 months were reviewed according to the Banff scoring scheme. The mean ages of donors and recipients were 59.6 +/- 13.8 and 34.4 +/- 8.7 years, respectively. Among all biopsies only 10% (4/40) showed no histopathological lesions. At the first month borderline rejection was shown in 35% and subclinical rejection in 10% of patients. At 6 months the proportion of findings was even higher, namely, 40% and 30%, respectively. When divided according to donor age, donors above 55 years showed a mean CAN score of 2.33 +/- 1.56 which increased to 5.0 +/- 2.26 on the 6 month biopsy (214.3%). Unexpectedly, the proportion of these changes in the younger donor group also increased by 173.3%, which might have been explained by the greater number of borderline and subclinical rejections in the younger donor group at the 1 month biopsy. In conclusion, 1 month biopsy may be valuable to determine borderline and subclinical rejection and to prognosticate the outcome of renal allograft function. Our findings suggest a greater susceptibility of histological deterioration among the older donor population. However, the presence of an untreated rejection in the younger donor pool leads to a rapid impairment of the graft function accelerating the process of chronic allograft nephropathy.

Adult↗

The evolution of untreated borderline and subclinical rejections at first month kidney allograft biopsy in comparison with histological changes at 6 months protocol biopsies.

Our study sought to identify the possible implications of histological findings of borderline and subclinical rejections as well as histological markers of chronic allograft nephropathy (CAN) in protocol biopsies at 1 and 6 months after living-related kidney transplantation. Twenty-eight paired allograft biopsies were blindly reviewed using Banff '97 criteria, among which only 10.7% (6/56) showed no histopathological lesions. BR was found in 9/28 (32.1%) and 6/28 (21.4%), and SR in 3/28 (10.7%) and 10/28 (35.7%) of the patients, in the 1 and 6 month biopsies, respectively. The mean CAN score (sum of histological markers for chronicity) increased significantly at 6 months biopsy, 1.57 +/- 1.36 vs. 4.36 +/- 2.32 (p < 0.01). When compared according to chronicity index (CI < 5 >), the high CI group had a mean CAN score of 2.36 +/- 1.15 at 1 month, which increased to 5.14 +/- 1.99 at 6 months biopsy (188.9%). The proportion of these changes in low CI group were also increased from 0.79 +/- 1.12 to 3.57 +/- 2.38 (451.9%). In conclusion, a protocol 1 month biopsy may uncover a high prevalence of BR or SR in stable allografts. The presence of an untreated BR or SR in biopsies with low chronicity index showed greater susceptibility to histological deterioration on the 6 month biopsy, associated with rapid impairment of graft function and chronic allograft nephropathy.

Adult↗

Membranoproliferative glomerulonephritis complicating diabetic nephropathy.

BACKGROUND: Renal diseases other than diabetic nephropathy can be found in diabetic patients who have undergone renal biopsy. Various forms of primary and secondary glomerular diseases were reported, but membranoproliferative glomerulonephritis was rare. METHODS: Analyzing data at our Department for the past three years, we noted 18 patients with primary membranoproliferative glomerulonephritis and 4 associated with diabetic nephropathy. RESULTS: Nodular glomerulosclerosis with diffuse membranoproliferative glomerulonephritis was registered in two patients and a diffuse form of diabetic nephropathy with a combination of segmental and diffuse changes characteristic of membranoproliferative glomerulonephritis in the other two patients. CONCLUSIONS: Analyzing what can be common for these two diseases we can conclude that they are at least three disorders: 1. hyperperfusion injury, hallmark for the diabetic nephropathy, but also with the highest incidence in membranoproliferative glomerulonephritis than in the other glomerulonephritides; 2. mesangial matrix expansion, and; 3. thickening of all extracellular membranes.

Adult↗

Recurrent glomerulonephritis in living kidney transplantation.

Glomerulonephritis (GN) is one of the most frequent causes of end-stage renal disease. Recurrent GN can occur very early after transplantation in up to 20% of renal-allograft recipients and should be considered with late graft dysfunction in 2-5%. Importantly, diagnosis of a clinically silent recurrence of the disease will pass undetected unless transplant centers have a policy of protocol biopsies. In addition, the classification of the type of recurrent GN should be done with data on electron microscopy and immunofluorescence, in order to promote prompt treatment and a strategy for long-term graft survival. The aim of our paper was to present a few typical cases of recurrent GN, showing the actuality of the problem in living related kidney transplant recipients and to ascertain the importance of precise and timely diagnosis by protocol biopsy. Recurrent focal segmental glomerular sclerosis (FSGS) in childhood is associated with the highest number of graft loss. The treatment of recurrent FSGN is difficult, so prophylactic plasmapheresis prior to transplantation appeared to be more effective in preventing recurrence than plasmapheresis after transplantation, especially in population of children. Mesangio proliferative GN type II is the second most frequent recurrent GN, followed by type I. Here, it is of paramount importance to classify the type of the disease. The family of the patient at risk for recurrent GN, a candidate for living related kidney transplantation, should be informed for the expected outcome and their voluntary decision whether to proceed with transplantation should be awaited.

Adolescent↗

Chronic allograft nephropathy (CAN) in early renal protocol biopsies: does treatment of borderline and subclinical acute rejections prevent development and progression of CAN?

Histological markers of chronic allograft nephropathy (CAN) in early protocol biopsies may ultimately result in deterioration of graft function. The aim of our study was to evaluate risk factors of early CAN histology and to determine whether treatment of borderline and subclinical acute rejections (BR/SAR) at 1-month posttransplant, prevents development and/or progression of CAN at 6-month biopsy. Thirty-five paired kidney allograft biopsies at 1 and 6 months after transplantation were blindly reviewed using Banff'97 criteria. The mean CAN score (sum of histological markers for chronicity) increased significantly at 6-month biopsy (1.83 +/- 1.46 vs 4.66 +/- 2.35; p < 0.01). No CAN was present in 27/70 biopsies (38.6%), 71.4% showed progression and 28.6% were with stable CAN at 6-month biopsy. When compared according to the progression, mean histological index (HI) score (sum of acute/chronic changes) in progressed CAN group (pCAN) increased significantly at 6-month biopsy (5.0 +/- 3.0 vs 9.5 +/- 2.8; p < 0.001). At 1-month biopsy, BR/SAR were found in 68% and 70%, in the pCAN and stable (sCAN) groups, respectively. The percentage of treated BR/SAR in sCAN group was significantly higher (57.1 vs 23.5%; p < 0.05), and the score of acute histological lesions lower (1.08 +/- 0.95 vs 0.35 +/- 0.66; p < 0.01) at 6-month biopsy. In conclusion, 1-month protocol biopsy may be valuable to uncover BR/SAR and the presence of early CAN in stable renal allografts. Progression of CAN at 6-month biopsy in our study was found to be associated with a greater number of untreated BR/SAR at 1-month biopsy. This observation may have important implications in the design of clinical trials aimed to prevent the progression of CAN.

Acute Disease↗

Diabetic glomerulosclerosis without overt diabetes mellitus.

The duration of diabetes mellitus and the presence of hyperglycaemia were thought to be important in the development of nodular glomerulosclerosis. We report on 3 patients without overt diabetes, but with glucose intolerance, all male, aged 43-66 years, with histological features of diabetic glomerulosclerosis. The nodular form was present in 2 patients and the diffuse form in 1. These cases suggest that factor(s) other than hyperglycaemia are responsible for diabetic renal damage.

Adult↗

Immunohistochemical and ultrastructural features of Gaucher's cells--five case reports.

Gaucher's disease is an autosomal recessive lysosomal storage disease resulting from glucocerebrosidase deficiency. In this report, five patients with adult Gaucher's disease are described. The clinical course of these patients was characterized by progressive diffuse aseptic necrosis in the large bones, so-called Erlenmeyer's flask deformity, and hepatosplenomegaly. Splenomegaly was accompanied by hypersplenism with anemia and thrombocytopenia, therefore splenectomy was performed. The diagnosis of Gaucher's disease was based on the finding of Gaucher's cells on bone marrow biopsy. Tissue blocks were cut and routinely processed. Slides staining for iron (Peris' blue) and PAS (periodic acid--Schiff) including immunohistochemical staining for CD68 and HLA-DR was performed in all five cases. Gaucher's cells were seen as large cells with granular or fibrillar distended cytoplasm, with the characteristic 'wrinkled tissue paper' appearance, and eccentric nuclei. PAS staining showed strongly positive granular or fibrillar material in the cytoplasm. Immunohistochemical stain for CD68 and HLA-DR helped identify isolated Gaucher's cells, which are hystiocytic in nature. This stain accentuates their fine linear striations. Small pieces were ultrastructurally analyzed.

Adolescent↗

Gastrointestinal malignant lymphomas in Macedonia.

The gastrointestinal tract including oral cavity is the most common location of extranodal lymphomas. In this retrospective study, the histomorphological, immunohistochemical and clinical features of 21 Macedonian cases with diagnosed malignant lymphomas were investigated. The series included 15 males and 6 females, mean age 44 (4-78) years. The most common locations were hard palate (n = 7), gastric site (n = 5), small intestinal wall (n = 2), large intestinal wall (n = 5), and lingual root (n = 2). All cases were B cell lymphomas, 23.8% of them low grade B cell lymphoma of mucosa associated lymphoid tissue, 4.7% mantle cell lymphoma, 47.6% diffuse large cell lymphoma, and 23.8% Burkitt type lymphoma. There was no T cell lymphoma. Most of the cases were positive for CD20 and CD79a. Monoclonality was confirmed by light chain restriction, except for nine cases where it failed due to poor tissue preservation. The fact that eight cases were in the clinically advanced third and fourth stage implied a conclusion that not only primary non-Hodgkin's lymphomas but also secondary lesions could invade the gastrointestinal tract. Immunohistochemical staining was helpful in differentiation between benign and malignant infiltration in low grade lymphomas, and in distinguishing diffuse large cell lymphomas from undifferentiated epithelial neoplasms.

Adolescent↗

How erythropoietin affects bone marrow of uremic patients.

In a prospective study, 40 maintenance hemodialysis patients, randomized in two equal groups, were treated with recombinant human erythropoietin (rHuEPO) for their renal anemia, for a period of 2 years. One group was treated for 2 years, while the other was untreated control during the first year, but received rHuEPO during the second year of the study. Anemia was corrected in all treated patients and hematocrit maintained between 30 and 35 vol% by low-dose subcutaneous treatment with Recormon (Boehringer Mannheim GmbH, Germany), according to the study protocol. Bone marrow biopsy (BMB), from the posterior iliac crest, was taken by the method of Jamshidi from 32 patients. Fourteen patients from the control group were biopsied twice: once at baseline and the second time at 12 months of treatment, while 15 patients from the other group were biopsied only once, at 24 months of rHuEPO treatment. The biopsies were embedded in wax and in epoxy resin, and after staining for light and electron microscopy, they were semiquantitatively examined for several parameters: cellularity, myeloid:erythroid (M:E) ratio, megakaryocytes, fatty tissue, megaloblasts, and marrow iron. Cellularity of the bone marrow increased significantly at 12 months of treatment and it remained so at 24 months. M:E ratio was significantly reduced indicating expansion of the erythroid pool, both at 12 and 24 months of therapy. The number of megakaryocytes in the bone marrow increased significantly at 12 months and remained high at 24 months of treatment, while fatty tissue was significantly reduced at 12 and 24 months compared to the baseline values. There was no significant change in the percentage of megaloblasts in the bone marrow. Hemosiderin was reduced after treatment indicating mobilization of the bone marrow iron stores upon treatment with rHuEPO. We concluded that rHuEPO had a beneficial long-term effect on bone marrow.

Anemia↗

Adult familial nephrotic syndrome--Balkan variant of congenital nephrotic syndrome.

We report on two families from the southern part of Former Yugoslav Republic of Macedonia (close to Mediterranean area) with autosomal dominant inherited nephrotic syndrome, documented with renal biopsy in three family members. Histopathological examination confirmed microcystic tubular changes and focal segmental glomerulosclerosis. In biopsied patients proteinuria was noted in the first decade, or second, but it was quantitatively documented as nephrotic in the second and third decade. The prognosis of the patients was poor: one patient died because of intracranial hemorrhage before developing end stage renal disease; the other two cases developed end stage chronic renal failure in the third and fourth decade.

Adolescent↗

Focal segmental glomerulosclerosis with acute renal failure associated with alpha-interferon therapy.

Both alpha- and beta- interferons (IFNs) have been increasingly used for the treatment of many types of malignancy, and recently the use of alpha-IFN in the management of hepatitis C virus (HCV) infection with or without renal involvement has been emphasized. We report a patient who developed nephrotic syndrome and acute renal failure while being treated with alpha-IFN for HCV infection. The renal biopsy showed focal segmental glomerulosclerosis and tubulointerstitial nephritis. Although several renal lesions have been described in association with either alpha-IFN treatment or HCV infection, focal segmental glomerulosclerosis has not been emphasized in either instance. This case also indicates that when renal abnormalities occur during treatment of HCV infection with alpha-IFN, kidney biopsy may define the responsible renal lesions, suggest possible association with other conditions, and serve as a guideline for proper management.

Acute Kidney Injury↗

Cell apoptosis and proliferation in experimental chronic obstructive uropathy.

Cell proliferation and apoptosis in kidneys with chronic obstructive uropathy (COU) have not been adequately studied. Whether these fundamental cellular processes play any role in the pathogenesis and evolution of COU remains undetermined. Sprague-Dawley rats with COU induced by unilateral ureteral ligation were sacrificed at postoperative days 1, 6, 9, 15, 34, 43, 60, 75, and 90, and were compared with control, sham-operated rats sacrificed at days 0, 15, 43, and 90. The kidneys with ureteral ligation, the contralateral kidneys, and the control kidneys were submitted to in situ end-labeling of fragmented DNAs for the detection of apoptotic cells, and to immunostaining with many monoclonal antibodies directed against the nuclear antigens associated with cell proliferation for the detection of proliferating cells. Additional rats with COU were also submitted to BrdU labeling to detect proliferating cells. The tubular, interstitial, and glomerular cells showing either apoptosis or proliferation were separately quantitated and the obtained data were correlated with dry kidney weight, tubular diameter, glomerular surface area and interstitial volume. Apoptotic tubular cells in kidney with COU increased rapidly, reaching 30-fold that of control at day 25, which was followed by an equally rapid decrease to the control level. During the same period, both the dry kidney weight and the mean tubular diameter decreased markedly. These data suggest that apoptosis may play a significant role in tubular atrophy and renal weight loss. The rapid increase in tubular cell apoptosis was immediately preceded by a 37% gain in the dry kidney weight over the control; just before that increase, there was also an approximate 60-fold increase in the proliferation rate of tubular cells detected by immunostaining for proliferating nuclear antigen or by BrdU labeling. The significance of this intriguing temporal relationship of tubular cell apoptosis and proliferation remains to be elucidated, but it may have pathogenetic implications. In contrast to the rise and fall of the frequency of tubular cell apoptosis and proliferation, the frequency of interstitial cell apoptosis and proliferation displayed continuous increase toward the end of the experiment, with a roughly parallel increase in the interstitial damage. Apoptosis and proliferation of glomerular cells in kidneys with COU did not show any significant changes throughout the experiment. In conclusion, the obtained data suggest that tubular cell apoptosis may be pathogenetically related to the tubular atrophy and renal tissue loss in COU, and that proliferation and apoptosis of interstitial cells may play a role in the observed interstitial changes in this model. This study should provide the impetus for further exploration of the mechanisms of cell death and cell proliferation as a novel venue for understanding the pathogenesis of COU.

Animals↗