Biomedical subjects

S Sund

Publications and source records attributed to S Sund.

At least 19 recordsLinked to original sources

PubMed2004

Glomerular monocyte/macrophage influx correlates strongly with complement activation in 1-week protocol kidney allograft biopsies.

BACKGROUND: The specific role of monocytes/macrophages (MO) in kidney graft rejection is not yet fully elucidated. In a recent protocol biopsy study of living-donor recipients, we demonstrated massive capillary influx of MO, associated with severe complement activation and acute rejection (AR) 1 week after transplantation [Sund et al.]. To gain further insight into the possible relationship between MO and complement activation, we analyzed glomerular and interstitial MO in these biopsies. METHODS: Twenty-seven protocol biopsies were stained with antibodies to calprotectin (L1) and CD68 as markers for MO. Cells were counted as an average number per glomerulus and as an average number per defined visual field in the interstitium. Polymorphonuclear leukocytes (PMN) were counted in glomeruli and interstitium by light microscopy. Baseline specimens from 10 of the patients served as controls. The results were compared with data on deposition of complement from the foregoing study, and with histopathologic and clinical data on AR. RESULTS: Cases with diffuse C4d deposition in peritubular capillaries consistent with acute antibody-mediated rejection (AbAR) (n = 4) had significantly higher numbers of intraglomerular MO than the other protocol biopsies (L1: median 20.7 vs 3.6, p = 0.0002; CD68: median 10.1 vs. 2.0, p = 0.0008). With a cut-off of 10 L1-positive and 6 CD68-positive MO, the specificity for the diagnosis of AbAR was 96% and 91%, respectively. The number of interstitial MO was significantly higher in patients with AR than in those without, but in contrast to glomerular MO, interstitial MO could not discriminate between complement positive and negative AR. The number of glomerular and interstitial PMNs was significantly higher in the AbAR group than in the other protocol biopsies. CONCLUSIONS: The strong correlation between complement activation and early glomerular influx of MO in the kidney allograft suggests a causal relationship between these 2 events. At 1 week after transplantation, a number of 10 L1-positive and 6 CD68-positive MO per glomerulus indicates AbAR.

Adult↗

PubMed2003

Recurrent angiolymphoid hyperplasia with eosinophilia mimicking temporal arteritis associated with nephrotic syndrome.

We report on a middle-aged Caucasian male who presented with nephrotic syndrome that on 2 consecutive recurrences was accompanied by a pulsating tumor suggesting temporal arteritis. Renal biopsies showed features of a low-grade mesangial-proliferative glomerulonephritis. The resected tumor in the temporal region revealed a lesion consistent with angiolymphoid hyperplasia with eosinophilia (ALHE), with moderate inflammatory involvement of the temporal artery. The patient was successfully treated with oral prednisolone in addition to removal of the tumor, but has remained steroid-dependent. To our knowledge, only 2 cases of ALHE and nephrotic syndrome have been reported so far in non-Japanese individuals [Altman et al. 1995, Sonkodi et al. 1987], and we are not aware of any previous case combining these features while simultaneuosly mimicking temporal arteritis.

Adult↗

PubMed2001

[Diagnostic transmission electron microscopy].

BACKGROUND: Transmission electron microscopy (TEM) is an important diagnostic tool in surgical pathology. MATERIAL AND METHODS: We give an overview, based on our own experience, of the application of TEM in diagnostic pathology. RESULTS: In spite of its potential for high-grade resolution, the actual use of TEM in diagnostic pathology is rather limited. TEM is mandatory in the examination of kidney and muscle biopsies and is often indicated when a metabolic disease is suspected. However, in many centres its importance in tumour pathology has declined because of the advances in the field of immunohistochemistry. TEM requires a great deal of resources and high levels of skills in tissue processing and diagnostic interpretation. INTERPRETATION: The TEM diagnosis must be integrated with light microscopical and, often, immunohistopathological findings, as well as with the clinical data. We therefore recommend close collaboration between the clinician and the laboratory with regard to biopsy indication, handling of samples, and the final diagnosis.

Humans↗

PubMed2001

Renal hemodynamic response to maximal vasodilating stimulus in healthy older subjects.

BACKGROUND: It is still unclear whether age per se is associated with preservation of renal functional reserve, that is, of the increase in glomerular filtration rate (GFR) induced by appropriate vasodilating stimulus. METHODS: To gain insights into this issue, we evaluated the renal response to a maximal vasodilating stimulus, represented by the combined infusion of mixed amino acid solution (AA) and dopamine at renal dose (D), in 10 young subjects (median age of 30 years, range of 19 to 32) and in 11 subjects of older age (median age of 67 years, range of 65 to 76). Two further age-matched groups of young (N = 15) and older (N = 11) living kidney donors underwent renal needle biopsy immediately before nephrectomy to perform semiquantitative scoring (0 to 3) of arteriosclerosis in intrarenal arteries. All of the study subjects were nonsmokers with healthy status proven by extensive diagnostic evaluation excluding any risk factor of renal dysfunction. RESULTS: Basal renal plasma flow (RPF) and GFR were proportionally lower in older subjects (RPF, 361 +/- 29 vs. 618 +/- 34 mL/min/1.73 m(2), P < 0.001; GFR, 79 +/- 4 vs. 127 +/- 5.8 mL/min/1.73 m(2), P < 0.001). After AA + D, a significant increase of RPF and GFR was observed in both groups, but the older subjects exhibited a smaller percentage increment (RPF, 25.5 +/- 4.8 vs. 42.4 +/- 5.8, P < 0.05; GFR, 19.6 +/- 5.7 vs. + 33.8 +/- 6.4, P < 0.05). Furthermore, the maximal vasodilating stimulus was not able to restore renal hemodynamics in older subjects to the level measured in young controls at baseline. Renal vascular resistances were higher (P < 0.05) in the older subjects both at baseline (0.19 +/- 0.02 vs. 0.09 +/- 0.004 mm Hg/mL/min) and after AA + D (0.14 +/- 0.01 vs. 0.06 +/- 0.004). Light microscopy examination detected the presence of a greater degree of arteriosclerosis at the level of interlobular and arcuate arteries (0.89 +/- 0.15 vs. 0.45 +/- 0.08) and interstitial fibrosis/tubular atrophy (1.18 +/- 0.13 vs. 0.53 +/- 0.13) in older than in young subjects. CONCLUSIONS: Therefore, aging has adverse effects on renal function despite the absence of any risk factor for renal disease, including chronic smoking: (1) GFR and RPF are lower, and (2) the renal response to maximal vasodilating stimulus is impaired. These aging-related alterations of renal hemodynamics are possibly due to organic lesions in renal vasculature.

Adult↗

PubMed2001

Neuronal cell death in the visual cortex is a prominent feature of the X-linked recessive mitochondrial deafness-dystonia syndrome caused by mutations in the TIMM8a gene.

The Mohr-Tranebjaerg syndrome (MIM 304700) and the Jensen syndrome (MIM 311150) were previously reported as separate X-linked recessive deafness syndromes associated with progressive visual deterioration, dystonia, dementia, and psychiatric abnormalities. In the most extensively studied Norwegian family, the Mohr-Tranebjaerg syndrome was reported to be caused by a one-basepair deletion (151delT) in the deafness/dystonia peptide (DDP) gene at Xq22. This gene has been renamed TIMM8a. We identified a stop mutation (E24X) in the TIMM8a gene segregating with the disease in the original Danish family with the Jensen syndrome, which confirms that the two disorders are allelic conditions. We also report abnormal VEP examinations and neuropathological abnormalities in affected males from the two unrelated families with different mutations. The findings included neuronal cell loss in the optic nerve, retina, striate cortex, basal ganglia, and dorsal roots of the spinal cord. The demonstration of mitochondrial abnormalities in skeletal muscle biopsies in some patients is compatible with the suggestion from recent research that the TIMM8a protein is the human counterpart of an intermembrane mitochondrial transport protein, Tim8p, recently characterized in yeast. The clinical and neuropathological abnormalities associated with mutations in the TIMM8a gene support that this X-linked deafness-dystonia-optic neuropathy syndrome is an example of progressive neurodegeneration due to mutations in a nuclear gene necessary for some, yet unknown mitochondrial transport function. We recommend sequencing the TIMM8a gene, thorough ophthalmological examination, and measuring visual evoked potentials in clinically suspected male patients with either progressive hearing impairment, dystonia, or visual disability in order to establish an early diagnosis and provide appropriate genetic counselling.

Adolescent↗

PubMed2000

Prenatal diagnosis of tracheal obstruction: possible association with maternal pertussis infection.

A fetus with the sonographic appearance of echogenic and enlarged lungs and dilated trachea and bronchi, indicating laryngotracheal obstruction, is reported. Additionally, the fetus had ascites and subcutaneous edema and the amniotic fluid volume was reduced. Doppler flow investigation of the systemic venous circulation revealed signs of heart failure, and color Doppler visualized possible increased pulmonary flow. Following termination of pregnancy, autopsy confirmed the sonographic observations and revealed a hypoplastic thymus. During the present pregnancy the mother suffered from sustained cough, and serological tests revealed acute pertussis infection. Polymerase chain reaction investigation for Bordetella pertussis in the amniotic fluid was negative. The possibilities of pertussis toxins as noxious factors and of an atypical presentation of DiGeorge anomaly are discussed.

Abortion, Therapeutic↗

PubMed1999

Gene expression of the renal endothelin system in renal transplant recipients on cyclosporine A based immunosuppression.

BACKGROUND: Immunosuppressive therapy based on cyclosporine A (CsA) is potentially nephrotoxic, and each dose of CsA is followed by a transient increase in plasma endothelin (ET)-1. The aim of this study was to investigate the effect of CsA based immunosuppressive therapy on renal gene expression of the ET(A) and ET(B) receptor subtypes and preproET-1 in human transplant needle biopsies. METHODS: Twelve living donor renal transplant recipients, median age 51.5 years (range 24-63 years) were included in the study. Immunosuppressive therapy consisted of CsA, azathioprine, and prednisolone. Baseline renal cortical needle biopsies from the living donor kidneys were obtained just before nephrectomy. Follow-up biopsies were obtained from the same transplanted kidneys after 2-6 weeks of immunosuppressive therapy. We used a quantitative, competitive reverse transcriptase polymerase chain reaction assay to measure renal ET(A) and ET(B) receptor subtype mRNAs as well as preproET-1 mRNA levels in each of the biopsies. RESULTS: The renal ET system was not significantly altered by CsA-based immunosuppressive therapy. Median ET(A) mRNA level was 185 (range 35-244) at baseline, and 120 (11-189) amol/microg total RNA after CsA based immunosuppressive therapy (P=0.11). ET(B) mRNA level was 506 (209-1411) at baseline, and 463 (267-1609) amol/microg total RNA at follow-up (P=0.44) and preproET-1 mRNA level was 160 (112-392) before and 221 (187-361) amol/microg total RNA after immunosuppressive therapy based on CsA (P=0.58). CONCLUSION: This study indicates that 2-6 weeks of CsA-based immunosuppression neither significantly influences renal gene expression of the ET(A) or ET(B) receptor subtypes nor preproET-1 in living donor renal transplant kidneys.

Adult↗

PubMed1999

Living donor kidney transplants: a biopsy study 1 year after transplantation, compared with baseline changes and correlation to kidney function at 1 and 3 years.

INTRODUCTION: Chronic changes in biopsies from long-term stable kidney allografts have been reported to correlate with graft prognosis. Morphological changes in baseline ('zero-hour') biopsies have been described as well, but their importance for long-term prognosis have been less clear. The aim of the present study was to evaluate biopsy changes from baseline to 1 year after transplantation in patients receiving kidneys from living donors, and to assess the possible prognostic implications of these findings. METHODS: Light microscopical changes in 18 gauge full-core biopsies were scored semi-quantitatively in 33 patients 1 year after transplantation, and compared to baseline changes previously reported [1]. All cases were also examined with transmission electron microscopy. The semi-quantitative data from baseline and at 1 year were correlated with kidney function 1 and 3 years after transplantation. The reproducibility of baseline findings regarding arteriosclerosis and arteriolar hyalinosis was tested by comparison with biopsies 1 week after transplantation (n = 43). RESULTS: We found a significant increase in mesangial glomerular sclerosis (P<0.001), interstitial fibrosis/tubular atrophy (if/ta) (P = 0.002), and mononuclear cell interstitial infiltration (P = 0.003) after 1 year, compared to baseline changes. There was an increase of arteriosclerosis (P = 0.028) and arteriolar hyalinosis (P = 0.006) when compared to biopsies taken 1 week after transplantation, but not when compared to the 'zero-hour' findings. Electron microscopy revealed one case of recurrent immune-complex glomerulonephritis and another case of recurrent light chain deposition kidney disease. Comparing 1-week vascular findings with baseline gave a low level of reproducibility, probably due to sampling error. Baseline biopsy findings could not predict long-term kidney function. In the 1-year biopsy, if/ta was significantly correlated with serum creatinine (P = 0.007) and glomerular filtration rate (GFR) (P<0.001) at 1 year, with serum creatinine at 3 years (P = 0.011), and with the first-year cumulative dose of methylprednisolone (P = 0.004). Serum creatinine at 1 year, however, was found to be the most accurate predictor of 3-year kidney function (P<0.001). Donor age was correlated to kidney function at 3 years (P = 0.013) but not at 1 year after transplantation. CONCLUSION: Morphological changes in baseline biopsies of living donor kidneys tend to become more pronounced in well-functioning allografts during the first year after transplantation. In the 1 year biopsy, if/ta seems to be the most reliable variate for grading of chronic changes. However, 1-year serum creatinine predicted long-term kidney function more precisely than did the biopsy scores. Based on the results of the present study, a protocol 1-year biopsy does not seem warranted in the management of the graft recipient with a stable kidney function.

Adult↗

PubMed1998

Postpartum renal failure: a complex case with probable coexistence of hemolysis, elevated liver enzymes, low platelet count, and hemolytic uremic syndrome.

BACKGROUND: Postpartum renal failure in previously healthy subjects is associated most often with preeclampsia and/or hypertension; hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome, hemolytic uremic syndrome; or thrombotic thrombocytopenic purpura. Transient oliguria associated with preeclampsia is common, but renal failure is rare. Coexistence of HELLP and hemolytic uremic syndromes has been suggested, but histopathologic documentation of this combination has been scarce. CASE: A 30-year-old primigravida with severe preeclampsia at 35 weeks and 3 days' gestation presented with the development of HELLP syndrome and renal failure postpartum. Histopathologic lesions characteristic of hemolytic uremic syndrome were present in the kidney. CONCLUSION: Probable overlapping of HELLP and hemolytic uremic syndromes in pregnancy or postpartum should be taken into consideration when treating patients with these syndromes and associated complications, such as renal failure.

Adult↗

PubMed1998

Morphological studies of baseline needle biopsies from living donor kidneys: light microscopic, immunohistochemical and ultrastructural findings.

Fifty-seven consecutive living donors (31 women and 26 men aged 20.7-72.3 years, mean 50.6 years) were subjected to needle biopsy during nephrectomy, immediately before removal of the kidney. By light microscopy, semiquantitative scoring (0-3) was performed for arteriosclerosis, arteriolar hyalinosis (hyalin arteriolosclerosis), glomerulosclerosis, interstitial mononuclear cell infiltration, and interstitial fibrosis/tubular atrophy. Whereas vascular changes were striking in many biopsies (arteriosclerosis grades 2-3: 28/54 cases, arteriolar hyalinosis grades 2-3: 15/55 cases), glomerular and tubulointerstitial changes were mostly low grade. The morphological changes tended to be more pronounced in middle-aged and older individuals, but, in particular, vascular changes were seen also in the younger age group. Immunofluorescence microscopy revealed glomerular granular staining for IgM in 52.7% of the cases, IgA in 9.1%), IgG in 1.8%, and C3 in 12.7%. The main ultrastructural finding was glomerulosclerosis; one case with diffuse glomerular IgA showed distinct dense deposits, and one case showed similar dense deposits without IgA deposition. Arteriolar wall deposition of C3 was found in 58.2% of the cases, and IgM in 10.9%. Especially C3 occurred both with arteriolar hyalinosis and in arterioles without light microscopic alterations. The observation of significant vascular changes in baseline biopsies is relevant especially in the differential diagnosis of chronic rejection and cyclosporine nephropathy. The immunohistochemical findings strongly indicate the occurrence of immunoglobulins and complement factor C3 in both glomeruli and arterioles without clinical or morphological signs of renal disease. The possible pathophysiological significance of such deposits remains, however, uncertain.

Adult↗

PubMed1998

Can a diagnosis of renal allograft rejection be based on histology alone?

Acute renal allograft rejection is suspected by the clinician when the serum creatinine value increases in a patient for no other particular cause. A renal allograft biopsy may confirm the diagnosis. This report describes 2 patients with stable serum creatinine; however, protocol biopsy showed acute rejection changes according to the Banff criteria. No anti-rejection treatment was started and their graft function remained stable for 6 months. These two cases focus on the fact that renal allograft rejection should first of all be regarded as a clinical diagnosis which could be substantiated by histological findings.

Acute Disease↗

PubMed1997

Cure of infantile myofibromatosis with severe respiratory complications without antitumour therapy.

UNLABELLED: The prognosis of infantile myofibromatosis (IMF) depends on the organs involved: the prognosis is very poor if vital viscera are affected, but excellent if there is no visceral involvement. We report the case of a boy presenting with a pathological fracture at the age of 6 weeks. Progressive osteolytic lesions in the whole skeleton until the age of 8 months led to respiratory failure due to a softened thoracic wall requiring mechanical ventilation for 11 months. No pulmonary, laryngeal or other visceral involvement was found. In spite of the rapidly progressing disease and serious complications only supportive therapy was given. The lesions subsided gradually leaving slight deformities but normal function. At the age of 3.5 years the boy has an excellent quality of life. CONCLUSION: This case illustrates that even in progressing, complicated multifocal infantile myofibromatosis (without visceral involvement) the lesions can resolve without antitumour treatment if high quality intensive care is supplemented.

Bone Neoplasms↗

PubMed1996

The histone-like protein H-NS acts as a transcriptional repressor for expression of the anaerobic and growth phase activator AppY of Escherichia coli.

The transcriptional activator AppY is required for anaerobic and stationary-phase induction of the cyx-appA and hya operons of Escherichia coli, and expression of the appY gene itself is induced by these environmental conditions. The sequence of the appY gene and its promoter region is unusually AT rich. The nucleoid-associated protein H-NS has a DNA-binding specificity for intrinsically curved AT-rich DNA. Using a single-copy transcriptional appY-lacZ fusion, we have shown that appY gene expression is derepressed in hns mutants during aerobic exponential growth. In the hns mutant, growth phase and growth rate regulation under aerobic conditions was maintained, while ArcA-dependent anaerobic induction was greatly diminished. Judged by two-dimensional gel electrophoresis, the appY promoter fragment exhibits the features characteristic of curved DNA. Gel retardation assays showed that purified H-NS protein bound with high affinity to two different segments of the appY promoter region. The role of H-NS in the AppY regulatory cascade is discussed and compared with its function in the regulatory cascades of the AppY homologs CfaD and VirF.

Anaerobiosis↗

PubMed1995

Autonomous hyperparathyroidism in X-linked hypophosphataemia.

Four patients with familial hypophosphataemic rickets developed significant hypercalcaemia which persisted after discontinuation of vitamin D therapy. They had increased PTH levels and were operated for hyperparathyroidism at the ages of 18, 20, 24 and 45 years, respectively. Three of the patients had previously received phosphate treatment and one patient developed hyperparathyroidism 7 years after treatment with calcitriol. Histological evaluation revealed different degrees of parathyroid hyperplasia in all patients, with persistently increased PTH and/or calcium levels after surgery. The possibility of autonomous hyperparathyroidism should be evaluated in the follow-up of patients with X-linked hypophosphataemic rickets.

Adult↗

PubMed1994

Small cell pleomorphic T-cell lymphoma presenting with cutaneous vasculitis.

The association between cutaneous vasculitis and lymphoproliferative disease has been increasingly recognized. We report a female patient who presented with cutaneous vasculitis which was due to a small cell pleomorphic T-cell lymphoma. In spite of aggressive therapy, she died two years after onset of disease. The clinical picture of vasculitis associated with lympho-proliferative disease is addressed with particular emphasis on symptoms and signs suggesting malignancy rather than vasculitis appearing in concert with well-defined connective tissue disorders.

Adrenal Cortex Hormones↗

PubMed1994

Morphological and functional renal effects of long-term low-dose cyclosporin A treatment in patients with rheumatoid arthritis.

To explore the possible nephrotoxic effects of low-dose cyclosporin A (CyA) treatment, we analyzed the data from 10 patients, aged 35-66 years (mean 51.8 years), who had a clinical diagnosis of rheumatoid arthritis and no known kidney disease. The study protocol included consecutive kidney biopsies and a pretreatment biopsy in all cases. A second biopsy was taken after 5-20 months (mean 17.8 months) of treatment and, in seven patients, a third biopsy was performed after 30-46 months (mean 38.6 months). Evaluation of the kidney biopsies included a semiquantitative estimation of different histological parameters as well as assessment of a chronicity index (CI). Transmission electronmicroscopic examination was performed on all biopsies. There was a significant reduction of glomerular function at the time of both the second (n = 10; p < 0.01) and third (n = 7; p < 0.05) biopsies. Five patients showed an increase in CI on the second biopsy and five on the third biopsy in comparison to pretreatment values. Only one patient showed a progressive increase in CI on three consecutive biopsies. The mean CI increased on both the second (n = 10) and third (n = 7) biopsies compared with baseline, but there was no increase on the third biopsy from the second. The morphological findings were, as a rule, slight or moderate, and focal interstitial fibrosis, tubular atrophy and arteriolar hyalinosis were the most consistent findings. Although even low-dose CyA treatment may be nephrotoxic and may induce morphological alterations in the kidney, such changes do not occur in all patients and may not necessarily be progressive.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

[Disseminated fungal infections in neonates--risk factors, treatment and course].

During 10 1/2 months in 1990/91 eight premature babies and one mature baby with an intra-abdominal disease had disseminated Candida albicans infections. The incidence in premature newborns was 9% (8/92 patients). Risk factors such as respirator therapy, the use of broad spectrum antibiotics, supplemental parenteral nutrition and central intravascular catheters were frequently seen. Four patients survived the fungal infection. These included three of five babies treated with amphotericin B 0.5 mg/kg/day. Two patients who received fluconazole 3 mg/kg/day died after three days. In one patient the diagnosis was obtained post-mortem, and one patient with possible fungemia survived without therapy. The treatment of these patients depends on optimal fungal cultures and good co-operation between paediatricians and microbiologists.

Anti-Bacterial Agents↗

PubMed1992

[Kasabach-Merritt syndrome. A differential diagnosis in thrombocytopenia].

The Kasabach-Merritt syndrome consists of hemangioma in association with thrombocytopenia and localized consumption coagulopathy. It is primarily a disease of childhood, but may be seen in adult patients too. When untreated, it involves considerable risk of mortality. Two adult patients are described. The disease can be cured by surgery. We discuss different options for treatment when surgery is not feasible.

Diagnosis, Differential↗