Assessing the relative impact of lupus nephritis on mortality in a population-based systemic lupus erythematosus cohort.

OBJECTIVE: There is limited knowledge on the relative impact of lupus nephritis (LN) on morbidity and mortality in population-based systemic lupus erythematous (SLE) cohorts. Here, the primary aim was to compare mortality rates between patients with and without LN in a population-based SLE cohort. METHODS: The study cohort included all SLE patients resident in the city of Oslo during 1999-2008. Follow-up time was median 14 (0-15) years. Presence of LN was defined according to the 1987 American College of Rheumatology classification criteria for SLE. LN class was determined by renal biopsy. Data on kidney function, including presence of end-stage renal disease (ESRD), were obtained from patient charts. Standardized mortality ratios (SMRs) were estimated by comparing deaths in the SLE cohort with age- and gender-matched population controls. RESULTS: We found that 98/325 SLE patients (30%) developed LN, 92% of whom had occurrence within the first five years from disease onset. Incidence rate of ESRD was 2.3 per 1000 patient-years. A total of 56 deaths occurred during the study period, corresponding to an overall SMR in the SLE cohort of 2.1 (95% confidence interval (CI) 1.2-3.4). Estimated SMR for LN patients was 3.8 (95% CI 2.1-6.2), and for SLE patients without LN it was 1.7 (95% CI 0.9-2.7). CONCLUSION: In this population-based SLE cohort, we found that LN was associated with increased morbidity and mortality, whereas SLE patients who did not develop LN had good overall prognoses regarding survival.

Immunoelectron microscopy on epoxy sections without deplasticizing to detect glomerular immunoglobulin and complement deposits in renal diseases.

Twenty renal biopsies were studied by immunoelectron microscopy (IEM) after embedding in epoxy resin. Immunogold labeling for immunoglobulins and complement C3 was performed on the epoxy sections, which were not subjected to any kind of etching or deplasticizing prior to the immunolabeling. The concentration of accelerator, DMP-30 (Tri (Dimethyl Amino Methyl) Phenol), was increased in the infiltration and embedding steps far beyond the values normally used to make immunolabeling of these antigens possible on epoxy sections. The sections were stained with tannic acid accompanied by uranyl acetate and lead citrate. Immunofluorescence (IF) for light microscopy was carried out on frozen sections of parallel tissue samples. Some cases with IgA-nephritis demonstrated a higher sensitivity for IEM than IF, in the sense that smaller amounts of antigen were detectable with IEM. Ultrastructural preservation with this method was approximately the same as that usually seen on epoxy-embedded material. By combining excellent immunolabeling with nearly optimal ultrastructural morphology in one procedure, this method is useful particularly in situations where the material available is limited, such as in studies of renal biopsies. As far as we know, this is the first time that immunoglobulins have been satisfactorily immunolabeled on epoxy sections without etching or deplasticizing.

Atrophy and sponginess of the mammillary bodies with neuronal sparing: not only inactive Wernicke's encephalopathy.

Two cases are reported in which old anoxic/ischemic damage to the Ammon's horns was associated with atrophy and sponginess of the mammillary bodies but with sparing of the neuronal perikarya. The lesions were unilateral in one case and bilateral in the other. The changes in the mammillary bodies closely resembled those seen in inactive Wernicke's encephalopathy but they were considered to be due to transneuronal atrophy following loss of hippocampal afferent fibres. Consequently, this condition may present a problem in diagnostic neuropathology. However, there was no reactive astrogliosis in these cases and this may serve to distinguish this condition from inactive Wernicke's encephalopathy in which gliosis is always present and often prominent.

The use of post-embedding immunoelectron microscopy in the diagnosis of glomerular diseases. Comparison of immunoelectron microscopic and immunofluorescence studies.

Fifty renal biopsies were studied by immunoelectron microscopy after embedding in a partly hydrophilic polyacrylic resin (LR White). Immunofluorescence studies were carried out on frozen sections of parallel tissue samples. Polyacrylic embedding gave good preservation of the renal ultrastructure and precise localization of immunoglobulin and C3c antibodies within glomerular electron-dense deposits. Non-specific staining of plasma proteins within vascular lumina could easily be detected. There was good correlation between immunoelectron and immunofluorescence microscopy. Immunoelectron microscopy is a very sensitive method, which can detect small amounts of antigen. More cases were, however, positive by immunofluorescence than by immunoelectron microscopy. This discrepancy may be explained by difference in sample size, and by difference in resolution of morphological details (electron microscopy versus fluorescence microscopy).

High incidence and aggressive growth of non-AIDS-defining cancers among AIDS patients in Oslo.

The spectrum of cancers advanced by AIDS is disputed. To supplement the register-based investigations, we have studied the occurrence of non-AIDS-defining malignancies in a closely followed population of AIDS patients. The population comprises 255 patients fulfilling CDC's clinical AIDS definition, representing 91% of all adult AIDS patients from Oslo 1983-1995. Full autopsy was performed on 73% of the 211 fatal cases. Adding patients with CD4 cell counts below 200 cells/mm3 to match the US AIDS definition, the population increases to 344, including 225 deceased. The expected number of cancer cases was calculated from age- and sex-specific cancer incidence rates for Oslo 1988-1992. The number of non-AIDS-defining cancers was six (clinical CDC criteria) or eight (US AIDS definition), compared to expected numbers of 0.54 and 1.0, respectively. At autopsy, four of eight cases showed extensive tumor dissemination with involvement of the heart. These observations suggest that (at least some) non-AIDS-defining cancers occur at increased rates and show aggressive growth pattern in AIDS.

Light chain deposition disease of the kidney. Morphological aspects in 24 patients.

Renal biopsies and autopsy specimens of 23 patients with light chain deposition disease (LCDD) and one with only heavy chain deposits, were studied by light (LM) and electron microscopy (EM) as well as immunohistology (IH). Thirteen patients had multiple myeloma; 1 had lymphoma, and 1 chronic myeloid leukaemia with polycythaemia vera. In nine patients, no lymphoproliferative disease was identified. The LM lesions most suggestive of LCDD, nodular glomerulosclerosis (NS) and thickening and wrinkling of the tubular basement membranes (TBM), were present in only ten and 13 patients, respectively. In five of seven specimens without NS or TBM thickening by LM, EM was negative, indicating a limited value of EM in confirming the diagnosis. Renal amyloidosis was not identified, but in one patient amyloid in the heart and tongue was seen at autopsy. One patient had both granular and extensive glomerular non-amyloid fibrillary deposits. In two patients myeloma casts were identified. Twenty-one patients showed renal LC immune reactivity, 1 had both alpha heavy and lambda LC, 1 had only detectable gamma heavy chain. One biopsy was negative by IH, but had characteristic electron dense deposits. In six patients with immune reactivity to LC, no electron dense deposits could be identified by EM. This study emphasizes the spectrum of renal changes by LM and EM in LCDD, the frequent lack of consistency between deposits detected by IH and EM and the difficulty in coming to a definite diagnosis without LM, EM and IH. The results of this study and examination of the literature indicates that extensive morphological changes are more often present in kappa than in lambda LCDD.

Ciclosporin-associated arteriolopathy: the renin producing vascular smooth muscle cells are more sensitive to ciclosporin toxicity.

The pathogenesis of ciclosporin (Cs) induced renal vasoconstriction and CS-associated arteriolopathy (CAA) has not been fully explained. CAA affects the part of the afferent arteriole where renin is most abundant, and an effect by Cs on the renin producing smooth muscle cells leading to necrosis has been suggested. Forty transplant biopsies with CAA of different degrees were compared with 10 transplant biopsies from Cs treated patients without CAA, and with 10 "zero-hour" control biopsies (taken from the donor kidney at implantation). Immunoreactivity to renin by the ABC method was recorded in the arterioles. Compared to the control group there was a slight increase in the proportion of renin positive arterioles in the Cs treated group without CAA, but with increasing CAA there was a decrease in the proportion of renin positive arterioles. In the group of arterioles with CAA, we found that with increase in the severity of CAA, there was an increase in renin negative arterioles, indicating a loss of renin containing cells in these arterioles. This suggests that a large proportion of the necrotic cells in CAA has once been renin producing smooth muscle cells. Our findings support the possibility that Cs stimulates renin production, and that the renin producing cells are more sensitive to Cs toxicity.

Renal disease and patient survival in light chain deposition disease.

We evaluated retrospectively the presenting clinical features, response to treatment and clinical course of 19 patients with LCDD, 11 of whom had multiple myeloma. At presentation, renal insufficiency was present in 18 patients and proteinuria in 16. Renal biopsy revealed typical LCDD in 16 patients, while in the remaining three LCDD was associated with other abnormal tissue deposits. Extrarenal signs were observed in 12 patients (63%), with the liver, heart and peripheral nerves being the most frequently involved organs. After diagnosis, 18 patients underwent therapy: 2 received steroids alone and 16 were treated with steroids and cytotoxic drugs; 7 patients also underwent plasma exchange. At the end of the first month of treatment renal function improved in 5 patients, worsened in 5 and remained unchanged in 8. All but 3 of the patients continued treatment beyond the first month: 7 patients developed end-stage renal disease, 5 an improvement and 4 a worsening in renal function. No effect on proteinuria was observed. Extrarenal symptoms developed in 4 previously unaffected patients and in 3 others they extended to more organs. Sixteen patients died: 12 during the first year of the follow-up, and 4 at 21st, 34th, 37th and 82nd month of observation. Five patients died from neoplastic cachexia, 4 from hypokinetic cardiopathy, 3 from hemorrhagic complications, 2 from pneumonia and one from unknown cause. Mean patient survival after presentation was 18.1 +/- 20.7 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Polycystic tumor of the atrioventricular nodal region in a man with Emery-Dreifuss muscular dystrophy.

Benign polycystic tumor of the atrioventricular nodal region is a lesion associated with cardiac conduction defects with atrioventricular block and sudden death. We present the clinical and light microscopical, immunohistochemical and ultrastructural findings of such a lesion in a young man with X-linked recessive Emery-Dreifuss muscular dystrophy who died suddenly. The tumor has not previously been described in this group of patients, who frequently suffers from cardiac electric instability and sudden death. Possible mechanisms by which the tumor may cause arrhythmia are discussed and the presence of neuroendocrine cells in the lesion is emphasized.

Solitary fibrous tumor of the pleura. An immunohistochemical, electron microscopic and tissue culture study of a tumor producing insulin-like growth factor I in a patient with hypoglycemia.

We report a patient with recurrent hypoglycemia most likely caused by a solitary fibrous tumor of the pleura. After removal of the tumor, hypoglycemia resolved. The bland histologic picture of this tumor is emphasized. Electron microscopic and immunohistochemical observations support its non-mesothelial derivation. In vitro studies demonstrated that the tumor tissue produced insulin-like growth factor I (IGF-I), and its role as the cause of hypoglycemia is discussed.

Craniopharyngioma in a boy with centronuclear (myotubular) myopathy: clinical and postmortem findings.

This report describes a case of centronuclear myopathy which was considered to represent an example of severe x-linked myotubular myopathy [van Wijngaarden et al. 1969]. The neonatal period was dramatic with weak movements and respiratory problems. This was followed by a gradual improvement of muscle strength but he continued to have severe respiratory problems. At the age of four he developed the symptoms of a craniopharyngioma, which was operated upon. He died from respiratory failure two months after the operation.

Ocular pathology in light chain deposition disease.

Light-chain deposition disease (LCDD), a rare form of monoclonal gammopathy, is characterized by deposits of amorphous light-chain material, mainly in the kidneys but also in various other organs. Here we present the first report of a light-, electron microscopic and immunohistochemical study of the globes of a patient suffering from LCDD secondary to multiple myeloma. Massive deposits of kappa light chains similar to those typically present in the kidneys were found beneath the basement membrane of the ciliary pigment epithelium, on vessels of the ciliary body, within the collagenous zones of Bruch's membrane, and in the innermost part of the choroid. The choriocapillaris in the macular area was partly obstructed by these deposits, and an exudative retinal detachment was present. Whether this detachment was the consequence of disturbed circulation of the choriocapillaris remains speculative.

Calcineurin inhibitor-free immunosuppression in renal allograft recipients with thrombotic microangiopathy/hemolytic uremic syndrome.

Thrombotic microangiopathy (TMA) and hemolytic uremic syndrome (HUS) represent serious threats to kidney allograft recipients. During a 4-year period, among 850 kidney transplantations, seven recipients with primary HUS and seven recipients (eight transplants) with previous or de novo TMA/HUS were identified and given calcineurin inhibitor (CNI)-free immunosuppression by sirolimus (SRL), mycophenolate mofetil and steroids. Thirteen out of 15 transplantations were successful in the long term; resulting in a mean creatinine of 101 mumol/L (16.4 months follow-up). In patients maintained on CNI-free regimen, no TMA/HUS recurrences were observed. A high rate of acute rejections (53%) may indicate insufficient immunosuppressive power and/or a causative relationship between TMA/HUS and rejection. Wound-related complications were abundant (60%), and call for surgical/immunosuppressive countermeasures. Our experience supports the idea that CNI's are major offenders in TMA/HUS induction. Total CNI elimination seems essential, as the nephrotoxic combination CNI + SRL may promote TMA. Features of TMA/HUS should be carefully explored in recurrent 'high responders'.

A new immunoelectron microscopy approach for the detection of immunoglobulin and complement deposits in epoxy-embedded renal biopsies.

The purpose of this study was to examine the diagnostic value of a new immunoelectron microscopy technique (IEM) for detection of immunoglobulin and complement deposits in epoxy-embedded renal biopsies. Twenty-four renal biopsies were embedded in epoxy resin following a tissue processing involving moderately increased amount of accelerator, DMP-30 (Tri(Dimethyl Amino Methyl) Phenol), in the infiltration steps. Following antigen retrieval by heating in citrate buffer, immunogold labeling was performed on ultrathin sections from these epoxy blocks with antibodies against immunoglobulins and complement. The sections were counterstained with urnayl acetate and lead citrate without any enhancing procedures. The preservation of the ultrastructure with this method was similar to that usually seen in epoxy embedded material. The immunogold labeling was intense and distinct. Immunofluorescence (IF) for light microscopy was carried out on frozen sections of parallel tissue samples. The correspondence between IF and IEM were good, but in some cases higher sensitivity for IgA with IEM than IF was observed in the sense that smaller amounts of antigen were detectable with IEM. The combination of moderately increased amount of accelerator and antigen retrieval is superior to previous methods with respect to ease of use, ultrastructural preservation, and intensity of the immunolabeling. Moreover, the renal tissue can be processed in an automatic ultraprocessor together with other specimens which are to be prepared for routine electron microscopy.

[Soft tissue tumors of the lung and pleura]. / Bløtdelssvulster i lunge og pleura.

We present two patients with lung and pleura soft tissue tumours. A 37 year-old man had a small, highly malignant tumour which had invaded the mitral valve. The presenting symptom was mitral stenosis. The tumour was classified as a leiomyosarcoma. A 65 year-old female had a large tumour, which was most probably a solitary fibrous mesothelioma. Hypoglycaemia was evident. Insulin-like growth factor I was produced by tumour cells, although the hormone was not found in the plasma.

Peridiverticulitis of the appendix: an unusual ultrasonic "target lesion".

In a 26-year-old man with perforating diverticulitis of the appendix ultrasonography demonstrated a "target lesion" with a hyperechoic center surrounded by a hypoechoic rim similar to the findings commonly seen in benign and malignant conditions of the gastrointestinal tract. This ultrasonographic appearance is quite different from the ultrasonic findings usual in acute appendicitis. We take this to be the first ultrasonic demonstration of appendiceal diverticulitis, and discuss the clinical features, ultrasonic differential diagnosis, and pathology of this condition.

[Adenocarcinoid (mucinous carcinoid) of the vermiform appendix]. / Adenokarsinoid (mucinøst karsinoid) i appendix vermiformis.

Adenocarcinoid (mucinous carcinoid or goblet cell carcinoid) is an unusual tumour of the appendix with histologic and prognostic features between those of carcinoid and adenocarcinoma. Most patients with adenocarcinoid tumours of the appendix present with symptoms consistent with those of acute appendicitis. We describe a 31 year-old male who presented with such symptoms. Ultrasonography demonstrated an acutely inflamed appendix with a hypoechoic area in the midportion of the appendix, suspicious of a tumour. This rare type of tumour is briefly presented.