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LCAT converts free cholesterol to cholesteryl esters in the process of reverse cholesterol transport. Familial LCAT deficiency (FLD) is a genetic disease that was first described by Kaare R. Norum and Egil Gjone in 1967. This report is a summary from a 2017 symposium where Dr. Norum recounted the history of FLD and leading experts on LCAT shared their results. The Tesmer laboratory shared structural findings on LCAT and the close homolog, lysosomal phospholipase A2. Results from studies of FLD patients in Finland, Brazil, Norway, and Italy were presented, as well as the status of a patient registry. Drs. Kuivenhoven and Calabresi presented data from carriers of genetic mutations suggesting that FLD does not necessarily accelerate atherosclerosis. Dr. Ng shared that LCAT-null mice were protected from diet-induced obesity, insulin resistance, and nonalcoholic fatty liver disease. Dr. Zhou presented multiple innovations for increasing LCAT activity for therapeutic purposes, whereas Dr. Remaley showed results from treatment of an FLD patient with recombinant human LCAT (rhLCAT). Dr. Karathanasis showed that rhLCAT infusion in mice stimulates cholesterol efflux and suggested that it could also enhance cholesterol efflux from macrophages. While the role of LCAT in atherosclerosis remains elusive, the consensus is that a continued study of both the enzyme and disease will lead toward better treatments for patients with heart disease and FLD.

Patients with high tacrolimus clearance are more likely to experience transient under-immunosuppression in case of a missed or delayed dose. We wanted to investigate the association between estimated tacrolimus clearance and development of graft interstitial fibrosis and tubular atrophy (IFTA) in kidney transplant recipients. Associations between estimated tacrolimus clearance [daily tacrolimus dose (mg)/trough concentration (μg/l)] and changes in IFTA biopsy scores from week 7 to 1-year post-transplantation were investigated. Data from 504 patients transplanted between 2009 and 2013 with paired protocol biopsies (7 weeks + 1-year post-transplant) were included. There were no differences in baseline biopsy scores (7 weeks) in patients with different estimated tacrolimus clearance. Increasing tacrolimus clearance was significantly associated with increased ci + ct score of ≥2 at 1 year, odds ratio of 1.67 (95% CI; 1.11-2.51). In patients without fibrosis (ci + ct ≤ 1) at 7 weeks (n = 233), increasing tacrolimus clearance was associated with development of de novo IFTA (i + t ≤ 1 and ci + ct ≥ 2) at 1 year, odds ratio of 2.01 (95% CI; 1.18-3.50) after adjusting for confounders. High tacrolimus clearance was significantly associated with development of IFTA the first year following renal transplantation.

Renal DNase I is lost in advanced stages of lupus nephritis. Here, we determined if loss of renal DNase I reflects a concurrent loss of urinary DNase I, and whether absence of urinary DNase I predicts disease progression. Mouse and human DNase I protein and DNase I endonuclease activity levels were determined by western blot, gel, and radial activity assays at different stages of the murine and human forms of the disease. Cellular localization of DNase I was analyzed by immunohistochemistry, immunofluorescence, confocal microscopy, and immunoelectron microscopy. We further compared DNase I levels in human native and transplanted kidneys to determine if the disease depended on autologous renal genes, or whether the nephritic process proceeded also in transplanted kidneys. The data indicate that reduced renal DNase I expression level relates to serious progression of lupus nephritis in murine, human native, and transplanted kidneys. Notably, silencing of renal DNase I correlated with loss of DNase I endonuclease activity in the urine samples. Thus, urinary DNase I levels may therefore be used as a marker of lupus nephritis disease progression and reduce the need for renal biopsies.

Background/aim The favorable prognosis of women with non-small-cell lung cancer (NSCLC) compared to men might be explained by sex hormone-related mechanisms. We investigated whether this observation could be explained by the expression of estrogen receptor-alpha (ER-α) in tumor tissue. Materials and methods Archived, formalin fixed, paraffin embedded tumor tissue samples were retrospectively analyzed for nuclear expression of ER-α with immunohistochemistry. Results Biopsies from 222 patients were analyzed. Twenty-three percent were ER-α positive. Fifty-four percent of the patients were men and 46% of the tumors were adenocarcinomas. One hundred-nine (49%) patients received pemetrexed and carboplatin and 113 (51%) received gemcitabine and carboplatin. Females with ER-α positive tumors who received PC had a substantial survival benefit over all other groups (20 vs. 4.6 months; p=0.003). Conclusion ER-α is an independent prognostic factor in advanced NSCLC and might also be a predictive factor for response to pemetrexed/carboplatin in women.

Loss of renal DNase I leads to progression of lupus nephritis. Therefore, we determined if loss of renal DNase I reflects a concurrent loss of urinary DNase I, and whether absence of urinary DNase I predicts disease progression, which thus may reduce the need for renal biopsies. Here, mouse renal DNase I mRNA was determined by qPCR, whereas mouse and human DNase I protein and DNase I endonuclease activity levels were determined by Western blots, and gel and radial zymography assays, respectively, during different stages of the murine and human forms of the disease. Cellular localization of DNase I was analysed by immunohistochemistry, immunofluorescence, confocal microscopy and immune electron microscopy. We further compared DNase I levels in human native and transplanted kidneys to determine if the disease depended on autologous renal genes, or whether the nephritic process proceeded also in transplanted kidneys. We also analysed if DNase I levels in urine samples reflected expression levels in the kidneys, and if the mouse data were translatable to humans. The data indicates that silencing of the renal DNase I gene expression level relates to serious progression of lupus nephritis in murine, human native, and transplanted kidneys. Notably, silencing of renal DNase I correlates with loss of DNase I protein and endonuclease activity in the urine samples. Thus, urinary DNase I levels reflects the renal DNase I expression and activity levels, and may therefore be used as a marker of lupus nephritis disease progression and reduce the need for renal biopsies.

Rezidive von Glomerulonephritiden nach Nierentransplantation stellen eine wichtige Ursache des Transplantatversagens speziell im Langzeitverlauf dar. Die genaue Häufigkeit hängt einerseits vom Typ der glomerulären Grunderkrankung ab und anderseits davon, ob die Rezidive klinisch-pathologisch oder nur histologisch festgestellt werden. Der Einfluss der Rezidive auf die Funktion und das Überleben des Nierentransplantats variiert je nach der Grunderkrankung ebenfalls stark. Rezidive nach IgA-Nephropathie (IgAN) treten beispielsweise je nach Beobachtungsdauer bei über 50 % der Transplantate mit oft relativ langsamer Progredienz auf. Fokal segmentale Glomerulosklerose und membranoproliferative Glomerulonephritis haben jedoch generell eine deutlich schlechtere Prognose. Die neueren Erkenntnisse der Pathogenese einiger Glomerulopathien haben zu neuen Therapien geführt, die in Studien kleinerer Patientengruppen teilweise recht positive Resultate gezeigt haben. Neue Therapieformen wurden insbesondere für folgende Erkrankungen berichtet: Fokal segmentale Glomerulosklerose, idiopathische membranöse Nephropathie, membranoproliferative Glomerulonephritis Typ 2 (Dense Deposit Disease), IgA-Nephropathie und atypisches hämolytisch-urämisches Syndrom (aHUS). Insbesondere Rituximab oder Eculizumab stellen bei einigen dieser Pathologien interessante neuere Therapieansätze dar. Das Rezidiv der Glomerulonephritis stellt nach Abstoßung und Tod mit funktionierendem Transplantat die dritthäufigste Ursache des Transplantatversagen dar. Insgesamt aber weisen Patienten mit einer glomerulären Grunderkrankung gegenüber den Patienten mit anderen renalen Grunderkrankungen ein etwa vergleichbares Transplantat-Langzeitüberleben auf. Trotzdem gibt es einzelne davon abweichende Untersuchungen; so zeigt eine neuere Arbeit ein leicht schlechteres Langzeitüberleben der Nierentransplantate bei wegen einer Glomerulonephritis transplantierten Patienten. Wichtig ist, dass die Glomerulonephritiden als Grundleiden insgesamt gesehen keine Kontraindikation zur Transplantation, inklusive der Lebendspende einer Niere, darstellen.

Introduction Early acute antibody-mediated rejection (ABMR) occurs more frequently in ABO-incompatible (ABOi) than in ABO-compatible (ABOc) kidney transplantation. This could lead to increased inflammation/scarring in the ABOi grafts. Protocol biopsy data in ABOi kidney recipients are scarce. Methods A single-center retrospective matched cohort study was conducted. Eighty adult living donor (LD) renal transplant recipients without HLA donor-specific antibodies (DSA) transplanted between 2009 and 2012 were included; 20 ABOi and 60 ABOc controls matched for donor age and transplantation year. Protocol biopsies at one yr were scored according to the Banff classification. Three sums of scores were constructed: tubulointerstitial inflammation (t + i = 0 vs. >0), microvascular inflammation (g + ptc = 0 vs. >0), scarring/hyalinosis (ci + ct + cv + ah ≤ 1 vs. >1. Scores and presence of subclinical rejection (SCR) at one yr were compared. Results Protocol biopsy findings at one yr in the ABOi vs. ABOc matched control group were not statistically different: (t + i) > 0, 30% vs. 20%; (g + ptc) > 0, 5% vs. 8%; (ci + ct + cv + ah) > 1, 85% vs. 60%, respectively. No transplant glomerulopathy occurred. SCR rate at one yr was 30% vs. 18%, subclinical ABMR 5% vs. 7% (all with de novo HLA DSA). Conclusion One-year protocol biopsies of ABOi and ABOc LD recipients do not differ in chronic changes, inflammation, or SCRs.

A 72-year-old woman experienced anterior ischemic optic neuropathy in her left eye. The funduscopic and fluorescein angiographic findings were strongly suggestive of giant cell arteritis. Temporal artery biopsy revealed extensive calcification in the vessel wall consistent with calciphylaxis. This unusual disorder should be considered in the differential diagnosis of anterior ischemic optic neuropathy, particularly the arteritic form.

Renal DNase I is lost in advanced stages of lupus nephritis. Here, we determined if loss of renal DNase I reflects a concurrent loss of urinary DNase I, and whether absence of urinary DNase I predicts disease progression. Mouse and human DNase I protein and DNase I endonuclease activity levels were determined by western blot, gel, and radial activity assays at different stages of the murine and human forms of the disease. Cellular localization of DNase I was analyzed by immunohistochemistry, immunofluorescence, confocal microscopy, and immunoelectron microscopy. We further compared DNase I levels in human native and transplanted kidneys to determine if the disease depended on autologous renal genes, or whether the nephritic process proceeded also in transplanted kidneys. The data indicate that reduced renal DNase I expression level relates to serious progression of lupus nephritis in murine, human native, and transplanted kidneys. Notably, silencing of renal DNase I correlated with loss of DNase I endonuclease activity in the urine samples. Thus, urinary DNase I levels may therefore be used as a marker of lupus nephritis disease progression and reduce the need for renal biopsies.

Objective To characterise a globotriaosylceramide (Gb3) storage cardiomyopathy mimicking Fabry. Methods We investigated five patients from two unrelated families with early adult onset unexplained left ventricular hypertrophy. Endomyocardial biopsy was performed in all patients and diagnostic kidney biopsies in two of them. We measured α-galactosidase A activity in all patients. Three patients were checked for LAMP1 or LAMP2 deficiency and screened for congenital disorders of glycosylation. Gb3 concentration was quantified in plasma, urinary sediment and cardiac muscle. We sequenced the Fabry and Danon genes and looked for other genetic causes by single-nucleotide polymorphism array haplotyping and whole exome sequencing. Results Three patients had a striking fat distribution around the buttocks and upper thighs. All patients developed bradyarrhythmias and needed pacemakers. Cardiac transplantation was performed in three patients due to end-stage heart failure, one patient died before transplantation. The cardiomyocytes contained lysosomal vacuoles with lamellar myelin-like deposits. Interstitial cells had vacuoles containing granular material. Deposits were found in the kidneys without renal dysfunction. The histological pattern was atypical for Fabry disease. Biochemical studies revealed normal activity of α-galactosidase A and other relevant enzymes. There was a selective accumulation of Gb3 in cardiomyocytes, at levels found in patients with Fabry disease, but no mutations in the Fabry gene, and Fabry disease was excluded. Other known lysosomal storage diseases were also excluded. Single-nucleotide polymorphism array haplotyping and whole exome sequencing could not identify the genetic cause. Conclusions We describe a novel familial Gb3-assoociated cardiomyopathy. Autosomal recessive inheritance is likely, but the genetic and metabolic cause remains to be identified.

ObjectiveLate gadolinium enhancement cardiac magnetic resonance (LGE-CMR) imaging is the reference standard for non-invasive assessment of fibrosis. In hypertrophic cardiomyopathy (HCM) patients the histological substrate for LGE is still unknown. The aim of this study was to assess the ability of LGE and strain echocardiography to detect type and extent of myocardial fibrosis in obstructive HCM patients undergoing septal myectomy.MethodsThirty-two HCM patients (age 60±10) were included in this cross-sectional study and preoperatively examined by speckle-tracking strain echocardiography and LGE-CMR (n=21). Histological fibrosis was classified as interstitial, replacement and total.ResultsHistological fibrosis was present in 31 patients. The percentage of total, interstitial and replacement fibrosis was 15(7, 31)%, 11(5, 24)% and 3(1, 6)%, respectively. Reduced longitudinal septal strain correlated with total (r=0.50, p=0.01) and interstitial (r=0.40, p=0.03), but not with replacement fibrosis (r=0.28, p=0.14). Septal LGE was detected in 13/21 (62%), but percentage LGE did not correlate with total fibrosis (r=0.25, p=0.28). Extent of fibrosis did not differ between patients with and without septal LGE (20(9, 58)% versus 14(5, 19)% p=0.41). Patients with ventricular arrhythmias (n=8) had lower septal longitudinal strain and increased extent total and interstitial fibrosis in myectomy specimens, but no differences were demonstrated in LGE. Reduced longitudinal septal strain and increased extent of interstitial fibrosis predicted ventricular arrhythmias independently of age and gender.ConclusionsIn myectomised HCM patients, reduced longitudinal septal strain correlated better with interstitial and total fibrosis in myectomy specimens, and was a more powerful tool to predict arrhythmias than LGE.

Aims Reduced echocardiographic strain is associated with ventricular arrhythmias in hypertrophic cardiomyopathy (HCM) patients. The aim of this cross-sectional study was to investigate which type of histological fibrosis contributes to ventricular arrhythmias and reduced septal longitudinal strain, in obstructive HCM-patients with or without additional coronary artery disease (CAD) and/or hypertension (HT). Methods and results Sixty-three HCM-patients (mean age 57 ± 13 years) were included. Strain by speckle tracking echocardiography was performed prior to either percutaneous transluminal septal ablation ( n = 37) or septal myectomy ( n = 26). In 24 patients myectomy specimens were available (histology population) and allowed determination of %area of interstitial and replacement fibrosis. Twenty-nine (46%) patients had concomitant CAD and/or HT, and 15 (24%) experienced ventricular arrhythmias defined as documented ventricular tachycardia or arrhythmogenic suspected syncope. The patients with ventricular arrhythmias had lower septal longitudinal strain compared with those without arrhythmias (−9.0 ± 4.0 vs. −13.6 ± 5.6%, P = 0.006). In the histology population reduced septal longitudinal strain correlated to interstitial ( R 2 = 0.36 P = 0.003), but not to replacement fibrosis ( R 2 = 0.03 P = 0.43). By logistic regression analyses, interstitial fibrosis predicted ventricular arrhythmias (OR 1.16, 95% CI 1.02–1.32, P = 0.03), while replacement fibrosis did not (OR 1.22, 95% CI 0.93–1.59, P = 0.15). Conclusion Total amount of fibrosis was a marker of ventricular arrhythmias in obstructive HCM-patients. Interstitial fibrosis seemed to be more important compared with replacement fibrosis in arrhythmogenesis, and was related to reduced septal myocardial function. These findings suggest that interstitial fibrosis may play an important role as the arrhythmogenic substrate, and that strain echocardiography can help detection of patients at risk.

Background Chronic allograft nephropathy (CAN) characterized by interstitial fibrosis and tubular atrophy is a major cause of renal transplant failure. The diagnosis can currently only be verified by a graft biopsy. Purpose To evaluate whether non-invasive dynamic color Doppler sonographic parenchymal perfusion measurements are different in grafts with various degrees of biopsy proven renal transplant fibrosis. Material and Methods Forty-nine adult patients were prospectively included. Four patients were excluded. Color Doppler videos from the renal cortex were recorded. Perfusion in the renal cortex was evaluated using a software package which calculates color pixel area and flow velocity, encoded by each pixel inside a region of interest of a video sequence. The software calculates parameters that describe tissue perfusion numerically. Two of these, the perfusion intensity and tissue pulsatility index, were compared to grade of interstitial fibrosis (0–3) in biopsies. Observer agreement was evaluated in a subset of 12 patients. Results Of the 45 patients analyzed, 18 patients had grade 0, 18 had grade 1, seven had grade 2 and two had grade 3 fibrosis. The mean perfusion intensity of grade 0 was significantly higher than that of grade 2 and 3 fibrosis in the proximal cortical layer (1.65 m/s vs. 0.84 m/s, P = 0.008). No significant difference was found between grade 0 and grade 1 fibrosis. Perfusion intensity was correlated to estimated glomerular filtration rate (Pearson r 0.51, P = 0.001, R2 = 0.26 and 0.46, P = 0.001, R2 = 0.22 in the distal and proximal cortex, respectively). Inter-observer agreement of the perfusion intensity, expressed as intraclass correlation coefficient was 0.69 in the proximal part of the cortex. Intra-observer agreement was 0.85 for observer 1 and 0.82 for observer 2. Conclusion Perfusion intensity assessed by dynamic color Doppler measurements is significantly reduced in allografts with grade 2 and 3 fibrosis compared to allografts without fibrosis. Further studies involving longitudinal assessment of allografts undergoing protocol biopsies would be of interest.

Familial lecithin:cholesterol acyltransferase (LCAT) deficiency is a rare metabolic disease with lipid deposition in several organs. The authors report a man with hypertension and proteinuria. Renal biopsy revealed glomerular changes, including peculiar thrombus-like deposits, consistent with LCAT deficiency. He was found to be compound heterozygous for two mutations of the LCAT gene. He received a kidney graft from his father. The authors also describe LCAT deficiency-related lesions in the explanted native kidneys and in biopsies at 2 days, 6 weeks, and 1 year after transplantation. The morphology of this disease is characteristic, and the diagnosis should be suspected from the ultrastructural findings.

Chronic allograft nephropathy characterized by interstitial fibrosis and tubular atrophy is a major cause of renal transplant failure. Acoustic radiation force impulse (ARFI) quantification is a promising noninvasive method for assessing tissue stiffness. We evaluated if the method could reveal renal transplant fibrosis. In a prospective study, 30 adult renal transplant recipients were included. ARFI quantification, given as shear wave velocity (SWV), of the renal cortex was performed by two observers. SWV was compared to grade of fibrosis (0-3) in biopsies. The median SWV was 2.8 m/s (range: 1.6-3.6), 2.6 m/s (range: 1.8-3.5) and 2.5 m/s (range: 1.6-3) for grade 0 (n = 12), 1 (n = 10) and grades 2/3 (n = 8) fibrosis respectively. SWV did not differ significantly in transplants without and with fibrosis (grade 0 vs. grade 1, P = 0.53 and grade 0 vs. grades 2/3, P = 0.11). The mean intraobserver coefficient of variation was 22% for observer 1 and 24% for observer 2. Interobserver agreement, expressed as intraclass correlation coefficient was 0.31 (95% CI: -0.03 to 0.60). This study does not support the use of ARFI quantification to assess low-grade fibrosis in renal transplants. ARFI quantification in its present stage of development has also high intra- and interobserver variation in renal transplants.

Objectives To determine the incidence of recurrent lupus nephritis (LN) in renal transplant recipients with systemic lupus erythematosus (SLE). Methods All patients with SLE that had undergone transplant with a functioning graft were asked in 2008 to participate in a cross-sectional study. The study included a standardised clinical examination, laboratory tests and a biopsy of the transplanted kidney. Results A total of 41 (93%) of a cohort of 44 patients with SLE with renal transplants participated. Of the biopsies, 3 were indication biopsies and 38 were surveillance biopsies. In all, 22 patients (54%) had biopsy-proven recurrence of LN. The majority of the cases were subclinical and characterised as class I/class II LN. Proteinuria (mg protein/mmol creatinine) was significantly increased in patients with recurrence, 70.6 (104.9) mg/mmol versus 11.9 (6.7) mg/mmol in patients without recurrence (p=0.038). Lupus anticoagulant was found more frequently in the patients with recurrence, nine versus two patients (p=0.033). Recurrence of LN was associated with receiving a kidney from a living donor (p=0.049). In all, 83% (34 of 41) had chronic allograft nephropathy in the transplanted kidneys with no difference between patients with recurrence or without. Conclusions Subclinical recurrence of LN is common in patients with renal transplants with SLE. The majority of the patients have chronic allograft nephropathy.

Background Systemic lupus erythematosus (SLE) is an autoimmune, multiorgan disease that usually affects young women. The kidneys are affected (lupus nephritis) in close to one fifth of the patients. Over the past decade earlier diagnosis and improved treatment of lupus nephritis has resulted in substantial improvement of renal function and patient survival. Despite these advances, 10 - 15 % of SLE patients with lupus nephritis progress to end-stage renal disease, requiring dialysis or renal transplantation. The article outlines main principles for diagnosing and treating lupus nephritis, according to current practice at Oslo University Hospital. Material and methods National and international guidelines (on treatment of lupus nephritis), literature identified through a non-systematic search in PubMed and our own clinical experience form the basis for the article. Results In lupus nephritis, low-dose cyclophosphamide and corticosteroids are topical treatment for induction therapy, and mycophenolate mofetil is an alternative treatment. We recommend maintenance treatment with azathioprine or mycophenolate mofetil for at least two years. Treatment with rituximab may be considered in patients with refractory lupus nephritis. Interpretation Subtypes and activity of the renal disease are decisive for choice of treatment.

Objective: The final outcome of patients with small cell lung cancer (SCLC) is poor with an overall 5-year survival rate of less than 10%. Therefore, the question of surgery in patients with a technically-operable solitary tumor has been raised. The purpose of this study was to identify the proportion of patients with operable SCLC and to assess the prognosis of different treatment strategies. For patients who were operated, we compared the resection specimens from patients with more than 5-year survival with those with shorter survival to see whether the specimens belonged to different subclasses of SCLC. Methods: In Norway all clinical and pathologic departments submit reports on cancer patients to the Cancer Registry. The Registry also has a law-regulated authority to collect supplemental information regarding diagnosis, treatment and outcome for all cancer patients from the hospitals in charge. All reports on patients diagnosed as having SCLC in limited disease or unknown stage during the time interval 1993 –1999 were reviewed. Patients with a T2-tumor, in whom a pneumonectomy would have to be performed, were classified as potentially operable. Five-year relative survival was calculated for patients diagnosed in 1993– 1997. Results: During the actual period 2442 individuals with SCLC were identified. The majority was treated with conventional chemotherapy or concurrent chemoradiotherapy while 38 underwent surgical therapy. Following reclassification of 697 patients reported to have limited disease or unknown stage 180 were judged to be in stage I. In addition to the 38 resected patients 14 were considered fit for surgery technically and medically while 97 were found to be potentially operable treatment modalities apart from surgery yielded a 5-year survival rate , 7%. For stage I ðN ¼ 96Þ the rate was 11.3% in conventionally treated patients compared to 44.9% for those who underwent surgical resection. By pathological review of surgical specimens a diagnosis of SCLC was confirmed in all patients treated by surgery in the groups with long and short survival. Conclusion: This investigation demonstrates that patients with SCLC having a peripherally located tumor should be referred to surgery, as long time survival is far better than for conventionally treated patients. q 2004 Elsevier B.V. All rights reserved.

Recurrence of glomerulonephritis after kidney transplantation is especially in the long term an important cause of renal allograft failure. The exact frequency depends on the one hand how the diagnosis of recurrence was established, either on clinical grounds or histologically via a kidney transplant biopsy, and on the other hand on the type of the underlying or primary glomerular disease. The consequences of a relapse on allograft function and survival vary, depending on the primary disease. For example, recurrences after IgA nephropathy occur depending on the length of the observation period in over 50 % of the allografts with often relatively slow progression. However, focal segmental glomerulosclerosis and membranoproliferative glomerulonephritis recurrence generally have a much more rapid progression and poorer prognosi. The recent findings on the pathogenesis of certain glomerulopathies have led to new therapies, which have shown quite positive results in studies of smaller patient groups. New therapeutical approaches have been reported in particular for the following diseases: focal segmental glomerulosclerosis, idiopathic membranous nephropathy, membranoproliferative glomerulonephritis type 2 (dense deposit disease), IgA nephropathy and atypical hemolytic uremic syndrome (aHUS). In particular, rituximab or eculizumab represent interesting therapeutic options in some of these entities. Recurrence of glomerulonephritis - after allograft rejection and death with a functioning organ - is the third most common cause of kidney transplant failure. Overall, patients transplanted because of glomerular diseases have a longterm allograft survival comparable to patients suffering from other primary renal disorders. Nevertheless, a recent investigation showed a slightly worse long-term renal transplant survival in patients with a glomerulonephritis as the primary kidney disease. It is important to state that glomerulonephritis as the primary renal disorder does not represent a contraindication for kidney transplantation, including living kidney donation.Rezidive von Glomerulonephritiden nach Nierentransplantation stellen eine wichtige Ursache des Transplantatversagens speziell im Langzeitverlauf dar. Die genaue Häufigkeit hängt einerseits vom Typ der glomerulären Grunderkrankung ab und anderseits davon, ob die Rezidive klinisch-pathologisch oder nur histologisch festgestellt werden. Der Einfluss der Rezidive auf die Funktion und das Überleben des Nierentransplantats variiert je nach der Grunderkrankung ebenfalls stark. Rezidive nach IgA-Nephropathie (IgAN) treten beispielsweise je nach Beobachtungsdauer bei über 50 % der Transplantate mit oft relativ langsamer Progredienz auf. Fokal segmentale Glomerulosklerose und membranoproliferative Glomerulonephritis haben jedoch generell eine deutlich schlechtere Prognose. Die neueren Erkenntnisse der Pathogenese einiger Glomerulopathien haben zu neuen Therapien geführt, die in Studien kleinerer Patientengruppen teilweise recht positive Resultate gezeigt haben. Neue Therapieformen wurden insbesondere für folgende Erkrankungen berichtet: Fokal segmentale Glomerulosklerose, idiopathische membranöse Nephropathie, membranoproliferative Glomerulonephritis Typ 2 (Dense Deposit Disease), IgA-Nephropathie und atypisches hämolytisch-urämisches Syndrom (aHUS). Insbesondere Rituximab oder Eculizumab stellen bei einigen dieser Pathologien interessante neuere Therapieansätze dar. Das Rezidiv der Glomerulonephritis stellt nach Abstoßung und Tod mit funktionierendem Transplantat die dritthäufigste Ursache des Transplantatversagen dar. Insgesamt aber weisen Patienten mit einer glomerulären Grunderkrankung gegenüber den Patienten mit anderen renalen Grunderkrankungen ein etwa vergleichbares Transplantat-Langzeitüberleben auf. Trotzdem gibt es einzelne davon abweichende Untersuchungen; so zeigt eine neuere Arbeit ein leicht schlechteres Langzeitüberleben der Nierentransplantate bei wegen einer Glomerulonephritis transplantierten Patienten. Wichtig ist, dass die Glomerulonephritiden als Grundleiden insgesamt gesehen keine Kontraindikation zur Transplantation, inklusive der Lebendspende einer Niere, darstellen.

To identify the combination of clinical data and high resolution computed tomography (HRCT) features that best identified biopsy verified usual interstitial pneumonia (UIP).The study included 91 patients with a tentative diagnosis of interstitial lung disease. All underwent clinical investigation, surgical lung biopsy and HRCT. Two independent readers assessed the HRCT images for the extent and pattern of abnormality. On the basis of the biopsy result the patients were categorized in three groups: 1) Usual interstitial pneumonia, 2) Other idiopathic interstitial pneumonias (IIPs) and hypersensitivity pneumonitis and 3) Other interstitial lung diseases. The diagnostic value of HRCT was investigated using likelihood ratio to estimate the post-test probability of UIP.We found that UIP was associated with significantly higher scores for reticular pattern and for bronchiectasis than the remaining patients (p 0.001). Moreover, these scores showed a steeper cranial-caudal increase in patients with histologically verified UIP than in the remaining patients (p 0.001). UIP was associated with lower scores for ground glass opacities (p 0.001). Using Bayes theorem and likelihood ratio estimation we found that UIP could be diagnosed with 90% certainty in patients 60 years or older and restrictive pattern in spirometry provided that HRCT demonstrated at least 15% reticular pattern and no ground glass opacities.In older patients with a restrictive spirometry in whom HRCT demonstrates a reticular pattern without ground glass opacities surgical lung biopsy is not warranted for the diagnosis of UIP.

Enzyme replacement therapy (ERT) has been introduced for Fabry disease and has been reported to clear some renal cell types of accumulated glycolipids and to reduce the accumulation in other cell types. We describe two patients without Fabry disease who were transplanted with kidney allografts from a male donor with Fabry disease. Biopsies were taken at transplantation and after 3 years in the first case and after 12 years in the second case. Even though these Fabry kidney allografts for many years had been exposed to normal levels of circulating α-galactosidase A (α-gal-A), the amount of accumulated lysosomal deposits in the podocytes remained unchanged. Additionally, small deposits were also found in tubular cells and glomerular endothelial cells as long as 12 years after transplantation.

Purpose An unusual case of choroidal metastases from an ovarian adenocarcinoma is described, and a brief review of the literature is presented. Methods Clinical and autopsy findings are presented. Results After having diagnosed bilateral choroidal metastatic lesions, a clinical investigation and a subsequent laparotomy disclosed bilateral ovarian tumors with histopathological features of mucinous adenocarcinoma. At autopsy the tumor was confirmed to be a primary ovarian mucinous adenocarcinoma with choroidal metastases. Conclusion This article describes what is believed to be the first case report of a primary epithelial carcinoma of the ovary with histopathologically documented metastases to the choroid. Metastatic disease must be considered in the evaluation of patients with choroidal lesions of unknown etiology.

IntroductionPemetrexed is effective in the treatment of non–small-cell lung cancer, mainly in nonsquamous cell carcinomas. Inhibition of thymidylate synthase (TS) is considered the key mechanism of action. Folate receptor-α facilitates uptake of pemetrexed. Polyglutamation by folylpolyglutamate synthetase enhances activity and prolongs cellular retention of pemetrexed. Thyroid transcription factor-1 (TTF-1) is mainly positive in nonsquamous cell carcinoma and has been proposed as a marker for sensitivity to pemetrexed. The aim was to investigate associations between these biomarkers and survival in patients who participated in a phase III trial comparing pemetrexed plus carboplatin with gemcitabine plus carboplatin as first-line chemotherapy in advanced non–small-cell lung cancer (n = 436). In this study, there was no difference in overall survival between the two regimens.MethodsFormalin-fixed, paraffin-embedded biopsies were collected. Percentages of tumor cells positive and highly positive for the biomarkers were assessed using immunohistochemistry (IHC) and an IHC score was calculated (range, 0–200).ResultsTwo hundred thirty-six biopsies were analyzed (pemetrexed plus carboplatin: n = 114, gemcitabine plus carboplatin: n = 122). There was a significant difference in overall survival between those with TTF-1–positive and –negative tumors (10.4 versus 6.0 months; p < 0.001) and those with a low and a high TS IHC score (9.7 versus 6.2 months; p < 0.001). Folate receptor-α and folylpolyglutamate synthetase were not significant prognostic factors. In multivariate analyses adjusting for established prognostic characteristics, TS (p = 0.002) and TTF-1 (p = 0.003) remained significant. There were no differences in survival between the treatment arms depending on biomarker scores.ConclusionsTTF-1 positivity and low TS level were associated with prolonged survival. The associations between the biomarkers and overall survival were similar for both chemotherapy regimens.

Over the last decade, the diagnostic precision for acute antibody-mediated rejection (aABMR) in kidney transplant recipients has improved significantly. The phenotypes of early and late aABMR may differ. We assessed the characteristics and outcomes of early versus late aABMR.Between January 1, 2005 and December 31, 2010, aABMR was diagnosed in 67 grafts in 65 kidney recipients, with a median follow-up of 3.6 years (range, 61 days-7.3 years). Recipients were stratified by early aABMR (3 months after transplantation; n=40) and late aABMR (3 months after transplantation; n=27). The main outcome was kidney allograft loss. Outcome of aABMR was compared with recipients with acute early (n=276) or late (n=100) non-ABMR during the same period.Recipients with late aABMR had significantly reduced graft survival compared with recipients with early aABMR (P0.001, log-rank test; 40% vs. 75% at 4 years; hazard ratio, 3.72; 95% confidence interval, 1.65-8.42). Graft survival in late aABMR was also inferior to late non-ABMR acute rejections (P=0.008). At transplantation, more patients were presensitized to human leukocyte antigens (22 [55%] vs. 4 [15%] in the early vs. late aABMR group). The late aABMR group was characterized by younger recipient age (37.9 ± 12.9 vs. 50.9 ± 11.6 years; P0.001), increased occurrence of de novo donor-specific antibodies (52% vs. 13%; P=0.001), and nonadherence/suboptimal immunosuppression (56% vs. 0%; P0.001).Compared with early aABMR, late aABMR had inferior graft survival and was characterized by young age, frequent nonadherence, or suboptimal immunosuppression and de novo donor-specific antibodies.

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/mm 3 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.

Background The relative clinical benefit of histopathology and computed tomography (CT) in patients with idiopathic interstitial pneumonia (IIP) is under debate. Purpose To analyze thin-section CT features and histopathologic findings in patients with usual interstitial pneumonia (UIP) in the clinical context of idiopathic pulmonary fibrosis (IPF), and to evaluate and compare diagnostic accuracy of the two methods among patients with an appropriate spectrum of IIP. Material and Methods The study included 91 patients (49 men; mean age 53.2 years; median follow-up 7.2 years) with clinically suspected interstitial lung disease. All underwent surgical lung biopsy and thin-section CT. Two independent readers retrospectively assessed the CT images for the extent and pattern of abnormality and made a first-choice diagnosis. Two pathologists retrospectively assessed the histopathologic slides. In 64 patients with IIP, a retrospective composite reference standard identified 41 patients with UIP. CT characteristics of UIP and IIPs other than UIP were compared with univariate and multivariate analyses. Results There was good agreement between the readers for the correct first-choice CT diagnosis of UIP (κ = 0.79). The sensitivity, specificity, and positive predictive value of the CT diagnosis of UIP were 63%, 96%, and 96%, respectively. The sensitivity, specificity, and positive predictive value of the histological diagnosis of UIP were 73%, 74%, and 83%, respectively. The CT feature that best differentiated UIP from IIPs other than UIP was the extent of reticular pattern (odds ratio, 5.1). Conclusion Surgical lung biopsy may not be warranted in patients with thin-section CT diagnosis of UIP.

Acoustic radiation force impulse (ARFI) quantification estimates tissue elasticity by measuring shear-wave velocity (SWV) and has been applied to various organs. We evaluated the impact of variations in the transducer force applied to the skin on the SWV ultrasound measurements in kidney transplant cortex and ARFI's ability to detect fibrosis in kidney transplants.SWV measurements were performed in the cortex of 31 patients with kidney allografts referred for surveillance biopsies. A mechanical device held the transducer and applied forces were equal to a compression weight of 22, 275, 490, 975, 2,040 and 2,990 g.SWV group means were significantly different by repeat measures ANOVA [F(2.85,85.91) = 84.75, P 0.0005 for 22, 275, 490, 975 and 2,040 g compression weight] and also by pairwise comparisons. Biopsy specimens were sufficient for histological evaluation in 29 of 31 patients. Twelve had grade 0, 11 grade 1, five grade 2 and one grade 3 fibrosis. One-way ANOVA showed no difference in SWV performed with any of the applied transducer forces between grafts with various degrees of fibrosis.SWV measurements in kidney transplants are dependent on the applied transducer force and do not differ in grafts with different grades of fibrosis.• Acoustic radiation force impulses (ARFI) can quantify tissue elasticity during ultrasound examinations. • Elasticity estimated by ARFI in kidney transplants depends on applied transducer force. • ARFI quantification cannot detect renal allograft fibrosis. • ARFI elasticity estimates may in general vary with applied transducer force.

To the Editor: We have read with interest the papers on human immunodeficiency virus (HIV)-related nephropathy from South Africa.1, 2 We have a comment concerning the HIV-related glomerulonephritis, where several biopsies showed ‘ball-in-cup’ lesions, characterized by subepithelial deposits with a peculiar basement membrane reaction. These lesions had the appearance of a hybrid between post-infectious and membranous glomerulonephritis. Gerntholtz et al.2 consider this lesion typical for HIV infection, and speculate that the deposits might contain viral particles.

Chronic allograft nephropathy characterized by interstitial fibrosis and tubular atrophy is a major cause of renal transplant failure. Acoustic radiation force impulse (ARFI) quantification is a promising noninvasive method for assessing tissue stiffness. We evaluated if the method could reveal renal transplant fibrosis. In a prospective study, 30 adult renal transplant recipients were included. ARFI quantification, given as shear wave velocity (SWV), of the renal cortex was performed by two observers. SWV was compared to grade of fibrosis (0-3) in biopsies. The median SWV was 2.8 m/s (range: 1.6-3.6), 2.6 m/s (range: 1.8-3.5) and 2.5 m/s (range: 1.6-3) for grade 0 (n = 12), 1 (n = 10) and grades 2/3 (n = 8) fibrosis respectively. SWV did not differ significantly in transplants without and with fibrosis (grade 0 vs. grade 1, P = 0.53 and grade 0 vs. grades 2/3, P = 0.11). The mean intraobserver coefficient of variation was 22% for observer 1 and 24% for observer 2. Interobserver agreement, expressed as intraclass correlation coefficient was 0.31 (95% CI: -0.03 to 0.60). This study does not support the use of ARFI quantification to assess low-grade fibrosis in renal transplants. ARFI quantification in its present stage of development has also high intra- and interobserver variation in renal transplants.

Summary Objectives Listeria monocytogenes is a foodborne pathogen with a high mortality rate. We report a large, nosocomial outbreak of Listeria monocytogenes infection. Methods Patients with L. monocytogenes isolated from a sterile site, or from faeces when diarrhoea and fever were present, were included. Clinical data were collected from the patient records. The incubation period was calculated as the time between exposure and start of symptoms. Results Seventeen patients (11 women, median age 64 years) were infected of whom 15 patients were at increased risk for listeriosis. Eleven patients received empiric antibiotic treatment, eight of them with cephalosporins. Three patients died with a resulting mortality rate of 18%. The source of the outbreak was a Camembert cheese made from pasteurised milk containing up to 360 million colony forming units per portion. The median incubation period was 3–4 days. Conclusions The incubation period in this outbreak was significantly shorter than previously reported, a fact that may be due to the high number of ingested bacteria. Furthermore, food restrictions in hospitals seem warranted, as do treatment with antibiotics effective against L. monocytogenes in at-risk populations.

Systemic lupus erythematosus (SLE) is an autoimmune, multiorgan disease that usually affects young women. The kidneys are affected (lupus nephritis) in close to one fifth of the patients. Over the past decade earlier diagnosis and improved treatment of lupus nephritis has resulted in substantial improvement of renal function and patient survival. Despite these advances, 10 - 15 % of SLE patients with lupus nephritis progress to end-stage renal disease, requiring dialysis or renal transplantation. The article outlines main principles for diagnosing and treating lupus nephritis, according to current practice at Oslo University Hospital.National and international guidelines (on treatment of lupus nephritis), literature identified through a non-systematic search in PubMed and our own clinical experience form the basis for the article.In lupus nephritis, low-dose cyclophosphamide and corticosteroids are topical treatment for induction therapy, and mycophenolate mofetil is an alternative treatment. We recommend maintenance treatment with azathioprine or mycophenolate mofetil for at least two years. Treatment with rituximab may be considered in patients with refractory lupus nephritis.Subtypes and activity of the renal disease are decisive for choice of treatment.

Objective: Few published reports have examined the incidence and outcomes for patients with carcinoid lung tumors. The aim of the current study was to explore incidence, type of surgical treatment given, and outcome for patients with typical (TC) and atypical (AC) lung carcinoids in a national cohort (Norway).Methods: All lung-cancer patients diagnosed in the period 1993—2005 and who were reported to the Cancer Registry of Norway were identified. Biopsies or resection specimens were reviewed and reclassified according to the World Health Organization (WHO) 2004 classification. Surgically treated patients were staged according to the seventh edition of the pathological tumor—node—metastasis (pTNM) staging system. Results: Of 26 665 lung cancers registered during the period, 265 (1%) had carcinoid tumors, of which 11 were diagnosed coincidentally at autopsy. In the remaining 254 patients, TCs were found in 188 cases, and ACs were found in 59 cases; seven cases had unclassifiable carcinoids. Of the 217 resected tumors, 173 (80%) were TCs. General surgeons performed 94 resections, including 11 of 17 pneumonectomies. All six bronchial resections were performed by thoracic surgeons. Of the 33 operated patients who died during follow-up, 18 had metastatic carcinoid tumors, of which 10 (56%) were ACs. In 37 non-resected patients (15 with AC and seven with unclassifiable histology), metastatic or locally advanced disease (N = 21, 12 of which were ACs) was the main cause of inoperability and death. Five-year survival for all patients was 92% for TC and 66% for AC; for resected patients, the survival rates were 96% and 79%, respectively. Conclusions:Carcinoids are rare malignant tumors and are, in most cases, resectable; the TC subgroup had better prognosis than the AC in univariate analyses. The main cause of death was metastasis/locally advanced tumor at presentation or recurrent disease following resection; both situations were three times more common in patients with AC. # 2010 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

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).

Niemann-Pick disease type C1 (NPC1) and type C2 (NPC2) display the same pattern of neurovisceral storage due to deficiencies within lysosomes. NPC2 is a much rarer condition, and as reports on the pathological changes are scarce, the morphological findings in the lungs and brain in two siblings who died at an early age from pulmonary involvement are described. The diagnosis of NPC2 was confirmed at postmortem mutational analysis.Both siblings presented with postnatal conjugated hyperbilirubinemia. They subsequently developed progressive respiratory insufficiency with opacification of the lungs on X-ray examination and died at the ages of 8 and 13 months. The lungs contained intra-alveolar accumulation of periodic acid-Schiff positive material, foamy macrophages, and hyperplasia of the alveolar cells, consistent with pulmonary alveolar lipoproteinosis. On neuropathological examination, storage material in swollen perikarya in the deep cerebellar nuclei, thalamus, medulla oblongata, and in the paravertebral ganglion cells was found. Meganeurites were present in the cerebral cortex. A few axonal spheroids were also observed. There seemed to be a reduced number of Purkinje cells in the cerebellum.Evidence that NPC2 is associated with severe pulmonary alveolar lipoproteinosis is supported. There were extensive neuropathological changes with storage material in swollen perikarya and a few axonal spheroids.

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'.

Myocarditis is defined as an inflammatory or infectious disease of the myocardium causing damage through production of a toxin or by immunologically mediated destruction. A rare type is idiopathic giant cell myocarditis.We present data from Rikshospitalet University Hospital in Norway, with two case reports and a discussion of the diagnostics and treatments currently available. The investigation is retrospective and includes 11 patients, two women and nine men with histologically verified idiopathic giant cell myocarditis.Median age was 46; four patients had autoimmune co-morbidity. The major onset symptom was rapid progressive heart failure; 64% had concomitant ventricular arrhythmias. Five patients received immunosuppressives in addition to conventional treatment for heart failure. Eight underwent cardiac transplantation and two patients had recurrence of idiopathic giant cell myocarditis in the graft. Mean interval from time of diagnosis to death or cardiac transplantation was six months.Idiopathic giant cell myocarditis is a rare inflammatory disease of the myocardium that often affects previously healthy young adults. Co-morbidity with autoimmune disorders has been reported. Idiopathic giant cell myocarditis is characterised by a history of rapid progression of severe heart failure associated with refractory ventricular arrhythmias. The diagnosis is made by endomyocardial biopsy. Treatment includes immunosuppressives, and the indication for cardiac transplantation should be evaluated early, as one should bear in mind an increased risk of recurrence in the graft.

In February, 2003, a 61-year-old woman presented at our hospital with abdominal pain. Her past medical history was unremarkable. A physical examination and CT scan showed generalised lymphadenopathy with a retroperitoneal bulky tumour without the involvement of any other organ. Laboratory tests showed moderate anaemia (haemoglobin concentration 11·2 g/L) and an IgM/ monoclonal gammopathy (7·33 mg/L). No signs of nephrotic syndrome, renal failure, arthritis, congestive heart-failure, or coagulopathy were detected. A supraclavicular lymph node and a bone-marrow trephine were taken, fixed in 10% buffered formalin for 24 h, and then paraffin-embedded. The patient was diagnosed with nodal marginal-zone lymphoma (NMZL) stage IVA and received eight cycles of CIOP chemotherapy (cyclophosphamide, idarubicin, vincristine, prednisolone). At the patient’s last follow-up (October, 2003), she was in a good condition with stable disease, although the lymph node was only slightly smaller. The IgM/ value had decreased (3·90 g/L) compared with the concentration measured at presentation. Histological analysis of the lymph-node biopsy sample showed almost complete destruction of the normal structure because of the deposition of hyaline material, which stained positively with periodic acid Schiff (with and without diastase digestion), Van Gieson, and toluidine blue, but not with Congo red. Furthermore, the hyaline material was more abundant around the small vessels (figure 1A, 1B). Atypical lymphoid elements with a monocytoid profile were mixed with the hyaline deposition, either singly or in small aggregates, and contained some blast cells and numerous plasma cells (figure 1C). By use of the paraffin-embedded sections of biopsied lymph-node tissue, immunohistochemical analysis, and the alkaline phosphatase antialkaline phosphatase complex (APAAP) technique, the atypical elements were found to express the IRTA1 (immunoglobulin superfamily receptor translocationassociated 1) molecule, CD20, CD79a, CD45RA, CD27, IgM/ , and BCL2. The tissue was negative for IgG, IgD, Ig light-chain, BCL6, CD10, DBA44, CD5, and CD3 (figure 1D–G and figure 2A–C). About 15% of the cells expressed Nodal marginal-zone lymphoma associated with monoclonal light-chain and heavy-chain deposition disease

A 36-year-old renal transplant patient developed 9 years after a successful transplantation a fatal secondary varicella infection. The disseminated varicella infection was associated with hepatitis with liver necrosis, disseminated intravascular coagulation and fibrinolysis and glomerulonephritis. To our knowledge this is the first description of glomerulonephritis associated with varicella infection in a renal transplanted patient. The autopsy showed morphologically a mesangial glomerulonephritis with minor proliferative activity and extensive deposits by electronmicroscopy, mainly in the mesangium. The ongoing immunosuppression may have modified the mesangial cell response to the deposition of immune complexes.

E.H. Strom, F.P. Reinholt, K. Midtvedt. JC virus-associated nephropathy: lack of convincing documentation of the diagnosis. Transpl Infect Dis 2011: 13: 93–94. All rights reserved

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.

Purpose: Identify the proportion of patients with small cell lung carcinoma (SCLC) who were alive five years or more after the diagnosis in the period 2000-2005. Of the 2 270 patients diagnosed with SCLC 94 had survived five years or more. All morphological diagnoses were reviewed and in 72 cases the diagnosis was maintained. In 15 patients the diagnosis was changed, and seven discarded. Of the maintained 7% were disseminated and 93% limited disease. The favorable survival of the 72 patients is most likely caused by the high percentage of limited disease. The application of biomarkers may hopefully assist in identifying patients with favorable prognosis in the future.