Pancreatic cancer mortality in Europe: the leveling of an epidemic

Mortality rates from pancreatic cancer have increased throughout Europe between the late 1950s and the 1980s. Trends in 22 European countries, the European Union (EU) and 6 selected eastern European countries have been updated using official death certification data for pancreatic cancer abstracted from the WHO database over the period 1980 to 1999. In EU men, a rise from 7.2 to 7.5/100,000 was observed between the early and the late 1980s, followed by a leveling off in the 1990s. For women, rates tended to rise up to the early 1990s, and to level off thereafter around 4.7/100,000. In eastern countries, rates for both sexes rose between the early 1980s and the mid-1990s, and leveled off thereafter around 8.5/100,000 men and 5/100,000 women. Thus, rates for men only were higher in Eastern Europe than in the EU. This analysis first documents a leveling of pancreatic cancer mortality in Europe, after decades of steady rises. This is partly or largely attributable to the decline in smoking, at least in men, but other factors, including mainly nutrition and diet, may also have played some role on these trends.     

A 20-year long term experience of the Italian Diamond-Blackfan Anaemia Registry: RPS and RPL genes,different faces of the same disease?

Diamond–Blackfan anaemia (DBA) is a rare and heterogeneous disease characterised by hypoplastic anaemia, congenital anomalies and a predisposition for malignancies. The aim of this paper is to report the findings from the Italian DBA Registry, and to discuss the Registry’s future challenges in tackling this disease. Our 20-year long work allowed the connection of 50 Italian Association of Paediatric Haematology and Oncology (AIEOP) centres and the recruitment of 283 cases. Almost all patients have been characterised at a molecular level (96%, 271/283), finding a causative mutation in 68% (184/271). We confirm the importance of determination of erythrocyte adenosine deaminase activity (eADA) and of ribosomal RNA assay in the diagnostic pipeline and characterisation of a remission state. Patients with mutations in large ribosomal subunit protein (RPL) genes had a significant correlation with the incidence of malformations, higher eADA levels and more severe outcomes, compared to patients with mutations in small ribosomal subunit protein (RPS) genes. Furthermore, as a consequence of our findings, particularly the incidence of malignancies and the high percentage of patients aged >18 years, we stress the importance of collaboration with adult clinicians to guarantee regular multi-specialist follow-up. In conclusion, this study highlights the importance of national registries to increase our understanding and improve management of this complex disease.     

Novel N-terminal domain mutation in prion protein detected in 2 patients diagnosed with frontotemporal lobar degeneration syndrome

Prion protein gene mutations have been associated with clinical pictures mimicking neurodegenerative diseases different from inherited prion diseases (IPD). We report a novel missense P39L mutation in the N-terminal domain of prion protein in 2 patients affected by frontotemporal lobar degeneration syndrome, negative for mutations in genes causative of dementia. Neither the first carrier, a 67-year-old male in which the onset was a progressive non-fluent aphasia, nor the second carrier, a 78-year-old male affected by frontotemporal dementia and parkinsonism, showed any clinical or instrumental findings suggestive of IPD. Genetic screening of healthy controls and in silico analysis provide support for the potential pathogenicity of this variant. Patient phenotypes, unclassifiable as prion disease, may depend on the location of the mutation in the N-terminal domain, outside the amyloid core of pathologic prion protein, although further functional studies are required to determine whether and how this mutation exerts its pathogenic effect. However, genetic screening of prion protein gene becomes relevant in familial degenerative dementia, particularly in geographical areas with high IPD prevalence.     

Success with plasmapheresis treatment for recurrent focal segmental glomerulosclerosis in pediatric renal transplant recipients

FSGS recurs in approximately 30% of transplanted kidneys and may lead to graft loss. We retrospectively examined the efficacy of early and intensive PP without additional IS in pediatric kidney transplant patients with recurrent FSGS at our center. Seven of 24 patients (29%) had nephrotic proteinuria and histologic evidence of FSGS recurrence within 1–5 days post‐transplantation. PP was initiated early after transplantation and initially performed daily until sustained decline in proteinuria. PP frequency was then individually tapered according to proteinuria. Recurrent FSGS in all seven patients responded to a four‐ to 32‐wk course of PP. Two of seven patients had a second recurrence of FSGS, and both recurrences remitted after an additional 3–6 wk of PP. Median observation period was 4.5 yr (0.8–16.3 yr). Complete remission of recurrent FSGS has been sustained in all seven patients, and all patients have stable graft function with recent plasma creatinine <1.5 mg/dL in six of seven patients. Most recent urine protein/creatinine is 0.13–0.61 mg/mg in six of seven patients. One patient has heavy proteinuria secondary to chronic allograft nephropathy 16 yr post‐transplant. Intensive and prolonged PP, when initiated early in the post‐operative period, is effective in treating recurrent FSGS and preventing graft loss without the use of additional immunosuppressants.     

Somatosensory evoked potentials during the ideation and execution of individual finger movements

Scalp somatosensory evoked potentials (SEPs) were recorded in 10 volunteers after median nerve stimulation, in four experimental conditions of hand movements performance/ideation, and compared with the baseline condition of full relaxation. The experimental conditions were (a) self-improvised hand-finger sequential movements; (b) the same movements according to a read sequence of numbers; (c) mental ideation of finger movements; and (d) passive displacement of fingers in complete relaxation. Latencies and amplitudes of the parietal (N20, P25, N33, and P45) and frontal peaks (P20–22, N30, and P40) were analyzed. Latencies did not vary in any of the paradigms. Among the parietal complexes, only the P25-N33 amplitude was significantly reduced in (a), (b), (c), and (d) and the N20-P25 was reduced in (a) and (d); among frontal waves, N30 and P40 were significantly reduced (20–75%) in (a) and (b). Coronal electrodes showed amplitude decrements maximal at the frontal-rolandic positions contralateral to the stimulated side. © 1996 John Wiley & Sons, Inc.     

Sulfated Progesterone Metabolites That Enhance Insulin Secretion via TRPM3 Are Reduced in Serum From Women With Gestational Diabetes Mellitus

Serum progesterone sulfates were evaluated in the etiology of gestational diabetes mellitus (GDM). Serum progesterone sulfates were measured using ultra-performance liquid chromatography–tandem mass spectrometry in four patient cohorts: 1) the Hyperglycemia and Adverse Pregnancy Outcomes study; 2) London-based women of mixed ancestry and 3) U.K.-based women of European ancestry with or without GDM; and 4) 11–13 weeks pregnant women with BMI ≤25 or BMI ≥35 kg/m² with subsequent uncomplicated pregnancies or GDM. Glucose-stimulated insulin secretion (GSIS) was evaluated in response to progesterone sulfates in mouse islets and human islets. Calcium fluorescence was measured in HEK293 cells expressing transient receptor potential cation channel subfamily M member 3 (TRPM3). Computer modeling using Molecular Operating Environment generated three-dimensional structures of TRPM3. Epiallopregnanolone sulfate (PM5S) concentrations were reduced in GDM (P < 0.05), in women with higher fasting plasma glucose (P < 0.010), and in early pregnancy samples from women who subsequently developed GDM with BMI ≥35 kg/m² (P < 0.05). In islets, 50 µmol/L PM5S increased GSIS by at least twofold (P < 0.001); isosakuranetin (TRPM3 inhibitor) abolished this effect. PM5S increased calcium influx in TRPM3-expressing HEK293 cells. Computer modeling and docking showed identical positioning of PM5S to the natural ligand in TRPM3. PM5S increases GSIS and is reduced in GDM serum. The activation of GSIS by PM5S is mediated by TRPM3 in both mouse and human islets.     

Alpha-synuclein as a biomarker in Parkinson's disease: focus on neural derived extracelluar vesicles

The prevalence of Parkinson’s disease(PD)is rapidly increasing,and more than 12 million people are expected to suffer from PD by 2040.PD is a highly invalidating neurodegenerative condition that arises from the progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta.The main cause for such degeneration is the formation of cytoplasmic inclusions known as Lewy bodies.     

C1q nephropathy in a child presenting with recurrent gross hematuria

C1q nephropathy is a rare glomerular disease characterized by mesangial immune deposits with dominant or codominant staining for C1q. The exact pathogenesis leading to the mesangial immune deposits of C1q remains unknown. C1q nephropathy often presents with proteinuria in the nephrotic range, with an unpredictable or poor response to corticosteroid therapy. It is seen more commonly in older children and young adults and is more common in African Americans compared with Caucasians. We present a 4-year-old African American girl who presented with recurrent gross hematuria in the absence of proteinuria or hypertension and whose renal biopsy demonstrated dominant mesangial deposits of C1q. We conclude that C1q nephropathy should be considered in patients who present with recurrent gross hematuria.