Amyotrophic lateral sclerosis and prolactinoma

A 59-year-old male with amyotrophic lateral sclerosis is presented. Investigations revealed the co-existence of a pituitary adenoma of the prolactinoma type. This combination has not been reported before. The possible relation between endocrinological disturbances and this neurological disease is discussed.     

The Endovascular Management of Iliac Artery Aneurysms

Background: Isolated aneurysms of the iliac arteries are uncommon. Previously treated by conventional surgery, there is increasing use of endografts to treat these lesions. Purpose: The purpose of this study was to assess the efficacy, safety, and durability of the stent-grafts for treatment of iliac artery aneurysms (IAAs). The results of endografting for isolated IAAs over a 10-year period were analyzed retrospectively. The treatment methods differed depending on the anatomic location of the aneurysms. Twenty-one patients (1 woman, 20 men) underwent endovascular stent-graft repair, with one procedure carried out under emergency conditions after acute rupture. The mean aneurysm diameter was 4.6 cm. Results: The procedural technical success was 100%. There was zero 30-day mortality. Follow-up was by interval CT scans. At a mean follow-up of 51.2 months, the stent-graft patency rate was 100%. Reintervention was performed in four patients (19%): one patient (4.7%) with a type I endoleak and three patients (14.3%) with type II endoleaks. Conclusion: We conclude that endovascular repair of isolated IAAs is a safe, minimally invasive technique with low morbidity rates. Follow-up results up to 10 years suggest that this approach is durable and should be regarded as a first treatment option for appropriate candidates.     

In situ cross-linkable hyaluronan hydrogels containing polymeric nanoparticles for preventing postsurgical adhesions

OBJECTIVE: To develop a combined barrier method and drug delivery system ("hybrid system") for preventing postoperative peritoneal adhesions, which could combine the biocompatibility and ease of application of in situ cross-linkable hydrogels with the controlled release features of polymeric nanoparticles. METHODS: Poly(lactic-co-glycolic acid) nanoparticles were dispersed in aldehyde- and hydrazide-modified hyaluronic acids (HA), then combined via a double-barreled syringe. The material was subjected to mechanical testing and was assayed for in vitro cytotoxicity to murine mesothelial cells. Subsequently, it was tested for biocompatibility by intraperitoneal injection in mice. The hybrid's effectiveness in preventing postsurgical adhesions was assessed using a rabbit sidewall defect-cecum abrasion model, where it was applied to both injured surfaces. RESULTS: The in situ hybrid gel system formed a flexible and durable hydrogel in less than 10 seconds. It had low in vitro cytotoxicity. In the mouse, the cross-linked HA maintained the polymeric nanoparticles in the peritoneum for 1 week, which we had previously shown would have cleared in less than 2 days, and no animals developed adhesions. Notably, the hybrid gel, even in the absence of encapsulated drug, was highly effective in preventing peritoneal adhesions in the rabbit model employed. Animals treated with the hybrid (n = 8) had no adhesions in 62.5% of cases, and none had adhesions that could only be separated by sharp dissection. In contrast, only 4.2% of untreated animals (n = 24) had no adhesions, and 58.3% developed adhesions requiring sharp dissection. CONCLUSIONS: The hybrid cross-linked HA-nanoparticle system described here appears to be a biocompatible and highly effective adhesion barrier, which could also deliver antiadhesion drugs.     

The m.3244G>A mutation in mtDNA is another cause of progressive external ophthalmoplegia

We sequenced all mitochondrial tRNA genes in a 61-year-old man with chronic progressive external ophthalmoplegia and mitochondrial myopathy but without mtDNA rearrangements, and identified a heteroplasmic m.3244G>A mutation in the tRNA^Leu(UUR) gene. This mutation had been previously associated with the MELAS phenotype, but not described in any detail.The mutation load in muscle was 84% and COX-negative fibers harbored greater levels of mutant genomes than COX-positive fibers. The m.3244G>A mutation affects a highly conserved nucleotide in the dihydrouridine loop and has been associated with a wobble modification deficiency of the mutant tRNA.     

The proteasome inhibitor bortezomib drastically affects inflammation and bone disease in adjuvant‐induced arthritis in rats

Objective

To explore the effect of bortezomib in splenocytes and fibroblast‐like synoviocytes (FLS) and its in vivo potency in a rat model of adjuvant‐induced arthritis (AIA), which resembles human rheumatoid arthritis (RA).

Methods

AIA was induced with Freund's complete adjuvant. Splenocyte and FLS proliferation and apoptosis were measured by radioactivity incorporation and flow cytometry, respectively. The invasiveness of FLS from rats with AIA was tested in a Transwell system. The pattern of cytokine secretion was evaluated by cytometric bead array in splenocyte supernatants. Bortezomib was administered prophylactically or therapeutically, and arthritis was assessed clinically and histologically. Immunohistochemistry was performed for markers of inflammation and angiogenesis in joints. Hematologic and biochemical parameters were tested in peripheral blood (PB). Representative animals were examined by computed tomography (CT) scanning before and after bortezomib administration. The expression of Toll‐like receptor 2 (TLR‐2), TLR‐3, and TLR‐4 in PB and FLS was measured by real‐time polymerase chain reaction, and alterations in specific cell populations in PB and spleen were determined by flow cytometry.

Results

In vitro, bortezomib exhibited significant inhibitory and proapoptotic activity in splenocytes and FLS from rats with AIA, altered the inflammatory cytokine pattern, and reduced the invasiveness of FLS from rats with AIA. In vivo, bortezomib significantly ameliorated disease severity. Remission was associated with improved histology and decreased expression of CD3, CD79a, CD11b, cyclooxygenase 1, and factor VIII in target tissues as well as down‐regulation of TLR expression in PB and cultured FLS. CT scanning demonstrated a bone healing effect after treatment.

Conclusion

Our findings suggest that bortezomib affects AIA in a pleiotropic manner and that this drug may be effective in RA.

     

Genetic variability of the fatty acid synthase pathway is not associated with prostate cancer risk in the European Prospective Investigation on Cancer (EPIC)

A western lifestyle, characterised by low rates of energy expenditure and a high-energy diet rich in animal protein, saturated fats and refined carbohydrates, is associated with high incidence of prostate cancer in men. A high-energy nutritional status results in insulin/IGF signalling in cells, which in turn stimulates synthesis of fatty acids. We investigated whether the genetic variability of the genes belonging to the fatty acid synthesis pathway is related to prostate cancer risk in 815 prostate cancer cases and 1266 controls from the European Prospective Investigation on Cancer (EPIC). Using a tagging approach and selecting 252 SNPs in 22 genes, we covered all the common genetic variation of this pathway. None of the SNPs reached statistical significance after adjusting for multiple comparisons. Common SNPs in the fatty acid synthase pathway are not major contributors to prostate cancer risk.     

Population attributable risk of tobacco and alcohol for upper aerodigestive tract cancer

Tobacco and alcohol are major risk factors for upper aerodigestive tract (UADT) cancer and significant variation is observed in UADT cancer rates across Europe. We have estimated the proportion of UADT cancer burden explained by tobacco and alcohol and how this varies with the incidence rates across Europe, cancer sub-site, gender and age. This should help estimate the minimum residual burden of other risk factors to UADT cancer, including human papillomavirus. We analysed 1981 UADT cancer cases and 1993 controls from the ARCAGE multicentre study. We estimated the population attributable risk (PAR) of tobacco alone, alcohol alone and their joint effect. Tobacco and alcohol together explained 73% of UADT cancer burden of which nearly 29% was explained by smoking alone, less than 1% due to alcohol on its own and 44% by the joint effect of tobacco and alcohol. Tobacco and alcohol together explained a larger proportion of hypopharyngeal/laryngeal cancer (PAR=85%) than oropharyngeal (PAR=74%), esophageal (PAR=67%) and oral cancer (PAR=61%). Tobacco and alcohol together explain only about half of the total UADT cancer burden among women. Geographically, tobacco and alcohol explained a larger proportion of UADT cancer in central (PAR=84%) than southern (PAR=72%) and western Europe (PAR=67%). While the majority of the UADT cancers in Europe are due to tobacco or the joint effect of tobacco and alcohol, our results support a significant role for other risk factors in particular, for oral and oropharyngeal cancers and also for UADT cancers in southern and western Europe.     

In vitro toxic effects of metal compounds on kinetic traits and ultrastructure of rabbit spermatozoa

Metal compounds have been associated with male reproductive toxicity in vivo. The aim of the present study was to investigate the in vitro effects of 20 metal compounds using rabbit ejaculated spermatozoa as a study model for spermiotoxicity. Five of the metals tested (arsenic, cadmium, chromium, mercury and vanadium) reduced sperm motility and curvilinear velocity. Ultrastructural analyses revealed three types of damage to sperm head membranes in relation to the metal used: acrosome breakage with formation of various sized microvesicles (arsenic, cadmium, mercury and platinum); a large round hole (arsenic, cadmium and chromium), and numerous folds in the acrosome membrane (vanadium). The vanadium compound, followed by chromium and mercury compounds, determined a higher number of damaged spermatozoa. In conclusion, all the studied metal compounds, at levels higher than 1 μM, may reduce sperm kinetic characteristics and probably fertilizing capacity by triggering specific morphological damages to the head and/or by inhibiting motility.     

The generation gap in numbers: parent-child disagreement on youth’s emotional and behavioral problems

Objective  

To evaluate discrepancies between parent and child reports on youth’s emotional and behavioral problems in a representative, community based sample of Greek 18-year-olds, and to identify associated factors.     

Fruit and vegetable consumption and lymphoma risk in the European Prospective Investigation into Cancer and Nutrition (EPIC)

Introduction Lymphomas are a heterogeneous group of malignant diseases of cells of the immune system. The best-established risk factors are related to dys-regulation of immune function, and evidence suggests that factors such as dietary or lifestyle habits may be involved in the etiology. Material and methods In the European Prospective Investigation into Cancer and Nutrition (EPIC), 849 lymphoma cases were identified in a median follow-up period of 6.4 years. Fruit and vegetable consumption was estimated from validated dietary questionnaires. Cox proportional hazard models were used to examine the association between fruit and vegetable intake with the risk of lymphomas overall and subentities. Results There was no overall association between total fruit and vegetable consumption and risk of lymphoma [hazard ratio (HR) = 0.95, 95% confidence interval (CI) 0.78–1.15 comparing highest with lowest quartile]. However, the risk of diffuse large B-cell lymphomas (DLBCL) tended to be lower in participants with a high intake of total vegetables (HR = 0.49, 95% CI 0.23–1.02). Conclusion In this large prospective study, an inverse associations between fruit and vegetable consumption and risk of lymphomas overall could not be confirmed. Associations with lymphoma subentities such as DLBCL warrant further investigation. The work described in this article was carried out with the financial support of: Europe Against Cancer Program of the European Commission (SANCO); Deutsche Krebshilfe, Deutsches Krebsforschungszentrum, German Federal Ministry of Education and Research; Danish Cancer Society; Health Research Fund (FIS) of the Spanish Ministry of Health, Spanish Regional Governments of Andalucia, Asturia, Basque Country, Murcia and Navarra; the ISCIII Network RCESP (C03/09), Spain; Cancer Research UK; Medical Research Council, United Kingdom; Stroke Association, United Kingdom; British Heart Foundation; Department of Health, United Kingdom; Food Standards Agency, United Kingdom; Wellcome Trust, United Kingdom; Greek Ministry of Health; Greek Ministry of Education; Italian Association for Research on Cancer (AIRC); Italian National Research Council, Fondazione-Istituto Banco Napoli, Italy; Compagnia di San Paolo; Dutch Ministry of Public Health, Welfare and Sports; World Cancer Research Fund; Swedish Cancer Society; Swedish Scientific Council; Regional Government of Sk?ne, Sweden; Norwegian Cancer Society; Research Council of Norway; French League against Cancer (LNCC); National Institute for Health and Medical Research (INSERM), France; Mutuelle Générale de l’Education Nationale (MGEN), France; 3M Co, France; Gustave Roussy Institute (IGR), France; and General Councils of France.