Melatonin pharmacotherapy for nocturia in men with benign prostatic enlargement

PURPOSE: Nocturia is a common condition often attributed in aging men to benign prostatic enlargement. Older adults are prone to nocturnal sleep disturbance, of which disturbed circadian rhythm may be a component since it improves with nighttime administration of melatonin. This study was designed to investigate melatonin as a potential treatment for nocturia associated with bladder outflow obstruction in older men. MATERIALS AND METHODS: A total of 20 men with urodynamically confirmed bladder outflow obstruction and nocturia were entered into a randomized, double blind, placebo controlled crossover study assessing the effect of 2 mg controlled release melatonin at night on nocturia. Symptoms were assessed at baseline and after each 4-week treatment period using a frequency volume chart, the International Prostate Symptom Score and symptom problem index. Maximum urinary flow rate and post-void residual urine volume were also assessed. RESULTS: Baseline frequency of nocturia was 3.1 episodes per night. There were 7 men (35%) with detrusor overactivity and 10 (50%) had nocturnal polyuria. Melatonin and placebo caused a decrease in nocturia of 0.32 and 0.05 episodes per night (p = 0.07) and a decrease in the nocturia bother score of 0.51 and 0.05, respectively (p = 0.008). Nocturia responder rates (a reduction from baseline of at least -0.5 episodes per night) differed between the active medication and placebo groups (p = 0.04). Daytime urinary frequency, International Prostate Symptom Score, relative nocturnal urine volume, maximum urinary flow rate and post-void residual were unaffected by melatonin treatment. CONCLUSIONS: Melatonin treatment is associated with a significant nocturia response rate, improvement in nocturia related bother and a good adverse effect profile. However, it is uncertain whether the observed changes in this study are clinically significant.     

Conservative management of hyperplastic and multicentric nephroblastomatosis

PURPOSE: The treatment of hyperplastic nephroblastomatosis remains controversial. We report the advantages of conservative management of hyperplastic and multicentric nephroblastomatosis associated with unilateral Wilms tumor (WT). MATERIALS AND METHODS: During the last 10 years 48 children with unilateral WT were consecutively treated at our 2 institutions. Children with multiple solid renal masses on imaging were treated with 2-drug chemotherapy until disappearance of the lesions. Stabilization or progression of the lesions despite chemotherapy, as well as heterogeneity of the lesions on imaging, prompted nephron sparing surgery (NSS). RESULTS: Three female infants (12, 13 and 20 months old, respectively) presented with multiple solid renal tumors at imaging. Despite chemotherapy, small and unilateral WT developed in 2 cases of hyperplastic nephroblastomatosis, which was excised. One of these infants subsequently presented with a small contralateral metachronous WT, which was excised. Both infants are disease-free with 2 normal kidneys at followup of 6 and 2 years, respectively. The third infant, who presented with unilateral multicentric WT and unilateral hyperplastic nephroblastomatosis nodules, was successfully treated with preoperative chemotherapy and enucleation of 5 tumors. Subsequently, nephrectomy was performed at another institution because the abnormal kidney outline due to NSS was misinterpreted as a recurrence of WT. She was lost to followup. CONCLUSIONS: Hyperplastic and multicentric nephroblastomatosis is not a rare lesion and is most often associated, either initially or subsequently, with WT. In some infants with multiple solid renal masses on imaging chemotherapy and for developing WT NSS may safely allow maximum sparing of the parenchyma of both kidneys.     

A pluridisciplinary point of view of hepatitis C virus infections

Various complementary actors are implied in the management of HCV infections: virologists, general practitioners, hepato-gastroenterologists and hospital residents, and they should all cooperate together. The role of biologist is crucial in assisting the practitioners in the choice of examinations to be prescribed for the diagnosis of HCV infections (search for RNA HCV), in establishing a prognosis and in deciding on the therapeutic strategy (genotyping, Fibrotest and Actitest). The role of the general practitioner is important at all stages of the management. The practitioner's involvement is also crucial in the recognition and follow-up of the concomitant diseases. THE ROLE OF THE SPECIALIST: The hepatologist, together with the general practitioner, are inseparable partners in the management of a patient suffering from hepatitis C. The specialist should only see patients exhibiting hepatitis C who are participating in a treatment program, since the indication for treatment is usually decided on by the specialist. The hepatologist should be informed of the various concomitant diseases and the treatments (replacement therapy or others) prescribed for them. CRUCIAL QUESTIONS: For the management of an HCV infection, in general 3 questions require an answer: who should be screened for such infections, what explorations should be performed in the case of positive serology and what follow-up is required during and after anti-HCV treatment?     

Multiple myeloma presenting with widespread osteosclerotic lesions

Sclerotic lesions are rare in malignant monoclonal gammopathies, although they are occasionally associated with POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes). In most cases, osseous lesions in POEMS syndrome present as an isolated sclerotic deposit or a combination of both lytic and sclerotic lesions. Diffuse osteosclerosis is extremely rare and may lead to the diagnosis of multiple myeloma, classically known to present as lytic lesions in the skeleton, with or without diffuse osteoporosis. We report a 74-year-old woman with widespread and substantial osteosclerotic lesions, associated with IgA-lambda myeloma, and with no other criteria for POEMS syndrome, and who was rapidly diagnosed with compression of the spinal cord. Detailed knowledge of imaging features in myeloma emphasises the need to consider plasma cell neoplasm in the differential diagnosis of any pattern of bone sclerosis. Although exceptional, multiple myeloma must be borne in mind in the presence of diffuse bone sclerosis.     

Infevers: an evolving mutation database for auto-inflammatory syndromes

The Infevers database (http://fmf.igh.cnrs.fr/infevers/) was established in 2002 to provide investigators with access to a central source of information about all sequence variants associated with periodic fevers: Familial Mediterranean fever (FMF), TNF Receptor Associated Periodic Syndrome (TRAPS), Hyper IgD Syndrome (HIDS), Familial Cold Autoinflammatory Syndrome/Muckle-Wells Syndrome/Chronic Infantile Neurological Cutaneous and Articular Syndrome (FCAS/MWS/CINCA). The prototype of this group of disorders is FMF, a recessive disease characterized by recurrent bouts of unexplained inflammation. FMF is the pivotal member of an expanding family of autoinflammatory disorders, a new term coined to describe illnesses resulting from a defect of the innate immune response. Therefore, we decided to extend the Infevers database to genes connected with autoinflammatory diseases. We present here the biological content of the Infevers database, including the introduction of two new entries: Crohn/Blau and Pyogenic sterile arthritis, pyoderma gangrenosum and acne (PAPA syndrome). Infevers has a range of query capabilities, allowing for simple or complex interrogation of the database. Currently, the database contains 291 sequence variants in related genes (MEFV, TNFRSF1A, MVK, CARD15, PSTPIP1, and CIAS1), consisting of published data and personal communications, which has revealed or refined the preferential mutational sites for each gene. This database will continue to evolve in its content and to improve in its presentation.     

CD45 isoforms in T cell signalling and development

The CD45 phosphotyrosine phosphatase is expressed on T cells as multiple isoforms due to alternative splicing. The panoply of isoforms expressed is tightly regulated during T cell development and on mature peripheral T cell subsets following activation. We describe the analysis of comparative CD45 isoform expression levels on thymic and T cell subsets from the C57BL/6 mouse. Only four isoforms were expressed at significant protein levels: CD45R0, CD45RB, CD45RBC and CD45RABC, although trace amounts of others may be present. The expression of CD45RBC was about nine-fold higher on CD8(+) than on CD4(+) peripheral T cells, whereas CD45R0 expression was higher on CD4(+) T cells. We provide a general overview of the current models that have been proposed to explain the molecular actions of the different CD45 isoforms. Achieving a thorough understanding of the biological reasons for the existence and tight regulation of CD45 isoform expression in immune cells remains one of the outstanding challenges in the CD45 research field.     

The rhinal cortices: a wall of inhibition between the neocortex and the hippocampus

Anatomical data indicate that the parahippocampal region, comprised of the perirhinal (PRC), postrhinal (POR) and entorhinal (ERC) cortices, is an essential link between neocortex and hippocampus. Lesion studies demonstrated that memory functions previously ascribed to the hippocampus depend on the integrity of the rhinal cortices. This review will consider recent data suggesting that the ERC and PRC, far from being passive relay stations, actively gate impulse traffic between neocortex and hippocampus, because they are endowed with a powerful intrinsic inhibitory system. It is proposed that the cross-talk between PRC and ERC is not organized to unrestrictedly transfer information, but to select relevant inputs. The implication of these new evidences for the propagation of epileptiform activity will be considered.     

Interleukin-15 delays human neutrophil apoptosis by intracellular events and not via extracellular factors: role of Mcl-1 and decreased activity of caspase-3 and caspase-8

Interleukin-15 (IL-15) induces the de novo protein synthesis of intracellular polypeptides and delays neutrophil apoptosis by a mechanism that is still unclear. Herein, we investigated the potential antiapoptotic role of newly synthesized proteins released into the external milieu in IL-15-induced neutrophils. We found that IL-15 induces the de novo synthesis of an approximately 23-kDa protein, representing the predominant protein detected in the milieu, and identified it as IL-1 receptor antagonist (IL-1Ra) by Western blot and immunoprecipitation. We quantified IL-1Ra, IL-1alpha, and IL-1beta concentrations by enzyme-linked immunosorbent assay in intracellular and extracellular fractions from IL-15-induced neutrophils and found that IL-15 does not increase IL-1alpha or IL-1beta production but induces IL-1Ra release. Also, we demonstrated that IL-1Ra does not modulate apoptosis, even at a concentration 250 times greater than that measured in the external milieu. In contrast to granulocyte macrophage-colony stimulating factor, the supernatant harvested from IL-15-induced neutrophils was devoid of antiapoptotic activity. Addition of cycloheximide demonstrates that IL-15 delays apoptosis via de novo synthesis of intracellular proteins and that it increases myeloid cell differentiation factor-1 stability. We demonstrated also that IL-15 decreases the activity of caspase-3 and caspase-8, resulting in an inhibition of vimentin cleavage. Our results indicate that IL-15 can activate an anti-inflammatory loop, based on its ability to induce the synthesis of IL-1Ra by neutrophils. We conclude that IL-15 delays human neutrophil apoptosis by intracellular events and not via extracellular factors.     

Anosmia and nasal sinus disease

Smell loss associated with nasal sinus disease can be a frustrating condition for patients and their physicians. A better understanding of the causes and pathophysiology of olfactory dysfunction can provide a framework from which the physician can plan appropriate treatment and counsel patients as to probable outcomes. This article reviews the pathophysiology of smell loss and the diagnostic paradigms and treatment approaches for the more common causes of anosmia.