Age-related variations in gene expression patterns of renal cell carcinoma

Background

Clear cell renal cell carcinoma (ccRCC) is known to occur across the adult lifetime traversing the spectrum of age-related organismal changes. Little is known as to how the aging process may affect the course of renal cell carcinoma (RCC) and the repertoire of genes involved.

Value of procalcitonin as a marker of surgical site infection following spinal surgery

Aim

To compare the value of Procalcitonin (PCT) as a marker of surgical site infection to other inflammatory markers, including C-Reactive Protein (CRP), White Cell Count (WCC) and Erythrocyte Sedimentation Rate (ESR) in patients undergoing a number of spinal procedures. This study also aims to describe the biokinetic profile of the above-named markers in patients developing surgical site infection and those remaining infection-free post-operatively.

Pulmonary thromboembolism in beta-thalassemia intermedia: are we aware of this complication?

We describe a case of pulmonary thromboembolism in a 61-year-old woman with beta-thalassemia intermedia and no other risk factors for thrombosis. Thromboembolism was documented by perfusion lung scan. We review the literature on this uncommon complication of thalassemia intermedia and discuss the pathogenesis and treatment options. A significant relationship between pulmonary thromboembolism and pulmonary hypertension in these patients was noted.     

Ocular penetration of acyclovir and its peptide prodrugs valacyclovir and val-valacyclovir following systemic administration in rabbits: An evaluation using ocular microdialysis and LC-MS

PURPOSE: To investigate the ocular penetration of acyclovir and its prodrugs following systemic administration and to elucidate the mechanism of penetration. METHODS: Hydrophilic peptide prodrugs of acyclovir were infused intravenously in New Zealand albino rabbits over 45 min at a dose equivalent to 30 mmoles/kg acyclovir. Aqueous and vitreous humor samples were obtained utilizing ocular microdialysis and blood samples were obtained from the mid ear vein using a cannula. RESULTS: The plasma bioavailability for acyclovir, valacyclovir and val-valacyclovir were similar with area under curve values being 896.24 (+/-143.58), 776.54 (+/-197.52), 824.69 (+/-217.43) min x micromoles/L respectively. Anterior segment area under curve values were 53.70 (+/-35.58), 139.85 (+/-9.43) and 291.05 (+/-88.13) min x micromoles/L respectively while the mean residence time values were 46.47 (+/-24.94), 76.30 (+/-7.24) and 188.39 (+/-80.73) min respectively. Vitreous levels of the prodrugs were not measurable. CONCLUSIONS: The valine and valine-valine ester prodrugs of ACV penetrated the anterior segment of the eye much better than acyclovir alone, probably via a carrier mediated transport mechanism.     

The evolving therapy of rheumatic diseases,the future is now

There are two main ways in which physicians will be urged to improve the outcome for their patients suffering from rheumatic diseases in the coming era, these are, early diagnosis and timely effective therapy. Current reserch suggests that in rheumatoid arthritis joint damage occurs early, often within the first 2 years and even in the absence of associating severe symptoms, is a call for action for primary care physicians as well as rheumatologists. Similarly in SLE patients, sometimes the treatments are ineffective or too toxic with sepsis or opportunistic infections often limiting their use or resulting in the death of the patient. As primary care physicians are the clinicians most frequently visited by patients with initial symptoms of the disease, they first need to learn when to suspect it as well as its complications, and when to refer the patient appropriately. Rheumatologists need to determine when and how to prescribe the most appropriate treatment, as well as how to incorporate the new drugs which are emerging on the scene. At the same time, earlier initiation of combination therapy with the disease modifying anti-rheumatic therapy holds an area of continued exploration. This new information has modified our approach to patients' management. The age of "wait and see" is over.     

Depersonalization-derealization syndrome induced by reboxetine

A high variety of factors have been implicated in the emergence of depersonalisation and derealisation episodes, including different drugs. A case abruptly induced by two applications of reboxetine, a selective and specific norepinephrine reuptake inhibitor, is reported occurring in a 50-year-old woman treated for a major depressive episode. The episode rapidly remitted after discontinuation of reboxetine. Previous data having indicated a role of the serotonin system in the pathophysiology of the phenomenon, a noradrenaline induced serotonin liberation of Raphe neurons is suggested as possible underlying mechanism.     

The neuronal ceroid lipofuscinoses: mutations in different proteins result in similar disease

The neuronal ceroid-lipofuscinoses (NCL) are the most common group of progressive neurodegenerative diseases in children, with an incidence as high as one in 12,500 live births. The main features of this disease are failure of psychomotor development, impaired vision, seizures, and premature death. Many biochemical and physiological studies have been initiated to determine the cellular defect underlying the disease, although only a few traits have been truly associated with the disorders. One of the paradox's of the NCL-diseases is the characteristic accumulation of autofluorescent hydrophobic material in the lysosomes of neurons and other cell types. However, the accumulation of this lysosomal storage material, which no doubt contributes to the neurologic disease, does not apparently lead to disease outside the CNS, and how these cellular alterations relate to the neurodegeneration in NCLs is unknown. Mutations have been identified in six distinct genes/proteins, namely CLN1, which encodes PPT1, a protein thiolesterase; CLN2, which encodes TPP1, a serine protease; and CLN3, CLN5, CLN6, and CLN8, which encode novel transmembrane proteins. Mutation in any one of these CLN-proteins results in a distinct type of NCL-disease. However, there are many shared similarities in the pathology of these diseases. The most obvious connection between PPT1, TPP1, CLN3, CLN5, CLN6, and CLN8 is their subcellular localization. To date, three of the four proteins whose subcellular localization has been confirmed, namely PPT1, TPP1, and CLN3, reside in the lysosome. We review the function of the CLN-proteins and discuss the possibility that a disruption in a common biological process leads to an NCL-disease.