The antisaccade: a review of basic research and clinical studies

The ability to suppress reflexive responses in favor of voluntary motor acts is crucial for everyday life. Both abilities can be tested with an oculomotor task, the antisaccade task. This task requires subjects to suppress a reflexive prosaccade to a flashed visual stimulus and instead to generate a voluntary saccade to the opposite side. This article reviews what is currently known about the neural structures and processes which are involved in the performance of this task. Current data show that a variety of brain lesions, neurological diseases and psychiatric disorders result in errors, i.e. prosaccades towards the stimulus, in this task. Brain imaging studies have shown that a widely distributed cortical and subcortical network is active during the generation of antisaccades. These findings are discussed and the potential of the antisaccade task for diagnostic purposes is evaluated.     

Alcohol and free radicals: from basic research to clinical prospects

An oxidative stress occurs in the liver of rats following various conditions of ethanol administration. The ethanol-inducible cytochrome P450 2E1 plays a key role in its generation, favoured itself by an increase in the "redox-active" fraction of intracellular non-heme iron. Administration of ethanol elicits the generation of the 1-hydroxyethyl radical, which has been identified in vivo. Its reactivity contributes to alcohol-induced immunological disturbances. Liver inflammatory and fibrotic disorders can be reproduced in rats by long-term ethanol administration associated with a high fat diet. The severity of these disorders is correlated to the intensity of the oxidative stress. Some conditions of ethanol administration to rats also elicit an oxidative stress in the myocardium and central nervous system. Through its inhibitory effect on glutamine synthetase activity and resulting excitotoxicity it may contribute to neuronal death and possibly to dependence on alcohol. Disorders related to an oxidative stress were also reported in the serum and erythrocytes as well as in liver biopsies from alcoholic individuals. Their detection may be useful to follow the evolution of alcoholic liver diseases. Supplementation with antioxidants such as vitamin E may be considered in the prevention of severe cellular disorders in individuals consuming large amounts of alcoholic beverages. An increase in free radical production is likely playing a role in the induction of severe cellular damage linked to repeated withdrawals occurring as a result of heavy and sporadic ethanol intake.     

Monoamniotic twin pregnancy and cord entanglement: a clinical dilemma

Although isoflurane inhibits TNF-alpha and IL-1 beta release from human monocytes stimulated by LPS in dose dependent fashion, it is unclear whether sevoflurane has the same effects. Therefore, we investigated whether sevoflurane could inhibit TNF-alpha and IL-1 beta secretions from human monocytes stimulated by LPS in dose dependent fashion in vitro. Human monocytes stimulated by LPS were cultured for 3 h in the presence of sevoflurane 1% or 5%. Another group of human monocytes were cultured in the absence of sevoflurane. TNF-alpha and IL-1 beta increased after stimulation of LPS and these increases were not inhibited by sevoflurane in a dose dependent fashion. We conclude that sevoflurane does not inhibit TNF-alpha and IL-1 beta release from monocytes stimulated by LPS.     

Cancer gene therapy: connecting basic research with clinical inquiry

Molecular genetics has spawned an impressive outpouring of insights into the biology of neoplastic transformation and the host-tumor relationship. This deeper understanding of cancer pathogenesis presents a rich opportunity to develop novel therapeutic agents with improved selectivity for cancer cells. One promising approach involves gene therapy, which is the introduction of genetic material into a patient's tissues with the intent to achieve therapeutic benefit. A number of gene transfer systems have been designed that enable the genetic modification of relevant target cells, albeit with varying strengths and limitations. Several strategies to exploit gene transfer as a tool to target specific molecular defects intrinsic to cancer cells, enhance tumor chemosensitivity, and augment tumor immunogenicity are under intensive investigation. A number of these approaches have entered initial clinical testing and already provide intriguing new information about the biology of cancer in patients. In this review, I will highlight the critical issues and controversies that underscore preclinical experiments in cancer gene therapy, discuss some of the preliminary findings from the first wave of clinical trials, and speculate about the prospects that cancer gene therapy will change the way that cancer medicine is practiced.     

Neurotoxins in neurobiology: from basic research to clinical application

Recently, we reported that in rat, cyclosporine A (CsA) markedly decreases the levels of calbindin-D (CABP-D) 28 kDa in kidney. CABP-D 28 kDa is a calcium-binding protein which is highly expressed in calcium-transporting tissues such as kidney or brain. In this study, we investigated whether, in addition to the kidney, CsA also has an effect on CABP-D 28 kDa in rat brain. Three groups of male Wistar rats received 15 mg/kg/day or 50 mg/kg/day of CsA orally for 12 days, whereas controls received vehicle solution for the same period. CABP-D 28-kDa protein and CsA were quantified in homogenates of kidney, cerebral cortex and cerebellum, and the localization of CABP-D 28 kDa was assessed in the different tissue sections by immunohistochemistry. In kidney, CABP-D 28 kDa was strongly and dose dependently decreased, and was located in tubular epithelial cells. In brain, CABP-D 28 kDa was not changed and was mainly located in pyramidal cells of the cortex and in cerebellum exclusively in Purkinje cells. High CsA concentrations were measured in kidney, more than 17-fold greater than those found in cortex. In cerebellum, CsA was below the limit of detection. These data suggest that at clinically relevant doses, CsA may not affect CABP-D 28-kDa levels in brain.     

Knowing the self: Building a bridge from basic research to clinical practice.

The articles under discussion give promise that basic research information about the self can be translated into useful information for the clinical practitioner. Several issues were delineated that require more careful attention and research: (a) The self needs to be more clearly defined in both basic and clinical literatures; (b) the process of self-experiencing must be studied in conjunction with the study of the acquisition, functions, and developmental trajectories of self-concepts; and (c) the complexities of identity formation in multicultural societies must be factored into future research designs. Psychotherapists need to be aware that many patients have internalized self-related ideas from several different cultures and subcultures, and puzzling out these culture-based conflicts may become a significant focus of psychotherapy. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Methodology for interfacing results of basic science research and clinical practice

The importance of the integration of basic vision sciences and applied clinical research is discussed. Steps which must be taken in optometry and in the schools and colleges in particular are reviewed. Some of the problems that will be encountered are discussed.     

The attrition dilemma: Toward a new strategy for psychotherapy research.

Presents an analysis of the attrition dilemma in psychotherapy research and reviews the methods used to compensate for data loss. It is argued that attrition is not ultimately a problem of bias but a problem of lack of information. A reformulation is offered that integrates single-case studies with traditional group comparison methodology in an attempt to find optimal causal relations of treatments to outcomes. (10 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Phospholipase A2--from basic research to clinical reality]

Phospholipase A2 (PLA2) is a group of secretory as well as intracellular enzymes that release phospholipids as an early step in inflammation and play a physiologic role in digestion. In humans, the group of secretory, low-molecular-weight PLA2 (sPLA2) is differentiated from the cytosolic, high-molecular-weight PLA2 (cPLA2). The two known cPLA2 mediate the intracellular response to inflammation by releasing arachidonic acid from membrane phospholipids. Secretory pancreatic PLA2 (sPLA2-I) is a digestive zymogen secreted from pancreatic acinar cells in its inactive form. Activated by trypsin in the duodenum, it is an important digestive enzyme. In acute pancreatitis, circulating sPLA2-I indicates pancreatic injury but is mostly inactive. Synovial-type secretory PLA2 (sPLA2-II), first isolated from synovial fluid of arthritis patients, is increased in inflammation, after surgery or trauma, and in various inflammatory diseases. Unlike sPLA2-I, its catalytic activity is held responsible for mediating the systemic inflammatory reaction and its complications by regulating the synthesis of prostaglandins, leukotrienes and platelet activating factor. Clinically, sPLA2-II offers new possibilities as an early marker for severe inflammation and predicting systemic complications in severely ill patients.     

Endothelial dysfunction in peripheral arterial occlusive disease: from basic research to clinical use

By checking the card indexes of seven out of twelve Social Insurance Offices covering 66% of the total wage-earning population in the city of G?teborg the patients recorded for 90 days of continuous sick-listing were classified into four diagnostic categories according to the doctor's certificate: "non-specific pain" and "specific pain" of the musculoskeletal system, "other pain" and "non-pain" diagnoses. The overall yearly incidence of 90 days' sick-listing averaged 5.4%. A significant correlation was found between the incidence of 90 days' sick-listing due to "non-pain" and musculoskeletal pain diagnoses and the proportion of demographic characteristics of the areas. The hypothesis of presuming the highest association between non-specific pain diagnoses and demographic factors was rejected.     

Making progress: does clinical research lead to breakthroughs in basic biomedical sciences?

Beta-catenin is a pivotal player in the signaling pathway initiated by Wnt proteins, mediators of several developmental processes. beta-catenin activity is controlled by a large number of binding partners that affect the stability and the localization of beta-catenin and is thereby able to participate in such varying processes as gene expression and cell adhesion. Activating mutations in beta-catenin and in components regulating its stability can contribute to the formation of certain tumors.     

Introduction to special section: Relapse to substance abuse: Recent findings from basic and clinical research.

A series of 6 articles concerning relapse to substance abuse and its treatment is introduced. Two articles review animal models of relapse and the potential role of drug priming effects, 2 articles present new data from experimental human research on cognitive and contextual determinants of relapse, while 2 articles describe clinical approaches and review the effectiveness of relapse prevention treatment. The series integrates clinical and basic research around a common theme and demonstrates that various types of research representing diverse perspectives are needed to understand this important feature of substance dependence. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dementia's impact on pain sensation: a serious clinical dilemma for dental geriatric care givers

Dementia's impact on pain sensation is not well understood. Very little research has been done in this area, our clinical knowledge is poor, and there is no published information available to practitioners. This article reviews the current literature and discusses the need for further research. The number of patients with dementia is growing. This patient group will require dental diagnosis and treatment, and cannot be ignored by dentists. A humane approach to treatment must be adopted.