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PubMed2003

Genetic basis of psoriasis vulgaris and its pharmacogenetic potential.

Psoriasis vulgaris is one of the most prevalent T cell-mediated inflammatory diseases in humans. It is multifactorial in origin and shows polygenic inheritance. Systemic immunosuppressive therapies play an important role in management of severe disease cases but are associated with variable response and toxicity. Within the last decade there have been significant advances in our understanding of the genetic basis of this complex disease and polymorphic candidate genes have been proposed. Susceptibility gene characterization together with an explosion in knowledge of its primary immune basis will further define disease pathways involved in psoriasis pathogenesis. This holds the promise of rational design of new therapeutic agents and pharmacogenetic testing to predict responders from non-responders and those at risk of toxicity.

Drug Design↗
PubMed1998

Constitutional and non-specific immunity to infection.

Most immunologists focus on elaborate non-specific and antigen-specific factors of reactive immunity produced by the vertebrate lymphoid system. Modern principles of immunogenic prophylaxis and therapy are based solely on the use of these agents. There is, however, a more effective system of specific resistance which is shared by all forms of life: hereditary constitutional immunity to infection and invasion. An explosive growth in knowledge of the constitutional immunogenic system has occurred during the past two decades. The author illustrates the nature and importance of constitutional immunity, using examples from genetics and molecular biology. Special attention is given to testing for genetic susceptibility to infection and genetic engineering of resistance.

Aging↗
PubMed2000

Future antiepileptic drug development.

The last decade has seen an explosion in the number of antiepileptic drugs approved. Despite these advances, however, there are still other basic mechanisms of epilepsy that could be the targets of new agents. This article discusses some of these novel sites for possible antiepileptic drug action in the context of the available data supporting the various mechanisms. While not all of these investigations will be translated into clinically useful agents, there is still great unrealized potential for the development of new and novel antiepileptic compounds.

Anticonvulsants↗
PubMed2004

Global dissemination of beta-lactamases mediating resistance to cephalosporins and carbapenems.

While the main era of beta-lactam discovery programs is over, these agents continue to be the most widely prescribed antimicrobials in both community and hospital settings. This has led to considerable beta-lactam pressure on pathogens, resulting in a literal explosion of new beta-lactamase variants of existing enzyme classes. Recent advances in the molecular tools used to detect and characterize beta-lactamases and their genes has, in part, fueled the large increase in communications identifying novel beta-lactamases, particularly in Gram-negative bacilli. It now seems clear that the beta-lactams themselves have shaped the field of new enzymes, and the evolution of key amino acid substitutions around the active sites of beta-lactamases continues to drive resistance. Over 130 variants of TEM beta-lactamase now exist, and more are reported in the scientific literature each month. The most disturbing current trend is that many bla structural genes normally limited to the chromosome are now mobilized on plasmids and integrons, broadening the spread of resistance to include carbapenems and cephamycins. Furthermore, in some Enterobacteriaceae, concomitant loss of outer membrane porins act in concert with these transmissible beta-lactamase genes to confer resistance to the most potent beta-lactams and inhibitor combinations available. Continued reviews of the literature are necessary in order to keep abreast of the ingenuity with which bacteria are changing the current genetic landscape to confer resistance to this important class of antimicrobials.

Anti-Bacterial Agents↗
PubMed1989

Acute myocardial infarction: treatment with thrombolytic therapy.

The past 5 years have witnessed an explosion in the amount of published clinical trial data for the use of intravenous thrombolytic therapy for acute myocardial infarction. This article reviews the properties of the various agents, the experiences of each in prospective, randomized clinical trials, and the future directions of thrombolytic intervention.

Fibrinolytic Agents↗
PubMed2006

Risperidone for the treatment of affective symptoms in children with disruptive behavior disorder: a post hoc analysis of data from a 6-week, multicenter, randomized, double-blind, parallel-arm study.

BACKGROUND: Despite the increasing recognition of bipolar disorder in childhood, there have been no controlled, randomized clinical trials of atypical antipsychotics in this population. Preliminary data from open-label trials in children suggest that these agents might be effective in treating pediatric bipolar disorder, however. OBJECTIVE: The purpose of this post hoc analysis of data from Aman et al was to determine the effects of risperidone in the management of affective symptoms in children with disruptive behavioral disorders (DBDs). METHODS: This report presents a secondary analysis of a previously reported 6-week, multicenter, double-blind, randomized, parallel-arm trial comparing 6 weeks of administration of risperidone (flexible dosing starting at 0.02 mg . kg .1 . d(-1) and titrated up to 0.06 mg kg(-1) d(-1)) versus placebo in children with DBDs and subaverage intelligence. Twenty-four candidate affective symptoms of mania and depression were extracted from the 64-item Nisonger Child Behavior Rating Form (NCBRF). To define independent dimensions of mood-disorder psychopathology, these 24 symptoms were assigned 1 of 3 independent dimensions (symptoms of mania) based on loading: explosive irritability; agitated, expansive, grandiose; and depression. A fourth, nonaffective independent dimension encompassed a combination of nonaffec tive symptoms on the NCBRF Conduct Problem subscale. To assess treatment effect, each independent dimension was assigned a score derived from the sum of the symptoms that loaded on that dimension at weeks 2, 4, and 6 of study drug administration. RESULTS: A total of 110 patients were included in the independent-dimension analysis (89 boys, 21 girls; risperidone, 49 patients; placebo, 61 patients; mean [SD] age, 8.6 [2.3] and 8.1 [2.4] years in the risperidone and placebo groups, respectively; mean [SD] weight, 33.9 [12.8] and 32.1 [12.0] kg in the risperidone and placebo groups, respectively). The treatment-effect analysis found that the mean scores of all 3 independent dimensions were significantly reduced with risperidone compared with placebo at weeks 2, 4, and 6 (all, P <or= 0.03). The effect sizes of improvement in these factors ranXged from 0.44 to 0.95 at end point. CONCLUSIONS: The results of this post hoc analysis of affective symptoms of DBDs using data from a previously published randomized, double-blind clinical comparison of risperidone and placebo in the treatment of children with DBDs and subaverage intelligence suggest that risperidone was effective in treating the factors of explosive irritability; agitated, expansive, grandiose; and depression.

Affective Symptoms↗
PubMed2006

Fluorescence of aromatic amines and their fluorescamine derivatives for detection of explosive vapors.

Nitroaromatics (such as dinitrotoluene, trinitrotoluene, and nitrobenzene) found in explosive vapors from buried landmines can be reduced to aminoaromatics by a novel process involving Pd metal nanocatalysts prepared in supercritical fluid carbon dioxide and supported on multi-walled carbon nanotubes. These aminoaromatics are fluorescent and, if desired, the fluorescence yield can be increased and the fluorescence maxima shifted further toward the red by reaction with appropriate derivatizing agents such as fluorescamine. Corrected spectra for these chemicals and their derivatives are included. Subpicomolar detection limits have already been achieved using a laboratory spectrofluorometer with a 150 W Xe arc lamp. Using lasers as excitation sources, this approach has the potential for developing a field sensor competitive with other methods currently used for detecting explosive vapors from land mines.

Journal Article↗
PubMed1999

Recognition and treatment of DSM-IV intermittent explosive disorder.

Although models of impulsive aggression are often associated with psychiatric disorders, some individuals demonstrate violent outbursts of rage that are variously referred to in the field as rage attacks, anger attacks, episodic dyscontrol, and intermittent explosive disorder. According to DSM-IV, intermittent explosive disorder is characterized by discrete episodes of failure to resist aggressive impulses resulting in serious assaults or destruction of property. Virtually no research has been done on intermittent explosive disorder as defined by DSM-IV criteria, and this article discusses the phenomenology, comorbidity, and treatment response of 27 individuals who met the DSM-IV criteria for the disorder. The association of the explosive episodes in these subjects with maniclike affective symptoms, the high rate of lifetime comorbid bipolar disorder, and the favorable response of explosive episodes to mood-stabilizing drugs suggest that intermittent explosive disorder may be linked to bipolar disorder.

Adolescent↗
PubMed1986

HTLV-I-associated T-cell leukemia in Hawaii.

Adult T-cell leukemia (ATL) is a disease found endemic in Southern Japan and the Caribbean basin. The human T-cell leukemia virus I (HTLV-I) has been implicated epidemiologically as the causative agent in this disease. This paper describes the identification of this disease in Hawaii in a second generation immigrant from Southern Japan. The disease was initially indolent, then clinically explosive, characterized by cutaneous lesions, leukemic lymphocytes with convoluted nuclei of T-cell phenotype, hypercalcemia, and a terminal infection.

Asian↗
PubMed1992

Burns mass disasters: aetiology, predisposing situations and initial management.

Many agents that are encountered daily are liable to cause burns mass disasters. These include flames, hot water and steam, combustible gases and liquids, molten liquids, boiling liquid expanding vapour explosion, chemicals and explosives. They result in disaster when certain lacks in safety occur. The proper management of such burns victims begins with rescue. At the disaster site, triage is important to separate the living from the dead, decide on priorisation for initial treatment and then evacuation to an appropriate facility. Proper management requires team effort and should be continued en-route to hospital. Repeat triage and use of clear guidelines in the Emergency Department ensure optimal and rapid care of the casualties. Finally psychological support for victims, relatives, rescuers and health workers must not be forgotten.

Burns↗
PubMed1987

Tragedy at Tunnel 13. The d'Autremont brothers and "The Edison of Crime Detection".

Train robbery was frequent in the United States from the late 1800s through the 1920s. On October 11, 1923, the southbound Southern Pacific Express was halted by three men at Tunnel 13 in southern Oregon just north of the California line. The railway mail car carrying +40,000 was then blown apart by an explosive charge, killing the clerk and rendering the money unobtainable. The men shot three other train crew members before escaping into the mountains. The investigation was headed by Chief Agent Dan O'Connell, who soon asked that California criminalist, Edward Heinrich, examine soiled overalls found nearby. Using primarily botanical evidence, Heinrich identified them as those of a woodsman, leading to the identification of three Oregon d'Autremont brothers as suspects. After an intensive manhunt, one was captured 3 years later in the Philippines and was tried and found guilty. The twins, captured in Ohio, then pleaded guilty. This crime, typical of those in which unforeseen events lead the perpetrators to panic and to murder, helped to establish criminology and particularly botanical studies as valid scientific disciplines. Its investigation and solution also remain models of scientific crime detection.

Crime↗
PubMed2000

beta -Lactamases: which ones are clinically important?

The introduction of a large array of beta-lactam antibiotics has spawned the emergence of an even larger variety of beta-lactamases designed to confer resistance to these agents. beta-lactamases are produced by both gram-positive and gram-negative bacteria, but their clinical importance is far greater among the gram-negatives. The virtual explosion in our knowledge about the variety of these enzymes can often create confusion and frustration among those not well versed in the field. In this paper, we attempt to focus the discussion of beta-lactamases on those enzymes that are of the greatest clinical importance, the Ambler Class A and C enzymes. We also discuss the growing importance of the Ambler Class B metallo beta-lactamases, which hydrolyze carbapenems and are increasing in prevalence in areas of significant carbapenem usage. Copyright 2000 Harcourt Publishers Ltd.

Journal Article↗
PubMed2001

Upper aerodigestive tract burn: a case report of firework injury.

The case of a 46 year-old German man with upper aerodigestive burn by firework was reported. He presented with the symptoms and signs of upper airway obstruction. Tracheostomy was done and direct laryngoscopy with microscopic examination revealed swelling and denudation of the mucosa of the oral cavity and supraglottic area. Intravenous steroids and antibiotics were administrated for treatment. It is suggested that proper management needs an understanding of the mechanism and effect of the corrosive agent. Careful airway management resulted in a good outcome in this patient.

Burns, Chemical↗
PubMed2002

Targeting intracellular signal transduction. A new paradigm for a brave new world of molecularly targeted therapeutics.

Significant advances in the field of molecular biology over the past decade have led to a new era in cancer therapeutics, with an explosion of rationally designed therapeutic strategies directed against selective molecular targets. The complex array of aberrant signal transduction proteins involved in carcinogenesis has been the focus of target-based anticancer agents. Inhibitors of intracellular signal transduction represent a unique approach in that they inhibit critical downstream regulatory proteins, which are vital to the process of cellular communication. Although these agents are in early-phase evaluations, the preliminary data suggest that they are well tolerated and capable of target inhibition in surrogate and tumor tissue. Although the primary therapeutic benefit of these agents is expected to be decreased tumor growth, evidence suggests that objective tumor responses may also be achieved. There are many unresolved questions pertaining to the development of this class of compounds, including selection of optimal dose and schedule, determination of relevant endpoints, methods for target validation, and strategies for combination with cytotoxic agents. However, despite the numerous unresolved issues, the emergence of this class of compounds has resulted in an undeniable impact on the present and future of cancer therapeutics.

Adult↗
PubMedDate not supplied

Progressing from eugenics to human genetics. celebrating the 70th birthday of professor Newton E. Morton.

Eugenics, unlike science, involves decision making on various issues, and decision making involves the risk of making errors. This communication first clarifies the nature and seriousness of making errors known as type II in the statistical literature, i.e. the error of punishing a person when he is not guilty of the crime attributed to him. Eugenic laws in China and the eugenic movements in England and the United States are briefly reviewed. The explosive advances made in medical and population genetics in the last 40 years are replacing the conventional eugenics programs by new approaches. Modern genetic counseling has been introduced as the intermediate agent between the scientist and the family that needs advice. It is stressed that individual rights must be respected under all circumstances.

China↗
PubMed1989

[Sleep disorders in adolescents and youths with atopic dermatitis and its pharmacologic correction].

Clinical and actographic examinations of various sleep stages in 52 patients with atopic dermatitis have revealed a variety of sleep disturbances in the majority of cases. 56% of the examinees fell asleep with difficulty; it took them 1.5 times longer to fall asleep, vs. the normal subjects. Not deep sleep with frequent awakening at night has been recorded in 67% of the patients, and 42% did not feel rested after night sleep. The type of sleep disturbances depended on the clinical structure of mental disorders, that included asthenic (42%) and depressive (39%) disturbances with explosive, anxiety, and phobic symptoms. Patients with atopic dermatitis should be administered multiple-modality therapy carried out by a dermatologist and a psychiatrist. Besides the drugs for skin condition, psychotropic agents should be administered for 3-4 weeks. Combined therapy of neurotic disorders is most effective with tranquilizers (phenazepam, nitrazepam, radedorm or éunoktin).

Adolescent↗
PubMed2005

Comparative toxicokinetics of explosive compounds in sheepshead minnows.

Juvenile sheepshead minnows Cyprinodon variegatus were exposed to the explosive compounds 2,4,6-trinitrotoluene (TNT), hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX), octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) and to the TNT transformation products 2-aminodinitrotoluene (2-ADNT) and 2,4-diaminonitrotoluene (2,4-DANT) in five separate water-only experiments. A one-compartment model was used to characterize uptake (k(u)) and elimination (k(e)) rate constants and to estimate bioconcentration factors (BCFs). The compounds investigated in this study are weakly hydrophobic. Kinetically derived BCFs (9.6, 13.1, 0.5, 1.7, and 0.5 ml g(-1) for TNT, 2-ADNT, 2,4-DANT, RDX, and HMX, respectively) confirmed the expected low bioaccumulative potential of those compounds and the positive relationship between log BCF and log K(ow) (1.6, 2.0, 0.8, 0.9, and 0.2 for TNT, 2-ADNT, 2,4-DANT, RDX, and HMX, respectively). The uptake clearance (k(u)) was relatively slow for all compounds (7.3, 12.6, 1.3, 0.15, and 0.06 ml g(-1)h(-1) for TNT, 2-ADNT, 2,4-DANT, RDX, and HMX, respectively), and overall, it decreased with decreasing compound hydrophobicity. Elimination was extremely fast for the nitroaromatic compounds (0.77, 0.96, and 2.74 h(-1) for TNT, 2-ADNT, and 2,4-DANT, respectively), thus resulting in very short biological half-lives (<1 hour), but it was much slower for the cyclonitramines (0.09 h(-1) for RDX and 0.12 h(-1) for HMX). Although ADNTs were present in fish exposed to TNT, the parent compound was the dominant compound in tissues during the uptake and elimination exposures. The rates of metabolite formation (0.06 h(-1)) and elimination (0.16 h(-1)) were much slower than the rate of elimination of the parent compound (0.80 h(-1)). Because of the fast elimination rate of TNT and its transformation products and the exceedingly low bioaccumulative potential of RDX and HMX, exposure conditions likely associated with the presence of explosives in aquatic systems are unlikely to pose unacceptable risks to fish.

Animals↗