Simian virus 40, poliovaccines and human tumors: a review of recent developments

Recently, wild-type SV40 and/or DNA sequences indistinguishable from SV40 have been detected in specific types of human tumors: ependymoma and choroid plexus tumors, mesothelioma, osteosarcoma and sarcoma. The same tumor types will develop in hamsters after injection with SV40. These findings are interesting in themselves for they could shed light on the pathogenesis of these tumors. These findings also have public health implications. SV40 was found to have contaminated the poliovaccines and the adenovaccines from 1955 until 1963, therefore resulting in the inadvertent injection of millions of people with this tumor virus. Moreover, our society pays a high cost for asbestos causality, a carcinogen associated with the development of mesothelioma. In addition to asbestos, the potential impact of finding another possible cause for mesothelioma (i.e., SV40), as well as the possible pathogenic role of the contaminated poliovaccines, has generated considerable public interest and concern. To discuss these recent findings, the NIH (National Institutes of Health) and the FDA (Food and Drug Administration), organized an International Conference at the NIH, Bethesda, MD, January 27-28, 1997. The association of SV40 with human mesothelioma was also discussed in a special session at the IV International Mesothelioma Conference that was held at the University of Pennsylvania, Philadelphia, PA, May 13-16, 1997. The purpose of this review is to summarize data, from the discovery of the contaminated poliovaccines, to the most recent findings presented at the meetings in Bethesda and Philadelphia, to discuss technical and other problems associated with this research, and the potential for using these findings to develop new diagnostic and therapeutic approaches for SV40-associated malignancies.     

Pediatric psychopharmacology: A review of new developments and recent research.

Advances in psychopharmacology have revolutionalized the management of emotional and behavioral disorders in children and adolescents. Recent developments in pediatric psychopharmacology and the prevalence of pharmacotherapy for various psychological disorders in children are examined, and clinical updates for classes of psychotropics are provided. Issues including monitoring and assessing drug effects, acceptability and satisfaction, and the social, political, and cultural issues surrounding the use of psychotropics in children are discussed. The authors conclude that the current clinical use of psychotropics in children exceeds extant efficacy and safety data. The involvement of practicing psychologists in pediatric psychopharmacology and the need for a firm empirical foundation for pediatric psychopharmacology are also discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Inflammatory pseudotumor of the pelvis: case report with review of recent developments

A case of a successfully treated inflammatory pseudotumor (IPT) of the pelvis in a 9-year-old male is presented. Review of the literature indicates that IPTs have been reported from a variety of anatomic locations. They form a spectrum of lesions ranging from benign, infection-related lesions to low-grade malignancies, capable of local recurrences and rare distant metastases. The site of involvement seems to have prognostic implication. Pulmonary IPTs are found in older patients and are almost always benign, whereas extrapulmonary IPTs tend to occur in younger patients and are, in general, more aggressive, with a recurrence rate of up to 24 per cent and mortality of up to 7 per cent. The treatment of choice is complete resection of the lesion.     

Perfluorocarbons: recent developments and implications for neurosurgery

Over the last 30 years, perfluorocarbons (PFCs) have been extensively investigated as oxygen carriers. Early studies indicated that these compounds could be used as blood substitutes or protective agents against ischemia. Adverse characteristics such as instability, short intravascular half-life, and uncertainties concerning possible toxicity precluded wide clinical application. However, advances in PFC technology have led to the development of improved second-generation oxygen carriers that incorporate well-tolerated emulsifiers (egg-yolk phospholipids). The authors review recent developments in this field and consider the potential role of PFCs in future neurosurgical practice. Diagnostic applications could include their use to assess cerebral blood flow, local oxygen tension, and brain metabolism or to achieve enhanced imaging and precise staging of inflammatory, neoplastic, or vascular disease processes by means of computerized tomography, ultrasonography, and magnetic resonance studies. Therapeutic applications could include cerebral protection, an adjunctive role in radiotherapy of malignant brain tumors, protection against air embolism, the preservation of organs for transplantation, and ventilatory support in head-injured patients with compromised lung function. In addition, PFCs have been used successfully as a tool in ophthalmic microsurgery and potentially they could fulfill a similar role in microneurosurgery.     

Levofloxacin: a therapeutic review

This therapeutic review discusses the pharmacology, pharmacokinetics, in vitro activity, drug interactions, and adverse effects of levofloxacin, a fluoroquinolone antibiotic. Particular emphasis is placed on the clinical efficacy of levofloxacin and its place in therapy. Compared with ciprofloxacin and the earlier quinolone agents, levofloxacin has an improved pharmacokinetic profile that allows convenient once-daily dosing in either an oral or parenteral formulation. Levofloxacin has enhanced activity against gram-positive aerobic organisms, including penicillin-resistant pneumococci. In published comparative trials involving commonly used treatment regimens, levofloxacin had equivalent if not greater activity in the treatment of community-acquired pneumonia, acute bacterial exacerbations of chronic bronchitis, acute bacterial sinusitis, acute pyelonephritis, and complicated urinary tract infection. Levofloxacin is well tolerated and induces minimal adverse drug reactions. Based on the above attributes, it may be reasonable to include levofloxacin on the hospital formulary in place of older quinolones. More recently released quinolones such as trovafloxacin exhibit similar advantages; however, until direct comparative trials between levofloxacin and these newer agents are conducted, it is difficult to advocate one agent over another. Regardless of which quinolone is the primary agent on the formulary, it is imperative that this class of antimicrobial drugs be used with discretion to minimize the development of resistance.     

Snake envenomation and protective natural endogenous proteins: a mini review of the recent developments (1991-1997)

The properties of several factors--antihaemorrhagic, antineurotoxic, antimyotoxic--isolated from the blood serum or plasma of different animals are described with more emphasis placed on the structural differences and similarities among the factors of the snake (Trimeresurus flavoviridis) and mammals (Didelphis marsupials and Herpestes edwardsii). Classification of antihaemorrhagic factors of snake and mammals according to structural homologies, and their effectiveness in neutralizing venom haemorrhagic activities in comparison with that of commercial antivenoms are also reviewed. The antineurotoxic factors isolated so far from the sera of viperid (Vipera palestinae, Daboia r. siamensis), crotalid (Crotalus d. terrificus, T. flavoviridis, Agkistrodon b. siniticus) and elapid (Naja naja atra) snakes, as reviewed, are inhibitors of phospholipase A2, and the amino acid sequences, particularly of those inhibitors from the sera of crotalid snakes, do not share significant sequence homology even within the same family Crotalidae. The amino acid sequences of antineurotoxic factors of the snake (Crotalus d. terrificus) also are not homologous to those of the antihaemorrhagic factors from the blood of the snake (T. flavoviridis) or mammals (Didelphis virginiana, Herpestes edwardsii). The mechanism of action of antihaemorrhagic and antineurotoxic factors is briefly discussed as well as the possibility that crotalids and viperids might possess both of those endogenous neutralizing factors in their blood. Some recent findings on the antimyotoxic factors from the snake serum or plasma with inhibition properties against PLA2 activity and myotoxicity of venoms or toxins are also shortly reviewed.     

A review on recent developments in binder jetting metal additive manufacturing: materials and process characteristics

ABSTRACT

Binder Jetting Metal Additive Manufacturing (BJ-MAM), known also as metal 3D-printing, is a powder bed-based additive manufacturing technology. It consists of the deposition of liquid binder droplets to selectively join powder particles to enable the creation of near-net shaped parts, which subsequently are consolidated via sintering process. This technology is known for its capability to process a wide range of different materials and for its orientation towards large volume production series. Binder Jetting has recently been drawing the attention of both the research sphere as well as several industrial sectors. The present review study encompasses the various and most remarkable aspects of BJ-MAM part fabrication. The review covers the material selection and characterisation considerations, followed by the manufacturing process features and the parameter effect on different part properties. It concludes with an overview concerning the most recent case studies with regards to diverse metal alloy developments.     

Diagnosis of contagious bovine pleuropneumonia: problems and recent developments

While it is easy to diagnose contagious bovine pleuropneumonia (CBPP) in an animal in the acute clinical stage, subacute and chronic forms are more difficult to diagnose. Recourse to laboratory tests is essential to confirm any suspicion of CBPP. As standard diagnostic procedures (isolation, culture, biochemical tests, serological tests) are lacking in specificity and sensitivity, improvements are needed. Progress in molecular biology techniques has led to new tests, among which are the polymerase chain reaction (PCR) and the enzyme-linked immunosorbent assay (ELISA) using monoclonal antibodies. Application of these techniques to CBPP offers a number of advantages, and has considerably enhanced the specificity and sensitivity of diagnosis.     

Tumor-reactive immunoglobulins in ovarian cancer: diagnostic and therapeutic significance? (review)

Inhibition of the immune system has been observed in association with most stages of ovarian cancer; however, the mechanisms involved in the induction and maintenance of this chronic immune unresponsiveness associated with cancer progression are poorly understood. This immunosuppressed state is primarily defined as the failure to eradicate the tumor. This immunosuppressed state is generally associated with decreased numbers and reactivity of lymphoid cells in women with ovarian cancer. The degree of immune dysfunction in ovarian cancer patients has been demonstrated to correlate with patient survival. While ovarian cancer patients generally fail to exhibit effective immunosurveillance, as manifested by continued tumor growth and progression, the presence of tumor-reactive immunoglobulins can be demonstrated in these women, indicating the continued presence of immune recognition. We have not only demonstrated the presence of tumor-reactive antibodies in ovarian cancer patients, but have also shown that the levels of these antibodies increase as the disease progresses. The antigens recognized by the patients' humoral response have been identified as either membrane-associated or intra-cellular. In general, the localization of these antigens tend to be linked to the patient's prognosis. The presence of a humoral response against intracellular proteins are correlated with poor prognosis, while autoantibodies reactive with surface components appear to have a better prognosis. In addition to general antigen recognition, these reactive antibodies have been utilized to define specific epitopes on tumor-associated proteins. Certain specific antigenic epitopes exhibit common recognition among patients with the same tumor type. The specific recognition of certain epitopes can provide early evidence of aberrant protein expression and this aberrant expression of certain proteins, such as procathepsin D, appear to be linked to the tumor's acquisition of specific malignant characteristics, including metastasis formation and chemoresistance. Despite the existence of circulating tumor-reactive immunoglobulins, their presence correlates, in general, with poor prognosis and poor host survival. Since tumor-reactive immunoglobulins are elicited and can be detected early in the development of tumors and their enhanced synthesis is induced prior to the clinical manifestation of recurrence, the assessment of the tumor-reactive immune response against specific antigenic epitopes should represent an early significant diagnostic and prognostic marker in ovarian cancer.     

Nuclear transfer in mammals: recent developments and future perspectives

A clone can be defined as a set of genetically identical animals. Small clones of two or occasionally up to four identical animals can be obtained by embryo splitting or blastomere separation. Embryo cloning by nuclear transfer involves the transfer of genetic material from a donor cell (karyoplast) to the cytoplasm of an oocyte or zygote from which the genetic material has been removed (cytoplast). In farm animals, metaphase II oocytes are most widely used as cytoplasts. There are now many factors known to influence the efficiency of embryo cloning by nuclear transfer. These include stage of development and cell cycle of donor cells, the choice of the recipient cell, the methods for activation of oocytes, the cell cycle coordination between donor cell and recipient cytoplast, and the method for fusion between nuclear donor and recipient cytoplast. Recent progress in cloning embryos and animals from cultured cells of embryonic, fetal, or adult origin offers a wide spectrum of potential applications of nuclear transfer, such as the unlimited multiplication of elite embryos or animals from selected matings and the potential for precise genetic modification of farm animals for gene farming or xenotransplantation.     

N-glycoprotein biosynthesis in plants: recent developments and future trends

This review summarizes the evolution of ideas concerning insulin signal transduction, the current information on protein ser/thr kinase cascades as signalling intermediates, and their status as participants in insulin regulation of energy metabolism. Best characterized is the Ras-MAPK pathway, whose input is crucial to cell fate decisions, but relatively dispensable in metabolic regulation. By contrast the effectors downstream of PI-3 kinase, although less well elucidated, include elements indispensable for the insulin regulation of glucose transport, glycogen and cAMP metabolism. Considerable information has accrued on PKB/cAkt, a protein kinase that interacts directly with Ptd Ins 3'OH phosphorylated lipids, as well as some of the elements further downstream, such as glycogen synthase kinase-3 and the p70 S6 kinase. Finally, some information implicates other erk pathways (e.g. such as the SAPK/JNK pathway) and Nck/cdc42-regulated PAKs (homologs of the yeast Ste 20) as participants in the cellular response to insulin. Thus insulin recruits a broad array of protein (ser/thr) kinases in its target cells to effectuate its characteristic anabolic and anticatabolic programs.     

Pulse oximetry--clinical implications and recent technical developments

The effects of felbamate on the pharmacokinetics of phenobarbital and one of its main metabolites, parahydroxyphenobarbital, were assessed in a parallel-group, placebo-controlled, double-blind study, in 24 healthy volunteers. Pharmacokinetic parameters of phenobarbital and parahydroxyphenobarbital were determined from plasma and urine samples obtained after 28 days of daily administration of 100 mg phenobarbital and after a further 9 days of phenobarbital plus 2400 mg/day felbamate or placebo. Felbamate increased phenobarbital values for area under the plasma concentration-time curve from 0 to 24 hours and maximum concentration by 22% and 24%, respectively, whereas placebo had no effect. This increase was caused by a reduction in parahydroxylation of phenobarbital and possibly through effects on other metabolic pathways. Because felbamate inhibits the S-mephenytoin hydroxylase (CYP2C19) isozyme in vitro, it appears that phenobarbital hydroxylation is mediated in part by this isozyme.     

Laparoscopic cholecystectomy and gallbladder cancer: a diagnostic and therapeutic dilemma

The correct treatment strategy of patients with unsuspected gallbladder cancer undergoing laparoscopy, and the prevention of delayed diagnosis are current issues. We report a case of late diagnosis with umbilical metastasis and poor survival. A policy of careful inspection of the gallbladder and a cautious strategy in the case of gross alteration of its external morphology seems advisable during laparoscopic cholecystectomy. Although no agreement exists concerning the best treatment in the event of delayed diagnosis, the adopted strategy is contingent on patient status, disease stage and the possibility of performing appropriate follow-up.     

Malaria: recent immunological acquisitions and therapeutic prospects

Malaria remains one of the major health problems in many tropical countries. The asymptomatic carrier status is common and about 100% of the children in highly endemic areas have Plasmodium falciparum parasitaemia at any given time. Consequently a case definition based on the mere presence of parasites in the blood is non-informative in terms of measuring morbidity. Acquired clinical and parasitological immunity develop progressively over several years after repeated exposure to infection. Protection is acquired first again death or severe clinical disease, but protection against infection is never complete, moreover it is still not known why some infections are mild an some fatal. Although virulence markers on the parasite have not been identified with certainty, there are some indications that parasites differ in virulence. The genetic composition of human many also play a role in the defence against the parasite, so the immune mechanisms responsible for the acquired immunity remain uncertain. In fact, an infection by Plasmodium falciparum induces a variety of immune responses, including humoral and cellular, which can be specific or non-specific responses, some of which are protective, but against which the parasite has evolved effective escape measures. Vaccines has proven a most effective measure to control infectious diseases, but no consistently effective vaccine has yet developed against a human parasitic disease. A malaria vaccine aimed at disrupting the parasites life cycle at one or more of the three stages (sporozoite or pre-erythrocytic stage, asexual blood or erythrocytic stage, and sexual or sporogonic stage) might be a long-term solution.     

Brain abscess: diagnostic and therapeutic problems

The uropygial gland of the white stork secrets mono- and diester waxes as well as triglycerides, all of which contain unbranched medium chain fatty acids. n-Decanol and n-dodecanol have been the only alcohols detected in both types of waxes. The diester waxes contain 2-hydroxy fatty acids.     

Anthracycline and anthraquinone anticancer agents: current status and recent developments

The clinical treatment of neoplastic diseases relies on the complementary procedures of surgery, radiation treatment, immunotherapy and chemotherapy. The latter technique has matured from its earliest applications of mustard alkylating agents in the 1940s to an increasingly rationally based discipline, which is contributing significantly to the management of human malignancies. As the field of chemotherapy matured, several promising natural anticancer agents were identified. However, a more urgent need soon arose from the common experience of clinically limiting toxicities of most anticancer drugs, i.e. the necessity to develop less toxic clinical drug candidates. Thus, the medicinal chemist turned towards analog development involving certain anthraquinones. Hand-in-hand with this considerable synthetic effort, which uncovered several promising clinical leads, biochemical pharmacology, or study of the mechanisms of action of clinical anticancer agents, afforded deeper insight into drug metabolism and mode of action. More recently, therefore, the field of synthetic organic chemistry, which has been complemented by the methods of microbial chemistry, has been faced with new synthetic challenges, occasioned by the identification of hitherto unrecognized cellular targets for anticancer drugs, such as topoisomerases and helicases. The armementarium of the oncologist currently includes about 40-50 clinically useful chemical agents. The paradigm of cytotoxic anticancer agents is doxorubicin, an anthracycline, which is still amongst the most widely prescribed and effective of anticancer agents. The review attempts to summarize the discovery of anthracyclines and the elucidation of their several mechanisms of action and efforts towards improvement of their therapeutic efficacy.     

Psychophysiology of pain: diagnostic and therapeutic implications

Pain problems occupy muct of the time and therapeutic efforts of physicians. Nonmedical practitioners and cultists have likewise attracted many people seeking pain relief. In many cases the cultists seem to do as well as the ethical practitioner. A realistic view of pain takes into account the significance of the pain to the individual, the degree of anxiety and/or depression that contributes to the aggravation and prepetuation of the pain, and finally the manipulative and defensive value that the pain may have to the individual. A purely mechanistic approach which would attempt to distinguish "real pain", ie, pain associated with a demonstrable lesion, and "imagined pain" will prove counterproductive. Likewise accusations of consciously pretended pain or malingering tend to be nontherapeutic. A sound therapeutic approach is to regard all pain as real, realizing that the pain of depression may be the most unendurable type of pain. Major psychotropic drugs for relief of anxiety and for treatment of depression have appplication in the management of selected pain problems.