The Treatment of Superficial Fungous Infections

Superficial fungous infections of the skin often are difficult therapeutic problems especially if the laboratory identification of the organism, necessary to guide selection of means of treatment, is not obtained. Proper diagnosis will reveal that some infections need certain specific antifungal drugs topically applied, another group will yield to other less specific topical therapy, and a third type can be successfully influenced only by oral administration of griseofulvin.     

Invasive Fungal Infections: A Continuing Challenge Report from the 17th International Symposium on Infections in the Immunocompromised Host, Genoa, Italy, 24–27 July 2012

The management of invasive fungal infections (IFIs) remains a challenge to the most experienced clinicians and mycologists as the therapeutic landscape continues to change. Delegates to the 17th International Symposium on Infections in the Immunocompromised Host heard that fungal epidemiology, patient demographics, diagnosis and treatment are all evolving. Diagnosis-driven therapy—pre-emptive or targeted—is the ideal approach to managing IFIs, but is dependent on reliable biomarker assays to identify, or at least strongly suggest, the organism(s) responsible. Biomarkers, however, are subject to ongoing research and so are also evolving. Some assays also may not be available in a particular centre. The same applies to investigations such as CT-scans and bronchoscopy that need to be performed in a timely fashion to help confirm an IFI. Thus, for patients with febrile neutropenia despite broad-spectrum antibiotic cover, clinicians without the appropriate diagnostic facilities prefer to start antifungal (AF) treatment immediately whilst attempting to confirm the diagnosis. Empirical therapy therefore looks likely to have a role for some time. For high-risk patients, such as those with haematological malignancies and/or undergoing haematopoietic stem cell transplantation (HSCT), the preferred strategy is to prevent IFIs using AF prophylaxis although regular screening with biomarkers is an alternative.     

Mycobacterium abscessus infection of a Norplant contraceptive implant site.

The authors report a case of Mycobacterium abscessus infection of a subdermal levonogestrel implant (Norplant) site. The infection lasted 12 weeks and was indolent, skin manifestations were low grade and difficult to detect. Culture of exudate samples showed that M. abscessus was the only causative agent. After the implant was removed the patient''s arm healed uneventfully without antimycobacterial therapy. The authors recommend that if Gram staining of apparently infected material from an implant site does not reveal a causative organism, then cultures should be done for mycobacteria and fungi. Kinyoun staining for acid-fast bacteria and calcoflour-white staining for fungi should also be performed. The implant should be removed and the patient given antimicrobial therapy as indicated. The authors emphasize the need to be aware of the potential for M. abscessus infection of implant sites and stress that appropriate microbiologic culture procedures are essential for accurate diagnosis.     

Branhamella catarrhalis Pneumonia

The diagnosis of Branhamella catarrhalis pneumonia in five cases was established by culture of pulmonary secretions obtained by transtracheal aspiration. B catarrhalis caused an acute lobar pneumonia which usually responded promptly to appropriate antimicrobial therapy. Recognition that this organism may cause pneumonia in a nonimmunocompromised person should alert clinicians to consider it as a possible pathogen when Gramnegative diplococci are seen on smears of specimens from the lower respiratory tract.     

Fungal endophthalmitis

Fungal endophthalmitis occurs secondary to trauma, as a complication of intraocular surgery, or as an extension of an adjacent or distant focus of fungal infection. In the United States, Candida species are the most common pathogens isolated, followed by Aspergillus species. Candida infections show a predilection towards vitreous involvement, whereas Aspergillus infections usually manifest as hemorrhagic infarcts of the retinal or choroidal vessels or as infiltration of the subretinal and subretinal pigment epithelial spaces. Endogenous Aspergillus endophthalmitis is associated with a high mortality rate, underscoring the severity of systemic infection. The prognosis of fungal endophthalmitis depends on the virulence of the organism, extent of intraocular involvement, and the timing and mode of interventions. Prompt therapy following early diagnosis helps to reduce significant visual loss. Despite the introduction of new-generation triazoles and echinocandins into clinical practice, successful therapy is limited by the delay in diagnosis and a lack of broad-spectrum antifungals with good intravitreal penetration that lack systemic toxicity.     

Proteomics technologies and challenges

Proteomics is the study of proteins and their interactions in a cell. With the completion of the Human Genome Project, the emphasis is shifting to the protein compliment of the human organism. Because proteome reflects more accurately on the dynamic state of a cell, tissue, or organism, much is expected from proteomics to yield better disease markers for diagnosis and therapy monitoring. The advent of proteomics technologies for global detection and quantitation of proteins creates new opportunities and challenges for those seeking to gain greater understanding of diseases. High-throughput proteomics technologies combining with advanced bioinformatics are extensively used to identify molecular signatures of diseases based on protein pathways and signaling cascades. Mass spectrometry plays a vital role in proteomics and has become an indispensable tool for molecular and cellular biology. While the potential is great, many challenges and issues remain to be solved, such as mining low abundant proteins and integration of proteomics with genomics and metabolomics data. Nevertheless, proteomics is the foundation for constructing and extracting useful knowledge to biomedical research. In this review, a snapshot of contemporary issues in proteomics technologies is discussed.     

The cardiovascular system in acute infectious disease

Myocarditis may result from a wide variety of acute infectious diseases, but electrocardiographic abnormalities interpreted as indicating myocarditis may arise from a number of other causes. Among the factors which may cause myocarditis are direct invasion by an organism, the toxic products of an organism, hypersensitivity to the products of an organism, drugs used in therapy, deficiency in nutrients, electrolyte imbalance, and, rarely, fever. Recently emphasis has been placed on the finding that circulatory failure in acute infectious diseases is often primarily peripheral, although heart failure due to myocarditis is not uncommon.     

Diagnosis of Midwestern Endemic Mycoses

Histoplasmosis and blastomycosis are the two most common midwestern endemic mycoses. A history of exposure to the geographic areas in which these organisms occur is central to raising suspicion for an endemic fungal infection. For infection with these organisms, the diagnosis is definitively established by recovery of the organism in tissue or body fluids, which may take weeks. A rapid diagnosis can be made by finding the distinctive yeasts in tissues or body fluids. Antigen testing allows a presumptive diagnosis of these endemic fungal infections while awaiting culture results, but cross-reactivity between assays for Histoplasma and Blastomyces is routinely seen. Antibody tests provide supportive evidence for infection with either of these endemic mycoses but are less useful in immunosuppressed patients.     

MicroRNA 与肿瘤的相关研究进展

微小RNA(microRNAs,miRNA)是一类22个核苷酸左右的非编码调控RNA。可以通过切割mRNA或者是抑制翻译两种机制,在转录后水平发挥调控生物生长发育的重要作用。目前的研究已经发现microRNA参与调控发育、细胞分化、细胞凋亡等多种生理过程。目前已证实miRNA参与肿瘤发生和进展,miRNA表达谱是肿瘤诊断和预后的指标,miRNA突变、缺失或表达水平的异常与人类肿瘤密切相关,它发挥类似于癌基因或抑癌基因的作用,参与肿瘤细胞的增殖、分化和细胞凋亡过程。本文就miRNA在肿瘤发生发展以及诊断治疗方面的研究进展作一综述。     

The theory of organism and the culturalist foundation of biology

Summary After the disappearance of organism was diagnosed, the discussion about the role of a theory of organism in biology is characterised by a significant contradiction. On the one hand, the importance of a theory of organism is stated. Particularly developmental biology demands organism-centred approaches as a basis for conceptual integration. On the other hand, several modern biological disciplines such as genetics and molecular biology simply don’t need a theory of organism for their work. Consequently, the determination of the status of the organism and its relevance for biology at all is an unsolved problem. In order to clarify the methodological status of the organism in biology we start with the reconstruction of three important propositions. A life oriented approach and a hierarchy concept - which both are from a neo-Darwinian origin - are confronted with a structuralist approach of organism, that can be characterised as a non-Darwinist approach. Our own attempt for the solution of the organism problem applies the tools of culturalist methodology. In accordance to this pragmatic approach, the term organism is introduced as a concept of notion. A constructional morphological case study exemplifies the applicability of this concept. From the culturalist point of view a methodological foundation of biology can be achieved, that provides a consistent basis for a comprehensive integration of biological knowledge.     

Diagnosis of damage to Norway spruce (Picea abies) through biochemical criteria

Bioindication can be carried out at different hierarchical levels, eg. cell, organism, and ecosystem. While the monitoring of damage by visible criteria (e.g. loss of needles) is connected with the organism as a whole, the monitoring of damage by biochemical indicators is above all connected with cell metabolism.
The degree of vitality of a tree can be ascertained through the integration of a number of biochemical parameters. Furthermore, a differential diagnosis of a particular stress pattern can be carried out because of the feedback pattern of several biochemical indicators. In order to describe and interpret biochemical or physiological changes that have been caused by a number of factors, multivariate statistical methods are being used more frequently. Apart from cluster and discriminant analysis, it is especially factor analysis which provides a helpful tool when dealing with problems in the field of environmental analysis. Factor analysis can be used for an integrating as well as a differentiating assessment.
Within the framework of forest damage research, numerous changes at the level of cell metabolism have been detected to which a bioindicative character can be attached. A number of physiological and biochemical parameters with bioindicative character concerning Norway spruce are presented.     

Computational tools for comparative phenomics: the role and promise of ontologies

A major aim of the biological sciences is to gain an understanding of human physiology and disease. One important step towards such a goal is the discovery of the function of genes that will lead to a better understanding of the physiology and pathophysiology of organisms, which will ultimately lead to better diagnosis and therapy. Our increasing ability to phenotypically characterise genetic variants of model organisms coupled with systematic and hypothesis-driven mutagenesis is resulting in a wealth of information that could potentially provide insight into the functions of all genes in an organism. The challenge we are now facing is to develop computational methods that can integrate and analyse such data. The introduction of formal ontologies that make their semantics explicit and accessible to automated reasoning provides the tantalizing possibility of standardizing biomedical knowledge allowing for novel, powerful queries that bridge multiple domains, disciplines, species, and levels of granularity. We review recent computational approaches that facilitate the integration of experimental data from model organisms with clinical observations in humans. These methods foster novel cross-species analysis approaches, thereby enabling comparative phenomics and leading to the potential of translating basic discoveries from the model systems into diagnostic and therapeutic advances at the clinical level.     

Pneumocystis carinii in pleural fluid. The cytologic appearance

We describe the cytologic appearance of Pneumocystis carinii in pleural fluid of a patient with acquired immunodeficiency syndrome and a rapidly accumulating pleural effusion. The diagnosis of P carinii infection was made by examination of air-dried, Diff-Quik-stained Cytospin preparations of the pleural fluid. The diagnostic appearances of P carinii organisms stained by this method and by the Papanicolaou stain are reviewed. The unusual predominance of the trophozoite forms of the organism in this case made Diff-Quik an ideal special stain for identifying the organisms. Furthermore, this case illustrates a novel presentation of P carinii infection and suggests that P carinii should be considered an etiologic agent in the differential diagnosis of pleural effusion in an immunocompromised host.     

Cytologic diagnosis of pulmonary nocardiosis: a report of 3 cases

BACKGROUND: Nocardiosis is an uncommon infection and presents as an opportunistic infection in an immunocompromised host. Pulmonary infection by Nocardia may be difficult to diagnose based on clinical and radiologic features, as these are not specific. Sputum examination, bronchoalveolar lavage and transthoracic ultrasound/computed tomography-guided fine needle aspiration cytology offer a simple means of procuring material for diagnostic evaluation. Very few articles have described the morphologic appearance of this uncommon pathogen in cytologic material. CASES: Three cases occurred in patients with an underlying immunocompromised state. Patient 1 was on steroid therapy for nephrotic syndrome, patient 2 was on immunosuppressant therapy after renal transplantation, and patient 3 was HIV positive. A diagnosis of pulmonary nocardiosis was suspected on Papanicolaou stain. Modified Ziehl-Neelsen stain and silver methanamine stains were useful in confirming the diagnosis. CONCLUSION: A high index of suspicion for nocardiosis must be maintained while assessing cytologic material in immunosuppressed individuals as it may be masked by the intense inflammatory exudate associated with this infection. A meticulous search may reveal the presence of delicate, thin, faintly stained, branching filaments of Nocardia on routine Papanicolaou stain. Special stains and culture studies are useful in confirming the diagnosis.     

Human Pythiosis: Emergence of Fungal-Like Organism

Pythiosis is an emerging infectious disease caused by the aquatic oomycete Pythium insidiosum, a fungal-like organism. It is believed that P. insidiosum’s zoospores, its infected form, play major role in pathogenesis. Vascular and ocular infections are the most common clinical manifestation in humans. It is difficult to establish the diagnosis given its relatively rarity and difficulty to distinguish P. insidiosum from other molds. Delay in diagnosis and treatment has been associated with poor outcomes. High index of suspicion is the key, particularly in thalassemia patients with arterial insufficiency and patients with fungal keratitis/endophthalmitis without improvement on antifungal therapy. Tissue culture and zoospore induction remain gold standard for diagnosis; however, DNA-based method should be performed simultaneously. The combination of radical surgery, antifungal agents, and immunotherapy has been recommended. It was previously believed that surgery with negative surgical margins was the essential to survive in vascular pythiosis; however, it was recently found that patients could have residual disease despite documented negative surgical margins as infected clot may be dislodged to proximal arterial sites prior to surgery. Serum β-d-glucan (BG) has been used to monitor disease response after treatment initiation in vascular pythiosis. A significant decrease in BG levels within 2 weeks after surgery is indicative of the absence of residual infection. Unfortunately, monitoring tools for ocular pythiosis are not yet available. Itraconazole plus terbinafine have generally been used in P. insidiosum-infected patients; however, antibacterial agents, including azithromycin and linezolid, have also been used with favorable outcomes in ocular disease. Recently, azithromycin or clarithromycin plus doxycyclin were used in two relapsed vascular pythiosis patients with good outcomes.

     

Current diagnosis of histoplasmosis

Histoplasmosis is a common infection endemic in many regions of America, Asia, India and Africa, with sporadic cases also occurring throughout the world. Although excellent laboratory methods for diagnosis are available, there are deficiencies that must be met by continued research. Clinicians and laboratory directors must be familiar with the uses and limitations of a battery of serologic and mycological tests to accurately diagnose histoplasmosis. Research is needed to reduce false-negative and false-positive results, and to improve the identification of the organism in tissues. Approaches to the diagnosis of histoplasmosis and areas that require further research will be reviewed.     

Blood coagulation factors and proteinase inhibitors in cytostatic therapy of acute leukemia

In 64 patients affected with acute leukaemia (51 patients with acute non-lymphatic leukaemia and 13 patients with acute lymphatic leukaemia) extensive investigations of blood coagulation were made during cytostatic therapy. The following conspicuous changes of haemostatasis could be observed in making the diagnosis: Lowered quick value and shortened PTT, increased fibrinogen, fibrinopeptide, A, alpha 1-antitrypsin and alpha 2-macroglobulin, diminished plasminogen and plasma fibrininectin. According to TAD (VP) protocol the induction therapy leads to hypercoagulability which can be recognized by an increase of fibrinopeptide A, coagulating factors and shortening of PTT. During the therapy with L-asparaginasis procoagulatoric as well as thromboprotective coagulating proteins are diminished. A dense laboratory control enables those disturbances of haemotasis caused by disease or therapy to be separated and contributes to preventing complications during the cytostatic induction therapy.     

Characterization of a Mycobacterium ulcerans-like infection in a colony of African tropical clawed frogs (Xenopus tropicalis)

A nontuberculous Mycobacterium ulcerans-like organism was identified as the causative agent of an epizootic of mycobacteriosis in a colony of African tropical clawed frogs, Xenopus (Silurana) tropicalis, at the University of California, Berkeley. Diverse clinical signs of disease were observed, including lethargy, excess buoyancy, coelomic effusion, cutaneous ulcers, and granulomas. Visceral granulomas, ulcerative and granulomatous dermatitis, coelomitis, and septicemia were common findings at necropsy. Identification of M. ulcerans-like organisms was based on molecular and phenotypical characteristics. The findings of this investigation indicate that this M. ulcerans-like organism is a primary cause of morbidity and mortality in aquatic anurans and should be considered in the differential diagnosis of coelomic effusion in amphibians. Furthermore, if this Mycobacterium species ultimately is identified as M. ulcerans, X. tropicalis should be considered a potential source of this important public health pathogen.     

Cytochemical study of the natural resistance of the body in Trichophyton rubrum-induced mycosis (tinea)

Clinical-cytochemical examination of 27 patients with tinea has permitted estimating nonspecific immune status of an organism. The NBT-test is shown to be highly informative and active. Differences in metabolic activity of phagocytizing subpopulations of peripheral blood are revealed. The results obtained underlie the development of the pathogenetically substantiated therapy method using diucyphon and chlorophyllipt, immunomodulators of different pharmacological groups.