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PubMed1995

[Fournier gangrene].

Fournier's gangrene is a relatively rare, mixed aerobic and anaerobic soft tissue infection in the perineoscrotal area. Although it is convenient to give it a separate name, it is really either necrotizing fasciitis or nonclostridial myonecrosis of the scrotal and perineal areas. The condition frequently develops from perineal diseases, including perianal abscess, and fistulas, inflamed haemorrhoids and indwelling urethral catheter. In patients with Fournier's gangrene morbidity is extreme and mortality high. This article is based on a retrospective study of 15 cases of Fournier's gangrene, 13 in male and 2 in female patients. A combination of surgery and antibiotics was used to treat 9 patients. The last 6 cases were treated with a combination of surgery, antibiotics and hyperbaric oxygen. In 13 cases, the diagnosis was made on the basis of the fulminating progression of the infection to a scrotal gangrene, identification of multiple underlying pathogenic organisms and toxaemia. In the 2 female patients, a similar infection developed in the labia majora and perineum and extended to the buttocks and the anterior abdominal wall.

Adult↗
PubMed1994

Identification of three chitin synthase genes in the dimorphic fungal pathogen Sporothrix schenckii.

Degenerate PCR primers were used to amplify a 600-bp conserved gene region for chitin synthases from genomic DNA of Sporothrix schenckii, a dimorphic fungal pathogen of humans and animals. Three chitin synthase gene homologs were amplified as shown by DNA sequence analysis and by Southern blotting experiments. Based on differences among the predicted amino acid sequences of these homologs, each was placed within one of three different chitin synthase classes. Phylogenies constructed with the sequences and the PAUP 3.1.1 program showed that S. schenckii consistently clustered most closely with Neurospora crassa in each of the three chitin synthase classes. These findings are significant because the phylogenies support by a new method the grouping of the imperfect fungus S. schenckii with the Pyrenomycetes of the Ascomycota.

Base Sequence↗
PubMed2004

Once-daily oral levofloxacin monotherapy versus piperacillin/tazobactam three times a day: a randomized controlled multicenter trial in patients with febrile neutropenia.

A prospective, randomized, controlled multicenter trial was performed to evaluate the efficacy and safety of once-daily oral monotherapy with 500 mg levofloxacin in comparison with 4.5 g piperacillin/tazobactam 3 times a day in patients with low-risk febrile neutropenia. Low risk was defined by oral temperature > or = 38.5 degrees C on one occasion or > or = 38.0 degrees C twice within 24 hours and granulocytopenia < or = 500/microL for less than 10 days. The primary end point was defined as defervescence after 72 hours followed by at least 7 afebrile days. Secondary end points were overall response, time to defervescence, survival on day 30, and toxicity. Thirty-four episodes were included. Fever of unknown origin accounted for 26 (76.5%) of the episodes, microbiologically defined infection for 5 (14.7%) of the episodes, and clinically defined infection for 3 (8.8%) of the episodes. On an intent-to-treat basis, all episodes were evaluable for the primary end point. Levofloxacin and piperacillin/tazobactam were successful after 72 hours of treatment in 76.5% and 88.3% of the episodes. Overall response was achieved in 94.1% and 100% of the episodes, respectively. One inpatient in the oral treatment group died of septic shock without identification of a causative pathogen. A larger phase III trial is warranted to further evaluate the lack of inferiority of the oral monotherapy regimen versus standard intravenous therapy.

Administration, Oral↗
PubMed2005

Identification and mapping of resistance gene analogs (RGAs) in Prunus: a resistance map for Prunus.

The genetically anchored physical map of peach is a valuable tool for identifying loci controlling economically important traits in Prunus. Breeding for disease resistance is a key component of most breeding programs. The identification of loci for pathogen resistance in peach provides information about resistance loci, the organization of resistance genes throughout the genome, and permits comparison of resistance regions among other genomes in the Rosaceae. This information will facilitate the breeding of resistant species of Prunus. A candidate gene approach was implemented for locating resistance loci in the genome of peach. Candidate genes representing NBS-LRR, kinase, transmembrane domain classes, as well as, pathogen response (PR) proteins and resistance-associated transcription factors were hybridized to a peach BAC library and mapped by using the peach physical map database and the Genome Database for Rosaceae (GDR). A resistance map for Prunus was generated and currently contains 42 map locations for putative resistance regions distributed among 7 of the 8 linkage groups.

Amino Acid Sequence↗
PubMed2003

The challenge of multidrug resistance: actual strategies in the development of novel antibacterials.

Bacterial resistance against established antibiotics is becoming an increasingly important global healthcare problem. Despite enormous efforts, the number of therapeutically useful compounds that emerge from chemical derivatisation programs, which aim at circumventing mechanisms of resistance, is continuously decreasing and no truly novel class of compound has been introduced into therapy for nearly four decades. Hopes are now set on a thorough elucidation of bacterial cell functions to identify new bacterial target sites, and on the development of novel compounds with alternative modes of action. The pursuit of these strategies is rendered possible by employment of biotechnologically based methods such as in vivo modification of biosynthetic routes in antibiotic-producing organisms, large-scale screening assays with isolated bacterial targets, the molecular profiling of bacterial genomes and proteomes, and the development and clinical use of biochips as diagnostic tools for rapid identification and characterization of pathogenic strains. As one of the most promising class of compounds known to date with unique modes of action that escape most known mechanisms of resistance, peptic agents have recently came under the focus of anti-infective research, just as extracellular signalling molecules (autoinducer) have emerged as new bacterial target sites.

Anti-Bacterial Agents↗
PubMed2002

Concurrence of alpha-synuclein and tau brain pathology in the Contursi kindred.

Previous genetic analysis of the familial Parkinson's disease Contursi kindred led to the identification of an Ala53Thr pathogenic mutation in the alpha-synuclein gene. We have re-examined one of the original brains from this kindred using new immunohistochemical reagents, thioflavin S staining and immunoelectron microscopy. Surprisingly, we uncovered a dense burden of alpha-synuclein neuritic pathology and rare Lewy bodies. Immunoelectron microscopy demonstrated fibrillar alpha-synuclein-immunoreactive aggregates. Unexpected tau neuritic and less frequent perikaryal inclusions were also observed. Some inclusions were comprised of both proteins with almost complete spatial disparity. We suggest that it is important to recognize that the neurodegenerative process caused by the Ala53Thr mutation in alpha-synuclein is not identical to that seen in typical idiopathic Parkinson's disease brains.

Adult↗
PubMed2003

PCR-based methodology for detecting multidrug-resistant strains of Mycobacterium tuberculosis Beijing family circulating in Russia.

The Beijing genotype of Mycobacterium tuberculosis has been identified in 40-50% of the clinical isolates studied in Russia during the last decade. This genotype has been reported to be associated with multiple drug resistance and possesses some significant pathogenic properties. Therefore, early identification of such strains is of extreme importance in the timely detection of drug resistance. The present study was performed on 354 strains isolated in Russia from 1996 to 2002 and previously characterised by IS 6110-restriction fragment length polymorphism (RFLP) typing and spoligotyping. These strains included 198 Beijing family strains and 156 strains of other genotypes (IS 6110-RFLP profiles). A subsequent polymerase chain reaction (PCR) analysis with IS 6110-derived outwardly oriented primers (IS 6110-PCR) easily discriminated the Beijing strains from non-Beijing strains. The multiplex allele-specific (MAS)-PCR assays were further used to detect mutations in katG315 and rpoB531, associated with resistance to isoniazid and rifampin, respectively. The katG315 and rpoB531 mutations were found to be more prevalent among Beijing (96.8% and 77.3%) than among non-Beijing strains (85.7% and 28%). Consequently, we propose a two-step methodology based on routine PCR and simple agarose gel electrophoresis in order to detect (i) a Beijing family strain using IS 6110-PCR, and, (ii) its possible resistance to the major anti-tuberculosis drugs using specific MAS-PCR assays.

Antitubercular Agents↗
PubMed2005

Epidemiological investigation of Chlamydophila psittaci in pigeons and free-living birds in Croatia.

During 2003, 278 adult pigeons (Columba livia) and 54 birds of 11 other free-living species were caught in the various locations in the City of Zagreb, Croatia. Sera from 182 pigeons were tested for the presence of antibodies against Chlamydophila (C.) psittaci by ELISA test and 174 of them (95.6%) were found positive. Because of the high positivity rate in sera, cloacal swabs of 278 pigeons as well as 54 other species of free-living birds were tested for the presence of C. psittaci antigen. Fourty-four of the 278 pigeons (15.83%) were antigen positive, whereas all 54 of the wild birds were negative. Antigen-positive pigeons were euthanised and examined pathomorphologically and cytologically. Findings of specific antibodies and antigen of C. psittaci confirmed the high rate of infection among urban pigeons in the City of Zagreb, fortunately not among other free-living birds. Although the pigeon serovars of C. psittaci are considered to be of moderate pathogenicity for humans, the identification of 15.8% antigen-positive birds represents a potential source of infection to humans, especially for elderly people and immunodeficient patients, as well as for poultry in the Zagreb city area.

Animals↗
PubMed1992

Diagnosis and interventions in lower respiratory tract infections.

In the elderly and in immunocompromised patients, respiratory tract infections are still a major cause of morbidity and mortality. The choice of a specific antibiotic treatment in pneumonia depends on the identification of the causative pathogen or on a judgment concerning the probable causative micro-organism. This judgment should be based on all the information obtained from clinical signs and symptoms, laboratory investigations of sputum and blood, and the pattern of infiltrations on chest X-ray. Different causative pathogens can be expected in bacterial and "atypical" community-acquired pneumonia than in hospital-acquired pneumonia. For the same reason, immunocompetent and immunocompromised patients have to be distinguished from each other. In chronic obstructive pulmonary disease, bronchial defenses will be impaired. Exacerbations can result from different causes, including infections of the bronchial mucosa. Most of these infections are of viral origin. Exacerbated pulmonary disease will result from bacterial bronchitis only in some patients. It is often difficult to assess the diagnosis "bacterial bronchitis." Evaluation of the effect of antibacterial treatment in exacerbated pulmonary disease is also difficult. Therapeutic interventions for these clinical conditions have to be directed primarily toward restoring or improving pulmonary host-defense factors. Fluoroquinolones, including lomefloxacin, have been shown to be effective in the treatment of lower respiratory tract infections caused by susceptible bacteria. Lomefloxacin presents a number of advantages: the drug has good bioavailability after oral and parenteral administration and penetrates well into bronchial secretions and lung tissue. In addition, lomefloxacin has no influence on the metabolic clearance of the methylxanthines theophylline and caffeine, which has been demonstrated for enoxacin, ciprofloxacin, and pefloxacin.

4-Quinolones↗
PubMed2005

Viral and host factors in the pathogenesis of HIV infection.

Recent studies suggest that the pathogenesis of HIV infection and AIDS involves two distinct phases. During acute infection, massive depletion of CD4+CCR5+ memory T cells within the mucosal-associated lymphoid tissue leads to major and potentially irreversible damage to CD4+ T-cell-mediated immune functions. The emergence of potent, but ultimately ineffective, cell-mediated and humoral responses to HIV leads to the chronic phase of infection, which is characterized by partial control of viral replication, chronic immune activation, progressive decline of the naïve and memory T-cell pool, and systemic CD4+ T-cell depletion. The identification of these two pathogenic phases of HIV infection could have important implications in terms of HIV therapy and vaccine development.

AIDS Vaccines↗
PubMed2005

Life-threatening chronic enteritis due to colonization of the small bowel with Stenotrophomonas maltophilia.

Chronic diarrheal illness and malabsorption are challenging diagnostic and clinical problems. The identification of the causative pathogens that are involved in gastrointestinal infections is often difficult. It took 85 years after the first description of a case of intestinal lipodystrophy by Georg Whipple in 1907 until the causative bacterium was characterized by using molecular genetics techniques. We here report the complicated clinical course of a young patient with chronic diarrhea accompanied by severe, life-threatening malabsorption with extensive weight loss. Histology and glucose hydrogen breath test were suggestive of a bacterial overgrowth syndrome in the small bowel, but standard culture-based techniques and serology failed to identify the causative bacteria. Thus, bacterial ribosomal DNA (16S ribosomal DNA) was extracted from duodenal biopsy samples and analyzed by community fingerprinting and species-specific polymerase chain reaction. Stenotrophomonas maltophilia was identified as the cause of chronic infectious enteritis. Only specific long-term antibiotic treatment with co-trimoxazole had a durable clinical effect and led to normalization of 16S ribosomal DNA profiles. This case shows the role of rare and uncommon bacteria in refractory and chronic human gastrointestinal infections. Genomic techniques, including 16S-based single-strand conformation polymorphism analysis, will play an increasing role in the diagnosis of chronic infections with facultatively pathogenic bacteria or in the clinical analysis of complex bacterial communities such as the intestinal bacterial microflora. Future enhancements in detection techniques will show that chronic bacterial infections are more frequent as a cause of gastrointestinal malfunction than commonly thought.

Adult↗
PubMed2005

Enterohaemorrhagic E. coli in veterinary medicine.

The emergence of enterohaemorrhagic Escherichia coli (EHEC) as major human pathogens began with the identification of serotype O157:H7 in the early 1980s as the cause of various food-borne outbreaks of severe intestinal disease. The key virulence factors include verocytotoxins (Vt) and effectors and adhesins associated with type III secretion systems. Tracing the origins of human outbreaks reveals that the primary source of this organism is the ruminant gastro-intestinal tract and a variety of transmission routes to humans have been identified. The epidemiology of E. coli O157:H7 within cattle and other ruminants has been studied extensively and the prevalence of non-O157:H7 serotypes contrasts with the observed dominance of E. coli O157:H7 amongst human EHEC isolates. Although there is some evidence that EHEC cause disease in young animals, the high prevalence of Vt within healthy ruminants suggests that this is not a virulence factor within these species. An understanding of the mechanisms underpinning EHEC persistence within their natural reservoir hosts and the development of a molecular understanding of EHEC biology and evolution could eventually allow a reduction in the incidence of human disease and may reduce future threats. The use of animal models to replicate and study human EHEC pathogenesis is described.

Animals↗
PubMed2004

Acute infectious mononucleosis and coincidental measles virus infection.

BACKGROUND: Both Epstein-Barr and measles viruses (MV) cause immune suppression, and the association of the two viruses is evaluated as life threatening. The cell immune impairment caused by simultaneous Epstein-Barr and measles viral infections was responsible for the complicated course of the disease in all described previously reports and for unfavorable outcomes in most of the cases. Timely diagnosis of coincidental viral infections could be a useful predictor for the clinical course and complications. Diagnosis must be based on an accurate assessment of clinical, hematologic, serologic manifestations and supported by appropriate laboratory methods. Recognizing the infectious etiology of concomitant infections is important for both clinicians and epidemiologists. OBJECTIVE: To describe a case report of a 20-year-old woman previously vaccinated against measles infected with acute mononucleosis and coincidental measles virus infection. STUDY DESIGN: The clinical, routine laboratory, as well as serological and virologic findings of this patient were scrutinized. Special emphasis was placed on the use of RT-PCR/PCR for confirming the involvement of both measles virus and Epstein-Barr virus (EBV) in this patient's illness. RESULTS: Infectious mononucleosis was not suspected at admission to the hospital. The final diagnosis of a concomitant measles virus infection and acute infectious mononucleosis was facilitated using viral serology to detect virus-specific IgG and IgM antibodies and by RT-PCR for the detection of measles virus RNA and EBV DNA from peripheral blood monocyte cells (PBMC). CONCLUSION: The present report highlights the difficulty of diagnosing two coincidental virus infections on clinical grounds. Serological and molecular laboratory methods, specifically the PCR (RT-PCR) analysis, are found to be useful for confirming the concomitant viral infections and proper identification of the infecting pathogens.

Acute Disease↗
PubMed2005

Antigenome technology: a novel approach for the selection of bacterial vaccine candidate antigens.

A novel approach for the identification of protein antigens from bacterial pathogens was previously developed in our laboratory that combines the advantages of full genome coverage and serological antigen identification. We have applied this technology to several bacterial pathogens of the genera Staphylococcus and Streptococcus and have, as a result, defined the "antigenome" of these pathogens. This catalogue defines the most relevant antigenic proteins that are targeted by the human immune system, including their antibody binding sites. The antigenome technology offers an integrated approach for antigen validation in order to select the most promising candidates for the development of subunit vaccines against the targeted bacterial diseases. Using this technology, novel protective antigens were discovered from several important human pathogens.

Animals↗
PubMed2002

Effects of genetic background on neonatal Borna disease virus infection-induced neurodevelopmental damage. II. Neurochemical alterations and responses to pharmacological treatments.

The gene-environment interplay is thought to determine variability in clinical conditions and responses to therapy in human neurodevelopmental disorders. Studying abnormal brain and behavior development in inbred strains of rodents can help in the identification of the complex pathogenic mechanisms of the host-environment interaction. This paper is the second one in a series of the two reports of the use of the Borna disease virus (BDV) infection model of neurodevelopmental damage to characterize effects of genetic background on virus-induced neurodevelopmental damage in inbred rat strains, Lewis and Fisher344. The present data demonstrate that neonatal BDV infection produced regional and strain-related alterations in levels of serotonin, norepinephrine and in levels of serotonin turnover at postnatal day 120. Neonatal BDV infection also induced upregulation of hippocampal 5-HT(1a) and cortical 5-HT(2a) receptors in Lewis rats and downregulation of cortical 5-HT(2a) receptors in Fisher344 rats. BDV-associated regional downregulation of D(2) receptors and dopamine transporter sites were noted in Fisher344 rats. In addition to the neurochemical disturbances, neonatal BDV infection induced differential responses to serotonin compounds. While 8-OH-DPAT suppressed virus-enhanced ambulation in BDV-infected Fisher344, fluoxetine inhibited virus-induced hyperactivity in BDV-infected Lewis rats only. The present data provide new insights into the pathogenic events that lead to differential responses to pharmacological treatments in genetically different animals following exposure to the same environmental challenge.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1998

The application of chaetotaxy in the discrimination of Gyrodactylus salaris Malmberg, 1957 (Gyrodactylidae: Monogenea) from species of the genus parasitising British salmonids.

The chaetotaxy of argentophilic structures on three species of the monogenean genus Gyrodactylus was investigated in an attempt to distinguish species of this genus. Maps were prepared for Gyrodactylus salaris from Scandinavia and compared with two native species of Gyrodactylus parasitising salmonids in Britain, namely Gyrodactylus derjavini and Gyrodactylus truttae. The maps were subsequently refined and analysed for zones of homology and differentiation. The results demonstrate that G. salaris can be readily distinguished by this technique, which is, therefore, of great potential value in the identification of this notifiable pathogen. The key aggregations of sensilla discriminating G. salaris are, ventrally, the antero-ventral set, the medio-lateral set and the postero-lateral set, and, dorsally, the postero-dorsal set.

Animals↗
PubMed2002

The complex nosological concept of vascular dementia.

The existence of vascular dementia (VaD) was first identified by Marie, who described the etat lacunaire, and by Binswanger, who identified white matter lesions in demented individuals. The role of cortical lesions, while clear to clinicians, was highlighted only later by the pathological studies of Tomlinson and the clinical demonstrations of Hachinski et al., who have defined multi-infarct dementia. Lately, the emphasis shifted to pathogenic mechanisms with the identification of a multitude of processes, such as lipohyalinosis, cardiac dysfunction and genetic causes, to name only a few. Epidemiologic studies have demonstrated the high frequency of VaD, as well as the fact that vascular factors can contribute to Alzheimer's disease (AD). All these considerations converge to the realization that VaD is an extremely important clinical entity and that its prevention and treatment are within reach. In fact, there is more data on how to prevent strokes (and presumably VaD) than on how to prevent AD. Moreover, many factors which were identified as contributing to cerebrovascular disease in general and VaD in particular are frequently suspected as predisposing to AD as well. These unexpected findings highlight the importance of mixed vascular-degenerative dementia as a disorder which has to be properly defined and has important implications on prevention and treatment.

Brain↗
PubMed1994

Diagnosing ventilator-associated pneumonia: the role of bronchoscopy.

OBJECTIVE: To discuss the two diagnostic procedures used most frequently to obtain uncontaminated lower airway secretions during bronchoscopy. DESIGN: This article reviews the contributing risk factors of ventilator-associated pneumonia (VAP) and the recent studies that have assessed the usefulness of the protected specimen brush (PSB) and bronchoalveolar lavage (BAL) in the nonimmunocompromised host. RESULTS: A prompt, accurate diagnosis of VAP, including specific identification of the bacterial pathogen, remains a common challenge in the intensive-care unit. Standard clinical criteria are of suboptimal specificity for making decisions, including selecting antibiotic therapy. Bronchoscopic techniques of lung secretion sampling can be used in the intensive-care unit in an effort to overcome the effects of oropharyngeal contamination. The PSB and BAL, used appropriately, can help intensive-care clinicians formulate specific antimicrobial therapy. Evaluation of intracellular bacteria obtained by BAL has been reported to be useful in guiding empiric antibiotic therapy while the final results of cultures obtained with the PSB are pending. Prior antibiotic therapy, however, may confound the interpretation and clinical utility of results. CONCLUSION: Currently, for a patient taking antibiotic therapy, no reliable technique nor quantitative culture threshold exists to help in diagnosing suspected VAP or in guiding antibiotic therapy. If the clinical situation allows, antibiotic therapy should be discontinued for 48 hours; then, the PSB, BAL, protected BAL, or endobronchial aspiration should be used. These contemporary modalities, however, necessitate further clinical trials before widespread use is warranted.

Anti-Bacterial Agents↗