Selective pacing sites.

he right ventricular apex (RVA) has always been the most used pacing site, because it is easily accessible and provides a stable lead position with a low dislodgment rate. However, it is well-known that long-term right ventricular apical pacing may have deleterious effects on left ventricular function by inducing a iatrogenic left bundle branch block, which can have strong influences on the left ventricle hemodynamic performances. More specifically, RVA pacing causes abnormal contraction patterns and the consequent dyssynchrony may cause myocardial perfusion defects, histopathological alterations, left ventricular dilation and both systolic and diastolic left ventricular dysfunction. All these long-term changes could account for the higher morbidity and mortality rates observe in patients with chronic RVA pacing compared with atrial pacing. This observation led to the reassessment of traditional approaches and to the research of alternative pacing sites, in order to get to more physiological pattern of ventricular activation and to avoid deleterious effects. Then, attempts were made with: right ventricular outflow tract (RVOT) pacing, direct His bundle pacing (DHBP), parahisian pacing (PHP) and bifocal (RVA + RVOT) pacing. For example, RVOT pacing, especially in its septal portion, is superior to the RVA pacing and it would determine a contraction pattern very similar to the spontaneous one, not only because the septal portions are the first parts to became depolarized, but also for the proximity to the normal conduction system. RVOT is preferable in terms of safety too. DHBP is an attractive alternative to RVA pacing because it leads to a synchronous depolarization of myocardial cells and, therefore, to an efficient ventricular contraction. So it would be the best technique, however the procedure requires longer average implant times and dedicated instruments and it cannot be carried out in patients affected by His bundle pathologies; furthermore, due to the His bundle fibrous area, higher pacing thresholds are required, causing accelerated battery depletion. For all these reasons, PHP could be considered an important alternative to DHBP, to be used on a large scale. Finally, bifocal pacing in CRT candidates, provides better acute hemodynamic performance than RVA pacing, derived from a minor intra- and interventricular dyssynchrony, expressed also by the QRS shortening. Then, bifocal pacing could be taken into account when RVA pacing is likely to be the origin of serious mechanical and electrical dyssynchrony or when CRT is contraindicated or technically impossible. So, whatever chosen as selective pacing site, you must look also at safety, effectiveness and necessary equipment for an optimal pacing site.

ST segment elevations: always a marker of acute myocardial infarction?

Chest pain is one of the chief presenting complaints among patients attending Emergency department. The diagnosis of acute myocardial infarction may be a challenge. Various tools such as anamnesis, blood sample (with evaluation of markers of myocardial necrosis), ultrasound techniques and coronary computed tomography could be useful. However, the interpretation of electrocardiograms of these patients may be a real concern. The earliest manifestations of myocardial ischemia typically interest T waves and ST segment. Despite the high sensitivity, ST segment deviation has however poor specificity since it may be observed in many other cardiac and non-cardiac conditions. Therefore, when ST-T abnormalities are detected the physicians should take into account many other parameters (such as risk factors, symptoms and anamnesis) and all the other differential diagnoses. The aim of our review is to overview of the main conditions that may mimic a ST segment Elevation Myocardial Infarction (STEMI).

Orbital pythiosis: a non-fungal disease mimicking orbital mycotic infections, with a retrospective review of the literature.

In the past decade there have been four well-documented cases of orbital pythiosis caused by Pythium insidiosum. All were recorded in apparently healthy children. Although pythiosis seems to be a rare infection in humans, we recently conducted a review of the medical literature to investigate misdiagnosed cases of orbital pythiosis in the past 100 years in children. To track putative cases of orbital pythiosis, we first identified orbital cases initially diagnosed as fungal infections. We were particularly interested in cases (a) involving apparently young healthy hosts, (b) the presence of hyaline, aseptate hyphal elements in the infected tissues, (c) the morphological features of the hyphal elements, (d) the presence of an eosinophilic granulomatous reaction with the Splendore-Hoeppli phenomenon around the mycelial elements, (e) resistance to antifungal therapy, (f) outcome after therapy, if any, and (g) cultural strategies. This study showed that indeed, there had been five other recorded cases of orbital infections, all in young children in the USA, with characteristics consistent with infections caused by P. insidiosum. The reports had described those cases of orbital-cranial-arterial diseases as patients with aspergillosis (one case), penicilliosis infection (one case), and zygomycosis (three cases). We reviewed those anomalous cases and discuss details about their clinical, pathologic, therapeutic, and etiologic evidence used to reclassify them as putative cases of orbital pythiosis.

Cavernicolous habitats harbouring Cryptococcus neoformans: results of a speleological survey in Apulia, Italy, 1999-2000.

Twenty-five caves of speleological and palaeontological interest were investigated for the presence of Cryptococcus spp. within the Apulia region of Italy. Five hundred and forty-five specimens of soil, mud, animal faeces, water and decayed animal and plant remains were examined. Faecal specimens from bats, pigeons and foxes in three caves yielded Cryptococcus neoformans var. neoformans and C. laurentii, C. neoformans var. neoformans and C. albidus were isolated from two soil specimens. Only three caves were positive for the presence of C. neoformans, but the survey documents the finding of a possible natural reservoir in Apulia. It is the first record of occurrence of this yeast in association with cavernicolous habitats, and indicates the potential role of caves in exposing speleologists to life-threatening fungal infections.

Phylogenetic analysis of Lacazia loboi places this previously uncharacterized pathogen within the dimorphic Onygenales.

Lacazia loboi is the last of the classical fungal pathogens to remain a taxonomic enigma, primarily because it has resisted cultivation and only causes cutaneous and subcutaneous infections in humans and dolphins in the New World tropics. To place it in the evolutionary tree of life, as has been done for the other enigmatic human pathogens Pneumocystis carinii and Rhinosporidium seeberi, we amplified its 18S small-subunit ribosomal DNA (SSU rDNA) and 600 bp of its chitin synthase-2 gene. Our phylogenetic analysis indicated that L. loboi is the sister taxon of the human dimorphic fungal pathogen Paracoccidioides brasiliensis and that both species belong with the other dimorphic fungal pathogens in the order Onygenales. The low nucleotide variation among three P. brasiliensis 18S SSU rDNA sequences contrasts with the surprising amount of nucleotide differences between the two sequences of L. loboi used in this study, suggesting that the nucleic acid epidemiology of this hydrophilic pathogen will be rewarding.

Adrenal bilateral incidentaloma by reactivated histoplasmosis.

We report a case of bilateral adrenal incidentaloma caused by the capsulatum variety of Histoplasma capsulatum diagnosed in a 74 years old man born in and a life time resident of Treviso, Italy, with the exception of two years spent in Pakistan (1964-1966) as a well-driller. The patient was hospitalized in 1995 for alcoholic chronic hepatitis, chronic Helicobacter pylori gastritis and post-infarction ischemic cardiomyopathy. Abdominal ultrasound incidentally showed bilateral adrenal masses (the right one 6.3 cm in diameter) confirmed by computed tomography, with adrenal function within normal limits. After three months, the patient was again hospitalized due to evening fever, asthenia, anorexia, weight loss and occasional hyperhidrosis. Abdominal ultrasound showed an increase of the right adrenal lesion with normal adrenal function. Ultrasound-guided fine needle aspiration did not prove useful for diagnosis. Accordingly, a laparotomy with bilateral biopsy was performed; histology showed the presence of numerous tissue form cells of H. capsulatum variety capsulatum. Serum anti-H. capsulatum antibodies were negative. Since March, 1996, the patient was given itraconazole and his symptoms quickly regressed but the computed tomography findings, however, have not changed and the patient has adrenal hypofunction that is being treated with cortisone acetate.

Phylogenetic analysis of Rhinosporidium seeberi's 18S small-subunit ribosomal DNA groups this pathogen among members of the protoctistan Mesomycetozoa clade.

For the past 100 years the phylogenetic affinities of Rhinosporidium seeberi have been controversial. Based on its morphological features, it has been classified as a protozoan or as a member of the kingdom Fungi. We have amplified and sequenced nearly a full-length 18S small-subunit (SSU) ribosomal DNA (rDNA) sequence from R. seeberi. Using phylogenetic analysis, by parsimony and distance methods, of R. seeberi's 18S SSU rDNA and that of other eukaryotes, we found that this enigmatic pathogen of humans and animals clusters with a novel group of fish parasites referred to as the DRIP clade (Dermocystidium, rossete agent, Ichthyophonus, and Psorospermium), near the animal-fungal divergence. Our phylogenetic analyses also indicate that R. seeberi is the sister taxon of the two Dermocystidium species used in this study. This molecular affinity is remarkable since members of the genus Dermocystidium form spherical structures in infected hosts, produce endospores, have not been cultured, and possess mitochondria with flat cristae. With the addition of R. seeberi to this clade, the acronym DRIP is no longer appropriate. We propose to name this monophyletic clade Mesomycetozoa to reflect the group's phylogenetic association within the Eucarya.

Indigenous disseminated Penicillium marneffei infection in the state of Manipur, India: report of four autochthonous cases.

We describe four cases of disseminated infection caused by endemic Penicillium marneffei in human immunodeficiency virus (HIV)-infected patients from the Manipur state of India. The most common clinical features observed were fever, anorexia, weight loss, hepatosplenomegaly, and, more importantly, skin lesions resembling molluscum contagiosum. The diagnosis in each of the four cases was achieved by direct examination of smears, observance of intracellular yeast-like cells multiplying by fission in biopsied tissue from skin lesions, and isolation of the dimorphic P. marneffei in pure culture in each case. In one case, fluorescent antibody studies allowed specific diagnosis. This report documents a new area in which P. marneffei is endemic, located in eastern India, and describes the first occurrence in India of P. marneffei in HIV-infected patients as well as the extension of the areas of P. marneffei endemicity westward to the northeastern state of Manipur.

Immunolocalization of an endogenous antigenic material of Rhinosporidium seeberi expressed only during mature sporangial development.

We investigated the immunolocalization of Rhinosporidium seeberi's antigens using sera from individuals infected with R. seeberi and tissue from Sri Lankan patients with rhinosporidiosis. The tissues were fixed in LR white resin, thin sectioned fixed onto nickel grids and evaluated by transmission electron microscopy for the presence of R. seeberi's sporangia. The tissue samples were reacted with the patients's sera and then labeled with protein A colloidal gold (PACG) for immunolocalization. It was found that the PACG had fixed to antibodies that specifically recognized an internal electron lucent layer situated immediately under the mature sporangium's wall. Strikingly, the endospores, the juvenile and intermediate sporangia did not undergo PACG labeling. This study found that the expression of this antigen occurs only in the final developmental stages of R. seeberi's mature sporangia. Our data may explain why circulating antibodies to R. Seeberi were not detected before in studies that used endospores as antigen in immunoassays. This is the first report in which an antigenic material with a potential role in the immunology of rhinosporidiosis has been detected.

In vitro studies on the mechanisms of endospore release by Rhinosporidium seeberi.

Studies of Rhinosporidium seeberi have demonstrated that this organism has a complex life cycle in infected tissues. Its in vivo life cycle is initiated with the release of endospores into a host's tissues from its spherical sporangia. However, little is known about the mechanisms of sporangium formation and endospore release since this pathogen is intractable to culture. We have studied the in vitro mechanisms of endospore release from viable R. seeberi's sporangia. It was found that watery substances visibly stimulates the mature sporangia of R. seeberi to the point of endospore discharge. The internal rearrangement of the endospores within the mature sporangia, the opening of an apical pore in R. seeberi's cell wall, and the active release of the endospores were the main features of this process. Only one pore per sporangium was observed. The finding of early stages of pore development in juvenile and intermediate sporangia suggested that its formation is genetically programmed and that it is not a random process. The stimulation of R. seeberi's sporangia by water supports the epidemiological studies that had linked this pathogen with wet environments. It also explains, in part, its affinities for mucous membranes in infected hosts. The microscopic features of endospore discharge suggest a connection with organisms classified in the Kingdom Protoctista. This study strongly supports a recent finding that placed R. seeberi with organisms in the protoctistan Mesomycetozoa clade.

Investigation of an outbreak of endemic coccidioidomycosis in Brazil's northeastern state of Piauí with a review of the occurrence and distribution of Coccidioides immitis in three other Brazilian states.

An outbreak of coccidioidomycosis is described that involved three individuals and eight of their dogs, who had engaged in a successful hunt for nine-banded armadillos (Dasypus novemcinctus) in the environs of Oeiras, a community in Brazil's north eastern state of Piauí. Diagnosis was based on clinical, serological and cultural findings. Four of 24 soil samples collected in and around the burrow of an armadillo yielded cultures of Coccidioides immitis, thus establishing the endemicity of that mould in the state of Piauí. A literature review revealed that C. immitis, aside from that state, is endemic in three other Brazilian states--Bahia, Ceará and Maranhão. These four contiguous states have semi-arid regions where climatic conditions and their flora are similar to those that exist in C. immitis's endemic regions in North, Central and South America.

Use of an immunotherapeutic vaccine to treat a life-threatening human arteritic infection caused by Pythium insidiosum.

A 14-year-old Thai boy presented because of a history of headache, mandibular swelling, and facial nerve palsy. A microorganism identified as Pythium insidiosum was cultured from the mandibular abscesses. Despite treatment with amphotericin B, iodides, ketoconazole, and surgery, the infection progressed. Magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) of the neck revealed an aneurysm in the external carotid artery. The aneurysm was removed. MRA performed later showed stenosis of the internal carotid artery. Immunotherapy was recommended as a last resort. One hundred microliters of the P. insidiosum vaccine was subcutaneously injected into the patient's left shoulder, and 14 days later a similar dose was administered. Four weeks following the first vaccination, the patient's headache had disappeared, the facial swellings had dramatically diminished, the cervical lymph node had shrunk, and the proximal left internal carotid artery stenosis had significantly improved. One year after the vaccinations, the boy was considered clinically cured.

Italian contributions to the history of general and medical mycology.

Important contributions by Italian mycologists that guided the field of medical mycology are discussed. Much of our current taxonomy resulted from their contributions.

Antigenic relationships among pathogenic Beauveria bassiana with Engyodontium album (= B. alba) and non-pathogenic species of the genus Beauveria.

Exoantigenic extracts of 15 isolates belonging to hyalohyphomycosis-causing Beauveria bassiana (1), and Engyodontium album (1), as well as other species of the genus Beauveria (one isolate each of B. brogniartii, B. densa, B. stephanoderis, B. velata, B. vermiconia and six isolates of unknown Beauveria species) were studied. Aqueous-merthiolated extracts derived from 10-day-old Sabouraud's dextrose agar slant cultures (25 degrees C) were concentrated (25X), and reacted against rabbit anti-B. bassiana serum in the presence of partially purified homologous antigen (20X) prepared from 5-week-old shaken cultures (30 degrees C), using a microimmunodiffusion procedure. Beauveria bassiana reference antigen and antiserum reacted to produce four bands of identity. With the exception of E. album, which was negative, extracts of the isolates of B. brogniartii, B. densa, B. stephanoderis, B. velata, B. vermiconia and the unknown Beauveria species all produced 2-4 lines of identity against the homologous anti-B. bassiana serum. These results suggested that all the species of the genus Beauveria tested were antigenically related to B. bassiana. Engyodontium album demonstrated antigenic distinctness, however, from B. bassiana and thus supported the validity of this taxon.

Occurrence of Penicillium marneffei infections among wild bamboo rats in Thailand.

Penicilliosis marneffei has emerged as an endemic systemic mycosis in Southeast Asia among humans and wild bamboo rats. To gain an insight into the epidemiology of this life-threatening disease, a survey of bamboo rats for natural infections by Penicillium marneffei was carried out in the central plains of Thailand during June-September, 1987. Thirty-one lesser bamboo rats (Cannomys badius) and eight hoary bamboo rats (Rhizomys pruinosus) were trapped. Portions of their internal organs were cultured to determine if they had been infected by P. marneffei. Six each of C. badius (19.4%) and R. pruinosus (75%) yielded cultures of this unique, dimorphic Penicillium species. All of the isolates were readily converted to their unicellular form that multiplies by the process of schizogony by incubating them at 37 degrees C on plates of brain heart infusion agar. Their identity was further confirmed by a specific immunological test. Among the internal organs of the positive rats, the lungs had the highest positivity (83.3%), next in decreased order of frequency were the liver (33.3%) and the pancreas (33.3%). The use and value of domestic and wild animals in locating and demarcating endemic areas of geophilic fungal pathogens are discussed. Penicilliosis marneffei is considered to be a zooanthroponosis--a disease that occurs in lower animals, as well as, humans.

Rhinosporidiosis: a description of an unprecedented outbreak in captive swans (Cygnus spp.) and a proposal for revision of the ontogenic nomenclature of Rhinosporidium seeberi.

Rhinosporidiosis is a mucocutaneous zooanthroponotic disease caused by Rhinosporidium seeberi, a fungal-like organism of uncertain classification with an unknown mode of transmission. Over a 3 year period, 41 captive swans (Cygnus olor and C. atratus) developed conjunctival and cutaneous polypoid lesions diagnosed as rhinosporidiosis by histopathological examination including light and electron microscopy. Investigation of this avian outbreak, the first of its kind, provides additional insight into the epidemiology of this enigmatic aetiologic agent, which has yet to be isolated and cultivated in vitro. The occurrence of rhinosporidiosis in swans supports an aquatic environment as the reservoir for R. seeberi, which is often associated with exposure to water. We report the first known occurrence of rhinosporidiosis in 41 captive mute (C. olor) and Australian black (C. atratus) swans dwelling on a lake in a Central Florida city. Additionally, we review the development stages of R. seeberi and propose a revision in its ontogenic nomenclature to reflect its probable taxonomic classification as a member of the kingdom Fungi.