Evidence for concealed fasciculo-ventricular connections as revealed by His bundle pacing.

BACKGROUND: It is almost 100 years ago since Mahaim described the so-called paraspecific connections between the ventricular conduction axis and the crest of the muscular ventricular septum, believing such pathways to be ubiquitous. These pathways, however, have yet to be considered as potential pathways for septal activation during His bundle pacing. MATERIALS: So as to explore the hypothesis that specialised septal pathways might provide the substrate for septal activation during His bundle pacing, we compared the findings from 22 serially sectioned histological datasets and 34 different individuals undergoing His bundle pacing. RESULTS: We found histologically specialised pathways connecting the branching component of the atrioventricular conduction axis with the crest of the muscular ventricular septum in almost four-fifths of the histological datasets. In 32 of 34 patients undergoing His bundle pacing, the QRS complex closely resembled published images of known conduction through fasciculo-ventricular pathways. In only two patients was a delta wave not seen at any pacing voltages. Capture of these connections varied according to pacing voltage, a finding which correlated with the distance of the pathways from the site of penetration of the ventricular conduction axis. Ventricular activation times remained normal in the presence of the delta wave at higher pacing voltage but were prolonged at lower voltages. CONCLUSIONS: Our histologic findings confirm fasciculo-ventricular connections, initially described by Mahaim as being paraspecific, are likely ubiquitous. Analysis of 12-lead electrocardiograms leads us to conclude that fasciculo-ventricular pathways, concealed during sinus rhythm, become manifest with His bundle pacing.

Miniseries 1-Part II: the comparative anatomy of the atrioventricular conduction axis.

AIMS: The arrangement of the conduction axis is markedly different in various mammalian species. Knowledge of such variation may serve to question the validity of using animals as prospective models for design of systems for clinical use. METHODS AND RESULTS: We compared the arrangement of the atrioventricular conduction axis in human, murine, canine, porcine, and bovine hearts, examining serially sectioned datasets from 20 human, 16 murine, 3 porcine, 5 canine, and 1 bovine hearts. We also analysed computed tomographic datasets obtained from bovines and one human heart. Unlike the situation in the human heart, there is no formation of an atrioventricular fibrous membranous septum in the murine, canine, porcine, nor bovine hearts. Canine, porcine, and bovine hearts also lack an infero-septal recess, when defined as a fibrous plate supporting the buttress of the atrial septum. In these species, half of the non-coronary leaflet is directly opposed to the ventricular septal surface. CONCLUSION: There is a long right-sided non-branching component of the axis, which skirts the attachment of the non-coronary sinus of the aortic root. In the bovine heart, moreover, the left bundle branch usually extends intramyocardially as a solitary tape before surfacing and ramifying on the left ventricular septal surface. The difference in the atrioventricular conduction axis between species may influence the anatomical substrates for atrioventricular re-entry tachycardia, as well as providing inferences for assessing the risks of transcatheter implantation of the aortic valve. Further studies are now needed to assess these possibilities.

The atrioventricular conduction axis and the aortic root-Inferences for transcatheter replacement of the aortic valve.

Conduction problems still occur following transcatheter aortic valvar replacement. With this in mind, we have assessed the relationship of the conduction axis to the aortic root. We used serial histological sections, made perpendicular to the base of the triangle of Koch in nine hearts, and perpendicular to the aortic root in 11 hearts. We first defined the extent of the fibrous tissues forming the boundaries of an infero-septal recess of the subaortic outflow tract, found in all datasets but one. When the recess was present, the axis penetrated through its rightward wall, giving rise to the left bundle branch prior to entering the outflow tract. The axis itself was usually on the crest of the ventricular septum, but could be deviated leftward or rightward. Its proximity to the virtual basal plane reflected the angulation of the muscular septum. On average, the superior edge of the left bundle was within 3.3 mm of the hinge of the right coronary leaflet, with a range from 0.4 to 10.2 mm. The arrangement was markedly different in the case lacking an infero-septal recess. Our findings necessitated a redefinition of the right fibrous trigone and the central fibrous body. The atrioventricular conduction axis, having entered the aortic root, is usually closest at the hinge of the right coronary leaflet. Knowledge of the depth of the infero-septal recess, and the angulation of the muscular ventricular septal, may help to avoid conduction problems following transcatheter implantation of the aortic valve.

Cutaneous Leishmaniasis Caused by an Unknown Leishmania Strain, Arizona, USA.

We investigated an autochthonous case of cutaneous leishmaniasis caused by a genetically different Leishmania sp. in a patient in Arizona, USA. This parasite was classified into the subgenus Leishmania on the basis of multilocus DNA sequence and phylogenetic analyses of the rRNA locus and 11 reference genes.

Three-dimensional visualization of the bovine cardiac conduction system and surrounding structures compared to the arrangements in the human heart.

In the human heart, the atrioventricular node is located toward the apex of the triangle of Koch, which is also at the apex of the inferior pyramidal space. It is adjacent to the atrioventricular portion of the membranous septum, through which it penetrates to become the atrioventricular bundle. Subsequent to its penetration, the conduction axis is located on the crest of the ventricular septum, sandwiched between the muscular septum and ventricular component of the membranous septum, where it gives rise to the ramifications of the left bundle branch. In contrast, the bovine conduction axis has a long non-branching component, which penetrates into a thick muscular atrioventricular septum having skirted the main cardiac bone and the rightward half of the non-coronary sinus of the aortic root. It commonly gives rise to both right and left bundle branches within the muscular ventricular septum. Unlike the situation in man, the left bundle branch is long and thin before it branches into its fascicles. These differences from the human heart, however, have yet to be shown in three-dimensions relative to the surrounding structures. We have now achieved this goal by injecting contrast material into the insulating sheaths that surround the conduction network, evaluating the results by subsequent computed tomography. The fibrous atrioventricular membranous septum of the human heart is replaced in the ox by the main cardiac bone and the muscular atrioventricular septum. The apex of the inferior pyramidal space, which in the bovine, as in the human, is related to the atrioventricular node, is placed inferiorly relative to the left ventricular outflow tract. The bovine atrioventricular conduction axis, therefore, originates from a node itself located inferiorly compared to the human arrangement. The axis must then skirt the non-coronary sinus of the aortic root prior to penetrating the thicker muscular ventricular septum, thus accounting for its long non-branching course. We envisage that our findings will further enhance comparative anatomical research.

The membranous septum revisited: A glimpse of our anatomical past.

The so-called membranous septum is the fibrous component of the septal structures within the heart. It is relatively subtle in its appearance, but of considerable significance to the understanding of cardiac function and cardiac disease, both congenital and acquired. Surprisingly, its existence was seemingly unknown until the early decades of the 19th century. At this time, those writing in the English language described it as the "undefended space," recognizing its importance in the setting of its aneurysmal dilation, and as the site of septal defects. By the initial decade of the 20th century, it had come to be recognized as the landmark to the site of atrioventricular bundle. Over the first decade of the 21st century, its clinical significance has been emphasized in the context of transcutaneous replacement of the aortic valve. In this review, we describe our own recent investigations of this fibrous part of the septal structures. At the same time, we provide a glimpse of our anatomic past, explaining how its initial description relied on the observations of young physicians taking their first steps in the investigation of cardiac anatomy.

A Second Case of Human Conjunctival Infestation With Thelazia gulosa and a Review of T. gulosa in North America.

We describe a second case of human infection caused by Thelazia gulosa (the cattle eye worm), likely acquired in California. For epidemiologic purposes, it is important to identify all Thelazia recovered from humans in North America to the species level.

Leishmania infantum in US-Born Dog.

Leishmaniasis is a vectorborne disease that can infect humans, dogs, and other mammals. We identified one of its causative agents, Leishmania infantum, in a dog born in California, USA, demonstrating potential for autochthonous infections in this country. Our finding bolsters the need for improved leishmaniasis screening practices in the United States.

The ox atrioventricular conduction axis compared to human in relation to the original investigation of sunao tawara.

It was Sunao Tawara who, in 1906, established the foundations for knowledge of the arrangement of the atrioventricular conduction axis in man and other mammals. Study of the hearts of ungulates was a central part in his investigation, which assessed other species, including man. He described several subtle differences between the mammals. We have now ourselves studied the cardiac conduction tissue of the ox heart, comparing our findings with our knowledge of the arrangement in man, and providing new insights into the differences illustrated by Tawara. It is, perhaps, surprising that these differences, although subtle, have not attracted more attention. We show that the major difference is the fact that the noncoronary aortic sinus in the ox heart is mainly supported by the myocardium of the ventricular septum, whereas in the human heart the sinus, and its leaflet, are in fibrous contiguity with the aortic leaflet of the mitral valve. It is this feature that determines the difference in the arrangement of the conduction axis between the species. We also show that the emergence of the left bundle branch on the left ventricular aspect of the muscular septum is more variable than previously described. Clin. Anat. 33:383-393, 2020. © 2019 Wiley Periodicals, Inc.

Formation of OSA and dispersion of polycyclic aromatic hydrocarbons in a tropical estuary as a tool in the prevention of environmental impacts: influence of the biogeochemical characteristics of the estuary.

The formation of an oil-suspended particulate material aggregate (OSA) is one of the weathering processes that occur after the spill of oil in marine environments, responsible for the dispersion of hydrocarbons. Oil and particle aggregates are formed from the interaction between small oil droplets and suspended particulate matter (SPM). In general, SPM are fine particles which may be inorganic minerals or organic particles in the water column. OSAs provide vertical dispersion of oil along the water column depending on the acquired density (buoyancy), and may remain near the surface, water column, or bottom of water bodies. The present study examines the formation of these aggregates through the laboratory simulation of an oil spill in the waters of the São Paulo river estuary. The main objective was to investigate the dispersion of polycyclic aromatic hydrocarbons (PAHs), verifying which estuary characteristics most influenced the formation of OSAs and in addition to determine the regions of probable ecotoxicological impact due to the negative buoyancy of the formed aggregate. The results show that there was greater dispersion to the water column, mainly of lighter PAHs, ranging from 85,804.05 ng g-1 (P11C) to 566,989.84 ng g-1 (P17C). The percentage of dispersed PAH concentration per experimental unit ranged from 9.90% in unit P2 to 75.27% in unit P18. The formation of OSAs was influenced mainly by salinity and chlorophyll a. As the most vulnerable regions, the impacts are one mouth (P2 and P4), one central region (P7, P8, and P10), and one source (P18).

Re-evaluating the electro-vectorcardiographic criteria for left bundle branch block.

The criteria for left bundle branch block have gained growing interest in the last few years. In this overview, we discuss diagnostic and prognostic aspects of different criteria. It was already shown that stricter criteria, including longer QRS duration and slurring/notching of the QRS, better identify responders to cardiac resynchronization therapy. We also include aspects of ST/T concordance and discordance and vectorcardiography, which could further improve in the fine-tuning of the left bundle branch criteria.

Why do we break one of the first rules of anatomy when describing the components of the heart?

A rule of human anatomy is that all structures within the body should be described relative to the so-called "anatomical position." Along with those describing structures such as the skull and liver, those accounting for the components of the heart consistently break this rule, describing the organ as if removed from the body and positioned on its apex, the so-called "Valentine position." Although potentially appropriate to some animal species, this approach produces problems when used in human anatomy, even if the right and left ventricles are only viewed in truly right-sided and left-sided positions when assessed in the Valentine fashion. The names of the ventricles, of course, are never going to change. This is not necessarily the case with other cardiac components. Consider the artery that extends between the ventricles on their diaphragmatic surface. Blockage produces inferior myocardial infarction, which is to be expected, since the vessel is located in inferior and interventricular position. It is incorrect to describe the artery as being posterior and descending. Such infelicities are now the more obvious with the advent of techniques that, in clinical cardiology, show the components of the heart as it lies within the chest. In this review, we have assessed the frequency of use of the Valentine approach in popular textbooks used by students of human anatomy. We show that, using the conduction tissues as a model, this system also being incorrectly described in the majority of the textbooks, the situation can be improved by use of attitudinally appropriate description. Clin. Anat. 32:585-596, 2019. © 2019 Wiley Periodicals, Inc.

Trichomonas vaginalis Brain Abscess in a Neonate.

We describe a case of cerebral trichomoniasis in a neonate in whom seizures and multiorgan failure developed during treatment for staphylococcal sepsis. Brain abscesses were identified with cranial sonography, and Trichomonas vaginalis was isolated from cerebrospinal fluid samples. The patient died despite metronidazole therapy.

Detection and Differentiation of Leishmania spp. in Clinical Specimens by Use of a SYBR Green-Based Real-Time PCR Assay.

Leishmaniasis in humans is caused by Leishmania spp. in the subgenera Leishmania and Viannia Species identification often has clinical relevance. Until recently, our laboratory relied on conventional PCR amplification of the internal transcribed spacer 2 (ITS2) region (ITS2-PCR) followed by sequencing analysis of the PCR product to differentiate Leishmania spp. Here we describe a novel real-time quantitative PCR (qPCR) approach based on the SYBR green technology (LSG-qPCR), which uses genus-specific primers that target the ITS1 region and amplify DNA from at least 10 Leishmania spp., followed by analysis of the melting temperature (Tm) of the amplicons on qPCR platforms (the Mx3000P qPCR system [Stratagene-Agilent] and the 7500 real-time PCR system [ABI Life Technologies]). We initially evaluated the assay by testing reference Leishmania isolates and comparing the results with those from the conventional ITS2-PCR approach. Then we compared the results from the real-time and conventional molecular approaches for clinical specimens from 1,051 patients submitted to the reference laboratory of the Centers for Disease Control and Prevention for Leishmania diagnostic testing. Specimens from 477 patients tested positive for Leishmania spp. with the LSG-qPCR assay, specimens from 465 of these 477 patients also tested positive with the conventional ITS2-PCR approach, and specimens from 10 of these 465 patients had positive results because of retesting prompted by LSG-qPCR positivity. On the basis of the Tm values of the LSG-qPCR amplicons from reference and clinical specimens, we were able to differentiate four groups of Leishmania parasites: the Viannia subgenus in aggregate; the Leishmania (Leishmania) donovani complex in aggregate; the species L (L) tropica; and the species L (L) mexicana, L (L) amazonensis, L (L) major, and L (L) aethiopica in aggregate.

The Emergence of Zoonotic Onchocerca lupi Infection in the United States--A Case-Series.

This case-series describes the 6 human infections with Onchocerca lupi, a parasite known to infect cats and dogs, that have been identified in the United States since 2013. Unlike cases reported outside the country, the American patients have not had subconjunctival nodules but have manifested more invasive disease (eg, spinal, orbital, and subdermal nodules). Diagnosis remains challenging in the absence of a serologic test. Treatment should be guided by what is done for Onchocerca volvulus as there are no data for O. lupi. Available evidence suggests that there may be transmission in southwestern United States, but the risk of transmission to humans is not known. Research is needed to better define the burden of disease in the United States and develop appropriately-targeted prevention strategies.

Ascariasis in humans and pigs on small-scale farms, Maine, USA, 2010-2013.

Ascaris is a genus of parasitic nematodes that can cause infections in humans and pigs. During 2010-2013, we identified 14 cases of ascariasis in persons who had contact with pigs in Maine, USA. Ascaris spp. are important zoonotic pathogens, and prevention measures are needed, including health education, farming practice improvements, and personal and food hygiene.

Performance of a real time PCR for leishmaniasis diagnosis using a L. (L.) infantum hypothetical protein as target in canine samples.

Visceral leishmaniasis represents an important public health issue in different parts of the world, requiring that measures be put in place to control the spread of the disease worldwide. The canine leishmaniasis diagnosis is not easy based on clinical signs, since dogs may not develop the infection with recognizable signs. Thus, the laboratorial diagnosis is essential to ascertain the incidence and prevalence of canine leishmaniasis especially in areas with major control efforts. Although, the diagnosis can be performed by the use of different approaches, the molecular methods such as PCR have become an indispensable tool for leishmaniases diagnosis. A TaqMan assay for real-time PCR (Linj31-qPCR) was developed to determine the parasite occurrence in clinical cases of leishmaniasis. The assay targets an L. (L.) infantum hypothetical protein region. The specificity of the assay was verified by using Leishmania World Health Organization reference strains including parasites belonging to subgenus L. (Leishmania), subgenus L. (Viannia), other Leishmania species and Trypanosoma cruzi. The sensitivity was verified by using isolates of L. (L.) amazonensis and L. (L.) infantum. The usefulness of the assay for diagnosis was ascertained by testing 277 samples from dogs in regions endemic for visceral and/or cutaneous leishmaniasis and from regions in which leishmaniasis was not endemic in São Paulo State, Brazil. Diagnosis of canine visceral leishmaniasis (CVL) was determined on these animals by conventional PCR and three serological tests. The dog samples were divided into four groups. I, dogs with CVL (n = 101); II, dogs with other diseases and without CVL (n = 97); III, dogs with American cutaneous leishmaniasis (n = 7), and, IV, dogs without CVL (n = 72) from areas where leishmaniasis was not endemic as control group. Results indicated that Linj31-qPCR was able to identify parasites belonging to subgenus L. (Leishmania) with no cross-amplification with other parasite subgenera. The Linj31-qPCR detected Leishmania parasites DNA in 98% of samples from Group I. In conclusion this methodology can be used as routine diagnostic tools to detect parasites from subgenus Leishmania.

Microsporidiosis acquired through solid organ transplantation: a public health investigation.

BACKGROUND: Encephalitozoon cuniculi, a microsporidial species most commonly recognized as a cause of renal, respiratory, and central nervous system infections in immunosuppressed patients, was identified as the cause of a temporally associated cluster of febrile illness among 3 solid organ transplant recipients from a common donor. OBJECTIVE: To confirm the source of the illness, assess donor and recipient risk factors, and provide therapy recommendations for ill recipients. DESIGN: Public health investigation. SETTING: Two transplant hospitals and community interview with the deceased donor's family. PATIENTS: Three transplant recipients and the organ donor. MEASUREMENTS: Specimens were tested for microsporidia by using culture, immunofluorescent antibody, polymerase chain reaction,immunohistochemistry, and electron microscopy. Donor medical records were reviewed and a questionnaire was developed to assess for microsporidial infection. RESULTS: Kidneys and lungs were procured from the deceased donor and transplanted to 3 recipients who became ill with fever 7 to 10 weeks after the transplant. Results of urine culture, serologic,and polymerase chain reaction testing were positive for E. cuniculi of genotype III in each recipient; the organism was also identified in biopsy or autopsy specimens in all recipients. The donor had positive serologic test results for E. cuniculi. Surviving recipients received albendazole. Donor assessment did not identify factors for suspected E. cuniculi infection. LIMITATION: Inability to detect organism by culture or polymerase chain reaction in donor due to lack of autopsy specimens. CONCLUSION: Microsporidiosis is now recognized as an emerging transplant-associated disease and should be considered in febrile transplant recipients when tests for routinely encountered agents are unrevealing. Donor-derived disease is critical to assess when multiple recipients from a common donor are ill.

Outbreak of Trichinella spiralis infections associated with a wild boar hunted at a game farm in Iowa.

BACKGROUND: Rates of trichinellosis have declined significantly in the United States due to improved pork production practices and public awareness of the danger of eating raw or undercooked pork. In April 2011, the Minnesota Department of Health received a report of presumptive trichinellosis in a 50-year-old man with a history of wild boar consumption. A public health investigation was initiated. METHODS: Medical record reviews and patient and family interviews were conducted. Trichinella species serology was performed on patient and family serum samples, and larval identification was attempted on clinical specimens and meat samples. RESULTS: The index patient harvested a wild boar from an Iowa game farm; he processed the meat after returning home and developed gastrointestinal symptoms 2 days later. Four days after his illness onset, all 5 family members consumed a roast from the boar. The index patient sought healthcare 4 times after illness onset before being definitively diagnosed with trichinellosis. Following initiation of albendazole therapy, the index patient developed atrial fibrillation. One additional family member who processed the raw meat was diagnosed with trichinellosis. Trichinella spiralis larvae were identified in wild boar meat samples. CONCLUSIONS: Trichinellosis has long been recognized as a potential hazard of consuming undercooked wild carnivore meat, and historically has been associated with consumption of pork from domestic swine, but may be unfamiliar to practicing clinicians in the United States. Education of hunters and the broader population on the potential for trichinellosis and the importance of proper handling and cooking meat from wild or free-range animals needs to be reinforced.

Dextran-functionalized magnetic fluid mediating magnetohyperthermia for treatment of Ehrlich-solid-tumor-bearing mice: toxicological and histopathological evaluations.

Dextran-functionalized maghemite fluid (DexMF) has been tested to treat Ehrlich-solid-tumor-bearing mice, evidencing its potential use in mediating magnetohyperthermia in breast cancer treatment. However, although magnetic nanoparticles tend to accumulate in tumor tissues, part of the nanomaterial can reach the blood stream, and then the organism. The aim of this study was to investigate the acute systemic effects of the intratumoral injection of DexMF mediating magnetohyperthermia in the treatment of an advanced clinical Ehrlich-solid-tumor, assessed through histopathological analyses of liver, kidneys, heart and spleen, comet assay, micronucleus test, hemogram, and serum levels of bilirubin, aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transferase, alkaline phosphatase, creatinine, and urea. The tumor's histopathology and morphometry were used to assess its aggressiveness and regression. DexMF mediating hyperthermia was effective in containing tumor aggressiveness and in inducing tumor regression, besides showing no toxic effects. Its physical characteristics also suggest that it is safe to use in other biomedical applications.