Massive Degeneration and Atrophy of the Native Heart After Heterotopic Transplantation: A Case Report

Extreme myocardial degeneration leading to advanced stages of cardiomyopathy with extensive atrophy is rarely observed before patients die. However, heterotopic transplantation is a special situation wherein this phenomenon can be observed. The greater part of the failed heart shows recuperation after receiving circulatory assistance by reduction of myocardial work. Herein we have reported an unusual behavior of degenerative cardiomyopathy associated with intense myocardial apoptosis resulting in extreme ventricular atrophy after heterotopic heart transplantation. An 11-year-old girl with end-stage heart failure due to dilated cardiomyopathy of undetermined etiology without pulmonary hypertension underwent heterotopic cardiac transplantation with an undersized (by weight mismatch) donor heart. After 9 years heart failure reappeared due to native heart enlargement leading to allograft compression. The patient underwent native heart replacement leaving her with 2 donor hearts. Despite normal hemodynamic recuperation, the patient experienced massive arterial microemboli which led to death. Pathological studies showed exuberant myocardial degeneration in the native heart with intense atrophy of the muscle and gigantic ventricular enlargement. The left ventricle wall was extremely thin with rarefaction of cardiomyocytes and replacement by fibrosis. The right ventricle showed old extensive thrombosis. In conclusion, this report is not usual as it is not frequent to observe cardiomyopathy with an intense degree of myocardial degeneration and atrophy, because the patient dies earlier. In special situations it is possible that a recipient may have 2 donor hearts with normal hemodynamics. Heterotopic heart transplantation is a surgical alternative in a priority situation offering excellent outcomes; however, the native heart must be removed when there is compromise of the function of the heterotopic allograft.

Clinical, dermoscopic and histopathological evaluation of the Meyerson nevus - Case report

Meyerson nevi occur whenever a rare focal and transitory eczematous eruption arises around melanocytic lesions. The same phenomenon has also been observed in non-melanocytic lesions as well. Herein we report the case of a 25 year old, male patient, who had noticed, two months before, the arising of a pruriginous and erithematous halo around two nevi localized on his abdomen. The lesions were found to be atypical on dermoscopic examination and he was submitted to surgical excision of both nevi. Histopathological examination revealed displastic compound melanocytic nevi, surrounded by intraepidermical vesicles and spongiosis. Present report suggests that Meyerson phenomenon does not seem to alter dermoscopic features of nevi.

Investigating the influence of achievement on self-concept using an intra-class design and a comparison of the PASS and SDQ-1 self-concept tests

Background. The formation and measurement of self-concept were the foci of this research. Aims. The study aimed to investigate the influence of achievement on academic self-concept and to compare the Perception of Ability Scale for Students (PASS, Boersma & Chapman, 1992) with the Self-Description Questionnaire-1 (SDQ-1, Marsh, 1988). Sample. The participants were 479 grade 5 (mean age 126.6 months) coeducational Australian students, located in 18 schools. Method. An intra-class research design was used to investigate the influence of frame-of-reference on self-concept development. Results. As students' academic scores rose above their class mean their self-concepts increased and as students' academic scores fell below their class mean their self-concepts decreased. Students' difference from class mean predicted their self-concept scores. This finding was consistently shown across the reading, spelling, and mathematics domains using test and teaching rating data. A comparison between the PASS and the SDQ-1 demonstrated concurrent validity across self-concept domains. Conclusion. The findings support the notions that the social environment is a significant agent that influences self-concept, and that teacher ratings and standardised tests of achievement and the PASS and the SDQ-1 are valid measures for self-concept research.

Differences Between ""Classical"" Risk Factors for Infections Caused by Methicillin-Resistant Staphylococcus aureus (MRSA) and Risk Factors for Nosocomial Bloodstream Infections Caused by Multiple Clones of the Staphylococcal Cassette Chromosome mec Type IV MRSA Strain

OBJECTIVE. To identify risk factors associated with nosocomial bloodstream infections caused by multiple clones of the staphylococcal cassette chromosome mec (SCCmec) type IV strain of methicillin-resistant Staphylococcus aureus (MRSA). DESIGN. An unmatched case-control study (at a ratio of 1 : 2) performed during the period from October 2002 through September 2003. SETTING. A 2,000-bed tertiary care teaching hospital affiliated with the University of Sao Paulo in Sao Paulo, Brazil. METHODS. Case patients (n = 30) were defined either as patients who had a bloodstream infection due to SCCmec type IV strains of MRSA diagnosed at least 48 hours after hospital admission or as neonates with the infection who were born in the hospital. Control patients (n = 60) were defined as patients with SCCmec type III MRSA infection diagnosed at least 48 hours after hospital admission. Genes n = 60 encoding virulence factors were studied in the isolates recovered from case patients, and molecular typing of the SCCmec type IV MRSA isolates was also done by pulsed-field gel electrophoresis and multilocus sequence typing. RESULTS. In multivariate analysis, the following 3 variables were significantly associated with having a nosocomial bloodstream infection caused by SCCmec type IV strains of MRSA: an age of less than 1 year, less frequent use of a central venous catheter (odds ratio [OR], 0.07 [95% confidence interval {CI}, 0.02-0.28]; P = .001), and female sex. A second analysis was performed that excluded the case and Pp. 001 control patients from the neonatal unit, and, in multivariate analysis, the following variables were significantly associated with having a nosocomial bloodstream infection caused by SCCmec type IV strains of MRSA: less frequent use of a central venous catheter (OR, 0.12 [95% CI, 0.03-0.55]; P = .007), lower Acute Physiology and Chronic Health Evaluation II score on admission (OR, 0.14 [95% CI, 0.03-0.61];), less frequent surgery (OR, 0.21 [95% CI, 0.06-0.83];), and female sex (OR, 5.70 [95% CI, 1.32-24.66]; P =.020). P = .009 Pp. 025 Pp). Of the 29 SCCmec type IV MRSA isolates recovered from case patients, none contained the Panton-Valentine leukocidin, gamma-hemolysin, enterotoxin B or C, or toxic shock syndrome toxin-1. All of the isolates contained genes for the LukE-LukD leukocidin and alpha-hemolysin. Genes for enterotoxin A were present in 1 isolate, and genes for beta-hemolysin were present in 3 isolates. CONCLUSIONS. ""Classical"" risk factors do not apply to patients infected with the SCCmec type IV strain of MRSA, which is an important cause of nosocomial bacteremia. This strain infects a patient population that is less ill and has had less frequent invasive procedures than a patient population infected with the multidrug-resistant strain of SCCmec type III MRSA. We found that virulence factors were rare and that Panton-Valentine leukocidin was absent. There were multiple clones of the SCCmec type IV strain in our hospital. Children under 1 year of age were at a higher risk. There was a predominant clone ( sequence type 5) in this patient population.

Narrowed lumen of the right coronary artery in chronic chagasic patients is associated with ischemic lesions of segmental thinnings of ventricles

Thinning of myocardial segments, mainly at the apex and basal posterior region of left ventricle, are frequent lesions in chronic chagasic cardiopathy (CCC), but still without a well determined etiology. Previously we found severe myocardial microvascular dilatation that could cause ischemia in watershed regions. In this study we analyzed whether narrowness in epicardial coronary arteries in CCC might explain these thinned ventricular lesions. Two groups of dilated hearts with similar weights were compared: eleven hearts from patients with CCC versus four hearts from patients with dilated cardiomyopathy (IDCM). As normal controls we studied three non dilated normal weight hearts. There were no atherosclerotic plaques in the main branches of epicardial coronary arteries and cross-sectional luminal areas of proximal and distal segments were histologically measured. It was found that CCC hearts presented a lower mean luminal area in the right coronary artery (RCA) branch than IDCM, in proximal (4.3 +/- 1.4 vs 6.6 +/- 2.0 mm(2); p = 0.02) and in distal (1.6 +/- 1.0 vs 3.4 +/- 0.9 mm(2); p = 0.01) segments, with no statistical differences with normal hearts (2.7 +/- 1.3 and 1.5 +/- 0.3 mm(2)) in proximal (p = 0.2) and distal (p = 0.11) sections. In conclusion thinning of ventricular wall in CCC patients seems to be ischemic lesions in the peripheral territory irrigated by the right coronary artery, possibly due to a steal phenomenon by the left coronary, induced by micro vessels dilatation.

Time- and Fluid-Sensitive Resuscitation for Hemodynamic Support of Children in Septic Shock Barriers to the Implementation of the American College of Critical Care Medicine/Pediatric Advanced Life Support Guidelines in a Pediatric Intensive Care Unit in a Developing World

Objectives: To analyze mortality rates of children with severe sepsis and septic shock in relation to time-sensitive fluid resuscitation and treatments received and to define barriers to the implementation of the American College of Critical Care Medicine/Pediatric Advanced Life Support guidelines in a pediatric intensive care unit in a developing country. Methods: Retrospective chart review and prospective analysis of septic shock treatment in a pediatric intensive care unit of a tertiary care teaching hospital. Ninety patients with severe sepsis or septic shock admitted between July 2002 and June 2003 were included in this study. Results: Of the 90 patients, 83% had septic shock and 17% had severe sepsis; 80 patients had preexisting severe chronic diseases. Patients with septic shock who received less than a 20-mL/kg dose of resuscitation fluid in the first hour of treatment had a mortality rate of 73%, whereas patients who received more than a 40-mL/kg dose in the first hour of treatment had a mortality rate of 33% (P < 0.05.) Patients treated less than 30 minutes after diagnosis of severe sepsis and septic shock had a significantly lower mortality rate (40%) than patients treated more than 60 Minutes after diagnosis (P < 0.05). Controlling for the risk of mortality, early fluid resuscitation was associated with a 3-fold reduction in the odds of death (odds ratio, 0.33; 95% confidence interval, 0.13-0.85). The most important barriers to achieve adequate severe sepsis and septic shock treatment were lack of adequate vascular access, lack of recognition of early shock, shortage of health care providers, and nonuse of goals and treatment protocols. Conclusions: The mortality rate was higher for children older than years, for those who received less than 40 mL/kg in the first hour, and for those whose treatment was not initiated in the first 30 Minutes after the diagnosis of septic shock. The acknowledgment of existing barriers to a timely fluid administration and the establishment of objectives to overcome these barriers may lead to a more successful implementation of the American College of Critical Care Medicine guidelines and reduced mortality rates for children with septic shock in the developing world.

Teleantagonism: A pharmacodynamic property of the primary nociceptive neuron

Previous work from our group showed that intrathecal (i.t.) administration of substances such as glutamate, NMDA, or PGE(2) induced sensitization of the primary nociceptive neuron (PNN hypernociception) that was inhibited by a distal intraplantar (i.pl.) injection of either morphine or dipyrone. This pharmacodynamic phenomenon is referred to in the present work as ""teleantagonism``. We previously observed that the antinociceptive effect of i.t. morphine could be blocked by injecting inhibitors of the NO signaling pathway in the paw (i.pl.), and this effect was used to explain the mechanism of opioid-induced peripheral analgesia by i.t. administration. The objective of the present investigation was to determine whether this teleantagonism phenomenon was specific to this biochemical pathway (NO) or was a general property of the PNNs. Teleantagonism was investigated by administering test substances to the two ends of the PNN (i.e., to distal and proximal terminals; i.pl. plus i.t. or i.t. plus i.pl. injections). We found teleantagonism when: (i) inhibitors of the NO signaling pathway were injected distally during the antinociception induced by opioid agonists; (ii) a nonselective COX inhibitor was tested against PNN sensitization by IL-1 beta; (iii) selective opioid-receptor antagonists tested against antinociception induced by corresponding selective agonists. Although the dorsal root ganglion seems to be an important site for drug interactions, the teleantagonism phenomenon suggests that, in PNNs, a local sensitization spreads to the entire cell and constitutes an intriguing and not yet completely understood pharmacodynamic property of this group of neurons.

GABA(A) receptor blockade in dorsomedial and ventromedial nuclei of the hypothalamus evokes panic-like elaborated defensive behaviour followed by innate fear-induced antinociception

Dysfunction in the hypothalamic GABAergic system has been implicated in panic syndrome in humans. Furthermore, several studies have implicated the hypothalamus in the elaboration of pain modulation. Panic-prone states are able to be experimentally induced in laboratory animals to study this phenomenon. The aim of the present work was to investigate the involvement of medial hypothalamic nuclei in the organization of panic-like behaviour and the innate fear-induced oscillations of nociceptive thresholds. The blockade of GABA(A) receptors in the neuronal substrates of the ventromedial. or dorsomedial hypothalamus was followed by elaborated defensive panic-like reactions. Moreover, innate fear-induced antinociception was consistently elicited after the escape behaviour. The escape responses organized by the dorsomedial and ventromedial hypothalamic nuclei were characteristically more elaborated, and a remarkable exploratory behaviour was recorded during GABA(A) receptor blockade in the medial hypothalamus. The motor characteristic of the elaborated defensive escape behaviour and the patterns of defensive alertness and defensive immobility induced by microinjection of the bicuculline either into the dorsomedial. or into the ventromedial hypothalamus were very similar. This was followed by the same pattern of innate fear-induced antinociceptive response that lasted approximately 40 min after the elaborated defensive escape reaction in both cases. These findings suggest that dysfunction of the GABA-mediated neuronal system in the medial hypothalamus causes panic-like responses in laboratory animals, and that the elaborated escape behaviour organized in both dorsomedial and ventromedial hypothalamic nuclei are followed by significant innate-fear-induced antinociception. Our findings indicate that the GABA(A) receptor of dorsomedial and ventromedial hypothalamic nuclei are critically involved in the modulation of panic-like behaviour. (C) 2009 Elsevier B.V. All rights reserved.

Role of the superior colliculus in the expression of acute and kindled audiogenic seizures in Wistar audiogenic rats

P>Purpose: The role of the superior colliculus (SC) in seizure expression is controversial and appears to be dependent upon the epilepsy model. This study shows the effect of disconnection between SC deep layers and adjacent tissues in the expression of acute and kindling seizures. Methods: Subcollicular transections, ablation of SC superficial and deep layers, and ablation of only the cerebral cortex were evaluated in the Wistar audiogenic rat (WAR) strain during acute and kindled audiogenic seizures. The audiogenic seizure kindling protocol started 4 days after surgeries, with two acoustic stimuli per day for 10 days. Acute audiogenic seizures were evaluated by a categorized seizure severity midbrain index (cSI) and kindled seizures by a severity limbic index (LI). Results: All subcollicular transections reaching the deep layers of the SC abolished audiogenic seizures or significantly decreased cSI. In the unlesioned kindled group, a reciprocal relationship between limbic and brainstem pattern of seizures was seen. The increased number of stimuli provoked an audiogenic kindling phenomenon. Ablation of the entire SC (ablation group) or of the cerebral cortex only (ctx-operated group) hampered the acquisition of limbic behaviors. There was no difference in cSI and LI between the ctx-operated and ablation groups, but there was a difference between ctx-operated and the unlesioned kindled group. There was also no difference in cSI between SC deep layer transection and ablation groups. Results of histologic analyses were similar for acute and kindled audiogenic seizure groups. Conclusions: SC deep layers are involved in the expression of acute and kindled audiogenic seizure, and the cerebral cortex is essential for audiogenic kindling development.

A Simple and Efficient Device for Demonstrating Cross-sectional Anatomy of the Head

Described in this article is a novel device that facilitates study of the cross-sectional anatomy of the human head. In designing our device, we aimed to protect sections of the head from the destructive action of handling during anatomy laboratory while also ensuring excellent visualization of the anatomic structures. We used an electric saw to create 15-mm sections of three cadaver heads in the three traditional anatomic planes and inserted each section into a thin, perforated display box made of transparent acrylic material. The thin display boxes with head sections are kept in anatomical order in a larger transparent acrylic storage box containing formaldehyde solution, which preserves the specimens but also permits direct observation of the structures and their anatomic relationships to each other. This box-within-box design allows students to easily view sections of a head in its anatomical position as well as to examine internal structures by manipulating individual display boxes without altering the integrity of the preparations. This methodology for demonstrating cross-section anatomy allows efficient use of cadaveric material and technician time while also giving learners the best possible handling and visualization of complex anatomic structures. Our approach to teaching cross-sectional anatomy of the head can be applied to any part of human body, and the value of our device design will only increase as more complicated understandings of cross-sectional anatomy are required by advances and proliferation of imaging technology. Anat Sci Educ 3: 141-143, 2010. (C) 2010 American Association of Anatomists.

Analysis of the Ontogenetic Variation in the Venom Proteome/Peptidome of Bothrops jararaca Reveals Different Strategies to Deal with Prey

Previous studies have demonstrated that the pharmacological activities displayed by Bothrops jararaca venom undergo a significant ontogenetic shift. Variation in the venom proteome is a well-documented phenomenon; however, variation in the venom peptidome is poorly understood. We report a comparative proteomic and peptidomic analysis of venoms from newborn and adult specimens of B. jararaca and correlate it with the evaluation of important venom features. We demonstrate that newborn and adult venoms have similar hemorrhagic activities, while the adult venom has a slightly higher lethal activity in mice; however, the newborn venom is extremely more potent to kill chicks. The coagulant activity of newborn venom upon human plasma is 10 times higher than that of adult venom. These differences were clearly reflected in their different profiles of SDS-PAGE, gelatin zimography, immunostaining using specific antibodies, glycosylation pattern, and concanavalin A-binding proteins. Furthermore, we report for the first time the analysis of the peptide fraction of newborn and adult venoms by MALDI-TOF mass spectrometry and LC-MS/MS, which revealed different contents of peptides, while the bradykinin potentiating peptides (BPPs) showed rather similar profiles and were detected in the venoms showing their canonical sequences and also novel sequences corresponding to BPPs processed from their precursor protein at sites so far not described. As a result of these studies, we demonstrated that the ontogenetic shift in diet, from ectothermic prey in early life to endothermic prey in adulthood, and in animal size are associated with changes in the venom proteome in B. jararaca species.

Stay-green: A consequence of the balance between supply and demand for nitrogen during grain filling?

Retention of green leaf area in grain sorghum under post-anthesis drought, known as stay-green, is associated with greater biomass production, lodging resistance and yield. The stay-green phenomenon can be examined at a cell, leaf, or whole plant level. At a cell level, the retention of chloroplast proteins such as LHCP2, OEC33 and Rubisco until late in senescence has been reported in sorghum containing the KS19 source of stay-green, indicating that photosynthesis may be maintained for longer during senescence in these genotypes. At a leaf level, longevity of photosynthetic apparatus is intimately related to nitrogen (N) status. At a whole plant level, stay-green can be viewed as a consequence of the balance between N demand by the grain and N supply during grain filling. To examine some of these concepts, nine hybrids varying in the B35 and KS19 sources of stay-green were grown under a postanthesis water deficit. Genotypic variation in delayed onset and reduced rate of leaf senescence were explained by differences in specific leaf nitrogen (SLN) and N uptake during grain filling. Matching N supply from age-related senescence and N uptake during grain tilling with grain N demand found that the shortfall in N supply for grain filling was greater in the senescent than stay-green hybrids, resulting in more accelerated leaf senescence in the former. We hypothesise that increased N uptake by stay-green hybrids is a result of greater biomass accumulation during grain filling in response to increased sink demand (higher grain numbers) which, in turn, is the result of increased radiation use efficiency and transpiration efficiency due to higher SLN. Delayed leaf senescence resulting from higher SLN should, in turn, allow snore carbon and nitrogen to be allocated to the roots of stay-green hybrids during grain filling, thereby maintaining a greater capacity to extract N from the soil compared with senescent hybrids.

History of the events leading to the formulation of the apoptosis concept

Histological studies of ischaemic liver injury performed between 1962 and 1964 distinguished two types of cell death: classical necrosis, and a process involving conversion of scattered cells into small round masses of cytoplasm that often contained specks of condensed nuclear chromatin. Enzyme histochemistry demonstrated rupture of lysosomes in the former, but preservation of lysosomes in the latter. Similar small round masses were also observed sparsely in normal liver. Electron microscopy showed that the small round bodies resulted from cellular condensation and budding, that they were bounded by membranes and contained intact organelles, and that they were phagocytosed and digested by resident tissue cells, including epithelial cells. In work done in association with Jeffrey Searle, the process was found to occur spontaneously in a variety of malignant tumours and to be enhanced in squamous cell carcinomas of skin responding to radiotherapy. During 1971-1972, I collaborated with Andrew Wyllie and Alastair Currie while on sabbatical leave in Scotland. The newly defined type of cell death was shown to be regulated by hormones in the adrenal cortex and in breast carcinomas. Further, review of published electron micrographs of the cell death known to play an essential role in normal development revealed the same morphological pattern. We proposed that this distinctive phenomenon subserves a general homoeostatic function and suggested it be called apoptosis. © 2002 Elsevier Science Ireland Ltd. All rights reserved.