Hypothesis: Is congestive cardiomyopathy caused by a hyperreactive myocardial microcirculation (Microvascular spasm)?

In most congested, dilated cardiomyopathies, pathologic analysis reveals focal myocardial necrosis, microscopic scarring, interstitial fibrosis, and myocellular hypertrophy. The focal nature of these processes indicates that the cardiomyopathies may not be due to diffuse abnormalities of cardiac muscle cells, at least in the early stages, but that the changes may represent focal events affecting discrete, small volumes of tissue. Experimental evidence of microvascular hyperreactivlty (spasm), both In the hereditary cardiomyopathy of the Syrian hamster and in the acquired cardiomyopathy of the hypertensive-diabetic rat, suggests that transient spasm of the myocardial microcirculation may lead to focal myocellular necrosis and scarring, which then causes the unaffected myocardial cells to undergo compensatory hypertrophy in order to normalize the increased load per unit of myocardium. When enough myocardium is lost and the compensatory hypertrophy results in decreased contractility, congestive heart failure ensues as a systemic response to altered ventricular function. The efficacy of verapamil therapy in the Syrian hamster in preventing microvascular spasm, cell necrosis, and the subsequent development of a cardiomyopathy has provided hope that similar preventive treatment can be applied to patients with early stages of cardiomyopathy.     

Treatment of residual common bile duct stones after cholecystectomy

This study was conducted to determine the occurrence of "open" residual common bile duct stones after cholecystectomy to establish predisposing factors and possible alternative treatments. Correct diagnosis of choledocholithiasis before or during surgery, adequate exploration of the common bile duct, and suitable selection of technical procedures are the most important points in preventing retained CBD stones. If these occur, an adequate alternative treatment may prove helpful. Classical "clysis" of the bile duct is least recommended because of its high failure rate. The best method of chemical dissolution seems to be the use of mono-octanoin with 60% good results and a no-response rate of 30-40%. Instrumental extraction has been reported to be very successful (80-98%). Endoscopic sphincterotomy is currently the most frequently employed procedure for retained CBD stones, especially in poor risk patients. The reported success rate is 82-93% according to literature, with an extremely low mortality (0.2%). Reoperation should be resorted to only if all the other methods fail. Sphincteroplasty or choledochoduodenostomy, whenever indicated, are good alternative operations, with a mortality rate of approx. 3.5%.     

Novel Application of Tissue Doppler Imaging: A Preliminary Observational Study

Tissue Doppler imaging was used with transthoracic and transesophageal echocardiography to determine its clinical usefulness beyond visualization of ventricular wall motion. Thirteen novel applications were found: acoustically difficult transthoracic studies, thrombus, mitral chordal motion, shunt detection using saline contrast, spontaneous echo contrast, intra-aortic balloon pump position and function, endocarditis (prosthetic and native), valve strands (prosthetic and native), mobile aortic atheroma, prosthetic valve motion, aortic valve motion in the presence of a calcified aortic annulus, systolic anterior motion of the mitral valve, and cardiac tumors. Tissue Doppler imaging directly affected the ability to make difficult diagnostic decisions with increased confidence and reduced the need for additional studies.     

Effects of glucose-insulin-potassium infusion on the angina response during treadmill exercise.

The effects of glucose-insulin-potassium (GIK) and placebo normal saline (S) infusion on treadmill-walking time to angina, ST depression, heart rate (HR), systolic blood pressure (SBP), rate pressure product (RPP), blood glucose (G), lactate (L) and free fatty acids (FFA) were studied in 14 non diabetic patients with exertional angina. For the whole group, the post-GIK walking time to angina (393 +/- 33 sec, mean +/- SEM) was greater than the values during control GIK (319 +/- 20 sec, p less than 0.02) and post-S infusion (334 +/- sec, p less than 0.05), but circulatory and ST responses were similar in post-GIK and post-S studies. 7 of the 14 patients experienced significantly greater improvement in exercise tolerance following GIK (467 +/- 39 sec) in comparison to control GIK (313 +/- 29 sec, p less than 0.001) and post-S infusion (334 +/- 32 sec, p less than 0.005) and exercised to a higher HR, SBP and RPP after GIK than after S infusion. At the onset of angina these patients had similar ST-segment depression before and after GIK but when ST segments were assessed after GIK at the same exercise duration when angina had occurred during the control and post-S studies, there was significantly less ST depression (p less than 0.01). Of the remaining 7 patients exercise tolerance following GIK deteriorated in 3, remained unchanged in 2 and increased by 12 and 48 sec in 2 patients in comparison to post-S values. Comparison of post-GUK and post-S values for G, L and FFA for the whole group showed significantly lower resting values of FFA and post-exercise values of G following GIK infusion. The differences in clinical and circulatory responses between patients who improved and those who did not improve following GIK were not related to the angiographically determined severity of coronary artery disease or to GIK-induced metabolic changes. Results suggest that some patients with angina pectoris do benefit from GIK infusion but the response in a given patient to this therapeutic modality is unpredictable.     

Echocardiographic features of carcinoid heart disease

We reviewed the records of the Mayo Clinic patients with known carcinoid syndrome in whom echocardiographic studies had been done. Nineteen patients had M-mode and 2-dimensional echocardiographic examinations, and 1 patient had an M-mode examination only. Of the 20 patients, 8 had no evidence by echocardiogram of carcinoid heart disease; 2 had changes in the tricuspid valve echogram suggestive of early carcinoid heart disease, and the other 10 patients had the following distinctive echocardiographic findings: (1) the pattern of right ventricular volume overload (enlarged right ventricle with abnormal septal motion); (2) abnormal right-sided valves, including (a) a striking appearance of the tricuspid valve, the leaflets appearing thickened, retracted, and fixed in a semiopen position throughout the cardiac cycle, and (b) thickened, retracted pulmonic valve cusps, when visualized; and (3) the left-sided valves and chambers rarely involved. These echocardiographic features are distinctive of advanced carcinoid heart disease and correlate closely with pathologic findings.     

Task-related motivation and academic achievement in children and adolescents with ADHD

European Child & Adolescent Psychiatry - Academic impairment in individuals with attention-deficit/hyperactivity disorder (ADHD) is in part due to reduced motivation for academic tasks, which...     

Deep Artificial Neural Networks Reveal a Distributed Cortical Network Encoding Propositional Sentence-Level Meaning

Understanding how and where in the brain sentence-level meaning is constructed from words presents a major scientific challenge. Recent advances have begun to explain brain activation elicited by sentences using vector models of word meaning derived from patterns of word co-occurrence in text corpora. These studies have helped map out semantic representation across a distributed brain network spanning temporal, parietal, and frontal cortex. However, it remains unclear whether activation patterns within regions reflect unified representations of sentence-level meaning, as opposed to superpositions of context-independent component words. This is because models have typically represented sentences as “bags-of-words” that neglect sentence-level structure. To address this issue, we interrogated fMRI activation elicited as 240 sentences were read by 14 participants (9 female, 5 male), using sentences encoded by a recurrent deep artificial neural-network trained on a sentence inference task (InferSent). Recurrent connections and nonlinear filters enable InferSent to transform sequences of word vectors into unified “propositional” sentence representations suitable for evaluating intersentence entailment relations. Using voxelwise encoding modeling, we demonstrate that InferSent predicts elements of fMRI activation that cannot be predicted by bag-of-words models and sentence models using grammatical rules to assemble word vectors. This effect occurs throughout a distributed network, which suggests that propositional sentence-level meaning is represented within and across multiple cortical regions rather than at any single site. In follow-up analyses, we place results in the context of other deep network approaches (ELMo and BERT) and estimate the degree of unpredicted neural signal using an “experiential” semantic model and cross-participant encoding.SIGNIFICANCE STATEMENT A modern-day scientific challenge is to understand how the human brain transforms word sequences into representations of sentence meaning. A recent approach, emerging from advances in functional neuroimaging, big data, and machine learning, is to computationally model meaning, and use models to predict brain activity. Such models have helped map a cortical semantic information-processing network. However, how unified sentence-level information, as opposed to word-level units, is represented throughout this network remains unclear. This is because models have typically represented sentences as unordered “bags-of-words.” Using a deep artificial neural network that recurrently and nonlinearly combines word representations into unified propositional sentence representations, we provide evidence that sentence-level information is encoded throughout a cortical network, rather than in a single region.     

Odontoblasts in odontogenic tumors

Odontoblasts are secretory cells displaying epithelial and mesenchymal features, which exist in a monolayer at the interface between the dentin and pulp of a tooth. During embryogenesis, these cells form a dentin shell and throughout life continue to produce dentin while, also acting as sensor cells helping to mediate tooth sensitivity. In this process, odontoblasts are forced to migrate inwards, resulting in an ongoing loss of pulp volume. Correspondingly, there is also a decrease in the surface area of the dentin which supports the odontoblast cell layer. As these events transpire, odontoblasts maintain a tightly controlled monolayer relationship to each other as well as to their dentin substrate. Stability is maintained laterally by epithelial attachment structures and transversely by complex cytoplasmic extensions into the supporting dentin. As a result, it is not possible for the layer to buckle to relieve the mechanical stresses, which develop during the inward migration. A theoretical consequence of this distinctive self-generated niche is the development of long term compressive stresses within the odontoblast population. We present a mechanobiology model, which causally relates the increase in cellular compressive stresses to contact inhibition of proliferation. We link this hypothesis to the observation that there are no reports of pulpal odontoblasts showing neoplasia or acquisition of changes suggestive of a pre-neoplastic phenotype.