In vivo Doppler optical coherence tomography of mucocutaneous telangiectases in hereditary hemorrhagic telangiectasia

BACKGROUND: Hereditary hemorrhagic telangiectasia is characterized by mucocutaneous telangiectases and visceral arteriovenous malformations. Knowledge is limited concerning the development hemodynamics of mucocutaneous telangiectases. Doppler optical coherence tomography can demonstrate microvascular blood flow at flow rates as low as 20 microm/second, which is up to approximately 100 times more sensitive than Doppler US. The aims of this study were to collect in vivo Doppler optical coherence tomography images of mucocutaneous telangiectases and normal surrounding mucosa and skin, and to gain experience for an in vivo GI endoscopic study. It was hypothesized that visibly normal areas may have occult telangiectases and that mucocutaneous telangiectases that have bled may have a higher rate of blood flow than mucocutaneous telangiectases with no history of bleeding. METHODS: Twelve patients with hereditary hemorrhagic telangiectasia and mucocutaneous telangiectases were studied. Two to 3 visible mucocutaneous telangiectases on the digits, lips, and tongue were imaged with Doppler optical coherence tomography, along with visually normal surrounding areas at each site. The Doppler optical coherence tomography images were obtained in 0.5 second by using 1310 nm light. RESULTS: A total of 67 mucocutaneous telangiectases from the 12 patients were imaged (38 digit, 16 lip, 13 tongue). Blood flow was demonstrated within every mucocutaneous telangiectasis imaged. Doppler optical coherence tomography did not identify any abnormal vasculature within visually normal areas. Mucocutaneous telangiectases with a history of bleeding (n = 18) were situated closer to the surface, compared with mucocutaneous telangiectases with no bleeding history (n = 49), but there was no difference in the Doppler flow appearance. CONCLUSIONS: Visually normal areas in patients with hereditary hemorrhagic telangiectasia did not appear to have abnormal vasculature. Mucocutaneous telangiectases with a history of bleeding were more superficial but were otherwise similar to mucocutaneous telangiectases with no bleeding history.     

Nodular regenerative hyperplasia of the liver associated with macroglobulinemia: A clue to the pathogenesis

Nodular regenerative hyperplasia of the liver is an infrequent condition characterized by transformation of the hepatic parenchyma into nodules with only mild fibrosis. Little is known about the etiology except that there is usually an underlying chronic disease, such as Felly's syndrome, which antedates the development of clinical liver disease. It is poorly understood how the associated diseases contribute to the pathogenesis of nodular regenerative hyperplasia. Presented are four cases of nodular regenerative hyperplasia in which macroglobulinemia was also present. This new association suggests to us a hypothesis for the pathogenesis of nodular regenerative hyperplasia.

Histologic examination of the livers in these and other cases of nodular regenerative hyperplasia reveals widespread obliteration of the small portal veins. Postmortem angiography of one liver in the present series demonstrated that the nodules were well perfused and that the atrophic areas were poorly perfused with portal blood. This supports the view that atrophy of lobules results from a lack of portal blood supply and that nodules develop from lobules well supplied with portal blood. In each of the clinical conditions associated with nodular regenerative hyperplasia, including macroglobulinemia, inflammatory or thrombotic vascular lesions are found in many organs. Therefore, nodular regenerative hyperplasia may be the hepatic expression of a more widespread vascular disease.     

Neural Network Analysis of Anal Sphincter Repair

PURPOSE: Prediction of success after anterior sphincter repair for incontinence is difficult. Standard multivariate analysis techniques have only 75 to 80 percent accuracy. Artificial intelligence, including artificial neural networks, has been used in the analysis of complex clinical data and has proved to be successful in predicting the outcome of other surgical procedures. Using a neural network algorithm, we have assessed the probability of success after anterior sphincter repair. METHODS: Prospective anorectal physiology data of 72 patients undergoing anterior sphincter repair was collected between 1995 and 1999. Complete data sets of 75 percent of the series were used to train an artificial neural network; the remaining 25 percent were used for data validation. The output was continence grading, ranging from 0 to 4 (worse to continent). RESULTS: The outcome at 3, 6, and 12 months postoperatively was obtained and assessed. The best correlation between actual data value and artificial neural network value was found at 12 months (r = 0.931; P = 0.0001). Clear correlations also were found at three months (r = 0.898; P = 0.0001) and six months (r = 0.742; P = 0.002). Results of applying a net to details excluding pudendal nerve latency were poor. CONCLUSIONS: Artificial neural networks are more accurate (93 percent correlation) than standard statistics (75 percent) when applied to the prediction of outcome after anterior sphincter repair. This assessment also confirms the usefulness of pudendal latency in the prediction of anterior sphincter repair outcome. The results obtained highlight the obvious usefulness of artificial neural networks, which could now be used in a prospective evaluation for application of the technique.     

Effects of level of processing but not of task enactment on recognition memory in a case of developmental amnesia

We report the performance in four recognition memory experiments of Jon, a young adult with early-onset developmental amnesia whose episodic memory is gravely impaired in tests of recall, but seems relatively preserved in tests of recognition, and who has developed normal levels of performance in tests of intelligence and general knowledge. Jon's recognition performance was enhanced by deeper levels of processing in comparing a more meaningful study task with a less meaningful one, but not by task enactment in comparing performance of an action with reading an action phrase. Both of these variables normally enhance episodic remembering, which Jon claimed to experience. But Jon was unable to support that claim by recollecting what it was that he remembered. Taken altogether, the findings strongly imply that Jon's recognition performance entailed little genuine episodic remembering and that the levels-of-processing effects in Jon reflected semantic, not episodic, memory.     

Age-dependent neurological phenotypes in a mouse model of PRRT2-related diseases

Paroxysmal kinesigenic dyskinesia is an episodic movement disorder caused by dominant mutations in the proline-rich transmembrane protein PRRT2, with onset in childhood and typically with improvement or resolution by middle age. Mutations in the same gene may also cause benign infantile seizures, which begin in the first year of life and typically remit by the age of 2 years. Many details of PRRT2 function at the synapse, and the effects of mutations on neuronal excitability in the pathophysiology of epilepsy and dyskinesia, have emerged through the work of several groups over the last decade. However, the age dependence of the phenotypes has not been explored in detail in transgenic models. Here, we report our findings in heterozygous and homozygous Prrt2 knockout mice that recapitulate the age dependence of dyskinesia seen in the human disease. We show that Prrt2 deletion reduces the levels of synaptic proteins in a dose-dependent manner that is most pronounced at postnatal day 5 (P5), attenuates at P60, and disappears by P180. In a test for foot slippage while crossing a balance beam, transient loss of coordination was most pronounced at P60 and less prominent at age extremes. Slower traverse time was noted in homozygous knockout mice only, consistent with the ataxia seen in rare individuals with biallelic loss of function mutations in Prrt2. We thus identify three age-dependent phenotypic windows in the mouse model, which recapitulate the pattern seen in humans with PRRT2-related diseases.

     

Cyclic mechanical stimulation rescues achilles tendon from degeneration in a bioreactor system

Physiotherapy is one of the effective treatments for tendinopathy, whereby symptoms are relieved by changing the biomechanical environment of the pathological tendon. However, the underlying mechanism remains unclear. In this study, we first established a model of progressive tendinopathy‐like degeneration in the rabbit Achilles. Following ex vivo loading deprivation culture in a bioreactor system for 6 and 12 days, tendons exhibited progressive degenerative changes, abnormal collagen type III production, increased cell apoptosis, and weakened mechanical properties. When intervention was applied at day 7 for another 6 days by using cyclic tensile mechanical stimulation (6% strain, 0.25 Hz, 8 h/day) in a bioreactor, the pathological changes and mechanical properties were almost restored to levels seen in healthy tendon. Our results indicated that a proper biomechanical environment was able to rescue early‐stage pathological changes by increased collagen type I production, decreased collagen degradation and cell apoptosis. The ex vivo model developed in this study allows systematic study on the effect of mechanical stimulation on tendon biology. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:1888–1896, 2015.