Cholesterol crystal embolization to the digestive system: characterization of a common,yet overlooked presentation of atheroembolism

In the 1359 published patients with multiorgan cholesterol crystal embolism (CCE), the digestive system seems to be the third most frequently affected system. Yet, this system received hitherto only little attention in the medical literature. Therefore, the aim of the present study was to clinically characterize the subset of patients with CCE involving the digestive system, based on our institutional experience and a review of the literature. Cases with CCE in a 7-yr period (1995-2001) were sought in the computerized records of our medical center. Of the CCE patients, those with digestive system involvement that could be related to CCE were included in this study. The clinical features of CCE were determined and compared with those found in published series. Fourteen cases with CCE were identified, giving an annual incidence of 0.8 per 10(5). Digestive system involvement was found in five (36%) of the 14 patients. All five patients had established atherosclerosis. Precipitating factors were vascular manipulations or anticoagulation treatment in four of these five patients. Two patterns of disease appeared: acute catastrophic multiorgan disorder with poor prognosis and chronic and more indolent GI disease. Abdominal pain, GI bleeding, fever, and diarrhea were the most common manifestations, resulting from bowel infarction, mucosal ulcerations, hepatocellular liver disorder, and/or pancreatitis. CCE is a systemic disorder with a frequent involvement of the digestive system and protean clinical manifestations. It should, therefore, be considered in any gastroenterological patient with atherosclerosis and recent vascular manipulations or systemic anticoagulation.     

Analysis of rearranged immunoglobulin genes indicating a process of clonal evolution in chronic lymphocytic leukaemia

Summary. Chronic lymphocytic leukaemia (CLL) is known to be a stable monoclonal neoplasm. In contrast to early studies demonstrating no more than two hybridizing immunoglobulin heavy chain bands corresponding to the two expected alleles, we have demonstrated an unexpected multiband pattern when the HindIII-digested DNA samples from 38 CLL patients were analysed by Southern blot hybridization using J_H and Cμ gene probes. In order to characterize the genetic basis for the multiband pattern, we molecularly cloned the immunoglobulin heavy chain genes of one of the patients whose leukaemic DNA sample demonstrated three hybridizing J_H bands and a loss of the germline band. The cloned rearranged immunoglobulin genes could be divided, based on the restriction mapping and the hybridization with the various probes, into two basic patterns representing two alleles. In one of the cloned rearranged immunoglobulin genes a secondary rearrangement occurred that resulted in the addition of 300 base-pair long sequence into the switch region, and the creation of a HindIII restriction site.
The results of the study suggest that clonal evolution occurs in some CLL, and that many of these neoplasms are indeed oligoclonal due to the accumulation of secondary genetic changes.     

Serum amyloid type a may be a predictor of restenosis

Background: Elevation of acute phase proteins [C-reactive protein (CRP) and serum amyloid type A (SAA)] has been demonstrated in unstable angina with an adverse clinical prognosis. Hypothesis: The study was undertaken to determine the effect of angioplasty on the levels of SAA and the correlation with postangioplasty restenosis. Methods: In a university-affiliated tertiary medical center, a prospective case study was undertaken in 55 patients who underwent successful percutaneous transluminal coronary angioplasty (PTCA) of a single coronary lesion for angina pectoris. Three groups of patients were clinically characterized according to Braunwald's classification of anginal syndrome: Group A: class III; Group B: class I; Group C: stable angina. Serum amyloid type A was measured by an ELISA method before PICA and after 24 h, 1, and 3 months. Patients were followed clinically for 12 months. A thallium stress perfusion scan was performed 3 months after PTCA and coronary angiography was repeated in patients with an abnormal thallium perfusion scan. Results: Serum amyloid type A levels >100 m?/ml could identify Group A patients with a high sensitivity and specificity (r = 0.85 and 0.86, respectively). Of the patients studied. 75% increased their SAA level 24 h after angioplasty. An increase of SAA by >100% was associated with an increased risk of restenosis, with a relative risk of 6.4 (p < 0.05). Conclusion: Increased levels of SAA characterize patients with unstable angina pectoris with a high specificity and sensitivity. Levels of SAA that increase > 100% 24 h after angioplasty may serve as a marker of restenosis.     

Cerebellar Inhibitory Output Shapes the Temporal Dynamics of Its Somatosensory Inferior Olivary Input

The cerebellum is necessary and sufficient for the acquisition and execution of adaptively timed conditioned motor responses following repeated paired presentations of a conditioned stimulus and an unconditioned stimulus. The underlying plasticity depends on the convergence of conditioned and unconditioned stimuli signals relayed to the cerebellum by the pontine nucleus and the inferior olive (IO), respectively. Adaptive timing of conditioned responses relies on the correctly predicted onset of the unconditioned stimulus, usually a noxious somatosensory stimulus. We addressed two questions: First, does the IO relay information regarding the duration of somatosensory stimuli to the cerebellum? Multiple-unit recordings from the IO of anesthetized rats that received periorbital airpuffs of various durations revealed that sustained somatosensory stimuli are invariably transformed into phasic IO outputs. The phasic response was followed by a post-peak depression in IO activity as compared to baseline, providing the cerebellum with a highly synchronous signal, time-locked to the stimulus’ onset. Second, we sought to examine the involvement of olivocerebellar interactions in this signal transformation. Cerebello-olivary inhibition was interrupted using temporary pharmacological inactivation of cerebellar output nuclei, resulting in more sustained (i.e., less synchronous) IO responses to sustained somatosensory stimuli, in which the post-peak depression was substituted with elevated activity as compared to baseline. We discuss the possible roles of olivocerebellar negative-feedback loops and baseline cerebello-olivary inhibition levels in shaping the temporal dynamics of the IO’s response to somatosensory stimuli and the consequences of this shaping for cerebellar plasticity and its ability to adapt to varying contexts.     

Biomechanics of milk extraction during breast-feeding

How do infants extract milk during breast-feeding? We have resolved a century-long scientific controversy, whether it is sucking of the milk by subatmospheric pressure or mouthing of the nipple–areola complex to induce a peristaltic-like extraction mechanism. Breast-feeding is a dynamic process, which requires coupling between periodic motions of the infant’s jaws, undulation of the tongue, and the breast milk ejection reflex. The physical mechanisms executed by the infant have been intriguing topics. We used an objective and dynamic analysis of ultrasound (US) movie clips acquired during breast-feeding to explore the tongue dynamic characteristics. Then, we developed a new 3D biophysical model of the breast and lactiferous tubes that enables the mimicking of dynamic characteristics observed in US imaging during breast-feeding, and thereby, exploration of the biomechanical aspects of breast-feeding. We have shown, for the first time to our knowledge, that latch-on to draw the nipple–areola complex into the infant mouth, as well as milk extraction during breast-feeding, require development of time-varying subatmospheric pressures within the infant’s oral cavity. Analysis of the US movies clearly demonstrated that tongue motility during breast-feeding was fairly periodic. The anterior tongue, which is wedged between the nipple–areola complex and the lower lips, moves as a rigid body with the cycling motion of the mandible, while the posterior section of the tongue undulates in a pattern similar to a propagating peristaltic wave, which is essential for swallowing.Breast-feeding is strongly publicized and encouraged by many societies and communities. It is well accepted that breast milk provides the infant both nutrients and immunities required for growth and development during the first months after birth. It is less known that breast-fed infants exercise and prepare their orofacial muscles for future tasks of speaking and chewing (1), and also have higher oxygen saturation than bottle-fed infants (2). Breast-feeding is the outcome of a dynamic synchronization between oscillation of the infant’s mandible, rhythmic motility of the tongue, and the breast milk ejection reflex that drives maternal milk toward the nipple outlet. First, the infant latches onto the breast and nipple so that the nipple, areola, and underlying mammary tissue and lactiferous ducts are drawn into the infant’s mouth with the nipple tip extended as far as the hard–soft palate junction (HSPJ). Then, the infant moves its mandible up and down, compressing the areola and the underlying lactiferous ducts with its gums in a suckling process that extracts the milk into its mouth (3, 4). Simultaneous with compression, spontaneous undulating motions of the infant tongue channel the milk posteriorly and trigger the swallowing reflex (5). During breast-feeding, suckling, swallowing, and breathing are coordinated by the central nervous system in a way that allows for the infant’s continuous feeding without breathing interruptions (2, 6, 7).The physical mechanisms that enable the infant to extract milk from the breast have intrigued scientists for more than a century (8). The two proposed mechanisms that have been a subject of scientific controversy to this day are (i) sucking—emptying of the nipple–breast contents by development of subatmospheric pressures within the infant oral cavity (9–12) and (ii) mouthing—squeezing out of the nipple–areola contents by compression between the jaws or other mouth parts (3). With the appearance of cine–X-ray and ultrasound (US) imaging modalities, a significant role was also attributed to tongue undulation which was naturally referred to as “tongue peristalsis” while chewing the nipple (13, 14). However, advanced computational modeling has not yet been used along with imaging data to perform hypothesis testing on the underlying explanations of the suckling behavior during breast-feeding.We have explored the physical aspects of infant feeding via noninvasive visualizations of the moving components in the oral cavity and a biophysical model. An objective dynamic analysis of submental US imaging of the midsagittal cross-section of the oral cavity during infant feeding was used to study the dynamic characteristics of tongue motion with respect to the rigid upper palate. A 3D fluid–structure interaction (FSI) biophysical model was developed to simulate milk extraction during breast-feeding.     

Promoting head CT exams in the emergency department triage using a machine learning model

Neuroradiology - In this study, we aimed to develop a novel prediction model to identify patients in need of a non-contrast head CT exam during emergency department (ED) triage. We collected data...     

Fine‐tuning of the automated [18F]PSMA‐1007 radiosynthesis

Radiolabeled prostate‐specific membrane antigen (PSMA) targeting PET‐tracers have become desirable radiopharmaceuticals for the imaging of prostate cancer (PC). Recently, the PET radiotracer [¹⁸F]PSMA‐1007 was introduced as an alternative to [⁶⁸Ga]Ga‐PSMA‐11, for staging and diagnosing biochemically recurrent PC. We incorporated a one‐step procedure for [¹⁸F]PSMA‐1007 radiosynthesis, using both Synthra RNplus and GE TRACERlab FxFN automated modules, in accordance with the recently described radiolabeling procedure. Although the adapted [¹⁸F]PSMA‐1007 synthesis resulted in repeatable radiochemical yields (55 ± 5%, NDC), suboptimal radiochemical purities of 87 ± 8% were obtained using both modules. As described here, modifications made to the radiolabeling and the solid‐phase extraction purification steps reduced synthesis time to 32 minutes and improved radiochemical purity to 96.10%, using both modules, without shearing the radiochemical yield.