Diagnostic modalities for the evaluation of anomalous left main coronary arteries

Anomalous coronary arteries are rare and usually identified as an incidental finding during cardiac catheterization. The particular difficulty with cardiac catheterization techniques is not necessarily the presence of the anomalous coronary artery, but its anatomic course. Oftentimes, surgical intervention is necessary once these anomalies are discovered. The identification and anatomic characterization of anomalous coronary arteries has been significantly advanced with the use of current diagnostic noninvasive imaging modalities. We present 3 cases of an anomalous left main coronary artery that arises from the right sinus of Valsalva. Noninvasive imaging methods provided a clear anatomic course of the anomalous vessel.     

Initial multicenter experience with a novel distal protection filter during carotid artery stent implantation.

Atheroembolization resulting in transient or permanent neurologic impairment is the most common complication of catheter-based percutaneous carotid artery intervention. Protection of the distal cerebral vasculature during carotid stent implantation may enhance procedural safety. Carotid stent implantation with distal cerebral protection using the FilterWire EX was performed in 35 consecutive patients undergoing 36 procedures at six centers. The FilterWire was delivered and deployed successfully in all 36 cases, and embolic material was retrieved from 74% of procedures. The 30-day rate of major adverse events (death, major or minor stroke) was 0%. Transient ipsilateral periprocedural neurologic ischemia developed in two patients (5.7%), both resolving within 30 min. Distal cerebral protection with the FilterWire during carotid stenting is feasible and safe, results in capture and extraction of atheroembolic debris in the majority of patients while affording uninterrupted cerebral perfusion, and in this initial multicenter experience was associated with a high rate of procedural success without major complications.     

sE‐selectin for stratifying outcome in rheumatoid arthritis

Objectives

To determine the usefulness of sE‐selectin as a marker for early diagnosis and stratification of rheumatoid arthritis.

Methods

We investigated several markers of disease activity, including circulating adhesion molecules and other standard laboratory tests, in a 2–3 year followup analysis of patients with rheumatoid arthritis.

Results

The mean ± SD levels of sE‐selectin (91.68 ± 31.8 ng/ml versus 49.83 ± 14.76 ng/ml) and rheumatoid factor (375.7 ± 394.4 U versus 44.66 ± 37.63 U) were strongly elevated in severe (n = 15) versus mild (n = 7) courses of disease. Statistical calculation of mean and standard deviation revealed that sE‐selectin represents a highly significant marker for the presence of persistent and aggressive disease over time, regardless of therapeutic intervention and observation time points (P = 0.0004). Notably, regression analysis identified constant values for all parameters analyzed and, therefore, a stable course of the disease could be predicted from the beginning.

Conclusion

sE‐selectin appears to be a powerful marker to predict the severity of rheumatoid arthritis.

     

Diminished peripheral blood memory B cells and accumulation of memory B cells in the salivary glands of patients with Sjögren's syndrome

OBJECTIVE: To delineate the mechanism of the abnormalities in B cell biology found in patients with primary Sj?gren's syndrome (SS). METHODS: The distribution of peripheral B cell subpopulations in 21 patients with primary SS was analyzed by immunofluorescence labeling and flow cytometry. Immunoglobulin rearrangements were analyzed in single B cells isolated from the peripheral blood and parotid glands by fluorescence-activated cell sorting. RESULTS: A significant reduction in the number of peripheral CD27+ memory B cells was found in SS patients, including a significantly reduced number of CD27+/IgD+/IgM+/CD5+ memory B cells. Remarkably, SS patients with secondary lymphoma uniquely exhibited an increase in CD27-expressing peripheral B cells, including CD27(high) plasmablasts. Molecular analysis for mutated Ig gene rearrangements confirmed that CD27 expression distinguished naive and memory cells in SS. In contrast to the peripheral blood, the majority of parotid B cells from 1 patient examined exhibited both the mutational status and phenotype of memory B cells. Accordingly, the mutational frequencies of V(H) rearrangements were significantly greater in parotid B cells than in peripheral blood B cells, whereas the V(H) gene repertoire appeared to be very similar between the compartments. CONCLUSION: These data indicate that there is an accumulation/retention of memory B cells in the inflamed salivary glands of SS patients. It is possible that preferential accumulation of CD27+ memory B cells in the inflamed parotid gland explains their reduction in the peripheral blood.     

Alteration in the response properties of primary somatosensory cortex related to differential aversive Pavlovian conditioning

The effects of differential aversive Pavlovian conditioning on the functional organization of primary somatosensory cortex (SI) were examined in 17 healthy participants. Neuroelectric source imaging from 60 electrodes was employed while nine subjects received an innocuous electric stimulus (conditioned stimulus, CS) to one finger (left or right) that was followed by painful electric shock to the lower back (unconditioned stimulus, US) and an innocuous stimulus to the other finger that was never followed by pain. Eight subjects received a presentation of the innocuous and painful stimuli with equal probability to both fingers (control group). The data included the electromyogram (EMG) from the left m. corrugator, and judgments of intensity, aversiveness, and CS-US contingency. Only the experimental group displayed EMG conditioning, differential contingency judgments, as well as a change of dipole orientation for the CS and an enhanced dipole moment for the US in the electroencephalogram. Intensity and unpleasantness ratings were altered in a more unspecific manner and did not differ between groups and stimulus conditions. The data suggest that SI contributes to memory processes in associative learning. Pavlovian conditioning of tactile responses might be important in the altered processing of painful stimuli in chronic pain patients where enhanced conditioning has been demonstrated.     

Preclinical anti‐myeloma activity of the novel HDAC‐inhibitor JNJ‐26481585

Pharmacological inhibitors of histone deacetylases (HDACs) are currently being developed and tested as anti‐cancer agents and may be useful to enhance the therapeutic efficiency of established anti‐myeloma treatments. This study preclinically evaluated the effects of the ‘second generation’ pan‐HDAC inhibitor JNJ‐26481585 on human multiple myeloma (MM) cells from established cell lines and primary MM samples (n = 42). Molecular responses in both groups of MM cells included histone acetylation, a shift in Bcl2‐family members towards proapoptotic bias, attenuation of growth and survival pathway activity and Hsp72 induction. Mcl‐1 depletion and Hsp72 induction were the most reliable features observed in JNJ‐26481585‐treated primary MM samples. The drug alone effectively induced myeloma cell death at low nanomolar concentrations. In vitro combination of JNJ‐26481585 with anti‐myeloma therapeutic agents generally resulted In effects close to additivity. In view of the favourable activity of this novel HDAC‐inhibitor towards primary myeloma cells further evaluation in a clinical setting is warranted.     

Gastrointestinal disturbances and their management in miglustat-treated patients

Miglustat (Zavesca®) is approved for the oral treatment of adult patients with mild to moderate type 1 Gaucher disease (GD1) for whom enzyme replacement therapy is unsuitable, and for the treatment of progressive neurological manifestations in adult and paediatric patients with Niemann-Pick disease type C (NP-C). Gastrointestinal disturbances such as diarrhoea, flatulence and abdominal pain/discomfort have consistently been reported as the most frequent adverse events associated with miglustat during clinical trials and in real-world clinical practice settings. These adverse events are generally mild or moderate in severity, occurring mostly during the initial weeks of therapy. The mechanism underlying these gastrointestinal disturbances is the inhibition by miglustat of intestinal disaccharidase enzymes (mainly sucrase and maltase), leading to sub-optimal hydrolysis of carbohydrates and subsequent osmotic diarrhoea and altered colonic fermentation. Transient decreases in body weight, which are often observed during initial miglustat therapy, are considered likely due to gastrointestinal carbohydrate malabsorption and associated negative caloric balance. While most cases of diarrhoea resolve spontaneously during continued miglustat therapy, diarrhoea also responds well to anti-propulsive medications such as loperamide. Dietary modifications such as reduced consumption of dietary sucrose, maltose and lactose have been shown to improve the gastrointestinal tolerability of miglustat and reduce the magnitude of any changes in body weight, particularly if initiated at or before the start of therapy. Miglustat dose escalation at treatment initiation may also reduce gastrointestinal disturbances. This article discusses these aspects in detail, and provides practical recommendations on how to optimize the gastrointestinal tolerability of miglustat.     

Intestinal pseudo-obstruction：An uncommon condition with heterogeneous etiology and unpredictable outcome

Intestinal pseudo-obstruction （IPO） either acute or chronic is a condition including features of intestinal ileus in absence of mechanical obstruction. Our paper presents such a rare case of idiopathic IPO in a 53-year-old male patient with recurrent episodes of pseudo-obstruction, which were successfully resolved by anticholinesterase agents, motilin agonists or colonic decompression. However, the patient finally underwent total colectomy. Huge colonic dilatation was identified intraoperatorily, while histology showed a neuropathic variant of chronic intestinal pseudo-obstruction. Etiologic mechanisms and current therapeutic methods are reviewed in this paper, which concludes that IPO is a condition in which conservative treatment usually fails. Total colectomy with ileoanal pouch may be the only solution in these situations.