Latex-allergic patients sensitized to the major allergen hevein and hevein-like domains of class I chitinases show no increased frequency of latex-associated plant food allergy

Allergies to certain fruits such as banana, avocado, chestnut and kiwi are described in 30-70% of latex-allergic patients. This association is attributed to the cross-reactivity between the major latex allergen hevein and hevein-like domains (HLDs) from fruit class I chitinases. We aimed to assess the extent of cross-reactivity between hevein and HLDs using sera from latex-allergic patients with and without plant food allergy. Hevein and HLDs of latex, banana, and avocado chitinases were expressed in Escherichia coli as fusion proteins with the maltose-binding protein and purified by affinity chromatography. IgE binding to these proteins was studied in sera from 59 latex-allergic patients and 20 banana-allergic patients without latex allergy by ELISA and ELISA inhibition. Additionally, 16,408 allergic patients’ sera were tested for IgE binding to hevein, latex chitinase, and wheat germ agglutinin using an allergen microarray. Hevein-specific IgE was detected in 34/59 (58%) latex-allergic patients’ sera. HLDs of latex, banana, and avocado chitinases were recognized by 21 (36%), 20 (34%), and 9 (15%) sera, respectively. In contrast, only one of 20 banana-allergic patients without latex allergy was sensitized to chitinase HLDs. In most tested latex-allergic patients’ sera, IgE binding to hevein was only partially reduced by preincubation with HLDs. Among hevein-sensitized, latex-allergic patients, the percentage of plant food allergy (15/34 = 44%) was equal to latex-allergic patients without hevein sensitization (11/25 = 44%). In the general allergic population, 230 of 16,408 sera (1.4%) reacted to hevein and/or a hevein-like allergen. Of these, 128 sera showed an isolated sensitization to hevein, whereas only 17 bound to latex chitinase or wheat germ agglutinin without hevein sensitization. In conclusion, the IgE response to HLDs is elicited by hevein as sensitizing allergen in most cases. Despite considerable cross-reactivity between these allergens, no correlation between latex-associated plant food allergy and sensitization to hevein or HLDs was found.     

An Improved Method of Assessing Esophageal Emptying Using the Timed Barium Study Following Surgical Myotomy for Achalasia

Introduction  The timed barium study (TBS) is used to assess esophageal emptying in patients with achalasia. Improvement in emptying correlates with outcome after endoscopic therapy, but the results of the TBS have been variable after myotomy. Our aim was to evaluate a new method for assessing improvement in emptying after myotomy. Methods  A TBS was performed before and 3–6 months after myotomy in 30 patients. Emptying was assessed by measuring the percent difference in area of the barium column on films obtained 1 and 5 min after ingesting 150 ml of barium. Initial esophageal clearance was also assessed by comparing the area of the barium column on 1-min images obtained before and after therapy. Both measures were compared to clinical outcome. Results  After myotomy, 21 patients (70%) had no symptoms, four (13%) had mild, and five (17%) had moderate/severe symptoms. Using the standard method, esophageal emptying before and after surgery were not significantly different (25% vs. 37%; p = 0.22) and did not correlate with clinical outcome. In contrast, initial esophageal clearance improved significantly (median 81%) and correlated with clinical outcome. Conclusion  Esophageal emptying measured by the standard method is not useful to assess outcome after myotomy. However, initial esophageal clearance correlates well with clinical outcome. Previous presentations: 49th SSAT Annual Meeting at Digestive Disease Week, San Diego, 2008 and 23rd Annual SSAT Residents and Fellows Research Conference, San Diego, 2008     

Glycoprotein IIb/IIIa inhibitors use in the setting of primary percutaneous coronary intervention for ST elevation myocardial infarction in patients pre‐treated with newer P2Y12 inhibitors

ObjectivesWe sought to investigate the safety and potential benefit of administrating glycoprotein IIb‐IIIa inhibitors (GPIs) on top of more potent P2Y12 inhibitors.BackgroundA number of clinical trials, performed at a time when pretreatment and potent platelet inhibition was not part of routine clinical practice, have documented clinical benefits of GPI in ST‐segment elevation myocardial infarction (STEMI) patients at the cost of a higher risk of bleeding.MethodsWe used the data of a prospective, ongoing registry of patients admitted for STEMI in our center. For the purpose of this study only patients presenting for primary percutaneous coronary intervention and pretreated with new P2Y12 inhibitors (prasugrel or ticagrelor) were included. We compared patients who received GPI with those who did not.ResultsEight hundred twenty‐four STEMI patients were included in our registry; GPIs were used in 338 patients (41%). GPI patients presented more often with cardiogenic shock and Thrombolysis in myocardial infarction (TIMI) flow grade <3. GPI use was not associated with an increase in in‐hospital or 3‐month mortality. Bleeding endpoints were similar in both groups.ConclusionsOur study suggests that GPI may be used safely in combination with recent P2Y12 inhibitors in STEMI patients in association with modern primary percutaneous coronary intervention strategies (radial access and anticoagulation with enoxaparin) with similar bleeding and mortality rates at hospital discharge and 3‐month follow‐up.     

Functional near infrared spectroscopy (fNIRS): an emerging neuroimaging technology with important applications for the study of brain disorders

Functional near-infrared spectroscopy (fNIRS) is an emerging functional neuroimaging technology offering a relatively non-invasive, safe, portable, and low-cost method of indirect and direct monitoring of brain activity. Most exciting is its potential to allow more ecologically valid investigations that can translate laboratory work into more realistic everyday settings and clinical environments. Our aim is to acquaint clinicians and researchers with the unique and beneficial characteristics of fNIRS by reviewing its relative merits and limitations vis-à-vis other brain-imaging technologies such as functional magnetic resonance imaging (fMRI). We review cross-validation work between fMRI and fNIRS, and discuss possible reservations about its deployment in clinical research and practice. Finally, because there is no comprehensive review of applications of fNIRS to brain disorders, we also review findings from the few studies utilizing fNIRS to investigate neurocognitive processes associated with neurological (Alzheimer's disease, Parkinson's disease, epilepsy, traumatic brain injury) and psychiatric disorders (schizophrenia, mood disorders, anxiety disorders).     

Radiography of successful bone marrow transplantation for osteopetrosis

Hematopoietic stem cell transplantation (HSCT) is the only curative therapy for autosomal recessive infantile malignant osteopetrosis, an otherwise fatal disease. HSCT has also been utilized in patients with the less severe autosomal recessive intermediate form in an attempt to correct hematologic abnormalities and halt cranial nerve deficits caused by progressive cranial foraminal stenosis. Successful engraftment is accompanied by rapid normalization of radiographic signs of osteopetrosis.     

Generation in vivo of peptide-specific cytotoxic T cells and presence of regulatory T cells during vaccination with hTERT (class I and II) peptide-pulsed DCs

Background

Optimal techniques for DC generation for immunotherapy in cancer are yet to be established. Study aims were to evaluate: (i) DC activation/maturation milieu (TNF-α +/- IFN-α) and its effects on CD8+ hTERT-specific T cell responses to class I epitopes (p540 or p865), (ii) CD8+ hTERT-specific T cell responses elicited by vaccination with class I alone or both class I and II epitope (p766 and p672)-pulsed DCs, prepared without IFN-α, (iii) association between circulating T regulatory cells (Tregs) and clinical responses.

Methods

Autologous DCs were generated from 10 patients (HLA-0201) with advanced cancer by culturing CD14+ blood monocytes in the presence of GM-CSF and IL-4 supplemented with TNF-α [DCT] or TNF-α and IFN-α [DCTI]. The capacity of the DCs to induce functional CD8+ T cell responses to hTERT HLA-0201 restricted nonapeptides was assessed by MHC tetramer binding and peptide-specific cytotoxicity. Each DC preparation (DCT or DCTI) was pulsed with only one type of hTERT peptide (p540 or p865) and both preparations were injected into separate lymph node draining regions every 2–3 weeks. This vaccination design enabled comparison of efficacy between DCT and DCTI in generating hTERT peptide specific CD8+ T cells and comparison of class I hTERT peptide (p540 or p865)-loaded DCT with or without class II cognate help (p766 and p672) in 6 patients. T regulatory cells were evaluated in 8 patients.

Results

(i) DCTIs and DCTs, pulsed with hTERT peptides, were comparable (p = 0.45, t-test) in inducing peptide-specific CD8+ T cell responses. (ii) Class II cognate help, significantly enhanced (p < 0.05, t-test) peptide-specific CD8+T cell responses, compared with class I pulsed DCs alone. (iii) Clinical responders had significantly lower (p < 0.05, Mann-Whitney U test) T regs, compared with non-responders. 4/16 patients experienced partial but transient clinical responses during vaccination. Vaccination was well tolerated with minimal toxicity.

Conclusion

Addition of IFN-α to ex vivo monocyte-derived DCs, did not significantly enhance peptide-specific T cell responses in vivo, compared with TNF-α alone. Class II cognate help significantly augments peptide-specific T cell responses. Clinically favourable responses were seen in patients with low levels of circulating T regs.     

The incidence of berry aneurysm in the Iranian population: an autopsy study

Intracranial berry aneurysms are the most common kind of aneurysms in the brain, and are caused by head trauma in 1% of cases. They may remain asymptomatic for a long time or may rupture and cause intracranial hemorrhage. These aneurysms are associated with a high mortality rate. A definitive diagnosis can be made by angiography or autopsy. We studied the cadavers of 425 people who passed away accidentally. The number and location of berry aneurysms were recorded. Twelve cases (2.82%) were found to have a single berry aneurysm and two (0.47%) had multiple aneurysms. The aneurysms had a tendency to occur in the frontal half of the Circle of Willis and in approximation of the bifurcation of arteries. The main characteristics of cases of berry aneurysm in the Iranian population were in agreement with that reported in previous Western studies.     

Cerebral blood flow response to flavanol-rich cocoa in healthy elderly humans

BACKGROUND AND PURPOSE: Cerebral ischemia is a common, morbid condition accompanied by cognitive decline. Recent reports on the vascular health benefits of flavanol-containing foods signify a promising approach to the treatment of cerebral ischemia. Our study was designed to investigate the effects of flavanol-rich cocoa (FRC) consumption on cerebral blood flow in older healthy volunteers. METHODS: We used transcranial Doppler (TCD) ultrasound to measure mean blood flow velocity (MFV) in the middle cerebral artery (MCA) in thirty-four healthy elderly volunteers (72 +/- 6 years) in response to the regular intake of FRC or flavanol-poor cocoa (FPC). RESULTS: In response to two weeks of FRC intake, MFV increased by 8% +/- 4% at one week (p = 0.01) and 10% +/- 4% (p = 0.04) at two weeks. In response to one week of cocoa, significantly more subjects in the FRC as compared with the FPC group had an increase in their MFV (p < 0.05). CONCLUSIONS: In summary, we show that dietary intake of FRC is associated with a significant increase in cerebral blood flow velocity in the MCA as measured by TCD. Our data suggest a promising role for regular cocoa flavanol's consumption in the treatment of cerebrovascular ischemic syndromes, including dementias and stroke.