QT Interval in Patients with Unstable Angina and Non‐Q Wave Myocardial Infarction

Background: Non‐Q wave mvocardial infarction (NQMI) and unstable angina (UAP) have similar clinical presentations and similar ST‐T changes on the electrocardiogram. The purpose of this study was to assess whether changes in QT interval might help differentiating between these entities. Methods: The QT intervals of 52 patients hospitalized with NQMI were compared to those of 52 patients hospitalized for UAP. All patients had repeated ECG for at least 4 days. Results: Maximal QTc in patients with NQMI was significantly longer than in patients with UAP (475 vs 439 ms, P < 0.0001). QTc on the admission ECG was 450 ms in patients with NQMI compared to 417 ms in UAP P < 0.005). QTc > 460 ms was present in 48% patients with NQMI and in 19% of UAP patients. Maximal QT prolongation was observed within 36 hours of admission with return to normal within 96 hours. QT dispersion was within normal range, being longer in patients with NQMI than patients with UAP (55 vs 43 ms, P < 0.003). QT prolongation was not associated with increased frequency of arrhythmia. The cause of QT prolongation in NQMI may be related to the damage of subendocardial layer exposing the M cells layer which markedly prolong action potential duration. Conclusion: Transient QT prolongation is observed in about half of patients with NQMI. These ECG changes may help differentiating between patients with NQMI and UAP already on admission. A.N.E. 2002;7(4):343–348     

Evidence for genetic modifiers of ovarian follicular endowment and development from studies of five inbred mouse strains

The laboratory mouse is the model of choice for genetic studies in mammals due to the availability of many genetically defined inbred strains and inbred congenic strains, as well as the ability to study the effects of over-expression (transgenics) or inactivation (knockouts) of a given gene on cells or tissues. During our studies using these technologies to uncover the importance of various genes to apoptosis in the ovary, we observed that the size of the primordial oocyte reserve was affected by mouse strain in the absence of any other genetic manipulation. To determine if genetic modifiers of oocyte endowment truly exist, herein we examined follicle numbers in one outbred (CD-1) and several inbred (129/Sv, DBA/2, C57BL/6, FVB, AKR/J) strains of mice at day 4 (neonatal) and day 42 (young adult) postpartum. In neonatal life, ovaries of AKR/J females had the lowest total number of follicles, whereas 129/Sv females possessed the highest total number of follicles (P < 0.05 for AKR/J versus 129/Sv). There were more primordial follicles in 129/Sv compared with DBA/2 (P < 0.05), C57BL/6 (P < 0.05), FVB (P < 0.05) or AKR/J (P < 0.05) females, and in CD-1 compared with AKR/J (P < 0.05) females. Although no significant strain-dependent differences in primary follicle numbers were noted, C57BL/6 females had the fewest number of small preantral follicles (P < 0.05 versus all other strains). Evaluation of ovaries at 42 days of age revealed the persistence of strain-dependent differences in early follicle growth patterns, although the total numbers of follicles were comparable. Of interest, marked strain-dependent differences in the rate of primordial follicle growth activation, as well as in the rate of follicle loss (atresia), between days 4 and 42 were observed. These results indicate that genetic modifiers play a major role in follicle endowment, development and atresia in the mouse ovary.     

Low prevalence of antibodies to glucose-6-phosphate isomerase in patients with rheumatoid arthritis and a spectrum of other chronic autoimmune disorders

OBJECTIVE: Arthritis in the K/BxN mouse model results from pathogenic immunoglobulins that recognize glucose-6-phosphate isomerase (GPI), a glycolytic enzyme residing in the cytoplasm of all cells. Antibodies directed against GPI can, alone, transfer arthritis to healthy recipients. Previous experiments have revealed significant titers of anti-GPI antibodies in the serum of many patients with rheumatoid arthritis (RA). We evaluated the generality of these observations in cohorts of patients with 12 different arthritic and chronic autoimmune diseases and in population-matched healthy control subjects. METHODS: Anti-GPI antibodies were assayed in 811 individual serum samples by enzyme-linked immunosorbent assay with 2 forms of GPI, recombinant and native. Results were confirmed by immunoblotting. RESULTS: Several patients had significantly elevated anti-GPI antibody titers, but without the prevalence or the specificity reported previously. Only 15% of RA patients had anti-GPI antibodies (range 12-29% in different cohorts), with a higher prevalence in patients with active disease. Psoriatic arthritis, undifferentiated arthritis, and spondylarthropathy patients also displayed anti-GPI antibodies at similar frequencies (12-25%). Similar titers were detected in a proportion (5-10%) of control subjects or patients with Crohn's disease or sarcoidosis. Very high titers were found in rare cases of RA and systemic lupus erythematosus. CONCLUSION: No disease-specific pattern of antibody positivity to GPI was apparent. While the antibody-mediated mechanism at play in the mouse model may exemplify a generic mechanism for some forms of arthritis in humans, GPI itself does not appear to be a target common to the majority of RA patients.     

A high-throughput, near-saturating screen for type III effector genes from Pseudomonas syringae

Pseudomonas syringae strains deliver variable numbers of type III effector proteins into plant cells during infection. These proteins are required for virulence, because strains incapable of delivering them are nonpathogenic. We implemented a whole-genome, high-throughput screen for identifying P. syringae type III effector genes. The screen relied on FACS and an arabinose-inducible hrpL sigma factor to automate the identification and cloning of HrpL-regulated genes. We determined whether candidate genes encode type III effector proteins by creating and testing full-length protein fusions to a reporter called Delta79AvrRpt2 that, when fused to known type III effector proteins, is translocated and elicits a hypersensitive response in leaves of Arabidopsis thaliana expressing the RPS2 plant disease resistance protein. Delta79AvrRpt2 is thus a marker for type III secretion system-dependent translocation, the most critical criterion for defining type III effector proteins. We describe our screen and the collection of type III effector proteins from two pathovars of P. syringae. This stringent functional criteria defined 29 type III proteins from P. syringae pv. tomato, and 19 from P. syringae pv. phaseolicola race 6. Our data provide full functional annotation of the hrpL-dependent type III effector suites from two sequenced P. syringae pathovars and show that type III effector protein suites are highly variable in this pathogen, presumably reflecting the evolutionary selection imposed by the various host plants.     

Can the critically ill consent to participation in commercial television programmes? An Australian prehospital and emergency medicine perspective

The fly‐on‐the‐wall medical documentary is a popular television phenomenon. When patients can give appropriate consent to filming, the final product can be both educational for the public and rewarding for its subjects. However, in the dynamic world of emergency and prehospital medicine, consenting critically ill patients before filming is a significant challenge. The main barriers to gaining valid consent in the field and in the ED are limited time to inform the patient and the diminished capacity of the sick patient. Although there is an argument that involvement in a commercial film might be beneficial to several parties, including the patient, these benefits do not amount to therapeutic necessity if prior consent is not obtainable. Despite this, we still see acutely incapacitated patients featured in some television programmes. In these cases, the conventional process of consent might be being sidestepped in order to obtain permission for broadcast retrospectively. This alternative process fails to recognise that incapacitated patients require protection from an invasion of privacy that occurs when a crew is filming their resuscitations. This harm has already occurred by the time consent is sought. Ultimate responsibility for defending the patients' interests during their medical treatment rests with the medical practitioner. We argue that filming a patient without prior consent in both the prehospital and emergency environment is ethically unsound: it threatens trust in the healthcare relationship and might compromise the patient's dignity and privacy. Robust guidelines should be developed for all healthcare professionals who engage with commercial film crews.     

In vivo multiplexed molecular imaging of esophageal cancer via spectral endoscopy of topically applied SERS nanoparticles

The biological investigation and detection of esophageal cancers could be facilitated with an endoscopic technology to screen for the molecular changes that precede and accompany the onset of cancer. Surface-enhanced Raman scattering (SERS) nanoparticles (NPs) have the potential to improve cancer detection and investigation through the sensitive and multiplexed detection of cell-surface biomarkers. Here, we demonstrate that the topical application and endoscopic imaging of a multiplexed cocktail of receptor-targeted SERS NPs enables the rapid detection of tumors in an orthotopic rat model of esophageal cancer. Antibody-conjugated SERS NPs were topically applied on the lumenal surface of the rat esophagus to target EGFR and HER2, and a miniature spectral endoscope featuring rotational scanning and axial pull-back was employed to comprehensively image the NPs bound on the lumen of the esophagus. Ratiometric analyses of specific vs. nonspecific binding enabled the visualization of tumor locations and the quantification of biomarker expression in agreement with immunohistochemistry and flow cytometry validation data.OCIS codes: (170.5660) Raman spectroscopy, (170.2150) Endoscopic imaging, (110.2350) Fiber optics imaging, (170.0170) Medical optics and biotechnology, (170.2680) Gastrointestinal, (160.4236) Nanomaterials     

Lens-term- and edge-effect in X-ray grating interferometry

X-ray grating interferometry requires gratings with periods in the micrometer range and allows the acquisition of the dark-field contrast. The analyzer grating is designed to match the period of the interference pattern in order to translate it into a measurable intensity modulation. In this study, we explore the influence of a sample-induced mismatch between the interference pattern and the analyzer grating on the dark-field contrast. We propose a formula for the calculation of the signal due to a period mismatch and present estimations varying periods and detector pixel size. Furthermore, numerical simulations of the X-ray wave-front demonstrate that the wave-front curvature, described by the lens-term, e.g. behind a parabolic lens or edges of a sample can change the period of the interference pattern. Our results give a concrete explanation for the formation of a dark-field contrast from object edges and thus allow a better understanding of the dark-field signal obtained with a grating interferometer.OCIS codes: (110.7440) X-ray imaging, (340.7450) X-ray interferometry