Right ventricular pressure-volume loops using simultaneous radionuclide angiography with a multiwire gamma camera and right heart catheterization

BACKGROUND: The purpose of this study was to generate right ventricular (RV) pressure-volume loops (PVLs) from time-activity curves obtained by first-pass radionuclide angiography (RNA) and RV pressures obtained by right heart catheterization. METHODS AND RESULTS: Short-lived tantalum 178 was used to obtain first-pass RNA at baseline (n = 31), after nitroglycerin (n = 5), or after the conclusion of cardiac catheterization (n = 13). From the radionuclide-derived RV ejection fraction and thermodilution stroke volume, the RV end-diastolic volume and end-systolic volume were measured. Special proprietary software was developed and used to integrate the pressure and the RNA data. The mean heart rate was 80 +/- 17 beats/min; RV ejection fraction, 39% +/- 12%; RV end-diastolic volume, 217 +/- 79 mL; RV end-systolic volume, 142 +/- 74 mL; and RV end-diastolic pressure, 10 +/- 7 mm Hg. The RV PVLs were of high quality and reproducible. CONCLUSIONS: This study provides proof of concept of the feasibility of generating RV PVL; the short half-life (10 minutes) and low energy (59 keV) of Ta-178 allow the generation of multiple loops at low radiation exposure. Such studies could be performed at the bedside and provide a wealth of information that may have clinical and research merits.     

Assessment of left ventricular function during upright treadmill exercise with tantalum 178 and multiwire gamma camera

BACKGROUND: Prior studies with first-pass radionuclide angiography (RNA) during treadmill exercise used a single-crystal (Anger) or multicrystal gamma camera and technetium 99m tracers. Motion correction, when done, used point sources, which limited correction to only plane movement. METHODS AND RESULTS: We examined the performance of a multiwire gamma camera (MWGC), generator-produced tantalum 178, and a novel method of motion correction during treadmill exercise testing. We studied 100 patients in whom rest and stress gated tomographic myocardial perfusion images were obtained. Eight patients were excluded because of incomplete data. There were 53 men and 39 women aged 52 +/- 12 years. The resting left ventricular (LV) ejection fraction (EF) was 61% +/- 12% by gated single photon emission computed tomography. Stress myocardial perfusion was normal in 83 patients and abnormal in 9 patients. The resting RNA EF in the upright position was 57% +/- 12% (r = 0.52, P = .0001 vs gated EF). At peak exercise, the EF by MWGC was 60% +/- 26% if uncorrected and 69% +/- 13% after motion correction. Among the 80 patients with normal perfusion and normal resting EF by gated single photon emission computed tomography, a normal response to exercise was seen in 52 (63%) without motion correction and 74 (89%) with motion correction (P < .05). CONCLUSION: Assessment of LV function is feasible with MWGC. The motion-corrected images significantly improved the results.     

Challenges in creating a vaccine to prevent hepatitis E

Recombinant hepatitis E virus capsid protein (HEV CP) assembles orally immunogenic virus-like particles (VLP) when expressed in an insect cell system. We used plant expression cassettes, pHEV101 and pHEV110, for transformation of potato to express HEV CP, and 10 independent transgenic lines of HEV101 and 6 lines of HEV110 were obtained. ELISA for HEV CP was performed on tuber extracts. Accumulation of HEV CP in tubers varied from about 5 to 30 microg/g fresh tuber depending on the transgenic plant line. We further compared the expression levels with the yield of tubers for each line. Tuber yield varied less than expression levels, and ranged from about 600 to 1000 g per pot. Although Western blot showed that apparently intact HEV CP accumulated, we observed very limited assembly of virus-like particles in potato tubers. Oral immunization of mice with transgenic potatoes failed to elicit detectable anti-CP antibody response in serum, suggesting that VLP assembly is a key factor in orally delivered HEV CP vaccines.     

Aberrant deltaPKC activation in the spinal cord of Wobbler mouse: a model of motor neuron disease

Protein kinase C (PKC) was suggested to play a role in the pathology of amyotrophic lateral sclerosis (ALS) patients. Activation of PKC delta (deltaPKC) modulates mitochondrially induced apoptosis. The goal of the present study was to define whether deltaPKC activation occurs in Wobbler mouse spinal cord (a model of motor neuron disease). The level of deltaPKC in the soluble fraction was significantly decreased in the spinal cord of Wobbler mice, which was associated with a significant increase in deltaPKC cleavage. Since caspase-3 is known to cleave deltaPKC, we determined caspase-3 activation in the Wobbler mice spinal cord, immunohistochemically. The results demonstrated intense immunoreactivity for activated caspase-3 in corticospinal tract motor neurons of Wobbler mice spinal cord. We hypothesize from these results that caspase-3 activation cleaves deltaPKC, which in turn promotes an aberrant signal transduction pathway in the Wobbler spinal cord.     

Remission of hormone-refractory prostate cancer attributed to Essiac

Essiac is a popular complementary and alternative medicine (CAM) that is utilized by many cancer patients in North America. Much anecdotal reporting exists about its cancer-fighting qualities, but so far no clinical trials have been preformed to validate those claims. We describe here the case of a 64-year-old man whose hormone-refractory prostate cancer responded well to Essiac tea.     

Ischemic preconditioning ameliorates excitotoxicity by shifting glutamate/gamma-aminobutyric acid release and biosynthesis

Excitotoxicity is recognized to play a major role in cerebral ischemia-induced cell death. The main goal of the present study was to define whether our model of ischemic preconditioning (IPC) promotes a shift from excitatory to inhibitory neurotransmission during the test ischemia to diminish metabolic demand during the reperfusion phase. We also determined whether gamma-aminobutyric acid (GABA) played a role in IPC-induced neuroprotection. Ten minutes of cerebral ischemia was produced by tightening the carotid ligatures bilaterally following hypotension. Samples of microdialysis perfusate, representing extracellular fluid, were analyzed for amino acid content by HPLC. IPC promoted a robust release of GABA after lethal ischemia compared with control rats. We also observed that the activity of glutamate decarboxylase (the predominant pathway of GABA synthesis in the brain) was higher in the IPC group compared with control and ischemic groups. Because GABAA receptor up-regulation has been shown to occur following IPC, and GABAA receptor activation has been implicated in neuroprotection against ischemic insults, we tested the hypothesis that GABAA or GABAB receptor activation was neuroprotective during ischemia or early reperfusion by using an in vitro model (organotypic hippocampal slice culture). Administration of the GABAB agonist baclofen during test ischemia and for 1 hr of reperfusion provided significant neuroprotection. We concluded that increased GABA release in preconditioned animals after ischemia might be one of the factors responsible for IPC neuroprotection. Specific activation of GABAB receptor contributes significantly to neuroprotection against ischemia in organotypic hippocampal slices.     

Three Diagnostic Approaches to Asperger Syndrome: Implications for Research

Objective: To examine the implications for research of the use of three alternative definitions for Asperger syndrome (AS). Differences across the three nosologic systems were examined in terms of diagnostic assignment, IQ profiles, comorbid symptoms, and familial aggregation of social and other psychiatric symptoms. Method: Standard data on diagnosis, intellectual functioning, comorbidity patterns, and family history were obtained on 65 individuals screened for a very high probability of having autism without mental retardation (or higher functioning autism, HFA) or AS. Diagnoses of AS were established based on three different approaches: DSM-IV, presence/absence of communicative phrase speech by 3 years, and a system designed to highlight prototypical features of AS. Results: Agreement between the three diagnostic systems was poor. AS could be differentiated from HFA (but not from PDD-NOS) on the basis of IQ profiles in two of the three systems. Differences in patterns of comorbid symptomatology were obtained in two of the three systems, although differences were primarily driven by the PDD-NOS category. Only one of the approaches yielded differences relative to aggregation of the broader phenotype in family members. Conclusions: Diagnostic assignments of AS based on three commonly used approaches have low agreement and lead to different results in comparisons of IQ profiles, patterns of comorbidity, and familial aggregation of psychiatric symptoms across the approach-specific resultant groups of HFA, AS, and PDD-NOS.