Mature liver stages of cloned Plasmodium falciparum share epitopes with proteins from sporozoites and asexual blood stages

The liver merozoites of malaria parasites are of paramount importance, as they initiate the parasite invasion of red blood cells and start the cycle associated with the clinical features of malaria. Investigating liver merozoite antigen is difficult because of the lack of a rodent model of human malaria. In addition, only a low proportion of cells are obtained in vivo, the parasites from Cebus and Aotus monkeys are immature, and in-vitro experiments with liver cells are often confounded by contamination with the natural mosquito flora copurified with the sporozoites used for seeding the liver cultures. In our study, mature liver schizonts were shown to possess many of the antigenic determinants recognized by MoAbs and sera specific for defined sporozoite and blood-stage antigens. We employed an immunofluorescence procedure based on evaluating parasites in cryosections prepared from infected chimpanzee liver. Sufficient numbers of sectioned parasites were evaluated with each antibody to assure the reproducibility of the results, and the fixation procedure used was sufficiently non-destructive to parasite antigens so that clear differences between reactions of specific antibodies and negative controls were observed. Our evidence for sharing of epitopes by liver merozoites and sporozoites or by liver merozoites and asexual blood-stage parasites raises the possibility that immune responses elicited against sporozoites or asexual stage antigens being considered as vaccine candidates may also act against this important, little-studied stage of the parasite.     

Encainide for the Treatment of Refractory Ventricular Tachycardia in Patients Undergoing Programmed Electrical Stimulation

Encainide was evaluated in 26 patients undergoing programmed electrical stimulation (PES) for ventricular arrhythmias. These patients had inducible symptomatic ventricular tachyarrhythmias during baseline PES and had previously failed a mean of 3.2 antiarrhythmic agents. Encainide was discontinued in six patients prior to PES because of spontaneous ventricular tachycardia (VT) (five patients) and adverse effect (one patient). Encainide increased, the PR, QRS, QTc intervals, and right ventricular effective refractory period (RVERP) significantly from baseline (P < 0.05) in 16 patients who were extensive metabolizers. Encainide, at a mean dose of 110 ± 28 mg/day increased the ventricular tachycardia cycle length (VTCL) from 278 ± 77.1 msec to 334 ± 68.8 msec (P < 0.05). Encainide alone was effective (< 15 beats induced) or partially effective (converting inducible sustained VT to < 15 beats asymptomatic nonsustained VT or increasing the VTCL < 100 msec with no symptoms) in two and seven patients respectively. In seven patients, encainide was also reevaluated at a higher dose (mean dose 148 ± 22 mg/day), but this dose did not significantly alter the overall response or measured parameters. Seven patients were subsequently evaluated on combination of encainide and another antiarrhythmic agent. The combination was effective in three patients and partially effective in three patients. Serum concentrations were measured during each testing period; a moderate correlation was observed between the PR and RR intervals and total concentrations in patients who were extensive metabolizers. Eleven patients who were effective or partially effective during acute testing were placed on long-term encainide therapy (three patients alone and eight patients on combination therapy). In a mean follow-up of 8.9 months (1–25 months) encainide was discontinued in five patients (two patients due to nonsudden cardiac death, one patient due to recurrent nonfatal VT, and two patients due to side effects of combination therapy.) Conclusion: Encainide alone is minimally effective (7.7%) for preventing inducible ventricular tachycardia, but partially effective in 38.9%. Retesting at a higher dose does not offer any additional benefit. However, encainide in combination with another antiarrhythmic agent may improve the response in patients who remain inducible on encainide alone. Further studies are needed to verify this observation.     

Image Integration Using Intracardiac Ultrasound and 3D Reconstruction for Scar Mapping and Ablation of Ventricular Tachycardia

Background: Ablation of ventricular tachycardia (VT) reduces implantable cardioverter defibrillator shocks. Intracardiac ultrasound (ICE) can visualize and quantify the function of all left ventricular wall segments. We thus hypothesized that ICE could identify scar tissue and provide a guide to facilitate substrate‐guided VT ablation. Methods: Eighteen patients underwent VT ablation with real time ICE mapping from the right atrium and ventricle with online 3D‐image reconstruction of scar segments. The left ventricle was also scar mapped by traditional electroanatomic mapping (CARTO) for comparison. Images from these 2 scar mapping techniques were compared to each other as well as to a preprocedure transthoracic echocardiogram. Results: The average age was 65 ± 12 years and 12 (67%) were male (15 [83%] had ischemic cardiomyopathy). Two patients (12%) had recurrence of their clinical VT (1 remained on an antiarrhythmic medication, the other had a repeat ablation) over a follow‐up of 127 ± 33 days. No periprocedural or long‐term adverse events occurred. A total of 248 wall segments were analyzed. All 3 modalities were concordant in scar identification in 193 (78%) segments. The ICE segments correlated with the electroanatomic map in 213 (86%) segments versus 198 (80%), which correlated with transthoracic echocardiography and electroanatomic mapping (P = 0.046). Specifically, the ICE wall motion scores were closer to the electroanatomic mapping in the basal segments and showed a higher accuracy in ischemic heart disease. Conclusion: These data demonstrate that real time ICE images provide accurate chamber geometries and scar boundaries of the left ventricle. These scar borders were more accurate than transthoracic echocardiography and illustrate the feasibility of ICE for substrate‐based ablation for VT. (J Cardiovasc Electrophysiol, Vol. 21, pp. 678‐684, June 2010)     

Late Gadolinium Enhancement of the Esophagus is Common on Cardiac MR Several Months after Pulmonary Vein Isolation: Preliminary Observations

Background: Pulmonary vein isolation (PVI) as a treatment for atrial fibrillation (AF) is commonly performed. This procedure can damage the esophagus. Late gadolinium enhancement (LGE) cardiovascular magnetic resonance imaging (CMR) offers noninvasive assessment of scar. We sought to examine the prevalence of esophageal hyperenhancement on LGE‐CMR prior to and following PVI. Methods: Seventy‐four patients underwent LGE‐CMR prior to and 1.7 ± 1.9 months post PVI for AF. Transmural esophageal hyperenhancement was visually assessed. The pre‐ and post PVI esophageal position was measured, relative to the vertebral body. Results: Prior to PVI, 3% (2/74) of patients had esophageal LGE on CMR. At post‐PVI follow‐up, 30% (23/74) of the studies demonstrated new esophageal hyperenhancement adjacent to an ablation site. Most (74%, 17/27) positive esophageal LGE studies were performed >30 days after PVI, while no (0/9) studies performed >2 months post PVI were positive for esophageal hyperenhancement. The presence of post‐procedural esophageal hyperenhancement was not associated with longer ablation time (P = 0.42), use of an irrigated catheter (74% with LGE vs 47% without, P = 0.16), right‐sided esophageal location (56% with LGE vs 39% without, P = 0.17), size of left atrium cavity (58 ± 8 mm with LGE vs 61 ± 10 mm without, P = 0.15), or the timing of the LGE‐CMR study after PVI (36 ± 10 days with LGE vs 60 ± 66 days without, P = 0.09). Conclusion: Though rare before PVI, new esophageal LGE is seen in almost one‐third of patients after PVI. The clinical implications to remain to be explored, but clinicians should be aware of this frequent imaging finding. (PACE 2010; 33:661–666)     

Radiation-induced Recurrent Intestinal Pseudo-obstruction

The syndrome of intestinal pseudo-obstruction is a complex of signs and symptoms of intestinal obstruction without evidence of mechanical obstruction of the intestinal lumen. A patient with radiation-induced intestinal pseudoobstruction is described. The patient is a 74-year old woman with a history of chronic diarrhea, recurrent episodes of crampy abdominal pain, nausea and vomiting since receiving a 13,000 rad radiation dose to the pelvis in 1954. She has been hospitalized on many occasions for symptoms and signs of bowel obstruction. Upper gastrointestinal contrast roentgenograms with small bowel follow-through done during these episodes revealed multiple dilated loops of small bowel with no obstructing lesion. Barium enemas revealed no obstructing lesion. Each episode resolved with conservative therapy. Other secondary causes for intestinal pseudo-obstruction were ruled out in our patient. She gave no history of familial gastrointestinal disorders. Although postirradiation motility abnormalities have been demonstrated experimentally this is the first report of radiation induced intestinal pseudo-obstruction.     

Fish and Amphibian Embryos -- A Model System for Evaluating Teratogenicity

Fish and Amphibian Embryos—A Model System for EvaluatingTeratogenicity. Birge, W.J., Black, J.A., Westerman, A.G. andRamey, B.A. (1983). Fundam. Appl. Toxicol. 3: 237–242.Developmental stages of fish and amphibians were used to evaluatereproductive impairments produced by environmental contaminants.Using static-renewal and flow-through procedures, exposure wasinitiated at, or soon after, fertilization and maintained through4 days posthatching. Trace concentrations of many environmentaltoxicants produced high frequencies of mortality and teratogenesis.When developmental stages of the trout were exposed to inorganicmercury, 10% control-adjusted mortality was observed at 1 µg/Land frequencies of terata in hatched populations ranged from8% to 43% for exposure concentrations of 2 to 25 µg/L-In similar tests with the narrow-mouthed toad, 45% mortalityoccurred when mercury was administered at 1 µg/L; frequenciesof teratogenesis ranged from 8% to 17% at exposure concentrationsof 1 to 5 µg/L; and complete mortality occurred at 7 µg/L.Boron-induced teratogenesis in trout ranged from 5% at 1 µg/Lto 51% at higher exposure levels. When catfish embryos wereexposed to atrazine at 0.06, 4.8, and 46.7 mg/L, terata appearedin surviving populations at frequencies of 4%, 69%, and 100%,respectively. Fish and amphibian developmental stages constitutesimple and effective models for 1) investigating mechanismsof teratogenesis, 2) evaluating the impact of environmentaltoxicants on aquatic biota, and 3) identifying environmentalteratogens which may be of concern to human health.     

Dental treatment of a patient with Friedreich's ataxia

The dental treatment of a patient with Friedreich's ataxia is discussed. Despite the patient's systemic conditions, treatment including oral hygiene instructions and an extraction was performed without complications. With knowledge of this disease, in conjunction with medical consultation, these patients can be treated successfully.