A very narrow preexisting isthmus in a case with typical atrial flutter

A 61-year-old woman with typical atrial flutter underwent an electrophysiologic study and radiofrequency catheter ablation. The electroanatomic mapping revealed two contiguous lines of distinct double potentials (DPs) extending anteriorly/posteriorly from the coronary sinus ostium to the inferior vena cava (IVC) border. A large part of the anterior line of the DPs was close and parallel to the tricuspid annulus (TA). An initial discrete radiofrequency application at the very narrow preexisting isthmus between the TA and anterior line of the DPs completed the IVC-TA isthmus conduction block.     

von Willebrand factor released from Weibel-Palade bodies binds more avidly to extracellular matrix than that secreted constitutively

Large multimers of von Willebrand factor (vWf) are released from the Weibel-Palade bodies of cultured endothelial cells following treatment with a secretagogue (Sporn et al, Cell 46:185, 1986). These multimers were shown by immunofluorescent staining to bind more extensively to the extracellular matrix of human foreskin fibroblasts than constitutively secreted vWf, which is composed predominantly of dimeric molecules. Increased binding of A23187-released vWf was not due to another component present in the releasate, since releasate from which vWf was adsorbed, when added together with constitutively secreted vWf, did not promote binding. When iodinated plasma vWf was overlaid onto the fibroblasts, the large forms bound preferentially to the matrix. These results indicated that the enhanced binding of the vWf released from the Weibel-Palade bodies was likely due to its large multimeric size. It appears that multivalency is an important component of vWf interaction with the extracellular matrix, just as has been shown for vWf interaction with platelets. The pool of vWf contained within the Weibel-Palade bodies, therefore, is not only especially suited for platelet binding, but also for interaction with the extracellular matrix.     

Elevated mutation rates in the germ line of first- and second-generation offspring of irradiated male mice

Mutation rates at two expanded simple tandem repeat loci were studied in the germ line of first- and second-generation offspring of inbred male CBA/H, C57BL/6, and BALB/c mice exposed to either high linear energy transfer fission neutrons or low linear energy transfer x-rays. Paternal CBA/H exposure to either x-rays or fission neutrons resulted in increased mutation rates in the germ line of two subsequent generations. Comparable transgenerational effects were observed also in neutron-irradiated C57BL/6 and x-irradiated BALB/c mice. The levels of spontaneous mutation rates and radiation-induced transgenerational instability varied between strains (BALB/c>CBA/H>C57BL/6). Pre- and postmeiotic paternal exposure resulted in similar increases in mutation rate in the germ line of both generations of CBA/H mice, which together with our previous results suggests that radiation-induced expanded simple tandem repeat instability is manifested in diploid cells after fertilization. The remarkable finding that radiation-induced germ-line instability persists for at least two generations raises important issues of risk evaluation in humans.     

Comparison of endocardial and epicardial programmed stimulation for the induction of ventricular tachycardia

Twenty-seven patients who had pairs of stainless steel wire electrodes placed on the right and the left ventricle during cardiac surgery underwent both epicardial and endocardial programmed ventricular stimulation to assess the inducibility of ventricular tachycardia. Twenty-six of the patients had coronary artery disease and were studied to evaluate map-guided surgery for treatment of ventricular arrhythmias. Burst ventricular pacing and up to three ventricular extrastimuli coupled to two drive train cycle lengths were delivered from the right and left ventricular epicardial wire electrodes and from endocardial catheter electrodes placed at the apex and outflow tract of the right ventricle. Ventricular tachycardia was reproducibly induced in three patients by both endocardial and epicardial stimulation. In one patient ventricular tachycardia was reproducibly induced by epicardial stimulation, but nonreproducible, nonsustained ventricular tachycardia was induced by endocardial stimulation. Ventricular tachycardia remained inducible by both endocardial and epicardial stimulation in three instances (two patients) during drug therapy. A negative study (less than 10 consecutive ventricular beats induced) was obtained in 23 patients by both endocardial and epicardial stimulation. The patients were followed up for 12 to 43 months (average 31). Sudden death or documented ventricular tachycardia occurred in two of the three patients with a positive study by both endocardial and epicardial stimulation. Nineteen (83%) of the 23 patients with concordantly negative studies remained free of arrhythmias. On the basis of concordant results of endocardial and epicardial stimulation (p = 0.001) these results suggest that epicardial stimulation of the right and the left ventricle is an acceptable method to assess the postoperative inducibility of ventricular tachycardia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Dietary quercetin glycosides: antioxidant activity and induction of the anticarcinogenic phase II marker enzyme quinone reductase in Hepalclc7 cells

It has recently been shown by Hollman et al. (Am. J. Clin. Nutr.,62, 1276–1282) that flavonoid glycosides are preferentiallyabsorbed from dietary onions compared to the flavonoid aglycone.In the light of this, we have compared the bioactivities ofthe two most abundant flavonoid glycosides that we have purifiedfrom onions (quercetin-3,4'-diglucoside and quercetin-4'-glucoside)to the quercetin aglycone, and also to the more commonly studiedcommercially-available flavonoid glycosides, rutin (quercetin-3-rutinoside)and isoquercitrin (quercetin-3-glucoside). Quercetin aglyconewas the most effective inducer of the anticarcinogenic phaseII marker enzyme, quinone reductase (QR), in mouse Hepalclc7cells. Of the glycosides, only quercetin-4'-glucoside was ableto induce QR activity in this assay. Inhibition of NADPH/iron-and ascorbate/iron-induced lipid peroxidation of human livermicrosomes, and the Trolox C-equivalent antioxidant capacity(TEAC), were also measured. The 4'-glycosylation dramaticallydecreased activity in the ‘antioxidant’ assays,whereas 3-substitutions produced much smaller changes. Theseresults show that the preferentially-absorbed quercetin glycosidesin onions have markedly different biological properties comparedwith the aglycone.     

Myeloid,B and T lymphoid and mixed lineage thymic lymphomas in the irradiated mouse

Thymic lymphoma is a very common spontaneous and/or induced malignancy in both inbred mice and in transgenic mouse models of human cancer. Although a thymic lymphoma is defined as thymus-dependent T-cell malignancy, diagnostic criteria vary between studies and considerable heterogeneity has been reported. To define and classify the thymic lymphomas that arose in our study of X-irradiated (CBA/HxC57BL/6)F1, F1 backcross and F1 intercross mice, 66 thymic lymphomas were immunogenotyped for immunoglobulin heavy chain (IgH) and T-cell receptor beta (TCRbeta) gene rearrangements, and/or analysed for expression of lineage-specific markers and allelic loss on chromosome 4. The data indicate that 33% of the thymic lymphomas are very similar to mouse radiation-induced acute myeloid (AML) and mixed lineage (IgH(R), TCRbeta(G)) pre-B lympho-myeloid (L-MLs) leukaemias, 33% are mixed lineage (IgH(R), TCRbeta(R)) B/T lymphoid and <33% can be described as single lineage (IgH(G), TCRbeta(R)) T-cell malignancies. As the myeloid and L-ML leukaemias are not thymus-dependent this suggests that a malignant myeloid or pre-B lympho-myeloid cell can colonize the spleen to give an AML or L-ML leukaemia, or can colonize the thymus where TCRbeta gene rearrangement(s) may be induced to give the mixed lineage thymic lymphomas. Thus, assuming the single lineage T-cell thymic lymphomas fulfil the criteria of a thymus-dependent T-cell malignancy, thymic lymphomas are comprised of at least three distinct malignancies.     

The bottom line: Outcomes after conservation treatment in anal cancer

At the Department of Radiation Oncology, Westmead Hospital, between 1980 and 2000, 60 patients with squamous cell carcinoma of anal canal or margin (including 15 with Stage IIIA or IIIB) were treated radically; 55 received chemoradiation (89% were prescribed mitomycin C and 5‐fluorouracil). Five‐year overall survival was 64% (95% confidence interval (CI): 48–79%), with a median survival of 9.75 years (median follow up 5.6 years, range 5 months to 22.5 years). Ten patients have died of disease. At 2 years the local control rate was 86%, and colostomy‐free survival was 83%. Relapse after 2 years was uncommon. Tumour size was the main factor driving outcomes, especially survival. Patients with larger tumours (T > 4 cm) had a hazard ratio for survival of 5.7 (95% CI: 1.8–17). Fourteen (24%) patients experienced treatment interruptions as a result of acute toxicity, including one death from neutropoenic sepsis. Seven (12%) patients, in total, experienced one or more late toxicities, grade 3 or above, including four women (all postmenopausal) who developed a radiation‐induced bone injury. Most patients with anal cancer can expect to retain a functional sphincter after chemoradiation/radiation. Further studies are in progress to determine the optimal chemoradiation protocol.