Role of echocardiography in patients undergoing elective cardioversion of atrial fibrillation

BACKGROUND: Performance of endomyocardial biopsy (EMB) to diagnose myocarditis in patients with dilated cardiomyopathy is controversial because of a lack of evidence favoring immunosuppressive therapy. In spite of advances in heart failure treatment, dilated cardiomyopathy carries a poor prognosis, and myocardial inflammation and viral infection are potential therapeutic targets. METHODS: We used decision analysis to determine the efficacy (5-year risk reduction in mortality or transplantation) that a treatment for myocarditis would require to favor a biopsy-guided approach over conventional therapy. Literature-based estimates included prevalence of myocarditis among patients with dilated cardiomyopathy with or without borderline myocarditis (16% and 11%, respectively); probability of 5-year transplantation-free survival (55%); sensitivity (50% and 63%, respectively), specificity (95.4%), and mortality rate (0.4%) of EMB; side effects resulting in withdrawal of immunosuppressive treatment (4%); and a 6-month mortality rate for immunosuppressive treatment (0.1%). All estimates were varied to determine impact on model results (sensitivity analysis). RESULTS: A therapy that decreased the rate of death or transplantation by 12.7% and 7.1% for patients without or with borderline myocarditis, respectively, favored EMB. Sensitivity analysis indicated that therapeutic efficacy was influenced by myocarditis prevalence and biopsy-related death, but not by accuracy of biopsy or probability of immunosuppressive therapy side effects. Randomized trials powered to detect 7% and 25% reductions in death and transplantation would require 5790 and 380 end points, respectively. CONCLUSION: Decreasing the rate of death or transplantation by 7.1% offsets therapy side effects, EMB-related death, and inaccuracies in histologic diagnosis. Prospective randomized trials of treatments for myocarditis may be more feasible during periods of high prevalence or with more sensitive diagnostic techniques.     

Local progression of atherosclerosis after optimal directional atherectomy. Endocoronary ultrasonography of 17 patients

In vivo endovascular ultrasonography has confirmed the extension of atheroma to angiographically normal segments. The authors set out to determine by endocoronary ultrasonography if the introduction of the atherotome changed the intimal thickness 20 mm proximal and distal to the site treated. The area circumscribed by the external elastic layer (EEL) and the surface area of the lumen was measured in 17 patients: 1) before atherectomy; 2) after atherectomy; 3) at control 6 months later. Atherectomy immediately increased the luminal area at the site dilated from 1.9 + 0.9 to 8.1 +/- 2mm (p < 0.001). At the proximal segment, the surface area of the lumen was unchanged (mean + 0.6 +/- 1.5 mm2; p = 0.13). Similarly the procedure did not change the surface circumscribed by the EEL (mean + 0.8 +/- 3.2 mm2; p = 0.32) in this zone. The same results were observed at the distal site. At 6 months, the areas under the EEL and those of the lumen were unchanged at the unoperated sites. The mean of the differences (+/- 1 SD) for the area under the EEL was respectively -0.2 +/- 1.5 mm2 proximally and +0.7 +/- 2.5 mm2 distally. The means for the luminal area were 0.2 +/- 1 mm2 proximally and -0.01 +/- 1.1 mm2; distally. At the site of atherectomy, the luminal surface increased (+2.0 +/- 2.6 mm2; p < 0.01) as did the area under the EEL (+2.0 +/- 3.5 mm2; p < 0.05). This preliminary series shows no significant progression of atherosclerosis at the sites not affected by atherectomy.     

Calibrated histochemistry of myoglobin concentration in cardiomyocytes

This article describes the calibration of a histochemical method to determine the myoglobin concentration in individual cardiomyocytes. Calibration is based on paired microdensitometric determinations in sections stained for myoglobin and on biochemical myoglobin determinations in tissue samples from different hearts. In addition, the staining intensity of sections from gelatin blocks containing known amounts of myoglobin is determined. To construct a calibration line, sections stained for myoglobin must be corrected for the degree of shrinkage caused by glutaraldehyde fixation and biochemical myoglobin determinations must be corrected for interstitial space. As an example, the method is used to determine the myoglobin concentration in individual skeletal muscle fibers and in control and hypertrophied rat cardiomyocytes. The amount of myoglobin per cardiomyocyte nucleus is increased two- to threefold in hypertrophied cardiomyocytes, whereas changes in myoglobin concentration depend on the model of hypertrophy used.     

Affinity purification and partial characterization of a yeast multiprotein complex for nucleotide excision repair using histidine-tagged Rad14 protein

The nucleotide excision repair (NER) pathway of eukaryotes involves approximately 30 polypeptides. Reconstitution of this pathway with purified components is consistent with the sequential assembly of NER proteins at the DNA lesion. However, recent studies have suggested that NER proteins may be pre-assembled in a high molecular weight complex in the absence of DNA damage. To examine this model further, we have constructed a histidine-tagged version of the yeast DNA damage recognition protein Rad14. Affinity purification of this protein from yeast nuclear extracts resulted in the co-purification of Rad1, Rad7, Rad10, Rad16, Rad23, RPA, RPB1, and TFIIH proteins, whereas none of these proteins bound to the affinity resin in the absence of recombinant Rad14. Furthermore, many of the co-purifying proteins were present in approximately equimolar amounts. Co-elution of these proteins was also observed when the nuclear extract was fractionated by gel filtration, indicating that the NER proteins were associated in a complex with a molecular mass of >1000 kDa prior to affinity chromatography. The affinity purified NER complex catalyzed the incision of UV-irradiated DNA in an ATP-dependent reaction. We conclude that active high molecular weight complexes of NER proteins exist in undamaged yeast cells.     

Traditional drug therapy of hypertension in transplant recipients

Nasopharyngeal angiofibroma (NAF), occurring mostly in young men, is a histologically benign tumor with aggressive clinical behavior that includes repeated epistaxis and intractable nasal obstruction. This paper reviews our recent experience at National Taiwan University Hospital (NTUH), and compares the results with those of a previous study (1955-1980) at NTUH to highlight the developments in the treatment of NAF. Fifteen patients with a diagnosis of NAF from 1984 to 1997 were included, and their clinical presentations, radiographic studies, treatments, and outcomes were retrospectively analyzed. The results showed that the clinical and demographic features were similar in the two studies. The average number of patients decreased from 2.1 patients in the previous study to 1.1 patients in this study. The duration of symptoms in the current study (8 months) was shorter than that of the previous study (16 months). Previously, the treatment consisted of radiation followed by surgery if there was residual tumor. The current treatment modality is preoperative transarterial embolization followed by surgery. The estimated intraoperative blood loss was reduced from 750 mL in the first study to 400 mL in this study. The recurrence rate decreased from 11% to 7% and the absolute relapse-free rate rose from 56% to 73%. Owing to the development of modern imaging techniques, the advent of preoperative arterial embolization, and advances in surgical techniques, successful removal of highly vascular tumors has become more feasible. Preoperative selective embolization followed by excision is an effective treatment modality. This strategy, an alternative to radiotherapy, not only avoids the long-term complications induced by radiation, but also reduces the tumor recurrence rate.     

The relationship between serum and saliva erythropoietin concentrations in adults, full-term and premature infants

Not only thyroid adenomas and carcinomas, but also the majority of single and well delimited goiter nodules, even if morphologically heterogeneous, are of clonal origin. However, it is still unknown whether the nodules of rapidly growing, recurrent goiters are clonal or polyclonal. We investigated by PCR-based analysis of exon 1 of the human androgen receptor gene clonality of nodules grown in recurrent multinodular goiters (MNG) of 14 female patients. The total goiter volume varied widely between 15 ml and 170 ml. The mean age of patients undergoing surgery for recurrent goiter at the time of their first operation was significantly lower with 34.6 +/- 10.9 yr in comparison to 50 consecutive patients who were operated for MNG for the first time (53.7 +/- 13.5 yr). The interval between first and recurrent operation was 18 +/- 8.5 yr. The mean volume of well circumscribed nodules selected for the present investigation was 3.8 +/- 1.4 ml. Assessment of clonality in at least 2 samples of each lesion revealed a polyclonal pattern in 10 out of 14 nodules, whereas only 3 nodules were clonal and in one case the result remained unclear. The unexpected finding that most nodules within MNG, that had re-grown after a first subtotal thyroidectomy, were of polyclonal rather than clonal composition, suggests that these lesions are generated by de novo-proliferation of cohorts of differing thyrocytes sharing the common trait of an exceedingly high intrinsic growth rate or alternatively, by unknown growth stimulating molecular events acting focally on clusters of cells derived from different ancestors. In addition, the relatively young age of patients with recurrent MNG at the time of their first surgery and the comparatively short interval between first and second operation point to a genetic element in the occurrence of growth-prone thyrocytes.     

Effect of resistance exercise training on cortical and cancellous bone in mature male rats

The thermal inactivation kinetics of Salmonella enteritidis PT4 between 49 and 60 degrees C were investigated. Using procedures designed to eliminate methodological artifacts, we found that the death kinetics deviated from the accepted model of first-order inactivation. When we used high-density stationary-phase populations and sensitive enumeration, the survivor curves at 60 degrees C were reproducibly biphasic. The decimal reduction time at 60 degrees C (D60 degrees C) of the tail subpopulation was more than four times that of the majority population. This difference decreased with decreasing temperature; i.e., the survivor curves became more linear, but the proportion of tail cells remained a constant proportion of the initial population, about 1 in 10(4) to 10(5). Z plots (log D versus temperature) for the two populations showed that the D values coincided at 51 degrees C, indicating that the survivor curves should be linear at this temperature, and this was confirmed experimentally. Investigations into the nature of the tails ruled out genotypic differences between the populations and protection due to leakage from early heat casualties. Heating of cells at 59 degrees C in the presence of 5 or 100 micrograms of chloramphenicol per ml resulted in reductions in the levels of tailing. These reductions were greatest at the higher chloramphenicol concentration. Our results indicate that de novo protein synthesis of heat shock proteins is responsible for the observed tailing. Chemostat-cultured cells heated at 60 degrees C also produced biphasic survivor curves in all but one instance. Cells with higher growth rates were more heat sensitive, but tailing was comparable with batch cultures. Starved cells (no dilution input) displayed linear inactivation kinetics, suggesting that during starvation a rapid heat shock response cannot be initiated.