Residual high-grade angina after enhanced external counterpulsation therapy

OBJECTIVE: We evaluated the degree of residual angina on the outcomes of enhanced external counterpulsation (EECP) therapy for chronic stable angina. BACKGROUND: Angina refractory to medical therapy is common in the pool of patients who are not completely revascularized by angioplasty or bypass surgery. METHODS: We examined 902 patients enrolled from 1998 to 2001 in the Second International Enhanced External Counterpulsation Patient Registry. Baseline and outcome variables were stratified by the last recorded Canadian Cardiovascular Society class. RESULTS: Residual Class 3 (12.1%) or 4 (2.3%) angina was uncommon among patients with severe coronary artery disease after treatment with EECP. Prevalence of diabetes, hypertension, dyslipidemia, and heart failure was similar among the anginal post-EECP anginal classes. Multivessel coronary disease was more common in those with higher-grade angina at completion. More frequent and severe angina at entry was more common in those with the higher anginal classes at EECP (P<.001). There were no differences in the rates of chronic medications utilized or prior revascularization. At 3-year follow-up, rates of death, myocardial infarction, percutaneous coronary intervention, and coronary artery bypass surgery tended to be higher across increasing residual angina classes. The composite cardiac event rates were 34%, 33%, and 44% for those with Class 0, Class 1/2, and Class 3/4 angina at EECP completion (P=.01), respectively. Multivariate analysis for the composite endpoint found residual Class 3/4 angina (OR=1.59, 95% CI=1.19-2.17, P=.002), diabetes (OR=1.57, 95% CI=1.23-2.01, P=.0003), age (per decile OR=1.17, 95% CI=1.04-1.31, P=.007), and greater EECP augmentation (OR=0.79, 95% CI=0.65-0.96, P=.02) as significant predictors. CONCLUSIONS: Residual high-grade angina after EECP occurs in those with more severe angina and multivessel disease at baseline and is associated with cardiac events over the next 3 years. These data suggest that close clinical observation and intensive management of those with high-grade angina post-EECP are warranted.     

Expression of Skp2, a p27(Kip1) ubiquitin ligase,in malignant lymphoma: correlation with p27(Kip1) and proliferation index

Reduced levels of p27(Kip1) are frequent in human cancers and have been associated with poor prognosis. Skp2, a component of the Skp1-Cul1-F-box protein (SCF) ubiquitin ligase complex, has been implicated in p27(Kip1) degradation. Increased Skp2 levels are seen in some solid tumors and are associated with reduced p27(Kip1). We examined the expression of these proteins using single and double immunolabeling in a large series of lymphomas to determine if alterations in their relative levels are associated with changes in cell proliferation and lymphoma subgroups. We studied the expression of Skp2 in low-grade and aggressive B-cell lymphomas (n = 86) and compared them with p27(Kip1) and the proliferation index (PI). Fifteen hematopoietic cell lines and peripheral blood lymphocytes were studied by Western blot analysis. In reactive tonsils, Skp2 expression was limited to proliferating germinal center and interfollicular cells. Skp2 expression in small lymphocytic lymphomas (SLLs) and follicular lymphomas (FCLs) was low (mean percentage of positive tumor cells, less than 20%) and was inversely correlated (r = -0.67; P <.0001) with p27(Kip1) and positively correlated with the PI (r = 0.82; P <.005). By contrast, whereas most mantle cell lymphomas (MCLs) demonstrated low expression of p27(Kip1) and Skp2, a subset (n = 6) expressed high Skp2 (exceeding 20%) with a high PI (exceeding 50%). Skp2 expression was highest in diffuse large B-cell lymphomas (DLBCLs) (mean, 22%) and correlated with Ki-67 (r = 0.55; P <.005) but not with p27(Kip1). Cytoplasmic Skp2 was seen in a subset of aggressive lymphomas. Our data provide evidence for p27(Kip1) degradative function of Skp2 in low-grade lymphomas. The absence of this relationship in aggressive lymphomas suggests that other factors contribute to deregulation of p27(Kip1) expression in these tumors.     

Prenatal Diagnosis of Spontaneous Septostomy in Dichorionic Diamniotic Twins and Review of the Literature

Objective. We present 2 cases of spontaneous septostomy in dichorionic diamniotic twins and review the literature regarding the incidence, etiology, and complications of this condition. Methods. The following key words were used in the literature search: “rupture dividing membrane twin,” “disruption dividing membrane twin,” “pseudomonoamniotic twin,” “spontaneous septostomy twin,” “interfetal membrane disruption,” “intertwin membrane rupture,” and “intertwin membrane disruption.” Results. We present 2 cases in which an intertwin membrane defect was found prenatally in dichorionic diamniotic twins. In both cases, a portion of one twin's body was found traversing the spontaneous septostomy and in the sac of its cotwin. Umbilical cord Doppler studies showed no abnormalities in either case as the cord crossed the membrane disruption. In both cases, the fetuses had no notable sequelae from the ruptured intertwin membrane. The literature review revealed no cases of spontaneous septostomy in dichorionic diamniotic twins but 15 cases in monochorionic diamniotic twins. Possible etiologies include chorioamnionitis, trauma or physical rupture by the fetuses, developmental disturbances represented by amniotic plica, and polyhydramnios. In cases of monozygotic twins, a vascular etiology could explain this rare defect with formation of anastomoses of the outer embryonic vasculature. Complications of the spontaneous septostomy cases identified in the literature included cord entanglement (8 cases), preterm delivery (9 cases), and death (8 cases), although our 2 cases had minimal complications. Conclusions. Spontaneous septostomy in dichorionic diamniotic twins has not previously been reported.     

Asthma symptom perception and obesity in children

This study examined the relationship between obesity and asthma symptom perception in 200 youth with asthma. Repeated subjective and objective peak flow measurements were summarized using the Asthma Risk Grid (Klein et al., 2004), resulting in Accurate, Symptom Magnification and Danger Zone scores. Analyses were stratified by age and included ethnicity.For younger children, obesity was not significantly related to perception scores. For older children, a significant obesity-by-ethnicity interaction for Accurate Symptom Perception scores indicated that obese white children had lower accuracy than white nonobese children, while there was no difference for obese versus nonobese minority children. Obesity was also related to higher Symptom Magnification scores regardless of ethnicity for older children.These findings suggest that obesity may complicate asthma management by interfering with the ability to accurately perceive symptoms for some patients. More remains to be learned about the role of sociodemographic factors underlying this relationship.     

Drug utilization and cost in a Medicaid population: A simulation study of community vs. mail order pharmacy

Background  

Outpatient drugs are dispensed through both community and mail order pharmacies. There is no empirical evidence that substitution of community pharmacy with mail order reduces overall drug expenditures. The need for evaluating the potential effects on utilization and costs of the possible extension of mail order services in Medicaid provides the rationale for conducting this study. This study compares drug utilization and drug product cost in community vs. mail order pharmacy dispensing services in a Medicaid population.     

Flashlamp-excited dye laser therapy of idiopathic vulvodynia is safe and efficacious

Objective: The management of chronic vulvovaginal pain, not explicable on specific histologic grounds, presents a major problem in referral centers for lower genital tract diseases.Study design: This article reports on a two-step protocol in a sample of 175 medical nonresponders, drawn from a 2-year cohort of 725 women with vulvovaginal pain. The first maneuver was the use of a flashlamp-excited dye laser to selectively photocoagulate symptomatic subepithelial blood vessels in 168 women; the second was the microsurgical removal of chronically painful Bartholin's glands in 52 women not responsive or not suited to flashlamp-excited dye laser photothermolysis.Results: Dye laser response rates werer independent of whether patients manifested macroscopic focl of painful erythema (“vestibular adenitis”) or just colposcopically apparent hyperemia-ectasia of the individual blood vessels (“pruritic papillomatosis”) (55% vs 45% after a single surgical procedure; 76% vs 65% after serial retreatment; p not significant). Conversely, response rates were much lower among women in whom pressure on the Bartholin's glands produced sharp, lancinating pain (15% vs 66% after a single surgical procedure; 22% vs 93% after serial retreatment; p < 0.001). Forty-two (85%) of 50 patients with flashlamp-excited dye laser failure had deep pain; however, the impasse to progress was broken by gland removal. Final response rates were 92.5% (complete response 62%; partial response 30%) in the “surface-only” group and 80.3% in the “surface-plus-deep” group (χ² = 14.9; p < 0.001). The major complication was acute bacterial cellulitis, occurring in the first postoperative week. Modification of the treatment protocol to include topical antibiotics with an occlusive dressing reduced the cellulitis rate from 17.2% to 2.5%. In four women (1.8%) Koebner-like exophytic condylomas also developed within 1 month of flashlamp-excited dye laser surgery.Conclusion: The availability of a safe, efficacious, and relatively noninvasive treatment should reduce the need for resective surgery in most patients with idiopathic vulvodynia. 1995; 172; 1684–1701.)