Prediction of outcomes in hypertensive patients with suspected coronary disease

Stress echocardiography has been shown to improve the diagnosis of coronary artery disease in the presence of hypertension, but its value in prognostic evaluation is unclear. We sought to determine whether stress echocardiography could be used to predict mortality in 2363 patients with hypertension, who were followed for up to 10 years (mean 4.0+/-1.8) for death and revascularization. Stress echocardiograms were normal in 1483 patients (63%), 16% had resting left ventricular (LV) dysfunction alone, and 21% had ischemia. Abnormalities were confined to one territory in 489 patients (21%) and to multiple territories in 365 patients (15%). Cardiac death was less frequent among the patients able to exercise than among those undergoing dobutamine echocardiography (4% versus 7%, P< 0.001). The risk of death in patients with a negative stress echocardiogram was <1% per year. Ischemia identified by stress echocardiography was an independent predictor of mortality in those able to exercise (hazard ratio 2.21, 95% confidence intervals 1.10 to 4.43, P=0.0001) as well as those undergoing dobutamine echo (hazard ratio 2.39, 95% confidence intervals 1.53 to 3.75, P=0.0001); other predictors were age, heart failure, resting LV dysfunction, and the Duke treadmill score. In stepwise models replicating the sequence of clinical evaluation, the results of stress echocardiography added prognostic power to models based on clinical and stress-testing variables. Thus, the results of stress echocardiography are an independent predictor of cardiac death in hypertensive patients with known or suspected coronary artery disease, incremental to clinical risks and exercise results.     

A safety analysis of oral prednisone as a pretreatment for rituximab in rheumatoid arthritis

The administration of 100?mg of methylprednisolone intravenously (IV) 1/2?h prior to rituximab decreases the incidence of acute infusion reactions (AIRs). However, this pretreatment adds considerable time and conveys potential risk. We performed an open-label prospective assessment of oral prednisone as a pretreatment to rituximab. This was a 26-week open-label trial of 40?mg of oral prednisone given 1/2?h prior to rituximab as a prophylaxis against AIRs in patients with rheumatoid arthritis (RA). The primary endpoint was AIRs in the first 24?h after their initial infusion. Secondary endpoints include AIRs during the 24?h following their second infusion and any adverse events experienced during the 26-week study; efficacy measures were also followed as secondary endpoints. Sixty-four subjects were screened, and 50 subjects qualified. Fourteen out of the 50 (28?%) subjects had AIRs within 24?h of their first infusion. There were four AIRs (8.3?%) within 24?h of their second infusion. One of day?0 AIRs required drug discontinuation (wheezing/bronchospasm). Forty out of 50 (80?%) subjects experienced an adverse event during the 26?weeks. There were three SAEs deemed not to be study-drug related. The DAS28 and HAQ-DI all improved significantly at weeks?8, 16, and 26 compared to baseline. Historical controls demonstrate that 27?% of RA subjects experience AIRs with their first rituximab infusion. Our data suggest a smaller dose of oral prednisone is an effective alternative to IV methylprednisolone as a pretreatment for rituximab in patients with RA.     

Comparative effectiveness analysis of amlodipine/renin-Angiotensin system blocker combinations

J Clin Hypertens (Greenwich). 2012; 14:601–610. © 2012 Wiley Periodicals, Inc. A comparative effectiveness analysis of antihypertensive therapy amlodipine (AML) and angiotensin receptor blocker (ARB) fixed‐ and loose‐dose combinations (FDCs and LDCs) in achieving blood pressure (BP) reduction and Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC 7) goal attainment was made using retrospective electronic medical record (EMR) data. Treatment goal rates ranged from 35.0% for LDC AML/losartan to 45.7% for FDC AML/olmesartan (OM). FDC AML/OM achieved significantly greater reductions in systolic BP than FDC AML/benazepril (BEN), FDC AML/valsartan (VAL), and LDC AML/ARBs, respectively, and significantly greater reductions in diastolic BP than FDC AML/VAL and LDC therapy, respectively. Compared with patients treated with AML/OM, patients prescribed AML/VAL and LDC AML/ARB were significantly less likely to attain JNC 7 BP goal. Among subpopulations, AML/OM yielded higher rates of goal attainment among both African Americans and obese/overweight patients relative to AML/VAL and combined LDCs. Switchers from monotherapy with AML, OM, or VAL to AML/OM were significantly more likely to attain JNC 7 goals than those switching to AML/VAL or AML/BEN.     

Gastric emptying and gastric myoelectrical activity in patients with diabetic gastroparesis: effect of long-term domperidone treatment

We measured gastric emptying and gastric myoelectrical activity with solid-phase gastric-emptying tests and cutaneously recorded electrogastrograms (EGGs), respectively, in six insulin-dependent diabetic patients with nausea and vomiting who did not respond to standard treatments. Baseline solid phase gastric emptying was markedly delayed (78 +/- 8% retained at 120 min) and EGG recordings revealed gastric dysrhythmias; tachygastria (4-9 cpm signals) in one patient, 1- to 2-cpm waves in two patients, and flatline patterns in three patients. No patient had a normal 3-cpm EGG pattern. After 6 months of domperidone treatment, mean upper gastrointestinal symptoms scores decreased from 17.8 to 3.7 (p less than 0.01), and normal 3-cpm EGG frequencies were recorded from each of the six patients. The mean percentage of meal retained at 120 min decreased but did not improve significantly. Thus, establishment of normal 3-cpm gastric myoelectric activity and resolution of dysrhythmias, not normalization of emptying rates, was associated with improvement in upper gastrointestinal symptoms in these diabetic patients.     

Human spleen cell generation of factors stimulating human pluripotent stem cell, erythroid, and myeloid progenitor cell growth

Mitogen-stimulated murine spleen cells produce humoral substances capable of supporting murine hematopoiesis and pluripotent stem cell proliferation in vitro. Thus, we evaluated conditioned media generated by human spleen cells (SCM) in the presence or absence of mitogens for factors stimulatory for human pluripotent (CFU-GEMM), erythroid (BFU- E), and myeloid (CFU-GM) precursors. Two and one half percent to 10% SCM stimulated proliferation of all three types of precursor cells from nonadherent buoyant human marrow target cells. Mitogen-stimulated SCM augmented CFU-GM (175% to 225%), whereas CFU-GEMM and BFU-E growth was essentially unchanged. Cell separation procedures used to determine which cells provided these microenvironmental stimuli indicated that nonadherent mononuclear spleen cells provided the bulk of the CSF-GM, whereas adherent cells (95% nonspecific esterase + monocyte- macrophages) and nonadherent cells provided similar proportions of CSF- mix and erythroid burst-promoting activity (BPA). The nonadherent cells generating high levels of CSF-mix, BPA, and CSF-GM were predominantly Leu-1-negative, ie, non-T, cells. In the presence or absence of mitogens, SCM was a more potent source (1.3- to 3.8-fold) than peripheral leukocyte CM of the growth factors for the three progenitor cell types. Specific in situ cytochemical stains for analyzing morphology of myeloid colonies demonstrated that SCM stimulated the proliferation of the same types and proportions of colonies as human placental CM, suggesting that these CMs may contain similar CSF-GMs. These data show the contribution of spleen cell subsets to the generation of hematopoietic growth factors and the responsiveness of these cells to various mitogenic stimuli.     

Native associations of early hematopoietic stem cells and stromal cells isolated in bone marrow cell aggregates

In suspensions of murine bone marrow, many stromal cells are tightly entwined with hematopoietic cells. These cellular aggregations appear to exist normally within the marrow. Previous studies showed that lymphocytes and stem cells adhered to stromal cells via vascular cell adhesion molecule 1 (VCAM1). Injection of anti-VCAM1 antibody into mice disrupts the aggregates, showing the importance of VCAM1 in the adhesion between stromal cells and hematopoietic cells in vivo. Early hematopoietic stem cells were shown to be enriched in aggregates by using a limiting-dilution culture assay. Myeloid progenitors responsive to WEHI-3CM in combination with stem cell factor (c-kit ligand) and B220- B-cell progenitors responsive to insulin-like growth factor-1 in combination with interleukin-7 are not enriched. We propose a scheme of stromal cell-hematopoietic cell interactions based on the cell types selectively retained within the aggregates. The existence of these aggregates as native elements of bone marrow organization presents a novel means to study in vivo stem cell-stromal cell interaction.     

Evidence of Cognitive Biases for Maximizing Indirect Fitness in Samoan Fa’afafine

The kin selection hypothesis posits that male androphilia (i.e., sexual attraction to males), although detrimental to reproduction (i.e., direct fitness), has persisted and evolved because androphilic males compensate by increasing their indirect fitness via increased investment in kin. In previous studies, Samoan androphilic males (known locally as fa’afafine) reported elevated avuncular (i.e., uncle-like) tendencies compared to Samoan gynephilic (i.e., sexually attracted to females) men. Their avuncular tendencies were also greater than the materteral (i.e., aunt-like) tendencies of androphilic women. The present study examined whether the avuncular cognition of fa’afafine was enhanced for maximizing indirect fitness. To do so, it examined whether fa’afafine had a stronger propensity than Samoan gynephilic men and androphilic women to invest in kin categories that would result in more reliable and substantive increases in indirect fitness (i.e., young, female kin) in hypothetical investment scenarios. In a forced-choice paradigm, although all individuals showed some degree of bias to invest in adaptive kin categories during non-frivolous investment contexts in which the consequences of investment were relatively non-trivial, fa’afafine showed greater adherence to the predicted pattern. In addition, shifting the context from frivolous investments, in which the consequences of investment were relatively trivial, to non-frivolous investments prompted fa’afafine to exhibit an enhanced preference, relative to Samoan gynephilic men and androphilic women, to invest in adaptive kin categories. These findings were consistent with the kin selection hypothesis and suggest that, although all individuals exhibit cognitive biases for increasing indirect fitness, the avuncular cognition of androphilic males has undergone selective enhancement to maximize the accrual of indirect fitness via kin-directed altruism.     

The relationship between fraternal birth order and childhood sex-atypical behavior among the Istmo Zapotec muxes

Research on male androphilia (i.e., sexual attraction towards adult males) consistently finds that androphilic males tend to have more older biological brothers than males who are gynephilic (i.e., sexually attracted to adult females). This fraternal birth order effect (FBOE) has been well replicated among androphilic males who present publically in a male-typical (cisgender) and a female-typical (transgender) manner. There is some evidence that the FBOE is more pronounced among transgender androphilic males. However, no studies have directly compared both forms of male androphilia within the same culture. This study tested the FBOE, and its association with childhood sex-atypical behavior (CSAB), among the Istmo Zapotec of Oaxaca, Mexico, where both forms of male androphilia are referred to as a third gender, muxes. Our results indicated that both cisgender muxe nguiiu (n = 124) and transgender muxe gunaa (n = 120) were more likely to be later born among brothers than gynephilic men (n = 194). However, the number of older brothers did not differentiate between transgender and cisgender muxes, nor did it predict CSAB among muxes. These findings replicate the FBOE among both cisgender and transgender muxes but show no evidence that it is more pronounced among transgender androphilic males.