Comparison of hemodynamic responses to nifedipine and nitroprusside in severe chronic congestive heart failure

The hemodynamic effects of 20 to 40 mg of oral nifedipine were compared with those of intravenous nitroprusside in 11 patients with severe chronic congestive heart failure (CHF). In each patient, both drugs were administered to produce similar reduction of systemic vascular resistance (SVR) (29 ± 13% with nifedipine and 29 ± 12% with nitroprusside, difference not significant [NS]). At this comparable decrease in systemic vascular resistance, significant differences in hemodynamic responses to both drugs were noted: Nifedipine caused a smaller increase in cardiac index (20 ± 20% vs 40 ± 24%, p < 0.02) and a larger decrease in mean blood pressure than nitroprusside (16 ± 9% vs 8 ± 10%, p < 0.05). In addition, nifedipine produced a smaller decrease in mean pulmonary artery wedge pressure (13 ± 24% vs 36 ± 21%, p < 0.001) and pulmonary vascular resistance than nitroprusside (6 ± 42% vs 26 ± 46%, NS. Mean right atrial pressure decreased with nitroprusside, from 10 ± 7 to 5 ± 3 mm Hg (p < 0.05), but not with nifedipine (10 ± 7 mm Hg before and after nifedipine administration, NS). Left ventricular stroke work index increased with nitroprusside (20 ± 8 to 27 ± 9 g-m/m², p < 0.05), but did not change with nifedipine (21 ± 9 vs 21 ± 10 g-m/m², NS). These data show that nifedipine has an arteriolar dilatatory action in patients with CHF. However, compared with nitroprusside, nifedipine had a significantly larger hypotensive effect and had a lesser effect on right and left ventricular filling pressure, cardiac output and left ventricular function.     

Are triglyceride-rich lipoproteins associated with aortic valve sclerosis? A preliminary report

Background: Evidence linking cardiovascular risk factors to aortic valve sclerosis (AVS) has led to the assumption that the latter is an atherosclerosis-like process. However, triglyceride (TG)-rich lipoproteins, an important risk factor for atherosclerosis, have been rarely investigated in connection with AVS. Methods: A cross-sectional study of 246 healthy individuals (mean age 59±6 years, 77% men) was conducted. Subjects underwent an echocardiographic assessment and extensive blood lipid measurements, including evaluation of TG-related indices, such as serum apolipoprotein (apo) C_II and C_III levels, apo C_III levels in VLDL+LDL particles, and apo C_III ratio (C_III level in HDL/C_III level in VLDL+LDL). Results: Twenty-three patients (9.3%) were diagnosed as having AVS. On average, these patients were 5 years older and had higher levels of serum cholesterol, LDL-C and LP(a), compared with non-AVS subjects. In addition, the AVS patients exhibited higher concentrations of serum apo C_II, serum apo C_III and apo C_III in VLDL+LDL, and a lower apo C_III ratio. Adjusting for age and gender, a 1 S.D. increment in apo C_III in VLDL+LDL was associated with odds ratio (OR) of 1.76 (95% CI: 1.17–2.65) for AVS. Further adjustment for atherosclerotic risk factors did not alter the association appreciably (OR=1.65, 95% CI: 1.06–2.58). Conclusion: TG-rich lipoproteins may be involved in the early development of AVS. Confirmation in prospective studies is required.     

Spontaneous evolution of modularity and network motifs

Biological networks have an inherent simplicity: they are modular with a design that can be separated into units that perform almost independently. Furthermore, they show reuse of recurring patterns termed network motifs. Little is known about the evolutionary origin of these properties. Current models of biological evolution typically produce networks that are highly nonmodular and lack understandable motifs. Here, we suggest a possible explanation for the origin of modularity and network motifs in biology. We use standard evolutionary algorithms to evolve networks. A key feature in this study is evolution under an environment (evolutionary goal) that changes in a modular fashion. That is, we repeatedly switch between several goals, each made of a different combination of subgoals. We find that such "modularly varying goals" lead to the spontaneous evolution of modular network structure and network motifs. The resulting networks rapidly evolve to satisfy each of the different goals. Such switching between related goals may represent biological evolution in a changing environment that requires different combinations of a set of basic biological functions. The present study may shed light on the evolutionary forces that promote structural simplicity in biological networks and offers ways to improve the evolutionary design of engineered systems.     

Low- and high-density lipoprotein cholesterol and ischemic cerebrovascular disease: the bezafibrate infarction prevention registry

BACKGROUND: Despite increasing evidence that beta-hydroxy-beta-methyglutaryl coenzyme A reductase inhibitors reduce the incidence of stroke in patients with coronary heart disease (CHD), the associations between blood lipid levels and cerebrovascular disease (CVD) are not clear. OBJECTIVE: To evaluate whether blood cholesterol level and its fractions are risk factors for stroke in a large group of patients with CHD. METHODS: We followed up 11 177 patients with documented CHD who were screened for but not included in the Bezafibrate Infarction Prevention study, a secondary prevention randomized clinical trial of lipid modification, and had no history of stroke for subsequent CVD. During a 6- to 8-year follow-up period, 941 patients were identified as having nonhemorrhagic CVD, of whom 487 had verified ischemic stroke or transient ischemic attack (TIA). RESULTS: Increases in age-adjusted rates of both nonhemorrhagic CVD and verified ischemic stroke or TIA were identified with increasing cholesterol and low-density lipoprotein cholesterol levels, decreasing high-density lipoprotein cholesterol levels, and decreasing percentage of total serum cholesterol contained in the HDL moiety. In logistic regression models, adjusting for clinical covariates, the following odds ratios (95% confidence intervals) were identified for lipid values in the upper vs lower tertile for the end point of nonhemorrhagic CVD: total cholesterol, 1.43 (1.20-1.70); low-density lipoprotein cholesterol, 1.52 (1.27-1.81), high-density lipoprotein cholesterol, 0.84 (0.70-1.00); and percentage of serum cholesterol contained in HDL, 0.69 (0.58-0.83). Similar trends appeared for the end point of verified ischemic stroke or TIA. CONCLUSION: These findings clearly support the role of total cholesterol and its fractions in prediction of ischemic CVD among patients with established CHD.     

Gas flow during bronchoscopic ablation therapy causes gas emboli to the heart: a comparative animal study

BACKGROUND: Thermal ablation is one of the most commonly used modalities to treat central airway obstruction. Both laser and argon plasma coagulation (APC) have been reported to cause gas emboli and cardiac arrest. We sought to determine whether bronchoscopic ablation therapy can result in systemic gas emboli, correlate their presence with the rate of gas flow, and establish whether a zero-flow (ZF) modality would result in the significant reduction or elimination of emboli. METHODS: CO(2) laser delivered through a photonic bandgap fiber (PBF) and APC were applied in the trachea and mainstem bronchi of six anesthetized sheep at varying dosages and gas flow rates. Direct epicardial echocardiography was used to obtain a four-chamber view and detect gas emboli. RESULTS: The presence of gas flow accompanying APC and the CO(2) laser with forward flow correlated significantly with the appearance of gas bubbles in the atria. A definite dose response was observed between the gas flow rate and the number of bubbles seen. When the CO(2) laser was delivered through a PBF with ZF to the trachea or bronchi, no bubbles were observed. CONCLUSION: Bronchoscopic thermal ablation therapy using gas flow is associated with gas emboli in a dose-dependent fashion. The use of the flexible PBF with ZF is not associated with the development of gas emboli. Further study is required to determine whether a clinically safe threshold of gas emboli exists, and the relationships among the pathologic depth of tissue destruction, gas flow, pulse duration, and the development of gas emboli.     

Anticoagulation in patients with atrial fibrillation,thrombocytopenia and hematological malignancy

Journal of Thrombosis and Thrombolysis - Managing anticoagulation in hematological malignancy patients with atrial fibrillation and thrombocytopenia is a clinical challenge with limited data. We...     

Early prediction of encephalopathic transformation in children with benign epilepsy with centro-temporal spikes

BackgroundMost children with Benign epilepsy with centro-temporal spikes (BECTS) undergo remission during late adolescence and do not require treatment. In a small group of patients, the condition may evolve to encephalopathic syndromes including epileptic encephalopathy with continuous spike-and-wave during sleep (ECSWS), or Landau-Kleffner Syndrome (LKS). Development of prediction models for early identification of at-risk children is of utmost importance.AimTo develop a predictive model of encephalopathic transformation using data-driven approaches, reveal complex interactions to identify potential risk factors.MethodsData were collected from a cohort of 91 patients diagnosed with BECTS treated between the years 2005–2017 at a pediatric neurology institute. Data on the initial presentation was collected based on a novel BECTS ontology and used to discover potential risk factors and to build a predictive model. Statistical and machine learning methods were compared.ResultsA subgroup of 18 children had encephalopathic transformation. The least absolute shrinkage and selection operator (LASSO) regression Model with Elastic Net was able to successfully detect children with ECSWS or LKS. Sensitivity and specificity were 0.83 and 0.44. The most notable risk factors were fronto-temporal and temporo-parietal localization of epileptic foci, semiology of seizure involving dysarthria or somatosensory auras.ConclusionNovel prediction model for early identification of patients with BECTS at risk for ECSWS or LKS. This model can be used as a screening tool and assist physicians to consider special management for children predicted at high-risk. Clinical application of machine learning methods opens new frontiers of personalized patient care and treatment.     

Treatment of renal angiomyolipoma: pooled analysis of individual patient data

Epididymal anomalies and patent processus vaginalis are frequently found in boys with cryptorchidism or hydrocele. We conducted this study to evaluate the association between epididymal anomalies and testicular location or patent processus vaginalis in boys with undescended testis or hydrocele. Children undergoing surgery with undescended testis (group A, 136 boys and 162 testes) or communicating hydrocele (group B, 93 boys and 96 testes) were included. Testicular locations and epididymal anomalies were investigated prospectively. An anomalous epididymis was defined as anomalies of epididymal fusion that consisted of loss of continuity between the testis, the epididymis, and the long looping epididymis. The epididymis was considered normal when a normal, firm attachment between the testis, the caput, and the cauda epididymis was present. The mean ages of groups A and B were 24.6 ± 19.7 (range, 8–52 months) and 31.4 ± 20.6 months (range, 10–59 months). The incidence of epididymal anomalies was significantly higher in group A than that in group B (65.4 % vs. 13.5 %, P < 0.001). The incidence of epididymal anomalies in boys with undescended testis was significantly different according to testis location. Epididymal anomalies were observed in 100 %, 91.4 %, and 39.3 % of cases when the testis was located in the abdomen, inguinal canal, and distal to the external inguinal ring, respectively (P < 0.001). We conclude that epididymal anomalies were more frequent in boys with undescended testis than in boys with hydrocele, and that these anomalies were more frequent when undescended testis was at a higher level. These results suggest that testicular location is associated with epididymal anomalies rather than patent processus vaginalis.