Complete repair in total atrioventricular canal defect with cyanosis

Atrioventricular septal defects account for 4% of congenital cardiac malformations and over 50% of cardiac defects seen in Down syndrome. Clinical presentation is marked by congestive heart failure early in infancy. Cyanosis is rarely found in infants and suggests irreversible pulmonary hypertension or associated cardiac defects as tetralogy of Fallot, double outlet right ventricle, Ebstein anomaly, persistent left superior vena cava draining in the left atrium (Barbero Marcial, personal communication). Children with Down's syndrome is particularly difficult to assess because they often suffer from upper airways obstruction, which may contribute to the increased pulmonary vascular resistance determined at cardiac catheterization. This association of factors becomes a challenge for operability and, we will report one such case.     

Autonomic cardiac modulation in obstructive sleep apnea: effect of an oral jaw-positioning appliance

BACKGROUND: Patients with obstructive sleep apnea (OSA) are characterized by deranged cardiovascular variability, a well-established marker of cardiovascular risk. While long-term treatment with continuous positive airway pressure leads to a significant improvement of cardiovascular variability, little is known of the possibility of achieving the same results with other therapeutic approaches. The aim of our study was to investigate the responses of autonomic indexes of neural cardiac control to another type of OSA treatment based on an oral jaw-positioning appliance. METHODS: In 10 otherwise healthy subjects with OSA (OSA+) and in 10 subjects without OSA (OSA-) we measured heart rate, BP, and indices of autonomic cardiac regulation derived from time-domain and spectral analysis of R-R interval (RRI), before and after 3 months of treatment with the oral device. High-frequency (HF) power of RRI was taken as an index of parasympathetic cardiac modulation, and the ratio between low-frequency (LF) and HF RRI powers as an indirect marker of the balance between sympathetic and parasympathetic cardiac modulation. RESULTS: At baseline, in comparison with OSA- subjects, OSA+ subjects displayed a significantly lower RRI variance (p < 0.02) and reduced HF RRI powers (p < 0.001). After 3 months of treatment with the oral device, the OSA+ group showed a marked reduction in apnea-hypopnea index (p < 0.001), a lengthening in RRI and a significant increase in its variance (p < 0,02), an increased HF RRI power (from 134 +/- 26 to 502 +/- 48 ms2, p < 0.001), and a reduction in LF/HF RRI power ratio (from 3.11 +/- 0.8 to 1.5 +/- 0.5). As a result of these changes, after the 3-month treatment there were no more significant differences between the two groups in these parameters. In both OSA+ and OSA- groups, body weight, heart rate, and BP did not change over time. CONCLUSIONS: Three months of treatment with a specific oral jaw-positioning appliance improves cardiac autonomic modulation in otherwise healthy patients with OSA of mild degree.     

Human albumin solution for resuscitation and volume expansion in critically ill patients

BACKGROUND: Human albumin solutions are used in a range of medical and surgical problems. Licensed indications are the emergency treatment of shock and other conditions where restoration of blood volume is urgent, burns, and hypoproteinaemia. Human albumin solutions are more expensive than other colloids and crystalloids. OBJECTIVES: To quantify the effect on mortality of human albumin and plasma protein fraction (PPF) administration in the management of critically ill patients. SEARCH STRATEGY: We searched the Cochrane Injuries Group trials register, Cochrane Central Register of Controlled Trials, Medline, Embase and BIDS Index to Scientific and Technical PROCEEDINGS: Reference lists of trials and review articles were checked, and authors of identified trials were contacted. The search was last updated in August 2004. SELECTION CRITERIA: Randomised controlled trials comparing albumin/PPF with no albumin/PPF, or with a crystalloid solution, in critically ill patients with hypovolaemia, burns or hypoalbuminaemia. DATA COLLECTION AND ANALYSIS: We collected data on the participants, albumin solution used, mortality at the end of follow up, and quality of allocation concealment. Analysis was stratified according to patient type. MAIN RESULTS: We found 32 trials meeting the inclusion criteria and reporting death as an outcome. There were 1632 deaths among 8452 trial participants. For hypovolaemia, the relative risk of death following albumin administration was 1.01 (95% confidence interval 0.92-1.10). This estimate was heavily influenced by the results of the SAFE trial, which contributed 91% of the information (based on the weights in the meta-analysis). For burns, the relative risk was 2.40 (1.11-5.19) and for hypoalbuminaemia the relative risk was 1.38 (0.94-2.03). There was no substantial heterogeneity between the trials in the various categories (chi2 = 21.86, df = 25, p = 0.64). The pooled relative risk of death with albumin administration was 1.04 (0.95-1.13). CONCLUSIONS: For patients with hypovolaemia there is no evidence that albumin reduces mortality when compared with cheaper alternatives such as saline. There is no evidence that albumin reduces mortality in critically ill patients with burns and hypoalbuminaemia. The possibility that there may be highly selected populations of critically ill patients in which albumin may be indicated remains open to question. However, in view of the absence of evidence of a mortality benefit from albumin and the increased cost of albumin compared to alternatives such as saline, it would seem reasonable that albumin should only be used within the context of well concealed and adequately powered randomised controlled trial. PLAIN LANGUAGE SUMMARY: There is no evidence that giving human albumin to replace lost blood in critically ill or injured people improves survival when compared to giving saline. Trauma, burns or surgery can cause people to lose large amounts of blood. Fluid replacement, giving fluids intravenously (into a vein), is used to help restore blood volume and hopefully reduce the risk of dying. Blood products (including human albumin), non-blood products or combinations can be used. The review of trials found no evidence that albumin reduces the risk of dying. Albumin is very expensive in which case it may be better to use cheaper alternatives such as saline for fluid resuscitation.     

Endothelium-dependent vasodilation and carotid artery wall remodeling in athletes and sedentary subjects

In this study, the relationship between age, carotid artery remodeling, and endothelium-dependent vasodilation is investigated in sedentary subjects and athletes. Thirty-two young and old healthy sedentary subjects and 32 age-matched endurance athletes underwent ultrasonography of the carotid wall for measuring intima-media thickness (IMT) and corrected integrated backscatter (C-IBS), two early indicators of the atherosclerosis process. Endothelium-dependent vasodilation was assessed by intra-brachial acetylcholine (strain-gauge plethysmography), at baseline and during NO sythase inhibitor NG-monomethyl-L-arginine (L-NMMA), and the antioxidant Vitamin C. Response to sodium nitroprusside (SNP) was also evaluated. Independently of trained status, IMT and C-IBS were higher in older than in young individuals (p<0.0001), while response to acetylcholine, but not to SNP, was lower (p<0.0001). Older athletes showed lower IMT, lower C-IBS (p<0.0001), greater response to acetylcholine (p<0.0001), and greater inhibition of acetylcholine by L-NMMA (p<0.001) than older controls. Only in older sedentary individuals, Vitamin C increased response to acetylcholine (p<0.001) and restored the inhibiting effect of L-NMMA (p<0.01). In the whole population maximal acetylcholine-induced vasodilation was inversely related to IMT (r=-0.60, p<0.0001) and to C-IBS (r=-0.56, p<0.0001). In conclusion, regular physical training can attenuate the age-related impairment of endothelium-dependent vasodilation, which is related to an attenuation of the age-induced remodeling of the carotid wall.     

Hormone replacement therapy and mortality in 52- to 70-year-old women: the Kuopio Osteoporosis Risk Factor and Prevention Study

OBJECTIVES: To analyze prospectively the association between hormone replacement therapy (HRT) and mortality in women before old age. DESIGN AND METHODS: A group of 11,667 women (91% of the age cohort of the area) aged 52-62 years from the population-based Kuopio Osteoporosis Risk Factor and Prevention Study were followed for 7 years in 1994-2001. Information about HRT use and health events was obtained from two repeated questionnaires in 1989 and 1994. Information about deaths and causes of death from the follow-up period was obtained from the Statistics Finland. Cox's proportional-hazards models were used to calculate risk of death related to the use of HRT. RESULTS: At the start of follow-up, 2203 women had used HRT > 5 years, 3945 women < or = 5 years and 5519 women had never used it. During the follow-up, 361 deaths occurred. Compared with non-users of HRT, the adjusted hazard ratio (HR) of death from any cause was 1.05 (95% confidence interval (CI) 0.80-1.36) in women who used HRT < or = 5 years and 1.06 (95% CI 0.78-1.46) in women who used HRT > 5 years. The adjusted HR for coronary heart disease (CHD) mortality in women who used HRT < or = 5 years was 0.79 (95% CI 0.36-1.73), and in women who used HRT > 5 years, 2.16 (95% CI 0.93-4.98). For breast cancer mortality the adjusted HR for < or = 5 years of HRT use was 0.96 (95% CI 0.32-2.82) and 2.62 (95% CI 0.98-7.00) for > 5 years of HRT use. CONCLUSIONS: History of HRT use does not affect overall or CHD mortality in women. More than 5 years of HRT use may increase the risk of breast cancer mortality.     

Carotid atherosclerotic plaque instability in patients with acute myocardial infarction

The instability of atherosclerotic plaque is partly determined by local factors, but systemic factors such as infection, inflammation, autoimmunity or genes might also be important. We aimed to analyze whether patients with acute myocardial infarction (AMI) might have a higher proportion of unstable plaques in the carotid arteries compared with patients who had had no acute coronary events. METHODS: Sixty-nine consecutive patients with AMI (Group 1) and 95 patients without acute coronary events (Group 2) had carotid artery duplex ultrasounds. Carotid atherosclerosis was quantified by number of plaques in the two carotid arteries, intimal media thickening and degree of maximal stenosis. According to their morphology, plaques were divided into stable (fibrocalcific) and unstable (soft and/or not homogeneous). RESULTS: The two groups did not differ as regards age (66+/-8 vs. 68+/-19; p=0.3), female sex (13% vs. 21%; p=0.3), mean number of carotid plaques (2.8+/-1 vs. 2.5+/-2; p=0.2), degree of stenosis (59+/-2% vs. 36+/-1%; p=0.2) or intimal media thickening (1.04+/-0.2 vs. 1.06+/-0.2; p=0.8). However, Group 1 pts more frequently had unstable carotid plaques compared with Group 2 (43% vs. 15%; p=0.004), and had a greater number of unstable carotid plaques (0.51+/-0.6 vs. 0.16+/-0.4: p<0.0001) and a higher ratio of unstable to stable plaque (19% vs. 8%; p=0.005). In the overall population, logistic regression analysis showed that after adjustment for degree of maximal stenosis, the presence of coronary artery event (AMI pts) predicted the presence of unstable carotid plaque (OR: 4.3 95% CI: 2.0-9.2; p=0.0002). CONCLUSION: Patients with unstable coronary artery disease expressed clinically as AMI, frequently had unstable atherosclerotic plaques in other arterial sites such as carotid arteries. This finding supports the hypothesis that plaque instability might reflect a systemic process.     

Achieving lipoprotein goals in patients at high risk with severe hypercholesterolemia: efficacy and safety of ezetimibe co-administered with atorvastatin

Background

Despite the efficacy of statins in lowering low-density lipoprotein cholesterol (LDL-C) levels, many patients who are at high risk for heart disease with hypercholesterolemia require additional LDL-C level reduction. The cholesterol absorption inhibitor, ezetimibe, has been shown to provide significant incremental reductions in LDL-C levels when co-administered with statins. This study was performed to compare the efficacy and safety of ezetimibe (10 mg) plus response-based atorvastatin titration versus response-based atorvastatin titration alone in the attainment of LDL-C goals in subjects who are at high risk for coronary heart disease (CHD) and are not at their LDL-C goal on the starting dose of atorvastatin.

Methods

This was a 14-week, multicenter, randomized, double-blind, active-controlled study conducted in 113 clinical research centers in 21 countries. Participants were adults with heterozygous familial hypercholesterolemia (HeFH), CHD, or multiple (≥2) cardiovascular risk factors, and a LDL-C level ≥130 mg/dL after a 6- to10-week dietary stabilization and atorvastatin (10 mg/day) open-label run-in period. Eligible subjects continued to receive atorvastatin (10 mg) and were randomized to receive blinded treatment with ezetimibe (10 mg/day; n = 305) or an additional 10 mg/day of atorvastatin (n = 316). The atorvastatin dose in both groups was doubled after 4 weeks, 9 weeks, or both when the LDL-C level was not at its goal (≤100 mg/dL), so that patients receiving combined therapy could reach 40 mg/day and patients receiving atorvastatin alone could reach 80 mg/day. The primary end point was the proportion of subjects achieving their LDL-C level goal at week 14. A secondary end point was the change in LDL-C level and other lipid parameters at 4 weeks after ezetimibe co-administration with 10 mg/day of atorvastatin versus 20 mg/day of atorvastatin monotherapy.

Results

The proportion of subjects reaching their target LDL-C level goal of ≤100 mg/dL was significantly higher in the co-administration group than in the atorvastatin monotherapy group (22% vs 7%; P <.01). At 4 weeks, levels of LDL-C, triglycerides, and non-high-density lipoprotein cholesterol were reduced significantly more by combination therapy than by doubling the dose of atorvastatin (LDL-C −22.8% versus −8.6%; P <.01). The combination regimen had a safety and tolerability profile similar to that of atorvastatin alone.

Conclusions

The addition of ezetimibe to the starting dose of 10 mg/day of atorvastatin followed by response-based atorvastatin dose titration to a maximum of 40 mg/day provides a more effective means for reducing LDL-C levels in patients at high risk for CHD than continued doubling of atorvastatin as high as 80 mg/day alone.     

Acute myeloid leukemia with t(8;21)(q22;q22) manifesting as granulocytic sarcomas in the rhinopharynx and external acoustic meatus at relapse after high-dose cytarabine: case report and review of the literature

We report a 31-year-old female with t(8;21)(q22;q22) acute myeloid leukemia (AML), M2 in the FAB classification. Complete remission was achieved with daunorubicin and cytarabine induction therapy followed by three courses of high-dose cytarabine consolidation. Only 3 months later, the patient relapsed with granulocytic sarcomas (GSs) in her rhinopharynx, external acoustic meatus, and bone marrow. She received focal radiation for the GSs and successfully underwent reinduction chemotherapy. Subsequently, she received a matched related donor peripheral blood stem cell transplantation followed by high-dose chemotherapy and is now in a second remission. We summarized 79 reported cases of t(8;21) AML with GS and reviewed the literature to identify differences in the characteristics of t(8;21) AML with GS between adults and children. To our knowledge, this is the first report of pharyngeal GS in t(8;21) AML, and focal irradiation plus more intensive postinduction therapy during first remission, such as allogeneic-SCT, may be effective in adult t(8;21) AML patients with GS.     

Matrix metalloproteinase 12–dependent cleavage of urokinase receptor in systemic sclerosis microvascular endothelial cells results in impaired angiogenesis

Objective

Defective angiogenesis, resulting in tissue ischemia, is particularly prominent in the diffuse form of systemic sclerosis (SSc). The present study was undertaken to identify possible differences between normal and SSc microvascular endothelial cells (MVECs) in the expression of the cell‐associated urokinase‐type plasminogen activator (uPA)/uPA receptor (uPAR) system, which is critical in the angiogenic process.

Methods

MVECs were isolated from the dermis of healthy individuals and from the dermis of patients with diffuse SSc. The uPA/uPAR system was examined at the protein and messenger RNA levels. Angiogenesis was assayed on Matrigel‐coated porous filters and plates to evaluate cell proliferation, invasion, and capillary morphogenesis. Cleavage of uPAR and the activity of matrix metalloproteinase 12 (MMP‐12) were evaluated by Western blotting.

Results

Compared with MVECs from healthy skin, MVECs from SSc patients showed higher expression of uPAR. However, in SSc MVECs, uPAR undergoes truncation between domain 1 and domain 2, as shown by flow cytometry, enzyme‐linked immunosorbent assay, and Western blotting, a cleavage that is known to impair uPAR functions. These properties of SSc MVECs were associated with poor spontaneous and uPA‐dependent invasion, proliferation, and capillary morphogenesis. The uPAR cleavage occurring in SSc MVECs was associated with overexpression of MMP‐12. SSc MVEC–conditioned medium impaired uPA‐dependent proliferation and invasion as well as capillary morphogenesis in normal MVECs in vitro. Both a general hydroxamate inhibitor of MMP activity and anti–MMP‐12 antibodies restored this SSc MVEC–induced impaired functioning.

Conclusion

Overproduction of MMP‐12 by SSc MVECs accounts for the cleavage of uPAR and the impairment of angiogenesis in vitro and may contribute to reduced angiogenesis in SSc patients.