Myocardial infarction and 5,10-methylenetetrahydro-folate reductase mutation

A 40-year-old woman with previous venous thrombosis in the lower limbs had recurrent myocardial infarction in the early puerperium. The only documented risk factor was an elevated level of plasma homocysteine, associated to a heterozygotic anomaly in the enzyme responsible for its metabolism, 5,10-methylenetetrahydrofolate reductase. The case and approaches to treatment are discussed.     

Antipyrine Clearance and Metabolite Formation in Primary Biliary Cirrhosis

The disposition of antipyrine is altered and may be a prognostic factor in the presence of various types of hepatic dysfunction. The object of the present study was to investigate whether antipyrine clearance and metabolite formation are useful to detect altered metabolic function in primary biliary cirrhosis. Saliva clearance of antipyrine and the formation clearance of antipyrine metabolites (hydroxymethylantipyrine, HMA; norantipyrine, NORA; and 4-hydroxyantipyrine, OHA) were investigated in a group of 34 women with biopsy-proven PBC (mean age 60 years; range 39–87 years) and in 15 healthy control women (mean age 62 years; range 46–78 years). Parameters of antipyrine clearance of patients in stage I and II were similar to those observed in healthy subjects. When compared to patients in stage I, patients in advanced stages showed a reduction in antipyrine clearance (–29% and –44% in stages III and IV, respectively) and increases in antipyrine half-life (+24% and +75% in stages III and IV, respectively). The reduction in antipyrine clearance was due to a reduction in the formation of all three antipyrine metabolites, with the formation clearance of both HMA and NORA decreasing to a slightly greater extent than that of OHA. Antipyrine clearance correlated significantly with serum bilirubin (P < 0.017) and the Mayo risk score (P < 0.001). Logistic regression analysis indicated that antipyrine clearance was an independent predictor of the histological stage of the disease (P < 0.001). Antipyrine clearance and metabolite formation is a sensitive parameter for assessing hepatic metabolic function in primary biliary cirrhosis.     

Preterm Infants with Paroxysmal Supraventricular Tachycardia: Presentation, Response to Therapy, and Outcome

Objectives: We investigated the clinical course of preterm infants with paroxysmal supraventricular tachycardia in comparison to their term counterparts. Background: Paroxysmal supraventricular tachycardia (PSVT) is the most common arrhythmia in childhood. It is known to cause significant morbidity and rarely mortality, most commonly in infants. Yet, there is minimal information in the literature on preterm infants with PSVT. Methods: Retrospective review of 40 infants, 26 term and 14 preterm, less than three months of age who presented with PSVT from January 1990 to January 1999. We compared the severity of first clinical presentation, in-hospital response to long-term medications, and outcome after discharge. Results: Symptomatic severity on presentation was not different between preterm and term infants. Preterm infants required fewer medication trials (p=0.01) and had no recurrences after discharge in contrast with 43% recurrence in the term infants (p<0.0001). No preterm infants had Wolff-Parkinson-White syndrome (WPW) in contrast to 42% of term infants (p=0.003). Term infants with WPW were more symptomatic (p=0.01), required more medications (p=0.004), but had a similar recurrence frequency as terms infants without WPW (p=0.95). Excluding infants with WPW, preterm infants were more severely symptomatic (p=0.02), yet no longer was there a difference in response to first medication trial (p=0.30). Conclusions: We found that preterm infants with PSVT are as severely symptomatic on presentation, require fewer medications for adequate in-hospital control, and have fewer recurrences than their term counterparts. Unexpectedly, preterm infants did not present with WPW. The presence of WPW only in the term infants may account for differences in the clinical course between preterm and term infants.     

MULTIPLEX SYBR? GREEN-REAL TIME PCR (qPCR) ASSAY FOR THE DETECTION AND DIFFERENTIATION OF Bartonella henselae AND Bartonella clarridgeiae IN CATS

A novel SYBR^® green-real time polymerase chain reaction (qPCR) was developed to detect two Bartonella species, B. henselae and B. clarridgeiae, directly from blood samples. The test was used in blood samples obtained from cats living in animal shelters in Southern Brazil. Results were compared with those obtained by conventional PCR targeting Bartonella spp. Among the 47 samples analyzed, eight were positive using the conventional PCR and 12 were positive using qPCR. Importantly, the new qPCR detected the presence of both B. henselae and B. clarridgeiae in two samples. The results show that the qPCR described here may be a reliable tool for the screening and differentiation of two important Bartonella species.     

Increased susceptibility to septic and endotoxic shock in monocyte chemoattractant protein 1/cc chemokine ligand 2-deficient mice correlates with reduced interleukin 10 and enhanced macrophage migration inhibitory factor production

The chemokine monocyte chemoattractant protein 1/CC chemokine ligand 2 (MCP-1/CCL2) is a potent chemoattractant of mononuclear cells and a regulatory mediator involved in a variety of inflammatory diseases. In the present study, we demonstrate that mcp-1/ccl2-deficient mice are more susceptible to systemic inflammatory response syndrome induced by lipopolysaccharide and to polymicrobial sepsis induced by cecum ligation and puncture (CLP) when compared with wild-type mice. Interestingly, in the CLP model, mcp-1/ccl2-deficient mice efficiently cleared the bacteria despite an impaired recruitment of leukocytes, especially mononuclear cells. The increased lethality rate in these models correlates with an impaired production of interleukin (IL) 10 in vivo. Furthermore, macrophages from mcp-1/ccl2-deficient mice activated with lipopolysaccharide also produced lower amounts of IL-10 and similar tumor necrosis factor compared with wild-type mice. We observed a drastic increase in the amounts of macrophage migration inhibitory factor at 6 and 24 h after CLP in mcp-1/ccl2-deficient mice. These results indicate that endogenous MCP-1/CCL2 positively regulates IL-10 but negatively controls macrophage migration inhibitory factor during peritoneal sepsis, thus suggesting an important immunomodulatory role for MCP-1/CCL2 in controlling the balance between proinflammatory and anti-inflammatory factors in sepsis.     

VSL#3 probiotic-mixture induces remission in patients with active ulcerative colitis

BACKGROUND AND AIMS: Intestinal bacteria have been implicated in the initiation and perpetuation of IBD; in contrast, "probiotic bacteria" have properties possibly effective in treating and preventing relapse of IBD. We evaluated the safety and efficacy of VSL#3 and the components, and the composition of the biopsy-associated microbiota in patients with active mild to moderate ulcerative colitis (UC). METHODS: Thirty-four ambulatory patients with active UC received open label VSL#3, 3,600 billion bacteria daily in two divided doses for 6 wk. The presence of biopsy-associated bacteria was detected using a nucleic acid-based method and the presence of VSL#3 species confirmed by DNA sequencing of 16S rRNA. RESULTS: Thirty-two patients completed 6 wk of VSL#3 treatment and 2 patients did not have the final endoscopic assessment. Intent to treat analysis demonstrated remission (UCDAI < or = 2) in 53% (n = 18); response (decrease in UCDAI > or = 3, but final score > or =3) in 24% (n = 8); no response in 9% (n = 3); worsening in 9% (n = 3); and failure to complete the final sigmoidoscopy assessment in 5% (n = 2). There were no biochemical or clinical adverse events related to VSL#3. Two of the components of VSL#3 were detected by PCR/DGGE in biopsies collected from 3 patients in remission. CONCLUSION: Treatment of patients with mild to moderate UC, not responding to conventional therapy, with VSL#3 resulted in a combined induction of remission/response rate of 77% with no adverse events. At least some of the bacterial species incorporated in the probiotic product reached the target site in amounts that could be detected.     

Acute pulmonary embolism is an independent predictor of adverse events in severe decompensated heart failure patients

BACKGROUND: Congestive heart failure (CHF) is a well-recognized risk factor for venous thromboembolism (VTE) and is associated with higher mortality in patients with an acute pulmonary embolism (PE). There are very few data on how acute PE affects the clinical course of patients with heart failure. The purpose of this study was to determine the impact of an acute PE on the short-term prognosis of patients hospitalized for decompensated CHF. METHODS: This was a prospective cohort study of 198 patients admitted to a coronary care unit between July 2001 and March 2003 with severe decompensated CHF. The primary outcome measure was death or rehospitalization at 3 months. RESULTS: PE was confirmed in 18 of 198 patients enrolled (9.1%). The groups with and without PE were comparable with regards to demographics, the prevalence of comorbid conditions, and severity of CHF (p > 0.05). The prevalence of cancer (p = 0.0001), previous VTE (p = 0.003), and right ventricular overload (p = 0.006) was higher in the PE group. The presence of PE was also associated with a longer hospital stay (37.5 +/- 71.6 days vs 15.4 +/- 15.0 days, p = 0.001) [mean +/- SD] and a higher incidence of death or rehospitalization at 3 months (72.2% vs 43.9%, p = 0.02). In a multiple logistic regression analysis, PE remained an independent predictor of death or rehospitalization at 3 months (odds ratio, 4.0; 95% confidence interval, 1.1 to 15.1; p = 0.038). CONCLUSIONS: Acute PE commonly complicates the hospital course of patients with severe CHF, increasing the length of hospital stay and the chance of death or rehospitalization at 3 months.     

Cardiovascular Disease Prognostic Models in Latin America and the Caribbean: A Systematic Review

Background

Cardiovascular prognostic models guide treatment allocation and support clinical decisions. Whether there are valid models for Latin American and Caribbean (LAC) populations is unknown.

Clinical Implication of Quantitative Flow Ratio After Percutaneous Coronary Intervention for 3-Vessel Disease

ObjectivesThe aim of this study was to investigate the impact of post–percutaneous coronary intervention (PCI) quantitative flow ratio (QFR) on clinical outcomes in patients with de novo 3-vessel disease (3VD) treated with contemporary PCI.BackgroundThe clinical impact of post-PCI QFR in patients treated with state-of-the-art PCI for de novo 3VD is undetermined.MethodsAll vessels treated in the SYNTAX (SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery) II trial were retrospectively screened and analyzed for post-PCI QFR. The primary endpoint of this substudy was vessel-oriented composite endpoint (VOCE) at 2 years, defined as the composite of vessel-related cardiac death, vessel-related myocardial infarction, and target vessel revascularization. The receiver-operating characteristic curve was used to calculate the optimal cutoff value of post-PCI QFR for predicting 2-year VOCE. All the analyzable vessels were stratified on the basis of the optimal cutoff value.ResultsA total of 968 vessels treated with PCI were screened. Post-PCI QFR was analyzable in 771 (79.6%) vessels. A total of 52 (6.7%) VOCEs occurred at 2 years. The mean value of post-PCI QFR was 0.91 ± 0.07. The diagnostic performance of post-PCI QFR to predict 2-year VOCE was moderate (area under the curve: 0.702; 95% confidence interval: 0.633 to 0.772), with the optimal cutoff value of post-PCI QFR for predicting 2-year VOCE 0.91 (sensitivity 0.652, specificity 0.635). The incidence of 2-year VOCE in the vessels with post-PCI QFR <0.91 (n = 284) was significantly higher compared with vessels with post-PCI QFR ≥0.91 (n = 487) (12.0% vs. 3.7%; hazard ratio: 3.37; 95% confidence interval: 1.91 to 5.97; p < 0.001).ConclusionsA higher post-PCI QFR value is associated with improved vessel-related clinical outcomes in state-of-the art PCI practice for de novo 3VD. Achieving a post-PCI QFR value ≥0.91 in all treated vessels should be a target when treating de novo 3VD. These findings require confirmation in future prospective trials.