The role of apolipoprotein AI domains in lipid binding

Apolipoprotein AI (apoAI) is the principal protein constituent of high density lipoproteins and it plays a key role in human cholesterol homeostasis; however, the structure of apoAI is not clearly understood. To test the hypothesis that apoAI is organized into domains, three deletion mutants of human apoAI expressed in Escherichia coli were studied in solution and in reconstituted high density lipoprotein particles. Each mutant lacked one of three specific regions that together encompass almost the entire 243 aa sequence of native apoAI (apoAI Δ44-126, apoAI Δ139-170, and apoAI Δ190-243). Circular dichroism spectroscopy showed that the α-helical content of lipid-free apoAI Δ44-126 was 27% while the other mutants and native apoAI averaged 55 ± 2%, suggesting that the missing N-terminal portion contains most of the α-helical structure of lipid-free apoAI. ApoAI Δ44-126 exhibited the largest increase in α-helix upon lipid binding (125% increase versus an average of 25% for the others), confirming the importance of the C-terminal half of apoAI in lipid binding. Denaturation studies showed that the N-terminal half of apoAI is primarily responsible for α-helix stability in the lipid-free state, whereas the C terminus is required for α-helix stability when lipid-bound. We conclude that the N-terminal half (aa 44–126) of apoAI is responsible for most of the α-helical structure and the marginal stability of lipid-free apoAI while the C terminus (aa 139–243) is less organized. The increase in α-helical content observed when native apoAI binds lipid results from the formation of α-helix primarily in the C-terminal half of the molecule.     

Diagnostic value of serial measurement of cardiac markers in patients with chest pain: limited value of adding myoglobin to troponin I for exclusion of myocardial infarction

Background

Despite improved laboratory assays for cardiac markers and a revised standard for definition of myocardial infarction (AMI), early detection of coronary ischemia in unselected patients with chest pain remains a difficult challenge.

Methods

Rapid measurements of troponin I (TnI), creatine kinase MB (CK-MB), and myoglobin were performed in 197 consecutive patients with chest pain and a nondiagnostic electrocardiogram for AMI. The early diagnostic performances of these markers and different multimarker strategies were evaluated and compared. Diagnosis of AMI was based on European Society of Cardiology/American College of Cardiology criteria.

Results

At a given specificity of 95%, TnI yielded the highest sensitivity of all markers at all time points. A TnI cutoff corresponding to the 10% coefficient of variation (0.1 μg/L) demonstrated a cumulative sensitivity of 93% with a corresponding specificity of 81% at 2 hours. The sensitivity was considerably higher compared to CK-MB and myoglobin, even considering patients with a short delay until admission. Using the 99th percentile of TnI results as a cutoff (0.07 μg/L) produced a cumulative sensitivity of 98% at 2 hours, but its usefulness was limited due to low specificities. Multimarker strategies including TnI and/or myoglobin did not provide a superior overall diagnostic performance compared to TnI using the 0.1 μg/L cutoff.

Conclusion

A TnI cutoff corresponding to the 10% coefficient of variation was most appropriate for early diagnosis of AMI. A lower TnI cutoff may be useful for very early exclusion of AMI. CK-MB and in particular myoglobin did not offer additional diagnostic value.     

Functional and Physiologic Assessment of the Colonic Reservoir or Side-to-End Anastomosis After Low Anterior Resection for Rectal Cancer: A Two-Year Follow-Up

PURPOSE Functional disturbances are common after anterior resection for rectal cancer. This study was designed to compare functional and physiologic outcome after low anterior resection and total mesorectal excision with a colonic J-pouch or a side-to-end anastomosis.METHODS Functional and physiologic variables were analyzed in patients randomized to a J-pouch (n = 36) or side-to-end anastomosis (n = 35). Postoperative functional outcome was investigated with questionnaires. Anorectal manometry was performed preoperatively and at six months, one year, and two years postoperatively.RESULTS There was no statistical difference in functional outcome between groups at two years. Maximum neorectal volume increased in both groups but was approximately 40 percent greater at two years in pouches compared with the side-to-end anastomosis. Anal sphincter pressures volumes were halved postoperatively and did not recover during follow-up of two years. Male gender, low anastomotic level, pelvic sepsis, and the postoperative decrease of sphincter pressures were independent factors for more incontinence symptoms.CONCLUSIONS Colonic J-pouch and side-to-end anastomosis gives comparable functional results two years after low anterior resection. Neorectal volume had no detectable influence on function. There was a pronounced and sustained postoperative decrease in sphincter pressures.Supported by the Stockholm County Council, Public Health and Medical Services Committee and the Swedish Research Council, grant #09101.Reprints are not available.     

Results of the arterial switch operation in patients with transposition of the great arteries and abnormalities of the mitral valve or left ventricular outflow tract

Between January 1983 and October 1989, 290 patients underwent an arterial switch operation for transposition of the great arteries; 30 (10.3%) of the patients had abnormalities of the left ventricular outflow tract or mitral valve, or both. These abnormalities included isolated pulmonary valve stenosis (n = 9), septal (dynamic) subpulmonary stenosis (n = 5), anatomic (fixed) subpulmonary stenosis (n = 7), abnormal mitral chordae attachments (n = 2) or a combination of abnormalities (n = 7). There were two early deaths, one of which was due to previously unrecognized mitral stenosis and a subpulmonary (neo-aortic) membrane and one late death due to presumed coronary obstruction. Of the nine patients with pulmonary valve abnormalities due to either a bicommissural (n = 5) or a thickened tricommissural (n = 4) valve, only one underwent valvotomy. Peak systolic ejection gradients in these nine patients measured preoperatively ranged from 0 to 50 mm Hg. At follow-up study 5 to 30 months postoperatively, the neo-aortic valve gradient was less than or equal to 15 mm Hg in all patients; three patients had mild neo-aortic regurgitation. Preoperative gradients may overestimate the degree of obstruction because of the increased pulmonary blood flow present in transposition. No patient with "dynamic" subpulmonary obstruction before the arterial switch operation had a surgical procedure performed on the left ventricular outflow tract; none had evidence of subaortic obstruction after the arterial switch.(ABSTRACT TRUNCATED AT 250 WORDS)     

Spiritual/religious coping and depressive symptoms in informal caregivers of hospitalized older adults

This aim of this study was assess whether positive and negative spiritual/religious coping (SRC) strategies are associated with depressive symptoms (DS) of informal caregiver (IC) of hospitalized older adults. A cross-sectional study was conducted among 98 IC of hospitalized older adults in the medical clinic of a Brazilian School Hospital. The functionality, Positive and Negative SRC strategies and DS were evaluated. The IC had high average use of SRC, with Positive SRC being more used than Negative SRC. In the unadjusted regression model, Positive and Negative SRC were associated with DS. However, when adjusted for confounding factors, only Negative SRC remained associated with DS. The IC had used their religious and spiritual beliefs as a way to cope with the stress that comes from caring for hospitalized older adults. Although the positive strategy use of these beliefs was more common, only the negative strategies were associated with a higher DS.