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Biomedical subjects

F J McGlynn

Publications and source records attributed to F J McGlynn.

7 recordsLinked to original sources

A randomized double-blind placebo-controlled trial of the effect of homocysteine-lowering therapy with folic acid on endothelial function in patients with coronary artery disease.

OBJECTIVES: This study was designed to determine the effects of folic acid therapy on endothelial function in patients with coronary artery disease (CAD). BACKGROUND: Hyperhomocysteinemia, a risk factor for CAD, may cause atherosderosis by oxidative endothelial injury. Folic acid reduces plasma homocysteine, but the effect on adverse vascular events is unknown. METHODS: In a double-blind placebo-controlled trial, 90 patients (mean age [range] 63 [46 to 79] years, 79 men) with CAD were randomized to either folic acid 5 mg or placebo daily for 12 weeks. Endothelial function was assessed by measuring: 1) flow-mediated endothelium-dependent dilation (EDD) of the brachial artery; 2) combined serum nitrite/nitrate (NOx) concentrations and; 3) plasma von Willebrand factor (vWF) concentration. RESULTS: At the end of the study, plasma homocysteine was lower in the folic acid group compared with the placebo group (mean [95% confidence interval] 9.3 (8.5 to 10.1) vs. 12.3 [11.3 to 13.4] micromol/l, p < 0.001). Although there were no significant differences in EDD, serum NOx or plasma vWF between the two groups, there was a greater increase in EDD from baseline in the folic acid group compared to placebo (1.2 [0.7 to 1.8] vs. 0.4 [-0.3 to 1.1]%, p = 0.07). CONCLUSIONS: Folic acid reduced plasma homocysteine and was associated with a trend toward improved endothelial function in patients with CAD. The absence of an unequivocally positive result may have been due to inadequate sample size or chance. This reinforces the need for the results of large randomized controlled trials before the implementation of routine folic acid supplementation.

Aged↗

Epidemiological evaluation of known and suspected cardiovascular risk factors in chronic renal impairment.

Patients with chronic renal impairment (CRI) are at greatly increased risk for premature vascular disease; however, little is known about its evolution. This paper describes a cohort of patients with CRI and reports study design, baseline demographic and biochemical data, and comparisons with two contemporaneous age- and sex-matched control groups, one with established coronary artery disease and the other without overt vascular disease. Among 369 individuals (median age, 63 years; range, 18 to 88 years; 67% men) with CRI, 34% had a history of vascular disease and 21% had electrocardiographic left ventricular hypertrophy (LVH). Even in those with mild renal impairment (serum creatinine < 2.1 mg/dL), approximately one third had vascular disease and 12% had LVH. A history of hypertension was present in 76% of the CRI group, but as compared with controls, systolic and diastolic blood pressures were not elevated. Low-density lipoprotein (LDL) cholesterol concentration also was not elevated, but CRI was associated with elevated serum triglyceride and plasma homocysteine levels and reduced high-density lipoprotein (HDL) cholesterol, hemoglobin, and serum albumin concentrations. Across the spectrum of CRI, more severe renal dysfunction was associated with lower levels of diastolic blood pressure, LDL and HDL cholesterol, albumin, and hemoglobin, but increased levels of plasma homocysteine. This cross-sectional analysis shows that vascular disease is common in individuals with mild CRI attending a nephrology program and also suggests trends in the levels of a number of potential vascular risk factors with respect to severity of renal dysfunction. These results will be further quantified in a prospective biennial follow-up.

Adolescent↗

Does folic acid decrease plasma homocysteine and improve endothelial function in patients with predialysis renal failure?

BACKGROUND: Considerable evidence suggests that hyperhomocysteinemia is an independent vascular risk factor that promotes atherosclerosis by inducing endothelial dysfunction. Although folic acid reduces hyperhomocysteinemia, the effect on adverse vascular events is unknown. We hypothesized that in patients with chronic renal failure, a condition associated with both hyperhomocysteinemia and atherosclerosis, treatment with folic acid would improve endothelial function. METHODS AND RESULTS: In a prospective, double-blind protocol, 100 patients (mean age 62 years, 67 men) with predialysis chronic renal failure were randomized to 5 mg folic acid or placebo daily for 12 weeks. Endothelial function was assessed by measuring (1) endothelium-dependent dilation of the brachial artery, (2) combined serum nitrite/nitrate concentrations, and (3) plasma von Willebrand factor concentration. Baseline characteristics of the 2 groups were similar. At the end of the study, both serum and red cell folate concentrations were greater in the folic acid group than the placebo group [mean (95% CI) 39.0 (29.8 to 51.0) versus 7.7 (6.6 to 8.9) microg/L and 739 (613 to 891) versus 220 (184 to 262) microg/L, respectively; both P<0.001]. Despite a reduction in hyperhomocysteinemia in the folic acid group compared with the placebo group [15.1 (14.1 to 16.2) versus 20.1 (18.2 to 22.2) micromol/L; P<0.001], there were no significant differences in endothelium-dependent dilation, combined serum nitrite/nitrate concentrations, or plasma von Willebrand factor concentration between the 2 groups. CONCLUSIONS: High-dose folic acid lowers but fails to normalize hyperhomocysteinemia in patients with predialysis chronic renal failure. This was not accompanied by an improvement of endothelial function and suggests that treatment with folic acid may not reduce the burden of vascular disease in uremia.

Aged↗

Abnormalities of endothelial function in patients with predialysis renal failure.

BACKGROUND: Endothelial dysfunction plays an important role in the development of atherosclerotic vascular disease, which is the leading cause of mortality in patients with chronic renal failure. OBJECTIVE: To examine the relation between predialysis renal failure and endothelial function. DESIGN: Two groups were studied: 80 patients with non-diabetic chronic renal failure and 26 healthy controls, with similar age and sex distributions. Two indices of endothelial function were assessed: high resolution ultrasonography to measure flow mediated endothelium dependent dilatation of the brachial artery following reactive hyperaemia, and plasma concentration of von Willebrand factor. Endothelium independent dilatation was also assessed following sublingual glyceryl trinitrate. The patients were divided into those with and without overt atherosclerotic vascular disease. RESULTS: Although patients with chronic renal failure had significantly impaired endothelium dependent dilatation compared with controls (median (interquartile range), 2.6% (0.7% to 4.8%) v 6.5% (4.8% to 8.3%); p < 0.001) and increased von Willebrand factor (254 (207 to 294) v 106 (87 to 138) iu/dl; p < 0.001), there was no difference between renal failure patients with and without atherosclerotic vascular disease. Within the chronic renal failure group, endothelium dependent dilatation and von Willebrand factor were similar in patients in the upper and lower quartiles of glomerular filtration rate (2.7% (0.7% to 6.7%) v 2.8% (1.1% to 5.0%); and 255 (205 to 291) v 254 (209 to 292) iu/dl, respectively). Endothelium independent dilatation did not differ between the renal failure or control groups and was also similar in patients with renal failure irrespective of the degree of renal failure or the presence of atherosclerotic vascular disease. CONCLUSIONS: Endothelial function is abnormal in chronic renal failure, even in patients with mild renal insufficiency and those without atherosclerotic vascular disease, suggesting that uraemia may directly promote the development of atherosclerosis early in the progression of chronic renal failure.

Arteriosclerosis↗

Arthroscopic findings in the subluxating shoulder.

The arthroscopic findings in 19 shoulders (18 patients) with subluxation are described. The clinical diagnosis of subluxation of the shoulder is primarily based on clinical history with inconsistent physical findings and radiographic studies. Arthroscopic findings in these patients were consistent. Increased translation of the humeral head in the anteroposterior plane was noted secondary to attenuation of the anteroinferior glenohumeral ligament. Incompetence of this ligamentous structure obviated its function as an anterior buttress and allowed the humeral head to translate anteriorly on the glenoid. Fraying, tearing, or detachment of the anteroinferior glenoid labrum and articular defects in the posterolateral humeral head were also consistent findings, thought to be secondary to repeated injury as the humeral head translates forward and backward in the glenoid fossa. In several cases the classic "click" that occurs with subluxation of the shoulder could be reproduced under arthroscopic visualization and corresponded to the defect in the posterolateral humeral head riding over the torn labrum and/or anterior glenoid rim. Shoulder arthroscopy is an accurate method for confirming the clinical impression of subluxation of the shoulder, especially in subtle glenohumeral instability, and should be helpful in selecting specific surgical reconstruction procedures.

Adolescent↗

Arthrotomography of the glenoid labrum in shoulder instability.

Instability of the shoulder is a disabling problem which may be difficult to evaluate by routine radiographs. As detachment or absence of the labrum can lead to shoulder instability, arthrotomography of the glenoid labrum is a helpful adjunct in substantiating this diagnosis and in planning the choice of surgical reconstruction. We have found excellent correlation between the arthrotomographic findings and the glenohumeral lesion found at operation. Thirty-eight arthrotomograms of the glenoid labrum were performed in thirty-seven patients who had either shoulder pain or instability, or both. The patients were divided into three groups: those with painful subluxation (Group I), those with voluntary subluxation (Group II), and those with persistent shoulder pain (Group III). Twenty-five of the twenty-eight patients in Group I had an abnormality of the labrum shown on arthrotomography. All of the Group-II and Group-III patients had a normal labrum. There were no false-positive arthrotomograms in the eighteen patients in whom a lesion of the labrum subsequently was found at operation. Three patients with a normal labrum on arthrotomography underwent surgical exploration and no abnormalities were found.

Adolescent↗

The fallen fragment sign in unicameral bone cyst.

The roentgenographic findings in unicameral bone cyst may be difficult to differentiate from a solid tumor of bone. When present, the fallen fragment sign may aid in determining the roentgenographic diagnosis of unicameral bone cyst. In this finding, with a pathologic fracture a fragment of cortical bone may become dislodged and gravitate to the dependent portion of the unicameral bone cyst. Two examples of the fallen fragment sign demonstrate the displacement of a fragment of cortical bone to the dependent portion of the cystic cavity.

Bone Cysts↗