Con Metreweli

Hyperhomocyst(e)inemia Is a Risk Factor for Arterial Endothelial Dysfunction in Humans

BACKGROUND Hyperhomocyst(e)inemia is associated with premature peripheral vascular, cerebrovascular, and coronary artery disease. Because homocysteine has been found to be damaging to endothelial cells in animal and cell culture studies, we evaluated the association between hyperhomocysteinemia and arterial endothelial dysfunction (a marker of early atherosclerosis) in asymptomatic adult subjects. METHODS AND RESULTS Using high-resolution ultrasound, we measured endothelium-dependent flow-mediated dilation (EDD) and endothelium-independent nitroglycerin-induced dilation (GTN) of the brachial artery in 14 prospectively defined hyperhomocysteinemic (mean plasma homocysteine, 34.8+/-8.5 micromol/L), nonsmoking, healthy subjects aged 53+/-9 years and 14 control subjects with low plasma homocysteine levels (9.9+/-3.2 micromol/L). The two groups were well matched for age; sex; body mass index; blood pressure, blood cholesterol, folate, and vitamin B12 levels; and vessel diameter. EDD was significantly lower in hyperhomocysteinemic subjects (6.5+/-1.7%) than in subjects with low homocysteine levels (10.8+/-1.7%) (P<.001). GTN responses were similar in the two subject groups (P=.90). Multivariate analysis confirmed homocysteine level as the strongest predictor for impaired EDD, independent of age, sex, body mass index, or blood pressure, folate, vitamin B12, and cholesterol levels. CONCLUSIONS Hyperhomocysteinemia is an independent risk factor for arterial endothelial dysfunction in healthy middle-aged adults.

Effects of Diet and Exercise on Obesity-Related Vascular Dysfunction in Children

Background—The prevalence of obesity in both adults and children is increasing rapidly. Obesity in children is independently associated with arterial endothelial dysfunction and wall thickening, key early events in atherogenesis that precede plaque formation. Methods and Results—To evaluate the reversibility of obesity-related arterial dysfunction and carotid intima-media thickening by dietary and/or exercise intervention programs, 82 overweight children (body mass index, 25±3), 9 to 12 years of age, were randomly assigned to dietary modification only or diet plus a supervised structured exercise program for 6 weeks and subsequently for 1 year. The prospectively defined primary end points were ultrasound-derived arterial endothelial function (endothelium-dependent dilation) of the brachial artery and intima-media thickness of common carotid artery. At 6 weeks, both interventions were associated with decreased waist-hip ratio (P <0.02) and cholesterol level (P <0.05) as well as improved arterial endothelial function. Diet and exercise together were associated with a significantly greater improvement in endothelial function than diet alone (P =0.01). At 1 year, there was significantly less thickening of the carotid wall (P <0.001) as well as persistent improvements in body fat content and lipid profiles in the group continuing an exercise program. Vascular function was significantly better in those children continuing exercise (n=22) compared with children who withdrew from the exercise program (n=19) (P <0.05). Conclusions—Obesity-related vascular dysfunction in otherwise healthy young children is partially reversible with diet alone or particularly diet combined with exercise training at 6 weeks, with sustained improvements at 1 year in those persisting with diet plus regular exercise.

Overweight in children is associated with arterial endothelial dysfunction and intima-media thickening.

OBJECTIVE: We sought to study arterial endothelial function and carotid intima-media thickness (IMT), both early markers of atherosclerosis, in overweight compared to normal children.DESIGN: Case–control comparison.SUBJECTS: A total of 36 asymptomatic overweight children (body mass index (BMI)>23; mean 25±3) aged 9–12 y and 36 age- and gender-matched nonobese healthy children (BMI<21) from a school community.MEASUREMENTS: The key parameters were: BMI, arterial endothelial function (ultrasound-derived endothelium-dependent dilation) and carotid artery IMT. The secondary parameters measured included body fat content, waist–hip ratio (WHR), blood pressures, blood lipids, insulin and glucose.RESULTS: The two groups were well matched for blood pressures, cholesterol and glucose levels, but BMI (P<0.0001), body fat (P=0.001), WHR (P<0.05), fasting blood insulin (P=0.001) and triglyceride levels (P<0.05) were higher in obese children. Overweight was associated with impaired arterial endothelial function (6.6±2.3 vs 9.7±3.0%, P<0.0001) and increased carotid IMT (0.49±0.04 mm vs 0.45±0.04 mm, P=0.006). The degree of endothelial dysfunction correlated with BMI (P<0.003) on multivariate analysis.CONCLUSION: Obesity, even of mild-to-moderate degree, is independently associated with abnormal arterial function and structure in otherwise healthy young children.

Folic acid improves arterial endothelial function in Adults with Hyperhomocystinemia

OBJECTIVES To evaluate whether oral folic acid supplementation might improve endothelial function in the arteries of asymptomatic adults with hyperhomocystinemia. BACKGROUND Hyperhomocystinemia is an independent risk factor for endothelial dysfunction and occlusive vascular disease. Folic acid supplementation can lower homocystine levels in subjects with hyperhomocystinemia; however, the effect of this on arterial physiology is not known. METHODS Adults subjects were recruited from a community-based atherosclerosis study on healthy volunteers aged 40 to 70 years who had no history of hypertension, diabetes mellitus, hyperlipidemia, ischemic heart disease or family history of premature atherosclerosis (n = 89). Seventeen subjects (aged 54 +/- 10 years, 15 male) with fasting total homocystine levels above 75th percentile (mean, 9.8 +/- 2.8 micromol/liter) consented to participate in a double-blind, randomized, placebo-controlled and crossover trial; each subject received oral folic acid (10 mg/day) and placebo for 8 weeks, each separated by a washout period of four weeks. Flow-mediated endothelium-dependent dilation (percent increase in diameter) of the brachial artery was assessed by high resolution ultrasound, before and after folic acid or placebo supplementation. RESULTS Compared with placebo, folic acid supplementation resulted in higher serum folate levels (66.2 +/- 7.0 vs. 29.7 +/- 14.8 nmol/liter; p < 0.001), lower total plasma homocystine levels (8.1 +/- 3.1 vs. 9.5 +/- 2.5 micromol/liter, p = 0.03) and significant improvement in endothelium-dependent dilation (8.2 +/- 1.6% vs. 6 +/- 1.3%, p < 0.001). Endothelium-independent responses to nitroglycerin were unchanged. No adverse events were observed. CONCLUSION Folic acid supplementation improves arterial endothelial function in adults with relative hyperhomocystinemia, with potentially beneficial effects on the atherosclerotic process.

Radiation pneumonitis after selective internal radiation treatment with intraarterial 90Yttrium-microspheres for inoperable hepatic tumors

PURPOSE To investigate the clinical, histopathological, and radiological features of radiation pneumonitis arising as a complication of selective internal radiation treatment for liver tumors. To correlate the development of radiation pneumonitis with the degree of lung shunting as assessed by 99mTechnetium-labeled macroaggregated albumin (Tc-MAA) scan. METHODS AND MATERIALS Five out of 80 patients who had inoperable hepatic tumors and underwent treatment with intraarterial 90Yttrium- (90Y)-microspheres, developed progressive restrictive ventilatory dysfunction without an infective or cardiovascular cause. Histopathological evidence of a pneumonitis and the presence of microspheres in the lung tissue suggested a diagnosis of radiation pneumonitis. The clinical course, radiological and histopathological findings, percentage tumor shunting to the lungs (lung shunting, as predicted by gamma camera scanning after intraarterial Tc-MAA), and the estimated radiation dose to the lungs were analyzed. In an attempt to reduce pulmonary shunting of the microspheres, three patients received partial hepatic embolization with inert particles before selective internal radiation therapy. RESULTS In the five patients who developed radiation pneumonitis, lung shunting percentages (as predicted by Tc-MAA scan) ranged from 13.1 to 45.6% (median 23.7%). The estimated whole lung radiation dose ranged from 10.43 Gy to 36.44 Gy (median 25.04 Gy). Among 75 patients who did not develop radiation pneumonitis, the percentage lung shunting ranged from less than 1% to 15% (median 6%). Nine patients had lung shunting greater than 13% and five of them developed radiation pneumonitis, whereas this developed in none of those in whom shunting was below 13%. The onset of radiation pneumonitis ranged from 1 to 6 months after internal radiation treatment. All five patients exhibited characteristic plain radiographic and computerized tomographic changes comprising extensive consolidation with well-defined lateral margins. Clinical improvement after corticosteroid treatment was seen in two patients. Three patients died from respiratory failure and two from other causes. Partial hepatic arterial embolization reduced the degree of lung shunting to less than 13%, but did not prevent the development of radiation pneumonitis. CONCLUSION Radiation pneumonitis may become a complication after intraarterial 90Y-microspheres treatment when lung shunting, as assessed by Tc-MAA scan, is high (above 13%). Prescribed activity of 90Y and lung shunting of Tc-MAA should be considered together before giving selective internal radiation (SIR) therapy for hepatic tumors, and preferably avoided if the lung shunting is above 13%.

Correlation between curve severity, somatosensory evoked potentials, and magnetic resonance imaging in adolescent idiopathic scoliosis.

STUDY DESIGN A prospective study in patients with adolescent idiopathic scoliosis of different clinical severity using whole-spine magnetic resonance imaging and somatosensory evoked potentials. OBJECTIVES To correlate the presence of magnetic resonance imaging structural abnormalities with somatosensory evoked potential-detected functional disorders in the hind brain and spinal cord and the Cobbs angle in patients with adolescent idiopathic scoliosis and to compare the result with those in healthy matched control subjects. SUMMARY OF BACKGROUND DATA Many different types of neurologic dysfunction have been reported in scoliosis. With the advent of magnetic resonance imaging, there are increased reports on the association of idiopathic scoliosis and syringomyelia, Chiari I malformation, or tonsillar ectopia. The actual link between structural and functional disorder in idiopathic scoliosis is, however, unclear. METHODS Posterior tibial nerve evoked potentials and whole-spine magnetic resonance imaging were performed in 36 healthy control subjects, 135 patients with adolescent idiopathic scoliosis with Cobbs angle less than 45 degrees, and 29 patients with Cobbs angle more than 45 degrees. RESULTS Tonsillar ectopia or syringomyelia, detected by magnetic resonance imaging, or functional disturbance in the somatosensory pathway, detected by somatosensory evoked potentials, was found to be significantly more frequent in the group of patients with severe scoliosis curvature, with an incidence of 31% and 27.6%, respectively. Incidence of tonsillar ectopia was 33.3% in patients with abnormal somatosensory evoked potentials in contrast to the much lower incidence of 2.9% in patients with normal somatosensory evoked potentials. There was a significant structural and functional link. The incidence of syringomyelia in patients with and without tonsillar ectopia was 33.3% and 0.7%, respectively. CONCLUSIONS In patients with adolescent idiopathic scoliosis with severe curve, the significant association with tonsillar ectopia and abnormal somatosensory function points to a neural origin. Disorders in the somatosensory function may be one of the mechanisms linking tonsillar ectopia to scoliosis. Somatosensory evoked potentials and magnetic resonance imaging may have important diagnostic and predictive value and may help in the management of adolescent idiopathic scoliosis.

Long-term improvement in homocysteine levels and arterial endothelial function after 1-year folic acid supplementation

PURPOSE Hyperhomocysteinemia, a risk factor for atherosclerosis, is associated with endothelial dysfunction that can be improved with short-term folic acid supplementation. The current study aimed to assess whether folic acid supplementation could produce longer-term improvements in homocysteine levels and arterial endothelial function. SUBJECTS AND METHODS Twenty-nine healthy adults with hyperhomocysteinemia were selected from 89 volunteers enrolled in a community-based atherosclerosis screening project. All subjects were given folic acid (10 mg/d) for 1 year. Fasting plasma homocysteine levels were measured by high-performance liquid chromatography. Arterial endothelial function was measured as flow-mediated dilation of the brachial artery using high-resolution B-mode ultrasound. RESULTS Folic acid supplementation for 1 year was associated with a significant increase in mean (+/-SD) plasma folate levels (24 +/- 5 nmol/L to 40 +/- 5 nmol/L; P < 0.001) and a significant decline in homocysteine levels (9.0 +/- 1.7 micromol/L to 7.9 +/- 2.0 micromol/L; P < 0.001). Flow-mediated dilation also improved significantly, from 7.4% +/- 2.0% to 8.9% +/- 1.5% (P <0.0001), but there was no change in nitroglycerin-induced (endothelium-independent) responses. CONCLUSIONS These results demonstrate that long-term folic acid improves arterial endothelial function and has potential implications for the prevention of atherosclerosis in adults with hyperhomocysteinemia.

Quantitative evaluation of thallium-201 uptake in predicting chemotherapeutic response of osteosarcoma.

Thallium-201 has been shown to be useful in predicting tumour viability in patients undergoing neoadjuvant chemotherapy for osteogenic sarcoma. Early studies relied upon qualitative assessment of analog images to obtain predictive results. Recently, the lesion to normal tissue uptake ratio of201Tl has been used in evaluating bone and soft tissue sarcomas. This study attempts to quantitate changes in tumour to normal tissue ratio following chemotherapy. Eight consecutive patients with classical osteosarcoma received standard preoperative chemotherapy with a combination of cisplatin, adriamycin and high-dose methotrexate.201Tl gamma scintigraphic images were obtained both before and after chemotherapy. The average counts taken over the tumour divided by that from the contralateral normal tissue area yielded a tumour-to-normal tissue (T/N) ratio. The percentage change in the T/N ratio before and after preoperative chemotherapy was correlated with the percentage of tumour necrosis from pathological section. The median post-chemotherapy T/N ratio was 1.85 (range 0.5–7.7). The median percentage change in T/N ratio after chemotherapy was -58% (range +26% to -83%). The median percentage of necrosis from pathological section was 80% (range 0%–95%). There was a good correlation between the percentage of tumour necrosis and the percentage change in TIN ratio (rank correlation coefficientr=0.84,P=0.0085). Quantitative assessment of changes in 201+1 uptake by osteosarcoma correlates well with tumour necrosis after preoperative chemotherapy. This method may be used to predict response to chemotherapy at an earlier stage, enabling the clinician to consider alternative chemotherapeutic regimens or salvage surgery.

Sonographic appearance and distribution of normal cervical lymph nodes in a Chinese population

In 100 normal subjects who had a sonographic examination of the neck, 1211 lymph nodes were detected. In all the subjects, at least five lymph nodes were seen. The distribution, number, echogenicity, shape, presence or absence of echogenic hilus, and the sharpness of nodal borders of normal cervical lymph nodes were determined. The usefulness of these sonographic features in understanding the normal distribution and characteristics of the nodes in the Chinese population is discussed. The relationship between the shape and size of lymph node also was assessed.

THE URETERIC JET DOPPLER WAVEFORM AS AN INDICATOR OF VESICOURETERIC SPHINCTER FUNCTION IN ADULTS AND CHILDREN. AN OBSERVATIONAL STUDY

The nature of the action of the vesicoureteric junction (VUJ) in humans is still controversial. We were interested in the reasons why the jet consists of several peaks. We hypothesised that the modification of the jet into a variable number of peaks is the result of an active sphincter mechanism at the VUJ. A total of 1,010 subjects of all ages and both genders were recruited into this study. The Doppler waveform of the jet was recorded bilaterally. We could identify six basic patterns of ureteric jet according to the number of peaks: monophasic, biphasic, triphasic, polyphasic (four or more peaks), square and continuous. By analysing the duration, maximum peak velocity and initial slope of the first four patterns, a mechanism of action of an active VUJ sphincter could be postulated. Furthermore, the basic patterns could be assigned to three modes of ureteric actions: the square and continuous are only seen during diuretic stress; the biphasic, triphasic and polyphasic patterns are variations of the adult physiological steady-state mode, and the monophasic is distinctly different and represents the immature mode.