High levels of T lymphocyte activation in Leishmania-HIV-1 co-infected individuals despite low HIV viral load

Background

Anti-viral prophylaxis is used to prevent the transmission of influenza. We studied serological confirmation of 2009 Influenza A (H1N1) infections during oseltamivir prophylaxis and after cessation of prophylaxis.

Methods

Between 22 Jun and 16 Jul 09, we performed a cohort study in 3 outbreaks in the Singapore military where post-exposure oseltamivir ring chemoprophylaxis (75 mg daily for 10 days) was administered. The entire cohort was screened by RT-PCR (with HA gene primers) using nasopharyngeal swabs three times a week. Three blood samples were taken for haemagglutination inhibition testing - at the start of outbreak, 2 weeks after completion of 10 day oseltamivir prophylaxis, and 3 weeks after the pandemic's peak in Singapore. Questionnaires were also administered to collect clinical symptoms.

Results

237 personnel were included for analysis. The overall infection rate of 2009 Influenza A (H1N1) during the three outbreaks was 11.4% (27/237). This included 11 index cases and 16 personnel (7.1%) who developed four-fold or higher rise in antibody titres during oseltamivir prophylaxis. Of these 16 personnel, 8 (3.5%) were symptomatic while the remaining 8 personnel (3.5%) were asymptomatic and tested negative on PCR. Post-cessation of prophylaxis, an additional 23 (12.1%) seroconverted. There was no significant difference in mean fold-rise in GMT between those who seroconverted during and post-prophylaxis (11.3 vs 11.7, p = 0.888). No allergic, neuropsychiatric or other severe side-effects were noted.

Conclusions

Post-exposure oseltamivir prophylaxis reduced the rate of infection during outbreaks, and did not substantially increase subsequent infection rates upon cessation. Asymptomatic infections occur during prophylaxis, which may confer protection against future infection. Post-exposure prophylaxis is effective as a measure in mitigating pandemic influenza outbreaks.     

Associations of plasma homocysteine levels with arterial stiffness in prehypertensive individuals

Prehypertension is associated with oxidative stress and increased arterial stiffness. While plasma homocysteine levels are associated with increased pulse wave velocity in hypertensive individuals, there is no report regarding this relationship in prehypertensives. Homocysteine levels and brachial-ankle pulse wave velocity (baPWV) were investigated in 4177 prehypertensives (3178 men, mean age 53 ± 11 years) with ankle-brachial indexes (ABIs) greater than 0.95 who had visited the Kangbuk Samsung Health Promotion Center. The subjects were subdivided into two groups according to baPWV; group I (1720 subjects) was defined as subjects with a baPWV of 1366 cm/sec or lower, while group II (2457 subjects) included subjects with a baPWV greater than 1366 cm/sec. Subjects were also divided into four quartile groups depending on homocysteine level. Homocysteine levels in group II were found to be significantly higher than those in group I. There were significant differences in baPWV value among the four quartile groups (quartile I, 1411 ± 213.9 cm/sec; quartile II, 1436 ± 223.3 cm/sec; quartile III, 1460 ± 220.4 cm/sec; quartile IV, 1494 ± 251.3 cm/sec; p-value <0.001). In multivariate regression models, the increasing quartile groups of homocysteine had higher odds ratios (ORs) for increased baPWV compared to that of the lowest quartile group (OR [95% confidence interval (CI)] in the second, third, and highest quartiles: 1.41 [1.12-1.77], 1.65 [1.30-2.10], and 1.82 [1.42-2.33], respectively, p < 0.001), irrespective of confounding factors. This study indicates an independent relationship between circulating homocysteine level and arterial stiffness in prehypertensives, suggesting that circulating homocysteine level could be a useful biomarker of subclinical target organ damage in prehypertensives.     

Vascular endothelial function and plasma homocysteine levels in Behcet's disease

The purpose of the present study was to test endothelial function and to determine if plasma homocysteine levels are associated with endothelial injury in patients with Behcet's disease (BD). Flow-mediated dilation in patients with BD was smaller than that of control subjects (p = 0.001), and mean plasma homocysteine levels in patients with BD were significantly higher (p = 0.0001). On regression analysis, only mean plasma homocysteine concentration was independently related to flow-mediated dilation (F = 5.7, p = 0.001).     

Variability of fasting and post-methionine plasma homocysteine levels in normo- and hyperhomocysteinaemic individuals.

To assess the variability of plasma homocysteine levels, fasting and post-methionine homocysteine levels were measured twice, at baseline and after follow-up of 1-4 months, in 16 individuals with normal and 26 with elevated homocysteine levels after methionine loading. The intra-individual coefficients of variation varied from 15 to 23% for fasting and post-methionine homocysteine levels, whether these levels were within the normal range or not. As a result, test-retest agreement was poor when subjects were dichotomized as having 'normal' or 'abnormal' homocysteine levels (itself a questionable concept). There was a relation between the average post-methionine homocysteine levels (at the first and second measurement) and the difference between both measurements (r = 0.37, P = 0.016). In normohomocysteinaemic individuals, delta (i.e., the difference between baseline and follow-up) fasting homocysteine and delta post-methionine homocysteine were correlated negatively with delta folate serum levels: r = -0.64, P = 0.007 and r = -0.50, P = 0.05, respectively. Individuals homozygous for the 677 C-->T mutation in the 5,10-methylenetetrahydrofolate reductase gene showed a greater variation of fasting homocysteine levels than those homozygous for the wild type (P = 0.017). In summary, we suggest that there is a substantial intra-individual variability in plasma homocysteine levels over time and that this variability is significantly related to the variability in serum folate levels, especially in normohomocysteinaemic individuals.     

Normal triglyceride levels despite insulin resistance in African Americans: role of lipoprotein lipase

Abstract Lipoprotein lipase (LPL), the enzyme responsible for hydrolyzing triglyceride (TG) in plasma lipoproteins, is a key regulator of plasma TG levels. In Caucasians, postheparin-LPL (PH-LPL) activity is impaired in the presence of insulin resistance and leads to elevated TG levels. However, African Americans are often both insulin-resistant and normotriglyceridemic. But in African Americans, the effect of insulin resistance on PH-LPL activity has not been studied. In African Americans, if insulin resistance is not associated with a decrease in PH-LPL activity, this could account for the simultaneous presence of insulin resistance and normotriglyceridemia. Therefore, our goal was to determine in African Americans the relationship between insulin resistance and PH-LPL activity. In a cross-sectional study of 107 nondiabetic African Americans (57 men and 50 women; age mean +/- SD, 35 +/- 8 years, range 22-50 years; body mass index 31.6 +/- 7.9 kg/m 2 , range 18.5-54.7 kg/m 2 ), fasting TG levels and PH-LPL activity were determined. Visceral adipose tissue was measured by abdominal computed tomographic scan. Insulin resistance was determined by the insulin sensitivity index ( S I ). Subjects were divided into tertiles by S I . The range of S I in each tertile was 12.75 to 3.99, 3.87 to 2.20, 2.06 to 0.17 mU . L -1 . min -1 . Insulin resistance was defined as being in the third tertile. TG levels in the men and women were 82.2 +/- 35.5 versus 56.4 +/- 30.1 mg/dL, P < .001. There were no sex difference in PH-LPL activity (8.9 +/- 2.5 vs 9.6 +/- 3.2 mmol/h per liter, P = .30) or S I (3.65 +/- 2.59 vs 3.23 +/- 1.89 L . mU -1 . min -1 , P = .49). Although 47% of the subjects were obese, only 4% of subjects had hypertriglyceridemia (TG > or =150 mg/dL). By 2 separate analyses, PH-LPL was a major determinant of TG levels. First, there was a significant inverse correlation between PH-LPL activity and TG levels (men: r = -0.46, P < .001; women: r = -0.28, P = .046). Second, in the multiple regression analysis with TG as the dependent variable and PH-LPL, age, sex, S I , and visceral adipose tissue as independent variables, adjusted R 2 was 54% and the effect of PH-LPL on TG levels was highly significant( P < .001). However, insulin resistance did not appear to influence PH-LPL activity. This is demonstrated in 3 ways: first, PH-LPL activity was not different in the S I tertiles (9.10 +/- 2.75, 9.52 +/- 2.91, 9.13 +/- 2.89 mmol/h per liter, P = .78); the correlation between PH-LPL and S I was not significant (men: r = 0.09, P = .51; women: r = -0.03, P = .78), and a multiple regression with PH-LPL as the dependent variable and age, S I , body mass index, and sex as independent variables, adjusted R 2 was <2% and the contribution of S I was not significant ( P = .53). Hence, in African Americans, increased PH-LPL activity is associated with a decrease in TG levels. The lack of an effect of insulin resistance on PH-LPL could allow LPL to clear TG even in the presence of insulin resistance and explain the coexistence of insulin resistance and normotriglyceridemia in African Americans.     

Normal spontaneous and stimulated GH levels despite decreased IGF-I concentrations in cystic fibrosis patients

OBJECTIVE: The aim of the present study was to investigate whether patients with cystic fibrosis (CF) are GH resistant with increased GH release and decreased concentrations of IGF-I as a result of malabsorption, increased catabolism and impaired glucose tolerance. DESIGN: Twenty CF patients were included, ten with normal glucose tolerance (five male, five female, median age 25.5 years (range 20-31)) and ten with diabetes mellitus (five male, five female, median age 25.3 years (range 17-45). Twenty healthy individuals served as controls (ten male, ten female, median age 28.4 years (range 18-36)). METHODS: GH status was evaluated by 12h spontaneous GH release during the night time, arginine-stimulated GH release and the basal concentrations of IGF-I and insulin-like growth factor-binding protein-3 (IGFBP-3). Twelve hour spontaneous GH profiles were estimated using a constant blood withdrawal technique with sampling every 30min and the Pulsar method was used for the analysis of profiles. RESULTS: No significant differences were found in spontaneous and stimulated GH release in CF patients compared with healthy controls, whereas IGF-I and IGFBP-3 were significantly decreased in CF patients compared with healthy controls. The combination of reduced IGF-I and IGFBP-3 with normal GH release points to a relative GH resistance or a disturbance in the pituitary axis in patients with CF. The spontaneous GH release, the stimulated GH release and the basal concentrations of IGF-I and IGFBP-3 were not significantly different in diabetic CF patients compared with CF patients with normal glucose tolerance and the presence of diabetes mellitus was not consistent with increased GH resistance in CF patients. CONCLUSION: CF patients with normal glucose tolerance and diabetic CF patients had normal GH release and decreased concentrations of IGF-I indicating a relative GH resistance.     

Normal endothelial function despite insulin resistance in healthy women with the polycystic ovary syndrome

Women with the polycystic ovarian syndrome (PCOS) carry a number of cardiovascular risk factors, including insulin resistance, lipid abnormalities, and an altered pattern of sex steroid exposure. Noninvasive measurements of endothelial function, which can demonstrate abnormalities well in advance of clinically apparent disease, have not been previously reported in this patient group. We undertook a cross-sectional evaluation of endothelium-dependent and -independent vascular function using brachial artery ultrasound. We studied healthy women with clinical and laboratory evidence of PCOS (n = 18) and age-matched controls (n = 19), not taking any antihypertensive, cholesterol-lowering, or hormonal therapies. Laboratory parameters of insulin resistance, glycemia, cholesterol status, and hormone levels were also measured. Despite marked differences in glucose/insulin ratio [6.1 +/- 1.1 mmol/pmol (PCOS) vs. 9.9 +/- 0.6 (controls)] and free androgen index [11.9 +/- 2.3 (PCOS) vs. 3.7 +/- 0.6 (controls); normal, <5], we did not find evidence of impaired endothelial function in our patients with PCOS. Both endothelium-dependent (8.7 +/- 3.1%) and endothelium-independent (23.2 +/- 3.4%) vascular responses were normal, and practically identical to the responses seen in the control group (endothelium-dependent, 9.0 +/- 0.7; endothelium-independent, 23.0 +/- 1.2%). The PCOS women were more obese, but baseline brachial arterial diameters were not different between groups. There was no correlation between degree of insulin resistance or hyperandrogenism and the brachial response. This group of healthy obese young women with insulin resistance and hyperandrogenism due to PCOS had normal endothelium-dependent and -independent vascular responses compared to age-matched controls. The factors resulting in preservation of these response are unclear and warrant further investigation.     

Normal opioid tone and hypothalamic-pituitary-adrenal axis function in chronic fatigue syndrome despite marked functional impairment

OBJECTIVE: To determine whether the functional impairment seen in chronic fatigue syndrome (CFS) is associated with reduced levels of central opioids and/or deficiency of the hypothalamic-pituitary-adrenal (HPA) axis. DESIGN: Single-blinded case-control study measuring functional and psychological status, basal hormonal parameters and ACTH/cortisol response to naloxone and ovine corticotrophin-releasing hormone (oCRH) vs. placebo in people with CFS and healthy controls. PATIENTS: Twelve people with CFS and 11 age-matched controls. MEASUREMENTS: Hormonal parameters: basal levels of 09:00 h plasma cortisol, dehydroepiandrosterone sulfate (DHEAS) and IGF-1. 24-h urinary free cortisol. Plasma ACTH and cortisol response to naloxone 125 microg/kg, oCRH 1 microg/kg and placebo (normal saline). Psychological parameters: SF-36, Hamilton Depression Score, Hospital Anxiety and Depression Scale and Fatigue Scale. RESULTS: There were highly significant differences between the CFS subjects and the controls with respect to the measures of fatigue and physical functioning. However, there were no differences in basal levels of 09:00 h cortisol (367 +/- 37 vs. 331 +/- 39 nmol/l, P = 0.51), DHEAS (4.2 +/- 0.6 vs. 4.0 +/- 0.5 micromol/l, P = 0.81), 24-h urinary free cortisol (182 +/- 27 vs. 178 +/- 21 nmol/24 h, P = 0.91) or IGF-1 (145 +/- 19 vs. 130 +/- 11 microg/l, P = 0.52) between the CFS group and controls, respectively. There was also no difference between the groups with respect to the ACTH and cortisol response to either oCRH or naloxone. CONCLUSIONS: Our data do not support an aetiological role for deficiency in central opioids or the HPA axis in the symptoms of CFS.     

不同甲状腺功能患者血浆总同型半胱氨酸水平的临床研究

目的 了解不同甲状腺功能用者血浆总同型半胱氨酸水平，探讨其与甲状腺功能的相关性。方法 收集12例甲状腺功能减退(甲减)患者、28例甲状腺功能亢进(甲亢)患者及30例正常体检人群的血浆，用高效液相色谱法测定总同型半胱氨酸水平，用放射免疫法测定叶酸和VitBl2，酶法测定胆固醇。结果 甲减组总同型半胱氨酸和胆固醇水平较正常对照组显著升高(P＜0.01)，甲减组叶酸水平较正常对照组降低(P＜0．01)；甲亢组总同型半胱氨酸和胆固醇水平较正常对照组降低(P＜0．01)，叶酸水平在此两组间无显著性差异(P＞0．05)；甲减组总同型半胱氨酸较甲亢组显著升高(P＜0．01)，甲减组胆固醇水平较甲亢组显著升高(P＜0．01)，甲减组叶酸水平较甲亢组显著降低(P＜0．01)；三组间VitBl2水平均无显著性差异(P＞0．05)。不同甲状腺功能人群血浆总同型半胱氨酸与其游离T4呈负相关。结论 血浆总同型半胱氨酸水平可能对判断甲状腺功能有辅助作用，甲减思者高同型半胱氨酸血症是其易思心血管疾病的一个独立危险因素。     

Normal individuals with high Hb A2 levels

Summary We report one case of acquired sideroblastic anaemia in a patient treated for Wilson's disease with triethylene tetramine dihydrochloride (TTH). No other cause of acquired sideroblastic anaemia was found, and neither iron nor pyridoxine therapy could correct this anaemia. In contrast, decreasing the dose of TTH led to disappearance of ringed sideroblasts.
Thus TTH should be added as a further cause of secondary acquired sideroblastic anaemia. The pathophysiology of this finding, probably linked to an abnormality of mitochondrial iron metabolism, is briefly discussed.