Epidemic of adenovirus-induced respiratory illness among US military recruits: epidemiologic and immunologic risk factors in healthy, young adults.

Adenovirus (Ad)-induced acute respiratory illnesses resurged among civilian adults and selected military training populations in the United States during the late 1990s. We examined the epidemiologic and immunologic correlates of Ad-induced respiratory illnesses during a large outbreak at an Army basic training installation in southeast United States during a 9-day period in November 1997. A total of 79 recruits hospitalized with acute respiratory illnesses were evaluated during the outbreak period; confirmation of Ad infection by isolation of Ad-like cytopathic agents from throat cultures was detected in 71 (90%) of these patients. Serotyping of 19 (27%) of these 71 isolates identified the etiologic agent to be Ad type 4 (Ad4). In addition, 30 (81%) of 37 patients in whom paired sera were collected demonstrated significant increases (i.e., 4-fold or higher) in serum anti-Ad4 neutralizing antibodies. Anti-Ad4 immunity in new recruits was found to be very low (15 to 22%). A case-control study involving 66 of the 79 hospitalized cases and 189 non-ill controls from the same units was conducted. A lower risk of hospitalization for acute respiratory illnesses was documented for female recruits (odds ratio[OR] = 0.47, P <.05) whereas, a higher risk was noted for smokers (OR = 1.89, P <.05). Unit (training company) attack rates as high as 8 to 10% per week were documented and the outbreak quickly subsided after live, oral Ad types 4 and 7 vaccination was resumed in November 1997. Re-establishment of a military Ad vaccination program is critical for control of Ad-induced acute respiratory illnesses.

Hyperglycemia-induced ascorbic acid deficiency promotes endothelial dysfunction and the development of atherosclerosis.

Dehydroascorbic acid, the oxidized form of vitamin C, is transported into mammalian cells via facilitative glucose transporters and hyperglycemia inhibits this process by competitive inhibition. This inhibited transport may promote oxidative stress and contribute to the increase in atherosclerotic cardiovascular disease observed in patients with diabetes mellitus. This review explores the importance of this proposed mechanism in light of current research. For example, recent reports suggest that administration of antioxidants, such as vitamin C, may slow atherogenesis by improving endothelium-dependent vasodilation in individuals with abnormal glucose and lipid metabolism, perhaps by preventing the oxidation of nitric oxide, an important regulator of vasomotor tone. Endothelial dysfunction plays a key role in the development of atherosclerosis and endothelial cells may be particularly affected by hyperglycemia-induced ascorbic acid deficiency as they line the interior of blood vessels. In addition, we discuss evidence of several other mechanisms by which vitamin C status may affect the development of atherosclerotic cardiovascular disease, particularly its inverse relationship to multiple cardiovascular disease risk factors and indicators. Given these factors, vitamin C administration is recommended during periods of both acute and chronic hyperglycemia to help preserve endothelial function.

Novel approach for the determination of the redox status of homocysteine and other aminothiols in plasma from healthy subjects and patients with ischemic stroke.

BACKGROUND: Plasma "redox" status can be assessed by measurements of reduced (r)-, free (f)-, oxidized (ox)-, and protein-bound (b)-homocysteine (Hcy) plus the related aminothiols cysteine, cysteinylglycine (CysGly), and glutathione (GSH), but sample collection has been complex. The redox status has not been determined in ischemic stroke patients and may provide increased understanding of its role in pathogenesis. We wished to examine the feasibility of this measurement in samples collected in readily available acidic sodium citrate. METHODS: We measured aminothiols and their stability in stabilized protein-free filtrate using acidic sodium citrate (BioPool Stabilyte, pH 4.3) vs EDTA whole blood. Before analysis, plasma samples were also ultrafiltered to obtain a protein-free filtrate. The concentrations of total Hcy (tHcy), fHcy, and rHcy and their related aminothiols, cysteine, cysteinylglycine, and glutathione were simultaneously determined on acidic sodium-citrated blood using reversed-phase HPLC with fluorescence detection. Bound and oxidized aminothiols were calculated by difference using the concentrations of the total, free, and reduced fractions. Using this approach, we compared the redox status in newly diagnosed ischemic stroke patients (n = 20) and healthy age- and sex-matched subjects (n = 20). RESULTS: tHcy, tCys, tCysGly, and tGSH concentrations in whole blood with Stabilyte were stable for 8 h; the reduced fraction of each aminothiol was stable for 4 h. Recovery in the protein-free filtrate was 90-100% for all reduced thiols in acidified sodium-citrated blood. Patients with ischemic stroke had higher plasma tHcy, fHcy, bHcy, rHcy, and oxHcy (P <0.0005) and higher plasma t-, f-, r-, and oxCys (P <0.05). t-, b-, and rCysGly concentrations were lower in the stroke patients (P <0.05), as were t-, b-, and oxGSH (P <0.005). CONCLUSIONS: Collection of blood in acidic sodium citrate (BioPool Stabilyte) permits the determination of the redox status of Hcy and its related aminothiols, which may add to the understanding of their relationship to the etiology of cerebrovascular disease.

Energy metabolism increases and regional body fat decreases while regional muscle mass is spared in humans climbing Mt. Everest.

The objectives of the study were to determine regional changes in body composition, energy expenditure by means of doubly labeled water, and net energy balance during exposure to high and extreme altitudes (5,300-8,848 m). This study focuses on a subset of subjects who consumed the doubly labeled water (three base camp personnel and seven climbers). Regional body composition was determined by measuring skinfold thicknesses and circumferences at 10 different sites on the body. Energy expenditure was measured by doubly labeled water excretion. Discrepancies between actual energy expenditure and data obtained from diet records and body weight changes suggested a chronic underreporting of dietary energy intake, especially by those subjects who reached the highest altitudes. This underreporting may be due in part to diminished cognition or to a preferential focus on survival, rather than on filling out diet records accurately. Mean adjusted dietary intakes were 10.50 +/- 0. 65 MJ/d (2510 +/- 155 kcal/d) for those who remained at base camp, and 20.63 +/- 6.56 MJ/d (4931 +/- 1568 kcal/d) for those who climbed above base camp. Energy expenditure averaged 2.5-3.0 times sea level resting energy expenditure. Differential changes in regional body composition suggested a preferential loss of fat mass and a relative sparing of muscle mass, despite insufficient energy intake to maintain body weight.

Intakes of high fat and high carbohydrate foods by humans increased with exposure to increasing altitude during an expedition to Mt. Everest.

The objectives of the study were to determine total energy intakes, distribution of energy derived from the macronutrients, and the effects of increasing altitudes on energy and macronutrient consumption during exposure to high altitudes. High fat, low carbohydrate diets (35% and 50% of energy, respectively) or low fat, high carbohydrate diets (20% and 65% of energy, respectively) were provided to two groups of subjects for a 3-wk period. Groups then consumed the alternate diet for 3 wk, followed by a return to the original diet for the remaining 3 wk of the study. Free choice of individual items and amounts within each diet was permitted. Intake of food and fluid was determined by means of monitored entries in daily food records. Five subjects remained at Base Camp (5300 m) and 10 subjects climbed to altitudes up to and including the summit of Mt. Everest (8848 m). Subjects consumed an average of 10.22 +/- 4.57 MJ/d (2442 +/- 1092 kcal) energy while at Base Camp, with climbers consuming significantly more than Base Camp personnel [11.89 +/- 4. 88 vs. 7.87 +/- 2.98 MJ/d (2841 +/- 1167 vs. 1881 +/- 713 kcal/d), P 0.05). Contrary to previous reports, subjects in this study did not shift their food selections away from the high fat items towards high carbohydrate items.

Use of the Mogen clamp for neonatal circumcision.

Most newborn circumcisions performed in the United States are done with either a Gomco clamp or a Plastibell device. The Mogen clamp, devised by a jewish mohel, provides a quick and simple surgical alternative. The foreskin is freed from the glans by blunt dissection, but no dorsal slit is made. A dorsal hemostat is placed, and traction is applied to bring the foreskin forward. Placement of the Mogen clamp follows the angle of the corona to avoid removing excess skin ventrally and to obtain a superior cosmetic result. The clamp crushes the foreskin along a line that is 1 mm wide, and the foreskin is excised distal to the clamp. After removal of the clamp, the glans is liberated by pulling the crush line apart. The procedure usually takes three to four minutes and is virtually bloodless.

Homocysteine metabolism and risk of myocardial infarction: relation with vitamins B6, B12, and folate.

Elevated plasma homocyst(e)ine levels are an independent risk factor for vascular disease. In a case-control study, the authors studied the associations of fasting plasma homocyst(e)ine and vitamins, which are important cofactors in homocysteine metabolism, with the risk of myocardial infarction. The cases were 130 Boston area patients hospitalized with a first myocardial infarction and 118 population controls, less than 76 years of age, enrolled in 1982 and 1983. Dietary intakes of vitamins B6, B12, and folate were estimated from a food frequency questionnaire. After adjusting for sex and age, the authors found that the geometric mean plasma homocyst(e)ine level was 11% higher in cases compared with controls (p = 0.006). There was no clear excess of cases with extremely elevated levels. The age- and sex-adjusted odds ratio for each 3-mumol/liter (approximately 1 standard deviation) increase in plasma homocyst(e)ine was 1.35 (95% confidence interval 1.05-1.75; p trend = 0/007). After further control for several risk factors, the odds ratio was not affected, but the confidence interval was wider and the p value for trend was less significant. Dietary and plasma levels of vitamin B6 and folate were lower in cases than in controls, and these vitamins were inversely associated with the risk of myocardial infarction, independently of other potential risk factors. Vitamin B12 showed no clear association with myocardial infarction, although methylmalonic acid levels were significantly higher in cases. Comparing the mean levels of several homocysteine metabolites among cases and controls, the authors found that impairment of remethylation of homocyst(e)ine (dependent of folate and vitamin B12 rather than on vitamin B6-dependent transsulfuration) was the predominant cause of high homocyst(e)ine levels in cases. Accordingly, plasma folate and, to a lesser extent, plasma vitamin B12, but not vitamin B6, correlated inversely with plasma homocyst(e)ine, even for concentrations at the high end of normal values. These data provide further evidence that plasma homocyst(e)ine is an independent risk factor for myocardial infarction. In this population, folate was the most important determinant of plasma homocyst(e)ine, even in subjects with apparently adequate nutritional status of this vitamin.

Hyperglycemia-induced latent scurvy and atherosclerosis: the scorbutic-metaplasia hypothesis.

Latent scurvy is characterized by a reversible atherosclerosis that closely resembles the clinical form of this disease. Acute scurvy is characterized by microvascular complications such as widespread capillary hemorrhaging. Vitamin C (ascorbate) is required for the synthesis of collagen, the protein most critical in the maintenance of vascular integrity. We suggest that in latent scurvy, large blood vessels use modified LDL--in particular lipoprotein(a)--in addition to collagen to maintain macrovascular integrity. By this mechanism, collagen is spared for the maintenance of capillaries, the sites of gas and nutrient exchange. The foam-cell phenotype of atherosclerosis is identified as a mesenchymal genetic program, regulated by the availability of ascorbate. When vitamin C is limited, foam cells develop and induce oxidative modification of LDL, thereby stabilizing large blood vessels via the deposition of LDL. The structural similarity between vitamin C and glucose suggests that hyperglycemia will inhibit cellular uptake of ascorbate, inducing local vitamin C deficiency.