Evaluation of the influence of the aqueous phase bioconstituent environment on the F-19 T1 of perfluorocarbon blood substitute emulsions

Oxygen-sensitive F-19 magnetic resonance imaging of perfluorocarbon compounds requires that fluorocarbon T1 changes correlate with the local Po₂ and not with the composition of the surrounding aqueous phase. The influence of various bioconstituents and paramagnetic ions within the aqueous phase on the F-19 fluorocarbon phase T1 for PFC emulsions was evaluated at 0.14 and 0.66 T. T1 was measured for FC-43, perflubron, and a fluorinated surfactant. Controlled variables introduced in the aqueous phase included annex solution constituents, blood, pH changes, and Gd-DTPA. For a constant Po₂, the F-19 T1s were independent of the emulsion constituents, blood concentration, and pH. For FC-43 and perflubron, F-19 T1 was independent of the Gd-DTPA concentration, while the aqueous phase T1 decreased by more than an order of magnitude. XMO-10 (smallest emulsion particle size) showed a slight decrease in F-19 T1 with increasing Gd-DTPA concentration at 0.66 T.     

Genotype prevalence and risk factors for severe clinical adenovirus infection, United States 2004-2006.

BACKGROUND: Recently, epidemiological and clinical data have revealed important changes with regard to clinical adenovirus infection, including alterations in antigenic presentation, geographical distribution, and virulence of the virus. METHODS: In an effort to better understand the epidemiology of clinical adenovirus infection in the United States, we adopted a new molecular adenovirus typing technique to study clinical adenovirus isolates collected from 22 medical facilities over a 25-month period during 2004-2006. A hexon gene sequence typing method was used to characterize 2237 clinical adenovirus-positive specimens, comparing their sequences with those of the 51 currently recognized prototype human adenovirus strains. In a blinded comparison, this method performed well and was much faster than the classic serologic typing method. RESULTS: Among civilians, the most prevalent adenovirus types were types 3 (prevalence, 34.6%), 2 (24.3%), 1 (17.7%), and 5 (5.3%). Among military trainees, the most prevalent types were types 4 (prevalence, 92.8%), 3 (2.6%), and 21 (2.4%). CONCLUSIONS: For both populations, we observed a statistically significant increasing trend of adenovirus type 21 detection over time. Among adenovirus isolates recovered from specimens from civilians, 50% were associated with hospitalization, 19.6% with a chronic disease condition, 11% with a bone marrow or solid organ transplantation, 7.4% with intensive care unit stay, and 4.2% with a cancer diagnosis. Multivariable risk factor modeling for adenovirus disease severity found that age <7 years (odds ratio [OR], 3.2; 95% confidence interval [CI], 1.4-7.4), chronic disease (OR, 3.6; 95% CI, 2.6-5.1), recent transplantation (OR, 2.7; 95% CI, 1.3-5.2), and adenovirus type 5 (OR, 2.7; 95% CI, 1.5-4.7) or type 21 infection (OR, 7.6; 95% CI, 2.6-22.3) increased the risk of severe disease.     

Variations in pregnancy outcomes by race among 10-14-year-old mothers in the United States.

This study used the 1983-86 U.S. Linked Live Birth-Infant Death Files to examine variations in pregnancy outcomes among 38,551 U.S. resident black and white adolescents ages 10 through 14. The birth rate was 4.29 per 1,000 for blacks, more than 7 times the rate for whites (.59 per 1,000). Black mothers had higher proportions of very low and low birth weight infants than did whites (very low birth weight: 3.7 versus 2.6; low birth weight: 15.0 versus 10.5). Neonatal and infant mortality rates were higher among very low birth weight and low birth weight white infants. Neonatal and infant mortality rates were similar for normal birth weight infants of both races, but were 3.7 to 7.4 times higher among black infants with birth weights more than 4,250 grams. Logistic regression indicated that black mothers were at higher risk for having infants who were low birth weight, very low birth weight, small for gestational age, preterm, and very preterm. There were no differences by race for neonatal, postneonatal, and infant mortality. While the risk for poor pregnancy outcomes is great among young adolescents, young black adolescents appear to be particularly vulnerable. Attempts to reduce unintended pregnancies in this group should receive highest priority.     

Variability in commercial histoplasma complement fixation antigens.

Using Immuno-Mycologics (IMMY; Norman, Okla.) histoplasmal yeast (HY) and mycelial (HM) antibody complement fixation test antigens, we retested 1,386 samples that were initially tested with Meridian Diagnostics, Inc. (Cincinnati, Ohio), antigens. Histoplasma antibody was identified (greater than or equal to 1:16) in 20% of HY and 5% of HM samples reported to have titers of less than 1:8 with Meridian reagents. IMMY titers were at least fourfold higher than Meridian titers in 39% of HY and 54% of HM samples that initially had titers of greater than or equal to 1:8 with Meridian antigens. Because 30 of 58 (52%) samples from confirmed cases of histoplasmosis yielded negative results with Meridian antigens and positive results upon retesting with IMMY antigens, we concluded that the Meridian antigens had less reactivity with human histoplasmal antibody.     

Suggested approaches for research protocols involving the potential for life-threatening reactions

These guidelines are intended to reduce the potential for serious or life-threatening reactions when clinical research is conducted. The following issues were addressed: identifying the risks involved in the research, providing adequate safeguards in the protocol design and during withholding of medication, anticipating risks, minimizing the chances for human error, providing resuscitative equipment sufficient to deal with the most serious anticipated life-threatening reactions, planning for medical support in case of a life-threatening emergency, and optimizing the use of medical personnel and expertise to handle emergency situations. The guidelines also discuss important general issues about protocol design and implementation and the human subject consent form, which should facilitate the approval of protocols by the governing institutional review board.The guidelines are not meant to be inflexible or applicable to all research situations. However, it is our hope that they will allow for clinical research to be conducted in a manner that affords the research subjects a high degree of protection from unnecessary and possibly fatal injuries.     

Clinical,hematologic, and immunologic effects of interleukin-10 in humans

We conducted a double-blind, placebo-controlled study to investigate the safety, pharmacokinetics, and immunological properties of interleukin-10 (IL-10) administration in healthy humans. Volunteers received a single intravenous bolus injection of recombinant human IL-10 (1, 10, or 25g/kg) or placebo. Cytokine production in whole blood and peripheral blood mononuclear cells (PBMC) was assessed before and 3, 6, 24, and 48 hr after the injection. Peak serum concentrations of IL-10 (15±1.1, 208±20.1, and 505±22.3 ng/ml) occurred after 2–5 min for 1, 10, and 25g/kg IL-10, respectively. The terminal-phase half-life was 3.18 hr. A transient leukocytosis (24–63% above baseline) was observed 6 hr after injection, which coincided with a dose-dependent decrease (12–24%) in neutrophil superoxide generation. There was a marked inhibition (60–95%) of endotoxin-induced IL-6 production from whole blood in each group receiving IL-10. Production of IL-8 in endotoxin-stimulated blood was reduced in the 10g/kg group. In PBMC stimulated with phytohemagglutinin and phorbol ester, there was a decrease (72–87%) in interferon- (IFN) production 6 hr after IL-10 with a return to pre-IL-10 levels after 24 hr. This reduction was only partially associated with a decrease in the number of CD2-bearing cells. We conclude that IL-10 administration into humans is without significant side effects, and a single injection reducesex vivo production of IL-6, IL-8, and IFN.     

The Mikulicz Cell in Rhinoscleroma: Light, Fluorescent and Electron Microscopic Studies

The stages in the development of the Mikulicz cell in human rhinoscleroma were studied in biopsy specimens obtained from 10 patients using light, immunofluorescent and electron microscopy. The Mikulicz cell was identified morphologically as a macrophage, not a plasma cell. Acutely inflamed areas of rhinoscleroma presented abundant bacteria with a slime layer. The microorganism was infrequent and the mucopolysaccharide was scanty in rhinoscleromal tissue, where plasma cells predominated, and in cicatricial fibrous tissue. In the granulomatous stage of rhinoscleroma, the mucopolysaccharide was found within the Mikulicz cells. The vacuoles observed in the Mikulicz cells were considered to be phagosomes containing, principally, bacterial mucopolysaccharide and few bacteria and, to a lesser extent, swollen mitochondria. It was concluded that the slime layer of Klebsiella rhinoscleromatis plays an important role in the pathogenesis of the disease. It is postulated that this material is a nondigestible mucopolysaccharide that resides in the phagosomes of macrophages, increases the osmotic pressure and forms multiple hydropic vacuoles that rupture not only the phagosomes but also the cells, resulting in the liberation of the mucopolysaccharide. This would initiate a cycle that would prolong the disease in the absence of the bacteria.     

Expression of high-affinity IL-4 receptors on murine tumour infiltrating lymphocytes and their up-regulation by IL-2.

Since interleukin-2 (IL-2) and IL-4 act in concert to support the development of cytotoxic T lymphocytes (CTL) and the generation of antigen-specific tumour infiltrating lymphocytes (TIL), we investigated the interaction of these cytokines with an established TIL line. TIL proliferated in an additive fashion in response to suboptimal concentrations of IL-2 and various concentrations of IL-4. TIL possessed high-affinity IL-4 receptors whether cultured in recombinant IL-2 (rIL-2) or rIL-4, but cells cultured in rIL-2 had higher numbers of IL-4 receptors than cells cultured in rIL-4. When TIL were cultured in increasing concentrations of rIL-2, a dose-dependent enhancement in IL-4 receptor number was observed. The maximum induction of IL-4 receptor expression was achieved by 4 hr of incubation with rIL-2 and was completely blocked by cycloheximide. Other cytokines, such as rIL-1, recombinant tumour necrosis factor (rTNF), recombinant interferon-alpha (rIFN-alpha) and rIFN-gamma, had no effect on IL-4 receptor number. rIL-2 also up-regulated IL-4 receptors on CTLL-2, a murine CTL line. These data indicate that high-affinity IL-4 receptors exist on murine TIL and they can be up-regulated by IL-2. Our observation that IL-2 up-regulates IL-4 receptor may help explain the additive effects of these lymphokines on the proliferation of TIL and other cell lines. It may also help explain their co-operative effects on the generation of antigen-specific TIL and the differentiation of CTL.