Controlling Kinetic Pathways in Demixing Microgel-Micelle Mixtures.

We investigate the temperature-dependent phase behavior of mixtures of poly(N-isopropylacrylamide) (pNIPAM) microgel colloids and a triblock copolymer (PEO-PPO-PEO) surfactant. Usually, gelation in these systems results from an increase in temperature. Here we investigate the role of the heating rate, and surprisingly, we find that this causes the mechanism of aggregation to change from one which is driven by depletion of the microgels by the micelles at low temperatures to the association of the two species at high temperatures. We thus reveal two competing mechanisms for attractions between the microgel particles which can be controlled by changing the heating rate. We use this heating-rate-dependent response of the system to access multiple structures for the same system composition. Samples were found to demix into phases rich and poor in microgel particles at temperatures below 33 °C, under conditions where the microgels particles are partially swollen. Under rapid heating full demixing is bypassed, and gel networks are formed instead. The temperature history of the sample, therefore, allows for kinetic selection between different final structures, which may be metastable.

Oxidative degradation of triblock-copolymer surfactant and its effects on self-assembly.

We investigate the degradation behaviour of a triblock-copolymer surfactant made from polyethylene oxide (PEO) and polypropylene oxide (PPO) (PEO-PPO-PEO), highlighting how the aggregation behaviour of this polymer in water alters with ageing. Samples aged at room temperature were compared to samples degraded using accelerated ageing at elevated temperatures. We find that large mass losses occurred to the polymer surfactant which resulted in a change in the aggregation behaviour, with larger, rod-like or planar aggregates forming at longer degradation times. We look at how this change in aggregation behaviour changes the formulation stability of these polymers, specifically, the interaction of the polymer surfactant with poly(N-isopropylacrylamide) microgels. It is known that these species associate and form gels at elevated temperatures. This paper highlights how commonly used polymeric surfactants can degrade over time, resulting in dramatic changes to aggregation behaviour and therefore, formulation properties.

Reversible temperature-controlled gelation in mixtures of pNIPAM microgels and non-ionic polymer surfactant.

We investigate the reversible gelation of poly(N-isopropylacrylamide) (pNIPAM) microgels in the presence of triblock-copolymer (PEO-PPO-PEO type) surfactant. We demonstrate that the association of these polymers with the microgel particles at elevated temperature is responsible for the gelation, due to the temperature responsive nature of the components. This is highlighted by an increase in the apparent hydrodynamic diameter of the particles in dynamic light scattering experiments, which only occurs above the volume phase transition temperature of pNIPAM. The gels that result shrink over a time period much larger than that of the collapse of pNIPAM microgels, and retain the shape of the container they form in. We investigate the mechanism that leads to this gelation and the structure of the gels that result. Confocal microscopy experiments show that both polymers are present in the gel network, indicating that an associative mechanism is responsible for the gelation. We vary the pNIPAM particle architecture to further investigate the gelation process, and find that the cross-link distribution plays a key role in the gelation mechanism, where for uniformly cross-linked particles the gelation is not observed. This shows that the fuzzy corona of the pNIPAM microgels is involved in the association of the polymers, allowing the triblock-copolymer to penetrate the outer corona of the microgels and bridge the particles. The phase transition observed is close to physiological conditions, so these gels have the potential for use in biomedical applications, including tissue engineering.

Choline and choline esters in human and rat milk and in infant formulas.

Large amounts of choline are required in neonates for rapid organ growth and membrane biosynthesis. Human infants derive much of their choline from milk. In our study, mature human milk contained more phosphocholine and glycerophosphocholine than choline, phosphatidylcholine, or sphingomyelin (P < 0.01). Previous studies have not recognized that phosphocholine and glycerophosphocholine exist in human milk. Concentrations of choline compounds in mature milk of mothers giving birth to preterm or full-term infants were not significantly different. Infant formulas also contained choline and choline-containing compounds. In infant formulas derived from soy or bovine milk, unesterified choline, phosphocholine, glycerophosphocholine, phosphatidylcholine, and sphingomyelin concentrations varied greatly. All infant formulas contained significantly less phosphocholine than did human milk. Soy-derived formulas contained significantly less glycerophosphocholine (P < 0.01) and phosphocholine (P < 0.01) and more phosphatidylcholine (P < 0.01) than did human or bovine milk or bovine milk-derived infant formulas. Rat milk contained greater amounts of glycerophosphocholine (almost 75% of the total choline moiety in milk) and phosphocholine than did human milk. When dams were provided with either a control, choline-deficient, or choline-supplemented diet, milk composition reflected the choline content of the diet. Because there are competing demands for choline in neonates, it is important to ensure adequate availability through proper infant nutrition. Although the free choline moiety is adequately provided by infant formulas and bovine milk, reevaluation of the concentrations of other choline esters, in particular glycerophosphocholine and phosphocholine, may be warranted.

Pulmonary veno-occlusive disease in an adult following bone marrow transplantation. Case report and review of the literature.

Pulmonary veno-occlusive disease (PVOD) was diagnosed in an adult following chemotherapy and bone marrow transplantation (BMT) for acute lymphoblastic leukemia. A medical literature review showed only three previous reports of PVOD following BMT occurring in children but no prior cases in adults.

Social and cognitive processes in interpersonal communication: implications for advanced telecommunications technologies.

Interactive multimedia conferencing systems, in which two or more remotely located people can work on cooperative tasks through shared audio, video, and data, appear to be the wave of the future. However, because of great advances in the underlying technology of multimedia conferencing systems, many design decisions have been driven by what is technically feasible as opposed to what will best suit the needs of the users. In this paper we provide a framework for the design and evaluation of features in advanced telecommunications products and services which is derived from empirical research on interpersonal communication. We also discuss implications of this research for the development and use of advanced telecommunications technologies.

Cytotoxic T lymphocyte precursor frequency does not correlate with either the incidence or severity of graft-versus-host disease after matched unrelated donor bone marrow transplantation.

BMT from matched unrelated donors or mismatched family members is associated with an increased risk of graft-versus-host disease (GVHD) compared with HLA-identical sibling donors. It has been suggested that the level of patient-specific CTL precursors (CTLp) present in matched unrelated donors correlates with the incidence and severity of GVHD after BMT. This study group consisted of 17 patients who all received unmanipulated bone marrow from an HLA-A,B,DR-matched unrelated donor. Patient-specific CTLp frequencies were estimated in the donor before transplant. The CTLp frequencies were then compared with the incidence and severity of GVHD experienced by the patient after transplantation. Statistical analysis revealed no correlation between donor precursor frequencies and the patient developing clinically significant acute GVHD after transplantation (X2 = 1.16). This study suggests that caution should be used before the inclusion of the CTLp frequency result in the clinical decision of selecting the most suitable matched unrelated donor for BMT. CTLp frequency does not correlate with either the incidence or severity of GVHD after matched unrelated donor BMT.

Coordination of knowledge in communication: effects of speakers' assumptions about what others know.

Two pairs of studies examined effects of perspective taking in communication, using a 2-stage methodology that first obtained people's estimates of the recognizability to others of specific stimuli (public figures and everyday objects) and then examined the effects of these estimates on message formulation in a referential communication task. Ss were good at estimating stimulus identifiability but were biased in the direction of their own knowledge. The amount of information in a referring expression varied inversely with the perceived likelihood that addresses could identify the target stimulus. However, effects were less strong than anticipated. Although communicators do take others' knowledge into account, the extent to which they do so involves a trade-off with other sorts of information in the communicative situation.

Disseminated sarcoidosis: a case report.

Sarcoidosis is a systemic granulomatous disease of unknown etiology, most frequently involving the lungs, lymph nodes, spleen, liver, eyes and skin. Gastrointestinal sarcoidosis is uncommon, with rare histological documentation of noncaseating granulomas. Bone marrow sarcoidosis is also infrequent, and we are only aware of one case of documented gastric and bone marrow sarcoidosis in the same patient, which was diagnosed at autopsy. We herein report a case of endoscopic biopsy proven gastric sarcoidosis in a patient with systemic sarcoidosis with known hepatic and bone marrow involvement. To our knowledge this is the first description in a living patient of gastrointestinal and bone marrow involvement of systemic sarcoidosis.

Comparison of two antibiotic regimens for neonatal necrotizing enterocolitis.

Treatment of neonatal necrotizing enterocolitis (NEC) regularly includes broad-spectrum antibiotics but there has been no comparative study of alternative regimens. We have studied 90 infants with definite NEC; 46 cases in 1982-3 were treated with ampicillin and gentamicin, while 44 cases in 1984-5 received cefotaxime and vancomycin. Groups were well matched and managed uniformly. Infants greater than or equal to 2200 g birthweight did well with either regimen. Smaller infants given cefotaxime and vancomycin had a lower risk of culture-positive peritonitis (P = 0.01), and as a result, were less likely to die (P = 0.048) or develop thrombocytopenia (P = 0.004). The better outcome might be explained by the greater suppression by cefotaxime and vancomycin of the gut flora of treated patients (P less than 0.001). Both regimens were well-tolerated. Our data suggest that carefully chosen antibiotic regimens can improve the outcome of NEC.

Spontaneous endotoxinemia in premature infants: correlations with oral feeding and bowel dysfunction.

Infants admitted to a tertiary care nursery were tested serially to determine the frequency and epidemiology of spontaneous endotoxinemia, a phenomenon suggested by previous studies. Plasma and stools were tested for endotoxin-like activity (ELA) using a Limulus amoebocyte lysate method and results were correlated with clinical data. We detected ELA in plasma of 28 of 47 infants (60%) tested throughout their hospital stay: only two of 58 separate episodes could be attributed to infection. Endotoxinemia was not consistently associated with classical signs of fever, shock, and jaundice. Prior to oral feeding, little or no ELA was detected in stools and endotoxinemia was ascertained in only six of 45 infants (13%). With feeding, fecal ELA concentrations rose sharply, and endotoxinemia was detected in 56% of remaining infants (p less than 0.001). Bowel disease predisposed to endotoxinemia: 16 of 20 infants (80%) with necrotizing entercolitis or difficult establishment on feeding were affected, compared to five of 17 infants (29%) without such problems (p less than 0.01). Fecal ELA concentrations were not abnormally elevated in those with bowel disease. We conclude that endotoxinemia occurs commonly in immature infants as their fecal flora develops with feeding but the amount of circulating endotoxin required for injury and the patterns this takes require further investigation.

Evaluation of skin antisepsis prior to blood culture in neonates.

In our Intensive Care Nursery, coagulase-negative staphylococcus is the most frequent blood culture isolate. As skin antisepsis is critical in preventing blood culture contamination, we examined the efficacy of the chlorhexidine tincture (CH) used in our nursery for this purpose. Staphylococcus epidermidis colonized the forearms of 88% of infants tested, in a mean density of 10(4) organisms/cm2. Following a 60-second application of CH (0.5% in 70% ethanol), bacterial growth from forearm skin remained abundant in 15/38 infants (39.4%). Cleansing with 70% isopropyl alcohol, followed by CH as above, left abundant residual growth in only 1/37 infants (2.7%) (P less than 0.001). All 136 S. epidermidis tested were susceptible to CH (MIC less than 5 micrograms/ml) and 14 of 15 exposed to CH 0.02% were rapidly killed (greater than or equal to 98% fall in viable counts within 90 sec). We conclude that two-phase antisepsis using isopropanol followed by CH is a more effective preparation for blood culture in neonates than is CH alone.

Bacterial endotoxins in umbilical cord blood of neonates.

We tested umbilical cord blood from 255 infants for evidence of bacterial endotoxins. Using a Limulus lysate gelation technique, endotoxin-like activity (ELA) was detected in 13 (9.1%) of 142 term infants and in 23 (20.3%) of 113 preterm infants (p less than 0.05), in concentrations ranging from 30 to 3,000 pg Escherichia coli equivalent activity per milliliter of plasma. No factors predisposing to endotoxemia could be detected in term pregnancies but among ELA+ premature infants, placental cultures more frequently revealed gram-negative species (p less than 0.05). Cord blood endotoxemia in the concentrations observed was without obvious consequence in mothers and term infants. Our data confirm the existence of natal endotoxemia, a potential mechanism of perinatal injury.

Potential significance of colonization with beta-lactamase-producing Haemophilus parainfluenzae in children.

Recent surveys in Vancouver showed most healthy children were colonized with beta-lactamase-producing Haemophilus parainfluenzae. Such organisms might alter the effects of penicillins on throat bacteria by local inactivation. To test this hypothesis in vitro, three isolates of beta-lactamase-producing Haemophilus parainfluenzae were each mixed on a membrane with ampicillin-sensitive strains of Haemophilus influenzae type b or group A Streptococcus pyogenes and exposed to ampicillin. When tested alone, susceptible strains were rapidly killed but when tested together with a beta-lactamase producer, they were protected, indicating efficient ampicillin degradation by Haemophilus parainfluenzae strains. If similar interactions occur in vivo, the effects of beta-lactams on throat bacteria could be significantly altered in the presence of beta-lactamase-producing Haemophilus parainfluenzae.

Characterization of ampicillin-resistant Haemophilus parainfluenzae.

Carriage of ampicillin-resistant (Ampr) Haemophilus parainfluenzae has become frequent among children in our community, although carriage of Ampr Haemophilus influenzae remains uncommon. In this study we characterized the mechanism of ampicillin resistance in 27 representative isolates of H. parainfluenzae. As determined by isoelectric focusing, each isolate had a TEM-1 beta-lactamase; substrate profiles assessed for enzymes from 10 strains were also consistent with TEM-1 enzyme. Agarose gel electrophoresis revealed a plasmid of 23 to 34 megadaltons in each isolate and a small plasmid (less than or equal to 4 megadaltons) in 14 isolates. Transfer of ampicillin resistance to H. influenzae Rd was achieved during membrane mating with 14 of 15 donors. The transconjugants exhibited high-level ampicillin resistance (greater than or equal to 50 micrograms/ml), which was stable despite serial passage of isolates on antibiotic-free media. The transconjugants tested retained fertility. Cryptic plasmids were discovered in 7 of 25 antibiotic-susceptible H. parainfluenzae isolates. Our data suggest that H. parainfluenzae may play an important role in the exchange of Ampr genes among throat bacteria.

Ampicillin-resistant Haemophilus influenzae colonizing ambulatory children.

The prevalence of ampicillin sodium-resistant Haemophilus influenzae was determined from throat cultures of 305 ambulatory children. Resistant strains were detected in 3% of children, amounting to 12% of Haemophilus isolates. Factors associated with carriage of ampicillin-resistant strains were sought: only ampicillin exposure was significant. Among children who had received ampicillin or amoxicillin trihydrate within six months, 9% harbored ampicillin-resistant strains compared with 1.4% among those not exposed. Colonization with H influenzae was more frequent following the use of ampicillin, and a higher proportion of isolates was resistant rates was observed with other antibiotics or with factors such as age, sex, otitis history, or day-care center exposure. The association between ampicillin/amoxicillin usage and carriage of ampicillin-resistant strains is increasingly clear. It remains to be determined whether the use of newer antibiotics for otitis also will encourage the development of resistance in H influenzae.

Frequency of ampicillin-resistant Haemophilus parainfluenzae in children.

Ampicillin resistance has been described in Haemophilus species other than Haemophilus influenzae, but its frequency and significance are uncertain. In a throat-culture survey, beta-lactamase-producing Haemophilus parainfluenzae was detected in 192 (72%) of 266 ambulatory children. Ampicillin-resistant H. parainfluenzae was more frequently found in children from three to four years of age (88%) or in those who attended day-care programs (97%) and less frequently in older children and parents (33%). Colonization was unrelated to previous exposure to antibiotics or to a history of otitis media. Colonization with ampicillin-resistant H. parainfluenzae occurred in 88% of subjects with H. influenzae, including all of seven subjects carrying ampicillin-resistant H. influenzae. Colonization with beta-lactamase-producing H. parainfluenzae was 26 times more frequent than with H. influenzae. If the mechanisms and genetics of resistance are the same, H. parainfluenzae may prove to be a vector for spread of resistance genes of H. influenzae.