Childhood outcomes following preterm prelabor rupture of the membranes (PPROM): a population-based record linkage cohort study.

OBJECTIVE: The objective of this study is to determine child health, development and educational outcomes for infants born following preterm prelabor rupture of the membrane (PPROM). STUDY DESIGN: Population-based record linkage cohort study using data from NSW, Australia, 2001 to 2014. RESULTS: Of 121 822 births at 20 to 37 weeks, 18 799 (15%) followed PPROM, 56 406 (46%) followed spontaneous labor and 46 617 (38%) were planned. Compared with infants of a similar gestational age born following spontaneous labor or planned delivery, exposure to PPROM did not increase the risk of childhood mortality, childhood hospitalization, developmentally vulnerable at school entry, low reading or numeracy scores. Median latency ranged from 12 days (interquartile range 3 to 37 days) at 25 weeks to 1 day (0 to 2 days) at 36 weeks. Longer latency and more advanced gestational age at birth were associated with better outcomes. CONCLUSION: Infants born following PPROM are at no greater risk of adverse child health, development and education outcomes than those of similar gestational age born without PPROM.

The influence of risk and monetary payment on the research participation decision making process.

OBJECTIVES: To determine the effects of risk and payment on subjects' willingness to participate, and to examine how payment influences subjects' potential behaviours and risk evaluations. METHODS: A 3 (level of risk) x 3 (level of monetary payment), between subjects, completely randomised factorial design was used. Students enrolled at one of five US pharmacy schools read a recruitment notice and informed consent form for a hypothetical study, and completed a questionnaire. Risk level was manipulated using recruitment notices and informed consent documents from hypothetical biomedical research projects. Payment levels were determined using the payment models evaluated by Dickert and Grady as a guide. Five dependent variables were assessed in the questionnaire: willingness to participate, willingness to participate with no payment, propensity to neglect to tell about restricted activities, propensity to neglect to tell about negative effects, and risk rating. RESULTS: Monetary payment had positive effects on respondents' willingness to participate in research, regardless of the level of risk. However, higher monetary payments did not appear to blind respondents to the risks of a study. Payment had some influence on respondents' potential behaviours regarding concealing information about restricted activities. However, payment did not appear to have a significant effect on respondents' propensity to neglect to tell researchers about negative effects. CONCLUSIONS: Monetary payments appear to do what they are intended to do: make subjects more willing to participate in research. Concerns about payments blinding subjects to risks could not be substantiated in the present study. However, the findings do raise other concerns--notably the potential for payments to diminish the integrity of a study's findings. Future research is critical to make sound decisions about the payment of research subjects.

Sale of tobacco products in pharmacies: results and implications of an empirical study.

OBJECTIVE: To provide national-level data concerning the percentage of pharmacies selling tobacco products, examine relationships between selling practices and pharmacy characteristic variables, and explore perceptions of conflicts between tobacco-selling activity and professional and personal values and the potential effects of such conflicts. DESIGN, SETTING, PARTICIPANTS: Data were collected from a geographically stratified systematic random sample of 899 pharmacies. Multiple mailings were sent to the attention of the pharmacy manager. A random sample of nonrespondents was also contacted by telephone, urging participation. MAIN OUTCOME MEASURES: Whether the pharmacy currently sold cigarettes and/or smokeless tobacco products, and if so, whether these practices differed from what respondents' personal or professional values tell them to do. Scales designed to measure job satisfaction, job-induced tension, and propensity to leave were also included. RESULTS: Slightly more than half (50.5%) of the pharmacies sold cigarettes and 35.4% sold smokeless tobacco products. Independents were less likely than chain pharmacies to sell tobacco products. For those respondents working in pharmacies where tobacco products were sold, 47.6% responded that this practice differs from what their personal values tell them to do and 63.9% replied that this practice differs from what their professional values tell them to do. Even when controlling for pharmacy type, respondents working in pharmacies that sold tobacco products had significantly lower levels of global job satisfaction, higher levels of job-induced tension, and a higher propensity to leave than did respondents working in pharmacies that did not. CONCLUSION: Decision makers in pharmacies where tobacco products are still sold should take a serious look at the justification for the continued availability of tobacco products in an environment that has a goal of promoting health.

Quality of life assessment by community pharmacists: an exploratory study.

Implicit in the evolving role of pharmacy is that its practitioners embrace the concept of quality of life (QoL). In recent years there has been an increased interest in incorporating health-related quality of life (HRQoL) measures into clinical practice, primarily focusing on the physician as the user of this information. Pharmacists may be able to use these instruments in their practices to provide better pharmaceutical care. To explore the feasibility of such an undertaking, questionnaires were mailed to a national sample of community pharmacies. In addition to the questionnaire, the respondents were provided with examples of two instruments: the Duke Health Profile and the QOLIE-10. A definition of HRQoL was provided to the respondents. After two mailings and a reminder postcard, a usable response rate of 27.2% was achieved. The results revealed that over 80% of the respondents currently discuss HRQoL issues with their patients. In addition, 66% reported that they attempt to assess the HRQoL of their patients, albeit usually on a subjective, informal basis. After viewing examples of HRQoL instruments, over three-quarters of the respondents reported a willingness to use HRQoL assessment tools in their practices. However, only 53.7% of the respondents were familiar with the concept of HRQoL. Less than 5% reported familiarity with formal instruments. The self-reported knowledge of pharmacists concerning HRQoL was low and the respondents recognized a significant gap between their current knowledge and the level of knowledge needed to assess the HRQoL of their patients formally. The results suggest a possible role for the pharmacist in HRQoL assessment. However, the use of HRQoL instruments in community pharmacies will require further training and education on the part of pharmacists concerning the concept of HRQoL, the issues involved in its measurement and how they can use HRQoL information in their practices. In addition, a number of unanswered questions must be addressed through the research process in order for HRQoL questionnaires to become clinical tools in the practice of pharmacy.

Values, participatory democracy, and healthcare resource allocation: an application to a campus community.

As healthcare reform is debated, it is important that decision makers consider the values of all citizens, that is, what people find desirable or useful about healthcare services. Several states have used town meetings in an effort to determine their citizens' views on the values in the realm of healthcare. In this article, the authors describe a process in which individuals actively participate in an open discussion about issues surrounding allocation of healthcare resources in a university setting. Three different groups from the university community participated in separate, structured meetings to discuss their values concerning the allocation of scarce healthcare resources. Such meetings give participants opportunities to learn about their values and those of other persons in the community.

The stabilization of fibrillar collagen matrices with 3,4-dihydroxyphenylalanine.

Pepsin-treated type I collagen fibrils were reconstituted by warming to 37 degrees C in the presence of DOPA at a concentration of 1 x 10(-3)M. Following a 1-1.5-h lag period the "gels" became progressively stabilized as indicated by an inability to disperse these at 0 degrees C. Following 24 h of incubation at 37 degrees C, the DOPA-collagen gels were insoluble in dilute acetic acid even under denaturing conditions. The effect on both gel stability and solubility was concentration-dependent and was maximum at 1 x 10(-3)M. Gel solubility changes were significant, with the greatest change occurring between concentrations of 3.1 x 10(-5)M and 1.65 x 10(-5)M. DOPA exposure did not alter the fibrillar banding pattern seen at the electron microscopic level. Collagen felts prepared by lyophilization of DOPA-collagen gels demonstrated an increase in shrinkage temperature which after 24 h exceeded that of rat tail tendon. Preformed collagen felts incubated for 24 h in the presence of 1 mM DOPA also had a greatly increased shrinkage temperature. Pepsin-treated collagen control felts were altered with respect to control felts in a time dependent manner. The wet tensile strength increased to four times that of control after 3 days of incubation at 37 degrees C. Matrix extensibility initially increased to 1.5 times that of control felts after 4 days of incubation at 37 degrees C, but decreased to below control values following 6 additional days of incubation. These properties suggest that DOPA may be useful as a stabilizing agent of collagen biomedical prostheses.

Peptides from live yeast cell derivative stimulate wound healing.

Live yeast cell derivative is an alcoholic extract from yeast (Saccharomyces cerevisiae) that has previously been shown by three groups of workers to stimulate wound healing. Live yeast cell derivative is a complex mixture, and it was not known which of its many components was responsible for the biological activity. This study describes the separation and analysis of the major components, one of which is a peptide fraction that stimulates wound healing. The fraction consists of a mixture of peptides from 6000 to 17,000 d. It causes angiogenesis in a chick embryo yolk sac membrane assay and in a rabbit cornea assay, and it dramatically stimulates wound healing in the "Schilling/Hunt" wire mesh cylinder model at concentrations 25-fold lower than those required for the intact live yeast cell derivative.

Increased hyaluronate and collagen biosynthesis and fibroblast estrogen receptors in macaque sex skin.

Sequential steroid administration of estradiol (E2) and progesterone (P) in spayed pigtailed macaques was used to precisely control the time course of sex skin swelling. After removal of the P implant, the sex skin swelled considerably and the water content of the sex skin increased manyfold over that of back skin. During the swelling phase, hyaluronate biosynthesis in sex skin increased dramatically compared with back skin of the same animals. Collagen synthesis also increased but to a lesser extent. Estrogen receptor levels were undetectable in back skin and very low in spayed animals that had been treated with both E2 and P. After removal of the P implant, both the level of estrogen receptor and the rate of hyaluronate biosynthesis increased. Immunocytochemistry with monoclonal antibodies against the estrogen receptor showed that the dermal fibroblast was the only cell type to stain positively for estrogen receptor. We conclude that the sex skin swelling that follows P withdrawal in pigtailed macaques bearing E2 implants is mediated by estrogen receptors in dermal fibroblasts and is a result of increased hyaluronic acid synthesis by these cells.

Effect of calcium on cell proliferation and extracellular matrix synthesis in arterial smooth muscle cells and dermal fibroblasts.

The effect of calcium on cell proliferation and connective tissue formation was studied in cultured vascular smooth muscle cells (SMC) and dermal fibroblasts. Calcium deficiency caused a modest decrease in proliferation of smooth muscle cells but this effect was small compared to that previously observed with fibroblasts. Synthesis of connective tissue components was affected differently in the two cell types. Biosynthesis of proteoglycans was assessed by metabolic labeling of their glycosaminoglycan side chains. Different levels of extracellular calcium did not affect proteoglycan production by fibroblasts, but it was significantly reduced in smooth muscle cells incubated in calcium-deficient medium. Both smooth muscle cells and fibroblasts were able to produce appreciable amounts of collagen in the complete absence of calcium and in both cell types collagen synthesis was increased when calcium was present. Fibroblasts, however, showed a much smaller response to calcium than did smooth muscle cells. In fibroblasts the maximum rate of collagen synthesis was achieved in a narrow range of calcium concentration which was slightly below that found commonly in the tissue culture medium. By contrast, in smooth muscle cells the rate of collagen synthesis increased greatly when calcium was present and this elevated rate persisted even when the cells were exposed to high levels of extracellular calcium. We conclude that these findings may be of significance to the development of atherosclerotic lesions.

Composition and metabolism of symptomatic distal aortic plaque.

This study examines the composition of advanced human atherosclerotic lesions removed by endarterectomy and compares the collagen synthesis in the lesion with that of the intima-media layer of uninvolved vessel wall. The most striking feature of the lesions is an enormous accumulation of calcium that was raised more than tenfold, from a level of about 3% of dry tissue weight in the normal tissue to values approaching 50% in the pathologic specimens. The composition of the organic matrix was also altered. Elastin and glycosaminoglycan content decreased, whereas collagen content more than doubled, thus becoming the major component of the organic matrix. The cholesterol content increased severalfold above normal but even then accounted for less than 10% of the organic matrix. The lesion specimens synthesized collagen in vitro at a greater rate than normal tissue. The endarterectomy specimens with the highest calcium content exhibited the highest rate of collagen synthesis.

Quantitation of type I to type III collagen ratios in small samples of human tendon, blood vessels, and atherosclerotic plaque.

A method is described whereby the ratio of the major interstitial collagens (Types I and III) can be measured in biopsy specimens of human tissue weighing as little as 25 mg. Marker peptides are solubilized from the tissue by digestion with cyanogen bromide. These peptides which are not known to be involved in collagen crosslinking are isolated and quantified by a combination of carboxymethyl-cellulose chromatography and polyacrylamide gel electrophoresis. The peptides used are alpha 1(I)-CB7 and alpha 1(III)-CB5. The use of the method is illustrated by analyzing the collagen type ratio in small specimens of tendon, aorta, and vena cava.

Age-related changes in reducible crosslinks of human dental pulp collagen.

Coronal pulp of human third molars from patients ranging in age from 16 to 40 yr was analysed for collagen, protein, calcium and reducible crosslink content. Dihydroxylsinonorleucine (DHLNL) was the major crosslink; it decreased with age. Hydroxylsinonorleucine (HLNL) and lysinonorleucine (LNL) appeared in insignificant amounts. Calcium content increased with age. Based on the premise that collagen synthesis is characterized by the presence of reducible crosslinks, the study showed that coronal pulp collagen synthesis decreases with age; this is accompanied by a decrease in collagen concentration in terms of dry weight and total protein between 16 and 30 hr of age.

Crosslink analysis as an indicator of collagen turnover in periodontal ligament from functioning and non-functioning teeth in the dog.

The assay of transiently-occurring reducible collagen crosslinks was used as an indication of collagen turnover in the periodontium from individual teeth. A tooth was removed on one side of the jaw to relieve the antagonist tooth of all occlusal forces. This did not influence the very high rate of collagen turnover observed in periodontal ligaments. It is concluded that this high rate of turnover is an intrinsic property of the tissue and is uninfluenced by occlusal or eruptive forces.

The effect of lysosomal enzymes on the proliferation of aortic smooth muscle cells and fibroblasts.

The rate of 3H-thymidine incorporation and cell multiplication was investigated in aortic smooth muscle cells and WI-38 fibroblasts exposed to lysosomal enzymes isolated from liver or alveolar macrophages. It was found that cells grown in the presence of lysosomal enzymes reached higher final densities than untreated cells and the rate of 3H-thymidine incorporation was markedly increased in the enzyme-exposed cultures. The stimulation of 3H-thymidine uptake was detected both in growing and quiescent cultures of smooth muscle cells and WI-38 fibroblasts. The precursor taken up by the lysosomal enzyme treated cells was incorporated into a DN-ase susceptible material. These experiments illustrate that lysosomal enzymes, when present in low concentration in the cellular environment, can act as mitogens and may play a role in the pathogenesis of atherosclerosis.

Structural glycoprotein, fact or artefact.

It has been repeatedly claimed that structural glycoprotein or SGP is a major component of many connective tissues, particularly aorta. SGP is usually defined as material extractable from tissue with chaotropic agents such as urea and having an amino acid composition matching that of other, similar extracts. It has been claimed that SGP comprises 10-60% of the dry weight of aortic tissue. This paper describes a study in which aorta was exhaustively extracted with agents previously claimed to extract SGP. All the extracts yielded mixtures of proteins which, upon separation by polyacrylamide gel electrophoresis, were found to consist largely of actin, collagen, myosin and other known proteins. No significant quantity of any one unidentified protein was found which could have been SGP. This study casts grave doubt upon the existence of SGP as a major component of aorta.

Arterial cholesterol content and collagen metabolism in cynomolgus monkeys.

The activity of prolyl hydroxylase and the rate of collagen synthesis were examined in two anatomically different arterial segments of cholesterol-fold cynomolgus monkeys. In the aortic arch vessels the activity of prolyl hydroxylase was increased after six months on a high fat and high cholesterol diet. In this tissue the enzyme activity showed positive correlation with the levels of plasma and tissue cholesterol content. By contrast in the abdominal aortas of the same animals no significant increase of arterial tissue cholesterol or prolyl hydroxylase activity was seen. Despite the elevation of prolyl hydroxylase activity in the arch vessels of hyper cholesterolemic animals, no concomitant increase of collagen synthesis was seen. Neither cholesterolemia nor arterial cholesterol showed a positive correlation with the rate of arterial collagen synthesis. No significant changes of the rate of collagen metabolism were detected at the end of an 18 months intervention phase when the cholesterol content both in plasma and in the arterial tissue was substantially reduced.

Aging of collagen.

Current knowledge of the structure and the mechanism of formation of the covalent cross-links that fuse individual collagen molecules into a stable fiber is reviewed. Some of the mechanical properties of dermal connective tissue and the way in which these change with age can be correlated with the types of cross-link present in the tissue. Cross-links are routinely detected by treatment of a tissue sample with tritium-labeled borohydride and subsequent isolation and quantification of the cross-linked compound, which has been rendered radioactive by reaction with this reducing compound. After maturity, the number of detectable cross-links decreases even though the mechanical stability of the tissue increases. This anomaly is examined in the light of recent data suggesting that cross-links may be oxidized in vivo and thus become undetectable since they can no longer react with borohydride.

Biosynthesis of aortic collagen and glycosaminoglycan following immunological injury.

The effect of immunological injury upon the early in vivo changes in aortic connective tissue metabolism was studied. It was found that a single antigen (bovine serum albumin), when administered in multiple doses, activated collagen synthesis and increased the rate of lgycosaminoglycan synthesis in the arterial wall. The degree of stimulation of both connective tissue components was higher in animals receiving a higher dose of antigen.

Sulfated glycolipids in ciliary body epithelium.

The sulfated material which locates in the basal membrane of ciliary body epithelium when immature rat eyes are incubated with Na235SO4 was studied. On the basis of its chromatographic behavior compared with standard preparations, we conclude that the material consists of sulfatides.

Excelsior: a retrospective view of collagen.

The current state of knowledge about the biosynthesis of the collagen molecule and the stabilization of fibers is reviewed. There have been a number of major breakthroughs during the past 25 years which will be described.