The broken circle method: a novel technique that enhances detection of Hill-Sachs lesions on internal rotation shoulder radiographs.

AIM: To describe and test a new method that increases the conspicuity of a Hill-Sachs lesion on internal rotation (IR) radiographs. MATERIALS AND METHODS: This study had institutional review board approval. A retrospective search for patients with a prior shoulder dislocation and a Hill-Sachs lesion documented on magnetic resonance imaging (MRI) was performed over a 10-year period identifying 256 test patients. In Part 1, the IR radiographs from test cases were randomised with controls, and three readers scored them independently for the defect. The readers were then taught the Broken Circle (BC) method and re-scored the radiographs. In Part 2, 15 cases of Hill-Sachs lesions that were missed by all readers in Part 1 were randomised with controls, and were shown to 25 radiology residents before (pre-test) and after (post-test) learning the BC method. A paired t-test was used to compare the differences in sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV). RESULTS: In Part 1, the sensitivity increased 19.7% (54.1%-73.8%; p<0.05) and NPV increased 10.8% (62.5%-73.3%; p<0.01). In Part 2, post-test sensitivity for residents increased 16.3% (55.2%-71.5%; p<0.0001), accuracy increased 13.4% (64%-77.4%; p<0.0001), and NPV increased 13.3% (40.8%-54.1%; p<0.0001) independent of the level of training. The change in accuracy was also statistically significant for every individual class. CONCLUSION: The BC method was an effective technique that facilitated detection of a Hill-Sachs lesion at all levels of training, and was useful as a teaching tool.

Cellular uptake and intracellular trafficking of oligonucleotides.

Oligonucleotides manifest much promise as potential therapeutic agents. However, understanding of how oligonucleotides function within living organisms is still rather limited. A major concern in this regard is the mechanisms of cellular uptake and intracellular trafficking of both 'free' oligonucleotides and oligonucleotides associated with various polymeric or nanocarrier delivery systems. Here we review basic aspects of the mechanisms of endocytosis and intracellular trafficking and how insights from these processes can be used to understand oligonucleotide delivery. In particular we discuss opportunities for escape of oligonucleotides from endomembrane compartments and describe recent studies using small molecules to enhance oligonucleotide effects.

Receptors, endocytosis, and trafficking: the biological basis of targeted delivery of antisense and siRNA oligonucleotides.

The problem of targeted delivery of antisense and siRNA oligonucleotides can be resolved into two distinct aspects. The first concerns devising ligand-oligonucleotide or ligand-carrier moieties that bind with high selectivity to receptors on the cell type of interest and that are efficiently internalized by endocytosis. The second concerns releasing oligonucleotides from pharmacologically inert endomembrane compartments so that they can access RNA in the cytosol or nucleus. In this review, we will address both of these aspects. Thus, we present information on three important receptor families, the integrins, the receptor tyrosine kinases, and the G protein-coupled receptors in terms of their suitability for targeted delivery of oligonucleotides. This includes discussion of receptor abundance, internalization and trafficking pathways, and the availability of suitable high affinity ligands. We also consider the process of oligonucleotide uptake and intracellular trafficking and discuss approaches to modulating these processes in a pharmacologically productive manner. Hopefully, the basic information presented in this review will be of value to investigators involved in designing delivery approaches for oligonucleotides.

Characterization of telomerase-immortalized, non-neoplastic, human Barrett's cell line (BAR-T).

Barrett's esophagus, a metaplasia predisposed to malignant transformation, has been studied in vitro using esophageal adenocarcinoma cell lines. However, findings in such transformed cells may not be applicable to the non-neoplastic cells of benign Barrett's esophagus. Therefore, we have developed and characterized a Barrett's cell line derived from a patient without malignancy or dysplasia. Human Barrett's epithelial cells were immortalized with the insertion of hTERT (human telomerase reverse transcriptase) using a Cre-lox recombination system. We then examined properties of this continuous cell line, such as in vitro tumorigenicity, growth patterns, histological differentiation characteristics, karyotype, and checkpoint arrest mechanisms (e.g., p16, p21, and p53). Non-neoplastic Barrett's epithelial cells infected with hTERT (BAR-T cells) have been sustained in culture beyond 200 population doublings. BAR-T cells maintain a diploid chromosome number and exhibit non-neoplastic properties, such as contact inhibition and anchorage-dependent growth. BAR-T cells express differentiation Barrett's epithelial markers, such as villin and cytokeratins 4, 8 and 18, and stain positive for Alcian blue, indicating the presence of mucin-producing cells. Expression of checkpoint arrest proteins p21 and p53 are intact, while p16 expression is lost. Thus, we have created a human Barrett's cell line that is not malignantly transformed, and yet can be maintained indefinitely in culture. BAR-T cells are diploid, have histological differentiation markers characteristic of benign Barrett's epithelium, and also maintain appropriate expression of p21 and p53. This cell line should be a useful model for the study of the early events in carcinogenesis in Barrett's esophagus.

Progressive age-related impairment of cognitive behavior in APP23 transgenic mice.

Transgenic APP23 mice expressing human APP(751) with the K670N/M671L mutation, were compared at ages 3, 18 or 25 months to non-transgenic littermates in passive avoidance and in a small and large Morris maze. The task in the smaller pool habituated their flight response to the platform. Impairments in passive avoidance and small pool performance in APP23 mice were clearly age-related. In the larger Morris maze APP23 mice at all ages were impaired in latency and distance swum before finding the platform. Identical performance of 18-month APP23 and controls in a visible platform condition indicates that the Morris maze performance deficit was not due to sensory, motor or motivational alterations. At age 3 months both groups initially unexpectedly avoided the visible platform, suggesting that in young mice neophobia may contribute significantly to performance in cognitive tests. In conclusion, APP23 mice exhibit both early behavioral impairment in the large Morris maze as well as impairments in passive avoidance and small pool performance that are marked only in old age.

Trends in parent and friend influence during adolescence: the case of adolescent cigarette smoking.

A common characterization of adolescence is that parent influence decreases and friend influence increases as adolescents age. From that, we hypothesized that the association between parent and adolescent smoking decreases and the association between friend and adolescent smoking increases as adolescents become older. The hypothesis is tested with data from The National Longitudinal Study of Adolescent Health. Adolescent smoking is measured as progressions to more frequent smoking and as continuations from prior smoking levels. There is no support for the hypothesis, a finding consistent with the earlier panel study that tested it. The age-specific findings are discussed in the context of programs designed to influence adolescent cigarette smoking and why the hypothesis that drove this study was not confirmed. Among supplementary findings reported is that adolescent smoking is more influenced by friend smoking than by parent smoking.

The effect of WIC and Medicaid on infant mortality in the United States.

OBJECTIVES: This study examine the impact of participation in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) and Medicaid on risk of infant death in the United States. METHODS: The 1988 National Maternal and Infant Health Survey was used to consider the risk of endogenous and exogenous death among infants of women participating in WIC and Medicaid during pregnancy and the infant's first year. RESULTS: Participation in the WIC program during pregnancy and infancy was associated with a reduced risk of endogenous and exogenous infant deaths (odds ratios [ORs] = 0.68 and 0.62, respectively). The risk of endogenous death among infants whose mothers participated in Medicaid during pregnancy was equal to that of the privately insured (OR = 1.04). Uninsured infants faced higher risks of endogenous death (OR = 1.42). CONCLUSIONS: These results show that it is important to consider the net effect of WIC and Medicaid participation and to differentiate both the timing of program receipt and cause of death. Evidence suggests that WIC and Medicaid programs have beneficial effects for poor women and their infants.

Hearing instruments and health technology--an evaluation.

This contribution compares a currently worn hearing instrument (i.e. R-HI) with a programmable multiband full-dynamic range compression behind-the-ear HI (i.e. T-HI), based on subject preference for HI, and, in addition, compares the preference for a linear/ non-linear amplification-mode (i.e. L-mode/C-mode). Finally, it evaluates some health technology aspects related to the devices. N = 34 experienced HI-users at a median age of 72 years (range 22-84) completed the trial, n = 5 being monaurally, and n = 29 being binaurally fitted. The trial comprises an unblinded comparative study of the R-HI and T-HI, in either C-mode or L-mode amplification, and a double-blind crossover study evaluating the C-mode versus the L-mode amplification. The results of the unblinded study showed that 94% (n = 32/34) preferred the T-HI, whereas two subjects preferred their current HI. The double-blind crossover study concerning the preference for the C-mode and L-mode, respectively, in the T-HI, showed that 72% (n = 23/32) had a significant preference for the non-linear amplification, whereas 28% (n = 9/32) preferred the linear amplification. Provided that the price of the T-HI is kept unchanged, a health technology evaluation may imply an estimate of 30 mill. DKR added costs on a national basis, which should be taken into account within the national hearing services.

Milk-induced eczema is associated with the expansion of T cells expressing cutaneous lymphocyte antigen.

The extravasation of T cells at sites of inflammation is critically dependent on the activity of homing receptors (HR) involved in endothelial cell recognition and binding. Two such HR (the cutaneous lymphocyte antigen [CLA] and L-selectin) have been shown to be selectively involved in T cell migration to skin and peripheral lymph nodes, respectively. This study was designed to assess the relationship between the organ specificity of an allergic reaction to food and the expression of HR on T cells activated in vitro by the relevant food allergen. Peripheral blood mononuclear cells were isolated from seven milk allergic children with a history of eczema when exposed to milk. All patients had a positive prick skin test and double-blind placebo-controlled food challenge to milk. 10 children with either allergic eosinophilic gastroenteritis or milk-induced enterocolitis and 8 nonatopic adults served as controls. Five-parameter flow cytometry using monoclonal antibodies was used for detection of the specific HR on freshly isolated T cells versus T cell blasts induced by a 6-d incubation with casein, as compared with Candida albicans. After in vitro stimulation with casein, but not C. albicans, patients with milk allergy and atopic dermatitis had a significantly greater percentage of CLA+ T cells (P < 0.01) than controls with milk-induced enterocolitis, allergic eosinophilic gastroenteritis, or nonatopic healthy controls. In contrast, the percentage of L-selectin-expressing T cells did not differ significantly between these groups. These data suggest that after casein stimulation allergic patients with milk-induced skin disease have an expanded population of CLA+ T cells, as compared with nonatopics or allergic patients without skin involvement. We postulate that heterogeneity in the regulation of HR expression on antigen-specific T cells may play a role in determining sites of involvement in tissue-directed allergic responses.

Legionella and Pneumocystis pneumonias in asthmatic children on high doses of systemic steroids.

Asthma is increasingly treated as an inflammatory disease with inhaled and/or systemic corticosteroids. We report 3 cases of unusual pneumonias associated with high doses of oral steroids. Two patients contracted Legionella pneumonia and one patient contracted Pneumocystis carinii pneumonia. With increasing usage, it is important for physicians to be aware of the possible infectious complications of high dose steroids. This report highlights the risk of corticosteroid treatment in asthma in predisposing to opportunistic infections that have not heretofore been readily associated with asthma.

Thirty years of Demography.

In this paper, we present a content analysis of Demography, the official journal of the Population Association of America. Our results reflect patterns of change and stability in a number of areas, including: subjects covered, number of authors, gender of authors, type of data used, source of data used, affiliation of authors and statistical procedures employed. The data suggest that the field of population research has become increasingly bureaucratized and complex, while at the same time continuing to focus on familiar research subjects. A relatively small number of population research centers contribute disproportionately to the journal.

Pregnant women at work: sociodemographic perspectives.

The 1988 National Maternal and Infant Health Survey, a stratified random sample of 9,953 live births, shows that women who work during pregnancy are more likely to be non-Hispanic white, married, of higher income and education, to have medical insurance, and of lower parity than nonemployed pregnant women (p < .0001). They begin prenatal care earlier, are less likely to smoke, and are more likely to state that the birth was wanted (p < .0001). Similar trends are seen for full-time as compared to part-time workers. Women employed as precision production workers, operators/fabricators, or in service occupations are disadvantaged with regard to sociodemographic and behavioral risks for pregnancy outcomes relative to women in professional and managerial occupations. Black race, parity, body mass index, and smoking, but not employment, are associated with low birth weight when gestational age is controlled. The effects of stress and its buffers, paternal characteristics, physical activity, and toxic exposures, both in and out of the workplace, should be considered, as should the normative and social policy context.

The meaning of living with AIDS: a study using Parse's theory of man-living-health.

This paper explores the meaning of living with Acquired Immune Deficiency Syndrome (AIDS) using Parse's theory of man-living-health as the conceptual framework. The design of the study is based on the qualitative descriptive method. Analysis of the data gathered from interviews with fourteen subjects reveals the emergence of three themes related to the meaning of living with AIDS: (a) an abrupt shift in patterns of being give rise to changing priorities, (b) fluctuating possibilities arise in the uncertainty of being with and away from close others, and (c) changing hopes and dreams surface from the insights of suffering. Practice propositions were identified from the findings of the study.

Photosynthetic pathway, chilling tolerance and cell sap osmotic potential values of grasses along an altitudinal gradient in Papua New Guinea.

A total of 22 grass species were examined from 5 sites spanning the altitudinal range 1550-4350 m.a.s.l. The presence of the C3 or C4 photosynthetic pathway was determined from δ13C values and chilling tolerance was assessed on the basis of electrolyte leakage from leaf slices incubated on melting ice. Most of the grasses studied at the lower altitude sites of 1550 m.a.s.l. (annual mean of daily minimum temperature, 14.6° C) and 2600 m.a.s.l. (9.4° C) possessed C4 photosynthesis and were chill-sensitive. The single except ion was Agrostis avenacea, a montane chill-resistant C3 species which occurred at 2600 m.a.s.l. The three species apparently most sensitive to chilling were Ischaemum polystachyum, Paspalum conjugatum and Saccharum robustum, all occurring at 1550 m.a.s.l. At the higher altitude sites of 3280 (5.6° C), 3580 (4.0° C) and 4350 (-0.7°C) m.a.s.l., most of the grasses exhibited C3 photosynthesis and were chill-resistant. However, an Upland population of the C4 species, Miscanthus floridulus was found at 3280 m.a.s.l. which had acquired chill-resistance as confirmed by additional in vivo variable chlorophyll fluorescence measurements. Cell sap osmotic potential values of the upland grasses at altitudes of 3280-4350 m.a.s.l. were lower (-8.1 to -19.8 bars) than values in grasses from 1550 and 2600 m.a.s.l. (-3.9 to -7.5 bars) due mainly to the presence of non-electrolyte osmoticants, which may be involved in frost avoidance mechanism(s).

Leaf anatomy, water relations and crassulacean acid metabolism in the chlorenchyma and colourless internal water-storage tissue of Carpobrotus edulis and Senecio ?mandraliscae.

Both Carpobrotus edulis and Senecio ?mandraliscae possess leaves with a peripheral chlorenchyma and colourless internal water-storage tissue. Water stress in C. edulis growing under semi-natural conditions resulted in the induction of weak Crassulacean acid metabolism (CAM) whereas well-watered plants of S. ?mandraliscae exhibited a similar degree of CAM. Titratable acidity in the separated water-storage tissue was substantially lower than in the chlorenchyma in both species but, nevertheless, increased during the night and decreased during the day either when sampled from the intact plant or from incubated tissue slices. Indeed, the increase in nocturnal titratable acidity produced by the water-storage tissue in situ accounted for approx. 30% of total acidification on a per-leaf basis. It appears that during the night the water-storage tissue in these species is able to fix CO2 which is subsequently released during the day to enter the photosynthetic carbon-reduction cycle of the chlorenchyma. Diurnal rhythms of water potential (Ψ) and osmotic potential (Ψs) were measured in separated chlorenchyma and water-storage tissue by thermocouple psychrometry. Both parameters increased during the latter part of the daytime and initial nocturnal period and decreased during the rest of the night and into the post-dawn period. The chlorenchyma of water-stressed plants of C. edulis appeared to possess a marked negative turgor pressure (as determined from Ψ-Ψs) but this was caused by a severe underestimation in the measurement of the chlorenchyma Ψ. It is suggested that this artefact arose from release of colloidal polysaccharide mucilage, or possibly tannins, from broken tannin cells producing a lowering of water activity when measured using thermocouple psychrometry.

Observation and characterisation of a transient in the yield of chlorophyll fluorescence in intact spinach chloroplasts.

A transient in chlorophyll fluorescence, which is associated with a transient in 9-aminoacridine fluorescence and a perturbation in the rate of oxygen evolution, has been observed in intact spinach chloroplasts. The results indicate that changes in the redox state of Q are, at least partially, responsible for the transient in chlorophyll fluorescence. The size of the transient is highly dependent upon the concentration of inorganic phosphate and upon the pH of the medium. The properties of the transient are consistent with the suggestion that it reflects changes in the levels of stromal intermediates during induction.

Altitudinal changes in the incidence of crassulacean acid metabolism in vascular epiphytes and related life forms in Papua New Guinea.

The occurrence of Crassulacean acid metabolism (CAM), as judged from δ13C values, was investigated in epiphytes and some related plant species at a series of sites covering the approximate altitudinal range of epiphytes in Papua New Guinea. Comprehensive collections were made at each site and the occurrence of water storage tissue and blade thickness was also determined. Some 26% of epiphytic orchids from a lowland rainforest (2-300 m.a.s.l) showed δ13C values typical of obligate CAM and possessed leaves thicker than 1 mm. A second group of orchids, mostly with succulent leaves, possessed intermediate δ13C values between -23 and -26% and accounted for 25% of the total species number. Some species of this group may exhibit weak CAM or be facultative CAM plants. The remainder of the lowland rainforest species appeared to be C3 plants with δ13C values between -28 and -35%. and generally possessed thin leaves. Obligate CAM species of orchids from a lower montane rainforest (1175 m.a.s.l) comprised 26% of the species total and mostly possessed thick leaves. The remainder of the species were generally thin-leaved with δ13C values between -26 and -35%. largely indicative of C3 photosynthesis. Orchids with intermediate δ13C values were not found in the lower montane rainforest. Obligate CAM appeared to be lacking in highland epiphytes from an upper montane rainforest and subalpine rainforest (2600-3600 m.a.s.l). However the fern, Microsorium cromwellii had a δ13C value of -21.28%. suggesting some measure of CAM activity. Other highland ferns and orchids showed more negative °13C values, up to-33%., typical of C3 photosynthesis. The highland epiphytic orchids possessed a greater mean leaf thickness than their lowland C3 counterparts due to the frequent occurrence of water storage tissue located on the adaxial side of the leaf. It is suggested that low daytime temperatures in the highland microhabitats is a major factor in explaining the absence of CAM. The increased frequency of water storage tissue in highland epiphytes may be an adaptation to periodic water stress events in the dry season and/or an adaptation to increased levels of UV light in the tropicalpine environment.

Adenine nucleotide status, phosphoglycerate reduction and photosynthetic phosphorylation in a reconstituted chloroplast system.

The concentrations of ADP and ATP were measured during illumination of a reconstituted chloroplast system to which NADP(+), 3-phosphoglycerate and ribose 5-phosphate were successively added. Their effects on photosynthetic oxygen evolution and on the concentrations of ATP and ADP are discussed in terms of the regulation of photosynthetic carbon assimilation.