Changes in bone density and biochemical markers of bone turnover in pregnancy-associated osteoporosis.
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Biomedical subjects
Publications and source records attributed to J Jones.
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OBJECTIVE: To evaluate the effect of altering pediatric triage criteria on ED triage scoring and patient flow. METHODS: A prospective observational study of a pediatric triage modification was performed. Data for all pediatric patients presenting to an urban general ED during a six-month study period were collected. After the first three months, pediatric triage criteria were altered by elevating the acuity of several historical items and specifically listing abnormal signs and symptoms. Outcome measures included triage score assignment, criteria making the patient emergent, proportion of emergent or urgent triage assignments, and times to examination, disposition, and admission. RESULTS: Altering pediatric triage criteria resulted in a significant (p < 0.05) increase in the number of patients triaged as emergent (2% vs 15%) or urgent (48% vs 55%). In addition, for emergent and urgent patients there was a significant decrease (p < 0.05) in the mean times to ED examination (50 vs 44 min), floor admission (355 vs 245 min), and intensive care unit admission (221 vs 132 min). The triage changes that had a significant impact on these results were a history of color change, decreased activity, and prematurity with complications. CONCLUSIONS: A significant improvement in pediatric patient flow occurred after posting age-specific abnormal signs and symptoms as well as elevating triage acuity for specific historical clues.
OBJECTIVE: To evaluate the effect of cartoon illustrations on patient comprehension of and compliance with ED release instructions. METHODS: A prospective, randomized, controlled study of consecutive patients who presented to the ED of a community teaching hospital with lacerations necessitating wound repair during a three-month study period. At ED release, the patients were randomly assigned to receive wound care instructions with or without cartoon illustrations. Three days later, the patients were followed up by telephone. A blinded investigator asked a series of questions designed to test the patient's recall of, understanding of, and compliance with wound care instructions. RESULTS: A total of 234 patients were successfully contacted by telephone; 105 (45%) had been given ED release instructions with cartoons, 129 (55%), without cartoons. There was no significant difference in age, gender, level of education, or satisfaction with the ED visit between the two groups. The patients given cartoon instructions were more likely to have read the instructions (98% vs 79%, p < 0.001), were more likely to answer all wound care questions correctly (46% vs 6%, p < 0.001), and were more compliant with daily wound care (77% vs 54%, p < 0.01). Subset analysis of those patients who had less than a high school education (n = 57) demonstrated even larger differences between the two treatment groups in terms of comprehension of and compliance with ED release instructions. CONCLUSION: Cartoon illustrations are an effective strategy for conveying information and may improve patient compliance with ED release instructions.
OBJECTIVE: To compare neutrophil Fc receptor (Fc gamma R) and CD59 signalling responses in normal healthy subjects and patients with active rheumatoid arthritis (RA). METHODS: Intracellular free calcium concentrations were measured in neutrophils loaded with the fluorescent calcium indicator fura-2, using a spectrofluorimeter. RESULTS: Basal intracellular calcium ion concentrations were similar in both groups when no primary antibody, CD59, or CD32 (Fc gamma RIII) antibody was added. When CD16 (Fc gamma RIII) antibody was added, there was a significantly greater basal calcium concentration in the patient group compared with the control group. Transient cytosolic calcium ion fluxes were observed after binding Fc gamma RII, Fc gamma RIII, or CD59 with specific monoclonal antibodies and cross linking with the F(ab)2 fragment of sheep antimouse IgG. Peak concentrations of intracellular free calcium, [Ca2+]i, after cross linking each of the three receptors, were comparable between normal healthy donors and patients with RA. The lag period between addition of cross linking antibodies and the increase in calcium was also similar between normal individuals and patients. CONCLUSION: Contrary to previous reports, these results demonstrate that Ca2+ signalling responses of cross linked Fc receptors in blood neutrophils from patients with RA are identical to those in neutrophils of normal subjects. Signalling responses of cross linked CD59 are also unaltered.
The purpose of this study was to assess the physiological responses of former elite distance runners during submaximal and maximal exercise after a mean period of 22 yr. Fifty-three men were initially tested (T1) in the late 1960s and early 1970s when they were all highly trained and competitive. For the current evaluation (T2), these men were classified as highly trained (HT; n = 10), fitness trained (FT; n = 18), untrained (UT; n = 15), and fit older (FO; n = 10), depending on their continued level of training and age. The mean (+/- SE) age for the HT, FT, and UT men during T2 was similar (46.5 +/- 1.6 yr), whereas the FO men were significantly (P < 0.05) older (68.4 +/- 2.7 yr). All groups experienced a significant decrease (P < 0.05) in maximal O2 uptake (VO2 max) from T1 to T2. However, this decrease was related to the amount of training between evaluations. The HT men had the smallest reduction (6% per decade) in VO2 max (from 68.8 to 59.2 ml.g-1.min-1). The FT men's VO2 max was approximately 10% lower per decade (from 64.1 to 48.9 ml.kg-1.min-1), whereas an approximately 15% decrease per decade was observed for the UT (from 70.7 to 46.7 ml.kg-1.min-1) and FO (from 60.3 to 40.7 ml.kg-1.min-1) men, despite the continued training of the FO men. Energy requirements for a standardized run at 12 km/run were similar from T1 to T2 for the HT and FT men, whereas the UT men required an increased (P < 0.05) O2 uptake (40.3-41.8 l/min), ventilation (53.7-72.7 l/min), and heart rate (127-142 beats/min). The perceived effort and %VO2 max for this submaximal run were greater during T2 for all groups, which was related to the decline in VO2 max. These longitudinal data indicate that after more than two decades the physiological capacities of these aging runners are compromised, regardless of training. These data also confirm previous cross-sectional findings that aerobic capacity of highly trained middle-aged men declines approximately 5-7% per decade.
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Between January 1992 and September 1993, 813 patients with stage D2 prostate cancer were enrolled in a multicentre, double-blind (for antiandrogen therapy) trial and randomised to antiandrogen therapy with Casodex (bicalutamide, 50 mg once daily) or flutamide (250 mg three times daily) and to luteinising hormone-releasing hormone (LHRH) analogue therapy with Zoladex (goserelin, 3.6 mg every 28 days) or leuprolide (7.5 mg every 28 days). Time to treatment failure was the primary efficacy endpoint. At a median follow-up time of 49 weeks, there was a significant (p = 0.005) difference between groups in time to treatment failure in favour of Casodex plus LHRH analogue. Overall, 168 (42%) of 404 patients in the Casodex plus LHRH analogue group and 218 (53%) of 409 patients in the flutamide plus LHRH analogue group reached a treatment failure endpoint. Although a cause-specific treatment-failure analysis was not performed, the difference between groups in treatment failure attributed to adverse events (mainly diarrhoea) was evident primarily in the first 7 months of therapy. The difference between groups in treatment failure for objective progression was most evident after 1 year of therapy. With further follow-up (median time of 95 weeks), the result for time to treatment failure, although no longer statistically significant, were consistent with the previous finding of an improvement in time to treatment failure associated with Casodex plus LHRH analogue therapy. With a median of 95 weeks of follow-up, 34% of deaths had occurred. The survival analysis was not dissimilar between the 2 groups. At 49 weeks median follow up, the incidence of diarrhoea was significantly (p < 0.001) lower among patients in the Casodex plus LHRH analogue group. Diarrhoea led to withdrawal from therapy for 2 patients in the Casodex plus LHRH analogue group, compared with 25 patients in the flutamide plus LHRH analogue group. In conclusion, Casodex plus LHRH analogue is well tolerated and effective with an improvement in time to treatment failure over flutamide plus LHRH analogue. Survival was not dissimilar between the 2 treatment groups.
OBJECTIVE: This study investigated the role of maternal smoking during pregnancy in the etiology of attention deficit hyperactivity disorder (ADHD). METHOD: Subjects were 6-17-year-old boys with DSM-III-R ADHD (N = 140) and normal comparison subjects (N = 120) and their first-degree biological relatives. Information on maternal smoking was obtained from mothers in a standardized manner by raters who were blind to the proband's clinical status. RESULTS: Twenty-two percent of the ADHD children had a maternal history of smoking during pregnancy, compared with 8% of the normal subjects. This positive association remained significant after adjustment for socioeconomic status, parental IQ, and parental ADHD status. Significant differences in IQ were found between those children whose mothers smoked during pregnancy and those whose mothers did not smoke (mean IQ = 104.9, SD = 12.3, and mean = 115.4, SD = 12.2, respectively). CONCLUSIONS: These findings suggest that maternal smoking during pregnancy is a risk factor for ADHD. If confirmed, these findings will stress the importance of programs aimed at smoking prevention in nonsmoking women and smoking cessation in smoking women of childbearing age.
Bronchoalveolar lavage (BAL) has been shown to be a rapid, relatively safe, and relatively noninvasive diagnostic procedure. Theoretically, BAL can be performed on all children hospitalized for pneumonia resistant to oral antibiotics, though practically and economically, this is not feasible. A 1-year retrospective review was conducted to define a cost-effective role for BAL in the management of hospitalized children with resistant pneumonia. The data revealed identification of at least one pathogen in 87% of sputum samples and in 95% of BAL specimens. Sputum samples provided the same information as the more invasive BAL technique in 60% of patients who had both sputum and BAL obtained for culture. Recommendations are made for the use of BAL as a diagnostic tool in the hospitalized child with resistant pneumonia.
Overexpression of elongation factor-1 alpha (EF1 alpha) mRNA has been correlated with increased metastatic potential in mammary adenocarcinoma; however, this relationship was not explored at the level of protein expression. As EF1 alpha has been shown in other cell types to be a component of the actin cytoskeleton, a likely effector in metastasis, the actin binding activity of EF1 alpha from metastatic and nonmetastatic rat breast tumors and cell lines was investigated. We have shown that EF1 alpha protein is overexpressed in metastatic compared to nonmetastatic cells and whole tumors. Similarly to other EF1 alpha s, both types of tumor EF1 alpha bind to F-actin, but EF1 alpha from metastatic cells has a reduced affinity for actin. In addition, there is a high correlation between the intracellular distribution of filamentous actin and EF1 alpha in those cytoskeletal structures thought to be important for supporting the cellular motility required for metastasis. Following stimulation with EGF, there is a parallel increase in the amount of F-actin and EF1 alpha associated with the cytoskeleton. The response to EGF can be blocked with cytochalasin D indicating that the binding of EF1 alpha to the cytoskeleton is mediated by F-actin. We propose that a weakened association of EF1 alpha with actin may be related to the metastatic process via an altered organization of the actin cytoskeleton and the differential translation of mRNAs associated with the cytoskeleton.
Surveys have been, and will most likely continue to be, the source of data for many empirical articles. Likewise, the difficulty of making valid statistical inferences in the face of missing data will continue to plague researchers. In an ideal situation, all potential survey participants would respond; in reality, the goal of an 80 to 90% response rate is very difficult to achieve. When nonresponse is systematic, the combination of low response rate and systematic differences can severely bias inferences that are made by the researcher to the population. It is important for the researcher to assess the potential causes of nonresponse and the differences between the observed values in the sample compared to what may have been gained if the sample was complete, particularly when the response rate is low. There are methods available that substitute imputed values for missing data, but these methods are useless if the researcher lacks knowledge of how the responders and nonresponders may differ. With regard to statistical inference, the researcher also should be aware of the difference between a convenient sample and a probability sample. Valid statistical inference assumes that the probability of characteristics observed in the sample bear some relationship to their occurrence in the population. For example, in a simple random sample each member of the accessible population has an equal chance of inclusion in the sample. A convenient sample lacks the statistical properties of a probability sample that allow the validity of its inferences to be assessed strictly from a mathematical framework. The context of the research and the type of data being gathered greatly affect the validity of any generalizations the researcher makes with regard to the population the convenient sample attempts to represent.
Loss of expression of specific integrins is a feature of poorly differentiated oral squamous cell carcinomas (SCCs) and cell lines derived from them. In order to test whether there is a direct link between reduced alpha 6 beta 4 integrin expression and abnormal keratinocyte growth and differentiation we 'repaired' an SCC line. H376, by transfection of the beta 4 integrin subunit. We analysed five independent beta 4 transfectant clones and compared them with four empty vector control clones and with the parental cell line. Elevated cell surface expression of alpha 6 beta 4 was not correlated with changes in anchorage dependent or independent growth and was not sufficient to induce expression of the terminal differentiation marker, involucrin. Introduction of the beta 4 integrin subunit did not have a major effect on cell adhesion to laminin 1 or 5 and did not result in formation of stable anchoring contacts. We conclude that loss of alpha 6 beta 4 is not directly responsible for the abnormal behaviour of the H376 cell line.
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Sophisticated tools can be applied to patient data accurately reflecting patient severity of illness for individuals diagnosed with an acute myocardial infarction or undergoing coronary artery bypass graft surgery. These tools have been utilized in northern New England, New York, and Pennsylvania to assess the impact of care on outcomes for patients undergoing coronary revascularization for atherosclerotic heart disease. Results confirm there is wide variation in outcome associated with surgical volume and hospital processes. Traditionally, efforts to assess the clinical performance of individual physicians have been met by the profession with resistance. The Pennsylvania Health Care Cost Containment Council has recently undertaken an extensive analysis of patient outcomes for patients admitted to hospital with acute myocardial infarction in 1993. The process by which the Council developed consensus between business, labor, and the medical community to bring about this effort was noteworthy in its collaborative underpinnings and can serve as a model for public efforts to scrutinize health care outcomes.
Cryptophycin-8 was prepared by the conversion of the epoxide group on cryptophycin-1 to a chlorohydrin. In the studies reported here, cryptophycin-8 was evaluated for preclinical activity against subcutaneous tumors of both mouse and human origin. At the highest non-toxic single course treatment, the following results were obtained (Table A). Cryptophycin-8 was less potent than cryptophycin-1 by approximately 4-fold; however, it was both more water soluble and had greater therapeutic efficacy, as demonstrated by % T/C, tumor cell log kill values, range of dose effectiveness and host cures.
The purpose of this study was to quantitate the expression of human MDR1 mRNA levels in normal endometrium and in endometrial carcinoma and to determine the association of MDR1 levels with prognostic indicators. Endometrial samples from 43 postmenopausal patients with endometrial carcinoma and 38 patients (controls) with benign disease undergoing hysterectomy were snap-frozen. MDR1 levels were determined by quantitative reverse transcription-PCR (RT-PCR) and compared to sensitive and resistant cell lines. Immunohistochemistry was done with MM4.17, an anti-MDR1 antibody, on paraffin sections, and the results were compared to those obtained from RT-PCR. Data was analyzed using the Kruskal-Wallis and Bonferroni tests, setting the P value at 0.05. In both postmenopausal endometrial tissue and tumors, MDR1 expression was localized to the epithelial cell layer. Comparison of immunohistochemistry and RT-PCR results demonstrated a correlation of 80%. In control patients, MDR1 expression was significantly higher in postmenopausal endometrium (n = 15) than in the proliferative premenopausal endometrium (n = 15; P = 0.0024). MDR1 expression in all tumors was lower than that measured in the postmenopausal controls. Between each tumor group, there was no significant difference in the MDR1 levels observed. MDR1 expression was significantly lower in patients with high nuclear grade (n = 18) tumors when compared to patients with low nuclear grade (n = 14; P = 0.04) tumors. Comparison of MDR1 levels with multiple prognostic indicators for endometrial cancer was only significant for nuclear grade. The data indicate that MDR1 expression is not a major component of the drug resistance observed in primary endometrial tumors.
The complement membrane attack complex (MAC), the cytolytic granule protein of cytotoxic lymphocytes perforin, the streptococcal exotoxin streptolysin O (SLO), and the bee venom polypeptide melittin utilize a similar mechanism to incorporate into cell membranes, induce a Ca2+ influx and a rise in intracellular Ca2+ concentration, and produce cell lysis. At sublytic concentrations, these proteins trigger several cellular activities, including protein phosphorylation and synthesis. We have recently demonstrated that human leukemic cells treated with sublytic doses of human complement become more resistant to lytic complement doses. The study has now been extended to include three other pore-formers: murine perforin, SLO and melittin. As shown here, sublytic MAC induces in the K562 human erythroleukemic cells protection from lytic perforin, and vice versa, sublytic perforin induces protection from complement. Also, sublytic SLO and melittin increase resistance of K562 cells to lytic complement and perforin doses. The capacity of Ca2+ ionophores to induce resistance to the lytic proteins has been examined. Exposure of K562 cells to sublytic concentrations of ionomycin or A23187 for 1 h at 37 degrees C confers on them resistance to complement- and perforin-mediated lysis. The protective effects of the ionophores can be abrogated by chelation of extracellular Ca2+ and by inhibition of RNA or protein synthesis in the cells. These results indicate the following: 1) nucleated cells exposed to sublytic complement MAC, perforin, SLO, or melittin may become resistant to the four pore-formers. Physiologically, this may be regarded as an immunologic tachyphylaxis. 2) Ca2+ influx induced by these pore-formers is an essential and sufficient factor to produce this tachyphylaxis.
Health providers face the problem of trying to make decisions in situations where there is insufficient information and also where there is an overload of (often contradictory) information. Statistical methods such as meta-analysis have been developed to summarise and to resolve inconsistencies in study findings--where information is available in an appropriate form. Consensus methods provide another means of synthesising information, but are liable to use a wider range of information than is common in statistical methods, and where published information is inadequate or non-existent these methods provide a means of harnessing the insights of appropriate experts to enable decisions to be made. Two consensus methods commonly adopted in medical, nursing, and health services research--the Delphi process and the nominal group technique (also known as the expert panel)--are described, together with the most appropriate situations for using them; an outline of the process involved in undertaking a study using each method is supplemented by illustrations of the authors' work. Key methodological issues in using the methods are discussed, along with the distinct contribution of consensus methods as aids to decision making, both in clinical practice and in health service development.