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Biomedical subjects

C Walters

Publications and source records attributed to C Walters.

At least 19 recordsLinked to original sources
PubMed2005

High risk health behaviours among adult Jamaicans.

The purpose of this study was to assess the prevalence of high risk health behaviours among adult Jamaicans aged 15-49 years in 2000, and to compare the results with the 1993 survey. A nationally representative sample of 2013 persons aged 15-74 years was surveyed in 2000 using cluster sampling in the Jamaica Healthy Lifestyle Survey (Wilks et al, unpublished). Interviewer administered questionnaires and anthropometrical measurements were done. Data for a sub-sample of adults aged 15-49 years were analyzed The sub-sample included 1401 persons (473 men and 928 women). Significantly more men (18.6%) than women (4.3%) reported never having had a blood pressure check (p = 0.0001). Approximately one-third of the women reported that they had never had a Pap smear (36.0%) or a breast examination (31.2%). Current cigarette smoking was reported in 28.6% of men and 7.7% of women (OR 3.73 CI 2.71, 5.15), while 49.0% of men and 15.0% of women ever smoked marijuana (OR 3.28 CI 2.56, 4.20). Significantly more men (28.0%) than women (11.7%) reported ever having a sexually transmitted disease (OR 2.93 CI 2.16, 3.97); having more than one sexual partner in the past year (49.1% vs 11.4%, OR 4.31 CI 3.22, 5.76) and usually using a condom during sexual intercourse (55.3% vs 40.5%, OR 1.3 CI 1.11, 1.68). Between 1993 and 2000, significant trends include: more persons reported having a blood pressure check, a reduction in multiple sexual partners, increased condom use at last sex (women), reduced crack/cocaine use (males) and increased marijuana smoking. Although there were some significant positive lifestyle trends between 1993 and 2000, high risk behaviours remain common among Jamaican adults. Comprehensive health promotion programmes are needed to address these risk behaviours.

Adolescent↗
PubMed2001

Crystallohydrodynamics for solving the hydration problem for multi-domain proteins: open physiological conformations for human IgG.

Hydrodynamic methods provide a route for studying the low-resolution conformation--in terms of time-averaged spatial orientation of the Fab' and Fc domains relative to each other--of the human IgG subclasses, IgG1, IgG2, IgG3 and IgG4 in the environment in which many exist naturally---a solution. Representative modelling strategies are now available using 'shell-bead' or 'shell' modelling of the surface of the molecules with the size-independent programme SOLPRO [J. Garcia de la Torre, S.E. Harding, B. Carrasco, Eur. Biophys. J. 28 (1999) 119-132]. The shell model fits to the equivalent inertial surface ellipsoids of the published crystal structures for the Fab' and Fc domains of IgG are made and an apparent hydration delta(app) of 0.51g/g for Fab' and 0.70 g/g for the glycoprotein Fc are obtained, which yield an average value of (0.59+/-0.07) g/g for the intact antibody (2 Fab'+1 Fc). The relative orientations of these domains for each of the IgG subclasses is then found (using where appropriate a cylindrical hinge) from SOLPRO by modelling the Perrin function, P (i.e. 'frictional ratio due to shape') using this delta(app) and experimentally measured sedimentation coefficients. All the IgG subclasses appear as open, rather than compact structures with the degree of openness IgG3>IgG1>(IgG2, IgG4), with IgG3 and IgG1 non-coplanar. The hingeless mutant IgGMcg, with s degrees (20,w) approximately 6.8 S yields a coplanar structure rather similar to IgG2 and IgG4 and consistent with its crystallographic structure. The extension of this procedure for representing solution conformations of other antibody classes and other multi-domain proteins is indicated.

Crystallography, X-Ray↗
PubMed2001

Quantitative real-time RT-PCR detection of breast cancer micrometastasis using a multigene marker panel.

Real-time RT-PCR is a relatively new technology that uses an online fluorescence detection system to determine gene expression levels. It has the potential to significantly improve detection of breast cancer metastasis by virtue of its exquisite sensitivity, high throughput capacity and quantitative readout system. To assess the utility of this technology in breast cancer staging, we determined the relative expression levels of 12 cancer-associated genes (mam, PIP, mamB, CEA, CK19, VEGF, erbB2, muc1, c-myc, p97, vim and Ki67) in 51 negative-control normal lymph nodes and in 17 histopathology-positive ALNs. We then performed a receiver operating characteristic (ROC) curve analysis to determine the sensitivity and specificity levels of each gene. Areas under the ROC curve indicated that the most accurate diagnostic markers were mam (99.6%), PIP (93.3%), CK19 (91.0%), mamB (87.9%), muc1 (81.5%) and CEA (79.4.0%). mam was overexpressed in 16 of 17 lymph nodes known to contain metastatic breast cancer at levels ranging from 22- to 2.8 x 10(5)-fold above normal mean expression, whereas PIP was overexpressed from 30- to 2.2 x 10(6)-fold above normal in 13 lymph nodes. Real-time RT-PCR analysis of pathology-negative LN from breast cancer patients revealed evidence of overexpression of PIP (6 nodes), mam (3 nodes) and CEA (1 node) in 8 of 21 nodes (38%). Our results provide evidence that mam, PIP, CK19, mamB, muc1 and CEA can be applied as a panel for detection of metastatic and occult micrometastatic disease.

Base Sequence↗
PubMed2001

Interactions among water content, rapid (nonequilibrium) cooling to -196 degrees C, and survival of embryonic axes of Aesculus hippocastanum L. seeds.

This study investigated the interactions among water content, rapid (nonequilibrium) cooling to -196 degrees C using isopentane or subcooled nitrogen, and survival of embryonic axes of Aesculus hippocastanum. Average cooling rates in either cryogen did not exceed 60 degrees C s(-1) for axes containing more than 1.0 g H(2)O g(-1)dw (g g(-1)). Partial dehydration below 0.5 g gg(-1) facilitated faster cooling, averaging about 200 and 580 degrees C s(-1) in subcooled nitrogen and isopentane, respectively. The combination of partial drying and rapid cooling led to increased survival and reduced cellular damage in axes. Electrolyte leakage was 10-fold higher from fully hydrated axes cooled in either cryogen than from control axes that were not cooled. Drying of axes to 0.5 g g(-1), reduced electrolyte leakage of cryopreserved axes to levels similar to those of control material. Axis survival was assayed by germination in vitro. Axes with water contents greater than 1.0 g g(-1), did not survive cryogenic cooling. Between 1.0 and 0.75 g g(-1), axes survived cryogenic exposure but developed abnormally. The proportion of axes developing normally after being cooled in isopentane increased with increasing dehydration below 0.75 g g(-1), reaching a maximum between 0.5 and 0.25 g g(-1) after being cooled at > or =300 degrees C s(-1). Cooling rates attained in subcooled nitrogen did not exceed 250 degrees C s(-1), and normal development of axes was observed only at < or =0.4 g g(-1). These results support the hypothesis that rapid cooling enhances the feasibility of cryopreservation of desiccation-sensitive embryonic axes by increasing the upper limit of allowable water contents and overall survival.

Cryopreservation↗
PubMed2001

A comparison of sonographic cervical parameters in predicting spontaneous preterm birth in high-risk singleton gestations.

OBJECTIVES: To assess the role of cervical sonography and to compare various sonographic cervical parameters in their ability to predict spontaneous preterm birth in high-risk singleton gestations. DESIGN: A prospective cohort of 469 high-risk gestations were longitudinally evaluated between 15 and 24 weeks' gestation on 1265 occasions with transvaginal cervical sonography and transfundal pressure. The cervical parameters obtained were funnel width and length, cervical length, percent funneling and cervical index. The information obtained was used for patient management. Restriction of physical activities was initiated at cervical lengths of < or = 2.5 cm with cerclage as an option for cervical lengths of < or = 2.0 cm. RESULTS: Receiver operating characteristic curve analyses showed that a cervical length of < or = 2.5 cm between 15 and 24 weeks' gestation was equal to the other sonographic cervical parameters in its ability to predict spontaneous preterm birth. The sensitivities for delivery at < 28, < 30, < 32 and < 34 weeks' gestation were 94%, 91%, 83% and 76%, respectively, while the negative predictive values were 99%, 99%, 98% and 96%, respectively. The placement of a cerclage did not influence the positive and negative predictive values. In comparison to women with other risk factors, cervical length was best in the prediction of preterm birth in women with a prior mid-trimester loss; an optimal cut-off of < or = 1.5 cm had sensitivities for delivery at < 28, < 30, < 32 and < 34 weeks' gestation of 100%, 100% 92% and 81%, respectively. The rate of preterm delivery at < 34 weeks' gestation increased dramatically when the cervical length was < or = 1.5 cm. Cervical length was the only independent variable that entered the logistic regression model for the prediction of preterm delivery at < 34 weeks' gestation. CONCLUSIONS: In high-risk singleton gestations a cervical length of < or = 2.5 cm was equal to other sonographic cervical parameters in its ability to predict spontaneous preterm birth and was better for the prediction of earlier forms of prematurity (at < 28 and < 30 weeks) than later forms (at < 32 and < 34 weeks). The optimal cervical lengths and their performance for predicting prematurity may be influenced by obstetric risk factors.

Adult↗
PubMed2000

Trp203 mutation in GroEL promotes a self-association reaction: a hydrodynamic study.

A combination of sedimentation equilibrium and sedimentation velocity in the analytical ultracentrifuge is used to investigate the hydrodynamic integrity and increased self-association interactions of the mutant GroEL Y203W when compared to the wild-type GroEL molecule, which may be derived from increased hydrophobic exposure caused by the mutation. Sedimentation velocity has revealed that three distinct species were present throughout the concentration ranges used, corresponding to 14-mer (GroEL "super monomer") and 28-mer ("super dimer") subunit compositions with a small amount of 42-mer ("super trimer"), which, from the relative concentration of each species, would give an estimated weight average molecular weight of (1.0 +/- 0.1) x 10(6) Da. Sedimentation equilibrium gave an apparent weight average molecular weight (Mw,app) of (910,000 +/- 5000) Da, which is in agreement with these findings. These results are in contrast to wild-type GroEL which, in excellent agreement with the previous findings of Behlke and co-workers, revealed a single species with an Mw,app of (805,000 +/- 5200) Da and a sedimentation coefficient s(0)20,w of (21.6 +/- 0.3) S. We therefore conclude that the tryptophan mutation at the Y203 location causes a significant degree of self-association of the GroEL 14-mer assembly (with dimer and trimer present). These findings would appear to correlate well with the findings of Gibbons et al., who showed an increase in hydrophobic exposure due to this mutation.

Amino Acid Substitution↗
PubMed2000

Use of cervical ultrasonography in prediction of spontaneous preterm birth in triplet gestations.

OBJECTIVE: The aim of this study was to assess the role of cervical ultrasonography in the prediction of spontaneous preterm birth in triplet gestations and to compare various ultrasonographic cervical parameters with respect to predictive ability. STUDY DESIGN: This prospective cohort study included 51 triplet gestations longitudinally evaluated between 15 and 28 weeks' gestation on 274 occasions with transvaginal cervical ultrasonography and transfundal pressure. The cervical parameters obtained were funnel width and length, cervical length, percentage of funneling, and cervical index. RESULTS: Receiver operating characteristic curve analyses showed that cervical lengths of < or =2.5 cm and < or =2.0 cm between 15 and 24 weeks' gestation and between 25 and 28 weeks' gestation, respectively, were at least as good as other ultrasonographic cervical parameters for the prediction of spontaneous preterm birth. A cervical length of < or =2.5 cm between 15 and 20 weeks' gestation had both a specificity and a positive predictive value of 100% for delivery at <28 weeks' gestation, and the sensitivities and negative predictive values ranged from 25% to 50% and from 72% to 91%, respectively, for deliveries at <28, <30, and <32 weeks' gestation. A cervical length of < or =2.5 cm between 21 and 24 weeks' gestation had an 86% sensitivity for prediction of spontaneous delivery at <28 weeks' gestation. A cervical length of < or =2.0 cm between 25 and 28 weeks' gestation had both a sensitivity and a negative predictive value of 100% for delivery at both <28 and <30 weeks' gestation. CONCLUSIONS: In triplet gestations cervical lengths of < or =2.5 cm between 15 and 24 weeks' gestation and < or =2.0 cm between 25 and 28 weeks' gestation were at least as good as other ultrasonographic cervical parameters for the prediction of spontaneous preterm birth.

Cervix Uteri↗
PubMed2000

Use of cervical ultrasonography in prediction of spontaneous preterm birth in twin gestations.

OBJECTIVE: This study was undertaken to compare various ultrasonographic cervical parameters with respect to ability to predict spontaneous preterm birth in twin gestations. STUDY DESIGN: This prospective study involved 131 women carrying twins who were longitudinally evaluated on 524 occasions between 15 and 28 weeks' gestation with transvaginal cervical ultrasonography and transfundal pressure. The following cervical parameters were obtained: funnel width and length, cervical length, percentage of funneling, and cervical index. Receiver operating characteristic curve analysis was used to determine the ultrasonographic cervical parameter evaluated at 15 to 20 weeks' gestation, 21 to 24 weeks' gestation, and 25 to 28 weeks' gestation that were best for prediction of spontaneous preterm birth at <28 weeks' gestation, <30 weeks' gestation, <32 weeks' gestation, and <34 weeks' gestation. RESULTS: The median gestational age at delivery was 36 weeks' gestation (range, 21-41 weeks' gestation). Receiver operating characteristic curve analysis indicted that a cervical length of < or =2.0 cm, regardless of gestational age category at cervical measurement, was at least as good as other ultrasonographic cervical parameters at predicting spontaneous preterm birth. Between 15 and 20 weeks' gestation a cervical length cutoff value of < or =2.0 cm had specificities of 97%, 98%, 99%, and 100% and negative predictive values of 99%, 98%, 95%, and 89% for delivery at <28, <30, <32, and <34 weeks' gestation, respectively. The positive predictive values for delivery at <32 and <34 weeks' gestation were 80% and 100%, respectively. Between 21 and 24 weeks' gestation a cervical length of < or =2.0 cm had specificities of 84%, 84%, 85%, and 86% and negative predictive values of 99%, 99%, 94%, and 87% for delivery at <28, <30, <32, and <34 weeks' gestation, respectively. Between 25 and 28 weeks' gestation cervical length had excellent negative predictive values of 99%, 98%, 95%, and 93% for delivery at <28, <30, <32, and <34 weeks' gestation, respectively. CONCLUSIONS: In twin gestations a cervical length of < or =2.0 cm measured between 15 and 28 weeks' gestation was at least as good as other ultrasonographic cervical parameters at predicting spontaneous preterm birth. The high specificities indicate that cervical length was better at predicting the absence than the presence of various degrees of spontaneous prematurity.

Cervix Uteri↗
PubMed1999

Pharmacy-based evaluation and treatment of minor illnesses in a culturally diverse pediatric clinic.

BACKGROUND: Among medically underserved immigrant parents, access to nonprescription medicines for home treatment of minor childhood illnesses may be limited by scarce financial resources or language barriers. OBJECTIVES: To design and implement a new clinical service for an urban ambulatory pediatric clinic with a large immigrant population that allows pharmacists to evaluate and to treat children and adolescents aged 6 months to 19 years with minor acute illnesses and to provide bilingual patient education materials. METHODS: We developed protocols and encounter forms for pharmacist evaluation of 5 pediatric conditions: cough/cold, fever, diaper rash, vomiting/diarrhea, and head lice. We published bilingual patient education materials for these conditions in 8 commonly spoken languages. We assessed safety by thoroughly reviewing the medical records of all patients who returned within 1 week of a pharmacy encounter and by asking parents in a telephone survey to compare services received through the pharmacy and the acute care clinic for treatment of the common cold. RESULTS: During the first year of this pilot program, 191 patients were evaluated and treated, 145 (76%) for cough/cold. Seventy percent of the patients were immigrants. No unexpected or adverse outcomes were detected, although occasional deviations from established protocols were noted. Parent satisfaction with the pharmacy service was high, and similar to that received through the standard acute care clinic. Patients evaluated by pharmacists were more likely to be attended to promptly (< 15-minute wait) and were more likely to receive written information than patients evaluated by physicians for similar conditions. CONCLUSIONS: Pharmacist evaluation and treatment of minor pediatric illnesses seems to be both safe and well accepted. Further studies are needed to evaluate the cost-effectiveness of this service in diverse settings. In states that allow pharmacists to have prescriptive authority, pharmacy-based evaluation and treatment may improve access to care for children with minor illnesses.

Adolescent↗
PubMed1999

Novel size-independent modeling of the dilute solution conformation of the immunoglobulin IgG Fab' domain using SOLPRO and ELLIPS.

The proliferation of hydrodynamic modeling strategies to represent the shape of quasirigid macromolecules in solution has been hampered by ambiguities caused by size. Universal shape parameters, independent of size, developed originally for ellipsoid modeling, are now available for modeling using the bead-shell approximation via the algorithm SOLPRO. This paper validates such a "size-independent" bead-shell approach by comparison with the exact hydrodynamics of 1) an ellipsoid of revolution and 2) a general triaxial ellipsoid (semiaxial ratios a/b, b/c) based on a fit using the routine ELLIPSE (. J. Mol. Graph. 1:30-38) to the chimeric (human/mouse) IgG Fab' B72.3; a similar fit is obtained for other Fabs. Size-independent application of the bead-shell approximation yields errors of only approximately 1% in frictional ratio based shape functions and approximately 3% in the radius of gyration. With the viscosity increment, errors have been reduced to approximately 3%, representing a significant improvement on earlier procedures. Combination of the Perrin frictional ratio function with the experimentally measured sedimentation coefficient for the same Fab' from B72.3 yields an estimate for the molecular hydration of the Fab' fragment of approximately (0.43 +/- 0.07) g/g. This value is compared to values obtained in a similar way for deoxyhemoglobin (0.44) and ribonuclease (0.27). The application of SOLPRO to the shape analysis of more complex macromolecules is indicated, and we encourage such size-independent strategies. The utility of modern sedimentation data analysis software such as SVEDBERG, DCDT, LAMM, and MSTAR is also clearly demonstrated.

Algorithms↗
PubMed1998

Longitudinal assessment of endocervical canal length between 15 and 24 weeks' gestation in women at risk for pregnancy loss or preterm birth.

OBJECTIVE: To determine the weekly cervical shortening rates of the endocervical canal between 15 and 24 weeks' gestation in women at risk for pregnancy loss or spontaneous preterm birth. METHODS: We performed a retrospective cohort study of transvaginal sonographic measurements of the endocervical canal length done at least twice between 15 and 24 weeks' gestation in women at risk for pregnancy loss and spontaneous preterm birth. The ultrasound diagnosis of cervical incompetence was defined as progressive shortening of the endocervical canal length to 2 cm or less either spontaneously or after application of transfundal pressure. Multivariable linear regression models were developed to determine the weekly crude rate of endocervical canal length shortening rates in cases of competent cervices and incompetent cervices, with incompetent cervices further stratified as those diagnosed at 15-19 weeks' and 20-24 weeks' gestation. Comparisons of the models for weekly rate of endocervical canal length shortening were performed. RESULTS: The endocervical canal lengths were measured in 61 women (180 measurements) who did not develop ultrasound evidence of cervical incompetence and 28 women (103 measurements) who had ultrasound evidence of cervical incompetence. Between 15 and 24 weeks' gestation, competent cervices had a nonsignificant rate of endocervical canal length shortening (-0.03 cm/week). During this period in gestation, incompetent cervices had significantly greater endocervical canal length shortening (-0.41 cm/week, P < .001). The rate of endocervical canal length shortening of incompetent cervices diagnosed between 15 and 19 weeks' gestation was -0.52 cm/week (P < .001). The rate of endocervical canal length shortening in incompetent cervices diagnosed between 20 and 24 weeks' gestation was significant and varied from -0.49 cm/week to -0.80 cm/week at 20 and 24 weeks' gestation, respectively (P < .001). The models describing the rate of cervical shortening in the two groups of incompetent cervices were significantly different (P < .001). The sonographic detection of endocervical canal length shortening in the 28 cases of cervical incompetence was identified at a median (range) gestational age of 20 (16-24) weeks. CONCLUSION: Weekly rates of endocervical canal length shortening were established, which may be useful for detecting and managing cervical incompetence in high-risk women examined with cervical sonography.

Abortion, Spontaneous↗
PubMed1998

Release of the angiogenic cytokine vascular endothelial growth factor (VEGF) from platelets: significance for VEGF measurements and cancer biology.

Vascular endothelial growth factor (VEGF) is a potent angiogenic factor with a key role in several pathological processes, including tumour vascularization. Our preliminary observations indicated higher VEGF concentrations in serum samples than in matched plasma samples. We have now demonstrated that this difference is due to the presence of VEGF within platelets and its release upon their activation during coagulation. In eight healthy volunteers, serum VEGF concentrations ranged from 76 to 854 pg ml(-1) and were significantly higher (P < 0.01) than the matched citrated plasma VEGF concentrations, which ranged from < 9 to 42 pg ml(-1). Using platelet-rich plasma, mean (s.d.) platelet VEGF contents of 0.56 (0.36) pg of VEGF 10(-6) platelets were found. Immunocytochemistry demonstrated the cytoplasmic presence of VEGF within megakaryocytes and other cell types within the bone marrow. From examination of the effects of blood sample processing on circulating VEGF concentrations, it is apparent that for accurate measurements, citrated plasma processed within 1 h of venepuncture should be used. Serum is completely unsuitable. The presence of VEGF within platelets has implications for processes involving platelet and endothelial cell interactions. e.g. wound healing, and in tumour metastasis, when platelets adhering to circulating tumour cells may release VEGF at points of adhesion to endothelium, leading to hyperpermeability and extravasation of cells.

Adult↗
PubMed1998

Pregnancy outcomes in women treated with elective versus ultrasound-indicated cervical cerclage.

OBJECTIVE: To compare pregnancy outcomes in women at risk for pregnancy loss treated with elective versus ultrasound-indicated placement of cerclage. METHODS: A retrospective cohort study was performed on two groups of patients with singleton gestations. The first group consisted of women at risk for pregnancy loss who were treated with an elective cerclage, while the second group was managed conservatively and followed with serial transvaginal cervical sonography and transfundal pressure. An emergency cerclage was placed in women in the second group when the endocervical canal length shortened to < 20 mm, either spontaneously or in response to transfundal pressure. The two groups were compared with respect to maternal demographics, obstetric and gynecological history, and gestational age, both at time of cerclage placement and delivery. RESULTS: A total of 138 patients were identified. Eighty-one patients were treated with an elective cerclage and 57 with an ultrasound-indicated cerclage. Patients treated with elective cerclages were older (32 versus 27 years, p = 0.0003), more commonly white (56.8% versus 38.6%, p = 0.0380), less commonly nulliparous (23.5% versus 43.9%, p = 0.0063), and more often private patients (92.6% versus 28.1%, p < 0.0001). A history of previous treatment with cerclage (45.7% versus 10.5%, odds ratio (OR) 0.2, 95% confidence interval (CI) 0.1-0.4) and one prior midtrimester loss (53.1% versus 33.3%, OR 0.4, 95% CI 0.2-0.9) were also more common in the elective versus ultrasound-indicated cerclage group. However, there was no difference in the rates of previous preterm delivery, two midtrimester losses, two terminations of pregnancy, in utero diethylstilbestrol exposure, uterine anomalies, history of cone biopsy or parity. As expected, gestational age at placement of cerclage was significantly earlier in the elective group (13.0 versus 20.0 weeks, p < 0.0001). The median (range) gestational age at delivery (37 (15-41) versus 37 (17-41) weeks, p = 0.90), the number of early (< 25 weeks) losses (9.9% versus 8.8%, OR 1.6, 95% CI 0.3-7.9), and preterm deliveries (< 37 weeks) (35.8% versus 36.8%, OR 1.1, 95% CI 0.4-3.2) were similar in the elective and ultrasound-indicated cerclage patients, respectively. CONCLUSION: In patients at risk for pregnancy loss, placement of cervical cerclages in response to ultrasonographically detected shortening of the endocervical canal length is a medically acceptable alternative to the use of elective cerclage.

Adult↗
PubMed1997

Pharmacokinetics of dexamethasone and its relationship to dexamethasone suppression test outcome in depressed patients and healthy control subjects.

The pharmacokinetics of dexamethasone (DEX) were studied in 9 drug-free melancholically depressed patients and 10 healthy control subjects matched by sex and age. Each subject received 1 mg of DEX administered orally and by the (i.v.) route at 11:00 PM and serial blood samples were collected over the next 17 hours until 4:00 PM. There were no significant differences between the diagnostic groups and DEX bioavailability, peak plasma level, time to maximum concentration, or in elimination half-life after oral administration. Bioavailability estimates indicated that DEX absorption was incomplete and variable mean = 61%, SD = 14) in controls as well as depressed patients. In both groups there was a wide interindividual variability in plasma DEX levels following both oral and i.v. routes of administration. This variability could not be reliably predicted by differences in age, sex, or weight between subjects. The factors that accounted for most the variability in 4:00 PM plasma DEX levels after oral administration were clearance, bioavailability, and time to reach maximum concentration. Plasma DEX levels were lower in 3 depressed nonsuppressors compared to 3 matched controls who suppressed. No single pharmacokinetic factor was shown to be responsible for the lower DEX levels in the depressed nonsuppressors. These results indicate that plasma DEX levels need to be measured in each individual during the DST procedure so that this information may be taken into consideration when interpreting DST results.

Administration, Oral↗
PubMed1997

Mast cell activation in arthritis: detection of alpha- and beta-tryptase, histamine and eosinophil cationic protein in synovial fluid.

1. Although mast cell hyperplasia is a feature of rheumatoid arthritis and osteoarthritis, the extent and nature of mast cell activation in joint disease have not been clearly established. 2. We have investigated the levels of mast cell tryptase and histamine and also of eosinophil cationic protein in synovial fluid collected from 31 patients with rheumatoid arthritis, 14 with seronegative spondyloarthritis and nine with osteoarthritis. Two RIAs for tryptase were employed: one with monoclonal antibody AA5, which was found to bind equally well to both alpha and beta isoforms on Western blots of the recombinant enzyme, and the other with antibody G5, which recognizes predominantly beta-tryptase. 3. alpha-Tryptase, which is likely to be released constitutively from mast cells, appeared to be the major form in synovial fluid, as the assay with antibody AA5 detected appreciably more tryptase than that with antibody G5. beta-Tryptase, which is released on anaphylactic activation of mast cells, was detected in 14 out of 45 synovial fluid samples studied, with concentrations of up to 12 micrograms/l measured by the G5 assay. The apparent levels of beta-tryptase, but not of alpha-tryptase, were closely correlated with those of histamine in the synovial fluid. Patients with osteoarthritis appeared to have a greater proportion of beta-tryptase in the synovial fluid than those with rheumatoid arthritis, as well as higher concentrations of histamine. Eosinophil cationic protein was present at high levels in the synovial fluid, although eosinophil numbers were low, and its concentrations were not correlated with the concentrations of the mast cell products. 4. These data suggest that anaphylactic degranulation of mast cells may have occurred to a greater extent in osteoarthritis than in rheumatoid arthritis, despite the relative lack of synovial inflammation in osteoarthritis. Although the eosinophil cationic protein detected may not reflect eosinophilic inflammation in the joint, the presence in synovial fluid of tryptase of both major forms, and of histamine, appears to indicate that mast cell products are secreted constitutively, as well as by processes of anaphylactic degranulation in rheumatoid arthritis, seronegative spondyloarthritis and osteoarthritis.

Adult↗
PubMed1997

Detection of parvovirus B19 in macerated fetal tissue using in situ hybridisation.

AIMS: To compare the application of a non-radioactive in situ hybridisation (ISH) technique with an immunocytochemical technique for the detection of human parvovirus B19 in formalin fixed, paraffin wax embedded sections of macerated fetal tissue. METHODS: Archived samples of liver, lung or kidney from 19 human fetuses were investigated for parvovirus B19 using a full length digoxigenin labelled DNA probe of 5.5 kb; bound probe was detected using an anti-digoxigenin (alkaline phosphatase) conjugate and visualised using NBT/BCIP. Immunocytochemical detection of parvovirus B19 was performed using a monoclonal mouse antiparvovirus B19 antiserum, with a streptavidin-biotin complex (horse radish peroxidase) method. Cases were selected to provide a range of diagnostic certainty and a range of degrees of macerative degeneration. RESULTS: Parvovirus B19 was found in 15 of 19 cases using the B19 ISH technique compared with 8 of 19 cases using the immunocytochemical technique. The four negative cases were all controls known to be parvovirus B19 free. All ISH positive cases showed excellent staining with low background regardless of extent of maceration and tissue type. In comparison, sections stained by the immunocytochemical method showed considerable non-specific immunoreactivity in many cases, particularly with severe maceration. Kidney and lung tissues gave the cleanest results. CONCLUSIONS: ISH is more effective than the immunocytochemical technique for the detection of human parvovirus B19 in macerated fetal tissue. The lack of detectable background staining with the ISH technique led to easier interpretation suggesting that this technique should be the method of choice for the investigation of parvovirus B19 in macerated postmortem tissues.

Female↗