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Characterization of viro-immunological responses in a closely followed cohort of heavily pretreated patients: evidence from the GenPheRex Study.

OBJECTIVES: To assess prevalence and predictive factors of viro-immunological discordant trends in a cohort of heavily pretreated patients. METHODS: Factors associated with viro-immunological discordant trends either as categorical or continuous measures have been studied in 159 heavily pretreated HIV-positive patients from a multicentre prospective study of real- vs. virtual-phenotype. Univariate and multivariate logistic regressions were used to assess risk factors for categorical discordant responses, ceasing follow-up at week 32 since enough patients had been on the original drug combination for a sufficient amount of time to evaluate their immune response. Complementary linear regression analysis was performed over the entire 48 weeks' follow-up considering CD4 and plasma viral load (pVL) as continuous measures. RESULTS: Among 58 virological responder patients (> or =1 log10 HIV-1 RNA copies/mL decrease) and 101 virologically non-responders, immunological discordances (increase in CD4 count of< or > or =100 cells/microL) were observed in 58.6% and 38.6%, respectively. Baseline CD4 count was associated with discordant responses in both groups. Multivariable linear regression over the entire 48 weeks' follow-up demonstrated significant correlation between absolute decrease in pVL and increase in CD4 count (HR 28.06, 95%CI 35.32-20.79; P<0.001), also the use of protease inhibitors (PIs) in the salvage regimen (HR 36.57, 95%CI 15.45-57.68; P<0.001) and >8 months on treatment (HR 41.64, 95%CI 19.27-64.01; P<0.001) correlated with highly significant immune recovery. CONCLUSIONS: These data confirm that therapy, possibly including PIs, should be continued in heavily pretreated patients and that hard-to-reach pVL undetectability is not essential to obtain immunologic recovery; however, this is strongly increased by the degree of pVL reduction that should be achieved.

Anti-HIV Agents↗

The oxygen uptake-heart rate relationship in trained female wheelchair athletes.

We examined the relationship between the percentage of peak heart rate (HR) and the percentage of peak oxygen uptake VO2 during steady-rate incremental wheelchair propulsion in 10 trained female wheelchair athletes (WAs) to determine the appropriateness of using American College of Sports Medicine (ACSM) target HRs for training prescription. Oxygen uptake was calculated during each submaximal exercise stage, and HR was monitored continuously. Peak VO2 was determined with the use of a separate protocol. Linear regression equations of percentage of peak HR versus percentage of peak VO2 were measured for each participant. Subsequently, we calculated the percentage of peak HR values corresponding with 40%, 60%, 80%, and 85% peak VO2. The linear regression formula (derived as the group mean of the slope and intercept terms determined from each individual participant) was % peak HR = 0.652 x % peak VO2 + 35.2 (standard error of the estimate [SEE] 3.41). The group mean of the individual correlation coefficients for the VO2-HR relationship was r = 0.973. The percentage peaks of HRs for the WAs were slightly, though not significantly, greater than those suggested by the ACSM across the exercise intensity continuum. These findings suggest that training programs prescribed on the basis of ACSM target HR guidelines need not be altered for trained female WAs with lesions of T6 and below. Notably, the discrepancy between the WA values and the population norm (ACSM) decreased from 6% at 40% peak VO2 (i.e., 61% vs. 55%) to <1% at 85% peak VO2 (i.e., 90.6% vs. 90.0%). This discrepancy indicates a tendency for the use of percentage of HR peak at the lower exercise intensities to slightly underestimate the relative exercise intensity (i.e., percentage of peak VO2) in the WA population.

Adolescent↗

Analysis of picogram quantities of protein in subnanoliter-size samples.

The ability to measure protein concentration in subnanoliter volumes would be helpful in many biological studies. A microassay for measuring nanogram protein quantities in nanoliter-size samples and an ultramicroassay for measuring picogram quantities in picoliter samples were developed to measure lymphatic protein concentration. Aliquots of a sample solution were mixed with an o-phthalaldehyde mercaptoethanol reagent using micropipetting techniques. Reaction product fluorescence was measured using a modified Leitz MPV-1 microscope as a microfluorometer. Fluorescence varied linearly with albumin concentrations between 1 and 8 g/100 ml. A typical microassay measuring albumin standards at 0.0, 1.0, 2.0, and 4.0 g/100 ml yielded a linear regression of y = 207x + 60 (r = 0.99). Minimum detectable protein concentration was 0.125 g/100 ml. The SE for the albumin standards varied from 0.02 to 0.17 g/100 ml. An ultramicroassay measuring similar standards yielded a linear regression of y = 1180x + 109 (r = 0.96). Minimum detectable protein concentration was 0.028 g/100 ml. The SE for the standards varied from 0.01 to 0.32 g/100 ml.

Albumins↗

The value of donor iliac artery pressure gradients in predicting the outcome of femorofemoral bypass.

PURPOSE: This study tests the clinical value of femoral artery pressure measurements by analysis of the relationship between iliac artery pressure gradients (PGs) and both femorofemoral bypass graft patency and the hemodynamic changes produced in the donor and recipient limbs. METHODS: Systemic and donor femoral artery systolic and mean pressures were measured during surgery at rest and during papaverine-induced hyperemia before 94 femorofemoral bypasses. Ankle/brachial (A/B) pressure ratios and pulse volume recordings (PVRs) were measured before and early after surgery. Donor iliac artery stenosis was 25% +/- 23% (mean +/- 1 SD). Follow-up was 23+/- 20 months. RESULTS: Eight bypasses failed at 21 +/- 20 months. Patients with failed bypasses had a resting systolic and mean PG of 23 +/- 22 mm Hg and 5 +/- 7 mm Hg, respectively, compared with 10 +/- 11 mm Hg (p = 0.007) and 1 +/- 2 mm Hg (p = 0.001) for the 86 patent bypasses. Donor limb A/B ratios and PVRs decreased 9% +/- 5% and 15% +/- 14%, respectively, had a linear regression slope less than 0 (p < 0.05) with resting and hyperemic PGs, and correlated best with resting PGs (p < 0.05). Recipient limb A/B ratios and PVRs increased 86% +/- 48% and 191% +/- 111%, respectively, had a linear regression slope greater than 0 (p < 0.05) with all resting and hyperemic PGs, and correlated best with hyperemic systolic PGs (p < 0.05). However, all regressions had a large SD, wide 95% confidence limit, and a low correlation coefficient. Sensitivity-specificity receiver-operating characteristic curves for optimal PG criteria for both graft failure and donor limb hemodynamic impairment are weak, with an accuracy of 50% to 75%. Recommended criteria for not performing a femorofemoral bypass are a resting systolic PG of 28 mm Hg or greater or a resting mean PG of 6 mm Hg or greater. CONCLUSIONS: Although iliac artery PGs correlate with graft failure and both the degree of donor limb hemodynamic impairment and recipient limb improvement, the large variability in PGs between patients with similar outcomes and the low accuracy of optimal PG criteria indicate that they have limited clinical value in decision making.

Aged↗

Cyanide removal by Chinese vegetation--quantification of the Michaelis-Menten kinetics.

BACKGROUND: Little is known about metabolism rates of environmental chemicals by vegetation. A good model compound to study the variation of rates among plant species is cyanide. Vascular plants possess an enzyme system that detoxifies cyanide by converting it to the amino acid asparagine. Knowledge of the kinetic parameters, the half-saturation constant (Km) and the maximum metabolic capacity (vmax), is very useful for enzyme characterization and biochemical purposes. The goal of this study is to find the enzyme kinetics (K(M) and vmax) during cyanide metabolism in the presence of Chinese vegetation, to provide quantitative data for engineered phytoremediation, and to investigate the variation of metabolic rates of plants. METHODS: Detached leaves (1.0 g fresh weight) from 12 species out of 9 families were kept in glass vessels with 100 mL of aqueous solution spiked with potassium cyanide at 23 degrees C for 28 h. Four different treatment concentrations of cyanide were used, ranging from 0.44 to 7.69 mg CN/L. The disappearance of cyanide from the aqueous solution was analyzed spectrophotometrically. Realistic values of the half-saturation constant (KM) and the maximum metabolic capacity (vmax) were estimated by a computer program using non-linear regression treatments. As a comparison, Lineweaver-Burk plots were also used to estimate the kinetic parameters. RESULTS AND DISCUSSION: The values obtained for K(M) and vmax varied with plant species. Using non-linear regression treatments, values of vmax and K(M) were found in a range between 6.68 and 21.91 mg CN/kg/h and 0.90 to 3.15 mg CN/L, respectively. The highest vmax was by Chinese elder (Sambucus chinensis), followed by upright hedge-parsley (Torilis japonica). The lowest Vmax was demonstrated by the hybrid willow (Salix matssudana x alba). However, the highest K(M) was found in the water lily (Nymphea teragona), followed by the poplar (Populus deltoides Marsh). The lowest K(M) was demonstrated by corn (Zea mays L.). The values of vmax were normally distributed with a mean of 13 mg CN/kg/h. CONCLUSIONS: Significant removal of cyanide from aqueous solution was observed in the presence of plant materials without phytotoxicity, even at high doses of cyanide. This gives rise to the conclusion that the Chinese plant species used in this study are all able to efficiently metabolize cyanide, although with different maximum metabolic capacities. A second conclusion is that the variation of metabolism rates between species is small. All these plants had a similar K(M), indicating the same enzyme is active in all plants. RECOMMENDATIONS AND OUTLOOK: Detoxification of cyanide with trees seems to be a feasible option for cleaning soils and water contaminated with cyanide. For phytoremediation projects, screening appropriate plant species adapted to local conditions should be seriously considered. More chemicals should be investigated to find common principles of the metabolism of environmental chemicals by plants.

Biodegradation, Environmental↗

Comparative efficacy of thallium adsorption by activated charcoal, prussian blue, and sodium polystyrene sulfonate.

BACKGROUND: Although Prussian blue is considered the antidote of choice for thallium poisoning, the lack of a Food and Drug Administration-approved pharmaceutical formulation has led to the search for other adsorbents. Activated charcoal has been demonstrated to adsorb thallium in vitro, and the similarity between thallium and potassium has led some authors to consider the use of sodium polystyrene sulfonate as a potential adsorbent. This experiment was designed to compare the relative thallium binding efficacy of these agents in a standard isotherm model. METHODS: A standard aqueous solution of thallium acetate buffered to pH 7.0 was agitated at 25 degrees C with activated charcoal, Prussian blue, or sodium polystyrene sulfonate at adsorbent:thallium ratios ranging from 1.5:1 to 100:1. In order to further simulate physiologic conditions, all trials were repeated in a solution containing 4 mmol/L potassium phosphate. After thorough agitation, the mixtures were allowed to settle and were centrifuged and filtered through a 0.22-micron filter. Supernatant thallium concentrations were measured by atomic absorption spectrophotometry. Langmuir isotherms were used to calculate the maximal adsorptive capacity of each adsorbent, using linear regression with Pearson's correlation coefficients (r). Maximal adsorptive capacities were compared statistically with a p < 0.05 considered significant. RESULTS: The maximal adsorptive capacities defined as milligrams of thallium per gram of adsorbent (shown with linear regression p and r values) were as follows: activated charcoal, 59.7 mg/g (p = 0.005, r = 0.995); Prussian blue, 72.7 mg/g (p = 0.004, r = 0.996); and sodium polystyrene sulfonate, 713 mg/g (p = 0.049, r = 0.951). All three values were statistically different from each other. At a physiologic potassium concentration, the maximal adsorptive capacities for activated charcoal and Prussian blue were essentially unchanged (58.3 mg/g and 69.8 mg/g, respectively, p > 0.05 for each vs trials without potassium), while the maximal adsorptive capacity for sodium polystyrene sulfonate fell to 39.1 mg/g (p = 0.003, r = 0.997, p = 0.005 vs sodium polystyrene sulfonate without potassium). CONCLUSIONS: This in vitro study confirms the utility of Prussian blue and activated charcoal as thallium adsorbents. Although sodium polystyrene sulfonate demonstrates exceptional in vitro adsorption of thallium, its greater affinity for potassium probably renders it clinically ineffective.

Adsorption↗

Sodium and potassium intake and blood pressure change in childhood.

OBJECTIVE: To assess the association between sodium and potassium intake and the rise in blood pressure in childhood. DESIGN: Longitudinal study of a cohort of children with annual measurements during an average follow up period of seven years. SETTING: Epidemiological survey of the population of a suburban town in western Netherlands. SUBJECTS: Cohort of 233 children aged 5-17 drawn at random from participants in the population survey. MAIN OUTCOME MEASURES: At least six annual timed overnight urine samples were obtained. The mean 24 hour sodium and potassium excretion during the follow up period was estimated for each participant and the sodium to potassium ratio calculated. Individual slopes of blood pressure over time were calculated by linear regression analysis. RESULTS: No significant association was observed between sodium excretion and the change in blood pressure over time. The mean systolic blood pressure slopes, however, were lower when potassium intake was higher (coefficient of linear regression -0.045 mm Hg/year/mmol; 95% confidence interval -0.069 to -0.020), and the change in systolic pressure was greater when the urinary sodium to potassium ratio was higher (0.356 mm Hg/year/unit; 95% confidence interval 0.069 to 0.642). In relation to potassium this was interpreted as a rise in blood pressure that was on average 1.0 mm Hg (95% confidence interval -1.65 to -0.35) lower in children in the upper part of the distribution of intake compared with those in the lower part. The mean yearly rise in systolic blood pressure for the group as a whole was 1.95 mm Hg. Urinary electrolyte excretion was not associated with diastolic blood pressure. CONCLUSION: Dietary potassium and the dietary sodium to potassium ratio are related to the rise in blood pressure in childhood and may be important in the early pathogenesis of primary hypertension.

Adolescent↗

Reproducibility of osmotic and nonosmotic tests of vasopressin secretion in men.

We have studied the reproducibility of the thirst and arginine vasopressin (AVP) responses to osmotic and hypoglycemic stimulation in healthy volunteers undergoing repeat hypertonic (855 mmol/l) saline infusion and insulin tolerance tests (ITTs). Hypertonic saline infusion caused similar mean rises in plasma osmolality, AVP, and thirst on each occasion. Linear-regression analysis defined close relationships between the slopes (r = +0.72, P less than 0.05) and the abscissal intercepts (r = +0.89, P less than 0.001) of the regression lines relating plasma osmolality (Posmol) and plasma AVP (PAVP), and the group intraindividual component of the variance for the slopes and intercepts was 7 and 0.6%, respectively. There were close correlations between the slopes (r = +0.79, P less than 0.02) and the intercepts (r = +0.84, P less than 0.01) of the regression lines relating Posmol and thirst, and group intraindividual component of the variance was 14 and 0.7%, respectively. Hypertonic saline infusion was infused on four occasions in four subjects, and the results showed that the linear regression lines relating PAVP and Posmol and thirst and Posmol were reproducible within an individual. There were similar falls in blood glucose and elevations in PAVP in both ITTs. No relationship was defined between the fall in blood glucose and either the rise in PAVP or the area under the AVP curve (AUC). The intraindividual component of the variance for the rise in AVP and the AUC was 77 and 22.5%, respectively. The AVP and thirst responses to osmotic stimulation are highly reproducible, but there is considerable intraindividual variation in the AVP response to hypoglycemia.

Adult↗

[Ultrasonography and surgical treatment of facial skin neoplasms].

In the second half of the 20 century, echosonography has been used in many medical specialities. In 1992 and 1993 highfrequencies echosonography was used in the examination of irritant and allergic skin lesions in order to examine the effects of different therapeutical agents on the skin lesions [1-4]. Hoffmann used highfrequencies echosonography in the examination of healing of skin lesions [3]. By their incidence skin tumours are the largest group of newly discovered tumours, and their usual location is on the face [5-7]. By clinical examination it is not possible to precisely determine the depth of tumour border; therefore, the radically performed surgical excision is the only correct surgical treatment. The aim of this study was to estimate the results of preoperatively performed high frequencies echosonography in order to reduce the number of incorrectly performed surgical excisions of skin tumours. The group was composed of 40 patients with 45 tumours, who first underwent echosonographic diagnostic procedure (20 MHz, Hadsund electronic, Hadsund Technology, Denmark) and then surgical excision; patients in control group (45 patients with 45 tumours) were only subjected to surgical excision. Excised tumours were then pathohistologically analyzed, and measurements of tumour depth progression were performed. Margins of pathohistological specimen were controlled for the presence of tumour cells. Results of measurements of tumour depth obtained by echosonography and pathohistological measurements were compared. By Jate's modification of c2 test results regarding correct and incorrect surgical excision in patients and control group were compared. By linear regression analysis results of tumour depth obtained by echosonographic and pathohistologic examinations were compared. Hypoechogen zone echosonographic results were used like criteria for tumour expansion. Results of tumour depth measurements are presented in Table 1. Linear regression analysis showed (R = 0.64) that echosonographic examination gave objective pictures of tumour depth. Six specimens were excluded from this examination, and only the presence of tumour cells on specimen margins were analysed. All tumours in patients were excised radically; in control group tumour cells were present on pathohistological specimens margins of six cases. In comparison p = 0.5016 was a not significant value. Success of 100% of specimens correctly excised in operated patients is the success which is very close to success of Moh's micrographic surgery (by Fleming only 1% of tumour relapse in a five-year follow-up period) [8]. Result of 13.33% of incorrect excision in control group is close to results obtained by Leshin and al [9]. Result of p = 0.05016 is not statistically significant, but is very close to statistically significant values. This might require future examinations in a larger group of patients. Results of R = 0.64 correlate with results obtained by Hoffmann [3], because they show that highfrequencies ultrasound examination gives an objective picture of skin tumours depth. Results of this examination show that preoperative highfrequencies ultrasound examination can determine the progression of tumour depth, and give to surgeon data which can help him to perform correct surgical excisions.

Basal Cell Carcinoma↗

Hyperinsulinemia and cognitive decline in a middle-aged cohort.

OBJECTIVE: Determining modifiable risks factors for cognitive decline and dementia are a public health priority as we seek to prevent dementia. Type 2 diabetes and related disorders such as hyperinsulinemia increase with aging and are increasing in the U.S. population. Our objective was to determine whether hyperinsulinemia is associated with cognitive decline among middle-aged adults without type 2 diabetes, dementia, or stroke in the Atherosclerosis Risk in Communities (ARIC) cohort. RESEARCH DESIGN AND METHODS: Middle-aged adults (aged 45-64 years at baseline) in the ARIC cohort had fasting insulin and glucose assessed between 1987 and 1989. Subjects with dementia, type 2 diabetes, or stroke at baseline were excluded from analysis. Three tests of cognitive function available at baseline and 6 years later were delayed word recall (DWR), digit symbol subtest (DSS), and first letter word fluency (WF). Cross-sectional comparisons and linear regression models were computed for cognitive tests at baseline and change in cognitive test scores to determine whether cognitive function was associated with two measures of insulin resistance, fasting insulin and homeostasis model assessment (HOMA). Linear regression models controlled for age, sex, race, marital status, education level, smoking status, alcohol use, depression, hypertension, and hyperlipidemia. RESULTS: In unadjusted and adjusted analyses, hyperinsulinemia based on fasting insulin and HOMA at baseline was associated with significantly lower baseline DWR, DSS, and WF scores and a greater decline over 6 years in DWR and WF. CONCLUSIONS: Insulin resistance is a potentially modifiable midlife risk factor for cognitive decline and dementia.

Cognition Disorders↗

[Medical consultation dynamics in Japanese cedar pollinosis patients at an office building clinic in central Tokyo].

To clarify medical consultation dynamics in Japanese cedar pollinosis patients visiting an office building clinic in an office block in central Tokyo, we surveyed number of patient at a private ENT clinic in Chiyoda-ku, Tokyo, during the Japanese cedar pollen season from 1990 to 1999. Based on questionnaires and CAP RAST tests in 1995, we studied the profiles of Japanese cedar pollinosis patients and determined positive rates of noncedar antigens. The gender ratio in 1995 was 674 men versus 501 women, most frequently men in their 40s and women in their 20s. Of these, 79.2% worked in Chiyoda-ku and Chuo-ku, but only 1.9% lived in these districts. Positive rates of noncedar antigens in 232 who received simultaneous CAP RAST tests were 64.7% for Japanese cypress, 38.3% for house dust, 35.3% for Dermatophagoides pteronyssinus, 34.4% for Epidermoptidae spp, 19.8% for mixed grasses, and 10.3% for mixed weeds (asteraceous plants). Patients positive for cedar alone were 19.0% and positive for both cedar and cypress but negative for other antigens were 23.3%; about 60% of these were suspected of multiple sensitization to antigens other than cedar and cypress. The number of pollens and patients were summarized weekly and compared. Those paying a first visit were peaked with an increase in pollen in the first week of March almost every year; second visits peaked 1 or 2 weeks later than the first visit. Little increase in first visit was noted even with increasing pollen dissemination from the latter half of March. The relationship between the number of pollen and patients each year from 1990 to 1999 correlated highly with the linear regression equation y = 0.1005x + 547.07 with R2 = 0.7562. The relationship between square roots of the number of pollen and patients each year for 5 year from 1995 to 1999 correlated very highly with the linear regression equation y = 11.167x + 376.72 with R2 = 0.9941. We concluded that the number of patients may be predicted with substantially higher accuracy based on the estimated amount of pollen in a given year.

Adult↗

Monoclonal antibodies for progesterone receptor assays and polymorphism studies in breast cancer. Comparison with radioligand assays.

Progesterone receptors (PR) from human breast tumors were assayed by a new method using monoclonal antibodies immobilized on beads (PR-EIA, Abbott Laboratories). EIA results were compared to those obtained with the dextran-coated charcoal method using a tritiated ligand (ORG 2058). The precision and reproducibility of the EIA method were studied over a 3-month period: intra-assay coefficients of variation were less than 6% for the range of the assay (between 5-250 fmol/ml), and inter-assay coefficients of variation calculated on 13 consecutive standard curves were less than 10%, except for standard 0 (33%). PR assays performed on 78 tumors both by EIA and radioligand (RLA) were compared. The linear regression obtained was: PR-EIA = 0.81 RLA+1 fmol/mg protein (r = 0.88). For reproducibility studies, cytosols were assayed twice during a period ranging from 1 week-3 months, both by EIA and RLA. The linear regression obtained between the second assay (B) and the first assay (A) was: B = 0.98 A + 11 fmol/mg protein for RLA (r = 0.98), and B = 0.99 A-7 fmol/mg protein for EIA (r = 0.98). To study the effect of KCl on PR-EIA, 26 tumors were homogenized in 0.4 M KCl Tris buffer and assayed both by EIA and RLA. A good correlation was obtained between the 2 methods, but higher values were obtained with PR-EIA (P = 1.6) in comparison with RLA. The addition of KCl to the cytosol showed that KCl had no effect on EIA results, but significantly lowered RLA results. To study the effect of KCl on progesterone receptor isoforms, cytosols were analyzed by chromatography on TSK G3000 SW columns, and the presence of PR was detected in each fraction by both EIA and RLA. In the absence of KCl, only the oligomeric form of PR was observed; however with both techniques, detection of this form different from tumor to tumor, emphasizing the inter-tumoral molecular heterogeneity of PR. After PR isoform dissociation by KCl (0.4 M) and chromatographic analysis of the forms obtained, monoclonal antibodies detected PR molecular forms different from those observed by radioligand; furthermore, chromatographic patterns obtained were different from one tumor to another and confirmed the inter-tumoral molecular heterogeneity of the progesterone receptor.

Antibodies, Monoclonal↗

Evaluation of the EMIT reagent system for measurement of caffeine with the EMIT Lab 5000 System and a centrifugal analyzer.

Using a Syva EMIT Lab 5000 System, we evaluated a newly developed EMIT assay for measurement of caffeine in serum of neonates. The method is rapid, and coefficients of variation for within-run and day-to-day precision were less than 5%. The accuracy of the method, as evaluated from analytical recovery and a calibrator-crossover study, is excellent. Comparison of the results analyzed by the EMIT caffeine assay (y) and the liquid-chromatographic comparison method (x) yielded the linear regression equation y = 1. 052x + 0.293 (n = 110, r = 0.987, and Sy . x = 0.625). The method was also adapted to a COBAS-BIO centrifugal analyzer (y) and optimized to minimize sample and reagent consumption. Linear regression analysis yielded the equation y = 1. 031x + 0.227 (n = 61, r = 0.992, and Sy . x = 0.488). As many as 400 assays per EMIT kit can be performed with the analyzer method, with excellent precision and accuracy. The kit assay and this centrifugal analyzer are well suited for rapid batch testing: 28 analyses (including six calibrators) in 10 min.

Adult↗

Assay of D-dimer based on immunofiltration and staining with gold colloids.

In this immunofiltration assay of D-dimer in plasma samples, the antigens are captured by a monoclonal antibody on a porous membrane, and labeled with the same antibody conjugated to gold colloids. The assay time is < 2 min, and a color of intensity proportional to the concentration of D-dimer is left on the membrane. The reference range (mean +/- 2 SD) was 0.336 +/- 0.133 mg/L (n = 69). Linearity was found up to 10 mg/L. Comparison with ELISA results (x) for 198 patients' samples demonstrated a linear regression equation of y = 0.99(+/- 0.05)x + 0.68(+/- 0.07) and a mean square error of 0.503. Comparison of visual reading of the color signal (y) vs reflectometric measurements (x) for 220 patients' samples demonstrated a linear regression equation of y = 2.5(+/- 0.06)x -0.22(+/- 0.04) and a mean square error of 0.095. Bilirubin, hemoglobin, fibrinogen, soluble fibrin, and fibrinogen degradation products and freezing/thawing of samples did not interfere. Some interference from rheumatoid factor, heparin, and the presence of cells or large lipid particles was seen. The variance (CV) was 8-12% within run, 10-18% between runs, and 13-20% between persons. The new assay constitutes a rapid and reliable analytical tool combining simplicity equivalent to that of latex tests with analytical information approaching that of ELISA.

Drug Stability↗

Prediction of myelotoxicity using radiation doses to marrow from body, blood and marrow sources.

UNLABELLED: Bone marrow is generally the dose-limiting organ in radioimmunotherapy (RIT). Although radiation doses to marrow estimated from tracer doses have been shown to be comparable to those from therapy doses of radionuclide, the correlation of marrow radiation dose and myelotoxicity has not been well documented. The purpose of this study was to evaluate the relationship between radiation dose to marrow and subsequent changes in peripheral blood cell counts. METHODS: Radiation doses to marrow from three sources, body, blood and marrow targeting, were compared with changes in blood counts after the first therapy dose of (131)I-Lym-1 in 16 patients. Doses of (131)I-Lym-1 ranged from 1.1-8.2 GBq (29-222 mCi). Cumulated radioactivity in the body and marrow were obtained using sequential, quantitative images of the body and lumbar vertebrae, respectively, and that in blood using activity in blood samples. The individual and sum of radiation doses from penetrating radiations in the body, and nonpenetrating radiations in the blood and marrow, were compared with blood counts. RESULTS: In this group of patients, median radiation doses were 15.1, 15.4 and 42.1 cGy from body, blood and marrow targeting, respectively. Linear regression of radiation doses from body and blood versus fractional decreases in blood counts produced correlation coefficients of 0.38, 0.06, 0.22 and less than 0.01 for platelets, granulocytes, white blood cells (WBCs) and hematocrit, respectively. Linear regression of targeted marrow radiation doses versus fractional decreases in blood counts produced correlation coefficients 0.61, 0.31, 0.54 and 0.20 for platelets, granulocytes, WBCs and hematocrit. The closest association was found between radiation dose to marrow from marrow targeting and change in platelet count (r = 0.61). CONCLUSION: In patients, such as those with non-Hodgkin's lymphoma (NHL), likely to have marrow targeting, prediction of myelotoxicity by conventional body and blood contributions to marrow is substantially improved by the use of radiation dose to marrow estimated from images.

Blood↗

Antenatal corticosteroids and placental histology in preterm birth.

To assess the effects of antenatal corticosteroid use on placental histopathology, we have reviewed a database of 463 consecutive non-anomalous singleton liveborns delivered at less than 32 weeks between April 1988 and December 1994, of which 280 received one or more doses of corticosteroids for promotion of fetal lung maturation. Patients were grouped by the number of corticosteroid doses received (analyzed as none, 1, 2 and 3 or more doses). Clinical and demographic factors were recorded prospectively. Placental histopathology was reviewed blinded to clinical factors except gestational age, and 42 distinct placental lesions were examined and scored for severity. Data were analyzed by contingency tables, one-way analysis of variance, and linear regression analysis. Among clinical variables, univariate analysis showed that the number of corticosteroid doses was significantly related to presence of labour prior to delivery, pre-eclampsia, premature rupture of membranes and clinical suspicion or diagnosis of chorioamnionitis. Using linear regression analysis with these clinical variables as confounders, increased number of doses of antenatal corticosteroids was related to increased severity of villous fibrosis and stromal mineralization, and fewer villous infarcts.

Adrenal Cortex Hormones↗

Cord blood thyroid-stimulating hormone level in twin pregnancy.

BACKGROUND: Cord blood thyroid-stimulating hormone level is elevated among neonates who undergo more perinatal stress. The aim of this study was to investigate the effect of twin pregnancy on the cord blood thyroid-stimulating hormone level. METHODS: The study group consisted of 24 910 singleton and 543 twin neonates over a 4-year period. The effect of twin pregnancy on the cord blood thyroid-stimulating level was evaluated. Linear regression analysis was used to control for the effect of mode of delivery, birth weight, and infant sex. RESULTS: The median cord blood thyroid-stimulating hormone levels (interquartile range) in the singletons and in the twins were 5.8mIU/l (4.2-8.6) and 5.6mIU/l (4.3-7.5), respectively. Linear regression analysis revealed no significant difference between singleton and twin cord blood thyroid-stimulating hormone levels (p = 0.23). Cord thyroid-stimulating hormone levels tended to be higher in second-born twins (p = 0.08) and monochorionic twins (p = 0.097) compared with singleton neonates. Twins with more than 20% weight discordance were associated with a significantly higher cord blood thyroid-stimulating hormone level (p = 0.035). CONCLUSION: Cord blood thyroid-stimulating hormone level is elevated in some subgroups of twins who are at higher risk of adverse perinatal outcomes. However, the overall effect of multiple pregnancy on the cord blood thyroid-stimulating hormone level is small. Cord blood thyroid-stimulating hormone screening for congenital hypothyroidism is also valid in twin pregnancies.

Adult↗

Are the lower incisors the best predictors for the unerupted canine and premolars sums? an analysis of a Peruvian sample.

The lower permanent incisor tooth width sum has been proposed as the best predictor for the tooth width sums of the unerupted canine and premolars (SPCP) for populations from different ethnic origins. Only two previous studies have refuted it. The purpose of the present study was to determine which sum or combination of sums of permanent tooth widths presented the best prediction capability for the SPCP in a Peruvian sample, to calculate a specific linear regression equation for this population, and to evaluate the clinical significance. A total of 150 children with complete permanent dentitions were selected. Fifty more children were used as a validation sample for the application of a multiple linear regression equation (MLRE). They did not present clinically visible dental caries or proximal restorations and no active or previous orthodontic treatment. Their dental casts were measured to 0.1 mm with a sliding caliper with a Vernier scale. Three-way analysis of variance, Pearson Correlation Test, Fisher Z values and a MLRE were used for the statistical analysis. The combination of the sums of permanent upper and lower central incisors and upper first molars was the best predictor for the SPCP in this sample. A MLRE was calculated including sex and arch as additional predictor variables. The MLRE determination coefficient was 60% with a standard error of 0.8 mm. This new MLRE underestimates (less than 1 mm discrepancy) the actual SPCP in only 7% of the cases on the basis of a validation sample.

Adolescent↗