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Diagnostic value of serological tests against Pseudomonas aeruginosa in a large cystic fibrosis population.

BACKGROUND: Serological methods to monitor Pseudomonas aeruginosa colonisation in patients with cystic fibrosis (CF) are advocated but the diagnostic value of a commercially available P aeruginosa antibody test to detect early and chronic P aeruginosa colonisation in a non-research setting has not been assessed. METHODS: Colonisation with P aeruginosa was estimated by regular culture of sputum or oropharyngeal swabs during three consecutive years in 220 patients with CF aged 0-65 years. Commercially available ELISA tests with three P aeruginosa antigens (elastase, exotoxin A, alkaline protease) were performed at the end of the study period. In a subgroup of 57 patients (aged 4-14 years) serological tests were performed annually. RESULTS: Using culture as the reference standard, the ELISA tests using the advised cut off values had a sensitivity of 79% and a specificity of 89% for chronic colonisation. Receiver-operator characteristic curves were created to optimise cut off values. Applying these new cut off values resulted in a sensitivity of 96% and a specificity of 79%. All three individual serological tests discriminated well between the absence and presence of chronic P aeruginosa colonisation. The sensitivity of the individual antibody test was 87% for elastase, 79% for exotoxin A, and 76% for alkaline protease. First colonisation was preceded by positive serological results in only five of 13 patients (38%). CONCLUSION: In patients with CF, serological tests using specific antigens are sensitive for diagnosing chronic P aeruginosa colonisation. However, the failure of serological tests to detect early colonisation in young patients emphasises the need for continued reliance on cultures.

Adult↗

Influence of transmitral filling dynamics on continuous-wave Doppler assessment of aortic regurgitation by half-time methods.

The influence of transmitral filling dynamics on the evaluation of aortic regurgitation (AR) by continuous-wave Doppler pressure half-time was assessed in 30 consecutive patients in sinus rhythm with chronic moderate to severe AR. Pulsed-wave Doppler-derived regurgitant fraction (obtained from aortic and pulmonary stroke volumes) and color flow mapping relative regurgitant area (obtained from the parasternal short-axis view) were chosen as reference standards for the severity of AR. An excellent correlation was found between these 2 parameters (r = 0.98), while correlations were poor between pressure half-time and either regurgitant fraction (r = -0.74) or relative regurgitant jet area (r = -0.69). The ratio of early (E) to late (A) transmitral peak velocities was used to divide the study population into 2 groups: group A (n = 16) with E/A less than 1 and group B (n = 14) with E/A greater than 1. In patients with a similar degree of AR (estimated from Doppler regurgitant fraction or relative regurgitant jet area), the pressure half-time was found to be significantly shorter. Thus, the severity of AR in group A patients was overestimated (p less than 0.01). Compared to group B, group A patients were significantly shorter. Thus, the severity of AR in group A patients was overestimated (p less than 0.01). Compared to group B, group A patients were significantly older (p less than 0.02) and had a larger left ventricular mass (p less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Aortic Valve Insufficiency↗

Diagnosis of iron deficiency in chronic renal failure.

The cause of anemia in chronic renal failure is multifactorial. Decreased erythropoietin (EPO) production is the main pathogenetic factor, but iron deficiency is the primary cause of unresponsiveness to EPO therapy. The diagnosis of iron deficiency in patients with chronic renal failure is difficult. We assessed the sensitivity and specificity of serum ferritin, total iron-binding capacity, transferrin saturation index, erythrocyte ferritin, and serum transferrin receptor in 63 patients with chronic renal failure undergoing dialysis (47 men, 16 women) with iron deficiency anemia. They were selected on the basis of clinical stability and absence of factors that may interfere with iron metabolism. None of the patients had received intravenous iron therapy or recombinant human erythropoietin (rHuEPO). Bone marrow biopsy with iron staining was the reference standard for iron stores. The receiver operating characteristic (ROC) curve and the area under the curve were calculated to assess the sensitivity and specificity of iron metabolism parameters. The parameter with the largest area under the ROC curve was serum ferritin (0.83). A cut point of 121 microgram/L showed a sensitivity and a specificity of 75%. The areas under the ROC curves of serum transferrin receptor and erythrocyte ferritin were 0.69 and 0.68, respectively. The remaining parameters showed areas under the ROC curve less than 0.65. Although serum transferrin receptor and erythrocyte ferritin may be acceptable markers for iron deficiency in stable chronic renal failure patients, serum ferritin level continues to be the most reliable diagnostic parameter. Transferrin saturation index is not a reliable parameter for the diagnosis of iron deficiency in stable patients not treated with rHuEPO.

Adult↗

Detection of flunixin in greyhound urine by a kinetic enzyme-linked immunosorbent assay.

A two-step kinetic enzyme-linked immunosorbent assay was developed to detect the presence of flunixin in the urine of greyhound dogs. The assay system was developed using polyclonal antiflunixin antisera, a rabbit albumin-flunixin conjugate adsorbed onto polystyrene microtiter strips, and flunixin reference standards for calibration. The assay parameters were optimized and the performance characteristics were determined. The quantitative intra- and inter-run precisions (%CV) of the analysis of replicate (n = 10) flunixin-spiked urine samples were 9.9-12.5% and 10.2-13.6%, respectively. The linear dynamic range was 1-100 ng/mL, and the quantitative accuracy, as determined by calculation of percent error of measured flunixin in flunixin-spiked drug-free greyhound urine, was -16% to +14% over this range. The I50 of the ELISA was 17.3 ng/mL. The limit of detection was 25 ng/mL in greyhound urine. The reactivity in the assay system relative to flunixin (100%) was 147% for flunixin glucuronide, 25% for clonixin, and 5% for niflumic acid. The ELISA was capable of detecting total flunixin for up to 72 h in dogs administered flunixin at 0.55 mg/kg orally and up to 96 h in a dog that was administered flunixin at 1.0 mg/kg orally.

Adjuvants, Immunologic↗

The emergency department versus the computer: which is the better electrocardiographer?

Electrocardiograms (ECGs) are frequently ordered in the pediatric emergency department (ED). Pediatric cardiologists are generally not asked to interpret every ECG; thus, ED patient management is often guided by the ED physicians' ECG interpretation. The objective of this study was to analyze the accuracy of ECG interpretation by ED physicians and a computer-generated interpretation and compare the two. A 12-month prospective study was performed in a pediatric ED. All patients (<22 years) who had an ECG in the ED were included. The ED physicians and the computer interpretation were compared to a reference standard. Each electrocardiographic diagnosis, as well as the ECG as a whole, was assigned to one of the following predetermined classes: I, normal sinus rhythm; II, minimal clinical significance; III, indeterminate clinical significance; IV, those of definite clinical significance. Both groups correctly interpreted all normal (class I) ECGs. The computer correctly interpreted approximately 75% of the class II and class III ECGs, whereas the ED physicians correctly interpreted 36% of both groups. For the class IV ECGs, both the computer and the ED physicians performed poorly, correctly interpreting just 14% and 28%, respectively. The computer proved to be more accurate than the ED physicians in interpreting ECGs of less than critical significance (classes II and III), but neither group was able to correctly interpret even a simple majority of the most significant abnormalities (class IV). We speculate that distributing the computer-generated interpretation to the ED physicians and formal review of all ED ECGs by a skilled interpreter may decrease the number of missed diagnoses.

Adolescent↗

Fecal progesterone analysis by time-resolved fluoroimmunoassay (TR-FIA) for monitoring of luteal function in the sika doe (Cervus nippon centralis).

Fecal progesterone content was measured by time-resolved fluoroimmunoassay (TR-FIA) in the sika doe (Cervus nippon). The total recovery rate of fecal progesterone by twice extraction with diethylether was about 60%. The displacement curve of TR-FIA with serial doses of fecal extract (0.156-5.0 mg feces) was closely parallel to that of the reference standard. Fecal progesterone content was correlated with that of plasma (r=0.829, n=16), but the values were 100-fold higher in feces than in plasma. Fecal progesterone content periodically changed during the breeding season suggesting the estrous cycle in the doe. The fecal progesterone content was higher between the estruses, and decreased after estrus. The time between the onset of estrous signs and the lowest fecal progesterone content was 1-2 days suggesting the time required for hepatic metabolism and intestinal passage. Fecal progesterone content was also decreased around the time of vaginal discharge. The discharge took place within a few days, suggesting a short luteal phase. Not of all decreases in fecal progesterone values were preceded by estrous behavior or vaginal discharge. Fecal progesterone content was further increased in pregnancy rather than in the preceding estrous cycle and the levels were maintained up to term. These results suggest that fecal progesterone measurement is a useful tool for non-invasive analysis of luteal function in the sika doe. The TR-FIA kit, designed for the human hospital market, was shown to be successfully utilized for fecal assay in the sika doe with minor modifications.

Animals↗

Real-time polymerase chain reaction-based approach for quantification of the pat gene in the T25 Zea mays event.

In Europe, a growing interest for reliable techniques for the quantification of genetically modified component(s) of food matrixes is arising from the need to comply with the European legislative framework on novel food products. Real-time polymerase chain reaction (PCR) is currently the most powerful technique for the quantification of specific nucleic acid sequences. Several real-time PCR methodologies based on different molecular principles have been developed for this purpose. The most frequently used approach in the field of genetically modified organism (GMO) quantification in food or feed samples is based on the 5'-3'-exonuclease activity of Taq DNA polymerase on specific degradation probes (TaqMan principle). A novel approach was developed for the establishment of a TaqMan quantification system assessing GMO contents around the 1% threshold stipulated under European Union (EU) legislation for the labeling of food products. The Zea mays T25 elite event was chosen as a model for the development of the novel GMO quantification approach. The most innovative aspect of the system is represented by the use of sequences cloned in plasmids as reference standards. In the field of GMO quantification, plasmids are an easy to use, cheap, and reliable alternative to Certified Reference Materials (CRMs), which are only available for a few of the GMOs authorized in Europe, have a relatively high production cost, and require further processing to be suitable for analysis. Strengths and weaknesses of the use of novel plasmid-based standards are addressed in detail. In addition, the quantification system was designed to avoid the use of a reference gene (e.g., a single copy, species-specific gene) as normalizer, i.e., to perform a GMO quantification based on an absolute instead of a relative measurement. In fact, experimental evidences show that the use of reference genes adds variability to the measurement system because a second independent real-time PCR-based measurement must be performed. Moreover, for some reference genes no sufficient information on copy number in and among genomes of different lines is available, making adequate quantification difficult. Once developed, the method was subsequently validated according to IUPAC and ISO 5725 guidelines. Thirteen laboratories from 8 EU countries participated in the trial. Eleven laboratories provided results complying with the predefined study requirements. Repeatability (RSDr) values ranged from 8.7 to 15.9%, with a mean value of 12%. Reproducibility (RSDR) values ranged from 16.3 to 25.5%, with a mean value of 21%. Following Codex Alimentarius Committee guidelines, both the limits of detection and quantitation were determined to be <0.1%.

Base Sequence↗

The non-invasive detection of intracranial aneurysms: are neuroradiologists any better than other observers?

Can non-neuroradiologists detect intracranial aneurysms as well as neuroradiologists, using CT and MR angiography? Sixty patients undergoing intra-arterial digital subtraction angiography (IADSA) to detect aneurysms also underwent computed tomographic angiography (CTA) and time-of-flight magnetic resonance angiography (MRA). Consensus review of IADSA by two neuroradiologists was the reference standard. Two neuroradiologists, a neurosurgeon, a neuroradiographer and a general radiologist blinded to IADSA, plain CT and clinical data, independently reviewed hard-copy base and reconstructed maximum intensity projection images of the CTA and MRA studies. Thirty patients had a total of 63 aneurysms, 71.4% were </=5 mm in size. Compared with IADSA, mean accuracy per patient for neuroradiologists was CTA 0.87 (95% CI 0.75-0.94), and MRA 0.82 (0.70-0.90); for the other observers it was CTA 0.81 (0.75-0.86), and MRA 0.78 (0.71-0.84). Sensitivity per aneurysm for neuroradiologists was CTA 0.63 (0.50-0.75), and MRA 0.43 (0.6-0.74); for the other observers it was CTA 0.52 (0.44-0.59), and MRA 0.38 (0.31-0.45). Differences between readers and modalities were not statistically significant. Agreement with IADSA was "good" for neuroradiologists: kappa 0.73 for CTA, and 0.63 for MRA. For the other observers, agreement with IADSA was "moderate": kappa 0.59 for CTA, and 0.56 for MRA. Neuroradiologists performed consistently better than the other observers, although differences did not reach statistical significance.

Adult↗

Reporting and concordance of methodologic criteria between abstracts and articles in diagnostic test studies.

OBJECTIVE: To evaluate the quality and concordance of methodologic criteria in abstracts versus articles regarding the diagnosis of trichomoniasis. STUDY DESIGN: Survey of published literature. DATA SOURCES: Studies indexed in MEDLINE (1976-1998). STUDY SELECTION: Studies that used culture as the gold or reference standard. DATA EXTRACTION: Data from abstract and articles were independently abstracted using 4 methodologic criteria: (1) prospective evaluation of consecutive patients; (2) test results did not influence the decision to do gold standard; (3) independent and blind comparison with gold standard; and (4) broad spectrum of patients used. The total number of criteria met for each report was calculated to create a quality score (0-4). MEASUREMENTS AND MAIN RESULTS: None of the 33 abstracts or full articles reported all 4 criteria. Three criteria were reported in none of the abstracts and in 18% of articles (95% confidence interval [95% CI] 8.6% to 34%). Two criteria were reported in 18% of abstracts (95% CI, 8.6% to 34%) and 42% of articles (95% CI, 27% to 59%). One criterion was reported in 42% of abstracts (95% CI, 27% to 59%) and 27% of articles (95% CI, 15% to 44%). No criteria were reported in 13 (39%) of 33 abstracts (95% CI, 25% to 56%) and 4 (12%) of 33 articles (95% CI, 4.8% to 27%). The agreement of the criteria between the abstract and the article was poor (kappa -0.09; 95% CI, -0.18 to 0) to moderate (kappa 0.53; 95% CI, 0.22 to 0.83). CONCLUSIONS: Information on methods basic to study validity is often absent from both abstract and paper. The concordance of such criteria between the abstract and article needs to improve.

Clinical Laboratory Techniques↗

Role of HPV DNA testing in predicting cervical intraepithelial lesions: comparison of HC HPV and ISH HPV.

Human papillomavirus (HPV) is widely accepted as the primary agent involved in the development of squamous intraepithelial neoplasia and cervical carcinoma. Several commercial tests are available for detecting HPV DNA. This study compares the efficacy of INFORM HPV (in situ hybridization [ISH] HPV) and HCII (HC HPV) in predicting cervical lesions. A total of 762 sequential Papanicolaou (Pap) smears determined by cytologic examination to be either atypical squamous cells of undetermined significance (ASC-US) or low-grade squamous intraepithelial lesions (LSIL) were tested by both Hybrid Capture (HC) HPV and ISH HPV; 250 follow-up biopsies were reviewed as the reference standard for presence or absence of a lesion. ISH HPV and HC HPV differed significantly in accurately predicting biopsy findings from ASC-US and LSIL cases. The overall sensitivity and specificity of ISH HPV were 97% (28/29) and 86% (191/221); and HC HPV was 79% (23/29) and 56% (123/221). The positive predictive value (PPV) of ISH HPV was 48% (28/58) vs HC HPV value of 19% (23/121). Negative predictive value (NPV) was also better with ISH HPV at 99% (191/192) and HC HPV at 95% (123/129). Of equal importance, ISH HPV demonstrated a lower false-positive rate compared to HC HPV, 12% (30/250) vs 39% (98/250), as well as having a slightly lower false-negative rate 0.4% (1/250) vs 2.4% (6/250). ISH HPV is more predictive of biopsy histopathology in patients with detectable cervical lesions than is HC HPV. Effective triage of patients by HPV analysis using ISH HPV as compared to HC HPV has the potential of significant public health impact by reducing unnecessary colposcopies, as well as adverse medical, social, and psychological patient consequences.

Adolescent↗

Monitoring surgical treatment of screen-detected breast lesions in Italy.

The object of this study was to assess quality of care and adherence to treatment guidelines of screen-detected lesions in Italy using a new audit system. Data on screen-detected cases surgically treated in 1997 were collected using a system (QT 2.3) developed within the Italian Group for Planning and Evaluating Mammographic Screening Programmes (GISMa) and the European Breast Cancer Screening Network. Results of 18 performance parameters were considered compared with the reference standards. In 1997, 515 lesions (335 invasive, 60 in situ and 120 benign) in 496 patients were collected from 14 departments in the Central and Northern area of Italy. The 18 indicators were analysed and grouped according to six quality objectives. Some results were good and others were excellent, such as intraoperative identification, breast conservation surgery, adequate axillary procedures and completeness of pathology reports, but most of them failed: waiting times, preoperative diagnosis, employment of frozen section on small lesions and avoiding axillary procedures in ductal carcinoma-in-situ. This work is a first attempt in Italy to evaluate and uniform the criteria adopted for quality control of breast cancer treatment, using a standardised system. Some results are good or excellent, the overall level of compliance with quality indicators is not satisfactory and corrective actions should be undertaken for a number of issues. A continuous monitoring should be performed and appropriate action taken in order to verify the effectiveness of the corrective actions and to provide screen-detected patients with the best quality of care.

Breast Neoplasms↗

Combining human papillomavirus testing or cervicography with cytology to detect cervical neoplasia.

CONTEXT: Cervicography and oncogenic human papillomavirus (HPV) testing have been proposed for improving the accuracy of cervical cancer screening. OBJECTIVE: To examine whether cervicography and HPV testing can improve beyond chance the detection of cervical intraepithelial neoplasia (CIN) 2 or 3 in women with atypical cells of undetermined significance or low-grade squamous intraepithelial lesions on cytology. DESIGN: Cross-sectional analysis. Oncogenic HPV testing by Hybrid Capture II assay or cervicography combined with cytology was compared with the reference standard of colposcopy with directed biopsy. SETTING: Community family practices. PARTICIPANTS: Three hundred four women with low-grade cytologic abnormality. MAIN OUTCOME MEASURES: The gain in accuracy for detecting histologic CIN 2 or 3 or carcinoma. Because an adjunct test may improve sensitivity by chance alone, the sensitivity or specificity if the second test performed randomly was estimated. RESULTS: Cervical intraepithelial neoplasia 2 or 3 was found in 11.8% (36/304) of the women and invasive squamous cell carcinoma in 0.3% (1/304). The sensitivity of cytology for detecting CIN 2 or 3 was 73.0% and increased by 21.6% to 94.6% with the addition of a cervigram showing a low-grade lesion or higher or a positive HPV test result. These gains were reduced to 8.1% and 10.8% above the sensitivities expected if the additional tests performed randomly. The corresponding specificities decreased from 49.1% to 32.2% and 33.0%. There was insufficient power to determine whether observed sensitivities were statistically significantly higher than the expected sensitivities. CONCLUSION: Adjunctive HPV testing or cervicography may provide similar gains in sensitivity, but they can appear misleadingly large if chance increases are not taken into account.

Adult↗

Magnetic resonance cystometry: accurate assessment of bladder volume with magnetic resonance imaging.

OBJECTIVES: To evaluate magnetic resonance hydrometry for the calculation of bladder volume. The reference standard to assess bladder volume is urethral catheterization, which may be linked with the risk of trauma and infection. Hence, ultrasonography is the preferred diagnostic method. However, ultrasonography is investigator dependent and inaccurate in the hands of an inexperienced operator. METHODS: Investigations were performed in a 1.0-Tesla clinical scanner with a manufacturer-provided single-shot turbo spin-echo sequence. We examined 30 healthy volunteers (21 males and 9 females) with a mean age of 26.4 years. To quantify the volume of fluid in a magnetic resonance image, a histogram algorithm was used and a calibration phantom applied. Prevoid and postvoid images were acquired. The bladder volume was calculated as the difference between the prevoid and postvoid image fluid volumes. The magnetic resonance-calculated data were compared with the actually voided volumes. RESULTS: The measured voided bladder volume was 400 +/- 33 mL, whereas magnetic resonance hydrometry yielded 390 +/- 31 mL. The difference between both measurements was not statistically significant. The 95% confidence interval for the difference of both measurements ranged from -22.6 to 2.4 mL. The regression had an r2 of 0.97. CONCLUSIONS: The feasibility of magnetic resonance hydrometry to quantify the bladder volume noninvasively was demonstrated.

Adult↗

Comparison of clinical criteria for the acute respiratory distress syndrome with autopsy findings.

BACKGROUND: The American-European Consensus Conference definition for the acute respiratory distress syndrome (ARDS) has never been validated. OBJECTIVE: To compare clinical criteria for ARDS with autopsy findings. DESIGN: Independent comparison of autopsy findings with clinical characteristics retrospectively abstracted from medical records. SETTING: Tertiary medical-surgical intensive care unit. PARTICIPANTS: 382 patients who underwent clinical autopsy. MEASUREMENTS: Sensitivity, specificity, and likelihood ratios for clinical criteria were calculated in 3 cohorts by using diffuse alveolar damage at autopsy as the reference standard. The 3 cohorts were 1) all patients, 2) patients with any risk factor for ARDS, and 3) patients who were separated according to their pulmonary or extrapulmonary risk factors. RESULTS: 127 patients (33%) met the clinical criteria, and 112 (29%) had diffuse alveolar damage. In all patients, the sensitivity of the clinical definition was 75% (95% CI, 66% to 82%) and the specificity was 84% (CI, 79% to 88%). In 284 patients with risk factors, the sensitivity was 76% (CI, 67% to 83%) and the specificity was 75% (CI, 68% to 81%). Compared with patients with pulmonary risk factors, patients with extrapulmonary risk factors had significantly higher sensitivity (61% vs. 85%; P = 0.009) and the specificity did not statistically significantly differ (69% vs. 78%; P > 0.2). LIMITATIONS: Only patients who died and underwent autopsy could be included in this study, so these results may not apply to less severe cases of ARDS. CONCLUSIONS: In a series of autopsy patients, the accuracy of the American-European Consensus Conference definition of ARDS was only moderate. The definition was more accurate for patients with extrapulmonary risk factors than for patients with pulmonary risk factors.

Aged↗

Pulmonary embolism: diagnosis with spiral CT and ventilation-perfusion scanning--correlation with pulmonary angiographic results or clinical outcome.

PURPOSE: To compare the accuracy of spiral computed tomography (CT) with that of ventilation-perfusion (V-P) scintigraphy in the diagnosis of pulmonary embolism (PE). MATERIALS AND METHODS: Fifty-four patients in whom indeterminate V-P scans or discordant clinical and scintigraphic results were obtained underwent both V-P scanning and contrast material-enhanced spiral CT. The reference standard was pulmonary angiographic results in 26 patients (group I) or clinical outcome in 28 (group II). RESULTS: Six (25%) of 24 group I patients had proved PE. The prospective sensitivity and specificity for segmental or subsegmental PE were 67% and 100%, respectively, and the positive and negative predictive values were 100% and 90%, respectively. In two group II patients, V-P scans had high probability for acute embolism, but spiral CT scans showed only chronic PE; in one patients, the V-P scan had low probability and the CT scan was positive for acute PE. An alternative CT diagnosis was established in four (31%) of 13 patients in whom a normal or low-probability V-P scan was obtained. Clinical outcome was consistent with spiral CT results in all cases. CONCLUSION: Spiral CT has greater accuracy and specificity than V-P scanning in patients with an unresolved diagnosis and may be useful as the primary screening technique for PE.

Acute Disease↗

Immune responses of young mice to pneumococcal type 9V polysaccharide-tetanus toxoid conjugate.

Pneumococcal type 9V polysaccharide (PS), contained in the current pneumococcal vaccine, induces only a weak antibody response in young children and therefore is not an effective vaccine for young children. To increase its immunogenicity, a conjugate of PS to a protein carrier, tetanus toxoid (TT), was prepared. To quantify the immune response, mouse anti-9V PS immunoglobulin G (IgG) and IgM reference standards were established. Young mice immunized at 2 weeks of age produced IgM antibody in response to 9V PS alone or 9V PS conjugated to TT. However, only the 9V PS-TT conjugate induced an IgG antibody response and an anamnestic effect. Thus, a covalent linkage between TT and 9V PS was required for isotype switching from IgM to IgG. 9V PS-TT adsorbed with aluminum hydroxide adjuvant resulted in a fivefold or greater increase in the IgG antibody level. We also studied the effect of maternal immunization on the immune response of young mice to 9V PS-TT. Maternal immunization before mating or before mating and during gestation primed 2-week-old progeny given two injections of 9V PS-TT to produce more IgM antibody than progeny from unimmunized mothers. The IgG antibody level of neonates at birth was similar to that observed in the mothers and was probably passive antibody. These results indicate that maternal immunization with an optimum dose of a PS-protein conjugate before and/or during pregnancy, followed by immunization of the offspring with the conjugate, could provide young children with an enhanced IgM antibody response to pneumococcal PSs.

Age Factors↗

The radiographic quantitation of aortic valve calcification: implications for assessing bioprosthetic valve calcification in vitro.

Calcification of natural aortic and bioprosthetic heart valves is a poorly understood phenomenon that results in valvular obstruction and tissue failure. We describe a non-destructive quantitative computed microtomographic (QCT) technique for determining both calcium content and local calcium distribution within explanted valves. As a reference standard, a dual-energy x-ray absorptiometry (DEXA) system with an accuracy demonstrated to be within 1% of the true calcium mass of test material was used to obtain the total calcium content of 24 human aortic valve cusps recovered at autopsy from patients aged 51-80 years. These cusps were then scanned using our unique volume QCT scanner, with multiple x-ray projections acquired by rotating the explanted tissue through a single axis of rotation. A three-dimensional cross-sectional map was reconstructed for each cusp. Voxel size was 0.003 mm3 and a calibration phantom was used to calculate calcium content. The minimum detection limit for calcium mass was 1 mg within the whole cusp. The DEXA and QCT scans were compared with respect to total calcium content, which ranged from 0 to 15 mg. An excellent correlation between the two independent techniques was demonstrated with an r2 value of 0.94 (p < 0.001). Non-destructive microtomographic CT scanning provided excellent volumetric density measurements, with quantitative 3D images permitting an assessment of any individual area of the cusp for calcium content and spatial distribution. This new approach to valve tissue analysis allows for subsequent histologic assessment.

Absorptiometry, Photon↗

Screening for diabetic retinopathy. The wide-angle retinal camera.

OBJECTIVE: To define the test characteristics of four methods of screening for diabetic retinopathy. RESEARCH DESIGN AND METHODS: Four screening methods (an exam by an ophthalmologist through dilated pupils using direct and indirect ophthalmoscopy, an exam by a physician's assistant through dilated pupils using direct ophthalmoscopy, a single 45 degrees retinal photograph without pharmacological dilation, and a set of three dilated 45 degrees retinal photographs) were compared with a reference standard of stereoscopic 30 degrees retinal photographs of seven standard fields read by a central reading center. Sensitivity, specificity, and positive and negative likelihood ratios were calculated after dichotomizing the retinopathy levels into none and mild nonproliferative versus moderate to severe nonproliferative and proliferative. Two sites were used. All patients with diabetes in a VA hospital outpatient clinic between June 1988 and May 1989 were asked to participate. Patients with diabetes identified from a laboratory list of elevated serum glucose values were recruited from a DOD medical center. RESULTS: The subjects (352) had complete exams excluding the exam by the physician's assistant that was added later. The sensitivities, specificities, and positive and negative likelihood ratios are as follows: ophthalmologist 0.33, 0.99, 72, 0.67; photographs without pharmacological dilation 0.61, 0.85, 4.1, 0.46; dilated photographs 0.81, 0.97, 24, 0.19; and physician's assistant 0.14, 0.99, 12, 0.87. CONCLUSIONS: Fundus photographs taken by the 45 degrees camera through pharmacologically dilated pupils and read by trained readers perform as well as ophthalmologists for detecting diabetic retinopathy. Physician extenders can effectively perform the photography with minimal training but would require more training to perform adequate eye exams. In this older population, many patients did not obtain adequate nonpharmacological dilation for use of the 45 degrees camera.

Diabetic Retinopathy↗