Comparison of human papilloma virus testing and spectroscopy combined with cervical cytology for the detection of high-grade cervical neoplasia.

OBJECTIVE: This study compared the performance of cervical cytology plus human papilloma virus testing (Pap + HPV) or cervical spectroscopy (Pap + CS) for identifying high-grade cervical neoplasia in a high-risk population of women referred for colposcopy. MATERIALS AND METHODS: Each of 113 subjects underwent spectroscopy, thin-layer cytology, HPV testing, colposcopy, biopsy when indicated, and/or endocervical curettage. Evaluable data for analysis were collected for 102 of the subjects. Sensitivity and specificity were calculated for both strategies. RESULTS: Pap + HPV and Pap + CS achieved equivalent sensitivities (95%) for high-grade lesions, with both detecting 17 of 18 histology confirmed cervical intraepithelial neoplasia (CIN) 2+ lesions. Pap + HPV had a specificity of only 27.4% compared with 65.5% for Pap + CS (p < .0001). CONCLUSIONS: Spectroscopic interrogation of the cervix is equally sensitive and 2-fold more specific than HPV testing when combined with cervical cytology for identifying high-grade cervical neoplasia.

Spectroscopic imaging as a triage test for cervical disease: a prospective multicenter clinical trial.

OBJECTIVE: The objective of the study was to evaluate the potential safety and effectiveness of tissue spectroscopy for the diagnosis of cervical cancer in a prospective multicenter study of women scheduled for colposcopy on the basis of an abnormal Pap test or other risk factor. MATERIALS AND METHODS: Five hundred seventy-two women underwent spectroscopy of the cervix during their colposcopy visit. Spectroscopy measurements taken over a scan period of 4 minutes and 30 seconds were integrated by a cross-validated pattern recognition model and compared with biopsy results to yield sensitivity and specificity of cervical spectroscopy. RESULTS: The median age of subjects enrolled in the study was 27.7 years. The sensitivity of cervical spectroscopy was 95.1% with a corresponding 55.2% specificity for benign lesions. Several potential confounding factors (eg, mucous, blood, patient motion, ambient light) were examined to determine their potential impact on the accuracy of the test. Ambient light seemed to have the greatest effect, but no single factor contributed significantly to the results. The subjects did not experience any adverse events from undergoing the test. CONCLUSIONS: Spectroscopy of the cervix has the potential to accurately detect cervical moderate and high-grade dysplasia while also reducing the false-positive rate for benign cervices. The test is relatively simple to implement and was well accepted by subjects enrolled in the study.

Minimally invasive sampling of transdermal body fluid for the purpose of measuring insulin-like growth factor-I during exercise training.

Insulin-like growth factor-I (IGF-I) is a ubiquitous hormone that is secreted in both an endocrine and an autocrine/paracrine manner. IGF-I has conventionally been measured in serum; however, transdermal body fluid (TDF) remains as an unexplored biocompartment in which IGF-I also resides and may be more biologically relevant because of its proximity to tissues and cells. The purpose of this study was to compare IGF-I in serum versus IGF-I in TDF before and after 8 weeks of physical training. Twenty-eight healthy men (28 +/- 5 years old, 176 +/- 8 cm tall, weighing 83 +/- 11 kg) had TDF obtained by a novel, minimally invasive method that included the application of continuous vacuum pressure on forearm skin perforated with tiny micropores created by a focused beam from a laser system and also had blood obtained by venipuncture. An enzyme-linked immunosorbent assay measured total IGF-I concentrations. A repeated-measures analysis of variance (biocompartment x time) and Pearson Product Moment Correlation coefficients (P < or = 0.05) were used for statistical analyses. Data are presented as mean +/- SE. Total TDF IGF-I was significantly lower than serum IGF-I both before (TDF, 91 +/- 6 ng/mL; serum, 375 +/- 17 ng/mL) and after (TDF, 83 +/- 5 ng/mL; serum, 363 +/- 19 ng/mL) the exercise training. Serum and TDF IGF-I values were not significantly different pre- to post-training. Serum and TDF IGF-I levels were significantly correlated pre-training (r = 0.41), but not post-training (r = 0.34). The percent change between serum and TDF was not correlated (r = 0.09). This study has demonstrated that total IGF-I can be sampled and measured in TDF via a minimally invasive manner and is appreciably (approximately 76%) less than total IGF-I measured in serum. Additionally, the IGF-I measurements in these two biocompartments were not closely associated, possibly indicating an uncoupled, rather than a linked, regulation of IGF-I among the body's biocompartments.

Real-time glucose sensing using transdermal fluid under continuous vacuum pressure in children with type 1 diabetes.

BACKGROUND: This study was designed to evaluate the accuracy and tolerance in children of an experimental device for continuous glucose monitoring. This real-time glucose sensing (RTGS) system measures transdermal fluid glucose through micropores in the stratum corneum that are kept open by continuous vacuum pressure. DESIGN AND METHODS: A comparison of self-monitored blood glucose values and RTGS values was obtained in 110 children with type 1 diabetes ranging in age from 2 to 18 years. The RTGS system was worn for two periods of 48-56 h each. Children went home and had no restrictions in diet during the data collection period. Physical activity also was not restricted, with the exception of swimming or other water immersion that would interfere with or damage the RTGS. RESULTS: The procedure for obtaining transdermal fluid was well tolerated, and adequate flow was maintained out to 48 h or more in most study participants. Comparison of RTGS glucose and self-measured glucose paired values (3,064 values) indicated 69% within Clarke Error Grid Zone A and 21% within Grid Zone B when device tracking was maintained. Errors in tracking occurred with displacement of the vacuum device, or damage to the glucose sensor. CONCLUSIONS: Transdermal fluid glucose measurements using a prototype device system were well tolerated by children with type 1 diabetes and showed good correlation with concomitant capillary glucose blood measurements. Changes in glucose as tracked by the RTGS system appeared accurate. The durability of the prototype system will need improvement.

Optical imaging of the cervix.

Recent advances in fiber optics, sources and detectors, imaging, and computer-controlled instrumentation have stimulated a period of unprecedented growth in the development of photonics technologies for a wide variety of diagnostic and therapeutic clinical applications. These include the application of quantitative optical spectroscopy and imaging for the detection of precancerous lesions in the uterine cervix, a topic of interest at the Second International Conference on Cervical Cancer, which was held April 11-14, 2002. Investigators have applied the Littenberg method of emerging technology assessment to new optical methods used to detect cervical neoplasia. Currently, such technologies as fluorescence spectroscopy (the combination of fluorescence and diffuse reflectance spectroscopy), tri-modal spectroscopy, and light-scattering spectroscopy that probe the spectral characteristics of tissue are being investigated. Optical technologies that create images of subcellular structure without biopsy subsequent to pathology that currently are under investigation include in vivo confocal imaging and optical coherence tomography. Numerous small studies have demonstrated the potential of these optical technologies. What remains to be elucidated are the fundamental biophysical origins of variations in remitted optical signals between normal and dysplastic tissue. Large multicenter randomized controlled trials are needed to confirm the detection and imaging capabilities of optical technology. Furthermore, the development of contrast agents that could boost detection with these technologies is needed, and basic biologic characterization of signals should be pursued. Applying the Littenberg assessment will help ensure that superior, not simply alternative, technologies are implemented.

Glucose sensing in transdermal body fluid collected under continuous vacuum pressure via micropores in the stratum corneum.

Application of continuous vacuum pressure on skin perforated with tiny micropores created by a focused beam from a low-cost laser system can result in access to a clear, transdermal body fluid (TDF) for the continuous measurement of glucose in vivo. Two clinical studies were performed to assess the feasibility of this approach. In the first study, 56 diabetic subjects were porated on either the arm or abdomen, and glucose was measured in their TDF using a custom assay system contained in a patch that was affixed to the skin above the poration site. The continuous readings of glucose in TDF were compared with fingerstick blood measured every half-hour over a 2-day period, resulting in 1,167 paired data points that yielded a correlation of 0.8745 with 97.75% of the readings in the Clarke Error Grid A and B zones. In a second study, 187 diabetic and 65 nondiabetic subjects had glucose measurements from their TDF made using a commercially available glucose strip and meter. A total of 4,059 data pairs (discrete TDF and capillary blood) were collected over a 2-day period, resulting in a correlation of 0.946 with 99% of the readings in the Clarke Error Grid A and B zones. These studies indicate that TDF drawn through micropores in the stratum corneum of the skin potentially can provide a lesser invasive and continuous method of measuring glucose in diabetic individuals.