Low-level environmental lead exposure may accelerate progressive renal insufficiency in patients without diabetes who have chronic renal disease. Repeated chelation therapy may improve renal function and slow the progression of renal insufficiency.

Abstract. Previous retrospective research suggests that lowlevel environmental lead exposure is associated with an acceleration of age-related impairment of renal function. For elucidating the long-term relationship between low-level environmental lead exposure and progression of chronic renal diseases in patients without diabetes, 121 patients who had chronic renal insufficiency, a normal body lead burden (BLB), and no history of exposure to lead were observed prospectively for 48 mo. Associations of both BLB and blood lead level (BLL) with renal function were evaluated, with reference to other covariates. The primary end point was an increase in the serum creatinine level to double the baseline value. Sixty-three patients had BLB Ն80 g and Ͻ600 g (high-normal group), and 58 patients had BLB Ͻ80 g (low-normal group). The primary end point occurred in 17 patients. Fifteen of them had high-normal BLB, whereas two patients had low-normal BLB (hazard ratio [95% confidence interval]: 1.01 [1.00 to 1.01] for each increment of 1 g; P ϭ 0.002). The BLB and BLL at baseline were the most important risk factors to predict progression of renal insufficiency. Each increase of 10 g in the BLB or 1 g/dl in the BLL reduced the GFR by 1.3 (P ϭ 0.002) or 4.0 ml/min (P ϭ 0.01) during the study period. In conclusion, low-level environmental lead exposure is associated with accelerated deterioration of renal insufficiency. Even at levels far below the normal ranges, both increased BLL and BLB predict accelerated progression of chronic renal diseases.A high occupational lead exposure is well documented to be able to induce nephropathy (1,2). Several studies have indicated a strong association between blood lead levels (BLL) and agerelated decline in renal function of the general population (3-6). However, these studies either were retrospective or did not adjust other confounding factors that affect the progression of renal function, such as hypertension, urinary protein excretion, and usage of angiotensin-converting enzyme (ACE) inhibitors.Furthermore, most of these studies measured BLL as an indicator of lead exposure. However, the BLL reflects recent lead exposure rather than the actual body lead burden (BLB). Calcium disodium EDTA mobilization tests and bone x-ray fluorescence studies are the most reliable methods for measuring the BLB (7). A BLB of Ͼ600 g (2.9 mol), as assessed by calcium disodium EDTA mobilization tests, indicates lead poisoning. The authors' previous studies, using EDTA-mobilization tests to assess the BLB, suggested that low-level environmental lead exposure may be associated with the progression of renal insufficiency in patients without known lead exposure (8 -10). Our recent work further established that repeated chelation therapy to reduce the BLB may slow the progression of renal insufficiency in a 27-mo clinical trial (11). However, the long-term relationship between low-level environmental lead exposure and the progression of chronic renal diseases remains unknown. A 48-mo prospective longitudinal stu...

We report a fully quantitative spectroscopy imaging instrument for wide area detection of early cancer (dysplasia). This instrument provides quantitative maps of tissue biochemistry and morphology, making it a potentially powerful surveillance tool for objective early cancer detection. We describe the design, construction, calibration, and first clinical application of this new system. We demonstrate its accuracy using physical tissue models. We validate its diagnostic ability on a resected colon adenoma, and demonstrate feasibility of in vivo imaging in the oral cavity.

No abstract

Long-term low-level environmental lead exposure may subtly affect progressive renal insufficiency in the general population. Progressive renal insufficiency may be improved for at least 1 year after lead chelating therapy. Further investigations are needed to clarify this observation.

Studies indicate that environmental exposure to lead is associated with reduced renal function. Whether lead affects progressive diabetic nephropathy is unclear. Eighty-seven patients with type II diabetes and diabetic nephropathy (serum creatinine of 1.5-3.9 mg/dl) with normal body lead burden and no lead exposure history were observed over a 12-month period. Thirty subjects with high normal body lead burdens (80-600 microg) were randomly assigned to a chelation and control group. For 3 months, the 15 chelation-group patients underwent lead-chelation therapy with calcium disodium ethylenediaminetetraacetic acid weekly until body lead burden fell <60 microg, and the 15 control group subjects received a weekly placebo. During the following 12 months, renal function was regularly assessed at 3-month intervals. The primary outcome was an elevation of serum creatinine to 1.5 times baseline value during the observation period. A secondary outcome was temporal changes in renal function following chelation therapy. Twenty-six patients achieved the primary outcome. Basal blood lead levels and body lead burden were the most important risk factors in predicting progressive diabetic nephropathy. Following chelation, the rates of decline in glomerular filtration rates in the chelation group and the control group, respectively, were 5.0+/-5.7 ml and 11.8+/-7.0 ml/min/year/1.73 m(2) of body surface area (P=0.0084) during follow-up, although both groups had similar rates of progression of renal function during the 12-month observation period. We concluded that low-level environmental lead exposure accelerates progressive diabetic nephropathy and lead-chelation therapy can decrease its rate of progression.

In order to evaluate the impact of anatomy on the spectral properties of oral tissue, we used reflectance and fluorescence spectroscopy to characterize nine different anatomic sites. All spectra were collected in vivo from healthy oral mucosa. We analyzed 710 spectra collected from the oral cavity of 79 healthy volunteers. From the spectra, we extracted spectral parameters related to the morphological and biochemical properties of the tissue. The parameter distributions for the nine sites were compared, and we also related the parameters to the physical properties of the tissue site. k- Means cluster analysis was performed to identify sites or groups of sites that showed similar or distinct spectral properties. For the majority of the spectral parameters, certain sites or groups of sites exhibited distinct parameter distributions. Sites that are normally keratinized, most notably the hard palate and gingiva, were distinct from nonkeratinized sites for a number of parameters and frequently clustered together. The considerable degree of spectral contrast (differences in the spectral properties) between anatomic sites was also demonstrated by successfully discriminating between several pairs of sites using only two spectral parameters. We tested whether the 95% confidence interval for the distribution for each parameter, extracted from a subset of the tissue data could correctly characterize a second set of validation data. Excellent classification accuracy was demonstrated. Our results reveal that intrinsic differences in the anatomy of the oral cavity produce significant spectral contrasts between various sites, as reflected in the extracted spectral parameters. This work provides an important foundation for guiding the development of spectroscopic-based diagnostic algorithms for oral cancer.

There continues to be a significant clinical need for rapid and reliable intraoperative margin assessment during cancer surgery. Here we describe a portable, quantitative, optical fiber probe-based, spectroscopic tissue scanner designed for intraoperative diagnostic imaging of surgical margins, which we tested in a proof of concept study in human tissue for breast cancer diagnosis. The tissue scanner combines both diffuse reflectance spectroscopy (DRS) and intrinsic fluorescence spectroscopy (IFS), and has hyperspectral imaging capability, acquiring full DRS and IFS spectra for each scanned image pixel. Modeling of the DRS and IFS spectra yields quantitative parameters that reflect the metabolic, biochemical and morphological state of tissue, which are translated into disease diagnosis. The tissue scanner has high spatial resolution (0.25 mm) over a wide field of view (10 cm×10 cm), and both high spectral resolution (2 nm) and high spectral contrast, readily distinguishing tissues with widely varying optical properties (bone, skeletal muscle, fat and connective tissue). Tissue-simulating phantom experiments confirm that the tissue scanner can quantitatively measure spectral parameters, such as hemoglobin concentration, in a physiologically relevant range with a high degree of accuracy (<5% error). Finally, studies using human breast tissues showed that the tissue scanner can detect small foci of breast cancer in a background of normal breast tissue. This tissue scanner is simpler in design, images a larger field of view at higher resolution and provides a more physically meaningful tissue diagnosis than other spectroscopic imaging systems currently reported in literatures. We believe this spectroscopic tissue scanner can provide real-time, comprehensive diagnostic imaging of surgical margins in excised tissues, overcoming the sampling limitation in current histopathology margin assessment. As such it is a significant step in the development of a platform technology for intraoperative management of cancer, a clinical problem that has been inadequately addressed to date.