BackgroundSeveral epidemiologic studies have suggested an association between Parkinson’s disease (PD) and exposure to heavy metals using subjective exposure measurements.ObjectivesWe investigated the association between objective chronic occupational lead exposure and the risk of PD.MethodsWe enrolled 121 PD patients and 414 age-, sex-, and race-, frequency-matched controls in a case–control study. As an indicator of chronic Pb exposure, we measured concentrations of tibial and calcaneal bone Pb stores using 109Cadmium excited K-series X-ray fluorescence. As an indicator of recent exposure, we measured blood Pb concentration. We collected occupational data on participants from 18 years of age until the age at enrollment, and an industrial hygienist determined the duration and intensity of environmental Pb exposure. We employed physiologically based pharmacokinetic modeling to combine these data, and we estimated whole-body lifetime Pb exposures for each individual. Logistic regression analysis produced estimates of PD risk by quartile of lifetime Pb exposure.ResultsRisk of PD was elevated by > 2-fold [odds ratio = 2.27 (95% confidence interval, 1.13–4.55); p = 0.021] for individuals in the highest quartile for lifetime lead exposure relative to the lowest quartile, adjusting for age, sex, race, smoking history, and coffee and alcohol consumption. The associated risk of PD for the second and third quartiles were elevated but not statistically significant at the α = 0.05 level.ConclusionsThese results provide an objective measure of chronic Pb exposure and confirm our earlier findings that occupational exposure to Pb is a risk factor for PD.

No abstract

Loss of heterozygosity (LOH) in chromosomal regions that harbor tumor suppressor genes from tumor tissue may lead to decreased survival time in cancer patients with squamous cell carcinoma of the head and neck (HNSCC). We studied 8 regions frequently lost in HNSCC in 150 patients having a primary diagnosis of HNSCC. Tumor and normal tissue DNA were genotyped for microsatellite repeat markers in 8 unlinked chromosomal regions. The association between LOH and death from HNSCC was investigated, weighted by number of informative markers per region and adjusted for age at diagnosis, self-reported race, tumor stage and current smoking status. LOH at 3 chromosomal regions were independently associated with reduced survival. A greater risk for cancer mortality was observed for LOH at chromosomal regions 3p24. Cure rates for patients with squamous cell carcinoma of the head and neck (HNSCC) are low. According to Surveillance, Epidemiology and End Results (SEER) data, the 5-year survival rate for cancers of the larynx is 65.9% and for cancers of the oral cavity and pharynx only 58.8%. 1 Few reliable postdiagnosis prognostic indicators exist. TNM tumor staging, which incorporates information regarding the size of the tumor (T) as well as descriptions of the regional nodes (N) and distant metastases (M), is the most common clinical method for assessing prognosis and aides the clinician in the selection of an appropriate treatment regimen for the individual patient. 2 To illustrate, SEER 5-year survival rates decrease from 81.9% for localized to 46.7% for regional and 23.4% for distant metastatic tumors of the pharynx and oral cavity with a similar trend seen in laryngeal tumors: 82.0%, 51.0% and 37.7%, respectively. 1 Although SEER data demonstrate the strong correlation between tumor stage and survival, there is much variation in outcome within each tumor stage that remains unresolved.Other established clinical factors that contribute to the treatment decision-making process include tumor site, pathologic grading of differentiation, performance status and overall treatment time. 3,4 Nevertheless, such indicators alone do not adequately predict outcome. Additional patient-specific prognostic indicators, such as genetic biomarkers, are needed to allow the physician to better identify those who are most likely to benefit from aggressive therapy. 5 Loss of heterozygosity (LOH) at specific markers may offer additional prognostic information to aid in the selection of an appropriate treatment course.Numerous genetic changes accumulate in HNSCC tumors, but the relative importance of specific genetic sites to patient survival remains uncertain. Our previous work had shown a high frequency of cytogenetic abnormalities, most commonly visible chromosomal deletions, at the following 8 chromosomal regions: 3p14. 2-p13, 3p24.3-p14.3, 5q11.2-q31.3, 8p21.3-11.21, 9p21-p24, 10p12.1-p11.22, 18q12.3-q23 and 21q21.1-q22.2. 6 We continue this work by examining allelic loss at the molecular level. Several of these regions have been supported ...

Pharmacy data help locate tuberculosis cases and assess their management.