Medical surveillance for antineoplastic-drug handlers

Elements of a medical surveillance program are described, with emphasis on a program for antineoplastic-drug handlers in a hospital setting. There are four data-gathering elements in any medical surveillance program: the history (medical and occupational), the physical examination, laboratory studies, and biological monitoring. Of these, the most useful and cost-effective is the history. The physical examination and laboratory tests should focus on the target organs of the hazardous agent in question. When results of biological monitoring are available for an unexposed control population, results for a group of exposed workers may be interpreted as greater than, similar to, or less than what was expected; thus, groups of unacceptably exposed workers may be identified. For antineoplastic-drug handling, the most important controls are use of a biological-safety cabinet and a worker education program. Estimating the average number of hours of drug handling per shift may serve as a surrogate measure of the potential exposure dose. Health-care professionals examining and testing workers who handle antineoplastic agents should give special emphasis to the skin and the hematopoietic, hepatic, renal, and urinary systems. Because of problems with assay sensitivity, cost, and interpretation of results, biological monitoring is not considered necessary in every medical surveillance program for antineoplastic-drug handlers. The Occupational Safety and Health Administration currently recommends that a permanent registry be maintained of all employees who routinely handle antineoplastic agents. Because of their opportunity for exposure to potentially hazardous drugs, pharmacy professionals should take a leading role in establishing surveillance programs that complement existing drug-handling practices and worker education programs.     

Hepatic artery thrombosis resulting in gas gangrene of the transplanted liver.

Early hepatic artery thrombosis after orthotopic liver transplantation results in massive injury to hepatocytes and the bile duct epithelium. In the fulminate form, impaired liver synthetic function is expressed by encephalopathy and coagulopathy. Ischemic bile duct injury is associated with the disruption of the biliary anastomosis, bile duct strictures, and intrahepatic bilomas. The inability of the liver macrophages to clear translocated portal blood intestinal pathogens results in persistent bacteremia and sepsis. The major radiologic finding is the radiographic evidence of gas gangrene of the liver graft. Early recognition and correct interpretation of the radiologic findings, immediate removal of the liver graft, and placement of the patient on venous-venous bypass or total hepatic devascularization while a new liver is being procured and retransplantation are the only hope for survival.     

Association of SULT1A1 phenotype and genotype with prostate cancer risk in African-Americans and Caucasians.

Exposure to heterocyclic amines may increase prostate cancer risk. Human sulfotransferase 1A1 (SULT1A1) is involved in the bioactivation of some dietary procarcinogens, including the N-hydroxy metabolite of the food-borne heterocyclic amine, 2-amino-1-methyl-6-phenylimidazo(4,5-b) pyridine. This study compares a polymorphism in the SULT1A1 gene, SULT1A1 enzyme activity, meat consumption, and the risk of prostate cancer in a population based case-control study. Prostate cancer patients (n = 464) and control individuals (n = 459), frequency matched on age and ethnicity, provided informed consent, answered a survey, and provided a blood sample. Platelets were isolated for phenotype analysis, and DNA was isolated from lymphocytes for genotype determination. Meat consumption was assessed using a dietary questionnaire. Caucasians homozygous for the SULT1A1*1 high activity allele were at increased risk for prostate cancer [odds ratio (OR), 1.68; 95% confidence interval (CI), 1.05-2.68] compared with individuals homozygous for the low-activity allele. The association between SULT1A1 genotype and prostate cancer risk in African-Americans did not reach significance (OR, 1.60; 95% CI, 0.46-5.62). When SULT1A1 activity was considered, there was a strong association between increased SULT1A1 activity and prostate cancer risk in Caucasians (OR, 3.04; 95% CI, 1.8-5.1 and OR, 4.96; 95% CI, 3.0-8.3, for the second and third tertiles of SULT1A1 activity, respectively) compared with individuals in the low enzyme activity tertile. A similar association was also found in African-American patients, with ORs of 6.7 and 9.6 for the second and third tertiles of SULT1A1 activity (95% CI, 2.1-21.3 and 2.9-31.3, respectively). When consumption of well-done meat was considered, there was increased risk of prostate cancer (OR, 1.42; 95% CI, 1.01-1.99 and OR, 1.68; 95% CI, 1.20-2.36 for the second and third tertiles, respectively). When SULT1A1 activity was stratified by tertiles of meat consumption, there was greater risk of prostate cancer in the highest tertile of meat consumption. These results indicate that variations in SULT1A1 activity contributes to prostate cancer risk and the magnitude of the association may differ by ethnicity and be modified by meat consumption.     

Efficacy of engineering controls in reducing occupational exposure to aerosolized pentamidine.

Aerosolized pentamidine administration may pose potential risks to health care workers exposed to fugitive drug and to infectious respiratory pathogens (eg, tuberculosis) generated by pentamidine-induced cough. Classic infection control methods may be applied to this problem, although the effectiveness of these measures in mitigating environmental pentamidine exposure is unknown. Lack of data fully characterizing pentamidine's mechanism of action or potential mutagenicity, carcinogenicity, or teratogenicity raises concern and suggests worker exposed and environmental contamination be minimized. We report herein on the efficacy of an aerosol containment hood in containing fugitive pentamidine aerosol during administration.     

Hodgkin lymphoma patients in first remission: routine positron emission tomography/computerized tomography imaging is not superior to clinical follow‐up for patients with no residual mass

There is no consensus regarding optimal follow‐up mode for Hodgkin lymphoma (HL) patients that achieve complete remission following chemotherapy or combined chemo‐ and radiation therapy. Several studies demonstrated high sensitivity of positron emission tomography/computerized tomography (PET/CT) in detecting disease progression; however, these techniques are currently not recommended for routine follow‐up. This retrospective study conducted in two Israeli (N = 291) and one New Zealand academic centres (N = 77), compared a group of HL patients, followed‐up with routine imaging every 6 months during the first 2 years after achieving remission, once in the third year, with additional dedicated studies performed due to symptoms or physical findings (Group I) to a group of patients without residual masses who underwent clinically‐based surveillance with dedicated imaging upon relapse suspicion (Group II). Five‐year overall survival (OS) was 94% and median time to relapse was 8·6 months for both modes. Relapse rates in Groups I and II were 13% and 9%, respectively. During the first 3 years of follow‐up, 47·5 and 4·7 studies were performed per detected relapse in Groups I and II, respectively. The current study demonstrated no benefit in either progression‐free survival (PFS) or OS in HL patients followed by routine imaging versus clinical follow‐up. The cost was 10 times higher for routine imaging.     

Impulse oscillometry measurement of distal airways obstruction in depleted uranium‐exposed Gulf War veterans

Introduction

A cohort of Gulf War I veterans who sustained exposure to depleted uranium undergoes biennial surveillance for potential uranium‐related health effects. We performed impulse oscillometry and hypothesized that veterans with higher uranium body burdens would have more obstructive abnormalities than those with lower burdens.

Methods

We compared pulmonary function of veterans in high versus low urine uranium groups by evaluating spirometry and oscillometry values.

Results

Overall mean spirometry and oscillometry resistance values fell within the normal ranges. There were no significant differences between the high and low uranium groups for any parameters. However, more veterans were classified as having obstruction by oscillometry (42%) than spirometry (8%).

Conclusions

While oscillometry identified more veterans as obstructed, obstruction was not uranium‐related. However, the added sensitivity of this method implies a benefit in wider surveillance of exposed cohorts and holds promise in identifying abnormalities in areas of the lung historically described as silent.