Assessment of the environmental fate and ecotoxicity of N,N-diethyl-m-toluamide (DEET).

N,N-diethyl-m-toluamide (DEET) is a key active ingredient in many insect repellents available commercially throughout the world. Owing to its popularity among consumers for nearly 30 years, considerable work conducted in the past has demonstrated-and continues to demonstrate-that human exposure to DEET poses no significant health risk to the general population. The results of several studies reported in this paper describe more recent work to understand the environmental fate of DEET, particularly in surface waters and soil, and the potential hazards to aquatic and terrestrial organisms. In summary, DEET enters the environment through several pathways: directly into air during spray application; to surface water from overspray and indirectly via wastewater treatment plant (WTTP) discharges (as a result of washing of skin and laundering of clothing); or to soil via overspray and application of treated sewage as an amendment. Multimedia environmental fate modeling predicts that DEET entering the environment is retained either in receiving waters (∼79%) or in soil (∼21%). Based on its physicochemical properties, DEET is expected to be moderately mobile in the soil column. In surface waters and soil, DEET degrades at a moderate to rapid rate (its half-life is measured in days to weeks). The small amounts of DEET retained in air are subject to rapid photo-oxidation via hydroxyl radical-mediated degradation or, if in droplet form, gravitational settling to soil or water. DEET does not interfere with ozone formation in the upper atmosphere. The bioaccumulation potential of DEET is low; it is neither a persistent, bioaccumulative toxicant nor a persistent organic pollutant. Among aquatic species, acute effect concentrations range between 4 and 388 mg/L. The chronic no-observed effect concentrations (NOEC) for daphnids and green algae range from approximately 0.5 to 24 mg/L. Measured concentrations of DEET in surface waters are several hundreds to thousands of times lower than the lowest NOEC measured, and thus the probability for adverse effects to environmental species is low. A separate paper by Aronson et al. (this issue) supports this conclusion by quantitatively exploring the risks to the aquatic environment using a combination of monitoring data and exposure modeling.

Use of hematopoietic colony-stimulating factors: comparison of the 1994 and 1997 American Society of Clinical Oncology surveys regarding ASCO clinical practice guidelines. Health Services Research Committee of the American Society of Clinical Oncology.

PURPOSE: The American Society of Clinical Oncology (ASCO) Health Services Research Committee sought to assess whether more appropriate patterns of colony-stimulating factor (CSF) use occurred after the publication of ASCO evidence-based practice guidelines in 1994 and 1996 for patients with solid tumors or lymphoma. METHODS: In 1994 and 1997, questionnaires describing clinical scenarios were mailed to ASCO members who practiced medical oncology. Physicians were asked the extent to which they preferred to use a CSF for primary prophylaxis, secondary prophylaxis, or treatment of neutropenic complications. Multiple regression analyses were used to determine predictors of overall propensity to use CSFs and, when using a CSF, propensity to support longer schedules of CSF use. RESULTS: Decreased use of CSFs was shown in the following situations: (1) treatment for febrile neutropenia without localizing signs (39% in 1994 v 29% in 1997) or with a right lower lobe infiltrate (54% v 46%); (2) primary prophylaxis with paclitaxel for ovarian cancer (20% v 11%) or cyclophosphamide, doxorubicin, and vincristine chemotherapy for small-cell lung cancer (8.4% v 4.6%); and (3) secondary prophylaxis after afebrile neutropenia following chemotherapy for germ cell tumors (44.5% v 36.0%). One third fewer physicians supported the extended use of CSFs until an absolute neutrophil count >/= 10,000/mm(3) or a WBC count >/= 10,000/mm(3) was reached, both counts serving as criteria for stopping CSF therapy. However, we observed high rates of CSF use despite ASCO guideline recommendations against use in the following clinical situations: (1) primary prophylaxis in patients at low risk of febrile neutropenia (6% v 16%); (2) secondary prophylaxis late in the course of curative and palliative therapy (80% v 53%); and (3) treatment of afebrile and uncomplicated febrile neutropenia (30% v 60%). In 1994 and 1997, fee-for-service physicians were more likely than other physicians to prefer use of CSF support while maintaining treatment dose and schedule instead of using dose-reduction strategies, and, when using a CSF, they were more likely to support longer CSF treatment schedules (P <.05 for both scenarios). CONCLUSION: Decreased use and more appropriate use of CSFs in accordance with ASCO guideline recommendations occurred from 1994 to 1997, but there remain many opportunities to reduce CSF use with no clinical harm. Many oncologists continue to support the use of CSFs in scenarios and with scheduling criteria that the guidelines and evidence do not support. ASCO's evidence-based guidelines should be linked with formal continuous quality improvement initiatives to substantially improve the quality of supportive oncology care.

Health policy for the aged. We don't study the right people.

A review of articles on aging published during one year in seven major U.S. journals in the fields of general medicine, public health and gerontology showed that only a minority of studies took into consideration the factual attributes of the population. Only 53% of the articles included any basic demographic information, usually age. Race was mentioned in 37%, but only 3% studied blacks or Hispanics; socioeconomic status was given in 25%, marital status in 9%, and education in 19%. Regardless of whether demographic factors were detailed in the description of the study, they were rarely used in the analysis. We conclude that information obtained in the course of studies of the elderly may not reflect the actual needs of this population group which must be recognized as heterogeneous. More specific and refined data are needed to set priorities and make policy decisions.

Assessment of fine-needle aspiration sampling technique in thyroid nodules.

BACKGROUND: A prospective two-yr study was undertaken to assess the heterogeneity of thyroid nodules using the fine-needle aspiration (FNA) technique of systematic regional sampling. In addition, we determined the number of regions to be sampled to minimize non-diagnostic results, and to optimally characterize thyroid nodules. DESIGN: FNA was performed on 74 nodules > or = 1.5 cm. in diameter in five distinct regions in sequence (center, then four quadrants starting at 12:00, clockwise). Slides from each region were coded, randomized, subjected to blind review, and categorized as non-diagnostic (ND), benign (B), indeterminate (ID), suspicious/neoplastic (S/N), or malignant (M). Final cytologic diagnosis (CD) was made from all slides of each nodule. RESULTS: The ND rate for center FNAs alone was 16%, but addition of the 12:00 region decreased it to 5.3%. With 3, 4, or 5 sequential sites the nondiagnostic rates were 4, 2.6, and 2.6%. The center region diagnosis was identical to the final CD in 71% of the cases. Addition of the 12:00 region increased the concordance to 88%. Three sequential regions equaled the CD in 93% of cases, and 4 regions equaled the CD in 99% of cases. All nodules characterized as M or S/N were resected as were 76% of the ID nodules. Of the 43 nodules characterized as B, 3 were resected, 24 involuted, 6 were unchanged, and 10 were lost to follow-up. All 3 M nodules proved malignant by histology, as did 7/10 S/N, 0/17 ID, and 0/43 B nodules; 3/10 S/N, 1/17 ID and 1/43 B were adenomas. Likelihood ratios for diagnosing neoplasia were ND:0, B:0.10, ID:0.21, S/N:infinity, M:infinity. CONCLUSIONS: Sampling of at least four distinct regions accurately assesses thyroid nodules while minimizing ND results. Regional sampling also addresses intranodular heterogeneity.

Giant adrenal myelolipoma.

Adrenal myelolipomas are nonfunctioning benign tumors composed of hematopoietic elements and mature adipose tissue. These tumors usually remain small and asymptomatic; occasionally, however, they reach massive proportions and become symptomatic. To date, only two giant adrenal myelolipomas (>4,000 g) have been described in the literature. We describe the diagnostic evaluation and the operative management of the third largest adrenal myelolipoma reported.

Etiologies for non-correlating cervical cytologies and biopsies.

To investigate the etiologies for discrepancies between cervicovaginal smear and corresponding cervical biopsy results, 615 patients with cytologic diagnoses of dysplasia or malignancy during 1 year were reviewed. Sixty-nine patients (11%) were identified in which the cytologic and histologic diagnoses differed. Utilizing an algorithm developed for the study, these cases were assigned an etiologic category for discrepancy: colposcopic biopsy or cytologic sampling, cytologic screening, histotechnical processing, histologic or cytologic interpretation. The most common cause for a discrepancy was colposcopic biopsy sampling (36 cases, 51%). There were nine errors (13%) in biopsy interpretation, with seven underdiagnoses and two overdiagnoses. Eight errors (11%) in cytologic interpretation occurred with half of these representing underdiagnoses. The other causes for discrepancy were less common--cytologic sampling (6 cases), histotechnical processing (3 cases), cytologic screening (2 cases), and a combination of factors (5 cases). Use of this algorithm allows laboratories to identify problem areas and design specific corrective protocols to improve diagnostic accuracy and patient care.

Malignant joint effusions secondary to solid tumor metastasis.

We describe the case of a patient with breast cancer who developed bilateral malignant knee effusions, and review the English language literature. Patients with solid tumors who develop malignant joint effusions are rare; 27 cases have been reported (including our patient). The knee is the predominant site of joint involvement (p < 0.001). Synovial fluid (SF) analysis often demonstrates noninflammatory bloody effusion. Synovial biopsy was positive in 11 of 16 cases in which it was performed. SF cytology was positive in one half of cases in which it was obtained. Arthritis secondary to metastasis is a poor prognostic finding. A strong clinical suspicion is necessary to make the diagnosis; SF cytology or synovial biopsy can confirm it.

Assessment of cervicovaginal smear adequacy. The Bethesda System guidelines and reproducibility.

Criteria for assessing adequacy of cervicovaginal smears according to the Bethesda System include cellular composition and quantity, specimen preservation, fixation, and absence of obscuring elements. The reproducibility of adequacy assessment using these parameters was the focus of this study. Specimens were chosen to include a wide spectrum of clinical history and adequacy interpretations, but excluded cases with epithelial abnormalities and those judged "limited" because of insufficient transformation zone component. The 114 specimens were independently evaluated twice by five reviewers, with interceding randomization. Full interobserver concordance was obtained in 50.4% of cases, with consensus reached by three or more observers in 97.4% of cases. Of 2280 paired interpretations, 74% (1692) concurred. Pairwise kappa values for interobserver agreement ranged from .71 to .54 (very good to fair), with overall kappa = .61. Interobserver agreement for each category was near excellent for "satisfactory" (kappa = .73), good for "unsatisfactory" (kappa = .63), and only fair for "satisfactory but limited" (kappa = .48). Paired intraobserver reproducibility (agreement for two separate readings by the same observer) ranged from 69% to 77% (average, 74%), with good to fair kappa values (.66-.51). These findings indicate that the specimen adequacy guidelines of the Bethesda System provide good inter- and intraobserver reproducibility. The "satisfactory but limited" category appears to show the lowest concordance. Problem areas include evaluation of adequate minimum cellularity and estimation of number of cells obscured.

Mediastinal dissection and reconstruction for recurrent Hürthle cell carcinoma of the thyroid.

A 69-year-old man presented with recurrent Hürthle cell carcinoma of the thyroid. Successful surgical resection of the recurrent tumor included the larynx and trachea; skin, soft tissues, and lymph nodes of the neck; and the tissues of the anterior mediastinum, including upper sternum and clavicular heads. Coverage of the wound was accomplished with an inferiorly based parasternal fasciocutaneous flap and a long pectoralis myocutaneous flap. This represents the first reported case of Hürthle cell carcinoma treated with mediastinal dissection for extensive local disease. Radical surgical resection should be considered for any patient with Hürthle cell carcinoma of the thyroid in view of the ineffectiveness of nonsurgical modalities.

Dose- and time-response of colon carcinogenesis in Fischer-344 rats after a single dose of 1,2-dimethylhydrazine.

The purpose of this experiment was to examine the development of colon tumors after the injection of a single dose of 1,2-dimethylhydrazine (DMH) in rats. Male Fischer-344 rats were injected with 0, 10, 30, 100 or 200 mg/kg of DMH dihydrochloride. No tumors were seen after 3 or 5 months at any dose, but were seen after 7 or 9 months. At 9 months, tumors were induced in a dose-dependent manner, with 64.7% of rats receiving the 200 mg/kg dose developing tumors. This study shows that a high incidence of colon tumors can be induced by a single dose of DMH after a 9-month latency period.

Cutaneous cryptococcal infection presenting as vulvar lesion.

A woman aged 60, who had been immunosuppressed since receiving a renal transplant 17 years before, developed a painless ulcerated lesion on her right labia majora. Cryptococcus neoformans was demonstrated by culture and biopsy of the lesion. This is the first reported case of a genital skin lesion caused by C neoformans.