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1. Tucaresol (589C80; 4[2-formyl-3-hydroxyphenoxymethyl] benzoic acid) interacts stoichiometrically with haemoglobin to increase oxygen affinity. By decreasing the proportion of insoluble deoxy sickle haemoglobin at capillary oxygen concentrations, tucaresol may be of therapeutic benefit in sickle cell anaemia. 2. In this study, which involved the first administration to man, the pharmacokinetics and pharmacodynamics of tucaresol were studied in healthy male volunteers following oral doses of 200-3600 mg. 3. Peak drug concentrations in plasma and erythrocytes were linearly related to dose; mean (s.d.) values were 95.8 (26.1) and 1035 (67) micrograms ml-1, respectively, at the highest dose. Median tmax in plasma was 6.5 h and in erythrocytes 24.5 h, when approximately 60% of the administered dose was in the target tissue. Plasma drug concentrations fell biexponentially with commencement of the apparent terminal elimination phase at approximately 24 h. The terminal elimination half-life from plasma increased with dose (r = 0.77; P < 0.0001) from 133-190 h at 400 mg to a mean (s.d.) of 289 (30) h at 3600 mg. Erythrocyte drug concentrations declined mono-exponentially with a half-life that was always shorter than the apparent terminal half-life in plasma: overall mean (95% CI) of t1/2 erythrocyte/t1/2 plasma ratio was 0.57 (0.53, 0.61). The erythrocyte AUC/plasma AUC ratio increased with dose (r = 0.67; P < 0.001). 4. The proportion of haemoglobin modified to a form with high oxygen affinity (%MOD) increased in a dose-related manner above doses of 800 mg reaching 19-26% after the 3600 mg dose.(ABSTRACT TRUNCATED AT 250 WORDS)

A cluster of biopsy-confirmed interstitial lung disease among workers at a nylon flock plant led to a request for National Institute for Occupational Safety and Health investigators to conduct a health hazard evaluation.Part of the overall evaluation, reported here, involved a cross-sectional medical survey of current employees. The survey consisted of a questionnaire, spirometry and diffusing capacity testing, and chest radiograph.Workers assigned to production and maintenance jobs reported frequent eye and throat irritation, respiratory symptoms, and systemic symptoms (i.e., generalized aches and fevers). Most reported improvement when away from work. Frequent respiratory/systemic symptom prevalence was significantly associated with departmental category, with days and hours worked per week, and with working on a flocking range. Compared to asymptomatic workers, symptomatic workers had similar mean ratios of forced expiratory volume in one second to forced vital capacity, but lower mean percent of predicted values for both forced vital capacity and diffusing capacity. All acceptable chest radiographs were classified as category 0 for small opacities.Findings of this study, along with those from studies reported elsewhere, implicate occupational exposure to flock-associated dust as a significant respiratory health hazard at this plant.

Intense flashes of light were observed in sodium bicarbonate and hydrogen peroxide solutions when they were exposed to pulsed microwave radiation, and the response was greatly enhanced by a microwave-absorbing, biosynthesized polymer, diazoluminomelanin. A FPS-7B radar transmitter, operating at 1.25 GHz provided pulses of 5.73 +/- 0.09 micros in duration at 10.00 +/- 0.03 pulses/s with 2.07 +/- 0.08 MW forward power (mean +/- standard deviation), induced the effect but only when the appropriate chemical interaction was present. This phenomenon involves acoustic wave generation, bubble formation, pulsed luminescence, ionized gas ejection, and electrical discharge. The use of pulsed microwave radiation to generate highly focused energy deposition opens up the possibility of a variety of biomedical applications, including targeting killing of microbes or eukaryotic cells. The full range of microwave intensities and frequencies that induce these effects has yet to be explored and, therefore, the health and safety implications of generating the phenomena in living tissues remain an open question.

Since 1985, the Louisiana State University School of Medicine in New Orleans, through its Office of Community and Minority Health Education, has operated the Summer Science Program for Louisiana high school students from underrepresented minorities. The authors conducted a survey during the 1997-98 academic year of the 773 students who had participated in the summer program from 1985 to 1997. The goal was to learn what education and career paths these students had taken since leaving the program. A total of 665 students (89.4%) responded. Sixty-one were still in high school, 11 had not continued their education after completing high school, but 432 of the remaining 583 students had chosen education paths in medicine, another health profession, or science, and 31 were enrolled in or had graduated from medical school. These findings indicate that the majority of the summer program students had maintained the health and/or science career interests they had expressed during their time in the program. Future studies will use control groups to better ascertain how influential the summer program was in helping students choose and maintain science and health education and career paths.

We performed flow cytometric analysis of CD34+ cell apoptosis in 59 patients with myelodysplastic syndrome (MDS) or acute myeloid leukaemia (AML) secondary to MDS (MDS-AML) using annexin V-FITC, which binds to exposed phosphatidylserine on apoptotic cells. Apoptosis was significantly increased in FAB subtypes RA, RARS and RAEB (10% blasts) (56.5% (15.1-86.5%)) compared to normal controls (18.5% (3.4-33.4%), P0.0001) and RAEB-t/MDS-AML (16% (2.1-43.2%), P0.0001). There was no correlation between % apoptosis, Full blood count or cytogenetics in any disease category. Two-colour cytometric analysis of permeabilized CD34+ cells stained with antibodies to Bcl-2, Bcl-X (anti-apoptotic), Bax and Bad (pro-apoptotic), demonstrated significantly higher ratios of pro- v anti-apoptotic proteins in early MDS (2.47 (1.19-9.42) compared to advanced disease (1.14 (0.06-3.32), P=0.0001). Moreover, using repeated measures of variants (ANOVA), we found that variations between individual Bcl-2-related proteins differed significantly according to disease subtype (P0.0005). Our results confirm that CD34+ cell apoptosis was significantly increased in MDS subtypes RA and RARS and fell with disease progression. Early MDS was also associated with a significantly higher CD34+ cell pro- v anti-apoptotic Bcl-2-family-protein ratio than advanced disease. Furthermore, patterns of expression of individual Bcl-2 related proteins differed significantly between different disease categories. However, no correlation between pro- v anti-apoptotic Bcl-2-family-protein ratios and the degree of apoptosis was observed.

1. Artists use many materials composed of the same chemicals that cause major occupational health problems in industry. 2. The majority of artists are unaware of the potential hazards in the materials and processes they use. 3. The pilot study revealed that greater than 90% of the amateur photographers did not use safety precautions in the darkroom. 4. The most common perceived barrier to the use of safety precautions was the lack of knowledge about chemical safety.

Since the early 1900s, it was recognized that many dust-exposed workers developed abnormal radiographs during life. Chest radiography remains the primary means of determining the presence and extent of dust-induced pneumoconiosis, although it is ineffective for detecting airways obstructions from mine dust exposure. This chapter reviews the uses and limitations of chest radiography in the study, surveillance, screening, clinical diagnosis, and disability determinations of occupational lung diseases in dust-exposed workers.

CWP is a disease distinct and separate from silicosis. Simple CWP is clearly related to the amount of dust deposited within the lungs. Complicated CWP (PMF) results from dust deposition plus other factors. Immunologic and local cellular factors may contribute to the development of this form of the disease. Studies of lung cell response and function may further elucidate mechanisms and mediators of lung dust reaction. Complicated CWP (PMF) is clearly associated with alterations in ventilatory, mechanical, and vascular function of the lungs. These abnormalities in PMF contribute to the observed premature morbidity and mortality of this disease.

One hundred and eleven patients with microinvasive carcinoma of the uterine cervix were studied over a 21-year period. Thirty-five cases of carcinoma in situ with questionable stromal invasion were excluded. Cases with pathologic examination of less than a cervical cone or the entire cervix were not accepted. The sole pathologic criterion for inclusion was unequivocal invasion to a depth of no more than 5.0 mm. Ninety-one patients were followed for 5 years or until death, and 80 patients for 10 years or until death. One patient was lost to follow-up at 5.5 years. The two deaths officially attributed to cervix cancer prior to 10 years were signed out by nonphysician assistant coroners. Available clinical evidence indicates that at least one of these patients, and probably both, did not die of cervix cancer. From these data, simple hysterectomy would seem to be the maximal treatment indicated. Since the prognosis of microinvasive carcinoma is similar to that of carcinoma in situ, it is suggested that such cases not be included when considering the end results of Stage I cervix cancer.

A study of 113 patients with histologically confirmed bronchogenic carcinoma and survival for at least 18 months was performed. Posttherapeutic cytologic specimens were submitted for only 52.2% (59/113), and for only 8.5% (5/59) of the individuals was specimen procurement related to clinic visits. Yet, when utilized as a diagnostic procedure for the hospitalized patient, a positive cytodiagnosis was made on 55.6% (15/27) of the patients with recurrent carcinoma, in 61.1% (11/18) with persistent disease and in all 5 patients with a metachronous primary bronchogenic carcinoma. Cytologic diagnoses of cancer compared favorably with concurrent histologic interpretations of biopsies and radiologic observations of chest films.

1. Nurses continue to experience back pain and injury as a result of occupational stressors, with most attributed to lifting clients. 2. Research found that only 2% of nurses lifted clients as prescribed by current nursing textbooks. 3. Nurses' lifting behavior was related to the age of the nurse and the type of client movement. 4. Ongoing education regarding prescribed lifting behavior in clinical settings and continued research regarding strategies to increase the prevalence of safe behavior in the workplace are recommended.

Qualitative cytologic evaluations of urinary bladder washings were performed on a selected population following photodynamic therapy for recurrent transitional cell carcinoma of the bladder. The seven patients were monitored trimonthly by cystoscopy, multiple biopsies and cytopreparations. Cancers reappeared in two of the five patients who initially responded to therapy. In the remaining two patients, the recurrent neoplasms were therapeutically refractory. Cytology detected recurrent cancer prior to biopsy confirmation and/or cytoscopic identification. Exfoliative cytology was correlated with the histopathology of the concurrent biopsies; a possible source for a false-positive cytodiagnosis was the cellular atypia of reepithelialized bladder mucosa. Dysplasia was not identified cytologically or histologically.

Two cases of smoke inhalation injury are reported with a brief review of the pertinent literature. The frequency of occurrence, the mortality rate, the clinical course of this common event are discussed with emphasis on the following facts: 1) Pulmonary injury is often associated with skin burns and, conversely, skin burns, particularly when severe, are accompanied by significant effects on pulmonary function; 2) Domestic fires, which account for most of these casualties, may involve complex exposure to a variety of aggressive agents (CO, HCN, NOx, etc.), causing systemic effects; 3) The clinical course of the most severe occurrences characteristically consists of three phases, namely acute pulmonary insufficiency, pulmonary edema and bronchopneumonia, in sequence; 4) The mortality rates of these clinical phases range at or about 50 per cent; 5) Significant laryngeal edema and even pulmonary edema may follow an interval of several hours, during which both subjective and objective evidence of injury may be minimal or unnoticed; and 6) The determination of carboxyhemoglobin levels often helps in gauging the severity of the exposure and related effects of either immediate or delayed appearance.

The role of education and training for cytopathologists in assuring quality in cytology laboratories is discussed, with particular attention given to (1) the problems in the diagnosis of Papanicolaou smears and (2) the contributions of the American Society of Cytology to cytology education. While many people contribute to the success or failure of gynecologic screening programs, poorly trained pathologists can be an especially weak link in the chain given their position in the diagnostic process. Well-formulated residency programs and the use of other educational resources can produce higher-caliber cytopathologists. The problems in Papanicolaou smear screening need to be defined, discussed and resolved by well-trained cytopathologists in conjunction with the clinicians and cytotechnologists involved.

Data from a 21-year period are presented to evaluate the effects of a mass cytologic screening program on uterine cancer morbidity and mortality in Louisville, Jefferson County, Kentucky. The success of screening was greatest in the younger age groups. There was a fall-off after age 45 years, especially in those age 60 years or older. Women at highest risk for cervical cancer, in the low socioeconomic quartile, had a better initial screening rate than the two middle-income quartiles, and had the highest rate of all women for subsequent rescreening. The greatest decrease in both morbidity and mortality was in women under the age of 50 years. Women age 30-39 and 50-59 years benefitted the most, as measured by mortality, with a decrease of 70.8 and 69.0%, respectively. There was no change in mortality rates for those age 70 years or older. Although the average annual age-adjusted rate increased from 13.2 to 15.3/100,000 women over the 21-year period.

An immunoperoxidase staining technique was employed in an effort to demonstrate prostatic acid phosphatase in sections of the effusion cell blocks in a retrospective investigation of the incidence of malignant prostatic cells in body cavity effusions in 33 patients with histologically confirmed prostatic cancer. An attempt was also made to identify the prostate as a possible anatomic site of origin in 26 patients with an unknown primary but with cytologically positive fluids. Neoplastic cells were identified in the effusion specimens in 21.2% of the patients with confirmed prostatic cancer; the sources, however, were either primary or metastatic carcinomas of nonprostatic origin. None of the cytologic specimens in this study demonstrated a positive prostate-specific acid phosphatase staining reaction, as did the prostatic metastases to the lungs used as controls.