Micronucleated erythrocytes as an index of cytogenetic damage in humans: demographic and dietary factors associated with micronucleated erythrocytes in splenectomized subjects.

Erythrocytes containing micronuclei serve as an indicator of genotoxic exposure in splenectomized individuals. Micronucleated erythrocytes, derived from cytogenetically damaged RBC precursors, are not selectively removed from peripheral blood in individuals who lack splenic function. The relationship between micronucleated cell frequencies and demographic, environmental, and dietary factors was examined in 44 subjects with previous splenectomy due to trauma. Their micronucleated cell counts fit a log-normal distribution, with geometric means of 3.3 micronucleus-containing cells/1000 reticulocytes and 2.7/1000 normochromatic erythrocytes. A multiple regression analysis showed that drinking five cups of coffee or tea/day (relative to none) was associated with an approximately 2-fold higher frequency of micronucleated cells. Weaker statistical associations were also noted with micronucleus frequency and the consumption of calcium supplements (associated with a higher frequency) and vitamins A, C, or E (lower frequency). An apparent trend of higher micronucleus counts with age was attenuated when other factors were considered in the regression. Cigarette smoking and decaffeinated coffee consumption were among the factors not associated with elevated micronucleated cell frequencies. Because the occurrence of micronuclei in reticulocytes reflects cytotoxic exposures within the past 3-8 days, it may be possible to test directly the relationship of these factors to micronucleus formation through intervention studies.

Long-term sweat collection using salt-impregnated pads.

To facilitate a study of the pharmacokinetics of drugs dissolved in sweat, a technique was devised for collecting sweat at a steady rate over an 8-day period. Three normal subjects each wore 4 absorbent pads applied to their skin under waterproof dressings for 8 days. The absorbent pads were either plain cotton or cotton impregnated with sodium chloride crystals. Each pad (3 cm x 3 cm) was applied to an area of skin (2 cm x 2 cm) defined by an adhesive template, and was removed daily, weighed, and replaced, to determine progressive uptake of sweat. Sweat uptake by plain cotton pads reached a plateau value within 2 to 3 days and did not significantly increase thereafter; in contrast, uptake by the salt-impregnated pads continued at a steady rate for the full 8 days of the study (mean rate 0.79 mg/cm2/hr, SD = 0.16, N = 6). This effect may be related to an osmotic gradient across the skin, but the physiologic mechanisms are not completely clear. This appears to be a convenient tool for the collection of sweat over long periods at a steady rate.

Pharmacokinetics of CaNa2EDTA and chelation of lead in renal failure.

The pharmacokinetics of 1 gm intramuscular doses of CaNa2 (14C-)EDTA and the chelation of lead (Pb) were studied in 10 subjects with varying degrees of renal function and normal body burdens of Pb. The clearance of CaNa2EDTA significantly correlated with creatinine clearances (CLCR) (r = 0.8373; P = 0.0097). Clearances were decreased in subjects with CLCR less than 70 ml/min as compared with subjects with CLCR greater than 100 ml/min (28 vs. 76 ml/min). Maximum serum CaNa2EDTA concentrations and volume of distribution (Varea) (0.05 to 0.23 L/kg) were similar in all subjects. The Varea is smaller than previously described and is more consistent with other experimental data. Considering all subjects, initial blood Pb concentrations correlated with cumulative urine Pb excretion over 3 days (r = 0.8967; P = 0.0005). Urine Pb excretion did not correlate with measures of renal function or measures of CaNa2EDTA kinetics. Subjects with abnormal CLCR showed significantly greater decreases in blood Pb from day 1 to day 4 (7.0 micrograms/dl vs. 1.2 micrograms/dl) compared with normal subjects. These decreases in blood Pb correlated with CLCR (r = 0.7774; P = 0.138) and urine protein (r = 0.8435; P = 0.0087) but not with urine Pb excretion. Renal dysfunction may alter Pb chelatability, bone-blood Pb reequilibration, PbEDTA distribution, or PbEDTA excretion.

Diazepam kinetics in acute alcohol withdrawal.

We performed a within-subject comparison of the kinetics of diazepam given to 7 alcoholic subjects during acute alcohol withdrawal and again after detoxification. The initial rapid exponential decline of plasma diazepam concentrations (t1/2 alpha) was more rapid during (0.21 +/- 0.03 hr) than after withdrawal (0.44 +/- 0.14 hr, p less than 0.05). Terminal t1/2, clearance, and volumes of distribution changed in individual patients, but mean values did not change. Protein binding was less in patients (93.4 +/- 2.4%) than in healthy controls (97.0 +/- 1.0, p less than 0.05). The effects of alcohol withdrawal on diazepam disposition do not explain the high doses of diazepam commonly required to treat the withdrawal.

Evidence of neurologic dysfunction related to long-term ethylene oxide exposure.

Eight hospital workers with chronic ethylene oxide exposure were age-sex matched with eight nonexposed controls with no significant differences in educational backgrounds and vocabulary scores. The exposed group performed more poorly on all eight measures of cognition, memory, attention, and coordination, with 71.3% less accuracy on the Hand-Eye Coordination Test. There was a dose-response relationship between exposure and the following: Continuous Performance Test and sural velocity. These findings suggest that neurologic dysfunction may result from long-term low-dose exposure to ethylene oxide, and that these effects may occur at exposure levels common in hospital sterilizer operations.

Organophosphate polyneuropathy: pathogenesis and prevention.

Organophosphorus-induced delayed polyneuropathy (OPIDP) is initiated by the phosphorylation of a protein neurotoxic esterase (NTE) in the nervous system. A second step, the "aging" of the phosphoryl-enzyme complex, is required to produce the toxic effect. The experimental evidence for this molecular target and the importance of the aging process are reviewed. The catalytic activity of NTE has been used to develop an in vitro screening test that may distinguish the organophosphorus compounds (OPs) that cause neuropathy from those that do not, thereby providing a means for prevention of OPIDP. Moreover, a biochemical screening test, the determination of NTE activity in blood lymphocytes, may predict the development of OPIDP after acute or chronic exposure to OPs, and requires evaluation by carefully designed studies of occupational exposure to OPs.

Blood pressure and blood lead concentration in bus drivers.

San Francisco bus drivers have an increased prevalence of hypertension. This study examined relationships between blood lead concentration and blood pressure in 342 drivers. The analysis reported in this study was limited to subjects not on treatment for hypertension (n = 288). Systolic and diastolic pressures varied from 102 to 173 mm Hg and from 61 to 105 mm Hg, respectively. The blood lead concentration varied from 2 to 15 micrograms/dL. The relationship between blood pressure and the logarithm of blood lead concentration was examined using multiple regression analysis. Covariates included age, body mass index, sex, race, and caffeine intake. The largest regression coefficient relating systolic blood pressure and blood lead concentration was 1.8 mm Hg/ln (micrograms/dL) [90% C. I., -1.6, 5.3]. The coefficient for diastolic blood pressure was 2.5 mm Hg/ln (micrograms/dL) [90% C. I., 0.1, 4.9]. These findings suggest effects of lead exposure at lower blood lead concentrations than those concentrations that have previously been linked with increases in blood pressure.

Formate in serum and urine after controlled methanol exposure at the threshold limit value.

Methanol will be present as a new air pollutant when methanol-powered vehicles are introduced in the United States. Little is known about the effect of low-dose methanol exposure. It is controversial whether or not formate, the main metabolite responsible for methanol's acute toxicity, is a sensitive biological marker of toxicity or exposure. We studied the effect of a 4-hr exposure at rest to 200 ppm of methanol vapors on endogenous serum formate and on urinary formic acid excretion. A randomized, double-blind study of human exposure to a constant concentration of methanol was performed in a whole-body exposure chamber. Twenty-six healthy volunteers, each serving as his or her own control, participated in sham and methanol exposures. Urine (at 0, 4, 8 hr) and serum specimens (15 time points over 8 hr) collected before, during, and after the exposure were measured for formate. We found no significant differences in serum formate concentration between exposure and control conditions either at any time point or for area under the curve. Mean concentrations at the end of the exposure were: exposed 14.28 +/- 8.90 mg/l and control 12.68 +/- 6.43 mg/l. A slight, but nonsignificant (p = 0.08), increase in urine formate excretion rate was found at 4 hr (exposed 2.17 +/- 1.69 mg/4 hr and control 1.67 +/- 1.02 mg/4 hr). Age, sex, folic acid level, and smoking were not significant covariates. At 200 ppm, methanol exposure does not contribute substantially to endogenous formate quantities. Serum and urine formate determinations are not sensitive biological markers of methanol exposure at the threshold limit value.

Hypertensive emergencies.

The clinical syndrome of accelerated hypertension is a relatively rare complication of hypertensive disease. The syndrome is recognized by high blood pressures, progressive neurologic and visual symptoms, acute renal damage, cardiac failure, and microangiopathic hemolytic anemia. When diagnosed, it must be recognized as an acute medical emergency. The patient should be admitted to an intensive care unit, arterial lines should be placed, and the blood pressure lowered as soon as possible. Once blood pressure has been controlled, oral medications should be begun. Long-term results in the treatment of hypertensive emergencies are gratifying. It is anticipated that with more experience gained in the use of medications in this situation, an even better prognosis will be achieved.

Comparison of the NES and CNS/B neuropsychological screening batteries.

Computer and hand administered neuropsychological tests are utilized in the evaluation of central nervous system changes associated with environmental or occupational exposure to neurotoxicants. This study compares the computerized Neurobehavioral Evaluation System (NES) developed by Baker et al., 1985, with the hand administered California Neuropsychological Screening Battery (CNS/B) developed by Bowler et al., 1986. Both batteries were designed for screening of the effects of neurotoxicants on the central nervous system and require less than one hr to administer. Both screening batteries consist of tests of: mood, word knowledge, attention, concentration, learning and memory and psychomotor and visuomotor and visuospatial abilities. They were administered in a standardized fashion to 106 subjects. Results indicate strong positive correlations for tests of word knowledge, moderate correlations for attention and concentration, while weaker correlations were obtained for tests of memory, psychomotor and visuomotor and visuospatial ability. The NES may be more useful for large epidemiological studies while the CNS/B appears more useful for individual screening and clinical studies.

Peritoneal clearance and total body elimination of vancomycin during chronic intermittent peritoneal dialysis.

Vancomycin is a useful antimicrobial agent in patients undergoing chronic hemodialysis treatment; its efficacy in chronic peritoneal dialysis (CPD) has not been established. Serum (VS) and peritoneal fluid (VPF) vancomycin concentrations were measured in two CPD patients with staphylococcal peritonitis. Half-life of VS agreed with the half-life of VPF in each patient, and the VS/VPF ratio was 1.27 in both patients. Distribution volumes were 37.2 and 58.7 l, values approximating total body water in these patients. VS and VPF persisted in the therapeutic range (greater than 5 microgram/ml) for more than 16 days. In one patient, mean peritoneal clearacne was 9.8 ml/min, and overall drug clearance averaged 2.3 ml/min; in the other patient, overall clearance was 2.1 ml/min. These results indicate that therapeutic vancomycin levels can be maintained for more than 16 days with a single 1 g intravenous dose in patients receiving intermittent CPD, as is the case for hemodialysis patients. Because of this, parenteral vancomycin is useful in the treatment of staphylococcal peritonitis in CPD patients.

Modeling the acute neurotoxicity of styrene.

Styrene is a widely used industrial solvent associated with acute neurotoxicity. To investigate the relationships between exposure, blood concentrations, and the appearance of neurotoxic effects, four healthy males were exposed to styrene concentrations of 5-200 ppm in four different exposure-time profiles. A digit recognition test and P300 event-related evoked potential were used to measure neurologic function. A physiologically based kinetic (PBK) model generated close predictions of measured styrene blood concentrations, in the range of 0.01-12 mg/L, from this and 21 previous studies. Simulated peak brain concentration, durationXaverage exposure, and peak exposure level were predictive of toxicity. Central nervous system effects were expected at a blood concentration near 2.4 mg/L. A standard of 20 ppm was expected to protect styrene-exposed workers from acute central nervous system toxicity under light work conditions.

Repair of rotator cuff tears in golfers.

PURPOSE: Golfers continue to play through the years that rotator cuff disease becomes more common. We sought to establish the results of acromioplasty and rotator cuff repair in golfers, including their ability to return to the sport. STUDY TYPE: Case series. METHODS: Of 30 golfers who underwent 32 rotator cuff repairs, 29 were interviewed, completed a detailed questionnaire, and returned for a physical examination. All of the patients were recreational or regional tournament golfers. Fifteen had open acromioplasty and rotator cuff repair and 16 had arthroscopic acromioplasty and mini-open repair. The average age at surgery was 60 years (range, 39 to 76 years). At surgery, most were moderate size tears (2 to 6 cm(2)). RESULTS: At average follow-up of 37 months (range, 24 to 60 months), all but 3 patients are currently golfing. For patients who are currently golfing, there was no significant difference in handicaps or drive distances at most recent follow-up compared with presymptomatic handicaps and drive distances (P >.05). Twenty-three patients report that they are playing at their presymptomatic competitive level without pain. Three patients report playing at a lower competitive level than before. CONCLUSION: In our experience, acromioplasty and rotator cuff repair predictably allow for eventual return to pain-free golfing at a similar competitive level for most recreational-level athletes.

The alcoholic patient as a toxic emergency.

The author reviews key physical findings in an alcoholic patient with a toxic emergency, important laboratory tests for alcoholic patients, and management of the intoxicated patient. Also considered are special alcohol toxidromes and other alcohol-related toxic emergencies.

Methanol poisoning.

Methanol poisoning is an uncommon but an extremely hazardous intoxication. Since methanol is a versatile fuel and is having increasing usage in an energy-conscious society, a high index of suspicion and swift laboratory confirmation is essential in managing this poisoning. Methanol poisoning may occur in sporadic or epidemic circumstances. Chronic exposure may occur in the occupational setting. Man is uniquely susceptible to methanol toxicity, perhaps dependent upon folate metabolism. Classic symptoms of methanol toxicity can only occur in laboratory animals who are rendered folate deficient. Folate may be useful in humans enhancing removal of the toxic products of methanol poisoning. The enzyme responsible for metabolism of methanol is alcohol dehydrogenase. Ethanol has a higher affinity for this enzyme and is preferentially metabolized. Simultaneous ethanol and methanol administration may confuse the onset of the intoxication. Pyrazoles may also be used to inhibit alcohol dehydrogenase thus preventing the intoxication. The most important initial symptom of methanol poisoning is visual disturbance. The symptoms may be delayed up to 24 hours after ingestion due to simultaneous alcohol administration and metabolic processes. Laboratory evidence of severe metabolic acidosis with increased anion and osmolar gaps strongly suggest the clinical diagnosis. There may be an important association between mean corpuscular volume which is significantly higher in cases of severe methanol poisoning than in mild cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Review of pharmacologic and toxicologic effects of alcohol.

Oral neglect and dental diseases are common; consumption of alcohol is common. To appreciate the frequency of alcoholism, the dental specialist must recognize that no persons will seek attention for alcoholism. Suspicion of alcohol related dental disease is the key. Heavy smoking, malnutrition, bleeding gingiva, cancer of the head and neck, and enlargement of the parotid glands should all raise a question of alcoholism. Alcohol affects most organ systems, but toxicity is extremely variable. Single organ systems may be severely damaged whereas others are spared. Current evidence suggests that variations on the total amount of alcohol consumed and genetic variations in specific pathways may contribute to the multifaceted clinical presentations of alcoholism. Because alcohol is the single most common drug ingested by patients, common interactions of drugs that have dental significance should be suspect. Most commonly, these interactions involve anesthetic agents and sedative hypnotic drugs. Dental specialists may encounter alcoholic persons in intoxicated, withdrawing, or rehabilitating states. In any of these phases, appropriate recognition and judicious support of the dental problems will contribute to the overall well-being of these persons.

Plantar fibromatosis: a review of primary and recurrent surgical treatment.

Plantar fibromatosis can be quite disabling to the patient, as well as a technical challenge to the surgeon. Patients who undergo previous local excisions and in whom aggressive recurrences develop are difficult to manage successfully. We present a consecutive series of five primary procedures on patients with painful plantar fibroma and seven revision operations on patients with recurrent plantar fibroma. The average follow-up was 47 months (range, 22-66 months) in the primary group and 40 months (range, 21-78 months) in the revision group. The overall results were satisfactory in four of the five primary operations, with only one recurrence. In the revision group, five of seven results were satisfactory with no recurrences. The major complication that led to unsatisfactory results was the development of a postoperative neuroma. In this article, we outline our present surgical techniques of wide primary excision and a staged revision procedure with delayed split-thickness skin graft closure. These techniques can be used successfully to manage this disabling, progressive disease.

Chemical dependency and drug testing in the workplace.

Urine testing for drug use in the workplace is now widespread, with the prevalence of positive drug tests in the work force being 0% to 15%. The prevalence of marijuana use is highest of the illicit drugs being tested. Highly prevalent drugs can be reliably tested. Although it is prudent to rid the workplace of drug use, there is little scientific study on the relationship of drug use and workplace outcomes, such as productivity and safety. Probable-cause testing and preemployment testing are the most common applications. Random testing has been less accepted owing to its higher costs, unresolved legal issues, and predictably poor test reliability. Legal issues have focused on the right to privacy, policy agreements, discrimination, and the lack of due process. The legal cornerstone of a good program is a policy that is planned and agreed on by both labor and management, which serves both as a contract and as a procedure in which expectations and consequences are known. Moreover, NIDA is certifying laboratories doing employee drug testing. Testing methods, when done correctly, are less prone to error than in the past, but screening tests can be defeated by adulterants. Although the incidence of false-positive results is low, such tests are less reliable when the prevalence of drug abuse is also low.

Body burdens of lead in hypertensive nephropathy.

Chronic lead exposure resulting in blood lead concentrations that exceed 1.93 mumol/l (40 micrograms/dl) or chelatable urinary lead excretion greater than 3.14 mumol (650 micrograms) per 72 h has been associated with renal disease. A previous study had found greater chelatable urine lead excretion in subjects with hypertension and renal failure than in controls with renal failure due to other causes, although mean blood lead concentrations averaged 0.92 mumol/l (19 micrograms/dl). To determine if chelatable urinary lead, blood lead, or the hematologic effect of lead (zinc protoporphyrin) were greater in hypertensive nephropathy (when hypertension precedes elevation of serum creatinine) than in other forms of mild renal failure, we compared 40 study subjects with hypertensive nephropathy to 24 controls having a similar degree of renal dysfunction due to causes other than hypertension. Lead burdens were similar in both the study and control groups as assessed by 72-h chelatable urinary lead excretion after intramuscular injection of calcium disodium EDTA (0.74 +/- 0.63 vs. 0.61 +/- 0.40 mumol per 72 h, respectively), and by blood lead (0.35 +/- 0.23 vs. 0.35 +/- 0.20 mumol/l). We conclude that subjects from a general population with hypertensive nephropathy do not have greater body burdens of lead than renal failure controls.

Elevated blood pressure in treated hypertensives with low-level lead accumulation.

The relationship between blood pressure (BP) and blood lead concentration (PbB) was examined in 51 bus drivers who were treated for hypertension. These drivers were a subset of a representative sample (N = 342) of the driver population (N = approximately 2,000), and were not selected for hypertension or lead exposure. Blood lead concentrations ranged from 2-24 micrograms/dl (median: 6.9 micrograms/ld). There were 33 subjects treated primarily with diuretics, and 18 subjects were treated with beta blockers. Adjusted regression coefficients relating systolic BP with PbB were -6.4 +/- 11.4 and 4.5 +/- 12.9 mmHg/In(micrograms/dl) in each group, respectively, but were not statistically significant. The adjusted coefficients for diastolic BP were 1.12 +/- 3.89 and 14.3 +/- 5.69 mmHg/In(micrograms/dl) (p = 0.036), respectively. The latter relationship represents an average increment of 12 mmHg in diastolic BP over the range of observed PbBs (2.0 to 11.4 micrograms/dl) in subjects treated with beta blockers. Thus, beta blocker therapy may be less effective in reducing diastolic pressure in individuals with higher PbBs and suggests an action of lead at PbBs below current standards.