Characterizing concentrations of diethylene glycol and suspected metabolites in human serum, urine, and cerebrospinal fluid samples from the Panama DEG mass poisoning.

CONTEXT: Diethylene glycol (DEG) mass poisoning is a persistent public health problem. Unfortunately, there are no human biological data on DEG and its suspected metabolites in poisoning. If present and associated with poisoning, the evidence for use of traditional therapies such as fomepizole and/or hemodialysis would be much stronger. OBJECTIVE: To characterize DEG and its metabolites in stored serum, urine, and cerebrospinal fluid (CSF) specimens obtained from human DEG poisoning victims enrolled in a 2006 case-control study. METHODS: In the 2006 study, biological samples from persons enrolled in a case-control study (42 cases with new-onset, unexplained AKI and 140 age-, sex-, and admission date-matched controls without AKI) were collected and shipped to the Centers for Disease Control and Prevention (CDC) in Atlanta for various analyses and were then frozen in storage. For this study, when sufficient volume of the original specimen remained, the following analytes were quantitatively measured in serum, urine, and CSF: DEG, 2-hydroxyethoxyacetic acid (HEAA), diglycolic acid, ethylene glycol, glycolic acid, and oxalic acid. Analytes were measured using low resolution GC/MS, descriptive statistics calculated and case results compared with controls when appropriate. Specimens were de-identified so previously collected demographic, exposure, and health data were not available. The Wilcoxon Rank Sum test (with exact p-values) and bivariable exact logistic regression were used in SAS v9.2 for data analysis. RESULTS: The following samples were analyzed: serum, 20 case, and 20 controls; urine, 11 case and 22 controls; and CSF, 11 samples from 10 cases and no controls. Diglycolic acid was detected in all case serum samples (median, 40.7 mcg/mL; range, 22.6-75.2) and no controls, and in all case urine samples (median, 28.7 mcg/mL; range, 14-118.4) and only five (23%) controls (median, < Lower Limit of Quantitation (LLQ); range, < LLQ-43.3 mcg/mL). Significant differences and associations were identified between case status and the following: 1) serum oxalic acid and serum HEAA (both OR = 14.6; 95% C I = 2.8-100.9); 2) serum diglycolic acid and urine diglycolic acid (both OR > 999; exact p < 0.0001); and 3) urinary glycolic acid (OR = 0.057; 95% C I = 0.001-0.55). Two CSF sample results were excluded and two from the same case were averaged, yielding eight samples from eight cases. Diglycolic acid was detected in seven (88%) of case CSF samples (median, 2.03 mcg/mL; range, < LLQ, 7.47). DISCUSSION: Significantly elevated HEAA (serum) and diglycolic acid (serum and urine) concentrations were identified among cases, which is consistent with animal data. Low urinary glycolic acid concentrations in cases may have been due to concurrent AKI. Although serum glycolic concentrations among cases may have initially increased, further metabolism to oxalic acid may have occurred thereby explaining the similar glycolic acid concentrations in cases and controls. The increased serum oxalic acid concentration results in cases versus controls are consistent with this hypothesis. CONCLUSION: Diglycolic acid is associated with human DEG poisoning and may be a biomarker for poisoning. These findings add to animal data suggesting a possible role for traditional antidotal therapies. The detection of HEAA and diglycolic acid in the CSF of cases suggests a possible association with signs and symptoms of DEG-associated neurotoxicity. Further work characterizing the pathophysiology of DEG-associated neurotoxicity and the role of traditional toxic alcohol therapies such as fomepizole and hemodialysis is needed.

Assessment of vaccination coverage among adults 30-49 years of age following a mass diphtheria vaccination campaign: Ukraine, April 1995.

Ukraine has been experiencing epidemic diphtheria since 1991. In efforts to control this epidemic, a mass vaccination campaign was held in April 1995. Persons not vaccinated in the previous 3 years were considered eligible for vaccination with tetanus-diphtheria toxoids (Td). Two cluster sample surveys were conducted to determine vaccination coverage achieved. In the urban and rural survey areas, respectively, 628 and 618 persons 30-49 years of age were interviewed. Fifty-nine percent of urban and 58% of rural participants were eligible for vaccination. During the vaccination campaign, 58% (95% confidence interval [95% CI], 47.1-69.2) of eligible persons received Td in the urban area, compared with 92% (95% CI, 89.2-95.3) in the rural area. Apparent barriers to vaccination included misconceptions about the safety, efficacy, and need for booster doses of Td. Future vaccination campaigns should include targeted information and education messages. Mass vaccination campaigns can be successful in vaccinating large numbers of adults; however, in urban areas, additional efforts may be required to achieve levels of coverage adequate to confer herd immunity and interrupt the diphtheria epidemic.

Safety of revaccination with pneumococcal polysaccharide vaccine.

CONTEXT: Revaccination of healthy adults with pneumococcal polysaccharide vaccine (PPV) within several years of first vaccination has been associated with a higher than expected frequency and severity of local injection site reactions. The risk of adverse events associated with revaccination of elderly and chronically ill persons 5 or more years after first vaccination, as is currently recommended, has not been well defined. OBJECTIVE: To determine whether revaccination with PPV at least 5 years after first vaccination is associated with more frequent or more serious adverse events than those following first vaccination. DESIGN: Comparative intervention study conducted between April 1996 and August 1997. PARTICIPANTS: Persons aged 50 to 74 years either who had never been vaccinated with PPV (n = 901) or who had been vaccinated once at least 5 years prior to enrollment (n = 513). INTERVENTION: PPV vaccination. MAIN OUTCOME MEASURES: Postvaccination local injection site reactions and prevaccination concentrations of type-specific antibodies. RESULTS: Those who were revaccinated were more likely than those who received their first vaccinations to report a local injection site reaction of at least 10.2 cm (4 in) in diameter within 2 days of vaccination: 11% (55/513) vs 3% (29/901) (relative risk [RR], 3.3; 95% confidence interval [CI], 2.1-5.1). These reactions resolved by a median of 3 days following vaccination. The highest rate was among revaccinated patients who were immunocompetent and did not have chronic illness: 15% (33/228) compared with 3% (10/337) among comparable patients receiving their first vaccinations (RR, 4.9; 95% CI, 2.4-9.7). The risk of these local reactions was significantly correlated with prevaccination geometric mean antibody concentrations. CONCLUSIONS: Physicians and patients should be aware that self-limited local injection site reactions occur more frequently following revaccination compared with first vaccination; however, this risk does not represent a contraindication to revaccination with PPV for recommended groups.

Gonococcal conjunctivitis in prepubertal children.

Four prepubertal children had confirmed gonococcal conjunctivitis. All were febrile and had hyperpurulent conjunctival discharge with periorbital inflammation. Cultures of pharyngeal, rectal, and genital specimens on selective media excluded infection at other sites. Detailed social evaluation revealed no evidence or suspicion of sexual abuse. Isolated gonococcal conjunctivitis occurs in prepubertal children. Unlike gonococcal infections at other locations, a nonsexual mode of transmission may exist. However, a careful physical examination and detailed social evaluation, looking for signs of sexual abuse, must be obtained in any prepubertal child with a gonococcal infection.

Malignant tumor embolism: a rare presentation of malignant disease.

Tumor emboli to peripheral vessels usually arise from atrial myxomas. A new case of non-myxomatous embolization is presented, as well as a review of the literature regarding embolization from previously unrecognized malignancies. Sites of origin of peripheral tumor emboli are discussed, as are possible pathological mechanisms.

Cell proliferation in developing brain after brief exposure to nitrous oxide or halothane.

Several inhalant anesthetics, including nitrous oxide and halothane, are known to be antimitotic in a variety of developing tissues, but none has been tested for antimitotic activity in developing brain. Concern about the safety of these agents has centered around behavioral effects reported in humans and animals after early exposure. Because interference with cell production during CNS development is a sufficient cause for later behavioral abnormalities, it is important to know whether cell production in the nervous system is altered by these agents. Mice were exposed to either nitrous oxide (75% N2O and 25% O2) or halothane (0.5% halothane in 75% N2 and 25% O2) or a mixture of 75% N2 and 25% O2. Prenatal treatment groups were exposed for 6 h on the 14th day of gestation, while postnatal treatment groups were exposed for 4 h on the second day after birth. Treated and control animals were then killed immediately after exposure, or 12, 24, or 48 h later, to be evaluated for CNS mitotic activity. Each of the four anesthetic-exposed groups showed some deviations from normal mitosis, but only the postnatal nitrous oxide group showed the pattern of reduced cell proliferation followed by a rebound that is characteristic of many antimitotic teratogens. Although prenatal nitrous oxides' effects on the fetal brain were not clearly interpretable, it did delay development of blood, as has been reported by other investigators. Both nitrous oxide and halothane significantly reduced body weight of fetuses in utero, but did not reduce body weight of neonates. The pattern of the body-weight effects suggests that they occur by some mechanism other than reduced cell production.(ABSTRACT TRUNCATED AT 250 WORDS)

Prognostic factors in acute meningococcaemia.

During a meningococcal (group A) epidemic, 47 Nigerian children with acute meningococcaemia without meningitis were studied. Their mortality rate was 43% compared with 8% during the whole epidemic. Those presenting with coma and shock had a mortality of 93%, but without shock or coma mortality was only 6%. Coma or shock occurring alone carried an intermediate prognosis. The outcome correlated with initial serum antigen titre, but not with the serum levels of endotoxin, cortisol, or fibrin degradation products. Chloramphenicol was as effective as penicillin. A predictor of expected mortality, based on serum antigen titre and the presence of coma or shock, may allow new forms of treatment to be assessed.