Antihistamines and/or decongestants for otitis media with effusion (OME) in children.

BACKGROUND: Otitis media with effusion (OME) is common and may cause hearing loss with associated developmental delay. Treatment remains controversial. The effectiveness of antihistamines, decongestants and antihistamine/decongestant combinations in promoting the resolution of effusions has been assessed by randomized controlled trials. OBJECTIVES: The objective of this review is to determine whether antihistamine, decongestant, or combination therapy is effective in treating children who present with OME. SEARCH STRATEGY: The Cochrane Ear, Nose and Throat Disorders Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1 2006), EMBASE (1974 to 2006), MEDLINE (1951 to 2006) and a gray literature database were searched using a search strategy created by an experienced medical librarian. The date of the last search was March 2006. Reference lists from included studies and relevant reviews were searched by hand; pharmaceutical manufacturers of antihistamines and decongestants and first authors of included studies were contacted to identify other potentially relevant studies. SELECTION CRITERIA: Randomized controlled trials (RCTs) using antihistamines, decongestants or antihistamine/decongestant combinations as treatment for OME in children were selected. We excluded trials that randomized on the basis of acute otitis media (AOM) even though OME was also studied in follow up. DATA COLLECTION AND ANALYSIS: Data were extracted from the published reports by two authors independently using standardized data extraction forms and methods. The methodological quality of the included studies was independently assessed by two authors. Dichotomous results were expressed as a relative risk with 95% confidence intervals using a fixed-effect model when homogeneous and a random-effects model when heterogeneous. Nearly all outcomes analysed were homogeneous. Continuous results were discussed qualitatively. Statistical analysis was conducted using RevMan software. MAIN RESULTS: No statistical or clinical benefit was found for any of the interventions or outcomes studied. However, treated study subjects experienced 11% more side effects than untreated subjects (number needed to treat to harm = 9). AUTHORS' CONCLUSIONS: Because the pooled data demonstrate no benefit and some harm from the use of antihistamines or decongestants alone or in combination in the management of OME, we recommend against their use.

Global hexachlorobenzene emissions.

Information from a variety of sources has been assembled to give a global picture of hexachlorobenzene (HCB) emissions in the mid 1990s. No single overwhelming source of HCB was identified. The best estimates of global HCB emissions from different categories of sources are as follows: pesticides application - 6500 kg/yr; manufacturing - 9500 kg/yr; combustion - 7000 kg/yr, includes 500 kg from biomass burning. This adds up to total current HCB emissions of approximately 23,000 kg/yr with an estimated range 12,000-92,000 kg/yr. A substantial portion of HCB measured in the atmosphere is thought to come from volatilization of "old" HCB on the soil from past contamination along with unidentified sources. No information on potential sources in developing countries was available.

Rapid bioanalytical determination of dextromethorphan in canine plasma by dilute-and-shoot preparation combined with one minute per sample LC-MS/MS analysis to optimize formulations for drug delivery.

The determination of dextromethorphan in canine plasma is used to demonstrate the high throughput bioanalytical approach of automated dilute-and-shoot (DAS) sample preparation followed by a 1 min isocratic liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis. Dilute-and-shoot preparation is commonly used for the determination of drugs in several biological matrices such as urine and saliva, but is not typically used with plasma samples because the amount of protein present in plasma can lead to a variety of problems including column failure. As a result, plasma sample preparation usually removes protein by precipitation, extraction or filtration; however, the dilute-and-shoot approach solubilizes proteins throughout the chromatographic portion of the assay. The attributes of this approach are compared with a previously validated liquid/liquid extraction procedure for determination of dextromethorphan in plasma. Accuracy and precision of both methods are similar. The lower limit of quantitation (LLOQ) of the dilute-and-shoot approach is much higher at 2 ng/ml versus 5 pg/ml with the liquid/liquid extraction; however, the sample throughput of the preparation portion of the dilute-and-shoot approach is more than 50-fold greater. The ruggedness of the dilute-and-shoot method was thoroughly investigated because of the problems traditionally associated with the direct injection of diluted plasma onto an LC-MS/MS instrument. With the optimal conditions, greater than 1,000 injections of diluted plasma have been successfully performed on a single column in less than 19 h making this technique an excellent approach for the rapid preparation and high throughput of plasma samples containing drug levels in the ng/ml range or higher. Application of this methodology to measure the levels of dextromethorphan in canine plasma to evaluate drug delivery from various formulations is also presented.

Comparison of packed-column supercritical fluid chromatography--tandem mass spectrometry with liquid chromatography--tandem mass spectrometry for bioanalytical determination of (R)- and (S)-ketoprofen in human plasma following automated 96-well solid-phase extraction.

The popularity of packed-column supercritical fluid, subcritical fluid, and enhanced fluidity liquid chromatographies (pcSFC) for enantiomeric separations has increased steadily over the past few years. The addition of a significant amount (typically 20-95%) of a viscosity lowering agent, such as carbon dioxide, to the mobile phase provides a number of advantages for chiral separations. For example, higher mobile-phase flow rates can often be attained without a concomitant loss in chromatographic efficiency since diffusion coefficients, and optimum velocities, are typically higher in pcSFC. Ultratrace enantioselective quantitation of drugs in biomatrixes is an ideal application for these chromatographic attributes. To demonstrate the utility of this approach, a pcSFC tandem mass spectrometry (pcSFC-MS/MS) method was compared to a LC-MS/MS method for quantitation of the (R)- and (S)-enantiomers of ketoprofen (kt), a potent nonsteroidal, anti-inflammatory drug, in human plasma. After preparation using automated solid-phase extraction in the 96-well format, kt enantiomers were separated on a Chirex 3005 analytical column using isocratic conditions. Validation data and study sample data from patients dosed with either orally or topically administered ketoprofen were generated using both pcSFC and LC as the chromatographic methods to compare and contrast these analytical approaches. Generally, most analytical attributes, including specificity, linearity, sensitivity, accuracy, precision, and ruggedness, for both of these methods were comparable with the exception that the pcSFC separation provided a roughly 3-fold reduction in analysis time. A 2.3-min pcSFC separation and a 6.5-min LC separation provided equivalent, near-baseline-resolved peaks, demonstrating a significant time savings for analysis of large batch pharmacokinetic samples using pcSFC.

Determination of (R)- and (S)-ketoprofen in human plasma by liquid chromatography/tandem mass spectrometry following automated solid-phase extraction in the 96-well format.

A sensitive and selective method was developed for the determination of (R)-ketoprofen ((R)-kt) and (S)-ketoprofen ((S)-kt) in human plasma using chiral liquid chromatography/tandem mass spectrometry (LC/MS/MS). Plasma samples spiked with stable-isotope-labeled [(13)C(1), (2)H(3)]-(R and S)-ketoprofen, for use as the internal standards, were prepared for analysis using automated solid-phase extraction (SPE) in the 96-well microtiter format. The enantiomers were separated on an (R)-1-naphthylglycine and 3,5-dinitrobenzoic acid (Chirex 3005) 250x2.0 mm i.d. analytical column, equipped with a 30x2.0 mm i.d. guard column using isocratic mobile phase conditions. The (R)- and (S)-kt levels were quantifiable from 0.05 to 2500 ng ml(-1) by constructing two separate curves from calibration standards covering the same range. The first curve ranged from 0.05 to 100 and the second from 100 to 2500 ng ml(-1). A concentration of 0.05 ng ml(-1) of either enantiomer was easily detected using a 1 ml plasma sample volume. The average method accuracy, evaluated at four levels over an extended period, was better than +/-3% over the entire range. The precision for the same set of quality control samples ranged from 4.0 to 7.0 % RSD (n = 24). The method was applied to the evaluation of pharmacokinetic parameters in human plasma obtained from volunteers who received 25 mg of kt by peroral administration of Actron caplets or by topical administration of Oruvail gel.

Stability of alatrofloxacin mesylate in 5% dextrose injection and 0.45% sodium-chloride injecion.

A high-performance liquid chromatographic assay method for the quantitation of alatrofloxacin in intravenous (IV) admixtures has been developed. The method is accurate and precise, with a percent relative standard deviation of 1.2% based on five injections. The method is stability indicating since the product of decomposition, trovafloxacin, did not interfere with the assay procedure. The IV admixtures of alatrofloxacin (1.88 mg/mL) in 5% dextrose and 0.45% sodium-chloride injections were stable for at least nine days when stored at room themperature. The pH values of the admixtures did not change and they remained clear throughout this study.

Design and assembly of an 8 tesla whole-body MR scanner.

PURPOSE: The purpose of this report is to describe the design and construction of an 8 T/80 cm whole-body MRI system operating at 340 MHz. METHOD: The 8 T/80 cm magnet was constructed from 414 km of niobium titanium superconducting wire. The winding of this wire on four aluminum formers resulted in a total inductance of 4,155 H. Gradient subsystems included either a body gradient or a head gradient along with a removable shim insert. The magnet and gradient subsystems were interfaced to two spectrometers. These provided the control of the gradient amplifiers and the two sets of four RF power amplifiers. The latter provide in excess of 8 kW of RF power from 10 to 140 MHz and 10 kW of RF power from 245 to 345 MHz. A dedicated computer-controlled patient table was designed and assembled. The entire system is located in a clinical setting, facilitating patient-based studies. RESULTS: The 8 T/80 cm magnet was energized without complication and achieved persistent operation using 198.9 A of current, thereby storing 81.5 MJ of magnetic energy. Exceptional performance was observed for nearly all components both in isolation and when combined within the complete system. CONCLUSION: An 8 T/80 cm MRI system has been assembled. The magnet subsystem is extremely stable and is characterized by good homogeneity and acceptable boil-off rates.

The impact of real wage and mortality fluctuations on fertility and nuptiality in precensus England.

"This paper explores the responses of fertility and nuptiality to fluctuations in real wages and mortality that can be inferred from annual series of English historical data over the period 1542 to 1800. The paper begins with a review of the time series properties of the data and summarizes the long-term equilibrium relationships identified in previous work.... An investigation is made of the impact of shocks to real wages and mortality on demographic variables as measured by generalized impulse responses and persistence profiles."

Stability of ketorolac tromethamine in 5% dextrose injection and 0.9% sodium chloride injections.

The stability of ketorolac tromethamine in 5% dextrose injection and 0.9% sodium cholride injection has been studied using a stability-indicating, high-performance liquid chromatography assay method developed in our laboratory. This method is precise and accurate, with a percent relative standard deviation of 0.85% based on five readings. The admixtures were stable for at least 50 days when stored at 5 deg C. At 25 deg C the 0.9% sodium chloride admixture was stable for at least 35 days, and in 5% dextrose injection for only seven days. After 14 days of storage at 25 deg C the pH value of the admixture in 5% dextrose injection had decreased from 6.6 to 4.3. The changes in pH values of all other admixtures were less than 0.55. This assay method can be used to quantify ketorolac tromethamine in injections and tablets.

Stability of cefmetazole sodium in 5% dextrose injection and 0.9% sodium chloride injection.

The stability of cefmetazole sodium in 5% dextrose injection and 0.9% sodium choloride injection has been studied using a stability-indicating, high performance liquid chromatography (HPLC) assay method developed in our laboratory. This HPLC method is precise and accurate, with a percent relative standard deviation of 1.4 based on five readings. The admixtures were stable for two days at 25 deg C and for 28 days at 5 deg C, and they remained clear throughout the study period. The pH values decreased from 4.7 to 4.0 in 0.9% sodium chloride injection and from 4.8 to 4.2 in 5% dextrose injection. The expiry date of seven days at 5 deg C recommended by the manufacturer appears to be conservative from a chemical-stability standpoint.

Stability of ceftriaxone sodium when mixed with metronidazole injection.

The chemical stabilities of ceftriaxone sodium and metronidazole in a mixture have been studied using a stability-indicating, high-performance liquid chromatography (HPLC) assay method. The HPLC method is precise and accurate, with a percent relative standard deviation of 1.4 based on five readings. Metronidazole did not lose any potency for four days when stored at 25+/-1 deg C. Ceftriaxone sodium lost less than 6% ofpotency in three days at 25+/-1 deg C. The products of decomposition did not interfere with the assay procedure. They eluted before the ceftriaxone peak. The solution remained clear (light yellow) throughout the study period, and the pH value did not change. Ceftriaxone sodium and metronidazole, when mixed together, were stable for three days at 25+/-1 deg C.

Stability of cefepime hydrochloride dextrose in 5% dextrose injection and 0.9% sodium chloride injection.

The stability of cefepime hydrochloride in 5% dextrose injection and 0.9% sodium chloride injection was studied using a stability-indicating assay method developed in our laboratory. This method is precise and accurate, with a percent relative standard deviation of 0.7% based on five readings. The admixtures were stable for two days at 25 deg C and 23 days at 5 deg C. The pH values of the admixtures did not change throughout this study, and the colors had changed from a very light yellow to a light yellow. The manufacturer recommends an expiry date of 24 hours at 20 to 25 deg C and seven days at 2 to 8 deg C.

Predisposing factors for individuals' Lyme disease prevention practices: Connecticut, Maine, and Montana.

OBJECTIVES: This study examined factors that predispose individuals to protect against Lyme disease. METHODS: Knowledge, attitude, and practice questions concerning Lyme disease prevention were included in the Behavioral Risk Factor Surveillance surveys in Connecticut, Maine, and Montana. A total of 4246 persons were interviewed. RESULTS: Perceived risk of acquiring Lyme disease, knowing anyone with Lyme disease, knowledge about Lyme disease, and believing Lyme disease to be a common problem were significantly associated with prevention practices. CONCLUSIONS: Predisposing factors differ substantially between states and appear related to disease incidence. Personal risk, knowing someone with Lyme disease, and cognizance about Lyme disease and acting on this information are consistent with social learning theories.

Serodiagnosis of Lyme disease: accuracy of a two-step approach using a flagella-based ELISA and immunoblotting.

An ELISA containing a purified flagellar antigen from Borrelia burgdorferi (FLA-ELISA) was evaluated. The FLA-ELISA, detecting IgM and IgG together, did not have adequate specificity by itself. Good accuracy was obtained, however, when the FLA-ELISA was the first step in a two-step protocol that used immunoblotting as a conditional second test. Samples that scored positive or equivocal by the FLA-ELISA were evaluated with separate IgM and IgG immunoblots. The sensitivity of the two-step process for patients with erythema migrans or with later manifestations of Lyme disease was 64% and 100%, respectively. The specificity for health blood donors was 100% and was 90% for the aggregate of all persons with illness that may cause serologic cross-reactivity (98% if the samples from relapsing fever patients were excluded). Test precision was 96% overall, 99% for Lyme disease case serum samples, 100% for specimens from blood donors, and 88% for samples from persons with other illness.

Cytokine responses to dengue infection among Puerto Rican patients.

Recently, a strong correlation between high concentration of tumor necrosis factor (TNF alpha) in blood and severity of dengue hemorrhagic fever/dengue shock syndrome has been reported from Asia and the Pacific. We wished to determine if a similar relationship could be found in dengue patients in the Americas where adult patients with severe syndromes have been observed more frequently than in Asia where severe cases have been observed mostly among children. The concentrations of interleukin-1 (IL-1 beta) in hospitalized adult groups were significantly lower than that in outpatient adults. In contrast, the levels of interleukin 6 (IL-6) were significantly higher in hospitalized adults and children than in the corresponding outpatients. Levels of TNF alpha were higher in hospitalized children than in outpatient children or hospitalized adults. There was no significant difference in the levels of these three cytokines among hospitalized patients with or without hemorrhagic manifestations. Thus, an elevated IL-6 level was positively associated with severity of dengue infection in both children and adults, but IL-1 beta level was negatively associated with severity in adults.

Diagnosis and treatment of infectious mononucleosis.

Infectious mononucleosis is caused by the Epstein-Barr virus (EBV) and most commonly affects young adults from 15 to 35 years of age. The diagnosis is made by accurate assessment of clinical, hematologic and serologic manifestations of the illness. Manifestations include the classic triad of fever, pharyngitis and cervical lymphadenopathy; lymphocytosis with a predominance of atypical lymphocytes; a positive heterophil (Monospot) antibody test; and in some cases, serologic evidence of EBV-specific antibodies produced against antigens related to the virus. The most valuable serologic finding is the presence of IgM antibody to EBV viral capsid antigen, which is found during acute primary EBV infection. Infectious mononucleosis is considered a self-limited illness, but it may result in serious complications involving the pulmonary, ophthalmologic, neurologic and hematologic systems. Treatment is focused on managing the symptoms, unless more severe disease involving other organ systems occurs. The most common potentially fatal complication is splenic rupture.

Eastern equine encephalitis (EEE): a description of the 1989 outbreak, recent epidemiologic trends, and the association of rainfall with EEE occurrence.

An Eastern equine encephalitis (EEE) outbreak in 1989 led to nine human and 196 equine cases, chiefly in coastal Atlantic and Gulf Coast counties. In the past two decades, EEE age-specific incidence and mortality rates have declined compared with earlier years. Analysis of rainfall patterns in areas where human EEE cases occurred between 1983 and 1989 revealed an association between occurrence of human cases and excess rainfall. The association was stronger with data from local weather stations than from statewide rainfall averages and the predictive models were best when applied to northern states. The sensitivity and specificity of these measures varied, depending on the model used, but the positive predictive value was no better than 50%, regardless of the rainfall model applied.