Identification of serologic markers for school-aged children with congenital rubella syndrone

BACKGROUND: Congenital rubella syndrome (CRS) case identification is challenging in older children since laboratory markers of congenital rubella virus (RUBV) infection do not persist beyond age 12 months. METHODS: We enrolled children with CRS born between 1998 and 2003 and compared their immune responses to RUBV with those of their mothers and a group of similarly aged children without CRS. Demographic data and sera were collected. Sera were tested for anti-RUBV immunoglobulin G (IgG), IgG avidity, and IgG response to the 3 viral structural proteins (E1, E2, and C), reflected by immunoblot fluorescent signals. RESULTS: We enrolled 32 children with CRS, 31 mothers, and 62 children without CRS. The immunoblot signal strength to C and the ratio of the C signal to the RUBV-specific IgG concentration were higher (P < .029 for both) and the ratio of the E1 signal to the RUBV-specific IgG concentration lower (P = .001) in children with CRS, compared with their mothers. Compared with children without CRS, children with CRS had more RUBV-specific IgG (P < .001), a stronger C signal (P < .001), and a stronger E2 signal (P ≤ .001). Two classification rules for children with versus children without CRS gave 100% specificity with >65% sensitivity. CONCLUSIONS: This study was the first to establish classification rules for identifying CRS in school-aged children, using laboratory biomarkers. These biomarkers should allow improved burden of disease estimates and monitoring of CRS control programs. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Effects of deoxynivalenol consumption on body weight and adiposity in the diet-induced obese mouse.

The potential for the obese state to alter sensitivity to toxic chemicals is poorly understood. In this study, dose-response effects of the trichothecene deoxynivalenol (DON), a common food-borne mycotoxin, were determined on body weight of diet-induced obese mice. In study 1, the effects of feeding adult female B6C3F1 mice a high-fat diet (HFD; 60% kcal from fat) containing 0, 2, 5, or 10 ppm DON for 10 wk on body weight and adiposity were compared. Mice consuming 5 or 10 ppm DON exhibited a 15 and 24% decrease in weight gain and a 50 and 83% reduction in periuterine fat, respectively. In study 2, mice were fed HFD for 8 wk to induce obesity and the effects of consuming HFD + 0, 2, 5, or 10 ppm DON for 8 wk were then determined. Mice fed 5 or 10 ppm DON exhibited a 16 and 23% weight reduction and a 0 and 40% periuterine fat reduction, respectively. In a follow-up experiment, food consumption was measured prior to and after the transition from HFD to HFD + 10 ppm DON. Exposure to DON was found to lower HFD consumption within 1 d, with significant weight loss in DON-fed mice evident after 6 d. In both studies 1 and 2, consumption of 5 or 10 ppm DON diminished circulating levels of insulin-like growth factor acid-labile subunit. Taken together, DON consumption lowered weight gain and produced weight loss in diet-induced obese mice at higher thresholds than that observed previously in normal B6C3F1 mice.

Estimating the vaccine-preventable burden of hospitalized pneumonia among young Mozambican children.

Polysaccharide-protein conjugate vaccines against Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae have proven efficacy against radiologically confirmed pneumonia. Measurement of pneumonia incidence provides a platform to estimate of the vaccine-preventable burden. Over 24 months, we conducted surveillance for radiologically confirmed severe pneumonia episodes among children <2 years of age admitted to a rural hospital in Manhiça, southern Mozambique. Study children were tested for HIV during the second year of surveillance. Severe pneumonia accounted for 15% of 5132 hospital admissions and 32% of in-hospital mortality among children <2 years of age. Also, 43% of chest radiographs were interpreted as radiologically confirmed pneumonia. HIV-infection was associated with 81% of fatal pneumonia episodes among children tested for HIV. The minimum incidence rate of radiologically confirmed pneumonia requiring hospitalization was 19 episodes/1000 child-years. Incidence rates among HIV-infected children were 9.3-19.0-fold higher than HIV-uninfected. Introduction of Hib and pneumococcal conjugate vaccines would have a substantial impact on pneumonia hospitalizations among African children if vaccine effects are similar to those observed in clinical trials.

The influence of hydrology and waterway distance on population structure of Chinook salmon Oncorhynchus tshawytscha in a large river.

Adult Chinook salmon Oncorhynchus tshawytscha navigate in river systems using olfactory cues that may be influenced by hydrologic factors such as flow and the number, size and spatial distribution of tributaries. Thus, river hydrology may influence both homing success and the level of straying (gene flow), which in turn influences population structure. In this study, two methods of multivariate analysis were used to examine the extent to which four indicators of hydrology and waterway distance explained population structure of O. tshawytscha in the Yukon River. A partial Mantel test showed that the indicators of hydrology were positively associated with broad-scale (Yukon basin) population structure, when controlling for the influence of waterway distance. Multivariate multiple regression showed that waterway distance, supplemented with the number and flow of major drainage basins, explained more variation in broad-scale population structure than any single indicator. At an intermediate spatial scale, indicators of hydrology did not appear to influence population structure after accounting for waterway distance. These results suggest that habitat changes in the Yukon River, which alter hydrology, may influence the basin-wide pattern of population structure in O. tshawytscha. Further research is warranted on the role of hydrology in concert with waterway distance in influencing population structure in Pacific salmon.

Impact of conjugate Haemophilus influenzae type b (Hib) vaccine introduction in South Africa.

OBJECTIVE: To analyse trends in reported invasive Haemophilus influenzae disease in South Africa within the first five years of introduction of conjugate Haemophilus influenzae type b (Hib) vaccine in the routine child immunization schedule. METHODS: We used national laboratory-based surveillance data to identify cases of invasive H. influenzae disease between July 1999 and June 2004, and submitted isolates for serotyping and antimicrobial susceptibility testing. FINDINGS: The absolute number of Hib cases (reported to the national surveillance system) among children below one year of age decreased by 65%, from 55 cases in 1999-2000 to 19 cases in 2003-04. Enhanced surveillance initiated in 2003, identified human immunodeficiency virus (HIV)-infection and incomplete vaccination as contributing factors for Hib transmission. The total number of laboratory-confirmed cases of H. influenzae remained unchanged because non-type b disease was being increasingly reported to the surveillance system concomitant with system enhancements. Children with non-typable disease were more likely to be HIV-positive (32 of 34, 94%) than children with Hib disease (10 of 14, 71%), P = 0.051. Recent Hib isolates were more likely to be multidrug resistant (2% in 1999-2000 versus 19% in 2003-04, P = 0.001). CONCLUSION: Data from a newly established national laboratory-based surveillance system showed a decrease in Hib disease burden among South African children following conjugate vaccine introduction and identified cases of non-typable disease associated with HIV infection.

Physicians practicing in methadone treatment programs: who are they and what do they do?

OBJECTIVE: This study examines the characteristics and roles of physicians practicing in methadone maintenance treatment programs (MTPs). METHODS: Physicians and clinic directors at 172 MTPs in the United States completed surveys. MTPs were selected for study participation based on their locations (large urban, urban, or nonurban area) ownership status (for profit and non-profit), and size (patient capacity of 1-100, 101-300, and 300+). Weighted data were analyzed with descriptive and multivariate methods. RESULTS. Physicians were primarily white males aged 45 or older; 44% had 10 or more years of experience working in methadone treatment. Physicians reported spending 26% of their time completing administrative tasks. Most reported that they determine dosing levels on an individual patient basis. Average maintenance dose was 69 mg/day. CONCLUSIONS: Physicians' treatment practices play a major role in overall treatment, treatment retention, and outcomes. Physicians at for-profit and large urban MTPs reported spending the most time in direct patient contact.

Extended-spectrum beta-lactamase-producing Klebsiella pneumoniae in a neonatal intensive care unit: risk factors for infection and colonization.

An outbreak of extended spectrum beta-lactamase-producing Klebsiella pneumoniae (ESBLKp) infections in a neonatal intensive care unit (NICU) prompted a prospective investigation of colonization and infection with this pathogen. From August 1, 1997 to May 30, 1999, neonates admitted to the NICU for more than 24 h were screened for ESBLKp acquisition. Neonatal gastrointestinal screening was performed by means of faecal sampling within 48 h of admission and then weekly until discharge. Isolates were typed using pulsed-field gel electrophoresis (PFGE). Time-dependent proportional hazard models were used to identify independent effects of invasive procedures and antimicrobials after controlling for duration of stay at the NICU. During the study period, 464 neonates were admitted and 383 were regularly screened. Infections occurred in 13 (3.4%) neonates and 206 (53.8%) became colonized. Independent risk factors for colonization during the first nine days in the NICU were the antimicrobial combination cephalosporin plus aminoglycoside [hazard rate (HR)=4.60; 95% CI: 1.48-14.31], and each NICU-day was associated with a 26% increase in the hazard rate for colonization (HR=1.26; 95% CI: 1.16-1.37). Previous colonization (HR=5.19; 95% CI: 1.58-17.08) and central vascular catheter use (HR=13.89; 95% CI: 2.71-71.3) were independent risk factors for infection. In an outbreak setting the proportion of neonates colonized with ESBLKp was observed to increase with the duration of stay and antimicrobial use, and once colonized, infants exposed to invasive devices may become infected.

Alcohol craving predicts drinking during treatment: an analysis of three assessment instruments.

OBJECTIVE: The purpose of this investigation was to examine the utility of thee craving instruments to predict drinking during treatment. The three assessments used were the Penn Alcohol Craving Scale (PACS), the Alcohol Urge Questionnaire (AUQ) and Items 1-6 of the Obsessive subscale (OBS) of the Obsessive Compulsive Drinking Scale (OCDS). METHOD: The three instruments were administered during the course of a 9-month, double-blind, placebo-controlled trial of 100 mg/day of naltrexone, and a manual-based psychosocial intervention using the BRENDA manual conducted at the University of Pennsylvania's Treatment Research Center. Participants (133 men and 50 women at the initiation of the study) used these instruments to self-report craving on a weekly or biweekly basis. The weekly number of drinks was reported using the Timeline Followback interview. The data were analyzed with generalized estimating equations using craving scores at 1 week as the independent variable and number of drinks in the subsequent treatment week as the dependent variable. RESULTS: Each of the three scales predicted drinking during the subsequent treatment week. The PACS was the strongest predictor followed closely by the OBS and then the AUQ. Most important, craving as measured by the three scales was a stronger predictor of subsequent drinking than was drinking during the prior treatment week. CONCLUSIONS: Craving assessment provides a useful means of predicting drinking during treatment. Such information would be helpful in designing clinical trials and for many treatment modalities.

Referral pattern of leptospirosis cases during a large urban epidemic of dengue.

During heavy seasonal rainfall in 1996, concurrent epidemics of dengue and leptospirosis occurred in an urban center in northeastern Brazil. We interviewed 110 cases of leptospirosis hospitalized a median of seven days after the onset of illness to evaluate the impact of the dengue epidemic on the triage of suspected leptospirosis from ambulatory clinics to the infectious disease reference hospital. Within the first three days of illness, 46 (42%) cases sought their first medical evaluation, and 28 (61% of 46) received a diagnosis of dengue. Dengue diagnoses were associated with a median of five days delay in referral to the infectious disease hospital. Patients who reported initial diagnoses of dengue were more likely than other patients to have required admission to the intensive care unit (odds ratio [OR] = 2.7, 95% confidence interval [CI] = 0.8-9.5) and to have died during hospitalization (OR = 5.1, 95% CI = 0.8-55.0). These findings indicate that diagnostic confusion between the early symptoms of leptospirosis and dengue may have contributed to the high mortality observed during the leptospirosis epidemic.

Predicting treatment response to naltrexone: the influence of craving and family history.

Naltrexone has repeatedly been shown to reduce drinking in alcohol-dependent patients. Previous clinical research suggests that naltrexone may be more effective at reducing drinking among patients with high levels of alcohol craving at the beginning of treatment. In addition, laboratory studies suggest that naltrexone may be more efficacious among patients with a high familial loading of alcohol problems. We explored both of these possibilities in the context of the first 12-week phase of a double blind, placebo-controlled naltrexone trial. A total of 121 patients were randomized to receive 100 mg/day naltrexone and 62 patients were randomized to receive placebo. Both naltrexone and placebo were given in conjunction with a psychosocial intervention designed to be integrated with the use of pharmacotherapy. This intervention was administered by nurse practitioners. Overall, patients randomized to naltrexone reported drinking five or more drinks on fewer days than did placebo controls (p = .04). Interactions were observed between medication group assignment and both craving level prior to randomization (p = .02) and family loading of alcohol problems (p = .05). In both cases, the interaction was in the predicted direction. These data suggest that patients with high levels of alcohol craving or a strong family history of alcoholism are more likely to benefit from naltrexone treatment.

Evaluation of recombinant Leptospira antigen-based enzyme-linked immunosorbent assays for the serodiagnosis of leptospirosis.

There is an urgent need for development of new serodiagnostic strategies for leptospirosis, an emerging zoonosis with worldwide distribution. We have evaluated the diagnostic utility of five recombinant antigens in enzyme-linked immunosorbent assays (ELISAs) for serodiagnosis of leptospirosis. Sera from 50 healthy residents of a high-incidence region were used to determine cutoff values for 96% specificity. In paired sera from 50 cases of leptospirosis confirmed by the microscopic agglutination test, immunoglobulin G (IgG) but not IgM reacted with the recombinant leptospiral proteins. The recombinant LipL32 IgG ELISA had the highest sensitivities in the acute (56%) and convalescent (94%) phases of leptospirosis. ELISAs based on recombinant OmpL1, LipL41, and Hsp58 had sensitivities of 16, 24, and 18% during the acute phase and 72, 44, and 32% during convalescence, respectively. Compared to sera from healthy individuals, patient sera did not react significantly with recombinant LipL36 (P > 0.05). Recombinant LipL32 IgG ELISA demonstrated 95% specificity among 100 healthy individuals, and specificities ranging from 90 to 97% among 30 dengue patients, 30 hepatitis patients, and 16 patients with diseases initially thought to be leptospirosis. Among 39 Venereal Disease Research Laboratory test-positive individuals and 30 Lyme disease patients, 13 and 23% of sera, respectively, reacted positively with the rLipL32 antigen. These findings indicate that rLipL32 may be an useful antigen for the serodiagnosis of leptospirosis.

Leptospiral proteins recognized during the humoral immune response to leptospirosis in humans.

Leptospirosis is an emerging zoonosis caused by pathogenic spirochetes belonging to the genus Leptospira. An understanding of leptospiral protein expression regulation is needed to develop new immunoprotective and serodiagnostic strategies. We used the humoral immune response during human leptospirosis as a reporter of protein antigens expressed during infection. Qualitative and quantitative immunoblot analysis was performed using sera from 105 patients from Brazil and Barbados. Sera from patients with other diseases and healthy individuals were evaluated as controls. Seven proteins, p76, p62, p48, p45, p41, p37, and p32, were identified as targets of the humoral response during natural infection. In both acute and convalescent phases of illness, antibodies to lipopolysaccharide were predominantly immunoglobulin M (IgM) while antibodies to proteins were exclusively IgG. Anti-p32 reactivity had the greatest sensitivity and specificity: positive reactions were observed in 37 and 84% of acute- and convalescent-phase sera, respectively, while only 5% of community control individuals demonstrated positive reactions. Six immunodominant antigens were expressed by all pathogenic leptospiral strains tested; only p37 was inconsistently expressed. Two-dimensional immunoblots identified four of the seven infection-associated antigens as being previously characterized proteins: LipL32 (the major outer membrane lipoprotein), LipL41 (a surface-exposed outer membrane lipoprotein), and heat shock proteins GroEL and DnaK. Fractionation studies demonstrated LipL32 and LipL41 reactivity in the outer membrane fraction and GroEL and DnaK in the cytoplasmic fraction, while p37 appeared to be a soluble periplasmic protein. Most of the other immunodominant proteins, including p48 and p45, were localized to the inner membrane. These findings indicate that leptospiral proteins recognized during natural infection are potentially useful for serodiagnosis and may serve as targets for vaccine design.

The role of craving in alcohol use, dependence, and treatment.

This article represents the proceedings of a symposium at the 2000 RSA Meeting in Denver, Colorado. The organizer and chair was Barbara A. Flannery, and the co-chairs were Barbara A. Flannery and Helen Pettinati. The presentations were (1) Animal models of alcohol craving and relapse, by Amanda Roberts; (2) Real-time field assessment of alcohol craving, by Ned Cooney; (3) Medications and alcohol craving, by Robert Swift; (4) The assessment of craving: Insights from the clinic and clinical laboratory studies, by Raymond Anton; (5) A comparison of three alcohol craving questionnaires, by Barbara Flannery; (6) and Assessing posttreatment urge to drink, by Damaris Rohsenow.

Mometasone furoate has minimal effects on the hypothalamic-pituitary-adrenal axis when delivered at high doses.

STUDY OBJECTIVES: To investigate the potential for mometasone furoate (MF) to exert systemic effects following administration by dry powder inhaler (DPI) or metered-dose inhaler (MDI). DESIGN: Three randomized, evaluator-blind, placebo-controlled, parallel-group, 28-day studies. PATIENTS: Adults with mild-to-moderate persistent asthma. INTERVENTIONS: Study 1 (12 patients per treatment group; MF DPI at 200 microg bid, 400 microg qd, 800 microg qd, or 1,200 microg qd). Study 2 (16 patients per treatment group; MF DPI at 400 microg bid or 800 microg bid, or oral prednisone at 10 mg qd). Study 3 (16 patients per treatment group; MF MDI at 400 microg bid or 800 microg bid, or fluticasone propionate [FP] at 880 microg bid by MDI). MEASUREMENTS AND RESULTS: Study 1. Plasma concentrations were near the lower limit of quantitation (50 pg/mL) at the MF DPI 400-microg qd dosage and approximately 250 pg/mL at the 1,200-microg qd dosage. The area under the curve for serum cortisol concentrations over 24 h (AUC(24)) was essentially unaltered at all doses. Study 2. Plasma levels over days 7 to 28 were 100.3 +/- 5.9 pg/mL (mean +/- SEM) for MF DPI 400 microg bid, and 181.0 +/- 10.9 pg/mL for 800 microg bid. Although there were relatively low levels of suppression (19 to 25%) at earlier time points for MF DPI 400 microg bid, serum cortisol AUC(24) levels at day 28 were similar to placebo. MF DPI 800 microg bid and oral prednisone both decreased serum cortisol AUC(24) levels at days 7 to 28 by 28.0 +/- 8.3% and 67.2 +/- 3.6%, respectively. The response to cosyntropin was normal in 15, 14, 11, and 1 of the patients in the placebo, MF DPI 400 microg bid, MF DPI 800 microg bid, and prednisone groups, respectively. Study 3. MF MDI caused even less systemic exposure than by DPI. MF MDI 800 microg bid (24.0 +/- 3.1%) and FP (51.7 +/- 3.8%) caused a significant decrease in serum cortisol AUC(24) on days 14 to 28. MF MDI 400 microg bid was similar to placebo treatment at all time points. CONCLUSIONS: The MF 800-microg bid dosage (1,600 microg/d), which is twice the highest projected clinical dosage, represents the lower limit for consistently detectable systemic effects of MF.

Psychometric properties of the Penn Alcohol Craving Scale.

BACKGROUND: This study introduces the Penn Alcohol Craving Scale (PACS), which has been used in several clinical trials at the University of Pennsylvania's Treatment Research Center. The PACS is a five-item, self-report measure that includes questions about the frequency, intensity, and duration of craving, the ability to resist drinking, and asks for an overall rating of craving for alcohol for the previous week. Each question is scaled from 0 to 6. METHODS: To examine the questionnaire's psychometric properties, we sampled responses from 147 individuals participating in a 9-month combined natrexone (100 mg/day)/psychotherapy trial. The psychotherapy consisted of weekly sessions of nurse-administered medication compliance and supportive treatment. RESULTS: The PACS proved to have excellent internal consistency. Predictive validity was demonstrated via a logistic regression analysis of craving during the 2nd week of the study on alcohol relapse during weeks 3-12 of the trial. Construct validity of the PACS was demonstrated via its convergence with two commonly used measures for assessing craving, the Obsessive Compulsive Drinking Scale and the Alcohol Urge Questionnaire. Lack of correlation between PACS scores and several other noncraving, self-report measures indicates that the PACS also had good discriminant validity. Additional analyses revealed that there were significant differences in craving scores during the initial 3 weeks of the trial among those who did and those who did not relapse during weeks 3-12. CONCLUSION: The PACS is a reliable and valid measure of alcohol craving and can predict which individuals are at risk for subsequent relapse.

Ribavirin and interferon alfa-2b in chronic hepatitis C: assessment of possible pharmacokinetic and pharmacodynamic interactions.

AIMS: The primary objective of this study was to determine whether pharmacokinetic interactions occurred between interferon alpha-2b (IFN) and ribavirin in patients with chronic hepatitis C infections. Additionally this study assessed the single and multiple-dose pharmacokinetics of ribavirin and IFN, and compared the safety, tolerability and antiviral pharmacodynamics of IFN plus ribavirin compared with either drug alone. METHODS: In this open label parallel group study, patients with chronic hepatitis C were randomized to receive IFN 3 million IU thrice weekly s.c. alone, ribavirin 600 mg twice daily p.o. alone or both drugs in combination over 6 weeks. Single and multiple dose pharmacokinetics and indices of antiviral pharmacodynamics were assessed during weeks 1 and 6, along with safety assessments during the study. RESULTS: The range of mean ribavirin terminal phase half-lives after single doses was 44-49 h. Comparison of week 1 and week 6 AUC(0,12h) values showed accumulation in plasma of approximately 6-fold. The range of mean washout half-lives after week 6 was 274-298 h, reflecting release of ribavirin from deep compartment stores. The range of single and multiple dose IFN terminal phase half-lives was 5-7 h. IFN demonstrated an increase in bioavailability (approximately 2-fold) upon multiple dose administration. Ribavirin and IFN pharmacokinetic parameters for combined ribavirin and IFN were similar to those during monotherapy with either compound, although the power of this study to detect differences was low. Serum HCV-RNA titers and ALT concentrations were reduced by IFN alone, ribavirin alone reduced ALT concentrations only, and combined IFN plus ribavirin produced numerically greater falls in both measurements than either treatment alone. Serum concentrations of neopterin and activity of 2',5'-oligoadenylate synthetase (2'5'-OAS) were increased by IFN alone and in combination with ribavirin, whereas serum 2'5'-OAS activity was decreased and neopterin concentrations unaltered by ribavirin monotherapy. IFN and ribavirin monotherapy produced characteristic changes in safety laboratory tests (IFN--reductions in white cells, neutrophils and platelets; ribavirin--reduced haemoglobin) and characteristic adverse event profiles (IFN--headache, flu-like symptoms, fatigue, anorexia, nausea, myalgia, and insomnia; ribavirin--headache, fatigue, myalgia, and pruritus). There was no additive effect of combination therapy on safety laboratory tests or reported adverse events. All changes were fully reversible upon treatment cessation. CONCLUSIONS: There was no evidence of pharmacokinetic interactions between IFN and ribavirin in this study. There were numerical trends indicating that the combination of IFN and ribavirin reduced titers of HCV-RNA to a greater extent than did either treatment alone, and the safety profile of combination therapy was similar to those of both monotherapy treatments.

Effects of wheat germ agglutinin on tunicate egg activation and fertilization: is there a plasma membrane sperm receptor system on Ascidia ceratodes eggs?

Little work has been carried out on the sperm recognition systems present on the egg plasma membrane. Here it is shown that wheat germ agglutinin (WGA) interferes with the sperm-interacting system on the plasma membrane of eggs of the ascidian, Ascidia ceratodes. The WGA activates the dechorionated egg, indicating that a plasma membrane sugar residue can be directly tied to egg activation. Low concentrations of this lectin do not activate the eggs, but reduce fertilizability. This observation suggests that the WGA binding site might be part of a sperm reception-activation complex in the plasma membrane. While WGA also affects sperm binding to the chorion, the mechanisms of sperm interaction at the plasma membrane and chorion show different sensitivities to lectins, sugars and enzymes.

Effect of food on the oral bioavailability of isosorbide-5-mononitrate administered as an extended-release tablet.

We evaluated the effect of a high-fat breakfast and gastric emptying rate on the oral bioavailability of a isosoribide-5-mononitrate (5-ISMN) controlled-release tablet formulation (IMDUR 60-mg tablets, Astra Hässle AB, Mölndal, Sweden) relative to an oral solution in 18 healthy men. Gastric emptying was monitored by radiotelemetry using the Heidelberg capsule technique. After administration of the 5-ISMN 60-mg solution, absorption was rapid with mean peak plasma 5-ISMN concentrations of 1533 ng/mL achieved in less than 1 hour. In contrast, after administration of IMDUR 60-mg tablets, the drug was more slowly absorbed, reaching mean peak plasma concentrations of 541 ng/mL in 3 to 4 hours. The bioavailability of 5-ISMN from IMDUR tablets under fasted conditions was approximately 78% relative to the solution; and, in the presence of food, the bioavailability was slightly increased to 86% (P = .057). The mean gastric residence time of IMDUR tablets under fasted conditions was 68 minutes, and in the presence of food was increased to 478 minutes, with 9 of the 18 subjects having gastric emptying delayed for at least 600 minutes. We conclude that in the presence of food, gastric emptying time is considerably increased causing a delay in drug absorption and a slight increase in the bioavailability of 5-ISMN from this controlled-release tablet formulation, however this effect is not clinically relevant.

Three-Dimensional X-ray Microtomography.

The new technique of x-ray microtomography nondestructively generates three-dimensional maps of the x-ray attenuation coefficient inside small samples with approximately 1 percent accuracy and with resolution approaching 1 micrometer. Spatially resolved elemental maps can be produced with synchrotron x-ray sources by scanning samples at energies just above and below characteristic atomic absorption edges. The system consists of a high-resolution imaging x-ray detector and high-speed algorithms for tomographic image reconstruction. The design and operation of the microtomography device are described, and tomographic images that illustrate its performance with both synchrotron and laboratory x-ray sources are presented.