Population Density and Health Outcomes in Women with HIV in the Southern United States: A Retrospective Longitudinal Analysis.

Purpose: Published studies have revealed challenges for people with human immunodeficiency virus (HIV) living in rural areas compared to those in urban areas, such as poor access to HIV care, insufficient transportation, and isolation. The purpose of this study was to examine associations between population density and multiple psychosocial and clinical outcomes in the largest cohort of women with HIV (WWH) in the United States. Methods: Women's Interagency HIV Study (WIHS) participants from Southern sites (n = 561) in 2013-2018 were categorized and compared by population density quartiles. The most urban quartile was compared with the most rural quartile in several psychosocial and clinical variables, including HIV viral load suppression, HIV medication adherence, HIV care attendance, depression, internalized HIV stigma, and perceived discrimination in healthcare settings. Results: Although women in the lowest density quartile were unexpectedly more highly resourced, women in that quartile had greater odds of not attending an HIV care visit in the last six months (odds ratio [OR] = 0.64, 95% confidence interval [CI] [0.43-0.95]), yet higher odds for having fully suppressed HIV when compared to women in the highest density quartile (OR = 1.64, 95% CI [1.13-2.38]). Highly urban WWH had greater likelihood of unsuppressed HIV, even after controlling for income, employment, and health insurance, despite reporting greater HIV care adherence and similar medication adherence. Discussion: Further investigation into the reasons for these disparities by population density is needed, and particular clinical attention should be focused on individuals from high population density areas to help maximize their health outcomes.

Measurement of the Positive Muon Anomalous Magnetic Moment to 0.20 ppm.

We present a new measurement of the positive muon magnetic anomaly, a_{µ}≡(g_{µ}-2)/2, from the Fermilab Muon g-2 Experiment using data collected in 2019 and 2020. We have analyzed more than 4 times the number of positrons from muon decay than in our previous result from 2018 data. The systematic error is reduced by more than a factor of 2 due to better running conditions, a more stable beam, and improved knowledge of the magnetic field weighted by the muon distribution, ω[over ˜]_{p}^{'}, and of the anomalous precession frequency corrected for beam dynamics effects, ω_{a}. From the ratio ω_{a}/ω[over ˜]_{p}^{'}, together with precisely determined external parameters, we determine a_{µ}=116 592 057(25)×10^{-11} (0.21 ppm). Combining this result with our previous result from the 2018 data, we obtain a_{µ}(FNAL)=116 592 055(24)×10^{-11} (0.20 ppm). The new experimental world average is a_{µ}(exp)=116 592 059(22)×10^{-11} (0.19 ppm), which represents a factor of 2 improvement in precision.

Neutral Silicon-Vacancy Center in Diamond: Spin Polarization and Lifetimes.

We demonstrate optical spin polarization of the neutrally charged silicon-vacancy defect in diamond (SiV^{0}), an S=1 defect which emits with a zero-phonon line at 946 nm. The spin polarization is found to be most efficient under resonant excitation, but nonzero at below-resonant energies. We measure an ensemble spin coherence time T_{2}>100 µs at low-temperature, and a spin relaxation limit of T_{1}>25 s. Optical spin-state initialization around 946 nm allows independent initialization of SiV^{0} and NV^{-} within the same optically addressed volume, and SiV^{0} emits within the telecoms down-conversion band to 1550 nm: when combined with its high Debye-Waller factor, our initial results suggest that SiV^{0} is a promising candidate for a long-range quantum communication technology.

Feasibility Analysis of an evidence-based positive prevention intervention for youth living with HIV/AIDS in Kinshasa, Democratic Republic of the Congo.

We evaluated the feasibility of a Positive Prevention intervention adapted for youth living with HIV/AIDS (YLWH) ages 15-24 in Kinshasa, Democratic Republic of the Congo. We conducted in-depth interviews and focus group discussions with intervention facilitators and YLWH participants on the following four areas of a feasibility framework: acceptability, implementation, adaptation, and limited-efficacy. The adapted intervention was suitable, satisfying, and attractive to program facilitators and participants and able to be implemented effectively. It performed well with a new population and showed preliminary efficacy. However, we identified certain aspects of the intervention that must be addressed prior to wider implementation such as: (1) including more content on navigating marriage while living with HIV and disclosure; (2) adjusting intervention timing and session length; and (3) simplifying the more complicated content. An adapted evidencebased intervention was found to be feasible and lessons learned can be applied to YLWH in other low-resource settings.

Adaptation of a U.S. evidence-based Positive Prevention intervention for youth living with HIV/AIDS in Kinshasa, Democratic Republic of the Congo.

Effective HIV prevention programs for people living with HIV/AIDS (PLWH) are important to reduce new infections and to ensure PLWH remain healthy. This paper describes the systematic adaptation of a U.S.-developed Evidence Based Intervention (EBI) using the Centers for Disease Control and Prevention (CDC) Map of Adaption Process for use at a Pediatric Hospital in Kinshasa, Democratic Republic of the Congo (DRC). The adapted intervention, Supporting Youth and Motivating Positive Action or SYMPA, a six-session risk reduction intervention targeted for youth living with HIV/AIDS (YLWH) in Kinshasa was adapted from the Healthy Living Project and guided by the Social Action Theory. This paper describes the process of implementing the first four steps of the ADAPT framework (Assess, Select, Prepare, and Pilot). Our study has shown that an EBI developed and implemented in the U.S. can be adapted successfully for a different target population in a low-resource context through an iterative process following the CDC ADAPT framework. This process included reviewing existing literature, adapting and adding components, and focusing on increasing staff capacity. This paper provides a rare, detailed description of the adaptation process and may aid organizations seeking to adapt and implement HIV prevention EBIs in sub-Saharan Africa and beyond.

Barriers to Provider-Delivered Sexual Behavior Counseling for Youth Living with HIV/AIDS in the Democratic Republic of the Congo.

AIMS: The study aimed to understand providers' role in delivering HIV transmission prevention counseling to youth living with HIV (YLWH). METHODS: We conducted 14 in-depth interviews with providers in Kinshasa, DRC. RESULTS: Providers' lack of knowledge and comfort in talking to youth about sex because of cultural and religious beliefs about sexuality, coupled with confusion about legal issues related to youth and contraception, made it difficult for them to effectively counsel youth. IMPLICATIONS FOR PRACTICE AND POLICY: In order for providers to deliver effective prevention counseling to YLWH, clinics should follow adolescent-friendly clinic standards, provide counseling in an adolescent-friendly style, and institute an effective referral system for additional prevention services. CONCLUSION: HIV prevention services can be improved through the creation of an adolescent-friendly environment and by providing "values clarification" and skill-based trainings so that providers are able to assess the role of their own beliefs and learn new skills.

Electron paramagnetic resonance studies of nitrogen interstitial defects in diamond.

We report on electron paramagnetic resonance (EPR) studies of nitrogen doped diamond that has been (15)N enriched, electron irradiated and annealed. EPR spectra from two new nitrogen containing [Formula: see text] defects are detected and labelled WAR9 and WAR10. We show that the properties of these defects are consistent with them being the ⟨001⟩-nitrogen split interstitial and the ⟨001⟩-nitrogen split interstitial-⟨001⟩-carbon split interstitial pair, respectively. We also provide an explanation for why these defects have previously eluded discovery.

Exposure to nicotine and a tobacco-specific carcinogen increase with duration of use of smokeless tobacco.

BACKGROUND: Smokeless tobacco is an efficient delivery vehicle for nicotine and can contain significant amounts of carcinogens. However, few studies have examined factors that might moderate levels of nicotine or carcinogen exposure. AIMS: To determine the effect of duration of smokeless tobacco use on the uptake of nicotine and a tobacco-specific carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). METHODS: Questionnaires on use of smokeless tobacco were administered, and urine samples from 212 smokeless tobacco users were analysed for biomarkers of uptake of nicotine and NNK. The biomarkers were cotinine and total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL). Male smokeless tobacco users were recruited for studies designed to investigate methods of reducing smokeless tobacco use. The questionnaire and biomarker data were obtained at baseline, prior to reduction. RESULTS: Levels of cotinine (p<0.001) and total NNAL (p<0.001) were significantly correlated with duration (in years) of use of smokeless tobacco products. Median cotinine and total NNAL were 2.4 and 2.1 times higher, respectively, in the > or = 21 years of use than in the 0-5 years of use category. CONCLUSIONS: Smokeless tobacco users adjust their intensity of use with experience in order to increase their nicotine dose, resulting in a corresponding increase in exposure to NNK, a powerful carcinogen. These results indicate the importance of educating smokeless tobacco users about the effects of prolonged use of these products.

Cardiovascular safety of sublingual apomorphine in patients on stable doses of oral antihypertensive agents and nitrates.

Sublingual (SL) apomorphine (2 to 6 mg) has been shown to be effective for treatment of male erectile dysfunction. Many patients with erectile dysfunction are also being treated for systemic hypertension and/or cardiovascular disease. In a double-blind, randomized, placebo-controlled, crossover trial, SL apomorphine 5 mg and placebo were administered on alternate days to 162 men who were on long-term therapy (> or =4 weeks) with angiotensin-converting enzyme inhibitors, beta blockers, diuretics, calcium channel blockers, alpha(1) blockers, or short- or long-acting nitrates. Blood pressure and heart rate were measured before and after dosing; cardiac rhythm was recorded by 4-hour Holter monitoring. The only potentially clinically significant interactions between SL apomorphine and the antihypertensive agents or short-acting nitrates were greater orthostatic decreases in systolic blood pressure in the alpha-blocker and calcium channel blocker groups (-10 and -6 mm Hg vs placebo, respectively). Administration of SL apomorphine after dosing with long-acting nitrates resulted in significant decreases in blood pressure when patients were standing (mean systolic change, -5 to -9 mm Hg 30 to 60 minutes postdose, p <0.05; mean diastolic change, -3 to -4 mm Hg 50 to 60 minutes postdose, p <0.05). The most common adverse events with SL apomorphine were dizziness, nausea, and headache. Syncope occurred in 1 patient in the beta-blocker group; symptomatic hypotension occurred in 2 patients each in the short- and long-acting nitrate groups. Thus, in patients receiving common antihypertensive agents and short-acting nitrates, as well as in most patients receiving long-acting nitrates, SL apomorphine at higher than recommended doses produced no clinically significant changes in heart rate or blood pressure greater than changes seen with SL apomorphine alone.

An open-label, uncontrolled dose-optimization study of sublingual apomorphine in erectile dysfunction.

BACKGROUND: Because apomorphine is a dopamine agonist that acts on areas of the central nervous system believed to mediate penile erection, its use in erectile dysfunction (ED) has been investigated. However, it also produces nausea by dopamine-receptor stimulation of the chemotrigger zone in the brain. Therefore, a low plasma concentration, achieved rapidly, would be selective for the desired erectile response but would be below the dopamine threshold for nausea. OBJECTIVE: We evaluated the efficacy and tolerability of a dose-optimized regimen of a sublingual formulation of apomorphine (apomorphine SL) in the treatment of ED. METHODS: This was a multicenter, open-label, uncontrolled, Phase III dose-optimization study of apomorphine SL in heterosexual men with ED. The 2-week screening period, during which baseline severity of ED was determined using the International Index of Erectile Function, was followed by a 3-week dose-optimization period beginning at a dose of 2 mg. Patients were to make at least 2 attempts at intercourse per week throughout the study, placing 1 apomorphine tablet under the tongue beforehand. At the end of the first week, the dose could be increased to 3 mg at the discretion of the investigator; at the end of the second week, the dose could be increased to a maximum of 4 mg or decreased as needed. In the following 4-week treatment period, patients took their individual optimal doses. The primary efficacy variable was the percentage of attempts resulting in erections firm enough for intercourse, as assessed by investigators' review of data from patients' diaries. Secondary variables included the percentage of attempts resulting in successful intercourse, time to erection, and duration of erection. Information about adverse events, including their severity and relation to treatment, was determined on the basis of direct questioning, spontaneous reports, and review of patient diaries. RESULTS: The study enrolled 849 heterosexual men whose ages ranged from 31 to 78 years (mean, 58.1 years). They had a mean 5.7-year history of ED of varbus causes. ED was mild in 11.5% of the men, moderate in 23.8 c, and severe in 48.1%. When results of the last 8 attempts were pooled, representing the period during which patients were taking their optimal doses of apomorphine SL, the mean percentage of attempts resulting in erections firm enough for intercourse was 39.4%, compared with 13.1% at baseline; attempts resulting in intercourse increased from a mean of 12.7% at baseline to 38.3% with treatment. The average median time to erection was 23 minutes, and the average median duration of erection was 13 minutes. Nausea, the most common treatment-related adverse event (11.7%). was dose related and diminished with continued dosing. One patient had a single syncopal episode that was judged to be related to apomorphine SL. CONCLUSIONS: In the present study, a dose-optimization regimen of apomorphine SL-with dosing initiated at 2 mg and adjusted up to a maximum of 4 mg as needed-was effective and well tolerated in the treatment of ED, regardless of its cause or severity.

Efficacy and safety of fixed-dose and dose-optimization regimens of sublingual apomorphine versus placebo in men with erectile dysfunction. The Apomorphine Study Group.

OBJECTIVES: A sublingual (SL) formulation of apomorphine has been developed and found effective in penile erectile dysfunction (ED). This study assessed the efficacy and safety of several doses of apomorphine SL in a dose-optimization schedule compared with placebo. METHODS: In this 8-week, multicenter, double-blind clinical trial, 569 patients were randomized to four groups: a dose-optimization group in which patients began with 2 mg, increased or decreased the dosage as needed for 4 weeks, and thereafter maintained an optimal dose for 4 weeks; two fixed-dose groups of either 5 or 6 mg; and a placebo group. Efficacy was assessed by patient and partner responses to home-use questionnaires about sexual function and activity and by responses to the International Index of Erectile Function and the Brief Sexual Function Inventory. RESULTS: In all apomorphine SL groups, a significantly higher percentage of patients compared with the placebo group achieved and maintained an erection firm enough for intercourse (48% to 53% versus 35% for placebo, P < or =0.001) and a significantly higher percentage of attempts resulted in intercourse (45% to 51% versus 33%, P < or =0.001). The responses to the questionnaires completed by the patients and partners were similar. Apomorphine SL was well tolerated; nausea, the most common side effect, was dose related and diminished substantially during the second 4-week period at all doses. The dose-optimization schedule resulted in fewer adverse events without impacting efficacy. CONCLUSIONS: Apomorphine SL is an effective and safe treatment for ED, with 2 and 4 mg providing the most acceptable therapeutic index.

Assessing readiness for death in hospice elders and older adults.

BACKGROUND: Readiness for death may affect the quality of the death experience and influence response to treatments. The psychologic vulnerability of the dying person is a major focus of palliative care. Accurate assessment of readiness for death may lead to earlier and more appropriate interventions. OBJECTIVE: The purpose of this study was to assess the psychometric properties of the revised readiness for death instrument. METHODS: Using a known groups technique and a cross-sectional study design, the revised instrument was administered to 52 elders in hospice care with a terminal diagnosis and 91 community dwelling adults without a terminal diagnosis. RESULTS: Instrument content validity (Kappa = 0.96) was supported by three expert panelists who were hospice researchers. Principal components factor analysis explained 43% of the variance and partially supported the proposed four-factor structure of the revised 26-item instrument. Internal consistency was acceptable (.76). Discriminant validity was significant as assessed by an independent t-test between two contrast groups (t = 5.98, p = 0.000). The factor analysis, reliability testing, and qualitative analysis of items supported deletion of 2 items. CONCLUSIONS: Results indicated that the revised instrument has sound psychometric properties but further testing with a larger sample of hospice subjects is needed to confirm the factor structure of the instrument.

Inhibitory effects of deferoxamine on UVB-induced AP-1 transactivation.

Production of reactive oxygen species (ROS) by iron can contribute directly to DNA and protein damage and may contribute to cell signaling and proliferation. We have examined the effects of the iron(III) chelator deferroxamine (DFO) and iron (FeCl(3)) on UVB (290-320 nm)-induced activator protein 1 (AP-1) signaling. The ability of DFO to inhibit UVB-induced AP-1 transactivation was tested in a human keratinocyte cell line stably transfected with a luciferase reporter driven by a single AP-1 element. DFO treatment 24 h prior to UVB irradiation reduced UVB-induced AP-1 transactivation by approximately 80%, with the effect of DFO diminishing as pre-treatment time was shortened. Treatment with FeCl(3) a minimum of 6 h prior to UVB potentiated the UVB induction of AP-1 transactivation by 2-3-fold. DFO was able to ablate both the UVB induction of AP-1 transactivation as well as the potentiation by FeCl(3). The antioxidants Trolox and N-acetyl cysteine were both able to inhibit UVB-induced AP-1 transactivation and Trolox was able to inhibit the potentiation of UVB-induced AP-1 by FeCl(3). These results indicate that UVB-induced AP-1 activation may be in part due to oxidant effects of UVB and intercellular iron.

Steady-state pharmacokinetics and electrocardiographic pharmacodynamics of clarithromycin and loratadine after individual or concomitant administration.

To evaluate the potential for an interaction between clarithromycin and loratadine, healthy male volunteers (n = 24) received each of the following regimens according to a randomized crossover design: 500 mg of clarithromycin orally every 12 h (q12h) for 10 days, 10 mg of loratadine orally q24h for 10 days, and the combination of clarithromycin and loratadine. A washout interval of 14 days separated regimens. The addition of loratadine did not statistically significantly affect the steady-state pharmacokinetics of clarithromycin or its active metabolite, 14(R)-hydroxy-clarithromycin. However, the addition of clarithromycin statistically significantly altered the steady-state maximum observed plasma concentration and the area under the plasma concentration-time curve over a dosing interval for loratadine (+36 and +76%, respectively) and for descarboethoxyloratadine (DCL), the active metabolite of loratadine (+69 and +49%, respectively). Clarithromycin probably inhibits the oxidative metabolism of loratadine and DCL by the cytochrome P-450 3A subfamily. Electrocardiograms (n = 12) were obtained over 24-h periods at baseline and steady state (day 10). The mean maximum QTc interval and area under the QTc interval-time curve on day 10 were modestly increased (<3%) from baseline for all three regimens, but no QTc interval exceeded 439 ms for any subject. Elevated steady-state concentrations of loratadine and DCL do not appear to be associated with adverse cardiovascular effects related to prolongation of the QTc interval. Loratadine and clarithromycin were well tolerated, alone and in combination.

Dose-related effects of N-demethyl-N-isopropyl-8, 9-anhydroerythromycin A 6,9-hemiacetal on gastric emptying of solids in healthy human volunteers.

The purpose of our study was to evaluate the effects of a new nonantibiotic motilide derived from erythromycin, EM574, on gastric emptying and to evaluate its safety. Thirty healthy volunteers received one of five oral doses of EM574 (5, 10, 20, 30 mg and placebo) in a randomized, double-blind, five-period, cross-over design; each dosing period was separated by 1-wk washout. Gastric emptying was measured by 13C-octanoic acid breath test. A total of 10, 20, 30 mg of EM574 significantly accelerated both lag phase and gastric half-emptying time (P < .001) compared to placebo. The 5-mg dose of EM574 also significantly shortened the gastric half-emptying time (P < .05). Mean gastric half-emptying times were 173, 158, 147, 149 min with EM574 5, 10, 20, 30 mg, respectively (placebo, mean 189 min). EM574 accelerated gastric emptying in a dose-related manner (P < .001 for linear trend, P < .05 for quadratic trend). However, the 30-mg dose did not accelerate gastric emptying more than the 20-mg dose. EM574 was well tolerated; 7 of 56 participants receiving the 20- or 30-mg dose developed nausea, and only 2 of 28 receiving the 30-mg dose experienced vomiting. EM574 accelerates gastric emptying in a dose-dependent manner with minimal side effects after a single administration of up to 20 mg. EM574 shows promise for treatment of patients with impaired gastric emptying.

Helicobacter pylori does not migrate from the antrum to the corpus in response to omeprazole.

BACKGROUND: Omeprazole is known to have an effect on Helicobacter pylori in vivo. One opinion is that H. pylori "migrates" from the antrum to the corpus in response to omeprazole therapy. METHODS: To determine whether H. pylori migrates in response to omeprazole, we assessed the presence of H. pylori in the antrum and corpus in duodenal ulcer patients receiving omeprazole for 4 wk. Culture and histological examination of antral biopsies (Genta stain) were performed before patients received omeprazole, at the end of therapy, and 4-6 wk later. The end points were presence or absence of H. pylori and the number of H. pylori colonies per biopsy. RESULTS: Seventy-two patients had H. pylori in both the antrum and corpus at entry and 4-6 wk after ending therapy. Three general patterns were prevalent at the end of omeprazole therapy: antrum- and corpus-positive (54%), antrum-negative and corpus-positive (24%), both antrum- and corpus-negative (21%), and one patient had antrum-positive with corpus-negative (1%). Evaluation of the number of colonies per biopsy in those who remained H. pylori-positive in both the antrum and corpus throughout showed that the number of H. pylori decreased in both the antrum and corpus during therapy (507 +/- 60 vs. 225 +/- 51, p < 0.01 and 415 +/- 58 vs. 290 +/- 46 0.1) for antrum and corpus, respectively, and tended to return to pre-therapy levels 4-6 wk later. The number of H. pylori in the corpus also decreased in the antrum-negative and corpus-positive group during therapy with omeprazole (433 +/- 87 vs. 185 +/- 61, p < 0.05). In most of the patients studied, the number of H. pylori in the corpus was less posttreatment than it was pretreatment. The decrease in H. pylori load was also reflected in the development of false-negative urea breath tests. CONCLUSIONS: Omeprazole is detrimental to H. pylori in both the antrum and the corpus; migration from the antrum to the corpus in response to omeprazole is a myth.

Oscillatory, stochastic and chaotic growth rate fluctuations in permittistatically controlled yeast cultures.

We describe a continuous culture system related to the turbidostat, but using a feedback system based on biomass estimation from the dielectric permittivity of the cell suspension rather than its optical density. It is shown that this system provides an excellent method of maintaining a constant biomass level within a fermentor. The computer-controlled system was able to effect the essentially continuous registration of growth rate by monitoring the rate of medium addition via the time-dependent activity of the pump. At some biomass setpoints for aerobically grown cultures of baker's yeast substantial time-dependent fluctuations in the growth rate of the culture were thereby observed. At some biomass setpoints, however, or under anaerobic conditions, or when using a non-Crabtree yeast, the growth rate was constant, indicating that the fluctuations were inherent to the biological system and not simply a property of the fermentor and control system. A variety of time series analyses (Fourier transformations, Hurst and Lyapunov exponents, the determination of embedding dimension, and non-linear time series predictions based on the methodology of Sugihara and May) were used to demonstrate, for the first time, that as well as stochastic and periodic components these fluctuations exhibited deterministic chaos. 'Trivial predictors' were unable to give accurate predictions of the growth rate in these cultures. The growth rate fluctuations were studied further by means of offline measurements of changes in percentage viability, bud count, and in the external ethanol and glucose concentrations; these data and other evidence suggested that the growth rate fluctuations were closely linked to the primary respiro-fermentative metabolism of this organism. The identification of chaotic growth rates in cell cultures suggests that there may be novel methods for controlling the growth of such cultures.

Effect of omeprazole on concentrations of clarithromycin in plasma and gastric tissue at steady state.

This study was conducted to determine (i) the effect of omeprazole on steady-state concentrations of clarithromycin and 14-(R)-hydroxyclarithromycin in plasma and gastric mucosa, (ii) the effect of clarithromycin on steady-state concentrations of omeprazole in plasma, and (iii) the effect of clarithromycin on the suppression of gastric acid secretion by omeprazole. Twenty healthy, Helicobacter pylori-negative male subjects completed this three-period, double-blind, randomized crossover study. In period 1, all subjects received 40 mg of omeprazole each morning for 6 days. Twenty-four-hour gastric pH monitoring took place on days -1 and 6. Pharmacokinetic sampling took place on day 6. In periods 2 and 3, subjects were randomly assigned to receive either 40 mg of omeprazole or omeprazole placebo daily for 6 days plus clarithromycin (500 mg) every 8 h for 5 days with a single 500-mg dose on day 6. Gastric tissue and mucus samples were obtained via endoscopy on day 5. Gastric pH monitoring and pharmacokinetic sampling took place on day 6. Two-week washout intervals separated the three study periods. Clarithromycin increased mean omeprazole area under the concentration-time curve from 0 to 24 h from 3.3 +/- 2.0 to 6.3 +/- 4.5 micrograms.h/ml (P < 0.05) and harmonic mean half-life from 1.2 to 1.6 h (P < 0.05) but did not significantly alter the effect of omeprazole on gastric pH. Mean clarithromycin area under the concentration-time curve from 0 to 8 h increased from 22.9 +/- 5.5 (placebo) to 26.4 +/- 5.7 micrograms.h/ml (omeprazole) (P < 0.05) when clarithromycin was administered with omeprazole. Analysis of variance revealed that mean concentrations of clarithromycin in tissue and mucus were statistically significantly higher when clarithromycin was given with omeprazole than when clarithromycin was given with placebo (P <0.001). Mean maximum observed concentrations of clarithromycin in the gastric fundus increased from 20.8 +/- 7.6 (placebo) to 24.3 +/- 6.4 micrograms/g (omeprazole), and those in the gastric mucous from 4.2 +/- 7.7 placebo to 39.3 +/- 32.8 micrograms/g (omeprazole). Similar increases were observed for the 14-(R)-hydroxyclarithromycin. These results show that omeprazole increases concentrations of clarithromycin in gastric tissue and mucus and may provide a mechanism for synergy between clarithromycin ad omeprazole that explains the excellent eradication of H. pylori seen in clinical trials.

Simple procedure for measuring the pharmacodynamics and analgesic potential of lipoxygenase inhibitors.

A model is described for determining the pharmacodynamics of inhibitors of arachidonate metabolism in mice. Bioavailability and selectivity were assessed by ex vivo RIA of TXB2, LTB4, and 12-HETE from ionophore-challenged blood. Inhibition of LTB4 and 12-HETE was measured using a single LTB4 RIA, following extraction and separation of these eicosanoids from plasma. Separation on cyanopropyl mini-columns yielded hexane/ether and methanol fractions, which contained 12-HETE and LTB4, respectively. Analgesic efficacy was measured by inhibition of phenylbenzoquinone-induced abdominal constriction. The NSAIDs, indomethacin ibuprofen, flurbiprofen, and benoxaprofen, were analgesic and selective cyclo-oxygenase inhibitors. BW775C was also analgesic, but inhibited cyclo-oxygenase, 5-lipoxygenase and 12-HETE formation. Other in vitro 5-lipoxygenase inhibitors, NDGA, quercetin, and nafazatrom, were inactive in vivo, although NDGA reduced abdominal constrictions. The results indicate that this model has utility in determining the mechanism/selectivity of action and analgesic potential of 5-lipoxygenase inhibitors.

Investigating the MESA (multipoint electrotactile speech aid): the transmission of segmental features of speech.

Four normal-hearing young adults have been extensively trained in the use of a tactile speech-transmission system. Subjects were tested in the recognition of various phonetic elements including vowels, and stop, nasal, and fricative consonants under three receiving conditions; visual reception alone (lipreading), tactile reception alone, and tactile plus visual reception. Subjects were artificially deafened using earplugs and white noise and all speech tokens were presented live voice. Analysis of the data demonstrates that the tactile transform enables receivers to achieve excellent recognition of vowels in CVC context and the consonantal features of voicing and nasality. This, in combination with high recognition of vowels and the consonantal feature place of articulation through visual receptors, leads to recognition performance in the combined condition (visual plus tactual) which far exceeds either reception condition in isolation.