Intraoperative reduction of vasopressors using processed electroencephalographic monitoring in patients undergoing elective cardiac surgery: a randomized clinical trial.

Intraoperative vasopressor and fluid application are common strategies against hypotension. Use of processed electroencephalographic monitoring (pEEG) may reduce vasopressor application, a known risk factor for organ dysfunction, in elective cardiac surgery patients. Randomized single-centre clinical trial at Jena University Hospital. Adult patients operated on cardiopulmonary bypass or off-pump coronary artery bypass grafting were randomised to receive anesthesia with visible or blinded pEEG using Narcotrend™. In blinded-Narcotrend (NT) depth of anesthesia was extrapolated from clinical signs, hemodynamic response and anesthetic concentration, supplemented by target indices between 37 and 64 in the visible-NT group. Intraoperative norepinephrine requirement (primary endpoint), fluid balance, extubation time, delirium occurrence and adverse events were evaluated. Patients of the intent-to-treat population (visible-NT: n = 123, blinded-NT: n = 122) had similar patient and procedural characteristics. Adjusted for type of surgery intraoperative Norepinephrine application was significantly reduced in visible-NT (n = 120, robust mean of cumulative dose 4.71 µg/kg bodyweight) compared to blinded-NT patients (n = 119, 6.14 µg/kg bodyweight) (adjusted robust mean difference 1.71 (95% CI 0.33-3.10) µg/kg bodyweight). Although reduction in patients operated on cardiopulmonary bypass was higher the interaction was not significant in post-hoc subgroup analysis. Intraoperative fluid balance was similar among both groups and strata. Extubation time was non-significantly lower in visible than in blinded-NT group. Overall postoperative delirium risk was 16.4% without differences among the groups. Adverse events-sudden movement/coughing, perspiration or hypertension-occurred more often with visible-NT, while one blinded-NT patient experienced intraoperative awareness. Titration of depth of anesthesia in elective cardiac surgery patients using pEEG allows to reduce application of norepinephrine.

Tau positron emission tomography imaging in C9orf72 repeat expansion carriers.

BACKGROUND AND PURPOSE: AV-1451 (18 F-AV-1451, flortaucipir) positron emission tomography was performed in C9orf72 expansion carriers to assess tau accumulation and disease manifestation. METHODS: Nine clinically characterized C9orf72 expansion carriers and 18 age- and gender- matched cognitively normal individuals were psychometrically evaluated and underwent tau positron emission tomography imaging. The regional AV-1451 standard uptake value ratios from multiple brain regions were analyzed. Spearman correlation was performed to relate the AV-1451 standard uptake value ratio to clinical, psychometric and cerebrospinal fluid measures. RESULTS: C9orf72 expansion carriers had increased AV-1451 binding in the entorhinal cortex compared to controls. Primary age-related tauopathy was observed postmortem in one patient. AV-1451 uptake did not correlate with clinical severity, disease duration, psychometric performance or cerebrospinal fluid markers. CONCLUSION: C9orf72 expansion carriers exhibited increased AV-1451 uptake in entorhinal cortex compared to cognitively normal controls, suggesting a propensity for primary age-related tauopathy. However, AV-1451 accumulation was not associated with psychometric performance in our cohort.

Participant satisfaction with group and individual components of Adolescent Impact: a secondary prevention intervention for HIV-positive youth.

Adolescent Impact, a developmentally targeted behavioral intervention aimed at decreasing risk behaviors and promoting health care adherence, was delivered to 83 HIV-infected youth, aged 13-21 years, receiving care in five urban HIV centers. Participants completed a patient satisfaction survey following the 12 part intervention consisting of seven groups and five individual sessions. A feedback questionnaire was also completed during each group session to gain more insight on participant experiences. Several indicators suggested high levels of satisfaction. First, overall attendance was relatively high. Second, participants rated their subjective experience and group content favorably. No differences in satisfaction ratings emerged between perinatally infected adolescents and those who acquired HIV through risk behaviors. However, differences emerged regarding perceived intervention utility and content-specific preferences. Findings suggest that Adolescent Impact participants were satisfied with the intervention and that a heterogeneous group of HIV-infected youth could be advantageously integrated into the same secondary prevention program.

Overview and implementation of an intervention to prevent adherence failure among HIV-infected adults initiating antiretroviral therapy: lessons learned from Project HEART.

Project HEART, an acronym for Helping Enhance Adherence to Retroviral Therapy, was a prospective, controlled study to develop, implement, and evaluate a clinic-based behavioural intervention to prevent adherence failure among HIV-infected adults beginning their first highly active antiretroviral therapy (HAART) regimen (N = 227). In this paper, we describe the conceptualisation of the Project HEART adherence intervention, characteristics of the participants, and lessons learned implementing HEART in an inner-city clinic setting. A multi-component intervention, HEART combined enhanced education, reminders, adherence feedback, social support and adherence-focused problem solving in an integrated manner to address common cognitive, motivational, and social barriers to adherence. Unique components of the intervention included use of participant-identified adherence support partners and a standardized adherence barriers assessment to develop and implement individualised adherence plans. Lessons learned regarding the feasibility of using participant-identified support partners were as follows. Few participants eligible for the study had trouble identifying a support partner. Over 90% of support partners attended at least one intervention visit. Support partners were most available and amenable to participate early in the initiation of therapy. Participants' experiences as the 'supported' partner were generally positive. Though many participants faced barriers not easily addressed by this intervention (for example, housing instability), formally integrating support partners into the intervention helped to address many other common adherence barriers. Family and friends are an under-utilised resource in HIV medication adherence. Enlisting the help of support partners is a practical and economical approach to adherence counselling.

The impact of image compression on diagnostic quality of digital images for detection of chemically-induced periapical lesions.

OBJECTIVES: To test the hypothesis that there is no significant difference in the detectability of chemically-induced periapical lesions between a non-compressed image and one subjected to a Joint Photographic Experts Group (JPEG) lossy compression technique at a ratio of 23:1 or less. METHOD: Chemically-induced periapical lesions were created by placing a solution of 70% perchloric acid at the apex of extracted teeth in 13 human jaw cadaver specimens. Acid was applied in seven incremental time periods from 0-32 h. Extracted teeth were replaced in the socket and images were made using the Schick CDR digital sensor. Using a JPEG lossy compression algorithm, five compression ratios of 2:1, 14:1, 23:1, 28:1 and 47:1 were applied to the images. Images were viewed three times by three observers who ranked the presence or absence of a lesion at three sites, the mesial area, distal area and apex of the tooth, on a 5-point confidence scale. Intraobserver and interobserver agreement and agreement between the compressed and the original images were assessed with intraclass correlation coefficients (ICCs). RESULTS: Overall ICCs for measuring intraobserver agreement using all images were 0.77, 0.84, and 0.50 for the three observers, respectively. The overall ICC for assessing agreement between observers was 0.57. There was no significant difference (P>0.05) between compressed and original images for any site at compression ratios of 2:1, 23:1 and 28:1. There were significant differences for a compression ratio of 47:1. CONCLUSION: JPEG compression does not impact detectability of artificial periapical lesions at low and moderate compression ratios up to and including 28:1.

Distributional characteristics of VOT in children's voiceless aspirated stops and interpretation of developmental trends.

Numerous researchers have measured voice onset time (VOT) in children. Authors attempting to trace developmental trends in consonant voicing have frequently framed their hypotheses in terms of how children's VOT means and/or standard deviations compare to adult norms. However, data from previous studies suggest that children's VOTs may not be normally distributed. Specifically, rightward skew is observed in the voiceless aspirated stops, such that mean values exceed the medians. The current work presents detailed distributional analyses of VOTs in /p, t/ from 7 five-year-old children and 14 adults. Distributional non-normality was common in both the adult and child data, as measured by Shapiro and Wilk's W statistic. The children showed an insignificant but consistent tendency towards higher values of skew than the adults and greater differences between VOT mean and median values. The results suggest that theories of VOT development should not be based solely on means and standard deviations, but need to address the distributional characteristics of the data more fully.

Self-reported zidovudine adherence among pregnant women with human immunodeficiency virus infection in four US states.

OBJECTIVE: Our purpose was to identify clinical and psychosocial factors associated with rates of prenatal zidovudine use and adherence among human immunodeficiency virus-infected pregnant women. STUDY DESIGN: Two hundred sixty-four women completed 2 interviews between October 1996 and November 1998 at prenatal clinics in Miami, Florida; Brooklyn, New York; Connecticut; and North Carolina. Interviews took place after 24 weeks' gestation and then between 32 weeks and delivery. RESULTS: Prenatal zidovudine had been prescribed for 94% of the women, 37% of whom received monotherapy. Among women taking zidovudine, 20% reported incomplete adherence. In multivariate analyses having missed zidovudine doses was positively associated with prenatal illicit drug use (odds ratio, 3.49; 95% confidence interval, 1.30-9.42; P <.05) and missing prenatal vitamins (odds ratio, 2.71; 95% confidence interval, 1.30-5.67; P <.01). CONCLUSIONS: Zidovudine therapies have been successfully implemented in prenatal care settings in the United States. The success of these therapies may be limited among some patients by incomplete regimen adherence, particularly among illicit drug users.

Infant birth weight among women with or at high risk for HIV infection: the impact of clinical, behavioral, psychosocial, and demographic factors.

The purpose of these analyses was to provide a prospective examination of the impact of HIV on birth weight using clinical, behavioral, psychosocial, and demographic correlates. HIV-positive (n = 319) and HIV-negative (n = 220) pregnant women matched for HIV risk factors (i.e., drug use and sexual risk behaviors) were interviewed during the 3rd trimester of pregnancy and 6 weeks postpartum. Medical chart reviews were also conducted for the HIV-seropositive pregnant women to verify pregnancy-related and birth outcome data. In a logistic regression analysis, model chi2(9, N = 518) = 124.8, p < .001, controlling for parity and gestational age, women who were HIV seropositive were 2.6 times more likely to have an infant with low birth weight. In addition, Black women and those who did not live with their partners were more than 2 times as likely to have infants with low birth weight, and those who smoked were 3.2 times more likely to have infants with low birth weight. Knowing that women with HIV, those who are Black, and those not living with a partner are at highest risk for adverse birth outcomes can help those in prenatal clinics and HIV specialty clinics to target resources and develop prevention interventions. This is particularly important for women with HIV because birth weight is associated with risk of HIV transmission from mother to child.

Laryngeal factors in voiceless consonant production in men, women, and 5-year-olds.

Voicing control in stop consonants has often been measured by means of voice onset time (VOT) and discussed in terms of interarticulator timing. However, control of voicing also involves details of laryngeal setting and management of sub- and supraglottal pressure levels, and many of these factors are known to undergo developmental change. Mechanical and aerodynamic conditions at the glottis may therefore vary considerably in normal populations as functions of age and/or sex. The current study collected oral airflow, intraoral pressure, and acoustic signals from normal English-speaking adults and children producing stop consonants and /h/ embedded in a short carrier utterance. Measures were made of stop VOTs, /h/ voicing and flow characteristics, and subglottal pressure during /p/ closures. Clear age and gender effects were observed for /h/: Fully voiced /h/ was most common in men, and /h/ voicing and flow data showed the highest variability among the 5-year-olds. For individual participants, distributional measures of VOT in /p t/ were correlated with distributional measures of voicing in /h/. The data indicate that one cannot assume comparable laryngeal conditions across speaker groups. This, in turn, implies that VOT acquisition in children cannot be interpreted purely in terms of developing interarticulator timing control, but must also reflect growing mastery over voicing itself. Further, differences in laryngeal structure and aerodynamic quantities may require men and women to adopt somewhat different strategies for achieving distinctive consonantal voicing contrasts.

Time normalization of voice signals using functional data analysis.

The harmonics-to-noise ratio (HNR) has been used to quantify the waveform irregularity of voice signals [Yumoto et al., J. Acoust. Soc. Am. 71, 1544-1550 (1982)]. This measure assumes that the signal consists of two components: a harmonic component, which is the common pattern that repeats from cycle-to-cycle, and an additive noise component, which produces the cycle-to-cycle irregularity. It has been shown [J. Qi, J. Acoust. Soc. Am. 92, 2569-2576 (1992)] that a valid computation of the HNR requires a nonlinear time normalization of the cycle wavelets to remove phase differences between them. This paper shows the application of functional data analysis to perform an optimal nonlinear normalization and compute the HNR of voice signals. Results obtained for the same signals using zero-padding, linear normalization, and dynamic programming algorithms are presented for comparison. Functional data analysis offers certain advantages over other approaches: it preserves meaningful features of signal shape, produces differentiable results, and allows flexibility in selecting the optimization criteria for the wavelet alignment. An extension of the technique for the time normalization of simultaneous voice signals (such as acoustic, EGG, and airflow signals) is also shown. The general purpose of this article is to illustrate the potential of functional data analysis as a powerful analytical tool for studying aspects of the voice production process.

Women, violence, and HIV: a critical evaluation with implications for HIV services.

OBJECTIVE: Violence is highly prevalent among women with HIV. Determining whether HIV is causally related to violence, and whether risk for violence is increased by certain HIV prevention practices, has been difficult. METHODS: We review recent literature concerning (1) violence and HIV serostatus, including the risk for violence associated with disclosure of a positive serostatus, and (2) violence associated with requests that male sex partners use condoms. RESULTS: Studies suggest that women with or at risk for HIV come from populations that are also at risk for violence. Violence is not statistically increased among HIV-infected women compared to demographically and behaviorally similar uninfected women. However, for a small proportion of women, violence may occur around disclosure or in response to condom negotiation. CONCLUSIONS: Integrating violence screening and referral into HIV services could help many women obtain the assistance they need while minimizing the risk for violence that may be associated with partner notification or condom requests.

Body piercing medical concerns with cutting-edge fashion.

OBJECTIVE: To review the current information on medical complications, psychological implications, and legislative issues related to body piercing, a largely unregulated industry in the United States. METHODS: We conducted a MEDLINE search of English language articles from 1966 until May 1998 using the search terms "body piercing" and "ear piercing." Bibliographies of these references were reviewed for additional citations. We also conducted an Internet search for "body piercing" on the World Wide Web. MAIN RESULTS: In this manuscript, we review the available body piercing literature. We conclude that body piercing is an increasingly common practice in the United States, that this practice carries substantial risk of morbidity, and that most body piercing in the United States is being performed by unlicensed, unregulated individuals. Primary care physicians are seeing growing numbers of patients with body pierces. Practitioners must be able to recognize, treat, and counsel patients on body piercing complications and be alert to associated psychological conditions in patients who undergo body piercing.

Pubertal development and school transition. Joint influences on depressive symptoms in middle and late adolescents.

The impact of simultaneous changes in biological and social context on the mental health of adolescents was examined by testing the hypothesis that normative developmental transitions can be associated with increased dysphoria if they occur in close temporal proximity. Girls experiencing physical changes associated with middle or later stage pubertal development during the initial high school or college year were predicted to experience more dysphoria than those experiencing these changes during non-transitional times, with negative pubertal attitudes exacerbating the relation. Pubertal status and dysphoria of high school and college students were assessed. Among females experiencing pubertal changes, dysphoria was indeed highest for the 15 and 19 year olds, and lower for the 16, 17, and 18 year olds with females viewing menstrual onset as negative experienced depressive symptoms of moderate clinical severity. This pattern did not emerge for males, or females not experiencing pubertal changes. In contrast, the hypothesis was not supported when transition time was operationalized using grade level. Implications for psychopathology risk are discussed.

Intrabony neurilemmoma: diagnosis and management.

The authors present a case of a mandibular neurilemmoma discovered on routine radiographic examination of an asymptomatic young woman. The lesion was surgically removed and there was no radiographic evidence of recurrence. A review of the literature is presented and the differential diagnosis, prognosis and treatment of this benign neurogenic tumor are discussed.

Effects of long term dietary phenethyl isothiocyanate on the microsomal metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol in F344 rats.

Phenethyl isothiocyanate (PEITC), a cruciferous vegetable component, inhibits lung tumor induction by the tobacco specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). To gain insight into the mechanism of PEITC lung tumor inhibition, we examined, in male F344 rats, the effects of dietary PEITC (3 micromol/g NIH-07 diet) in combination with NNK treatment (1.76 mg/kg, s.c., three times a week) for 4, 12 and 20 weeks on liver and lung microsomal metabolism of NNK and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), a major metabolite of NNK and also a lung carcinogen. This was compared with rats fed NIH-07 diet, without PEITC, and treated with NNK alone or saline. The protocol was identical to that employed for inhibition of lung tumorigenesis by PEITC. We observed decreased rates of alpha-hydroxylation of NNK and NNAL in lung microsomes of 4-, 12- and 20-week PEITC + NNK treated rats compared with those treated with NNK or saline. NNK treatment alone also decreased lung alpha-methylene hydroxylation of NNK. Long-term NNK + PEITC administration did not significantly affect liver oxidative metabolism of NNK or NNAL, and did not affect the rate of glucuronidation of NNAL in liver microsomes when compared with rats treated with NNK or saline. Thus, PEITC selectively inhibited lung metabolic activation of NNK and NNAL. These results support the hypothesis that PEITC inhibits NNK-induced lung tumors by inhibiting metabolic activation of NNK in the lung. This study also demonstrated that PEITC inhibits lung alpha-hydroxylation of NNAL; this may play a role in PEITC inhibition of lung tumorigenesis by NNK.

Fleroxacin 400 mg once daily versus ofloxacin 400 mg twice daily in skin and soft tissue infections.

The efficacy and safety of 10 days' oral treatment with fleroxacin 400 mg once daily were compared with those of ofloxacin 400 mg twice daily in adults with skin and soft tissue infections. The most common diagnoses were skin abscess, cellulitis and wound infection. The most commonly-isolated pathogens were Staphylococcus aureus, Staphylococcus epidermidis and other coagulase-negative staphylococci. Overall bacteriological cure rates in patients with susceptible pathogens were 89% for 158 fleroxacin-treated patients and 97% for 157 ofloxacin-treated patients (treatment difference 8%; 95% confidence intervals 2-14%; p < 0.05). Clinical cure rates were 78% for fleroxacin and 83% for ofloxacin (treatment difference 5%; 95% confidence intervals-5-14%, not statistically significant). The overall safety profiles were similar and the most frequently reported events were insomnia, headache, dizziness, and digestive system disorders. More fleroxacin-treated patients experienced phototoxicity and treatment-limiting adverse events. In conclusion, compared to twice-daily ofloxacin, fleroxacin had similar clinical efficacy and the advantage of once-a-day dosing, but with slightly lower bacteriological cure rate and a higher rate of treatment-limiting adverse events.

Comparative metabolism of the tobacco-related carcinogens benzo[a]pyrene, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol, and N'- nitrosonornicotine in human hepatic microsomes.

We compared the metabolism in human hepatic microsomes of three tobacco smoke carcinogens believed to be involved in the induction of cancer in humans: benzo[a]pyrene (BaP),4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and N'-nitrosonomicotine (NNN). The metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), a major metabolite of NNK, was also investigated. Although the metabolism of some of these compounds by human enzymes or tissue preparations has been previously examined in some studies, they have never been compared in the same human hepatic samples. Moreover, there have been no previous reports of NNAL metabolism by human tissues or enzymes. The tritium-labeled carcinogens (3 microM) were incubated with 10 different human hepatic microsomal preparations and cofactors for 10-20 min, and the products were analyzed by radioflow HPLC. NNN was the best substrate for oxidative metabolism, with the 5'-hydroxylation pathway being the predominant one observed (mean +/- SD = 31 +/- 17 pmol/min/mg protein). alpha-Hydroxylation of NNK by the methylene and methyl hydroxylation metabolic activation pathways was the next fastest reaction, with rates of 3.1 +/- 1.9 and 3.3 +/- 1.1 pmol/min/mg protein, respectively. Metabolism of BaP resulted in the formation of dihydrodiols and phenols; trans-7,8-dihydro-7,8-dihydroxy-BaP, its major proximate carcinogen, was formed at a rate of 1.1 +/- 0.61 pmol/min/mg protein. alpha-Hydroxylation of NNAL proceeded at a rate of 0.53 +/- 0.26 pmol/min/mg protein. The results of this study demonstrate that human hepatic microsomes metabolize all of these tobacco carcinogens resulting in a substantial stream of electrophilic intermediates capable of binding to DNA. The relative rates of oxidative metabolism to electrophiles or their precursors were NNN > NNK > BaP > NNAL. Correlation studies indicated involvement of cytochrome P4502A6 in the 5'-hydroxylation of NNN and cytochrome P4503A4 in the alpha-methylene hydroxylation and pyridine-N-oxidation of NNK and NNAL. The results of this study provide the first data on the comparative metabolism of these important carcinogens in human hepatic microsomes.

A double-blind, randomized, placebo-controlled, crossover trial of pentoxifylline for the prevention of chemotherapy-induced oral mucositis.

Oral mucositis is a frequent side effect of cancer therapy. No effective method of prophylaxis is currently available. We conducted a randomized, double-blind, placebo-controlled, crossover trial of pentoxifylline to evaluate its potential in preventing mucositis in cancer patients receiving chemotherapy. Ten cancer patients were randomized for treatment with a 15-day course of 400 mg of pentoxifylline given orally four times daily. Concurrent chemotherapy consisted of bolus cisplatin and infusional 5-fluorouracil. Mucositis was evaluated with the use of the Oral Assessment Guide developed at the University of Nebraska. Patients completing two cycles of chemotherapy--one with pentoxifylline and one with placebo--were evaluated for prophylaxis efficacy. Comparison of the oral assessment scores of the two cycles with a two-sided Student's t test failed to demonstrate a cytoprotective effect for pentoxifylline over placebo. We conclude that pentoxifylline as given in this study is ineffective for preventing mucositis in patients receiving cisplatin and 5-FU.