Minimum effective dose of spinal ropivacaine with and without fentanyl for postpartum tubal ligation.

BACKGROUND: Ropivacaine may be the ideal spinal anesthetic for postpartum tubal ligation due to its medium duration of action, low incidence of side effects and possibly reduced post-anesthetic care unit (PACU) stay. METHODS: Two prospective up-down sequential allocation studies were performed using hyperbaric spinal ropivacaine via a combined spinal-epidural anesthetic technique for patients undergoing postpartum tubal ligation. The first study was performed using an initial dose of 12.5 mg hyperbaric ropivacaine, which was adjusted in testing intervals of 0.5 mg. The second study used an initial dose of 16 mg hyperbaric ropivacaine, a testing interval of 1.0mg, and a fixed dose of fentanyl 10 µg. The need to supplement the block with intravenous or epidural agents was defined as a failure. Failures were treated with epidural lidocaine. RESULTS: The first and second studies recruited 24 and 17 patients, respectively. The median effective dose (ED50) for hyperbaric spinal ropivacaine was 16.4 mg (95% CI 13.7-19) with an ED95 estimate of 21.9 mg. The median effective dose of spinal ropivacaine with fentanyl 10 µg was 17.0 mg (95% CI 15.4-18.7) with an ED95 estimate of 21.3 mg. When data were combined, the overall ED50 for ropivacaine was 16.7 mg (95% CI 15.1-18.4) with an ED95 estimate of 22.5 mg (95% CI 16.3-28.8). A T8 block was not achieved in 4 patients receiving spinal ropivacaine alone, and 1 patient receiving spinal ropivacaine with fentanyl. The majority (82%) of patients who did not receive epidural local anesthetic supplementation had recovery of motor block within 60 min following PACU admission. CONCLUSION: Spinal hyperbaric ropivacaine 22 mg with or without fentanyl 10 µg could be used for postpartum tubal ligation surgery.

Anaesthetic management of a parturient with the postural orthostatic tachycardia syndrome: a case report.

Postural orthostatic tachycardia syndrome encompasses a group of disorders characterized by orthostatic intolerance. We describe the anaesthetic management of analgesia for labour and of Caesarean section in a parturient suffering from this disorder. Worsening of her symptoms during pregnancy was managed with an increase in the dose of beta-blockers taken by the patient. Epidural analgesia was instigated early to attenuate the stress of labour and avoid consequent triggering of a tachycardic response. Slow titration of epidural analgesia and anaesthesia after an adequate fluid preload was undertaken to minimize hypotension and subsequent tachycardia. Neuraxial opioid, combined with non-steroidal anti-inflammatory drugs and bilateral iliohypogastric and ilioinguinal nerve blocks were used to optimize postoperative analgesia.

Promoting safer sex among HIV-positive youth with haemophilia: theory, intervention, and outcome.

The goal of the project was to develop and evaluate theory-based interventions designed to change sexual behaviour and promote safer sex practices of HIV seropositive young men and adolescents with haemophilia to prevent transmission to sexual partners and offspring. Safer sex was defined as abstinence, consistent condom use, or 'outercourse' (intimate, non-intercourse sexual behaviour). This project utilized the Transtheoretical Model developed by Prochaska and DiClemente, which describes behaviour change as an incremental, stage-based process. The 1-year intervention protocol consisted of two individual sessions and two peer-centred activities. One hundred and four adolescents, residing in 22 states, participated. Pre- and post-intervention evaluations were conducted to measure stage progression for participants. The number who were in the action or maintenance stage of change for safer sex was significantly greater at post-test than at pre-test (79 vs. 62%, P < 0.0001). Participants also reported an increased use of outercourse. In addition, significant increases in self-efficacy and knowledge regarding safer sex were demonstrated. Following these stage-based interventions, participants were significantly more likely to be engaging in safer sex behaviours than they were previously. These intervention activities can be adapted for use with other adolescent populations and for other behaviour change goals in adolescents with haemophilia.

Parental expectations regarding discussions on psychosocial topics during pediatric office visits.

Parents from urban (n=67) and suburban (n=76) primary care settings responded to a survey determining the extent to which 9 common psychosocial concerns have affected their children. Parents also reported their expectations of their pediatrician to discuss such topics during a health care visit. Within both settings, discipline was the most frequently experienced (41%), commonly discussed (34.3%), and frequently expected (75.4%) topic to be discussed. The frequency of discussions on psychosocial topics was less than half that of the actual reported occurrence of the psychosocial concern. When discussions on psychosocial topics did occur, however, most parents (87.3%) perceived pediatricians as helpful.

Developing theory-based risk-reduction interventions for HIV-positive young people with haemophilia.

Eleven haemophilia treatment centres in the United States collaborated in the Hemophilia Behavioural Intervention Evaluation Projects (HBIEP) to develop theory-based interventions to reduce the risk of HIV transmission from seropositive adolescents and young adults with haemophilia. While the Transtheoretical Model of Behaviour Change and the Theory of Reasoned Action provided the theoretical underpinnings, the exact form in which these theories would be applied depended on developmental research. This paper presents the various phases of the process to develop the theory based interventions: literature review, qualitative interviews, quantitative surveys, a provider survey, a materials review, and the actual planning. All or portions of this process could be applied to the development of interventions for many behaviour-change projects. A description of the HBIEP interventions is also provided.

Role of LXRs in control of lipogenesis.

The discovery of oxysterols as the endogenous liver X receptor (LXR) ligands and subsequent gene targeting studies in mice provided strong evidence that LXR plays a central role in cholesterol metabolism. The identification here of a synthetic, nonsteroidal LXR-selective agonist series represented by T0314407 and T0901317 revealed a novel physiological role of LXR. Oral administration of T0901317 to mice and hamsters showed that LXR activated the coordinate expression of major fatty acid biosynthetic genes (lipogenesis) and increased plasma triglyceride and phospholipid levels in both species. Complementary studies in cell culture and animals suggested that the increase in plasma lipids occurs via LXR-mediated induction of the sterol regulatory element-binding protein 1 (SREBP-1) lipogenic program.

Sexual behavior change among human immunodeficiency virus-infected adolescents with hemophilia. Adolescent Hemophilia Behavioral Intervention Evaluation Project Study Group.

PURPOSE: To determine the factors associated with the adoption or maintenance of consistent safer sexual behaviors among human immunodeficiency virus-positive adolescents and young adults with hemophilia. METHODS: One hundred eleven adolescents at 10 hemophilia care sites participated in an intervention program designed to increase safer sexual behaviors (abstinence, condom use, or nonpenetrative behavior). The theory-based intervention spanned 1 year. Adolescents attended individual sessions, small group activities, and an intensive group retreat. RESULTS: Patients who maintained or improved safer sexual behaviors were compared with those who relapsed or did not improve. Logistic regression analyses found that improvement and maintenance of safer sexual behavior were significantly associated with perceived peer support for outercourse (odds ratio [OR]: 5.47; confidence interval [CI]: 1.4-20.8), perceived peer support for abstinence (OR: 5.08; CI: 1.2-20.1), and decreased general emotional distress (OR: 4.65; CI: 1.04-20.6). Perceived health status and previous sexual behavior were unrelated to change in safer sexual behavior. CONCLUSIONS: These longitudinal data indicate that improvement and maintenance of safer sexual behavior among adolescents during an intervention is strongly associated with perceptions of peer support for safer sex and lesser degrees of emotional distress. Programs for human immunodeficiency virus-infected adolescents may require developmentally appropriate social and psychological approaches to impact peer norms and emotional well-being.

Distinct central amphipathic alpha-helices in apolipoprotein A-I contribute to the in vivo maturation of high density lipoprotein by either activating lecithin-cholesterol acyltransferase or binding lipids.

Recombinant adenoviruses with cDNAs for human apolipoprotein A-I (wild type (wt) apoA-I) and three mutants, referred to as Delta4-5A-I, Delta5-6A-I, and Delta6-7A-I, that have deletions removing regions coding for amino acids 100-143, 122-165, and 144-186, respectively, were created to study structure/function relationships of apoA-I in vivo. All mutants were expressed at lower concentrations than wt apoA-I in plasma of fasting apoA-I-deficient mice. The Delta5-6A-I mutant was found primarily in the lipid-poor high density lipoprotein (HDL) pool and at lower concentrations than Delta4-5A-I and Delta6-7A-I that formed more buoyant HDL(2/3) particles. At an elevated adenovirus dose and earlier blood sampling from fed mice, both Delta5-6A-I and Delta6-7A-I increased HDL-free cholesterol and phospholipid but not cholesteryl ester. In contrast, wt apoA-I and Delta4-5A-I produced significant increases in HDL cholesteryl ester. Further analysis showed that Delta6-7A-I and native apoA-I could bind similar amounts of phospholipid and cholesterol that were reduced slightly for Delta5-6A-I and greatly for Delta4-5A-I. We conclude from these findings that amino acids (aa) 100-143, specifically helix 4 (aa 100-121), contributes to the maturation of HDL through a role in lipid binding and that the downstream sequence (aa 144-186) centered around helix 6 (aa 144-165) is responsible for the activation of lecithin-cholesterol acyltransferase.

A highly conserved enhancer in the Dlx5/Dlx6 intergenic region is the site of cross-regulatory interactions between Dlx genes in the embryonic forebrain.

Four Dlx homeobox genes, Dlx1, Dlx2, Dlx5, and Dlx6 are expressed in the same primordia of the mouse forebrain with temporally overlapping patterns. The four genes are organized as two tail-to-tail pairs, Dlx1/Dlx2 and Dlx5/Dlx6, a genomic arrangement conserved in distantly related vertebrates like zebrafish. The Dlx5/Dlx6 intergenic region contains two sequences of a few hundred base pairs, remarkably well conserved between mouse and zebrafish. Reporter transgenes containing these two sequences are expressed in the forebrain of transgenic mice and zebrafish with patterns highly similar to endogenous Dlx5 and Dlx6 expression. The activity of the transgene is drastically reduced in mouse mutants lacking both Dlx1 and Dlx2, consistent with the decrease in endogenous Dlx5 and Dlx6 expression. These results suggest that cross-regulation by Dlx proteins, mediated by the intergenic sequences, is essential for Dlx5 and Dlx6 expression in the forebrain. This hypothesis is supported by cotransfection and DNA-protein binding experiments. We propose that the Dlx genes are part of a highly conserved developmental pathway that regulates forebrain development.

Brief report: learning to parent: a survey of parents in an urban pediatric primary care clinic.

OBJECTIVE: To survey parents bringing children to an urban pediatric primary care clinic about (1) how they learned parenting skills, (2) role of the clinic in teaching parenting, (3) helpfulness of information sources, and (4) preferred modalities for teaching. METHODS: A total of 108 adults completed an oral survey in clinic, consisting of open-ended questions, yes/no endorsements, Likert ratings, and demographic questions. RESULTS: The majority reported learning to parent from their families or "by just doing it." Talking with professionals was rated as very helpful. Most had parenting questions. Almost half wanted information regarding specific developmental/behavioral issues, while only 8% wanted medical information. Most felt they could talk with clinic professionals about concerns but fewer had done so. Modality preferences were reported. CONCLUSIONS: Inner-city parents value working with primary care providers to improve knowledge of developmental/behavioral issues. Results have implications for the anticipatory guidance process, content of information provided, and the training of pediatric healthcare providers. We determined preferences for information delivery.

Characterization of Saccharomyces cerevisiae ubiquinone-deficient mutants.

Ubiquinol (QH2) is a lipid-soluble molecule that participates in cellular redox reactions. Previous studies have shown that yeast mutants lacking QH2 are hypersensitive to treatment with polyunsaturated fatty acids (PUFAs) indicating that QH2 can function as an antioxidant in vivo. In this study the effect of 1 mM linolenic acid on levels of Q6 and Q6H2 is assessed in both wild-type and respiration-deficient (atp2 delta) strains. The response of Q-deficient mutants to other forms of oxidative stress is further characterized to define those conditions where QH2 acts as an antioxidant. Endogenous antioxidant defense systems were also assessed in wild-type, Q-deficient, and atp2 delta strains. Superoxide dismutase (SOD) activity decreased and catalase activity increased in both Q-deficient and atp2 delta mutants compared to wild-type cells, suggesting that such changes result from the loss of respiration rather than the lack of Q.

Cigarette smoking as a cause of aneurysmal subarachnoid hemorrhage and risk for vasospasm: a report of the Cooperative Aneurysm Study.

OBJECT: Cigarette smoking is associated with aneurysmal subarachnoid hemorrhage (SAH) and subsequent vasospasm. The purpose of this study was to quantify this association. METHODS: Nearly 3500 patients with SAH from North America and Europe have been enrolled in five different multicenter, controlled studies coordinated at the Neuroclinical Trials Center of the Virginia Neurological Institute at the University of Virginia. Among the prospective data gathered were whether the patient smoked at the time of their most recent SAH and the evolution of angiographic vasospasm. The rate of smoking in the patients enrolled in the studies was compared with the expected rate by using a chi-square statistic adjusted for age and gender, in the general population in the United States (U.S.) and Europe. In virtually all age and gender subgroups, and for the combined populations in the five clinical trials, patients with SAH reported current smoking rates 2.5 times higher than expected based on U.S. and European national surveys (p < 0.0001). Cigarette smoking was also associated with younger age at onset of SAH (5-10 years, p < 0.0001) and increased incidence of clinically confirmed vasospasm (p < 0.005). CONCLUSIONS: The findings of a significantly increased representation of current cigarette smokers in the study populations and significant association with younger age at the time of SAH and increased incidence of vasospasm concur with recent reports of smoking as a significant risk factor for ruptured aneurysms and subsequent vasospasm.

Classifying complex pediatric feeding disorders.

BACKGROUND: This study defines the multiple characteristics associated with complex pediatric feeding problems and determines the relative frequency of each classification in a population referred to an interdisciplinary feeding team. METHODS: The written reports from team evaluations on 103 children (64 males, 39 females; age range 4 months to 17 years) were reviewed. Prematurity and/or presence of developmental delay was coded. Identified factors related to current feeding problems were coded according to five categories: structural abnormalities, neurological conditions, behavioral issues, cardiorespiratory problems, metabolic dysfunction. RESULTS: Interrater reliability for the classification coding was 88%. Thirty-eight percent of the children had a history of pre- maturity and 74% were reported to have evidence of developmental delay. The following five categories or combinations were coded most frequently: structural-neurological-behavioral (30%), neurological-behavioral (27%), behavioral (12%), structural-behavioral (9%), and structural-neurological (8%). Overall, behavioral issues were coded more often (85%) than neurological conditions (73%), structural abnormalities (57%), cardiorespiratory problems (7%), or metabolic dysfunction (5%). CONCLUSIONS: Data analysis using this classification system revealed that the majority of children in this sample had a behavioral component to their complex feeding problem, regardless of concurrent physical factors. These findings suggest that complex pediatric feeding problems are biobehavioral conditions in which biological and behavioral aspects mutually interact, and both need to be addressed to achieve normal feeding.

Hepatic lipase affects both HDL and ApoB-containing lipoprotein levels in the mouse.

Transgenic mice were created overproducing a range of human HL (hHL) activities (4-23-fold increase) to further examine the role of hepatic lipase (HL) in lipoprotein metabolism. A 5-fold increase in heparin releasable HL activity was accompanied by moderate (approx. 20%) decreases in plasma total and high density lipoprotein (HDL) cholesterol and phospholipid (PL) but no significant change in triglyceride (TG). A 23-fold increase in HL activity caused a more significant decrease in plasma total and HDL cholesterol, PL and TG (77%, 64%, 60%, and 24% respectively), and a substantial decrease in lipoprotein lipids amongst IDL, LDL and HDL fractions. High levels of HL activity diminished the plasma concentration of apoA-I, A-II and apoE (76%, 48% and 75%, respectively). In contrast, the levels of apoA-IV-containing lipoproteins appear relatively resistant to increased titers of hHL activity. Increased hHL activity was associated with a progressive decrease in the levels and an increase in the density of LpAI and LpB48 particles. The increased rate of disappearance of 125I-labeled human HDL from the plasma of hHL transgenic mice suggests increased clearance of HDL apoproteins in the transgenic mice. The effect of increased HL activity on apoB100-containing lipoproteins was more complex. HL-deficient mice have substantially decreased apoB100-containing low density lipoproteins (LDL) compared to controls. Increased HL activity is associated with a transformation of the lipoprotein density profile from predominantly buoyant (VLDL/IDL) lipoproteins to more dense (LDL) fractions. Increased HL activity from moderate (4-fold) to higher (5-fold) levels decreased the levels of apoB100-containing particles. Thus, at normal to moderately high levels in the mouse, HL promotes the metabolism of both HDL and apoB-containing lipoproteins and thereby acts as a key determinant of plasma levels of both HDL and LDL.

Analysis of water from the Space Shuttle and Mir Space Station by ion chromatography and capillary electrophoresis.

Drinking water and condensate samples collected from the US Space Shuttle and the Russian Mir Space Station are analyzed routinely at the NASA-Johnson Space Center as part of an ongoing effort to verify water quality and monitor the environment of the spacecraft. Water quality monitoring is particularly important for the Mir water supply because approximately half of the water consumed is recovered from humidity condensate. Drinking water on Shuttle is derived from the fuel cells. Because there is little equipment on board the spacecraft for monitoring the water quality, samples collected by the crew are transported to Earth on Shuttle or Soyuz vehicles, and analyzed exhaustively. As part of the test battery, anions and cations are measured by ion chromatography, and carboxylates and amines by capillary electrophoresis. Analytical data from Shuttle water samples collected before and after several missions, and Mir condensate and potable recovered water samples representing several recent missions are presented and discussed. Results show that Shuttle water is of distilled quality, and Mir recovered water contains various levels of minerals imparted during the recovery processes as designed. Organic ions are rarely detected in potable water samples, but were present in humidity condensate samples.

Yeast Clk-1 homologue (Coq7/Cat5) is a mitochondrial protein in coenzyme Q synthesis.

Mutations in the clk-1 gene result in slower development and increased life span in Caenorhabditis elegans. The Saccharomyces cerevisiae homologue COQ7/CAT5 is essential for several metabolic pathways including ubiquinone biosynthesis, respiration, and gluconeogenic gene activation. We show here that Coq7p/Cat5p is a mitochondrial inner membrane protein directly involved in ubiquinone biosynthesis, and that the defect in gluconeogenic gene activation in coq7/cat5 null mutants is a general consequence of a defect in respiration. These results obtained in the yeast model suggest that the effects on development and life span in C. elegans clk-1 mutants may relate to changes in the amount of ubiquinone, an essential electron transport component and a lipid soluble antioxidant.

Diacylglycerol is the preferred substrate in high density lipoproteins for human hepatic lipase.

The hydrolysis of HDL phospholipids (PL) and glycerides by hepatic lipase (HL) has been investigated in native and reconstituted HDL particles (Lp2A-I). Fasting, normolipidemic HDL exhibit total lipid hydrolytic rates of between 10 and 36 nM FA/h per microM PL. Of the total fatty acids liberated with HDL3 only 1% are from triolein (TG), while 49% are from diolein (DG) and 50% are from PL. A spherical reconstituted particle containing 2 molecules of apoA-I, 120 molecules of PL, and 20 molecules of TG exhibits a total lipid hydrolytic rate of 18 nM FA/h per microM PL and 93% of the fatty acids liberated are from PL. Inclusion of 40 molecules of TG into the Lp2A-I particle doubles the rate of fatty acid hydrolysis by HL through a stimulation of TG hydrolysis. Further addition of 10 molecules of DG to the Lp2A-I complex has no effect on the overall rates of hydrolysis, but changes the substrate specificity, wherein 61% of the fatty acids are from DG and both TG and PL hydrolytic rates are significantly reduced. Increasing the amount of DG in the Lp2A-I particle further stimulates total lipid hydrolysis by raising DG hydrolytic rates at the expense of PL and TG hydrolysis. A particle containing 10 molecules of TG and 40 molecules DG yields the fastest lipid hydrolytic rate of 143 nM FA/h per microM PL, which constitutes 96% DG hydrolysis, 3% TG hydrolysis, and 1% PC hydrolysis. These data indicate that hepatic lipase acts primarily as a surface lipid lipase with HDL particles. DG is the preferred substrate of HL in HDL and the HDL-DG content regulates the hydrolysis of both PL and TG by HL.

Sexual behavior of HIV-seropositive young men with congenital coagulopathies. Hemophilia Behavioral Intervention Projects (HBIEP) Study Group.

PURPOSE: To describe the self-reported sexual behaviors of human immunodeficiency virus (HIV)-seropositive youths with congenital coagulopathies in order to guide the development of interventions to prevent secondary transmission. SUBJECTS: A total of 297 HIV-seropositive males, 12-24 years of age, were sampled from 11 hemophilia treatment centers and 28 affiliated subsites. METHODS: Review of clinical records and self-administered survey of HIV-related knowledge, attitudes and behaviors. Subjects were classified and compared by self-reported sexual behavior over the lifetime and the prior 6 months into five mutually exclusive groups (G1-5). RESULTS: A total of 42% of subjects were virgins who never had oral, vaginal, or rectal sex (G1); 10% were nonvirgins who had abstained (G2); 13% were virgins and nonvirgins who had intimate touch only (G3); 21% had intercourse and always used condoms (G4); and 13% had had unsafe intercourse (G5). Among the groups, G5 was the oldest, least likely to forego sex, most angry and anxious when reminded of HIV, and most reluctant to disclose serostatus to friends. CONCLUSIONS: Most subjects (87%) had safer sex or abstained in the last 6 months. A relatively small group of HIV-seropositive youth with bleeding disorders were engaged in unprotected intercourse and in need of intensive help with HIV risk reduction.

Numerical simulation of iodine speciation in relation to water disinfection aboard manned spacecraft I. Equilibria.

Elemental iodine (I2) is currently used as the drinking water disinfectant aboard the Shuttle Orbiter and will also be incorporated into the water recovery and distribution system for the International Space Station Alpha. Controlled release of I2 is achieved using the Microbial Check Valve (MCV), a flow-through device containing an iodinated polymer which imparts a bacteriostatic residual concentration of approximately 2mg/L to the aqueous stream. During regeneration of MCV canisters, I2 concentrations of approximately 300 mg/L are used. Dissolved iodine undergoes a series of hydrolytic disproportionation and related reactions which result in the formation of an array of inorganic species including: I-, I3-, HOI, OI-, IO3-, HIO3, I2OH-, I2O(-2), and H2OI+. Numerical estimation of the steady-state distribution of inorganic iodine containing species in pure water at 25 degrees C has been achieved by simultaneous solution of the multiple equilibrium expressions as a function of pH. The results are reported herein.