Assessment of the mechanical errors of a prototype of an optical multilateration system.

We are developing a multilateration system at a reasonable cost that aims at an accuracy better than 50 µm determined with a consistent metrological approach. In this context, an absolute distance meter, developed in-house, is used as a unique telemetric system to feed the different measurement heads of the multilateration system through a network of optical fibers. The uncertainty contribution for a distance measurement of the telemetric system itself, in a controlled environment, is from 2 µm up to 100 m (k = 1). In this paper, the uncertainty contribution due to mechanical designs of the measurement heads and the target is estimated: the gimbal mechanisms we have designed are presented and their sources of error are identified, experimentally quantified, and minimized. At the end, we demonstrate that the current design of the measurement head does not induce errors higher than 2 µm on the measured distances and the design of the target does not induce errors higher than 9 µm.

Spiritual activities as a resistance resource for women with human immunodeficiency virus.

BACKGROUND: Few studies have investigated the role that spiritual activities play in the adaptational outcomes of women with human immunodeficiency virus (HIV) disease. OBJECTIVE: To examine the role of spiritual activities as a resource that may reduce the negative effects of disease-related stressors on the adaptational outcomes in HIV-infected women. METHODS: A theoretically based causal model was tested to examine the role of spiritual activities as a moderator of the impact of HIV-related stressors (functional impairment, work impairment, and HIV-related symptoms) on two stress-related adaptational outcomes (emotional distress and quality of life), using a clinic-based sample of 184 HIV-positive women. RESULTS: Findings indicated that as spiritual activities increased, emotional distress decreased even when adjustments were made for HIV-related stressors. A positive relationship between spiritual activities and quality of life was found, which approached significance. Findings showed that HIV-related stressors have a significant negative effect on both emotional distress and quality of life. CONCLUSIONS: The findings support the hypothesis that spiritual activities are an important psychological resource accounting for individual variability in adjustment to the stressors associated with HIV disease.

Experiences of violence in HIV-seropositive women in the south-eastern United States of America.

Women represent one of the fastest growing groups being diagnosed with HIV infection. Because of the circumstances under which they live, women at the highest risk for HIV infection may also be at risk for verbal, physical and sexual violence. The purpose of this study was to examine the frequency and type of violence experienced by women infected with HIV, and describe associations between reported violence, self-esteem and sense of competence. The study used a descriptive design and was conducted in the south-eastern United States. The sample consisted of 194 women infected with HIV. Women were primarily single, African-Americans residing in urban areas with an annual household income of less than $10,000 per year. Participants completed face-to-face interviews using a structured questionnaire which included a frequency of violence scale, Rosenberg's self-esteem scale, and Pearlin and Schooler's mastery scale. Approximately 15% of women reported at least one event of physical abuse and 55% at least one event of verbal abuse in the past 6 months. Verbal abuse experienced by women was the strongest net negative predictor of self-esteem and competence. These findings indicate that HIV-infected women are at risk for experiencing physical abuse and verbal abuse, and the experience of violence is associated with lower self-esteem and competence.

An exploration of the meaning and use of spirituality among women with HIV/AIDS.

Disease progression and the onset of AIDS slowly strip away the human form and dignity. As the physical body succumbs to the disease, those with HIV/AIDS search for meaning in life as they seek ways to prolong survival. The purpose of this study was to explore the meaning and use of spirituality in women infected with HIV/AIDS. Data were generated through the use of focus group methodology in eight sessions. The sample was composed of 45 women, aged 20 to 63, of whom 12 were white and 33 were black. Focus group sessions generated 76 descriptions of spirituality and six major themes: relationship with a supreme being, prayer and meditation, healing, peace, love, and religiosity. The acceptance of spirituality as a component of health and quality of life requires a shift in perspective that may allow for the development of new treatment and care strategies that are meaningful to those whose conditions are presently incurable.

Self-care activities of women infected with human immunodeficiency virus.

The article describes a qualitative focus group study exploring the self-care activities undertaken by women testing positive for human immunodeficiency virus (HIV) to promote and maintain their health. The sample included 27 women who participated in one of four focus group sessions. Participants represented women from both rural and urban settings in the South. Subjects talked about and described the ways in which they took care of themselves. Content analysis was used to code the data and to determine major categories of activities. Seven categories were identified: special dietary and nutrition practices, choosing not to use medically prescribed therapies, spiritual reliance and rituals, staying active, cognitive strategies, self-education, and adopting healthy life styles. These findings support the value of developing a holistic approach to health care of women infected with HIV.

Quantitation of taurolidine decomposition in polymer solutions by chromotropic acid formaldehyde assay method.

A sensitive, selective, and specific assay was needed to study the degradation kinetics of taurolidine and its stabilization by polyvinylpyrrolidone (PVP). The purpose of the present study was to evaluate the usefulness of the chromotropic acid method and other formaldehyde or amine derivatization methods. The methods evaluated included formaldehyde derivatization with chromotropic acid, acetylacetone, 4-amino-5-hydrazino-3-mercapto-1,2,4-triazole, semicarbazide hydrochloride, or 2,4-dinitrophenylhydrazine and taurolidine decomposition product derivatization with dansylchloride or 7-chloro-4-nitrobenz-2-oxa-1,3-diazole chloride. Results indicated that the chromotropic acid method provided sufficient selectivity, reproducibility and sensitivity. It was able to quench taurultam decomposition and avoided PVP interference. The method was optimized by performance based selection of reagent lots, appropriate reagent storage and preparation, and controlled derivatization conditions. In conclusion, the optimized chromotropic method was the most appropriate method for quantitating taurolidine decomposition.

Barriers to health-seeking behaviors for women infected with HIV.

There is a growing need to develop services for women with human immunodeficiency virus (HIV) infection, despite the reluctance of many to seek help. Yet, there is limited knowledge of the forces that act as barriers to health-seeking behaviors among these women. In the analysis of this focus group study of 46 women with HIV, eight distinct categories of perceived barriers to care were identified. These were: Lack of knowledge on the part of health care providers, fear of negative treatment, insensitivity of health care providers, fear by providers, lack of patient education, lack of confidentiality, lack of honesty, and blaming the victim. The women's descriptions of their experiences with health care providers are presented and discussed in the context of the potential impact of such behaviors on women's willingness to accept or continue treatment for HIV infection.

Perceptions of stigma in women infected with HIV.

This qualitative focus group study explored perceptions of stigma in HIV-seropositive women. The sample included 19 HIV-positive women who participated in one of four focus group sessions. Participants were asked to talk about and describe their perceptions of how others think about and respond to them and other HIV-infected individuals. Content analysis was used to code the data and identify participant perceptions. Four themes representing distinctly different perceptions of stigma were identified: distancing, overgeneralizing stereotypes, social discomfort, and pity. The implications of the findings for intervention and future research are discussed.

Experiences of disclosure in women infected with HIV.

In this qualitative focus group study, we explored issues of disclosure for women infected with HIV. The sample included 19 women who participated in one of four focus group sessions. Participants talked about and described their experiences sharing information about their HIV infection with others. Content analysis was used to code the data and identify major issues. Participants uniformly expressed concern about disclosing their HIV status because they expected and feared negative responses from others. Descriptions of disclosure revealed an evaluative process involving an analysis of potential risks and benefits. Three themes that represent concerns about disclosure were identified: discrimination, confidentiality, and the context of disclosure. Based on the findings, we concluded that these concerns are important factors influencing disclosure decisions and the use of supportive services and resources. The findings have implications for designing interventions to assist women in coping with the diagnosis of HIV and to promote their quality of life.

Solid state characterization of dehydroepiandrosterone.

Three polymorphs (forms I-III), a monohydrate (form S2), and three new solvates [4:1 hydrate (form S1), monohydrate (form S3), and methanol half-solvate (form S4)] were isolated and characterized by X-ray powder diffractometry (XRPD), IR spectroscopy, differential scanning calorimetry (DSC), hot stage microscopy, solution calorimetry, and their dissolution rates. A new polymorph, designated as form V, melting at 146.5-148 degrees C, was observed by hot stage microscopy. Our results indicate that only forms I and S4 exhibit reproducible DSC thermograms. Five of the isolated modifications undergo phase transformation on heating, and their DSC thermograms are not reproducible. Interpretation of DSC thermograms was facilitated by use of hot stage microscopy. The identification of each modification is based on XRPD patterns (except forms S3 and S4, for which the XRPD patterns are indistinguishable) and IR spectra. In the IR spectra, a significant difference was observed in the OH stretching region of all seven modifications. In a purity determination study, 5% of a contaminant modification in binary mixtures of several modifications could be detected by use of XRPD. To obtain a better understanding of the thermodynamic properties of these modifications, a series of increasing heating rates and different pan types were used in DSC. According to Burger's rule, forms I-III are monotropic polymorphs with decreasing stability in the order form I > form II > form III. The melting onsets and heats of fusion for forms I-III are 149.1 degrees C, 25.5 kJ/mol; 140.8 degrees C, 24.6 kJ/mol; and 137.8 degrees C, 24.0 kJ/mol, respectively. For form III the heat of fusion was calculated from heat of solution and DSC data. In the case of form S1 the melting point, 127.2 degrees C, was obtained by DSC using a hermetically sealed pan. The relative stabilities of the six modifications stored under high humidity conditions were predicted to be, on the basis of the heat of solution and thermal analysis data, from S2 > form S3 > form S1 > form I > form II > form III. However, the results of the dissolution rate determination were inconsistent with the heat of solution data. The stable form I shows a higher initial dissolution rate than the metastable form II and unstable form III. All modifications were converted into the stable monohydrate, form S2, during the dissolution study, suggesting that the moisture level in solid formulations should be carefully controlled.

The effect of excipients on glass transition temperatures for FK906 in the frozen and lyophilized states.

FK906, a tripeptide, has been used as a model compound to study the effect of excipients on the glass transition temperature for peptides and related compounds in the frozen solution and lyophilized states. Three kinds of excipients were chosen for study, low molecular weight sugars, high molecular weight polymers and salts. Our results indicate that the Gordon-Taylor equation can be used to predict the glass transition temperature of FK906 in the presence of sucrose, lactose, trehalose and maltose in the frozen solutions and in lyophilized products. Dextrans having different molecular weights can have different effects on the glass transition temperature of FK906 in the frozen state. Cooling rate can also have an effect on the glass transition temperature for FK906 frozen solutions in the presence of dextran. Finally, salts have a significant effect on the glass transition temperature of FK906 in the frozen state but not in lyophilized FK906.

Some physicochemical properties of FK906: glass transition and relaxation.

FK906, a tripeptide antihypertensive agent, was used as a model compound to study some physicochemical properties of peptides and peptide-related compounds. Our results indicate that lyophilization, grinding and melting or storing the samples under conditions of high relative humidity affect chemical stability and crystallinity of FK906. In a preliminary study of lyophilization process design, an extended phase diagram for FK906 in aqueous solution was constructed, and the effects of cooling rate and and heating rate on the glass transition temperatures of lyophilized FK906 and the FK906 solution were investigated. Following lyophilization, the DSC thermogram of FK906 exhibits an endothermic peak whose area is storage temperature- and time-dependent. The endothermic peak shifts to higher temperatures as the heating rate is increased. Our results indicate that the endothermic peak is related to structural change during incubation of lyophilized FK906.

Formulation, in vitro dissolution, and ocular bioavailability of high- and low-melting phenylephrine oxazolidines.

The in vitro dissolution and the relative ocular bioavailability of high- and low-melting phenylephrine oxazolidines (HMP and LMP) from a nonaqueous suspension (silicone fluid) were compared. Stability-indicating HPLC assays were developed for evaluation of the prototype formulations, in which a normal-phase HPLC method was necessary for analysis of PO, while a reverse-phase HPLC method was required for analysis of the primary degradation product, phenylephrine (PE), following its separation from the formulation using a short silica gel column. PO was formulated as an ophthalmic suspension in silicone fluid (20 cs) because of its property of undergoing rapid hydrolysis in aqueous media. An experimental test system for measuring the dissolution characteristics of a water-immiscible multiparticulate suspension was designed to obtain the dissolution profiles of suspensions of HMP and LMP. The dissolution rates, which were nearly identical for LMP and HMP, were obtained assuming a quasi-infinite reservoir. A reverse-phase HPLC assay with fluorescence detection was used for measuring the concentrations of PE in aqueous humor and corneal samples. Statistical analysis of the bioavailability data showed that suspensions containing HMP and LMP were equal in extent of absorption following a single topical application to the rabbit eye. The results correlated well with the in vitro dissolution rates of the suspensions of HMP and LMP.

Physicochemical characterization of high- and low-melting phenylephrine oxazolidines.

Phenylephrine oxazolidine is a new prodrug of phenylephrine developed for improving ocular absorption and reducing systemic side effects. In the present study, high- and low-melting phenylephrine oxazolidines (HMP and LMP) were characterized in terms of their stereochemistry and crystal properties. It was found that the molecular configuration of the prodrug in the crystals of either HMP or LMP is identical (5R/2R). The two crystals were shown to have the same IR spectra and X-ray diffraction patterns but different crystal habits, thermal properties, solubilities and intrinsic dissolution rates. Single crystal X-ray structure analysis indicates that crystals of both HMP and LMP are orthorhombic and belong to the P2(1)2(1)2(1) space group with four molecules in a unit cell (a = 20.697 A, b = 7.065 A, and c = 9.304 A). The molecules in the crystal are held together by an intermolecular hydrogen bonding interaction between N(3) and O(13). The different physical properties observed for LMP result from crystal imperfections caused by the presence of trace amounts (often at levels < 0.5%) of an unidentified, structurally related synthetic impurity which can be dispersed in the prodrug. It was observed that both HMP and LMP can sustain thermal and mechanical treatment in the solid state. However, LMP was partially converted to HMP when suspended in certain solvents.

A high-performance liquid chromatographic method for the quantitative enantioselective analysis of mefloquine stereoisomers.

A rapid quantitative, enantioselective HPLC method for the analysis of the four stereoisomers, (+) and (-) erythro and (+) and (-) threo forms, of mefloquine has been developed using a Chiralpak Ad analytical column containing amylose tris-3,5-dimethylphenyl carbonate coated on silica gel and hexane/ethanol/diethylamine (96:4:0.1, v/v%) as the mobile phase. This method made it possible to quantitate small amounts of threo form in the presence of the erythro form of mefloquine, the form which is used as the active ingredient in commercial mefloquine tablets. Tablets from three sources were studied to estimate their optical purity, and it was found that tablets from one source contain 0.27 w/w% of the (-)-threo and 0.25 w/w% of the (+)-threo form, tablets from the second source contain 0.056 and 0.042 w/w% (-)- and (+)-threo, respectively, and tablets from the third source contain 0.052 w/w% (+)-threo, with the remainder erythro.

Coronary artery bypass grafting within thirty days of acute myocardial infarction. Early and late results in 406 patients.

Between 1981 and 1987, 1726 coronary artery bypass operations were performed by a single group of surgeons at a community hospital. Overall hospital mortality in this group was 2.4% (41/1726). Of these patients 406 were operated on within 30 days of an acute myocardial infarction. The hospital mortality rate in this group was 6.7% (27/406) versus 1.1% (14/1320) in patients operated on without evidence of recent acute myocardial infarction (p less than 0.0001). In these 406 patients, sex, location of acute myocardial infarction, type of infarction, coronary anatomy, presence of postinfarction angina, technique of myocardial preservation, and the time from infarction to operation were not associated with hospital mortality. Univariate and multivariate analyses showed that three factors were significantly associated with increased hospital death: poor ejection fraction, less than 30% (p less than 0.0001), preoperative shock (p = 0.0005), and age greater than 70 years (p = 0.004). Follow-up was 90% complete (365/406 patients) at a mean time of 35 +/- 21 months. Of these patients 80% (292/365) were in New York Heart Association functional class I, and 10% (36/365) were in functional class II. Of all patients 88% were alive at 3 years, and 84% were alive at 5 years after operation. Multivariate comparison of survival curves showed that ejection fraction less than 30% was associated with decreased survival (p = 0.0002), followed by age (p = 0.0009). Patients younger than 70 years with an ejection fraction greater than 30% and not in cardiogenic shock can be operated on at any time after acute myocardial infarction without increased risk. Long-term survival and freedom from symptoms can be expected in these patients.

Structural effects on the binding of amine drugs with the diphenylmethyl functionality to cyclodextrins. II. A molecular modeling study.

Molecular modeling has been used to study the complexation between alpha, beta, or gamma-cyclodextrin (CD) and a group of amine compounds having the diphenylmethyl functionality. The computer program SYBYL 5.3 and the Tripos force field (version 5.2) were used for all the calculations. Three-dimensional structures of 13 amine compounds were built individually from their atoms, and CDs were built based on the X-ray crystallographic coordinates. The diphenylmethyl derivative-CD complexes were constructed and optimized. Based on the calculated binding energies accompanying the inclusion process, the preferred method of approach of the compounds to the cavities of the CD molecules, and the structural effects on the binding between amine compounds and three CDs were explored. The calculated binding energies exhibited a good correlation with the stability constants obtained from solution calorimetric titrations. The present study shows that for similar ligand molecules, the molecular modeling technique should enable us to visualize the structure of the inclusion complexes and will also assist us in determining the ability of a potential drug molecule to form a stable complex with CDs.

Structural effects on the binding of amine drugs with the diphenylmethyl functionality to cyclodextrins. I. A microcalorimetric study.

Solution calorimetry has been employed to evaluate the stability constants and enthalpy changes associated with complex formation between alpha-, beta, or gamma-cyclodextrin (CD) and a group of amine compounds having the diphenylmethyl functionality. Data from thermal titrations of the compounds were analyzed using nonlinear least squares. The standard free energy decrease accompanying the formation of inclusion complexes is generally due to a negative standard enthalpy change (delta H degrees). The standard entropy change (delta S degrees) was negative, except in the case of complexes formed with gamma-CD. Of the 13 compounds studied, only 2 formed complexes with 1:2 (compound:beta-CD) stoichiometry, terfenadine . HCl and cinnarizine . 2HCl. All the others formed 1:1 complexes. The structural effect on the stability constants, thermodynamics, and inclusion geometry was explored by relating the calorimetric results to the chemical structures of the guest molecules and the cavity sizes of the CD molecules. The results suggest that one of the phenyl groups of the diphenylmethyl functionality resides in the CD cavity and is in van der Waals contact with the inside wall of the CD cavity. In the case of alpha- and beta-CDs, van der Waals interaction dominates in the stabilization. On the other hand, the interaction between these compounds and gamma-CD is largely entropically driven. Adiphenine . HCl forms a more stable complex with beta-CD than proadifen . HCl, suggesting that hydrogen bonding to the carbonyl oxygen by the hydroxyl group on the rim of the CD ring can influence the strength of the binding interaction.

Physical properties of the complexes formed between heptakis(2,6-di-O-methyl)-beta-cyclodextrin, beta-cyclodextrin, and chlorambucil.

The solid complex of chlorambucil (CHL) and heptakis-(2,6-di-O-methyl)-beta-cyclodextrin (DIMEB) has been isolated from ethanol and analyzed by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and powder X-ray diffractometry. The carbonyl stretching band of the complex, observed in the FTIR spectrum, was shifted to higher frequency, suggesting that intermolecular hydrogen bonds between CHL molecules are broken when the complex is formed. Since no melting endotherm was observed for CHL when the DSC thermogram of the complex was obtained, the crystal lattice of the compound must be disrupted upon complexation. X-ray diffraction patterns of the inclusion complex were different from those of the physical mixture and contained no peaks corresponding to free CHL, thus indicating the formation of a new crystalline material. The 1:1 CHL:beta-cyclodextrin (beta-CD) complex was isolated from aqueous solution at 3 degrees C. Results of analyses using FTIR and DSC were similar to those obtained with the CHL:DIMEB complex. The X-ray diffraction patterns of the complex suggest that its degree of crystallinity is higher than that of the CHL:DIMEB complex.

Microcalorimetric investigation of the complexation between 2-hydroxypropyl-beta-cyclodextrin and amine drugs with the diphenylmethyl functionality.

Solution calorimetry has been employed to evaluate the stability constants and standard-enthalpy changes (delta H degrees) associated with complex formation between 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CD) and a group of amine compounds having the diphenylmethyl functionality in aqueous solution at 298.15 K. Data from microcalorimetric titrations of the compounds were analysed using a nonlinear least-squares method. Of the 12 compounds studied, only terfenadine.HCl formed a 1:2 (compound:HP-beta-CD) complex. All the others formed 1:1 complexes. The standard free energy decrease accompanying the formation of inclusion complexes is generally due to a negative delta H degrees. This exothermic delta H degrees can be interpreted as indicating that the binding forces for complexation include both the hydrophobic effect and strong van der Waals interactions. When a halogen substituent is in the aromatic ring, stability constants are higher and standard-entropy changes (delta S degrees) become positive, suggesting greater hydrophobic interaction. Both adiphenine.HCl and proadifen.HCl form more stable complexes, suggesting that hydrogen bonding to the carbonyl oxygen by the hydroxyl-group on the rim of the CD ring could be an important contributor to the complexation. Substitution on the aliphatic carbon of the diphenylmethyl group was also found to be important in determining the ability of compounds to bind with HP-beta-CD. The independence of the thermodynamic constants on the degree of protonation in the case of bifunctional amines indicates that the amine functional groups do not penetrate into the HP-beta-CD cavity.