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S R Wilson

Publications and source records attributed to S R Wilson.

At least 91 records · Page 5Linked to original sources
PubMed1994

An X-ray crystallographic study of the nonsteroidal contraceptive agent centchroman.

We have determined an X-ray crystal structure for the N-methyl iodide derivative of the nonsteroidal contraceptive centchroman. The pendant aromatic substituents on C-3 and C-4 of the chroman system are nearly perpendicular to the plane of the chroman system, an orientation expected in such a chroman, but perturbed to some degree by the gem dimethyl substituents at C-2. Structural superposition with other nonsteroidal antiestrogens, tamoxifen and nafoxidine, shows a similar disposition of the tertiary amine side chains responsible for antagonist activity. The aryl rings also show good superposition, but in contrast to tamoxifen and nafoxidine, which have the potential for ring double bond conjugation, the centchroman aryl rings show a larger dihedral twist. While different superpositions between the enantiomers of centchroman and the bioactive enantiomer of estradiol (d-estradiol, 8 beta,9 alpha,13 beta,14 alpha,17 beta) are possible, when the chroman ring system is positioned over the AB rings of estradiol, then (3R,4R)-centchroman makes the best fit. The aryl substituents in both enantiomers make comparable overlays with the steroidal skeleton, but the axial methyl group at C-2 in (3R,4R)-centchroman is directed downward along the C-7 alpha axis of estradiol, a site where many substituents are known to be well tolerated by the estrogen receptor, while in the 3S,4S-enantiomer, this methyl group is projected upward. Thus, we suggest that the bioactive l-enantiomer of centchroman will have the 3R,4R absolute configuration.

Centchroman↗
PubMed1994

Estimates for different stages of HIV/AIDS disease.

Software for estimating current and future numbers in different stages of the natural history of HIV infection has been developed. This is based on a general multistage model for the natural history of HIV/AIDS disease, allowing for treatment effects. The multistage model has been incorporated into the general back-projection procedure. For illustration, Australian AIDS data are used here.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Opsonic antibodies to Staphylococcus epidermidis: in vitro and in vivo studies using human intravenous immune globulin.

Staphylococcus epidermidis is a major cause of nosocomial infections, including sepsis in premature infants. Intravenous immune globulin (IVIG) has been used to prevent neonatal sepsis, but efficacy has varied in different clinical trials. The role of IgG antibody in immunity to S. epidermidis was studied using an opsonophagocytic assay and a lipid-emulsion-induced lethal model of neonatal S. epidermidis sepsis. Opsonic antibody to S. epidermidis varied between IVIG preparations and between lots: Lots with > or = 90% opsonic activity promoted bacterial clearance from blood and significantly enhanced survival when compared with lots with < or = 50% opsonic activity. Absorption of IVIG with S. epidermidis removed in vitro opsonic and in vivo protective activity. These studies suggest that opsonic antibody may play an important role in S. epidermidis immunity in immunocompromised patients, such as premature infants. Standard IVIG, however, may not provide therapy effective in preventing S. epidermidis infections, as many IVIG lots contain insufficient levels of opsonic S. epidermidis antibody.

Animals↗
PubMed1994

Ultrasonography in obstetric and gynecologic emergencies.

In conclusion, both transabdominal and transvaginal sonography are valuable tools in the evaluation of the patient who presents with a gynecologic or obstetric emergency and can very quickly lead to a definitive diagnosis or limited differential. Sonography also can be useful in excluding the presence of other pathologies that may mimic obstetric or gynecologic disease including appendicitis, diverticulitis, and renal obstruction.

Diagnosis, Differential↗
PubMed1993

Molecular structures, conformational analysis, and preferential modes of binding of 3-aroyl-2-arylbenzo[b]thiophene estrogen receptor ligands: LY117018 and aryl azide photoaffinity labeling analogs.

Structural and computational modeling studies were performed on the antiestrogen LY117018 (3) and two photoaffinity labeling analogs, in which an azide replaces the basic ether side chain (methyl ether tetrafluoro azide 7 and its protio analog 8). These studies were undertaken in order to determine the conformational preferences of these compounds and to propose favorable orientational modes for their binding to the estrogen receptor. In the crystallographic studies, we found that, unlike tetrafluoro azide 7, which adopts a face-to-face stacking of the p-hydroxyphenyl and benzoyl groups in the solid state, the pendant rings in the corresponding protio analog 8 are found in a predominantly offset pi-stacked array. In LY117018, which has an ether on the benzoyl ring, stacking of the pendant rings does not occur in the crystal structure; it assumes a T-shape, with the benzoyl group oriented perpendicular to the benzo[b]thiophene nucleus. In modeling studies, analogs of LY117018, 7, and 8 were subjected to a conformational grid search by molecular mechanics, and for each compound, three low-energy conformers (and their atropisomers) were obtained. These conformers were further geometry optimized by semiempirical molecular orbital calculations. For each compound, one of the three minimum-energy conformers is quite similar to the solid-state geometry. The computational structure of the tetrafluoro azide showed the greatest stacking between the benzoyl group and the p-methoxyphenyl ring, but less stacking than was observed in the crystallographic structure. The orientational preferences of these benzo[b]thiophene ligands with the estrogen receptor were analyzed with the receptor volume mapping technique, a method based on the correspondence of the hydroxyl groups and the volume that the benzo[b]thiophene compound shares with a composite molecular volume of high-affinity estradiol-type ligands (the receptor excluded volume, RExV). If the benzo[b]thiophene nucleus is overlapped with the steroid AB rings, the best overlap with the RExV is achieved, but there is poor correspondence of the hydroxyl groups. An orientation and conformation in which the benzoyl group of the 3-benzoyl-2-aryl-benzo[b]thiophenes occupies a 7 alpha-like position relative to the steroid produces both ample volume overlap with the RExV and close approximation of the hydroxyl groups and is presented as the putative bioactive conformation.

Affinity Labels↗
PubMed1993

A controlled trial of two forms of self-management education for adults with asthma.

PURPOSE: Excess morbidity and mortality due to asthma, aggravated by demonstrably poor patient self-management practices, suggest the need for formal patient education programs. Individual and group asthma education programs were developed and evaluated to determine their cognitive, behavioral, and clinical effects. PATIENTS AND METHODS: We compared changes in asthma symptoms, utilization of medical services, knowledge about asthma, metered-dose inhaler (MDI) technique, and self-management behaviors for 323 adult Kaiser Permanente patients with moderate to severe asthma who were randomly assigned to small-group education, individual teaching, or 1 of 2 control conditions--an information (workbook) control or usual control (no formal asthma education). Data were collected from patients by questionnaire, diary, and physical examination at enrollment and at 5 months and 1 year after intervention. Medical record data on these patients were abstracted for a total 3-year period, from 1 year before to 2 years after enrollment. RESULTS: Compared with the usual control, the self-management education programs were associated with significant improvements in control of asthma symptoms (reduced "bother" due to asthma and increased symptom-free days), MDI technique, and environmental control practices. Small-group education also was associated with significant improvements in physician evaluation of the patients' asthma status and in patients' level of physical activity. For both group and individual education recipients, improvement in MDI technique was positively correlated with improved control of symptoms; however, the degree of improvement in symptoms was greater than that which could be accounted for on the basis of improvement in MDI technique alone. The time course over which changes occurred in the various outcome measures suggests the mechanism by which education resulted in improvement in the patient's status. Significant improvements in MDI technique and environmental control practices were manifest immediately following education (5-month follow-up) and at the 1-year follow-up. Significant improvements in symptom measures were not apparent until the 1-year follow-up. The rate of utilization of medical care for acute exacerbations decreased between baseline and the 2-year follow-up period, but this decrease did not differ significantly among treatment conditions. However, there was a trend toward greater reduction in patients receiving small-group education. An ad hoc finding of a significant difference favoring small-group education between the baseline and the second follow-up year acute visit rates was observed. This result must be regarded as tentative, since it is not clear that unambiguous statistical significance is attained in the light of multiplicity issues. However, this trend is consistent with the antecedent benefits of the small-group education, and appears to warrant further investigation. CONCLUSIONS: Carefully designed asthma education programs for adults can improve patients' understanding of their condition and its treatment and increase their motivation and confidence that the condition can be controlled, thereby increasing their adherence to the treatment regimen and management of symptoms, and, in turn, improving control of symptoms. Both small-group education and individual education were associated with significant benefits, but the group program was simpler to administer, better received by patients and educators, and more cost-effective. The results show promise for improving clinical outcomes, through well-designed educational programs, for patients with asthma and other chronic health problems.

Acute Disease↗
PubMed1993

A synthesis of 7 alpha-substituted estradiols: synthesis and biological evaluation of a 7 alpha-pentyl-substituted BODIPY fluorescent conjugate and a fluorine-18-labeled 7 alpha-pentylestradiol analog.

In an effort to assist in the preparation of ligands for the study of the estrogen receptor (ER), we have developed a new synthesis of 7 alpha-substituted estradiols. The key step in the synthesis involves a copper-catalyzed, alpha-selective, 1,6-conjugate addition of 4-pentenyl magnesium bromide to a suitably protected 6-dehydrotestosterone derivative. Desaturation and then reductive aromatization of the resulting 7 alpha-pentenyl androgen gave the 7 alpha-pentenylestradiol in good yields. The alpha-stereoselectivity of this addition in the testosterone series, compared with the 19-nortestosterone series, is significantly improved by the presence of the C-19 methyl group, which shields the beta face from attack. A key intermediate was functionalized further by substitution with fluorine-18 to provide a potential imaging agent for positron emission tomography, and by conjugation with a BODIPY (Molecular Probes Inc., Eugene, OR, USA) fluorophore to make a fluorescent probe for the estrogen receptor. The synthesis and biological evaluation of these analogs is presented, as well as a discussion of the improvements in the synthetic procedure.

Boron Compounds↗
PubMed1993

Effective and ineffective management behaviors of parents of infants and young children with asthma.

To define the specific objectives of a planned behavioral intervention directed toward parents of very young children with asthma, 574 detailed descriptions of ineffective and effective asthma management behaviors of parents of infants and young children (through 6 years of age) with asthma were collected via interviews with 117 physicians and other health professionals and 112 parents. Analysis of these data resulted in the identification of 130 ineffective and effective asthma management behaviors of parents that could be grouped in five major areas of responsibility: symptom intervention; symptom prevention; use of medical and educational resources; communication among caregivers; and child development and family relationships. This report presents the methodology of the study, describes the identified behaviors, and discusses implications of the results for the development of a behavioral intervention to improve asthma management by parents.

Adaptation, Psychological↗
PubMed1993

Patient and physician behavior models related to asthma care.

This article summarizes the considerable progress that has been made in characterizing the behaviors of patients and family members that contribute to good or poor outcomes of asthma care and in developing educational programs shown to be effective in improving patient outcomes. Research needs are identified, including the need for better understanding of the antecedents of patient behaviors and their relative (quantitative) contribution to outcomes of asthma care of techniques to alter patient and family management behavior to improve outcomes, especially among particular patient subgroups are described. In addition, the asthma management practices of physicians are examined, such as the frequency with which recommended versus less desirable approaches to the diagnosis and treatment of asthma are used. Critical to this research was the development or refinement and the standardization of measures of individual patient behavior (including compliance behaviors), asthma morbidity, and utilization of medical services related to asthma.

Adolescent↗
PubMed1993

Acute effects of inhaled salbutamol on the metabolic rate of normal subjects.

BACKGROUND: This study was designed to investigate the contribution of inhaled salbutamol to the increase in resting metabolic rate found in patients with chronic airflow limitation who were receiving bronchodilator therapy. METHODS: The resting metabolic rate of 10 normal subjects (age 20-47 years, weight 42-105 kg, seven men) was studied after inhalations of salbutamol or placebo. An open canopy method of indirect calorimetry was used to measure resting oxygen consumption (VO2) and resting carbon dioxide production (VCO2). Subjects inhaled two, four, eight, or 12 puffs (100 micrograms/puff) of salbutamol or placebo in a double blind manner. Recordings of VO2 and VCO2 were made after inhalation of the four doses of salbutamol or placebo, integrated over one hour, and compared. RESULTS: VO2 and VCO2 increased in a dose dependent manner after inhaled salbutamol with a maximum effect at five minutes after inhalation. After four puffs, VO2 was 203 and 188 ml/kg/h for salbutamol and placebo respectively. After eight puffs, VO2 was 207 and 185 and VCO2 was 167 and 155 ml/kg/h. After 12 puffs, VO2 was 220 and 190 with a VCO2 of 181 and 168 ml/kg/h. Twelve puffs of salbutamol increased the mean (SE) respiratory quotient from 0.85 (0.01) to 0.93 (0.04) at five minutes indicating an increase in ventilation in excess of metabolic demand. Mean heart rate increased in parallel with VO2. CONCLUSION: Inhaled salbutamol significantly increases resting metabolic rate in a dose dependent manner.

Administration, Inhalation↗
PubMed1993

Modification of the thermogenic effect of acutely inhaled salbutamol by chronic inhalation in normal subjects.

BACKGROUND: Acute inhalation of clinical doses of salbutamol in normal volunteers increases resting metabolic rate by up to 20% above control values. This study was designed to see if chronic treatment with salbutamol causes a sustained increase in metabolic rate and whether it modifies the acute thermogenic response to the drug. METHODS: The effects of chronic inhaled salbutamol on resting oxygen consumption (VO2) and carbon dioxide output (VCO2) were studied in seven normal subjects (age 20-47 years, weight 52-105 kg, five men). An open canopy method of indirect calorimetry was used to measure VO2, VCO2, and respiratory quotient (RQ). Subjects inhaled two puffs of salbutamol or placebo four times a day in a double blind manner. Measurements of resting VO2 and VCO2 after 10 days of salbutamol were compared with the values after 10 days of placebo and with those taken at the start of the study. At the end of each treatment period subjects inhaled eight puffs (800 micrograms) of salbutamol and the acute effects on VO2, VCO2 and RQ were monitored for one hour. RESULTS: Resting VO2, VCO2, and RQ were not significantly different at the end of the salbutamol and placebo periods but the acute response to eight puffs of salbutamol was abolished by regular inhalation. The mean VO2 integrated over one hour after 800 micrograms salbutamol given acutely was different (241.3 and 210.7 ml/kg/h in the placebo and salbutamol groups respectively). Differences were not significant between placebo and salbutamol groups for changes in VCO2, heart rate, blood pressure, and RQ after acute inhalation. CONCLUSION: Regular treatment with inhaled salbutamol (800 micrograms/day) does not cause a sustained increase in resting metabolic rate but prevents the increase in VO2 that occurs after acute inhalations in normal subjects.

Administration, Inhalation↗
PubMed1993

Atypical hepatic hemangioma: a suggestive sonographic morphology.

A retrospective review of the sonographic appearances of 29 proved atypical hemangiomas in 29 patients and a prospective study of the predictive capacity of these features were performed. The main confirmatory imaging examinations were computed tomography and technetium-labeled red blood cell radioisotope scanning with single photon emission computed tomography. The retrospective review showed that all tumors were solid. Twenty-seven tumors had an echogenic border, seen as a thick echogenic rind (n = 15) and a thin rim (n = 12). Unlike typical hemangiomas, which have a uniformly increased echogenicity relative to normal liver, all 29 tumors had an internal echo pattern that was at least partially hypoechoic. These morphologic criteria (a solid tumor with an echogenic border and partially hypoechoic internal pattern) were then prospectively applied to all hepatic tumors detected with sonography during a 6-month period. Fifteen lesions with these features were identified from among more than 5,000 abdominal scans. Twelve of these lesions were confirmed as, and two were presumed to be, cavernous hemangiomas; in one lesion, the diagnosis was false-positive. Recognition of these atypical features should increase suspicion of the presence of hemangiomas on sonograms.

Adult↗
PubMed1993

Ultrasonographically guided biopsy of small intra-abdominal masses.

Ultrasonography (US) has traditionally been considered inferior to computed tomography (CT) for guidance in fine-needle aspiration biopsy (FNAB) of small intra-abdominal masses. To assess the validity of this view, the results obtained for 58 consecutive patients referred for US-guided FNAB of intra-abdominal masses of diameter 25 mm or less were retrospectively analysed. In each case two to four (usually three) aspirations were initially performed with a 22-gauge needle; sufficient tissue for diagnosis was obtained in 53 of the 58 cases (91%). The procedure had to be repeated in the other five patients to acquire diagnostic tissue. Apart from some minor abdominal pain, no complications were encountered. Proof of the cytologic diagnosis was available for 49 of the 58 patients (84%)--from histologic examination in 22 cases and from the appropriate clinical and radiologic course in 27. A sensitivity of 95% and a specificity of 90% for the technique were found for the patients for whom adequate follow-up information was available. The authors conclude that FNAB of intra-abdominal masses measuring 25 mm or less can be accurately and safely performed under US guidance.

Abdominal Neoplasms↗