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D Stephens

Publications and source records attributed to D Stephens.

At least 19 recordsLinked to original sources
PubMed2000

Investigation of the in vitro release of gentamicin from a polyanhydride matrix.

Septacin¿trade mark omitted¿ is a sustained release formulation consisting of gentamicin sulfate dispersed in a biodegradable polyanhydride matrix. The polyanhydride matrix is a copolymer of erucic acid dimer (EAD) and sebacic acid in a 1:1 weight ratio. In vitro drug release was performed in both water and pH 7.4 phosphate buffer. The drug release in water was faster than that in the buffer, which was the opposite of what would be expected based upon a faster polymer hydrolysis rate in the buffer. Theoretical treatment of the data using the Peppas model revealed that release in water was anomalous, while the release in pH 7.4 phosphate buffer was diffusion-controlled. Profound bead morphology differences were observed between beads in these two in vitro release media. Cracking was observed in beads in water and swelling with no apparent cracking was seen in beads in buffer. Concurrent monitoring of drug and sebacic acid release indicated that drug release is not via surface erosion. Osmotic effects were found to play little role in the in vitro drug release. There was no spectroscopic evidence of amide formation between the drug and copolymer. Sulfate release was monitored along with drug release and the results indicate that there is ion-exchange occurring during the pH 7.4 in vitro release. It was subsequently demonstrated that gentamicin can form an insoluble salt with EAD. This salt formation explains the slower drug release in pH 7.4 phosphate buffer.

Decanoic Acids↗
PubMed2000

Ambulatory blood pressure monitoring in children: a large center's experience.

Ambulatory blood pressure monitoring (ABPM) is well established in adults and is becoming common in children. We reviewed 190 ABPM studies retrospectively (since 1990) to assess the failure rate, and analyzed the data from 97 patients 5-19 years old (1992-1996) to review the experience gained from the use of this technique in children and adolescents. Seventeen percent (32/190) of studies failed. Most children accepted ABPM, provided it was clearly explained in advance. There were differences between day and night readings of systolic blood pressure (BP), diastolic BP, and heart rate. BP did not correlate with height or weight. "White coat" effect apparently exists in children: clinic systolic BPs were higher than daytime systolic ABPM (no difference in diastolic). Eighty-nine percent (86/97) had an elevated BP load (>30% of readings >95th percentile). The antihypertensive medications of 16% (16/97) of patients were changed after ABPM. The nocturnal fall in BP (expressed as a percentage of the individual mean daytime values) was approximately normally distributed and was independent of age and height. Nocturnal systolic and diastolic dipping were closely correlated. Attenuation of nighttime dipping was observed in children with kidney disease and those with organ transplants. There is a need for normative data for ABPM for North American children. In our study, the technique was useful in selected cases, such as borderline or secondary hypertension, and for therapeutic monitoring when BP control is difficult.

Adolescent↗
PubMed2000

Canadian Acute Respiratory Illness and Flu Scale (CARIFS): development of a valid measure for childhood respiratory infections.

Although acute respiratory infection (ARI) is the most frequent clinical syndrome in childhood, there is no validated measure of its severity. Therefore a parental questionnaire was developed: the Canadian Acute Respiratory Illness Flu Scale (CARIFS). A process of item generation, item reduction, and scale construction resulted in a scale composed of 18 items covering three domains; symptoms (e.g., cough); function (e.g., play), and parental impact (e.g., clinginess). The validity of the scale was evaluated in a study of 220 children with ARI. Construct validity was assessed by comparing the CARIFS score with physician, nurse, and parental assessment of the child's health. Data were available from 206 children (94%). The CARIFS correlated well with measures of the construct (Spearman's correlations between 0.36 and 0.52). Responsiveness was shown, with 90% of children having a CARIFS score less than a quarter of its initial value, by the tenth day.

Acute Disease↗
PubMed2000

Function-based isolation of novel enzymes from a large library.

Here we describe a high-throughput, quantitative method for the isolation of enzymes with novel substrate specificities from large libraries of protein variants. Protein variants are displayed on the surface of microorganisms and incubated with a synthetic substrate consisting of (1) a fluorescent dye (2) a positively charged moiety (3) the target scissile bond, and (4) a fluorescence resonance energy transfer (FRET) quenching partner. Enzymatic cleavage of the scissile bond results in release of the FRET quenching partner while the fluorescent product is retained on the cell surface, allowing isolation of catalytically active clones by fluorescence-activated cell sorting (FACS). Using a synthetic substrate with these characteristics, we enriched Escherichia coli expressing the serine protease OmpT from cells expressing an inactive OmpT variant by over 5,000-fold in a single round. Screening a library of 6 x 10(5) random OmpT variants by FACS using a FRET peptide substrate with a nonpreferred Arg-Val cleavage sequence resulted in the isolation of variant proteases with catalytic activities enhanced by as much as 60-fold. This approach represents a potentially widely applicable method for high-throughput screening of large libraries on the basis of catalytic turnover.

Boron Compounds↗
PubMed2000

Particle size determination of a three-component suspension using a laser-scattering particle size distribution analyzer.

In this study, a rapid and accurate particle size determination method using a light-scattering particle size analyzer was developed to measure the particle size and size distribution of a suspension containing three solid components: clotrimazole, triamcinolone, and sarafloxacin, which have different refractive indices. To ensure that data represent the size distribution of the primary particles of the suspension, the optimal sonication prior to and during measurement was determined. It was found that the results obtained using the average relative refractive index (RRI) of the three components agreed with the results obtained using three individual RRIs. In addition, the results from two analysts demonstrated good reproducibility of this method. The size distribution data of the suspension were also compared to those of the bulk drugs. The results showed that the median particle size of this three-component suspension is relatively close to that of clotrimazole, which accounts for 80% of solid particles in the suspension. Furthermore, the results obtained using the light-scattering technique were comparable to those obtained using a polarized light microscope equipped with an image analyzer, indicating acceptable accuracy of this technique.

Anti-Infective Agents↗
PubMed2000

A profile of the members of FASEB societies: NIH awards, degrees, and institutional affiliations, 1999.

Data from the FASEB Directory of Members and NIH were used to develop a statistical profile of the members of FASEB Societies. For the U.S.-based scientists (exclusive of retired and student members), the most frequently reported degree was a research doctorate (69. 6%). A substantial fraction, however, reported medical degrees (19. 2%) or both research and medical degrees (8.0%). The majority of members of FASEB Societies listed academic affiliations in the directory. Industrial affiliations were reported, however, in 9.7% of the entries with smaller fractions listing associations with hospitals, independent research institutes, and government agencies. Just over one-fourth of the members of FASEB Societies were principal investigators on NIH research grants. These investigators received one-half of all NIH grants and nearly 60% of the RO1 grants.

Awards and Prizes↗
PubMed2000

Recruitment for a pilot case control study of oxidative DNA damage and breast cancer risk.

Oxidative DNA damage (ODD) can result from numerous endogenous metabolic processes as well as from exposure to environmental and dietary oxidants. One important type of ODD that may have a role in carcinogenesis is the formation of hydroxylated DNA bases. Our major purpose was to determine the potential for subject accrual for a multisite case-control study of ODD and breast cancer risk within a large urban university medical center. We examined the levels of a hydroxylated thymine residue, 5-hydroxymethyl-2'-deoxyuridine in DNA obtained from the peripheral blood of 26 women with breast cancer and an age-matched group of 29 control women without breast cancer. The isolated DNA was analyzed for levels of 5-hydroxymethyl-2'-deoxyuridine by gas chromatography with mass spectral detection. Our recruitment methods resulted in a relatively high yield of eligible cases (72%) and a lower yield of controls (46%). We evaluated the dose-response relationship of ODD level to breast cancer risk, using quartiles of ODD. The covariate-adjusted odds ratio of breast cancer exceeded 2.0 for women in the highest quartile of ODD (compared with the lowest quartile), although this result was not statistically significant. ODD levels were significantly more variable among African-American controls (SD = 224.1) than among white controls (SD = 57.5), p < 0.001. Overall, these results suggest a possible slight increase in breast cancer risk among women in the highest ODD quartile, after adjusting for race, menopausal status, and family history of breast cancer.

Antineoplastic Agents↗
PubMed2000

The use of outcome measures to formulate intervention strategies.

OBJECTIVE: To investigate the relative value of the use of open-ended and structured questionnaires in the determination of the most appropriate management of patients in a busy audiological rehabilitation clinic. DESIGN: An open set questionnaire was sent to 56 consecutive patients before clinic attendance, and they were asked to rate the severity of the problems listed on arrival at the clinic. They subsequently were administered the Hearing Disability and Handicap Scale (HDHS), which was not scored until after management decisions had been made. The implications of the results of both questionnaires separately and together for patient management were compared. RESULTS: The Problem Questionnaire highlighted a number of areas in terms of Activity Limitation (Disability) not covered in the HDHS, some of which, such as employment effects, were considered to be of considerable importance to the patients. However, in the field of more general Participation Restriction (Handicap), the structured questionnaire highlighted a number of important areas not volunteered by the patient. CONCLUSION: Although the open-set Problem Questionnaire approach is valid in the domain of Activity Limitation, it needs to be supplemented by an additional measure of Participation Restriction, either open-set or structured, to ensure optimal patient management.

Adult↗
PubMed2000

Optimal outcome measures, research priorities, and international cooperation.

The participants in the Eriksholm Workshop on "Measuring Outcomes in Audiological Rehabilitation Using Hearing Aids" debated three issues that are reported in this article. First, it was agreed that the characteristics of an optimal outcome measure vary as a function of the purpose of the measurement. Potential characteristics of outcome self-report tools for four common goals of outcome measurement are briefly presented to illustrate this point. Second, 10 important research priorities in outcome measurement were identified and ranked. They are presented with brief discussion of the top five. Third, the concept of generating a brief universally applicable outcome measure was endorsed. This brief data set is intended to supplement existing outcome measures and to promote data combination and comparison across different social, cultural, and health-care delivery systems. A set of seven core items is proposed for further study.

Correction of Hearing Impairment↗
PubMed2000

Comparison of family therapy and family group psychoeducation in adolescents with anorexia nervosa.

OBJECTIVE: To compare the effects of 4 months of 2 family-oriented treatments, family therapy and family psychoeducation, on female adolescents with newly diagnosed restrictive eating disorders. METHOD: Twenty-five female adolescents requiring hospitalization were randomized into either family therapy or family group psychoeducation. Outcome measures included medical (body weight) and psychosocial (specific and nonspecific eating disorder psychopathology) variables at baseline and after 4 months of treatments every 2 weeks. RESULTS: A significant time effect was found in both treatment groups for the restoration of body weight (percentage of ideal body weight, P < 0.00001). The group averages ranged from 75% to 77% ideal body weight before treatment to 91% to 96% after it. A time effect was also seen on the Family Assessment Measure (P < 0.018), in that the patients of both groups acknowledged more family psychopathology at the end of treatment. No significant group differences were found on any of the self-report measures of specific and nonspecific eating disorder pathology. CONCLUSIONS: Weight restoration was achieved following the 4-month period of treatment in both the family therapy and family psychoeducation groups, but no significant change was reported in psychological functioning by either adolescents or parents. Family group psychoeducation, the less expensive form of treatment, is an equally effective method of providing family-oriented treatment to newly diagnosed, medically compromised anorexia nervosa patients and their families.

Adolescent↗
PubMed2000

Subcategories of patients with King-Kopetzky syndrome.

King-Kopetzky syndrome (Obscure Auditory Dysfunction, OAD) has been recognized as a clinically distinct condition in audiological and ENT clinics. It is characterized by normal hearing thresholds on pure tone audiometry (PTA) but complaints of difficulties in understanding speech in the presence of background noise. In a study on 110 consecutive patients with King-Kopezky syndrome referred to the Welsh Hearing Institute, subjects were subdivided into seven subcategories based on sensitized measures of auditory dysfunction and on psychological assessment. These were: (1) middle ear dysfunction; (2) mild cochlear pathology; (3) central/medial olivocochlear efferent system (MOCS) auditory dysfunction; (4) purely psychological problems; (5) multiple auditory pathologies; (6) combined auditory dysfunction and psychological problems and (7) unknown. Different subgroups may represent different pathogenic and aetiological factors. Thus, subcategorization provides further understanding of the basis of King-Kopetzky syndrome, and hence may guide the rehabilitative management of these patients.

Adolescent↗
PubMed1999

Risk factors for resistance to "first-line" antimicrobials among urinary tract isolates of Escherichia coli in children.

BACKGROUND: There are increasing concerns regarding antimicrobial resistance in Canada. Data are limited on the prevalence, patterns of resistance and risk factors associated with resistant organisms, including coliforms, in children. This study was done to address these issues as they relate to urinary tract isolates of Escherichia coli in a tertiary care pediatric centre in Ottawa. METHODS: A surveillance study was conducted from December 1992 to December 1994. Susceptibility testing of urinary tract isolates of E. coli was performed using a panel of antimicrobial agents. A case-control study was also conducted for subjects with isolates resistant to trimethoprim-sulfamethoxazole (T-S), this drug being used a representative "first-line" agent. RESULTS: A total of 1636 consecutive isolates were obtained from 967 subjects. Of the 1636 isolates, 736 (45.0%) were resistant to ampicillin, 514 (31.4%) were resistant to T-S, 363 (22.2%) were resistant to both ampicillin and T-S, and 27 (1.7%) were resistant to both ampicillin and gentamicin. In the case-control study 274 children with isolates resistant to T-S were matched with 274 children who had T-S-sensitive isolates obtained during the study period or the preceding or subsequent 6 months. Multivariate analyses indicated that subjects who had received antimicrobials for more than 4 weeks in the previous 6 months were about 23 times more likely to have isolates resistant to T-S than were subjects without this risk factor (odds ratio [OR] 23.4, 95% confidence interval [CI] 12.0-47.6). Children with genitourinary tract abnormalities were 2.4 times more likely to have resistant isolates than those without such abnormalities (95% CI 1.2-4.5). Compared with children who had no hospital admissions in the previous year, those with 1 admission in that period were more likely to have resistant isolates (OR 2.3, 95% CI 1.4-7.5), as were those with 2 or more admissions in that period (OR 3.2, 95% CI 1.1-4.8). Compared with children aged 2-6 years, children under 2 years of age were less likely to have resistant isolates (OR 0.3, 95% CI 0.2-0.8). INTERPRETATION: Selective antimicrobial pressure and multiple admissions to hospital were among the risk factors associated with antimicrobial resistance. The finding of a low but definite level of resistance to both ampicillin and gentamicin is important for the selection of empiric therapy for sepsis in neonates. The role of inexpensive first-line agents in the outpatient treatment and prevention of urinary tract infections requires re-examination, particularly in children who have recently received antimicrobial therapy.

Anti-Bacterial Agents↗
PubMed1999

Comparison of albuterol delivered by a metered dose inhaler with spacer versus a nebulizer in children with mild acute asthma.

OBJECTIVE: In children with mild acute asthma, to compare treatment with a single dose of albuterol delivered by a metered dose inhaler (MDI) with a spacer in either a weight-adjusted high dose or a standard low-dose regimen with delivery by a nebulizer. STUDY DESIGN: In this randomized double-blind trial set in an emergency department, 90 children between 5 and 17 years of age with a baseline forced expiratory volume in 1 second (FEV1 ) between 50% and 79% of predicted value were treated with a single dose of albuterol, either 6 to 10 puffs (n = 30) or 2 puffs (n = 30) with an MDI with spacer or 0.15 mg/kg with a nebulizer (n = 30). RESULTS: No significant differences were seen between treatment groups in the degree of improvement in percent predicted FEV1 (P =.12), clinical score, respiratory rate, or O2 saturation. However, the nebulizer group had a significantly greater change in heart rate (P =.0001). Our study had 93% power to detect a mean difference in percent predicted FEV1 of 8 between the treatment groups. CONCLUSION: In children with mild acute asthma, treatment with 2 puffs of albuterol by an MDI with spacer is just as clinically beneficial as treatment with higher doses delivered by an MDI or by a nebulizer.

Adolescent↗
PubMed1999

Detrimental effects of alcohol on tinnitus.

The present study has examined the detrimental effects which alcohol has on tinnitus in a consecutive series of 51 patients seen in a tinnitus clinic and reporting such an effect. Eighty-four per cent of those studied reported that the level of the tinnitus was increased by the alcohol, 73% that they became more aware of it, and 47% that it increased the effect of the alcohol on their sleep. Compared with patients reporting beneficial effects on tinnitus, they consumed less alcohol, they comprised a higher proportion of younger females, and they were more likely to report that their tinnitus was worse the next day. There were no marked differences between the effects of different types of alcohol.

Adult↗
PubMed1999

A patient-based voucher system of brief hospitalisation.

OBJECTIVE: The aim of this study was to demonstrate the clinical use of a patient-based voucher system for brief hospitalisation. CLINICAL PICTURE: A 31-year-old male, chronically disabled, with schizophrenia, polysubstance, and borderline personality disorders presented concerns for the treating team. TREATMENT: Management was community based except for a single admission in which the patient chose the timing and duration via a predetermined set of vouchers. OUTCOME: In contrast to previous admissions, a patient-chosen, voucher-based admission was single, brief and uneventful. CONCLUSIONS: Novel approaches to chronically disabled patients with psychiatric illness enable change from therapeutic pessimism. A patient-based voucher system seemed to be of use in one patient.

Adult↗
PubMed1999

Audioscan testing in patients with King-Kopetzky syndrome.

In this study, the Audioscan test has been used to detect early signs of hearing abnormalities in 80 patients with King-Kopetzky syndrome. A significantly higher prevalence of Audioscan notches between 500 and 3,000 Hz was found for each age band and gender in patients with King-Kopetzky syndrome than in control subjects. This indicates that Audioscan notches between 500 and 3,000 Hz may represent a fine hearing deficit as an indicator of mild auditory dysfunction in patients with King-Kopetzky syndrome. However, there was no significant difference in the percentage of notches in the 3,001-8,000 Hz frequency band between the King-Kopetzky syndrome and control groups.

Acoustic Stimulation↗
PubMed1999

Test-retest variability of distortion-product otoacoustic emissions in human ears with normal hearing.

In the present study, the test-retest variability of distortion product otoacoustic emissions (DPOAEs) due to various causes has been assessed quantitatively at individual frequencies using the ILO88/92 system. The short-term variance was generally lower than 3 dB2. Changing the position and the fit of the probe may affect the level of background noise in the ear canal, which interferes with the responses of the DPOAEs mainly at low frequencies and can also influence the interaction of the resonances of the outer ear and acoustic stimuli. The long-term variance was significantly greater than short-term variance, but did not differ significantly from variance of refitting the probe. The total DPOAE variance was small across all the frequencies above 1000 Hz except for a small peak in the 2500 Hz range. This may be related to the low response amplitudes in this region. The limitation of DPOAE detection at frequencies below 1000 Hz must lead to caution in the interpretation of results in this frequency range. The magnitude of the total variance was similar to that found in audiometric studies.

Acoustic Stimulation↗