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Biomedical subjects

J S Roberts

Publications and source records attributed to J S Roberts.

At least 19 recordsLinked to original sources

Ultrasound pasteurization: the effects of temperature, soluble solids, organic acids and pH on the inactivation of Escherichia coli ATCC 25922.

The objectives of this research were to study the effects of temperature, sugar concentration (8, 12, and 16 g/100ml), organic acids (citric and malic acids) and pH (2.5 and 4.0) on ultrasound pasteurization. The model organism used for the research was Escherichia coli ATCC 25922, and ultrasound treatment times were conducted to achieve a 5 log (base 10) reduction. Ultrasound generates heat, therefore the study involved removing the heat using a jacketed beaker with refrigerant (-30 degrees C) to maintain processing temperature at or below 30 degrees C and eliminate the thermal inactivation effects. Overall, ultrasound increased the sensitivity of E. coli to thermal inactivation. The presence of soluble solids had a protective effect where the sonication time requirement increased. Similar to heat sensitivity, the lower pH environment resulted in E. coli having less resistance to sonication. The type of organic acid had the least significant effect on ultrasound inactivation of E. coli.

Acids↗

Dominant effect of polariton-polariton interactions on the coherence of the microcavity optical parametric oscillator.

The importance of interaction effects in determining the temporal coherence of spectrally and spatially isolated single modes of the microcavity optical parametric oscillator (OPO) is demonstrated. As a function of macroscopic occupancy, the coherence time (tau c) first increases linearly and then exhibits saturation behavior, reaching maximum values of up to 500 ps. Good agreement is found with a model including fluctuations in polariton number and polariton-polariton interactions between the OPO states. tau c is a property of the coupled OPO system, a result confirmed by the finding of equal coherence times for signal and idler, even though the idler is subject to strong additional scattering.

Journal Article↗

Enhanced all-optical tuning of leaky eigenmodes in photonic crystal waveguides.

We demonstrate all-optical switching in an active two-dimensional photonic crystal waveguide, observing as large as 16 nm blueshifts of a leaky eigenmode at 839 nm and switching ratios of almost 70%. These results are larger than those previously observed in similar experiments performed on passive photonic crystal waveguides; the enhancement is due to resonant photogeneration of carriers by In(0.12)Al(0.2)Ga(0.68)As quantum wells in the core of the waveguide. The effective change in the refractive index of the structure is approximately10(-2), with a rise time of approximately1 ps and a decay time of approximately10 ps, potentially allowing high-speed switching and fast modulation rates.

Journal Article↗

Posttreatment results of combining naltrexone with cognitive-behavior therapy for the treatment of alcoholism.

Naltrexone, an opiate antagonist medication, has been reported to be efficacious in the treatment of alcohol dependence when added to psychosocial treatments. Although the within-treatment efficacy of naltrexone has received primary attention, there has been little published on the outcome of individuals once the medication is discontinued. Animal studies have led to concern regarding a quick rebound to heavy drinking. This report extends the data previously reported by evaluating the outcome in alcoholic subjects during the 14 weeks after a 12-week treatment with naltrexone or placebo in conjunction with cognitive behavioral therapy. Of the 131 subjects evaluated during the treatment phase, 124 (95%) had up to 14 weeks of posttreatment drinking data available for analysis. Measures of craving and blood markers of heavy drinking were also evaluated. By the end of treatment, naltrexone demonstrated significantly greater efficacy than placebo. However, once the medication was discontinued, there was a gradual increase in relapse rates, heavy drinking days, and drinks per drinking day, and fewer days of abstinence were reported. By the end of the 14-week follow-up period, although naltrexone-treated subjects were, on average, still doing better than control subjects, the effectiveness of naltrexone was no longer statistically significant. There was no evidence that naltrexone subjects had an immediate return to heavy alcohol use as suggested in animals. These data suggest that, for a number of alcoholic subjects, continued treatment with naltrexone, or perhaps psychosocial intervention, for longer than 3 months is indicated. Future research should identify which alcohol-dependent individuals may need prolonged treatment to improve treatment success in the long term.

Adult↗

Multiple previous detoxifications are associated with less responsive treatment and heavier drinking during an index outpatient detoxification.

Investigators have found a relationship between the number of previous alcohol withdrawals (AWs) and severity of withdrawal. We evaluated patients with multiple previous AWs, as compared to those with 0-1 previous withdrawals, in an outpatient detoxification trial comparing lorazepam (LZ) to carbamazepine (CBZ). A mixed model analysis of covariance was used to analyze Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-Ar) scores as a function of detoxification history (0-1 vs. 2 or more), drug group (CBZ vs. LZ), assessment day, and hours since last drink. The mixed model analysis of covariance (ANCOVA) indicated a significant detoxification history by assessment day interaction (P< or =.03). Least square means associated with this interaction suggested that the CIWA-Ar scores for the multiple detox patients declined more slowly than those with 0-1 previous detoxifications. Patients with multiple detoxes were 150% more likely to experience a heavy drinking day during treatment (P< or =.03). The multiple detox group drank more each drinking day (P=.001) and a greater proportion of this group had early heavy drinking (P=.0002). In the present study, intensity of AW symptoms and early heavy drinking were independent of treatment medications and were more common in patients who had previously undergone multiple treatments for AW.

Adult↗

Anticipating response to predictive genetic testing for Alzheimer's disease: a survey of first-degree relatives.

Two hundred and three children and siblings of patients with Alzheimer's disease (AD) (age range: 30-92 years, 75% female) were surveyed regarding potential predictive testing options for the disorder. A mailed questionnaire posed various hypothetical scenarios and assessed the following variables: interest in testing, perceptions of its pros and cons, and psychological and demographic predictors of test intentions. In 5 of 6 scenarios, a majority of participants expressed intentions to pursue testing, with perceived pros outweighing cons. The most important reasons for seeking testing were informing later-life decisions and planning future AD care. Predictors of test intentions were male gender, information-seeking style, higher perceived AD threat, and appraisal of test pros versus cons. Situational factors such as available treatment options and certainty of test information also affected responses. Results suggest a positive view of predictive testing, with its limitations and risks underrated. Study findings may inform AD genetic counseling and health education efforts.

Adult↗

Age-group differences in treatment outcomes for male veterans with severe schizophrenia: a three-year longitudinal study.

Treatment outcomes in later-life schizophrenia are poorly understood and of serious concern for clinicians and mental health policy makers. Age-group differences were examined for 499 male veterans with severe schizophrenia enrolled in enhanced treatment programs at 12 Veterans Affairs hospitals. Participants were separated into three age groups (20-39 years, 40-59 years, 60 years and above), with the following outcomes assessed at enrolment and 1 and 3 years afterwards: psychiatric symptomatology, global functioning, impairment in Instrumental Activities of Daily Living (IADL), and hospital use. All three age groups experienced significant improvement in psychiatric symptoms over time. The oldest group fared worse than younger patients in terms of global functioning and generally required more inpatient services and assistance with IADL. Innovative programming is needed to meet the special needs of the growing population of older adults with schizophrenia.

Adult↗

Race, psychiatric diagnosis, and mental health care utilization in older patients.

To evaluate the impact of race on mental health care utilization among older patients within given clinical psychiatric diagnoses, the authors examined a retrospective sample of 23,718 elderly veterans treated in Department of Veterans Affairs inpatient facilities in 1994. Significant racial differences in mental health care utilization found over a subsequent 2-year period were related to outpatient (but not inpatient) care; for instance: 1) African American patients with psychotic disorders had significantly fewer outpatient psychiatric visits; and 2) African American patients with substance abuse disorders had significantly more psychiatric visits than Caucasian patients in their respective groups. Although inpatient utilization appeared to be similar among races, findings related to outpatient utilization may be associated with such factors as compliance, treatment efficacy, access to health care, or possible clinician bias.

Black or African American↗

Phase I safety and antigenicity of TA-GW: a recombinant HPV6 L2E7 vaccine for the treatment of genital warts.

A phase I double-blind, randomized, placebo-controlled study was carried out in healthy subjects to assess the safety and immunogenicity of TA-GW, a recombinant HPV6 L2E7 fusion protein vaccine for the treatment of genital warts. Forty-two healthy male volunteers were randomised to receive three intramuscular injections of either 0, 3, 30 or 300 microg of recombinant L2E7 adsorbed onto Alhydrogel. Two vaccination schedules were compared: weeks 0, 1 and 4 (accelerated schedule) and weeks 0, 4 and 8 (classical schedule). Subjects were monitored for adverse events throughout. Immunogenicity was assessed by measuring L2E7 specific in vitro T cell proliferative responses, production of IFNgamma and IL-5 and serum antibodies. Dose-dependent and long-lived T and B cell immune responses were elicited by TA-GW with both vaccination schedules. In conclusion, TA-GW is both safe, well-tolerated and immunogenic. The results allow the selection of the 300-microg vaccine formulation and accelerated vaccination schedule for phase II trials in patients with genital warts.

Adult↗

Phase IIa safety and immunogenicity of a therapeutic vaccine, TA-GW, in persons with genital warts.

A fusion protein vaccine consisting of human papillomavirus 6 L2E7 with Alhydrogel was developed for the treatment of genital warts. Twenty-seven subjects with genital warts received 3 immunizations over 4 weeks in an open-label study. The vaccine was well-tolerated, and all subjects made serum IgG antibodies, predominantly IgG1, against L2E7. Nineteen of 25 tested persons made antigen-specific T cell proliferative responses to L2E7, and peripheral blood mononuclear cells when cultured with L2E7 in vitro produced both interferon-gamma and interleukin (IL)-5, although IL-5 predominated after the final vaccination. Five subjects completely cleared warts within 8 weeks. Subjects whose warts were not cleared by 8 weeks were offered conventional therapy. Recurrence of warts was not seen in any of the 13 persons whose warts cleared by vaccine alone or with conventional therapy. While these preliminary results of the use of this therapeutic immunogen are encouraging, proof of efficacy will require randomized double-blind trials.

Adult↗

Telescoping of landmark events associated with drinking: a gender comparison.

OBJECTIVE: The literature suggests that women exhibit "telescoped" development of (i.e., faster progression to) alcoholism, with fewer years drinking than men. The purpose of this study was to use data gathered in the course of a large clinical trial to further examine this issue. METHOD: Subjects in this retrospective study were from a pool of 1,307 men and 419 women enrolled in Project MATCH, a multisite alcohol treatment matching study. MATCH subjects were recruited from both outpatient and aftercare settings over a 2-year period. Age-of-onset for landmark events in the development of alcoholism were determined from self-report and clinical interviews given at baseline entry into the study. Gender differences in age-of-onset variables were assessed within both outpatient and aftercare settings. Gender differences in progression times between successive landmarks were also examined. Differences were tested with both multivariate and univariate ANOVA techniques. RESULTS: Women generally began getting drunk regularly at a later average age than men (26.6 versus 22.7 years, p< or =.001), began experiencing their first drinking problems at a later average age than men (27.5 versus 25.0 years, p< or =.001) and exhibited loss of control over their drinking at a later average age than men (29.8 versus 27.2 years, p< or =.001). However, these gender differences were most pronounced for older individuals and attenuated for younger subjects. Women also progressed faster than men, on average, between first getting drunk regularly and first encountering drinking problems (0.9 versus 2.3 years, p< or =.001) and between first loss of drinking control and onset of worst drinking problems (5.5 versus 7.8 years, p< or =.001). Women also exhibited shorter average progression times between first getting drunk regularly and first seeking treatment (11.6 versus 15.8 years, p< or =.001), although this effect was negligible for younger subjects. CONCLUSIONS: Telescoping is a relatively robust phenomenon in treatment-seeking alcoholics and indicates that women are more likely to progress faster through the landmark events in the development of alcoholism than are men.

Adult↗

Factor structure and predictive validity of the Obsessive Compulsive Drinking Scale.

BACKGROUND: The Obsessive Compulsive Drinking Scale (OCDS) is a 14-item, self-report instrument developed to measure obsessive thoughts about alcohol use and compulsive behaviors toward drinking. The objective of this study was to ascertain the factor structure underlying responses to the OCDS, and to further assess whether subscale scores derived from this structure were distinctive, internally consistent, predictive of future drinking, and able to differentiate between patients receiving naltrexone versus placebo in a controlled alcoholism treatment trial. METHODS: OCDS data were collected from a total of 132 alcohol-dependent subjects at up to 15 assessment points during the study. Interitem correlations were pooled across assessment periods, and an iterated principal axis factor analysis with oblique promax rotation was performed. The factor analysis suggested that three primary factors could parsimoniously account for the common variance in item responses. Subscale scores were formed by summing responses to the most salient items on each factor. RESULTS: The three common factors were interpreted as "resistance/control impairment," "obsession," and "interference." The subscale scores corresponding to these three factors were internally consistent, and their correlation with other baseline measures of alcohol use and severity suggested that they were distinct. Scores on each subscale reliably distinguished between subjects who remained abstinent, exhibited "slip" drinking, or relapsed to heavy drinking during the 12 weeks of active treatment. Additionally, scores on the resistance/control impairment subscale distinguished between those patients receiving treatment with naltrexone or placebo. Scores from each subscale also were able to predict the hazard for heavy drinking in the following week of treatment. CONCLUSIONS: The three OCDS factors are easily estimated with the summated scoring approach, and the resulting subscales appear to be internally consistent and distinctive. Moreover, the group differentiation capability and predictive utility of the subscale scores suggest that they might be useful as either predictor or outcome variables in alcoholism treatment trials. The duration of time for which a given OCDS assessment maintains its predictive utility awaits further confirmation.

Adult↗

The effect of drinking intensity and frequency on serum carbohydrate-deficient transferrin and gamma-glutamyl transferase levels in outpatient alcoholics.

Whereas heavy alcohol consumption is known to elevate serum carbohydrate-deficient transferrin (CDT) and gamma-glutamyl transferase (GGT) levels, the contribution of drinking pattern to these effects is not completely understood. We present data on 423 men and 146 women evaluated 1 year after treatment in a large-scale alcoholism treatment study (Project MATCH). Relationships between drinking frequency (number of days drinking), intensity (drinks per drinking day), and blood levels of CDT and GGT were analyzed by using response surface regression models and thin-plate spline-smoothing techniques. Both models indicated differences between CDT- and GGT-drinking pattern relationships in men and, also, a difference between men and women in CDT drinking-pattern relationships. For men, CDT levels appeared to respond primarily to frequency of drinking, whereas GGT was influenced primarily by drinking intensity. For women, both CDT and GGT were influenced more by drinks per drinking day (intensity) than by number of days drinking (frequency). The data confirm both the independent nature of these biological markers of alcohol consumption and gender differences in alcohol-induced CDT response reported previously.

Adult↗

Efficacy and complications of percutaneous pigtail catheters for thoracostomy in pediatric patients.

OBJECTIVE: To describe the efficacy of percutaneous pigtail catheters in evacuating pleural air or fluid in pediatric patients. DESIGN: A case series of children with percutaneous pigtail catheters placed in the pediatric ICU between January 1996 and August 1997. SETTING: Urban pediatric teaching hospital in Seattle, WA. METHODS: A retrospective chart review. RESULTS: Ninety-one children required 133 chest catheters. Most patients were infants with congenital heart disease (80%). One hundred thirteen of the catheters (85%) were placed for pleural effusion, with 20 tubes (15%) placed for pneumothorax. Efficacy of drainage of pleural fluid was significantly greater in serous (96%) and chylous (100%) effusions compared with empyema (0%) or hemothorax (81%). Evacuation of pneumothorax was achieved by a pigtail catheter in 75% of patients. Resolution of pleural air or pneumothorax was significantly greater in patients < 10 kg compared with larger children. Complications due to placement of the pigtail catheters included hemothorax (n=3, 2%), pneumothorax (n=3, 2%), and hepatic perforation (n= 1, 1%). There were also complications arising from the use of the catheters, including failure to drain, dislodgment, kinking, loss of liquid ventilation fluid, empyema, and disconnection in 27 of 133 catheters (20%). Significantly more complications during catheter use occurred in patients <5 kg than in larger children. CONCLUSIONS: Percutaneous pigtail catheters are highly effective in drainage of pleural serous and chylous effusions, somewhat less efficacious in drainage of hemothorax or pneumothorax, and least efficacious in drainage of empyema. Infants and smaller children had higher rates of resolution of pleural air and fluid from placement of a pigtail catheter than larger children. Complications from catheter placement were uncommon (5%) but serious, whereas complications associated with continued use of the catheters were more common (20%) but less grave. Strict attention to anatomic landmarks and close monitoring may reduce the number of complications.

Adolescent↗

Colloid volume expanders. Problems, pitfalls and possibilities.

Colloid solutions have been developed and used over the past 70 years as expanders of the intravascular space, based on an understanding of Starling's law. Increasing osmotic pressure with colloidal products has remained an attractive theoretical premise for volume resuscitation. Indeed, colloids have been shown to increase osmotic pressure in clinical practice; however, the effects are short-lived. Lower molecular weight colloids exert a larger initial osmotic effect, but are rapidly cleared from the circulation. Larger molecules exert a smaller osmotic pressure that is sustained longer. The main drawback to colloid therapy lies in pathological states with endothelial injury and capillary leak, precisely the clinical scenario where colloids are commonly given. The colloid solution may leak into the interstitium and remain there exerting an osmotic gradient, pulling additional water into the interstitium. There are 4 general types of colloid products available for clinical use. Albumin is the predominant plasma protein and remains the standard against which other colloids are compared. Albumin, pooled from human donors, is in short supply and remains expensive. Dextrans have been used to prevent deep venous thrombosis and to lower blood viscosity during surgery. Hetastarch has been widely used as a plasma volume expander. It provides equivalent plasma volume expansion to albumin, but has been shown to alter clotting parameters in studies (prolonging the activated partial thromboplastin time and prothrombin time). Although severe coagulopathies have been reported in sporadic cases, hetastarch has not been shown to increase postoperative bleeding compared with albumin therapy, even in large doses (3 L/day). Despite some theoretical advantages compared with crystalloid therapy, colloid administration has not been shown to decrease the risk of acute lung injury or to improve survival. Specific indications for colloid products include hypoproteinaemic or malnourished states, patients who require plasma volume expansion who are unable to tolerate larger amounts of fluid, orthopaedic and reconstructive procedures requiring prevention of thrombus formation and leukapheresis.

Colloids↗

Acute lethal toxicity following passive immunization for treatment of murine cryptococcosis.

Passive immunization with monoclonal antibodies (MAbs) specific for the major capsular polysaccharide of Cryptococcus neoformans alters the course of murine cryptococcosis. During studies of passive immunization for treatment of murine cryptococcosis, we noted the occurrence of an acute, lethal toxicity. Toxicity was characterized by scratching, lethargy, respiratory distress, collapse, and death within 20 to 60 min after injection of antibody. The toxic effect was observed only in mice with a cryptococcal infection and was reduced or absent in the early and late stages of disease. The clinical course and histopathology were consistent with those for shock. There was considerable variation between mouse strains in susceptibility to toxicity. Swiss Webster mice from the Charles River colony were most susceptible, followed by C3H/He, BALB/c, and C57BL/6 mice. DBA/2 mice and Swiss Webster mice from the Simonsen colony were resistant. Acute toxicity was mimicked by injection of preformed complexes of MAb and purified polysaccharide. The toxic effect was also produced by injection of MAbs into mice that were preloaded with polysaccharide. The toxic effect was not blocked by treatment of mice with chloropheniramine or anti-tumor necrosis factor alpha antibodies or by depletion of complement components via pretreatment with cobra venom factor. Toxicity was reduced by treatment of mice with high doses of epinephrine, dexamethasone, or chlorpromazine. Finally, the toxic effect was completely blocked by treatment of mice with the platelet-activating factor antagonist WEB 2170 BS or by pretreatment of mice with the liposome-encapsulated drug dichloromethylene diphosphonate, a procedure which depletes macrophages from the spleen and liver.

Animals↗

Quantifying the clinical significance of drug-drug interactions: scaling pharmacists' perceptions of a common interaction classification scheme.

OBJECTIVE: To develop a precise, interval level scale of the clinical significance of drug-drug interactions that reflects the professional judgments of practicing pharmacists. PARTICIPANTS: A convenience sample of 63 practicing pharmacists representing hospital (clinical and staff) and retail (chain and independent) practice settings. METHOD: Pharmacists judged the similarity among 15 interaction categories that have been commonly used to classify drug-drug interactions. A multidimensional scaling technique produced a spatial representation (i.e., a psychological map) of the structure inherent in those similarity judgments. Pharmacists' ratings of clinical significance were projected onto that same spatial representation using a multiple regression procedure, and the resulting information was used to develop a scale of clinical significance. RESULTS: The clinical significance scale developed from pharmacists' judgments was substantially different from a comparison scale published in a popular reference. The new scale was more precise than the comparison scale, and it also approximated an interval level of measurement. The judgments used to produce the new clinical significance scale were not reliably influenced by pertinent demographic characteristics of the sample. CONCLUSIONS: Inconsistencies between published clinical significance scales and the professional judgments of practitioners could affect patient care to the degree that a summary measure of clinical significance affects a practitioner's response to a potential drug-drug interaction. The clinical significance scale developed in this study has good measurement characteristics and reflects the professional judgments of practicing pharmacists. Use of the new scale is recommended on these grounds, although further assessment of its generality is warranted.

Drug Interactions↗