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Biomedical subjects

J Grabowski

Publications and source records attributed to J Grabowski.

At least 19 recordsLinked to original sources

Tobacco, alcohol and caffeine use in a low-income, pregnant population.

This study examined the relationship between smoking, drinking and heavy caffeine use (> three caffeinated drinks per day) among pregnant women who reported smoking cigarettes and drinking alcohol prior to conception. Demographic predictors of smoking, drinking and caffeine use during pregnancy were also identified. Pregnant women (n = 237) attending a university-based, public clinic were identified during screening for a larger intervention study. Logistic regression analyses revealed a significant relationship between pregnancy smoking and drinking (OR= 8.1), as well as between smoking and harmful caffeine use (OR=3.1). Age predicted smoking and drinking in pregnancy, with older women being more likely to use both substances. Caucasian women were more likely to continue smoking, while African-American women were more likely to continue drinking. Increased attention should be paid to the co-occurrence of multiple health risk behaviours during pregnancy and to the specific needs of subgroups of high-risk women.

Adult↗

Fluoxetine treatment of cocaine-dependent patients with major depressive disorder.

Sixty-eight male and female individuals with both DSM-IV diagnoses of cocaine dependence and major depressive disorder were randomly assigned to one of two medication conditions (placebo vs. 40 mg per day) as part of a double-blind, placebo-controlled clinical efficacy trial of fluoxetine for the treatment of this dual diagnosis. During the 12-week outpatient treatment phase all participants also received individual cognitive-behavioral psychotherapy targeting both cocaine use and depression. Depressive symptoms remitted as a function of time in treatment, with no significant medication effects found. Fewer cocaine positive urines were found during the first 6 weeks of treatment in the placebo group compared with the 40-mg group. Cocaine use and depressive symptoms during treatment were significantly correlated. The findings fail to support the role of fluoxetine for treatment of cocaine use and depression in dually-diagnosed patients.

Adolescent↗

Synthesis and biological evaluation of nonylprodigiosin and macrocyclic prodigiosin analogues.

Nonylprodigiosin (4) and various of its analogues have been prepared by Suzuki cross-coupling reactions of a well accessible pyrrolyl triflate with (hetero)aryl boronic acid derivatives bearing alkenyl side chains. The resulting alkenes or dienes were subjected to metathesis dimerization or ring-closing metathesis (RCM) reactions, respectively, by using a ruthenium indenylidene complex as the catalyst. The biological activity of the products thus obtained was tested in two different assays monitoring i) the proliferation of murine spleen cells induced by lipopolysaccharides (LPS) and concanavalin A (Con A), and ii) the vacuolar acidification of baby hamster kidney (BHK) cells. Compounds 4 and 21 suppressed Con A-induced T-cell proliferation much more potently than LPS-induced B-cell proliferation. Furthermore, compounds 4 and 26 markedly inhibited vacuolar acidification, although other compounds exhibited no or only marginal effects. Thus, the immunosuppressive activity of prodigiosins toward T-cell proliferation seems to be mediated through cellular targets distinct from vacuolar acidification, and the prodigiosin analogues might be powerful tools to dissect these biological responses. The X-ray crystal structure of the macrocyclic product 25 has been determined, showing that the replacement of one pyrrole ring of the parent compound 4 by a phenyl group does not alter the overall electronic features of the remaining heterocyclic ring system of these alkaloids.

Animals↗

Reinforcement by orally delivered methadone, cocaine, and methadone-cocaine combinations in rhesus monkeys: are the combinations better reinforcers?

RATIONALE: Polydrug abuse is a problem that has been infrequently examined. In the present study, drug self-administration procedures were used to investigate the reinforcing effects of drug combinations. OBJECTIVES: To determine the absolute and relative response rates maintained by orally delivered methadone, cocaine, and their combinations under sequential and concurrent access. Choice between drug combinations containing different concentrations of cocaine was also determined. METHODS: Oral intake of methadone, cocaine, and their combinations was studied with rhesus monkeys during daily 3-h sessions. Lip contact (the operant response) was reinforced by delivery of liquid contingent upon completion of a fixed-ratio schedule. In one series, the drugs and drug combinations were studied sequentially with the water vehicle concurrently available. In the next series, the drugs and drug combinations were concurrently available. In the third series, pairs of drug combinations containing different concentrations of cocaine were also concurrently available. RESULTS: Methadone, cocaine and their combinations functioned as reinforcers. Under sequential access, response rates for the drug combinations and the component drugs were often similar. However, under concurrent access, response rates for the drug combinations were greater than response rates for the component drugs at the highest FR size for each condition. Also, drug combinations containing higher cocaine concentrations were preferred to combinations containing lower cocaine concentrations. CONCLUSIONS: Combinations of methadone and cocaine have relatively greater reinforcing effects than the component drugs, and these greater reinforcing effects are better detected with concurrent measures than with sequential measures.

Administration, Oral↗

The impact of impulsivity on cocaine use and retention in treatment.

To determine whether impulsivity was related to severity of drug use and treatment outcome, 50 cocaine dependent subjects underwent baseline measures of severity of current cocaine use and the Barratt Impulsiveness Scale (BIS-11). The hypothesis of the study was that there would be a significant correlation between impulsivity and cocaine use severity. As predicted, there was a significant correlation between BIS-11 total scores and self-reported average daily cocaine use as well as cocaine withdrawal symptoms. A subset of 35 patients underwent a 12-week double-blind placebo controlled trial of buspirone and group therapy. Subjects with high baseline impulsivity remained in the study a significantly shorter period than did subjects with lower baseline impulsivity. This study shows that impulsivity is a significant predictor of cocaine use and treatment retention, and suggests the need for targeting impulsivity in cocaine dependence treatment.

Adult↗

Motivational interviewing with cocaine-dependent patients: a pilot study.

A brief motivational interviewing (MI) intervention was evaluated within the context of an outpatient, cocaine-detoxification program. MI was hypothesized to assist patients in completing the detoxification program and to improve outcomes during subsequent treatment. Participants (N = 105) were randomly assigned to MI or to detox-only conditions. Results indicated that although participants completed the detoxification program at equal rates, completers who received MI increased use of behavioral coping strategies and had fewer cocaine-positive urine samples on beginning the primary treatment. MI patients with lower initial motivation were more likely to complete detoxification.

Adult↗

Human methadone self-administration: effects of diazepam pretreatment.

The effect of diazepam on methadone self-administration was examined. Five methadone-maintained patients with a history of benzodiazepine abuse were recruited. Patients were stabilized on 80 mg of methadone per day. After stabilization patients participated in methadone self-administration sessions. During each session, 128 presses (fixed ratio 128) of 1 button delivered 10 ml of 0.054 mg/ml methadone solution. The same number of button presses on a 2nd button delivered 10 ml of vehicle. Forty-five min prior to the self-administration session, 0 (placebo), 5, 10, or 20 mg per 70 kg body weight diazepam was administered. Ratings of drug liking, goodness, strength, and high were collected 5, 30, 60, 90, and 150 min after the end of the self-administration session. Diazepam pretreatment significantly decreased the amount of methadone consumed. The 10- and 20-mg diazepam doses significantly increased reports of good, like, strong, and high.

Adult↗

Systemic fat and thrombus embolization in patients undergoing total knee arthroplasty with regional heparinization.

A double-blind, randomized, controlled study was undertaken to determine if a technique of intraoperative anticoagulation would decrease the incidence or severity of venous embolization after tourniquet release during total knee arthroplasty. Sixty-six patients were randomized to receive either the heparin or placebo treatment. Transesophageal echocardiography was performed before and after tourniquet release to detect embolic material in the right atrium. Transient opacification of the right atrium was observed in all patients within the first 30 seconds after tourniquet release. Regional limb heparinization is not effective in reducing the intensity of right atrium opacification because much of the echogenic material was composed of fat rather than thrombus.

Aged↗

Dextroamphetamine for cocaine-dependence treatment: a double-blind randomized clinical trial.

A properly implemented agonist treatment regimen should improve retention and reduce illicit drug use. Cocaine-dependent subjects (N = 128) were enrolled in a 12-week randomized, double-blind, placebo-controlled trial. In the multistage dosing design, subjects initially received placebo (PBO) or 15 to 30 mg of dextroamphetamine sulfate, sustained-release capsules. At week 5, the dose doubled to 30 mg or 60 mg for active groups. Subjects attended the clinic twice a week, provided urine samples, obtained medication, and had one behavioral therapy session a week. Retention was best for the 15- to 30-mg group, whereas the proportion of benzoylecgonine-positive urine screens was, from lowest to highest, 30 to 60 mg, 15 to 30 mg, and PBO at study end. Dosing must be refined. The results provide support for additional examination of the agonist model in psychostimulant-dependence treatment.

Adult↗

3-Foot standing AP versus 45 degrees PA radiograph for osteoarthritis of the knee.

OBJECTIVE: Flexion and erect standing radiographs were evaluated in the current study to compare their sensitivity in detecting articular cartilage wear. DESIGN: Prospective cohort study. SETTING: A tertiary care hospital outpatient orthopedic clinic. PATIENTS: All patients with osteoarthritis of the knee ages 40 to 75 scheduled for arthroscopic debridement between March 1995 and November 1997 were considered for the current study. INTERVENTION: Radiographs were obtained 1 week preoperatively in both the 3-foot standing anteroposterior (AP) and a 45 degrees posteroanterior (PA) flexion weight-bearing projection. Joint space height was measured with a ruler in millimeters at the narrowest point of each compartment. All radiographs were assessed by two independent observers who were blinded to the arthroscopic findings and clinical symptoms of the subjects. MAIN OUTCOME MEASURES: Prediction accuracy of each radiograph for severe Grade IV articular cartilage wear in tibio-femoral compartments. RESULTS: One hundred fifty-two patients with a mean (+/- SD) age of 60.5+/-8.5 years were enrolled in the study. Fifty-one percent were female. Twelve patients were categorized as having severe lateral compartment articular chondropathy (Grade IV) at the time of arthroscopy. The lateral joint space height averaged 1.0+/-1.7 mm SD on the 45 degrees PA radiograph compared with 2.7+/-1.1 mm SD on the 3-foot standing AP view. Using a cutoff of 2 mm or less, the 45 degrees PA view was much more sensitive (83% versus 42%) at correctly detecting the most severe chondropathy. Forty-one patients were classified with severe Grade IV medial compartment chondropathy at arthroscopy. There was little difference in the average joint space height measured by the 45 degrees PA view (1.4+/-1.4 mm SD) or the 3-foot standing AP view (1.9+/-1.6 mm SD). A number of cutoff measures were evaluated, but no significant advantage could be found for either view in evaluating the medial compartment severity. CONCLUSIONS: The bilateral 45 degrees PA is superior for detecting lateral compartment wear but offers no advantage on the medial side. This view should be considered as the screening radiograph of choice in evaluating osteoarthritis of the knee.

Adult↗

Physicians' accuracy and interrator reliability for the diagnosis of unstable meniscal tears in patients having osteoarthritis of the knee.

OBJECTIVE: To determine clinicians' accuracy and reliability for the clinical diagnosis of unstable meniscus tears in patients with symptomatic osteoarthritis of the knee. DESIGN: A prospective cohort study. SETTING: A single tertiary care centre. PATIENTS: One hundred and fifty-two patients with symptomatic osteoarthritis of the knee refractory to conservative medical treatment were selected for prospective evaluation of arthroscopic debridement. INTERVENTION: Arthroscopic debridement of the knee, including meniscal tear and chondral flap resection, without abrasion arthroplasty. OUTCOME MEASURES: A standardized assessment protocol was administered to each patient by 2 independent observers. Arthroscopic determination of unstable meniscal tears was recorded by 1 observer who reviewed a video recording and was blinded to preoperative data. Those variables that had the highest interobserver agreement and the strongest association with meniscal tear by univariate methods were entered into logistic regression to model the best prediction of resectable tears. RESULTS: There were 92 meniscal tears (77 medial, 15 lateral). Interobserver agreement between clinical fellows and treating surgeons was poor to fair (kappa < 0.4) for all clinical variables except radiographic measures, which were good. Fellows and surgeons predicted unstable meniscal tear preoperatively with equivalent accuracy of 60%. Logistic regression modelling revealed that a history of swelling and a ballottable effusion were negative predictors. A positive McMurray test was the only positive predictor of unstable meniscal tear. "Mechanical" symptoms were not reliable predictors in this prospective study. The model was 69% accurate for all patients and 76% for those with advanced medial compartment osteoarthritis defined by a joint space height of 2 mm or less. CONCLUSIONS: This study underscored the difficulty in using clinical variables to predict unstable medial meniscal tears in patients with pre-existing osteoarthritis of the knee. The lack of interobserver agreement must be overcome to ensure that the findings can be generalized to other physician observers.

Adult↗

Ring-closing alkyne metathesis. Application to the total synthesis of sophorolipid lactone.

The first total synthesis of a major component of the microbial biosurfactant sophorolipid has been achieved. This approach to the 26-membered macrolide 1 containing a Z-configured alkene group in its lipidic tether spanning the sophorose backbone is based on a ring-closing metathesis reaction of diyne 21 catalyzed by Mo[N(t-Bu)(Ar)](3) (5; Ar = 3,5-dimethylphenyl) activated in situ by CH(2)Cl(2), followed by Lindlar reduction of the resulting cycloalkyne 22. The two beta-glycosidic linkages of compound 21 were installed by means of the glucal epoxide method and a modified Koenigs-Knorr reaction promoted by AgOTf/lutidine, respectively.

Journal Article↗

Cocaine dependence with and without comorbid depression: a comparison of patient characteristics.

This study compared depressed cocaine dependent patients (CD, N=50) with patients who were cocaine dependent only (CO, N=101) on pre-treatment psychiatric symptomatology, substance use, and psychosocial functioning. Results indicated that the CD group had more overall distress and poorer psychiatric functioning than the CO group. CD individuals scored higher on all subscales of the SCL-90-R, had a higher prevalence of antisocial personality disorder, reported higher craving for cocaine, lower self-efficacy to refrain from drug use, and lower perceived social support. These findings support the need for more intensive treatment approaches for dually-diagnosed patients.

Adult↗

Comparison of patient self-reports and urinalysis results obtained under naturalistic methadone treatment conditions.

This study examined under naturalistic assessment conditions the validity of self-reported opiate and cocaine use among 175 veterans enrolled in methadone treatment, and factors related to self-report validity, such as stage in treatment and drug of abuse. Veterans were interviewed by clinical staff about past 30-day drug use with the addiction severity index (ASI), and urinalysis results were obtained for the same 30-day interval assessed with the ASI. Analysis revealed that urinalysis generally produced higher rates of substance use than patient self-report, and with the exception of reported opiate use among new patients presenting for treatment, validity of patient self-reported drug use generally was poor with patients under-reporting both opiate and cocaine use. The findings are in marked contrast to those obtained in other studies in which participants are ensured confidentiality regarding their self-reports. Further, the results raise questions about the utility of self-report measures of substance use to assess patient progress or methadone program performance.

Adult↗

Self-reported disability following distal radius fractures: the influence of hand dominance.

The purpose of this study was to record the spectrum of self-reported disability following distal radius fractures and to gauge for differences in hand dominance in the use of subjective outcome data. Items were generated through patient interviews, literature review, and peer consultation. Fifty-three items were evaluated by a group of 55 patients recovering from a fracture of the distal radius, which established the prevalence, mean severity score, and overall severity score (or impact) of each item as it related to physical function and social/emotional impact. Hand dominance, age, and gender were also recorded. The results confirm that many patients who sustain distal radius fractures experience substantial impairment across a spectrum of quality of life domains. Because patients who sustain a dominant wrist injury are likely to report greater functional impairment across a wider range of activities, they also possess a greater potential for improvement. The practical implication is that outcome studies for the treatment of distal radius fractures should take hand dominance into account.

Activities of Daily Living↗

Percent body fat and bone mass in healthy Canadian females 10 to 19 years of age.

The primary aim of the investigation was to assess the relationship between whole-body fat expressed as a percentage of body weight with whole-body bone mineral content relative to age and anthropometry. Sixty females between 10 and 19 years of age were recruited to this cross-sectional study, which included measurements of weight and height and whole-body fat and bone mineral content using dual-energy X-ray absorptiometry. To assess bone mineral content, data were expressed as a weight or standard deviation scores using age and bone area. Relationships between outcome variables were determined using multiple correlation analysis followed by multiple linear regression with age, weight, height, and fat as predictor variables for outcomes of bone mineral content and density. Correlation analysis indicated that whole-body fat expressed as a percent was significantly related to weight (p < 0.01), but was not related to age or bone mineral content or density unless bone mineral content was corrected to age or bone area using standard deviation scores. In addition, body fat was associated with bone area for age and height (p < 0.01). However, multiple linear regression yielded opposite results. When included in regression, body fat had a negative impact on bone mineral content (p = 0.003), mineral content corrected to bone area (p = 0.02), and bone density (p = 0.003), while age, weight, and height had positive impacts on these outcome measurements. The data suggest that for younger children, the relative influence of percent body fat will be greater and could be linked with suboptimal attainment of peak bone mass. The females in this study appeared to be within reference limits for percent body fat. However, greater amounts of body fat relative to weight could be a marker for lifestyles that do not support attainment of optimal peak bone mass.

Absorptiometry, Photon↗

Laboratory measures of methylphenidate effects in cocaine-dependent patients receiving treatment.

Two experiments examined the effects of methylphenidate in male and female patients enrolled in an outpatient treatment program for primary cocaine dependence. The first study was a component of a double-blind efficacy trial wherein 57 patients were first tested in a human laboratory for their initial responsiveness to medication. Patients were randomly assigned to receive either placebo or methylphenidate treatment and received their first dose in the human laboratory environment before continuing in outpatient treatment. Methylphenidate was given as a 20-mg sustained-release dose (twice daily) plus an additional 5-mg immediate-release dose combined with the morning dose. Methylphenidate increased heart rate and subjective ratings; however, the subjective effects were primarily of a "dysphoric" nature, and significant effects were limited to increases in anxiety, depression, and anger on the Profile of Mood States; shaky/jittery ratings on a visual analog scale; and dysphoria on the lysergic acid diethylamide (LSD) scale of the Addiction Research Center Inventory. Methylphenidate did not increase cocaine craving nor ratings suggesting abuse potential (i.e., Morphine-Benzedrine Group or drug-liking scores, etc.). None of the drug effects observed in the human laboratory was of clinical concern, and no subject was precluded from continuing in the outpatient study. After outpatient treatment completion, 12 patients were brought back into a second double-blind human laboratory study in which three doses (15, 30, and 60 mg) of immediate-release methylphenidate were administered in an ascending series preceded and followed by placebo. Methylphenidate produced dose-related increases in heart rate, subjective ratings of shaky/jittery, and LSD/dysphoria without significantly altering cocaine craving or stimulant euphoria ratings. These results suggest that stimulant substitution-type approaches to the treatment of cocaine dependence are not necessarily contraindicated because of cardiovascular toxicity or medication abuse potential. However, they also suggest that the subjective effects of methylphenidate may not be positive enough for an adequate replacement approach.

Adult↗

Risperidone for the treatment of cocaine dependence: randomized, double-blind trial.

A partial blockade of the multiple actions of cocaine is one strategy by which cocaine dependence may be treated. Risperidone, a 5-hydroxytryptamine and dopamine D2 antagonist, is an atypical antipsychotic and was a candidate medication for the treatment of cocaine dependence. One hundred ninety-three cocaine-dependent subjects were enrolled in a 12-week, randomized, double-blind, placebo-controlled trial. Subjects initially received either placebo or 4 or 8 mg of risperidone, with a subsequent change to active doses of 2 mg and 4 mg. Subjects attended the clinic twice each week, provided urine samples, obtained medication, and underwent one behavioral therapy session per week. The study was terminated at the interim analysis. Retention was worse for the 4- and 8-mg active medication groups. Side effects were primarily associated with the 8-mg dose, although neither 2 mg nor 4 mg was well accepted by subjects. There was no reduction in cocaine use associated with risperidone. The results suggest that although antagonists might be a useful treatment approach, such as in the treatment of opiate dependence, risperidone is unlikely to find broad acceptance with the treatment-seeking population.

Adult↗