Development and evaluation of peptide-based prolyl oligopeptidase inhibitors--introduction of N-benzyloxycarbonyl-prolyl-3-fluoropyrrolidine as a lead in inhibitor design

Different supplementation schemes to build iron stores in female Indonesian adolescents were investigated. Subjects were 273 high-school girls allocated randomly to four treatment groups. During a 3-mo period one group received 60 mg Fe, 750 micrograms retinol, 250 micrograms folic acid, and 60 mg vitamin C per day; a second group received 60 mg Fe, 6000 micrograms retinol, 500 mg folic acid, and 60 mg vitamin C once a week; a third group received 120 mg Fe and the same amount of the other three micronutrients as the second group once a week; and a fourth group received only placebos. All subjects were dewormed and supplement allocation was double blind. Blood samples were collected at baseline, after 2 and 3 mo of supplementation, and 6 mo after the last supplement. After 2 mo of supplementation, groups supplemented weekly and daily showed similar significant improvements (P < 0.001) in hemoglobin and retinol concentrations, and supplementation for 3 instead of 2 mo did not significantly increase these two indicators. After 3 mo, the increase in ferritin was approximately equal to 27 micrograms/L in the daily and 14-15 micrograms/L in the weekly groups (P < 0.001), the latter having a final concentration of 42-45 micrograms/L. At 6 mo postsupplementation there were no significant differences among daily and weekly groups, but the ferritin concentration was still approximately equal to 10-12-micrograms/L higher (P < 0.001) than in the placebo group. The group supplemented weekly with 60 mg Fe complained less about side effects than the other supplemented groups (P < 0.05). Weekly supplementation with 60 mg Fe and 6000 micrograms retinol for 3 mo was optimal for improving the iron status of the adolescents for approximately equal to 9 mo.     

Beneficial effects of treatment of early subclinical rejection: a randomized study

The prevalence of subclinical rejection, by the Banff criteria, is approximately 30% in the first 3 mo in renal transplant recipients. A randomized study was performed to determine whether the treatment of subclinical rejection with corticosteroids was associated with improved outcomes in these patients. Seventy-two patients, stratified by donor source, were randomized to biopsies at 1, 2, 3, 6, and 12 mo (Biopsy group), or to 6- and 12-mo biopsies only (Control group). Patients were analyzed by "intent to treat" and were followed for a minimum of 2 yr. Patients in the Biopsy arm of the study had a significant decrease in early (months 2 and 3) and late (months 7 to 12) acute rejection episodes, a reduced chronic tubulointerstitial score at 6 mo, and a lower serum creatinine at 24 mo than did patients in the Control arm. There was a trend toward an increase in infectious morbidity, but no increase in mortality, in the patients randomized to the Biopsy group. The results of this study suggest that early protocol biopsies and the treatment of subclinical rejection with corticosteroids may lead to better histologic and functional outcomes in renal transplant recipients.     

Cross-age stability in emotional expressions during learning and extinction.

Three groups of infants who initially learned an arm-pull contingency at 2, 4, or 6 mo of age were seen again in the same procedure 2 mo later. Correlational analysis across a 2-mo period for each group indicated that individual differences in emotional expressions were stable during learning and extinction. Specifically, anger during extinction and interest and enjoyment during learning were stable over a 2-mo interval. Repeated experience did not affect learning performance or emotion. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Managing organizational stress: A field experiment.

79 public agency employees (mean age 39 yrs) were randomly assigned to stress-management training or control conditions. The training program consisted of 16 hrs of group exposure over 8 wks. Using procedures based on those developed by D. H. Meichenbaum (1975), treatment Ss were taught to recognize and alter their cognitive interpretations to stressful events at work. Ss were also taught progressive relaxation techniques to supplement this process. Dependent variables were epinephrine and norepinephrine excretion at work, anxiety (State-Trait Anxiety Inventory), depression, irritation, and somatic complaints, all measured at 3 times (pretest, posttest, and 4 mo after treatment). Treatment Ss exhibited significantly lower epinephrine and depression levels than did controls at posttest, and 4-mo follow-up levels did not regress to pretest levels. However, treatment effects were not replicated in a subsequent intervention on the original control group. The general adoption of such stress management programs is not recommended. (26 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cross-modal and intramodal transfer as predictors of mental development in full-term and preterm infants.

25 full-term (FT) and 33 preterm (PT) infants who had participated in studies of cross-modal (CM) and intramodal (IM) transfer at 12 mo of age were seen at older ages to assess the predictive validity of these early measures for later cognition. FT Ss were administered the Bayley Scales of Infant Development at 24 mo of age; PT Ss were administered these scales at 12 and 24 mo of age, the Stanford-Binet Intelligence Scale (Form L-M) at 34 and 40 mo of age, and the Wechsler Intelligence Scale for Children—Revised and the Developmental Test of Visual-Motor Integration at 6 yrs of age. For FT Ss, both 12-mo measures were significantly related to 24-mo Bayley Mental Development Index (MDI) scores; for PT Ss, both 12-mo measures were related not only to 24-mo Bayley MDI but to each subsequent measure of cognitive outcome through 6 yrs. 12-mo IM scores were highly correlated with the 6-yr assessment of visual–motor integration. A measure of object permanence obtained at 12 mo was also related to cognitive outcome, but not so consistently as were the other 2 12-mo measures. Although parental education was a significant predictor beginning at 24 mo, multiple regression analyses indicated that the CM and the IM measures substantially increased the percentage of variance in outcome that could be accounted for by parental education alone. (61 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A comparative study of four forms of psychotherapy.

Compared 4 forms of psychoanalytically oriented psychotherapy involving 3 male experienced psychiatrists and 106 18–56 yr old psychiatric outpatients. Patients received either individual therapy or group therapy that lasted either 6 or 24 mo. A comprehensive set of outcome scores (e.g., a version of the 16PF and the Cornell Index) provided by patients, therapists, and an independent assessor was monitored each 6 mo, including a 6-mo follow-up assessment. Therapy outcome, therapy process as viewed by the therapists, and cost-effectiveness were examined. What emerged as important was the particular form of therapy received, not the general type of therapy or the general duration of therapy when considered as independent dimensions. Results favor long-term group therapy and short-term individual therapy over long-term individual therapy and short-term group therapy. Advantages and difficulties associated with each form of therapy are discussed. (18 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effectiveness of neglect rehabilitation in a randomized group study

The effectiveness of neglect rehabilitation training has been studied in two randomly selected groups of right brain-damaged patients. All patients proved heminattentive on a standard battery 2 months or more after the CVA. One group received 2 months of treatment immediately after admission to a clinic, and the other group received only general cognitive stimulation for the same amount of time. At the end of this period a comparison showed significant improvement in the first group, based on a standard test battery and a functional scale. The second group was then given rehabilitation training for neglect for the same amount of time and obtained similar improvement. It is concluded that the rehabilitation program produces significant results, which generalize to situations similar to those of everyday life. The importance of the duration of training on the generalization of learning is briefly discussed with reference to previous negative reports in the literature.     

Perceived stress, quitting smoking, and smoking relapse.

Assessed perceptions of stress prior to quitting smoking and at 1, 3, and 6 mo after quitting in 211 Ss. Analyses provide evidence for a relation between changes in stress levels and changes in smoking status. Ss who failed to quit smoking for more than 24 hrs maintained a relatively high and consistent level of stress over the 6-mo period. For continuously abstinent Ss, stress decreased as duration of abstinence increased. Increased stress with relapse was found across all time periods, and decreased stress after quitting was observed at 2 time periods. The relationship between smoking and stress may be bidirectional. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The Kaiser-Permanente Smoking Control Program: Its purpose and implications for an HMO.

Investigated the effects of posttreatment maintenance on the cessation of smoking within 4 behavioral treatment modalities. 72 Ss (mean age 50 yrs) were randomly assigned to either aversive conditioning (rapid smoking), covert conditioning, behavioral group therapy, or a combined treatment group. Treatment involved 5 consecutive treatment sessions and 14 maintenance sessions over a 12-mo period. Results show that after 6 mo of treatment, the combined condition yielded 77% complete abstinence; the covert condition, 67%; the aversive condition, 57%; and the group therapy condition, 15%. 12 mo following treatment, the combined condition yielded 77% complete abstinence, the covert condition, 56%; the aversive condition, 36%; and the group therapy, 15%. It is concluded that psychologists, because of their particular training and skills, can make important innovative contributions to the prevention of illness in health maintenance organizations. (3 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Better efficacy of a 12-month interferon alfa-2b retreatment in patients with chronic hepatitis C relapsing after a 6-month treatment: a multicenter, controlled, randomized trial. Le Groupe D'étude et De Traitement du Virus De L'hépatite C (Get.Vhc)

We studied the efficacy of three interferon alfa-2b (IFN-2b) regimens for the retreatment of patients with chronic hepatitis C (CHC) with prior complete response followed by relapse. Consecutive patients with CHC who had a complete biochemical response but relapse after a first course of 6 months of IFN with 3 million units (MU) given subcutaneously three times per week were enrolled in the study. Six to 24 months after the end of the first treatment, the patients were randomly assigned to receive IFN with either the same regimen (group 1), a regimen of 12 months with 3 MU (group 2), or a regimen of 6 months with 10 MU (group 3). Sustained biochemical response was defined as normal serum alanine transaminase (ALT) values during the follow-up and sustained virological response as a clearance of hepatitis C virus (HCV) RNA from the serum at the end of follow-up (6 months' posttreatment). Histological improvement was defined as a decrease of 1 point in Metavir score between the first liver biopsy and a biopsy performed at 6 months' postretreatment. Two hundred forty-seven patients were randomized: 75 to group 1, 91 to group 2, and 81 to group 3. In an intent-to-treat analysis, 12%, 36.3%, and 18.5% of patients had a sustained biochemical response after retreatment in groups 1, 2, and 3, respectively (P <.001); 13. 8%, 32.4%, and 17.2% of patients had a sustained virological response after retreatment in groups 1, 2, and 3, respectively (P <. 05). A low viral load and patients in group 2 were independently associated with a sustained biochemical response. A low Knodell score index before treatment, patients with a high level of ALT before retreatment, genotype 3, low viral load, and patients in group 2 were independently associated with sustained virological response. Younger age, a high level of ALT, a low level of gamma-glutamyl transferase before retreatment, low viral load, and patients in group 2 were independently associated with sustained biochemical and virological response. Among the 80 patients with repeated liver biopsies, 47.6% had improved histological activity scores; this improvement was associated with a sustained biochemical and virological response. In patients with CHC initially treated with 3 MU of IFN given subcutaneously three times per week over a 6-month period, and who subsequently developed a relapse after a biochemical response, retreatment with a regimen of 3 MU of IFN given three times per week for 12 months produced better biochemical and virological sustained response rates than regimens involving a higher dose or a shorter duration of retreatment. The biochemical and virological sustained response was associated with histological improvement.     

Characterization of major depression symptoms in multiple sclerosis patients

Retrospective review of affective disturbances in 238 patients with multiple sclerosis (MS) seen over a 6-month period revealed: 1) 51 patients (22%) received pharmacologic treatment for depressive symptoms during or within 4 years of the study period, and 17 (7%) received treatment for rapid mood swings; 2) among the 51 depressed patients, response rate to medication was extremely high; 3) relapse of depressive symptomatology after discontinuation of medication was also high (17/29); 4) first episodes of major depression frequently occurred during periods of MS progression or exacerbation, but first episodes also occurred during periods of relative clinical stability; 5) suicidal ideation was common (12 patients), but only 1 patient had a history of attempted suicide; and 6) side effects were tolerable in most patients.     

Increased height gain of children fed a high-protein diet during convalescence from shigellosis: a six-month follow-Up study

The impact of dietary supplementation on catch-up growth was evaluated in 69 malnourished children ages 24-60 mo after recovery from shigellosis. They were fed either a high-protein (HP) diet with 15% of energy as protein, or a standard-protein (SP) diet with 7.5% energy as protein, for 3 wk in a metabolic study ward. Children were followed up bi-weekly for 6 mo by trained health assistants when anthropometric measurements and information of any illness were collected. Thirty-one children in the HP group and 28 children in the SP group completed 6-mo follow-up. The increase in height (mean +/- SD) was 5.3 +/- 1.0 cm vs. 4.1 +/- 1.1 cm for HP and SP groups, respectively (P < 0.001), whereas increase in body weight was 1.39 +/- 0.58 and 1.29 +/- 0.72 kg for children fed HP and SP, respectively (P = 0.59). The proportion of children who were severely stunted (< -2 SD height-for-age) decreased from 45 to 29% in the HP group compared to 50 to 46% in the SP group (P < 0.05) at 6-mo follow-up. The number of diarrheal episodes per child tended to be lower in the HP vs. SP than in the SP group (1.9 vs. 2.3, P = 0.41). These results demonstrate that feeding an HP diet to the malnourished children during recovery from shigellosis enhanced linear growth with a modest reduction in diarrheal morbidity during the 6-mo follow-up period.     

Enhancing creativity in an informal educational framework.

Studied the effects of a creativity-enhancing program in an experimental summer camp for disadvantaged children. The experimental group of 94 6th–7th graders spent 4 hrs/day in creativity games; the control group of 48 Ss participated in a regular recreational program. Two different creativity measures—the Torrance Tests of Creative Thinking and the Origence and Intellectual scales of the Welsh Figure Preference Test—were administered to all Ss at 3 different times: before treatment, after treatment, and in a 4-mo follow-up. Both after treatment and in the follow-up, the experimental group showed significantly higher scores than the control group. Results indicate resistance to extinction over time and are discussed in terms of content–context planning. (23 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Therapist and group contact as variables in the behavioral treatment of obesity.

Randomly assigned 29 obese females (average age 48.7 yrs), to 1 of 3 experimental conditions: (a) a "standard" behavioral treatment (SBT) group emphasizing self-management techniques (Ss attended group therapy meetings weekly for 10 wks, then monthly for 6 mo and were given a weight control manual); (b) a group receiving the weight control manual via mail with little professional contact (MMC); and (c) a waiting list control condition. Results reveal a superiority of both treatment conditions over the control condition at posttreatment. SBT Ss did significantly better than MMC Ss at posttreatment but not at the 6-mo follow-up. Weight loss for MMC Ss was minimal. The use of "do-it-yourself" treatment manuals is challenged. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Alprazolam in chronic tension type headache

Alprazolam was evaluated in the treatment of 62 patients of chronic tension type headache using a double blind cross over design with random allocation to drug or placebo. The duration of the trial was 4 months with a 2 week run in period and 2 week washout period separating two treatment periods of 4 weeks each. The patients were followed up for 4 weeks at the completion of the trial. 48 patients completed the trial. There was no significant difference in the overall response rate based in terms of percentage reduction in headache frequency per week, however a significant decrease in headache index was observed during treatment with alprazolam as compared to placebo (P < 0.05). The mean analgesic intake per week was also significantly lower during treatment with alprazolam as compared to the run in period. Side effects were seen in 16.67% patients. In none of the patients was it significant enough to require withdrawal from the study.     

Clinical trials of GH treatment in patients with Turner's syndrome in Japan--a consideration of final height. The Committee for the Treatment of Turner's Syndrome

Clinical trials of human GH (hGH) therapy in Turner's syndrome were started in 1986. Between 1986 and 1990. 362 patients were enrolled; 115 were treated for more than 6 years. The age at the start of treatment ranged from 5 to 18 years (mean 10 years). Fifty-one patients received hGH at a weekly dosage of 0.5 IU/kg and 64 received 1.0 IU/kg by daily s.c. injection. Both treatment groups showed a statistically significant growth increase during the initial 4 years of treatment. The rate of increase in height was significantly greater for the initial 2 years with the high dose than with the low dose. The increases in height over 6 years of treatment (expressed by S.D. score for chronological age) were 1.48 +/- 0.8 with 0.5 IU/kg per week and 1.80 +/- 1.0 with 1.0 IU/kg per week. To date, 260 patients have stopped GH therapy. In 32% of them, the height attained was above the -2 S.D. value for normal girls. In 27%, the growth rate was not sufficient when they stopped treatment. The mean final height (growth rate < or = 1.0 cm/year) of patients treated for more than 6 years was 142.2 +/- 6.5 cm (n = 15) with 0.5 IU/kg per week, and 144.3 +/- 3.9 cm (n = 15) with 1.0 IU/kg per week. The adult height was improved by GH treatment, although final height did not differ statistically between the two dose regimens. No remarkable adverse events occurred during the treatment. These results indicate that hGH treatment improves the final height in patients with Turner's syndrome.     

Comparison of functional outcomes and treatment cost between a computer-based cognitive rehabilitation teletherapy program and a face-to-face rehabilitation program.

The authors compared outcomes of 19 participants who received computer-based cognitive teletherapy rehabilitation with 20 participants who received face-to-face speech-language rehabilitation. The study compared outcomes from 2 "real-word" treatment programs provided by an outpatient rehabilitation center. A total of 39 participants with moderate to severe closed head traumatic brain injuries and a minimum of 1 year following injury were analyzed. Outcome measures included clinical indicators of independent living status, return to work or school, and independent driving. Cost measures included the total cost of the treatment and a measure of service costs per hour. Time since injury was a covariate, and an analysis of covariance revealed no differences between groups in independent living, driving status, return to work or school, or total treatment costs. The computer-based teletherapy cognitive rehabilitation program provided similar functional outcomes as face-to-face speech-language therapy at a similar total cost. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of contingency-contracting and decision-making groups with chronic mental patients.

Placed 74 29-74 yr. old institutionalized male mental patients in 1 of 3 treatment conditions for a 4-mo period. Ss in the milieu condition received the customary hospital treatment; Ss in the interaction condition received the same treatment as the milieu condition but received 2 hr. additional weekly group therapy; Ss in the incentive condition were placed in groups responsible for making decisions concerning group members. Ss in the incentive condition were rewarded with funds and canteen books contingent upon recommendations from the groups and attendance of Ss in each group at all activities. Results show the incentive condition as superior on percentage of attendance at activities, town passes taken, and days spent out of the hospital, while the interaction condition was superior on nurses' rating scales. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Temporal generalization of treatment effects over a three-year period for a parent training program: Directive Parental Counseling (DPC).

Assessed the permanence of the treatment effects (temporal generalization) obtained by a parent-training program, Directive Parental Counseling (DPC), developed by the 2nd author (1983). 20 parents who participated in the program completed the Walker Problem Behavior Identification Checklist and the Missouri Children's Behavior Checklist at pretreatment, treatment termination, 3 mo posttreatment, and 3 yrs posttreatment. The parents were part of a larger treatment group of 36 Ss who demonstrated superiority in altering targeted behaviors of their children (mean age 6 yrs 11 mo), in contrast to a waiting-control group, at the completion of a 10-wk program. The positive changes noted on the behavior rating scales obtained from the parents in the treatment group at the posttreatment period were still evident at the 3-mo follow-up and continued to increase over the 3-yr interval. Results are discussed in light of the issues surrounding temporal generalization and the structure of the DPC program. (French abstract) (26 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)