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PubMed2003

Selegiline in the treatment of attention deficit hyperactivity disorder in children: a double blind and randomized trial.

Attention deficit hyperactivity disorder (ADHD) is a common disorder of childhood that affects 3% to 6% of school-age children. Conventional stimulant medications are recognized by both specialists and parents as useful symptomatic treatment. Nevertheless, approximately 30% of ADHD children treated with them do not respond adequately or cannot tolerate the associated adverse effects. Such difficulties highlight the need for alternative safe and effective medications in the treatment of this disorder. Selegiline is a type B monoamine oxidase inhibitor (MAOI) that is metabolized to amphetamine and methamphetamine stimulant compounds that may be useful in the treatment of ADHD. The authors undertook this study to further evaluate, under double-blind and controlled conditions, the efficacy of selegiline for ADHD in children. A total of 28 children with ADHD as defined by DSM IV were randomized to selegiline or methylphenidate dosed on an age and weight-adjusted basis at selegiline 5 mg/day (under 5 years) and 10 mg/day (over 5 years) (Group 1) and methylphenidate 1 mg/kg/day (Group 2) for a 4-week double-blind clinical trial. The principal measure of the outcome was the Teacher and Parent ADHD Rating Scale. Patients were assessed by a child psychiatrist at baseline, 14 and 28 days after the medication started. No significant differences were observed between the two protocols on the Parent and Teacher Rating Scale scores. Although the number of dropouts in the methylphenidate group was higher than in the selegiline group, there was no significant difference between the two protocols in terms of the dropouts. Decreased appetite, difficulty falling asleep and headaches were observed more in the methylphenidate group. The results of this study must be considered preliminary, but they do suggest that selegiline may be beneficial in the treatment of ADHD. In addition, a tolerable side effect profile may be considered as one of the advantages of selegiline in the treatment of ADHD.

Analysis of Variance↗
PubMed2001

A comparison of the characteristics of profiles produced with the AMPFlSTR SGM Plus multiplex system for both standard and low copy number (LCN) STR DNA analysis.

DNA STR profiles have been generated from 1 ng and low copy number (LCN) templates using 28 and 34 cycles of amplification, respectively. Characteristics which facilitate the interpretation of profiles, such as heterozygous balance, allelic dropout and stutter proportions have been quantified. We demonstrate that a reduction in DNA template coupled with an increase in amplification cycle number produces an increased rate of allelic dropout out which can be correlated to the peak areas of those alleles observed. In addition, the LCN conditions increase the degree of peak area asymmetry observed from heterozygotes and the size range of stutters. Analysis of the data allows us to develop sets of guidelines appropriate for interpreting both single and mixed DNA profiles.

Alleles↗
PubMed2001

STR primer concordance study.

Over 1500 population database samples comprising African Americans, Caucasians, Hispanics, Native Americans, Chamorros and Filipinos were typed using the PowerPlex 16 and the Profiler Plus/COfiler kits. Except for the D8S1179 locus in Chamorros and Filipinos from Guam, there were eight examples in which a typing difference due to allele dropout was observed. At the D8S1179 locus in the population samples from Guam, there were 13 examples of allele dropout observed when using the Profiler Plus kit. The data support that the primers used in the PowerPlex 16, Profiler Plus, and COfiler kits are reliable for typing reference samples that are for use in CODIS. In addition, allele frequency databases have been established for the STR loci Penta D and Penta E. Both loci are highly polymorphic.

Alleles↗
PubMed2000

Predicting retention in a residential drug treatment alternative to prison program.

One hundred and fifty felony drug offenders diverted from prison to community-based, residential drug treatment alternative to prison program completed a comprehensive interview as part of a longitudinal study. Treatment completion predictors were sought examining intake data (demographics, family, social, employment, medical, psychological, criminal, sexual behavior, drug use and treatment histories). Logistic regression results found completers had more social conformity and close friends, and less need for employment counseling, felony drug convictions, drug dealing income, and unprotected sex than dropouts. Completers were also less likely to encounter recent problems with significant other, have a psychiatric history, experience gunshot or stabbing, and commenced heroin use at older ages than dropouts. However, completers reported higher alcohol use than counterparts. Further analyses explored subcategory models: "life choice" (substance use, criminal and sexual behavior), static (background and dispositional), and dynamic situational influences (employment, psychological state, recent and past encounters). Treatment implications considering findings are discussed.

Adult↗
PubMed2001

Lofexidine versus clonidine in rapid opiate detoxification.

The aim of the present study is to evaluate lofexidine and clonidine, in an accelerated opiate detoxification procedure (3 days), without anaesthesia. Forty heroin-dependent individuals were detoxified, evaluating withdrawal symptoms, craving levels, mood changes, urine toxicologic screens, and dropout during therapy with either (1) clonidine, oxazepam, baclofen, and ketoprofene, with naloxone and naltrexone for 3 days (20 subjects) or (2) lofexidine, oxazepam, baclofen, and ketoprofene with naloxone and naltrexone for 3 days (20 subjects). Both clonidine and lofexidine rapid detoxifications were found effective. The subjects treated with lofexidine showed significantly lower levels of withdrawal symptoms, fewer mood problems, less sedation and hypotension. No significant differences in craving levels, morphine metabolites in urine, or dropout rate were evidenced between the two groups. The early use of naltrexone during detoxification in combination with either alpha-2-agonist facilitated the acceptance for long-term naltrexone treatment. Lofexidine appeared to be more useful than clonidine in a 3-day accelerated opiate detoxification, not only to counteract withdrawal symptoms, but also in the treatment of dysphoria and mood changes. Because lofexidine does not produce hypotension, safe outpatient treatment, without hospital support, could be possible.

Adult↗
PubMed2001

Exposure therapy in the treatment of PTSD among cocaine-dependent individuals: preliminary findings.

Individuals (n = 39) participated in an outpatient, 16-session individual, manual-guided psychotherapy designed to treat concurrent PTSD and cocaine dependence. Therapy consisted of a combination of imaginal and in-vivo exposure therapy techniques to treat PTSD symptoms and cognitive-behavioral techniques to treat cocaine dependence. Although the dropout rate was high, treatment completers (i.e., patients who attended at least 10 sessions; n = 15) demonstrated significant reductions in all PTSD symptom clusters and cocaine use from baseline to end of treatment. Significant reductions in depressive symptomatology, as measured by the Beck Depression Inventory, and psychiatric and cocaine use severity, as measured by the Addiction Severity Index, were also observed. These improvements in PTSD symptoms and cocaine use were maintained over a 6-month follow-up period among completers. The average pre- to posttreatment effect size was 1.80 for PTSD symptoms and 1.26 for drug and alcohol use severity. Baseline comparisons between treatment completers and noncompleters revealed significantly higher avoidance symptoms, as measured by the Impact of Events Scale, and fewer years of education among treatment noncompleters as compared to completers. This study provides preliminary evidence to suggest that exposure therapy can be used safely and may be effective in the treatment of PTSD in some individuals with cocaine dependence. However, the study is limited by the uncontrolled nature of the study design, small number of subjects, and high dropout rate.

Adult↗
PubMed2001

A comprehensive substance abuse treatment program for women and their children: an initial evaluation.

This article examines a comprehensive, residential substance abuse treatment program for women and their children. A majority of the 72 participants studied were African American single mothers, for whom crack/cocaine was the drug of choice. The women and their children were assessed repeatedly during treatment, and at 3, 6, and 12 months postdischarge. Program impact was estimated by comparing the outcomes of three groups that differed in the amount of treatment they received: early dropouts, late dropouts, and treatment graduates. Program graduates showed more positive outcomes than the nongraduate comparison groups in the areas of drug use and negative consequences of use, employment and self-sufficiency, and family interaction skills. Young children enrolled in treatment with their mothers were assessed using a developmental screening test, and older children with a measure of drug refusal skills. Results from both child measures suggest substantial improvement.

Adolescent↗
PubMed2002

Change in retinal nerve fiber layer thickness after laser in situ keratomileusis.

PURPOSE: To determine the effect of laser in situ keratomileusis (LASIK) on retinal nerve fiber layer (RNFL) dropout. SETTING: Nevyas Eye Associates, Philadelphia, Pennsylvania, USA. METHODS: This prospective consecutive study comprised 120 eyes. The GDx((R)) nerve fiber analyzer (Laser Diagnostic Technologies, Inc.) was used to measure RNFL thickness, an early indicator of glaucomatous damage, preoperatively and 1 week to 4 months and 6 months postoperatively to determine whether any change in apparent RNFL thickness was due to corneal change or to actual RNFL damage and to determine whether apoptotic cascade caused ongoing RNFL dropout. Humphrey visual fields were done in eyes with an abnormal GDx (increase of 20 in GDx number). RESULTS: The GDx was normal in 89 eyes, including 6 eyes with tilted discs, an abnormal number, and a normal image and 15 eyes with a nonprogressive increase in the GDx number. Three eyes, normal at the interim, were abnormal at 6 months but had a normal visual field. Eleven eyes had a significant increase in the number at 6 months, including 1 eye that showed a possible glaucomatous visual field defect at 9 months and a normal visual field at 14 months. CONCLUSIONS: There was no evidence of RNFL thinning or glaucomatous damage. A new baseline GDx should be established post LASIK to correct for corneal change.

Adult↗
PubMed2001

Depletion of glial cell line-derived neurotrophic factor in substantia nigra neurons of Parkinson's disease brain.

The distribution of nerve growth factor (NGF), ciliary neurotrophic factor (CNTF), glial cell line-derived neurotrophic factor (GDNF), brain derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and neurotrophin-4 (NT-4) in substantia nigra pars compacta (SNc) of Parkinson's disease (PD) brains was investigated by immunofluorescence. Cases studied included four 69-77 year old neurologically normal male controls and four 72-79 year old male PD patients. Integrated optical densities (IODs) of immunofluorescence over individual neuromelanin-containing neurons and in areas of neuropil and the number of neurons on H & E stained adjacent sections were quantitated with the use of the BioQuant Image Analyzer. Data were statistically analyzed by ANOVA, including the unpaired two-tailed Student t-test and the Mann-Whitney test. The results showed 55.8% (P<0.0001) dropout of SNc neurons in PD brains compared to age-matched controls. Despite considerable neuronal dropout, immunofluorescent NTFs in the PD brains showed differential reductions that were consistent within the group as compared to age-matched controls: reductions were GDNF, 19.4%/neuron (P<0.0001), 20.2%/neuropil (P<0.0001); CNTF, 11.1%/neuron (P<0.0001), 9.4%/neuropil (P<0.0001); BDNF, 8.6%/neuron (P<0.0001), 2.5%/neuropil. NGF, NT-3 and NT-4 showed no significant differences within surviving neurons or neuropil. Since the depletion of GDNF both within surviving neurons and neuropil was twice as great as that of CNTF and BDNF and since the other NTFs showed no changes, GDNF, of the tested NTFs, is probably the most susceptible and the earliest to decrease in the surviving neurons of SNc. These observations suggest a role for decreased availability of GDNF in the process of SNc neurodegeneration in PD.

Aged↗
PubMed1998

Schizophrenia: do we really need placebo-controlled studies?

OBJECTIVE: To investigate whether placebo control is necessary to prove efficacy in short-term studies in schizophrenia. DESIGN: This study compares the efficacy results of placebo-controlled studies versus positive controlled studies, that is controlled studies without a placebo control, in the short-term treatment of chronic schizophrenia. RESULTS: Concerning mean improvement on the BPRS, the placebo arms showed in two cases a worsening, in one case almost no change, and in the remaining studies (6) the improvement was between 1 and 5%. The percentage mean improvement in the haloperidol arms of the placebo-controlled studies was comparable to the percentage mean improvement in the corresponding arms of the non-placebo-controlled studies. The highest percentage responders in the placebo-groups was 43% and the lowest was 6%. Moreover the responder rates in the atypical antipsychotic and haloperidol arms of the non-placebo-controlled studies were, in two of the three studies, in the same order of magnitude as the responder rates of the placebo arms in the placebo-controlled studies. The overall dropout rates in the placebo arms was between 48% and 80% and were higher than the drop out rates in the atypical neuroleptic arms and haloperidol arms of the placebo-controlled studies. The dropout rates due to an insufficient response in the atypical neuroleptic arms and haloperidol arms of the non-placebo-controlled studies were lower when compared to corresponding treatment arms of the placebo-controlled studies. CONCLUSION: In contrast to the mean improvement on the BPRS, responder rates in the placebo arms varied considerably from study to study. Responder rates in the atypical antipsychotic and haloperidol arms of the non-placebo-controlled studies were, in two of the three studies, of the same order of magnitude as the responder rates of the placebo arms in the placebo-controlled studies. These results indicate that placebo control is necessary. Moreover as responders are a more clinically relevant outcome measure when compared to mean improvement on a rating scale, placebo-controlled studies are still needed. However, consensus on responder definition should be agreed upon. For the moment, alternatives to placebo-controlled studies are inadequate in demonstrating efficacy in studies with schizophrenic patients.

Antipsychotic Agents↗
PubMed2000

A randomized comparative study of two methods for controlling Tendo Achilles contracture in Duchenne muscular dystrophy.

A 30-month prospective randomized study of 27 Scandinavian boys with confirmed diagnosis of Duchenne muscular dystrophy was done to compare the effect of passive stretching combined with the use of night splints (group A) or passive stretching (group B) on the evolution of Tendo Achilles contractures. Assessments were based on the methodology of Scott et al. (Muscle Nerve 1982;5:291-301)Analysis of the pattern and mechanism of dropout was done to eliminate bias between the two groups. Logistic regression showed that Tendo Achilles contracture was the most important variable (P=0.0020) for dropout. Methods of statistical analysis for longitudinal data avoiding induced serial correlations were used in the analysis. The expected annual change in Tendo Achilles contracture was found to be 23% less in group A than in group B after equalization for total muscle strength (%MRC).

Achilles Tendon↗
PubMed2002

Motor unit number estimates in idiopathic Parkinson's disease.

We previously reported changes in motor unit morphology in patients with Parkinson's disease (PD) using subjective and computerized quantitative electromyography. Now, we present data on motor unit number estimates (MUNE) to address the hypothesis of motor neuron dropout in PD. Twenty patients with PD and 20 age-matched control subjects were screened by clinical criteria and nerve conduction studies to exclude those with neuropathy. Motor unit number estimates in the extensor digitorum brevis and hypothenar group were assessed by three different MUNE techniques. The MUNE technique types included (1) the statistical method developed by Daube, (2) a threshold method, and (3) an F-wave method. The overall multivariate comparison for the six MUNE measurements was significantly lower for the patients than the controls (P=0.02). The only significant difference in the individual measures was found in the threshold MUNE method of the hypothenar group (P<0.05). These results are consistent with those of our previous work, and both support the hypothesis that mild motor neuron dropout occurs in idiopathic PD. However, MUNE methods characteristically have large standard deviations which make it difficult to detect small changes. Progress in decreasing the variance of MUNEs will facilitate their use in detecting small motor unit number changes in neurodegenerative disease.

Aged↗
PubMed2002

Older adults and functional decline: a cross-cultural comparison.

BACKGROUND: The study was conducted to examine the relationships between functional decline, health risk factors, lifestyle practices, and demographic variables in two culturally diverse, community-based samples of White and Japanese American older adults. DESIGN: The study was an analysis of data from two ongoing studies of aging and dementia in King County, Washington. Functional status at baseline was evaluated, and factors associated with functional decline over a 4-year follow-up period were identified. The sample included 1,083 Japanese American and 1,011 White cognitively intact, community-dwelling adults aged 65 and older, who had no functional limitations at baseline and participated in at least one follow-up examination. RESULTS: In 4 years of follow-up, 70% of the subjects reported no increase in functional limitation, and fewer than 5% of subjects declined in five or more activities. Risk factors associated with functional decline included increased age, female gender, medical comorbidity (particularly cerebrovascular disease, arthritis, and hypertension), elevated body mass index, poorer self-perceived health, and smoking. Depression and diabetes were also significant for persons with the greatest functional decline over the 4-year follow-up. Japanese speakers were significantly less likely to decline over the follow-up period than White or English-speaking Japanese American subjects. However, Japanese speakers were more likely to discontinue participation during the follow-up period, and may also have been more likely to underreport symptoms of functional decline. CONCLUSIONS: The present study provides further support that healthy lifestyle practices and prevention of chronic disease are important for maintaining functional independence in older adults. Japanese-speaking subjects were less likely to decline over time, although this could be due in part to differential dropout and reporting bias. These findings have important implications for the design and interpretation of longitudinal studies of older adults. Researchers interested in the effects of ethnicity on health and aging should be cognizant of differences in recruitment and enrollment strategies among studies, and the ways in which these affect study findings. This study also demonstrates the importance of devoting adequate resources to minimize dropouts, and of including measures of health and functioning that are culturally equivalent and less reliant on self-report data.

Aged↗
PubMed2001

Direct comparison of detection systems used for the development of single-cell genetic tests in preimplantation genetic diagnosis.

PURPOSE: Single-cell polymerase chain reaction (PCR) requires efficient amplification and accurate detection. We compare the accuracy of heteroduplex, fluorescent-fragment, and fluorescent single-strand conformation polymorphism (F-SSCP) analysis as detection systems for analysis of a PCR assay developed for preimplantation genetic diagnosis. METHODS: A single-cell, fluorescent multiplex PCR assay was developed for the cystic fibrosis delta F508 mutation and the short tandem repeat, D21S11. Detection systems were compared by analyzing blinded PCR products. RESULTS: Amplification rates for cystic fibrosis were 89% by heteroduplex and 91% by fragment analysis, while it was 72% for D21S11 by fragment analysis. No difference in allele dropout was detected for cystic fibrosis by any method (2%). Overall accuracy was high, > 97%, although SSCP was the least accurate. CONCLUSIONS: Heteroduplex and fragment analysis proved equal in the diagnosis of a single amplified locus. We determined that fragment analysis allows maximal accuracy of detection and permits analysis of a second loci, controlling for DNA contamination and allelic dropout.

Cystic Fibrosis↗
PubMed1999

Preimplantation genetic diagnosis using fluorescent polymerase chain reaction: results and future developments.

PURPOSE: Fluorescent polymerase chain reaction (PCR) is a multipurpose technique that can be used for diagnosing sex, single-gene defects, and trisomies as well as determining DNA fingerprints from single cells. However, its effectiveness must be assessed before clinical preimplantation genetic diagnosis (PGD) application. METHODS: Single and multiplex fluorescent PCR was applied to single cells and blastomeres. RESULTS: Fluorescent PCR can be used to diagnose sex from blastomeres and has been successfully applied in a clinical PGD sexing program resulting in a confirmed pregnancy. A further major advantage of fluorescent PCR is the ability to multiplex, providing multiple diagnoses and DNA fingerprints with a high reliability (approximately 75% for trisomy, 86% for DNA fingerprint) and good accuracy (70-80%). Allele dropout in multiplex PCR is approximately 20% per allele and does not appear to be associated with the fragment size. CONCLUSIONS: Fluorescent PCR is a powerful technique for PGD, and the effects of allele dropout must be considered, particularly in multiplex PCR.

Blastomeres↗
PubMed1998

Interpretive and supportive forms of psychotherapy and patient personality variables.

A randomized clinical trial investigated the efficacy of interpretive and supportive forms of short-term individual psychotherapy and the interaction of each form with the patient's quality of object relations (QOR) and psychological mindedness (PM). The psychiatric outpatient sample included 144 therapy completers and 27 dropouts. Eight experienced therapists provided distinct forms of manual-guided therapy. Outcome was assessed by a comprehensive battery. The dropout rate was higher for interpretive therapy than for supportive therapy. Patients in both forms improved, but they did not differ on outcome from each other. A multivariate interaction effect indicated a direct relation between QOR and outcome for interpretive therapy and almost no relation for supportive therapy. A multivariate main effect indicated a direct relation between PM and outcome for both forms. The relevance of patient personality to outcome in different forms of therapy is addressed.

Adolescent↗
PubMed2002

Does imaginal exposure exacerbate PTSD symptoms?

Symptom exacerbation (i.e., treatment side effects) has often been neglected in the psychotherapy literature. Although prolonged exposure has gained empirical support for the treatment of chronic posttraumatic stress disorder (PTSD), some have expressed concem that imaginal exposure, a component of this therapy, may cause symptom exacerbation, leading to inferior outcome or dropout. In the present study, symptom exacerbation was examined in 76 women with chronic PTSD. To define a "reliable" exacerbation, we used a method incorporating the standard deviation and test-retest reliability of each outcome measure. Only a minority of participants exhibited reliable symptom exacerbation. Individuals who reported symptom exacerbation benefited comparably from treatment. Further, symptom exacerbation was unrelated to dropout. Thus, although a minority of individuals experienced a temporary symptom exacerbation, this exacerbation was unrelated to outcome.

Adult↗
PubMed1994

Recurrent corneal erosion: clinical features.

The clinical features of a group of 30 patients with recalcitrant recurrent corneal erosions (i.e. those who failed to respond to conventional therapy) were evaluated. Associated ocular and facial abnormalities were documented. Meibomian gland dysfunction was present in all patients as manifest by dropout and inspissation of the meibomian glands, reduced tear film break-up time and debris in the tear film. Dropout of meibomian glands was present in 25 (83%) patients and was maximum in the medial half of the lid in 21 (84%) of these 25 patients. Tear film break-up time was reduced in all patients, being instant in 7 (23%), between 1 and 5 seconds in 22 (74%) and between 10 and 15 seconds in 1 (3%) patient. Superficial corneal abnormalities were present in 28 (93%) patients as manifest by maps, dots and fingerprints. Facial abnormalities such as telangiectasia, rhinophyma and acne rosacea were present in 22 (73%) patients. The findings of our study suggest an association between recalcitrant recurrent corneal erosions and meibomian gland dysfunction.

Adult↗