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PubMed2006

Distribution of human SNPs and its effect on high-throughput genotyping.

Utilizing the results of extensive single nucleotide polymorphism (SNP) studies in humans, stimulated by the International HapMap Project, we present evidence that SNPs are not randomly spaced across the genome, but are somewhat clustered. This observation has important consequences for assay design, since hidden variants in primer sites can affect the accuracy of data. Indeed, using data from the calibration exercises of the HapMap Project, we found instances in which primer site mutations caused allele dropout and other genotyping failures. Given the dynamic nature of SNP discovery, it was inevitable that SNPs would be identified in the primer sites of many assays used for HapMap genotyping. We found that assays with such primer site mutations were correlated with elevated rates of genotype failure and allele dropout. This suggests that taking nearby SNPs into account is important for optimal genotyping assay design.

Alleles↗

PubMed1994

Comparison of fixed-dose transdermal nicotine, tapered-dose transdermal nicotine, and buspirone in smoking cessation.

The authors compared the outcome of 208 smokers treated with fixed-dose transdermal nicotine (n = 69), tapered-dose transdermal nicotine (n = 71), or buspirone (n = 68). At baseline, there were no significant differences among the three treatment groups with regard to age, gender, educational level, duration of smoking, number of cigarettes smoked per day, concomitant disease states or drug use, or Fagerstrom score. All smokers participated in a behavior modification program. Fixed-dose transdermal nicotine was given at a dose of 21 or 22 mg/day for 6 weeks. Tapered-dose transdermal nicotine was given at a dose of 21 or 22 mg/day for 4 weeks, 14 mg/day for 4 weeks and 7 mg/day for 4 weeks. Both transdermal nicotine regimens were initiated on the evening before the attempted quit date. Buspirone was started 21 days before the quit attempt and continued for 7 days after the quit attempt. Buspirone was initiated at 5 mg TID for 7 days and then 10 mg TID for 21 days. Smoking cessation was assessed by patient diaries and random plasma thiocyanate determinations. Dropouts for any reason were considered treatment failures. Quit rates were as shown in the Table I. Discontinuation of treatment for perceived side effects and dropouts for all reasons were not significantly different among the treatment groups. The authors conclude that fixed-dose transdermal nicotine, tapered-dose transdermal nicotine, and buspirone are associated with similar efficacy and safety when combined with behavior modification in smoking cessation.

Administration, Cutaneous↗

PubMed1986

Digital averaging to facilitate two-dimensional echocardiographic measurements.

A problem in quantitative two-dimensional echocardiography is myocardial dropout of still frame images. This study was designed to evaluate the ability of digital averaging to overcome myocardial dropout without distorting quantitative measurements. Forty-one percent of 80 digitally averaged images were thought to be improved by five independent observers, whereas 7% showed some deterioration. Measurements obtained from processed images were statistically identical (r greater than or equal to 0.9) to those from three arithmetically averaged, unprocessed images in 60 patients. Digital averaging can improve image quality without measurement distortion and should facilitate two-dimensional echocardiographic quantitation.

Analog-Digital Conversion↗

PubMed2006

Feasibility of dynamic susceptibility contrast perfusion MR imaging at 3T using a standard quadrature head coil and eight-channel phased-array coil with and without SENSE reconstruction.

PURPOSE: To investigate changes in image and dynamic signal-to-noise ratios (SNRs) of the DeltaR2* curve, as well as magnetic susceptibility-induced artifacts between a standard quadrature head coil and an eight-channel phased-array coil with and without sensitivity-encoding (SENSE) at 3T, compared to the current clinical standard head coil acquisition at 1.5T. MATERIALS AND METHODS: Dynamic susceptibility contrast (DSC) perfusion MRI was performed on 80 brain tumor patients using a gradient-echo, echo-planar imaging (EPI) sequence. Image and dynamic SNR were compared between 1.5T and 3T field strengths, a quadrature and eight-channel phased-array coil, and a conventional vs. partially parallel EPI acquisition with SENSE reconstruction. The amount of geometric distortion and signal dropout was quantified and compared between conventional and SENSE EPI acquisitions within the same exam at 3T. RESULTS: An initial 2.6-fold elevation in dynamic SNR was observed in normal-appearing white matter when doubling the field strength (P < 0.001), with an additional 1.7-fold increase found when employing an eight-channel phased-array coil (P < 0.002). Compared to the standard 3T eight-channel coil acquisition, the implementation of SENSE reduced the number of voxels experiencing large anterior shifts in the phase-encode direction, lowered the volume of signal dropout by 2.0-11.5%, and allowed a 1.4-fold increase in slice coverage, while only decreasing the dynamic SNR by 22%. CONCLUSION: SENSE EPI at 3T yielded a significant improvement in dynamic SNR over the 1.5T acquisitions. A significant reduction in magnetic susceptibility-induced artifacts was achieved with SENSE EPI compared to the standard EPI eight-channel coil acquisition at 3T.

Adult↗

PubMed2005

Coregistration of quantitative proton magnetic resonance spectroscopic imaging with neuropathological and neurophysiological analyses defines the extent of neuronal impairments in murine human immunodeficiency virus type-1 encephalitis.

Relatively few immune-activated and virus-infected mononuclear phagocytes (MP; perivascular macrophages and microglia) may affect widespread neuronal dysfunction during human immunodeficiency virus type 1 (HIV-1)-associated dementia (HAD). Indeed, histopathological evidence of neuronal dropout often belies the extent of cognitive impairment. To define relationships between neuronal function and histopathology, proton magnetic resonance spectroscopic imaging (1H MRSI) and hippocampal long-term potentiation (LTP) were compared with neuronal and glial immunohistology in a murine model of HIV-1 encephalitis (HIVE). HIV-1(ADA)-infected human monocyte-derived macrophages (MDM) were stereotactically injected into the subcortex of severe combined immunodeficient (SCID) mice. Sham-operated and unmanipulated mice served as controls. Seven days after cell injection, brain histological analyses revealed a focal giant cell encephalitis, with reactive astrocytes, microgliosis, and neuronal dropout. Strikingly, significant reductions in N-acetyl aspartate concentration ([NAA]) and LTP levels in HIVE mice were in both injected and contralateral hemispheres and in brain subregions, including the hippocampus, where neuropathology was limited or absent. The data support the importance of 1H MRSI as a tool for assessing neuronal function for HAD. The data also demonstrate that a highly focal encephalitis can produce global deficits for neuronal function and metabolism.

AIDS Dementia Complex↗

PubMed2002

Multiecho segmented EPI with z-shimmed background gradient compensation (MESBAC) pulse sequence for fMRI.

A MultiEcho Segmented EPI with z-shimmed BAckground gradient Compensation (MESBAC) pulse sequence is proposed and validated for functional MRI (fMRI) study in regions suffering from severe susceptibility artifacts. This sequence provides an effective tradeoff between spatial and temporal resolution and reduces image distortion and signal dropout. The blood oxygenation level-dependent (BOLD)-weighted fMRI signal can be reliably obtained in the region of the orbitofrontal cortex (OFC). To overcome physiological motion artifacts during prolonged multisegment EPI acquisition, two sets of navigator echoes were acquired in both the readout and phase-encoding directions. Ghost artifacts generally produced by single-shot EPI acquisition were eliminated by separately placing the even and odd echoes in different k-space trajectories. Unlike most z-shim methods that focus on increasing temporal resolution for event-related functional brain mapping, the MESBAC sequence simultaneously addresses problems of image distortion and signal dropout while maintaining sufficient temporal resolution. The MESBAC sequence will be particularly useful for pharmacological and affective fMRI studies in brain regions such as the OFC, nucleus accumbens, amygdala, parahippocampus, etc.

Adult↗

PubMed2006

High-resolution FMRI at 1.5T using balanced SSFP.

The resolution in conventional BOLD FMRI is considerably lower than can be achieved with other MRI methods, and is insufficient for many important applications. One major difficulty in robustly improving spatial resolution is the poor image quality in BOLD FMRI, which suffers from distortions, blurring, and signal dropout. This work considers the potential for increased resolution with a new FMRI method based on balanced SSFP. This method establishes a blood oxygenation sensitive steady-state (BOSS) signal, in which the frequency sensitivity of balanced SSFP is used to detect the frequency shift of deoxyhemoglobin. BOSS FMRI is highly SNR efficient and does not suffer from image distortions or signal dropout, making this method an excellent candidate for high-resolution FMRI. This study presents the first demonstration of high-resolution BOSS FMRI, using an efficient 3D stack-of-segmented EPI readout and combined acquisition at multiple center frequencies. BOSS FMRI is shown to enable high-resolution FMRI data (1 x 1 x 2 mm(3)) in both visual and motor systems using standard hardware at 1.5 T. Currently, the major limitation of BOSS FMRI is its sensitivity to temporal and spatial field drift.

Brain Mapping↗

PubMed1995

Differentiation between axonal and demyelinating neuropathies: identical segments recorded from proximal and distal muscles.

The presence of significant slowing of motor nerve conduction velocity is considered one of the electrodiagnostic hallmarks of demyelinating neuropathies; however, slowing of conduction velocity may also accompany severe axonal loss. When compound muscle action potential (CMAP) amplitudes are markedly reduced, it is frequently difficult to determine if conduction velocity slowing is due to axonal loss with dropout of the fastest conducting fibers or demyelination. To evaluate the relationship between conduction velocity and axonal dropout, we compared conduction velocities through the same segment of nerve recording from distal and proximal peroneal muscles in patients with chronic neuropathies, in patients with motor neuron disease, and in control subjects. In controls and patients with motor neuron disease, conduction velocities were normal with no significant difference between proximal and distal sites. In patients with axonal neuropathies, conduction velocities were preferentially slowed when recording from distal muscles and relatively normal when recording from proximal sites. Patients with demyelinating neuropathies showed marked slowing of conduction at both sites. We conclude that comparing conduction velocity obtained from proximal versus distal muscle recordings provides a simple, reliable aid for differentiating between chronic axonal and demyelinating polyneuropathies, especially in cases with conduction velocity slowing and low CMAP amplitudes.

Action Potentials↗

PubMed1986

The effects of culture-compatible intervention on the utilization of mental health services by minority clients.

This study examined the relationship between a culture-compatible approach to mental health service and utilization as measured by dropout and total number of outpatient visits. The sample (N = 300) was 23.5% Mexican, 22.8% White, 18.1% Black, 17.1% Vietnamese, 16.8% Pilipino, and 1.7% other ethnic group. A culture-compatible approach was found to be effective in increasing utilization. Three culture-compatibility components were the best predictors of dropout status: language match of therapists and clients, ethnic/racial match of therapists and clients, and agency location in the ethnic/racial community. Pharmacotherapy, education, previous treatment and a diagnosis of psychosis were significantly related to remaining in therapy.

Adolescent↗

PubMed1995

"Essential" phospholipids versus nicotinic acid in the treatment of patients with type IIb hyperlipoproteinemia and ischemic heart disease.

In patients with moderate, dietary noncorrigible hyperlipoproteinemia type IIb and ischemic heart disease, treatment with nicotinic acid is limited by the side effects of the drug. In 100 patients, 6-month treatment with nicotinic acid (n = 50) or "essential" phospholipids (EPL); Lipostabil, manufacturer: Rhône-Poulenc Rorer) (n = 50) indicated comparable efficacy for both substances: Significant (p < .001) reductions of serum total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglyceride values were similar in both groups, while nicotinic acid increased high-density lipoprotein (HDL) cholesterol significantly (p < .01) better than Lipostabil. A detailed analysis of ultracentrifugal lipoprotein profiles, hydroperoxide concentrations in LDL, and cholesterol-accepting properties of HDL in a small number of Lipostabil- and nicotinic acid-treated patients revealed favorable shifts in the lipoprotein profile, significant (p < .05) reductions of LDL hydroperoxides, and favorable increases of the most antiatherogenic HDL2b subfraction only in the Lipostabil-treated group. Clinically, both medications reduced the intensity and number of angina pectoris attacks per week (p < .05), but only Lipostabil-treated patients significantly (p < .05) increased their working capacity in the veloergometric test. Since in the nicotinic acid-treated group dropouts (nine patients, eight related to the drug) and side effects [14] exceeded those in the Lipostabil-treated group (two dropouts not related to the drug, no side effects), it is suggested that Lipostabil is a preferable alternative in the treatment of patients with moderate, dietary noncorrigible hyperlipoproteinemia IIb and ischemic heart disease.

Cholesterol, HDL↗

PubMed1992

Ethnic minority adolescents and the use of community mental health care services.

Examined the utilization rates, treatment dropout rates, and length of treatment for minority adolescents in the mental health care system. Data from the Los Angeles County Department of Mental Health from 1983 to 1988 were used. Ss were 853 African Americans, 704 Asian Americans, 964 Hispanics, and 670 whites. Analyses showed that Asian Americans and Hispanics are underrepresented in existing public mental health facilities while African Americans are overrepresented. For dropout rates, no ethnic differences are found between minority groups and whites; but, for length of treatment, Asian Americans tend to stay longer in treatment while African Americans tend to stay in treatment for a shorter period of time than whites. African Americans also have more outpatient episodes than whites. Implications of the results are discussed, and recommendations for future research are suggested.

Adjustment Disorders↗

PubMed1980

Some considerations for the planning of total-community prevention trials--when is sample size adequate?

Despite the large accumulated experience of statisticians with sample-size calculations for clinical trials, little information is available on extending this methodology to total community trials, in which the units of randomization are total communities and surveillance methods are used to assess event rates. As in clinical trials, the asymptotic formula for total sample size is used. However, the assumptions underlying the usual method of computing the expected T-year even rate for the experimental group, pe, are no longer valid in total community trials: all emigrants (dropouts) from large communities cannot practically be identified or followed. Immigrants, similar to dropouts in clinical trials in that they are exposed to the treatment for only a portion of the period but are followed to the end of the study, present an additional problem. This paper presents a method for the computation of pe in total community trials, taking into account in- and out-migration as well as the determinants usually considered in clinical trials. Sample computations are presented, and general problems of design, execution and data analysis of total community prevention trials are briefly discussed.

Clinical Trials as Topic↗

PubMedDate not supplied

Evaluation of vaccination coverage.

The cluster sampling methodology based on WHO module on "Evaluate Vaccination Coverage" recommended by Ministry of Health and Family Welfare, Government of India, 1987 was followed to evaluate the vaccination coverage of eligibles. Out of the 215 eligible children between 12-23 months of age, 44.65 38.61 and 16.74 per cent were found to be fully, partially and unimmunized respectively. The dropout rate for OPV and DPT was 21.23 while it was 4.03 per cent for TT. Based on the studied facts responsible for non or partial immunization, suggestions have been made to accelerate the coverage and reduce the dropout rate.

BCG Vaccine↗

PubMed2004

Prevalence of depression among adolescents.

OBJECTIVE: To find out the prevalence and pattern of depression among adolescents. METHODS: Adolescents of age group from 13 to 19 belonging to school/college students and school dropouts were assessed using Beck's Depression Inventory (BDI) by a team consisting of a pediatrician, psychologist and PGDCCD (Post Graduate Diploma in Clinical Child Development) students. RESULTS: 11.2% of school dropouts had severe and extreme grades of depression as against 3% among school going and nil among college going adolescents.

Adolescent↗

PubMed2000

[Detoxification of poly-substance abusers with buprenorphine. Effects on affect, anxiety, and withdrawal symptoms].

We used an open-labeled, 21-day inpatient detoxification treatment to compare the short-term effects of a 10-day buprenorphine plus 19-day carbamazepine regimen (n = 15) to a 14-day oxazepam plus 19-day carbamazepine regimen (n = 12) during rapid detoxification from opioids and other abused drugs. Somatic and psychopathological changes were assessed using the following rating scales: ASI, HAMD, SCL-90-R, and SOWS. Eighteen of 27 patients (67%) completed the study. Four dropouts (27%) were treated with buprenorphine/carbamazepine (BPN/CBZ) and the other five dropouts (42%) were treated with oxazepam/carbamazepine (OXA/CBZ). Repeated measures analysis of variance showed that SOWS scores were significantly less pronounced with BPN-CBZ than with OXA/CBZ. On the first day of admission, no significant difference in HAMD scores was detected (BPN/CBZ 11.6, BPN/CBZ 1.0). On day 14, HAMD was significantly less pronounced in BPN/CBZ (3.0) than in OXA/CBZ (6.1). BPN/CBZ showed a significant improvement in the ASI score on days 7 and 14 compared with OXA/CBZ. Three of nine items of the SCL-90-R showed a trend toward less pronounced outcome in BPN-CBZ. No severe side effects occurred during treatment in either group. The buprenorphine/carbamazepine regimen provided significantly more effective relief from affect disturbances and withdrawal syndromes than the oxazepam/carbamazepine regimen. The pharmacological basis of these effects of buprenorphine (kappa-antagonism activity,mu-agonism activity) are discussed.

Adult↗

PubMed1997

Prevalence of diabetic retinopathy in children and adolescents with IDDM. A population-based multicentre study.

Vision-threatening diabetic retinopathy can be prevented if it is diagnosed before becoming too advanced. Since diabetic retinopathy has been reported to occur only rarely before the end of pubertal development, children and adolescents are seldom included in screening programmes. We invited 780 children and adolescents with insulin-dependent diabetes mellitus diagnosed before the age of 15.0 years (disease duration of < 12 years) and who were older than 9.0 years at the time of examination from eight regions of Sweden. Retinal examination was performed with stereoscopic fundus photograph. The photograph were rated according to a modified Airlie House classification. The dropouts (223/780, 28.6%) were significantly older and with a longer duration of diabetes than the examined children (p < 0.001 and 0.001, respectively). Photographs from 557 patients aged (median [interquartile range]:14.6 [12.4-17.0]) years and with a diabetes duration of 8.0 (5.5-9.9) years were evaluated. Retinopathy was demonstrated in 81 patients (14.5%):66 with background retinopathy, 2 with microaneurysms and hard exudates, 12 with preproliferative retinopathy, 1 with proliferative retinopathy. Preproliferative retinopathy was diagnosed in a 12.8-year-old girl in pubertal stage 3 and an 11.8-year-old boy in pubertal stage 2, and proliferative retinopathy was found in a 21.5-year-old girl. Retinopathy was demonstrated in 6% and 18% of patients in pubertal stages 1 and 5, respectively. The overall prevalence of retinopathy in this population may even be higher since the dropouts were older and had a longer duration of diabetes. Since background and preproliferative retinopathy were found in children before puberty, we recommend including children and adolescents in screening programmes for diabetic retinopathy from the age of 10 years.

Adolescent↗

PubMed2001

Incorrect use and limited weight reduction of orlistat (Xenical) in clinical practice. A cohort study.

OBJECTIVE: To study the prescribing of the antiobesity drug orlistat in relation to the approved indication and its weight-reducing effect in clinical practice during the first 3 months of treatment. METHODS: Anonymous postal questionnaire survey to prescribers of orlistat concerning a random sample of 1000 of 20,000 prescriptions. PARTICIPANTS: Useful information was obtained for 789 patients. SETTING: Primary and secondary care in Sweden. MAIN OUTCOME MEASURES: Beginning and continued treatment according to the approved indication. Dropout from treatment. Weight loss during treatment. RESULTS: Four percent of the patients were prescribed orlistat despite having a body mass index (BMI) less than 28 kg/m2. Only 24% of the patients had a diet period with a weight loss of 2.5 kg or greater before the start of therapy. Half of the patients with a weight loss of less than 5% after 3 months continued the treatment. Ten percent gained weight or had no weight loss at all while 43% lost less than 5% in weight. At least one-quarter of the patients stopped the treatment within the observation period. CONCLUSION: Orlistat was not prescribed according to the approved indication in the majority of cases. The dropout rate was high and most patients had minor gain from the treatment.

Adult↗

PubMed2006

Understanding the needs and objectives of erectile dysfunction patients.

Consideration of the needs and objectives of individual patients significantly influences the behavior of erectile dysfunction (ED) patients and their partners. Evaluation of an erectile dysfunction (ED) patient requires individualized consideration of the expectations, needs, and objectives of the affected couple. These factors can influence attitudes toward diagnosis, treatment seeking, and ultimately treatment compliance and dropout. Relevant ED market research studies were presented at the 2006 annual meeting of the American Urological Association. The studies explored the prevalence of ED, access to treatment, and ED patient attitudes and preferences. Several barriers continue to influence treatment-seeking behavior in men with ED. These barriers have had a negative impact on the ED patient and marketplace resulting in low rates of utilization and high rates of dropout from therapies for ED.

Clinical Trials as Topic↗