Biomedical subjects

J Brandt

Publications and source records attributed to J Brandt.

At least 109 records · Page 6Linked to original sources

PubMed2001

Construction of a generic reaction knowledge base by reaction data mining.

As synthesis by combinatorial chemistry and high throughput screening have become well-established strategies in the drug discovery process, chemists face increased challenges in managing large amounts of data and using these data to design more diverse and focused libraries. As synthesis is an intuitive and empirical process, however, the classical approaches to computer-assisted synthesis planning do not fully satisfy the needs of the synthetic chemist. We describe a novel computational technique for extracting reaction data and building a generic reaction knowledge base (GRKB) to provide chemists with useful and well-organized knowledge. The method consists of three key steps: (1) the automatic recognition of reaction centers, (2) the definition of a hierarchy of reaction patterns, and (3) the organization of the generic reaction knowledge. Significant reaction knowledge has been discovered via mining a subset of the InfoChem Reaction database. A frame system has been constructed to store and retrieve the GRKB. Applications of this GRKB to synthesis planning are illustrated.

Artificial Intelligence↗

PubMed2001

Effects of ketogenic diet on development and behavior: preliminary report of a prospective study.

The ketogenic diet is increasingly used for the management of difficult-to-control seizures in children. Here, we describe the first prospective study of the effects of the diet on development, behavior, and parenting stress. Participants were 65 children (36 males, 29 females) with intractable seizures, ages 18 months to 14 years 6 months, enrolled in a prospective study at the Johns Hopkins Hospital, Baltimore, MD, USA, to study the diet's efficacy. Children were assessed before diet initiation and at 1-year follow-up. At follow-up, 52% (34 of 65) children remained on the diet. Mean seizure frequency decreased from 25 per day before diet initiation to less than two per day 1 year later. At follow-up, mean developmental quotient showed statistically significant improvement (p<0.05), with significant behavioral improvements in attention and social functioning. Parental stress was essentially unchanged. No baseline factor examined predicted diet adherence, and the primary reason for diet discontinuation was insufficient seizure control. These preliminary results support prior anecdotal reports of the beneficial effects of the diet on cognition and behavior.

Adolescent↗

PubMed2001

Inhibition of return in aging and Alzheimer's disease: performance as a function of task demands and stimulus timing.

Inhibition of return (IOR) is a phenomenon of spatial attention that biases attention toward novel events in the environment. Recent evidence suggests that the magnitude and timing of IOR varies as a function of task conditions (e.g., detection vs. discrimination tasks, short vs. long cue-target intervals, intrinsic vs. extrinsic cues). Although IOR appears relatively preserved with both normal aging and Alzheimer's disease (AD), it has been tested under relatively simple task conditions. To test whether IOR is resistant to age and / or AD when cognitive demands are increased, we employed a double-cue IOR paradigm that required categorization as well as detection responses. The stimulus onset asynchrony (SOA) between the cue and target events was varied to determine whether group differences existed in IOR effects over time. Younger normal adults and older normal adults exhibited significant IOR effects on both the detection task and the categorization task at a short cue-target SOA (950 ms). In contrast, AD patients exhibited significant IOR effects at the short SOA on the detection task but not on the categorization task. From the short to the long SOA (3500 ms), IOR effects exhibited by younger normal adults declined significantly during both the detection and the categorization tasks, suggesting that inhibition resolved over time. In contrast, neither older normal adults nor AD patients exhibited SOA-related IOR reductions on the detection task. These results suggest that IOR may show differential age- and AD-related vulnerabilities depending on task conditions and timing characteristics.

Adult↗

PubMed2001

Gender and time differences in initial location and histological grade of non-Hodgkin's lymphomas in Southern Sweden.

In accordance with international data, non-Hodgkin's lymphomas (NHL) in the Southern Health Care Region of Sweden were more common in men than in women and there was an inreasing incidence for both genders in the 1980s and 1990s. A study of the years 1983 and 1992, i.e. the beginning and the end of a 10-year period, was carried out. Case records for 94% of all adults diagnosed in 1983 and 1992 (220 men and 171 women) were reviewed. The sites of the lymphomas and malignancy grade (Kiel classification) were recorded. Comparisons were made between the genders and between the two years studied. Among 170 men with nodal lymphomas, 49 were localized (stage I-II) in lymphoid tissue regional to the respiratory tract, 18 were localized elsewhere and 103 were generalized (stage III-IV). The corresponding sites in 138 women were 28, 33 and 77, respectively (p = 0.002), implying a predominance of stage I-II lymphomas regional to the respiratory tract in men and a larger number of localized lymphomas elsewhere, mostly abdominal retroperitoneal with or without inguinal engagement in women. High-grade nodal lymphomas were more common in 1992 (54%) than in 1983 (34%, p = 0.01). suggesting an increasing number of mainly high-grade lymphomas. For extranodal lymphomas (50 in men and 33 in women), no clear differences were observed for gender and the years studied. Risk factors, e.g. occupational hazards, are probably different for men and women. The gender differences in initial nodal location suggest that initial lymphoma sites may be related to different risk factors. Epidemiologic studies where both malignancy grade and initial lymphoma locations are taken into account may be helpful in defining risk factors.

Adolescent↗

PubMed2001

Predictor index of mortality in dementia patients upon entry into long-term care.

BACKGROUND: The purpose of this study was to develop an algorithm that predicts survival in patients with dementia upon entry into long-term care. There are, as yet, no predictive equations developed for those in the late stages of Alzheimer's disease (AD). METHODS: This was a prospective, observational study of 132 patients with dementia (61% with AD) followed for up to 5.0 years (median of 41.0 months) after admission to a long-term care facility for dementia patients. Information on demographic characteristics, physical health, and cognitive, emotional, and behavioral characteristics was collected shortly after admission and entered as predictors of time until death in Cox regressions. Findings were used to derive an index predicting mortality. RESULTS: There were 60 deaths among the 132 patients (45.4% mortality), with an average survival of 22.4 months in those who died. Better physical health and the presence of delusions were associated with longer survival. These two variables were aggregated into the Copper Ridge Index (CRI). Each one-point increase on the CRI was associated with a four-fold greater likelihood of death over 5 years. CONCLUSIONS: A predictive equation incorporating measures of general physical health and delusions accurately predicted time to death in dementia patients in long-term care.

Aged↗

PubMed2001

New treatment options in spondyloarthropathies: increasing evidence for significant efficacy of anti-tumor necrosis factor therapy.

Tumor necrosis factor-alpha is a major effector and regulatory cytokine, which seems to have an outstanding position in rheumatic and other inflammatory states. Because TNF-alpha has been detected in the inflamed gut and sacroiliac joints of patients with chronic inflammatory bowel diseases and spondyloarthritides, like ankylosing spondylitis, there was need for studies of the efficacy of the modern biologic anti-TNF agents infliximab and etanercept in these diseases. Infliximab is approved for the treatment of Crohn disease. In addition, there are now also positive data for infliximab in the treatment of ankylosing spondylitis and for etanercept and infliximab in the treatment of psoriatic arthritis.

Antibodies, Monoclonal↗

PubMed2001

Structural and functional characteristics of the B-domain-deleted recombinant factor VIII protein, r-VIII SQ.

Recombinant factor VIII SQ (r-VIII SQ), ReFacto, is a recombinant factor VIII product similar to the smallest active factor VIII protein found in plasma-derived factor VIII (p-VIII) concentrates. The protein comprises two polypeptide chains of 80 and 90 kDa and lacks the major part of the heavily glycosylated B-domain i.e. amino acids Gln744 to Ser1637. r-VIII SQ retains six potential glycosylation sites for N-linked oligosaccharides at asparagine residues 41, 239, 582, 1685, 1810 and 2118. We describe a thorough comparison of the characteristics of r-VIII SQ with those of p-VIII. The primary and secondary structures of r-VIII SQ were in good agreement with that of B-domain-deleted p-VIII (p-VIII-LMW) as shown by SDS-PAGE, Western blotting with antifactor VIII antibodies, tryptic mapping, amino acid sequence analysis and circular dichroism spectroscopy. A few divergences also existed. Thus r-VIII SQ was shown to contain a small amount of the single chain primary translation product of 170 kDa and also the product specific sequence of 14 amino acids, the SQ-link, in the C-terminal end of the 90 kDa chain. It was shown that r-VIII SQ had a high specific activity of about 14,000 IU VIII:C/mg as determined by use of a chromogenic substrate assay. The r-VIII SQ protein was comparable to p-VIII forms with a retained B-domain, in terms of potency measured by a chromogenic substrate or a two-stage clotting assay, in interactions with thrombin, and with activated protein C (APC) in combination with Protein S. The ability of r-VIII SQ to participate as a cofactor in factor Xa generation in a mixture of factors IXa and X, phospholipid and calcium was in conformity with that of p-VIII. Furthermore r-VIII SQ had a good binding capacity for phospholipid vesicles and von Willebrand factor (vWF) as shown in gel filtration studies. The same kinetics in binding to von Willebrand factor was found for r-VIII SQ and p-VIII as determined by real-time biospecific interaction analysis (BIA) with use of the BIAcore instrument. The apparent association rate constant was 4 x 10(6) M(-1)s(-1). Two dissociation rate constants were found, 1 X 10(-2)s(-1) and 4 x 10(-4)s(-1). The results extend the present knowledge that the factor VIII B-domain is dispensable for the factor VIII cofactor function in hemostasis.

Binding Sites↗

PubMed2001

Longitudinal study of quality of life in people with advanced Alzheimer's disease.

The authors examined three indicators of health-related quality of life in people with advanced Alzheimer's disease ([AD]; N=150): confinement to home, null activity, and null positive affect, as reported by patient proxies. Dementia severity predicted time-to-onset for all three disease milestones in models that controlled for sociodemographic indicators, nursing home status, and death in the follow-up period. Patients whose dementia worsened over follow-up were more likely to reach each milestone. These outcomes represent key milestones in the care of patients; they are sensitive to disease progression, and they are likely to be useful for studying treatment in advanced AD.

Activities of Daily Living↗

PubMed2000

The use of artificial intelligence technology to predict lymph node spread in men with clinically localized prostate carcinoma.

BACKGROUND: The current study assesses artificial intelligence methods to identify prostate carcinoma patients at low risk for lymph node spread. If patients can be assigned accurately to a low risk group, unnecessary lymph node dissections can be avoided, thereby reducing morbidity and costs. METHODS: A rule-derivation technology for simple decision-tree analysis was trained and validated using patient data from a large database (4,133 patients) to derive low risk cutoff values for Gleason sum and prostate specific antigen (PSA) level. An empiric analysis was used to derive a low risk cutoff value for clinical TNM stage. These cutoff values then were applied to 2 additional, smaller databases (227 and 330 patients, respectively) from separate institutions. RESULTS: The decision-tree protocol derived cutoff values of < or = 6 for Gleason sum and < or = 10.6 ng/mL for PSA. The empiric analysis yielded a clinical TNM stage low risk cutoff value of < or = T2a. When these cutoff values were applied to the larger database, 44% of patients were classified as being at low risk for lymph node metastases (0.8% false-negative rate). When the same cutoff values were applied to the smaller databases, between 11 and 43% of patients were classified as low risk with a false-negative rate of between 0.0 and 0.7%. CONCLUSIONS: The results of the current study indicate that a population of prostate carcinoma patients at low risk for lymph node metastases can be identified accurately using a simple decision algorithm that considers preoperative PSA, Gleason sum, and clinical TNM stage. The risk of lymph node metastases in these patients is < or = 1%; therefore, pelvic lymph node dissection may be avoided safely. The implications of these findings in surgical and nonsurgical treatment are significant.

Acid Phosphatase↗

PubMed2000

Comparative in vitro isolation of Trypanosoma theileri from cattle in Belgium.

Ten blood samples randomly collected from cows on a farm nearby Antwerp, Belgium, were inoculated into KIVI culture medium (Kit for In Vitro Isolation of trypanosomes) and RPMI 10%+feeder medium. Within 3 weeks of incubation all KIVI cultures and four RPMI 10%+feeder revealed presence of Trypanosoma theileri. Some practical implications regarding the use of KIVI for isolation of pathogenic African trypanosomes from cattle and other Bovidae are discussed.

Animals↗

PubMed2000

Sero-epidemiological study of Taenia saginata cysticercosis in Belgian cattle.

A sero-epidemiological survey of Taenia saginata cysticercosis was carried out to determine the prevalence of the infection in cattle presented for slaughter in Belgium. Between November 1997 and June 1998, a total of 1164 serum samples were collected in 20 export abattoirs. Meat inspection was routinely carried out by veterinary inspectors. Serum samples were examined for circulating parasite antigen using a monoclonal antibody-based sandwich enzyme-linked-immunosorbent assay (Ag-ELISA). Thirty six serum samples (3.09%) were found positive in the Ag-ELISA, while by meat inspection on the same animals cysticerci were detected in only three carcasses (0.26%). Sero-prevalence was positively correlated with the age of the animals. The sero-prevalence found in this study was more than 10 times higher than the annual prevalence (0.26%) reported by the Institute for Veterinary Inspection. This study clearly indicates that the classical meat inspection techniques detect only a minor fraction of the carcasses infected with cysticerci.

Abattoirs↗

PubMed2000

Motor disorder in Huntington's disease begins as a dysfunction in error feedback control.

A steady progression of motor dysfunction takes place in Huntington's disease (HD). The origin of this disturbance with relation to the motor control process is not understood. Here we studied reaching movements in asymptomatic HD gene-carriers (AGCs) and subjects with manifest HD. We found that movement jerkiness, which characterizes the smoothness and efficiency of motion, was a sensitive indicator of presymptomatic HD progression. A large fraction of AGCs displayed elevated jerk even when more than seven years remained until predicted disease onset. Movement termination was disturbed much more than initiation and was highly variable from trial to trial. Analysis of this variability revealed that the sensitivity of end-movement jerk to subtle, self-generated early-movement errors was greater in HD subjects than in controls. Additionally, we found that HD corrective responses to externally-generated force pulses were greatly disturbed, indicating that HD subjects display aberrant responses to both external and self-generated errors. Because feedback corrections are driven by error and are delayed such that they predominantly affect movement termination, these findings suggest that a dysfunction in error correction characterizes the motor control deficit in early HD. This dysfunction may be observed years before clinical disease onset and grows worse as the disease progresses.

Age of Onset↗

PubMed2000

Evaluation of prostate cancer patients receiving multiple staging tests, including ProstaScint scintiscans.

BACKGROUND: Multiple serum tests were performed on archival samples from patients who participated in trials to assess the ProstaScint scan staging ability. Traditional statistical analysis as well as artificial neural network (ANN) analysis were employed to evaluate individual patients and the group as a whole. The results were evaluated so that each factor was tested for prognostic value. METHODS: Data obtained from serum tests, bone scans, and ProstaScint scans were evaluated by traditional statistical methods and ANN to determine the individual value in clinical staging of prostate cancer. RESULTS: Two hundred seventy-five patients (180 postprostatectomy, 95 intact prostate) with prostate cancer (14 with distant metastases) were available for analysis. Data available included: clinical state (remission or progression), most recent clinical TNM stage, bone scan, and ProstaScint scan. Serum was tested for prostate-specific membrane antigen(PSMA), prostate-specific antigen(PSA), free PSA (fPSA), and complexed PSA (cPSA). Additional calculations included percent free PSA, and percent complexed PSA. Spearman individual statistical assessment for traditional group evaluation revealed no significant factors for T-stage. The free PSA and complex PSA had a significant association with node (N)-status. The distant metastases (M) stage correlated well with the bone scan and clinical stage. ANN analysis revealed no significant T-stage factors. N-stage factors showed a 95% sensitivity and 49% specificity. These factors included the presence or absence of a prostate, PSA serum levels, bone scan, and ProstaScint scans as major associated indicators. ANN analysis of the important variables for M-stage included ProstaScint scan score, and PSA levels (total, percent complexed, percent free, and fPSA). These factors were associated with a 95% sensitivity and 15% specificity level. CONCLUSIONS: Two hundred seventy-five patients receiving treatment for prostate cancer were evaluated by ANN and traditional statistical analysis for factors related to stage of disease. ANN revealed that PSA levels, determined by a variety of ways, ProstaScint scan, and bone scan, were significant variables that had prognostic value in determining the likelihood of nodal disease, or distant disease in prostate cancer patients.

Bone and Bones↗

PubMed2000

Use of artificial neural networks in evaluating prognostic factors determining the response to dendritic cells pulsed with PSMA peptides in prostate cancer patients.

BACKGROUND: Our purpose was to compare the importance of over 22 measurements used in evaluating the clinical responses of patients with metastatic or locally recurrent prostate cancer, treated by dendritic cell (DC) infusions with prostate-specific membrane antigen (PSMA) peptides. METHODS: Artificial neural networks (ANNs) were employed for assessment, as well as the traditional methods of logistic regression. RESULTS: Twenty-six patients with metastatic disease and 37 patients with local recurrence were available for evaluation and comparison. ANN evaluation ranked the collective effects of DC infusion, immune responses (CD3+ cells, CD16+ cells, zeta chain+ cells), and cytokines, e.g., IL-6 and PSMA levels, very highly. Logistic regression identified all of these parameters to some degree, but in a different rank order. Patients with metastases showed a sharp rate of response secondary to the level of DC infusion, in contrast to those patients with local recurrence, in which it was more gradual. CONCLUSIONS: ANN analysis emphasizes the importance of level of DC infusion, immune parameters, cytokines, and markers such as PSMA in determining the response to PSMA peptide immunotherapy. The criteria of response were judged to be correct in 86% of metastatic patients and 83% of locally recurrent patients evaluated in this study.

Clinical Trials, Phase II as Topic↗

PubMed2000

Quality of life in dementia patients in long-term care.

OBJECTIVE: To evaluate variables associated with quality of life (QOL) in dementia residents in a long-term care facility using a recently standardized and validated dementia-specific QOL scale (ADRQL). METHOD: A cross-sectional, case-control design was employed using validated scales to assess dementia-related symptomatology. Thirty-two facility staff members were interviewed to assess the QOL of 120 patients meeting DSM-IV for dementia criteria residing in long-term care. RESULTS: ADRQL scores were higher in assisted living residents than in skilled nursing facility residents. In univariate analyses, worse orientation, greater physical dependency, depression, and treatment with anxiolytics were associated with lower ADRQL scores. In multivariate analyses, lower scores were associated with worse orientation, greater physical dependency, depression, and anxiolytic treatment. CONCLUSIONS: Residents exhibited better QOL than expected. Future longitudinal studies should address if reorientation, activity therapy, treatment of depression, and avoidance of benzodiazepines might improve QOL in this population. Interventions that might improve orientation and physical abilities, such as cholinomimetic therapies, psychosocial interventions, or behavioral strategies, should also be studied in future research on QOL.

Activities of Daily Living↗

PubMed2000

Characteristics and outcomes of dementia residents in an assisted living facility.

BACKGROUND: Assisted living (AL) is the fastest growing segment of residential long-term care in the US. At least half of the estimated 1 million AL residents have dementia or cognitive impairment, with many AL facilities offering specialized dementia services. Little research has been done on the demographics, outcomes, or clinical variables of this population. METHODS: Participants were a cohort of 144 residents admitted to the AL unit of Copper Ridge, a specialized dementia-care facility. Comparison samples included 737 patients with dementia residing in other locations (home, nursing home, and other assisted living facilities). Selected measures of cognition, behavior, medical health, and function were taken at admission to AL and at 6-month intervals. RESULTS: When compared with residents of the dementia-specialized AL facility, dementia patients at home were younger, less cognitively impaired, and less likely to exhibit wandering, delusions, or aggression. Residents of a dementia-specialized nursing home had more cognitive impairment, greater medical comorbidity, and were more dependent on caregivers. The 2-year mortality rate in the dementia-specialized AL was 23%, significantly lower than rates reported for nursing homes. Primarily due to increasing care needs, most residents in the specialized AL relocated to a nursing home after a median stay of 10.9 months. Depression, falling, and wandering were significant predictors of the transition. CONCLUSION: Dementia-specialized AL facilities occupy a unique position in the long-term care continuum that is distinct from home-care and nursing home facilities. This research is the first step toward understanding the significant dementia population residing in assisted living.

Aged↗

PubMed2000

Successful treatment of active ankylosing spondylitis with the anti-tumor necrosis factor alpha monoclonal antibody infliximab.

OBJECTIVE: Tumor necrosis factor alpha (TNFalpha) has been detected in sacroiliac joint biopsy specimens from patients with spondylarthropathy. The present open pilot study was undertaken to test the efficacy of the anti-TNFalpha monoclonal antibody infliximab in the treatment of active ankylosing spondylitis (AS). METHODS: Eleven patients with AS of short duration (median 5 years, range 0.5-13 years) that had been active for at least 3 months (range 3-72 months) were treated with 3 infusions of infliximab (at weeks 0, 2, and 6), in a dosage of 5 mg/kg. Ten of the 11 patients had elevated C-reactive protein (CRP) levels (>6 mg/liter) before treatment; these elevations were known to have had persisted > 1 year in at least 3 patients. The Bath AS Disease Activity Index (BASDAI), the Bath AS Functional Index (BASFI), pain as measured on a visual analog scale, and the Bath AS Metrology Index (BASMI) were assessed. Quality of life was assessed using the Short Form 36 instrument. Laboratory markers of disease activity, including interleukin-6 (IL-6) levels, were determined. Dynamic magnetic resonance imaging (MRI) of the spine was performed in 5 patients. RESULTS: One patient withdrew from the study due to the occurrence of urticarial xanthoma 8 days after the first infusion. At study enrollment, 3 of 5 patients had evidence of spinal inflammation (spondylitis and spondylodiscitis) as detected by MRI; followup MRI 2-6 weeks after the third infusion revealed improvement in 2. Improvement of > or = 50% in activity, function, and pain scores was documented in 9 of 10 patients; the median improvement in the BASDAI after 4 weeks was 70% (range 41-94%). This clear-cut benefit lasted for 6 weeks after the third infusion in 8 of 10 patients. The median CRP level decreased from 15.5 mg/liter (range <6-90.8) to normal, and the median IL-6 level from 12.4 mg/liter (range 0-28.4) to normal (<5). There was improvement in all 9 SF-36 concepts; the improvement was significant for 6 concepts. CONCLUSION: These data suggest that anti-TNFalpha therapy is very effective for several weeks in AS. Whether this therapy, in addition to its antiinflammatory effect, prevents ankylosis remains to be determined.

Adult↗

PubMed2000

Rate of caudate atrophy in presymptomatic and symptomatic stages of Huntington's disease.

Previous research by our group demonstrated a longitudinal change in caudate volume for symptomatic subjects with Huntington's disease (HD), and suggested that volume of the caudate may be a useful outcome measure for therapeutic studies in symptomatic patients. The current study was designed to determine whether longitudinal change in caudate atrophy could be documented in presymptomatic carriers of the HD gene mutation, and to compare rate of change in these subjects with rate of change in mildly and moderately affected symptomatic patients. We measured caudate volumes on serial magnetic resonance image scans from 30 patients at three stages of HD: 10 presymptomatic; 10 with mild symptoms, as indicated by scores on the Quantified Neurological Exam (QNE) < or =35; and 10 with moderate symptoms (QNE >45). The mean interscan interval was 36 months. When analyzed separately, both symptomatic groups and the presymptomatic group demonstrated a significant change in caudate volume over time. Amount of change over time did not differ significantly among the three groups. We conclude that change in caudate volume may be a useful outcome measure for assessing treatment effectiveness in both presymptomatic and symptomatic subjects.

Adult↗