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Biomedical subjects

C A Brandt

Publications and source records attributed to C A Brandt.

At least 19 recordsLinked to original sources
PubMed2000

Reengineering a database for clinical trials management: lessons for system architects.

This paper describes the process of enhancing Trial/DB, a database system for clinical studies management. The system's enhancements have been driven by the need to maximize the effectiveness of developer personnel in supporting numerous and diverse users, of study designers in setting up new studies, and of administrators in managing ongoing studies. Trial/DB was originally designed to work over a local area network within a single institution, and basic architectural changes were necessary to make it work over the Internet efficiently as well as securely. Further, as its use spread to diverse communities of users, changes were made to let the processes of study design and project management adapt to the working styles of the principal investigators and administrators for each study. The lessons learned in the process should prove instructive for system architects as well as managers of electronic patient record systems.

Clinical Trials as Topic↗
PubMed2000

A guideline implementation system using handheld computers for office management of asthma: effects on adherence and patient outcomes.

OBJECTIVE: To evaluate effects on the process and outcomes of care brought about by use of a handheld, computer-based system that implements the American Academy of Pediatrics guideline on office management of asthma exacerbations. DESIGN: A before-after trial with randomly selected, office-based Connecticut pediatricians. In both the control and intervention phases, physicians collected data from 10 patient encounters for acute asthma exacerbations. During the intervention phase, the computer provided for structured encounter documentation and offered recommendations based on the guideline of the American Academy of Pediatrics. Patients were contacted by telephone 7 to 14 days after the visit to assess outcomes. RESULTS: Nine study-physicians enrolled 91 patients in the control phase and 74 in the intervention phase. Follow-up information was available for 93% of encounters. Use of the intervention was associated with increased mean frequency/visit of: 1) measurements of peak expiratory flow rate (2.18 vs 1.57) and oxygen saturation (1.12 vs.42), and 2) administration of nebulized beta2-agonists (1.25 vs.71). Visits in the intervention phase lasted longer and fees were higher ($145.61 vs $103.11). There were no significant differences in immediate disposition or subsequent emergency department visits, hospitalizations, missed school, or caretaker's missed work during the 7 days post visit. CONCLUSION: Use of handheld computers that provide guideline-based decision support was associated with increased physician adherence to guideline recommendations; however, visits were prolonged, fees were higher, and no improvement could be demonstrated with regard to the observed intermediate-term patient outcomes. Guideline implementers (and users) should be cautious about putting unvalidated recommendations into practice.

Adolescent↗
PubMed1999

Behavioural problems associated with dementia: the role of newer antipsychotics.

Behavioural disorders are a common feature in dementia, especially in the later stages of the disease. The most frequent disorders are agitation, aggression, paranoid delusions, hallucinations, sleep disorders, including nocturnal wandering, incontinence and (stereotyped) vocalisations or screaming. Behavioural disorders, rather than cognitive disorders, are the main reason why caregivers place patients with dementia in a nursing home. However, although behavioural disorders are important, there is still no international agreement with respect to the description and definition of symptoms and syndromes. This also holds true for the wide variety of scales for quantification and measurement of behavioural disorders. Drug therapy should be considered after possible underlying causes such as physical illness, drug adverse effects and environmental stressors have been ruled out, or specifically addressed, and a behavioural approach has also failed. This article briefly reviews the evidence for non-antipsychotic drug therapies, which include a variety of substances. However, antipsychotics are the group of drugs which have been most frequently studied for the treatment of behavioural syndromes in dementia. Drug responsive symptoms include anxiety, verbal and physical agitation, hallucinations, delusions, uncooperativeness and hostility, whereas wandering, hoarding, unsociability, poor self-care, screaming and other stereotyped behaviour seem to be unresponsive to all drugs. Although the use of classical antipsychotics is limited by extrapyramidal symptoms, anticholinergic adverse effects, sedation and postural hypotension, the newer antipsychotics offer the chance of a better risk:benefit ratio. This article reviews the small amount of data published on the use of the newer antipsychotics, and concludes that risperidone at low dosages (0.5 to 2 mg/day) seems to be especially useful for the treatment of behavioural symptoms in dementia because of its negligible anticholinergic adverse effects. The use of clozapine is limited by its anticholinergic activity, at least in dementia of the Alzheimer and Lewy body types. However, in patients with psychosis arising from Parkinson's disease it seems to be the drug of choice, and similar activity is likely for olanzapine. There are no published data on other newer drugs, such as sertindole, quetiapine or ziprasidone. Future studies should also address questions of dementia heterogeneity and should compare different drug treatments and treatment combinations.

Antipsychotic Agents↗
PubMed1999

An object-oriented framework for the development of computer-based guideline implementations.

Clinical practice guidelines provide a means of directing medical care towards clinically appropriate and cost-effective interventions. A direct relationship exists between the integration of a guideline into clinical workflow and the effectiveness of the guideline in influencing clinicians' behavior. Computer-based guideline implementations, used at the point-of-care, accomplish this integration. Employing object-oriented technologies, we propose a framework of reusable components for the development of guideline implementation systems. We have identified eight information management services that are common to such systems. Our framework integrates these services and their respective reusable components into clinical workflow to promote the development of comprehensive guideline implementation systems, which should ultimately enhance guideline compliance and the overall quality of care.

Guideline Adherence↗
PubMed1998

Increased benzodiazepine receptor density in the prefrontal cortex in patients with panic disorder.

There are published studies concerning a regionally changed function of GABA-benzodiazepine-receptor-complexes in anxiety disorder. These studies implicate the limbic lobe, the brainstem and the prefrontal cortex. Using 123I-Iomazenil and single photon emission tomography (SPET) we investigated the benzodiazepine receptor density in twelve patients with panic disorder who had never been treated with benzodiazepines before. Nine age- and sex-matched volunteers who were free of mental illness served as controls. Patients with panic disorder showed a significant increase of benzodiazepine receptor binding in the right supraorbital cortex and a trend to an increased uptake in the right temporal cortex. There was no correlation between receptor density and scores on Spielberger's State Trait Anxiety Inventory in the patient group. Since the findings cannot be explained by benzodiazepine exposure we hypothesize an upregulation due to functional or neuroanatomic changes (at least) in the frontotemporal cortex.

Adult↗
PubMed1997

Transition to a computer-based record using scannable, structured encounter forms.

OBJECTIVE: To evaluate the quality of documentation and user satisfaction with a structured documentation system for pediatric health maintenance encounters, using scanned paper-based forms to generate an electronic medical record. DESIGN: (1) A retrospective medical record review comparing 16 structured (ST) records with 16 contemporaneously created unstructured records, (2) a questionnaire evaluation of user satisfaction, and (3) an electronic records review of patients seen 1 year following the full implementation of the system to evaluate persistence of the effect. SETTING: The Yale-New Haven Hospital Pediatric Primary Care Center, New Haven, Conn, an inner-city clinic in an academic center. PARTICIPANTS: (1) A random sample of 16 health maintenance records completed by first- and second-year residents in February 1996 matched for patient's age and provider training level with 16 contemporaneously documented visits, (2) 16 of 18 pediatric level 1 residents and 14 of 16 pediatric level 2 residents who completed questionnaires, and (3) all electronic records of health maintenance visits during February 1997. MAIN OUTCOME MEASURES: The number of data elements documented and the percentage of records that record specific components of the health maintenance encounter. User satisfaction was specified on a Likert scale. RESULTS: Overall, residents in the ST records group documented more data elements per visit than did those in the unstructured records group. The number of developmental items documented was 11.5 per visit in the ST records group and 4.8 per visit in the unstructured records group (P = .004). Likewise, anticipatory guidance was more thoroughly documented in the ST records group--8.3 items per visit vs 2.5 items per visit (P < .001). Ninety percent of the users preferred the ST records. One year after the adoption of the ST recording system, high levels of thoroughness persisted. CONCLUSIONS: Structured, scannable encounter forms can facilitate documentation of patient care and are well accepted by users. They can provide an effective mechanism to ease the transition to a computer-based patient record.

Computers↗
PubMed1997

A de nevo complex t(7;13;8) translocation with a deletion in the TRPS gene region.

Molecular cytogenetic analyses have resolved the pathogenetic aberration of an 8-year-old girl with tricho-rhino-phalangeal syndrome type I (TRPS I), normal intelligence, and a karyotype originally described as 46,XX,t(8;13)(q24;q21). R- and Q-banding and high resolution R-banding analyses have also disclosed a seemingly mosaic abnormality of the distal short arm of chromosome 7 but have not fully characterized this abnormality. Combined primed in situ labelling and chromosome painting, and three-colour chromosome painting have revealed a complex, apparently balanced translocation t(7;13;8). Fluorescence in situ hybridization with yeast artificial chromosome and cosmid clones from 8q24.1 has shown an interstitial deletion of at least 3 Mb covering most of the TRPS I critical region.

Child↗
PubMed1997

A patient with Edwards syndrome caused by a rare pseudodicentric chromosome 18 of paternal origin.

We present an unusual case of trisomy 18 due to a pseudodicentric chromosome 18 of paternal origin. The karyotype was: 46,XY, -18, +psu dic(18)(qter-->cen-->p11.31::p11.31-->psucen-->qter). The origin of the abnormal chromosome was verified by FISH with a painting probe from chromosome 18. Absence of short-arm telomeres was shown by multicolor FISH, and the results of DNA analysis showed monosomy for loci D18S59 and D18S170 as well as paternal inheritance of the aberrant chromosome. The child's phenotype was characteristic of trisomy 18.

Centromere↗
PubMed1997

Visualizing the logic of a clinical guideline: a case study in childhood immunization.

IMM/Graph is a visual model designed to help knowledge-base developers understand and refine the guideline logic for childhood immunization. The IMM/Graph model is domain-specific and was developed to help build a knowledge-based system that makes patient-specific immunization recommendations. A "visual vocabulary" models issues specific to the immunization domain, such as (1) the age a child is first eligible for each vaccination dose, (2) recommended, "past due" and maximum ages, (3) minimum waiting periods between doses, (4) the vaccine brand or preparation to be given, and (5) the various factors affecting the time course of vaccination. Several lessons learned in the course of developing IMM/Graph include the following: (1) The intended use of the model may influence the choice of visual presentation; (2) There is a potentially interesting interplay between the use of visual and textual information in creating the visual model; (3) Visualization may help a development team better understand a complex clinical guideline and may also help highlight areas of incompleteness.

Child, Preschool↗
PubMed1996

Primed IN situ labelling (PRINS) as a rational procedure for identification of marker chromosomes using a panel of primers differentially tagging the human chromosomes.

PRimed IN Situ labelling (PRINS) is a highly specific and sensitive technique for detecting DNA sequences on human chromosomes in situ. PRINS is currently being introduced for research and routine analysis in clinical and cancer genetics. In this paper, we report a rational PRINS procedure for the rapid identification of marker chromosomes. Using this method it is possible to test a sample from a patient with up to eight different primers simultaneously on one slide. We have synthesized oligonucleotide primers that can differentially tag the human chromosomes, and with the protocol presented in this report we are able to identify the chromosomal origin of a marker chromosome within 2 hours.

Amniocentesis↗
PubMed1995

[Hereditary motor and sensory neuropathy (Charcot-Marie-Tooth disease). Molecular-genetic aspects].

Hereditary motor and sensory neuropathy (HMSN) comprises a heterogenous group of peripheral neuropathies which are classified on the basis of symptoms, mode of inheritance and electrophysiological and neuropathological investigations. HMSN type I, or Charcot-Marie-Tooth disease (CMT) type 1, is a hypertrophic and demyelinating neuropathy with reduced nerve conduction velocity, and most often with dominant inheritance. HMSN type II (CMT type 2), the neuronal or axonal form, is dominantly inherited with normal or only moderately reduced nerve conduction velocity. HMSN type III, also called Déjérine-Sottas disease, is a hypertrophic neuropathy with markedly reduced nerve conduction velocity. HMSN type I is genetically heterogenous with at least four autosomal loci and at least two X-linked loci. The most frequent form, HMSN type Ia, is associated with a specific duplication on chromosome 17, which can be detected by DNA-analysis. The genes for HMSN type Ia, Ib and an X-linked dominant form have been identified as PMP22, MPZ and GJB1 respectively. Analysis for these molecular defects will become important in the differential diagnosis of peripheral neuropathies and will surely prove invaluable in the genetic counselling of the families.

Charcot-Marie-Tooth Disease↗
PubMed1995

Simultaneous detection of centromere-specific probes and chromosome painting libraries by a combination of primed in situ labelling and chromosome painting (PRINS-painting).

In situ techniques for the detection of specific chromosomes using centromeric probes and the decoration of entire chromosomes using chromosome painting are well established. However, in the deciphering of complex chromosomal aberrations it is valuable to be able to detect the centromere and the entire DNA of a specific chromosome in different colours simultaneously on the same metaphase. In this report we describe a combination of the primed in situ labelling (PRINS) technique and chromosome painting for simultaneous visualization of centromere-specific oligonucleotides and chromosome painting libraries. A key feature is that the denaturation step in the PRINS reaction is sufficient to keep the chromosomes denatured for chromosome painting. This means that PRINS and consecutive chromosome painting can be performed as a single procedure (PRINS-painting).

Centromere↗
PubMed1995

Epidemic streptococcal disease among Army trainees, July 1989 through June 1991.

Outbreaks of group A streptococcal infection occurred at four of seven US Army basic training installations between 1 July 1989 and 30 June 1991. Study data were collected through a respiratory disease surveillance program and on-site epidemiologic investigations. Although hospitalizations were frequent (range, 191-334) during each outbreak, average rates of hospitalization were low (2.4-4.8 hospitalizations/1000 trainees/week). Outbreak-associated morbidity included streptococcal toxic shock syndrome (2 cases, 1 fatal), acute rheumatic fever (6), acute glomerulonephritis (1), scarlet fever (1), and numerous other invasive sequelae. Four serotypes of Streptococcus pyogenes (M-1, -3, -5, and -18) were identified; M-18 caused significant disease at 2 installations. Disease control was rapidly achieved through prophylaxis programs using benzathine penicillin G in nonallergic trainees. These outbreaks extend other reports that document an evolution of the nature and severity of circulating S. pyogenes in the United States.

Disease Outbreaks↗
PubMed1994

Charcot-Marie-Tooth disease type 1A: the parental origin of a de novo 17p11.2-p12 duplication.

Charcot-Marie-Tooth disease type 1A (CMT1A) is an autosomal dominant peripheral neuropathy associated with a DNA duplication on chromosome 17p11.2-p12 in the majority of cases. Most of the sporadic cases are due to a de novo duplication. We have screened for this duplication in 11 Danish patients with CMT type 1, using four different techniques, and identified a de novo duplication in a sporadic case. Analysis of the fully informative pVAW409R3a alleles in this family showed the duplication to be of paternal origin.

Adult↗
PubMed1994

Pseudodicentric chromosome 18 diagnosed by chromosome painting and primed in situ labelling (PRINS).

We report on a newborn white male infant with marked dysmorphic features and various congenital malformations. The initial clinical evaluation showed Crouzon-like features as well as some features of trisomy 18 syndrome and trisomy 13 syndrome. The results from conventional cytogenetic analysis showed a structurally abnormal chromosome replacing one normal chromosome 18, but only by applying molecular cytogenetic methods could the architecture of this abnormal chromosome be characterised clearly. The primed in situ labelling (PRINS) technique, using a newly synthesised alpha 18 oligonucleotide, showed the dicentric pattern and direct chromosome painting established the origin to be from chromosome 18. The combination of conventional cytogenetics and molecular cytogenetics showed the karyotype in the proband to be 45,XY,-14,-18,-21,+t(14;21),+psu dic(18) (qter-->cen-->p11.3: :p11.3-->psu cen-->qter). This was supported by molecular analysis using chromosome 18 specific DNA markers, which showed the paternal origin of the abnormal chromosome.

Abnormalities, Multiple↗
PubMed1994

Value of chromosome painting in determining the chromosomal outcome in offspring of a 12;16 translocation carrier.

We currently use direct and reverse chromosome painting in prenatal diagnosis. In a family with a subtle 12;16 translocation, adjacent 1 segregation was diagnosed in the first child, a boy, in whom symptoms compatible with partial trisomy 16p and partial monosomy 12q were seen. In the next pregnancy, a chorionic villus biopsy was tested using chromosome painting. Only by supplementing conventional cytogenetic methods with molecular cytogenetic techniques could the true karyotype be unequivocally determined. Reverse painting, using DOP-PCR amplified, flow sorted paternal derivative chromosomes as a DNA library to paint the chorionic villus cells, was especially informative.

Abnormalities, Multiple↗
PubMed1994

Fast, sensitive multicolor detection of nucleic acids in situ by PRimed IN Situ labeling (PRINS).

PRimed IN Situ labeling (PRINS) has become an alternative to traditional fluorescence in situ hybridization (FISH) methods for detection of nucleic acids in situ. PRINS is based on sequence-specific annealing in situ of an unlabeled DNA probe. The probe serves as a primer for chain elongation in situ, catalyzed by a suitable DNA polymerase that uses labeled nucleotides as substrate. The fact that the probe is unlabeled means that high probe concentrations can be utilized, making the hybridization very fast. We describe here a fast method for detection of three different target sequences visualized in different colors with PRINS. An advantage, relative to FISH, is that even probes with different melting temperatures can be detected in the same metaphase with optimal stringency for each probe.

DNA Probes↗