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Biomedical subjects

B Heller

Publications and source records attributed to B Heller.

At least 19 recordsLinked to original sources
PubMed2005

AdaptFlow: protocol-based medical treatment using adaptive workflows.

OBJECTIVES: In many medical domains investigator-initiated clinical trials are used to introduce new treatments and hence act as implementations of guideline-based therapies. Trial protocols contain detailed instructions to conduct the therapy and additionally specify reactions to exceptional situations (for instance an infection or a toxicity). To increase quality in health care and raise the number of patients treated according to trial protocols, a consultation system is needed that supports the handling of the complex trial therapy processes efficiently. Our objective was to design and evaluate a consultation system that should 1) observe the status of the therapies currently being applied, 2) offer automatic recognition of exceptional situations and appropriate decision support and 3) provide an automatic adaptation of affected therapy processes to handle exceptional situations. METHODS: We applied a hybrid approach that combines process support for the timely and efficient execution of the therapy processes as offered by workflow management systems with a knowledge and rule base and a mechanism for dynamic workflow adaptation to change running therapy processes if induced by changed patient condition. RESULTS AND CONCLUSIONS: This approach has been implemented in the AdaptFlow prototype. We performed several evaluation studies on the practicability of the approach and the usefulness of the system. These studies show that the AdaptFlow prototype offers adequate support for the execution of real-world investigator-initiated trial protocols and is able to handle a large number of exceptions.

Clinical Protocols↗
PubMed2004

Gait, cost and time implications for changing from PTB to ICEX sockets.

The ICEX system (Ossur, Iceland), allows a socket to be manufactured directly onto the stump and is thought to provide improved comfort due to better pressure distribution whilst being easier to fit and manufacture. The aims of this project were to a) compare gait performance by measuring several gait characteristics, b) compare production and fitting times, c) investigate financial implications and d) attempt to gauge the amputees' subjective opinions of socket comfort. A randomised, controlled trial was conducted on 27 trans-tibial amputees with an existing patellar tendon bearing (PTB) socket on the Endolite system (Chas A. Blatchford, UK). Twenty one (21) subjects completed the study. Of these, 10 in the control group received new PTB sockets while 11 in the experimental group received ICEX. Gait analysis wearing existing sockets was performed and kinetic data obtained from a force plate. This was repeated with the new sockets after a 6 week period of adjustment. Mann-Whitney tests were used in statistical evaluations with a significance level of 5%. Subjects were asked to score their prosthesis for comfort using the Socket Comfort Score (Hanspal et al., 2003) and the frequency of visits for socket adjustments over a three-month period post-delivery of the sockets was recorded. This study demonstrates no significant difference in any of the gait parameters measured. Though the time required to manufacture a PTB prosthesis was found to be considerably longer than the ICEX, the overall cost for producing the ICEX was significantly greater. Subjects showed only minor comfort preference for the ICEX design and there was no significant difference in the mean number of visits for socket adjustments. In view of the considerable additional cost of providing ICEX and the lack of evidence of improvement in any parameter tested, the routine provision of ICEX prostheses to unselected trans-tibial amputees cannot be recommended.

Adolescent↗
PubMed2004

Standardized terminology for clinical trial protocols based on top-level ontological categories.

This paper describes a new method for the ontologically based standardization of concepts with regard to the quality assurance of clinical trial protocols. We developed a data dictionary for medical and trial-specific terms in which concepts and relations are defined context-dependently. The data dictionary is provided to different medical research networks by means of the software tool Onto-Builder via the internet. The data dictionary is based on domain-specific ontologies and the top-level ontology of GOL. The concepts and relations described in the data dictionary are represented in natural language, semi-formally or formally according to their use.

Clinical Trials as Topic↗
PubMed2001

Computer experiments to determine whether over- or under-counting necessarily affects the determination of difference in cell number between experimental groups.

Computer cell counting experiments were performed in order to examine the consequences of over- or under-counting. The three-dimensional reaggregate culture laboratory environment for cell counting was used as a model for computer simulation. The laboratory environment for aggregate and cell sizes, numbers and spatial placement in gelatin blocks was mimicked in the computer setup. However, in the computer, cell counting was set to be either ideally unbiased, or deliberately biased in regard to over- or under-counting so as to compare eventual results when using the various cell counting methods. It was found that there was no effect of the cell counting methods used in determining whether there was a significant difference in cell number between two experimental groups. In addition, it was found that under the conditions of these simulations, the optical dissector method behaved similarly, on the average, as the ideal method of counting cell centers and in both of those cases, the average ratio between actual cell number in a flask and estimated number was close to 1.00.

Animals↗
PubMed2001

A new hybrid spring brake orthosis for controlling hip and knee flexion in the swing phase.

In this study it is proposed that active contraction of muscles might be artificially replaced by a spring brake orthosis (SBO) to provide near-natural knee and hip swing phase trajectories for gait in spinal cord injured subjects. The SBO is a new gait restoration system in which stored spring elastic energy and potential energy of limb segments are utilized to aid gait. It is also shown that hip flexion can be produced without the need for withdrawal reflex, hip flexor stimulus or any mechanical actuator at the hip. A hip flexion angle of 21 degrees was achieved by a nonimpaired subject wearing a prototype orthosis.

Biomechanical Phenomena↗
PubMed2001

Wires should not be used routinely on skin scars for mammograms after breast-conserving surgery.

The accuracy of skin wire markers on surgical incision scars during mammography to locate the primary tumor excision site was prospectively determined for 100 women. The shortest distance between the excision site and skin scar wire on either the craniocaudal or mediolateral oblique projection was 10 mm or greater in 48 per cent of patients and 20 mm or greater in 30 per cent of patients. Wire markers placed on skin incision scars during mammography after breast-conserving surgery are inadequate for the localization of the primary excision site and should not be used routinely.

Breast Neoplasms↗
PubMed2001

Gender-dependent enhanced adult neurotoxic response to methamphetamine following fetal exposure to the drug.

Methamphetamine use by females of child-bearing age has become a major public health concern in terms of the long-term risk to the exposed fetus. We examined the possibility of enhanced adult neurotoxic potential of the drug in offspring that had been exposed to methamphetamine in utero during gestational days 7 to 18. While basal levels of monoamines were not affected by prenatal exposure to methamphetamine, we observed an enhanced neurotoxicity in adult male offspring following drug challenge with effects localized primarily to the dopaminergic nigrostriatal projection. This was evidenced by greater methamphetamine-induced reductions of dopaminergic markers in the striatum [dopamine (DA), dihydroxyphenylacetic acid, homovanillic acid (HVA), and 3-methoxytyramine (3-MT)] and ventral brainstem (DA) of prenatal methamphetamine-treated males compared with saline-treated animals. Some effects of prenatal methamphetamine exposure were observed in female offspring, but these were limited to striatal levels of 3-MT and HVA. Differential gender sensitivity to the neurotoxic effect of methamphetamine was shown to be correlated with hyperthermic response. Hyperthermic effects, however, do not account for the increased susceptibility of prenatal methamphetamine-treated males to drug-induced striatal DA neurotoxicity since methamphetamine challenge did not evoke a significantly greater hyperthermic response in these animals compared with prenatal saline-treated males. The findings raise the concern that male methamphetamine abusers may be at risk for an enhanced neurotoxic risk if they were exposed to the drug in utero.

Animals↗
PubMed2000

Evidence of elevated intracellular calcium levels in weaver homozygote mice.

1. A mutation in the G-protein-linked, inwardly rectifying K+ channel GIRK2 leads to the loss of cerebellar and dopaminergic mesencephalic neurons in weaver mice. The steps leading to cell death are not well understood but may involve constitutive influx of Na+ and Ca2+ into the neurons. 2. We found that resting [Ca2+]i was dramatically higher in cerebellar neurons from weaver mice compared to wild-type neurons. 3. High-K+ stimuli elicited much smaller changes in [Ca2+]i in weaver cerebellar neurons compared to wild-type neurons. 4. weaver cerebellar granule cells could be rescued from cell death by the GIRK2wv cationic channel blocker, QX-314. 5. QX-314 lowered resting intracellular Ca2+ levels in weaver cerebellar granule cells. 6. These results suggest that changes in resting [Ca2+]i levels and alterations in K+ channel function are most likely to contribute to the developmental abnormalities and increased cerebellar cell death observed in weaver mice.

Animals↗
PubMed2000

Cell-to-cell variation in store-operated calcium entry in HEK-293 cells and its impact on the interpretation of data from stable clones expressing exogenous calcium channels.

To investigate the effect of cell-to-cell variation in store-operated calcium entry (SOCE) on the evaluation of data from stable cell clones selected following gene transfection, we measured SOCE in 2700 individual HEK-293 cells from the parent population and in 1900 individual cells from a clonal subpopulation of HEK-293 cells. We applied statistical resampling techniques to model conditions where one would compare the average SOCE in n control clones to the average SOCE in n experimental clones (n = 1-200). For an overexpression experiment with n = 1, there is a 27% chance of observing a 100% or higher difference in SOCE between clones, with n = 10 there is a 34% probability of observing a 20% or greater difference in SOCE, and with n = 100, there is less than a 10% chance of seeing a 10% or greater difference in SOCE, based solely on random selection of clones from the parent HEK-293 cell population. To assure that the degree of cell-to-cell variation was predictive of the degree of clone-to-clone variation, we measured SOCE in 270 clones, each arising from a single cell, and found the variation to be very similar to that observed for individual cells.

Calcium↗
PubMed2000

Mammographic considerations for patients undergoing ancillary surgical procedures in the breast: a need for pre- and postoperative mammograms.

Mammographic evaluation of the pre- and postoperative breast has been primarily emphasized for patients undergoing diagnostic breast biopsies and breast-conserving surgery. There is limited literature addressing ancillary surgical procedures involving breast tissue that may complicate mammographic evaluation of the breasts during breast cancer screening. We present mammographic diagnostic dilemmas after ancillary surgical procedures in the breast. The placement and removal of devices, such as central venous access ports and pacemakers, may result in scarring that may appear suspicious for malignancy on mammography. In addition, the placement of devices can obscure lesions that are being followed mammographically. These cases illustrate the need for the application of a basic principle of breast surgery, that of pre- and postoperative mammography, to ancillary surgery of the breast to allow optimal mammographic evaluation of women who are breast screening candidates.

Adult↗
PubMed1999

Mice lacking the poly(ADP-ribose) polymerase gene are resistant to pancreatic beta-cell destruction and diabetes development induced by streptozocin.

Human type 1 diabetes results from the selective destruction of insulin-producing pancreatic beta cells during islet inflammation. Cytokines and reactive radicals released during this process contribute to beta-cell death. Here we show that mice with a disrupted gene coding for poly (ADP-ribose) polymerase (PARP-/- mice) are completely resistant to the development of diabetes induced by the beta-cell toxin streptozocin. The mice remained normoglycemic and maintained normal levels of total pancreatic insulin content and normal islet ultrastructure. Cultivated PARP-/- islet cells resisted streptozocin-induced lysis and maintained intracellular NAD+ levels. Our results identify NAD+ depletion caused by PARP activation as the dominant metabolic event in islet-cell destruction, and provide information for the development of strategies to prevent the progression or manifestation of the disease in individuals at risk of developing type 1 diabetes.

Animals↗
PubMed1997

In vitro evidence that the reduction in mesencephalic dopaminergic neurons in the weaver heterozygote is not due to a failure in target cell interaction.

The murine weaver (wv) mutation is characterized by a genetically determined loss of several neuronal populations, which include the nigrostriatal dopaminergic neurons. Animals homozygous for the wv gene exhibit marked deficits in dopaminergic morphological and neurochemical parameters. The wv gene shows incomplete dominance in that heterozygous (wv/+) mice exhibit moderate reductions in midbrain dopaminergic neuron number. It is unclear whether the dopaminergic neuronal loss in homozygous and heterozygous animals results from an effect of the wv gene solely on the dopaminergic neurons or is due to a failure of interaction of dopaminergic neurons with target cells of the striatum. This issue has been addressed utilizing three-dimensional reaggregate tissue cultures to determine whether the wv gene acts directly on the mesencephalic dopaminergic neurons. Embryonic mesencephalon and striatum from wv/+ and wild-type (+/+) brains were dissociated and the cells recombined into four mesencephalic-striatal aggregate combinations: (1) mesencephalic(+/+)-striatal(+/+)aggregates; (2) mesencephalic(wv/+)-striatal(wv/+)aggregates; (3) mesencephalic(wv/+)-striatal(+/+)aggregates; and (4) mesencephalic(+/+)-striatal(wv/+)aggregates. At 29 days and 57 days of culture, the number of dopaminergic neurons and dopamine content from mesencephalic-striatal aggregates consisting of mixed genotype or from only wv/+ tissue were quantitated and compared with that from mesencephalic-striatal cultures prepared from +/+ tissue alone. At both culture time points, aggregates containing wv/+ mesencephalon coaggregated with either wv/+ or +/+ striatum contained fewer dopaminergic neurons than mesencephalic-striatal cultures composed of only +/+ cells. Coaggregation of +/+ mesencephalon with wv/+ striatum did not have a detrimental effect on dopaminergic cell number. The findings demonstrate that the difference in the number of mesencephalic dopaminergic neurons between wv/+ and +/+ animals seen in vivo can be reproduced in three-dimensional reaggregate culture. Since the coculture of +/+ striatum with wv/+ mesencephalon did not appear to rescue wv/+ dopaminergic neurons in the aggregates as compared to wv/+ striatum and, wv/+ striatum proved to be a perfectly adequate target for +/+ mesencephalic dopaminergic neurons, it appears that the effect of the wv gene is on the dopaminergic neurons themselves.

Animals↗
PubMed1996

[Flupirtine in comparison with chlormezanone in chronic musculoskeletal back pain. Results of a multicenter randomized double-blind study].

METHOD: The analgesic and muscle-relaxing properties of flupirtine maleate, chlormezanone and placebo were compared in a total of 184 patients. Of these patients, 164 met the criteria of the treatment plan (intention to treat), and the data of 140 patients were finally evaluated in accordance with the test protocol. A positive response was defined as a reduction in pain intensity and muscle tension by 2 categories on the 5-category verbal scale "very severe/severe/moderate/mild/ none" on the seventh day of treatment. RESULTS: In the per-protocol-analysis the responder rate was 60.9% for flupirtine, 47.8% for chlormezanone, and 43.8% for placebo, the difference between drugs and placebo not being significant. The overall assessment of the physicians involved was very good/ good in 47.8% and satisfactory in 37.0% of the flupirtine group, very good/good in 45.6% and satisfactory in 17.4% of the chlormezanone group, the corresponding figures for the placebo group being 33.4% and 20.6%, respectively. Flupirtine was thus superior to placebo (p = 0.007). The incidence of adverse drug reactions was 14.8% (8/54) for flupirtine, 19.3% (11/57) for chlormezanone, and 7.3% (4/55) for placebo.

Adult↗