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Biomedical subjects

A Sandberg

Publications and source records attributed to A Sandberg.

At least 19 recordsLinked to original sources
PubMed2002

A Bayesian attractor network with incremental learning.

A realtime online learning system with capacity limits needs to gradually forget old information in order to avoid catastrophic forgetting. This can be achieved by allowing new information to overwrite old, as in a so-called palimpsest memory. This paper describes an incremental learning rule based on the Bayesian confidence propagation neural network that has palimpsest properties when employed in an attractor neural network. The network does not suffer from catastrophic forgetting, has a capacity dependent on the learning time constant and exhibits faster convergence for newer patterns.

Bayes Theorem↗
PubMed2001

NIH symposium summary: organ preservation therapies for squamous cancers of the head and neck.

This symposium, sponsored by the NIH Office of Rare Diseases, the National Cancer Institute, the National Institute of Deafness and Other Communication Disorders, and the National Institute of Dental and Craniofacial Diseases, reviewed the current status of organ preservation therapies for head and neck cancers, as well as promising newer approaches for therapy and for toxicity amelioration.

Carcinoma, Squamous Cell↗
PubMed2000

Electrophysiologic evaluation of muscle fatigue development and recovery in late polio.

OBJECTIVES: To study aspects of fatigue in late-polio patients and healthy controls. We hypothesized that late-polio subjects would develop more peripheral fatigue, assessed with surface electromyography (EMG), and that no major differences would exist between the two groups in neuromuscular junction transmission. DESIGN: Case-control study. SETTING: University hospital laboratory. SUBJECTS: Ten patients with a history of polio (mean age, 54 yrs, SD = 5; mean time since polio onset, 49 yrs, SD = 7) and a matched control group (mean age, 52 yrs, SD = 8). METHODS: A protocol with a stepwise force increase up to 80% of maximal voluntary contraction ending with an 8-minute recovery period was performed twice, first with surface EMG and then with electrical stimulation and surface-recorded evoked M-response. MAIN OUTCOME MEASURES: Surface EMG analysis of voluntary activity and evoked M-response. RESULTS: No significant differences existed between groups in the relative decrease during the fatigue protocol. The recovery of force was slower in the late-polio subjects. A reduction in the root mean square (RMS) value during recovery was seen in the polio group, although a normalization of the mean power frequency (MPF) was seen in both groups. CONCLUSION: The weakness during the fatigue procedure was not caused by neuromuscular blockade, because electrical nerve stimulation evoked a normal response. The weakness after exercise was the result of a slow recovery that may reflect both central and peripheral fatigue.

Case-Control Studies↗
PubMed1999

Comparison between concentric needle EMG and macro EMG in patients with a history of polio.

OBJECTIVES: Acute poliomyelitis causes degeneration of anterior horn cells, followed by denervation. Reinnervation and muscle fibre hypertrophy are mechanisms that compensate this loss of neurones. Concentric needle EMG (CNEMG) and macro EMG are two methods to assess the magnitude of initial involvement and the compensatory reinnervation. The aim of this study is to explore the difference between CNEMG and macro EMG describing the status of the motor unit in patients previously affected by polio. METHODS: Macro and concentric needle EMG investigations were performed in 261 muscles in 121 patients with a remote history of polio. RESULTS: CNEMG was abnormal in 211 muscles, macro EMG was abnormal in 246 muscles. The macro amplitude was 3-4 times 'more abnormal' than CNEMG amplitude relative to the reference values. CNEMG duration was less abnormal and showed only weak correlation with macro amplitudes. The most likely explanation for the difference in magnitude of deviation from reference values for CNEMG and macro EMG, is a more pronounced 'phase cancellation' between single fibre action potentials in CNEMG. This is supported by simulation studies reported here. CONCLUSIONS: In conclusion macro EMG better reflects the size of the motor unit than the CNEMG. For detection of concomitant disorders, CNEMG is the method of choice.

Action Potentials↗
PubMed1998

Motor unit size estimation of enlarged motor units with surface electromyography.

Surface EMG is hardly used to estimate motor unit (MU) characteristics, while its non-invasiveness is less stressful for patients and allows multi-electrode recordings to investigate different sites of the muscle and MU. The present study compares motor unit potentials (MUPs) obtained with surface EMG and macro EMG during voluntary contraction of the biceps brachii muscle of patients with enlarged MUs caused by prior poliomyelitis. Averaged surface MUPs were obtained by means of needle EMG (SMUP1) and surface EMG (SMUP2) triggering. The MUPs area and peak amplitudes correlated well when comparing the macro MUP and SMUP1 of the same MUs. When MU populations of different patients were compared, the SMUP1s and SMUP2s were equally sensitive to pathology as macro MUPs. In this, the late non-propagating positive wave (only present in unipolar recordings) is more robust than the triphasic propagating wave. Therefore, surface EMG can be used for detecting enlarged MUs.

Adult↗
PubMed1998

An 8-year longitudinal study of muscle strength, muscle fiber size, and dynamic electromyogram in individuals with late polio.

Twenty-one subjects with polio 24 to 51 years prior to the first examination were studied on three occasions, each 4 years apart with measurements of muscle strength and endurance for knee extension, macro EMG, and muscle biopsy from vastus lateralis. On average the muscle strength decreased during the 8-year follow-up by 9-15%. Endurance decreased during the observation period. The muscle fiber area was markedly increased in most subjects. There was a decrease in the capillarization during the follow-up. Macro EMG was increased in all subjects (range 3-42 times control) and increased in 20 legs during the 8-year follow-up, but showed a decrease in 8 of 9 legs with an approximative breakpoint when macro MUPs were around 20 times the normal size. Thus, evidence of on-going denervation/reinnervation as well as of failing capacity to maintain large motor units was demonstrated. SFEMG showed a moderate degree of disturbed neuromuscular transmission.

Adult↗
PubMed1998

Pre-clinical evaluation of probes to detect t(8;21) AML minimal residual disease by fluorescence in situ hybridization.

The 8;21 translocation in acute myeloid leukemia (AML) results in a consistent fusion transcript, AML1/ETO. Long-term clinical remission occurs in some patients despite incomplete eradication of AML1/ETO as demonstrated by RT-PCR, thus limiting the usefulness of this assay. An important future goal will be to determine if there is a level of minimal residual disease (MRD) in patients below which relapse is unlikely. For the detection of MRD, we have developed reagents for fluorescence in situ hybridization (FISH) that identify both derivative 8 and 21 chromosomes with a high analytical sensitivity. In t(8;21) AML cells, two fused signals were detected in addition to the normal 8 and 21 alleles. The sensitivity and specificity of this probe mixture were analyzed in cell lines and patient bone marrows. One and two randomly juxtaposed signals were observed in 2.4 and 0.04% of normal cells, respectively. However, these were easily differentiated from t(8;21) cells by the absence of signals from the normal alleles. Using as criteria the presence of two fused signals plus the normal alleles, we observed no false positives among 5,000 normal cells. The probe correctly identified 20/20 patients with t(8;21) AML and 10/10 non-t(8;21) patients. In cell dilution experiments, the analytical sensitivity of this reagent was equal to that of the X chromosome and Y chromosome alpha-satellite probes. These optimized probes should facilitate the quantitative assessment and study of MRD in t(8;21) AML.

Bone Marrow Cells↗
PubMed1994

Post-decision consolidation, as a function of the instructions to the decision maker and of the decision problem.

The effects of instructions and decision problems on post-decision processes were studied by varying the instructions to subjects. Subjects made a medical policy decision based on information on four attributes in Experiments 1-2. The subjects were given different instructions: (1) no instruction at all about a second session, (2) instruction to remember his/her decision until a session a week later, and (3) instruction to justify the decision at a later occasion one week later. The results indicated post-decision consolidation in the first group, as predicted by the Differentiation and Consolidation Theory (Svenson, 1992). The effect showed up in attractiveness restructuring in support of the chosen alternative on the most important attributes. The instruction to remember the decision until a later time increased the consolidation effect. Contrary to our expectations, the instruction to later justify the decision did not produce any consolidation. This effect was replicated in the second experiment and could not be interpreted as a random result. In a third experiment the decision problem was framed as an environmental pollution problem and it was preceded by a carefully designed booklet presenting arguments for and against different materials used in manufacturing packages for coffee. Subjects were then asked to make a choice of the same coffee in two different packages. The data indicated no difference in structural consolidation as a result of the instruction to justify or not. The paper concludes with a discussion pointing out the importance of the involvement in a decision task for decision differentiation and consolidation.

Adolescent↗
PubMed1993

Steady-state bioavailability and day-to-day variability of a multiple-unit (CR/ZOK) and a single-unit (OROS) delivery system of metoprolol after once-daily dosing.

Steady-state bioavailability and day-to-day variability of plasma levels were evaluated in 18 healthy male subjects in a crossover study of multiple once-daily administration of two novel oral drug delivery systems of metoprolol and an immediate-release tablet (100 mg metoprolol tartrate). Data were collected over two consecutive 24-hr dosing intervals on treatment days 6 and 7. The two extended-release formulations investigated were metoprolol CR/ZOK (95 mg metoprolol succinate), a multiple-unit system consisting of several hundred membrane-coated delivery units, and metoprolol OROS (95 mg metoprolol fumarate), a single-unit osmotic delivery system. The extended drug release and absorption observed after administration of metoprolol CR/ZOK and metoprolol OROS resulted in similar steady-state plasma concentrations after once-daily dosing. Compared to the immediate-release tablet, they produced considerably lower plasma peaks, three- to fourfold higher trough concentrations, 8-9 hr longer mean residence times, and 20% lower relative bioavailability. Moreover, the two once-daily metoprolol products were found bioequivalent in Cmax and AUC based on 90% confidence intervals for the mean ratio CR/OROS. Repeated plasma concentration measurements on two consecutive 24-hr periods suggested that all three metoprolol treatments produced reproducible and consistent plasma concentrations from day to day at steady state. Assessment of day-to-day variability, however, resulted in significantly lower variation in AUC for the multiple-unit CR/ZOK formulation compared to the single-unit OROS tablet. These results imply that there may be formulation-related differences in the in vivo behavior of the two products despite their being bioequivalent in extent and rate of absorption.

Adult↗
PubMed1991

Controlled release metoprolol. Clinical pharmacokinetic and therapeutic implications.

Metoprolol is a relatively beta 1-selective beta-blocker used extensively to treat hypertension and angina and as a prophylaxis after myocardial infarction. Conventional formulations are usually administered twice daily and the drug has a tendency to lose its selectivity of action at higher plasma concentrations. Two controlled release formulations, metoprolol CR and metoprolol 'Oros', have made it possible to achieve sustained beta 1-blockade over an entire 24h period and to minimise the loss of selectivity associated with higher plasma concentrations. The CR formulation has been extensively investigated and is the major subject of this review. The 'Oros' formulation is pharmaceutically different from the CR, yet both produce similar plasma concentration profiles and comparable beta 1-blocking effects. The availability of these preparations occurs at a time when increasingly persuasive data are becoming available on the cardioprotective or coronary preventive action of metoprolol.

Biological Availability↗
PubMed1990

Pharmacokinetic and biopharmaceutic aspects of once daily treatment with metoprolol CR/ZOK: a review article.

In the development of a new controlled release preparation and its subsequent assessment there are a number of factors that need to be considered both related to the drug itself and to the pharmaceutical preparation. This review describes the biopharmaceutical and pharmacokinetic properties of metoprolol CR/ZOK, a recently introduced formulation of a widely used beta 1-selective adrenoceptor antagonist intended for once daily usage. The metoprolol CR/ZOK preparation provides reproducible dissolution and absorption properties resulting in stable plasma concentrations with minimum fluctuations over a 24-hour dosage interval. This has been shown in extensive studies comprising over 200 healthy volunteers. Considerations for a new drug preparation such as bioavailability and variability in relation to a standard treatment and the clinical significance of taking the drug with food and in increasing doses, are potential concerns that do not seem to be a problem for the therapeutic use of metoprolol CR/ZOK. Furthermore, the pharmacokinetic data achieved in young healthy subjects appear to be relevant for the treatment of patients, as shown by the consistent plasma concentration profiles obtained in elderly and in hypertensive patients.

Biopharmaceutics↗
PubMed1990

Pharmacokinetic and pharmacodynamic evaluation of metoprolol controlled release (CR/ZOK) 50 mg in young subjects.

In this steady state, cross-over study, the bioavailability and beta 1-blocking effects of metoprolol CR/ZOK 50 mg, conventional metoprolol 50 mg tablets and placebo were evaluated in 12 healthy male subjects (mean age 25 years) after once daily treatment in 5 days. The drugs were administered in a randomized order. The beta 1-blocking effect was defined as percent reduction from baseline in exercise heart rate. The plasma concentration-time profile following metoprolol CR/ZOK 50 mg administration was more even compared to conventional metoprolol tablets, with significantly lower Cmax (mean: 71 vs 221 nmol/L) and significantly higher Cmin (mean: 39 vs 6 nmol/L) for the CR/ZOK formulation. This difference in plasma concentrations was also well reflected by a significantly lower fluctuation index for metoprolol CR/ZOK 50 mg compared with the conventional 50 mg tablet (mean: 69 vs 529%). There was, however, no difference in systemic bioavailability between the two metoprolol formulations (90% confidence limits: 86-106%). The beta 1-blockade was also more even after metoprolol CR/ZOK 50 mg compared to conventional tablets with a significantly lower Emax (mean: 14 vs 19%) and higher Emin (mean: 9 vs 0%) for CR/ZOK. The total effect over a dosage interval, defined as area under the effect curve, was significantly higher for metoprolol CR/ZOK compared to conventional tablets (90% confidence limits: 123-213%). In conclusion, once daily administration of metoprolol CR/ZOK 50 mg to young healthy subjects resulted in smooth plasma concentration and produced a significant beta 1-blocking effect for 24 hours.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

The relationship between metoprolol plasma concentration and beta 1-blockade in healthy subjects: a study on conventional metoprolol and metoprolol CR/ZOK formulations.

Four studies using different daily doses (100 mg, 200 mg, 300 mg and 400 mg) have examined the bioequivalence of the once daily formulation metoprolol CR/ZOK and conventional metoprolol tablets (CT). These studies showed metoprolol CR/ZOK to have a similar beta 1-blocking activity to metoprolol CT but that the bioavailability of the new formulation was lower. This paper presents the analysis of data from all four studies, looking at the relationship between plasma concentrations and beta 1-blockade measured as reduction of exercise induced tachycardia. The log linear pharmacodynamic model was used for each of the four doses to compare the two formulations. Mean slopes and intercepts in the linear regression analysis of log plasma concentration of metoprolol versus beta 1-blockade did not differ significantly between CR/ZOK and CT in any of the four studies. After having shown lack of influence of the absorption rate of the plasma concentration-effect relationship, data for CR/ZOK and CT formulations from the 200 mg study were pooled for each individual subject and fitted to an Emax model. The maximal beta 1-blocking effect (Emax) was 28% (95% confidence interval: 25-31%) and the plasma concentration for obtaining 50% of Emax (C50) was 105 nmol/L (95% confidence interval: 74-135 nmol/L). The plasma concentration-effect data from the 100 mg, 300 mg and 400 mg studies were reasonably well within the 95% prediction interval based on the 200 mg study, which showed the validity of the obtained relationship.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1988

Design of a new multiple-unit controlled-release formulation of metoprolol--metoprolol CR.

A new controlled-release (CR) formulation of the beta 1-selective adrenoceptor antagonist metoprolol has been developed, aiming at an even 24-h pharmacological effect. In order to achieve this, using a once-daily dose, factors such as absorption characteristics, physicochemical properties, and technological aspects had to be considered. The new formulation, called metoprolol CR, is a disintegrating tablet consisting of several hundred coated pellets of metoprolol succinate, each pellet being its own CR delivery unit. In vitro testing and in vivo studies in healthy volunteers show that the new CR formulation gives continuous delivery of metoprolol throughout the day, resulting in smooth plasma concentration profiles, without peaks and troughs. The release of the drug is independent of pH and other physiological variables, such as food intake, which do not seem to alter the biopharmaceutical properties of the formulation.

Delayed-Action Preparations↗
PubMed1988

Pharmacokinetic and pharmacodynamic properties of a new controlled-release formulation of metoprolol: a comparison with conventional tablets.

The pharmacokinetic and pharmacodynamic properties of a new multiple-unit, controlled-release (CR) formulation of metoprolol (metoprolol succinate, 95 mg once daily), which has almost constant (zero-order) release properties over most of a 24-h dose interval, have been compared with those of conventional metoprolol tablets (metoprolol tartrate, 100 mg once daily and 50 mg twice daily), in 12 healthy male volunteers. The steady-state plasma concentrations of metoprolol after five days of treatment varied less throughout the day with the CR than with the conventional formulation. This was associated with a considerably lower peak plasma concentration and the achievement of a significantly higher plasma concentration at the end of the dose interval. Similarly, the effect on exercise-induced tachycardia was maintained at a relatively constant level throughout the day after treatment with the CR formulation. A significantly greater effect 24 h after administration was achieved with the CR formulation, when compared with once-daily dosing with metoprolol tablets, 100 mg. Twice-daily dosing with metoprolol tablets, 50 mg, produced a similar beta 1-blocking effect at the end of the dose interval to that observed with metoprolol CR. Although the steady-state plasma concentrations indicated significantly lower systemic availability for the CR formulation, compared with both regimens of metoprolol tablets, the total effect over the dose interval, expressed as the area under the efficacy curve (AUEC), was similar for the three treatments. The relationship between steady-state plasma concentrations and the pharmacodynamic efficacy at corresponding times, indicated that plasma concentrations were more effectively utilized after the administration of the CR formulation than after the conventional tablet regimens.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Pharmacokinetics and pharmacodynamics of controlled-release metoprolol: a comparison with atenolol.

Pharmacokinetic and pharmacodynamic properties of a new controlled-release (CR) formulation of metoprolol have been compared with those of atenolol. Metoprolol CR (100 mg and 200 mg), atenolol (50 mg and 100 mg) and placebo were each given once daily for four days in a double-blind, cross-over study to ten healthy men. The plasma concentration-time profiles were more even with metoprolol CR than with atenolol over the 24-h dose interval, shown by the lower fluctuation ratio and the longer time period during which the plasma concentration exceeded 50% of the maximum concentration. All four active treatment regimens reduced exercise heart rate over the 24-h period compared with placebo. However, the reduction in both exercise heart rate and systolic blood pressure (SBP) was more even with metoprolol CR than with atenolol. The remaining beta 1-blockade after 24 h, expressed as the percentage reduction in exercise heart rate in relation to placebo, was significantly greater after the administration of metoprolol CR, 200 mg, than after either dose of atenolol. At this time the beta 1-blockade with metoprolol CR, 100 mg, was similar to that with atenolol, 100 mg. At peak plasma concentrations, 4 h after the dose, the subjects experienced less fatigue during exercise with metoprolol CR than with atenolol.

Adult↗
PubMed1987

Intensive remission consolidation therapy in the treatment of acute nonlymphocytic leukemia.

A pilot study was conducted to determine the possible efficacy and the toxicities associated with the administration of four courses of intensive consolidation chemotherapy to patients with acute nonlymphocytic leukemia in remission. All therapy was completed within 6 months. The median duration of remission was 22 months, with 45+% of patients in remission at 3 years and few relapses to date thereafter. Sixty percent of patients experienced significant side effects after each course of therapy. The therapy appeared to be particularly efficacious for patients less than 45 years of age, since 65% are alive at 3 years and there is no projection for a median duration of remission as yet. The cytogenetic characteristics of the leukemic cells, the percentage of S phase cells, and the height of the WBC count were the most important prognostic characteristics at diagnosis.

Acute Disease↗