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Biomedical subjects

D P Lewis

Publications and source records attributed to D P Lewis.

12 recordsLinked to original sources

Two analytical solutions for a model of pulsed arterial spin labeling with randomized blood arrival times.

A fairly general theoretical model for pulsed arterial spin labeling perfusion methods has been available for some time but analytical solutions were derived for only a small number of arterial blood input functions. These mostly assumed a sudden and simultaneous arrival of the tagged blood into the imaged region. More general cases had to be handled numerically. We present analytical solutions for two more realistic arterial input functions. They both allow the arrival times of the molecules of tagged arterial blood to be statistically distributed. We consider cases of (1) a uniform distribution on a finite time interval and (2) a normal distribution characterized by its mean and standard deviation. These models are physiologically meaningful because the statistical nature of the arrival times reflects the distribution of velocities and path lengths that the blood water molecules undertake from the tagging region to the imaged region. The model parameters can be estimated from the measured dependency of the perfusion signal on the tag inversion time.

Algorithms↗

RF excitation profiles with FAIR: impact of truncation of the arterial input function on quantitative perfusion.

This study investigates the impact of imaging coil length and consequent truncation of the arterial input function on the perfusion signal contrast obtained in the flow-sensitive alternating inversion recovery (FAIR) perfusion imaging measurement. We examined the difference in perfusion contrast achieved with head, head and neck, and body imaging coils based on the hypothesis that the standard head coil provides a truncated input function compared with that provided by the body coil and that this effect will be accentuated at long inversion times. The TI-dependent cerebral response of the FAIR sequence was examined at 1.5 T by varying the TI from 200 to 3500 msec with both the head and whole body coils (n = 5) as well as using a head and neck coil (n = 3). Difference signal intensity DeltaM and quantitative cerebral blood flow (CBF) were plotted against TI for each coil configuration. Despite a lower signal-to-noise ratio, relative CBF was significantly greater when measured with the body or head and neck coil compared with the standard head coil for longer inversion times (two-way ANOVA, P < or = 0.002). This effect is attributed to truncation of the arterial input function of labeled water by the standard head coil and the resultant inflow of unlabeled spins to the image slice during control image acquisition, resulting in overestimation of CBF. The results support the conclusion that the arterial input function depends on the anatomic extent of the inversion pulse in FAIR, particularly at longer mixing times (TI > 1200 msec at 1.5 T). Use of a head and neck coil ensures adequate inversion while preserving SNR that is lost in the body coil.

Adult↗

Velocity sensitivity of slice-selective excitation.

The purpose of this study was to investigate how flow affects slice-selective excitation, particularly for radiofrequency (rf) pulses optimized for slice-selective excitation of stationary material. Simulation methods were used to calculate the slice profiles for material flowing at different velocities, using optimal flow compensation when appropriate. Four rf pulses of very different shapes were used in the simulation study: a 90 degrees linear-phase Shinnar-LeRoux pulse; a 90 degrees self-refocusing pulse; a minimum-phase Shinnar-LeRoux inversion pulse; and a SPINCALC inversion pulse. Slice profiles from simulations with a laminar flow model were compared with experimental studies for two different rf pulses using a clinical magnetic resonance imaging (MRI) system. We found that, for a given rf pulse, the effect of flow on slice-selective excitation depends on the product of the selection gradient amplitude, the component of velocity in the slice selection direction, and the square of the rf pulse duration. The shapes of the slice profiles from the Shinnar-LeRoux pulses were relatively insensitive to velocity. However, the slice profiles from the self-refocusing pulse and the SPINCALC pulse were significantly degraded by velocity. Experimental slice profiles showed excellent agreement with simulation. In conclusion, our study demonstrates that slice-selective excitation can be significantly degraded by flow depending on the velocity, the gradient amplitude, and characteristics of the rf excitation pulse used. The results can aid in the design of rf pulses for slice-selective excitation of flowing material.

Computer Simulation↗

Drug and environmental factors associated with adverse pregnancy outcomes. Part II: Improvement with folic acid.

OBJECTIVE: To provide a comprehensive review of periconceptional folic acid supplementation and factors affecting folate supplementation trials. DATA SOURCES: A MEDLINE search was conducted through December 1997. Additional sources were obtained from Current Contents and citations from the references obtained. Search terms included folate, folic acid, neural tube defect, spina bifida, and anencephaly. STUDY SELECTION: Relevant animal and human studies examining the effects of folate were reviewed. DATA EXTRACTION: Data collected included: type of study, folate dosing, dietary folate intake, serum and red blood cell folate concentrations, type of defect(s) studied, vitamin usage, parental risk factors, factors affecting trial results. DATA SYNTHESIS: Nine key factors have been identified that affect outcomes of folic acid supplementation trials. Daily doses of 0.8 mg decreased the occurrence and doses of 4 mg decreased the recurrence of neural tube defects in randomized clinical trials. Since lower folic acid doses were effective in nonrandomized trials, research is needed to determine the lowest effective dosage. Other benefits involving pregnancy outcome are suggested. CONCLUSIONS: Women of childbearing age should take a daily folic acid supplement to reduce the risk of pregnancies resulting in infants with a neural tube defect and other potential adverse pregnancy outcomes. Further health benefits from folic acid supplementation are reviewed in Part III of this series.

Animals↗

Drug and environmental factors associated with adverse pregnancy outcomes. Part III: Folic acid: pharmacology, therapeutic recommendations, and economics.

OBJECTIVE: To review folic acid's mechanism of action, adverse effects, therapeutic recommendations, compliance, and cost. DATA SOURCES: A MEDLINE search was conducted through December 1997. Additional sources were obtained from Current Contents and citations from the references obtained. Search terms included folate, folic acid, neural tube defect, homocysteine, and methylenetetrahydrofolate reductase. STUDY SELECTION: Animal and human studies examining the effects of folate were reviewed. DATA EXTRACTION: Data collected included mechanism of action, safety issues, dosing recommendations, compliance with recommendations, and economics. DATA SYNTHESIS: Folic acid decreases neural tube defect risk through an effect on methionine-homocysteine metabolism. In addition, increased folate intake may reduce cardiovascular morbidity and mortality. Since toxicity is minimal, everyone can potentially benefit from increased folate consumption. To help achieve this, the Food and Drug Administration has mandated that cereal grain be fortified with 140 micrograms of folic acid per 100 g of grain, which will add approximately 0.1 mg of folate to the average diet. Studies recommend supplementing with 0.2 mg to promote optimal homocysteine concentrations and for preventing neural tube defects. CONCLUSIONS: Despite fortification, most women will still receive less folate than the 0.4 mg/d recommended by the Public Health Service. All population groups would benefit from increased folate intake. Current studies indicate 200 micrograms/d may be the minimum effective amount of fortification needed for normalizing homocysteine concentrations and preventing a significant number of neural tube defects; thus, a higher level of food fortification may be warranted.

Environmental Exposure↗

Aspirin idiosyncrasy.

Aspirin idiosyncrasy is infrequently discussed in the dental literature. The severity of the case described illustrates the importance of complete familiarity with the syndrome. Because the patient who is sensitive to the drug may not volunteer this information, the dentist must include specific questions about asthma, nasal polyps, and adverse clinical reaction to aspirin in the initial interview of the patient. Suspicion of this idiosyncrasy will result in avoidance of aspirin; this may well prevent a life-threatening reaction. Acetaminophen is a safe alternative analgesic agent for such patients.

Aspirin↗

The coronary: "will I have another?".

Awareness by medical practitioners of the need to keep their patients adequately informed of their conditions is of paramount importance in caring for those people who have had a myocardial infarction. This includes a realization that these people have questions to be answered at all stages of the illness, from the initial contact when in pain, throughout the hospital admission, and during rehabilitation.

Adult↗

Phenytoin-folic acid interaction.

OBJECTIVE: To review information regarding the dual and interdependent drug-nutrient interaction between phenytoin and folic acid and other literature involving phenytoin and folic acid. DATA SOURCES: Information was retrieved from a MEDLINE search of English-language literature conducted from 1983 (time of the last review) to March 1995. Search terms included folic acid, phenytoin, and folic acid deficiency. Additional references were obtained from Current Contents and from the bibliographies of the retrieved references. STUDY SELECTION: All human studies examining the effects of phenytoin on serum folate concentrations and folic acid supplementation on serum phenytoin concentrations were selected. These included studies of patients with epilepsy and healthy volunteers as well as case reports. Case reports were included because of the extensive length of time needed to study this drug interaction. DATA EXTRACTION: Data extracted included gender, dosing, serum folate concentrations if available, pharmacokinetics, and adverse events. DATA SYNTHESIS: Serum folate decreases when phenytoin therapy is initiated alone with no folate supplementation. Folic acid supplementation in folate-deficient patients with epilepsy changes the pharmacokinetics of phenytoin, usually leading to lower serum phenytoin concentrations and possible seizure breakthrough. Folate is hypothesized to be a cofactor in phenytoin metabolism and may be responsible for the "pseudo-steady-state," which is a concentration where phenytoin appears to be at steady-state, but in reality, is not. Phenytoin and folic acid therapy initiated concomitantly prevents decreased folate and phenytoin obtains steady-state concentrations sooner. CONCLUSIONS: Folic acid supplementation should be initiated each time phenytoin therapy commences because of the hypothesized cofactor mechanism, decreased adverse effects associated with folate deficiency, and better seizure control with no perturbation of phenytoin pharmacokinetics.

Anticonvulsants↗

Drug and environmental factors associated with adverse pregnancy outcomes. Part I: Antiepileptic drugs, contraceptives, smoking, and folate.

OBJECTIVE: Part I of this review examines the relationship between antiepileptic drugs (AEDs) and pregnancy outcomes. Drug-induced folate deficiency and the role of AED metabolism are emphasized. Part II will discuss periconceptional folate supplementation for prevention of birth defects. Part III will discuss the mechanism of folate's protective effect, therapeutic recommendations, compliance, and cost. DATA SOURCES: A MEDLINE search was conducted for journal articles published through December 1997. Additional sources were obtained from Current Contents and citations from the references obtained. Search terms included phenytoin, carbamazepine, phenobarbital, primidone, valproic acid, oral contraceptives, clomiphene, drug-induced abnormalities, spina bifida, anencephaly, neural tube defect, folate, folic acid, and folic acid deficiency. STUDY SELECTION: Relevant animal and human studies examining the effects of AEDs, smoking, and oral contraceptives on folate status and pregnancy outcome are reviewed. DATA EXTRACTION: Studies and case reports were interpreted. Data extracted included dosing, serum and red blood cell folate concentrations, teratogenicity of anticonvulsant medications, metabolism of AEDs and folate, and genetic susceptibility to AED-induced teratogenicity. DATA SYNTHESIS: Low serum and red blood cell folate concentrations are associated with adverse pregnancy outcomes. Decreases in serum folate are seen with AEDs, oral contraceptives, and smoking. Since similar birth defects are observed with multiple AEDs, metabolism of aromatic AEDs to epoxide metabolites and genetic factors may play a role in teratogenesis. CONCLUSIONS: Adequate prepregnancy planning is essential for women who have epilepsy. Women receiving folate-lowering drugs may be at increased risk of adverse pregnancy outcomes. Therefore, epileptic women contemplating pregnancy should be treated with the minimum number of folate-lowering drugs possible and receive folic acid supplementation.

Anticonvulsants↗