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Biomedical subjects

R Miller

Publications and source records attributed to R Miller.

At least 217 records · Page 12Linked to original sources
PubMed1999

Factors influencing the population pharmacokinetic parameters of phenytoin in adult epileptic patients in South Africa.

The influence of various covariates (including weight, race, smoking, gender, age, mild-to-moderate alcohol intake, and body surface area) on the population pharmacokinetic parameters of phenytoin in adult epileptic patients in South Africa was investigated. The parameters were the maximum metabolic rate (Vm) and the Michaelis-Menten (MM) constant (Km) of phenytoin. The study population comprised 332 black and colored epileptic patients (note: "black" refers to indigenous people of South Africa, who speak one of the Bantu languages as their native language; "colored" refers to people considered to be of mixed race, classified as such by the apartheid former government of South Africa). The influence of covariates on Vm and Km estimates was determined using nonlinear mixed-effects modeling (NONMEM). Parameter models describing the factors that could potentially influence Vm and Km were tested using the Michaelis-Menten parallel MM and first-order elimination models, to which 853 steady state dose-to-serum concentration pairs were fitted. The results indicated that body weight, smoking, race, and age (65 years or older), in descending order of importance, significantly influenced Vm (p < 0.05). Although a significant difference (p = 0.03) in Km was found between black and colored patients, incorporating the influence of race in Km in the final regression model did not improve the fit of the model to the data, which indicated that the variability in Km was accounted for by Vm. The scaling factors for smoking, colored patients and age (65 years or older) in Vm were 1.16, 1.10, and 0.88, respectively. These factors should be taken into account when adjusting phenytoin dose.

Adolescent↗
PubMed1999

Optimizing Shake-and-Bake for proteins.

Shake-and-Bake is a direct-methods procedure which has provided ab initio solutions for protein structures containing as many as 1000 independent non-H atoms. This algorithm extends the range of conventional direct methods by repetitively, unconditionally and automatically alternating reciprocal-space phase refinement with filtering in real space to impose constraints. The application of SnB to protein-sized molecules is significantly affected by the choice made for certain critical parameters, including the number of peaks used for density modification, the choice of phase-refinement method and the number of refinement cycles. The effects of parameter variation have been studied for six protein structures, all of which are solvable by Shake-and-Bake using data at 1.1 A or higher resolution. Solvability in the resolution range 1.2-1.4 A appears to be enhanced by the presence of heavier atoms (S, Cl). Furthermore, it appears that in this range the ratio of refinement cycles and triplet phase invariants to atoms in the structure must be increased. Large structures lacking atoms of any element heavier than oxygen also require non-traditional parameter values.

Methods↗
PubMed1999

Influences on clinical practice: the case of glue ear.

A case study of clinical practice in children with glue ear is presented. The case is part of a larger project, funded by the North Thames Research and Development Programme, that sought to explore the part played by clinicians in the implementation of research and development into practice in two areas: adult asthma and glue ear in children. What is striking about this case is the differences found in every area of the analysis. That is, diversity was found in views about diagnosis and treatment of glue ear; the organisation of related services; and in the reported practice of our interviewees, both between particular groupings of clinical staff and within these groupings. The challenge inherent in the case is to go beyond describing the complexity and differences that were found, and look for patterns in the accounts of practice and tease out why such patterns may occur.

Attitude of Health Personnel↗
PubMed1999

Changing clinical practice: views about the management of adult asthma.

A case study of clinical practice in adult asthma is presented. The case is part of a larger project, funded by the North Thames NHS Executive Research and Development Programme, that sought to explore the part played by clinicians in the implementation of research and development into practice in two areas: adult asthma and glue ear in children. The first case of glue ear in children was reported in a previous issue of this journal (Quality in Health Care 1999;8:99-107). Background information from secondary sources on the condition, treatment, and organisation and location of care is followed by an account of the results of semistructured interviews with 159 clinicians. The findings are reported in two sections: clinical management and the organisation of care, and clinicians' accounts of what, why, and how they introduce changes into their practice. The way clinicians talk about their learning, their expressed views on acceptable practice, and their willingness to change were shown to be informed by construction of legitimate and sufficient evidence, respected colleagues, and accumulated individual experience. There was little open acknowledgment of the influence of organisational factors in influencing practice. To investigate whether relationships between task performance and organisational arrangements found in other sectors apply to UK health, more robust measures by which performance can be evaluated are needed.

Adult↗
PubMed1999

Incidence rates of first-ever ischemic stroke subtypes among blacks: a population-based study.

BACKGROUND AND PURPOSE: The aim of this study was to determine the incidence rates of ischemic stroke subtypes among blacks. METHODS: Hospitalized and autopsied cases of stroke and transient ischemic attack among the 187 000 blacks in the 5-county region of greater Cincinnati/northern Kentucky From January 1, 1993, through June 30, 1993, were identified. Incidence rates were age- and sex-adjusted to the 1990 US population. Subtype classification was performed after extensive review of all available imaging, laboratory data, clinical information, and past medical history. Case-control comparisons of risk factors were made with age-, race-, and sex-matched control subjects. RESULTS: Annual incidence rates per 100 000 for first-ever ischemic stroke subtypes among blacks were as follows: uncertain cause, 103 (95% confidence interval [CI], 80 to 126); cardioembolic, 56 (95% CI, 40 to 73); small-vessel infarct, 52 (95% CI, 36 to 68); large vessel, 17 (95% CI, 8 to 26); and other causes, 17 (95% CI, 9 to 26). Of the patients diagnosed with an infarct of uncertain cause, 31% underwent echocardiography, 45% underwent carotid ultrasound, and 48% had neither. Compared with age-, race-, and sex- (proportionally) matched control subjects from the greater Cincinnati/northern Kentucky region, the attributable risk of hypertension for all causes of first-ever ischemic stroke is 27% (95% CI, 7 to 43); for diabetes, 21% (95% CI, 11 to 29); and for coronary artery disease, 9% (95% CI, 2 to 16). For small-vessel ischemic stroke, the attributable risk of hypertension is 68% (95% CI, 31 to 85; odds ratio [OR], 5.0), and the attributable risk of diabetes is 30% (95% CI, 10 to 45; OR, 4.4). For cardioembolic stroke, the attributable risk of diabetes is 25% (95% CI, 4 to 41; OR, 3.1). CONCLUSIONS: Stroke of uncertain cause is the most common subtype of ischemic stroke among blacks. Cardioembolic stroke and small-vessel stroke are the most important, identifiable causes of first-ever ischemic stroke among blacks. The incidence rates of cardioembolic and large-vessel stroke are likely underestimated because noninvasive testing of the carotid arteries and echocardiography were not consistently obtained in stroke patients at the 18 regional hospitals. Most small-vessel strokes in blacks can be attributed to hypertension and diabetes.

Black or African American↗
PubMed1999

A regulatory perspective on pharmacokinetic/pharmacodynamic modelling.

We present an integrated summary from statistical and pharmacological perspectives of pharmacokinetic/pharmacodynamic (PK/PD) modelling and its use in drug development and regulation for guiding appropriate dosing. An overview of the technical aspects of PK/PD modelling describes how structural models are constructed and refined using pharmacokinetic and pharmacodynamic principles and how random effects models are used to account for individual differences in desired (and undesired) responses due to patient characteristics. Lastly, we describe applications of PK/PD modelling for the purposes of drug labelling, for resolving a safety concern, and for improving therapeutic monitoring of anaesthetic depth during surgery.

Biometry↗
PubMed1999

Treatment of multiple glomangioma with tuneable dye laser.

BACKGROUND: Multiple glomangiomas are a rare clinical occurrence. In the past, various treatments have been proposed for eradication of these tumours. OBJECTIVE: An alternative and effective therapy for multiple glomangioma is proposed. RESULTS: The effective clinical response of multiple, painful, bluish-black lesions on the soles of the feet and the hands, diagnosed as multiple glomangioma, to flashlamp tuneable dye laser is reported. CONCLUSION: The flashlamp tuneable dye laser is an effective modality in the treatment of multiple glomangioma.

Adult↗
PubMed1999

Screening methods for thyroid hormone disruptors.

The U.S. Congress has passed legislation requiring the EPA to implement screening tests for identifying endocrine-disrupting chemicals. A series of workshops was sponsored by the EPA, the Chemical Manufacturers Association, and the World Wildlife Fund; one workshop focused on screens for chemicals that alter thyroid hormone function and homeostasis. Participants at this meeting identified and examined methods to detect alterations in thyroid hormone synthesis, transport, and catabolism. In addition, some methods to detect chemicals that bind to the thyroid hormone receptors acting as either agonists or antagonists were also identified. Screening methods used in mammals as well as other vertebrate classes were examined. There was a general consensus that all known chemicals which interfere with thyroid hormone function and homeostasis act by either inhibiting synthesis, altering serum transport proteins, or by increasing catabolism of thyroid hormones. There are no direct data to support the assertion that certain environmental chemicals bind and activate the thyroid hormone receptors; further research is indicated. In light of this, screening methods should reflect known mechanisms of action. Most methods examined, albeit useful for mechanistic studies, were thought to be too specific and therefore would not be applicable for broad-based screening. Determination of serum thyroid hormone concentrations following chemical exposure in rodents was thought to be a reasonable initial screen. Concurrent histologic evaluation of the thyroid would strengthen this screen. Similar methods in teleosts may be useful as screens, but would require indicators of tissue production of thyroid hormones. The use of tadpole metamorphosis as a screen may also be useful; however, this method requires validation and standardization prior to use as a broad-based screen.

Animals↗
PubMed1999

A phase I single-dose trial of gadolinium texaphyrin (Gd-Tex), a tumor selective radiation sensitizer detectable by magnetic resonance imaging.

Gadolinium Texaphyrin (Gd-Tex) is a radiation sensitizer with a novel mechanism of action that sensitizes both oxic and hypoxic cells, localizes selectively in tumors, and is detectable by magnetic resonance imaging (MRI). This Phase I single-dose trial of Gd-Tex administered concurrently with radiation therapy was carried out to determine the maximally tolerated dose (MTD), dose-limiting toxicities, pharmacokinetics, and biolocalization of Gd-Tex as determined by MRI. Adults with incurable cancers of any histology requiring radiation therapy were eligible. A single i.v. dose of Gd-Tex was followed at least 2 h later by radiation therapy. The Gd-Tex dose was escalated in cohorts of 3 to 5 patients. Thirty-eight patients (median age, 58 years; range, 35-77 years) with incurable cancers of the lung (26), cervix (3), or other solid tumors (9) received a total of 41 single administrations of Gd-Tex. The Gd-Tex dose was escalated from 0.6 to 29.6 mg/kg. Irradiated sites included the thorax, brain, pelvis, bone, soft tissue, and sites of nodal metastases. The MTD was 22.3 mg/kg, determined by reversible acute tubular necrosis as the dose-limiting toxicities. Gd-Tex selectively accumulated in primary and metastatic tumors as demonstrated by MRI. No increase in radiation toxicity to normal tissues was seen. The median half-life of Gd-Tex after single-dose administration is 7.4 h. This study demonstrates that Gd-Tex is well tolerated in doses below the MTD, and that there is selective biolocalization in tumors. The maximum recommended dose for single administrations is 16.7 mg/kg.

Adult↗
PubMed1999

Re-analysis of 2,4-D use and the occurrence of canine malignant lymphoma.

An independent scientific review panel had concerns involving study design, analysis and interpretation of results in a case-control study investigating the relationship between canine malignant lymphoma (CML) and the use of 2,4-D herbicide. To address these concerns, a re-analysis was done to examine 2,4-D use and its association with CML. This case-control study re-analyzed the data using the exposure definition used in the original study, re-analyzed the data using a redefinition of exposure, and conducted a dose-response analysis with the redefined exposure criteria. Our results agreed with the original author's analyses that no effects were found when stratifying by survey method and geographic region, and that there were no significant differences between separated and pooled control groups. However, we did not confirm a dose-response relationship between 2,4-D use and CML. Additionally, the occurrence of CML was not found significantly associated with the use of 2,4-D.

2,4-Dichlorophenoxyacetic Acid↗
PubMed1999

Effects of the Medicare Alzheimer's Disease Demonstration on nursing home entry.

STUDY QUESTION: Did the Medicare Alzheimer's Disease Demonstration, with its goal of improving caregiver outcomes through case management and subsidized community services, affect the nursing home entry rate of treatments with dementia compared to controls? DATA SOURCES: Interviews conducted at baseline and six months thereafter. Measures include date of nursing home entry, client and caregiver health, and income. STUDY DESIGN: The demonstration randomly assigned voluntary applicants into treatment and control groups. Treatment group cases were eligible for case management and for an 80 percent discount on community care benefits, up to about $600 per month. DATA COLLECTION: All cases received baseline and semi-annual assessment interviews for up to three years after enrollment. Analyses are among cases that remained in the demonstration for more than 30 days after enrollment (n = 8,095). PRINCIPAL FINDINGS: The intervention of case management and subsidized community service had no effect on nursing home entry rates for treatments overall, compared to those of controls, and few effects on treatment subgroups, with the exception of one site where it may have increased nursing home entry rates. CONCLUSIONS: Providing case management and subsidized community services with the goal of improving caregiver outcomes may have little effect on nursing home entry rates for people with dementia.

Adult↗
PubMed1999

Comparison of the Bayesian approach and a limited sampling model for the estimation of AUC and Cmax: a computer simulation analysis.

OBJECTIVES: To compare two limited sampling methods (Bayesian and the limited sampling model) for the estimation of AUC and Cmax following a single oral dose of a hypothetical drug. METHODS: The plasma concentration vs time data sets for 50 subjects using a linear one- or two-compartment pharmacokinetic model were generated by simulation. The limited sampling model (LSM) was developed using samples from 10 subjects using one or two time points. The simulated plasma concentrations were also used for Bayesian evaluation. Bayesian analysis was performed on Non-Mem and mean pharmacokinetic parameters used for simulation were assumed as population pharmacokinetic parameters. In addition a test drug was also used to compare the predicted AUC and Cmax for the two approaches. RESULTS: Both methods were validated in 40 subjects for the hypothetical drug and in 12 subjects for the test drug. Both methods provided good estimates of AUC and Cmax. CONCLUSION: The results indicate that the LSM is similar to the Bayesian method and may be used in lieu of the Bayesian approach in estimating AUC and Cmax using one or two samples in clinical settings without detailed pharmacokinetic studies.

Area Under Curve↗
PubMed1999

Presentation of ALS to the otolaryngologist/head and neck surgeon: getting to the neurologist.

Patients with early symptoms of bulbar amyotrophic lateral sclerosis (ALS) are usually referred to the otolaryngologist without a diagnosis. Careful examination of the speech quality and a physical exam, including the vocal cords, should be undertaken. The emotional state of the patient should be considered, and a diagnosis should not be offered before a neurologic consultation has been obtained. Patients with late symptoms of bulbar ALS almost always present with both significant speech and swallowing abnormalities. Evaluation can be difficult because many abnormalities are found on examination. Advanced progression of symptoms is a clear indication for rapid referral to a neurologist if a diagnosis has not already been made. Supportive and symptomatic care should be offered to the patient immediately. The University of Washington Neuromuscular Clinic for Speech and Swallowing Disorders has seen 600 new neurologic patients since 1986, 211 of whom were ALS patients. The introduction of percutaneous gastrostomy has greatly changed the management of ALS patients, and 75 patients have undergone this procedure (32% because of inadequate swallowing, 68% for declining vital capacity). Medical management to improve symptoms may be indicated before surgery. Surgical options for patients with late salivary presentation are uncommon and include removal of the submaxillary glands, tracheostomy, and laryngeal or salivary diversion procedures. Laryngectomy or laryngeal diversion procedures are only very rarely indicated. Although tracheostomy usually interferes with swallowing and worsens aspiration, it may rarely be indicated in patients with late airway presentation for glottic narrowing or artificial respiratory support. Symptomatic management of patients with bulbar ALS is usually best undertaken by a multidisciplinary clinic that can provide a physically and psychologically supportive environment.

Aged↗
PubMed1999

A programmable rules engine to provide clinical decision support using HTML forms.

The authors have developed a simple method for specifying rules to be applied to information on HTML forms. This approach allows clinical experts, who lack the programming expertise needed to write CGI scripts, to construct and maintain domain-specific knowledge and ordering capabilities within WizOrder, the order-entry and decision support system used at Vanderbilt Hospital. The clinical knowledge base maintainers use HTML editors to create forms and spreadsheet programs for rule entry. A test environment has been developed which uses Netscape to display forms; the production environment displays forms using an embedded browser.

Artificial Intelligence↗
PubMed1999

Phase-specific psychosocial interventions for first-episode schizophrenia.

Phase-specific psychosocial interventions for first-episode schizophrenia are outlined and described using examples from clinical practice with 68 patients. These interventions are based on the unique aspects of the first episode and patients' clinical states. Although schizophrenia may run an uneven and often unpredictable course, most patients experience three distinct phases: (1) the acute phase, (2) the healing phase, and (3) the maintenance phase. The timeliness of phase-specific interventions is crucial in helping both patients and families understand the illness, evaluate options, accept treatment, and adjust to changes in functioning and expectations.

Acute Disease↗
PubMed1999

A phase II trial of docetaxel (Taxotere) in hormone-refractory prostate cancer: correlation of antitumor effect to phosphorylation of Bcl-2.

Twenty-one patients with hormone refractory prostate cancer were enrolled to receive single-agent docetaxel (Taxotere; Rhône-Poulenc Rorer, Collegeville, PA) 75 mg/m2 intravenously every 21 days. Six patients consented to biopsies of the prostate tumor before and following the first cycle of chemotherapy and 11 patients underwent periodic blood collection for isolation of the mononuclear cell fraction. The toxicities of treatment were moderate but included eight episodes of grade III and two episodes of grade IV nonhematologic toxicity as well as seven episodes of grade III and 11 episodes of grade IV hematologic toxicity (primarily neutropenia, including four episodes of febrile neutropenia). An objective response of more than 50% reduction in prostate-specific antigen was observed in seven patients (38%) and more than half of the patients with symptomatic disease at the initiation of therapy had improvements on treatment. Radiographic or scintigraphic evidence of tumor regression was observed in six patients. Nine patients experienced a prolonged period of stable disease on treatment (median, six cycles). Tumor specimens are currently being analyzed for bcl-2 expression and phosphorylation. The current series confirms the substantial single-agent activity of docetaxel in hormone refractory prostate cancer and may help to further elucidate its mechanism of action at the molecular level.

Aged↗