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Biomedical subjects

J P Miller

Publications and source records attributed to J P Miller.

At least 19 recordsLinked to original sources
PubMed1992

Mild senile dementia of the Alzheimer type. 4. Evaluation of intervention.

The design of trials of interventions intended to slow or arrest the progression of senile dementia of the Alzheimer type must be based on analysis of the natural history of the disease. Using a random coefficients statistical model, we analyzed the natural history of senile dementia of the Alzheimer type in carefully defined subjects with mild disease (n = 68) for periods of up to 10 years. Subject performance was assessed longitudinally on batteries of clinical and psychometric measures. The characteristics of these measures were analyzed relevant to their utility as outcome measures for long-term trials in patients with senile dementia of the Alzheimer type. Estimates were made of sample sizes required to show arrest, and 50% or 25% slowing in the progression of mild disease. We suggest that a clinically relevant global measure, such as the Sum of Boxes of the Clinical Dementia Rating scale, and a performance-based clinical scale or psychometric measure would be appropriate in a 12- or 24-month trial enrolling subjects with mild senile dementia of the Alzheimer type.

Actuarial Analysis↗
PubMed1992

A comparison of two computer-administered versions of the NIMH Diagnostic Interview Schedule.

This study compared three versions of the NIMH Diagnostic Interview Schedule (DIS): "traditional" interviewer-administered DIS; computer-administered DIS (subject interacting alone with computer); computer-prompted DIS (interviewer using computer program as a guide). Kappas for 20 diagnoses ranged from .15 to .94, and averages for the three method pairs ranged from .57 to .64, which are comparable to other DIS reliability studies. Agreement between pairs of methods were comparable. Subjects' attitudes toward the computer interview were positive. While they felt they could better describe their feelings and ideas to a human, they found the computer contact less embarrassing. Overall, subjects had no preference for one method over another. Measures of social desirability and deviant response biases were correlated with diagnostic results. Reading ability did not affect subject's ability to respond to the DIS, although subjects with lower reading levels preferred the computer interview more.

Adult↗
PubMed1992

Intrarater reliability of manual muscle test (Medical Research Council scale) grades in Duchenne's muscular dystrophy.

The purpose of this study was to document the intrarater reliability of manual muscle test (MMT) grades in assessing muscle strength in patients with Duchenne's muscular dystrophy (DMD). Subjects were 102 boys, aged 5 to 15 years, who were participating in a double-blind, multicenter trial to document the effects of prednisone on muscle strength in patients with DMD. Four physical therapists participated in the study. Two identical (duplicate) evaluations were performed within 5 days of each other by the same examiner initially and after 6 and 12 months of treatment. A total of 18 muscle groups were tested on each patient, 16 of them bilaterally, using a modification of the Medical Research Council scale. Reliability of muscle strength grades obtained for individual muscle groups and of individual muscle strength grades was analyzed using Cohen's weighted Kappa. The reliability of grades for individual muscle groups ranged from .65 to .93, with the proximal muscles having the higher reliability values. The reliability of individual muscle strength grades ranged from .80 to .99, with those in the gravity-eliminated range scoring the highest. We conclude the MMT grades are reliable for assessing muscle strength in boys with DMD when consecutive evaluations are performed by the same physical therapist.

Adolescent↗
PubMed1992

Use of a modified shell vial technique to quantitate cytomegalovirus viremia in a population of solid-organ transplant recipients.

A quantitative modification of the shell vial assay was used to investigate cytomegalovirus viremia in solid-organ transplant recipients. The level of viremia detected in 109 of 407 specimens ranged from 0.02 to 28 infectious foci per 100,000 leukocytes. By using a Poisson model, a technique was developed to determine 95% confidence limits for the measured levels of viremia. These confidence limits were used to determine the level of viremia that could be excluded by culturing a given number of cells. Longitudinal assessment of two transplant recipients revealed different patterns of viremia and demonstrated that significant disease sometimes occurred with low-level viremia. On the basis of the results of the studies, culture of at least 4 x 10(6) leukocytes is recommended for the sensitive detection of cytomegalovirus viremia.

Cytomegalovirus↗
PubMed1992

Laboratory facilities for investigating lipid disorders in the United Kingdom: results of the British Hyperlipidaemia Association survey.

AIMS: To determine the availability of facilities for the investigation of hyperlipidaemia in the United Kingdom. METHODS: A questionnaire was sent to all health districts in the United Kingdom. RESULTS: The response rate was 81%. All laboratories used enzymatic techniques to measure serum triglyceride and cholesterol concentrations, although there were differences in standardisation procedures. Reference ranges for serum lipids were quoted by 58% of laboratories while 50% quoted "desirable limits". Almost half specified that fasting blood samples were required. High density lipoprotein cholesterol concentrations were estimated by 75% and apolipoproteins AI and B by 14% of laboratories; there were differences in specimen type and considerable diversity in procedures used for measurement. CONCLUSIONS: Many laboratories were unaware of current recommendations for screening for hypercholesterolaemia in the community. The present survey indicated an urgent need for the introduction of better reference methods, standardisation, and quality assurance procedures before apolipoproteins become a routine part of coronary heart disease risk assessment.

Apolipoproteins↗
PubMed1992

Difficulties in diagnosing hypertension: implications and alternatives.

OBJECTIVE: To estimate the magnitude of misclassification rates with commonly used algorithms for the detection of hypertensives and to suggest a sequential approach to screening. DESIGN: A conventional statistical model was used with several different algorithms to determine the number and types of errors made in categorizing two different populations, a general population sample and a population with a high risk of hypertension. METHODS: The calculations were made for single-visit screens, similar to those used in epidemiologic studies, for three-visit screens commonly used in clinical practice and clinical trials for cutoff points of 85, 95 and 105 mmHg. A sequential probability ratio screen was proposed and the error rates estimated. RESULTS: Perhaps only one-third to two-thirds of people whose measured diastolic pressures exceed 95 mmHg actually have average pressures that high. The disparity between a single measured diastolic pressure and the mean of many pressure values also leads to errors in identifying individual subjects with mild hypertension. In a general population, single measurements of diastolic pressure exceed 95 mmHg in approximately equal numbers of normotensive, borderline and hypertensive subjects; moreover, one-third of those who are usually in the hypertensive range are not identified. All commonly used screening algorithms give too many false-positive and/or false-negative results. A sequential screening algorithm averaged 3.8 visits per subject and identified 95% of the hypertensives, with only 2.5% of those identified having usual diastolic pressures below 90 mmHg. CONCLUSIONS: Population-based surveys like the National Health and Nutrition Examination Survey (NHANES) may markedly overestimate the true prevalence of hypertension. This overestimate is greatest for mild hypertension and could significantly affect the cost/benefit analyses of public health policy. Alternative screening methods, such as the sequential algorithm proposed, may have significant benefits in providing a correct classification.

Adult↗
PubMed1991

Electrocardiographic subset analysis of diltiazem administration on long-term outcome after acute myocardial infarction. The Multicenter Diltiazem Post-Infarction Trial Research Group.

The effect of diltiazem on long-term outcome after acute myocardial infarction (AMI) was assessed in 2,377 patients enrolled in the Multicenter Diltiazem Post-Infarction Trial and subsequently followed for 25 +/- 8 months. The study population included 855 patients (36%) with at least 1 prior AMI before the index infarction and 1,522 patients (64%) with a first AMI, of whom 409 (27%) had a first non-Q-wave AMI, 664 (44%) a first inferior Q-wave AMI, and 449 (30%) a first anterior Q-wave AMI. This post hoc analysis revealed that, among patients with first non-Q-wave and first inferior Q-wave AMI, there were fewer cardiac events during follow-up in the diltiazem than in the placebo group, and that the reverse was true for patients with first anterior Q-wave AMI or prior infarction. The diltiazem:placebo Cox hazard ratio (95% confidence limits) for the trial primary end point (cardiac death or nonfatal reinfarction, whichever occurred first) was: first non-Q-wave AMI-0.48 (0.26, 0.89); first inferior Q-wave AMI-0.66 (0.40, 1.09); first anterior Q-wave AMI-0.82 (0.51, 1.31); and prior AMI-1.11 (0.85, 1.44). Use of cardiac death alone as an end point gave an even more sharply focused treatment difference: first non-Q-wave AMI-0.46 (0.18, 1.21); first inferior Q-wave AMI-0.53 (0.27, 1.06); first anterior Q-wave AMI-1.28 (0.68, 2.40); prior infarction-1.26 (0.90, 1.77). Further analysis revealed that these differences in the effect of diltiazem in large part reflected the different status of the 4 electrocardiographically defined subsets in terms of left ventricular function.(ABSTRACT TRUNCATED AT 250 WORDS)

Diltiazem↗
PubMed1991

Prednisone in Duchenne dystrophy. A randomized, controlled trial defining the time course and dose response. Clinical Investigation of Duchenne Dystrophy Group.

A randomized, controlled trial of daily prednisone was conducted in 99 boys (aged 5 to 15 years) with Duchenne dystrophy to define the time course of improvement and the dose response to treatment. Prednisone at 0.3 mg/kg (n = 33), prednisone at 0.75 mg/kg (n = 34), and placebo (n = 32) were administered for 6 months. Patients were examined using manual muscle and myometry testing, timed functional testing, pulmonary function testing, and laboratory measurements at 10 days, 1 month, 2 months, 3 months, and 6 months of treatment. Boys treated with prednisone had stronger average muscle strength scores, than did boys treated with placebo as early as 10 days after starting therapy. At the 3-month visit, the boys in the group given 0.75 mg/kg of prednisone were significantly stronger than those in the group given 0.3 mg/kg of prednisone, indicating a dose response. At 6 months, significant side effects occurred in the group treated with 0.75 mg/kg of prednisone, including weight gain, cushingoid appearance, and excessive hari growth. Only weight gain was observed in the group taking prednisone at a dose of 0.3 mg/kg. Importantly, no side effects were evident at 10 days or 1 month of treatment, despite improvement in muscle strength and function. We conclude that prednisone produces a rapid increase in muscle strength in patients with Duchenne dystrophy and that this improvement is maximal at a prednisone dosage of 0.75 mg/kg or less.

Adolescent↗
PubMed1991

A comparison of daily and alternate-day prednisone therapy in the treatment of Duchenne muscular dystrophy.

We previously reported the results of a randomized, double-blind 6-month trial of prednisone therapy in which 102 boys aged 5 to 15 years with Duchenne muscular dystrophy received daily doses of 1.5 and 0.75 mg/kg per day and were compared with those receiving placebo. The strength and function in both prednisone-treated groups improved equally and were significantly better than in the placebo group. To compare alternate-day and daily dosing of prednisone with respect to benefits and adverse side effects, the placebo group was started on alternate-day prednisone therapy, and the treatment group regimens were changed to equivalent doses of alternate-day prednisone without breaking the double-blind nature. At the end of 6 months, the group that was changed from daily to alternate-day therapy had declined in strength back to levels observed 12 months previously, at the start of daily therapy. The group in which alternate-day therapy was started showed a significant improvement in strength at 3 months, similar in magnitude to the response of boys treated with daily therapy. However, their strength declined significantly in the subsequent 3 months compared with boys who received daily therapy. The frequency of side effects was not significantly different for alternate-day therapy compared with daily therapy. We conclude that alternate-day prednisone therapy effectively increases strength but does not sustain the improvement to the same extent as daily therapy or mitigate side effects.

Adolescent↗
PubMed1991

Anatomy and physiology of identified wind-sensitive local interneurons in the cricket cercal sensory system.

1. A group of wind sensitive local interneurons (9DL Interneurons) in the terminal abdominal ganglion of the cricket Acheta domesticus were identified and studied using intracellular staining and recording techniques. 2. The 9DL interneurons had apparent resting potentials ranging from -38 mV to -45 mV. At this membrane potential, these cells produced graded responses to wind stimuli; action potentials were never observed at these resting potentials. However, when the 9DL interneurons were hyperpolarized to a membrane potential of approximately -60 mV, a single action potential at the leading edge of the wind stimulus response was sometimes observed. 3. The wind stimulus threshold of the 9DL interneurons to the types of stimuli used in these studies was approximately 0.01 cm/s. Above this threshold, the excitatory responses increased logarithmically with increasing peak wind velocity up to approximately 0.5 cm/s. 4. The 9DL interneurons were directionally sensitive; their response amplitudes varied with wind stimulus orientation. 9DL1 cells responded maximally when stimulated with wind directed at the front of the animal. The apparent peak in directional sensitivity of the 9DL2 interneurons varied between the side and the rear of the animal, depending upon the site of electrode penetration within the cell's dendritic arbor. 5. The locations of dendritic branches of the 9DL interneurons within the afferent map of wind direction were used to predict the excitatory receptive field of these interneurons.

Action Potentials↗
PubMed1991

A mathematical model for resolution enhancement in layered sensory systems.

Heiligenberg (1987) recently proposed a model to explain how the representation of a stimulus variable through an ordered array of broadly tuned receptors could allow a degree of stimulus resolution greatly exceeding the resolution of the individual receptors which make up the array. In his model, this "hyperacuity" is achieved by connecting the receptors to a higher level pool interneuron according to a linear synaptic weighting function. We have extended this model to the general case of arbitrary polynomial synaptic weighting functions, and showed that the response function of this higher level interneuron is a polynomial of the same order as the weighting function. We also proved that Hermite polynomials are eigenfunctions of the system. Further, by allowing multiple interneurons in the higher level pool, each of which is connected to the receptors according to a different orthogonal weighting function, we demonstrated that extended stimulus functions can be represented with enhanced precision, rather than just the value of individual point stimuli. Finally, we suggest a solution to the problem of "edge effect" errors arising near the ends of finite receptor arrays.

Animals↗
PubMed1991

Age-related sensitivity to kainate neurotoxicity.

Domoate, a glutamate analog, is believed to be responsible for a seafood poisoning incident that caused acute neurological disturbances and chronic memory impairment in some victims, with the incidence of mortality and neuropsychological morbidity being highest among the aged. Domoate expresses neurotoxic (excitotoxic) activity in vitro by an action at the kainate subtype of glutamate receptor, and when administered to adult rats, it mimics kainate in causing status epilepticus and a severe seizure-brain damage syndrome. Because domoate is exceedingly expensive, we explored the feasibility of using kainate to study the age-linked features of domoate neurotoxicity. We administered kainate subcutaneously in various doses to young (5-6 months), middle-aged (12-13 months), and old (22-25 months) rats and found the middle-aged and old rats significantly more sensitive than young rats to the neurotoxic actions of kainate. Low doses of kainate, which were nontoxic to young rats, frequently triggered status epilepticus, associated brain damage, and precipitous death in old rats. Middle-aged rats were more sensitive than young rats, but less sensitive than old rats to kainate neurotoxicity. These results suggest that the kainate-treated rat may be a useful model for studying mechanisms underlying age-related aspects of the human domoate neurotoxic syndrome.

Age Factors↗
PubMed1991

Rapid screening for specific mutations in patients with a clinical diagnosis of familial hypercholesterolaemia.

We describe a rapid screening procedure to identify known DNA sequence changes in individuals diagnosed as having heterozygous familial hypercholesterolaemia (FH). The screening is made possible by combining a rapid DNA extraction protocol and small scale polymerase chain reaction DNA amplification, followed by oligonucleotide melting or restriction enzyme digestion. We have screened for two different mutations; firstly a mutation in the apolipoprotein B (apo B) gene that results in the substitution of glutamine (Gln) for arginine (Arg) at amino acid residue 3500 (apo B3500 mutation). Apo B is the principal component of the protein moiety of low density lipoprotein (LDL) and the mutation reduces the affinity for the LDL receptor (LDL-R). Secondly we have screened for a point mutation in the LDL-R gene itself that creates a new Pst I restriction enzyme site. This mutation in the LDL-R gene (LDL-R664 mutation) results in the substitution of leucine (Leu) for proline (Pro) at amino acid 664 and is known to slow processing of the LDL-R precursor to the mature form and to reduce the affinity of the receptor on the cell surface for LDL. In 77 unrelated patients with a clinical diagnosis of FH two out of 77 (2.6%) were positive for the apo B3500 mutation. Three (3.9%) were positive for the LDL-R664 mutation. Thus these two mutations might account for 5-6% of patients in the U.K. with a clinical diagnosis of FH (5000-6000 people).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

The effect of tube gastrostomy on gastroesophageal reflux in patients with esophageal atresia.

Gastroesophageal reflux (GER) occurs frequently in infants with esophageal atresia (EA). The definitive management is primary repair and often includes tube gastrostomy. The recent finding of lower esophageal sphincter (LES) pressure changes with tube gastrostomy suggests that GER might be related to gastrostomy rather than EA per se. To evaluate this thesis, two populations of patients from different children's hospitals were reviewed: EA with and without routine gastrostomy. The two populations were similar with respect to number of infants, associated anomalies, distribution in the Waterston classification, morbidity, and mortality. One hundred sixteen patients were studied. Of the 66 survivors who underwent gastrostomy and repair of EA, 30 were found to have GER (45.5%) and 12 required fundoplication (18.2%). Of 31 surviving patients who underwent repair of EA without gastrostomy, 11 had GER (35.5%) and four required fundoplication (12.9%). These data suggest that tube gastrostomy does not significantly contribute to the GER associated with EA.

Esophageal Atresia↗
PubMed1991

The newborn with hydrops and sacrococcygeal teratoma.

The combination of fetal hydrops and sacrococcygeal teratoma (SCT), is considered to be lethal. We report two such babies who survived. Case 1 exhibited oliguric acute renal failure (ARF) immediately after birth, and severe respiratory insufficiency despite maximal ventilatory support and vasodilator infusions. Tumor resection on the 2nd day of life resulted in an immediate improvement in pulmonary function as reflected by the ratio of arterial to alveolar oxygen. Renal function returned in a pattern typical of recovery from acute tubular necrosis. Case 2, less desperately ill, developed nonoliguric ARF, in part due to deliberate fluid restriction during the 7 days that followed birth and preceded surgery. This resolved following liberalization of fluid intake that occurred at the time of tumor removal on the 7th day of life. The baby also had respiratory insufficiency that improved after surgery. Respiratory insufficiency may be a severe and life-threatening complication of SCT and hydrops fetalis. Pulmonary function may improve dramatically by removal of the tumor. Why this improvement occurs is unclear. Improvement of respiratory function may result from the elimination of excess tumor blood volume with an improvement of the ventilation-perfusion ratio. Alternatively, the tumor may be a source of vasoactive substances or extremely desaturated blood that leads to pulmonary hypertension and right-to-left shunting. Uncertainties in postnatal fluid shifts and exaggerated fluid compartment volumes demand close attention to details of renal function.

Acute Kidney Injury↗
PubMed1991

Effect of pre- and postmortem variables on specific mRNA levels in human brain.

The method of polymerase chain reaction was used to investigate the pre- and postmortem factors which affect the stability of specific mRNAs in the C1 region of human autopsy brain. Eight premortem and 4 postmortem factors were correlated to levels of phenylethanolamine N-methyltransferase (PNMT), three splice forms of amyloid precursor protein (APP) and actin mRNAs in 10 control brains using Pearson's correlation coefficient. Significant negative correlations were found between hypoxia and PNMT mRNA, and between postmortem and storage intervals and APP751 and beta-actin mRNAs. A positive correlation was found between death-refrigeration interval and total APP and APP695 mRNAs. There was also a positive correlation between seizure activity and APP770 mRNA. The results indicate that a variety of pre- and postmortem factors can affect mRNA levels. The possible effect of pre- and postmortem factors on specific mRNA levels should be investigated prior to comparing mRNA levels in different disease states.

Adult↗