Search PubMed⌕ Search

Biomedical subjects

L L Miller

Publications and source records attributed to L L Miller.

At least 19 recordsLinked to original sources
PubMed1995

The PREP system of nursing interventions: a pilot test with families caring for older members. Preparedness (PR), enrichment (E) and predictability (P).

The PREP system of nursing interventions, designed to increase preparedness (PR), enrichment (E), and predictability (P) in families providing care to older people, was pilot tested for acceptability and preliminary effectiveness. Eleven family units were assigned to the PREP group and 11 to a standard home health control group. The PREP group scored approximately one SD higher than the control group (p < .05) on the Care Effectiveness Scale, indicating greater preparedness, enrichment, and predictability. Further, on a rating of overall usefulness, the PREP group rated their assistance from PREP nurses (M = 9.75) as significantly higher (p < .01) than the control group rated assistance from the home health nurse or physical therapist (M = 6.57). Although not statistically significant, mean hospital costs for the PREP group ($2,775) were lower than for the control group ($6,929). Results provided support for a full intervention trial.

Aged↗
PubMed1995

Infraputaminal 'lacunes'. Clinical and pathological correlations.

BACKGROUND AND PURPOSE: Single, oval lesions greater than 5 mm in diameter lying inferior to the lateral putamen (infraputaminal lacunes [IPLs]) seen on CT or MR images are commonly reported as lacunar infarcts. To determine the clinical relevance and underlying pathology of IPLs, we evaluated the imaging appearances, clinical features, vascular risk factors, and histopathology in patients with IPLs. METHODS: Consecutive MR scans were reviewed for the presence of IPLs. Serial patients seen in routine clinical practice with IPLs were also included. Vascular risk factors were obtained from a prescan questionnaire. Histology and microangiography were performed on postmortem material. A MEDLINE search for putaminal infarcts was performed to look for imaging lesions typical of IPLs. RESULTS: Three of 100 serial MR scans had IPLs (3%). Nine other patients with in vivo (7) or postmortem (2) MR scans had IPLs. No neurological symptoms could be related to the IPLs. There were no differences in age, hypertension, diabetes, or presence of cortical enlarged perivascular spaces (EPVSs) between patients with and without IPLs. Unlike infarcts, IPLs were isointense with the cerebrospinal fluid on proton density MR sequences. Histological correlation of three MR scans showed IPLs to be a single large EPVS, situated lateral to the anterior commissure. IPLs were located at a point where multiple lenticulostriates turn sharply dorsally. An IPL was the probable cause of the apparent infarct in six publications from peer-reviewed literature that linked different clinical signs to putaminal infarct. CONCLUSIONS: IPLs are EPVSs that can be differentiated from infarcts on proton density MR images.

Adult↗
PubMed1995

Effect of aging on animal response to chronic fluoride exposure.

This study was conducted to test the hypothesis that physiological changes which occur during aging increase the biological impact of fluoride and reduce the threshold of safe fluoride exposure. Four groups of rats were fed a low-fluoride diet (< 1.2 ppm) ad libitum and received 0, 5, 15, or 50 ppm fluoride in their drinking water. Animals were killed after three, six, 12, or 18 months of treatment. Blood and urine were monitored for biochemical markers of tissue function, and plasma, urine, feces, and representative tissues were analyzed for fluoride. In addition, bone marrow cells from animals killed after 18 months of treatment were examined for frequency of sister chromatid exchange (SCE), a marker of genetic damage. Study results indicated that, within treatment groups, fluoride intake, excretion, and retention did not change significantly between three and 18 months. Fluoride concentration in soft tissues did not change with treatment duration in the fluoride-treated animals. Mineralized tissue fluoride concentration and the total fluoride in the carcasses increased continually as the animals aged. In spite of significant, dose-related differences in tissue fluoride levels which occurred in all age groups in this study, there were no indications that increased fluoride in the tissues caused any adverse physiological or genotoxic effects. None of the monitored clinical "wellness" markers of tissue integrity and function was altered by fluoride in a clinically significant manner. Therefore, there was no evidence from this study that aging reduces the threshold of safe chronic fluoride exposure.

Age Factors↗
PubMed1995

Effect of sodium hexametaphosphate on dental calculus formation in dogs.

A series of studies was conducted to identify a practical measure for preventing dental calculus formation in dogs. The studies involved a colony of 27 Beagles that received an initial dental prophylaxis. The dogs were then stratified on the basis of their normal rate of calculus formation and randomly assigned to parallel groups within each strata. During 4-week test periods, a variety of experimental regimens were instituted, followed by clinical assessments of calculus. Major observations were that a crystal growth inhibitor, soluble pyrophosphate, incorporated into a dry dog food modestly reduced calculus formation when used at high concentration; anticalculus effects attributable to this agent were significant (P < 0.05) only when it was used as a surface coating; the coating of dry dog chow or plain biscuits with a calcium sequestrant, sodium hexametaphosphate (HMP), provided the greatest benefit and resulted in significant (P < 0.05) reductions in calculus formation of about 60 to 80%, depending on the dosage regimen; and the feeding of a single daily snack of 2 HMP-coated plain biscuits (0.6% HMP) decreased calculus formation by nearly 80%. We concluded that the coating of dry dog chow or plain dog biscuits with HMP is an effective means of reducing calculus formation in dogs.

Aging↗
PubMed1995

Cerebellomedullary ganglioglioma: CT and MR findings.

We present a case of cerebellomedullary ganglioglioma in a young child with indolent clinical symptoms. CT demonstrated a region of hypodensity with central contrast enhancement in the right cerebellar hemisphere and the inferior peduncle. On MR the lesion was iosintense on T1-weighted images with fairly homogeneous enhancement with gadolinium, and of high signal intensity on T2-weighted images.

Cerebellar Neoplasms↗
PubMed1995

Prominence of coronary arterial wall lipids in human heart allografts. Implications for pathogenesis of allograft arteriopathy.

Transplant arteriopathy is a major late complication in human heart allograft recipients and the pathogenesis of such arteriopathy remains uncertain. The degree to which lipids and atheromata are involved in the arteriopathic lesions remains unsettled, and there is uncertainty regarding the significance of insudation or retention of lipids within the coronary artery walls of transplanted hearts. On current immunosuppressive regimens, most patients experience an increased serum total cholesterol and low-density lipoprotein cholesterol after transplant. Elevation of these blood lipids has an undetermined relationship to arteriopathy. We carried out morphological, morphometric, immunohistochemical, ultrastructural, and biochemical studies of particular coronary artery segments from 23 unselected explant or autopsy allografts and donor age-matched native coronary controls. Patients died of cardiac and non-cardiac reasons over a period of 4 to 1610 days after transplant. Atheromata were frequent, and diffuse intra- and extra-cellular accumulation of lipids in both intimal and medial walls was documented by oil red O positivity, immunohistochemical staining (muscle-specific alpha-actin), transmission and scanning electron microscopy, and biochemical analysis. Mean total cholesterol, esterified cholesterol, free cholesterol, and phospholipid content (microgram/cm2 intimal surface area) and concentration (microgram/mg dry defatted weight) in arteriopathic coronaries were > 10-fold higher than in comparable native coronary segments. Extent of lipids in the arterial walls was highly correlated with digitized percent luminal narrowing, mean daily and cumulative cyclosporin dose, and mean cumulative prednisone dose. Our data suggests strongly that lipid accumulation is an important early and persistent phenomenon in the development of transplant arteriopathy.

Adolescent↗
PubMed1995

Infrequency of cytomegalovirus genome in coronary arteriopathy of human heart allografts.

In heart transplantation, long-term engraftment success is severely limited by the rapid development of obliterative disease of the coronary arteries. Data from various groups have been suggestive of a pathogenetic role of herpesviruses, particularly human cytomegalovirus, in accelerated allograft coronary artery disease; however, results are not yet conclusive. This study examines the hypothesis that human cytomegalovirus infection of allograft tissues is related pathogenetically and directly to accelerated coronary artery disease. Using in situ DNA hybridization and polymerase chain reaction, we examined particular coronary artery segments from 41 human heart allografts (ranging from 4 days to greater than 4 years after transplantation; mean, 457 days) and 22 donor age- and gender-comparable, coronary site-matched trauma victims for presence of human cytomegalovirus DNA. Human cytomegalovirus genome was detected in 8 of 41 (19.5%) allografts and in 1 of 22 (4.5%) control hearts. This difference in positivity was not statistically significant (P = 0.10). In the human cytomegalovirus-positive hearts, viral genome was localized to perivascular myocardium or coronary artery media or adventitia. Human cytomegalovirus genome was not detected in arterial intima of any allograft or control heart, although human cytomegalovirus genome was readily identified within intima of small pulmonary arteries from lung tissue with human cytomegalovirus pneumonitis. By statistical analyses, the presence of human cytomegalovirus genome was not associated with the nature or digitized extent of transplant arteriopathy, evidence of rejection, allograft recipient or donor serological data suggestive of human cytomegalovirus infection, duration of allograft implantation, or causes of death or retransplantation. Thus, our data indicate a low frequency of detectable human cytomegalovirus genome in accelerated coronary artery disease and do not support a direct role for human cytomegalovirus in vascular wall infection or in the development of accelerated coronary artery disease.

Adolescent↗
PubMed1994

A randomized study of erythropoietin and granulocyte colony-stimulating factor (G-CSF) versus placebo and G-CSF for patients with Hodgkin's and non-Hodgkin's lymphoma undergoing autologous bone marrow transplantation.

Anemia is a universal finding in patients undergoing autologous bone marrow transplantation (BMT). Effective therapies to increase the number of autologous red blood cells could result in a lower morbidity and mortality associated with red blood cell transfusions. We examined whether the addition of erythropoietin (Epo) to intensive therapy supported by progenitor cell transplantation and granulocyte colony-stimulating factor (G-CSF) would result in a lower requirement for red blood cell transfusions. Thirty-five patients with lymphoma were randomized to receive Epo versus placebo. Epo (600 U/kg three times per week) or placebo was begun 3 weeks before administration of high-dose therapy. Epo was held during the week of the preparatory regimen, and restarted on the day after BMT. All patients also received G-CSF following BMT. No significant differences were noted between the two groups in terms of patient characteristics at pretreatment or post-BMT evaluation. There were no differences in the total number of red blood cell units transfused (median Epo: 8 v placebo: 6, P = .22) nor the number of platelet transfusions given (median Epo: 12 v placebo 5, P = .14). Engraftment of granulocytes (absolute neutrophil count > or = 500/microL) occurred in a median of 12 days (range, 9 to 33) for the patients receiving Epo and G-CSF, compared with a median of 10 days (range, 8 to 22) for those receiving placebo and G-CSF (P = .70). Likewise, there were no differences in the time to platelet count > or = 20,000/microL without further transfusions with a median of 22 days (range, 15 to 150+) for those receiving Epo and G-CSF compared with a median of 20 days (range, 11 to 54) for those patients receiving placebo and G-CSF (P = .28). The combination of G-CSF and Epo as administered in this study appears to be safe but does not result in an improvement in the total number of red blood cell transfusions or total number of single donor platelet units transfused.

Adult↗
PubMed1994

Spontaneous palpebromandibular synkinesia: a localizing clinical sign.

In the classical corneomandibular reflex (CMR), corneal stimulation elicits a bilateral eyelid blink and a brisk anterolateral jaw movement. We here describe 14 patients with a spontaneous palpebromandibular (eyelid-jaw) synkinesia (SPMS) in whom jaw movements, similar to those in CMR, regularly accompanied spontaneous eye blinks without an external corneal stimulus. Eleven of the patients with SPMS also had CMRs on corneal stimulation. Four patients had clinical and imaging evidence of brainstem lesions above the mid-pons, 5 patients had autopsy or imaging evidence of both bilateral cerebral and upper brainstem lesions, and 5 patients had clinical or imaging evidence of bilateral cerebral dysfunction. Topical corneal anesthesia administered to patients who had both CMR and SPMS blocked the CMR but had no effect on the SPMS. In patients with both SPMS and CMR, measurements of latency from onset of orbicularis oculi electromyographic activity to onset of lateral pterygoid EMG activity, and mandibular kinesiography of jaw velocity and direction showed that the eyelid-jaw synkinesias of CMR and SPMS had similar characteristics. We conclude that SPMS is pathophysiologically the same as the eyelid-jaw synkinesia of CMR and both synkinesias originate centrally, probably in the pons. In CMR, the jaw movement is primarily related to the blink rather than the corneal stimulus, but corneal stimulation may be necessary to overcome a higher threshold for expression of the synkinesia than in patients with SPMS. Like CMR, SPMS emerges in patients with upper brainstem or bilateral cerebral lesions and SPMS may therefore be a useful localizing clinical sign.

Adult↗
PubMed1994

Shade selection.

Explore the source record for details and available documents.

Crowns↗
PubMed1993

Heterogeneity testing for Alzheimer's disease within and between data sets.

We examined the three Alzheimer's disease (AD) family data sets for heterogeneity. Four markers that were represented in all three data sets were selected for analysis. Markers BCL3/EcoR-Mlu and D19S13/TaqI were chosen for chromosome 19 and D21S13/TaqI and D21S16/XbaI for chromosome 21. Homogeneity testing was performed on the data by use of Morton's pre-divided samples test (PS-test) and Smith's admixture test (A-test). The C-test of MacLean et al. [1992] was also used to test for linkage in the presence of heterogeneity. Assuming homogeneity, there was significant evidence of linkage to AD for BCL3, D19S13, D21S16 in the Duke data set and D19S13, D21S16 in the Boston data set. C-tests also provided evidence of linkage for BCL3 and D21S13 in the Duke data set, and D21S16 in the Boston data set. No evidence for heterogeneity within the data sets was found for any of the four markers using either the A-test or the C-test. For marker BCL3, PS-tests found evidence of heterogeneity between the three data sets and between early-versus late-onset families combined over all data sets.

Aged↗
PubMed1993

Stopping a clinical trial very early because of toxicity: summarizing the evidence.

When a trial is stopped early because of a specific toxicity, it may be important to summarize the statistical evidence for stopping. Such a summary needs to take into account the sequential nature of the stopping rule. We address some practical issues involved in analyzing such toxicity data coming from a trial that was stopped after the fourth patient was evaluated.

Bayes Theorem↗
PubMed1993

Current status of G-CSF in support of chemotherapy and radiotherapy.

It is now 2 years since the commercial availability of G-CSF, and thus it seems appropriate to reassess the clinical merits of this cytokine in the context of current knowledge; such an evaluation seems best founded not only on an analysis of the biology of G-CSF itself, but also on a critical assessment of whether its biologic actions translate into a cost-effective alleviation of patient suffering and improved cancer cure. As is so often the case, the knowledge base upon which clinicians must rely to make prescribing decisions is smaller than we might wish, but a substantial body of existent information can provide a guide to clinical strategy until a number of ongoing trials give more concrete information.

Blood Cell Count↗
PubMed1992

Inhibition of interleukin-1-alpha-induced nitric oxide synthase in vascular smooth muscle and full reversal of interleukin-1-alpha-induced hypotension by N omega-amino-L-arginine.

BACKGROUND: Interleukin-1-alpha (IL-1) is a cytokine with potentially therapeutic immunoproliferative and tumoricidal activities. Preliminary clinical studies suggest that use of IL-1 may be restricted by dose-limiting hypotension. PURPOSE: The purpose of this study was to investigate the role of nitric oxide (NO.) as a possible mediator of this hypotension. METHODS: Cytokine-treated rat aortic smooth muscle cells were assayed for nitrite production, a stable breakdown product of nitric oxide. Nitric oxide synthase from smooth muscle cells was partially characterized in cytosol preparations using a novel Fe(2+)-myoglobin method to test for nitric oxide production. To determine the role of NO. on the immunorestorative and antineoplastic activity of IL-1, N omega-amino-L-arginine (NAA) or N omega-monomethyl-L-arginine (NMA), inhibitors of nitric oxide synthase, were added to either cultures of IL-1-dependent T cells or A375 melanoma cells exposed to IL-1. To investigate the effects of NAA in vivo, pentobarbital anesthetized dogs, which were made hypotensive by administration of IL-1, received a single intravenous bolus dose of NAA. The effects of NAA were then reversed by the administration of L-arginine. RESULTS: Our results show that cultured IL-1-activated rat aortic smooth muscle cells synthesize nitric oxide, a potent vasodilator. Induction of nitric oxide synthase is augmented by interferon-gamma and blocked by IL-1 receptor antagonist and by inhibitors of RNA or protein synthesis. Nitric oxide synthesis by IL-1-activated smooth muscle cells is inhibited by NAA, NMA, and N omega-nitro-L-arginine (NNA) with ED50 (i.e., effective dose for 50% inhibition) values of 20, 60, and 1000 microM, respectively; this rank order of inhibition is characteristic of an agonist-unregulated, inducible isoform of nitric oxide synthase. In smooth muscle cells, inhibition of NO. synthesis by NAA is reversed by excess L-arginine. Consistent with the induction of unregulated NO. synthesis in vascular smooth muscle in vivo, administration of IL-1 (50 micrograms/kg) to dogs caused a 33.5% decrease in systemic vascular resistance and a 28% decrease in blood pressure within 3 hours. Subsequent administration of NAA (20 mg/kg) rapidly and completely reversed the hypotension and increased systemic vascular resistance; these effects of NAA were reversed by L-arginine. Neither the immunoproliferative nor the tumoricidal activity of IL-1 was diminished by NAA. CONCLUSIONS: Our results indicate that (a) vascular smooth muscle is a likely source as well as a target of IL-1-induced NO. synthesis, causing vasodilatation and hypotension, (b) nitric oxide synthase inhibitors can fully reverse this hypotension, and (c) the therapeutically useful properties of IL-1 are not diminished by nitric oxide synthase inhibitors. IMPLICATIONS: Administration of inhibitors of nitric oxide synthase can reverse the pathological cardiovascular effects of IL-1 at concentrations that do not interfere with the potentially useful immunoproliferative or tumoricidal effects of this cytokine. In the context of the current clinical trials of IL-1, this finding would represent a very significant advantage.

Amino Acid Oxidoreductases↗
PubMed1992

The toxic and hematologic effects of interleukin-1 alpha administered in a phase I trial to patients with advanced malignancies.

PURPOSE: A phase I trial was undertaken because interleukin-1 alpha (IL-1 alpha) possesses antiproliferative, immunostimulatory, antiinfection, myeloprotective, and myelorestorative properties that could be beneficial in cancer treatment. PATIENTS AND METHODS: In this phase I trial, IL-1 alpha was administered intravenously (IV) during a 15-minute period daily for 7 days to patients with advanced solid malignancies. RESULTS: The maximum-tolerated dose (MTD) of IL-1 alpha alone was 0.3 microgram/kg. A second group of patients received indomethacin plus IL-1 alpha based on preclinical studies, which indicated that indomethacin could abrogate IL-1 alpha-induced hypotension; however, the MTD of IL-1 alpha plus indomethacin was 0.1 microgram/kg lower than IL-1 alpha alone. Fever, chills, headache, nausea, vomiting, and myalgia were common but were not dose-limiting. Hypotension resulted from a marked decrease in systemic vascular resistance and required pressors at 0.3 and 1.0 micrograms/kg IL-1 alpha. Dose-limiting toxicities included hypotension, myocardial infarction, confusion, severe abdominal pain, and renal insufficiency. IL-1 alpha treatment caused a significant, dose-related increase in the total WBC count (mainly segmented neutrophils and neutrophilic bands). Bone marrow cellularity increased because of enhanced numbers of relatively mature myeloid cells and megakaryocytes. Platelet counts decreased during therapy but were significantly elevated above baseline values 1 to 2 weeks posttreatment; this may have been an effect of IL-6 that was shown to be induced by IL-1 alpha treatment. Significant increases in triglycerides, cortisol, C-reactive protein, thyroid-stimulating hormone and decreases in cholesterol, testosterone, and protein-C were observed with treatment. CONCLUSION: We conclude that at doses of IL-1 alpha that can be given safely to cancer patients, significant, potentially beneficial hematopoietic effects occur.

Adult↗