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Biomedical subjects

D Miller

Publications and source records attributed to D Miller.

At least 217 records · Page 12Linked to original sources

Costs and effectiveness of a nurse specialist anticoagulant service.

AIMS: To determine the costs and effectiveness of an anticoagulant nurse specialist service compared with a conventional consultant service based on two hospital sites in northwest Hertfordshire. METHODS: Sequential design comparing retrospectively the conduct and outcomes of a consultant service with a nurse specialist service over two six month periods. In each of the six month study periods, all new patients consecutively referred for anticoagulation over a three month period (group A) at the start of each study period and a random selection of patients who had already been attending the anticoagulant service for one year or more (group B) were included in the study. Group A patients wre followed for up to three months and group B patients for six months. The main outcome measures were costs of service provision and effectiveness. Costs included those for the use of the anticoagulant service, those related to general practitioner (GP) visits and hospitalisations, and running costs (staff time, laboratory tests, patient transport). Measures of effectiveness were the mean proportion of time patients spend in the therapeutic range, the number of drugs being taken that could interact adversely and/or inhibit haemostatic function, and patient and GP satisfaction with service provision. RESULTS: In the consultant service, for group A there were more patients aged 66-75 years (p = 0.004) and fewer patients aged more than 76 years (p = 0.001); and for group B, there were fewer patients on anticoagulation for cardiac conditions (p = 0.001), but more on anticoagulation for thromboembolic conditions (p = 0.02) than in the nurse specialist service. The clinic running costs of the nurse specialist service were 4.99 Pounds per attendance, compared with 4.75 Pounds in the consultant service. Including all other costs related to treatment, there was no statistically significant difference in cost per patient. There was no significant difference in the proportion of time patients spent in the therapeutic range between the consultant service and the nurse specialist service. In the nurse specialist service, fewer patients in group A were taking drugs that could interact adversely and/or inhibit haemostatic function (p = 0.01) and more patients were satisfied with service provision (p = 0.04) compared with the consultant service. There was no significant variation in GP satisfaction between the two services. CONCLUSION: In the provision of outpatient anticoagulation, the nurse specialist service was no more expensive than the consultant service and, using our primary outcome, at least as effective. The nurse specialist service has some clear advantages compared to the consultant service: provision of domicilliary care for housebound patients, fewer new patients taking drugs that could interact adversely and/or inhibit haemostatic function patients, it is preferred by newly referred patients to the consultant service, and it is as acceptable to their GPs.

Aged↗

Therapeutic effect of mitoxantrone combined with methylprednisolone in multiple sclerosis: a randomised multicentre study of active disease using MRI and clinical criteria.

OBJECTIVE: To evaluate the efficiency of mitoxantrone in multiple sclerosis. METHODS: Forty two patients with confirmed multiple sclerosis, selected as having a very active disease on clinical and MRI criteria were randomised to receive either mitoxantrone (20 mg intravenously (IV) monthly) and methylprednisolone (1 g iv monthly) or methylprednisolone alone over six months. In the steroid alone group five patients dropped out due to severe exacerbation. RESULTS: Blinded analysis of MRI data showed significantly more patients with no new enhancing lesions in the mitoxantrone group compared with the steroid alone group, (90% v 31%, P < 0.001). In the mitoxantrone group there was a month by month decrease almost to zero in the number of new enhancing lesions, and in the total number of enhancing lesions, whereas both remained high in the steroid alone group. The differences were significant for both indices at all months from 1-6. Unblinded clinical assessments showed a significant improvement in change in EDSS at months 2-6 in the mitoxantrone group, with a final mean improvement of more than one point (-1.1 v + 0.3; P < 0.001). There was a significant reduction in the number of relapses (7 v 31; P < 0.01), and an increase in the number of patients free of exacerbation (14 v 7; P < 0.05). CONCLUSION: In this selected group of patients with multiple sclerosis with very active disease, mitoxantrone combined with methylprednisolone was effective in improving both clinical and MRI indices of disease activity over a period of six months whereas methylprednisolone alone was not. Further double blinded long term studies are needed to properly evaluate the effect of mitoxantrone on progression in disability.

Adjuvants, Immunologic↗

Managing TMD.

Explore the source record for details and available documents.

American Dental Association↗

Neuroimaging in late-life mood disorders.

Neuroanatomical and physiological imaging provide unprecedented opportunities to examine the biological substrates of major mental disorders such as late life major depression (MDD). Studies using positron emission tomography (PET) and single photon emission computed tomography (SPECT) demonstrate focal and global abnormalities in patients with MDD when compared with controls. Magnetic resonance imaging (MRI) allows us to examine specific neuroanatomical perturbations in depression and to study the impact of comorbid medical disorders on brain structure and function. These technologies have the potential to provide biological information critical to a better understanding and conceptualization of the neuroscientific basis and treatment of the major mental disorders in late life.

Aged↗

Corneal chromoblastomycosis.

PURPOSE: We sought to illustrate the difficulty in managing uncommon, pigmented mold-related corneal ulceration and to highlight the role of itraconazole in treating these patients. METHOD: We describe the management and clinical course of a patient with a recurring corneal infection caused by Fonsecaea pedrosoi and discuss this experience in the light of existing literature on management of cutaneous chromoblastomycosis. RESULTS: A corneal ulcer caused by this organism healed initially on treatment with topical and systemic antifungal medication, but infection recurred in the deep stroma 4 months after cessation of therapy. After failure to respond to a further period of medical therapy, a small therapeutic penetrating keratoplasty was performed. Culture of a fibrinous membrane from the anterior iris surface demonstrated intraocular fungal infection, and postoperatively, an episode of marked fibrinous uveitis developed, suggesting the presence of viable intraocular fungal elements. A large penetrating keratoplasty was therefore performed with excision of involved iris in combination with extracapsular cataract extraction. F. pedrosoi was again cultured from the fibrinous membrane adherent to the iris and from the anterior lens capsule. Postoperatively the patient received a 5-month course of systemic itraconazole, and no further recurrences have been encountered after a further 2 months. CONCLUSION: F. pedrosoi is the organism most commonly isolated from the chronic cutaneous mycosis, chromoblastomycosis, and is relatively resistant to medical therapy. As has been reported for cutaneous disease, surgery in combination with systemic itraconazole may provide the best chance of cure in corneal chromoblastomycosis.

Antifungal Agents↗

Endophthalmitis caused by Serratia marcescens.

BACKGROUND AND OBJECTIVE: To describe the clinical features and treatment outcomes of 10 patients with culture-proven Serratia marcescens endophthalmitis. PATIENTS AND METHODS: Records from the microbiology laboratory for the period from January 1980 through June 1993 were reviewed. Ten patients were identified who had positive anterior chamber or vitreous cultures and clinical signs of endophthalmitis. The medical records for these 10 patients were reviewed, and the patients were contacted for reexamination when possible. RESULTS: All 10 cases of S. marcescens endophthalmitis occurred after ocular surgery. Eight eyes received intraocular antibiotics and 2 eyes were primarily enucleated or eviscerated. All organisms were sensitive to aminoglycosides and to ceftazidime. Repeat vitreous cultures were positive in 5 cases despite appropriate initial therapy with intravitreal and intravenous antibiotics. Final visual acuity was 20/400 or better in 4 of 10 eyes. A total of 4 eyes were enucleated or eviscerated at final follow-up. Eyes with light perception or better visual acuity had a mean follow-up of 23 months. CONCLUSION: S. marcescens can cause persistent endophthalmitis despite appropriate intravitreal and systemic antibiotic therapy. Eyes with S. marcescens endophthalmitis have a poor visual prognosis.

Aged↗

Quantitative anatomic measures and comorbid medical illness in late-life major depression.

The authors examined the individual and relative roles of atrophy, comorbid medical illness, and cerebrovascular risk factors in the pathogenesis of late-life major depressive disorder (MDD). They used magnetic resonance imaging techniques to study 28 subjects with late-life MDD, 29 healthy control subjects, and 34 subjects with probable dementia of the Alzheimer type (DAT). Depressed subjects showed increases in cerebrospinal fluid volumes comparable to the DAT group but significantly different from control subjects. High-intensity signals, but not measures of atrophy correlated significantly with cerebrovascular risk factor scores. A logistic regression revealed that both brain atrophy and medical illness are associated with an increased risk of developing MDD. Data suggest that both atrophy and comorbid medical illness increase the likelihood of developing MDD in late life.

Aged↗

Effects of fumonisin B1 on the immune system of sprague-dawley rats following a 14-day oral (gavage) exposure.

The effects of fumonisin B1 (FB1) on the immune system of Sprague-Dawley rats were investigated. Groups of male and female rats (10 rats/group) were gavaged daily for 14 days with doses of 0, 5, 15, and 25 mg/kg body wt/day and the primary (IgM) response to sheep red blood cells expressed as plaque-forming cell numbers/10(6) spleen mononuclear leukocytes (PFC/10(6) splenocytes) and PFC/spleen was determined. There was a significant dose-related linear trend toward decreased PFC/10(6) splenocytes (p = 0.003) and PFC/spleen cells (p = 0.001) in the male rats. Body weights, expressed as a percentage of the control, were significantly reduced (p = 0.002) in the male rats administered 15 and 25 mg/kg doses. The PFC numbers in female rats were not affected significantly by treatment (p > 0.05). For the remaining immunotoxicity studies, groups of male rats (10 rats/group) were gavaged with FB1 doses of 0, 1, 5, and 15 mg/kg body wt/day for 14 days. There was a weakly significant dose-related trend toward increased numbers of serum immunoglobulin class G (p = 0.04). Also a significant dose-related increase (p = 0.013) in Listeria monocytogenes numbers was observed in the spleen at 24 hr postinfection. Treatment did not have a significant effect on organ weights, hematology, mitogen-induced lymphocyte transformation, calcium mobilization, the numbers of leukocytes and T-lymphocyte subsets, the natural killer cell activity, and phagocytosis (p >/= 0. 05). These observations suggested that FB1 may have indirect consequences for human health and warrant further investigations.

Administration, Oral↗

Pharmaceutical treatment of obesity.

The prevalence of obesity in America has increased steadily in the past 7 decades, especially in the last decade. Health factors that lead to obesity are discussed. This article focuses on the treatment of obesity and potential results.

Anti-Obesity Agents↗

Building laminate veneers and fixed bridges with polymer glass technology.

A new type of material is being introduced to American dentistry. The material is a polymer glass, tested in Europe as Artglass. The material is purported to be equal to or better than porcelain for esthetic dentistry. The strength, color translucency, and color vitality allow minimal destruction of enamel for esthetics. An Artglass occlusal is less abrasive to enamel than porcelain and approximates gold. The characteristics of this material system introduces "minimal invasive dentistry" to routine dental repair and reconstruction. A case study of the senior author's reconstruction of his anterior teeth is presented.

Dental Bonding↗

Reliability of trans-cervical recovery of placental cells from the lower uterine pole using a minimally invasive procedure. Evidence based on fetal sexing and analysis of recovered cell populations.

OBJECTIVE: Efficient recovery of placental cells (and their subsequent characterisation) from the lower uterine pole (L.U.P) by trans-cervical flushing or aspiration. SUBJECTS: Women attending for termination of pregnancy (7-17 weeks' gestation) for social reasons. All patients gave their consent to the procedures outlined below. METHODS: Trans-cervical intrauterine flushing (using 0.15 M NaCl) or mucus aspiration. Embryo transfer catheters were used in both procedures. Fetal sexing was achieved by gene amplification of Y-specific DNA sequences (Y-PCR), and by in situ hybridisation (bright-field and fluorescence) to the Y-chromosome. Data were compared with results obtained from fetal tissues recovered following termination of pregnancy. Gender-independent tests for fetal cells utilised immunocytochemistry with trophoblast-specific antibodies and dual immunocytochemistry/ISH, where appropriate. RESULTS: (1) Fetal sexing by Y-PCR: 71/122 (58%) aspirates contained Y-specific DNA. In addition, the sexing of 72/86 (84%) aspirates and their corresponding samples of placental tissue, agreed exactly. (2) Microscopic detection of fetal cells. Placentally-derived syncytiotrophoblast was detected in 17/45 (38%) flushings and 39/173 (23%) aspirates. In most other Y-PCR+ samples which were negative for syncytiotrophoblast, Y-chromosome-bearing nuclei of unknown origin, were observed by ISH and immunocytochemical evidence for cytotrophoblastic cells was also uncovered. CONCLUSIONS: Since Y-derived DNA can be detected in > 50% of flushings and aspirations, and gender-independent evidence for placental cells was obtained, regardless of fetal sex, we believe that most or all of these samples contained placental cells, including trophoblasts and naked nuclei. Trans-cervical placental cell recovery is a potentially valuable alternative to more invasive methods of aneuploid detection which require amniocentesis and CVS, provided its level of accuracy and above all, safety, can be evaluated.

Cervix Uteri↗

A novel membrane receptor with high affinity for lysosphingomyelin and sphingosine 1-phosphate in atrial myocytes.

Activation of IK(ACh) is the major effect of the vagal neutrotransmitter acetylcholine in the heart. We report that both lysosphingomyelin (D-erythro-sphingosyl-phosphorylcholine; SPC) and sphingosine 1-phosphate (SPP) activate IK(ACh) in guinea pig atrial myocytes through the same receptor with an EC50 of 1.5 and 1.2 nM, respectively. Pertussis toxin abolished the activation of IK(ACh) by either lipid. The putative receptor showed an exquisite stereoselectivity for the naturally occurring D-erythro-(2S,3R)-SPC stereoisomer, the structure of which was confirmed by mass spectroscopy and NMR. These lipids caused complete homologous and heterologous desensitization with each other but not with ACh, indicating that both act on the same receptor. This receptor displays a distinct structure-activity relationship: it requires an unsubstituted amino group because N-acetyl-SPC, lysophosphatidic acid and lysophosphatidylcholine were inactive. Because SPP and SPC are naturally occurring products of membrane lipid metabolism, it appears that these compounds might be important extracellular mediators acting on a family of bona fide G protein-coupled receptors. Expression of these receptors in the heart raises the possibility that sphingolipids may be a part of the physiological and/or pathophysiological regulation of the heart. Based on their ligand selectivity we propose a classification of the sphingolipid receptors.

Animals↗

In vitro characterization of a novel series of platelet-derived growth factor receptor tyrosine kinase inhibitors.

In this report, we describe the discovery and characterization of a novel biarylhydrazone series of platelet-derived growth factor (PDGF) receptor tyrosine kinase inhibitors typified by the prototype WIN 41662 (3-phenyl-N1-[1-(4-pytidyl)pyrimidine]hydrazone). WIN 41662 inhibited PDGF-stimulated autophosphorylation of PDGF receptors from human vascular smooth muscle cells (hVSMC) with an IC50 value of 60 nM. The inhibitor appeared to be competitive with respect to substrate (Mn(2+)-ATP), having a calculated Ki of 15 +/- 5 nM. WIN 41662 was approximately 500-fold more potent in inhibiting the PDGF receptor tyrosine kinase than the p56lck tyrosine kinase. It was inactive against other serine/threonine and tyrosine kinases tested. WIN 41662 produced concentration-dependent inhibition of PDGF-stimulated receptor autophosphorylation in intact hVSMC with an IC50 < 100 nM. Intracellular Ca2+ mobilization and cell proliferation were events that occurred in hVSMC subsequent to PDGF receptor activation. WIN 41662 inhibited PDGF-stimulated Ca2+ mobilization and cell proliferation ([3H]TdR incorporation) with IC50 values of 430 nM and 2.3 microM, respectively. These effects appeared to be specifically related to PDGF receptor tyrosine kinase inhibition since WIN 41662 was not cytotoxic (in vitro) and since WIN 72039, a close structural analog that does not inhibit PDGF receptor tyrosine kinase, also did not inhibit PDGF-stimulated receptor autophosphorylation, Ca2+ mobilization, or hVSMC proliferation. Thus, WIN 41662 is representative of a novel class of selective PDGF receptor tyrosine kinase inhibitors that inhibit PDGF-regulated secondary events in intact cells.

Adenosine Triphosphate↗

Mapping striate and extrastriate visual areas in human cerebral cortex.

Functional magnetic resonance imaging (fMRI) was used to identify and map the representation of the visual field in seven areas of human cerebral cortex and to identify at least two additional visually responsive regions. The cortical locations of neurons responding to stimulation along the vertical or horizontal visual field meridia were charted on three-dimensional models of the cortex and on unfolded maps of the cortical surface. These maps were used to identify the borders among areas that would be topographically homologous to areas V1, V2, V3, VP, and parts of V3A and V4 of the macaque monkey. Visually responsive areas homologous to the middle temporal/medial superior temporal area complex and unidentified parietal visual areas were also observed. The topography of the visual areas identified thus far is consistent with the organization in macaque monkeys. However, these and other findings suggest that human and simian cortical organization may begin to differ in extrastriate cortex at, or beyond, V3A and V4.

Adult↗

In vivo structural studies of the hippocampus in normal aging and in incipient Alzheimer's disease.

Population trends indicate that in the near future the size of the elderly population will increase. This will result in a large increment in the numbers of persons suffering mild to severe levels of cognitive impairment. While considerable efforts continue to be made to explain brain changes associated with Alzheimer disease (AD), little is known of the brain changes in aging without dementia or so-called normal aging. Pathologic studies suggest that the medial temporal lobe is informative in the examination of the early brain changes related to AD. However, pathologic studies only offer a single observation and considerable uncertainty exists regarding the likelihood of progression of disease and the development of dementia. Several structural neuroimaging studies have recently investigated this anatomy and recent reports are encouraging for a medial temporal lobe based diagnosis for age-related cognitive impairments. We will present our findings on the MRI anatomy of the hippocampal formation as well as data bearing on the use of hippocampal formation imaging in the diagnosis of AD and as a predictive marker for future dementia. Our findings suggest an anatomically specific relationship between hippocampal volume and secondary memory performance. Because these observations apply to nondemented and normal elderly subjects, we are encouraged that the anatomy of age-related cognitive impairments can be reliably recognized and possibly put to use in therapeutic studies.

Aged↗

Rescue of Drosophila labial null mutant by the chicken ortholog Hoxb-1 demonstrates that the function of Hox genes is phylogenetically conserved.

Hox complexes are important players in the establishment of the body plan of invertebrates and vertebrates. Sequence comparison demonstrates a remarkable phylogenetic conservation of key structural features of Hox genes. The correlation between the physical order of genes along the chromosomes and their domains of function along the body axis is conserved between arthropods and vertebrates. Ectopic expression experiments suggest that the functions of homeo proteins also are conserved between invertebrates and vertebrates. However, it remains an open question whether vertebrate Hox genes expressed under the control of Drosophila regulatory sequences can substitute the function of Drosophila Hox genes. We have studied this issue with the Drosophila labial (lab) gene and its chicken ortholog gHoxb-1. We fused the entire protein-coding region of gHoxb-1 with previously identified regulatory sequences of lab. This approach places gHoxb-1 into the normal embryonic spatiotemporal context in which lab acts. Ten transgenic lines carrying gHoxb-1 were established and tested for their ability to rescue lab null mutant animals. Eight lines rescued with high efficiency, embryonic lethality, and abnormal head morphogenesis, two defects observed in lab null mutant embryos. The rescue with the gHoxb-1 minigene was close to the efficiency of that obtained with the Drosophila lab minigene. This indicates that gHoxb-1 protein can regulate lab target genes and thereby restore embryonic viability. This is striking, as Lab and gHoxb-1 proteins are divergent except for their homeo domains and a short stretch of amino acids amino-terminal to the homeo domain. Our findings demonstrate a functional conservation of the lab class homeo proteins between insects and vertebrates and support the view that function of Hox genes resides in relatively few conserved motifs and largely in the homeo domain.

Amino Acid Sequence↗

Association of elevated serum lipid levels with retinal hard exudate in diabetic retinopathy. Early Treatment Diabetic Retinopathy Study (ETDRS) Report 22.

OBJECTIVE: To evaluate the relationship between serum lipid levels, retinal hard exudate, and visual acuity in patients with diabetic retinopathy. DESIGN: Observational data from the Early Treatment Diabetic Retinopathy Study. PARTICIPANTS: Of the 3711 patients enrolled in the Early Treatment Diabetic Retinopathy Study, the first 2709 enrolled had serum lipid levels measured. MAIN OUTCOME MEASURES: Baseline fasting serum lipid levels, best-corrected visual acuity, and assessment of retinal thickening and hard exudate from stereoscopic macular photographs. RESULTS: Patients with elevated total serum cholesterol levels or serum low-density lipoprotein cholesterol levels at baseline were twice as likely to have retinal hard exudates as patients with normal levels. These patients were also at higher risk of developing hard exudate during the course of the study. The risk of losing visual acuity was associated with the extent of hard exudate even after adjusting for the extent of macular edema. CONCLUSIONS: These data demonstrate that elevated serum lipid levels are associated with an increased risk of retinal hard exudate in persons with diabetic retinopathy. Although retinal hard exudate usually accompanies diabetic macular edema, increasing amounts of exudate appear to be independently associated with an increased risk of visual impairment. Lowering elevated serum lipid levels has been shown to decrease the risk of cardiovascular morbidity. The observational data from the Early Treatment Diabetic Retinopathy Study suggest that lipid lowering may also decrease the risk of hard exudate formation and associated vision loss in patients with diabetic retinopathy. Preservation of vision may be an additional motivating factor for lowering serum lipid levels in persons with diabetic retinopathy and elevated serum lipid levels.

Adult↗