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Biomedical subjects

D Miller

Publications and source records attributed to D Miller.

At least 307 records · Page 17Linked to original sources

Olfactory neurons in vitro show phenotypic orientation in epithelial spheres.

Production and differentiation of olfactory neurons occur in spherical, multi-neuronal aggregates that form in cultures where dissociated newborn rat nasal cells are plated on to CNS glial cells. We show here that neuronal cell bodies were primarily located in the peripheral layers of the spheres, and almost every neuronal sphere contained one or several non-cellular central cavities. The dendrite-like processes of the olfactory neurons, immunostained for neuron-specific tubulin or the olfactory marker protein, were aligned and directed towards the central cavities. Olfactory neurons in the intact animal show a similar relationship with the nasal lumen. Non-neuronal cells formed multiple layers centrally, bordering the cavities. This degree of phenotypic re-creation is unusual in a dissociated monolayer culture system.

Animals↗

Mouse rump-white mutation associated with an inversion of chromosome 5.

The rump-white (Rw) mutation in the mouse was previously mapped as part of a cluster of spotting genes on Chromosome (Chr) 5 that includes the dominant spotting (W) and patch (Ph) loci. Recent studies have shown that the W locus encodes the KIT tyrosine kinase cell surface receptor and that Ph is a deletional mutation encompassing the platelet-derived growth factor receptor alpha subunit (Pdgfra) gene. However, the molecular basis of the Rw mutation remains to be established. We have analyzed an interspecific Mus spretus backcross segregating Rw and several loci proximal and distal to the W/Ph/Rw region to study the basis of this mutation. These studies indicated that loci within the En2 to Kit region of the chromosome do not recombine with one another even though they have been separated in other mapping studies presented here and elsewhere. We conducted a series of fluorescent in situ hybridization (FISH) studies with genomic probes to En2, Msx1, D5Buc1, and Kit to compare the physical order of these loci on the Rw and wild-type chromosomes. The Kit locus mapped to approximately the same region on both chromosomes of the Rw heterozygotes, while the positions of En2, Msx1, and D5Buc1 were reversed on the two chromosomes. Taken together, both the genetic and physical mapping data establish that the Rw mutation is associated with an inversion involving loci in the proximal region of Chromosome 5.

Animals↗

Transfected MCF-7 cells as a model for breast-cancer progression.

The MCF-7 human breast carcinoma cell line has been used as a recipient for eukaryotic plasmid expression vectors to determine the effects of growth factor and growth factor receptor overexpression on the estrogen-dependent, antiestrogen sensitive and poorly metastatic phenotypes exhibited by this line. Overexpression of some members of the erbB family of ligands and receptors were found to have some effects on these phenotypes. However, only when two members of the fibroblast growth factor family, FGF-1 and FGF-4, were overexpressed was progressive in vivo growth observed is either ovariectomized nude mice without estrogen supplementation or in mice that received tamoxifen treatment. FGF transfected cells also exhibited an increased ability to form micrometastases. The implications of these results with regard to the possible role of the paracrine and autocrine effects of angiogenic growth factor production in breast cancer progression are discussed.

Adenocarcinoma↗

Large scale production and semi-purification of kedarcidin in a 1000-L fermentor.

Actinomycete strain ATCC 53650 was grown in a 1000-L fermentor containing 680 L of medium and the production of kedarcidin was monitored by HPLC. The titers of kedarcidin in the fermentor cultures were 0.49-0.53 mg ml-1. A quick and efficient purification method involving the use of anion exchange resin DE23 (batch adsorption-desorption) and an ultrafiltration system yielded high recovery (65% yield) of kedarcidin from the fermentor culture. Over 200 grams of lyophilized kedarcidin of 70% purity was recovered from each of two 1000-L fermentor cultures using this process.

Actinomycetaceae↗

Evaluation of cost minimization strategies of anaesthetic drugs in a tertiary care hospital.

A survey was undertaken to compare anaesthetic drug expenditures over a three-year period, to evaluate the impact of strategies offered to curtain continuously rising drug costs. Suggestions to control rising expenditures were based primarily on education of staff and residents regarding drug costs, emphasizing rational use of the more expensive drugs, and minimizing drug wastage. To assess the impact of these measures, a review of annual hospital budgets, global pharmacy expenditures, and anaesthetic drug expenditures was conducted for the period 1991 to 1993. Both absolute and proportional costs of anaesthetic drugs were compared, by year, according to six major classes: opioid analgesics (OA), muscle relaxants (MR), inhalational anaesthetic drugs (INH), intravenous anaesthetic drugs (i.v.), local anaesthetic drugs (LA) and a category labelled other drugs (OTH). In addition, the utilization patterns and unit price changes were compared for each drug for the periods 1991-92, and 1992-93. Total hospital drug costs increased from $7.1 M to $8.5M over the three years. During the same period, the cost of anaesthetic drugs decreased from $379K to $361K, despite an augmentation in annual case load from 12,507 to 13,076 surgical procedures. For the entire survey period, the mean cumulative anaesthetic drug cost was 4.6% of the pharmacy budget, or 0.24% of the hospital budget. Analysis by drug class revealed a $51K decrease in expenditures on OA. due to decreased utilization of fentanyl and alfentanil, and a decrease in the price of fentanyl. The increased expenditure on INH drugs was primarily due to an increase in acquisition costs.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Functional magnetic resonance imaging (FMRI) of the human brain.

Functional magnetic resonance imaging (FMRI) can provide detailed images of human brain that reflect localized changes in cerebral blood flow and oxygenation induced by sensory, motor, or cognitive tasks. This review presents methods for gradient-recalled echo-planar functional magnetic resonance imaging (FMRI). Also included is a discussion of the hypothesized basis of FMRI, imaging hardware, a unique visual stimulation apparatus, image post-processing and statistical analysis. Retinotopic mapping of striate and extrastriate visual cortex is discussed as an example application. The described echo-planar technique permitted acquisition of an image in 40 ms with a repetition rate of up to 2 per second. However, FMRI responses are slow compared to changes in neural activity. Onset of a visual checkerboard test pattern evoked a response that was delayed by 1-2 s and reached 90% of peak in 5 s. Return to baseline following stimulation was slightly slower. Alternating control (blank) and test (checkerboard) patterns every 20 s induced a cyclic response that was detected in the presence of noise using a cross-correlation technique that was verified by parametric statistics. FMRI revealed retinotopically organized patterns of visually evoked activity in response to annular stimuli that increased in visual field eccentricity. Retinotopy was also observed with test patterns rotated around the fixation point (center of gaze). Results from repeated tests 1 week apart were highly similar. Compared to passive viewing, an active visual discrimination task enhanced responses from extrastriate association cortex.

Brain↗

Blood donor counselling for HIV: results of a multi-country feasibility study.

A qualitative characterisation study was conducted by the World Health Organisation's Global Programme on AIDS, and the International Federation of Red Cross and Red Crescent Societies, in six developing countries in order to determine the feasibility of introducing blood donor counselling into procedures for blood donation at blood transfusion sites. After careful preparation of consultants, in-country visits were made to include structured discussions with key BTS and Red Cross, and national AIDS programme staff, and donors, and observations of relevant facilities. Necessary resources, management requirements, obstacles to and options for blood donor counselling were explicated, together with information on the role of HIV testing in motivating blood donation, and problems associated with this and with donor notification. Blood donor counselling is seen as feasible, provided minimum conditions can be established to ensure appropriate standards and availability of resources.

Acquired Immunodeficiency Syndrome↗

The changing spectrum of fungal keratitis in south Florida.

PURPOSE: To review the clinical experience with fungal keratitis in south Florida over a 10-year period. METHODS: One hundred twenty-five cases of fungal keratitis were identified in the microbiology laboratory records between January 1982 and January 1992. The medical record of each patient was reviewed. RESULTS: The most commonly associated risk factor was trauma (44%). Fungal keratitis developed in five patients using extended wear contact lenses and one patient wearing a therapeutic bandage contact lens. Clinical features included irregular, feathery margins (62%), a dry, rough texture (47%), and satellite lesions (41%). An initial positive culture was obtained in 90% of patients, with a majority of cultures becoming positive within 48 hours. The Fusarium sp accounted for 62% of the isolates, with Fusarium oxysporum being the most commonly isolated organism. New fungal isolates include Candida parapsilosis, Aspergillus terreus, Candida tropicalis, and Trichosporon beigellii. Natamycin 5% suspension was the initial antifungal agent used for 91% of the patients, with an average duration of treatment of 38 days. Twenty-five patients were treated with oral ketoconazole for a median duration of 2 weeks, in addition to topical antifungal therapy. Thirty-four patients (27%) required a penetrating keratoplasty. Six patients had recurrence of fungal keratitis after penetrating keratoplasty. CONCLUSIONS: Trauma, including contact lens wear, is the most commonly associated risk factor. The fungal organisms can be readily identified in culture. F. oxysporum is the most common organism, with new isolates identified. The mainstay of therapy is topical natamycin with the increasing use of imidazoles.

Antifungal Agents↗

Nutritional risk in New England elders.

BACKGROUND: To better define nutritional risk among older Americans, a cross-sectional study of nutrition and health status was carried out in a probability sample of 1,156 free-living elders, 70 years and older, from 67 communities representing urban and rural areas of the six New England states. METHOD: All participants completed telephone interviews concerning demographic and health characteristics. A subsample of 1,156 individuals underwent in-home assessments of oral health, anthropometrics, and nutritional risk, including a 24-hour dietary recall. RESULTS: Nutrition-related problems were common and diverse among New England elders. Some 41.5% were overweight (BMI > 27 kg/m2), and mean dietary lipid intakes were considerably above recommended levels (Healthy People 2000 (National Health Promotion and Disease Prevention Objectives). Some 16% were underweight (BMI < 22 kg/m2), mean dietary calcium levels were low, and about 28% of older individuals failed to consume adequate levels (> 75% the Recommended Dietary Allowance for persons 51 years and older) for three or more key nutrients. Persons of advanced age or who smoked were more likely to have high dietary lipid intakes or less than adequate nutrient intake. Higher dietary lipid levels were also more common among men and individuals who lived with others. Low nutrient intake was more prevalent in those with lower educational attainment and dental problems. CONCLUSION: Nutrition policies and multidisciplinary interventions for older Americans need to emphasize the spectrum of nutritional problems in the elderly, including dietary excesses and potential nutrient deficiencies. The demographic and life-style characteristics that place older individuals at high nutritional risk need to be considered, particularly advanced age, gender, living situation, smoking, dietary behavior, educational attainment, and dental health.

Activities of Daily Living↗

Differential RNA fingerprinting as a tool in the analysis of spermatozoal gene expression.

The apparent decline in human male fertility and the concomitant increase in testicular pathology have prompted discussion of the underlying molecular mechanisms which may underpin these observations. While monitoring the expression of protamine-2 genes in the human ejaculate, we found a representative complement of sperm mRNAs following sequence-independent amplification of reverse-transcribed cDNAs with the polymerase chain reaction (RT-PCR). The revelation of unique sperm-derived PCR products using this method suggests that it should now be possible to investigate gene expression in human spermatogenesis by differential RNA fingerprinting of ejaculate spermatozoa. The identification of molecular markers and the corresponding genes associated with male infertility will be considerably enhanced by these investigations while obviating the requirement for invasive biopsy.

Base Sequence↗

Expression of heat shock protein 70 kDa in human endometrium of normal and infertile women.

The expression of heat shock protein (hsp) 70 was investigated in endometrial samples from patients with unexplained infertility associated (n = 5) or not associated (n = 10) with endometriosis, and compared with a control group consisting of fertile women (n = 27) with reported menstrual disturbance. The expression of hsp, and in particular hsp 70, is up-regulated in response to many physico-biochemical insults as well as infection and possibly oncogenic transformation and is a good indicator of a biological system under stress. A significant over-expression of hsp 70 was found in the infertile groups (P < 0.001), suggesting that a stress response may be involved in the aetiology of unexplained infertility irrespective of the presence of endometriosis.

Adult↗

Establishing an internal medicine practice: a model to determine economic feasibility.

To make informed career decisions, physicians must acquire a basic knowledge in medical management and health care economics as they evaluate the potential survival and growth of a primary care practice. Health care providers considering a specific community and local leaders and hospital administrators attempting to recruit internal medicine physicians need a method by which they can evaluate a community's potential for supporting a first or additional primary care physician. To develop this method, we conducted a detailed survey of nonmetropolitan internal medicine generalists and primary care physicians. Data collected from internal medicine physicians and their administrative staff reflected the volume of ambulatory and hospital visits and the direct and indirect costs of the practice over the previous 24 months. Using the fixed and operating cost data, as well as number of patient visits and patient care revenue, we designed a model to project the economic feasibility of establishing an internal medicine practice in a specific community. This model can be used to project the number of adult primary care visits a community can generate for a prospective physician, as well as to estimate the direct and indirect costs, annualized capital costs, gross revenue, and net income of the practice.

Adolescent↗

Laparoscopic appendectomy, is it worth it?

The recent experience with open appendectomy was compared to our initial experience with laparoscopic appendectomy. Thirty-eight patients had open appendectomy for acute appendicitis. Two major and four minor complications occurred. Concurrently, 39 patients had laparoscopic appendectomy. There was one major and one minor complication. Of the laparoscopic patients, 69% received less than 24 hours of parenteral postoperative analgesia, compared to 44% of the patients in the open group. Fifteen of 39 laparoscopic patients (38%) were discharged within 24 hours of operation versus 3 of 38 (8%) in the open group. Total mean hospital cost for the laparoscopic group, $7,500, was significantly greater than for the open group, $5,700, because of increased laparoscopic equipment charges. Both open and laparoscopic appendectomy procedures were performed with minimal morbidity. The benefits of laparoscopy were earlier hospital discharge and less parenteral analgesic use, but it was significantly more expensive.

Acute Disease↗

Famotidine increases plasma alcohol concentration in healthy subjects.

The effect of famotidine on plasma alcohol concentration was studied in 24 healthy male subjects who demonstrated high apparent ethanol first-pass metabolism after oral (p.o.) and intravenous (i.v.) ethanol administration (i.e. AUC(po) < or = 40% of AUC(i.v.), where AUC is area under the plasma ethanol concentration-time curve). Six of the original 30 subjects screened (20%) did not demonstrate high first-pass metabolism and were excluded. In a randomized open crossover study, oral ethanol pharmacokinetics were assessed after breakfast in the morning following a 3-day regimen of famotidine, 40 mg/day, and following a no-drug control period. Famotidine increased the area under the plasma ethanol concentration-time curve (AUC0-t) by 29% (7.1 vs 5.5 mg.h/dL, P = 0.006) and maximal plasma concentration (Cmax) by 23% (9.2 vs 7.5 mg/dL, P = 0.013). The changes in ethanol AUC0-t and Cmax may have been associated with changes in gastric emptying, as they were inversely correlated with changes in the time at which maximal plasma concentration was attained. There was considerable intra-individual variation in ethanol AUC and Cmax. As a result, regression to the mean is a potentially confounding problem in ethanol pharmacokinetic studies when subjects are selected on the basis of having low AUC(po), and properly controlled randomized studies of substantial size are required to detect modest drug effects. Small effects on ethanol pharmacokinetics have now been demonstrated with all four of the major H2-receptor antagonists, but these effects are seen only under specific experimental conditions and appear to be unimportant clinically.

Administration, Oral↗

Fetal pulse oximetry: a new method of monitoring the fetus.

Experimental pulse oximetry devices, similar to the existing systems used in adult and neonatal monitoring, can be used on the fetus to provide safe, and rapid information about oxygenation. They have been calibrated using fetal lambs and validated in human cross-sectional studies. Experiments have shown that fetal oxygen saturation decreases during normal labour, and drops after a uterine contraction especially with oxytocin-induced tachysystole. When the mother is given oxygen the fetal oxygen saturation increases. Readings are effected by caput and movement, and trends seem to be more meaningful than absolute values. Pulse oximetry can predict fetal outcome and a normal oxygen saturation result is specific for a good outcome perhaps even if the CTG is abnormal. However the technique is still experimental and there is insufficient data to support its use as a replacement for fetal blood sampling or a discriminator for an abnormal fetal heart trace.

Animals↗

Sequential injection of 3% sodium tetradecyl sulfate and 20% sodium chloride in the treatment of refractory varicosity of the greater saphenous vein.

BACKGROUND: American practitioners of sclerotherapy are limited by United States Food and Drug Administration (FDA) restrictions. The strongest FDA-approved sclerosant is sodium tetradecyl sulfate. In the United States, when a varicose vein is refractory to treatment with this drug, there are no effective FDA-approved pharmaceutical alternatives. OBJECTIVE: A method of sequential injection of sodium tetradecyl sulfate followed immediately by sodium chloride is described. We have theorized that this drug combination should be more effective than equivalent doses of either drug alone. METHODS: The injections are done under ultrasonic guidance. Sodium tetradecyl sulfate is injected first. After the vessel goes into spasm, a second injection of sodium chloride is made through the same needle. RESULTS: In the majority of varicose veins that had been refractory to repeated large doses of sodium tetradecyl sulfate alone, a single sequential injection treatment has brought about sclerosis and rapid atropy. CONCLUSION: This method should be considered for any case in which sclerotherapy is indicated, if it is known or anticipated that sodium tetradecyl sulfate alone will be ineffective or inefficient.

Adult↗