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Biomedical subjects

J A Barker

Publications and source records attributed to J A Barker.

16 recordsLinked to original sources

Redistribution of contaminants by a fluctuating water table in a micro-porous, double-porosity aquifer: field observations and model simulations.

Large seasonal fluctuations of the water table are characteristic of aquifers with a low specific yield, including those fractured, double-porosity aquifers that have significant matrix porosity containing virtually immobile porewater, such as the Chalk of northern Europe. Where these aquifers are contaminated, a strong relationship between water table elevation and contaminant concentration in groundwater is commonly observed, of significance to the assessment, monitoring, and remediation of contaminated groundwater. To examine the processes governing contaminant redistribution by a fluctuating water table within the 'seasonally unsaturated zone', or SUZ, profiles of porewater solute concentrations have been established at a contaminated site in southern England. These profiles document the contaminant distribution in porewater of the Chalk matrix over the SUZ at a greater level of detail than recorded previously. A novel double-porosity solute transport code has been developed to simulate the evolution of the SUZ matrix porewater contaminant profiles, given a fluctuating water table, when the groundwater is initially contaminated and the SUZ is initially free of contamination. The model is simply characterised by: the matrix-fracture porosity ratio, the matrix block geometry, and a characteristic diffusion time. De-saturation and re-saturation of fractures is handled by a new approximation method. Contaminant accumulates in the upper levels of the SUZ, where it is less accessible to mobile groundwater, and acts as a persistent secondary source of contamination once the original source of contamination has been removed or has become depleted. The 'SUZ process' first attenuates the progress of contaminants in groundwater, and subsequently controls the slow release of contamination back to the mobile groundwater, thus prolonging the duration of groundwater contamination by many years. The SUZ process should operate in any fractured, micro-porous lithology e.g. fractured clays and mudstones, making this approach widely applicable.

Diffusion↗

Life-threatening upper airway edema caused by a distal rattlesnake bite.

A 36-year-old man captured a timber rattlesnake and was accidentally envenomated in the thumb by the severed head. At a local emergency department, hypotension and confusion developed. Facial and glossal edema were also observed. Oxygen was delivered by face mask, and crystalloids and dopamine were administered. Respiratory distress developed with progressive hypoxemia. Intubation was unsuccessful because of massive glossal and epiglottic (laryngeal) edema, and an emergency cricothyrotomy was performed. High-dose antivenom therapy was administered, and mechanical ventilation was started. Recovery was rapid, and the patient was discharged from the hospital a week later. This is the first report of life-threatening upper airway edema caused by snake envenomation not in the vicinity of the head or neck.

Adult↗

Inverted electron-hole alignment in InAs-GaAs self-assembled quantum dots.

New information on the electron-hole wave functions in InAs-GaAs self-assembled quantum dots is deduced from Stark effect spectroscopy. Most unexpectedly it is shown that the hole is localized towards the top of the dot, above the electron, an alignment that is inverted relative to the predictions of all recent calculations. We are able to obtain new information on the structure and composition of buried quantum dots from modeling of the data. We also demonstrate that the excited state transitions arise from lateral quantization and that tuning through the inhomogeneous distribution of dot energies can be achieved by variation of electric field.

Journal Article↗

Cytogenetics and the biological basis of sarcomas.

Recently, much research has been directed toward gaining a better understanding of sarcoma biology. To accomplish this goal, researchers have focused on characterizing the cytogenetic abnormalities that are detectable by routine karyotyping. With the use of widely-available molecular biologic tools, new information on the genetic abnormalities of sarcomas is rapidly emerging. In addition, physicians are beginning to successfully apply cytogenetic and molecular biologic findings to clinical settings in the form of molecular diagnostic and prognostic tests. Moreover, detailed study of these genetic abnormalities is leading to a better understanding of the molecular pathology of sarcomas, which may eventually lead to better therapy. In this paper, we will review the important new findings on genetic abnormalities in sarcomas, clinical applications of cytogenetic studies, and insight into the biology of sarcomas.

Chromosome Aberrations↗

Microcytic anemia with iron malabsorption: an inherited disorder of iron metabolism.

Two siblings were identified with severe hypoproliferative microcytic anemia and iron malabsorption, in the absence of any gastrointestinal disorder or blood loss. These children had severe microcytosis (MCV 48 fl, hemoglobin 7.5 g/dl) with decreased serum iron, elevated serum TIBC, and decreased serum ferritin, despite prolonged treatment with oral iron. An iron challenge study with an oral dose of 2 mg/kg elemental iron as ferrous sulfate documented iron malabsorption. After treatment with intravenous iron dextran, there was an absence of the expected reticulocytosis and only a partial correction of the hemoglobin, hematocrit, and microcytosis. The bone marrow was hypocellular with abnormal iron incorporation into erythroid precursor cells. This appears to be a rare form of inherited anemia characterized by iron malabsorption and disordered iron metabolism that only partially corrects after the administration of parenteral iron. These features resemble those found in the microcytic mouse (mk/mk), which also has severe microcytic anemia and iron malabsorption that partially responds to parenteral iron.

Administration, Oral↗

Forage characteristics, steer performance, and water quality from bermudagrass pastures fertilized with two levels of nitrogen from swine lagoon effluent.

Four .8-ha pastures of bermudagrass (Cynodon dactylon [L.] Pers.) were fertilized with either 456 or 873 kg/ha of nitrogen (N) from swine lagoon effluent (two replicates per treatment) and grazed by steers over two summers. Within each pasture, steers received forage only, an energy source (corn), a mixture of corn and soybean meal, or a mixture of corn and blood meal via electronic Calan feeders. All supplements were offered at a level of 1.36 kg/d, and the soybean meal and blood meal supplements provided similar among quantities of protein. Weight gains were similar among supplemented steers, but supplemented steers gained faster (P < .05) than controls. Nitrogen fertilization level had no effect on steer gains, steer grazing days per hectare, or in vitro dry matter disappearance, NDF, and ADF of clipped forage samples. Plant protein and nitrate ion concentrations were greater (P < .06) in clipped forage samples receiving the higher N application rate. Nitrate ion concentrations were greater in available forage samples from the pastures with the high N application rate. Mean total N and nitrate N concentrations were similar in water samples obtained from monitoring wells for the two N treatments over the 2 yr and there were no year x N interactions. Chloride concentrations were greater (P < .05) and pH and specific conductance were less in water samples collected from the 873 kg than from the 456 kg/ha N treatment. Long-term studies are needed to examine the possible cumulative effects of applying various levels of swine waste to the same land area.

Animal Feed↗

Genotoxic activity of 1-chloromethylpyrene in stomach epithelium in vivo: insensitivity of the stomach scintillation UDS assay.

An acknowledged weakness of current testing programmes for genotoxic hazard has been the potential insensitivity of the established mouse bone marrow micronucleus test and rat liver unscheduled DNA synthesis (UDS) assays to direct-acting or short-lived mutagens, which may be consumed at the site of initial contact. In such cases, in vivo test systems sampling tissues such as the skin or the stomach would provide valuable data. To test these principles a stomach UDS assay was evaluated using the potent locally active mutagen 1-chloromethylpyrene (1-CMP). Contrary to expectations, no UDS response was observed 16 h following 1-CMP dosage by oral gavage. To confirm the integrity of the 1-CMP used for the stomach UDS assay, a sample of the stored chemical was re-evaluated in vitro and shown to be still strongly positive in the Ames assay and to have alkylating activity at least 15 min after incubation at stomach acid pH. No UDS response was observed when test dose levels were reduced or when earlier sampling times were used. Other genotoxic endpoints were examined in stomach. 32P-Postlabelling analysis revealed high levels of adduct formation in gastric DNA. An assay utilizing electrophoresis of DNA (the comet assay) showed the occurrence of DNA damage following dosing with 1-CMP in vivo. These positive results confirmed that 1-CMP should be regarded as a potential in vivo genotoxin. The failure to detect a UDS response to 1-CMP in stomach was investigated; a strong UDS response was observed in an in vitro hepatocyte UDS assay of 1-CMP indicating that the rat was capable of repairing 1-CMP-derived DNA adducts. Pretreatment of rats with hydroxyurea depressed the level of incorporation of thymidine into DNA both in negative and positive [methyl-N-nitrosoguanidine (MNNG)] controls. The results of these studies indicated that the protease digestion method employed did not selectively or efficiently sample those cells with any UDS response to 1-CMP or MNNG, and the activity seen for the latter was most likely due to the presence of S phase cells within the digests. As a result of the finding that UDS responses were not demonstrated for the potent direct-acting mutagens 1-CMP and MNNG, the protease digestion/scintillation method for stomach UDS does not appear to have general value in a screening programme for locally active genotoxic agents.

Administration, Oral↗

Right upper lobectomy twenty years after left pneumonectomy. Preoperative evaluation and follow-up.

Quantitative perfusion lung scanning coupled with spirometry and balloon occlusion of the pulmonary artery supplying the lung to be resected have been used to predict the potential operability of patients being considered for pneumonectomy. These techniques were adapted for the lobar level prior to performing a right upper lobectomy in a 59-year-old man who had undergone a left pneumonectomy 20 years previously. This case demonstrates how physiologic reserve can be predicted in patients who require sequential pulmonary resection.

Carcinoma, Bronchogenic↗

Measurement of airway mucosal perfusion and water volume with an inert soluble gas.

The purpose of this study was to develop and validate a new in vivo technique for the measurement of tracheal mucosal blood flow (Qtr) and tissue water volume (VH2O) with an inert soluble gas. The technique was based on the notion that the uptake of dimethyl ether (VDME) from an isolated tracheal segment is governed by VH2O (transient state) and Qtr (steady state). In lightly anesthetized sheep, an endotracheal tube with two cuffs placed 14.5-16.5 cm apart was placed to create a chamber into which dimethyl ether was introduced and from which VDMME into the mucosa was determined with a sensitive pneumotachograph. Mean Qtr was 1.20 ml/min (range 0.87-1.73), and mean VH2O was 1.67 ml (range 1.27-2.26). Qtr correlated with cardiac output but not with body weight or tracheal mucosal surface area determined by He dilution. VH2O did not show a correlation with any of these parameters. The response to selected pharmacological agents suggested that the measurements of Qtr and VH2O are independent of each other and from changes in tracheal diameter. Mean Qtr was 80% of mean tracheal mucosal blood flow measured with radiolabeled microspheres. We concluded that the inert soluble gas method is capable of measuring in vivo the perfusion and a water compartment of the intact tracheal mucosa.

Animals↗

Tracheal mucosal blood flow responses to autonomic agonists.

In lightly anesthetized adult sheep, we determined tracheal mucosal blood flow (Qtr) by measuring the steady-state uptake of dimethyl ether from a tracheal chamber created by an endotracheal tube provided with two cuffs. Qtr normalized for carotid arterial pressure [Qtr(n)] was determined before and after the exposure of the tracheal mucosa to aerosolized phenylephrine (0.25-2.0 mg), isoproterenol (0.05-0.8 mg), and methacholine (2.5-20 mg). The same doses of methacholine were also administered during the intravenous infusion of vasopressin. The measurements were repeated after intravenous pretreatment with the respective antagonists phentolamine, propranolol, and atropine. Mean +/- SE base-line Qtr(n) was 1.2 +/- 0.1 ml.min-1.mmHg-1.10(2). The autonomic antagonists had no effect on mean Qtr(n). Phenylephrine produced a dose-dependent decrease in mean Qtr(n) (-70% at the highest dose), which was blunted by phentolamine, and isoproterenol produced a dose-dependent increase in mean Qtr(n) (40% at the highest dose), which was blocked by propranolol. Methacholine failed to alter mean Qtr(n) even when Qtr was first decreased by vasopressin. We conclude that in lightly anesthetized adult sheep 1) base-line Qtr(n) is not under adrenergic or cholinergic control, 2) a locally administered alpha-adrenergic agonist decreases and beta-adrenergic agonist increases Qtr(n) via specific receptor activation, and 3) a locally administered cholinergic muscarinic agonist has no effect on Qtr(n).

Administration, Inhalation↗

Hormonal control of lipolysis in perifused adipocytes from diabetic rats.

The responsiveness of adipocytes from diabetic rats to lipolytic and antilipolytic stimuli was examined in both an incubation system and a perifusion system. Lipolysis, measured by glycerol release, was initiated with varying concentrations of epinephrine or other agents. Incubated adipocytes prepared from streptozotocin-diabetic rats were more sensitive to low doses of epinephrine than controls, but at higher concentrations of hormone, glycerol release was greater from the control cells. However, maximal lipolytic responses to nonhormonal stimuli, forskolin and methylisobutylxanthine, were clearly greater in incubated adipocytes from diabetic animals. In vivo treatment of both control and diabetic animals with insulin decreased the responsiveness of perifused adipocytes to epinephrine in vitro, further demonstrating the importance of the in vivo hormone levels to lipolytic response of adipocytes. In vitro perifusion with insulin and epinephrine of cells from untreated diabetic animals demonstrated a reduced response to the acute administration of insulin. The interaction of insulin with diabetic adipocytes was further examined by incubating cells with [125I]iodoinsulin and examining the release of intact and degraded hormone during perifusion. The diabetic cells bound more labeled hormone than the control cells, but the release of intact hormone was similar in both types of cells. The diabetic cells, however, released more degraded hormone than did control cells. This suggests that the binding and degradation of insulin in diabetic cells is not impaired and that the decreased responsiveness of these cells to insulin is due to a postreceptor defect. Together these data show that decreased insulin in streptozotocin-diabetes results in increased sensitivity to lipolytic agents. In addition, the diabetes enhances the adipocyte's ability to remove insulin, i.e. increased binding and degradation. Thus, it is likely that the in vitro findings of up-regulation of receptors and increased degradation by the adipocytes are a true reflection of the in vivo insulin deficiency.

1-Methyl-3-isobutylxanthine↗

Perceptions of family practice residents toward care of the elderly.

Family practice residents were surveyed to determine their perceptions of working with geriatric patients. Three areas were surveyed: residents' views of the elderly, their comparisons of the elderly with younger patients and their ideas of what it would be like to work with elderly patients. The results show that generally residents have positive views of geriatric patients. Residents see the elderly as comparing favorably with younger people. Also, they view the elderly as possessing favorable personality characteristics, such as a sense of humor, preference for independence, flexibility, and being easy to work with. Although residents are positive about working with the elderly, they do feel some ambivalence toward working in stroke-rehabilitation programs, as well as with geriatric patients who have lost contact with reality. Medical educators need to be aware of the perceptions that residents have concerning the geriatric patient, since this type of patient will in the future comprise a larger percentage of the resident's practice.

Aged↗

Knowledge and attitudes of family practice residents toward geriatric patients.

The knowledge and attitudes of family practice residents toward geriatric patients was surveyed in eight residencies. Since geriatric care will, in the future, become a more important aspect of the family physician's practice, it is important to ascertain the knowledge and attitude level of physicians in training concerning their geriatric patients. Three aspects of this study indicate serious deficits in the educational background of these residents: the number and quality of courses offered to them is inadequate; they demonstrate a paucity of knowledge concerning the aged; the residents show a low preference for working with the aged. Clearly, medical education should address these needs and deficits.

Aged↗