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Biomedical subjects

D Julian

Publications and source records attributed to D Julian.

At least 19 recordsLinked to original sources

Guidelines on the management of secondary prophylaxis of vascular events in stable patients in primary care.

Atherothrombosis, thrombus formation superimposed on an existing atherosclerotic plaque, is an acute process leading to ischaemic events such as myocardial infarction, stroke and critical limb ischaemia. Patients presenting with clinical conditions associated with atherothrombosis are at increased risk of subsequent vascular events. The beneficial effect of antiplatelet therapies for short-term and long-term secondary prevention of atherothrombotic events has been established. These guidelines aim to provide evidence-based recommendations that will assist in the antiplatelet-mediated secondary prophylaxis of vascular events in patients with stable cardiovascular disease treated in the primary healthcare setting. Medline and the Cochrane library were accessed using free-text strategies in the domains of antiplatelet agents and antithrombotics. Development of the guidelines was driven by a series of Steering Committee meetings, in which the quality of relevant studies was assessed and identified using narrative summary. These guidelines present evidence and recommendations for the treatment of numerous atherothrombotic indications depending on individual patient circumstances.

Acute Disease↗

A developmental time line in a retinal slice from rainbow trout.

The retina in teleost fish continues to grow throughout much of the life of the animal, in part by the continuing differentiation of new tissue at the retinal margin, an area termed the peripheral growth zone (PGZ) (Lyall, Q J Micros Sci, 1957:98:101-110). We have developed a retinal slice preparation--including the PGZ--from juvenile rainbow trout (Onchorynchus mykiss), a species in which retinal growth is rapid and the PGZ is correspondingly pronounced. The PGZ slice preparation contains a time line of retinal development, with cells at different stages of maturation present side by side. We present evidence that the birth sequence of the various retinal cell types in the PGZ recapitulates the sequence during embryonic development. We also report data on the rate of growth of the PGZ in juvenile trout in vivo. Finally, we have used the PGZ slice preparation to make whole-cell voltage clamp recordings from individual retinal GCs at both early and late stages of maturation. We report that the amplitude of delayed rectifier and A-type potassium currents increases during GC maturation.

Animals↗

Roots as a site of hydrogen sulfide uptake in the hydrocarbon seep vestimentiferan Lamellibrachia sp.

Vestimentiferan tubeworms have no mouth or gut, and the majority of their nutritional requirements are provided by endosymbiotic bacteria that utilize hydrogen sulfide oxidation to fix CO(2) into organic molecules. It has been assumed that all vestimentiferans obtain the sulfide, O(2) and CO(2) needed by the bacteria across the plume (gill) surface, but some live in locations where very little sulfide is available in the sea water surrounding the plume. We propose that at least some of these vestimentiferans can grow a posterior extension of their body and tube down into the sea-floor sediment, and that they can use this extension, which we call the 'root', to take up sulfide directly from the interstitial water. In this study of the vestimentiferan Lamellibrachia sp., found at hydrocarbon seeps in the Gulf of Mexico at depths of approximately 700 m, we measured seawater and interstitial sulfide concentrations in the hydrocarbon seep habitat, determined the structural characteristics of the root tube using transmission electron microscopy, characterized the biochemical composition of the tube wall, and measured the sulfide permeability of the root tube. We found that, while the sulfide concentration is less than 1 (micro)mol l(-)(1) in the sea water surrounding the gills, it can be over 1.5 mmol l(-)(1) at a depth of 10-25 cm in sediment beneath tubeworm bushes. The root tube is composed primarily of giant (&bgr;)-chitin crystallites (12-30 % of total mass) embedded in a protein matrix (50 % of total mass). Root tubes have a mean diameter of 1.4 mm, a mean wall thickness of 70 (micro)m and can be over 20 cm long. The tubeworm itself typically extends its body to the distal tip of the root tube. The root tube wall was quite permeable to sulfide, having a permeability coefficient at 20 degrees C of 0. 41x10(-)(3 )cm s(-)(1), with root tube being 2.5 times more permeable to sulfide than trunk tube of the same diameter. The characteristics of the root suggest that it reaches down to the higher sulfide levels present in the deeper sediment and that it functions to increase the surface area available for sulfide uptake in a manner analogous to a respiratory organ.

Animals↗

Biopsychobehavioral model of risk of severe hypoglycemia. Self-management behaviors.

OBJECTIVE: To identify self-management antecedents of low blood glucose (BG) (< 3.9 mmol/l) that might be easily recognized, treated, or avoided altogether. RESEARCH DESIGN AND METHODS: Ninety-three adults with type 1 diabetes (age, 35.8 +/- 8 years [mean +/- SD]; duration of diabetes, 17.0 +/- 11 years; daily insulin dose, 0.58 +/- 0.18 U/kg; and HbAlc, 8.6 +/- 1.8%) were recruited to participate in the study. Of the 93 subjects, 42 had a history of severe hypoglycemia (SH), defined as two or more hypoglycemic episodes in the preceding 12 months, and 51 subjects had no history of SH (No-SH) in the same time period. Before each of 70 BG measurements obtained over a 3-week period, subjects used a handheld computer to record whether their most recent insulin, food, and exercise was more than, less than, or the same as usual. Associations among self-management behaviors preceding BG readings < 3.9 mmol/l versus those preceding BG readings of 5.6-7.8 mmol/l were determined using chi 2 tests, analyses of variance, and logistic regression analyses. RESULTS: Analysis of 6,425 self-management/self-monitoring of BG events revealed that the usual amounts of insulin, food, and exercise preceded the events 58.3% of the time. No significant differences were observed for changes in insulin before readings of BG < 3.9 mmol/l versus 7.8 < BG > 5.6 mmol/l, but significantly less food (P < 0.01) was eaten and more exercise (P < 0.001) was performed before the low BG measurement. No interactions between SH and No-SH groups and management behaviors were observed. However, each of the three management variables entered significantly in a logistic model that predicted 61% of all readings of BG < 3.9 mmol/l. CONCLUSIONS: Subjects with a history of SH did not report managing their diabetes differently from those with no such history. Specifically, when low BG occurred, the preceding management behaviors, although predictive of low BG, were not different in SH and No-SH subjects. Overall, self-management behaviors did not distinguish SH from No-SH subjects. Thus, even though it might be beneficial for all patients to review their food and exercise management decisions to reduce their frequency of low BG, an educational intervention whose content stresses insulin, food, and exercise would be unlikely by itself to be sufficient to reduce the frequency of SH.

Adult↗

Birth and fate of proliferative cells in the inner nuclear layer of the mature fish retina.

In teleost fish, unlike other vertebrates, the retina continues to grow throughout the animal's life both by stretching of the mature tissue and by the addition of new cells. Following larval development, new retinal cell birth is known to occur in a rim at the periphery of the mature retina and in the outer nuclear layer (ONL). We have now found that cell birth and proliferation also occurs in the inner nuclear layer (INL) of the mature fish retina. In rainbow trout (Onchoryncus mykiss), proliferative cells exist in the INL of fish of all ages, at least up to 2 years posthatching. The proliferative cells form clusters in the INL that align in radial columns, reaching from the inner to the outer plexiform layers. The density of proliferative cell clusters changes along the equatorial plane of the retina and is highest near both the nasal and temporal poles. Our data suggest that, after birth, the proliferative cells migrate away from the INL and into the ONL, with a half-time of about 3 days, and their cell bodies can be seen in the outer plexiform layer. Once they are in the ONL, the proliferative cells continue to divide and likely give rise to the precursor cells that differentiate into new rod photoreceptors.

Animals↗

An avian model for comparative studies of insulin teratogenicity.

This study was designed to explore the effects of purified insulin during early stages of chick embryo development, and to search for variations between different molecular structures of the hormone. Chicken embryos were treated in ovo with a single dose of insulin (porcine or bovine), in only one stage of development between day 0 and day 9. Two susceptible periods were found. The earliest period (day 0 to day 3), characterized by abnormalities in the caudal vertebrae and a high mortality rate, was followed by a period with a different set of malformations, a syndrome classified as achondroplasia. The rate of achondroplastic embryos was significantly higher with porcine rather than with bovine insulin. Paradoxically, insulin at physiological doses has stimulatory effects in growth and development but, in contrast, has inhibitory effects at higher doses. The precise signalling cascade of events in the target cells is still unclear. The possible interpretations of our results are discussed. The similarity between the insulin-induced abnormalities in the chicken embryos and the caudal regression syndrome, the most common malformation found in infants of diabetic women, suggests a common mechanism. This circumstance offers the chicken embryos as an excellent in vivo model for research on the mechanism of action of insulin during normal and abnormal development.

Abnormalities, Drug-Induced↗

Neuromuscular sensitivity to hydrogen sulfide in the marine invertebrate Urechis caupo.

Hydrogen sulfide (HS) is a well-known inhibitor of aerobic respiration via its reversible binding of mitochondrial cytochrome c oxidase, but recent studies have suggested that HS may have other non-respiratory actions. We have studied the effects of HS on spontaneous and evoked contractions in vitro under hypoxic and anoxic conditions in nerve-muscle preparations from the echiuran worm Urechis caupo. Contraction amplitude in response to electric field stimulation under anoxic conditions was completely abolished by HS within minutes in a classic dose-response relationship (Kd=31 mmol l-1, r2=0.86). Exposure of body wall and esophagus to HS in vitro for up to 6 h demonstrated that the contraction amplitude and frequency of spontaneous activity were relatively insensitive to anoxia, but that the sensitivity to HS was similar to that seen in field-stimulated muscle (Kd=2.7-32 mmol l-1). The toxic effects of HS were reversible, with almost complete recovery under anoxic conditions within the first hour. These data indicate that HS at millimolar concentrations can directly inhibit muscle contraction. Although the mechanism of this action is unknown, it does not appear to involve metabolic pathways or oxygen transport.

Animals↗

The psychosocial impact of severe hypoglycemic episodes on spouses of patients with IDDM.

OBJECTIVE: No previous studies have examined the psychosocial impact of severe hypoglycemic episodes in IDDM patients on their spouses. This study compared spouses of IDDM patients with and without a history of recent severe hypoglycemia (SH) using traditional measures of psychosocial status and marital conflict, as well as diabetes-specific measures. RESEARCH DESIGN AND METHODS: A total of 61 nondiabetic spouses (23 wives and 38 husbands) of IDDM patients participated in the study. Spouses completed a battery of traditional psychometric measures (depression, anxiety, marital conflict) and diabetes-specific measures (fear of hypoglycemia, marital conflict over diabetes, sleep disturbance caused by hypoglycemia). Scores of spouses of IDDM patients with and without a recent history of SH were compared with t tests. RESULTS: Spouses of IDDM patients with and without a recent history of SH showed no differences on traditional psychometric measures of depression, anxiety, and marital conflict. However, spouses of patients with a recent history of SH showed significantly more fear of hypoglycemia, marital conflict about diabetes management, and sleep disturbances caused by hypoglycemia. Exploratory analyses of variance (ANOVAs) found no differences on psychometric measures between wives and husbands, with the exception that husbands of SH patients reported more sleep disturbance. Nondiabetic spouses, on average, showed greater fear of hypoglycemia than their diabetic partners. CONCLUSIONS: Although SH in IDDM patients can have a significant impact on the psychosocial status of their spouses, in this study the negative impact was restricted to areas of life that are directly related to diabetes and its management. Thus, SH per se is not necessarily associated with significant increases in spousal anxiety, depression, or marital conflict, but may be associated with types of diabetes-specific psychosocial distress that are not easily identified by traditional psychometric measures.

Adult↗

Water lung and body wall contributions to respiration in an echiuran worm.

The modified hindgut of the echiuran marine worm Urechis caupo functions as a water lung and has been assumed to be a much more important respiratory surface than its thick, muscular body wall. We tested this assumption by measuring whole animal O2 consumption, hindgut O2 uptake, and hindgut ventilation activity simultaneously in unrestrained worms in artificial burrows from 25 to 300 Torr O2. Under experimental conditions the contribution of the hindgut to total O2 uptake is variable and strongly correlated to hindgut ventilatory activity. Over a PO2 range simulating that encountered in the natural environment, the hindgut accounts for approximately half of total O2 uptake on average. Under progressive hypoxic exposure total O2 consumption decreased by 50%, yet O2 conductance and extraction increased. The results suggest that the water lung function of the modified hindgut supplements O2 uptake across the body wall, and may be especially important during periods of high activity such as may occur during feeding and burrowing.

Animals↗

Reduced awareness of hypoglycemia in adults with IDDM. A prospective study of hypoglycemic frequency and associated symptoms.

OBJECTIVE: To prospectively evaluate the frequency and severity of hypoglycemic episodes in IDDM subjects who declare themselves to have reduced awareness of hypoglycemia, to validate their self-designations in their natural environment, and to determine objectively the presence or absence of autonomic and neuroglycopenic symptoms associated with their low blood glucose (BG) levels. RESEARCH DESIGN AND METHODS: A total of 78 insulin-dependent diabetes mellitus (IDDM) subjects (mean age 38.3 +/- 9.2 years; duration of diabetes 19.3 +/- 10.4 years) completed two sets of assessments separated by 6 months. The assessments included reports of frequency and severity of low BG, symptoms associated with low BG, and a BG symptom/estimation trial using a hand-held computer (HHC). Diaries of hypoglycemic episodes were kept for the intervening 6 months. HbA1 levels were determined at each assessment. RESULTS: Of the subjects, 39 declared themselves as having reduced awareness of hypoglycemia (reduced-awareness subjects). There were no differences between these reduced-awareness subjects and aware subjects with regard to age, sex, disease duration, insulin dose, or HbA1. During the HHC trials, reduced-awareness subjects were significantly less accurate in detecting BG < 3.9 mmol/l (33.2 +/- 47 vs. 47.6 +/- 50% detection, P = 0.001) and had significantly fewer autonomic (0.41 +/- 0.82 vs. 1.08 +/- 1.22, P = 0.006, reduced-awareness vs. aware) and neuroglycopenic (0.44 +/- 0.85 vs. 1.18 +/- 1.32, P = 0.004, reduced-awareness vs. aware) symptoms per subject. Prospective diary records revealed that reduced-awareness subjects experienced more moderate (351 vs. 238, P = 0.026) and severe (50 vs. 17, P = 0.0062) hypoglycemic events. The second assessment results were similar to the first and verified the reliability of the data. CONCLUSIONS: IDDM subjects who believe they have reduced awareness of hypoglycemia are generally correct. They have a history of more moderate and severe hypoglycemia, are less accurate at detecting BG < 3.9 mmol/l, and prospectively experience more moderate and severe hypoglycemia than do aware subjects. Neither disease duration nor level of glucose control explains their reduced awareness of hypoglycemia. Reduced-awareness individuals may benefit from interventions designed to teach them to recognize all of their potential early warning symptoms.

Adult↗

A multicenter evaluation of blood glucose awareness training-II.

OBJECTIVE: Blood glucose awareness training (BGAT) teaches individuals with insulin-dependent diabetes to more accurately estimate/detect their blood glucose (BG) fluctuations. It has not, however, consistently resulted in improved ability to detect low BG. To assess an enhanced version of BGAT (BGAT-II), with more focus on increasing sensitivity to low BG events, a multicenter study was undertaken. Following up on previous findings that BGAT is most effective with individuals who are least accurate in estimating BG, this study explicitly recruited subjects who did and did not report reduced awareness of hypoglycemia. RESEARCH DESIGN AND METHODS: Seventy-eight subjects from three research sites participated in a repeated baseline design. Subjects' BG estimation accuracy and BG profiles were assessed 6 months before, immediately before, and immediately after BGAT-II. RESULTS: Post-treatment, BGAT-II led to better overall accuracy in detecting BG fluctuations and better detection of both low and high BG levels. This was achieved while the number of low readings of self-monitoring of blood glucose (SMBG) was reduced. Reduction in the number of low SMBG events was significant only for subjects reporting awareness of hypoglycemia. Detection of low BG was significant only for subjects reporting reduced awareness of hypoglycemia. Both groups demonstrated equivalent improvements in detection of high BG levels. CONCLUSIONS: BGAT may be an effective behavioral strategy for reversing hypoglycemic unawareness and an adjunct to intensive insulin therapy to reduce the occurrence of severe hypoglycemia.

Adult↗

The European Myocardial Infarct Amiodarone Trial (EMIAT). EMIAT Investigators.

The objective of the European Myocardial Infarct Amiodarone Trial (EMIAT) is to assess the efficacy of amiodarone on mortality of patients with depressed left ventricular (LV) function following myocardial infarction (MI). The rationale for the trial is as follows: patients with poor LV function after acute MI have a high sudden cardiac death (SCD) mortality; amiodarone is a successful prophylactic therapy against SCD in patients with ventricular arrhythmias; a number of small studies (Canadian Amiodarone Myocardial Infarction Arrhythmia Trial [CAMIAT] pilot study, Basel Antiarrhythmic Study & Infarct Survival [BASIS], and the Polish Amiodarone Trial [PAT]) of prophylactic amiodarone post AMI have shown a beneficial response attributable to amiodarone. Patients are enrolled between 5 and 21 days after acute MI if LV ejection fraction (assessed by multiple-gated image acquisition nuclear angiography) is < or = 40%. The study group is stratified according to ejection fraction (stratum 1, 31-40%; stratum 2, < 31%). Amiodarone or placebo treatment (blind, randomized) is initiated prior to the discharge of the patient from the hospital and each patient is followed up for the duration of the study, at least 1 year. Recruitment began on November 30, 1990, and will continue for 4 years; > 700 patients are enrolled from > 60 centers (13 countries). The total study mortality (10% at 500 days) and the differential mortality of both strata are as anticipated. Side effects have been infrequent and very few patients have been withdrawn from the study. Trial conclusion is forecast for October 1995.

Amiodarone↗

Regional cerebral blood flow and tissue oxygenation during hypocarbia in geese.

Very low arterial CO2 tension (PaCO2) experienced by birds during high-altitude flight may result in cerebral vasoconstriction and reduced cerebral O2 delivery. To examine this possibility, we measured regional cerebral blood flow (CBF) and tissue PO2 in pentobarbital-anesthetized geese (Anser domesticus). Twenty-five-micrometer Teflon-coated platinum electrodes for H2-clearance measurements of local blood flow or tissue PO2 were implanted in the cerebral cortex in 11 geese. Tissue H2 and O2 were measured by voltage clamping the electrodes at +0.30 and -0.5 V, respectively. Washout kinetics of H2 gas administered via unidirectional lung ventilation was used to calculate local blood flow for those electrodes exhibiting one- or two-compartment washout kinetics of H2 (128 of 296 washouts in 31 electrodes). PaCO2 was controlled between 8 and 55 mmHg by altering pulmonary gas flow or by adjusting inspired PCO2. CBF decreased as PaCO2 fell from 50 to 20 mmHg but did not decrease further as PaCO2 was reduced below 20 mmHg. CBF was uniformly distributed in different regions of the cortex. Despite the plateau in CBF during severe hypocapnia, tissue PO2 continued to decline as PaCO2 fell below 20 mmHg. Severe alkalosis may limit cerebral O2 delivery in birds during high-altitude flight.

Animals↗