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Biomedical subjects

A Ingram

Publications and source records attributed to A Ingram.

At least 19 recordsLinked to original sources
PubMed2005

The effect of the amount of binder liquid on the granulation mechanisms and structure of microcrystalline cellulose granules prepared by high shear granulation.

The structure of granules changes during the high shear granulation process. The purpose of this research was to investigate the effect of the amount of binder liquid on the structure of the granules and the structural changes which occur during the granulation process, using microcrystalline cellulose (MCC) and water as the model system. The structure is the result of the granulation mechanism; therefore, conclusions can be drawn about the latter by studying the former. X-ray microtomography and scanning electron microscopy (SEM) were applied in order to visualise the densification process of granules, which were first freeze dried in order to preserve their structure. Variations in their porosity were quantified by applying image analysis to the tomography results. In order to link the granule mechanical properties to their structural differences, a micromanipulation technique was used to measure granule resistance to deformation. MCC granules granulated with 100% (w/w) water showed increased densification with time, as expected; detailed examination showed that densification is more pronounced in the core of the granule; whereas the outer part remained more porous. Increased densification reduces deformability, so that granules become more resistant to breakage. The lower deformability of the densified granules in the final stages of granulation might result in establishment of equilibrium between attrition and growth, without substantial gross breakage. On the other hand, when more water was used (125%, w/w), densification was hardly observed; the porosity of the granule core was still high even after prolonged granulation times. This may be explained by the fact that higher water content increases the ease of deformation of granules. This increased deformability led to significant granule breakage even during the final phases of the granulation process. Therefore, for these granules a final equilibrium between breakage and coalescence might be established. This also explains why more granules produced with 125% granulation liquid were composed of fragments of irregular shape. Our results establish the link between the granulation behaviour of MCC in the latter stages and the material structure of these granules, which is determined by their liquid content. The process conditions (amount of liquid) to be chosen depend largely on the final purpose for which the granular material is produced.

Cellulose↗
PubMed2005

The relation between granule size, granule stickiness, and torque in the high-shear granulation process.

PURPOSE: To investigate the background of the observed relationship between measured torque and granule size in high-shear granulation processes. METHODS: Torque was measured during the granulation process; the behavior of individual wet granules during compaction was investigated using micromanipulation. Surface properties of wet granules were manipulated by coating them with talc. RESULTS: The torque-granule size relationship could not be explained by the rise in mass of the individual granules; it occurs rather through an increase in stickiness of the granules when the moisture content is increased. Obviously, the increased stickiness that causes the granules to grow also increases the torque. Increased stickiness was shown to be the result of an increased deformability of the granules at higher moisture contents, in combination with a change in surface properties. The elastic-plastic behavior (ratio of elastic to plastic deformation) was found to change at increasing moisture contents. CONCLUSIONS: Our results imply that changes in the stickiness of the granular material that may be caused by changes in composition shift the torque-size relationship. This may be of particular importance when, for example, granulation results from placebo batches are used to predict the granule size of drug-containing batches.

Particle Size↗
PubMed2005

Severe retinopathy of prematurity: longitudinal observation of disease and screening implications.

PURPOSE: To test the effectiveness of our Canadian retinopathy of prematurity (ROP) screening guidelines as applied to high-risk premature infants. STUDY DESIGN: Retrospective longitudinal cohort study. SUBJECTS: A total of 969 infants were examined longitudinally between 1991 and 2000 and 46 of these infants screened were treated for severe ROP. METHODS: Data from weekly ROP screening examination results were collected from a geographical area and analysed. RESULTS: The average incidence of severe ROP requiring treatment in the population of premature infants eligible for screening was 48.3 per 1000. In all, 46 infants were treated in this cohort. The mean gestational age (GA) was 25.5 weeks of age and the mean birth weight was 750 g. The mean chronological age (CA) and postmenstrual age (PMA) at the time of first screening was 36 days and 30.7 weeks, respectively. The first identification of any ROP in this group was at a mean CA 60 days and PMA of 34.1 weeks. The mean CA and PMA of the first observation of stage 3 were 74 days and 36.3 weeks. The mean CA and PMA at the time of treatment were 86 days and 37.7 week. CONCLUSIONS: Our observations and analysis indicate the following ROP screening recommendations: infants of 28 weeks of GA or less, infants with a GA between 28 weeks and 30 weeks should have a single 'spot examination' at approximately 37 weeks of PMA (or prior to discharge from hospital) to include possible outliers; infants born with a birth weight of 1250 g or less; initial screening examination should be at 31 weeks of PMA or 4 weeks of CA, whichever is later; in the presence of any active ROP, the infant should be followed every 1-2 weeks; and stage 3 should be followed at least every 7 days.

Age Factors↗
PubMed2001

Permanent pacemaker implantation via the femoral vein: an alternative in cases with contraindications to the pectoral approach.

BACKGROUND: This paper presents a consecutive series of permanent pacemakers (PPM) implanted via the femoral vein in patients with contraindications to pacing systems via the superior vena cava (SCV). The femoral vein approach is a less invasive and feasible alternative to epicardial lead placement. METHODS: Twenty-seven patients had femoral pacemakers inserted. Indications for femoral vein pacemaker insertion were: SVC/subclavian obstruction (12 patients, 44.4%), previous infection in SVC leads (four patients, 14.8%), mastectomy and/or radiotherapy to chest (four patients, 14.8%), multiple leads in SVC (two patients, 7.4%), recurrent erosion (two patients, 7.4%), abnormal anatomy (one patient, 3.7%), painful pacemaker pocket (one patient, 3.7%) and burns (one patient, 3.7%). Fifty-one leads, 25 atrial and 26 ventricular, were inserted. The majority of leads were active fixations (96% of atrial leads and 85% ventricular leads). RESULTS: During a mean follow-up of 36.5 months (range 0.9-116.5), six additional unplanned procedures were performed in four patients. Atrial lead displacement occurred in five leads (20%). There were no ventricular lead displacements. In two patients, box revision for pre-erosion was required. One patient had persistent pain at the site of abdominal pacemaker generator. Infection, thromboembolic events, thromophlebitis, evidence of lower limb venous occlusion and lead fracture did not occur. CONCLUSION: Femoral vein PPM are a simple and feasible alternative in patients in whom the SVC approach is contraindicated.

Adult↗
PubMed2001

Angiotensin II activates the GFAT promoter in mesangial cells.

Expression of glutamine:fructose-6-phosphate amidotransferase (GFAT), the rate-limiting enzyme for glucose entry into the hexosamine pathway, is transcriptionally regulated. Immunohistochemical studies of human kidney biopsies demonstrate increased GFAT expression in diabetic glomeruli, but the mechanism responsible for this overexpression is unknown. Given the role of ANG II in diabetic kidney disease, we chose to study the effect of ANG II on GFAT promoter activity in mesangial cells (MC). Exposure of MC to ANG II (10(-7) M) increased GFAT promoter activity (2.5-fold), mRNA (3-fold), and protein (1.6-fold). ANG II-mediated GFAT promoter activation was inhibited by the ANG II type I receptor antagonist candesartan (10(-8) M) but was unaffected by the ANG II type II receptor antagonist PD-123319 (10(-8) M). The intracellular calcium chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (10(-6) M), protein kinase C (PKC) inhibitors bisindoylmaleimide-4 (10(-6) M) and calphostin C (10(-7) M), protein tyrosine kinase (PTK) inhibitor genistein (10(-4) M), Src family kinase inhibitor PP2 (2.5 x 10(-7) M), p42/44 mitogen-activated protein kinase (MAPK) inhibitor PD-98059 (10(-5) M), and the epidermal growth factor (EGF) inhibitor AG-1478 all attenuated GFAT promoter activation by ANG II. We conclude that the GFAT promoter is activated by ANG II via the AT1 receptor. Promoter activation is calcium dependent and PKC dependent but also involves PTK signaling pathways including Src, the EGF receptor, and p42/44 MAPK.

Angiotensin II↗
PubMed2001

Trials comparing early vs late extubation following cardiovascular surgery.

We identified 10 randomized trials that compared alternative management approaches to patient care during and following cardiovascular surgery. One overall strategy involved a modification of anesthesia, in particular, a reduction in the dosage of fentanyl and benzodiazepine or the substitution of fentanyl for propofol (five randomized controlled trials [RCTs]). Pooled results show a shorter duration of ventilation (7 h) and a shorter duration of hospital stay (approximately 1 day) associated with lower anesthetic doses. The second strategy involved early vs late extubation once patients were admitted to the ICU (five RCTs). Pooled results show a shorter duration of ventilation (13 h) and a shorter duration of ICU stay (half a day) associated with early extubation. An additional 8 nonrandomized trials had findings that were consistent with the 10 RCTs. Reintubation, complications, and mortality rates were too low to draw conclusions about these outcomes. Overall, these studies indicate that anesthetic, sedation, and early-extubation strategies in selected cardiac surgery patients are associated with a shorter duration of mechanical ventilation and shorter lengths of ICU and hospital stays.

Cardiac Surgical Procedures↗
PubMed2001

First records of Culex gelidus from Australia.

Culex gelidus Theobald was recorded for the 1st time in Australia in May 1999 from 2 locations (Brisbane and Mackay, Queensland) approximately 820 km apart. Larval samples were collected from a semi-permanent freshwater swamp and an open drain and reared to adults in laboratories. Implications for Australia are discussed.

Animals↗
PubMed2000

Effects of diabetes and hypertension on glomerular transforming growth factor-beta receptor expression.

BACKGROUND: Several studies have suggested that transforming growth factor-beta1 (TGF-beta1) is an important determinant of diabetic glomerular injury. TGF-beta1 forms a heteromeric complex with two cellular receptor subtypes, designated TGF-beta RII and TGF-beta RI, but the effects of diabetes mellitus on glomerular TGF-beta receptor expression have not been completely elucidated. We first compared the effect of experimental type I diabetes mellitus and uninephrectomy on glomerular TGF-beta receptor expression in spontaneously hypertensive rats (SHRs), and then sought to determine whether changes in TGF-beta receptor expression were strain specific by studying normotensive Wistar-Kyoto (WKY) rats. METHODS: Five groups of male SHRs were studied. The first group received streptozotocin (60 mg/kg IV) and was studied after one week. The second group received streptozotocin and was studied after two weeks. The third group received streptozotocin (60 mg/kg IV) but received insulin to maintain euglycemia. The fourth group of age-matched SHRs served as the control group, while a fifth group of SHRs underwent uninephrectomy. Four groups of male WKY rats were also studied. The first group of WKY rats served as the age-matched control group. The second group of WKY rats received streptozotocin, while a third group of WKY rats underwent uninephrectomy. The fourth group underwent uninephrectomy and received streptozotocin. At each time point, glomeruli were isolated for protein extraction, and the protein was subjected to Western blot analysis of TGF-beta RII and TGF-beta RI expression. RESULTS: Basal expression of both TGF-beta receptors per microgram of glomerular protein was similar in normotensive WKY rats and hypertensive SHRs. Hyperglycemia (blood glucose level, 17.8 +/- 2.9 mmol/L) led to an early twofold increase in TGF-beta RII protein expression and a fourfold increase in TGF-beta RI protein expression in the glomeruli of hypertensive diabetic SHRs compared with euglycemic SHRs (blood glucose level, 5.8 +/- 0.8 mmol/L), which was sustained after two weeks. Insulin treatment (blood glucose level, 5. 2 +/- 0.9 mmol/L) normalized both TGF-beta RII and TGF-beta RI expression in the glomeruli of SHRs that received streptozotocin. Glomerular capillary hypertension in the uninephrectomized SHRs led to a twofold increase in glomerular TGF-beta RII protein expression, but did not reproduce the effect of diabetes mellitus on TGF-beta RI expression. In contrast to the findings in SHRs, neither hyperglycemia (blood glucose level, 15.5 +/- 2.1 mmol/L), uninephrectomy, nor hyperglycemia (blood glucose level, 16.8 +/- 3.0 mmol/L) and uninephrectomy altered TGF-beta receptor expression in the glomeruli of normotensive WKY rats. CONCLUSION: These studies support the hypothesis that hemodynamic factors and metabolic factors influence glomerular TGF-beta receptor in vivo in the SHRs.

Animals↗
PubMed2000

The North Carolina Black Churches United for Better Health Project: intervention and process evaluation.

The North Carolina Black Churches United for Better Health project was a 4-year intervention trial that successfully increased fruit and vegetable (F&V) consumption among rural African American adults, for cancer and chronic disease prevention. The multicomponent intervention was based on an ecological model of change. A process evaluation that included participant surveys, church reports, and qualitative interviews was conducted to assess exposure to, and relative impact of, interventions. Participants were 1,198 members of 24 intervention churches who responded to the 2-year follow-up survey. In addition, reports and interviews were obtained from 23 and 22 churches, respectively. Serving more F&V at church functions was the most frequently reported activity and had the highest perceived impact, followed by the personalized tailored bulletins, pastor sermons, and printed materials. Women, older individuals, and members of smaller churches reported higher impact of certain activities. Exposure to interventions was associated with greater F&V intake. A major limitation was reliance on church volunteers to collect process data.

Adult↗
PubMed1999

Mode switching for atrial tachyarrhythmias.

Mode switching for atrial tachyarrhythmias is a concept that originated from use of DDI mode and was introduced in the early 1990s to prevent dual-chamber pacemakers from ventricular tracking of rapid atrial rates. This article describes the currently available systems and discusses the advantages and disadvantages of the technique. The results of a preliminary randomized controlled trial of 1 algorithm and plans for a second study are presented.

Algorithms↗
PubMed1996

Glomerular dysfunction in the aging Fischer 344 rat is associated with excessive growth and normal mesangial cell function.

BACKGROUND: Fischer 344 (F344) rats display focal and diffuse glomerulosclerosis with aging postulated to result from loss of normal mesangial cell intrinsic function, e.g., vasoactive hormone signaling, or preservation of normal responsiveness to extrinsic growth factors. METHODS: In 3-, 17-, and 24-month-old F344 male rats, glomerular structure, measured by PC-based morphometry, and function were compared. Immunoperoxidase staining of glomerular proliferating cell nuclear antigen (PCNA) detected cellular proliferation. Primary cultured mesangial cells from the 3 age groups were studied in parallel. Calcium (Ca2+) signaling, measured by Fura-2 fluorescence, contraction to vasopressin (AVP) 1 microM, measured by videomicroscopy, and proliferative response to platelet-derived growth factor-beta beta (PDGF) were compared. RESULTS: Proteinuria was 13 +/- 4, 38 +/- 17, and 110 +/- 35 mg/24 hours at 3, 17, and 24 months, respectively (n = 5, mean +/- SE, p < .01, 3 vs 24 months), with no change in 24-hour creatinine clearances. Glomerular volumes (n = 200/group) for 3, 17, and 24 months, respectively, were .30 +/- .01, .60 +/- .02, .74 +/- 0.2 x 10(6) micron3 (p < .001, 3 months vs 17 months, and 17 vs 24 months). Glomerular basement membrane (GBM) widths and fractional mesangial volumes increased significantly with aging. Glomerular cell PCNA staining remained positive at 24 months. Cultured mesangial cell Ca2+ signaling and contraction to AVP were unchanged with aging. Proliferation to PDGF, which was partially inhibited with verapamil, was similar at 3 and 24 months. CONCLUSIONS: In the Fischer 344 rat, mesangial cell Ca2+ signaling, contraction, and proliferation responsiveness are unchanged with aging. Continued growth is associated with the glomerulosclerosis of aging.

Aging↗
PubMed1996

Immediate early protein IE63 of herpes simplex virus type 1 binds RNA directly.

The herpes simplex virus type 1 (HSV-1) immediate early protein IE63 acts post-transcriptionally to affect RNA 3'-processing and splicing. Functional domains such as the RGG box and zinc-finger motifs potentially provide the protein with RNA binding capacity. Here, IE63 protein expressed in E. coli, purified by affinity chromatography and used in RNA binding assays, demonstrated similar binding to RNA substrates containing poly(A) sites from different temporal classes of HSV-1 genes, RNA containing splice site recognition sequences and RNA containing no recognized processing motifs. Competition binding assays showed that IE63 binding could be competed out, suggesting that IE63 binds RNA weakly. HSV-1 infection results in an increase or stabilization in vitro of protein binding to poly(A) site-containing RNAs; IE63 is required for this effect. RNA binding assays combining purified IE63 with protein from mock-infected and HSV-1 infected nuclear extracts demonstrated no effect on protein-RNA binding patterns.

Binding Sites↗
PubMed1995

Single-run separation and detection of multiple metabolic intermediates by anion-exchange high-performance liquid chromatography and application to cell pool extracts prepared from Escherichia coli.

A method is described for analysis of the intracellular concentrations of metabolic intermediates of the Embden-Meyerhof-Parnas pathway, the Entner-Doudoroff pathway, the pentose phosphate pathway, and the tricarboxylic acid cycle in cell pool extracts of Escherichia coli. A single anion-exchange HPLC run of 40 min allowed resolution of 27 anionic metabolite standards. Detection limits of 0.1 nmol per injection were achieved by use of a conductivity detector equipped with an anion self-regenerating suppressor and a uv detector. A boiling water extraction procedure was used to prepare cell pool extracts. Cochromatography of cell pool extracts and metabolite standards was used to confirm the identities of metabolites in the cell pool. As many as 16 metabolites could be detected and quantified in the cell pool extracts by using the described HPLC method. An analysis of metabolite concentrations in E. coli showed the dynamics of glucose metabolism during a 2-min transition from starvation to steady-state metabolism following addition of glucose. The ease and power of this method suggests general utility for in vivo metabolite analysis in a variety of experimental systems.

Carbohydrates↗
PubMed1995

Dietary supplementation with L-arginine limits cell proliferation in the remnant glomerulus.

One effect of L-arginine is to increase nitric oxide (NO) production by endothelial cells. NO directly reduces endothelin-1 production by endothelial cells and also inhibits platelet-derived growth factor (PDGF) induced cell proliferation. Since subtotal renal ablation is associated with an early phase of cell proliferation in the glomerulus that precedes injury, we examined the effect of dietary supplementation with L-arginine on glomerular cell proliferation and expression of the cytokine endothelin-1 (ET-1). A first group of renal-ablated rats was untreated. A second group of renal-ablated rats received L-arginine (1%) in the drinking water. Two weeks after subtotal ablation renal cortical tissue was snap frozen for immunohistochemical analysis for proliferating cell nuclear antigen (PCNA) expression and ET-1. Protein and total RNA was extracted from sieved glomeruli. mRNA levels were quantitated by co-amplification RT-PCR utilizing specific 5' and 3' primers for rat ET-1 and beta-actin. L-arginine reduced the number of PCNA positive nuclei in remnant glomeruli, and Western blot Analysis of glomerular proteins also showed that L-arginine reduced PCNA expression. Glomerular ET-1 mRNA levels and protein immunostaining declined in the rats receiving L-arginine. We conclude that dietary supplementation with L-arginine reduces early cell proliferation in the remnant glomerulus, an effect that may be mediated, in part, by a decrease in ET-1 production.

Animals↗
PubMed1994

Reasons for reprogramming dual chamber pacemakers to VVI mode: a retrospective review using a computer database.

Seven hundred seventy-one dual chamber pacemakers implanted over a 13-year period were identified using a computer database. The mean follow-up period was 40.4 +/- 30.9 months (mean +/- SD). Thirty-three (4.3%) patients were reprogrammed to the VVI mode after a mean period of 26.4 +/- 29 months. Indications for pacing in those reprogrammed were: complete heart block 45.7%, impaired AV conduction 5.7%, sick sinus syndrome 34.2%, carotid sinus syndrome 11.4%, and vasovagal syndrome 2.8%. The most common reason for reprogramming was development of sustained atrial arrhythmias (atrial fibrillation or flutter), which occurred in 25 patients (3.3% of entire group). The remaining 8 (1% of entire group) were reprogrammed because of atrial lead related problems.

Arrhythmias, Cardiac↗
PubMed1994

Permanent pacing for cardioinhibitory malignant vasovagal syndrome.

OBJECTIVE: To evaluate the effect of permanent pacing in cardioinhibitory malignant vasovagal syndrome. PATIENTS AND METHODS: 37 patients with permanent pacemakers for cardioinhibitory malignant vasovagal syndrome. All presented with syncope (median six episodes, median frequency two episodes a year) and after conventional investigation and invasive electrophysiological assessment they remained undiagnosed, and without a generally accepted indication for pacemaker implantation. In all vasovagal syncope with cardioinhibition (heart rate at syncope < 60 beats/min) developed during tilt tests performed according to the Westminster protocol (head up tilt at 60 degrees with a footplate support for 45 minutes or until syncope intervenes). Dual chamber pacemakers were implanted in 35 (95%) and VVI pacemakers in the remaining two (5%). RESULTS: Over a mean (SD) follow up since implantation of 50.2 (23.9) months symptomatic improvement occurred in 89%: 62% remained free of syncope and 27% were completely symptom free. The collective syncopal burden of these 37 patients was reduced from 136 to 11 episodes each year. During follow up three patients died from unrelated causes. Patients who become asystolic during the tilt test (sinus pause of at least four seconds) experienced no greater benefit from pacing than those with less extreme cardioinhibition. Patients who remained free of syncope since implantation were younger than those who continued to experience syncope. Patients who remained completely symptom free after implantation were younger, more likely to be male, and had had fewer syncopal episodes before implantation than those who continued to experience syncope or presyncope. No other demographic, clinical, investigative, or pacing variable suggested a more favourable outcome after implant. CONCLUSIONS: This retrospective and uncontrolled experience suggests a possible role for permanent pacing in selected patients with cardioinhibitory malignant vasovagal syndrome. Improved acquisition of tilt test data may enable better selection of patients who are suitable for permanent pacing. A randomised prospective study to compare permanent pacing with no treatment or with medical treatment in cardioinhibitory malignant vasovagal syndrome is indicated.

Adult↗