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Biomedical subjects

A G Harris

Publications and source records attributed to A G Harris.

At least 19 recordsLinked to original sources
PubMed2000

Automation of the use of fluorescent microspheres for the determination of blood flow.

Fluorescent-labeled microspheres (FM) are a new tool for the determination of organ blood flow. However, the FM-method is labor intensive, because of the necessity to recover the microspheres from the tissue samples. The aim of this study was to automate the FM-method. A Zymate-Robotic System (Zymark, Idstein, Germany) was modified to handle a novel filtration device. The robot is surrounded by 12 different stations which are necessary to process the samples. It performs the sequential steps which are needed to recover the microspheres from the samples. The dyes are finally released from the FM with a solvent and their fluorescent intensity is measured online using a spectrophotometer (Perkin Elmer, Uberlingen, Germany). The robotic system is able to recover the FM through digestion and filtration of the tissue samples using the new filter, to dissolve the FM and to release the dyes so that their fluorescent intensities can be measured for the calculation of organ blood flow.

Animals↗
PubMed2000

Use of digoxigenin-labelled ampicillin in the identification of penicillin-binding proteins in Helicobacter pylori.

Amoxycillin is used in current therapeutic regimens to treat the infection caused by the human gastric pathogen, Helicobacter pylori. The penicillin-binding proteins (PBPs) are the primary targets for the beta-lactam antibiotics, such as amoxycillin, and are involved in the terminal stages of peptidoglycan synthesis. They also play active roles in the determination and maintenance of cellular morphology. It was believed that an organism with a complex morphology, such as H. pylori, would have more than the three PBPs previously suggested. Using digoxigenin-labelled ampicillin (DIG-ampicillin), we report the identification of eight PBPs in H. pylori with masses of 72, 62, 54, 50, 44, 33.5, 30.5 and 28 kDa. A smaller (21 kDa) ninth band was also detected, which may represent another PBP. However, the relatively small size of this apparent PBP raises questions as to whether this is a true PBP. In an attempt to identify the PBPs to which amoxycillin preferentially binds, amoxycillin was used in competition assays with DIG-ampicillin. It appeared that amoxycillin inhibited the binding of DIG-ampicillin to only the 72 kDa PBP. The experimental data were also compared with the seven putative PBPs identified in the two published H. pylori genomes, most of which correlate with the experimental data. To investigate further the properties of these PBPs, the seven putative PBP genes identified in the H. pylori genomes were examined. The derived amino acid sequences of the putative PBPs were examined for the three characteristic motifs found in all conventional PBPs, SXXK, SXN and KTG. We were able to determine that all of the putative PBPs had at least one of these motifs, but none possessed all three motifs with the characteristics of conventional PBPs. These findings suggest that the PBPs of H. pylori are unique.

Ampicillin↗
PubMed1999

Implementation of the microdialysis method in the hamster dorsal skinfold chamber.

The aim of this study was to implement the microdialysis method, a well-established technique for measuring the local concentration of neurotransmitters and metabolites in the brain, in the dorsal skinfold chamber of the awake hamster. First, the effects of implanted, nonperfused microdialysis probes on the microcirculation were examined. Skinfold chambers were prepared with and without probes. Two and 3 days later, the following parameters were assessed: diameter, red blood cell (RBC) velocity, macromolecular leakage, leukocyte rolling fraction, and adherent leukocytes in venules, diameter and macromolecular leakage in arterioles, and functional capillary density (FCD). No significant differences between the animals of the two groups were observed in any of the parameters on either day. Second, the interstitial lactate concentration was measured at two perfusion rates in groups with and without a 4-h tourniquet ischemia. The induction of ischemia resulted in a significant increase in lactate concentration over the control values in the tissue within 1 h to 8000 +/- 860 microM, where it remained until the reperfusion, at which point the concentration returned to control values within 1 h. The microdialysis method provides the opportunity to measure the concentration of metabolites in the extravascular space of the hamster dorsal skinfold chamber.

Animals↗
PubMed1999

Comparison between nasal provocation tests and skin tests in patients treated with loratadine and cetirizine.

BACKGROUND: The effect of H1-blockers may differ depending on the target organ. OBJECTIVE: A double-blind, placebo-controlled study was carried out to compare the effect of a 7-day treatment with loratadine (10 mg daily) or cetirizine (10 mg daily) on nasal challenge with grass pollen grains and skin tests with allergen or histamine. METHODS: Twenty-four patients were enrolled, but the analysis was carried out on 23. Nasal challenge was carried out by using 5-fold increasing numbers of pollen grains. Skin prick tests were done with serial concentrations of allergens and 1 concentration of histamine. Patients were tested in a cross-over design, with each treatment being administered for the previous 7 days and with a 2-week washout period. RESULTS: By comparison with placebo, loratadine and cetirizine increased significantly the threshold number of pollen grains required to induce a positive nasal challenge (P <.001). There was no difference between loratadine and cetirizine. Skin test responses to allergen were significantly reduced by loratadine and cetirizine by comparison with placebo. Skin test responses to histamine were significantly decreased by the 2 H1-blockers, but they were more profoundly decreased by cetirizine than by loratadine. CONCLUSIONS: Both H1-blockers reduced similarly allergen-induced skin test and nasal challenge responses. Cetirizine was more effective on histamine skin test responses.

Adult↗
PubMed1999

Allergic rhinitis in Rochester, Minnesota residents with asthma: frequency and impact on health care charges.

BACKGROUND: Asthma is a common and costly condition. Concomitant asthma and allergic rhinitis (AR) have been shown to increase the medication costs for people with asthma. No studies have compared medical care costs of those with and without concomitant AR. OBJECTIVES: We sought to determine the prevalence and incremental medical care costs of concomitant AR. METHODS: For each member of a population-based asthma cohort, we used all their medical charts within Olmsted County to record age at first diagnosis of asthma; the presence and age of any diagnosis of AR; and the total, ambulatory, and respiratory care-related costs of medical care. Costs were compared for age- and sex-specific strata of people with asthma who did and did not have AR. RESULTS: AR was most commonly diagnosed in people whose asthma was diagnosed before age 25 (prevalence of 59%) and uncommonly diagnosed in anyone after age 40 (prevalence <15%). Yearly medical care charges were on average 46% higher for those with asthma and concomitant AR than for persons with asthma alone, controlling for age and sex. We were unable to assess the impact of treatment of AR on medical care charges. CONCLUSIONS: Physicians should consider the diagnosis of AR (prevalence >50%) in all symptomatic children and young adults with asthma. Further evaluation is necessary to evaluate the ability of treatment to decrease the incremental costs of AR in persons with asthma.

Adolescent↗
PubMed1999

Loratadine: a non-sedating antihistamine. Review of its effects on cognition, psychomotor performance, mood and sedation.

Although equally potent at blocking the H1 receptor, first- and second-generation antihistamines can be distinguished with respect to their different effects on the central nervous system (CNS). First-generation antihistamines readily cross the blood-brain barrier leading to significant drowsiness, altered mood, reduced wakefulness, and impaired cognitive and psychomotor performance. This paper reviews of studies CNS functioning conducted with loratadine, a second-generation H1-receptor antagonist, at its therapeutic dose of 10 mg per day. Studies employing self-report measures, such as diary cards, visual analogue scales, rating scales, and mood inventories have shown that the effect of loratadine on somnolence, fatigue, and mood was comparable to those found with placebo. In studies exploring physiological indices of CNS functioning, such as EEG-evoked potentials, and sleep latency tests, loratadine has been shown to be free of CNS effects. In addition, studies have investigated the effects of loratadine on actual driving performance, and on tests of cognitive and psychomotor functioning. On all of these performance measures, loratadine has been shown to have effects comparable to placebo. In contrast, diphenhydramine, a common first-generation antihistamine, usually available without a doctor's prescription, has significant adverse effects on vigilance, divided attention, working memory and psychomotor performance. Impairment has been shown to occur even in the absence of self-reported sleepiness.

Affect↗
PubMed1999

A new sample-processing unit for the fluorescent microsphere method.

The use of fluorescent-labeled microspheres (FM) for measurement of regional blood flow is an attractive alternative to the use of radioactive-labeled microspheres. In the FM method the FM have to be completely recovered from the tissue samples in a time- and labor-intensive process. For this reason, a considerable loss of FM is possible. The aim of this study was to develop a filtration device that allows the tissue sample to remain in a single container throughout the procedure to make the process easier and to avoid the loss of FM. The core of the sample-processing unit (SPU) is a single-tube filtration device with a polyamide wire mesh. The protocol for processing tissue from different organs (heart, kidney, liver, spleen, intestine, muscle, bone, lung, brain) was modified and thus shortened significantly. Furthermore, the SPU allows direct filtration of the blood reference sample without previous digestion. Different experiments showed that the SPU in combination with the new protocol excludes the loss of 15-micrometers FM. The modifications of the whole procedure render it faster and highly standardized.

Animals↗
PubMed1999

Mast cell degranulation and parenchymal cell injury in the rat mesentery.

OBJECTIVE: The objective of this study was to explore the degree of parenchymal cell injury after mast cell degranulation by application of compound 48/80 (CMP 48/80) in the absence of adherent leukocytes in the rat mesentery. METHODS: Rats were rendered leukopenic by injection of an antibody against leukocytes, and the mesentery was superfused with CMP 48/80 during intravital microscopy. The extent of cell injury was determined using a fluorescent cell-viability indicator, propidium iodide (PI). In an additional group, mast cell degranulation with CMP 48/80 was prevented by using the mast cell stabilizer Ketotifen. RESULTS: After a reduction in the number of circulating leukocytes, mast cell degranulation produced a mild increase in parenchymal cell injury. The injury levels significantly increased when individual regions of the mesentery were compared. Stabilization of the mast cells with Ketotifen reduced the injury to below baseline values. CONCLUSIONS: In the absence of leukocyte adhesion to the endothelium, mast cell degranulation contributes to parenchymal cell injury in the mesentery.

Animals↗
PubMed1999

In vivo assessment of synovial microcirculation and leukocyte-endothelial cell interaction in mouse antigen-induced arthritis.

OBJECTIVE: The microcirculation and leukocyte-endothelial cell interaction in synovial tissue of an inflamed joint are known to play a crucial role in the pathogenesis of rheumatoid arthritis. The aim of this study was to characterize the in vivo changes in the microvasculature and in leukocyte-endothelial cell interactions in the mouse synovial tissue using intravital fluorescence microscopy in three stages of antigen-induced arthritis. The expression of E- and P-selectin and ICAM-1 were also studied using immunohistochemistry. METHODS: Antigen-induced arthritis (AiA) was produced in Balb/c mice. The severity of arthritis at three different phases was quantified using a clinical and histological score. For the intravital fluorescence microscopy measurements, the patella tendon was partially resected for visualization of the intraarticular synovial tissue of the knee joint. The number of rolling and adherent leukocytes, functional capillary density (FCD) and RBC velocity were quantitatively measured in synovial microvessels. Expression of ICAM-1, E- and P-selectin was assessed by immunohistochemistry. RESULTS: There was a significant increase in the leukocyte rolling fraction in postcapillary venules in the acute phase of AiA (from 0.26 +/- 0.05 in controls to 0.45 +/- 0.04 8 d after AiA induction). The number of leukocytes adherent to the endothelium was significantly elevated in all phases of arthritis (from 121 +/- 27 in controls to 376 +/- 62 mm2 63 d after AiA-induction). Functional capillary density was significantly enhanced in the acute (332 +/- 15 cm/cm2) and intermediate phases (320 +/- 15 cm/cm2) compared to control values (227 +/- 15 cm/cm2). Arthritis resulted in a distinct increase in the expression of ICAM-1 on the synovial endothelium in all phases of AiA. E- and P-selectin expression were detected only in the acute phase. CONCLUSION: Our model provides new insights into the microcirculatory changes which occur in the synovial tissue of an arthritic joint.

Animals↗
PubMed1998

Plasma cortisol responses after intramuscular corticotropin 1-24 in healthy men.

Intravenous infusion of corticotropin 1-24 (ACTH 1-24) followed by a plasma cortisol measurement after 60 minutes of less than 20 microg/dL indicates clinically important glucocorticoid deficiency. In this study, we evaluated the morning plasma cortisol response to an intramuscular (IM) injection of ACTH 1-24 (250 microg) in 64 healthy men. Plasma cortisol increased significantly 30 and 60 minutes after IM ACTH 1-24 (P < .0001). In most subjects, a maximal response was obtained at 60 minutes. The cortisol response correlated positively with the morning basal cortisol concentration. The lowest cortisol peak and the lowest increment observed after IM ACTH 1-24 were, respectively, 12.6 and 3.5 microg/dL after 30 minutes and 16.3 and 5.3 microg/dL after 60 minutes. We conclude that a plasma cortisol level less than 16.0 microg/dL 60 minutes after IM ACTH 1-24 can be used as an index of glucocorticoid deficiency.

Adult↗
PubMed1998

Subjective and objective assessments in patients with seasonal allergic rhinitis: effects of therapy with mometasone furoate nasal spray.

BACKGROUND: Efficacy of topical nasal steroid therapy for allergic rhinitis is usually evaluated by patient and clinician assessments of subjective symptom changes in diaries and at clinical interviews. OBJECTIVE: We sought to complement the subjective measures with objective measures of nasal cytology, biochemistry, and function. METHODS: In this double-blind, randomized study patients with seasonal allergic rhinitis (SAR) 12 years of age or older received 200 microg mometasone furoate nasal spray (n = 80) or placebo spray (n = 41) once daily for 2 weeks. Subjective assessments by clinician and patient comprised symptom/sign scores and overall therapeutic response evaluations. Objective measures included nasal cytology, nasal biochemistry, nasal airway resistance (NAR), mucociliary clearance, and olfactory functions. RESULTS: Mometasone furoate produced a significantly greater decrease than placebo in subjective measures of SAR for total symptom score (-46% vs -30%, p < 0.05), total nasal score (-47% vs -30%, p < 0.024), individual nasal symptom scores, and overall therapeutic response. The objective measures of eosinophil, basophil, and neutrophil counts and mucociliary clearance were significantly better in mometasone furoate- than in placebo-treated patients. Similarly, within-treatment statistically significant improvements were produced by mometasone furoate but not by placebo sprays for levels of eosinophilic cationic protein, tryptase and albumin, NAR, and odor identification. Significant positive correlations were found between NAR and nasal stuffiness and between eosinophils, basophils, and neutrophils and both eosinophilic cationic protein and albumin. CONCLUSION: Subjective measures of SAR were significantly improved in the mometasone furoate group by comparison with placebo-treated patients. Objective assessments supported the subjective findings because within-treatment measures were frequently significantly improved after mometasone furoate treatment but not after placebo treatment.

Administration, Intranasal↗
PubMed1998

Comparative clinical study of inhaled beclomethasone dipropionate and triamcinolone acetonide in persistent asthma.

UNLABELLED: At this time, no placebo-controlled studies in the clinical literature compare the efficacy and safety of the most widely prescribed oral inhaled corticosteroids when dosed at their recommended daily doses. This study compared the efficacy and safety of beclomethasone dipropionate (BDP) 336 microg/day administered by metered dose inhaler (MDI) alone, and triamcinolone acetonide (TA) 800 microg/day by MDI with a built-in tube extender in adults with persistent asthma. METHODS: This 56-day, randomized, double-blind, double-dummy, placebo-controlled, multicenter trial was conducted in 328 adults with mild to moderately severe asthma (FEV1 50% to 90% of predicted while maintained on inhaled corticosteroids). Patients were seen at a baseline visit and on study days 28 and 56. Efficacy variables included pulmonary function tests, physician and patient assessments of asthma condition, and use of rescue medication. RESULTS: Statistically significant improvements from baseline in most efficacy measures were demonstrated for both active treatments versus placebo, and with the following exception were the same between active treatments: mean increase in FEV1 in the beclomethasone dipropionate group was statistically significantly greater than in the triamcinolone acetonide group on day 28. Throughout the study, BDP was statistically superior to TA with respect to mean change from baseline in total asthma symptom scores and for 3 of 8 weeks in reducing the mean average weekly use of rescue albuterol (the two active treatments were comparable for this variable at all other time points). Beclomethasone dipropionate and TA were comparable in safety. CONCLUSION: In adult patients with mild to moderately severe persistent asthma, treatment with BDP consistently conferred greater improvement from baseline in mean FEV1 than TA. This difference achieved statistical significance after 28 days of therapy but was not maintained to endpoint. Decreases in overall asthma symptom scores and in the use of rescue albuterol were statistically significantly greater for the BDP group compared with the TA group. Based on these findings, we conclude that BDP is at least as effective as TA in the treatment of persistent asthma in adults, and judged by some measures, may be superior.

Administration, Inhalation↗
PubMed1998

Decreased regional blood flow in patients with acromegaly.

BACKGROUND AND AIMS: One-third of acromegalic patients have hypertension. Acromegaly is also associated with intrinsic cardiac abnormalities known collectively as a hyperkinetic heart syndrome, which is characterized by an increased cardiac index and decreased systemic vascular resistance. As a result, blood flow should be increased in the regional vascular beds of acromegalic patients. The aim of the study was to measure, using direct methods, blood flow and vascular resistance at the level of the brachial artery in acromegalic patients with a confirmed hyperkinetic heart syndrome. PATIENTS AND CONTROLS: Twelve patients with active acromegaly (five females, seven males; mean (+/- SD) age, 43 +/- 10 years) were studied. Twelve age- and sex-matched normal subjects served as controls. METHODS: Right heart catheterization was used to measure the cardiac index and stroke volume and to calculate systemic vascular resistance in the acromegalic patients. Brachial haemodynamics were evaluated with a two-dimensional pulsed Doppler system (double transducer probe and range-gated time system of reception). The mean diameter of the brachial artery and mean blood velocity were measured and used to calculate mean blood flow. Vascular resistance was calculated in the brachial artery as the mean arterial pressure/blood flow ratio. RESULTS: Age, body weight, height, body surface area and heart rate were similar in the acromegalic patients and controls, while mean arterial pressure was higher in patients. The cardiac index and stroke volume were increased in the acromegalic patients, at 4.08 +/- 0.47 (mean +/- SD) l/min/m2 body surface area and 116.7 +/- 19.4 ml, respectively, while systemic vascular resistance was low (12.5 +/- 2.1 U). Brachial artery diameter was similar in the patients and controls. Brachial artery mean blood velocity (P < 0.01) and mean blood flow (P < 0.05) were lower in the patients than in the controls (3.35 +/- 1.26 vs. 5.12 +/- 1.74 cm/s, and 16.4 +/- 9.4 vs. 25.6 +/- 11.6 ml/min/m2, respectively). The higher mean arterial pressure and lower mean blood flow resulted in higher forearm vascular resistance in the patients than in the controls (132 +/- 61 vs. 83.8 +/- 47 mmHg/ml/s/m2, respectively, P < 0.01). CONCLUSION: While cardiac output is increased and systemic vascular resistance is decreased in active acromegaly, direct measurement of brachial artery haemodynamics showed lower regional blood flow and increased local resistance relative to healthy controls. These results suggest a heterogeneous distribution of cardiac output in acromegaly.

Acromegaly↗
PubMed1998

Impact of dextran on microvascular disturbances and tissue injury following ischemia/reperfusion in striated muscle.

The aim of this study was to evaluate the effect of dextran (Dx) 1 versus Dx 60 (molecular weights 1,000 and 60,000) on microvascular disturbances and tissue injury in striated muscle after ischemia/reperfusion (I/R). Experiments were performed using a 4 h pressure-induced ischemia model in the hamster dorsal skinfold chamber. Three groups (n=6) of animals received a continuous infusion (45 min, 3 microL/min) of either Dx 1 or Dx 60 (total dose 5 mg/kg) or saline solution beginning 15 min before reperfusion. Intravital fluorescence microscopy allowed for quantification of functional capillary density, leukocyte adherence, extravasation of fluorescein isothiocyanate-Dx, and nonviable (propidium-positive) cell count before ischemia and .5, 2, and 24 h after reperfusion. Experiments were terminated with tissue preservation for electron microscopy. Postischemic functional capillary density was significantly improved by Dx 60 (at 24 h, 88% vs. 51% in controls). In animals receiving postischemic Dx 1 or Dx 60, leukocyte adherence was significantly reduced (at .5 h, 44% and 58%, respectively) as compared with controls, whereas macromolecular extravasation was unchanged. Nonviable cell count was significantly decreased by both Dx fractions (at 24 h, Dx 1, 75%; Dx 60, 87%), indicating a reduction of tissue injury, which was also confirmed by electron microscopy. These results provide evidence that Dx 60 at 5 mg/kg attenuates I/R injury more effectively than Dx 1. Leukocytes play a major role in the development of I/R injury, but macromolecular extravasation does not always correlate with the leukocyte-endothelium interaction and the manifestation of I/R injury.

Animals↗
PubMed1998

Mechanisms of cell injury in rat mesentery and cremaster muscle.

The events responsible for cell injury after a tissue stimulation are only incompletely understood. The purpose of this study was to examine mechanisms of cell injury in two tissues, rat mesentery and cremaster muscle, after tissue stimulation with N-formylmethionyl-leucyl-phenylalanine (FMLP) and platelet-activating factor (PAF). The response was studied in the same animal in random order using normal and leukopenic rats. The tissues were exteriorized after pentobarbital anesthesia. Five to six vascularized areas were chosen in each tissue, and cell injury and hydroperoxide production were assessed visually by continuous superfusion with 1 microM propidium iodide and 5 microM dichlorofluorescin diacetate (DCFH), respectively. FMLP (1 x 10(-8) M) and then PAF (1 x 10(-8) M) were added to the superfusate, and measurements were made at several time points. The second tissue was then examined using the same protocol. In the cremaster, there was little hydroperoxide production, and the tissue injury was eliminated after leukopenia. Leukopenia had no effect on tissue injury in the mesentery. Although hydroperoxide production was observed, there was no correlation between it and the tissue injury. The level of preactivation showed no correlation with either tissue injury or hydroperoxide production. In light of these results, mast cell degranulation may be an important mechanism of tissue injury in the mesentery.

Abdomen↗
PubMed1998

A comparison of triamcinolone acetonide MDI with a built-in tube extender and beclomethasone dipropionate MDI in adult asthmatics.

STUDY OBJECTIVE: In this study, the efficacy and safety of triamcinolone acetonide (TA) metered-dose inhaler with a built-in tube extender and beclomethasone dipropionate (BDP) metered-dose inhaler without a spacer device were compared. Both treatments were dosed at their most commonly used daily doses (within labeling). DESIGN: A 56-day, randomized, double-blind, double-dummy, placebo-controlled trial. SETTING: Seventeen asthma/allergy centers. PATIENTS: We enrolled 339 patients 18 to 65 years of age, with a documented history of bronchial asthma (FEV1, 50 to 90% of predicted value) for > or = 2 years who required inhaled corticosteroid therapy. INTERVENTIONS: Patients were randomized to receive BDP 336 microg/d (4 puffs bid) plus TA placebo (4 puffs bid), TA 800 microg/d (4 puffs bid) plus BDP placebo (4 puffs bid), or TA and BDP placebos (4 puffs of each bid). The only other asthma medication permitted was inhaled albuterol that was used as a rescue medication. All medications were administered via the closed-mouth inhalation technique. MEASUREMENTS AND RESULTS: At 8 weeks and at study end point, both active treatment groups had statistically significant and comparable improvements in FEV1 relative to baseline, and statistically significant increases relative to placebo. At study end point, improvements in forced expiratory flow (FEF25.75%), clinic peak expiratory flow (PEFR), and FVC were statistically significant for the active treatment groups compared with placebo. At end point, the mean difference between BDP and TA for mean change in FEV1 from baseline in the efficacy population was 0.02 and the 95% confidence interval was -0.11, 0.15. Asthma symptoms recorded at clinic visits showed statistically significant improvements for the BDP and TA groups compared with the placebo group. Treatment-related adverse events occurred with similar frequency in all patient groups-25.5% of placebo-treated patients, 22.3% of BDP patients, and 20.4% of TA patients. The incidence of oropharyngeal adverse events, including cough, thrush, and dysphonia, was not statistically different between the two active treatment groups. CONCLUSION: In this randomized, double-blind, placebo-controlled study of adult asthmatics treated with either BDP without a spacer or TA with its built-in tube extender, BDP and TA were comparable in efficacy as measured by FEV1 and other pulmonary function tests, and by improvement in asthma symptoms. Both active treatments were significantly more effective than placebo. All treatment groups were comparable in safety as measured by the incidence of adverse events.

Administration, Inhalation↗