Search PubMed⌕ Search

Biomedical subjects

D F Anderson

Publications and source records attributed to D F Anderson.

At least 37 records · Page 2Linked to original sources

Seasonal allergic conjunctivitis is accompanied by increased mast cell numbers in the absence of leucocyte infiltration.

BACKGROUND: Seasonal allergic conjunctivitis (SAC) is the most common allergic disease to affect the eye, occurring alone or in association with allergic rhinitis. Infiltration with mast cells and eosinophils is characteristic of the chronic forms of allergic conjunctivitis such as vernal and atopic keratoconjunctivitis, and these cell types also contribute significantly to allergic inflammation in the skin. Indirect evidence for a similar pattern of cellular events in SAC comes from studies which demonstrate raised eosinophil and neutrophil numbers in conjunctival scrapings and elevated levels of mast cell tryptase in tears following allergen challenge. OBJECTIVE: To directly characterize the inflammatory cell infiltrate in SAC and to determine its clinical relevance. METHODS: We employed specific immunohistochemical staining to count mast cells, eosinophils and neutrophils in the conjunctival epithelium and lamina propria of eight atopic patients with SAC in, and 12 SAC patients out of the hay fever season. Sixteen patients with no history of ocular allergy were used as control subjects. RESULTS: Mast cells were absent from normal epithelium. During the pollen season median mast cell numbers in the lamina propria were found to be increased by 61% in patients with SAC compared with normals (P=0.012). Eosinophils were found in the lamina propria in less than half of the symptomatic patients with SAC and in only three patients were eosinophils present in the epithelium. The neutrophil numbers in the lamina propria of patients with SAC tended to be higher than normals but these changes did not reach statistical significance. CONCLUSION: These data based on the direct assessment of conjunctival tissue provide evidence that symptoms occur in SAC in the absence of detectable recruitment of eosinophils or neutrophils. This suggests that this disorder is related to mast cell-mediated changes.

Adult↗

Predictive factors for the development of rubeosis following proton beam radiotherapy for uveal melanoma.

AIMS/BACKGROUND: Proton beam radiotherapy can effectively treat primary uveal melanomas of any size. Some patients, however, develop adverse late effects following treatment and the purpose of this study was to determine which factors give rise to a poor local outcome. METHODS: The hospital records from a first cohort of 127 patients treated by protons from 1989 to 1992 were reviewed retrospectively. The presence of rubeosis was selected as a measure of significant ocular damage. Split file analysis was performed with 73 cases forming a test group with the remaining 54 cases acting as a validation group. RESULTS: Large tumour size and the presence of retinal detachment were significant, independent risk factors for developing rubeosis for both the test and validation groups. These factors also predicted subsequent enucleation for uncontrolled ocular pain. Patients with tumours too large to plaque and with an associated retinal detachment had a 90% chance of developing rubeosis within 4 years of proton beam radiotherapy. CONCLUSIONS: Patients with a uveal melanoma too large for plaque therapy and an associated retinal detachment run a very high risk of developing rubeosis after proton beam radiotherapy and one third of individuals developing rubeosis required enucleation for pain even if local tumour control was satisfactory.

Adult↗

Immunolocalization of cytokines to mast cells in normal and allergic conjunctiva.

BACKGROUND: Recently, the potential role of mast cells in allergic reactions has been extended by the discovery that these cells synthesize, store and secrete multifunctional cytokines. Seasonal allergic conjunctivitis is characterized as an immediate hypersensitivity reaction, in which allergen binds to specific IgE on mast cells, leading to release of pre-formed and newly synthesized inflammatory mediators. OBJECTIVE: In this study we aimed to localize the cytokines IL-4, IL-5, IL-6, IL-8 and TNF alpha to conjunctival mast cells and to examine the relationship between mast cell-associated cytokines and allergic conjunctivitis. METHODS: Immunohistochemistry was performed on serial sections of conjunctival biopsies from patients with seasonal allergic conjunctivitis, in and out of the hay fever season, as well as from non-allergic volunteers. RESULTS: IL-4, IL-5, IL-6 and TNF alpha were localized to mast cells in normal and allergic conjunctiva. IL-8 was localized to mast cells in two patients with seasonal allergic conjunctivitis, one during and the other outside the pollen season. Using the monoclonal antibody 3H4, which identifies the secreted form of IL-4, biopsies from patients with active seasonal allergic conjunctivitis contained a significantly higher proportion of mast cells positive for IL-4, than those from out-of-season patients (P=<0.016). There was no difference between the two groups in the number of mast cells immunostained by the antibody 4D9 which identifies the stored form of IL-4. CONCLUSIONS: These results suggest that conjunctival mast cells can store a range of multifunctional cytokines and release IL-4 during active disease, which may give them an important role in upregulating allergic inflammation in the conjunctiva.

Adult↗

Concentrations of Na+ and Cl- in transplacental ultrafiltrate in sheep.

1. Maternal blood was made transiently hypertonic by rapid I.V. infusion of a concentrated mannitol solution into pregnant ewes bearing lambs with an indwelling flow sensor and vascular catheters. 2. The transplacental flows of water and of Na+ and Cl- were calculated from the umbilical arteriovenous differences in the concentrations of 125I-labelled albumin and electrolytes, and the fetal placental blood flow. 3. The reflection coefficients of Na+ and Cl- were calculated by means of the Patlak equation and found to be 0.85 +/- 0.04 and 0.68 +/- 0.04 (means +/- S.E.M.). The filtration coefficient was 1.02 x 10(-7) +/- 0.12 x 10(-7) cm5 dyne-1 s-1. 4. The results fitted best to an equivalent pore radius in the placental barrier smaller than the currently accepted 0.44 nm but not less than 0.35 nm.

Animals↗

Excess extrafetal fluid without demonstrable changes in placental concentration gradients after week-long infusions of angiotensin into fetal lambs.

It is known that a week-long infusion of angiotensin into fetal sheep produces polyhydramnios. The purpose of the present experiments was to determine whether an increased osmotic force across the placental barrier could account for the excess transfer of water. Six fetuses with indwelling catheters were infused with angiotensin-I and one with angiotensin-II; all, except one fetus in the first group, developed gross polyhydramnios. None of the transplacental concentration differences of the small plasma solutes Na+, Cl-, HCO3-, K+, urea, or glucose showed a demonstrable change and the same was true of the transplacental difference in freezing point osmolality and for the transplacental difference in plasma protein concentration. It is concluded that the infusion of angiotensin at a low dose rate is a reliable protocol for producing polyhydramnios. However, the present findings lend no support to the hypothesis that a primary change in transplacental osmotic force is the cause of the increased transplacental water transfer in this form of polyhydramnios. Alternative hypotheses are discussed in the light of recent discoveries.

Angiotensin I↗

Relationship between physical activity and risk factors for cardiovascular disease among law enforcement officers.

This investigation examined the associations between exercise habits, measures of physical fitness, and 10-year cardiovascular disease risk (CVD10, expressed as %) among 470 law enforcement officers of differing ages (range = 21 to 63 y). Only 32% of this group exercised regularly (> or = 3 days/week, > or = 20 min/session, > or = preceding 4 weeks). Only exercising subjects > 48 years old exhibited a significantly (P < .01) lower 10-year risk of a CVD event than their inactive peers (12.2 +/- 5.6 vs 16.3 +/- 6.9%, mean +/- SD). At all ages, the peak oxygen consumption per unit time was higher (50.1 +/- 6.7 vs 44.8 +/- 6.1 mL.kg-1.min-1) in the exercising than in the nonexercising group. Exercising subjects < or = 36 years old were significantly (P < .05) leaner than nonexercisers (16.3 +/- 5.5 vs 19.6 +/- 5.5% body fat, respectively) and had greater muscular endurance (45 +/- 9 vs 40 +/- 9 60-s sit-ups, respectively). These data suggest that exercise reduces CVD risk by modifying major CVD risk factors only in law enforcement officers > 48 years old.

Adult↗

Substantial reductions in blood pressure after bilateral nephrectomy in fetal sheep.

The role of the kidneys in the maintenance of arterial blood pressure was examined in fetal sheep. Surgery was performed on 11 pregnant sheep (8 twin pregnancies) at approximately 125 days. All 19 fetuses were instrumented with hindlimb arterial and venous catheters. Eleven of the fetuses (but only 1 of each twin) were also bilaterally nephrectomized. Fetal arterial blood pressure was measured several times between 2 and 14 days after surgery. Arterial blood pressure in the intact fetuses increased from 44 +/- 1 to 47 +/- 1 mmHg (SE) but gradually decreased from 37 +/- 4 to 25 +/- 3 mmHg in the nephrectomized group. Whereas the arterial blood pressures measured on the first day of the experiment were not statistically significantly different between the two groups, by the final day of the experiment the arterial blood pressure of the intact fetuses was much higher than that of the nephrectomized fetuses. Venous blood pressure was similar in the two groups. We conclude that bilateral nephrectomy in fetal sheep not only stops the normal gestational increase in arterial blood pressure but also leads to a progressive decline.

Animals↗

Hydrops fetalis in nephrectomized fetal lambs infused with angiotensin I.

Nine bilaterally nephrectomized fetal sheep were infused for 6 days with angiotensin I in sterile water, and five nephrectomized fetal sheep were infused for 6 days with water alone. Total dose of angiotensin was 13.8 +/- 8.6 (SD) mg/kg fetal dry wt, and the total volumes of infused water were 303 +/- 201 and 423 +/- 164 ml, respectively. Of the fetuses infused with angiotensin I, one was of normal appearance, two showed moderate hydrops fetalis, and the remaining fetuses were grossly hydropic. All water-infused fetuses were normal. Their wet-to-dry weight ratios were 7.98 and 6.36 (P < 0.015), representing a 25% of normal body weight excess of water in the angiotensin I-infused fetuses. Six days of angiotensin I infusion caused a gradual rise in fetal arterial blood pressure from 37 +/- 15 to 81 +/- 15 mmHg (P < 0.05) and a gradual rise in venous blood pressure from 2.7 +/- 1.0 to 10.5 +/- 1.7 mmHg (P < 0.05). It was concluded that the fetal edema was due to the elevation in venous pressure. Plasma concentrations of Na+, K+, Cl-, HCO3-, total alpha-amino acids, fructose, glucose, and lactate in the fetus and the ewe did not identify an osmotically active solute responsible for the transplacental attraction of excess water into the conceptus, and the mechanism that attracted this excess water across the placenta remains unclear.

Angiotensin I↗

Development of an exercise identity scale.

This study examined an instrument measuring the salience of an individual's identification with exercise as an integral part of the concept of self. The 9-item Exercise Identity Scale was given to 51 college students. Test-retest reliability (1 wk.) was .93 and Cronbach alpha. 94. Assessment of the relationship between exercise identity scores and other variables related to participation in exercise documents evidence for validity. A measure of exercise identity may help identify persons least likely and most likely to maintain an exercise program and so may assist in the development of effective intervention strategies.

Adult↗

Effect of atrial natriuretic peptide on vascular permeation in the ovine fetus.

To study the effect of atrial natriuretic peptide (ANP) on vascular permeation of albumin in the fetus, ANP (167-600 ng/min) was infused into eight ovine fetuses and saline vehicle was infused into eight twin controls (gestational age 127 +/- 3 d) over a 50-min period. Using two different radiolabeled albumin markers, we determined the tissue to blood isotope ratio (TBIR), an index of albumin permeation, and the albumin clearance. Although ANP had no hemodynamic effect, a marked increase in the hematocrit was observed in ANP-infused fetuses compared with initial values (0.37 +/- 0.04 vs 0.42 +/- 0.04, p < 0.005) but was unchanged in the twin fetuses receiving saline vehicle (0.35 +/- 0.03 versus 0.35 +/- 0.02). TBIR and albumin permeation were increased in combined tissues of ANP-infused fetuses compared with saline controls (TBIR: 1.49 +/- 0.58 versus 1.29 +/- 0.3, p < 0.001; albumin clearance: 1091 +/- 1279 versus 827 +/- 1464 nL/g/min, p < 0.01). In individual tissues, TBIR was significantly increased in skin (2.88 +/- 0.67 versus 1.55 +/- 0.35, p < 0.02), muscle (1.6 +/- 0.27 versus 1.24 +/- 0.26, p < 0.02), adrenal (1.33 +/- 0.10 versus 1.13 +/- 0.15, p < 0.02), bone (1.67 +/- 0.45 versus 1.20 +/- 0.40, p < 0.02), kidney (1.52 +/- 0.25 versus 1.24 +/- 0.26, p < 0.03), and gut (1.69 +/- 0.20 versus 1.39 +/- 0.34, p < 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

Albumins↗

Mild hypoxaemia does not alter red blood cell production in fetal sheep.

1. Fetal sheep at 120 days gestation were fitted with upper and lower body arterial and venous catheters in addition to a flow sensor and occluder placed around the aorta below the renal arteries. 2. After 7 days of recovery, the occluder was partially inflated to reduce aortic blood flow to 70% of control. Blood flow reduction was maintained at this level for the remainder of the experiment. 3. Blood samples were taken after 60 min of blood flow reduction and again after 3 or more days of blood flow reduction. 4. There was no change in upper body arterial or venous blood pressure. Lower body arterial blood pressure decreased, as expected. Arterial PO2 decreased while packed cell volume and haemoglobin concentration increased. There was no change in plasma erythropoietin concentrations or plasma renin activity. 5. While both red cell mass and haemoglobin mass increased during the period of the study, the rate of increase was no different from the rate of blood volume increase.

Animals↗

Plasma renin activity responses to graded decreases in renal perfusion pressure in fetal and newborn lambs.

We examined the relationship between acute reductions in renal perfusion pressure, as approximated by femoral arterial blood pressure, and plasma renin activity in the uninephrectomized fetal lamb. Renal perfusion pressure was reduced and maintained at a constant value by controlled partial occlusion of the aorta above the renal artery. After 15 min of reduced blood pressure, blood samples were taken for determination of plasma renin activity. This protocol was performed 22 times in 11 fetal lambs. Additionally, three of the fetuses were delivered by cesarean section and studied as newborns for the first week of life. In the fetus, there was a linear relationship between log plasma renin activity and femoral arterial blood pressure (P less than 0.01). After birth, the relationship still existed, although it was shifted to the right (P less than 0.0001). We conclude that there is a significant relationship between plasma renin activity and renal perfusion pressure in the fetal lamb, and as early as 1 day after birth, this relationship shifts to the right in the newborn lamb.

Analysis of Variance↗

Short-term saralasin blockade of renal hypertension in fetal lambs.

1. In the fetal lamb, suprarenal aortic blood flow reduction is known to lead to an upper body hypertension. The dependency of this hypertension on the renin-angiotensin system was investigated. 2. Intravenous infusions of saralasin or saline vehicle were begun before suprarenal aortic blood flow reduction and continued for 24 h. 3. In those fetuses receiving saline, upper body arterial blood pressure was significantly elevated both 60 min (P < 0.05) and 24 h (P < 0.05) after blood flow reduction. In those fetuses receiving an infusion of saralasin, upper body arterial blood pressure failed to rise after 60 min of blood flow reduction. However, 24 h later, blood pressure was elevated (P < 0.05), though the increase was not as great as that seen in the saline infused fetuses (P < 0.05). 4. From these results, we conclude that the initial increase in upper body arterial blood pressure seen after suprarenal aortic blood flow reduction is dependent upon the renin-angiotensin system. However, as early as 1 day later, some other mechanism is responsible for sustaining the hypertension.

Animals↗

Failure of acute saralasin to reverse chronic hypertension in fetal lambs.

Upper body arterial hypertension developed in 12 fetal lambs after chronic suprarenal aortic blood flow reduction. Sixty minutes after blood flow reduction, intravenous saralasin infusion was able to reduce upper body mean arterial blood pressure to control levels. Although saralasin infusion was able to decrease upper body arterial blood pressure after 1 day of hypertension, it was not able to return blood pressure to control levels. Three or more days later, saralasin was unable to cause a significant reduction in upper body arterial blood pressure. We conclude that, although the renin-angiotensin system has a role in maintaining the elevated blood pressure after greater than or equal to 1 day of suprarenal aortic blood flow reduction, some other mechanism also participates. We have ruled out a role for changing blood volume, and our results suggest that an elevation of plasma catecholamines is not responsible. Some other pathway for fluid regulation available to the fetus may be responsible.

Angiotensin II↗