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Biomedical subjects

J E Harrison

Publications and source records attributed to J E Harrison.

At least 91 records · Page 5Linked to original sources

Aluminum toxicity to the brain.

The association between elevated brain aluminum levels and Alzheimer's disease (AD) is examined and critically reviewed. We found elevated aluminum levels in the brains of patients with AD (greater than 4 micrograms/g dry wt.) compared with normal subjects (approximately 1.5 micrograms/g dry wt.). Nine laboratories from different geographical regions have confirmed this finding. Two laboratories did not find any differences between AD and control brains. This discrepancy is traced to differences in sample sizes used for the aluminum assay and the sample selection criteria. It is found that it is essential to use small sizes (approximately 10 mg dry wt.) and to ensure that control brains do not contain neurofibrillary tangles (NFT) and that AD brains do. The exact pathogenic role of aluminum in AD is, as yet, unclear. It is the only element (other than calcium, which non-specifically accumulates at all degenerating tissue sites) that is found in elevated concentrations in NFTs. It is found elevated at four loci in the brain, i.e. the DNA-containing structures of the nucleus, the protein moities of NFTs, the amyloid cores of senile plaques and cerebral ferritin. The evidence thus far indicates that aluminum is toxic to the brain and it is probable that it has a pathogenic role in Alzheimer's disease.

Aluminum↗

One-year follow-up of weight, total body potassium, and total body nitrogen in obese adolescents treated with the protein-sparing modified fast.

Seventeen obese adolescents were treated with the protein-sparing modified fast (PSMF), a high-protein, low-carbohydrate, low-calorie diet, for approximately 3 mo and then followed for a total of 12 mo. The diet provided a mean of 880 kcal.kg-1. d-1 and 2.5 g protein. kg IBW-1. d-1. Body composition was determined using four skinfold measurements, total body potassium (TBK), and total body nitrogen (TBN) at baseline, 3 mo, and 12 mo. Twelve subjects returned for follow-up at 1 y (71%) and 48% had sustained weight loss with the percentage ideal body weight for height decreased from 154 to 125 over the year. Six subjects had TBK and TBN measured and TBK decreased 13.0% and TBN decreased 14.3% over the year. This reflected a change toward normalization of the predicted TBK from 121 to 102% and TBN from 119 to 102%.

Adolescent↗

Changes in body composition in children following kidney transplantation.

Rapid weight gain has been observed following kidney transplantation. To determine the accompanying changes in body composition, we studied 8 patients (7 females, 1 male) aged 3-17.5 years who underwent renal transplantation. Body composition measurements included weight, height, triceps skinfold thickness, total body potassium, total body water, and extracellular water. Excessive weight gain was observed in most of the patients. Weight as a percentage of ideal weight for height increased from 96.0 +/- 13.8 to 116.3 +/- 13.0% (p less than 0.01). This was accompanied by a gain in fat mass in the first 3 months and a subsequent increase in lean body mass in the next 3 months. Extracellular water was increased before transplantation (32.9 +/- 6.5% of body weight) and returned to normal (27.3 +/- 8.6%) 3 months after transplantation (p less than 0.01). The weight gain following kidney transplantation in children resulted mainly from increases in adipose tissue and lean body mass, and was not related to water retention.

Adolescent↗

Fluoride inhibition of bone mineralization may depend on physical/chemical properties.

The properties of fluoride (F) incorporation into bone powder in vitro were studied in an attempt to clarify possible mechanism for F inhibition of bone mineralization and soft tissue mineral deposition in vivo. Rat bone powder was prepared with minimal physical and chemical stress, and exposed to F (less than 1 mmol) in aqueous solutions buffered to pH 7.4. Initial experiments confirmed reported data that the rates of F incorporation into bone mineral in vitro resemble F clearance from blood in vivo. The rate of F incorporation was inversely proportional to the amount of F added to supernatants and decreased exponentially with time. Following F incorporation, the bone mineral became less soluble, with solubility inversely proportional to bone F concentration. However, a fraction (about 20%) of F freshly incorporated in bone powder dissolved readily in pH 7.4 buffer and appears to be adsorbed F. The fraction of incorporated F that was readily dissolved decreased with time over the initial 24 h after incorporation, was proportional to the amount of F freshly incorporated, and was associated with an inhibition of further F incorporation.

Animals↗

Effect of two randomised exercise programmes on bone mass of healthy postmenopausal women.

The effect of two structured exercise programmes on the bone mass of 48 healthy postmenopausal white women aged 50-62 was studied after one year. Volunteers were randomised to group 1 (control), group 2 (aerobic exercise), or group 3 (aerobic and strengthening exercises). Before and after the training programme each subject had evaluations of bone mass (determined by neutron activation analysis and expressed as calcium bone index) and maximum oxygen uptake attained on a multistage exercise treadmill test. After one year both exercise groups had higher levels of fitness and greater bone mass than controls. Mean values (2 SEM) for changes in the calcium bone index were -0.011 (0.037), 0.039 (0.035), and 0.066 (0.036) for groups 1, 2, and 3, respectively. Analysis of variance on the observed data and analysis of covariance adjusting changes to the initial mean value for the whole group showed significant differences between each exercise group and the controls but no difference between the exercise groups themselves. Both exercise groups showed a significant improvement in maximum oxygen uptake. This study suggests that exercise may modify bone loss in healthy postmenopausal women.

Bone and Bones↗

In vivo analysis of bone fluoride content via NMR.

In vivo free induction decay signals have been detected from the fluoride ion (F) content of human finger bones by a 27 MHz pulsed single-coil nuclear magnetic resonance (NMR) spectrometer. The intensity of these dipolar-broadened NMR signals can be used to estimate the F content of the middle phalanx of the index finger. This NMR procedure is the first non-invasive method capable of monitoring bone F contents. The preliminary results we report were obtained from patients known by previous biopsies to have relatively high bone F concentrations in their pelvis. This new monitoring technique does not yet have adequate sensitivity or accuracy for routine clinical use. As a research technique, it has applications to the diagnosis of fluorosis (both industrial and endemic) as well as renal osteodystrophy, and to the establishment of optimal NaF does for the treatment of osteoporosis.

Bone and Bones↗

Relationship of kyphosis to physical fitness and bone mass on post-menopausal women.

Kyphosis is commonly associated with ageing and osteoporosis of the spine. This study was conducted to evaluate whether physical fitness and bone mass in post menopausal women, between the ages of 50-60 years, may influence the degree of kyphosis. The level of physical fitness was determined by 1) calculating maximum oxygen uptake, (VO2 max), attained by a graded exercise treadmill test, and 2) evaluating the muscle strength in performing one repetition maximum on the bench press. In vivo neutron activation analysis was used to measure the bone mineral content in the axial skeleton and proximal femurs. It is expressed as Calcium Bone Index (CaBI). The normal range was 1.00 +/- 0.12 (I.S.D.). The degree of kyphosis was measured indirectly by calculation of an index of kyphosis, (I/K), using a surveyor's flexicurve. Individuals with I/K greater than 13 showed a clinically apparent kyphosis. Fit individuals (VO2 max greater than 29 ml/kg/min) had a significantly lower I/K (p less than 0.001) than average persons. Individuals with normal bone mass (CaBI greater than 0.8) also had a significantly lower I/K (p less than 0.05) than those with bone loss. Similarly, subjects who were fit, and had normal bone mass, had a significantly lower I/K (p less than 0.001) than those who were less fit and had bone loss. There was a significant correlation between I/K and VO2 max (p less than 0.02, df 45), I/K and CaBI (p less than 0.05, df 45) and I/K and bench press (p less than 0.05, df 45).(ABSTRACT TRUNCATED AT 250 WORDS)

Bone and Bones↗

The effect of exercise on bone mass of osteoporotic patients on fluoride treatment.

The study was conducted in order to determine the effect of exercise on osteoporotic patients with a mean age of 65 years. The majority of these patients had been on sodium fluoride for at least 2 years. Thirty-eight patients were assigned to either the hospital or home group. Nineteen were in the former group, which performed the 1 hour exercise twice weekly in the Hospital. The patients in the latter group were taught the exercises and were expected to continue them at home. The exercise protocol consisted of muscle-strengthening and aerobic activities. Bone mineral mass was determined by neutron activation analysis, which measured total calcium in the trunk and pelvis. It is expressed as a calcium bone index (CaBI), with a normal range of 0.75 to 1.2. The level of physical performance was determined by calculating the maximum oxygen uptake, VO2max, attained by a graded exercise test on the treadmill. Calcium bone index and VO2max were obtained before and after the 12.5 month study. Prior to the study, the hospital and home groups had low calcium bone index values (0.68 and 0.66 respectively). Both groups showed a significant increase in calcium bone index (p less than 0.001 for the hospital group, p less than 0.01 for the home group) after the study. When compared to the home group the hospital group was found to have a significantly higher post-study calcium bone index value (p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Effects of peritoneovenous shunting on body composition.

The effect of peritoneovenous shunting on body composition has been studied in 7 cirrhotic patients undergoing a successful shunt and 3 patients in whom the shunt was unsuccessful. In the 7 patients with functioning shunts, their weight had decreased by a mean of 9 kg (p less than 0.001) by 6 wk after initial diuresis, natriuresis, and kaliuresis, and was associated with a decrease in total body potassium (TBK) but not total body nitrogen (TBN). This resulted in a significant decrease in the TBK/TBN ratio from 2.12 +/- 0.74 to 1.66 +/- 0.20 (p less than 0.01). By a mean of 14 mo, in these 7 patients there was a significant increase in mean TBN (from 1.54 +/- 0.10 to 1.84 +/- 0.10, p less than 0.005) associated with an improvement in the mean nitrogen index (from 0.74 +/- 0.04 to 0.88 +/- 0.04, p less than 0.005). These changes were associated with a significant increase in nonalcoholic calories, a nonsignificant increase in protein consumption, and a positive nitrogen balance. After the initial kaliuresis, mean potassium balance remained constantly positive (+22.7 +/- 3.4 mmol/day), serum aldosterone levels normalized, and TBK increased. In contrast, 3 patients with failed peritoneovenous shunting continued to lose weight significantly despite the presence of ascites; TBN and nitrogen index also decreased. In conclusion, body composition studies appear to have confirmed the clinical observation that cirrhotic patients with massive ascites have depleted body protein which is gradually repleted only after successful shunting. In this situation TBK, long used as a measure of lean body mass, is less satisfactory than TBN and nitrogen index. This improvement in body protein appears to be explained by an increased dietary intake associated with improved nitrogen balance, but these changes are not found in patients in whom the shunt failed.

Adult↗

The relationship between bone apposition rate and vitamin D activity in phosphate-deficient rats.

In rats, phosphorus deficiency (P-) has been shown previously to stimulate the linear bone apposition rate (BAR) and this P- effect is dependent on adequate intake of vitamin D. To investigate further the relative importance of the vitamin D3 metabolites, 1,25(OH)2D3, 24,25(OH)2D3, and 25(OH)D3, in BAR stimulation, we studied, in P- rats, the relationships between BAR and plasma levels of these three vitamin D3 metabolites following vitamin D3 deprivation. Three groups of rats were placed on diets differing only in phosphorus (P) and vitamin D3(D3) content, with one group diet deficient in both P and D3, one diet, P-, D3 replete, and one diet both P and D3 replete. Plasma levels of the three vitamin D3 metabolites, plasma Ca and P, isotopic Ca absorption and BAR measurements were carried out at 1, 3, and 5 weeks after onset of the test diets. In P-, D3 replete rats, both plasma levels of 1,25(OH)2D3 and BAR were increased throughout the 1 to 5 week study period, while 25(OH)D3 and 24,25(OH)2D3 levels were not significantly different from P and D3 replete controls. In P-, D3 restricted rats, BAR was decreased by one week, prior to any reduction in plasma levels of 25(OH)D3 and 24,25(OH)2D3 and while plasma 1,25(OH)2D3 levels were still well above control values. In this P- rat model, the vitamin D dependent BAR stimulation does not appear to be directly related to alterations in the plasma levels of 1,25(OH)2D3, 24,25(OH)2D3, or 25(OH)D3.

24,25-Dihydroxyvitamin D 3↗

A system for in vivo measurement of bone calcium by local neutron activation of the hand.

A 252Cf neutron-irradiation facility designed specifically for clinical in vivo measurement of calcium in the hand is described. Results of preliminary measurements are presented. Hand phantoms were exposed to the neutron beam for 10 min and the induced 49Ca activities were counted for 10 min after an elapsed time of 2 min. The results indicate that with a 2 X 100 micrograms 252Cf neutron source and two 20.3 X 12.7 cm NaI crystals, the counts per gram of bone mineral mass changes by about 4% for each 100 cm3 change in the overall volume (soft tissue plus bone) of the hand. For hands of equal volumes the counts per gram are expected to be almost independent of the bone volume. With an absorbed dose equivalent of 150 mSv (15 rem), the sensitivity is about 200 counts per 10 min per gram Ca. The statistical reproducibility of the results is better than 3% for the average value of 11 g Ca in the normal hand.

Adult↗

The relationship between fluoride effects on bone histology and on bone mass in patients with postmenopausal osteoporosis.

Twenty-one patients with postmenopausal osteoporosis were studied for 4 years after initiation with sodium fluoride (NaF), 20-25 mg b.i.d., elemental calcium, 1.0 g/day, and vitamin D2, 50,000-100,000 I.U. weekly. Histomorphometry was carried out on bone biopsies taken prior to and while on NaF treatment. The total bone mineral mass of the central third of the skeleton was measured by neutron activation analysis at 0.5-1.0 year intervals, and the result expressed as the Calcium Bone Index (CaBI), which normalizes the mineral mass to values for normal subjects of the same size. Twelve patients (57%) who developed, within the first 2 years of treatment, histological effects of fluoride (F) (increased bone formation surfaces together with thickened osteoid seams or hyperosteoidosis) increased their CaBI significantly (P less than 0.01) over the 4 year period, from 0.64 +/- 0.02 to 0.78 +/- 0.03 (or 21.0 +/- 2.9%). No other agent is known to stimulate bone growth to this degree. The remaining nine patients showed no histological evidence of F stimulation and no increase in CaBI (from 0.67 +/- 0.03 to 0.66 +/- 0.03 over 4 years). The results suggest that the histological findings of hyperosteoidosis are prerequisite for the increases in bone mass of osteoporotic patients. Although serum and bone F levels were higher in patients with F response compared to those without response, there was considerable overlap in values between the two groups so that these parameters of F retention were not reliable for predicting F response. Histological evidence of hyperosteoidosis appears to be a more reliable predictor of subsequent increase in bone mass. The effect on fracture prevention of the hyperosteoidosis associated with the increases in bone mass remains to be shown.

Aged↗

Physical fitness effect on bone mass in postmenopausal women.

This study was conducted to determine if bone mineral mass is influenced by the level of physical fitness in active, healthy, postmenopausal women from 50 through 59 years of age. In vivo neutron activation analysis (NAA) was used to measure calcium or bone mineral in the trunk and proximal femurs. The NAA measurement is expressed as calcium bone index (CaBI), which relates the subject's Ca value to the estimated mean value for normal subjects of the same size based on height and arm span. The normal CaBI is 1.00 +/- 0.12 (ISD). The level of physical fitness was determined by calculating the maximum oxygen uptake (VO2max), attained by a graded exercise test on the treadmill, and evaluating the muscle strength in performing one repetition maximum in the bench press and leg press. The "above-average fit" group (VO2max greater than 29 ml/kg/min) when compared to the "average fit" group (VO2max 21-29 ml/kg/min) had significantly higher CaBI (p less than 0.001) and leg press (p less than 0.01). There was significant correlation between VO2max and CaBI (p less than 0.01). The findings suggest that level of physical activity may modify the amount of bone loss in postmenopausal women.

Bone and Bones↗

Inhibition of passive cutaneous anaphylaxis (PCA) by azelastine: dissociation of its antiallergic activities from antihistaminic and antiserotonin properties.

Azelastine and methysergide injected i.v. 5 min prior to antigen challenge and disodium cromoglycate (DSCG) injected i.v. immediately before antigen challenge produced dose-dependent inhibition of IgE-mediated 72 h passive cutaneous anaphylaxis (PCA) responses with ID50S of 0.3, 0.2 and 1.0 mg/kg, respectively. Thus, azelastine is about three times as effective as DSCG (a mast cell stabilizing agent) and somewhat less active than methysergide (a specific serotonin "D" receptor antagonist). Oral administration of azelastine and other drugs 2 h prior to antigen challenge produced strong inhibitory effects on PCA. The ID50S (mg/kg) were as follows: azelastine = 1.4; astemizole = 1.6; ketotifen = 2.0; aminophylline = 4.6; and diphenhydramine = 10.9. After 4 h of oral administration, azelastine and other drugs inhibited PCA responses with the following ID50S (mg/kg): azelastine = 1.8; astemizole = 2.3; ketotifen = 2.3; and aminophylline = 12.5. Azelastine administered orally 24 h before antigen challenge was still capable of exerting significant anti-PCA activity with an ID50 of 2.6 mg/kg, whereas none of the other drugs tested produced any significant inhibitory effects on PCA. In subsequent experiments, it was established that the antiallergic and antihistaminic activities of azelastine are inseparable 2 h after oral administration (ID50 of azelastine mg/kg, p.o., 2 h: PCA = 2.6 and histamine = 3.1). However, the persistence of the oral antiallergic (anti-PCA) effects of azelastine for 24 h (ID50 = 3.7 mg/kg) does not seem to be associated with its antihistaminic or antiserotonin activities.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The effect of fluoride on nephrocalcinosis in rats.

To investigate the effects of fluoride on soft tissue calcification, female weanling rats were fed a nephrocalcinogenic diet and NaF in drinking water over a 4 week period. The diet contained adequate Ca (0.5%) and high phosphorus (1.0%, P). The nephrocalcinosis is attributed to the relatively low dietary Ca/P ratio since addition of Ca to provide a Ca/P ratio of 2.0 prevents kidney calcification. With NaF in drinking water at levels of 1.19 to 4.76 mmol/L kidney calcification was decreased from 127 +/- 24 to 17.3 +/- 1.7 mumol/g wet weight, with no significant differences over this dose range. With the increasing NaF doses, serum F, at 4 weeks, increased from 4.4 +/- 0.8 to 36.5 +/- 6.0 mumol/L compared to untreated F levels of 1.2 +/- 0.1 mumol/L. Bone histology showed no evidence of F stimulation with any of these NaF doses. Previously reported work has shown that, for weanling rats on this diet, greater than 4.8 mumol/L NaF in drinking water is required to produce histological fluorosis within 5 weeks. To inhibit kidney calcification, NaF treatment must be maintained throughout the 4-week study period since calcification occurred if NaF was withheld over either the initial or final 2-week period. These findings indicate a possible therapeutic value of NaF, clinically, in the prevention of soft tissue calcification.

Animals↗

Apparent reduction in baroreflex sensitivity to adenosine in conscious dogs.

Relative effects of equihypotensive doses (-35 mmHg) of adenosine (5.0 mumol/kg) and nitroglycerin (25 micrograms/kg) on heart rate and, therefore, baroreflex sensitivity were studied in conscious dogs. Nitroglycerin increased heart rate 133 +/- 24% from 78 +/- 5.5 beats/min, whereas adenosine increased heart rate only 79 +/- 16% from 78 +/- 5.2 beats/min (P less than 0.01). Injection of nitroglycerin during combined beta-adrenergic and muscarinic receptor blockades caused arterial pressure to fall 38 +/- 3.4% from 107 +/- 3.2 mmHg without any significant change in heart rate (3.8 +/- 3.8 from 162 +/- 9.2 beats/min). During combined beta-adrenergic and muscarinic receptor blockades adenosine also reduced arterial pressure 45 +/- 2.7% from 106 +/- 2.9 mmHg but unexpectedly reduced heart rate as well by 37 +/- 1.7% from 160 +/- 9.7 beats/min. This bradycardia reflected an effect on the sinoatrial (SA) node rather than an induction of heart block, since the R-R interval increased by 70 +/- 7.8% from 371 +/- 20 ms (P less than 0.01), while the P-R interval increased only 13 +/- 2.3% from 97 +/- 7.2 ms (P less than 0.05) with no electrocardiographic evidence of nonconducted beats. Arterial plasma adenosine levels were 43 +/- 5 nmol/ml at this time. Adenosine also caused bradycardia during muscarinic blockade alone (-43 +/- 3.4% from 201 +/- 6.4 beats/min) and following bilateral vagal section (-33 +/- 1.9% from 151 +/- 5.9 beats/min). In summary, adenosine appears to alter normal baroreflex function in the conscious dog by reducing the tachycardia that normally follows a fall in systemic arterial pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗