Response of Plasmodium falciparum to chloroquine in hospital patients at Muheza, Tanzania.
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Adolescent↗
Biomedical subjects
E Hills
Publications and source records attributed to E Hills.
The effect of age on bone composition and viability in the femoral head.
We studied the effect of age on bone composition and osteocyte viability in femoral heads from fifty-one subjects. The assessment included determination of: bone volume, ash weight, calcium, and phosphorus content; osteocyte viability in fresh sections stained for lactate dehydrogenase activity; microfractures in fresh sections after removal of marrow elements; bone area, the presence of metabolic bone disease, and the histology of microfractures in embedded calcified sections; and the extent of trabecular microfractures. Bone area and numbers of microfractures were also assessed in eight elderly hip-fracture patients. Bone volume decreased with age, but there was considerable variation in each age group, and no significant difference between men and women. Ash weight and the bone content of calcium and phosphorus also decreased with age, but were constant if corrected for bone volume. Almost all osteocytes were viable in subjects who were younger than twenty-five years, and thereafter viability progressively decreased to a mean of 74 per cent in the eighth decade of life. There was a significant negative correlation between osteocyte viability and age. There was no evidence of metabolic bone disease in any patient. The numbers of microfractures increased with age and correlated negatively with bone viability (r = -0.31, p less than 0.05); in simple linear correlation a relationship between bone area and microfractures could not be demonstrated but in multiple linear correlation, after the inclusion of bone viability, there was an additional negative correlation between numbers of microfractures and bone area (p less than 0.005). Bone area and numbers of microfractures in hip-fracture patients were similar to those in age-matched controls.
Adolescent↗
The pathogenesis of renal osteodystrophy: role of vitamin D, aluminium, parathyroid hormone, calcium and phosphorus.
Biochemical data and bone histology from 44 haemodialysis patients was compared using an histologic technique capable of evaluating separately the individual components of osteodystrophy. Hyperparathyroid bone disease was diagnosed by an elevated osteoclast count, and in advanced disease there was also fibrosis and woven bone. Osteomalacia, defined as an impairment in the rate of bone mineralisation, was present in two distinct forms: osteomalacia type I, characterised by wide osteoid seams, and osteomalacia type II, characterised by extensive thin, inactive osteoid. The histologic diagnoses were hyperparathyroid bone disease (15), osteomalacia type I (3), osteomalacia type II (6), hyperparathyroid bone disease and osteomalacia type I (12), hyperparathyroid bone disease and osteomalacia type II (6), normal (2). Aluminium was evident histochemically in 17 biopsies. Vitamin D metabolite levels were low in most patients and did not correlate with any biochemical or histological parameter. Parathyroid hormone levels were highly correlated with histological features of hyperparathyroid bone disease, and also correlated with plasma calcium, suggesting a degree of autonomy of parathyroid hormone secretion. Urea and creatinine were higher in the hyperparathyroid bone disease than the osteomalacia groups suggesting that poor dialysis contributes to the former. Statistical analysis showed that osteomalacia type I was associated with relatively low plasma calcium and phosphorus levels; osteomalacia type II was associated with increased bone aluminium and with the uraemic process itself, as reflected in the plasma creatinine level. This study shows relationships between renal osteodystrophy and plasma calcium and phosphorus levels, but no relationship with vitamin D metabolites. Aluminium appears to impair mineralisation even at relatively low levels of accumulation. However there are other unidentified factors associated with the uraemic process, contributing to all three components of renal osteodystrophy.
Adult↗
Effect of aluminum and parathyroid hormone on osteoblasts and bone mineralization in chronic renal failure.
Bone aluminum, quantitative bone histology, and plasma parathyroid hormone (PTH) were compared in 29 patients undergoing chronic hemodialysis. Histologic techniques included double tetracycline labeling and histochemical identification of osteoclasts and osteoblasts. Bone aluminum was measured chemically by flameless atomic absorption spectrophotometry, and histochemically. When measured chemically, the bone aluminum was 67 +/- 46 (SD) mg/kg dry weight (normal 2.4 +/- 1.2 mg/kg); histochemically, aluminum was present at 2.9 +/- 4.4% of trabecular surface. The biochemical and histochemical results agreed well (r = 0.80, P less than 0.001). No double tetracycline labels were seen at the mineralization front where aluminum was deposited, indicating cessation of mineralization at these sites. The osteoblast surface correlated positively with plasma PTH (r = 0.67, P less than 0.001) and negatively with bone aluminum level (r = -0.42, P less than 0.05). Multiple linear regression showed a correlation of aluminum with osteoblasts additional to that of PTH, consistent with a direct effect of aluminum in depressing osteoblast numbers. Though a relationship between PTH and chemically determined bone aluminum level could not be demonstrated, there was a negative correlation between osteoclast count and aluminum, and the nine patients with severe hyperparathyroid bone disease had lower chemically determined aluminum levels than the other patients. These results suggest that aluminum (a) directly inhibits mineralization, (b) is associated with decreased PTH activity and hence osteoblast numbers, and (c) directly reduces osteoblast numbers. In addition to inducing severe, resistant osteomalacia, aluminum appears to contribute to the mild osteomalacia commonly seen in renal failure, characterized by extensive thin osteoid and low tetracycline and osteoblast surfaces.
Adult↗
Immobilisation hypercalcemia.
We studied 5 patients with immobilisation hypercalcemia. Plasma calcium was 3.28 +/- (SD) 0.26 mmol/l. Plasma parathyroid hormone (PTH) level was elevated in 3 patients and inappropriately detectable in 1. Nephrogenous cAMP, measured in 3 patients, was low-normal in 1 who had a normal PTH and zero in 2 who had elevated PTH. Quantitative bone histology was performed in 3 patients. 1 had evidence of increased resorption (osteoclast count 7.1/mm2 section area, normal 1.0 +/- 0.5) and had a high-normal bone formation rate. Another had a normal osteoclast count but no evidence of bone formation. The third had normal bone histology. We conclude that (a) the PTH appears to be biologically inactive and its elevation may be due, in some patients, to renal retention of carboxyterminal fragments; (b) the histologic pattern in bone is variable and not predictable from the duration of illness; (c) the mechanism by which immobilisation induces these changes is obscure, and (d) careful clinical assessment may be necessary to avoid misdiagnosing the condition as primary hyperparathyroidism.
Adolescent↗
The pathogenesis of idiopathic hypercalciuria: evidence for parathyroid hyperfunction.
We studied the effect of calcium deprivation and loading in 17 healthy subjects and 76 patients with renal calculi. Five had primary hyperparathyroidism with an elevated plasma ionised calcium and detectable plasma parathyroid hormone. Forty-nine had idiopathic hypercalciuria, defined by a urine calcium greater than 7 mmol/day on a free diet. Twenty-two were normocalciuric. Fasting plasma calcium, corrected for albumin, was higher in the patients with idiopathic hypercalciuria (2.40 +/- 0.10 mmol/l) than in controls (2.28 +/- 0.05 mmol/l, p less than 0.005). Plasma calcium was intermediate in the normocalciuric stone formers (2.35 +/- 0.08 mmol/l) and elevated in the patients with primary hyperparathyroidism (2.62 +/- 0.07 mmol/l). Nephrogenous cyclic adenosine monophosphate (cAMP) and parathyroid hormone levels were highest in the primary hyperparathyroid group and did not differ significantly within the other groups. Nephrogenous cAMP correlated positively with plasma calcium in the patients with primary hyperparathyroidism and negatively in controls; there was no correlation in the idiopathic hypercalciuria group. Following an oral calcium load, plasma calcium rose and nephrogenous cAMP fell similarly in all groups. Fasting urinary calcium and its increase after load were greatest in the idiopathic hypercalciuria and primary hyperparathyroid groups, with intermediate results in the normocalciuric patients. Neither the initial metabolic patterns nor the response to thiazide fitted with the previously described patterns of absorptive and renal hypercalciuria. Increased parathyroid gland activity is the most probable cause of idiopathic hypercalciuria.
Adult↗
Bone metabolism in idiopathic juvenile osteoporosis: a case report.
A previously healthy 12-year-old boy developed pain on walking and x-rays showed osteoporosis. Over the next 2 years deterioration occurred, the condition became extremely severe, and he was confined to a wheelchair. After 5 years, marked kyphoscoliosis and pigeon chest deformity were present and little increase in height occurred. A wheelchair accident at the age of 17 resulted in several major long bone fractures. Iliac crest biopsies were taken at ages 15 and 17, and subjected to quantitative histology. A histochemical technique for osteoclast recognition by acid phosphatase activity showed resorption parameters to be normal. Double tetracycline labeling and histochemical identification of osteoblasts showed no abnormality of endosteal bone formation. Because of "coupling" of endosteal formation and resorption, these measurements might primarily reflect bone turnover. Failure of periosteal bone formation as shown by failure of radial growth of long bones and of epiphyseal growth was clearly evident. It is likely that osteoporosis developed in this patient due to a reduction in bone formation of unknown etiology rather than by increased bone resorption.
Adolescent↗
Effect of aluminum on normal and uremic rats: tissue distribution, vitamin D metabolites, and quantitative bone histology.
The effects of intraperitoneal aluminum chloride (1.5 mg aluminum/kg/day for 9 weeks) were studied in normal and uremic rats. Parameters measured included tissue aluminum, serum vitamin D metabolites, and quantitative bone histology. Aluminum administration increased tissue concentrations of this metal in uremic and nonuremic animals. Bone aluminum concentrations were higher in uremic rats (121 +/- 27 mg/kg compared to 47 +/- 4), whereas liver values were higher in the nonuremic group (175 +/- 47 mg/kg compared to 100 +/- 36). Serum concentrations of 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D were reduced in uremia, but aluminum was without apparent effect on any vitamin D metabolite. Aluminum, in the doses administered, caused no skeletal changes in nonuremic animals. Some uremic, non-aluminum-treated rats developed osteomalacia and marrow fibrosis. However, osteomalacia was more severe and the osteoclast count was higher in the uremic, aluminum-treated rats. In this group of animals the mineral apposition rate was reduced at the metaphyseal endosteum but increased at the periosteum, indicating different control mechanisms at the two sites.
Aluminum↗
Pathologic fracture due to severe osteomalacia following low-dose diphosphonate treatment of Paget's disease of bone.
Ethane-I-hydroxy-I,I-diphosphonate (EHDP) 5 mg/kg body weight/day was administered to a patient suffering from Paget's disease of bone. After 150 days of treatment, when the plasma alkaline phosphatase was 40% of initial, he suffered a pathologic fracture of his Pagetic right patella, which was found to have osteomalacia of extreme severity. An iliac crest bone biopsy, following double tetracycline labels, also showed severe osteomalacia of Pagetic bone. Osteoclast acid phosphatase activity was reduced, as occurs in diphosphonate-treated rats. The patient's history included two previous pathologic fractures of Pagetic bone and unusual sensitivity to EHDP. It might be prudent to perform needle bone biopsy in order to exclude osteomalacia in EHDP-treated patients with these clinical manifestations.
Etidronic Acid↗
Quantitative bone histology in the hypercalcemia of malignant disease.
Quantitative bone histology was studied in 23 patients with malignant hypercalcemia (MH) due to carcinoma (16) or immunoproliferative disease (7). Plasma calcium was 3.37 +/- 0.47 (mean +/- SD) mmol/liter. Bone resorbing surface (RS) was measured using a sensitive histochemical stain to identify osteoclasts. In the MH patients with carcinoma, the RS was 3.1 +/- 2.6% compared to 1.0 +/- 0.3% in controls (P less than 0.02). In the myeloma patients it was 2.3 +/- 1.7%, and in normocalcemic patients with malignant disease 0.8 +/- 1.1%. RS did not correlate with serum PTH, and several high RS values were associated with undetectable PTH. RS correlated with forming surface (FS) in MH patients (r = 0.44, P less than 0.05) and controls (r = 0.68, P less than 0.005), but there was a greater RS relative to FS in MH patients than in controls (P less than 0.005). "Excess" RS in the MH patients was calculated by subtracting the RS accounted for by the measured FS, using the relationship defined by the controls. Bone loss, as reflected in urinary calcium excretion, correlated weakly with excess RS (r = 0.44, P less than 0.05) but was high even when excess RS was zero. Thus, the histological findings do not account for the bone loss, and additional resorption around bone metastases is likely; the results of this study are consistent with a humoral substance produced by the malignant tissue causing generalized bone resorption in addition to bone dissolution around metastases.
Adult↗
The determination of bone viability: a histochemical method for identification of lactate dehydrogenase activity in osteocytes in fresh calcified and decalcified sections of human bone.
We have developed a technique for assessing bone viability by the histochemical demonstration of lactate dehydrogenase (LDH) activity in osteocytes. Fresh sawn and ground (75 microns) sections were prepared from femoral heads removed at operation from patients with osteoarthritis of the hip. The sections were decalcified overnight in cold 10% EDTA, pH 7.0. LDH activity was shown by the tetrazolium-formazan reaction with nitroblue tetrazolium as indicator and lithium lactate as substrate. Osteocytes were regarded as viable if their cytoplasm stained dark blue, indicating LDH activity; lacunae containing non-viable osteocytes could be identified by interference contrast illumination. Nearly all osteocytes were viable in the samples studied. Small trabecular fragments, such as could be obtained by needle biopsy, were also suitable for staining after grinding to approximately 50 microns. The method should have application both in research and in diagnosis of ischemic bone disease.
Bone and Bones↗
The effect of long-term low-dose diphosphonate treatment on rat bone.
Weaning, male rats were given ethane-1-hydroxy 1,1-diphosphonate (EHDP) or dichloromethylene diphosphonate (Cl2MDP) 0.5 mgP/kg/day for 140 days. Samples prepared after sacrifice were: (1) thin ground (30 micrometers) transverse tibial sections, (2) methacrylate-embedded 5 micrometers sections of the proximal tibial metaphysis, and (3) ultrathin calcified metaphyseal sections for electron microscopy. Cl2MDP reduced the diaphyseal medullary cavity, and EHDP increased the osteoid width. Both drugs increased endosteal bone apposition (possible secondarily to the impaired resorption) and, perhaps as a result, periosteal apposition was increased. Consequently, diaphyseal bone area was unchanged. Metaphyseal bone area was increased and osteoclast numbers reduced, in contrast to the increased osteoclast numbers reported previously in animal experiments with diphosphonates. Acid phosphatase activity within osteoclasts was markedly reduced with EDHP and unchanged with Cl2MDP. The ultrastructural changes in osteoclasts, i.e., a deficiency of ruffled borders, reduced numbers of cytoplasmic vacuoles and the presence of crystals between bone and the osteoclastic plasmalemma, were more marked with EHDP than Cl2MDP.
Animals↗
Long-term experience with a calcium-thiazide treatment for Paget's disease of bone.
75 patients with Paget's disease of bone were treated with a drug combination intended to increase the production of endogenous calcitonin and decrease that of parathyroid hormone. The first regimen of oral calcium, thiazide diuretic, aluminum hydroxide and low-phosphorus diet was given to 41 patients for a mean of 800 days. A simpler regimen of oral calcium and thiazide diuretic was given to 34 patients for a mean of 750 days. There was a similar fall in mean plasma alkaline phosphatase to 71 +/- 24 (SD)% of initial with the first regimen and 72 +/- 17% with the second at 150 days, with a gradual rise after 500 days. Urinary hydroxyproline fell from 165 +/- 111 to 112 +/- 93 mg/day. Plasma calcium rose slightly with both regimens and plasma inorganic phosphorus fell with the first. Serum parathyroid hormone and calcitonin levels were unchanged. Urinary calcium was not changed by the first regimen and rose by 40 +/- 54 mg/24 h with the second. Clinical improvement approximately paralleled biochemical improvement. It is suggested that, in view of its low cost and convenience, this treatment has a place in the management of Paget's disease of bone.
Adult↗
Bone metabolism in systemic mastocytosis. A case report.
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Adult↗
Noncondylomatous cervical wart virus infection.
Human papillomavirus (HPV) infections of the genital tract frequently involve cervical epithelium and produce a macroscopically flat lesion that the authors have called noncondylomatous cervical wart virus infection (NCWVI). Over a 6-month period, 92 of 7281 routine cervical smears (1.3%) and 46 of 183 colposcopically directed punch biopsies (25%) showed morphologic evidence of wart virus infection. The etiologic role of HPV was confirmed by the demonstration of virus particles in 24 of 53 cases (45%) examined by electron microscopy. The colposcopic features of NCWVI consist principally of epithelial opacity and vascular atypia, leading to frequent confusion with cervical intraepithelial neoplasia. Differences in surface contour, color, vascular patterns, and topography generally permit colposcopic differentiation. These 2 conditions sometimes coexist; whether the association is causal or casual in not presently known.
Colposcopy↗
Noncondylomatous wart virus infection of the postmenopausal cervix.
Noncondylomatous papilloma virus infection of the cervix is much more common than formerly realized. The majority of patients are young, but two cases are reported here in postmenopausal women.
Animals↗
Unusual manifestations of lung cancer.
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Cardiovascular Diseases↗
Comparison of peak flow gauge and peak flow meter.
A comparison has been made of the new peak flow gauge and the Wright peak flow meter. Close correlation was found between measurements made with the two instruments both in normal subjects and in patients. The peak flow gauge is as consistent as the peak flow meter but is cheaper and more portable. It should be useful in survey work in general practice and for loan from hospital outpatient departments where serial measurements are used to monitor patients' progress.
Female↗