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Biomedical subjects

E Hills

Publications and source records attributed to E Hills.

At least 19 recordsLinked to original sources
PubMed2001

Chlorproguanil-dapsone for treatment of drug-resistant falciparum malaria in Tanzania.

BACKGROUND: Resistance to the affordable malaria treatments chloroquine and pyrimethamine-sulfadoxine is seriously impeding malaria control through treatment in east Africa. We did an open, alternate drug allocation study to assess the efficacy of chlorproguanil-dapsone in the treatment of falciparum malaria clinically resistant to pyrimethamine-sulfadoxine. METHODS: Children younger than 5 years with non-severe falciparum malaria, attending Muheza district hospital in Tanzania, were treated with the standard regimen of pyrimethamine-sulfadoxine. Patients whose clinical symptoms resolved but who remained parasitaemic 7 days after pyrimethamine-sulfadoxine were followed up for 1 month. Clinical malaria episodes were retreated with either single dose pyrimethamine-sulfadoxine or a 3-day regimen of chlorproguanil-dapsone. Those with parasitaemia after 7 days were treated with chlorproguanil-dapsone. Parasite DNA was collected on day 7 after first treatment with pyrimethamine-sulfadoxine and we looked for point mutations in the genes encoding dihydrofolate reductase (dhfr) and dyhydropteroate synthetase (dhps). FINDINGS: 360 children were enrolled and treated with pyrimethamine-sulfadoxine. On day 7, 192 (55%) of 348 had cleared parasitaemia. Of the remaining 156 parasitaemic children, 140 (90%) were followed up to day 28, and 92 (66%) of 140 developed clinical malaria. These 92 patients were alternately retreated with either pyrimethamine-sulfadoxine (46) or chlorproguanil-dapsone (46). 28 (61%) of 46 children retreated with pyrimethamine-sulfadoxine were still parasitaemic at day 7, compared with three (7%) of 44 [corrected] children retreated with chlorproguanil-dapsone. Resistance to pyrimethamine-sulfadoxine increased from 45% (156/348) at the first treatment to 61% (28/46) after retreatment. 83 of 85 parasite isolates collected after the first pyrimethamine-sulfadoxine treatment, and before and after the second treatments with pyrimethamine-sulfadoxine and chlorproguanil-dapsone showed triple-mutant dhfr alleles, associated with a variety of dhps mutations. INTERPRETATION: Most patients treated with pyrimethamine-sulfadoxine, who remain parasitaemic at day 7, develop new malaria symptoms within 1 month. Chlorproguanil-dapsone was a practicable therapy under these circumstances. Analysis of parasite dhfr and dhps before and after treatment supports the view that pyrimethamine-sulfadoxine resistance in this part of Africa is primarily due to parasites with three mutations in the dhfr domain.

Adolescent↗
PubMed2001

The association between Porphyromonas gingivalis-specific maternal serum IgG and low birth weight.

BACKGROUND: In Alabama, low birth weight (LBW) infants are about 20 times more likely to die before their first birthday compared to normal birth weight infants. While the rate of LBW has been consistently higher among African Americans compared to whites, there has been a gradual increase in LBW for both African Americans and whites over the last 15 years. In an attempt to identify modifiable risk factors for LBW, we have previously reported that a pregnant woman's poor periodontal health may be an independent risk factor for low birth weight. METHODS: A predominantly African American and socioeconomically homogeneous group of 448 women was followed from the second trimester of their first pregnancy. Thirty-nine LBW cases were observed at the end of follow-up. Using 17 preterm LBW cases and 63 randomly selected controls from the above cohort, the periodontal pathogen-specific maternal serum IgG levels during the second trimester of pregnancy were evaluated in relation to birth weight of the infant, while controlling for known risk factors for LBW. RESULTS: Porphyromonas gingivalis (P.g.)-specific maternal serum IgG levels were higher in the LBW group (mean 58.05, SE = 20.00 microg/ml) compared to the normal birth weight (NBW) group (mean 13.45, SE = 3.92 microg/ml; P= 0.004). Women with higher levels of P.g.-specific IgG had higher odds of giving birth to LBW infants (odds ratio [OR] = 4.1; 95% confidence interval [CI] for odds ratio = 1.3 to 12.8). This association remained significant after controlling for smoking, age, IgG levels against other selected periodontal pathogens, and race. CONCLUSIONS: Low birth weight deliveries were associated with a higher maternal serum antibody level against P. gingivalis at mid-trimester.

Adult↗
PubMed1994

Hands across the equator: the Hereford-Muheza link eight years on.

Short elective sabbatical visits have been arranged between Herefordshire Health Authority in England and Muheza Health District in Tanzania over the past eight years. Any employee can apply, and the 64 who have participated include midwives, physiotherapists, engineers, and nurse tutors. The possibility of being chosen adds to the attractiveness of working in both districts, and costs have been small. The visits are believed to have led to new ideas and a willingness and confidence to consider change.

Clinical Competence↗
PubMed1994

Community treatment with ivermectin for onchocerciasis in the east Usambara mountains.

Ivermectin 150mcg/kg was given orally to 743 patients with positive skin snips for Onchocerca volvulus and to 697 residents in two villages in the Usambara mountains. 620 villagers attended for a second dose. On direct questioning, 98.7% patients with +ve skin snips and 91.8% villagers given mass chemotherapy admitted to adverse reactions. After a second dose, 16.6% had mild reactions. No serious problems were encountered. 167 of 170 repeat skin snips were negative. Repeated administration of ivermectin is well tolerated and offers a chance of reducing the burden of onchocerciasis in the Usambara mountains.

Adolescent↗
PubMed1992

Metabolic studies in kidney stone disease.

Patients with kidney stones (n = 59) and healthy controls (n = 31) collected a 24-hour urine sample and later underwent a 6-hour 'fast and load' test in which an oral calcium load was taken after 2 hours. In the 24-hour urine sample, mean calcium excretion was higher in patients than controls, while mean urate, oxalate and citrate levels were similar. The patients had higher levels of fasting plasma calcium, serum calcitriol and fasting urinary calcium, and lower levels of plasma phosphate than did the controls. Following the calcium load, plasma and urinary calcium increased similarly in both groups. Serum parathyroid hormone (PTH) levels were similar in both groups and decreased similarly following the calcium load. Multiple linear regression, relating the presence or absence of stone formation to all variables, found the only variables significantly related to stone formation to be plasma levels of calcium (p less than 0.001) and phosphate (p = 0.001) and fasting urinary urea (p less than 0.001), and 24-hour urinary calcium excretion (p less than 0.05). Urinary oxalate and citrate were not related to stone formation. The data do not support the hypothesis that primary stimulation by calcitriol produces a normal fasting plasma calcium level, with an exaggerated increase after an oral calcium load. The findings instead suggest an abnormality of parathyroid cell 'set point', such that PTH secretion continues until the plasma calcium level is a little higher and the phosphate a little lower than in controls.

Adult↗
PubMed1991

Treatment of Paget's disease of bone with a combination of intranasal salmon calcitonin and oral calcium and thiazide.

The purpose of this study was to establish the smallest dose of nasally administered salmon calcitonin (SCT) which, if given in conjunction with a previously published calcium/thiazide treatment, would be as effective as parenteral SCT in the treatment of Paget's disease of bone. Forty patients suffering from symptomatic Paget's disease were treated with 0.5 g calcium three times daily, 10 mg/day clopamide, and 400 IU nasally administered salmon calcitonin given once or twice weekly. This regimen was given for 5 months, after which all treatment was ceased for 4 months. Parenteral SCT (100 IU) was then given three times weekly for 5 months to 25 of the patients. With the oral/nasal treatment, the plasma alkaline phosphatase level (AP) decreased by 30 +/- 15 (SD)% when the SCT was given once weekly and by 39 +/- 11% (P less than 0.05) when the SCT was given twice weekly. There were similar decreases in the fasting urinary hydroxyproline:creatinine ratios. The parenteral SCT reduced the AP by 33 +/- 23%. Though reduction in bone pain was similar with both treatments, most patients preferred the oral/nasal treatment. It is concluded that the oral/nasal treatment, when the SCT is given twice weekly, has similar efficacy to parenteral SCT, and is a well tolerated, effective initial treatment for Paget's disease of bone.

Administration, Intranasal↗
PubMed1990

Bone death in hip fracture in the elderly.

We examined femoral head bone from 50 cadavers and from 21 patients who had suffered pathologic fracture of the femoral neck. We used a histochemical technique for lactate dehydrogenase (LDH) activity to demonstrate osteocyte viability. The femoral heads were removed within 36 hours of death or fracture, as LDH activity persists in the cytoplasm of viable cells for this time at 37 degrees after interruption of the blood supply. In the controls, there was an age-related reduction in mean osteocyte viability, from 88 +/- 7% (mean +/- SD) at age 10-29 years to 58 +/- 12% at age 70-89 years. In the hip fracture patients, mean osteocyte viability was 58 +/- 21% but there was much variability in both osteocyte viability and bone mass. In 5 fracture patients, there was extensive osteocyte death, suggesting that most of the femoral head bone was nonviable; these patients had little microfracture callus. Others had predominantly viable bone which was usually osteoporotic, and their bone frequently showed microfracture callus. Osteomalacia was not seen in any patient. It is suggested that bone death, in addition to osteoporosis, may sometimes contribute to hip fracture in the elderly.

Aged↗
PubMed1989

Measurement of bone in the os calcis: a clinical evaluation.

Bone mineral content (BMC) was measured in the os calcis of 232 normal subjects aged 17-82 years. The mean reproducibility (coefficient of variation) of the measurement was 1.8%. Substantial bone loss occurred between the ages of 20 and 50 years, and in females the menopause was associated with additional bone loss. There was no significant difference in the rate of bone loss in females and males, but the mean BMC was greater at all ages in males than in females. We also compared os calcis BMC with spinal bone mineral density (BMD), measured by quantitative computed tomographic (CT) scanning, in 85 subjects: 33 were normal controls, 19 had osteoporosis defined by the presence of one or more pathological fractures, and in the remainder the CT examination was performed at the patient's request. Os calcis BMC correlated with spinal BMD in both females (r = 0.69, p less than 0.001) and males (r = 0.84, p less than 0.001). However, the os calcis BMC did not reliably predict spine values around the CT "fracture threshold" of 90-100 mg/cm3 and did not correlate with osteoporotic fracture as well as did spinal BMD. It is concluded that measurement of the os calcis BMC is of limited clinical usefulness for the early diagnosis of osteoporosis.

Adolescent↗
PubMed1989

Disorders of calcium and bone metabolism.

Calcium levels in blood are maintained within narrow limits by parathyroid hormone, acting on kidney, bone and gut. Our understanding of the mechanisms of these actions has increased greatly in recent years, for example by identification of new hormones (eg 1,25 dihydroxy vitamin D) and by the study of isolated bone cells. Though most clinical disorders of calcium metabolism are now readily diagnosed and many are effectively treated, some serious problems still remain. Foremost amongst these are the early diagnosis of osteoporosis and the treatment of osteoporosis after fractures have occurred. Most disorders of calcium metabolism have ophthalmologic manifestations, sometimes troublesome to the patient, and sometimes diagnostically helpful.

Bone Diseases, Metabolic↗
PubMed1989

Bone histology in young adult osteoporosis.

Bone histology was quantitated in 10 osteoporotic patients aged between 17 and 51 years and in six healthy subjects aged between 23 and 43 years. The osteoporosis was of varying aetiology and was clinically stable. All patients were given tetracycline before biopsy and double tetracycline labelling was used in seven patients. Bone forming and resorbing surfaces were defined by the presence of osteoblasts and osteoclasts, respectively, which were identified by histochemical techniques. The associations between bone forming and resorbing surfaces were similar in patients and controls, though the range of values was wider in the patients than in the controls. Mineral apposition rate was normal in the osteoporotic patients, but there was a reduction in mineralising (tetracycline) surface, whether related to osteoid surface or to osteoblast surface. This did not indicate osteomalacia as the directly and indirectly measured mineralisation lag times were normal. The osteoid seams were thinner in osteoporotic patients than in controls. The data suggest that osteoclast and osteoblast numbers were normal in this group of osteoporotic patients but that the metabolic activity of osteoblasts was impaired.

Adolescent↗
PubMed1989

Candidiasis-endocrinopathy syndrome with progressive myopathy.

A women suffering from the candidiasis-endocrinopathy syndrome, developed severe myopathy in her fourth decade and died from it at the age of 37 years. Associated conditions were hypoparathyroidism, vitiligo, chronic mucocutaneous candidiasis, short stature, intellectual disability, ovarian failure and alopecia totalis. Muscle biopsy findings were non-specific with focal atrophy of type 2 fibres. Serum immunoglobulin levels were normal. The only demonstrable abnormalities of her immune system were impaired T-cell function and antibody production by B-cells (detectable to smooth muscle, mitochondria and gastric parietal cells). The T-cell abnormality may have been part of a more generalized cell defect, resulting from an unidentified genetic abnormality, whilst the circulating antibodies could have been a response to tissue damage. There was no convincing evidence of primary autoimmune damage.

Adult↗
PubMed1987

The pathogenesis of osteoarthritis of the hip. Evidence for primary osteocyte death.

Osteocyte viability was investigated in femoral head bone removed from 38 patients with chronic hip disease, with the use of a histochemical stain to demonstrate lactate dehydrogenase (LDH) activity in osteocytes. Where the osteocyte cytoplasm did not show LDH activity, the cell was considered dead; when several adjacent osteocytes were dead, the bone in that area was regarded as nonviable. The preoperative diagnoses were idiopathic osteoarthritis in 25, chondrocalcinosis in six, rheumatoid arthritis in two, Paget's disease in two, avascular necrosis in two, and congenital dislocation of the hip in one patient. In 16 of the patients with idiopathic osteoarthritis and the two with avascular necrosis, nonviable osteocytes were present in the central regions of many trabeculae, these areas usually being separated by cement lines from viable bone. The pattern suggested previous necrosis of part of the femoral head, with later new bone formation. The pattern was not observed in either control subjects, or patients with known articular disease, such as chondrocalcinosis. Bone collapse of variable severity was apparent radiographically in nine patients with histologic bone death, but not in other patients. Bone death is commonly present in idiopathic osteoarthritis and could be a cause rather than a result of the arthritis.

Adult↗
PubMed1986

Immobilization hypercalcaemia due to low bone formation and responding to intravenous sodium sulphate.

A young man developed acute renal failure and hypercalcaemia following severe burns. The hypercalcaemia was initially controlled by haemodialysis, but it persisted after return of renal function. Plasma PTH was inappropriately elevated, but the nephrogenous cyclic adenosine monophosphate level was low; thus the PTH was probably not biologically active, and may have been artefactually elevated by the moderate renal impairment. Bone histology, showed a normal resorbing surface, but a zero forming surface, implying that the bone dissolution leading to hypercalcaemia resulted from a failure of bone formation. Because of widespread infection and impaired renal function, the hypercalcaemia could not be treated by corticosteroid drugs, mithramycin or phosphate, and there was no response to salmon calcitonin. He was therefore treated with intravenous sodium sulphate, which increased urinary calcium excretion and reduced the plasma calcium. Sodium sulphate still has a role in the treatment of patients with hypercalcaemia.

Adult↗
PubMed1985

Investigation and treatment of renal calculi.

We have investigated and treated 176 patients who were suffering from renal calculi. The stones contained calcium in 87% of patients, predominantly urate in 11%, and rarely contained magnesium ammonium phosphate or cystine. Of the patients with calcium stones, hypercalciuria was present in 75% and was identified in 57% by the measurement of the 24-hour urinary calcium excretion, and in a further 18% by a standardization calcium "fast-and-load" test. Nine patients were found to have primary hyperparathyroidism and were treated surgically. A further 21% were suspected to have normocalcaemic hyperparathyroidism, and metabolic studies are being developed to clarify this. The treatment of hypercalciuria included a low-calcium diet, and various combinations of a thiazide diuretic, phosphate supplements and sodium cellulose phosphate. Hypercalciuria was controlled in all compliant patients, and only two developed further stones. Hyperuricosuria was rarely the sole metabolic abnormality in patients with calcium stones, though this might reflect the referral pattern of the Unit. Uric acid stones were frequently, but not invariably, associated with hyperuricosuria and acid urine, and even large uric acid calculi dissolved with a combined therapy of high fluid intake, allopurinol and an alkalinizing agent. Surgical treatment was rarely required in these patients. A stone in the renal pelvis of one patient was removed percutaneously and did not require ultrasonic fragmentation. Modern methods of investigation and treatment have greatly improved the outlook for patients with recurrent renal calculi.

Calcium↗
PubMed1985

Treatment of childhood renal osteodystrophy with calcitriol or ergocalciferol.

Quantitative bone histology, biochemistry and height velocities were studied in 18 children suffering from chronic renal failure. Eight received calcitriol, 7 ergocalciferol and 3, though alloted to a treatment group, failed to comply with therapy. A histochemical stain for aluminum showed heavy deposition at the calcification front in 3 patients; 2, in the calcitriol group had severe osteomalacia which worsened during treatment, and 1 in the ergocalciferol group had osteomalacia which did not improve. One had never undergone hemodialysis. Bone histology improved markedly in the remaining 12 patients, whichever vitamin D preparation was used; it was unchanged in 3 non-compliant children. Plasma calcium levels rose while parathyroid hormone and alkaline phosphatase levels fell following both treatments, and were unchanged in non-compliant children. Hypercalcemia occurred more frequently following calcitriol therapy (11 episodes) than following ergocalciferol therapy (3 episodes). Height velocities, studied in 11 children, increased in 5 (3 on ergocalciferol and 2 on calcitriol) and were unchanged in 6 (1 on ergocalciferol, 5 on calcitriol). Improved bone histology did not correlate with increase in height velocity. As ergocalciferol and calcitriol had similar therapeutic effects and as side-effects were more common with calcitriol, it is concluded that calcitriol provides no advantage over ergocalciferol in the treatment of renal bone disease in children.

Alkaline Phosphatase↗
PubMed1985

Treatment of hemodialysis bone disease with 24,25-(OH)2D3 and 1,25-(OH)2D3 alone or in combination.

We studied the effects of vitamin D metabolites in 29 patients established on chronic hemodialysis. The patients were divided into four groups; one was treated with 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] 0.5 microgram/day, one with 24R,25-dihydroxyvitamin D3 [24,25-(OH)2D3] 10 micrograms/day, and one with both metabolites. The control group was not given vitamin D. Plasma levels of both metabolites were low before treatment. 1,25-(OH)2D3 levels became normal, and 24,25-(OH)2D3 increased to supranormal levels after administration of the corresponding metabolite. Combined treatment produced still higher plasma levels of 24,25-(OH)2D3, suggesting an interaction between the two metabolites. Patients receiving 1,25-(OH)2D3 alone had a greater increase in plasma calcium than those receiving both metabolites. In control patients, hyperparathyroid bone disease worsened over the 10-month observation period. 1,25-(OH)2D3 improved hyperparathyroid bone disease in most patients, as reflected by a reduction in osteoclast and osteoblast numbers, but had no demonstrable effect on mild osteomalacia. 24,25-(OH)2D3 had no significant effect on plasma biochemistry or bone histology, and the effect of combined treatment on histology was similar to that of 1,25-(OH)2D3 alone. Stainable bone aluminum increased slightly in patients given 1,25-(OH)2D3, but aluminum did not affect the response to treatment. We conclude that 1,25-(OH)2D3 is a useful agent in the treatment of renal bone disease, but no therapeutic role is apparent for 24,25-(OH)2D3.

24,25-Dihydroxyvitamin D 3↗