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Biomedical subjects

T Cundy

Publications and source records attributed to T Cundy.

At least 55 records · Page 3Linked to original sources
PubMed1997

Evidence for secular change in Paget's disease.

Death certification data has shown that death rates due to Paget's disease of bone and osteosarcoma in older people (assumed to be attributable to Paget's) declined in the latter part of the 19th and in the early 20th century, suggesting that there may be a secular trend toward less severe disease. We have reviewed a 21 year experience in a clinic specializing in Paget's disease. Data from all 1041 patients attending the clinic in this period were reviewed. Despite an increase in the susceptible population and an increased rate of referral to the clinic over this time (p = 0.012), there was a fall in the absolute numbers of patients referred with severe disease, as judged by the initial plasma alkaline phosphatase activity at presentation. In the years 1973-1978 the initial plasma alkaline phosphatase was > 500 U/L in an average of 22 new patients per year and > 1000 U/L in 12 per year. In the years 1988-1993, the figures were 12 and 3 per year, respectively. During this period, there were no other facilities offering scintigraphy or intravenous treatment for Paget's disease in the Auckland region, making it unlikely that patients with severe disease were being seen and treated elsewhere. The average age of newly referred patients rose steadily from a mean 62 years, in 1971-1973 to 71 years in 1991-1993 (p < 0.001). 534 subjects had scintiscans (52%) from which the extent of skeletal involvement was calculated. Skeletal involvement showed a significant negative correlation with year of birth (p < 0.01) but not with age or year of presentation. The proportion of patients with > 20% skeletal involvement had fallen by a third in the cohort born after 1926, compared to the cohort born before 1915. Our data demonstrate that, on average, newly referred patients with Paget's disease have less severe disease and are significantly older at diagnosis than was the case two decades ago.

Aged↗
PubMed1996

Longer femoral necks in the young: a predictor of further increases in hip fracture incidence?

AIMS: To determine whether femoral neck length, a risk factor for hip fracture, is likely to increase in the coming decades in normal elderly New Zealand women. METHODS: Femoral neck length was measured from dual-energy x-ray absorptiometry scans of the proximal femur in white women aged 19-88 years (n = 211). Since this length remains constant throughout adult life, it is possible to predict future trends in this index in the elderly, from its measurement at the present time in younger adults. RESULTS: Femoral neck length was inversely related to age (p = 0.018) such that a 3.7 mm (5.7%) difference occurred over the age-range of this sample. CONCLUSIONS: Femoral neck length in elderly New Zealand women is likely to increase in the coming decades. As a result of the dependence of hip fracture risk on femoral neck length, future age-adjusted hip fracture incidence will increase by about 50% over the next 50 years unless significant public health initiatives are taken, either to increase bone density or to reduce fall frequency.

Absorptiometry, Photon↗
PubMed1996

Effects of vertical-banded gastroplasty on bone and mineral metabolism in obese patients.

The surgical treatment of obesity can have adverse effects on bone, but there are few published data on the effects of vertical-banded gastroplasty. Serial measurements of bone mineral density at the lumbar spine and three upper femoral sites, using dual-energy X-ray absorptiometry, and also of biochemical indices of bone and mineral metabolism at intervals up to 2 years after operation were performed in 18 patients with morbid obesity who had vertical-banded gastroplasty. Bone mineral density measurements were also made in age- and sex-matched non-obese controls. Bone density before operation was significantly greater in the obese than in the controls (P < 0.02 at all sites). The obese patients lost weight rapidly after vertical-banded gastroplasty (mean weight loss 29 kg at 1 year, P < 0.001). This was accompanied by a measurable loss of bone density from the trochanter and Ward's triangle sites in the upper femur (P < 0.05), but not from the lumbar spine. Bone density values remained stable over 14 months in the controls. Hydroxyproline excretion increased significantly (P < 0.005), indicating an increase in bone resorption. Alkaline phosphatase levels decreased significantly (P < 0.001), but this probably represents the reversal of hepatic steatosis. There was no evidence of hyperparathyroidism or vitamin D deficiency. In conclusion, vertical-banded gastroplasty causes modest bone density loss from femoral sites, but not the lumbar spine. The difficulties of assessing bone density changes in the obese are discussed.

Adult↗
PubMed1996

High-dose pamidronate in the management of resistant Paget's disease.

Current recommendations for the total dose of intravenous pamidronate to be used in the treatment of Paget's disease range up to 400 mg per course, although up to 980 mg has been suggested for resistant cases. However, in a proportion of Paget's disease patients remission is difficult to induce and maintain. In five patients with resistant symptomatic Paget's disease, in whom a variety of antipagetic therapies had failed to induce remission, we have examined the effects of high dose pamidronate (1.44-2.52 g intravenously over 12-42 weeks). All five subjects had a marked symptomatic improvement, and disease activity was suppressed to a greater extent than had been achieved previously, but in only one did alkaline phosphatase activity suppress into the normal range. A plateau in the biochemical response was evident, with successive pamidronate doses of 120 mg producing smaller decrements in alkaline phosphatase. The plateau was reproducible on repeated courses. Bone biopsies in two patients showed continued pagetic activity with an increased mineralization rate and no osteomalacia. Worthwhile clinical and biochemical improvements can be obtained in patients with resistant Paget's disease by the use of high-dose pamidronate. Though this approach does not seem to cause defective mineralization, it may be difficult to suppress disease activity completely.

Aged↗
PubMed1996

Biochemical and radiologic improvement in Paget's disease of bone treated with alendronate: a randomized, placebo-controlled trial.

PURPOSE: The potent bisphosphonates offer great promise in the management of Paget's disease of bone, but are currently available only as parenteral preparations in most countries. There is a need for a well-tolerated, oral therapy. Furthermore, none of the currently available therapies have been rigorously demonstrated to heal the lytic bone lesions characteristic of this condition. Alendronate is a potent new oral aminobisphosphonate that has shown promising effects on Paget's disease in preliminary studies. METHODS: We report a double-blind, randomized comparison of oral alendronate 40 mg/day and placebo over 6 months in 55 patients with Paget's disease. Efficacy was determined from measurements of biochemical indices of bone turnover (serum alkaline phosphatase and urine N-telopeptide) and blinded radiologic assessment of lytic bone lesions. RESULTS: N-telopeptide excretion declined by 86% and serum alkaline phosphatase by 73% in patients receiving alendronate, but remained stable in patients receiving placebo (P < 0.001 between groups for both indices). Responses were similar whether or not patients had previously received bisphosphonate treatment. Alendronate treatment normalized alkaline phosphatase in 48% of patients. Forty-eight percent of alendronate-treated patients showed radiologic improvement in osteolysis whereas in the placebo group only 4% improved (P = 0.02 for between-groups comparison). No patient in either group showed worsening of osteolysis. Bone histomorphometry indicated that alendronate tended to normalize turnover indices. There was no evidence of abnormal mineralization in bone biopsies taken from 12 alendronate-treated subjects. The treatment was well tolerated. CONCLUSION: Oral alendronate appears to be a safe and effective therapy for Paget's disease and results in healing of lytic bone lesions.

Administration, Oral↗
PubMed1996

Medroxyprogesterone acetate enhances the spinal bone mineral density response to oestrogen in late post-menopausal women.

OBJECTIVES: The relative contributions of administered oestrogen and progestin to protection of the post-menopausal skeleton remain unclear. We have compared the effect on spinal bone mineral density of continuous combined oestrogen/medroxyprogesterone therapy with that of unopposed oestrogen in late post-menopausal women. DESIGN: Observational study. SUBJECTS: Seventy-three osteoporotic post-menopausal women attending the Auckland Hospital Bone Clinic. Twenty-three hysterectomized women were treated with unopposed oestrogen (0.625 mg oral conjugated oestrogens daily), and 50 non-hysterectomized women were treated with continuous combined oestrogen/medroxyprogesterone therapy (5 mg medroxyprogesterone acetate and 0.625 mg oral conjugated oestrogens daily). MEASUREMENTS: Baseline and one-year measurements of lumbar spine bone mineral density were performed using dual-energy X-ray absorptiometry. RESULTS: After one year of therapy, spinal bone mineral density increased by 6.6% (95% confidence interval 5.6-7.6, P < 0.001 vs baseline) in the combined oestrogen/medroxyprogesterone therapy group, compared to 4.0% (CI 2.4-5.7, P < 0.001 vs baseline) in the unopposed oestrogen group (difference between means 2.6% (CI 0.8-4.4, P < 0.01). CONCLUSION: In osteoporotic post-menopausal women, one year of continuous combined oestrogen/medroxyprogesterone therapy is associated with a 65% greater increment in spinal bone mineral density than is observed in response to unopposed oestrogen. The prescription of combined oestrogen/progestin therapy should be considered in osteoporotic post-menopausal women who have undergone hysterectomy, in order to maximize the skeletal protection provided by hormone replacement therapy.

Absorptiometry, Photon↗
PubMed1996

Short-term effects of high dose oral medroxyprogesterone acetate on bone density in premenopausal women.

Despite the widespread use of the C21 progestin medroxyprogesterone acetate (MPA) in hormone replacement therapy and gynecological practice, its effects on bone density are uncertain, with contradictory reports in the literature. We have examined the short term changes in bone density at the lumbar spine (a predominantly trabecular site) and the femoral neck (a predominantly cortical site) in 13 premanopausal women prescribed high dose MPA (50 mg/day) for gynecological disorders and in 12 control subjects. Compared to basal values, lumbar spine bone mineral density (measured by dual energy x-ray absorptiometry) fell progressively by a mean 2.4% at 6 months and 4.1% at 12 months (both P < 0.01); in five subjects who continued the drug, it had fallen by a mean 5.9% at 20 months (P < 0.002). The spinal bone loss in the MPA users was significantly greater than that in controls (P < 0.005 at 6 months; P < 0.01 at 12 months) and occurred despite a significant gain in body weight in the women using MPA (median, 3.5 kg at 6 months; P < 0.01). In four subjects in whom bone density was measured 6 months after cessation of MPA, spinal bone density showed significant recovery (mean increment, 2.8%; P < 0.025). Femoral neck bone density measurements did not differ between the groups. MPA induced amenorrhea in all subjects who continued with it beyond 6 months, and the amenorrheic subjects were estrogen deficient (median plasma estradiol, 70 pmol/L). We conclude that, when given in doses sufficient to induce hypogonadism, MPA use is associated with significant early loss of trabecular bone, which is probably the consequence of estrogen deficiency.

Administration, Oral↗
PubMed1995

Sources of interracial variation in bone mineral density.

Many studies have demonstrated significant differences in bone mineral density between various racial groups. Although it has been suggested that differences in body weight contribute to such interracial variation, the artifactual effect of the skeletal size inherent in projectional absorptiometry methods has been largely ignored. We have measured bone mineral density by dual-energy X-ray absorptiometry in the lumbar spine and at three femoral sites in 200 premenopausal women of Chinese, Indian, European, or Polynesian origin (50 of similar mean age in each group). In the Chinese and Indian women the measured bone mineral density measurements (g/cm2) were similar, but significantly less, at all sites, than those of European women (p < or = 0.005). The European women were, however, significantly taller than both the Chinese and Indian women (p < 0.0001), and when the scale artifact of absorptiometry was removed by dividing the measured bone mineral density either by the height of the subject, or by the square root of the area over which the X-ray beam was projected, then the differences in mean bone mineral density between the Chinese, Indian, and European women were almost completely eliminated. The Polynesian women were significantly more obese (as judged from mean body mass index) than all the other groups (p < 0.0001) and had significantly greater bone mineral density at all sites than all the other groups both before (p < 0.0001) and after (p < 0.0001) correcting for the scale artifact.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗
PubMed1994

Mechanisms of cortical bone loss from the metacarpal following digital amputation.

Immobilization bone loss, whether due to whole body immobilization or local causes, is associated with an initial rapid phase of trabecular bone loss, but the long-term effects of immobilization on cortical bone are not well described. We have studied metacarpal morphometry in 16 men who had undergone partial or complete traumatic digital amputations 4-71 years earlier. Noninvolved metacarpals from the affected and unaffected hands were used as controls. Cortical bone width was significantly reduced in the metacarpals proximal to the amputated digits (P = 0.001). In the 7 subjects who suffered amputation before the age of 19, the cortical bone deficit was primarily due to a reduction in the total width of the medullary shaft (P = 0.007), whereas medullary width was not changed. In these subjects the metacarpal was also significantly reduced in length, by a mean 2.9 mm (P = 0.35). In the 9 subjects who had their amputation after the age of 19, both a reduction in total width and an increase in medullary width (P = 0.017) accounted for the cortical bone deficit. The deficit in total width was related to the time since amputation (P = 0.008) and could be accounted for by loss of the normal age-related increase in total width (0.01 mm/year). We conclude that in this model of immobilization osteoporosis, the metacarpal proximal to the amputated digit demonstrates cortical osteopenia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Glomerular hyperfiltration in young Polynesians with type 2 diabetes.

An increase in glomerular filtration rate (hyperfiltration) may be an important early event in the initiation of diabetic nephropathy but the prevalence of hyperfiltration appears to vary between different populations with type 2 diabetes. We have measured glomerular filtration rate using 51Cr EDTA clearance in 15 young Polynesians (mean age 32 years), 1-30 months after the initial diagnosis of type 2 diabetes and 15 control Polynesian subjects of comparable age and sex distribution. The mean glomerular filtration rate in the diabetic subjects (216 ml/min) was 57% greater than that of the controls (137.5 ml/min, P < 0.0001). About one-third of their excess in glomerular filtration rate could be accounted for by the marked obesity of the diabetic subjects, but even after correcting for body size the diabetic subjects still had a significantly higher mean glomerular filtration rate than controls (165.6 vs. 119.6 ml/min per 1.73 m2, P < 0.001); 73% of the diabetic subjects had hyperfiltration (> 140 ml/min per 1.73 m2). The diabetic subjects were normotensive but nonetheless had increased rates of albumin excretion (median 61 versus 9 mg/day, P < 0.001). We conclude that hyperfiltration is common in young Polynesians with recently diagnosed type 2 diabetes. Prospective studies are needed to determine whether this early abnormality of renal function heralds the later development of overt nephropathy.

Adult↗
PubMed1994

Fetal liver length in diabetic pregnancy.

OBJECTIVES: Our purpose was to investigate whether liver size is increased in the fetuses of pregnant women with diabetes and whether there is any relationship between fetal liver size and maternal glycemic control. STUDY DESIGN: Eighty pregnant women with diabetes had ultrasonographic measurement of fetal liver length made at 18, 28, and 36 weeks' gestation. Twenty-four obese, nondiabetic women were studied at 36 weeks as controls. RESULTS: Fetal liver length measurements were significantly greater than normal by 18 weeks' gestation (12% above normal mean values; p < 0.001) and increased further (19%, p < 0.02) by 36 weeks. In the obese controls liver length was increased 9% and was significantly lower than in the diabetic subjects (p < 0.001). CONCLUSIONS: Fetal liver size in increased in pregnant women with diabetes and cannot be explained solely by maternal obesity. The major increase in liver size occurs early in pregnancy but appears to be modifiable by glycemic control later in gestation.

Adult↗
PubMed1994

Rates of progression to end stage renal failure in nephropathy secondary to type 1 and type 2 diabetes mellitus.

BACKGROUND: Diabetic nephropathy is now the commonest single cause of end-stage renal failure (ESRF) in New Zealand. AIMS: To investigate differences in the natural history of established nephropathy in Type 1 and 2 diabetes. METHODS: Retrospective analysis of the rate of progression to ESRF in 17 subjects with Type 1 diabetes (predominantly European) compared to 29 subjects with Type 2 diabetes (all Polynesian). The rate of decline of renal function was determined from serial creatinine measurements (median 5, range 3-8) during progression of chronic renal failure to end stage. Glomerular filtration rate (GFR) was estimated from creatinine measurements using the Cockcroft Gault equation, and the regression slope of these measurements against time was used to determine rate of change of renal function. RESULTS: GFR fell significantly more rapidly in the group with Type 2 diabetes than in those with Type 1 diabetes: median 1.7 (interquartile range 1.2 to 2.3) mL min-1 month-1 vs 1.1 (interquartile range 0.4 to 1.5) mL min-1 month-1, p = 0.017. During the study period the mean reduction in diastolic blood pressure in subjects with Type 1 diabetes (15 mmHg) was greater than that in the Type 2 subjects (8 mmHg), but the stage at which antihypertensives were commenced was similar in the two groups. Glycaemic control was worse in the subjects with Type 1 diabetes (p < 0.005). The differences in blood pressure control were not significant on analysis of covariance which indicated that ethnicity was the major determinant of the different rates of decline of GFR between the groups. We conclude that in subjects with diabetic nephropathy the rate of progression to ESRF is more rapid in Polynesians with Type 2 diabetes than in Europeans with Type 1 diabetes. This could contribute to the apparent excess of Type 2 diabetic subjects of Polynesian origin on renal replacement programmes in New Zealand.

Adult↗
PubMed1994

A comparison of oral and intravenous alfacalcidol in the treatment of uremic hyperparathyroidism.

The i.v. bolus administration of 1 alpha hydroxylated vitamin D derivatives is effective in the treatment of uremic hyperparathyroidism. However, few of the published studies of this mode of treatment have been adequately controlled, and recent reports have suggested that p.o. bolus administration may be just as effective. In this study, 16 hemodialysis patients with mild to moderate hyperparathyroidism were assigned, after a 4-wk run-in period, to receive a 6-wk course of either thrice-weekly i.v. or p.o. alfacalcidol (initial dose, 4 micrograms). Then, after a further control period, they received a second 6-wk course, with either p.o. or i.v. alfacalcidol (whichever was not given in the first treatment period). Plasma parathyroid hormone (PTH) was measured weekly by the use of an intact hormone assay. Both routes of therapy resulted in a significant suppression of plasma PTH (P = 0.005) and an elevation in plasma ionized calcium (P = 0.01). The magnitude of the responses was similar for the two treatment phases, as was the relationship between the increment in calcium and the decrement in PTH. The most complete suppression of PTH was seen in those with the greatest increment in plasma calcium. The incidence of hypercalcemia and the mean dose reductions necessary were also similar in the two treatment phases. Oral bolus therapy and i.v. bolus therapy with alfacalcidol are equally effective in suppressing hyperparathyroidism. The postulated advantages of i.v. over p.o. therapy with 1 alpha hydroxylated vitamin D derivatives remain to be confirmed by controlled studies.

Administration, Oral↗
PubMed1993

Severe vitamin D deficiency in Auckland.

AIMS: To study the presentation of severe vitamin D deficiency in Auckland and to determine if appropriate therapy was given. METHODS: Retrospective review of records of patients with very low plasma 25 hydroxyvitamin D concentrations (< or = 12.5 nmol/L or 5 micrograms/L). RESULTS: Fifty cases were identified over a two year period. 28 subjects had recognised risk factors for vitamin D deficiency (such as gastrointestinal disease or greatly reduced food intake). The majority of the other 22 subjects were elderly residents of rest homes or private hospitals. Low body weight and reduced mobility were common features of both groups. Increased plasma alkaline phosphatase activity and hypocalcaemia were the most frequent biochemical findings. Appropriate treatment with high dose calciferol had been given to only 28% of the subjects. CONCLUSIONS: Severe vitamin D deficiency does occur in Auckland despite its low latitude. Low body weight, reduced mobility and lack of sun exposure are particular risk factors. Appropriate therapy is cheap, safe and effective but many patients with severe vitamin D deficiency are being managed suboptimally.

Adolescent↗