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Biomedical subjects

T F Cundy

Publications and source records attributed to T F Cundy.

15 recordsLinked to original sources

Bone mineral density of the proximal femur and lumbar spine in glucocorticoid-treated asthmatic patients.

The importance of the proximal femur as a site of osteoporotic fractures, the development of techniques for bone mineral density (BMD) measurement at this site and the apparent selectivity of the osteopenic effects of glucocorticoids have focused attention on the assessment of proximal femoral BMD in steroid-treated subjects. We have, therefore, measured BMD (Lunar DPX) in the lumbar spine and proximal femur of 31 asthmatic patients receiving long-term glucocorticoid therapy (mean +/- SEM dose 16 +/- 1 mg prednisone/day, mean duration 10 +/- 2 years). BMD values expressed as the percentage of normal age- and sex-appropriate mean values, after weight adjustment, were as follows: lumbar spine 80 +/- 2%, femoral neck 83 +/- 2%, Ward's triangle 78 +/- 3% and trochanter 86 +/- 2%. All these values were significantly less than control (p less than 0.0001) and the decrement in BMD was more marked in Ward's triangle than at the other two femoral sites (p less than 0.05). In all regions BMD was unrelated to dose or duration of steroid treatment. It is concluded that there are reductions in the BMD of the lumbar spine and proximal femur in glucocorticoid-treated asthmatics, probably reflecting the mixed cortical/trabecular make-up of both regions.

Adult

Measuring the albumin excretion rate: agreement between methods and biological variability.

A timed urine collection is necessary to determine the excretion rate of albumin (AER) but such specimens are tedious to collect and frequently inaccurate. Albumin excretion can also be quantified by the use of the albumin:creatinine ratio in randomly obtained specimens. In the present study the agreement between AER as measured on a 24-h urine collection and as estimated from the albumin:creatinine ratio is determined. Previously published studies have examined the correlation rather than the agreement between these methods and not taken into account the biological variability of AER. Thirty patients with diabetes who had normal renal function, but varying degrees of albuminuria, produced two 24-h specimens and two random daytime specimens of urine. AER was measured on the former and estimated from the latter by multiplying the albumin:creatinine ratio by an estimate of that individual's creatinine excretion rate. Agreement between the methods and the biological variability was determined by using appropriate statistical methodology, the main outcome measure being the limits of agreement between repeat values for both measurements and both estimates of AER, and between the averages of the measurements and the estimates. The limits of agreement between repeated 24-h measurements were wide, the second specimen being 33 to 490% of the first. The estimates of AER gave values numerically similar to the measurements. The limits of agreement between the two estimates did not differ significantly from those of the measurements, nor did the limits of agreement when the average of the measurements and the average of the estimates were compared (all NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Albuminuria

Determinants of total body and regional bone mineral density in normal postmenopausal women--a key role for fat mass.

In order to determine which clinical, anthropometric, dietary, and biochemical variables are independent predictors of total and regional bone mineral density (BMD) in normal postmenopausal women, a cross-sectional study of 140 normal postmenopausal women has been carried out. Subjects were white, aged 45-71 yr (mean 58 yr), and had no history of disorders or medication use likely to influence bone or calcium metabolism. Multiple regression analysis was used to derive models for total and regional BMD in terms of the other variables measured. The analysis indicated that total body BMD was positively related to fat mass (P less than 0.0001), serum estrone (P = 0.0095) and age at menopause (P = 0.0165), and negatively related to age (P less than 0.0001), 24-h urine calcium (P = 0.0002), sex hormone-binding globulin (P = 0.0003), and serum alkaline phosphatase activity (P = 0.0029) (R2 = 0.61). Similar relationships were found in the subregions of the total body scans and in the lumbar spine and proximal femur, with insulin-like growth factor-1, parity, and age at menarche also being related to BMD at at least two of these sites. Lean body mass was not an independent correlate of BMD at any site once fat mass was taken into account. Muscle strength, physical activity, alcohol intake, and dietary intakes of calcium, sodium and protein did not emerge as significant predictors of BMD in this homogeneous group of postmenopausal women. We conclude that total body fat is the most significant predictor of BMD throughout the skeleton and this relationship is not explicable in terms of either estrone production in fat tissue or the dependence of skeletal load-bearing on fat mass. The mechanism underlying this relationship is an important question to be addressed in bone biology.

Aged

The osteodystrophy of congenital erythropoietic porphyria.

Congenital erythropoietic porphyria (CEP) is a rare disorder of heme biosynthesis that results in the production of large quantities of photoactive porphyrins. The clinical syndrome is dominated by extreme photosensitivity with mutilation of light exposed extremities and hemolytic anemia. Bone disease has been occasionally noted, but is not well characterised. We describe a man with CEP who developed bone pain and spinal crush fractures at the age of 22. Skeletal radiographs revealed features typical of other severe hemolytic anemias, but in addition there was loss of the terminal phalanges of the hand as a result of photomutilation. Spinal bone density (assessed by DPA) was reduced and at the hip bone density was at the lower limit of normal. The metacarpal cortical bone density was 2.9 standard deviations below normal. Biochemical and histological studies accelerated bone turnover. Although the serum 250H vitamin D concentration was very low (because of light avoidance) there was no evidence that the bone disease was a consequence of this. Treatment for one year with clodronate and a high transfusion regime was associated with small reductions in serum alkaline phosphatase and urine hydroxyproline excretion, but there was no improvement in bone mineral density. We conclude that CEP has a distinctive osteodystrophy comprising osteolysis of light-exposed extremities and a high turnover type of osteoporosis. Privational vitamin D deficiency may also occur. The effect upon bone of the new therapies for CEP should be considered.

Alkaline Phosphatase

Amenorrhoea in women with non-alcoholic chronic liver disease.

Amenorrhoea is common in women with non-alcoholic chronic liver disease, but little is known about its causes or consequences. We investigated 12 young women with non-alcoholic chronic liver disease and amenorrhoea and compared them with 11 healthy age matched controls studied in the follicular phase of the menstrual cycle. None of the patients had raised serum concentrations of follicle stimulating hormone suggesting primary gonadal failure, but the variance in serum concentrations of testosterone, oestradiol, prolactin, and luteinising hormone were significantly greater in chronic liver disease patients than control subjects (p less than 0.01). Seven of the 12 chronic liver disease patients had low serum luteinising hormone concentrations, and compared with controls these patients also had significantly reduced median values of oestradiol (64 pmol/l), testosterone (1.1 nmol/l), and follicle stimulating hormone, and were significantly underweight as assessed by skinfold thickness measurements (all comparisons p less than 0.025). In the group with chronic liver disease skinfold thickness was significantly correlated with serum luteinising hormone (p less than 0.02). The five patients with normal serum luteinising hormone had higher median values of both oestradiol (237 pmol/l) and testosterone (3.0 nmol/l) than the control subjects (oestradiol: 113 pmol/l, testosterone: 1.9 nmol/l) but were not more obese or hirsute. Amenorrhoea was unrelated to the duration or severity of liver disease. The metacarpal cortical bone area (an index of bone density) was inversely related to the duration of amenorrhoea (p less than 0.02). We conclude that amenorrhoea in women with non-alcoholic chronic liver disease arises from hypothalamic-pituitary dysfunction and can occur at any stage. The hormonal findings in amenorrhoeic chronic live disease patients are not uniform. In some, hypogonadotrophic hypogonadism is related to undernutrition whereas others have normal to high values of luteinising hormone and sex steroids. Prolonged oestrogen deficiency can be a risk factor for osteoporosis in women with chronic liver disease.

Adult

Recovery of menstruation and pregnancy after liver transplantation.

The effect of successful liver transplantation on menstrual function was assessed by questionnaire in 44 women transplanted for various types of end stage liver disease, acute liver failure or malignant disease. Significant amenorrhoea (greater than one year) was present in 48% of women with chronic liver disease before transplantation, and was reversed within 10 months of surgery in all but one of the premenopausal patients who had primary amenorrhoea and hypogonadotrophic hypogonadism. Two patients became pregnant five months and 1.5 years after transplantation, but in one instance the pregnancy was unsuccessful, possibly as a consequence of cyclosporin related intrauterine growth retardation.

Adolescent

Patterns of cellular immune responses to thyrocyte membrane antigens and specific immunoregulatory defects in autoimmune thyroid disease.

Although Graves' disease (GD), Hashimoto's thyroiditis (HT) and idiopathic myxoedema (Myx) are clinically distinct autoimmune thyroid diseases, previous studies using crude thyroid preparations as a source of antigens have failed to identify differences in cellular immune responses. In this study, we have assessed cellular immunity in patients with these disorders to two antigen preparations (derived from thyroid gland and cervical fat) enriched in cell membranes and known to share a functional TSH receptor. Using an indirect T-lymphocyte migration inhibitory factor (T-LIF) assay, T-cell immunity to thyroid membranes was demonstrated in 11/11 patients with GD, 4/5 with HT and 4/5 with Myx, but in none of 18 patients with chronic active hepatitis (another organ-specific autoimmune disease) or sixteen healthy controls. In contrast, T lymphocytes responsive to adipocyte membranes were detected only in patients with GD. TSH binding inhibiting antibodies were found exclusively in six patients with GD, and thyroid stimulating antibodies in five of these patients. In co-culture experiments designed to study the activity of antigen-specific suppressor T cells, low numbers of T cells from 6/6 normal controls, 4/4 patients with HT and 5/5 patients with myxoedema suppressed the response to adipocyte membranes of T lymphocytes from patients with Graves' disease. The results of this study demonstrate different patterns of T-cell reactivity to thyroid antigens in patients with Graves' disease, Hashimoto's thyroiditis and myxoedema and suggest that cellular immunity to the TSH receptor is restricted to patients with Graves' disease and associated with a defect in the specific immunoregulatory control of this response.

Adolescent

Hyperparathyroid bone disease in diabetic renal failure.

Hyperparathyroid bone disease is a common complication of end stage renal failure, particularly in patients on maintenance haemodialysis. Several studies have, however, shown a near absence of hyperparathyroid bone disease in diabetic patients who have been receiving haemodialysis for periods of up to 4 years. We have studied biochemical indices of mineral metabolism in 54 consecutive pre-dialysis patients with moderate to severe renal impairment. Deteriorating renal function was associated with developing hypocalcaemia and hyperphosphataemia. Hypocalcaemia was strongly related to increased severe alkaline phosphatase activity (p less than 0.001), suggesting the development of hyperparathyroidism. Five patients with hypocalcaemia and increased alkaline phosphatase were studied in detail. All had elevated serum concentrations of parathyroid hormone and histological signs of hyperparathyroidism on bone biopsy. Three of the patients had low serum 25 hydroxyvitamin D levels with associated osteomalacia, the other 2 patients were notable for their long duration of renal failure. In the long-term (greater than 4 years) we also observed the development of hyperparathyroidism in a small group of diabetic patients maintained on haemodialysis. We conclude that diabetic patients are not uniquely protected against renal osteodystrophy. Although the prevalence of hyperparathyroidism may be lower in diabetic patients than in those with other types of renal disease, the same factors which predispose to bone disease in non-diabetic patients (long duration of renal failure, low serum 25 hydroxyvitamin D and long periods on haemodialysis) also operate in the diabetic population.

Adult

Renal osteodystrophy.

Over the past decade important advances in our understanding of the pathophysiology and treatment of renal osteodystrophy have been made. In particular, the role of calcitriol deficiency in the genesis of hyperparathyroidism in early renal failure is now better understood. So too are the effects of aluminium on bone, and whereas the more florid aluminium related disease is now unusual the more subtle effects of aluminium are now being appreciated. There is still a major problem in the long-term treatment of hyperparathyroid bone disease. The reasons why parathyroid gland proliferation continues to occur on dialysis therapy require a better understanding of cellular events regulating hormone production and parathyroid cell replication. The case for early intervention with vitamin D is now strong but whether such an approach materially influences the long-term outcome is not yet established. Changes in the approach to treatment and in the modalities used for renal replacement therapy will continue to modify the nature of the bone disease.

Aluminum

Antepartum pituitary necrosis in diabetes mellitus.

Pituitary infarction occurred during pregnancy in two insulin-dependent diabetic patients aged 32 and 33 years. The diagnosis was delayed in each case before being confirmed biochemically and radiologically. A decreasing insulin requirement and recurrent hypoglycaemia made it possible to determine the exact time that pituitary infarction occurred during pregnancy. The clinical features of these cases should alert physicians to the possibility of pituitary infarction in diabetic pregnancy and minimize the delay in diagnosis.

Adult

Remission of psoriasis with etidronate treatment of underlying Paget's disease of bone.

The case is reported of a 64-year-old man in whom psoriasis developed in relation to Paget's disease of the underlying bone. Treatment of Paget's disease was associated with remission of psoriasis. We suggest that local hyperaemia is the common link in this association and that this lends support to the theory that vascular factors are important in the pathogenesis of psoriasis.

Etidronic Acid

Mild androgen insensitivity presenting with sexual dysfunction.

A man presented with sexual dysfunction and was found to have elevated serum levels of both gonadotropins and T, suggesting AIS. Small external genitalia were the only phenotypic abnormality. Serum T levels increased appropriately in response to hCG and CC, but the patient was severely oligospermic, and testicular biopsy study revealed profoundly impaired spermatogenesis. Studied on androgen receptors in genital skin fibroblasts were normal. PAIS with a virtually normal male phenotype can present in adulthood with sexual dysfunction as well as infertility. As with the syndrome of complete AIS, androgen receptor studies indicate that this is a heterogeneous group of disorders.

Adult

Osteopenia and metatarsal fractures in diabetic neuropathy.

Radiographs of the hands and feet of 19 diabetic patients with severe neuropathy were compared to those of 22 control patients without neuropathy. The two groups were matched for age, sex, and duration of diabetes. Cortical bone mass, measured by x-ray morphometry, was significantly lower in both the hands (p less than 0.002) and the feet (p less than 0.001) of those with neuropathy. The osteopenia was worse in the feet than the hands and also worse in women. Serum alkaline phosphatase levels were also significantly higher in the neuropathy group (p less than 0.005). Metatarsal fractures were a frequent finding in the neuropathic patients, but were not seen in controls. The presence of metatarsal fractures was strongly associated with the subsequent development of diabetic osteopathy (p less than 0.001). We conclude that cortical bone mass in the feet and hands is reduced in severe diabetic neuropathy. This may contribute to the predisposition to metatarsal fracture and diabetic osteopathy.

Adult

Renal bone disease.

Advances in the last few years have led to an understanding of some of the mechanisms by which renal bone disease arises with the result that, despite their complexity, the objectives of treatment and the way in which these might be realized have become more accurately defined.

Aluminum