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T Diamond

Publications and source records attributed to T Diamond.

At least 19 recordsLinked to original sources

Hip fracture in elderly men: the importance of subclinical vitamin D deficiency and hypogonadism.

OBJECTIVE: To determine the major risk factors for hip fracture in elderly men. DESIGN: Prospective recruitment, followed by analysis of clinical and biochemical variables. PATIENTS AND SETTING: Men aged 60 years and older who presented to St George Hospital (a 650-bed tertiary-care centre) in 1995, comprising all 41 men with hip fractures, as well as 41 hospital inpatient and 41 outpatient control subjects without hip fractures. MAIN OUTCOME MEASURES: Osteoporotic risk factors (including age, body weight, comorbid illnesses, alcohol intake, cigarettes smoked, and corticosteroid use) and serum concentrations of creatinine, urea, calcium, albumin, alkaline phosphatase, parathyroid hormone, 25-hydroxyvitamin D and free testosterone. RESULTS: There were no significant differences between the hip fracture and two control groups on any of the osteoporotic risk factors. Men with hip fracture had significantly lower mean serum 25-hydroxyvitamin D concentration (45.6 nmol/L; 95% confidence interval [CI], 36.9-52.3 nmol/L) than both inpatient (61.1 nmol/L; 95% CI, 50.0-72.2 nmol/L) and outpatient (65.9 nmol/L; 95% CI, 59.0-72.8 nmol/L) controls (P=0.007). Subclinical vitamin D deficiency (defined as <50 nmol/L serum 25-hydroxyvitamin D) was 63% in the fracture group, compared with 25% in the control groups combined (odds ratio, 3.9; 95% CI, 1.74-8.78; P=0.0007). Inpatients with and without hip fractures had significantly lower mean serum albumin, calcium and free testosterone concentrations than outpatients (P< 0.05). In a multiple regression analysis, subclinical vitamin D deficiency was the strongest predictor of hip fracture (beta [regression coefficient], 0.34+/-0.19; P=0.013). CONCLUSIONS: Subclinical vitamin D deficiency in Australian men may contribute significantly to the development of hip fracture through the effects of secondary hyperparathyroidism, resulting in increased bone loss.

Aged

Body mass and body composition after total thyroidectomy for benign goiters.

To date there are no data available as to whether postmenopausal women who undergo total thyroidectomy for benign euthyroid goiter demonstrate changes in body mass or body composition. We prospectively evaluated 8 postmenopausal women (mean age 57 +/- 7; range 48 to 70 years) who underwent total thyroidectomy for benign goiter. All patients were euthyroid preoperatively (serum free thyroxine [FT4] 12.7 +/- 0.6 pmol/L and serum thyrotropin [TSH] 0.98 +/- 0.2 mU/L) and were commenced on adequate thyroxine replacement immediately postoperatively in order to maintain a serum TSH within the normal range (0.5-4 mU/L). Body mass, body composition, and thyroid function were assessed preoperatively, and at 4 and 12 months postoperatively. Body composition was assessed by anthropometry and dual energy x-ray absorptiometry (Lunar DPX-L scanner). Eight healthy postmenopausal women without evidence of thyroid disease matched for age, weight, and estrogen therapy who were followed over the same period were used as controls. All patients were maintained in a euthyroid status throughout the study. No significant changes in body mass or any parameter of body composition were demonstrated at 4 and 12 months postoperatively. Similar findings were recorded in our control group. We conclude that total thyroidectomy in euthyroid postmenopausal women with benign goiter does not result in a significant change in either body mass or body composition if adequate thyroxine replacement is maintained.

Aged

Acute effects of oral glibenclamide on blood pressure and forearm vascular resistance in diabetics.

1. To determine the effects of an acute oral dose of glibenclamide on blood pressure (BP), basal forearm vascular resistance (FVR) and FVR responses to the K+(ATP) channel activating vasodilator diazoxide, a placebo-controlled, double-blind cross-over study was performed in eight male volunteers with non-insulin-dependent diabetes mellitus. 2. Changes in vascular responses to progressively increasing concentrations of diazoxide (3.75-30 mg/kg per min) and noradrenaline (25-100 ng/kg per min) were measured by venous occlusion plethysmography. 3. Glibenclamide significantly lowered plasma glucose levels compared with placebo (P < 0.02) and attenuated the decrease in FVR (P < 0.05) and the decrease in systolic BP (P < 0.05) that followed a meal. However, vasodilator responses to diazoxide were potentiated by the administration of oral glibenclamide (P < 0.01). 4. Acute administration of oral glibenclamide attenuates the normal decrease in FVR and systolic BP that follows a meal and potentiates rather than inhibits forearm vasodilator responses to intra-arterial diazoxide, probably via indirect humoral effects. These results suggest that glibenclamide has direct or indirect vasoconstrictor effects that antagonize the normal increase in forearm blood flow that follows a meal and that the inhibition of vascular K+(ATP) channels following acute oral glibenclamide administration is clinically insignificant compared with other indirect vascular effects of the drug.

Adult

Familial slipped capital femoral epiphysis: a report and considerations in management.

BACKGROUND: Familial inheritance of slipped capital femoral epiphysis (SCFE) is known. It has not been described in non-identical twins. A family where the mother and three of five siblings developed SCFE were investigated and managed. METHODS: Anthropometric measurement consisted of height-weight ratios. Serum sex hormone levels and bone Gla Protein was measured. Bone mineral densities were evaluated. RESULTS: The affected siblings had higher bodyweight percentiles. Other investigations were within normal limits. CONCLUSION: The unfavourable height-to-weight ratio was one of the mainstays in developing a management protocol for all siblings. The management protocol developed for the family is discussed.

Algorithms

Biochemical, histomorphometric and densitometric changes in patients with multiple myeloma: effects of glucocorticoid therapy and disease activity.

It is unknown whether bone changes which can occur in multiple myeloma (MM) are due to cytokine-induced osteoclastic bone resorption from a clone of abnormal plasma cells or high-dose glucocorticoid therapy. We studied 25 MM patients treated for 1-12 years with combination chemotherapy, subdivided into two groups. Group 1 consisted of 12 patients with stage I and II myeloma and group 2 consisted of 13 patients with stage III MM. Their serum biochemistry, tetracycline-labelled bone histomorphometry and bone densitometry were compared to age- and sex-matched controls. Patients with MM demonstrated increased indices of bone resorption (P < 0.001 versus controls) and, to a lesser extent, increased indices of bone formation (P < 0.01 versus controls). No patient had evidence of a mineralization defect. Lumbar spine, femoral neck and total body bone mineral density measurements (BMD) were significantly lower in group 2 compared with group 1 (P < 0.05). Following 12 months of therapy, lumbar spine BMD decreased by 6.6% (95% CI, 2.7% to -9.3%) and femoral neck BMD decreased by 9.5% (95% CI, -3.2% to -15.9%). In a stepwise regression analysis, cumulative prednisolone dosage (B Coef. = -0.39; P = 0.03) and plasma cell infiltrate (B Coef. = -0.08; P = 0.05) were the most important predictors of lumbar spine bone loss, whereas serum paraprotein (B Coef.= -0.35; P = 0.02) and plasma cell infiltrate (B Coef. = -0.20; P = 0.04) were the most important predictors of femoral neck bone loss. We conclude that MM is characterized by high bone turnover with osteoblast-osteoclast uncoupling. Both disease activity and high-dose glucocorticoid therapy may be responsible for the ongoing bone loss seen with MM.

Absorptiometry, Photon

Acute effects of oral glibenclamide on blood pressure and forearm vascular resistance in diabetics.

1. To determine the effects of an acute oral dose of glibenclamide on blood pressure (BP), basal forearm vascular resistance (FVR) and FVR responses to the K+ATP channel activating vasodilator diazoxide, a placebo-controlled, double-blind cross-over study was performed in eight male volunteers with non-insulin-dependent diabetes mellitus. 2. Changes in vascular responses to progressively increasing concentrations of diazoxide (3.75-30 mg/kg per min) and noradrenaline (25-100 ng/kg per min) were measured by venous occlusion plethysmography. 3. Glibenclamide significantly lowered plasma glucose levels compared with placebo (P < 0.02) and attenuated the decrease in FVR (P < 0.05) and the decrease in systolic BP (P < 0.05) that followed a meal. However, vasodilator responses to diazoxide were potentiated by the administration of oral glibenclamide (P < 0.01). 4. Acute administration of oral glibenclamide attenuates the normal decrease in FVR and systolic BP that follows a meal and potentiates rather than inhibits forearm vasodilator responses to intra-arterial diazoxide, probably via indirect humoral effects. These results suggest that glibenclamide has direct or indirect vasoconstrictor effects that antagonize the normal increase in forearm blood flow that follows a meal and that the inhibition of vascular K+ATP channels following acute oral glibenclamide administration is clinically insignificant compared with other indirect vascular effects of the drug.

Adenosine Triphosphate

Delayed presentation of porta hepatis injury following blunt abdominal trauma.

A 73 year old lady developed abdominal pain, anaemia and obstructive jaundice 18 days after a road traffic accident. The jaundice was due to compression of the biliary confluence by a haematoma which was caused by a laceration of the left portal vein. The portal vein was repaired (lateral venorrhaphy) and post-operative recovery was uncomplicated. Porta hepatis injuries are difficult to diagnose and delayed presentation is not uncommon. Significant morbidity and mortality may ensue if aggressive management is not adopted.

Abdominal Injuries

Comparative effects of glibenclamide and metformin on ambulatory blood pressure and cardiovascular reactivity in NIDDM.

OBJECTIVE: To compare the effects of chronic glibenclamide and metformin therapy on blood pressure (BP) and cardiovascular responsiveness in patients with NIDDM. RESEARCH DESIGN AND METHODS: Fourteen patients with NIDDM received metformin or glibenclamide for 1 month in a double-blind, randomized crossover study. At the end of each treatment period, patients were tested for forearm vascular responsiveness to intrabrachial arterial infusion of diazoxide (an ATP-sensitive potassium channel opener), acetylcholine, sodium nitroprusside, and norepinephrine, BP responses to intravenous infusions of NE and angiotensin II, BP responses to cold pressor testing and isometric exercise, and 24-h ambulatory BP monitoring. RESULTS: Metformin and glibenclamide produced similar glycemic control. Mean 24-h BPs did not differ between the two groups, but mean 24-h heart rates were significantly lower (75 +/- 6 bpm vs. 80 +/- 6 bpm) on glibenclamide therapy than on metformin. Plasma norepinephrine levels were significantly higher on glibenclamide (6.41 +/- 1.77 vs. 4.26 +/- 1.54 mmol/l, P < 0.01), and systolic BP responses to intravenous norepinephrine and angiotensin II were significantly higher on glibenclamide than on metformin (P < 0.02 and P < 0.05, respectively). Systolic BP responses to cold pressor testing appeared higher on glibenclamide than on metformin, but the difference did not quite achieve statistical significance (P = 0.052). Baseline forearm vascular resistance did not differ between the two drugs, nor did forearm vascular resistance responses to diazoxide, acetylcholine, sodium nitroprusside, and norepinephrine differ. CONCLUSIONS: Glibenclamide therapy is accompanied by greater systolic BP responses to norepinephrine and angiotensin II and higher plasma norepinephrine levels than those that occur on metformin therapy. Lower heart rates on glibenclamide therapy despite evidence of greater sympathetic activity suggests that glibenclamide may have negative chronotropic effects.

Acetylcholine

Intestinal barrier dysfunction in clinical and experimental obstructive jaundice and its reversal by internal biliary drainage.

Intestinal mucosal barrier function in obstructive jaundice was assessed in an animal model and in patients. The effect of internal biliary drainage in patients was also examined. Bile duct ligation for 1 week in the rat resulted in significant bacterial translocation (in seven of 12 animals following ligation versus none of the shamoperated controls, P < 0.01). Intestinal permeability, measured by the urinary recovery of orally administered polyethylene glycol, was also significantly increased (+66.2 per cent for ligation versus -11.6 per cent for sham, P < 0.01). A prospective study was performed on 33 patients with obstructive jaundice undergoing internal biliary drainage, and results were compared with those in six non-jaundiced patients undergoing laparotomy or endoscopic retrograde cholangiopancreatography and in 11 health volunteers. The lactulose: mannitol ratio was used as an intestinal permeability index. Mean(s.e.m.) intestinal permeability assessed before operation was significantly increased in jaundiced patients compared with control patients (0.050(0.010) versus 0.016(0.003), P < 0.005). The mean(s.e.m.) lactulose: mannitol ratio in the healthy volunteers was 0.020(0.003), which was similar to that in control patients. In the jaundiced group of patients the intestinal permeability index fell to within normal levels after 28 days of internal biliary drainage (0.050 before operation versus 0.021 at 28 days, P < 0.02). These data indicate that intestinal barrier function is impaired in obstructive jaundice and that this impairment is reversed by return of bile to the gastrointestinal tract.

Animals

Estrogen replacement may be an alternative to parathyroid surgery for the treatment of osteoporosis in elderly postmenopausal women presenting with primary hyperparathyroidism: a preliminary report.

Parathyroid surgery is indicated in patients presenting with primary hyperparathyroidism (PHPT) and osteoporosis (defined as bone mineral density more than 2 standard deviations below normal). Many are elderly women with complex medical problems, either unwilling or considered unfit for surgery. Estrogen replacement therapy (ERT) may potentially be an alternative form of therapy in this group. We studied 15 consecutive postmenopausal women presenting with PHPT and osteoporosis. Group 1 comprised 5 women who elected to be treated with ERT (conjugated equine estrogen, 0.3-0.625 mg/day). The other 10 women underwent successful parathyroidectomy. These 10 patients were randomly subdivided into group 2 (5 patients who received calcitriol 0.25 micrograms b.i.d. for 12 months following surgery) and group 3 (5 patients who received elemental calcium 1 g/day for 12 months following surgery). Lumbar spine and femoral neck bone mineral density (BMD) were measured prior to and after 12 months of therapy, using a dual-energy X-ray absorptiometer (Lunar DPX-L). The three groups did not differ with respect to their ages (group mean 71.8 years), or baseline serum calcium (group mean 2.77 mmol/l), serum parathyroid hormone (group mean 11.0 pmol/l), lumbar spine BMD (group mean 0.93 g/cm2) and femoral neck BMD (group mean 0.73 g/cm2). Serum calcium normalized in all patients who underwent surgery and none developed hypoparathyroidism. A non-significant decrease in serum calcium was seen in patients treated with ERT only. Lumbar spine (+5.3% per year; 95% CI, 1.1% to 9.6%) and femoral neck BMD (+5.5% per year; 95% CI, -2.1% to 13.2%) increased significantly after 12 months of ERT (p < 0.001 compared with pre-therapy values). These increases in BMD did not differ significantly from those in patients who underwent successful parathyroidectomy followed by either calcitriol therapy or calcium replacement (lumbar spine BMD increase of +6.2% per year, 95% CI 3.1% to 9.4%; and femoral neck BMD increase of +3% per year, 95% CI 0 to 6%). In summary, increases in lumbar spine and femoral neck BMD occur following treatment of PHPT. ERT appeared as effective as parathyroidectomy (combined with either calcitriol or calcium supplements) for the treatment of osteoporosis in elderly postmenopausal women presenting with PHPT.

Aged

Acquired osteosclerosis associated with intravenous drug use and hepatitis C infection.

Hepatitis C has recently been recognized as a secondary cause of osteosclerosis; a further example, the first outside of North America, is described. A 37-year-old man with a history of intravenous drug use and known to be hepatitis C antibody positive presented with bone pain. Radiographs and magnetic resonance imaging demonstrated an increase in cortical and trabecular bone that on biopsy was of a normal lamellar pattern but markedly sclerotic. Biochemical markers of bone formation (serum osteocalcin) and resorption (urinary hydroxyproline excretion rate) were both markedly elevated. Pain lessened following administration of pamidronate. Biochemical markers of bone turnover fell towards their reference ranges 12 months after initiating pamidronate therapy but without significant change in bone mineral density. Osteosclerosis is a rare complication of hepatitis C infection, the symptoms of which are controllable with diphosphonate therapy.

Adult

The identification of false positive responses to the pentagastrin stimulation test in RET mutation negative members of MEN 2A families.

OBJECTIVE: The pentagastrin stimulation test is the traditional test used for the identification of asymptomatic individuals in multiple endocrine neoplasia type 2A (MEN 2A) and familial medullary thyroid carcinoma (FMTC). The identification of mutations in the RET proto-oncogene segregating with the disease phenotype in MEN 2A and FMTC families has made it possible to re-examine the validity of using this test for the identification of affected family members. DESIGN: Sequential and single pentagastrin stimulation test data were collected following the identification of RET mutation positive and RET mutation negative members of families with MEN 2A or FMTC. PATIENTS: RET mutations were identified in 16 Australian and New Zealand MEN 2A or FMTC families. An analysis of 39 individuals from these families was included in this study. Thirty-two individuals (14 males, 18 females) had previously been determined as RET mutation negative. Seven individuals (6 males, 1 female) had previously been determined as RET mutation positive. Two RET mutation negative males had thyroidectomy based on prior pentagastrin test results. MEASUREMENTS: Serum calcitonin levels in response to stimulation with pentagastrin were measured at 0, 1, 2, 5 and 10 minutes post injection. Mutation analysis of the RET proto-oncogene was performed in all individuals. In two RET mutation negative individuals from two MEN 2A families, thyroidectomy was performed and C-cells were quantitated in order to determine the diagnosis of C-cell hyperplasia. RESULTS: There was a statistically significant difference (P < 0.013) between RET mutation negative male and female mean peak calcitonin responses of 282 +/- 236 and 96 +/- 62 (mean +/- SD) ng/l respectively. False positive responses to pentagastrin stimulation were identified in seven individuals who were RET mutation negative in two of the 16 families. Histologic examination of the thyroid glands in the two RET mutation negative individuals who had thyroidectomy demonstrated C-cell hyperplasia in one but not in the other. CONCLUSIONS: There is considerable overlap between pentagastrin test results in individuals who are RET mutation positive and those who are RET mutation negative. These results indicate a need for routine performance of RET proto-oncogene analysis on all individuals at risk of developing MEN 2A or FMTC and a coupling of pentagastrin test results and RET proto-oncogene analysis in the decision to proceed with thyroidectomy.

Adolescent