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A strain-transducer to measure bone strength is presented. Cancellous bone specimens were taken at autopsy from the iliac crests of 28 women and 66 men. There was a good correlation between bone strength, age and bone mineral density. Females had a lower bone strength than males. The bone strength of patients who died of chronic disease known to cause osteoporosis was lower than that of subjects who suffered sudden death. The equipment is also suitable for in vivo studies of human cancellous bone strength.

Adrenocortical adenoma is the most common cause of primary hyperaldosteronism. Most tumours are small, less than 2 cm in diameter and, therefore, their localization may be difficult. We have compared two different methods, adrenal scintigraphy (AS) and computed tomography (CT) in the differential diagnosis of 12 patients with primary hyperaldosteronism. AS was performed using either [131I]cholesterol or 6-iodomethyl-19-norcholesterol during dexamethasone suppression. Of the patients, five showed a normal CT and symmetrical uptake of the isotope as AS. They were considered representative of bilateral hyperplasia. All showed good therapeutic response to spironolactone. Seven patients had an adrenocortical adenoma verified at operation. The CT finding indicated a tumour in five patients. This was correct in four, but in one patient the adenoma was found in the contralateral adrenal gland. In two patients with an adenoma, CT was considered normal. AS correctly indicated the tumour in all seven patients. The uptake was unilateral in six, and bilateral but clearly asymmetrical in one patient. The results indicate that AS is superior to CT in the pre-operative localization of aldosteroma. Although CT remains the primary method for the investigation of these patients, AS should be applied always when CT does not unequivocally indicate the presence and localization of an adrenal tumour.

Three cases of malignant lymphoma of the breast are described, seen over a 14 year period in the district of Kuopio University Central Hospital. The neoplasms were either of high or intermediate grade of malignancy: one immunoblastic, one Burkitt-type, and one centroblastic-centrocytic malignant lymphoma. The patient with centroblastic-centrocytic malignant lymphoma had advanced disease with pulmonary and adenoidal involvement and died 15 months after the detection of the breast tumor. The two other neoplasms were confined to the breast with no evidence of further dissemination. The patient with immunoblastic malignant lymphoma developed intestinal lymphoma 3 years later which was treated with surgery and cytostatic therapy. The patient has since been in remission for a period of 10.5 years. The patient with Burkitt-type malignant lymphoma was subjected to surgical resection which was followed by cytostatic treatment. The patient has remained in good health during the 20-month follow-up. The correct diagnosis is especially important in breast lymphoma because without it the appropriate treatment cannot be applied.

A 51-year-old woman with a history of several years' watery diarrhoea caused by a vasoactive intestinal peptide (VIP) secreting tumour of the pancreas (VIPoma) is presented. Measured stool outputs ranged from 1000 to 2600 ml/24 h. S-K 2.5 mmol/I. The pancreatic VIPoma was localised by abdominal angiography and removed. The plasma concentration of vasoactive intestinal peptide was 80 pmol/l before and 5 pmol/I after the operation (normal under 30 pmol/I). The patient has been symptom-free for 15 months since surgery.

The mineral density of bone was measured in 45 patients with primary hyperparathyroidism before surgical treatment and during follow-up averaging 6.5 years, using the Am241 gamma transmission method. Statistically significant demineralization was found at the time of surgery. Removal of pathologic gland(s) was followed by healing of bone density during periods up to 4-5 years. Thereafter bone loss was again faster than in controls. The cause may be a persistent disturbance in the bone-remodelling process.

A series of 29 patients with primary osteoarthrosis of the hip were studied to evaluate their bone mineral status. A comparison was made with a series of persons with healthy bones. The bone mineral content of the osteoarthrotics, as measured either by gamma ray attenuation in the forearm bones, or as cortical indexes, or obtained from the combined cortical thicknesses of the second metacarpals from the radiographs, was not higher than in the control series. These findings do not support the concept that patients with osteoarthrosis tend to have a higher "mineral density" than healthy people.

A new technique was developed for determination of the trabecular bone mineral density in the distal radius. The method is based on measurement of the intensity ratio of coherently and Compton scattered photons using a 241Am radionuclide as the radiation source and a semiconductor crystal as the detector. The bone material consisted of 28 autopsy samples from distal radii of female subjects. A good correlation was observed between bone ash content and the coherent/Compton scattering ratio. The trabecular bone mineral density correlated well with the mineral density values obtained by the gamma transmission method. The method was reproducible within 3%.

A new approach for measuring blood flow in bone is presented. It consists of the local injection of 133Xe into the proximal femur of adult beagles and the external measurement of isotope washout curves. The curves were analyzed using a two-compartment exponential model. The half-times for the tracer washout from the fast and slow compartment were 3.34 +/- 0.48 min and 33.6 +/- 11.7 min (mean +/- 1 S.D.) respectively. Blood flow was calculated using a measured blood to bone partition coefficient of 1.55 ml/g. The mean blood perfusion in proximal femur of the dog was 10.8 +/- 4.3 ml/100 g/min (mean +/- 1 S.D.). This value agrees well with most estimates of bone circulation. Due to rapid disappearance of 133Xe the method is easy to repeat and is thus suitable for physiological studies of local blood flow in bones.

In three different areas of Finland, fluoride in bone and its effect on the histomorphometry of trabecular bone was studied. Bone samples were taken from cadavers from a low-fluoride area (fluoride concentration under 0.3 ppm), an area with fluoridated drinking water (1.0-1.2 ppm) and a high-fluoride area (over 1.5 ppm). The fluoride content in trabecular bone was greatly increased in the high-fluoride area, and it was also higher in the fluoridated-water area than in the low-fluoride area. Histomorphometric bone changes were markedly increased when the fluoride content in water exceeded 1.5 ppm.

Twenty-three patients who had been given a proximal gastric vagotomy and 29 patients who had had an antrectomy were examined periodically for 5 years after their operations for duodenal ulcers. Five years after surgery, 83% of the proximal gastric vagotomy patients and 86% of the antrectomy and selective vagotomy patients were included in Visick grades I-II. We found 4/24 recurrent ulcers in the vagotomy group and 1/29 in the antrectomy group; in addition 3 of the antrectomy patients had to be reoperated. Acid secretion was reduced by 54% in the vagotomy patients and by over 90% in the antrectomized patients. In the group that had had a proximal gastric vagotomy, maximal acid secretion in the insulin test decreased by 78%. Body weight did not decrease and haematological status did not worsen in either group. Intestinal absorption of fat, xylose and vitamin B12, serum calcium levels and urinary excretion did not change during the follow-up. One year after the operation, the level of serum alkaline phosphatase had risen, and urinary excretion of hydroxyproline had increased in the resected group but after five years, these values were unchanged. Mineral density of bone unchanged decreased significantly in both groups. We conclude that during five years after surgery antrectomy with selective vagotomy does not cause more metabolic disturbances than proximal gastric vagotomy, but is followed by more mechanical problems than proximal gastric vagotomy.

The bone mineral density (g/cm3) of the distal cancellous radius was determined in a consecutive series of 21 women and 54 men with urolithiasis with the Americium-241 gamma ray attenuation method. Bone mineral density was statistically significantly lower in both sexes compared with coeval healthy subjects. Further study is needed to examine the relationship between the bone mineral density and disturbances in calcium metabolism in patients with renal stone disease.

The zinc content of cancellous bone from the iliac crest was determined by the X-ray fluorescence technique in an autopsy series of 28 women and 66 men. The bone-zinc content was statistically related to age, but there was a large variation. It reached a maximum value in the fifth decade and thereafter decreased with age in both sexes. Men with a chronic disease had a lower zinc content than those who had died suddenly. There was a significant correlation between the zinc content and the bone strength in women (p less than 0.01) and in men (p less than 0.05). Zinc is thought to play a part in osteoporosis.

To study its pharmacokinetics and especially microCi/100 mg was infused i.v. in 8 patients with a T-tube inserted in the common bile duct at choledocholithotomy 7-10 days prior to the study. Bile was collected in fractions by continuous suction over a 24 h period. Blood samples were taken and urine collected up to 48 h after the dose. Tolfenamic acid and its metabolites were separated by TLC and were quantitated by liquid scintillation counting. The pharmacokinetics of tolfenamic acid could be described by a two compartment open model with V1 of 3.67 +/- 0.681 and VSS of 8.0 +/- 1.01. The total plasma clearance of tolfenamic acid averaged 106 +/- 8 ml/min and t1/2 beta was 1.38 +/- 0.32 h. A three compartment open model was required to describe the kinetics of total 14C. The plasma clearance of total 14C was 15.4 +/- 3.9 ml/min and its terminal half life averaged 19.0 +/- 4.1 h. The long half-life was caused by the slow elimination of tolfenamic acid metabolites. Four metabolites were measured in plasma and bile. The principal metabolites in bile were glucuronide/sulphate conjugates of hydroxylated derivatives of tolfenamic acid. The recovery of tolfenamic acid in bile was 1.1 +/- 0.3% of the dose, whereas the recovery of total 14C was 18.6 +/- 4.9%. The biliary clearances of tolfenamic acid and total 14C were 1.2 +/- 0.3 and 5.0 +/- 2.1 ml/min, respectively. Thus, biliary excretion plays a considerable part in the pharmacokinetics of tolfenamic acid.

Iliac crest biopsies were taken from patients with hip fracture from a low-fluoride area (less than 0.3 ppm), from an area with fluoridated drinking water (1.0-1.2 ppm), and from a high-fluoride area (greater than 1.5 ppm). Fluoride content analysis and histomorphometry of bone were performed. The hip fracture incidence during 1972-1981 was studied in the same areas. The fluoride content of the bone samples correlated with drinking water fluoride. In patients with hip fracture, both osteomalacia and osteoporosis were common. In the high-fluoride area also osteofluorosis was found in many patients. Osteofluorosis may occur if the fluoride content of trabecular bone exceeds 4,000 ppm and either the volumetric density of osteoid or the osteoid-covered trabecular bone surface is abnormally increased. There was no difference in incidence of hip fracture in the three areas.

A method for routine determination of vitamin D and its major metabolites 25-hydroxyvitamin D (25(OH)D), 24,25-dihydroxyvitamin D (24,25(OH)2D) and 1,25-dihydroxy-vitamin D (1,25(OH)2D) in serum samples from normal children and adults has been developed. Methodological improvements enable a rapid and accurate analysis of 25(OH)D and also the microscale screening of other metabolites present in large concentrations in serum. Vitamin D and its metabolites are extracted from serum samples using hexane/propan-2-ol, which allows a convenient separation of the water soluble and lipid soluble fractions from each other and also from proteins. Preparative silicic acid chromatography was used to separate vitamin D from its metabolites and also from the major portion of co-eluting lipid contaminants. An automated LC solvent delivery and sample introduction system was used to achieve the rapid separation of metabolites. Vitamin D was further purified using adsorption high-performance liquid chromatography and assayed using reverse phase high-performance liquid chromatography connected with UV detection. The 25(OH)D fraction from the preparative chromatography was measured by a competitive protein-binding assay along with 24,25(OH)2D, which was purified by reverse phase high-performance liquid chromatography along with 1,25(OH)2D. A diluted human serum from a pregnant woman (3rd trimester of pregnancy) was used as source of the binding protein for 25(OH)D and 24,25(OH)2D. 1,25(OH)2D was determined by a competitive protein-binding assay using a diluted cytoplasmic 1,25(OH)2D receptor protein isolated from the intestinal mucosa of rachitic chicks. Vitamin D and its metabolite levels were assayed in serum samples from normal children and adults.

The prevalence of lactose malabsorption (LM) was determined by lactose tolerance tests in 18 women with spinal fragility fractures and 28 women with hip fractures and compared with 35 female controls of the same ethnic background. The association of LM with bone density in the spine, bone mineral density in the distal radius and histomorphometric values of iliac crest biopsies was also evaluated. The prevalence of LM did not differ between the fracture groups and the control subjects. Patients with LM did not differ from those with normal lactose tolerance with regard to bone densitometry or histomorphometric findings in iliac crest biopsies. These results suggest that in Finland LM is not a risk factor for osteopenic fractures in the elderly.