Ursodeoxycholic acid treatment lowers the serum level of antibodies against pyruvate dehydrogenase and influences their inhibitory capacity for the enzyme complex in patients with primary biliary cirrhosis.

A two-year randomized, double-blind, placebo-controlled clinical trial used paired serum samples from 122 patients with primary biliary cirrhosis to compare the effect of ursodeoxycholic acid and colchicine on their immune parameters. IgG antibodies to pyruvate dehydrogenase, the major autoantigen in primary biliary cirrhosis, were determined by enzyme-linked immunosorbent assay and immunoblot; enzyme inhibition assay against pyruvate dehydrogenase was used to test the changes of the functional reactivity of the serum autoantibodies. Treatment with ursodeoxycholic acid decreased both the level of IgG antibodies to pyruvate dehydrogenase (P < 0.01) and the inihibitory titer of the sera for pyruvate dehydrogenase (P < 0.01). Treatment with colchicine or placebo showed no statistically significant changes in either the antibody levels or the inhibitory titers. Ursodeoxycholic acid thus alters the immune parameters of patients with primary biliary cirrhosis. The mechanism of these changes needs further investigation.

Antihypertensive effect of diltiazem in a slow-release formulation for mild to moderate essential hypertension.

The antihypertensive efficacy and frequency of adverse reactions following administration of diltiazem in a new slow-release formulation were compared with placebo in 34 patients with mild to moderate essential hypertension in a randomized, double-blind, crossover study. After 6 weeks of treatment with diltiazem (240 or 360 mg/day), average supine blood pressure (BP) decreased from 165 +/- 21/101 +/- 5 mm Hg at baseline to 152 +/- 16/93 +/- 4 mm Hg compared with 160 +/- 19/100 +/- 7 mm Hg with placebo (p less than 0.01/p less than 0.001). Standing BP decreased from 162 +/- 20/107 +/- 6 mm Hg at baseline to 150 +/- 14/101 +/- 5 mm Hg compared to 159 +/- 18/107 +/- 8 mm Hg with placebo (p less than 0.01/p less than 0.001). The supine heart rate after diltiazem was 65 +/- 7 beats/min and after placebo 69 +/- 9 beats/min (p less than 0.01). There were no hematologic side effects. Only minor differences between diltiazem and placebo were observed in some of the biochemical laboratory values. Four patients were withdrawn due to side effects during treatment with diltiazem and 2 with placebo. Diltiazem in a slow-release formulation given twice a day lowered blood pressure significantly as monotherapy in patients with mild to moderate hypertension and was well tolerated.

Clinical features of Crohn's disease: a clinical study of one hundred patients found in an unselected population.

One hundred patients (mean age 34 years, range from 12 to 70 years) were treated at Tampere University Hospital during the thirteen year period, 1972-1984. Our hospital takes responsibility for the treatment of patients with Crohn's disease found in an unselected population of 400,000 inhabitants. In 73% of cases Crohn's disease was diagnosed before the age of forty. The mean interval between the first clinical signs and the diagnosis was 3.3 years. In 57% of the patients the diagnosis was reached within one year. In nine patients the primary diagnosis was colitis ulcerosa. Most patient were anemic and were in the state of inflammation and/or catabolism suggested by low blood hemoglobin concentration and high ESR and CRP values on admission. Three percent of the patients had macroscopic Crohn's disease in all parts of the gastrointestinal tract, whereas 22% had it only in the small intestine and 18% only in the colon. Fifty of the hundred patients had lesions in the terminal ileum and 20% in the anus. The specific finding for the present series was a high frequency of rectal lesions, in 29% of the patients. Histologically the condition was more often (P less than 0.001) revealed by the laparatomy specimen than the endoscopic biopsy, which gave a positive histology more often (P less than 0.001) in the lower than in the upper gastrointestinal tract. No gastrointestinal malignancies were found.

Is fluoride treatment justified today?

Fluoride has been used for the treatment of osteoporosis since 1961, because it increases trabecular bone mass in the spine and may be effective in the treatment of spinal osteoporosis. Fluoride treatment is still controversial because of its side effects, the high rate of non-responders, possible osteomalacic effect on bone, deleterious effects on cortical bone, and especially because of its uncertain effect on fracture rate. At present, fluoride therapy is highly questionable in the prophylaxis and treatment of osteoporosis.

Once daily compared with twice daily administration of slow-release diltiazem as monotherapy for hypertension.

We compared the efficacy of the antihypertensive drug diltiazem in a slow release formulation administered once daily with its twice daily administration as monotherapy in 34 patients with mild to moderate essential hypertension. All subjects received placebo for three weeks before the randomised, double blind, crossover study, and their supine diastolic blood pressure (BP) ranged from 95 mmHg to 115 mmHg. After the patients had received the placebo for three weeks diltiazem was titrated in the open label treatment to either 120 mg or 180 mg twice daily until the target BP level was achieved. After the open three weeks' of treatment with diltiazem twice daily patients were allocated randomly for either once daily or twice daily administration. After a six week, double blind period, the treatment was changed according to the crossover design. With a dose of 120 mg or 180 mg twice daily patients' supine and standing BP readings were significantly lower than when they took the drug once daily. In the subgroup (n = 19) with the maximum dose of diltiazem given twice daily and once daily BP levels were lower in those subjects on twice daily treatment than in those treated once a day with the same total daily dose, the differences being significant. Administration of diltiazem once a day in a slow release formulation was not as effective as a twice daily dose when the dose titration was greatest or when compared with the same dosage (240 mg x 1/day or 120 mg x 2/day).

Prophylactic fluoride treatment and aged bones.

In a double-blind trial with monofluorophosphate (25 mg fluoride per day) given to 460 aged persons (237 treated, 233 control) for eight months no difference was observed in height, admission to hospital, or mortality. Fractures and exacerbation of arthrosis were more frequent in the fluoride group. Vertebral x-ray films showed no difference. The free ionized fluoride levels in the plasma of the fluoride-treated group were still twice as high two months after treatment ended. Fluoride treatment in the prophylaxis of osteoporosis is not recommended unless there is simultaneous measurement of plasma ionized fluoride levels.

Calcium, vitamin D and anabolic steroid in treatment of aged bones: double-blind placebo-controlled long-term clinical trial.

In a double-blind trial, 327 patients (57 men) over 65 (mean age 79.5) years received all possible combinations of calcium carbonate 3 g, vitamin D3 1000 iu, methandienone 2.5 mg and/or placebos daily for 9 months. The higher incidence of bone fractures in the placebo group was not significant. Serum calcium, phosphorus, creatinine, aspartate aminotransferase and alkaline phosphatase were followed: the greatest changes occurred with methandienone, which thus reduced osteoporotic activity and increased the muscular mass most effectively; calcium carbonate had the poorest effect. Surprisingly, coronary mortality was higher among those taking all three active substances. With two treatments the increase was not significant, but when both the groups receiving a combination of any two of the treatments were compared with those taking only one or neither of these two treatments, a significant increase in coronary deaths was seen, most significant (P less than 0.001) in those receiving vitamin D3 and methandienone.

Effect of calcium p-chlorphenoxyisobutyrate and calcium carbonate on plasma lipids and lipoproteins of patients with hyperlipoproteinaemia.

Since dietary calcium had been reported to reduce plasma lipids, the effects of calcium carbonate (CaCO3, 2 g/day) and the calcium salt of p-chlorphenozyisobutyrate (Ca-CPIB, 2 g/day), both singly and in combination, were studied in outpatients with primary hyperlipidaemia. Three groups of five patients were followed in a double-blind cross-over study, in which placebo and the drugs were given alternately during four-week periods. The main results were: 1) CaCO3 alone did not produce any significant changes in plasma lipids. 2) Ca-CPIB reduced LDL-cholesterol in patients with type IIa and IIb by an average of 29 and 21%, respectively. It also lowered VLDL-triglyceride by 50% in type IIb and by 48% in four out of five patients with type IV. 3) The combination of CaCO3 and Ca-CPIB reduced LDL-cholesterol by 31 and 25% in types IIa and IIb, respectively. It also lowered VLDL-triglyceride by 48-52% in types IIa and by 46% in four out of five patients with type IIb. 4) Three out of five patients with type IV had a rise of LDL-cholesterol while on Ca-CPIB alone; two of the patients had the rise while on the combination. 5) After treatment with Ca-CPIB, either singly or in combination, there was a statistically significant lowering of ESR and of plasma inorganic phosphate and alkaline phosphatase. No clinical side effects were noted.

Thyroid autoimmunity and cardiovascular diseases.

The relationship of thyroid autoantibodies and elevated TSH level to indices of cardiovascular diseases was studied in two population series monitored for 5 years and in a cross-sectional hospital series. In a cohort of 1105 males, initially 55-74 years of age, deaths due to cardiovascular causes occurred in 19% of subjects with thyroid autoantibodies and in 11% of controls matched for age (P less than 0.05). In another cohort of 1045 males and 1223 females, initially 40-64 years of age, no difference emerged in males, while 6 out of 20 females who died of cardiovascular causes had thyroid autoantibodies, compared with 18% in the whole series. In a series of 97 hospital patients with myocardial infarction, 7 patients had thyroid autoantibodies as opposed to 12 antibody-positive subjects among controls matched for age and sex. Elevated TSH level appeared to be no better an indicator of cardiovascular morbidity or mortality than thyroid autoantibodies. It is concluded that thyroid autoimmunity may act as a cardiovascular risk factor under certain circumstances, but it does not have any general significance and the mechanism of action remains unclear.

Efficacy and tolerability of isradipine and metoprolol in treatment of hypertension: the Finnish Isradipine Study in Hypertension (FISH).

Eight hundred seventy-six men and women with diastolic blood pressure (DBP) of 95-115 mm Hg during a 4-week placebo period were included in a multicenter trial; 479 patients had previously been treated for hypertension. The patients were randomized to receive isradipine or metoprolol; both groups were comparable for age, weight, height, smoking habits, and duration of hypertension. By the end of the placebo period, 79 patients did not fulfill the final entry criteria and were withdrawn. The isradipine group consisted of 398 patients (164 women and 234 men), and the metoprolol group consisted of 399 patients (173 women and 226 men). The initial dose of isradipine was 1.25 mg twice daily (b.i.d.), and the initial dose of metoprolol was 50 mg b.i.d.; the doses were doubled after 4 weeks if DBP had not decreased to less than or equal to 90 mm Hg. After 8 weeks, the isradipine group began combination therapy with metoprolol 50 mg b.i.d. and the metoprolol group began combination therapy with isradipine 1.25 mg b.i.d. if DBP was not less than or equal to 90 mm Hg. After 8 weeks monotherapy, mean BP (MBP) was reduced by 13/11 mm Hg (161/104 to 148/93) in the isradipine group and by 15/12 mm Hg (160/103 to 145/91) in the metoprolol group. Monotherapy with isradipine normalized DBP to less than or equal to 90 mm Hg in 52% with a mean dose of 4.26 mg daily, and monotherapy with metoprolol normalized DBP in 58% with a mean dose of 155 mg daily.1+

Serum vitamin D level after an annual intramuscular injection of ergocalciferol.

An annual intramuscular injection of ergocalciferol (150,000 IU) normalized low serum (25(OH)D concentrations in elderly people for 1 year. The treatment had a slight effect on serum 24,25(OH)2D levels but no effect on 1,25(OH)2D levels.

Annual injection of vitamin D and fractures of aged bones.

In order to investigate the effect of a supplementation of vitamin D in the prophylaxis of fractures of the bones of aged people, an annual intramuscular injection of ergocalciferol (150,000-300,000 IU) was given to two series of aged subjects: first to 199 (45 male) of 479 subjects (110 male) aged more than 85 years who were living in their own home, and second to 142 (29 male) of 320 (58 male) subjects aged 75-84 and living in a home for aged people. This prospective series was divided into treatment groups according to month of birth. These injections were given annually from September to December in the years 1985-1989, two to five times to each participant. The fracture rates, laboratory values, vitamin D levels, possible side effects, and mortality were followed until October 1990. A total of 56 fractures occurred in the 341 vitamin D recipients (16.4%) and 100 in 458 controls (21.8%) (P = 0.034). The fracture rate was about the same in both outpatient and municipal home series. Fractures of the upper limb were fewer in the vitamin D recipients, 10/341 = 2.9% (P = 0.025), than in the controls, 28/458 = 6.1%, during the follow-up. A similar result was obtained in fractures of ribs, 3/341 = 0.9% and 12/458 = 2.6%, respectively. Fractures of the lower limbs occurred almost as frequently, 31/341 = 9.1%, among the vitamin D recipients as among the controls, 49/458 = 10.7%. The fracture rate was higher in females (22.2%) than in males (9.5%). The fractures were fewer in the vitamin D recipients only in females.(ABSTRACT TRUNCATED AT 250 WORDS)